bluuebunny/crossref_metadata_2025 huggingface dataset:
Health literacy, source of information and impact on adherence to therapy in people living with HIV
Authors: Ernst Dorner Thomas , Schulte‐Hermann Kathrin , Zanini Matteo , Leichsenring Birgit , Stefanek Wiltrut
Published: November 2014

Introduction

Adequate information and health literacy (HL) has a high impact on patients understanding on the causes and consequences of many chronic diseases, including HIV, and is a crucial prerequisite to ensure adherence to therapy regimens. Several Austrian patient organizations developed an online survey together with MSD (the so‐called “PAB‐test”) aimed to evaluate how people living with HIV perceive the level of care in Austria.

Materials and Methods

An online survey has been developed to assess HL in people living with HIV and to evaluate the impact of HL on therapy adherence. HL was assessed with seven items regarding the self‐rated comprehension of HIV related information, which showed a high reliability (Cronbach's alpha=0.876). A low health literacy was defined by reaching a score below the median of 20 points in the related indicator.

Results

A total of 303 subjects completed the questionnaire. Women slightly had more often a low HL than men (57.1% vs 44.7%, p=0.335). Heterosexual subjects had more often a low HL compared to homosexual ones (58.3% vs 38.1%, p=0.007). Health literacy slightly increased with age (not significant). An increasing education level correlated with higher HL, (66.7%, 46.2%, and 38.9% of persons showed low HL with primary, secondary and tertiary education, respectively, p=0.037). The number of missed appointments with the HIV physician was significantly higher in the low HL population (30.0% vs 14.4%, p=0.002), which also showed to be more prone to interrupt the therapy without consulting a physician (22.4% vs 9.8%, p=0.006). The low HL population, however, did not report of having forgotten the medication intake more often than the one with high HL (33.1% vs 39.1%, p=0.305). The most important source of information is the treating physician, followed by NGOs/patient organizations and the internet (Figure 1).

Conclusions

There are significant differences in HL between different sub‐groups in the HIV community. Low HL is significantly associated with a higher frequency of missed doctor appointments and interruptions of treatment, but does not impact adherence to therapy (self‐reported). The identified information providers (medical doctors, NGOs/patient organizations) should be encouraged to contribute towards increased HL in HIV patients.
High rates of viral suppression in a cohort of HIV‐positive adults receiving ART in Ethiopian health centers irrespective of concomitant tuberculosis
Authors: Reepalu Anton , Tolera Balcha Taye , Skogmar Sten , Habtamu Jemal Zelalem , Sturegård Erik , Medstrand Patrik , Björkman Per
Published: November 2014

Introduction

Antiretroviral therapy (ART) initiation during treatment for tuberculosis (TB) improves survival in HIV/TB co‐infected patients. Data on ART outcome for HIV/TB co‐infected patients managed in primary health care in low‐income regions is limited. We compared virological suppression rates, mortality and retention in care in HIV‐positive adults receiving care in five Ethiopian health centres with regard to TB co‐infection.

Materials and Methods

HIV‐positive ART‐naïve adults eligible for ART initiation were prospectively recruited from October 2011 until March 2013. At inclusion, all patients submitted sputum for microbiological TB testing (smear microscopy, liquid culture and PCR). Virological suppression rates after six months of ART (VS; viral load <40 and <400 copies/mL) with regard to TB status was the primary outcome. The impact of HIV/TB co‐infection on VS rates was determined by multivariate regression analysis. Mortality and retention in care were analyzed by proportional hazard models.

Results

Among 812 participants (TB 158; non‐TB 654), 678 started ART during the follow‐up period (TB 135; non‐TB 543). Median CD4 cell counts at ART initiation were 161 cells/µL (interquartile range [IQR], 98–243) and 184 (IQR, 118–256) for TB and non‐TB patients, respectively (p=0.05). No difference in retention in care between TB and non‐TB patients was observed during follow‐up; 25 (3.7%) patients died and 17 (2.5%) were lost to follow‐up (p=0.30 and p=0.83, respectively). Overall rates of VS at six months were 72.1% (<40 copies/mL) and 88.7% (<400 copies/mL), with similar results for subjects with and without TB co‐infection (<40 copies/mL: 65/92 (70.7%) vs. 304/420 (72.4%), p=0.74; <400 copies/mL: 77/92 (83.7%) vs. 377/420 (89.8%), p=0.10, respectively). CD4 cell count increase during treatment was 87 (IQR, 26–178) and 103 cells/µL (IQR, 38–173) for TB and non‐TB patients, respectively, with no significant difference between the two groups (p=0.49).

Conclusions

High rates of VS were achieved in adults receiving ART at Ethiopian health centres managed by non‐physician clinicians, with no significant difference with regard to TB co‐infection. These findings demonstrate the feasibility of combined ART and anti‐TB treatment at primary health care level in low‐income countries. This study is registered with clinicaltrial.gov, NCT01433796.
Hepatic safety of RPV/FTC/TDF single tablet regimen in HIV/HCV‐coinfected patients. Preliminary results of the hEPAtic Study
Authors: Neukam Karin , Espinosa Nuria , Merino Dolores , Rivero‐Juárez Antonio , Carrero Ana , José Ríos María , Ruiz‐Morales Josefa , Gómez‐Berrocal Ana , Téllez Francisco , Díaz‐Menéndez Marta , Collado Antonio , Pérez‐Camacho Inés , Delgado‐Fernández Marcial , Vera‐Méndez Francisco , Pineda Juan A
Published: November 2014

Introduction

Although hepatotoxicity related to antiretroviral treatment (ART) has become less frequent, hepatotoxic events, such as transaminase elevations (TE), are still a matter of concern. RPV/FTC/TDF (EPA) is a new single tablet regimen which is widely used in real life practice. Clinical trials showed an adequate profile of liver safety in the sub‐population of HIV/HCV‐coinfected patients receiving rilpivirine. However, the number of individuals included in these analyses is low [1]. The aim of this ongoing study is to evaluate the incidence of TE and total bilirubin elevations (TBE) during the first 48 weeks of EPA‐based therapy in a large population of HIV/HCV‐coinfected subjects outside of clinical trials.

Patients and Methods

This is a retrospective analysis of HIV/HCV‐coinfected subjects who started EPA at the infectious diseases units of 14 centres throughout Spain, included as cases. Subjects who started an ART different to EPA during the study period at the same hospitals were selected as controls. The primary outcome variables were grade 3 or 4 TE and grade 4 TBE.

Results

Of the 191 patients included, 31 (16.2%) subjects were naïve to ART. Eighty‐seven individuals started EPA and the remaining ones were controls. The most common NRTI backbone among the controls was TDF/FTC [59 (56.7%) patients] followed by NRTI‐sparing regimens [24 (23.1%) individuals] and ABC/3TC [17 (16.3%) subjects]. Among controls, 67 (64.4%) started a ritonavir‐boosted protease inhibitor, mainly DRV/r [41 (39.4%) patients] followed by ATV/r [16 (15.4%) subjects]. EFV, ETV and RAL were started in 16 (15.4%), 12 (11.5%) and 13 (12.5%) subjects, respectively. The median (Q1–Q3) follow‐up was 5.79 (3.65–8.61) months for the cases and 11.44 (5.8–12.88) months for the controls. TE was observed in two (2.3%) cases versus five (4.8%) controls (p=0.358), accounting for a density of incidence of 4.32/100 person‐years versus 5.51/100 person‐years [incidence rate difference (95% confidence interval): −1.88 (−9.95–6.2), p=0.354]. All TE were grade 3 and no patient discontinued ART due to TE. None of the cases developed TBE versus four (3.8%) controls, all of them receiving ATV/r.

Conclusions

The frequency of grade 3–4 TE associated with EPA in HIV/HCV‐coinfected patients under real life conditions is very low. In addition, TE in HIV/HCV‐coinfected patients treated with EPA are usually mild and do not lead to treatment discontinuation. TBE was not seen in patients taking EPA. All these data confirm that EPA is safe in this particular subpopulation.
Efficacy and tolerability of telaprevir (TVR)‐based triple therapy in HIV/HCV‐coinfected patients
Authors: De Los Santos Ignacio , Montes Marisa , Sanz‐Moreno Jose , De Miguel Julio , Sanz‐Sanz Jesus , Gaspar Gabriel , Perez‐Caballero Laura
Published: November 2014

Introduction

Clinical trials (CT) on triple therapy against HCV infection in HIV‐infected patients including TVR plus pegylated interferon and ribavirin (PR) have reported considerably higher response rates than with PR alone. This study was aimed to evaluate the efficacy and safety of triple therapy including TVR in HIV/HCV‐coinfected patients in real‐life conditions.

Materials and Methods

HIV/HCV genotype 1 patients seen at four Hospitals in Madrid who received therapy including TVR plus PR for at least two weeks were included. The response was evaluated during treatment, and sustained viral response (SVR) was evaluated 12 and 24 weeks after the end of the treatment.

Results

Fifty‐eight patients have been included; 79% male, median age 48 y.o.; 38% were IL28B rs12979860 genotype CT or TT, 58.6% of patients presented cirrhosis and 24.1% presented fibrosis F3. Infection with genotype 1a was observed in 53.4% of patients. Median baseline HCV‐RNA was 3,282,263 IU/mL (77.5% had >800,000 IU/mL). The most commonly used antiretroviral (ARV) drugs were tenofovir/emtricitabine [36 (62%) patients], etravirine [21 (36%) patients], abacavir/lamivudine [18 (31%) patients], boosted protease inhibitors [16 (27.5%) patients] and raltegravir [12 (20.6%) patients]. Of the 42 (72.4%) patients who had received previous HCV treatment, 13.7% were null responders, 25.8% were partial responders and 31% had relapsed. In an ITT approach, proportions of patients with undetectable HCV RNA were 67.8% (38/56) at TW4, 83.3% (40/48) at TW12, 80% (36/45) at TW24, 79.4% at TW36 (31/39) and 72% (26/36) at TW48. Fifteen (25.8%) patients discontinued HCV therapy [8 (13.8%) because they fulfilled stopping rules, 5 (8.6%) individuals due to adverse events and 2 (3.4%) were lost to follow‐up]. Rash associated with TVR (grade 1) was observed in two cases (3.4%) and all the patients showed anaemia at some point of treatment. In an analysis by ITT in the 31 patients who had a 60 week follow‐up after starting therapy, SVR‐12 was observed in 21 (67.7%) patients. And in the analysis by ITT in 28 patients who had a 72 week follow‐up after starting therapy, SVR‐24 was observed in 17 (60.7%) patients.

Conclusions

Response to triple therapy with TVR plus PR in HIV/HCV‐patients under real‐life conditions, and therefore, including a high proportion of difficult to treat patients, is similar to that found in CT. The safety profile of TVR‐based therapy is also comparable to that shown in CT, with only a rate of discontinuation of 8.6% of individuals related to toxicity.
Telaprevir or boceprevir in HIV/HCV‐1 co‐infected patients in a real‐life setting. Interim analysis (24 weeks). COINFECOVA‐SEICV study
Authors: Minguez Carlos , Ortega Enrique , Flores Juan , Carmena Jorge , Masiá Mar , Montero Marta , Reus Sergio , Tornero Carlos , Jose Galindo Maria , Garcia‐Deltoro Miguel , Amador Concepción , María Cuadrado Jose , Usó Jorge , López‐Aldeguer Jose
Published: November 2014

Introduction

In general, HIV co‐infected patients included in clinical trials evaluating the hepatitis C virus (HCV) therapy with telaprevir (TVR) or boceprevir (BOC) with advanced fibrosis, are scarce. We analyze data concerning the use of these drugs in a real‐life clinical setting with patients affected by a more advanced degree of fibrosis in a Spanish cohort.

Methods

We evaluated safety and efficacy in an interim analysis encompassing the first 24 weeks of triple therapy with peginterferon (alfa‐2a or alfa‐2b), ribavirin and TVR or BOC in an observational, multicentre study. HIV/HCV genotype 1 co‐infected patients beginning therapy from January 2012 to July 2013 were included.

Results

Enrolled patients were 155 (144 patients on TVR and 11 on BOC), average age was 47 years, 83% were male. With respect to HCV treatment, 44% were naïve, 13% relapsers, 17% partial responders, 21% null responders, and in seven patients, the previous response was unknown. All but three (98%) were under antiretroviral therapy (ART) (other than reverse transcriptase inhibitors, the backbone was raltegravir 43%, atazanavir 35%, and etravirine 28%). Median HCV‐RNA at baseline was 6.1 log10, 54% were cirrhotic and 38% F3. At week 4, 93% of patients continued on therapy, 81% at w12, and 73% at w24. Virological failure was observed more frequently in: cirrhotic patients (19% [95% CI, 11–27]) vs F3 (12% [CI, 4–20]); patients with TT allele of the IL28B polymorphism (40% [CI, 18–61]) vs CT (21% [CI, 12–31]), or CC (2,2% [CI, −2–6]); previous null responders (37.5% [CI, 21–54]) vs partial responders (15.4% [CI, 1–29]), naïve (13% [CI, 5–21]) or relapsers (0% [CI, 0–0]); and in patients with a genotype subtype 1a (23.6% [CI, 57–76]) vs 1b (8.1% [CI, −1–17]). Overall, 17% had virological failure and in 8% treatment was discontinued due to adverse events. Severe adverse events occurred in 30 patients (19%). Haematologic disorders were the most common type including severe anaemia in 12 (7.7%) patients. Erythropoietin was employed in 41 patients (26.4%) and 11 (7.1%) received blood transfusions. Nineteen patients (12.2%) were treated with G‐CSF, and 17 (11%) with thrombopoietin‐receptor agonists. Five patients died (3.2%), three due to hepatic decompensation, one due to pneumonia and one due to pulmonary hypertension.

Conclusions

In a real‐life setting, therapy against HCV in co‐infected patients with advanced liver fibrosis shows high virologic success at 24 weeks. However, frequent haematologic disorders are observed and a close monitoring and an intensive therapy are needed to optimize the results.
Safety analysis of raltegravir/truvada regimen in HIV/HCV co‐infected patients without switchback after HCV treatment
Authors: Ehret Robert , Walter Hauke , Ingiliz Patrick , Baumgarten Axel , Obermeier Martin , Krznaric Ivanka
Published: November 2014

Introduction

Due to drug‐drug interactions of HIV‐ and HCV‐specific antivirals when initiating an HCV‐therapy, the antiretroviral therapy (ART) often has to be changed. The spectrum of applicable antiretrovirals is small, therefore many patients were switched to raltegravir/truvada (RAL/TVD) in our cohort. Due to the relatively low genetic barrier of RAL, this regimen may be endangered to fail, if the NRTI backbone is not fully active because of pre‐existing NRTI resistance. We investigated the long‐term follow‐up and safety of RAL/TVD in co‐infected patients after hepatitis C virus (HCV) therapy was stopped and the protective antiretroviral effect of interferon ended.

Materials and Methods

Twenty patients initiated a direct‐acting antiviral (DAA) containing HCV therapy (8x faldaprevir, 6x telaprevir, 2x daclatasvir and 4x simeprevir) between 11/2011 and 01/2013. Seventeen were switched to RAL/TVD, three patients were not treated before, but started with the regimen. Diagnosis of HIV infection was dated between 1985 and 2010. The HI‐viral suppression was monitored retrospectively to date.

Results

Thirteen of the twenty patients (65%) remained on RAL/TVD after finishing HCV treatment, for seven patients, no data about their ART continuation was available, after HCV therapy had stopped. All remaining thirteen patients showed an HI‐viral load below detection limit up to date (for 15 to 22 months, median 20 months). Only for four patients, historic resistance data were available but none showed NRTI mutations.

Conclusions

Switch to RAL/TVD as HIV ART due to initiating HCV therapy was safe for the observed small cohort even in long‐term follow‐up without switchback or a second ART switch. However, resistance data for the cohort was little, showing no NRTI mutations, indicating a relatively safe setting. Since no further data is available, physicians should keep in mind ART history, historical therapy failure and HIV‐resistance while switching ART to treat HCV in co‐infected patients. Further investigation in larger cohorts is needed, especially thinking of upcoming interferon‐free HCV regimen in heavily pre‐treated co‐infected patients.
Autologous stem cell transplantation in HIV‐related lymphoma in the rituximab era – a feasibility study in a monocentric cohort
Authors: Wieters Imke , Atta Johannes , Kann Gerrit , Owasil Junaid , Goepel Siri , Haberl Annette , Stephan Christoph , Wolf Timo
Published: November 2014

Introduction

Since the introduction of highly active antiretroviral therapy (HAART) [1] and later on the availability of anti‐CD20 monoclonal antibody treatment [2], the therapeutic options as well as the prognosis of AIDS related lymphoma (ARL) have been improved. There is however no uniform agreement on how to treat patients who do not achieve a partial remission, who experience a relapse or who have very aggressive subtypes. Autologous hematopoietic stem cell transplantation (ASCT) has become an option for those patients. We retrospectively examined ARL patients to elucidate the feasibility of high‐dose chemotherapy and autologous stem cell transplantation.

Patients and methods

Data of seven male and one female HIV+ patients with ARL was collected and informed consent was obtained. Age, HIV disease characteristics (CD4 count, HIV‐RNA‐PCR, ART) and transplantation‐related details (histopathology, myeloablative therapy, neutrophil engraftment and NCI‐CTCAE during/after transplantation as well as follow up and survival) were obtained from the patients’ medical records.

Results

Eight patients were treated with the intent of ASCT. The median age was at 64 years. Four patients had experienced prior AIDS. The median CD4 NADIR was at 157/µl, the median CD4 count at diagnosis of lymphoma at 81/µl. Five patients were receiving combination antiretroviral therapy (cART) at the time of lymphoma diagnosis, four of which had achieved a viral load of less than 50/µl. Two patients have died, due to (Nr. 8) a transplant‐related complication (non‐infectious leukoencephalophathy). The other patient died of an unknown reason (351 days after transplantation). The median survival is at 345 days to date. The time until engraftment was well at 11 days. Grade 3/4 haematological toxicity was present in all patients. Five out of three patients developed infectious complications, but there were no infection‐related deaths. One patients (Nr. 4) developed a Kaposi Sarcoma reactivation that necessitated further chemotherapy.

Conclusions

ASCT is feasible in high risk ARL with good engraftment. Toxicity was substantial and studies are needed to define which patients have an unduly high risk of toxicity.
Evolution trends over three decades of HIV infection late diagnosis: the experience of a Portuguese cohort of 705 HIV‐infected patients
Authors: Claudia Miranda Ana , Moneti Virginia , Brogueira Pedro , Peres Susana , Baptista Teresa , Aldir Isabel , Ventura Fernando , Borges Fernando , Mansinho Kamal
Published: November 2014

Introduction

Late HIV diagnosis is common and associated with an increased risk of clinical progression, blunted immune response on antiretroviral (ARV) therapy and higher risk of drug toxicity. Across Europe, more than a third of patients are diagnosed late and consequently delay medical care. European Consensus definition group identify as late presentation (LP) persons, presenting for care, with a CD4 count below 350 cell/mm3 or presenting with AIDS‐defining event, regardless of CD4 cell count. Additionally, advanced HIV disease (AD) is defined by a CD4 count below 200 cell/mm3 or an AIDS defining condition in persons presenting to care.

Materials and Methods

Retrospective observational study of a cohort of 705 HIV‐infected patients diagnosed between 1986 and 2014 and medically followed at an Infectious Diseases Service in Lisbon.

Objectives

Evaluate LP rate evolution in the last three decades (10‐year time intervals considered: 1986–1995; 1996–2005; 2006–2014); compare clinic, immunologic, virologic and therapeutic response over time. Identify main reasons responsible for late HIV diagnosis in order to promote optimized intervention strategies. SPSS version 20.0 was used for statistical analysis.

Results

Study included 705 patients HIV diagnosed during 3 time intervals: group A n=82 [1986–1995]; group B n=332 [1996–2005]; group C n=291 [2006–2014]. Demographic and epidemiological characterization revealed (A vs B vs C): male predominance of 79% vs 66% vs 66%; mean age at diagnosis 30 vs 36 vs 42 years; Portugal (82% vs 70% vs 58%) and Africa (13% vs 23% vs 29%) as the main places of birth; transmission by heterosexual contact in 21% vs 47% vs 62%, MSM in 21% vs 15% vs 23% and IVDU in 57% vs 35% vs 13%. Mean CD4 at diagnosis was 362 vs 344 vs 377 cell/mm3. Considering the time intervals, LP was found in 52% vs 56% vs 52% of patients and AD in 31% vs 38% vs 35%, respectively. At first health care encounter, 46% vs 43% vs 39% of individuals presented with AIDS. Over follow up, the vast majority initiated ARV (95% vs 98% vs 84%) and mean CD4 at that time was 254 vs 282 vs 250 cell/mm3. The last immunologic and virologic determination available registered mean CD4 of 657 vs 644 vs 584 cell/mm3 and undetectable HIV plasma RNA in 92% vs 84% vs 82% of treated patients.

Conclusions

This study evidenced a maintained LP rate, slightly above 50% in each of the three analyzed last decades, and one‐third of patients presented AD at HIV diagnosis. At initial health care contact, nearly 40% of individuals met AIDS clinical or immunological criteria.
Late diagnosis among our ageing HIV population: a cohort study
Authors: Mensforth Sarah , Goodall Lisa , Bodasing Neena , Coultas James
Published: November 2014

Introduction

With the advent of combined antiretroviral therapy (cART), more people infected with HIV are living into older age; 22% of adults receiving care in the UK are aged over 50 years [1]. Age influences HIV infection; the likelihood of seroconversion illness, mean CD4 count and time from infection to development of AIDs defining illnesses decreases with increasing age. A UK study estimates that half of HIV infections in persons over 50 years are acquired at an age over 50 [2]. Studies exploring sexual practices in older persons have repeatedly shown that we cannot assume there is no risk of STI and HIV infection [3,4]. Physicians should be alert to risk of HIV even in the older cohort, where nearly half diagnoses are made late [2]. Local audit has demonstrated poor testing rates in the over 50's on the Acute Medical Unit. Late diagnosis (CD4<350) results in poorer outcomes and age confounds further; older late presenters are 2.4 times more likely to die within the first year of diagnosis than younger counterparts [2].

Materials and Methods

A retrospective case notes review was conducted of all patients aged 60 years and over attending HIV clinic in the last 2 years. Outcomes audited included features around diagnosis; age, presentation, missed testing opportunities and CD4 count at diagnosis.

Results

Of the current cohort of 442 patients, 34 were over 60 years old (8%). Age at diagnosis in this group ranged from 36 to 80 years, mean 56.6 years. Presentation triggers included opportunistic infections or malignancies (n=10), constitutional symptoms (n=6), diagnosis of another STI (n=4), seroconversion illness (n=2), partner status (n=3). Eight patients were diagnosed through asymptomatic screening at Sexual Health. We identified missed opportunities in five patients who were not tested despite diagnoses or symptoms defined as clinical indicators for HIV. Half of older patients had a CD4 count of <200 at diagnosis.

Conclusions

It is imperative that general medical physicians and geriatricians are alert to enquiring about risk and testing for HIV where clinical indicators are present, irrespective of age. The oldest patient in the cohort was diagnosed with HIV aged 80 years. All patients with missed opportunities for testing were over 47 years old.
Prevention of mother‐to‐child transmission: experience of a Portuguese centre
Authors: Piñeiro Carmela , Fernandes Sofia , Figueiredo Cristóvão , Sofia Santos Ana , Moucho Marina , Serrão Rosário , Montenegro Nuno , Sarmento António
Published: November 2014

Introduction

HIV infection during pregnancy still raises controversial issues. Combined antiretroviral therapy (cART) has been successful in reducing mother‐to‐child transmission (MTCT). Routine screening in pregnancy and in pre‐conception consultation proved to be one of the best methods able to get this treatment on time. We review our experience with pregnant patients with HIV infection.

Materials and Methods

Retrospective and descriptive study. Data obtained from HIV‐infected pregnant women from 1999 to 2012 with delivery and subsequent infectious diseases follow‐up at our hospital.

Results

We evaluated 136 patients (169 pregnancies), with a total of 147 living newborns (2 twin pregnancies) and 1 stillbirth. Median age at pregnancy was 30 (SD 5.7) years. Four patients were HIV‐2 infected and one HIV‐1+2 infected. 26 (19.1%) women were HCV co‐infected and 6 (4.4%) HBV co‐infected; 1 patient has HCV and HBV co‐infection. Sexual risk for HIV acquisition was determined in 102 (75%) patients and 31 (22.8%) were intravenous drug users. 33/136 (24.2%) women were diagnosed on routine screening in pregnancy, 4 during delivery and 2 immediately after delivery. 36 (26.4%) patients had an AIDS‐defining entity before pregnancy and no new opportunistic infections were diagnosed. ART was used in 157 (92.9%) pregnancies and 15 (9.5%) of them were treated only with NRTIs. At the time of delivery 86/144 (59.7%) patients had undetectable viral load (VL) (25 patients without VL determined), 91.7% of those on ART. 119 (70.4%) had a TCD4 cell count above 200 cells/mm3. MTCT occurred in 3/147 cases (2%): in one mother HIV‐1 infection was diagnosed three weeks before delivery, other immediately after delivery and the third woman started cART (2NRTI+1PI/r) in the second trimester of pregnancy, always adherent and without secondary effects, VL at delivery was 50 copies/mL and elective C‐section was performed.

Conclusions

The fact that 24% of patients were diagnosed during pregnancy shows the importance of routine screening to all pregnant women. MTCT occurred in three children, but only one was administered cART for prevention.
Universal Tre (uTre) recombinase specifically targets the majority of HIV‐1 isolates
Authors: Karpinski Janet , Chemnitz Jan , Hauber Ilona , Abi‐Ghanem Josephine , Paszkowski‐Rogacz Maciej , Surendranath Vineeth , Chakrabort Debojyoti , Hackmann Karl , Schröck Evelin , Teresa Pisabarro María , Hauber Joachim , Buchholz Frank
Published: November 2014

Current drugs against HIV can suppress the progression to AIDS but cannot clear the patient from the virus. Because of potential side effects of these drugs and the possible development of drug resistance, finding a cure for HIV infection remains a high priority of HIV/AIDS research. We recently generated a recombinase (termed Tre) tailored to efficiently eradicate the provirus from the host genome of HIV‐1 infected cells by specifically targeting a sequence that is present in the long terminal repeats (LTRs) of the viral DNA [1]. In vivo analyses in HIV‐infected humanized mice demonstrated highly significant antiviral effects of Tre recombinase [2]. However, the fact that Tre recognizes a particular HIV‐1 subtype A strain may limit its broad therapeutic application. To advance our Tre‐based strategy towards a universally efficient cure, we have engineered a new, universal recombinase (uTre) applicable to the majority of HIV‐1 infections by the various virus strains and subtypes. We employed the search tool SeLOX [3] in order to find a well‐conserved HIV‐1 proviral sequence that could serve as target site for a universal Tre from sequences compiled in the Los Alamos HIV Sequence Database. We selected a candidate (termed loxLTRu) with a mean conservation rate of 94% throughout the major HIV‐1 subtype groups A, B and C. We applied loxLTRu as substrate in our established substrate‐linked protein evolution (SLiPE) process [4] and evolved the uTre recombinase in 142 evolution cycles. Highly specific enzymatic activity on loxLTRu is demonstrated for uTre in both Escherichia coli and human cells. Naturally occurring viral variants with single mutations within the loxLTRu sequence are also shown to be efficiently targeted by uTre, further increasing the range of applicability of the recombinase. Potential off‐target sites in the human genome are not recombined by uTre. Furthermore, uTre expression in primary human T cells shows no obvious Tre‐related cytopathic or genotoxic effects. Finally, uTre expressing mice show no undesired phenotypes during their normal lifespan. We have developed a broad‐range HIV‐1 LTR specific recombinase that has the potential to be effective against the vast majority of HIV‐1 strains and to cure HIV‐1 infected cells from the infection. These results strongly encouraged us in our confidence that a Tre recombinase‐mediated HIV eradication strategy may become a valuable component of a future therapy for HIV‐infected patients.
A comparison of inpatient admissions in 2012 from two European countries
Authors: Tittle Victoria , Cenderello Giovanni , Pasa Ambra , Patel Preya , Artioli Stefania , Dentone Chiara , Fraccaro Paolo , Giacomini Mauro , Setti Maurizio , Di Biagio Antonio , Nelson Mark
Published: November 2014

Introduction

This study compares the trends of HIV inpatient admissions between a London tertiary HIV centre (United Kingdom) and four infectious disease wards in Italy (IT) to recognize common patterns across Europe.

Methods

Data regarding HIV inpatient admissions was collected by using discharge diagnostic codes from 1 January to 31 December 2012, including patient demographics, combined antiretroviral therapy (cART) history, CD4, viral load (VL) and mortality rates. Discharge diagnoses were categorized according to the International Classification of Disease (ICD) 9 and 10 system. All ICD categories that reach a 3% threshold of total admissions were analyzed.

Results

A total of 731 admissions (257 in Italy and 474 in the United Kingdom) for 521 patients (1.5 mean admission per patient). Female admissions were higher in Italy at 22.6% (n=58) compared to 14.9% (n=47) in the United Kingdom. Median age of patients was 47 years old. There was an undetectable VL in 65.8% (n=169) of admissions in Italy and 67.1% (n=319) in the United Kingdom (p=0.385); 86.4% (n=222) and 82.4% (n=389) of admissions were on cART, respectively. Mean CD4 was 302 in Italy compared to 368 in the United Kingdom (p=0.003). Average length of admission was 16 days with a 10.2% (n=21) mortality rate in Italy compared to 8 days with 2.8% (n=9) mortality in the United Kingdom (p<0.001). HCV co‐infection was present in 64.6% (n=166) in Italy and 13.5% (n=64) in the United Kingdom and commonest mode of transmission was needle use in Italy (67.3%, n=173) and men who have sex with men in the UK cohort (59.9%, n=284). The cause of inpatient admissions according to ICD codes can be seen in following Figure 1.

Conclusions

Significant differences in the duration of inpatient admission and mortality rates can be observed between these two cohorts which is secondary to the impact of Hepatitis C co‐infection in Italy. However increases in the number of Hepatitis C co‐infection patients amongst MSM in London has been reported [1] and route of transmission in Italy is shifting towards MSM [2], therefore it is important to learn how HIV is developing and managed in a global context to help plan future for services. The UK cohort demonstrates a wider range of conditions necessitating admission, and with an ageing HIV population, this is expected to increase in the future, requiring general and specialist HIV physicians to work closely together. The HIV‐RNA threshold is 400 copies/mL to account for blips according to British HIV Association (BHIVA) Guidelines 2012 [3].
The CD4:CD8 ratio is associated with IMT progression in HIV‐infected patients on antiretroviral treatment
Authors: Bernal Enrique , Serrano Jose , Perez Ana , Valero Salvador , Garcia Eva , Marín Irene , Muñoz Angeles , Miguel Gomez Verdú Jose , Vera Carmen , Cano Alfredo
Published: November 2014

Introduction

Inversion of the CD4:CD8 ratio (<1) has been identified as a hallmark of immunosenescence and an independent predictor of mortality in the general population. We aimed to assess the association between the CD4:CD8 ratio and intima‐media thickness (IMT) progression in treated HIV‐infected patients as a marker of early atherosclerosis.

Materials and Methods

A longitudinal study during three years was conducted in 120 HIV‐infected patients receiving antiretroviral treatment (ART). We analyzed the associations between the CD4:CD8 ratio, cardiovascular risk factor and antiretroviral (ARV) treatment and progression of subclinical atherosclerosis assessed using carotid IMT at baseline and after three years.

Results

Finally, 96 patients completed the study. Seventy‐six (79.1%) patients were male, aged 44±10 years, 39 (40.6%) were on treatment with Protease inhibitors, 49 (51.04%) with non‐nucleoside reverse transcriptase inhibitors (NNRTI), 6 (6.25%) with integrase inhibitors, 3 (3.12%) with maraviroc and 2 (2.08%) only with nucleoside reverse transcriptase inhibitors (NRTI). The mean of ARV exposition was 6.9±5.9 years. Twenty six (27 %) patients had family history of ischemic heart disease, 51 (53.12%) were smokers, 12 (12.5%) hypertensive, 4 (4.16%) type 2 diabetes, 23 (23.9%) with dyslipidemia and 31 (32.3%) were infected with C hepatitis virus. Baseline IMT was significantly associated with age (rho=0.497; p<0.001), basal glucemia (rho=0.323; p=0.001), triglycerides (rho=0.232; p=0.023), Framingham score (rho=0.324; p=0.001), CD4:CD8 ratio (rho=−0.176; p=0.05) and dyslipidemia (0.72±0.16 mm vs 0.63±0.11 mm; p=0.029). In multivariable analysis where cardiovascular risk factor and ARV were included, IMT progression was inversely associated with CD4:CD8 ratio (OR=0.283; CI 95% 0.099–0.809; p=0.019) and treatment with NNRTI (OR=0.283; CI 95% 0.099–0.809; p=0.019).

Conclusions

The inversion of CD4:CD8 ratio in treated HIV‐infected patients is independently associated with IMT progression, a marker of age‐associated disease. Therefore, it might be clinically useful as predictor of cardiovascular events. Surprisingly, there was a positive correlation between receiving NNRTI and progression of IMT.
Acceptability of PrEP among HIV negative Portuguese men who have sex with men that attended 2014 Lisbon pride fair
Authors: Miguel Rocha Luís , José Campos Maria , Brito João , Fuertes Ricardo , Rojas Jesus , Pinto Nuno , Mendão Luís , Esteves Julio
Published: November 2014

Introduction

Consistent use of PrEP reduces HIV transmission from sexual practices amongst men who have sex with men (MSM) up to 92% [1]. Lisbon MSM cohort study estimates point that 59.3% of their participants at entrance (1593 HIV negative MSM enrolled between April 2011 and May 2013) were eligible for PrEP [2], according to the 2014 USA PrEP guidelines [3]. Studies about PrEP acceptability and implementation support policies aimed at increasing and rolling out its use. Hence, the exploratory study about PrEP acceptability in MSM at Lisbon.

Materials and Methods

A street‐based intercept survey, adapted from Mantell et al. study [4], was the one used on MSM attending the 2014 Lisbon pride fair. The survey included socio‐demographic data, PrEP awareness and readiness to use it, probability of MSM's social network to also use it, promptness to join PrEP‐related studies, type of PrEP warranted and condomless anal sex practice in the last six months.

Results

A total of 110 HIV negative Portuguese MSM responded, with a median age of 33% and 84% of them identified themselves as gay. A majority of MSM were unaware of PrEP (59%); those that were aware, had heard of it trough CheckpointLx (31%), internet (22%) or health professionals (20%). 66% were likely or very likely to participate in PrEP‐related studies. 57% of MSM were likely or very likely to use PrEP if available and reported that some, if not almost all of their social network, will do it too (70%). Type of PrEP preferred was oral, a pill a day (43%), followed by oral, intermittent intake (32%). Overall 41% of MSM had condomless anal sex practice in the last six months.

Conclusions

In this MSM Portuguese sample, a general willingness to adopt PrEP was predominant, specially the oral daily intake. Forty‐one percent of participants had had condomless anal sex practice in the last six months and therefore fitted within the criteria to be on Pre‐Exposure Prophylaxis (PrEP), according to MSM Risk Index in 2014 USA PrEP guidelines. PrEP, when available in Portugal, should be a powerful tool for HIV prevention in this key population.
HIV‐1 group O integrase displays lower susceptibility to raltegravir and has a different mutational pathway for resistance than HIV‐1 group M
Authors: Depatureaux Agnès , Mesplède Thibault , Quashie Peter , Oliveira Maureen , Moisi Daniela , Brenner Bluma , Wainberg Mark
Published: November 2014

Introduction

HIV‐1 group O (HIV‐O) is a rare HIV‐1 variant characterized by a high number of polymorphisms, especially in the integrase gene, e.g. positions L74I, S153A, G163Q and T206S. As HIV‐O integrase enzymes have not previously been studied, our aim was to assess the impact of HIV‐O integrase polymorphisms on susceptibility to integrase inhibitors and emergence of resistance associated mutations.

Viruses and Methods

We cloned and purified integrase proteins from each of HIV‐1 Group O clades A (HIV‐O/A) and B (HIV‐O/B), a HIV‐O divergent strain (HIV‐O/Div), and HIV‐1 group M (subtype B, HIV‐M/B) and characterized these enzymes for susceptibility to integrase strand transfer inhibitors (INSTIs) in cell‐free assays and in tissue culture, in the absence or presence of varying concentrations of several INSTIs. The inhibition constant (Ki) and IC50 were calculated and compared for HIV‐M and HIV‐O integrases. Selections for resistance‐related mutations were performed using cord blood mononuclear cells and increasing concentration of INSTIs.

Results

HIV‐O integrase and viruses were more susceptible to raltegravir (RAL) in competitive inhibition assays and in tissue culture than were HIV‐M enzymes and viruses, respectively. During selection, we observed different pathways of resistance depending on the drug and clade. Mutations selected in HIV‐O can be classified as follows: (1) mutations described for HIV‐M such as T97A, Q148R, V151A/I (RAL), T66I, E92Q, E157Q (EVG) and M50I, R263K (DTG) and (2) signature mutations for HIV‐O (i.e. not described in HIV‐M) F121C (HIV‐O/B for RAL), V75I (HIV‐O/A for RAL) and S153V (HIV‐O/A for DTG). Only the HIV‐O/Div selected the Q148R mutation for RAL and R263K+M50I for DTG, as previously described for HIV‐M. None of the HIV‐O viruses selected either N155H or Y143C. The selection of the specific S153V mutation could be explained at the nucleotide level: HIV‐O at this position contains an alanine and substitution of alanine to valine (153AGGC→153VGTC) is easier than substitution of alanine to tyrosine (153AGGC→153YTAC), with only a transversion needed instead of one transition plus one transversion.

Conclusions

This is the first report of susceptibility and resistance in vitro to INSTIs for HIV‐O. Our study confirmed the impact of HIV‐O polymorphism, on susceptibility to INSTIs and the emergence of resistance mutations.
Seroincidence of HIV and prevalence of transmitted drug resistance of HIV‐1 strains among persons seeking voluntary counselling and testing in Taiwan
Authors: Liu Wen‐Chun , Chang Lan‐Hsin , Wu Pei‐Ying , Luo Yu‐Zhen , Wu Cheng‐Hsin , Su Yi‐Ching , Lai Chung‐Chi , Chang Sui‐Yuan , Hung Chien‐Ching
Published: November 2014

Introduction

The total case number of persons who are newly diagnosed with HIV continues to increase in Taiwan and men who have sex with men (MSM) have re‐emerged as the leading risk group for HIV transmission. In this study, we aimed to estimate the incidence rate of HIV infection among those individuals who sought voluntary counselling and testing (VCT) service at a university hospital.

Methods

Between 1 April, 2006 and 31 December, 2013, 18,246 tests for HIV antibody were performed among 12143 individuals at the VCT service. A total of 2157 individuals who tested negative for anti‐HIV antibody had subsequent follow‐up tests at the same VCT service, which composed the study population for estimation of incidence rate of recent HIV infection. The BED assays were used to identify recent HIV infections that occurred within the previous six months before seeking VCT service.

Results

During the 6.5‐year study period, 647 individuals were diagnosed as being HIV‐positive, with an overall HIV seroprevalence of 3.55% (95% CI 3.27–3.82). The overall incidence rate of HIV infection was estimated 4.13 per 100 person‐years of follow‐up (95% CI 3.67–4.69 per 100 person‐years of follow‐up). MSM had an estimated 10‐fold higher seroprevalence and seroincidence of HIV than heterosexuals. Of 647 clients testing positive for HIV, 603 clients were MSM (93.2%) and 477 patients (70.8%) subsequently sought HIV care at the hospital; 226 (47.4%) were diagnosed as having recent HIV infections by the BED assay, while 244 (51.2%) long‐term infection and 7 without data by the BED assay. Of those patients, 173 (75.6%) and 178 patients (73.0%) with recent HIV infection and long‐term infection had data of transmitted drug resistance mutations, respectively. The prevalence of transmitted drug resistance mutations to any class of antiretroviral therapy was 9.0% and 10.6% (p=0.68), respectively, of the HIV‐1 strains from the patients with recent HIV infection and long‐term infection, respectively.

Conclusions

The seroincidence rate of HIV among persons seeking VCT was estimated 4.13 per 100 person‐years of follow‐up. The prevalence of transmitted drug resistance to any class of antiretroviral agents was similar between those who were recently infected with HIV and those who had long‐term infection in Taiwan.
Lamivudine monotherapy as a safe option for HIV‐infected paediatric clients with adherence challenges: new evidence from a large South African cohort
Authors: Linder Verena , Goldswain Cheree , Boon Gerald , Carty Craig , Jackson Valerie , Harper Kim , Lambert John
Published: November 2014

Introduction

HIV‐infected children in resource‐poor settings comprise a unique population who require antiretroviral therapy (ART) in careful consideration of social and structural barriers to compliance. Given these aggregate challenges and emerging research into “holding” treatment options, we investigated the efficacy of lamivudine monotherapy (LM) as an alternative to more complex second and third line therapies.

Methods

A retrospective review of all eligible LM events (=6 months) from a cohort of two linked health facilities in the Eastern Cape Province, South Africa was undertaken. Events were disaggregated according to absolute CD4 count at initiation (Group 1: >200 cells/L, n=64; Group 2:=200cells/L, n=10). Study endpoints were defined as a decline of absolute CD4=200 cells/L (Group 1), WHO stage 3 or 4 event (Groups 1& 2), or initiation of second or third line (Groups 1 & 2).

Results

Seventy‐four eligible LM events were identified among 71 HIV‐positive children (58% male; median age at LM 9.7 years and median LM duration 11.5 months). CD4 decreases and measured WHO stage 3 or 4 events did not yield overall significance between groups (Table 1). No deaths were recorded.

Conclusions

LM offers a promising alternative approach to ART management in young patients with an absolute CD4 >200 cells/L pending availability and/or willingness to adhere to second or third line therapies. In more immunocompromised children, LM may be considered as a last option if either the child or caretaker has concerns about second or third line management, or has defaulted repeatedly.
Time on drug analysis based on real life data
Authors: Schülter Eugen , Kaiser Rolf , Zazzi Maurizio , Sönnerborg Anders , Camacho Ricardo , Verheyen Jens
Published: November 2014

Introduction

The health condition of HIV‐1 infected patients has improved during the last years, but lifelong antiretroviral treatment is still needed. However resistance, multiple side effects and drug to drug interactions of antiretrovirals challenge the establishment of a long lasting regimen. The average running time of each antiretroviral drug composing the therapy episodes combination antiretroviral therapy (cART) may be seen as an indicator of effectiveness and tolerability.

Materials and Methods

To evaluate the running time of each drug used in HIV‐1 treatment, we extracted therapy episodes from the latest release of the EuResist database (www.euresist.org). The evaluation period was from Oct 2006 to Oct 2012. Inclusion criteria for this analysis were continuous patient monitoring for at least two years (i.e. latest therapy start in Oct 2010), and the extraction of at least 100 cases per drug analyzed. Drug intake interruptions of less than a month were ignored.

Results

At the time of data extraction (Feb 2013), the EuResist database contained data from 61,953 patients of which 11,499 fulfilled the inclusion criteria. We obtained 37,035 drug treatment lines from 38,153 cARTs and the overall average length of drug intake was 18.7 months. For each single drug these average durations measured in months were: 18.3 (3TC); 20.8 (ABC); 12.3 (d4T); 14.3 (ddI); 23.2 (FTC); 23.0 (TDF); 13.4 (ZDV); 19.8 (EFV); 21.9 (ETR); 17.7 (NVP); 19.2 (ATV); 22.7 (DRV); 18.7 (FPV); 17.9 (LPV); 15.2 (SQV); 14.6 (TPV); 22.6 (RAL); 21.9 (MVC) and 8.9 (T20). Overall drug discontinuation rates at one, two and three years were 35.0, 48.8 and 95.8%, respectively. Average discontinuation rates for the different drug classes at two years these were: 46.2% for NRTIs; 49.7% for NNRTIs; 55.4% for PIs and 37.6% for Raltegravir/Maraviroc.

Conclusions

In this cohort the overall frequency of therapy changes is high. After two years of treatment, on average 49% of the patients change at least one drug in their cART. Thus, we have to expect numerous changes in the long term perspective of treatments. The observed differences in durations suggest that newer drugs might have advantages over older ones. However possible reasons and confounding factors (such as number of past treatment lines, co‐medication, risk group, etc.) were not addressed at this time of the analysis.