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Impact of Food Insecurity and Undernutrition on Frailty and Physical Functioning in Aging People With HIV in the United States.

We conducted an observational cross-sectional study to explore whether food insecurity or undernutrition was associated with frailty or low physical functioning in aging persons with HIV (PWH). Forty-eight PWH aged 50 years and older were enrolled. Independent samples t-tests and chi-square tests were used to examine the relationship of food insecurity or undernutrition to frailty or physical function. Participants were 58.6 (±6.3) years old, 83% male, 77% White, 21% Hispanic. In total, 44% experienced food insecurity and 71% experienced undernutrition, whereas 23% were frail and 69% were prefrail. Food insecurity was associated with impaired total short physical performance battery score (p .02), impaired balance (p .02), slower chair rise time (p .03), and weight loss within 12 months (p .05). Undernutrition was related to female gender (p .01), worse frailty (p .04), and weaker grip strength (p .03). In this sample of undernourished and frail PWH, strong relationships between undernutrition and frailty were observed.

Nursing Workforce Optimization Study A Multi-method Evaluation and Process Improvement Intervention for HIV Service Delivery in Tanzania and Zambia.

Nurses are often suboptimally used in HIV care, due to misalignment of training and practice, workflow inefficiencies, and management challenges. We sought to understand nursing workforce capacity and support implementation of process improvement strategies to improve efficiency of HIV service delivery in Tanzania and Zambia. We conducted time and motion observations and task analyses at 16 facilities followed by process improvement workshops. On average, each nurse cared for 45 clients per day in Tanzania and 29 in Zambia. Administrative tasks and documentation occupied large proportions of nurse time. Self-reported competency was low at baseline and higher at follow-up for identifying and managing treatment failure and prescribing antiretroviral therapy. After workshops, facilities changed care processes, provided additional training and mentorship, and changed staffing and supervision. Efficiency outcomes were stable despite staffing increases. Collaborative approaches to use workforce data to engage providers in improvement strategies can support roll-out of nurse-managed HIV treatment.

Emergency Department Co-testing for Human Immunodeficiency Virus When Testing for Gonorrhea and Chlamydia.

Conducting human immunodeficiency virus (HIV) testing in emergency departments (EDs) can be an effective approach to testing and reaching populations at highest risk of contracting HIV. All gonorrhea and chlamydia (GC) and HIV tests ordered in the Cleveland Clinic Health Systems 14 EDs were included in the analysis. Data were collected from electronic health records. Descriptive statistics, with medians and means, were computed. From January 1, 2019, to December 31, 2021, we reviewed ED visits for the purpose of sexually transmitted infection (STI) screening, with an emphasis on GC screening. In October 2019, both HIV rapid testing and GC testing began across all 14 Cleveland Clinic EDs. The overall rate of co-testing for HIV when obtaining a GC test for STI evaluation increased overall to around 30% for our health system EDs, with some individual EDs approaching 60%. The approach the Cleveland Clinic implemented is an effective way to test for HIV in the ED. Local health departments and stakeholders in HIV communities should support and collaborate with EDs in their jurisdictions to accelerate HIV testing initiatives by using an HIV plus GC co-testing metric.

Uptake and spending on biosimilar infliximab and etanercept after new start and switching policies in Canada An interrupted time series analysis.

Uptake of biosimilars has been suboptimal in North America. This study quantified the impact of various policy interventions-namely, new start and switching policies- on uptake and spending on biosimilar infliximab and etanercept in British Columbia (BC), Canada. We used administrative claims data to identify BC residents ≥18 years with rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis andor plaque psoriasis who qualified for public drug coverage from January 2013 to November 2020. Using interrupted time series analysis, we studied the change in proportion spent on and prescriptions dispensed of the biosimilar infliximab and etanercept out of the total amount per agent after new start and biosimilar switching policies were implemented. Our study included 208,984 individuals living with rheumatoid arthritis, ankylosing spondylitis, plaque psoriasis andor psoriatic arthritis corresponding to 5,884 utilizers of infliximab and etanercept. After the new start policy, we detected a small gradual increase in the proportion of biosimilar etanercept prescriptions dispensed of 0.65% per month (95%CI 0.44,0.85). The trend related to the proportion of total spending on biosimilar etanercept also increased (0.51%, 95%CI 0.28,0.73). After the switching policy, there was a sustained increase in the proportion of biosimilar etanercept and infliximab prescriptions dispensed of 76.98% (95%CI 75.56,78.41) and 58.43% (95%CI 52.11,64.75), respectively. Similarly, there was a persistent increase in monthly spending on biosimilar etanercept and infliximab of 78.22% (95%CI 76.65, 79.79) and 71.23% (95%CI 66.82, 75.65), respectively. We found that mandatory switching policies were much more effective than new starting policies for increasing the use of biosimilar medications.

Shikimate kinase inhibitors An update on promising strategy against Mycobacterium tuberculosis.

Humanity has been battling with tuberculosis (TB) for a long period, and despite the availability of drugs well-known to act against the deadly microbe, the menace is still very far from reaching its end. Moreover, problems related to TB chemotherapy, such as lengthy treatment periods leading to poor patient compliance, increasing drug resistance, and association with another deadlier disease HIV-AIDS, make the situation alarming, thereby pressing the need for the discovery of new potent drugs urgently. Therefore, a drug target that is essential for survival and exclusive to M. tuberculosis presents a promising platform to explore novel molecules against the microorganism for better pathogen clearance with minimal toxicity. The shikimate pathway that leads to the synthesis of essential aromatic amino acids is one such attractive target. Shikimate kinase, the fifth enzyme of this pathway, converts shikimate to shikimate-3-phosphate by using ATP as a co-substrate. Targeting shikimate kinase could be an effective strategy in light of its essentiality and absence of any homologue in mammals. This review discusses different strategies adopted for discovering novel compounds or scaffolds targeting M. tuberculosis shikimate kinase (MtSK) in vitro. The application of substrate analogues, their structure, and ligand-based approach for screening a library of anti-mycobacterial compounds, marine-derived molecules, and commercially available libraries have yielded promising MtSK inhibitors exhibiting micro-molar activities. To develop these leads into future drugs with minimum off-target effects on the host microenvironment, the molecules need to be structurally optimized for improved activities against enzymes and whole-cell organisms.

Synthesis and anti-HIV activity of non-nucleoside reverse-transcriptase inhibitor DB02 phosphate derivatives based on water-soluble optimization.

To improve the water solubility of anti-human immunodeficiency virus (HIV) agent DB02, an excellent non-nucleoside reverse-transcriptase inhibitor (NNRTI) obtained in our previous efforts, we designed and synthesized four phosphate derivatives of DB02 based on the molecular model of DB02 with RT. Here, the antiviral activity of these four derivatives was detected, leading to the discovery of compound P-2, which possessed a superior potency to the lead compound DB02 against wild-type HIV-1 and a variety of HIV-resistant mutant viruses significantly. Furthermore, the water solubility of P-2 was nearly 17 times higher than that of DB02, and the pharmacokinetic test in rats showed that P-2 demonstrate significantly improved oral bioavailablity of 14.6%. Our study showed that the introduction of a phosphate ester group at the end of the C-2 side chain of DB02 was beneficial to the improvement of its antiviral activity and pharmacokinetic properties, which provided a promising lead for the further development of S-DACOs type of NNRTIs.

Monkeypox a review of the 2022 outbreak.

In May 2022, the World Health Organisation declared a multi-country monkeypox outbreak in non-endemic countries following cases reported from 12 member states that were not endemic for monkeypox virus. Pubmed search. The virology, epidemiology, transmission, incubation and aspects of infection control are described. Clinical features of previous and current outbreaks are described, with growing observations that the current outbreak presents with clinical features distinct from previous outbreaks. There are variations in clinical presentations seen in the current outbreak that have not been seen in prior outbreaks. More research is needed to investigate the reasons for these differences. The higher numbers of HIV-positive patients in the current outbreak has allowed better description of the disease in patients co-infected with HIV and monkeypox. The absence of more severe symptoms in HIV-positive patients in the current outbreak could possibly be due to the fact that most of these patients had well-controlled HIV, although further characterization of this cohort of patients would be useful. Current treatment and vaccination options have been extrapolated from studies of other Orthopox viruses. There remains a need for more data on the safety and efficacy of these options in the context of monkeypox infections.

Incidence and Risk Factors for Early Syphilis Among Men Who Have Sex With Men in Australia, 2013-2019 A Retrospective Cohort Study.

We aimed to examine the incidence of syphilis in men who have sex with men (MSM) and identify subgroups of MSM at a higher risk of syphilis infection. We conducted a retrospective cohort study of MSM attending a sexual health clinic in Australia, during 2013-2019, who had at least 2 syphilis serological tests during the study period. The incidence of syphilis was expressed as per 100 person-years. A cox regression analysis was conducted to identify risk factors for syphilis. A total of 24 391 individual MSM (75 086 consultations) were included. A total of 1404 new syphilis cases were diagnosed with an incidence of 3.7100 person-years (95% confidence interval, 3.5-3.9). Syphilis incidence was higher in MSM with human immunodeficiency virus (HIV 9.3100 person-years) than in MSM taking HIV pre-exposure prophylaxis (PrEP) (6.9100 person-years) or HIV-negative MSM not taking PrEP (2.2100 person-years). Risk factors associated with high incidence of syphilis included the following MSM with HIV (adjusted hazard ratio aHR 2.7), MSM taking HIV PrEP (aHR 2.1), past history of syphilis infection (aHR 2.4), injecting drug use (aHR 2.7), condomless anal sex (aHR 1.7), >4 sexual partners in the last 12 months (aHR 1.2), and concurrent sexually transmitted infection (chlamydia and gonorrhoea) (aHR 1.6). The incidence of syphilis remains high among MSM, particularly in subgroups with associated risk factors for syphilis infections. These data highlight the need for biomedical and behavioral interventions to be targeted to subgroups of MSM at the highest risk of syphilis infection.

Disparity of HIV-1 Pretreatment Drug Resistance in Men Who Have Sex With Men and the Heterosexual Population in Guangxi, China.

The prevalence of human immunodeficiency type 1 (HIV-1) pretreatment drug resistance (PDR) in men who have sex with men (MSM) in Guangxi remains unclear, and its effect on antiretroviral therapy (ART) needs to be further studied. Individuals newly diagnosed with HIV in Guangxi from 2016 to 2020, which mainly included MSM and the heterosexual (HES) population, were recruited in this study. Pol sequences were sequenced to analyze PDR and construct a genetic network. The risk factors for PDR and the effect on ART were respectively analyzed. The PDR of MSM in Guangxi was 4.7% (34716), consisting of nonnucleoside reverse transcriptase inhibitors (3.5%), protease inhibitors (0.8%), integrase strand transfer inhibitors (0.7%), and nucleoside reverse transcriptase inhibitors (0.4%), and lower than that of HES (9.3% 77827). The subtype was associated with PDR, and MSM was lower than HES (CRF01AE 3.0% vs 8.0% CRF07BC 4.1% vs 7.2%). CRF5501B (adjusted odds ratio aOR, 3.35) was a risk factor for PDR in MSM, while CRF08BC (aOR, 2.34) and older (aOR, 2.75) were risk factors for PDR in HES. Six of 18 (33.3%) PDR of MSM in the network connected to each other, lower than that of HES (61.1% 2236). CRF5501B (aOR, 5.69) was a risk factor for PDR transmission in MSM, while CRF08BC (aOR, 4.08) was a risk factor in HES. Pretreatment CD4 The prevalence of PDR was different between MSM and HES, which may be associated with subtype. Thus, the monitoring of subtype and PDR should be strengthened.

Cumulative Human Immunodeficiency Virus (HIV)-1 Viremia Is Associated With Increased Risk of Multimorbidity Among US Women With HIV, 1997-2019.

To evaluate the effect of cumulative human immunodeficiency virus (HIV)-1 viremia on aging-related multimorbidity among women with HIV (WWH), we analyzed data collected prospectively among women who achieved viral suppression after antiretroviral therapy (ART) initiation (1997-2019). We included WWH with ≥2 plasma HIV-1 viral loads (VL) <200 copiesmL within a 2-year period (baseline) following self-reported ART use. Primary outcome was multimorbidity (≥2 nonacquired immune deficiency syndrome comorbidities NACM of 5 total assessed). The trapezoidal rule calculated viremia copy-years (VCY) as area-under-the-VL-curve. Cox proportional hazard models estimated the association of time-updated cumulative VCY with incident multimorbidity and with incidence of each NACM, adjusting for important covariates (eg, age, CD4 count, etc). Eight hundred six WWH contributed 6368 women-years, with median 12 (Q1-Q3, 7-23) VL per participant. At baseline, median age was 39 years, 56% were Black, and median CD4 was 534 cellsmm Among ART-treated WWH, greater cumulative viremia increased the risk of multimorbidity and of developing each NACM, and hence this may be a prognostically useful biomarker for NACM risk assessment in this population.

Effect of obesity on dolutegravir exposure in Black Southern African adults living with HIV.

Dolutegravir, a component of the preferred first-line antiretroviral therapy regimen, has been associated with increased weight gain. South Africa has a high prevalence of obesity, especially among women. Understanding dolutegravir exposure in patients with obesity is important for dose optimisation. We compared the pharmacokinetic parameters of dolutegravir in Southern African adults living with HIV with and without obesity. Blood samples were collected at various time points over a 24 h-period for dolutegravir assays. Non-compartmental analysis was conducted and geometric mean ratios (GMRs), with 90% confidence intervals (CIs), were generated to compare dolutegravir pharmacokinetic parameters between the groups. Regression analyses to assess predictors of dolutegravir exposure were done. Forty participants were enrolled, 26 were women and 10 had obesity. Dolutegravir area under the concentration-time curve to 24-h and the maximum concentrations were not statistically significantly lower in participants with obesity GMR 0.91 (90% CI 0.71-1.16) and GMR 0.86 (90% CI 0.68-1.07), respectively. In a multivariate linear regression analysis adjusting for age, gender, body mass index, creatinine clearance and randomisation arm (tenofovir alafenamide or tenofovir disoproxil fumarate), a unit increase in body mass index was associated with 1.2% lower dolutegravir area under the concentration-time curve to 24-h ( Dolutegravir exposure was marginally lower in participants with obesity, but this is not clinically significant. Our findings suggest that there is no need to dose adjust dolutegravir in people with obesity.

Effect of a ward-based outreach team and adherence game on retention and viral load suppression.

Only 66% of South African people living with HIV (PLWH) are virologically suppressed. Therefore, it is important to develop strategies to improve outcomes. Assess the effect of interventions on 12-month retention in care and virological suppression in participants newly initiated on antiretroviral therapy. Fifty-seven clinics were randomised into four arms Ward-based primary health care outreach teams (WBPHCOTs) Game WBPHCOT-Game in combination and Control (standard of care). Sixteen clinics were excluded and four re-allocated because lay counsellors and operational team leaders failed to attend the required training. Seventeen clinics were excluded due to non-enrolment. A total of 558 participants from Tshwane district were enrolled. After excluding ineligible participants, 467 participants were included in the analysis WBPHCOTs ( This study demonstrated that an adherence game intervention could help keep PLWH in care. Evidence that interventions, especially Games, could improve retention in care.

The cytological diagnosis of

Immunosuppressed individuals are more prone for opportunistic infections. We analysed the clinical and detailed cytological features of 15 patients with PJP who were diagnosed on examination of bronchoalveolar lavage (BAL) fluid. The mean age of the patients was 38.4 years (range 13 - 61 years). A total of seven patients were HIV positive five patients were post renal transplant, and one patient was a known case of acute leukaemia on immunosuppression. Presence of foamy alveolar casts (FACs) was the distinctive feature and was noted in 14 out of 15 cases. We detected 14 out of 15 cases accurately in BAL fluid cytology. BAL cytology is one of the important modes of investigations which can detect PJP infection. The history of fever, cough, immunosuppression, bilateral haziness in the radiography of lung and the characteristic alveolar cast indicate the possibility of PJP infection. Cytology can provide early diagnosis and can reduce the mortality of immunocompromised patients.

Human rights violations among men who have sex with men and transgender people in South Africa.

Men who have sex with men (MSM) and transgender (TG) people face human rights violations (HRVs) which impact their access to critical interventions for HIV prevention, treatment, and related services. This study describes how Beyond Zero, a not-for-profit organisation in South Africa, built an HRV reporting system and discusses data on the HRVs experienced by MSM and TG people who accessed HIV prevention services between 01 January 2021 and 31 December 2021. This was a cross-sectional study using secondary analysis of programmatic data routinely collected as part of HIV prevention programmes for MSM and TG in 10 rural districts of South Africa. A total of 249 individuals reported having experienced HRVs. Of these, 113 (54.6%) were physical violations, 145 (58.2%) were psychosocial harassment, 15 (18.3%) were experienced within the workplace, and 59 (23.7%) were experienced at a healthcare or social services institution. Overall, 77% of the physical violations and 70.4% of the psychosocial violations occurred in the home and local community settings 76.1% of the perpetrators of physical violence and 79.3% of the perpetrators of psychosocial harassment were known. Most incidents of physical violence (80.5%) and psychosocial harassment (92.4%) were not reported due to fear of homophobic or transphobic violence. Our findings demonstrate the feasibility of documenting HRVs among MSM and TG people within HIV prevention programmes. Men who have sex with men and TG people should be systematically screened for HRVs and linked to legal or other services. Our findings present data on the nature of HRVs in 10 districts outside of the large urban centres where research documenting the lived experiences of MSM, TG people and other key populations is traditionally conducted in South Africa. This data contribute to addressing the gap in the literature on the needs of MSM and TG people in South Africa caused by the delayed inclusion of rural MSM and TG people in research.

COVID-19 severity and in-hospital mortality in an area with high HIV prevalence.

HIV infection causes immune dysregulation affecting T-cell and monocyte function, which may alter coronavirus disease 2019 (COVID-19) pathophysiology. We investigated the associations among clinical phenotypes, laboratory biomarkers, and hospitalisation outcomes in a cohort of people hospitalised with COVID-19 in a high HIV prevalence area. We conducted a prospective observational cohort study in Tshwane, South Africa. Respiratory disease severity was quantified using the respiratory oxygenation score. Analysed biomarkers included inflammatory and coagulation biomarkers, CD4 T-cell counts, and HIV-1 viral loads (HIVVL). The analysis included 558 patients, of whom 21.7% died during admission. The mean age was 54 years. A total of 82 participants were HIV-positive. People living with HIV (PLWH) were younger (mean age 46 years) than HIV-negative people most were on antiretroviral treatment with a suppressed HIVVL (72%) and the median CD4 count was 159 (interquartile range 66-397) cellsµL. After adjusting for age, HIV was not associated with increased risk of mortality during hospitalisation (age-adjusted hazard ratio 1.1, 95% confidence interval 0.6-2.0). Inflammatory biomarker levels were similar in PLWH and HIV-negative patients. Detectable HIVVL was associated with less severe respiratory disease. In PLWH, mortality was associated with higher levels of inflammatory biomarkers. Opportunistic infections, and other risk factors for severe COVID-19, were common in PLWH who died. PLWH were not at increased risk of mortality and those with detectable HIVVL had less severe respiratory disease than those with suppressed HIVVL. This study advances our understanding of severe COVID-19 in PLWH.

Late-onset efavirenz toxicity A descriptive study from Pretoria, South Africa.

The neuropsychiatric side effects of efavirenz occur mainly early during treatment and are usually mild. A lesser-known and serious complication is late-onset efavirenz toxicity causing ataxia and encephalopathy. Data regarding this condition are limited. We describe the clinical picture of late-onset efavirenz toxicity, investigate co-morbidities and report outcomes. This descriptive study of all patients with late-onset efavirenz toxicity was conducted over three years at Kalafong Provincial Tertiary Hospital, Pretoria, South Africa. Forty consecutive patients were identified. Mean age was 42.1 years, three patients (7.5%) were male and the mean efavirenz level was 49.0 μgmL (standard deviation s.d. 24.8). Cerebellar ataxia (82.5%) and encephalopathy (47.5%) were the most common presenting features (40.0% had both) four patients presented with psychosis. Presence of encephalopathy andor cerebellar ataxia was associated with higher efavirenz levels compared with psychosis (52.1 μgmL, s.d. 24.1 vs 25.0 μgmL, s.d. 17.1). In most patients, symptoms resolved, but four patients (10.0%) died, and one patient remained ataxic. Late-onset efavirenz toxicity typically presented with ataxia and encephalopathy, but psychosis can be the presenting feature. The outcome after withdrawal was good, but the mortality of 10.0% is concerning. Recent changes in guidelines favour dolutegravir, but many patients remain on efavirenz, and awareness of the condition is vital. This large, single-centre study contributes to the limited data of HIV-positive patients with late-onset efavirenz toxicity and emphasises its ongoing relevance in clinical practice.

Assessment of POC CD4 Detecting Mode in District or County Labs - Jiangsu Province, China, 2021.

This study seeks to explore efficient and multiple-item detection modes in new-style HIV labs, as well as access the accuracy and reliability of CD4 cell count detected by point of care (POC) to analyze POC work feasibility in district or county labs. POC devices adopted in grassroots-level labs and flow cytometers adopted in prefecture-level labs were used to analyze the same group of blood samples. The individual results were collected and compared for parametric tests in correlation and consistency. The Pearson correlation coefficients (r) between results detected by FACSPresto and those by FACSCalibur, FACSVia, FACSCantoII, and EPICSXL were 0.922, 0.938, 0.914, and 0.823, respectively the average deviations were -25.64, 24.68, 3.05, and 70.97 cellsμL, respectively the Pearson correlation coefficient (r) between results by Pima and FACSCalibur, FACSVia, FACSCantoII, and EPICSXL were 0.900, 0.950, 0.954, and 0.876, respectively and the average deviations were -73.99, -40.78, -29.32, and -22.75 cellsμL, respectively. Strong positive correlations and good consistency were observed between the CD4 count tested by POC and flow cytometers. These findings provide theoretical support for new-style HIV labs and one-stop services, which can provide shorter testing duration and simpler testing processes, so that the most comprehensive testing results can be obtained in the shortest amount of time.

HIV-Related Knowledge, Attitude, and Practices Research Among College Students - Six Chinese Cities, 2021.

The number of newly diagnosed human immunodeficiency virus (HIV) cases among Chinese youth 15-24 years of age shows an upward trend between 2010 and 2019. This survey is on a larger scale as compared to previous studies. It shows inadequate HIV knowledge - especially on HIV treatment, self-testing, and post-exposure prophylaxis - among college students. A significant gap exists between knowledge and behavior as indicated by the low condom use rate despite a high knowledge level. Findings suggest priorities for future HIV education and awareness creation of existing services. A low condom use rate at sexual debut suggests that HIV prevention education should start early.

A Case of Pericardial Effusion and Human Immunodeficiency Virus in the Postmodern Era.

Pericardial effusion is a relatively common cardiac pathology associated with various infectious and non-infectious etiologies. In developed countries, viral pericarditis and idiopathic reasons are the two most common causes of this condition. Mycobacterium tuberculosis is prevalent in developing countries and is the most common cause of pericardial effusion in these regions. Parasitic and bacterial etiologies are encountered less frequently. In this report, we describe the case of a large pericardial effusion in a patient with HIV and latent tuberculosis (TB). Pericardiocentesis and analysis of pericardial fluid did not reveal any specific etiology, indicating viral or idiopathic pericarditis as an etiology. We also present an analysis of global data related to pericardial effusion in HIVAIDS patients, and the impact that the increasing availability of antiretroviral therapy (ART) worldwide over the last three decades had had on it. The CD4 count has been described as an essential factor for the prognosis of this condition. Patients with lower CD4 count levels would be at higher risk of severe pericardial effusion.

Clinical Research A Review of Study Designs, Hypotheses, Errors, Sampling Types, Ethics, and Informed Consent.

Recently, we have been noticing an increase in the emergence and re-emergence of microbial infectious diseases. In the previous 100 years, there were several incidences of pandemics caused by different microbial species like the

Investigational drugs for HIV trends, opportunities and key players.

Since the first antiretroviral drug was described, the field of HIV treatment and prevention has undergone two drug-based revolutions the first one, enabled by the virtually concomitant discovery of non-nucleoside reverse transcriptase and protease inhibitors, was the inception of combined antiretroviral therapy. The second followed the creation of integrase strand-transfer inhibitors with improved safety, potency, and resistance profiles. Long-acting antiretroviral drugs, including broadly neutralizing antibodies, now offer the opportunity for a third transformational change in HIV management. Our review focused on HIV treatment and prevention with investigational drugs that offer the potential for infrequent dosing, including drugs not yet approved for clinical use. We also discussed approved drugs for which administration modalities or formulations are being optimized. We performed a literature search in published manuscripts, conference communications, and registered clinical trials. While the field focuses on extending dosing intervals, we identify drug tissue penetration as an understudied opportunity to improve HIV care. We repeat that self-administration remains an essential milestone to reach the full potential of long-acting drugs. Treatments and prevention strategies based on broadly neutralizing antibodies require a deeper understanding of their antiretroviral properties.

Molecular basis of RNA recognition by TBP of HIV-1 from multiple molecular dynamics simulations and energy predictions.

The frequent outbreaks of the AIDS (Acquired Immune Deficiency Syndrome) pandemic and the limited availability of anti-Human Immunodeficiency Virus (HIV) drugs highlight the urgent need to develop new antiviral drugs. A detailed understanding of the interactions between TAR-Binding Proteins (TBP) and RNA will facilitate the discovery of new anti-AIDS drugs. In order to characterize and explore the key interactions between RNA and TBP, we focused on the wild type (WT) and three mutant TBPs (TBP6.9, TBP6.7, and TBP6.3) with RNA, multiple molecular dynamics simulation and energy computation were performed. The results showed that 12 key residues played a major role in the interaction between TBP and RNA. The mutated residues of TBP changed the interaction between their surrounding residues and RNA, thus affecting the binding of TBP to RNA. In addition, structural and energy analyses showed that in contrast with WT TBP-RNA complex, the mutated residues had little effect on the backbone structure of TBP, but changes in the van der Waals interactions and electrostatic interaction associated with the side chains are responsible for the altered the binding between three mutant TBPs and RNA complexes. The discovery of TBP-RNA recognition mechanism in our work provides some useful insights and new opportunities for the development of anti-aids drugs.

Lower prospective memory is associated with higher neurocognitive dispersion in two samples of people with HIV A conceptual replication study.

People living with HIV (PLWH) often experience deficits in the strategicexecutive aspects of prospective memory (PM) that can interfere with instrumental activities of daily living. This study used a conceptual replication design to determine whether cognitive intraindividual variability, as measured by dispersion (IIV-dispersion), contributes to PM performance and symptoms among PLWH. Study 1 included 367 PLWH who completed a comprehensive clinical neuropsychological test battery, the Memory for Intentions Test (MIsT), and the Prospective and Retrospective Memory Questionnaire (PRMQ). Study 2 included 79 older PLWH who completed the Cogstate cognitive battery, the Cambridge Prospective Memory Test (CAMPROMPT), an experimental measure of time-based PM, and the PRMQ. In both studies, a mean-adjusted coefficient of variation was derived to measure IIV-dispersion using normative Higher IIV-dispersion was significantly associated with lower time-based PM performance at small-to-medium effect sizes in both studies (mean Extending prior work in healthy adults, these findings suggest that variability in performance across a cognitive battery contributes to laboratory-based PM accuracy, but not perceived PM symptoms, among PLWH. Future studies might examine whether daily fluctuations in cognition or other aspects of IIV (e.g., inconsistency) play a role in PM failures in everyday life.

Perceived motivators, knowledge, attitude, self-reported and intentional practice of female condom use among female students in higher training institutions in Dodoma, Tanzania.

Unplanned pregnancies and sexually transmitted infections (STIs) Human Immunodeficiency Virus (HIV) inclusive, have remained to be a significant public health challenges among young people, especially across middle and low-income countries. Self-efficacy on the right ways of using condoms appears to be effective against the aforementioned health-related problems. However, most women of reproductive age tend not to use them when they are using highly effective contraceptives such as implants, andor injectable hormones. It is unknown whether the uptake of female condoms among young girls is significantly high or not. Examining female students perceived motivators, knowledge, attitudes, and self-reported and intentional female condom practice in training institutions seems to be a key precursor in addressing the challenge. The institutional-based analytical cross-sectional survey in a quantitative research approach was adopted to study 384 randomly selected female students from higher training institutions, in Tanzania. Interviewer-administered structured questionnaires from previous studies were the main data collection tools. Data analysis was done using a statistical package for social science (SPSS) with the strength of statistical limits set at a 95% confidence interval and a 5% significance level. The response rate of the study was 100% with 24 ± 2.122 years respondents mean age while and 32.7% of them were in the third year of their studies. Only 6.2% of the respondents reported having used female condoms while 26.3% of them have not ever seen packages of female condoms. The minority of the respondents (21.7%, 23.3%, and 9.4%) demonstrated good knowledge, positive attitude, and intention to use female condoms respectively. Their age, accommodation, marital status, peer groups, previous training, knowledge, and attitude related significantly to their intentional practices of female condom use (p < 0.05). Given the existing governmental and non-governmental efforts that advocate awareness creation and the uptake of various contraceptives, this study has found that knowledge, attitude, self-reported and intentional practices of female students admitted in higher training institutions within Dodoma region, Tanzania is low. Institutionalized educational programs on sexual and reproductive health matters may need to be prioritized to increase the availability, accessibility, and uptake of female condoms among female students in higher training institutions.

Project T-SHARP study protocol for a multi-site randomized controlled trial of tele-harm reduction for people with HIV who inject drugs.

The resurgence of HIV outbreaks and rising prevalence among people who inject drugs (PWID) remain exigent obstacles to Ending the HIV Epidemic in the USA. Adapting a low threshold, comprehensive treatment model for PWID with HIV can leverage syringe services programs (SSPs) to increase availability and accessibility of antiretrovirals (ART), medications for opioid use disorder (MOUD), and hepatitis C cure. We developed Tele-Harm Reduction, a telehealth-enhanced, harm reduction intervention delivered within an SSP venue. The T-SHARP trial is an open-label, multi-site, randomized controlled superiority trial with two parallel treatment arms. Participants (n240) recruited from SSPs in Miami, Ft. Lauderdale, and Tampa, Florida, who are PWID with uncontrolled HIV (i.e., HIV RNA>200) will be randomized to Tele-Harm Reduction or off-site linkage to HIV care. The primary objective is to compare the efficacy of Tele-Harm Reduction for initiation of ART at SSPs vs. off-site linkage to an HIV clinic with respect to viral suppression across follow-up (suppression at 3, 6, and 12 months post randomization). Participants with HIV RNA<200 copiesml will be considered virally suppressed. The primary trial outcome is time-averaged HIV viral suppression (HIV RNA <200 copiesml) over 3-, 6-, and 12-month follow-up. Secondary outcomes include initiation of MOUD measured by urine drug screen and HCV cure, defined as achieving 12-week sustained virologic response (negative HCV RNA at 12 weeks post treatment completion). A cost-effectiveness analysis will be performed. The T-SHARP Trial will be the first to our knowledge to test the efficacy of an innovative telehealth intervention with PWID with uncontrolled HIV delivered via an SSP to support HIV viral suppression. Tele-Harm Reduction is further facilitated by a peer to support adherence and bridge the digital divide. This innovative, flipped healthcare model sets aside the traditional healthcare system, reduces multi-level barriers to care, and meets PWID where they are. The T-SHARP trial is a pragmatic clinical trial that seeks to transform the way that PWID access HIV care and improve HIV clinical outcomes. ClinicalTrials.gov NCT05208697. Trial registry name Tele-Harm Reduction. Registration date January 26, 2022.

The prevalence and predictors of herb-drug interactions among Iranian cancer patients during chemotherapy courses.

The concurrent usage of herbal medicines with conventional therapies is an important concern in cancer treatment which can lead to unexpected consequences like herb-drug interactions. This study aimed to determine the prevalence of potential herb-drug interactions and to predict factors associated with herb-drug interactions for cancer patients. This cross-sectional study was conducted among a convenience sample of 315 cancer patients referring to the oncology clinics of Kerman city in 2018. Data were collected via comprehensive face-to-face interviews and medical chart reviews. A drug interaction checker was used to determine herb-drug interactions. The information of patients was compared based on herb-drug interactions using bivariable logistic regression models, and predictors were determined by the multivariable logistic regression model. All analyses were performed by Stata software version 16. Of 262 patients (83.2% of the patients) who used herbal medicines, 209 patients 79.8% (95% Confidence Intervals (CI) 75.2 - 85.1) had potential herb-drug interactions. Chamomile was the most popular herbal medicine (n 163, 78.0%), and minor and moderate herb-drug interactions were caused by green tea (n 34, 16.3%) and peppermint (n 78, 37.5%). The number of chemotherapeutic agents (OR 1.92, 95% CI 1.43-2.58 P-value < 0.0001) and the experienced of pain during chemotherapy courses (OR 2.22, 95%CI1.00-4.94 P-value 0.04) were some of the predictors of herb-drug interactions among cancer patients. Herbal medicine use during chemotherapy was found prevalent among cancer patients of them, the experience of potential herb-drug interactions was highly frequent. Oncologists and clinical pharmacologists are recommended to take into account challenges associated with herb-drug interactions in their routine practices, particularly during chemotherapy among these patients.

Potential molecular mechanisms of chronic fatigue in long haul COVID and other viral diseases.

Historically, COVID-19 emerges as one of the most devastating diseases of humankind, which creates an unmanageable health crisis worldwide. Until now, this disease costs millions of lives and continues to paralyze human civilizations economy and social growth, leaving an enduring damage that will take an exceptionally long time to repair. While a majority of infected patients survive after mild to moderate reactions after two to six weeks, a growing population of patients suffers for months with severe and prolonged symptoms of fatigue, depression, and anxiety. These patients are no less than 10% of total COVID-19 infected individuals with distinctive chronic clinical symptomatology, collectively termed post-acute sequelae of COVID-19 (PASC) or more commonly long-haul COVID. Interestingly, Long-haul COVID and many debilitating viral diseases display a similar range of clinical symptoms of muscle fatigue, dizziness, depression, and chronic inflammation. In our current hypothesis-driven review article, we attempt to discuss the molecular mechanism of muscle fatigue in long-haul COVID, and other viral diseases as caused by HHV6, Powassan, Epstein-Barr virus (EBV), and HIV. We also discuss the pathological resemblance of virus-triggered muscle fatigue with myalgic encephalomyelitischronic fatigue syndrome (MECFS).

Factors that influence the satisfaction of people living with HIV with differentiated antiretroviral therapy delivery models in east Central Uganda a cross-sectional study.

The World Health Organization (WHO) and the Uganda Ministry of Health recommend differentiated service delivery models (DSDMs) as patient-centered antiretroviral therapy (ART) mechanisms for people living with HIVAIDS (PLHIV) with undetectable viral loads. We studied patient satisfaction with ART services, and its associated factors amongst PLHIV enrolled in DSDMs in Uganda. This cross-sectional study involved a random sample of PLHIV accessing DSDM-related ART at nine facilities in East Central Uganda. Eligible patients were adult PLHIV (≥18 years), on ART, and enrolled for at least 12 months in one of three DSDMs Community Client-Led ART Delivery (CCLAD), Community Drug Distribution Points (CDDP), or Fast-Track Drug Refill (FTDR). We collected data from June to July 2019. A validated tool measured satisfaction. General Estimating Equations with modified Poisson regression and exchangeable correlation structures accounted for clustering at health facilities and identified DSDM-related satisfaction factors. Of 842 participants enrolled, 530 (63.5%) accessed HIV care through CDDP, 166 (20.1%) through CCLAD, and 146 (16.3%) through FTDR 541 (64.2%) were satisfied with DSDM services 78.7% in CDDP, 42.8% in CCLAD, and 36.3% in FTDR. The delivery and treatment factors positively associated with satisfaction included being enrolled on CDDP adjusted prevalence ratio (aPR) 1.51, 95% CI1.47-1.56 or FTDR aPR 1.47, 95% CI1.26-1.71 relative to CCLAD and being enrolled in a DSDM for more than 3 years aPR 1.28, 95% CI1.11-1.48. Poor ART adherence aPR 0.33, 95% CI0.19-0.56 and having a baseline WHO HIV stage of 3 or 4 aPR 0.36, 95% CI0.20-0.64 relative to stages 1 and 2 were negatively associated. Among socioeconomic factors, having lower transport costs (< $1.35) per clinic visit aPR 1.34, 95% CI1.17-1.53, being employed aPR 1.61, 95% CI1.38-1.87, and being single aPR 1.10, 95% CI1.08-1.13 were positively associated with satisfaction drinking alcohol at least once a week aPR 0.77, 95% CI0.63-0.93 was negatively associated with patient satisfaction. Results showed that 64.2% of patients were satisfied with DSDM services. HIV service delivery and treatment factors (DSDM type, time in DSDM, WHO stage, ART adherence), plus social factors (employment and marital status, transport costs, alcohol consumption), were associated with patient satisfaction. DSDM implementers should tailor services to address these factors to improve patient satisfaction.

Potential role of doravirine for the treatment of HIV-1-infected persons with transmitted drug resistance.

Doravirine has a unique resistance profile but how this profile might increase its usefulness beyond first-line therapy in persons with susceptible viruses has not been well studied. We sought to determine scenarios in which doravirine would retain activity against isolates from ART-naïve persons with transmitted drug resistance (TDR) and to identify gaps in available doravirine susceptibility data. We analyzed published in vitro doravirine susceptibility data and applied the results to 42,535 RT sequences from ART-naïve persons published between 2017 and 2021. NNRTI drug resistance mutations (DRMs) were defined as those with a Stanford HIV Drug Resistance Database doravirine penalty score either alone or in combination with other mutations. V106A, Y188L, F227CL, M230L, and Y318F were associated with the greatest reductions in doravirine susceptibility. However, several NNRTI DRMs and DRM combinations lacking these canonical resistance mutations had > tenfold reduced susceptibility including G190E, one isolate with G190S, three isolates with L100I K103N, one isolate with K103N P225H, and isolates with L100I K103N V108I and K101E Y181C G190A. Of the 42,535 ART-naïve sequences, 3,374 (7.9%) contained a NNRTI DRM of which 2,788 (82.6%) contained 1 DRM (n 33 distinct mutations), 426 (12.6%) contained 2 DRMs (79 distinct pairs of mutations), and 143 (4.2%) contained ≥ 3 DRMs (86 distinct mutation patterns). Among the 2,788 sequences with one DRM, 112 (4.0%) were associated with ≥ 3.0-fold reduced doravirine susceptibility while 2,625 (94.2%) were associated with < 3.0-fold reduced susceptibility. Data were not available for individual NNRTI DRMs in 51 sequences (1.8%). Among the 426 sequences with two NNRTI DRMs, 180 (42.3%) were associated with ≥ 3.0 fold reduced doravirine susceptibility while just 32 (7.5%) had < 3.0 fold reduced susceptibility. Data were not available for 214 (50.2%) sequences containing two NNRTI DRMs. First-line therapy containing doravirine plus two NRTIs is expected to be effective in treating most persons with TDR as more than 80% of TDR sequences had a single NNRTI DRM and as more than 90% with a single DRM were expected to be susceptible to doravirine. However, caution is required for the use of doravirine in persons with more than one NNRTI DRM even if none of the DRMs are canonical doravirine-resistance mutations.

PrEP disclosure and discussions within social networks of people who inject drugs experiencing homelessness a brief report.

In the context of increasing injection-related HIV outbreaks across the United States, particularly among people who inject drugs (PWID) experiencing homelessness, there is an urgent need to expand access to pre-exposure prophylaxis (PrEP) for HIV prevention. Peer-based interventions for PrEP could be helpful for promoting PrEP uptake, yet the social experiences of using PrEP among PWID experiencing homelessness have not been thoroughly explored. To better understand social experiences surrounding PrEP use among PWID experiencing homelessness, we conducted qualitative interviews from March-December 2020 with current and former PrEP patients of an innovative, low-threshold program implemented by Boston Health Care for the Homeless Program (BHCHP) in Boston, MA. Thematic analysis of coded interview data explored participants perspectives and experiences with PrEP disclosure and discussions within their social networks. Among interviews with 21 participants, we identified the following four interrelated aspects of their social experiences using PrEP (1) participants were aware of increasing HIV transmission within their social networks, which motivated their PrEP use and disclosure (2) participants generally avoided disclosing their PrEP use within public spaces or casual conversations (3) participants expressed greater willingness to discuss PrEP with their close social contacts and (4) some participants self-identified as leaders or expressed interest in leading the dissemination of PrEP information within their social networks. Findings highlight the significance of PrEP disclosure and discussions within the social networks of PWID experiencing homelessness, suggesting a need for continued social network and intervention research-particularly to establish the feasibility and acceptability of peer-based interventions for promoting PrEP-with this marginalized population.

Assessment of an instrument scale measuring the knowledge of antiretroviral therapy among people living with HIV.

Antiretroviral therapy (ART) is currently the most effective way to treat people living with human immunodeficiency virus (PLHs) and reduce HIV transmission. While there are many factors that reduce adherence to ART, PLHs knowledge about ART may determine the level of adherence. It is necessary to design and assess an instrument scale that measures the knowledge of antiretroviral therapy among PLHs. A cross-sectional study was conducted among PLHs in Honghe Hani and Yi Autonomous Prefecture, China. Both exploratory and confirmatory factor analyses were used to examine the latent factors of antiretroviral therapy knowledge scale. Internal consistency was assessed separately for the scale and its dimensions by estimating Cronbachs alphas, split-half reliability and Spearmans correlation coefficient. ANOVAs were used to compare the scores of different dimensions with sociodemographic characteristics. Four factors were extracted according to factor loadings. They had high internal consistency reliability (Cronbachs alpha 0.70-0.95) and good construct validity (standardized factor loading range 0.46-0.86) in the scale. Goodness of fit indices indicated that a four-factor solution fit the data at an accepted level (χ The psychometric assessment indicated that this ART knowledge scale had accepted internal consistency and discriminant construct validity. It can be used to assess the knowledge of antiretroviral therapy for PLHs.

Student nurses perceptions and experiences in caring for people living with HIVAIDS a qualitative study.

Caring for people living with HIVAIDS (PLWHA) requires clinical experience and quality care delivery skills. This study aimed to explore the perceptions and experiences of nursing students in caring for PLWHAs. This qualitative descriptive study interviewed 18 student nurses who had cared for PLWHAs from 14 tertiary hospitals across 7 provinces in China through semi-structured telephone interviews. Two themes emerged from the narratives student nurses perceptions and attitudes toward PLWHAs and student nurses practical experiences with PLWHAs. Five theme clusters were revealed, namely negative attitudes held before the care-giving, a series of psychological struggles in care-giving, favorable attitudes increased after the care-giving, consensus on care delivery for PLWHAs, and considerations regarding contamination reduction. Findings shed light on the development and changes in student nurses perspectives on PLWHAs throughout their clinical experiences. Student nurses perceptions and attitudes toward PLWHAs progressed through three distinct stages, and positive changes were observed after care-giving. Participants perceptions and practical experiences with patients with AIDS enable patients to receive fair and high-quality care and provide valuable insights for nursing educators better prepare HIV nurses.

Population size estimation of female sex workers using network scale-up method in Kermanshah city.

Appropriate estimate of size of the female sex workers as well as the other hard-to-reach-populations plays a crucial role in reaching them with effective preventive measures. This study aimed to estimate the population size of female sex workers in Kermanshah City using the network scale-up method. In this cross-sectional study, of the 1000 pedestrians aged between 18 and 65 years, selected from the population of Kermanshah City via a multistage sampling, were recruited in the study. Face-to-face interview using a questionnaire including the number of FSWs in the social network of the respondent was used to collect the data. The overall estimated number of female sex workers in the general population was 4848(UI 95% 4597, 5074). Accordingly, the prevalence of FSWs among women 18 years and older in Kermanshah in 2018 was about 11.92 (UI 95% 11.30, 12.47) in one thousand. More than half of the female sex workers in the respondents social network were unmarried and were in the age range of 18 to 29, and had a high school or university degree. Among high-risk behaviors, a history of alcohol consumption accounted for the highest percentage. The number of female sex workers estimated in this study is considerable, which highlights the importance of planning harm reduction interventions in order to alleviate the burden of HIV infection in the population.

New designs for HIV-1 integrase inhibitors a patent review (2018-present).

Combination antiretroviral therapy (cART) has dramatically reduced morbidity and mortality of HIV-1-infected patients. Integrase strand transfer inhibitors (INSTIs) play an important role as a key drug in cART. The second-generation INSTIs are very potent, but due to the emergence of highly resistant viruses and the demand for more conveniently usable drugs, the development of third-generation INSTIs and mechanistically different inhibitors is actively being pursued. This article reviews the patents (from 2018 to the present) for two classes of HIV-1 integrase inhibitors of INSTIs and integrase-LEDGFp75 allosteric inhibitors (INLAIs). Since the approval of the second-generation INSTI dolutegravir, the design of new INSTIs has been mostly focused on its scaffold, carbamoylpyridone (CAP). This CAP scaffold is used not only for HIV-1 INSTIs but also for drug discoveries targeting other viral enzymes. With the approval of cabotegravir as a regimen of long-acting injection in combination with rilpivirine, there is a growing need for longer-acting agents. INLAIs have been intensely studied by many groups but have yet to reach the market. However, INLAIs have recently been reported to also function as a latency promoting agent (LPA), indicating further development possibilities.

Impact of COVID-19 Pandemic on HIV Testing Uptake Among Key Populations Enrolled in Targeted Intervention Program in Maharashtra, India.

The COVID-19 pandemic posed unprecedented challenges to HIV services globally. We evaluated the impact of the COVID-19 pandemic on the uptake of HIV testing in the Targeted Intervention (TI) program in Maharashtra-a high HIV burden state in India. Annual HIV testing was sustained during the pandemic year (2020-2021), at levels similar to the pre-pandemic year (2019-2020), among Female Sex Workers (FSW), Men having Sex with Men (MSM), Transgender (TG), and Truckers but not among Migrants and Intravenous Drug Users (IDU). There was an acute decline during the lockdown across all typologies. Sharp recovery was seen among FSW, MSM, and TG during the early months of the un-lockdown. The community-based screening (CBS) approach primarily contributed to this recovery. Among migrants and truckers, recovery was delayed. There was an overall reduction of 58% in annual HIV-positive registrations. The community-based networks, participatory structures, and processes of HIV programs played an essential role in reaching the community during the pandemic.

Learning from community-based HIV prevention to inform control and mitigation of the COVID-19 pandemic.

The current COVID-19 pandemic and the likelihood of future viral pandemics demonstrate a need for strategic prevention campaigns that integrate biomedical, structural, and behavioral interventions within larger scale comprehensive public health initiatives. In Human Immunodeficiency Virus (HIV) prevention, community-based efforts have resulted in reductions in transmission rates, increases in testing, increases in biomedical prevention uptake, and increased engagement in secondary and tertiary prevention efforts. In this paper, we review three community-based strategies (health communication, accessible screening, and accessible prevention resources) that have demonstrated effectiveness in HIV prevention and offer recommendations for utilizing these strategies in the COVID-19 pandemic. For example, health communication strategies have positively influenced HIV testing behavior, sex communication, and condom use among HIV negative individuals and treatment initiation, treatment adherence, and retention in care among people living with HIV. In addition, studies have shown that improving accessibility of HIV screening and prevention resources in community venues such as schools, pharmacies, mobile-testing sites, churches, hair salons, and bars is useful for increasing the uptake of HIV testing, especially among disproportionately affected populations and those deemed hard to reach. Despite differences in modes of transmission, it is plausible that a synergistic multilevel response with emphasis on community-based efforts could lead to similar outcomes for the current COVID-19 pandemic and future viral pandemics. Community-based prevention strategies offer an opportunity to integrate, and bolster disconnected and siloed initiatives that achieve limited impacts independently.

Predictors for Recurrence of Cytomegalovirus Retinitis in HIV-Negative Patients.

To investigate the incidence of and predictive factors for recurrent cytomegalovirus retinitis (CMVR) in human immunodeficiency virus (HIV)-negative patients. A retrospective review of HIV-negative patients who were newly diagnosed with CMVR between January 2005 and February 2019. Of 28 patients (44 eyes), 35.9% of eyes had a recurrence of CMVR after discontinuation of anti-CMV therapy. The incidence of CMVR recurrence was 17 per 100 eye-years. The factors significantly associated with CMVR recurrence were eyes with retinitis area of more than 25% ( Eyes with a large area of retinitis, absence of vitreous haze, and neutropenia at presentation are predictive of CMVR recurrence while receiving systemic immunosuppression prior to CMVR presentation has a lower risk of CMVR recurrence.

Health care provider decisions to initiate oral HIV pre-exposure prophylaxis (PrEP) in New York City (NYC) public sexual health clinics.

Oral HIV pre-exposure prophylaxis (PrEP) is safe and effective but underutilized. Health care providers beliefs about PrEP and attitudes toward people who could benefit may affect PrEP access. This mixed-methods study (2016-2018) was conducted in eight New York City public sexual health clinics (SHCs) that implemented a PrEP program. Data included 32 in-depth qualitative interviews with clinicians, quantitatively coded to reflect their PrEP beliefs a provider questionnaire and six months of medical record visit data for these providers. Among patients with a PrEP indication, we examined the odds of a patient being initiated on PrEP associated with providers PrEP beliefs and demographic characteristics, and patient characteristics. Providers reported strong support for offering PrEP to eligible patients. The majority denied concerns about possible development of drug-resistant viral strains, giving PrEP to people who might not benefit, and PrEP toxicity. Nevertheless, about one-third agreed with each of these concerns, and 55% thought PrEP use might limit condom use. Of 2176 patients with a PrEP indication, 20% were initiated. Providers with more restrictive PrEP beliefs did not have lower odds of initiating patients on PrEP. Women as well as Black and Latinx patients were less likely to be initiated on PrEP. Contrary to our hypotheses, providers negative PrEP beliefs did not appear to reduce initiation of PrEP for eligible patients. This may be attributable to clear clinical protocols, strong staff support, and training on implementing PrEP in this setting. Racial and gender disparities in PrEP uptake urgently require attention.

Screening and diagnostic testing protocols for HIV and Syphilis infections in health care setting in Qatar Evaluation and recommendations.

HIV and Syphilis are common STIs, which have become a concern and burden on healthcare systems, as many infections go untreated and lead to potentially serious complications. HIV is usually diagnosed with Western blot, PCR, and p24 antigen testing. Whereas, Syphilis is mainly diagnosed through clinical findings and serologic testing. The Medical Commission Department (MC) under MOPH is responsible for screening all newcomers to Qatar, aiming to keep the country free from serious infectious diseases. We aimed to evaluate the diagnostic efficiency of the protocols used in the MC for screening HIV and Syphilis infections. We conducted a retrospective study of samples analyzed by 4th Generation ARCHITECT® HIV AgAb Combo and Rapid Plasma Reagin (RPR) between January to December 2019. ARCHITECT® HIV AgAb Combo positive samples were confirmed by INNO-LIA™ HIVIII and RT-PCR. RPR-reactive samples were confirmed by ARCHITECT® Syphilis Treponema pallidium Antibody (Syphilis TPA) assay. For HIV, data were collected from 585,587 individuals, of which 595 (0.1%) were positive by the ARCHITECT® HIV AgAb Combo (Analyzer A). When all initially positive sera were re-tested on newly collected blood samples using different ARCHITECT® HIV AgAb Combo analyzer (analyzer B), 99.8% (594595) of samples were also positive, suggesting high reproducibility. The positive predictive value (PPV) between ARCHITECT® HIV AgAb Combo and the INNO-LIA™ HIVIII confirmatory assay was 31.8%. The PPV between ARCHITECT® HIV AgAb Combo and HIV-PCR assay was 26.8%. Retrospective data for Syphilis were collected from a total of 97,298 individuals who visited the MC, of which 198 (0.20%) were initially positive by RPR. The PPV between RPR and Syphilis TPA confirmatory assay was 36.6%. Despite the high rate of false positivity using ARCHITECT® HIV AgAb Combo and RPR screening assays, both assays have proven to be highly effective as screening testing methods.

Impact of adverse drug reactions on the outcomes of tuberculosis treatment.

Adverse drug reactions (ADR) challenge successful anti-tuberculosis treatment (ATT). The aim of this study was to evaluate the impact of ATT-associated ADR and related factors on ATT outcomes. A prospective cohort study of persons with tuberculosis (TB) at a referral center in Rio de Janeiro, Brazil, from 2010 to 2016. Baseline information race, sex, schooling, economic status, tobacco, drugs and alcohol abuse, HIV-infection status and comorbidities were captured during TB screening and diagnosis. Laboratory exams were performed to confirm TB diagnosis and monitor ADRs, favorable (cure and treatment completion) and unfavorable (death, loss to follow up and failure) outcomes were prospectively captured. The Kaplan-Meier curve was used to estimate the probability of ADR-free time. A logistic regression analysis (backward elimination) was performed to identify independent associations with unfavorable outcomes. 550 patients were enrolled, 35.1% were people living with HIV (PLHIV) and ADR occurred in 78.6% of all participants. Smoking (OR 2.32 95% CI1.34-3.99) and illicit-drug use (OR2.02 95% CI1.15-3.55) were independent risk factors for unfavorable outcomes. In PLHIV, alcohol abuse and previous ART use were associated with unfavorable outcomes. In contrast, ADR increased the odds of favorable outcomes in the overall population. PLHIV more frequently experienced grade 34-ADR (18.36%), especially liver and biliary system disorders. Lower CD4 counts (<100 cellsuL) were associated with hepatotoxicity (p 0.03). ART-naïve participants presented a higher incidence of ADR in comparison with ART-experienced patients. Substance use was associated with unfavorable outcomes, highlighting the need for better strategies to reduce this habit. In contrast, ADRs were associated with favorable outcomes. Attention to the occurrence of ADR in PLHIV is essential, especially regarding hepatotoxicity in those with high immunosuppression.

Late gene expression-deficient cytomegalovirus vectors elicit conventional T cells that do not protect against SIV.

Rhesus cytomegalovirus (RhCMV)-based vaccine vectors induce immune responses that protect 60% of rhesus macaques (RMs) from SIVmac239 challenge. This efficacy depends on induction of effector memory (EM)-biased CD8 T cells recognizing SIV peptides presented by major histocompatibility complex (MHC)-E instead of MHC-Ia. The phenotype, durability, and efficacy of RhCMVSIV-elicited cellular immune responses were maintained when vector spread was severely reduced by deleting the anti-host intrinsic immunity factor pp71. Here, we examined the impact of an even more stringent attenuation strategy on vector-induced immune protection against SIV. Fusion of the FK506-binding protein (FKBP) degradation domain to Rh108, the orthologue of the essential human CMV (HCMV) late gene transcription factor UL79, generated RhCMVSIV vectors that conditionally replicate only when the FK506-analog Shield-1 is present. Despite lacking in vivo dissemination and reduced innate and B cell responses to vaccination, Rh108-deficient 68-1 RhCMVSIV vectors elicited high frequency, durable, EM-biased, SIV-specific T cell responses in RhCMV-seropositive RM at doses of ≥106 PFU. Strikingly, elicited CD8 T cells exclusively targeted MHC-Ia-restricted epitopes and failed to protect against SIVmac239 challenge. Thus, Rh108-dependent late gene expression is required for both induction of MHC-E-restricted T cells and protection against SIV.

Hemiballism and chorea with acutesubacute onset a retrospective series.

Chorea is a hyperkinetic movement disorder with sudden, irregular, random, dance-like involuntary movements, and ballism is usually one-sided, high-amplitude movements at the proximal of the extremities. In the etiology of acute choreahemiballismus, it is necessary to distinguish drugs first and then focus on metabolic causes. The most important etiological causes that may provoke acutesubacute onset choreahemiballismus are hypo-hyperglycemia and electrolyte disorders. In this study, we aim to present 19 patients who were admitted to our clinic with movement disorder with acutesubacute onset and diagnosed with choreahemiballismus. The study was completed with 19 patients. Routine biochemistry, HbA1c level, hemogram, sedimentation, CRP, hepatitis panels, detailed infective parameters, HIV, vitamin B12 level, folate levels, and thyroid function tests were studied. All patients underwent neuro-imaging. 16(84.2%) were female and 3(15.8%) were male. The lowest age of the patients was 48 years, the highest age was 89 years, and the mean age was 72.21 years. Thirteen (68.42%) patients had a diagnosis of diabetes mellitus in their history. The blood glucose levels of these patients at the time of admission the lowest was 99 mgdl and the highest was 1200 mgdl. HbA1c values of 11(84.61%) of the 13 patients were also found elevated. Thirteen (68.4%) patients had hemiballismus, 4(21.1%) patients had bilateral choreoathetosis in the four extremities, and 2(10.2%) patients had ballism limited to one upper extremity. Choreahemiballismus is a movement disorder that is rare and can occur due to a wide range of etiologies. The most common metabolic cause is NKHHS.

Pneumocystis pneumonia in a patient with diabetes mellitus A case report.

Pneumocystis pneumonia (PCP) is an opportunistic infection of patients with congenital or acquired immunodeficiency. It is most frequently occurred in human immunodeficiency virus (HIV) infection, organ transplantation, leukemia, and immunosuppressive therapy. Here we describe the rare case of PCP in a non-HIV-infected diabetic patient and find possible reasons for the association through a literature review. A 65-years-old male was admitted to our hospital due to a 10-year history of abnormal blood glucose levels and edema of both lower extremities for half a month. However, the patient developed a high fever and progressive dyspnea during hospitalization. The patient had elevated blood sugar levels, a low white blood cell count within normal limits, and severe lymphopenia. His blood G test and lactate dehydrogenase levels increased significantly. Multiple sputa and bronchoalveolar lavage fluid specimens for Pneumocystis jirovecii (PJ) nucleic acid detection were positive. Chest computed tomography scan demonstrated hazy patchy shadows in the lungs suspected to be pulmonary infections. No tumor, transplantation, or an autoimmune disease was found in the examinations. The patient was diagnosed with PCP finally. A combination of oral trimethoprim-sulfamethoxazole and intravenous caspofungin was administered immediately against PJ. The patient was also treated with noninvasive ventilator-assisted ventilation, subcutaneous insulin, and hemodialysis therapy. The patient was discharged home finally with a fair general condition and was followed up without respiratory symptoms. The compromised immunity in HIV-negative patients with diabetes may be related to lymphocyte decrease and dysfunction, which may cause diabetic patients prone to PJ. Although PCP is rare in diabetes, it should be paid attention to the high rate of misdiagnosis and missed diagnosis.

Predictors of death among TBHIV co-infected patients on tuberculosis treatment in Sichuan, China A retrospective cohort study.

Mycobacterium tuberculosis is the most common opportunistic infection among patients with human immunodeficiency virus (HIV) infection, and it is also the leading cause of death, causing approximately one-third of acquired immune deficiency syndrome deaths worldwide. China is on the World Health Organizations global list of 30 high-tuberculosis (TB) burden countries. The objective of this study was to evaluate the mortality rate, survival probabilities, and factors associated with death among patients with TBHIV co-infection undergoing TB treatment in Sichuan, China. A retrospective cohort study was conducted using the Chinese National TB Surveillance System data of TBHIV co-infected patients enrolled in TB treatment from January 2020 to December 2020. We calculated the mortality rate and survival probabilities using the Kaplan-Meier estimator, and a Cox proportional hazard model was conducted to identify independent risk factors for TBHIV co-infection mortality. Hazard ratios and their respective 95% confidence intervals were also reported in this study. Of 828 TBHIV co-infected patients, 44 (5.31%) died during TB treatment, and the crude mortality rate was 7.76 per 1000 person-months. More than half of the deaths (n 23) occurred in the first 3 months of TB treatment. Overall survival probabilities were 97.20%, 95.16%, and 91.75% at 3rd, 6th, and 12th month respectively. The independent risk factors for mortality among TBHIV co-infected patients were having extra-pulmonary TB and pulmonary TB co-infection, history of antiretroviral therapy interruption, and baseline cluster of differentiation 4 T-lymphocyte counts <200 cellsμL at the time of HIV diagnosis. Antiretroviral therapy is important for the survival of TBHIV co-infected patients, and it is recommended to help prolong life by restoring immune function and preventing extra-pulmonary TB.

Evolution of Antibody Responses in HIV-1 CRF01AE Acute Infection Founder Envelope V1V2 Impacts the Timing and Magnitude of Autologous Neutralizing Antibodies.

Understanding the dynamics of early immune responses to HIV-1 infection, including the evolution of initial neutralizing and antibody-dependent cellular cytotoxicity (ADCC)-mediating antibodies, will inform HIV vaccine design. In this study, we assess the development of autologous neutralizing antibodies (ANAbs) against founder envelopes (Envs) from 18 participants with HIV-1 CRF01AE acute infection. The timing of ANAb development directly associated with the magnitude of the longitudinal ANAb response. Participants that developed ANAbs within 6 months of infection had significantly higher ANAb responses at 1 year (50% inhibitory concentration IC

The Antiviral Activity of Equine Mx1 against Thogoto Virus Is Determined by the Molecular Structure of Its Viral Specificity Region.

Mammalian myxovirus resistance (Mx) proteins are interferon-induced, large dynamin-like GTPases with a broad antiviral spectrum. Here, we analyzed the antiviral activity of selected mammalian Mx1 proteins against Thogoto virus (THOV). Of those, equine Mx1 (eqMx1) showed antiviral activity comparable to that of the human

Whats new in childhood tuberculosis.

The current review identifies recent advances in the prevention, diagnosis, and treatment of childhood tuberculosis (TB) with a focus on the WHOs updated TB management guidelines released in 2022. The COVID-19 pandemic negatively affected global TB control due to the diversion of healthcare resources and decreased patient care-seeking behaviour. Despite this, key advances in childhood TB management have continued. The WHO now recommends shorter rifamycin-based regimens for TB preventive treatment as well as shorter regimens for the treatment of both drug-susceptible and drug-resistant TB. The Xpert Ultra assay is now recommended as the initial diagnostic test for TB in children with presumed TB and can also be used on stool samples. Point-of-care urinary lipoarabinomannan assays are promising as rule-in tests for children with presumed TB living with HIV. Treatment decision algorithms can be used to diagnose TB in symptomatic children in settings with and without access to chest X-rays bacteriological confirmation should always be attempted. Recent guideline updates are a key milestone in the management of childhood TB, and the paediatric TB community should now prioritize their efficient implementation in high TB burden countries while generating evidence to close current evidence gaps.

Differences in hospitalizations associated with severe COVID-19 disease among foreign- and Swedish-born.

Differences in pre-existing health conditions are hypothesized to explain immigrants excess COVID-19 mortality compared to natives. In this study, we evaluate whether immigrants residing in Sweden before the outbreak were more likely to be hospitalized for conditions associated with severe COVID-19 disease. A cohort study using population-register data was conducted with follow-up between 1 January 1997 and 31 December 2017. Poisson regression was fitted to estimate incidence rate ratio (RR) and 95% confident intervals (95% CI) for 10 causes of hospitalization. Compared to Swedish-born individuals, most immigrant groups showed a decreased risk of hospitalization for respiratory chronic conditions, CVD, cancer, chronic liver conditions and neurological problems. All immigrant groups had increased risk of hospitalization for tuberculosis RR between 88.49 (95% CI 77.21 101.40) for the Horn of Africa and 1.69 (95% CI 1.11 2.58) for North America, HIV RR between 33.23 (95% CI 25.17 43.88) for the rest of Africa and 1.31 (95% CI 0.93 1.83) for the Middle East and, with a few exceptions, also for chronic kidney conditions, diabetes and thalassemia. Foreign-born individuals-including origins with excess COVID-19 mortality in Sweden-did not show increased risk of hospitalizations for most causes associated with severe COVID-19 disease. However, all groups showed increased risks of hospitalization for tuberculosis and HIV and, with exceptions, for chronic kidney conditions, diabetes and thalassemia. Although studies should determine whether these health conditions explain the observed excess COVID-19 mortality, our study alerts to an increased risk of hospitalization that can be avoidable via treatment or preventive measures.

Bone and joint tuberculosis in paediatrics a 13-year retrospective study.

Liver Injury Patterns and Hepatic Toxicity among People Living with and without HIV and Attending Care in Urban Uganda.

The evaluation of the patterns of liver injury, derived from liver chemistry panels, often may narrow on probable causes of the liver insult especially when coupled with clinical history, examination, and other diagnostic tests. Among people living with and without HIV and attending care, we used the Overall, the proportions of participants with cholestatic liver injury, mixed liver injury, and hepatocellular liver injury were 55%, 34%, and 4%, respectively, with similar distribution when stratified by HIV status. Alcohol use among participants without HIV was associated with all patterns of liver injury (cholestatic liver injury (OR 4.9 CI (1.0-24.2) Liver injury is prevalent among both people living with and without HIV in care, and cholestatic liver injury is the most common pattern. Alcohol is associated with all patterns of liver injury and increasing age associated with cholestatic liver injury among people living without HIV and people living with HIV, respectively.

Recurrent herpes simplex virus mimicking vulvar carcinoma in patient with Human Immunodeficiency Virus A case report.

Patients with human immunodeficiency virus (HIV) are at increased risk for developing other gynecologic conditions, including herpes simplex virus (HSV) and vulvar intraepithelial neoplasia (VIN)carcinoma. We describe the case of a woman with a history of microinvasive vulvar squamous cell carcinoma who presented with hypertrophic ulcerated vulvar and

Structural characterization of HIV-1 Env heterotrimers bound to one or two CD4 receptors reveals intermediate Env conformations.

HIV-1 envelope (Env) exhibits distinct conformational changes in response to host receptor (CD4) engagement. Env, a trimer of gp120gp41 heterodimers, has been structurally characterized in a closed, prefusion conformation with closely associated gp120s and coreceptor binding sites on gp120 V3 hidden by V1V2 loops, and in fully-saturated CD4-bound open Env conformations with changes including outwardly rotated gp120s and displaced V1V2 loops. To investigate changes resulting from sub-stoichiometric CD4 binding, we solved 3.4Å and 3.9Å single-particle cryo-EM structures of soluble, native-like Envs bound to one or two CD4 molecules. Env trimer bound to one CD4 adopted the closed, prefusion Env state. When bound to two CD4s, the CD4-bound gp120s exhibited an open Env conformation including a four-stranded gp120 bridging sheet and displaced gp120 V1V2 loops that expose the coreceptor sites on V3. The third gp120 adopted an intermediate, occluded-open state that included gp120 outward rotation but maintained the prefusion, three-stranded gp120 bridging sheet and showed only partial V1V2 displacement and V3 exposure. We conclude that engagement of one CD4 molecule was insufficient to stimulate CD4-induced conformational changes, while binding two CD4 molecules led to Env opening in CD4-bound protomers only. Together, these results illuminate HIV-1 Env intermediate conformations and illustrate the structural plasticity of HIV-1 Env.

Early HIV-1 Gag Assembly on Lipid Membrane with vRNA.

Mass photometry (MP) was used to investigate the assembly of myristoylated full-length HIV-1 Gag (myr-Gag) and vRNA 5’ UTR fragment in a supported lipid bilayer (SLB) model system. The MP trajectories demonstrated that Gag trimerization on the membrane is a key step of early Gag assembly in the presence of vRNA. Growth of myr-Gag oligomers requires vRNA, occuring by addition of 1 or 2 monomers at a time from solution. These data support a model where formation of the Gag hexamers characteristic of the immature capsid lattice occurs by a gradual edge expansion, following a trimeric nucleation event. These dynamic single molecule data involving protein, RNA, and lipid components together, provide novel and fundamental insights into the initiation of virus capsid assembly.

Association of Plasma Aflatoxin With Persistent Detection of Oncogenic Human Papillomaviruses in Cervical Samples From Kenyan Women Enrolled in a Longitudinal Study.

Background Cervical cancer is common among Kenyan women and is caused by oncogenic human papillomaviruses (HR-HPV). Identification of factors that increase HR-HPV persistence is critically important. Kenyan women exposed to aflatoxin have an increased risk of cervical HR-HPV detection. This analysis was performed to examine associations between aflatoxin and HR-HPV persistence. Methods Kenyan women were enrolled in a prospective study. The analytical cohort for this analysis included 67 HIV-uninfected women (mean age 34 years) who completed at least two of three annual study visits and had an available blood sample. Plasma aflatoxin was detected using ultra-high pressure liquid chromatography (UHPLC)-isotope dilution mass spectrometry. Annual cervical swabs were tested for HPV (Roche Linear Array). Ordinal logistic regression models were fitted to examine associations of aflatoxin and HPV persistence. Results Aflatoxin was detected in 59.7% of women and was associated with higher risk of persistent detection of any HPV type (OR 3.03, 95%CI 1.08-8.55, P 0.036), HR-HPV types (OR 3.63, 95%CI 1.30-10.13, P 0.014), and HR-HPV types not included in the 9-valent HPV vaccine (OR 4.46, 95%CI 1.13-17.58, P 0.032). Conclusions Aflatoxin detection was associated with increased risk of HR-HPV persistence in Kenyan women. Further studies are needed to determine if aflatoxin synergistically interacts with HR-HPV to increase cervical cancer risk.

Assessing HLA imputation accuracy in a West African population.

The Human Leukocyte Antigen (HLA) region plays an important role in autoimmune and infectious diseases. HLA is a highly polymorphic region and thus difficult to impute. We therefore sought to evaluate HLA imputation accuracy, specifically in a West African population, since they are understudied and are known to harbor high genetic diversity. The study sets were selected from Gambian individuals within the Gambian Genome Variation Project (GGVP) Whole Genome Sequence datasets. Two different arrays, Illumina Omni 2.5 and Human Hereditary and Health in Africa (H3Africa), were assessed for the appropriateness of their markers, and these were used to test several imputation panels and tools. The reference panels were chosen from the 1000 Genomes dataset (1kg-All), 1000 Genomes African dataset (1kg-Afr), 1000 Genomes Gambian dataset (1kg-Gwd), H3Africa dataset and the HLA Multi-ethnic dataset. HLA-A, HLA-B and HLA-C alleles were imputed using HIBAG, SNP2HLA, CookHLA and Minimac4, and concordance rate was used as an assessment metric. Overall, the best performing tool was found to be HIBAG, with a concordance rate of 0.84, while the best performing reference panel was the H3Africa panel with a concordance rate of 0.62. Minimac4 (0.75) was shown to increase HLA-B allele imputation accuracy compared to HIBAG (0.71), SNP2HLA (0.51) and CookHLA (0.17). The H3Africa and Illumina Omni 2.5 array performances were comparable, showing that genotyping arrays have less influence on HLA imputation in West African populations. The findings show that using a larger population-specific reference panel and the HIBAG tool improves the accuracy of HLA imputation in West African populations. For studies that associate a particular HLA type to a phenotypic trait for instance HIV susceptibility or control, genotype imputation remains the main method for acquiring a larger sample size. Genotype imputation, process of inferring unobserved genotypes, is a statistical technique and thus deals with probabilities. Also, the HLA region is highly variable and therefore difficult to impute. In view of this, it is important to assess HLA imputation accuracy especially in African populations. This is because the African genome has high diversity, and such studies have hardly been conducted in African populations. This work highlights that using HIBAG imputation tool and a larger population-specific reference panel increases HLA imputation accuracy in an African population.

Dual Trajectories of Antiretroviral Therapy Adherence and Polypharmacy in Women with HIV in the United States.

Background Polypharmacy, using five or more medications, may increase the risk of nonadherence to prescribed treatment. We aimed to identify the interrelationship between trajectories of adherence to antiretroviral therapy (ART) and polypharmacy. Methods We included women with HIV (aged ≥ 18) enrolled in the Womens Interagency HIV Study in the United States from 2014 to 2019. We used group-based trajectory modeling (GBTM) to identify trajectories of adherence to ART and polypharmacy and the dual GBTM to identify the interrelationship between adherence and polypharmacy. Results Overall, 1,538 were eligible (median age of 49 years). GBTM analysis revealed five latent trajectories of adherence with 42% of women grouped in the consistently moderate trajectory. GBTM identified four polypharmacy trajectories with 45% categorized in the consistently low group. Conclusions The joint model did not reveal any interrelationship between ART adherence and polypharmacy trajectories. Future research should consider examining the interrelationship between both variables using objective measures of adherence.

Traumatic aortic injury from pellet gun A case report.

Acute traumatic aortic injuries are of the most lethal sequelae of penetrating thoracic injuries and require rapid detection and management. The American College of Radiology currently recommends the use of noncontrast CT, followed by computed tomography angiography (CTA) as the first-line imaging modalities when traumatic aortic injury is suspected. Direct signs of aortic injury on CTA include pseudoaneurysm, focal contour abnormality, intimal flap, intramural hematoma, an abrupt change in aortic caliber, and contrast extravasation. Aortic pseudoaneurysms are most often caused by blunt or penetrating trauma that results in damage to the vessel wall, turbulent blood flow, and formation of a surrounding hematoma contained by a wall of products from the clotting cascade. This wall is weaker than those of a true aneurysm and will ultimately rupture over time if not repaired. Traumatic aortic pseudoaneurysms are preferably treated by thoracic endovascular aortic repair using a prosthetic stent graft. Here, we present a 44-yearold female with a history of homelessness, polysubstance use disorder, and HIV who presented to the emergency department after being found down. She reported being shot by a pellet gun, and physical examination revealed a penetrating left-sided chest wound that appeared to be several days old. A STAT CTA was obtained and revealed a hemopneumothorax and possible thoracic aortic pseudoaneurysm. A left-sided chest tube was placed and the patient underwent thoracic endovascular aortic repair through right femoral arterial access and tolerated the procedure well. The patient was placed on daily aspirin postoperatively and discharged on post-op day 5.

Health related quality of life of HIV-positive women on ART follow-up in north Shewa zone public hospitals, central Ethiopia Evidence from a cross-sectional study.

Evidence revealed that there is a statistically significant gender difference in Health-related quality of life (HRQoL) among HIV-positive people on Antiretroviral therapy (ART). Consequently, HIV-positive women have low scores in all HRQoL domains than men. Despite this fact, previous studies in Ethiopia focused on general HIV-positive people and paid less attention to HIV-positive women. Therefore, this study was intended to measure HRQoL and associated factors among HIV-positive women on ART follow-up in north Shewa zone public hospitals, central Ethiopia. An institution-based cross-sectional study was conducted from February 01-April 30, 2022. Four hundred twenty-six women on ART were included using a systematic random sampling technique. Face-to-face interviews and medical record reviews were used to collect data. Both bivariable and multiple linear regressions were computed to identify the factors associated with HRQoL. A p-value <0.05 was used to assert statistically significant variables in multiple linear regression analysis. The overall mean (SD) score of the HRQoL was 11.84 (2.44). And, 44.7% 95% CI 40.3, 49.5 of the women have poor HRQoL. In multiple linear regression analysis, factors like depression (β -0.35), Post-Traumatic Stress Disorder (PTSD) (β -0.16), age (β -0.07), rural residence (β -0.52), and bedridden functional status (β -1.02) were inversely associated with HRQoL. Oppositely, good treatment adherence (β 0.46) was positively associated with overall HRQoL, keeping other factors constant. This study reveals a high magnitude of poor HRQoL among HIV-positive women. Therefore, as HRQoL domains are comprehensive indicators of living status, healthcare service providers should be dedicated to screening and supporting HIV-positive women with poor HRQoL. Additionally, healthcare providers should also pay special attention to routine PTSD screening and management for HIV-positive women due to its detrimental effect on HRQoL.

Exploring HIV status as a mediator in the relationship of psychological distress with socio-demographic and health related factors in South Africa findings from the 2012 nationally representative population-based household survey.

Psychological distress as measured by mental disorders like depression and anxiety is more prevalent in people living with HIV (PLHIV) than in the general population. However, the relationship between mental disorders and HIV is complex and bidirectional. Improved understanding of the relationship between mental disorders and HIV is important for designing interventions for this group. This paper explores the interrelationships of psychological distress with HIV and associated socio-demographic and health-related factors. This secondary data analysis used the 2012 South African population-based household survey on HIV collected using a cross-sectional multi-stage stratified cluster sampling design. Generalized structural equation modelling (G-SEM) path analysis was used to explore the direct and indirect relationships of socio-demographic, health and HIV-related factors with psychological distress as measured by Kessler 10 scale using HIV status as a moderator variable. A total of 20,083 participants were included in the study, 21.7% reported psychological distress, of whom (32.6%) were HIV positive. In the final path model with HIV status as a moderator, psychological distress was significantly more likely among age group 25-49 years (AOR 1.4 95% CI 1.3-1.6), age 50 years and older, (AOR 1.4 95% CI 1.2-1.6), females (AOR 1.6 95% CI 1.4-1.8), high risk drinkers (AOR 1.9 1.6-2.2) hazardous drinkers (AOR 4.4 95% CI 3.1-6.3), ever tested for HIV (AOR 1.2 95% CI 1.1-1.3). Psychological distress was significantly less likely among the married AOR 0.8 (0.7-0.9), other race groups AOR 0.5 (0.5-0.6), those with secondary level education (AOR 0.9 95% CI 0.8-0.9), and tertiary level education (AOR 0.7 95% CI 0.6-0.9), those from rural informal AOR 0.8 (0.7-0.9), and rural formal AOR 0.8 (0.7-0.9) areas and those who rated their health as excellentgood AOR 0.4 (0.4-0.5). The findings highlight the importance of designing tailored interventions targeted at psychological distress among PLHIV especially the elderly, females, those with no education and or low education attainment and those residing in informal urban areas.

HIV prevalence and associated risk factors among young tertiary student men who have sex with men (MSM) in Nairobi, Kenya a respondent-driven sampling survey.

Young men who have sex with men (MSM), are a key population at higher risk of HIV infection yet they are underrepresented in research. We conducted a bio-behavioral survey to estimate HIV prevalence and associated risk factors among tertiary student MSM (TSMSM) in Nairobi, Kenya. Between February and March 2021, 248 TSMSM aged ≥ 18 years who reported sex with another man in the past year participated in a respondent-driven sampling (RDS) based cross-sectional survey. Participants completed an electronically self-administered behavioral survey and provided a blood sample for HIV antibody testing, alongside urine, anorectal and oropharyngeal swabs for pooled testing of sexually transmitted infections using a multiplex nucleic acid amplification test. RDS-Analyst v.0.72 and Stata v.15 software were used for data analysis. Differences in proportions were examined using chi-square (χ HIV prevalence among study participants was 8.3%, whereas the weighted prevalence was 3.6% (95% CI 1.3-6.0%). Median ages of participants, and at self-reported first anal sex with a man were 21(interquartile range IQR 20-22) and 18 (IQR 17-19) years, respectively. A majority (89.3%) of TSMSM owned a smart phone, 46.5% had ever used a geosocial networking app for MSM such as Grindr ® to find a sex partner, and a third (33.6%) met their last sex partner online. Almost three-quarters (71.3%) had > 1 male sex partner in the year before the survey. A third (34.3%) did not use condoms with their last sex partner, 21.2% received money from their last sex partner and 40.9% had taken alcoholanother drug during their last sexual encounter. HIV infection was associated with studying in private institutions (adjusted odds ratioAOR 6.0 95% confidence intervals CI 1.2-30.0, p 0.027), preferring a sex partner of any age-younger, same or older (AOR 5.2 95 CI 1.1-25.2, p 0.041), last sex partner being > 25 years (AOR 6.4 95% CI 1.2-34.6, p 0.030), meeting the last sex partner online (AOR 4.2 95% CI 1.1-17.0, p 0.043) and testing positive for Neisseria gonorrhea (AOR 7.8 95% CI 2.0-29.9, p 0.003). HIV prevalence among TSMSM in Nairobi is alarmingly high, demonstrating a need for tailored prevention and control interventions for this young key population.

It gives you a road map of what to do to solve your problems acceptability of a combination HIV prevention intervention among adolescent girls in Uganda.

The HIV burden remains a critical public health concern and adolescent girls are at significantly higher risk compared to the general adult population. Similar to other sub-Saharan African countries, Uganda reports high HIV prevalence among adolescent girls and young women. Yet, both evidence-based HIV prevention interventions and their acceptability among adolescent girls have not been widely studied. In this study, we examined the acceptability of the Suubi4Her intervention, an evidence-based combination intervention aimed at reducing HIV risk among adolescent girls in Uganda. We conducted semi-structured in-depth interviews with 25 adolescent girls upon intervention completion to explore their experiences with the Suubi4Her intervention that was tested in a clinical trial in Uganda (2017-2023). Specifically, we explored their decision-making process for participating in the intervention, experiences with program attendance, and their feedback on specific intervention characteristics. Informed by the Theoretical Framework of Acceptability, the data were analyzed using thematic analysis. The main motivation for participation was access to health-related information, including information on STIs, HIV, and pregnancy as well as information on banking, saving, and income-generating activities. Though many participants did not have any initial concerns, mistrust of programs, initial paperwork, caregivers ability to commit time, concerns about ability to save, and HIVSTI and pregnancy testing were raised by some participants. Facilitators to session attendance included motivation to learn information, caregiver commitment, reminder calls, and incentives received for participation. The main challenges included household responsibilities and obligations, difficulty raising transport money, and weather challenges. Adolescent girls appreciated the group format and found the location and times of the sessions convenient. They also found the content relevant to their needs and noted positive changes in their families. The results showed high intervention acceptability among adolescent girls. These findings have important programmatic and policy implications in Uganda, especially given the higher HIV prevalence among adolescent girls in the country. NCT03307226 (Registered 101117).

Recombinant anti-HIV MAP30, a ribosome inactivating protein against plant virus and bacteriophage.

The ribosome inactivating proteins (RIPs) efficiently decrease the microbial infections in plants. Momordica charantia MAP30 is a type I RIP that has not been investigated against plant viruses or bacteriophages. To evaluate of these activities, the recombinant MAP30 (rMAP30) was produced in the hairy roots of Nicotiana tabacum. Inoculation of 3 μg of transgenic total protein or 0.6 μg of rMAP30 against 0.1 μg of TMV reduced the leaf necrotic spots to 78.23% and 82.72%, respectively. The treatment of 0.1 μg of CMV with rMAP30 (0.6 μg) showed the reduction in the leaf necrotic spots to 85.8%. While the infection was increased after rMAP30 dilution. In the time interval assays, the leaves were first inoculated with 1 μg of rMAP30 or 0.1 μg of purified TMV or CMV agent for 6 h, then virus or protein was applied in order. This led the spot reduction to 35.22% and 67% for TMV, and 38.61% and 55.31% for CMV, respectively. In both the pre- and co-treatments of 110 or 120 diluted bacteriophage with 15 μg of transgenic total protein, the number and diameter of the plaques were reduced. The results showed that the highest inhibitory effect was observed in the pre-treatment assay of bacteriophage with transgenic total protein for 24 h. The decrease in the growth of bacteriophage caused more growth pattern of Escherichia coli. The results confirm that rMAP30 shows antibacterial activity against Streptococcus aureus and E. coli, antifungal activity against Candida albicans, and antiviral activity against CMV and TMV. Moreover, rMAP30 exhibits anti-phage activity for the first time. According to our findings, rMAP30 might be a valuable preservative agent in foods and beverages in the food industry as well as an antiviral and antimicrobial mixture in agriculture.

Mediation of the Effect of Incarceration on Selling Sex Among Black Sexual Minority Men and Black Transgender Women in the HPTN 061 Study.

Incarceration among Black sexual minority men and Black transgender women (BSMMBTW) is disproportionately high in the United States. Limited research has documented the disruptive effect of incarceration on sexual networks and sexual partnership exchange among BSMMBTW. We estimate the influence of incarceration on selling sex and mediating pathways among 1169 BSMMBTW enrolled in the HIV Prevention Trials Network (HPTN) 061 cohort to assess this relationship. Mediators investigated were social support, violence, illicit drug use, and distress due to experienced racism and homophobia. During the 6 months following baseline, 14% of the cohort was incarcerated, including 24% of BTW. After adjustment, recent incarceration was associated with 1.57 (95% CI 1.02, 2.42) times the risk of subsequently selling sex. The hypothesized mediators together explained 25% of the relationship, with an indirect effect risk ratio of 1.09 (95% CI 0.97, 1.24). Our results document an association and call for more research investigating mechanisms.

Triple Benefit Impact of an Integrated Early Childhood Development and PMTCT Intervention on ART Outcomes Among Mothers Living with HIV and Infants in Malawi-An Endline Evaluation.

We conducted a programmatic, observational cohort study with mother-infant pairs (MIPs) enrolled in prevention-of-mother-to-child-transmission (PMTCT) programs in Malawi to assess the feasibility and potential HIV-related benefits of integrating Early Childhood Development (ECD) services into PMTCT programs. Six health facilities were included in the intervention. We offered ECD counseling from the WHOUNICEF Care for Child Development package in PMTCT waiting spaces while MIPs waited for PMTCT and broader treatment consultations. Primary outcomes were mothers retention in HIV care at 12 months and infant HIV testing at 6 weeks and 12 months after birth. Routine facility-level data from six comparison health facilities were collected as an adhoc standard of care comparison and used to calculate the cost of delivering the intervention. A total of 607 MIPs were enrolled in the integrated ECD-PMTCT intervention between June 2018 and December 2019. The average age of MIPs was 30 years and 7 weeks respectively. We found that 86% of mothers attended ≥ 5 of the 8 ECD sessions over the course of 12 months 88% of intervention mothers were retained in PMTCT versus 59% of mothers in comparison health facilities, and 96% of intervention infants were tested for HIV by six weeks compared to 66% of infants in comparison health facilities. Costing data demonstrated the financial feasibility of integrating ECD and PMTCT programs in government health facilities in Malawi. Integrating ECD into PMTCT programs was feasible, acceptable, resulted in better programmatic outcomes for both mothers and infants. Further investigation is required to determine optimal delivery design for scale-up.

What We Lost in the Fire Endemic Tropical Heart Diseases in the Time of COVID-19.

The COVID-19 pandemic has profoundly influenced the effort to achieve global health equity. This has been particularly the case for HIVAIDS, tuberculosis, and malaria control initiatives in low- and middle-income countries, with significant outcome setbacks seen for the first time in decades. Lost in the calls for compensatory funding increases for such programs, however, is the plight of endemic tropical heart diseases, a group of disorders that includes rheumatic heart disease, Chagas disease, and endomyocardial fibrosis. Such endemic illnesses affect millions of people around the globe and remain a source of substantial mortality, morbidity, and health disparity. Unfortunately, these conditions were already neglected before the pandemic, and thus those living with them have disproportionately suffered during the time of COVID-19. In this perspective, we briefly define endemic tropical heart diseases, summarizing their prepandemic epidemiology, funding, and control statuses. We then describe the ways in which people living with these disorders, along with the healthcare providers and researchers working to improve their outcomes, have been harmed by the ongoing COVID-19 pandemic. We conclude by proposing the path forward, including approaches we may use to leverage lessons learned from the pandemic to strengthen care systems for these neglected diseases.

Post-auricular teratoma in an HIV-exposed newborn.

Teratomas in the neonatal age group are mostly benign at first, and the common site is the sacrococcygeal region. They are rarely associated with HIV infection. We report a case of an HIV-exposed newborn with a congenital teratoma at the post-auricular site who developed an infection. Early intervention by total surgical resection will prevent complications such as infections and malignant transformation. A term baby was delivered spontaneously by an HIV-positive mother who was on her regular medications. Prenatal ultrasound carried out in the third trimester showed a cyst swelling on the right post-auricular region. Radiological imaging and the histopathological result revealed a congenital teratoma. A wide major excision with preservation of the facial nerve was performed at the age of 8 weeks. Post-auricular teratomas are the rarest anatomical location and the prevalence of malignant transformation from benign is very low. If left untreated, this tumour is associated with high mortality and malignant transformation rates. An early complete surgical excision allows a good result with a low risk of complications and recurrence.

Lung cancer resection after immunochemotherapy vs. chemotherapy in oligometastatic NSCLC.

Background Neoadjuvant immunochemotherapy is currently being tested in pivotal trials for stage I-III NSCLC. The impact of immunochemotherapy in patients with oligometastastic disease remains undefined. This study aimed to compare the outcomes of radical treatment after the neoadjuvant course of immunochemotherapy versus chemotherapy. Methods We retrospectively analyzed patients with oligometastastic disease who were treated with immunochemotherapy or chemotherapy combined with local ablation of metastases and radical primary tumor resection between 2017 and 2021. Group A included eight patients with immunochemotherapy Group B included seven patients with chemotherapy. Descriptive statistical analysis included the characteristics of the patients, tumors, and outcomes. Results There was no difference in postoperative morbidity rates between the groups (p0.626). The 30-day mortality in both groups was 0%. The median overall survival for Group A was not reached, with a median follow-up time of 25 (range13-35) months the median overall survival for Group B was 26 (range5-53) months. In Group A, all patients remained alive in contrast, in Group B, four patients died (p0.026). There was no local thoracic recurrence in either group. In Group B, recurrent disease was identified significantly more often (12.5% vs. 85.75%p0.009). The rates of complete and major pathologic response were 37.5% and 0% in Group A and 42.85% and 14.25% in Group B, respectively. Conclusion Despite the small patient number and short-term results, the progression-free and overall survival in patients with oligometastastic disease after local therapy for metastases and primary tumor resection following neoadjuvant course of immunochemotherapy might be promising compared to chemotherapy.

Overview of the role and action mechanism of microRNA-128 in viral infections.

Recently in vivo and in vitro studies have provided evidence establishing the significance of microRNAs (miRNAs) in both physiological and pathological conditions. In this regard, the role of miRNA-128 (miR-128) in health and diseases has been found, and its critical regulatory role in the context of some viral diseases has been recently identified. For instance, it has been found that miR-128 can serve as an antiviral mediator and significantly limit the replication and dissemination of human immunodeficiency virus type 1 (HIV-1). Besides, it has been noted that poliovirus receptor-related 4 (PVRL4) is post-transcriptionally regulated by miR-128, representing possible miRNA targets that can modulate measles virus infection. Of note, the downregulation of seminal exosomes eca-miR-128 is associated with the long-term persistence of Equine arteritis virus (EAV) in the reproductive tract, and this particular miRNA is a putative regulator of chemokine ligand 16 (C-X-C motif) as determined by target prediction analysis. In this review, the latest information on the role and action mechanism of miR-128 in viral infections will be summarized and discussed in detail.

Pregnancy and neonatal safety outcomes of timing of initiation of daily oral tenofovir disoproxil fumarate and emtricitabine pre-exposure prophylaxis for HIV prevention (CAP016) an open-label, randomised, non-inferiority trial.

The safety of tenofovir disoproxil fumarate and emtricitabine as pre-exposure prophylaxis (PrEP) in pregnant women not living with HIV is uncertain. We aimed to compare pregnancy and neonatal outcomes in women exposed and not exposed to PrEP during pregnancy. In this single-site, open-label, randomised, non-inferiority trial in Durban, South Africa, we evaluated pregnancy and neonatal outcomes in pregnant women aged 18 years or older, not living with HIV, and at 14-28 weeks gestation at the time of enrolment. Eligible participants were randomly assigned (11) using a computer-generated permuted block (block size of ten) randomisation list to immediate initiation or deferred initiation of PrEP until breastfeeding cessation. Participants in the immediate PrEP group received a monthly supply of once daily oral tenofovir disoproxil fumarate 300 mg and emtricitabine 200 mg. Participants in the deferred PrEP group received standard of care for HIV prevention. The primary outcomes were the occurrence of preterm live birth (<37 weeks gestational age) and very preterm birth (<34 weeks gestational age) determined by menstrual dating, low birthweight (<2500 g), very low birthweight (<1500 g), stillbirth (≥20 weeks gestational age), and small for gestational age (birthweight less than the tenth percentile). Post-natal safety outcomes will be reported elsewhere. We used binomial regression models to estimate risk differences and two-sided 90% CIs. Immediate PrEP was non-inferior to deferred PrEP if the upper bound of the 90% CI of the risk difference was less than the upper predefined non-inferiority margin for preterm birth (7·5%), very preterm birth (2·6%), low birthweight (5·5%), very low birthweight (1·2%), stillbirth (1·0%), and small for gestational age (3·7%). All outcomes were analysed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT3227731. Between Sept 25, 2017, and Dec 6, 2019, we screened 693 women, of whom 540 were randomly assigned to immediate PrEP (n271) or deferred PrEP (n269). The median gestational age was 19 weeks (IQR 15-23 for immediate PrEP and 16-23 for deferred PrEP). The risk difference between the immediate PrEP group and the deferred PrEP group for preterm birth was -4·7% (90% CI -10·7 to 1·2 immediate PrEP was non-inferior), for very preterm birth was 0·6% (-3·4 to 4·6 upper limit exceeded the non-inferiority margin), for low birthweight was 2·5% (-1·6 to 6·6 upper limit exceeded the non-inferiority margin), for very low birthweight was 0% (-1·4 to 1·4 upper limit exceeded the non-inferiority margin), for stillbirth was 1·2% (-1·5 to 3·8 upper limit exceeded the non-inferiority margin), and for small for gestational age was 0·9% (-1·2 to 2·9 immediate PrEP was non-inferior). In our study, PrEP was not associated with preterm birth or small for gestational age infants. Our data support the use of tenofovir disoproxil fumarate and emtricitabine in pregnancy and our reassuring findings can be used to allay safety concerns among pregnant women. South African Medical Research Council and Gilead Sciences.

Blood Biomarkers of NeuronalAxonal and Glial Injury in Human Immunodeficiency Virus-Associated Neurocognitive Disorders.

Approximately half of the people living with HIV (PLWH) experience HIV-associated neurocognitive disorders (HANDs). However, the neuropathogenesis of HAND is complex, and identifying reliable biomarkers has been challenging. This study included 132 participants aged 50 and older from greater San Diego County. The participants were divided into three groups PLWH with HAND (n 29), PLWH without HAND (n 73), and seronegatives without cognitive impairment (n 30). Peripheral blood was collected at the clinical assessment, and plasma levels of neurofilament light chain (NfL), phosphorylated Tau 181 (pTau181), and glial fibrillary acidic protein (GFAP) were measured by enzyme-linked immunosorbent assay (ELISA). Plasma levels of NfL (but not pTau181 and GFAP) were significantly associated with HAND at a medium effect size (p 0.039, Cohens d 0.45 for HAND vs. HAND-). Notably, higher levels of NfL were significantly associated with HAND diagnosis even after adjusting for sex. Our data suggest that neuronal degeneration (as evidenced by increased levels of NfL), but not tau pathology or glial degeneration, is related to cognitive status in PLWH. Our results corroborate the view that blood NfL is a promising biomarker of cognitive impairment in PLWH.

Examining recruitment strategies in the enrollment cascade of youth living with HIV Descriptive findings from a nationwide online adherence protocol.

Digital strategies and broadened eligibility criteria may optimize enrollment of youth living with HIV (YLH) in mobile health adaptive interventions. Prior research suggests that digital recruitment strategies are more efficient than traditional methods to overcome enrollment challenges among YLH in the United States. This paper highlights challenges and strategies that explain screening and enrollment milestones in a national online adherence protocol for YLH. Baseline data from a national online HIV adherence protocol of YLH collected from July 2018 through February 2021 were analyzed. A centralized recruitment procedure was developed which utilized (1) online recruitment via Online Master Screener, (2) paid online targeted advertisements on social media platforms (e.g., Facebook, Reddit) and geosocial networking dating applications (e.g., Grindr, Jackd apps), and (3) site and provider referrals from Subject Recruitment Venues and other AIDS service organizations, website referrals, and text-in recruitment. Three distinct cohorts of YLH were identified, marked by changes in recruitment strategies. Overall, 3,270 individuals consented to screening, 2,721 completed screening, 581 were eligible, and 83 completed enrollment. We examined sociodemographic and behavioral differences in completing milestones from eligibility to full enrollment (i.e., submitting antiretroviral therapy and viral load data and completing baseline online survey). Those with most recent viral load tests more than 6 months ago were half as likely to enroll (OR 0.45, CI 0.21, 0.94). Moreover, eligible participants with self-reported antiretroviral therapy adherence (SRA) between 50% and 80% were significantly more likely to enroll than those with SRA greater than 80%. The findings add to our knowledge on the utility of digital technologies for YLH before and during the COVID-19 pandemic and provide insight into the impact of expanding eligibility criteria on enrollment. As the COVID-19 pandemic continues and usage of and engagement with social media and dating apps among YLH changes, these platforms should continue to be investigated as potential recruitment tools. Employing a wide variety of recruitment strategies such as using social media and dating apps as well as provider referral mechanisms, increasing compensation amounts, and including SRA in enrollment criteria should continue to be studied with respect to their ability to successfully recruit and enroll eligible participants. ClinicalTrials.gov (NIH U.S. National Library of Medicine) Identifier NCT03535337 httpsclinicaltrials.govct2showNCT03535337. RR2-10.219611183.

Missed opportunities to address common mental disorders and risky alcohol use among people living with HIV in Zomba, Malawi A cross sectional clinic survey.

Common mental disorders (CMDs) and risky alcohol use are highly prevalent among people living with HIV, yet many do not receive treatment for these mental health problems. In Malawi, despite a mental health policy aiming to include mental healthcare into primary health care, many clients with HIV go unscreened and untreated for mental illnesses, indicating missed opportunities to offer mental health care to people living with HIV. The aim of this study was to determine the numbers and types of missed opportunities for screening and treatment of CMDs and risky alcohol use amongst a sample of people living with HIV attending anti-retroviral (ART) clinics in Zomba Malawi. A descriptive cross-sectional clinic survey was used, at three ART clinics in the Zomba district. Random sampling was conducted for all clients attending their ART clinics on specific days. The study surveyed 382 participants living with HIV. Of these participants, the majority were women (N 247, 64.7%), and 87 (22.8%) screened positive for CMDs andor alcohol misuse using the self-reporting questionnaire 20 (SRQ-20) and alcohol use disorder identification test (AUDIT). Of these, only 47 (54%) had been screened by health workers for CMDs or risky alcohol use in the past 12 months, and 66 (76%) wanted to receive treatment. Of the total sample of 382 participants, only 92 (24%) and 89 (23%) had been screened for CMDs or risky alcohol use by health workers. Failures by clinical officers and nurses to screen or treat CMDs and risky alcohol use in ART clinics represent missed opportunities to address the mental health of people living with HIV. Providing psychoeducation for staff, guidelines for screening and managing CMDs and alcohol use, increasing human resources, and accelerating implementation of the mental health policy in Malawi may be a few ways of improving mental health service provision at ART clinics in Malawi.

The Endocannabinoid System as a Potential Therapeutic Target for HIV-1-Associated Neurocognitive Disorder.

Transgender and gender diverse adults reflections on alcohol counseling and recommendations for providers.

Transgender and gender diverse (TGD) populations experience health disparities due to societal stigma that increases TGD individuals sources of stress and decreases access to health protective resources. Research has linked experiences of stigma to risky alcohol use, yet there remains a dearth of culturally sensitive alcohol use interventions that meet the needs of TGD people. The present study was conducted to inform modifications to the content and delivery of an existing brief, telehealth, motivational intervention to decrease at-risk alcohol use among TGD adults. Individual semi-structured in-depth qualitative interviews were conducted with TGD adults who reported recent alcohol use (

The Drug-Induced Interface That Drives HIV-1 Integrase Hypermultimerization and Loss of Function.

Allosteric HIV-1 integrase (IN) inhibitors (ALLINIs) are an emerging class of small molecules that disrupt viral maturation by inducing the aberrant multimerization of IN. Here, we present cocrystal structures of HIV-1 IN with two potent ALLINIs, namely, BI-D and the drug candidate Pirmitegravir. The structures reveal atomistic details of the ALLINI-induced interface between the HIV-1 IN catalytic core and carboxyl-terminal domains (CCD and CTD). Projecting from their principal binding pocket on the IN CCD dimer, the compounds act as molecular glue by engaging a triad of invariant HIV-1 IN CTD residues, namely, Tyr226, Trp235, and Lys266, to nucleate the CTD-CCD interaction. The drug-induced interface involves the CTD SH3-like fold and extends to the beginning of the IN carboxyl-terminal tail region. We show that mutations of HIV-1 IN CTD residues that participate in the interface with the CCD greatly reduce the IN-aggregation properties of Pirmitegravir. Our results explain the mechanism of the ALLINI-induced condensation of HIV-1 IN and provide a reliable template for the rational development of this series of antiretrovirals through the optimization of their key contacts with the viral target.

Optimizing Moxifloxacin Dose in MDR-TB Participants with or without Efavirenz Coadministration Using Population Pharmacokinetic Modeling.

Moxifloxacin is included in some treatment regimens for drug-sensitive tuberculosis (TB) and multidrug-resistant TB (MDR-TB). Aiming to optimize dosing, we described moxifloxacin pharmacokinetic and MIC distribution in participants with MDR-TB. Participants enrolled at two TB hospitals in South Africa underwent intensive pharmacokinetic sampling approximately 1 to 6 weeks after treatment initiation. Plasma drug concentrations and clinical data were analyzed using nonlinear mixed-effects modeling with simulations to evaluate doses for different scenarios. We enrolled 131 participants (54 females), with median age of 35.7 (interquartile range, 28.5 to 43.5) years, median weight of 47 (42.0 to 54.0) kg, and median fat-free mass of 40.1 (32.3 to 44.7) kg 79 were HIV positive, 29 of whom were on efavirenz-based antiretroviral therapy. Moxifloxacin pharmacokinetics were described with a 2-compartment model, transit absorption, and elimination via a liver compartment. We included allometry based on fat-free mass to estimate disposition parameters. We estimated an oral clearance for a typical patient to be 17.6 Lh. Participants treated with efavirenz had increased clearance, resulting in a 44% reduction in moxifloxacin exposure. Simulations predicted that, even at a median MIC of 0.25 (0.06 to 16) mgL, the standard daily dose of 400 mg has a low probability of attaining the ratio of the area under the unbound concentration-time curve from 0 to 24 h to the MIC (

A Virus-Packageable CRISPR System Identifies Host Dependency Factors Co-Opted by Multiple HIV-1 Strains.

At each stage of the HIV life cycle, host cellular proteins are hijacked by the virus to establish and enhance infection. We adapted the virus packageable HIV-CRISPR screening technology at a genome-wide scale to comprehensively identify host factors that affect HIV replication in a human T cell line. Using a smaller, targeted HIV Dependency Factor (HIVDEP) sublibrary, we then performed screens across HIV strains representing different clades and with different biological properties to define which T cell host factors are important across multiple HIV strains. Nearly 90% of the genes selected across various host pathways validated in subsequent assays as bona fide host dependency factors, including numerous proteins not previously reported to play roles in HIV biology, such as UBE2M, MBNL1, FBXW7, PELP1, SLC39A7, and others. Our ranked list of screen hits across diverse HIV-1 strains form a resource of HIV dependency factors for future investigation of host proteins involved in HIV biology.

Can Contingency Management Solve the Problem of Adherence to Antiretroviral Therapy in Drug-Dependent Individuals

Drug misuse among people living with HIV (human immunodeficiency virus) is associated with higher mortality. It is a frequently observed reason for treatment abandonment, with people who misuse drugs showing a 10 to 25 times higher risk of HIV than the general population. The authors conducted a systematic review and meta-analysis to assess the efficacy of contingency management (CM) to improve adherence to antiretroviral therapy in people living with HIV and substance use disorder (SUD). The inclusion criteria consisted of studies written in English, Italian, Spanish, German, and French studies conducted with humans and clinical trials that combined SUD treatment with CM for people living with HIV. Two hundred twenty-two articles were identified, five met all inclusion criteria, and three provided enough data to perform the meta-analysis. We considered treatment adherence by measuring the increase in the CD4 count as our primary outcome. We found a significant increase in treatment adherence in the patient group compared with the control groups during the intervention phase. Positive findings did not persist after the cessation of the incentives. The meta-analysis showed that the intervention improved patient adherence by 2.69 (95% confidence interval 0.08, 0.51

Intimate Partner Violence and Health Outcomes Among Women Living With HIVAIDS in Ghana A Cross-Sectional Study.

Intimate partner violence (IPV) is known to have negative health consequences for victims. For women living with HIVAIDS, whose health may be compromised, exposure to IPV can be devastating. Yet few (if any) studies have explored the health implications of exposure to IPV among HIV-positive women. We begin to fill this gap by examining the effects of various dimensions of IPV (physical, sexual, psychologicalemotional, and economic) on the cardiovascular, psychosocial, and sexual reproductive health outcomes of HIV-positive women in Ghana. Data were collected from a cross-section of 538 HIV-positive women aged 18 years and older in the Lower Manya Krobo District in the Eastern Region. We used logit models to explore relationships between IPV and health. The findings indicate high prevalence of IPV in our sample physical violence (61%), sexual violence (50.9%), emotionalpsychological violence (79.6%), and economic violence (66.8%). Generally, participants with experiences of IPV reported cardiovascular health problems, unwanted pregnancies and pregnancy loss, and poor psychosocial health. Our findings suggest the importance of screening for IPV as part of HIV care in Ghana.

Demographic diversity of US-based participants in GSK-sponsored interventional clinical trials.

Demographic diversity among clinical trials is required for representing the real-world populations intended for treatment and disease prevention. Moreover, genetic and environmental differences between ethnic and racial groups necessitate appropriately powered trials for relevant subgroups. We investigate the racial and ethnic demographic diversity of US-based participants in GSK-sponsored interventional trials. We also assess the evaluation of demographic diversity against US Census and epidemiologic data. GSK-sponsored interventional phase I-IV clinical trials conducted from 2002 to 2019 across three areas were analyzed pharmaceutical (includes therapeutic medicines except for vaccines and human immunodeficiency virus (HIV)), vaccine (includes prophylactic and therapeutic vaccines), and ViiV (includes HIV therapies). A total of 1005 global trials encompassing 460,707 global participants were identified, of which 495 had US-based sites with a total of 108,261 (23.5% of global) US participants (pharmaceutical, n 357 trials vaccine, n 45 trials and ViiV, n 93 trials). We evaluated how GSK US-based trial recruitment compares with US Census (in line with previously published studies from other groups) and with epidemiologic data. GSK participant data for race and ethnicity combined across areas were generally similar to US Census levels (e.g. GSK versus census White, 76.5% versus 76.3% Black or African American, 15.1% versus 13.4% Asian, 1.8% versus 5.9% Hispanic or Latino, 14.0% versus 18.5% Non-Hispanic White, 63.5% versus 60.1%). However, this was not the case for the individual pharmaceutical, vaccine, and ViiV data sets least represented groups were Asian individuals for pharmaceutical and ViiV trials and American Indian or Alaskan Native individuals for vaccine trials (6.2%, 11.8%, and 11.1% of trials metexceeded census level representation, respectively). The percentage of trials reachingexceeding census levels also varied per trial phase for race and ethnicity. Furthermore, disparities in the percentage of trials reachingexceeding census levels versus epidemiology-based prevalence levels have revealed opportunities to improve industry success metrics in HIV trials, the proportion of Black or African American individuals (35.1%) exceeded census (13.4%) but not epidemiologic levels (55.3%). Further work is required to achieve demographic diversity across clinical trials. We conclude that US Census data are an inappropriate universal benchmark. A shift to epidemiology benchmarking will enable the consideration of global participants into US analyses for highly intrinsic (i.e. influenced by ancestry) diseases and more firm requirements for US-based participants into US analyses for extrinsic (i.e. influenced by location or culture) diseases. Benchmarking in line with epidemiologic data will allow us to set better trial enrollment goals, with the aim of conducting more demographically balanced, diverse, and representative clinical trials and enabling a better understanding of drug safety and efficacy per demographic group.

The therapeutic threshold in clinical decision-making for TB.

Because TB control is still hampered by the limitations of diagnostic tools, diagnostic uncertainty is common. The decision to offer treatment is based on clinical decision-making. The therapeutic threshold, test threshold and test-treatment threshold can guide in making these decisions. This review summarizes the literature on methods to estimate the therapeutic threshold that have been applied for TB. Only five studies estimated the threshold for the diagnosis of TB. The therapeutic threshold can be estimated by prescriptive methods, based on calculations, and by descriptive methods, deriving the threshold from observing clinical practice. Test and test-treatment thresholds can be calculated using the therapeutic threshold and the characteristics of an available diagnostic test. Estimates of the therapeutic threshold for pulmonary TB from intuitive descriptive approaches (20%-50%) are higher than theoretical prescriptive calculations (2%-3%). In conclusion, estimates of the therapeutic threshold for pulmonary TB depend on the method used. Other methods exist within the field of decision-making that have yet to be implemented or adapted as tools to estimate the TB therapeutic threshold. Because clinical decision-making is a core element of TB management, it is necessary to find a new, clinician-friendly way to unbiasedly estimate context-specific, agreed upon therapeutic thresholds.

Acute kidney injury among hospitalised patients who died due to COVID-19 in the Eastern Cape, South Africa.

Acute kidney injury (AKI) commonly occurs in coronavirus disease 2019 (COVID-19) patients who have been hospitalised and is associated with a poor prognosis. This study aimed to determine the incidence of AKI among COVID-19 patients who died in a regional hospital in South Africa. This retrospective record review was conducted at the Mthatha Regional Hospital in South Africas Eastern Cape province. Data were collected between 10 July 2020 and 31 January 2021. The incidence of AKI was 38% among the hospitalised patients who died due to COVID-19. Most study participants were female, with a mean age of 63.3 ± 16 years. The most common symptom of COVID-19 at the time of hospitalisation was shortness of breath, followed by fever and cough. Half of the patients had hypertension, while diabetes, human immunodeficiency viruses (HIV) and tuberculosis (TB) were other comorbidities. At admission, the average oxygen saturation was 75.5% ± 17. The study revealed a high incidence of AKI among hospitalised patients who died due to COVID-19. It also found that those received adequate crystalloid fluids at the time of admission had a lower incidence of AKI.Contribution Acute kidney injury can be prevented by adequate fluid management during early stage of COVID-19. Majority of COVID-19 patients were referred from lower level of care and primary care providers have their first encounter with these patients. Adequate fluid resuscitation in primary care settings can improve the outcome of hospitalised COVID-19 patients.

Vitamin D for the management of asthma.

Since the previous Cochrane Review on this topic in 2016, debate has continued surrounding a potential role for vitamin D in reducing risk of asthma exacerbation and improving asthma control. We therefore conducted an updated meta-analysis to include data from new trials completed since this date. To evaluate the effectiveness and safety of administration of vitamin D or its hydroxylated metabolites in reducing the risk of severe asthma exacerbations (defined as those requiring treatment with systemic corticosteroids) and improving asthma symptom control. We searched the Cochrane Airways Group Trial Register and reference lists of articles. We contacted the authors of studies in order to identify additional trials. Date of last search 8 September 2022. We included double-blind, randomised, placebo-controlled trials of vitamin D in children and adults with asthma evaluating exacerbation risk or asthma symptom control, or both. Four review authors independently applied study inclusion criteria, extracted the data, and assessed risk of bias. We obtained missing data from the authors where possible. We reported results with 95% confidence intervals (CIs). The primary outcome was the incidence of severe asthma exacerbations requiring treatment with systemic corticosteroids. Secondary outcomes included the incidence of asthma exacerbations precipitating an emergency department visit or requiring hospital admission, or both, end-study childhood Asthma Control Test (cACT) or Asthma Control Test (ACT) scores, and end-study % predicted forced expiratory volume in one second (FEV1). We performed subgroup analyses to determine whether the effect of vitamin D on risk of asthma exacerbation was modified by baseline vitamin D status, vitamin D dose, frequency of dosing regimen, form of vitamin D given, and age of participants. We included 20 studies in this review 15 trials involving a total of 1155 children and five trials involving a total of 1070 adults contributed data to analyses. Participant ages ranged from 1 to 84 years, with two trials providing data specific to participants under five years (n 69) and eight trials providing data specific to participants aged 5 to 16 (n 766). Across the trials, 1245 participants were male and 1229 were female, with two studies not reporting sex distribution. Fifteen trials contributed to the primary outcome analysis of exacerbations requiring systemic corticosteroids. The duration of trials ranged from three to 40 months all but two investigated effects of administering cholecalciferol (vitamin D3). As in the previous Cochrane Review, the majority of participants had mild to moderate asthma, and profound vitamin D deficiency (25-hydroxyvitamin D (25(OH)D) < 25 nmolL) at baseline was rare. Administration of vitamin D or its hydroxylated metabolites did not reduce or increase the proportion of participants experiencing one or more asthma exacerbations treated with systemic corticosteroids (odds ratio (OR) 1.04, 95% CI 0.81 to 1.34 I In contrast to findings of our previous Cochrane Review on this topic, this updated review does not find evidence to support a role for vitamin D supplementation or its hydroxylated metabolites to reduce risk of asthma exacerbations or improve asthma control. Participants with severe asthma and those with baseline 25(OH)D concentrations < 25 nmolL were poorly represented, so further research is warranted here. A single study investigating effects of calcidiol yielded positive results, so further studies investigating effects of this metabolite are needed. Desde la revisión Cochrane anterior sobre este tema en 2016, ha continuado el debate en torno a una posible función de la vitamina D en la reducción del riesgo de exacerbación del asma y la mejora de su control. Por lo tanto, se realizó un metanálisis actualizado para incluir los datos de los nuevos ensayos completados desde esta fecha. Evaluar la eficacia y seguridad de la administración de vitamina D o sus metabolitos hidroxilados para reducir el riesgo de exacerbaciones graves del asma (definidas como aquellas que requieren tratamiento con corticosteroides sistémicos) y mejorar el control de sus síntomas. MÉTODOS DE BÚSQUEDA Se buscó en el registro de ensayos del Grupo Cochrane de Vías respiratorias (Cochrane Airways Group) y en las listas de referencias de los artículos. Se estableció contacto con los autores de los estudios para identificar ensayos adicionales. Fecha de la última búsqueda 8 de septiembre de 2022. CRITERIOS DE SELECCIÓN Se incluyeron los ensayos doble ciego, aleatorizados, controlados con placebo de vitamina D en niños y adultos con asma que evaluaron el riesgo de exacerbación o el control de los síntomas del asma, o ambos. OBTENCIÓN Y ANÁLISIS DE LOS DATOS Cuatro autores de la revisión aplicaron de forma independiente los criterios de inclusión de los estudios, extrajeron los datos y evaluaron el riesgo de sesgo. Cuando fue posible, se obtuvieron los datos faltantes a través de los autores de los estudios. Los resultados se informaron con intervalos de confianza (IC) del 95%. El desenlace principal fue la incidencia de exacerbaciones graves del asma que requirieron tratamiento con corticosteroides sistémicos. Los desenlaces secundarios incluyeron la incidencia de exacerbaciones del asma que precipitaron acudir al servicio de urgencias o requirieron ingreso hospitalario, o ambas, las puntuaciones de la childhood Asthma Control Test (cACT) o la Asthma Control Test (ACT) al final del estudio, y el % previsto de volumen espiratorio forzado en un segundo (VEF1) al final del estudio. Se realizaron análisis de subgrupos para determinar si el efecto de la vitamina D sobre el riesgo de exacerbación del asma se veía modificado por el estado inicial de vitamina D, la dosis de vitamina D, la frecuencia de la posología, la formulación de la vitamina D administrada y la edad de los participantes. En esta revisión se incluyeron 20 estudios 15 ensayos con un total de 1155 niños y cinco ensayos con un total de 1070 adultos aportaron datos para los análisis. Las edades de los participantes variaron entre 1 y 84 años, con dos ensayos que proporcionaron datos específicos de participantes menores de 5 años (n 69) y ocho ensayos que proporcionaron datos específicos de participantes de 5 a 16 años (n 766). En todos los ensayos, 1245 participantes eran hombres y 1229 mujeres, y dos estudios no informaron acerca de la distribución por sexos. Quince ensayos contribuyeron al análisis del desenlace principal exacerbaciones que requirieron corticosteroides sistémicos. La duración de los ensayos fue de entre 3 y 40 meses todos menos dos investigaron los efectos de la administración de colecalciferol (vitamina D3). Al igual que en la revisión Cochrane anterior, la mayoría de los participantes presentaban asma de leve a moderada y la deficiencia importante de vitamina D (25‐hidroxivitamina D 25(OH)D < 25 nmoll) al inicio del estudio fue poco frecuente. La administración de vitamina D o sus metabolitos hidroxilados no redujo ni aumentó la proporción de participantes que presentaron una o más exacerbaciones del asma tratada con corticosteroides sistémicos (odds ratio OR 1,04 IC del 95% 0,81 a 1,34 I En contraposición con los hallazgos de la revisión Cochrane anterior sobre este tema, esta revisión actualizada no encuentra evidencia que respalde una función de los suplementos de vitamina D o sus metabolitos hidroxilados en la reducción del riesgo de exacerbaciones del asma o la mejoría del control del asma. Los participantes con asma grave y aquellos con concentraciones iniciales de 25(OH)D < 25 nmoll estuvieron escasamente representados, por lo que se justifica la realización de más estudios de investigación. Un único estudio que investigó los efectos del calcidiol proporcionó resultados positivos, por lo que se necesitan más estudios que investiguen los efectos de este metabolito.

Enrollment and retention of female sex workers in HIV care in health facilities in Mbarara city.

Sex work is a global driver of the HIV epidemic, and the risk of acquiring HIV is 13 times higher for female sex workers (FSWs) compared to the general population. The enrollment and retention of FSWs in HIV care is a challenge and has been a major contributing factor to increased new HIV infections. We conducted a qualitative study among 30 FSWs and 21 healthcare workers (HCWs) working in antiretroviral therapy (ART) clinics at the selected three primary health facilities in Mbarara City, Southwestern Uganda. The study participants were enrolled by both purposive and snowball sampling techniques. We obtained informed consent from all the participants, and data were collected using in-depth interviews and thematically analyzed. Three themes emerged as facilitators toward enrollment and retention of FSWs into HIV care, namely, (1) good health living, (2) receptive HCWs and availability of health services, and (3) community outreach services and peer support. The barriers are summarized into four major themes (1) stigma, community discrimination, and beliefs (2) social obstacles (3) adverse effects of ART and (4) inadequate services at the health facilities. FSWs are challenged by unsupportive environments and communities where they live and work, which hinders their enrollment and retention in HIV care. Creating awareness of the utilization of HIV care services and extending such services to hotspot communities could enhance the response of HIV-positive FSWs to ART.

Quality of life, social support, coping strategies, and their association with psychological morbidity among people living with HIV.

Enhancement of quality of life and social support havebecome important therapeutic goals among people living with HIV. However, research from developing countries is sparse in this area. Index study was aimed to assess association of social support, coping, and quality of life with psychological morbidity among people living with HIV. In this cross-sectional study, 100 people with HIV were recruited through purposive sampling who were not receiving antiretroviral therapy. To assess social support, coping, and quality of life social support questionnaire, coping strategy check list and World Health Organization quality of life-HIV BREF were administered, respectively. Quality of life domain scores fell in the moderate category and spirituality, religion, and personal belief domain had maximum score. Educated, married, employed, and male subjects reported better quality of life. Females reported greater use of internalization and emotional outlet coping strategies. Low social support, lower quality of life (in all domains and total score), and greater use of internalization coping strategy were significantly associated with psychiatric morbidity. Internalization coping, low social support, and lower quality of life were associated with greater psychiatric morbidity. Therefore, to improve their mental health and overall course of HIV, multipronged interventions should be implemented for promoting the adaptive coping, social support and quality of life.

Performance of Xpert MTBRIF and sputum microscopy compared to sputum culture for diagnosis of tuberculosis in seven hospitals in Indonesia.

Tuberculosis (TB) is a major public health concern in Indonesia, where the incidence was 301 cases per 100,000 inhabitants in 2020 and the prevalence of multi-drug resistant (MDR) TB is increasing. Diagnostic testing approaches vary across Indonesia due to resource limitations. Acid-fast bacilli (AFB) smear is widely used, though Xpert MTBRIF has been the preferred assay for detecting TB and rifampicin resistance since 2012 due to higher sensitivity and ability to rapidly identify rifampicin resistance. However, <1,000 Xpert instruments were available in Indonesia as of 2020 and the Xpert supply chain has suffered interruptions. We compared the performance of Xpert MTBRIF and AFB smear to facilitate optimization of TB case identification. We analyzed baseline data from a cohort study of adults with pulmonary TB conducted at seven hospitals across Indonesia. We evaluated sensitivity and specificity of AFB smear and Xpert MTBRIF using Sensitivity of AFB smear was significantly lower than Xpert MTBRIF (86.2 vs. 97.4%, Additional evaluation using sputa from primary and secondary Indonesian health centers will increase the generalizability of the assessment of AFB smear and Xpert MTBRIF performance, and better inform health policy. httpsclinicaltrials.gov, identifier NCT027 58236.

Joint replacement and human immunodeficiency virus.

The incidence of human immunodeficiency virus (HIV)-infected cases that need total joint replacement (TJR) is generally rising. On the other hand, modern management of HIV-infected cases has enabled them to achieve longevity while increasing the need for arthroplasty procedures due to the augmented dege-nerative joint disease and fragility fractures, and the risk of osteonecrosis. Although initial investigations on joint replacement in HIV-infected cases showed a high risk of complications, the recent ones reported acceptable outcomes. It is a matter of debate whether HIV-infected cases are at advanced risk for adverse TJR consequences however, the weak immune profile has been associated with an increased probability of complications. Likewise, surgeons and physicians should be aware of the complication rate after TJR in HIV-infected cases and include an honest discussion of the probable unwelcoming complication with their patients contemplating TJR. Therefore, a fundamental review and understanding of the interaction of HIV and arthroplasty are critical.

Case Series of HIV-Associated Oral Lesions Among Antiretroviral-Naive Patients During the COVID-19 Pandemic.

The coronavirus disease 2019 (COVID-19) pandemic has a serious impact on HIV-infected individuals due to limited access to treatment services. This report aimed to describe four cases of oral lesions in HIV-infected antiretroviral-naive patients found during the COVID-19 pandemic. Four patients, males, with an age ranged from 29 to 53 years, came to Oral Medicine Department with chief complaints of lesions on their mouth. They had postponed their visit to healthcare services due to limited access during pandemic. Three patients had just been diagnosed with HIV and had not yet received anti-retrovirus, while 1 patient had not yet been detected with HIV. From the clinical examination and laboratory findings, we diagnosed the lesions with mucous patches, chronic atrophic candidiasis, angular cheilitis, necrotizing ulcerative gingivitis, linear gingival erythema, cytomegalovirus-associated ulcers, and oral hairy leukoplakia. We gave chlorhexidine gluconate 0.2% mouthwash for mucous patches, nystatin oral suspension for chronic atrophic candidiasis, miconazole cream 2% for angular cheilitis, debridement with hydrogen peroxide 1.5% and rinsed with normal saline for necrotizing ulcerative gingivitis, and diphenhydramine hydrochloride and 0.2% chlorhexidine gluconate for CMV ulcers. All patients showed good clinical improvement after the treatments. Oral lesions are still commonly found in HIV-infected patients during COVID-19 pandemic. Dentists remain to have a crucial role in the early diagnosis and treatment of HIV-associated oral lesions during COVID-19 pandemic that will have an impact on HIV treatments, also in implementing the Bali Declaration on oral health in HIVAIDS 2019 to support UNAIDS goal to end AIDS by 2030.

The Impact of the COVID-19 Pandemic on HIV-Positive Men Who Have Sex With Men (Dis)connection to Social, Sexual, and Health Networks.

The COVID-19 pandemic has disproportionately affected HIV-positive cisgender men who have sex with men (MSM). Between May and June in 2020, we conducted one-on-one semi-structured qualitative interviews with 20 HIV-positive MSM aiming to describe their (dis)connection to social, sexual, and health networks during the COVID-19 pandemic. All participants relied on social support networks to manage pandemic-based distress, using computer-mediated communication as well as physical proximity. To connect to sexual networks, this sample described adaptations to their partner selection strategies, such as enumerating harm reduction approaches. To connect to health networks, participants depended on reassuring providers, resourceful case managers, telehealth, and streamlined access to their antiretroviral therapy (ART) medications. Nonetheless, stay-at-home recommendations reduced community connection, sexual activity, and healthcare access for many participants, and perceptions of these losses were shaped by psychosocial burdens (e.g., loneliness), structural burdens (e.g., environmental barriers, financial difficulties), and health-protective factors (e.g., hopeful outlook, adherence to a regular routine). The COVID-19 pandemic appears to have exacerbated health-related issues for HIV-positive MSM. Given the ongoing COVID-19 mutations, community-based organizations, clinicians, and researchers might use these findings to modify HIV prevention and intervention efforts.

Roles of Social Capital in the Association Between Internalized Homophobia and Condomless Sex Among Men Who Have Sex With Men in Southwest China A Four-Way Decomposition.

Association of IFN-γ 874 AT SNP and hypermethylation of the -53 CpG site with tuberculosis susceptibility.

Tuberculosis (TB) is now the 2nd leading infectious killer after COVID-19 and the 13th leading cause of death worldwide. Moreover, TB is a lethal combination for HIV-patients. Th1 responses and particularly IFN-γ are crucial for immune protection against Mycobacterium tuberculosis infection. Many gene variants for IFNG that confer susceptibility to TB have been described in multiple ethnic populations. Likewise, some epigenetic modifications have been evaluated, being CpG methylation the major epigenetic mark that makes chromatin inaccessible to transcription factors, thus avoiding the initiation of IFNG transcription. We evaluated both genetic and epigenetic changes involved in IFN-γ production and TB susceptibility in Argentine population. Amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) was performed for the IFN-γ 874 AT polymorphism (rs2430561) genotyping in 199 healthy donors (HD) and 173 tuberculosis (TB) patients. IFN-γ levels from M. tuberculosis-stimulated PBMCs were measured by ELISA. The methylation status at the -53 CpG site of the IFNG promoter in individuals with latent infection (LTBI), TB and HD was determine by pyrosequencing. Using a case-control study, we found that A allele and, consequently, AA genotype were overrepresented in patients with active disease. Moreover, HD carrying T allele (AT or TT genotype) evidenced an augmented IFN-γ secretion compared to TB patients. Codominance was the genetic model that best fits our results according to the Akaike information criterion (AIC). In addition, increased methylation levels at the -53 CpG site in the IFN-γ promoter were observed in whole blood of patients with active TB compared to LTBI individuals. IFN-γ is regulated by genetic variants and epigenetic modifications during TB. Besides, AA genotype of the rs2430561 single nucleotide polymorphism could be considered as a potential TB susceptibility genetic biomarker in Argentina and the methylation of the -53 CpG site could result in a useful predictor of TB reactivation.

Bowens disease on two different unrelated anatomical sites (genitals and nail) in succession in an immunocompromised patient.

Bowens disease (BD) is a premalignant condition. Its exact etiology is unknown but chronic arsenic and sun exposure, and human papillomavirus infection is known predisposing factors. Pigmented lesions of BD represent 1.7%-5.5% of all BD cases. BD in the nail unit is challenging due to its varied clinical presentations such as fissure, ulceration, warty lesion, paronychia, onychocryptosis, and nail dystrophy. We present the case of a 43-year-old married, immunocompromised male (HIV), with a CD 4 count of 478, on tenofovir, atazanavir boosted with ritonavir regimen, known diabetic presented with multiple asymptomatic discrete, rounded, hyperpigmented verrucous papules on both surfaces of shaft of penis and scrotum and a single, 4 cm × 3 cm, irregular, smooth surfaced, hyperpigmented plaque, on the base of the penis extending to the upper part of the scrotum of 1-year duration with history of multiple unprotected sexual exposures with unknown female partners. Regional lymphadenopathy and systemic complaints were absent. Biopsy from hyperpigmented verrucous papule and hyperpigmented plaque was consistent with verruca vulgaris and pigmented Bowens disease, respectively. The patient was lost to follow-up. Ten months later, he presented with longitudinal melanonychia with a subungual hyperpigmented mass protruding beyond the distal nail margin near the lateral nail fold of the right middle finger nail with an absent Hutchinsons sign. Longitudinal excisional biopsy of nail lesion was consistent with BD. He was started on 5-fluorouracil 5% for BD of genitals and podophyllin application for verruca vulgaris with remarkable improvement in both the lesions and there is no recurrence of nail lesion after 9 months of excision.

Understanding drug resistance patterns across different classes of antiretrovirals used in HIV-1-infected treatment-Naïve and experienced patients in Mumbai, India.

The aim of this study is to find out the proportion of treatment-naïve (Tn) and treatment-experienced (Te) patients experiencing HIV drug resistance (DR) to different classes of antiretrovirals (ARVs) being used for HIV treatment and their in class DR correlation. A cross-sectional study was done on 109 HIV patients enrolled at a private hospital in Thane, India, from 2014 to 2019. All patients were tested for CD4 count, viral load, and resistance to ARVs. Sixty-six patients were Tn and 43 patients were Te. Among Tn and Te patients, the percentage of high-level resistance (HLR) for nonnucleoside reverse transcriptase inhibitors (NNRTI) was 4.55% and 37.8%, respectively, for nucleoside reverse transcriptase inhibitors (NRTI) was 0.43% and 36.4%, respectively. No HLR was observed for protease inhibitors (PIs) among Tn patients, while Te patients showed 2.62% HLR. Tn and Te patients showed high susceptibility for Darunavir (98.48% and 95.34%, respectively) followed by Atazanavir and Lopinavir (96.96%, each and 90.69%, each). Tn patients showed HLR for Lamivudine and Emtricitabine (1.52%, each). Integrase Strand Transfer Inhibitors were susceptible (100%) in both Tn and Te patients. A positive correlation was observed for within class across ARVs. An increased incidence of HLR was observed for NNRTI as compared to NRTI while PIs and integrase strand transfer inhibitors (INSTIs) demonstrated no HLR in either group of patients. When selecting a regimen for Tn patients consisting of NRTIs NNRTIs genotypic DR test is essential. While with PIs or INSTIs its optional. Among Te patients, DR testing is recommended for all classes of drugs.

Syphilis in the era of re-emergence A 6-year retrospective study from a tertiary care center in South India.

During the last several years, we have observed a rise in the number of patients with syphilis in our center. To find out the trends in the presentation of syphilis to our clinic over a 6-year period and to analyze the clinicoepidemiological features of those patients. A retrospective chart review. We analyzed the case records of all cases of syphilis registered in our sexually transmitted infection (STI) clinic from October 1, 2012, to September 30, 2018. Syphilis was diagnosed based on clinical or serological evidence. We also evaluated these patients for any concomitant STI, including hepatitis B, hepatitis C, and HIV. The data were analyzed using SPSS software (version 20). Chi-square test was done for comparing categorical data, and During the study period, 215 patients with STI attended our clinic. Of these, 66 (31%) patients had acquired syphilis. Among them, 3 (4.5%) had primary syphilis, 23 (34.8%) had secondary syphilis, and 40 (60.6%) had latent syphilis. Fifteen (22.7%) patients had concomitant HIV infection. A statistically significant rise in the number of cases of syphilis compared with other STIs was noted in the latter half of the study period ( We observed a marked increase in the number of cases of syphilis during the latter half of the study period. Primary and secondary syphilis were more frequent among MSM, suggesting a need to strengthen targeted intervention programs among them. More rigorous antenatal screening is necessary to prevent congenital syphilis.

Disseminated histoplasmosis as a presenting manifestation in an HIV patient - A case report from South India.

Histoplasmosis has heterogenous clinical presentation ranging from mild and self-limiting respiratory disease to disseminated forms with high mortality. In progressive disseminated histoplasmosis (PDH), patient presents with fever, lymphadenopathy, hepatosplenomegaly, adrenal enlargement, hemophagocytic lymphohistiocytosis and non-specific mucocutaneous lesions, usually in late stage of HIV. Cutaneous involvement is upto 25% in PDH which are papules, plaques, nodules and ulcers. Forty-two year old male, recently diagnosed as HIV positive presented with complaints of multiple painful ulcerated lesions over face, neck, tongue, arms, trunk genitalia. Skin Biopsy was suggestive of histoplasmosis. Patient showed excellent response with amphotericin B and itraconazole. Since histoplasmosis is relatively uncommon, there should be a high-index of suspicion when an HIV patient presents with disseminated skin lesions.

Study of clinical profile and outcomes in progressive multifocal leukoencephalopathy in acquired immunodeficiency syndrome patients in the highly active antiretroviral therapy era - An observational study.

Progressive multifocal leukoencephalopathy (PML) is a viral infection affecting the central nervous system (CNS) seen mostly in advanced human immunodeficiency virus (HIV) infection. There is limited data on the epidemiology and disease course of these patients from India. This study was aimed to determine the frequency of PML in patients with HIVacquired immunodeficiency syndrome (AIDS) and the clinical presentation and prognosis of these patients. The study was conducted at a tertiary care HIV center in New Delhi. Data of 765 patients from our anti-retroviral therapy (ART) clinic during a span of 4 years were retrospectively analyzed and reviewed. The diagnosis was based on the clinical and radiological picture and exclusion of other differential diagnosis by cerebrospinal fluid and serological studies. Of 765 patients with HIVAIDS, 12 (1.56%) were diagnosed with PML on the basis of consistent clinical and radiological features after ruling out other differential diagnosis. PML was the initial presentation of HIV infection in 8 (55.5%) patients. 11 (89%) patients had CD4 count <200μl. Insidious onset focal limb weakness (50%) and dysarthria (50%) were common symptoms. Magnetic resonance imaging of the brain revealed characteristic white matter lesions in all the patients. The estimated median survival was 40 months (95% confidence interval, 23.88-53.19 months). Our results show that PML is associated with high morbidity despite the institution of highly active ART (HAART), but mortality has significantly declined if ART is started early. Key to good response is early diagnosis and HAART.

Prozone phenomenon in secondary syphilis with HIV co-infection Two cases.

Prozone phenomenon is defined as a false-negative response resulting from higher antibody titer which interferes with formation of antigen-antibody lattice, necessary to visualize a positive flocculation test. The prozone effect can be observed in syphilis testing with cases of very high antibody titers, such as secondary syphilis, or with human immunodeficiency virus (HIV) co-infection. We report two cases of prozone phenomenon in secondary syphilis with HIV co-infection who initially tested nonreactive for rapid plasma reagin test but tested positive with further higher dilution.

Serum galactomannan in histoplasmosis in HIV.

Histoplasmosis is an opportunistic infection (OI) in HIV infected patients. The Diagnosis is challenging due to lack of testing facilities. Hereby we report a young male who presented with fever rash, was diagnosed with HIV and disseminated histoplasmosis. The timely management with antifungals was started after the of positive serum galactomannan report in the background of appropriate clinical setting.

Emerging trends in sexually transmitted diseases in a tertiary care center in Davangere, Karnataka A five year study.

Sexually transmitted diseases (STDs) are a public health challenge, and the epidemiological profile is variable by geographical region and distinct from that of other diseases. Accurate knowledge of emerging disease trends is crucial for formulating effective control strategies. The aim and objective of this study were to identify the changing scenario and emerging trends of STDs in Davangere, Karnataka, by evaluating patients attending a tertiary care center. A tertiary care-based retrospective study was conducted by analyzing the clinical records of the attendees presenting to the STD clinic at Chigateri General Hospital affiliated to JJM Medical College in Davangere, Karnataka, for a period of 5 years from January 2015 to December 2019. The collected data were analyzed and statistically compared with other studies. Out of the 614 patients studied, the male-to-female ratio was 21, with 30-39 age groups being most affected. Eighty-eight percent of patients were married, with 36.64% giving a history of extramarital contact. Homosexual and bisexual contacts were observed to be 5.21% and 0.65%, respectively. Viral STDs affected nearly half of the patients (49.51%), followed by fungal (28.88%), bacterial (22.63%), and others (3.1%). The most common STD observed was herpes genitalis as seen in 101 (24.48%) patients, followed by candidal balanoposthitis (17.1%). Thirty-three (5.7%) patients were diagnosed with more than one STD. Of these patients, 13 were seropositive for HIV, resulting in a prevalence of 2.12%. The epidemiological profile of STDs is ever changing, and this study found an increase in viral and fungal STDs and downward trend of bacterial STDs comparable to that of studies from other regions.

Adult-onset Recurrent Respiratory Papillomatosis at a South African Referral Hospital.

The aim of this study was to describe the clinical presentation and outcome of patients with adult-onset recurrent respiratory papillomatosis (AoRRP) in a developing country with the challenges of poor health care access and high prevalence of HIV infection. This was a retrospective study of patients diagnosed with AoRRP who were managed in the Department of Otorhinolaryngology at Universitas Academic Hospital in Bloemfontein, South Africa over a 10 year period. There were a total of 41 patients, of which 26 (63.4%) were male. The age at diagnosis ranged between 16.4 and 67.4 years (mean 39.4 ± 14.9 years). All patients presented with a hoarse voice, with three patients also having upper airway obstruction. Eight (19.5%) patients were HIV positive. HPV typing was performed in 29 patients 14 had HPV11 disease, 12 had HPV6 disease and in 3 patients HPV DNA was not detected. There was no significant difference in initial presentation or outcome between HIV negative and HIV positive patients, or between patients with HPV6 and HPV11 disease. Two patients had malignant transformation of the papillomas. In both these patients, HPV was not detected in the papillomas. HPV type and HIV infection did not appear to influence the clinical presentation and outcome in patients with AoRRP. There is a risk of malignant transformation in patients in which HPV is not detected in the papillomas.