Prescriptions of generic antiretroviral drugs in three healthcare centers in the Paris area, France.

In a retrospective study conducted in three hospitals in Paris, generic antiretroviral accounted for 30.2% of all prescriptions. Tenofovir disoproxil/emtricitabine (TDF/FTC) was the most prescribed generic ART (82.3% of generic prescriptions). Generic ART (gART) was more likely to be prescribed to women, to patients less than 50 years, and with recent HIV diagnosis less than 3 years. Physicians prescribed more gART if they were men, older than 55 years or worked at a university teaching hospital.

Brief Report: Incidence and Management of Complex Kidney Situations Among On-Demand and Daily HIV Pre-Exposure Prophylaxis Users.

BACKGROUND: We evaluated complex pre-exposure prophylaxis (PrEP) situations linked to kidney issues in a cohort of on-demand and daily PrEP users. SETTING: We conducted a single-center retrospective cohort study in France including all PrEP users who received a tenofovir disoproxil (TD)-emtricitabine (FTC) prescription between January 1, 2012 and December 31, 2019 with at least 1 creatinine measurement available before and after PrEP initiation. METHODS: A complex kidney situation (CKS) was defined as an estimated glomerular filtration rate (eGFR) <60 mL/minute/1.73m 2 on 2 consecutive measurements. We estimated the incidence of this event, described case management, and identified associated factors using a Cox model. RESULTS: Three thousand one hundred and fourteen individuals were included in this study. Almost all were men (99%) with a median age of 35 years, 25% had an eGFR <90 mL/minute/1.73m 2 at baseline, and 65% used on-demand PrEP. Nine users (0.29%) had a CKS at baseline; 8/9 initiated on-demand PrEP without renal function worsening after a median (interquartile range [IQR]) follow-up time of 14 months (7-31). Thirteen cases of CKS occurred during the follow-up for a 0.25 per 100 person-years incidence (95% confidence interval [CI]: [0.14; 0.45]). On-demand PrEP was used in 7/13 participants with no further episode of confirmed eGFR <60 mL/minute/1.73m 2 after a 17-month median follow-up (IQR 4-18). CKS was associated with an age ≥50 years (hazard ratio [HR] 13, 95% CI: [4-39]) or with a baseline eGFR <90 mL/minute/1.73m 2 (HR 34, 95% CI: [4-261]). 9/22 CKS were linked to high-protein intake for weight training. CONCLUSIONS: CKS were rare in our cohort. On-demand PrEP did not result in subsequent renal function worsening in these few situations.

Updated mortality and causes of death in 2020-2021 in people with HIV: a multicenter study in France.

OBJECTIVE: The aim of this study was to assess updated mortality and causes of death in people with HIV (PWH) in France. DESIGN AND METHODS: We analyzed all deaths in PWH followed up between January 1, 2020, and December 31, 2021, in 11 hospitals in the Paris region. We described the characteristics and causes of death among deceased PWH, and evaluated the incidence of mortality and associated risk factors using a multivariate logistic regression. RESULTS: Of the 12 942 patients followed in 2020--2021, 202 deaths occurred. Mean annual incidence of death [95% confidence interval (95% CI)] was 7.8 per 1000 PWH (6.3-9.5). Forty-seven patients (23%) died from non-AIDS nonviral hepatitis (NANH)-related malignancies, 38 (19%) from non-AIDS infections (including 21 cases of COVID-19), 20 (10%) from AIDS, 19 (9%) from cardiovascular diseases (CVD), 17 (8.4%) from other causes, six (3%) from liver diseases, and five (2.5%) from suicides/violent deaths. The cause of death was unknown in 50 (24.7%) patients. Risks factors for death were age [adjusted odds ratio (aOR) 1.93; 1.66-2.25 by additional decade), AIDS history (2.23; 1.61-3.09), low CD4 + cell count (1.95; 1.36-2.78 for 200-500 cells/µl and 5.76; 3.65-9.08 for ≤200 versus > 500 cells/µl), and viral load more than 50 copies/ml (2.03; 1.33-3.08), both at last visit. CONCLUSION: NANH malignancies remained in 2020-2021 the first cause of death. COVID-19 accounted for more than half of the mortality related to non-AIDS infections over the period. Aging, AIDS history, and a poorer viro-immunological control were associated with death.

Safety and efficacy of switching to elvitegravir, cobicistat, emtricitabine, tenofovir disoproxil fumarate in treatment-experienced people with HIV: a multicenter cohort study.

OBJECTIVES: We assessed the virologic efficacy of switching to co-formulated elvitegravir, cobicistat, emtricitabine, tenofovir disoproxil fumarate (E/C/F/TDF) in patients with controlled HIV infection. METHODS: We conducted a retrospective multicenter observational cohort study including adult patients with controlled HIV-1 infection on any stable antiretroviral (ART) regimen, who switched to E/C/F/TDF. Success was measured by the proportion of patients with plasma viral load < 50 copies/ml at W48 using the FDA snapshot algorithm. We also assessed risk factors associated with virological failure (VF). RESULTS: 382 patients with HIV RNA < 50 copies/mL who switched to E/C/F/TDF were included in the study. Most patients (69.9%) were male, with median age 44 years (IQR 38-51), who had been on ART for a median of 7 years (IQR 4-13). Median CD4 count was 614/mm3 and 24.6% of the patients had a history of previous virological failure. The reasons for switching were simplification (67.0%) and tolerance issues (22.0%). At week 48, 314 (82.0% [95% CI 78.4-86.0]) patients had HIV RNA < 50 copies/mL, 13 (3.5% [95% CI 3.64-8.41]) experienced virological failure. Genotype at failure was available in 6/13 patients with detection of resistance-associated mutations to integrase inhibitors and NRTIs in 5/6 (83.3%) patients. We found no predictive factor associated with virological failure except for a borderline significance with the duration of viral suppression before the switch. Tolerability of E/C/F/TDF was good with 23/382 (6.0%) patients experiencing mild adverse reactions. CONCLUSION: In our cohort, switching well-suppressed patients to E/C/F/TDF resulted in few virologic failures and was well tolerated. However, resistance to integrase inhibitors emerged in patients with virological failure.

Proof of concept of a sexual health outreach program led by community health workers in homeless hostels in the greater Paris region.

Context: Homeless individuals face exacerbated risks of infectious diseases, including sexually transmitted infections (STIs). Programs led by Community Health Workers (CHWs) have demonstrated potential to enhance healthcare access for marginalized groups such as homeless families. This study aims to evaluate the feasibility and effectiveness of a novel CHW-based outreach program addressing sexual health issues among individuals residing in homeless hostels. Methods: Twelve social homeless hostels in the greater Paris region were selected as program implementation sites. An outreach program was developed consisting of two interventions: sexual health workshops and STI screening sessions (HIV and hepatitis B and C) accompanied by individual interviews, both conducted by CHWs within each hostel over an 8-week period and scheduled weekly. Feasibility, participation and engagement were evaluated using complementary methods including qualitative field observations, semi-structured interviews and focus groups with CHWs, satisfaction questionnaires for participants, and quantitative outcome data collection of each intervention. Results: A total of 80 program activities (workshops and screening sessions) were conducted. Among the participants, 542 women and 30 men engaged in workshops. During the 30 Rapid Diagnostic Testing sessions, 150 individuals underwent testing for HIV, hepatitis B, and/or hepatitis C. Positivity rates were 6.7% for hepatitis B and 0.9% for hepatitis C. No HIV infections were detected. Participant satisfaction rates were consistently high (>76%) across workshops. Qualitative analysis unveiled two critical axes influencing program feasibility and effectiveness: program organization and CHW involvement. Discussion: This assessment of the program highlights its feasibility among a population that is difficult to reach through conventional healthcare efforts. The intervention's potential effectiveness is suggested by self- and CHW-reported improvements in sexual health literacy and high rates of referral to the healthcare system, as well as holistic well-being considerations. CHW involvement is a vital determinant of program success, as are robust coordination among stakeholders, deep understanding of the target population, and strong partner engagement. Conclusion: This outreach program amplifies the voices of often-overlooked populations while empowering them to navigate health and social challenges. Although these workshops serve as lifelines for those frequently excluded from mainstream services, long-term improvements to the health and wellbeing of homeless populations will necessitate systemic governmental intervention.

Mortality of People Living with HIV in Paris Area from 2011 to 2015.

In high-income countries, causes of death in people living with HIV (PLHIV) have changed. Three French national surveys from 2000 to 2010 showed a decrease in AIDS-related and an increase in non-AIDS-related deaths. Deaths notified in PLHIV followed between January 1, 2011 and December 31, 2015 in 1 of 13 participating hospitals northeast of Paris area were described. Risk factors for death were assessed, using a multivariable logistic regression model. Of 14,403 individuals, 295 died. Median age at death was 52 years (interquartile range = 47-60) and 77% were men. Sixty-seven individuals (23%) died from non-AIDS-defining nonviral hepatitis-related (NaNH) malignancy, 40 (14%) from AIDS, 34 (12%) from cardiovascular disease (CVD), 33 (11%) from non-AIDS infection, 21 (7%) from liver disease, and 12 (4%) from suicide. Men and women born in sub-Saharan Africa had a lower adjusted odds ratio (aOR) of dying than men having sex with men (MSM) born in France (0.70, 95% confidence interval = 0.45-1.09; and 0.45, 0.28-0.73, respectively). Risk factors for death were older age (aOR = 2.26, 1.36-3.77 for 40-49 years and 2.91, 1.75-4.84 for >50 years vs. 18-39 years), male intravenous drug users (IVDU) transmission (2.24, 1.42-3.54 vs. MSM born in France), AIDS (2.75, 2.10-3.59), antiretroviral therapy initiation in earlier periods, time since HIV diagnosis <1 year, low CD4 cell count nadir, hepatitis B virus and/or hepatitis C virus coinfection (1.69, 1.23-2.30), and psychiatric disorders (1.73, 1.27-2.38). Our study confirms the increasing frequency of non-AIDS-related deaths, mainly NaNH malignancies and CVD, in PLHIV, justifying overall and in some specific populations (psychiatric and IVDU) prevention and screening.

Daily or on-demand oral tenofovir disoproxil fumarate/emtricitabine for HIV pre-exposure prophylaxis: experience from a hospital-based clinic in France.

BACKGROUND: On-demand oral tenofovir disoproxil fumarate and emtricitabine (TDF/FTC) has been approved for pre-exposure prophylaxis (PrEP) in MSM in France following the results of clinical studies, but data are limited on real-world experience. DESIGN: A single-center, open-label, prospective cohort study that recruited people at high risk of HIV infection in Paris. METHODS: Participants were enrolled in a single hospital-based outpatient clinic and were proposed to start PrEP with daily or on demand TDF/FTC. At baseline and every 3 months thereafter, patients were tested for HIV and creatinine plasma levels, and data on sexual behavior, other sexually transmitted infections (STIs), and tolerability were collected. RESULTS: From 10 November 2015 to 30 April 2017, 1069 patients were screened and 1049 (98.1%) started PrEP. Median age was 36 years, 99.4% were MSM with a median number of partners of 10, and 793 (75.6%) opted for on demand PrEP. Over 486 person-years of follow-up, four HIV-infections were diagnosed in poorly or nonadherent patients (incidence 0.82/100 person-years). Rate of condomless sex at last intercourse increased from 53.3% at baseline to 79% at month 12 (P < 10), but increase in bacterial STI rates was modest (14.6% at baseline vs. 19.2% at month 12; P < 10). Most adverse events were gastrointestinal and did not lead to PrEP discontinuation. CONCLUSIONS: Most PrEP users were high-risk MSM and opted for on-demand PrEP. PrEP use was associated with a low HIV incidence and a high rate of condomless sex with a modest increase in bacterial STIs.

Efficacy and safety of a switch to rilpivirine-based regimens in treatment-experienced HIV-1-infected patients: a cohort study.

BACKGROUND: Rilpivirine (RPV) is a second-generation once-daily non-nucleoside reverse transcriptase inhibitor (NNRTI) which has shown non-inferior antiviral activity to efavirenz in treatment-naive patients. Data in treatment-experienced patients are more limited. We wished to assess the efficacy and safety of a switch to RPV-based regimens in well-suppressed treatment-experienced patients. METHODS: Between September 2012 and June 2013, all antiretroviral therapy (ART)-experienced HIV-1-infected patients with a plasma HIV RNA level <50 copies/ml, and switching to an RPV-based regimen, were analysed in this retrospective observational monocentric cohort study. The primary end point was the proportion of patients with virological success defined as a plasma HIV RNA level <50 copies/ml at 12 months using the FDA snapshot algorithm. RESULTS: A total of 281 participants were studied and 97% received a combination of RPV/tenofovir disoproxil fumarate/emtricitabine. At month 12, the rate of virological success was 59% and increased to 72% using available data beyond month 12. Sixteen (6%) patients experienced virological failure, which was associated with the presence of the M184V/I resistance mutation in prior genotypes (P=0.02) and the use of a non-NNRTI as third agent before the switch (P=0.03). RPV-based regimens were overall well tolerated and only 23 (8%) patients discontinued ART because of adverse events, mostly neuropsychiatric adverse events. Switching to RPV was associated with significant but modest improvement of the lipid profile. CONCLUSIONS: In patients fully suppressed on ART, a switch to an RPV-based regimen should only be considered in the absence of prior virological failure or resistance mutations to nucleoside reverse transcriptase inhibitors and NNRTIs to avoid virological failures.

On-Demand Preexposure Prophylaxis in Men at High Risk for HIV-1 Infection.

BACKGROUND: Antiretroviral preexposure prophylaxis has been shown to reduce the risk of human immunodeficiency virus type 1 (HIV-1) infection in some studies, but conflicting results have been reported among studies, probably due to challenges of adherence to a daily regimen. METHODS: We conducted a double-blind, randomized trial of antiretroviral therapy for preexposure HIV-1 prophylaxis among men who have unprotected anal sex with men. Participants were randomly assigned to take a combination of tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) or placebo before and after sexual activity. All participants received risk-reduction counseling and condoms and were regularly tested for HIV-1 and HIV-2 and other sexually transmitted infections. RESULTS: Of the 414 participants who underwent randomization, 400 who did not have HIV infection were enrolled (199 in the TDF-FTC group and 201 in the placebo group). All participants were followed for a median of 9.3 months (interquartile range, 4.9 to 20.6). A total of 16 HIV-1 infections occurred during follow-up, 2 in the TDF-FTC group (incidence, 0.91 per 100 person-years) and 14 in the placebo group (incidence, 6.60 per 100 person-years), a relative reduction in the TDF-FTC group of 86% (95% confidence interval, 40 to 98; P=0.002). Participants took a median of 15 pills of TDF-FTC or placebo per month (P=0.57). The rates of serious adverse events were similar in the two study groups. In the TDF-FTC group, as compared with the placebo group, there were higher rates of gastrointestinal adverse events (14% vs. 5%, P=0.002) and renal adverse events (18% vs. 10%, P=0.03). CONCLUSIONS: The use of TDF-FTC before and after sexual activity provided protection against HIV-1 infection in men who have sex with men. The treatment was associated with increased rates of gastrointestinal and renal adverse events. (Funded by the National Agency of Research on AIDS and Viral Hepatitis [ANRS] and others; ClinicalTrials.gov number, NCT01473472.).

Efficacy and safety of rilpivirine-based regimens in treatment-experienced HIV-1 infected patients: a prospective cohort study.

INTRODUCTION: Rilpivirine (RPV) is a new once-daily, non-nucleoside, reverse transcriptase inhibitor (NNRTI). In treatment-naïve patients, RPV has shown non-inferior antiviral activity to efavirenz but data in treatment-experienced patients are more limited. We assessed the efficacy and safety of RPV in treatment-experienced patients switching to a RPV-based regimen. METHODS: Between September 2012 and June 2013, all antiretroviral therapy (ART) experienced HIV-1 infected patients with a plasma HIV-RNA level <50 cp/mL, and switching to a RPV-based regimen, were enrolled in this prospective monocentric cohort study. Clinical and laboratory data were collected every 3 months to assess safety and efficacy. The primary endpoint was the proportion of patients with virologic success (HIV-RNA load <50 cp/mL) at 12 months using the FDA snapshot algorithm. RESULTS: A total of 281 patients (76% male, median age: 47 years, 56% MSM) were enrolled in this study. Median lymphocyte CD4 count at baseline was 640/mm(3). Patients have received ART for a median of 7 years and viral replication was fully suppressed for a median of 3 years. Before the switch, 39% patients were treated with NNRTI, 52% with protease inhibitor and 7% with integrase inhibitor-based regimens. Reasons for switch were simplification (176 cases), adverse events (AEs) (93 cases) and others (12 cases). At month 12 (database frozen on June 2014) in the snapshot analysis, 56% of patients met virologic success, 5% experienced virologic failure (n=14) and 39% had no data in the window period. In the LOCF analysis (using data from the previous available visit before month 12), 89% patients were suppressed, 5% had virologic failure and 6% had no data. Genotypic resistance analysis was performed in 7/14 patients at the time of virologic failure (3 of whom had previous NRTI/NNRTI resistance-associated mutations (RAMs)), and new NNRTI and NRTI RAMs emerged in 4 patients. RPV-based regimen was generally well tolerated and only 6% of patients discontinued treatment for AEs. Grade 2-4 treatment-related AEs occurred in 39 patients: 6 had rashes, 13 neuropsychiatric symptoms, 10 GI symptoms, 10 biological abnormalities. At month 12, significant changes from baseline were seen for total and LDL cholesterol (-0.5 and -0.28 mmol/L, respectively, p<0.05 for both), and plasma creatinine (+5.8 µmol/L, p<10-4). CONCLUSIONS: In patients fully suppressed on ART, switching to a RPV-based regimen in clinical practice was well tolerated and associated with few virologic failures.

Lopinavir/r no longer recommended as a first-line regimen: a comparative effectiveness analysis.

INTRODUCTION: We compared the effectiveness of tenofovir/emtricitabine (TDF/FTC) combined with either lopinavir/r (LPV/r) or another recommended third drug in the 2010 French guidelines in antiretroviral-naïve patients starting combination antiretroviral therapy in 2004-2008 in the French Hospital Database on HIV. METHODS: The outcomes were stop or switch of the third component, viral load (VL) <500 copies/ml, an increase of at least 100 CD4 cells/mm(3), AIDS-defining event and non-AIDS-defining hospitalization or death. Propensity scores were estimated by logistic regression based on the clinical centre and other confounders. In each clinical centre, each patient initiating LPV/r was matched with a patient initiating another third drug (efavirenz or atazanavir/r) and having a close propensity score. Cox's proportional hazards models were then used, with treatment as covariate. Time was right-censored at four years. RESULTS: 1269 patients started LPV/r plus TDF/FTC, and 890 could be matched to 890 patients receiving another third drug. Baseline characteristics were well balanced between these two groups. LPV/r was associated with a higher risk of third drug stop (hazard ratio (HR): 1.69; 95% confidence interval (CI), 1.42-2.00) and with less rapid viral suppression (HR: 0.83; 95% CI, 0.72-0.95). There was no difference in the time required for a CD4 cell increment of at least 100/mm(3), or to the occurrence of an AIDS-defining event. Non-AIDS-defining hospitalizations or deaths were more frequent with LPV/r (HR: 1.79; 95% CI, 1.33-2.39). CONCLUSIONS: For first-line therapy, in this observational setting, TDF/FTC plus LPV/r were less durable than TDF/FTC plus another recommended third drug, led to a less rapid viral suppression and were associated with a higher risk of non-AIDS morbidity.

French HIV experts on early antiretroviral treatment for prevention: uncertainty and heterogeneity.

Early use of highly active antiretroviral treatment (ART) in people living with HIV for HIV prevention has gained legitimacy but remains controversial. Nineteen French HIV experts with diverse specializations (over half of whom were clinicians) were qualitatively interviewed on their views about ART irrespective of CD4 count of more than 500 cells/mm3 for purposes of HIV prevention, which is not systematically recommended in France. Content analysis identified 2 broad categories: individual considerations (subcategories: patient health and well-being; patient preparedness and choice) and collective considerations (subcategories:HIV transmission risk; impact on the epidemic; cost). Uncertainty surrounded many experts' considerations, and unity was lacking on key issues (eg, candidacy for early preventive treatment, expected clinical- and population-level effects). An umbrella theme labeled "Weighing the merits of early ART in the face of uncertainties was identified. Our analyses raise doubts about the current acceptability of widespread implementation of early ART for HIV prevention in France.

Challenges and opportunities for oral pre-exposure prophylaxis in the prevention of HIV infection: where are we in Europe?

Following US Food and Drugs Administration approval in July 2012 of daily oral tenofovir and emtricitabine for pre-exposure prophylaxis (PrEP) to prevent HIV infection in high-risk individuals in the USA, there has been much controversy about the implementation of this PrEP regimen in other countries throughout the world, and in Europe in particular. In this review, we focus on the challenges and opportunities of a daily oral PrEP regimen to curb the rising incidence of HIV infection in high-risk groups, and particularly in men who have sex with men. A number of issues would need to be addressed before PrEP could be implemented, including assessing the real effectiveness and cost-effectiveness of daily PrEP, the sustainability of daily adherence, the risk of selecting resistance, the long-term safety, and the risk of change in sexual behavior that might offset the benefit of PrEP. Alternatives to a daily oral PrEP regimen are being explored.

Minimal interference: A basis for selecting ART for prevention with positives.

Given international interest in "treatment as prevention" (TasP) and the pertinence of optimizing antiretroviral treatment (ART) regimens for TasP, 19 French HIV experts were interviewed on their criteria for ART if used specifically for prevention with HIV-positive persons. Through content analysis of the interview material, nine criteria were identified. The most endorsed criteria, collectively, suggest a choice of treatment based on "minimal interference" where negative impacts of ART are minimized and ease of treatment integration maximized in the lives of people living with HIV/AIDS (PLHIV) for both the short and long term. These criteria were the tolerance, side effects, and/or toxicity profile of ART, simplicity (e.g., of treatment schedule, dosage form) and the individualization of treatment (e.g., adapted to lifestyle). While virologic efficacy (i.e., a durable, undetectable viral load) was also deemed important, several experts specified that it was virtually assured with current treatments. To a much lesser extent, experts endorsed diffusion of ART into the genital compartments, a strong genetic barrier (against resistance), validated treatments (as opposed to new classes of ART), a rapid reduction in HIV viral load, and treatment cost. Pharmacologically, minimal interference calls for further improvements in the tolerance, side effects and toxicity profile of ART and in the simplicity of ART administration. Clinically, it means avoiding a one-size-fits-all approach to ART in TasP and engagement with and of PLHIV in ART selection and side effects management. Strategically, it emphasises keeping the health and quality of life of PLHIV at the forefront of a TasP-oriented public health intervention.

Antiretroviral therapy initiation in France: adherence to national guidelines and outcome.

OBJECTIVES AND METHODS: Retrospective study of all patients who started antiretroviral therapy (ART) in 2007 in a single center in Paris, with baseline characteristics and 1-year outcome, to assess adherence to national guidelines. RESULTS: We analyzed 118 patients. Time of ART initiation was in agreement with the guidelines for only 64 (54.2%) patients. Fifty patients (42%) started ART with AIDS or a CD4 count <200 cells/mm(3). In all, 62 (52%) and 47 patients (40%) received a combination of 2 nucleoside analogues with efavirenz (EFV) and 1 ritonavir-boosted protease inhibitor (PI/r), respectively. Treatment regimens were in accordance with the guidelines for 114 patients (97%). At 1 year, 16 patients (13.5%) were lost to follow-up, only 5 (4.9%) experienced HIV disease progression or death, but 19 (18.6%) required hospitalization. Antiretroviral therapy was changed in 21 patients (21%). Ten patients (8.4%) experienced virologic failure. CONCLUSION: Antiretroviral therapy was in agreement with guidelines for the choice of combination but was often initiated too late.

Four year follow-up of simplification therapy with once-daily emtricitabine, didanosine and efavirenz in HIV-infected patients (ALIZE ANRS 099 trial).

BACKGROUND: once-daily combinations of efavirenz and two nucleoside analogues are recommended for the treatment of HIV infection. Long-term efficacy and safety data are scarce for the combination of efavirenz, emtricitabine and didanosine. METHODS: the ALIZE ANRS 099 trial enrolled 355 adults with plasma HIV RNA levels of <400 copies/mL under a protease inhibitor-based regimen, who were randomized to remain on this regimen or to switch to a once-daily regimen of emtricitabine, didanosine and efavirenz for 48 weeks. An extended 4 year follow-up was available for the 178 patients who switched to the efavirenz-containing regimen, and assessed plasma HIV RNA levels, CD4 cell counts, safety and tolerability. RESULTS: after a median follow-up of 42 months, 121 patients (68%) remained on an efavirenz-based regimen, and 62% and 57% had plasma HIV RNA levels of <400 and <50 copies/mL, respectively, in an intent-to-continue analysis with missing data and treatment discontinuation considered as failure. There was a significant increase in CD4 cell count of 41 cells/mm(3). Drug-related adverse events were the main reason for treatment discontinuation in 26 patients (15%), and 15 were reported during the first year of therapy (58%). There was no emergence of clinically defined lipodystrophy, and lipid and glucose profiles were favourable with a significant increase from baseline of high-density lipoprotein cholesterol levels (median increase 12 mg/dL, P < 10(-4)). CONCLUSIONS: a once-daily regimen of emtricitabine, didanosine and efavirenz provided a durable antiretroviral response and was well tolerated through 4 years of therapy.

Sensitivity of five rapid HIV tests on oral fluid or finger-stick whole blood: a real-time comparison in a healthcare setting.

BACKGROUND: Health authorities in several countries recently recommended the expansion of human immunodeficiency virus (HIV) antibody testing, including the use of rapid tests. Several HIV rapid tests are now licensed in Europe but their sensitivity on total blood and/or oral fluid in routine healthcare settings is not known. METHODS AND FINDINGS: 200 adults with documented HIV-1 (n=194) or HIV-2 infection (n=6) were prospectively screened with five HIV rapid tests using either oral fluid (OF) or finger-stick whole blood (FSB). The OraQuick Advance rapid HIV1/2 was first applied to OF and then to FSB, while the other tests were applied to FSB, in the following order: Vikia HIV 1/2, Determine HIV 1-2, Determine HIV-1/2 Ag/Ab Combo and INSTI HIV-1/HIV-2. Tests negative on FSB were repeated on paired serum samples. Twenty randomly selected HIV-seronegative subjects served as controls, and the results were read blindly. Most patients had HIV-1 subtype B infection (63.3%) and most were on antiretroviral therapy (68.5%). Sensitivity was 86.5%, 94.5%, 98.5%, 94.9%, 95.8% and 99% respectively, with OraQuick OF, OraQuick FSB, Vikia, Determine, Determine Ag/Ab Combo and INSTI (p<0.0001). OraQuick was less sensitive on OF than on FSB (p=0.008). Among the six patients with three or more negative tests, two had recent HIV infection and four patients on antiretroviral therapy had undetectable plasma viral load. When patients positive in all the tests were compared with patients who had at least one negative test, only a plasma HIV RNA level<200 cp/ml was significantly associated with a false-negative result (p=0.009). When the 33 rapid tests negative on FSB were repeated on serum, all but six (5 negative with OraQuick, 1 with INSTI) were positive. The sensitivity of OraQuick, Determine and Determine Ag/Ab Combo was significantly better on serum than on FSB (97.5%, p=0.04; 100%, p=0.004; and 100%, p=0.02, respectively). CONCLUSION: When evaluated in a healthcare setting, rapid HIV tests were less sensitive on oral fluid than on finger-stick whole blood and less sensitive on finger-stick whole blood than on serum.

Effect of pioglitazone on HIV-1-related lipodystrophy: a randomized double-blind placebo-controlled trial (ANRS 113).

BACKGROUND: Although thiazolidinediones have been shown to increase subcutaneous fat in congenital lipodystrophy, rosiglitazone did not show convincing results in HIV lipoatrophy. We assess a potential specific effect of pioglitazone in this setting. METHODS: One-hundred and thirty HIV-1-infected adults with self-reported lipoatrophy confirmed by physical examination were randomized to receive pioglitazone 30 mg once daily (n=64) or placebo (n=66) for 48 weeks. Changes in limb fat between weeks 0 and 48 were measured using dual-energy Xray absorptiometry. Subcutaneous and visceral fat was measured by single-slice computed tomography; fasting plasma measurements of glucose, insulin and lipids levels were recorded. RESULTS: Limb fat increased by 0.38 kg in the pioglitazone group and 0.05 kg in the placebo group at week 48 (mean difference 0.33 kg, 95% confidence interval [CI] 0.10-0.56; P=0.051) by intention-to-treat analysis. In patients not receiving stavudine, an increase of 0.45 kg versus 0.04 kg was observed (mean difference, 0.40 kg, 95% CI 0.12-0.69; P=0.013), but this was not seen in patients on stavudine (n=36; P=0.404). Overall, there was no significant difference in subcutaneous abdominal fat or in visceral fat areas on computed tomography at L4 vertebra. The lipid profile was not significantly different at week 48 except for levels of high-density lipoprotein cholesterol, which was improved in the pioglitazone group (+0.08 mmol/l versus -0.08; P=0.005). CONCLUSIONS: Pioglitazone 30 mg once daily for 48 weeks improved limb fat atrophy in antiretroviral-treated HIV-1-infected patients, although clinical benefits were not perceived by the patients. Treatment did lead to a favourable lipid profile, however, suggesting that this thiazolidinedione should be considered in the context of HIV-related lipoatrophy.