bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brief Report: No Evidence for an Association Between Statin Use and Lower Biomarkers of HIV Persistence or Immune Activation/Inflammation During Effective ART
Authors: Bedimo Roger J. , Mar Hanna , Bosch Ronald J. , Drechsler Henning , Cyktor Joshua C. , Macatangay Barnard J. C. , Lalama Christina , Rinaldo Charles , Collier Ann , Godfrey Catherine , Hogg Evelyn , Hensel Christopher , Eron Joseph J. , Mcmahon Deborah K. , Mellors John W. , Tebas Pablo , Gandhi Rajesh T. ,   A5321 Study Team
Published: July 2019

Background:
Statins exert pleiotropic anti-inflammatory and immune-modulatory effects, which might translate into antiviral activity. We evaluated whether reported current statin exposure is associated with lower levels of markers of HIV persistence and immune activation/inflammation.

Methods:
We compared levels of markers of HIV viral persistence [cell-associated HIV RNA (CA-RNA), CA-DNA, and single copy assay plasma HIV RNA] and immune activation/inflammation (IL-6, IP-10, neopterin, sCD14, sCD163, and TNF-alpha) between statin users and nonusers among participants of ACTG A5321 who initiated antiretroviral therapy (ART) during chronic infection and maintained virologic suppression (HIV-1 RNA levels ≤50 copies/mL) for ≥3 years.

Results:
A total of 303 participants were analyzed. Median time on the current statin was 2.9 years (1.2–5.1). There were no differences between statin users and nonusers in levels of CA-DNA (median 650 vs. 540 copies/106 CD4+ T cells; P = 0.58), CA-RNA (53 vs. 37 copies/106 CD4+ T cells; P = 0.12), or single copy assay (0.4 vs. 0.4 copies/mL; P = 0.45). Similarly, there were no significant differences between statin users and nonusers in markers of inflammation/activation, except for IP-10 (137 vs. 118 pg/mL; P = 0.028). Findings were unchanged after adjustment for factors including pre-ART CD4 and HIV RNA, and years on ART.

Conclusions:
In this cohort of persons on long-term suppressive ART, current statin use was not associated with lower levels of HIV persistence or immune activation/inflammation. These results do not support a major role for statins in reducing HIV persistence, although an early transient effect cannot be excluded. Prospective, randomized studies are needed to confirm these findings.
Transition Pathways Out of Pediatric Care and Associated HIV Outcomes for Adolescents Living With HIV in South Africa
Authors: Haghighat Roxanna , Toska Elona , Cluver Lucie , Gulaid Laurie , Mark Daniella , Bains Anurita 
Published: July 2019

Background:
Research on adolescent transitions out of pediatric HIV care has focused on high-income countries, with limited understanding of transitions in sub-Saharan Africa's public health sector.

Methods:
Patient file data were extracted through December 2017 for all 10- to 19-year olds ever initiated on antiretroviral therapy in a health district of the Eastern Cape, South Africa (n = 951). Pathways in HIV care were identified by tracing movements across facility care types and levels. Associations between pathways and viral failure, mortality, loss to follow-up, and viral load change were tested in sequential multivariable regressions. Analyses controlled for sociodemographic and treatment-related variables. Thematic analyses of semistructured health care provider interviews identified transition support at included facilities.

Results:
Only 57.8% of adolescents had initiated antiretroviral therapy in pediatric care, and 20.4% of the total cohort had transitioned out of pediatric HIV care. Among the 42.2% who had initiated in nonpediatric care, 93.8% remained exclusively in nonpediatric care. Median age at first transition was 14 years. Two main pathways were identified: classical transition to adult HIV care (43.3%) and down referral transition to primary health care clinics (56.7%). Across pathways, 27.3% experienced cyclical transition or repeated movement between pediatric and nonpediatric care. Independent of covariates, adolescents with down referral transition were less likely to demonstrate viral failure (adjusted odds ratio, 0.21; 95% confidence interval: 0.10 to 0.42; P < 0.001). Mortality and loss to follow-up were not associated with either pathway. Median posttransition viral load change was not clinically significant (median, 0.00; interquartile range: 0.00–0.35) or associated with transition pathways. Health care providers described informal “protocols” for mitigating risk of negative posttransition HIV outcomes.

Conclusions:
This study proposes a contextually relevant model for transitions out of pediatric HIV care in South Africa. Feasible, scalable “protocols” may mitigate risk of worsening posttransition HIV outcomes.
Clinical and Virological Outcomes of TB/HIV Coinfected Patients Treated With Dolutegravir-Based HIV Antiretroviral Regimens: Programmatic Experience From Botswana
Authors: Modongo Chawangwa , Wang Qiao , Dima Mbatshi , Matsiri Ogopotse , Kgwaadira Botshelo , Rankgoane-Pono Goabaone , Shin Sanghyuk S. , Zetola Nicola M. 
Published: July 2019

Background:
Dolutegravir (DTG) has recently been recommended as a preferred first-line regimen for the treatment of new and treatment-experienced HIV-infected patients. However, potential drug interactions between DTG and rifampicin remain a clinical and public health concern.

Methods:
We analyzed HIV and Tuberculosis (TB) treatment outcomes of HIV-infected patients concomitantly receiving rifampicin- and DTG-based regimens under programmatic conditions in Botswana. The outcomes of interest were successful TB treatment and viral load suppression. We used multivariable logistic models to determine predictors for each outcome of interest.

Results:
A total of 1225 patients were included in the analysis to evaluate predictors of successful TB outcome. Among patients on DTG and non-DTG regimens, 90.9% and 88.3% achieved favorable TB treatment outcomes, respectively. Of those who received DTG-based regimen; 44% received once-daily dosing and 53% twice-daily dosing. We found that DTG was associated with favorable TB treatment outcome (adjusted odds ratio = 1.56; 95% confidence interval = 1.06 to 2.31), after adjusting for age, gender, and CD4 cell counts. High rates of viral load suppression were found across all antiretroviral therapy (ART) regimen categories (>92% for all). We did not find an independent association between DTG and viral suppression after adjustment of other covariates.

Conclusions:
The use of DTG-based ART regimens in patients coinfected with TB and HIV lead to favorable TB and HIV treatment outcomes, comparable to those achieved with alternative ART regimens. Our results provide reassurance to TB and HIV programs about the overall programmatic concomitant use of these first-line treatment regimens for the management of HIV and TB coinfected patients.
Short- and Long-Term Pharmacologic Measures of HIV Pre-exposure Prophylaxis Use Among High-Risk Men Who Have Sex With Men in HPTN 067/ADAPT
Authors: Velloza Jennifer , Bacchetti Peter , Hendrix Craig W. , Murnane Pamela , Hughes James P. , Li Maoji , Curlin Marcel E. , Holtz Timothy H. , Mannheimer Sharon , Marzinke Mark A. , Amico K. Rivet , Liu Albert , Piwowar-Manning Estelle , Eshleman Susan H. , Dye Bonnie J. , Gandhi Monica , Grant Robert M. ,   HPTN 067/ADAPT Study Team
Published: July 2019

Background:
The effectiveness of oral emtricitabine (FTC)/tenofovir (TFV) disoproxil fumarate–based HIV pre-exposure prophylaxis (PrEP) depends on adherence. Pharmacologic measures help interpret patterns and predictors of PrEP adherence.

Setting:
We analyzed data from the subsample of men who have sex with men enrolled in HPTN 067/ADAPT in Bangkok, Thailand, and Harlem, NY, U.S.

Methods:
After a 5-week directly observed therapy period, participants were randomized to daily, time-driven, or event-driven PrEP. Follow-up occurred at weeks 4, 12, and 24 after randomization. Plasma and hair FTC/TFV levels indicated short- and long-term PrEP use, respectively. Electronic pill bottle data (Wisepill) were collected weekly. Pearson correlation coefficients between PrEP use measures were calculated; linear mixed models assessed predictors of plasma and hair drug concentrations.

Results:
Among 350 participants (median age: 31 years, interquartile range: 25–38), 49.7% were from Harlem, half had less than college education, and 21% reported heavy alcohol use. In multivariable models, being enrolled in Harlem, being in non–daily arms, and having less than college education were associated with lower hair FTC/TFV concentrations; heavy alcohol use was associated with higher concentrations. Similar results were found for plasma concentrations by site and arm, but older age and greater number of sex partners were associated with higher concentrations. Hair and plasma FTC/TFV concentrations were moderately correlated with Wisepill data (r ≥ 0.29) across visits.

Conclusions:
In HPTN067, plasma, hair, and Wisepill data correlated with one another and served as complementary adherence measures. Site, arm, education, age, alcohol, and sexual behavior influenced patterns of adherence.
Polypharmacy, Hazardous Alcohol and Illicit Substance Use, and Serious Falls Among PLWH and Uninfected Comparators
Authors: Womack Julie A. , Murphy Terrence E. , Rentsch Christopher T. , Tate Janet P. , Bathulapalli Harini , Smith Alexandria C. , Bates Jonathan , Jarad Samah , Gibert Cynthia L. , Rodriguez-Barradas Maria C. , Tien Phyllis C. , Yin Michael T. , Gill Thomas M. , Friedlaender Gary , Brandt Cynthia A. , Justice Amy C. 
Published: July 2019

Background:
Medication classes, polypharmacy, and hazardous alcohol and illicit substance abuse may exhibit stronger associations with serious falls among persons living with HIV (PLWH) than with uninfected comparators. We investigated whether these associations differed by HIV status.

Setting:
Veterans Aging Cohort Study.

Methods:
We used a nested case–control design. Cases (N = 13,530) were those who fell. Falls were identified by external cause of injury codes and a machine-learning algorithm applied to radiology reports. Cases were matched to controls (N = 67,060) by age, race, sex, HIV status, duration of observation, and baseline date. Risk factors included medication classes, count of unique non–antiretroviral therapy (non-ART) medications, and hazardous alcohol and illicit substance use. We used unconditional logistic regression to evaluate associations.

Results:
Among PLWH, benzodiazepines [odds ratio (OR) 1.24; 95% confidence interval (CI) 1.08 to 1.40] and muscle relaxants (OR 1.29; 95% CI: 1.08 to 1.46) were associated with serious falls but not among uninfected (P > 0.05). In both groups, key risk factors included non-ART medications (per 5 medications) (OR 1.20, 95% CI: 1.17 to 1.23), illicit substance use/abuse (OR 1.44; 95% CI: 1.34 to 1.55), hazardous alcohol use (OR 1.30; 95% CI: 1.23 to 1.37), and an opioid prescription (OR 1.35; 95% CI: 1.29 to 1.41).

Conclusion:
Benzodiazepines and muscle relaxants were associated with serious falls among PLWH. Non-ART medication count, hazardous alcohol and illicit substance use, and opioid prescriptions were associated with serious falls in both groups. Prevention of serious falls should focus on reducing specific classes and absolute number of medications and both alcohol and illicit substance use.
Increased Risk of Executive Function and Emotional Behavioral Problems Among Virologically Well-Controlled Perinatally HIV-Infected Adolescents in Thailand and Cambodia
Authors: Kerr Stephen J. , Puthanakit Thanyawee , Malee Kathleen M. , Thongpibul Kulvadee , Ly Penh Sun , Sophonphan Jiratchaya , Suwanlerk Tulathip , Kosalaraksa Pope , Ounchanum Pradthana , Aurpibul Linda , Kanjanavanit Suparat , Ngampiyaskul Chaiwat , Chettra Kea , Robbins Reuben , Paul Robert , Ananworanich Jintanat , Mellins Claude A. ,   on behalf of the PREDICT Resilience Study
Published: July 2019

Background:
Large numbers of perinatally HIV-infected (PHIV) children are aging into adolescence. We examined cognitive and behavioral outcomes in a longitudinal cohort of Asian youth.

Methods:
We followed up 231 PHIV, 125 perinatally HIV-exposed, uninfected (HEU), and 138 HIV-unexposed, uninfected (HUU) adolescents (aged 10 years and older), matched by age/sex, in Thailand and Cambodia for 3 years. Executive function was assessed with Children's Color Trails Tests 1 and 2 (CCTT-1 and -2), the design fluency test, and the verbal fluency test. Working memory (Freedom from Distractibility Index) and processing speed index were assessed using WISC-III. Visual memory was assessed by design memory and design recognition subtests of the Wide Range Assessment of Memory and Learning (WRAML-2) and behavioral problems using the Child Behavior Checklist (CBCL). Generalized estimating equations examined adjusted odds ratios of cognitive impairment (Z-scores ≥2 SD below age-adjusted means of the HUU group) and CBCL T-scores in the borderline-clinical range (T-Scores ≥60) in PHIV and HEU versus HUU youth, adjusting for ethnicity, household income, and caregiver characteristics.

Results:
The median age at enrollment was 13.8 years, with 58% women and 63% Thai participants. PHIV youth had >86% virological suppression and significantly higher impairment rates on CCTT-1 and -2 tests, design fluency test, verbal fluency tests, design memory, and CBCL internalizing and externalizing problems. Results were mostly similar between HEU and HUU groups, apart from higher impairment rates on CCTT-1 and internalizing problems in HEU.

Conclusion:
Asian adolescents with PHIV remain at risk of cognitive and mental health problems despite HIV treatment. Selective risks are observed among HEU youth.
Brief Report: Urine Emtricitabine and Tenofovir Concentrations Provide Markers of Recent Antiretroviral Drug Exposure Among HIV-Negative Men Who Have Sex With Men
Authors: Haaland Richard E. , Martin Amy , Livermont Tamee , Fountain Jeffrey , Dinh Chuong , Holder Angela , Lupo Lindsey D. , Hall LaShonda , Conway-Washington Christopher , Kelley Colleen F. 
Published: July 2019

Background:
Urine provides a minimally invasive specimen that may allow for development of rapid tests to detect antiretroviral drugs and provide opportunities to improve individual adherence. This study sought to determine whether urine could provide a biomarker of adherence for currently approved pre-exposure prophylaxis and HIV treatment regimens.

Methods:
Urine and blood were collected from 34 HIV-negative men who have sex with men aged 18–49 years, enrolled in a clinical trial comparing 2 antiretroviral regimens. Specimens were collected 4 and 24 hours after a single oral dose of tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) (n = 10) or tenofovir alafenamide (TAF)/FTC/cobicistat (COBI)/elvitegravir (EVG) (n = 8), or after 4 and 10 days of daily oral TDF/FTC (n = 9) or TAF/FTC/COBI/EVG (n = 7). Tenofovir (TFV), FTC, and EVG were measured by high-performance liquid chromatography-mass spectrometry.

Results:
Median urine FTC concentrations at 4 and 24 hours were similar between men receiving TDF/FTC (4 hours 147 µg/mL; 24 hours 10 µg/mL) and men receiving TAF/FTC/COBI/EVG (4 hours 333 µg/mL, P = 0.173; 24 hours 13 µg/mL, P = 0.681). Median urine TFV concentrations were lower among men receiving TAF/FTC/COBI/EVG (4 hours 1.2 µg/mL; 24 hours 0.8 µg/mL) compared with men receiving TDF/FTC (4 hours 17 µg/mL, P < 0.001; 24 hours 7 µg/mL, P = 0.001). Urine TFV concentrations remained reduced among men receiving TAF/FTC/COBI/EVG compared with men receiving TDF/FTC after daily dosing. EVG was not consistently measurable in urine.

Conclusions:
High urine FTC and TFV concentrations could provide an indication of adherence to daily oral dosing with TDF or TAF-based regimens used for treatment and prevention.
Brief Report: Relationship Between ABCC4 SNPs and Hepatitis B Virus Suppression During Tenofovir-Containing Antiretroviral Therapy in Patients With HIV/HBV Coinfection
Authors: Archampong Timothy , Ojewale Oluwayemisi , Bears Kristi , Chen Yiqing , Lartey Margaret , Sagoe Kwamena W. , Obo-Akwa Adjoa , Gong Yan , Langaee Taimour , Kwara Awewura 
Published: July 2019

Background:
Incomplete hepatitis B virus (HBV) suppression during antiretroviral therapy (ART) in HIV and HBV coinfected patients is common, but underlying factors are not fully elucidated. We hypothesize that genetic factors that influence nucleoside analog pharmacokinetics will affect HBV treatment response.

Methods:
HIV/HBV coinfected patients on tenofovir disoproxil fumarate/lamivudine (TDF/3TC)-containing ART were enrolled. Selected ABCC4 single nucleotide polymorphisms (SNPs) with known effects on nucleoside pharmacokinetics were genotyped using TaqMan assays. Relationship between ABCC4 SNPs and unsuppressed HBV DNA (HBV DNA ≥20 IU/mL) were examined.

Results:
Of the 50 participants on TDF/3TC-containing ART for a median (range) of 1.5 (1–7.4) years, 20 (40%) had unsuppressed HBV DNA. Participants with unsuppressed compared with those with suppressed HBV DNA were more likely to have negative HBe antibody, lower body mass index, and lower CD4 count at enrollment. Carriers of ABCC4 rs11568695 (G3724A) variant allele were more likely than noncarriers to have unsuppressed HBV (61.1% vs. 29.0%, P = 0.038). Among 36 patients with suppressed HIV RNA (presumed good ART adherence), ABCC4 rs11568695 variant carriers were more likely than noncarriers to have unsuppressed HBV (58.8% vs. 20.0% P = 0.021). Logistic regression analysis that included genetic and nongenetic factors identified ABCC4 rs11568695 variant allele, body mass index, and male sex as predictors of unsuppressed HBV DNA.

Conclusions:
We identified a novel association between ABCC4 rs11568695 SNP and poor HBV treatment response. If confirmed in further studies, ABCC4 genotyping could be used to identify individuals who may need intensified HBV therapy.
Use of Recommended Preventive Health Care Services and Variations in HIV Care Among Women With HIV in the United States, 2013–2014: Opportunities for Expanded Partnerships in Support of Ending the HIV Epidemic
Authors: Short William R. , Sutton Madeline Y. , Luo Qingwei , Frazier Emma L. 
Published: July 2019

Background:
Despite recommendations for preventive health services and routine HIV care for HIV-positive women, limited data are available regarding uptake of recommendations.

Methods:
We used data from the 2013–2014 data cycles of the Medical Monitoring Project. We calculated weighted estimates and used multivariable logistic regression with adjusted prevalence ratios and 95% confidence intervals to examine associations between preventive health screenings, routine HIV care [based on viral load (VL) and CD4 measures as proxies], and sociodemographic factors.

Results:
Of 2766 women, 47.7% were 50 years and older, 61.7% non-Hispanic black, 37.2% had >high school education, 63.3% had been living with HIV for ≥10 years, 68.4% were living ≤the federal poverty level, 67.3% had public health insurance, 93.8% were prescribed antiretroviral therapy, and 66.1% had sustained/durable suppression (12 months). For women aged 18 years and older, cervical cancer, breast cancer, and sexually transmitted infection screenings were documented for 44.3%, 27.6%, and 34.7%, respectively; 26% did not meet 6-month, and 37% did not meet 12-month, VL and CD4 test measure goals. In multivariable analyses, women with no VLs in the past 6 months were less likely to be durably suppressed, and women who did not have ≥3 CD4 or VL tests (past 12 months) were less likely to be living above the poverty level and more likely to have public insurance compared with private health insurance (P < 0.05).

Conclusion:
Receipt of recommended preventive care was suboptimal. Targeted interventions are warranted to help ensure access to comprehensive HIV care and prevention services for women.
Influence of histo blood group antigen expression on susceptibility to enteric viruses and vaccines
Authors: Ramani Sasirekha , Giri Sidhartha 
Published: July 2019

Purpose of review
Gastroenteritis results in substantial morbidity and mortality worldwide, especially in young children in low-and-middle-income settings. Rotavirus and norovirus are the leading causes of viral gastroenteritis. Although introduction of rotavirus vaccines into childhood immunization programmes has reduced disease burden, vaccine effectiveness remains low in developing countries. Norovirus is replacing rotavirus as the most common cause of diarrhea hospitalization in settings where rotavirus vaccines are highly effective. Genetically determined host factors, such as expression of histo blood group antigens (HBGAs) are hypothesized to play key roles in susceptibility to infections and gastroenteritis caused by these virus, as well as influence vaccine take.

Recent findings
Epidemiology studies provide strong support for virus genotype-dependent effects of host HBGA expression, specifically secretor status on susceptibility to rotavirus and norovirus. Secretor-positive persons are significantly more susceptible to gastroenteritis caused by rotavirus P[8] genotype, and to infection with the GII.4 genotype of human norovirus. There is increasing data on the role of secretor status on rotavirus vaccine take but results are currently conflicting. For analyses involving young infants, maternal HBGA status is an important factor to be considered in future studies.

Summary
Genetically determined HBGA expression influences susceptibility to enteric viruses of public health importance.
Fractional-dose yellow fever vaccination: how much more can we do with less?
Authors: Visser Leonardus G. 
Published: July 2019

Purpose of review
Climate change, deforestation, urbanization, and increased population mobility have made the risk of large outbreaks of yellow fever more likely than ever. Yellow fever vaccine production barely meets demands. In this review, we address the causes of the recent yellow fever outbreaks, why fractional dose yellow fever vaccination works, the role of virus neutralizing antibodies in the protection against yellow fever, and the need for revaccination.

Recent findings
Human activities have profoundly changed the epidemiology of yellow fever. The excess of infectious viral particles in routine yellow fever vaccine batches allows for off-label use of fractional dose yellow fever vaccination in response to emergency situations. Two studies have confirmed long-term protection after fractional dose yellow fever vaccination. The need for the presence of virus neutralizing antibodies (VNA) to protect an individual against yellow fever depends on the epidemiological setting. In case of sylvatic transmission, population immunity is irrelevant for individual protection, as mosquitoes are transmitting the virus from infected nonhuman primates to human.

Summary
With the growing connectivity through air travel, countries with high densities of nonimmune populations and of the urban mosquito vector, Aedes aegypti, should ensure that their citizens are properly vaccinated against yellow fever before traveling to a yellow fever endemic country. In the situation of sylvatic transmission, the presence of protective levels of VNA will determine the outcome and may require revaccination at some point in time.