Perception of PrEP-related stigma in PrEP users: Results from the ANRS-PREVENIR cohort.

INTRODUCTION: Since the advent of HIV pre-exposure prophylaxis (PrEP), stigma has been shown to be a major barrier to its uptake and adherence. It is therefore essential to define the proportion of users who consider that PrEP can negatively impact their image and the factors associated with this perception. METHOD: We performed a multivariable logistic regression on data from the 2567 participants in the ANRS-PREVENIR study who answered the outcome question. RESULTS: Almost one-third of the sample (comprising mostly cisgender men who have sex with men [94.3%]) considered that taking PrEP could give others a negative image of them. Younger participants (adjusted odds ratio [aOR] 0.98; 95% confidence interval [CI] 0.97-0.99) and more psychologically vulnerable participants (i.e., lower self-esteem score [aOR 0.98; 95% CI 0.96-0.99] and higher depression score [aOR 1.02; 95% CI 1.00-1.03]) were also more likely to have this perception. In contrast, participants encouraged to take PrEP by their main partner (aOR 0.67; 95% CI 0.51-0.88) and friends (aOR 0.79; 95% CI 0.66-0.95), and those who protected themselves more because they had knowledge of their most recent sexual partner's HIV status (aOR 0.83; 95% CI 0.69-0.99) and systematic use of PrEP and/or condoms during intercourse in the previous 3 months (aOR 0.80; 95% CI 0.67-0.96) were less likely to have this perception. DISCUSSION: Given the strong interrelation between stigmatization (real or perceived), risky behaviours and adherence, our results emphasize the need for HIV prevention campaigns to promote a positive image of PrEP users. They also show that stigmatization and its effects need to be fully considered to improve HIV prevention offers to current and potential PrEP users who are most likely to be psychologically vulnerable.

How PrEP users constitute a community in the MSM population through their specific experience and management of stigmatization. The example of the French ANRS-PREVENIR study.

The ANRS-PREVENIR (2017-2020) prospective cohort study aims to reduce the number of new HIV infections in the "Ile-de-France" region in France, by enrolling individuals at high risk of HIV infection and proposing daily and on-demand pre-exposure prophylaxis (PrEP). The qualitative component of the ANRS-PREVENIR study aimed to investigate social and relational evolutions associated with PrEP use in men who have sex with men (MSM). In 2018, 12 focus groups with MSM (n = 68) were conducted by a social sciences researcher in Paris. A thematic analysis was performed. Results showed that stigma concerning PrEP use is a complex issue, with various kinds of stigmatization being practiced, sometimes even by the wider MSM population and PrEP users themselves. All types of stigma identified were expressed in forms of verbal abuse which made PrEP use taboo. Inside the wider MSM population a PrEP-user "community" was identified which shared a certain complicity in terms of values and a positive attitude towards PrEP. The emergence of new intragroup and intergroup social norms should be taken into account by policy makers to promote a more positive image of PrEP users.

First year of pre-exposure prophylaxis implementation in France with daily or on-demand tenofovir disoproxil fumarate/emtricitabine.

BACKGROUND: In January 2016, the French Medicine Agency initiated a Temporary Recommendation for Use (TRU) to allow the use of oral intake of tenofovir disoproxil fumarate and emtricitabine for pre-exposure prophylaxis (PrEP) in adults at high risk of HIV. We report the results of the first year of PrEP implementation in France. METHODS: Data were collected by physicians using a secured web subject-monitoring interface, with two forms: an initiation form, with patients' baseline characteristics, and an HIV seroconversion form. Univariate and adjusted multivariate analysis using a logistic regression model were performed to identify baseline factors associated with on-demand PrEP regimen prescription. RESULTS: From 4 January 2016 to 28 February 2017, 3405 subjects were enrolled, with 2774 initiation forms completed; 98.1% were male and 96.9% were MSM. An on-demand regimen was prescribed to 57% of subjects. Older age (OR for participants older than 50 years = 1.76, 95% CI 1.35-2.3, P < 0.001) and site of prescription (OR of former IPERGAY sites = 2.28, 95% CI 1.84-2.83, P < 0.001) were associated with on-demand prescription. Those reporting sexually transmitted infection (STI) and condomless anal sex with at least two different partners were less likely to receive on-demand PrEP (OR = 0.68, 95% CI 0.57-0.82 and 0.75, 95% CI 0.57-0.98, respectively; P < 0.05 for all). Four breakthrough HIV infections were reported during the study, in the context of PrEP interruption or acute infection at the time of PrEP initiation. CONCLUSIONS: In a real-life setting in France, PrEP was used, either daily or on-demand, mostly by MSM, with breakthrough infections being rare.

Lessons learned from the experiences of informal PrEP users in France: results from the ANRS-PrEPage study.

Before January 2016, Pre-Exposure Prophylaxis (PrEP), a new biomedical HIV-prevention tool, was only available in France via ANRS-Ipergay clinical study but informal use was reported outside this setting. PrEPage qualitative study reports profiles and experiences of participants who used PrEP outside of a biomedical trial before this prevention method was authorized. Between March 2015 and February 2016, a cross-section of twenty-four informal PrEP users, mostly MSM, was recruited to complete in-depth semi-structured interviews. While ANRS-Ipergay was still ongoing (2012-2016), participants described their initiation to PrEP, the way they used it and the difficulties they faced to acquire antiretroviral drugs in an environment where PrEP was still not widely known and often criticized . Through the testimonies, different user profiles and motivation toward informal PrEP use emerged: (a) participants who have increasing difficulties using condoms, (b) "opportunists" who tried PrEP without the intention of using it regularly and (c) participants with a risk aversion who sought additional protection against HIV. Participants chose to use PrEP and/or their usual prevention strategies depending on available supplies, type of partners and individual attitudes toward risk. The feeling of living a safer sex life helped participants to outweigh the fear of possible toxicity and drug resistance. Participants' needs and expectations about PrEP implementation in France were also presented.

Reference curves for CD4 T-cell count response to combination antiretroviral therapy in HIV-1-infected treatment-naïve patients.

OBJECTIVES: The aim of this work was to provide a reference for the CD4 T-cell count response in the early months after the initiation of combination antiretroviral therapy (cART) in HIV-1-infected patients. METHODS: All patients in the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) cohort who were aged ≥ 18 years and started cART for the first time between 1 January 2005 and 1 January 2010 and who had at least one available measurement of CD4 count and a viral load ≤ 50 HIV-1 RNA copies/mL at 6 months (± 3 months) after cART initiation were included in the study. Unadjusted and adjusted references curves and predictions were obtained using quantile regressions. RESULTS: A total of 28 992 patients were included in the study. The median CD4 T-cell count at treatment initiation was 249 [interquartile range (IQR) 150, 336] cells/µL. The median observed CD4 counts at 6, 9 and 12 months were 382 (IQR 256, 515), 402 (IQR 274, 543) and 420 (IQR 293, 565) cells/µL. The two main factors explaining the variation of CD4 count at 6 months were AIDS stage and CD4 count at cART initiation. A CD4 count increase of ≥ 100 cells/mL is generally required in order that patients stay 'on track' (i.e. with a CD4 count at the same percentile as when they started), with slightly higher gains required for those starting with CD4 counts in the higher percentiles. Individual predictions adjusted for factors influencing CD4 count were more precise. CONCLUSIONS: Reference curves aid the evaluation of the immune response early after antiretroviral therapy initiation that leads to viral control.

Higher rates of triple-class virological failure in perinatally HIV-infected teenagers compared with heterosexually infected young adults in Europe.

OBJECTIVES: The aim of the study was to determine the time to, and risk factors for, triple-class virological failure (TCVF) across age groups for children and adolescents with perinatally acquired HIV infection and older adolescents and adults with heterosexually acquired HIV infection. METHODS: We analysed individual patient data from cohorts in the Collaboration of Observational HIV Epidemiological Research Europe (COHERE). A total of 5972 participants starting antiretroviral therapy (ART) from 1998, aged < 20 years at the start of ART for those with perinatal infection and 15-29 years for those with heterosexual infection, with ART containing at least two nucleoside reverse transcriptase inhibitors (NRTIs) and a nonnucleoside reverse transcriptase inhibitor (NNRTI) or a boosted protease inhibitor (bPI), were followed from ART initiation until the most recent viral load (VL) measurement. Virological failure of a drug was defined as VL > 500 HIV-1 RNA copies/mL despite ≥ 4 months of use. TCVF was defined as cumulative failure of two NRTIs, an NNRTI and a bPI. RESULTS: The median number of weeks between diagnosis and the start of ART was higher in participants with perinatal HIV infection compared with participants with heterosexually acquired HIV infection overall [17 (interquartile range (IQR) 4-111) vs. 8 (IQR 2-38) weeks, respectively], and highest in perinatally infected participants aged 10-14 years [49 (IQR 9-267) weeks]. The cumulative proportion with TCVF 5 years after starting ART was 9.6% [95% confidence interval (CI) 7.0-12.3%] in participants with perinatally acquired infection and 4.7% (95% CI 3.9-5.5%) in participants with heterosexually acquired infection, and highest in perinatally infected participants aged 10-14 years when starting ART (27.7%; 95% CI 13.2-42.1%). Across all participants, significant predictors of TCVF were those with perinatal HIV aged 10-14 years, African origin, pre-ART AIDS, NNRTI-based initial regimens, higher pre-ART viral load and lower pre-ART CD4. CONCLUSIONS: The results suggest a beneficial effect of starting ART before adolescence, and starting young people on boosted PIs, to maximize treatment response during this transitional stage of development.

HIV-1 subtype influences susceptibility and response to monotherapy with the protease inhibitor lopinavir/ritonavir.

OBJECTIVE: PI susceptibility results from a complex interplay between protease and Gag proteins, with Gag showing wide variation across HIV-1 subtypes. We explored the impact of pre-treatment susceptibility on the outcome of lopinavir/ritonavir monotherapy. METHODS: Treatment-naive individuals who experienced lopinavir/ritonavir monotherapy failure from the MONARK study were matched (by subtype, viral load and baseline CD4 count) with those who achieved virological response ('successes'). Successes were defined by viral load <400 copies/mL after week 24 and <50 copies/mL from week 48 to week 96. Full-length Gag-protease was amplified from patient samples for in vitro phenotypic susceptibility testing, with susceptibility expressed as fold change (FC) relative to a subtype B reference strain. RESULTS: Baseline lopinavir susceptibility was lower in viral failures compared with viral successes, but the differences were not statistically significant (median lopinavir susceptibility: 4.4 versus 8.5, respectively, P = 0.17). Among CRF02_AG/G patients, there was a significant difference in lopinavir susceptibility between the two groups (7.1 versus 10.4, P = 0.047), while in subtype B the difference was not significant (2.7 versus 3.4, P = 0.13). Subtype CRF02_AG/G viruses had a median lopinavir FC of 8.7 compared with 3.1 for subtype B (P = 0.001). CONCLUSIONS: We report an association between reduced PI susceptibility (using full-length Gag-protease sequences) at baseline and subsequent virological failure on lopinavir/ritonavir monotherapy in antiretroviral-naive patients harbouring subtype CRF02_AG/G viruses. We speculate that this may be important in the context of suboptimal adherence in determining viral failure.

Phylogenetic investigation of HCV-4d epidemic in Paris MSM HIV population reveals a still active outbreak and a strong link to the Netherlands.

OBJECTIVES: The hepatitis C virus (HCV) epidemic is evolving quickly despite new treatments, and due to behaviour changes increasing at-risk situations. We investigated potential origins and evolution of the HCV-4d French emergence among human immunodeficiency virus (HIV)-infected men who have sex with men (MSM), in Paris in 2003. METHODS: We analysed all HCV sequences from the initial Paris outbreak with all newly available sequences publicly available, including sampling date and geographical location, resulting in 184, 68, 156, 107, 13 and 2 sequences from France, The Netherlands, other European countries, Africa, the Middle East or Turkey, Americas and Asia, respectively. Phylogenetic reconstruction was performed using maximum likelihood and Bayesian approaches. RESULTS: HCV-4d sequences from Europe were strongly separated from non-European sequences. Sequences from the initial Paris outbreak were all included into two well-separated and supported clusters with branch support at 100%, mean genetic distance <2.8 substitutions/100 nucleotides and >3.4 substitutions/100 nucleotides between their common ancestor and the previous node. The largest cluster interleaved French (n = 98) and Dutch (n = 28) sequences, suggesting several translocations between these countries. This cluster included 41 French sequences from Lyon sampled after 2014, highlighting its continuous spread within France since the initial outbreak. The smallest cluster included one Paris sequence with UK sequences (n = 9). DISCUSSION: A few previous works have shown HCV-4d transmissions occurring between a few countries. In our work, we suggest a new and large connection between France and The Netherlands MSM communities and highlight a well-separated pan-European transmission network. Large collaborative networks are needed to investigate ongoing transmissions across countries and help specific prevention measures.

[Autoimmune myelofibrosis with dermatomyositis]. / Myélofibrose auto-immune secondaire à une dermatomyosite.

We report a second observation of autoimmune myelofibrosis associated with an inflammatory myositis in a 30-year-old female. The links between myelofibrosis and autoimmunity are discussed.

[Evaluation of compliance with antiretroviral treatment in a cohort of 200 patients in Djibouti, 2005]. / Evaluation de l'observance au traitement antirétroviral au sein d'une cohorte de 200 patients à Djibouti (2005).

We determined the rate of compliance with antiretroviral therapy and investigated the factors that influence it among 86 HIV patients. Compliance ratio (number of tablets taken/number prescribed) was assessed by tablet count. The mean ratio of compliance was 92%. By tablet count, 77% of the patients were compliant (compliance ratio > or =90%). Non-compliance was significantly associated with side-effects, degree of confidentiality of the care centre and travelling. Compliance correlated significantly with viral load. In multivariate analysis, community support and level of education protected against non-compliance. Patients having already missed a dose and those dissatisfied with confidentiality had a 4 times greater risk of non-compliance.

Acute hepatitis C infection in HIV positive men who have sex with men in Paris, France, 2001-2004.

In mid-2004, three Parisian hospital wards informed the Institut de veille sanitaire of recent acute hepatitis C in HIV-infected (HIV+) men who had sex with men (MSM). These cases for whom none of the usual bloodborne routes for hepatitis C (HCV) transmission was found, reported having had unprotected sex. In October 2004, we conducted a retrospective investigation in Parisian hospital wards to explore HCV modes of transmission in recent acute hepatitis C in HIV+ MSM. Patient demographics, clinical and biological status of HIV infection, reasons for HCV testing, sexual behaviour and risk factors for HCV transmission within the 6 months before hepatitis onset were collected from medical records. An anonymous self-administered questionnaire on sexual behaviour within the six months before hepatitis onset was also offered to all cases. We identified 29 cases of acute hepatitis C in HIV+ MSM with onset from April 2001 to October 2004. HIV infection was asymptomatic for 76%. Median age at hepatitis C onset was 40 (28-54) years. In all records, were noted unprotected anal sex, fisting in 21% and a concomitant sexually transmitted infection (STI) in 41%. Median time between HIV diagnosis and HCV infection was 6.5 years (0-22). From the 11 self-administered questionnaires completed, 10 reported an STI, 8 'hard' sexual practices, 6 bleeding during sex and 5 fisting. HCV transmission probably occurred through bleeding during unprotected traumatic anal sex among HIV+ MSM and may be facilitated by STI mucosal lesions. This report stresses the continuous need to strongly advocate safer sex to MSM.

[Male genital tract infection: the point of view of the virologist]. / Infection du tractus génital masculin: le point de vue du virologue.

Attention to viral infection of the male genital tract has been renewed over the last 15 years as a result of the prolific ongoing research on AIDS. Epidemiological studies of the virus in sperm and male genital tract contributes to the understanding of STD physiopathology and helps assessing their impact on male fertility. Recent advances in this field have allowed to offer Assisted reproductive techniques to couples with chronic viral infection, under strict and specific protocols. This paper presents an overview of these recent developments.

Bias learning, knowledge sharing.

Biasing properly the hypothesis space of a learner has been shown to improve generalization performance. Methods for achieving this goal have been proposed, that range from designing and introducing a bias into a learner to automatically learning the bias. Multitask learning methods fall into the latter category. When several related tasks derived from the same domain are available, these methods use the domain-related knowledge coded in the training examples of all the tasks as a source of bias. We extend some of the ideas presented in this field and describe a new approach that identifies a family of hypotheses, represented by a manifold in hypothesis space, that embodies domain-related knowledge. This family is learned using training examples sampled from a group of related tasks. Learning models trained on these tasks are only allowed to select hypotheses that belong to the family. We show that the new approach encompasses a large variety of families which can be learned. A statistical analysis on a class of related tasks is performed that shows significantly improved performances when using this approach.

[Legionellosis in HIV-1 infected patients. 4 case reports]. / Légionellose chez les patients infectés par le VIH-1. 4 observations.

INTRODUCTION: Contrary to patients exhibiting cellular immunodepression, legionellosis is rare in HIV-infected patients. We report 4 cases. OBSERVATIONS: Four men aged 41 to 48 were infected by HIV-1. Three of them were treated with antiretroviral therapy. The clinical and biological manifestations were unspecific. Evolution was favourable with adapted antibiotic therapy (erythromycine for three patients and ciprofloxacine for the fourth). COMMENTS: Legionella pneumophila serotype Lp1 remains the principle etiological agent. Frequent use of contrimoxazole in prophylaxis against pneumocystosis and toxoplasmosis, macrolides, rifamycines and fluoroquinolones in the preventive and curative treatment of mycobacterioses, and the relative conservation of monocyte/macrophage function and immune repair with efficient antiretroviral therapy, may explain the low prevalence of this disease in HIV infections.

Prevalence of CXCR4-tropic viruses in clustered transmission chains at the time of primary HIV-1 infection.

During 2003-2010, 555 strains isolated from sexually-infected patients at the time of primary HIV-1 infection (PHI) were characterized. Tree topology revealed that 11.7% of PHIs segregated into transmission clusters. CXCR4-usage was identified in 27 strains (4.9%) and was significantly associated with subtype B (p 0.003) and low CD4 cell count (p 0.01). In clustered and unique PHIs, the prevalence of CXCR4-tropic strains was 1.5% and 5.3%, respectively (p 0.35). Our results are in line with the hypothesis of a mucosal bottleneck contributing to the high prevalence of CCR5 variants during PHI.

[Enhancing immune restoration in human immunodeficiency virus infection]. / Stratégies de restauration immunitaire chez les patients infectés par le virus de l'immunodéficience humaine.

The primary objective of antiretroviral therapy has recently evolved from a virologic endpoint towards the achievement of normal CD4T cell count (greater than 500/mm(3)) to avoid progression to AIDS. This shift in the primary objective is supported by many clinical and epidemiological studies. Recent data have shown that HIV-infected adults with a CD4T cell count greater than 500cells/mm(3) on long-term combination antiretroviral therapy reach same mortality rates as the general population. However, less than 50% of patients receiving long-term suppressive antiretroviral combination reach such a CD4T cell level. New antiretroviral strategies to improve immune reconstitution, such as specific or non-specific immune-based therapy on one hand and the use of novel antiretroviral drugs from new classes on the other hand are currently under investigation. Here we review several current strategies that may improve immune reconstitution, keeping in mind that the best way to reach normal CD4T cell count is an early treatment initiation.

Hospitalization for gastrointestinal bleeding associated with non-steroidal anti-inflammatory drugs among elderly patients using low-dose aspirin: a retrospective cohort study.

OBJECTIVES: Many elderly patients are prescribed both low-dose aspirin (ASA), for cardiovascular protection and non-steroidal anti-inflammatory drugs (NSAIDs) for pain control. Compared with non-selective NSAIDs (NS-NSAIDs), celecoxib has a superior gastrointestinal (GI) safety profile in general. It is unclear, however, whether this fact holds good among patients taking ASA. We compared GI hospitalization rates among elderly patients taking celecoxib, NS-NSAIDs, celecoxib and ASA or NS-NSAIDs and ASA. METHODS: This was a retrospective cohort study using Quebec government databases. All patients 65 yrs of age or older who filled a prescription for celecoxib or an NS-NSAID between April 1999 and December 2002 were included. Cox regression models were used to compare the GI hospitalization rates between the four exposure categories adjusting for potential confounders. RESULTS: A total of 332 491 patients were included. Among 1 522 307 celecoxib prescriptions, 430 214 were filled by patients concurrently receiving ASA (celecoxib and ASA); 195 369 of 863 646 NS-NSAID prescriptions were filled by patients receiving ASA (NS-NSAID and ASA). Celecoxib without ASA was less likely than NS-NSAID without ASA to be associated with GI hospitalization [hazard ratio (HR) 0.41, 95% confidence interval (CI) 0.33-0.50]; celecoxib and ASA was also less likely to be associated with GI hospitalization than NS-NSAID and ASA (HR 0.62, 95% CI 0.48-0.80); GI hospitalization rates were similar for celecoxib and ASA and NS-NSAID without ASA (HR 1.01, 95% CI 0.81-1.25). CONCLUSION: Among elderly patients receiving cardiovascular protection with ASA and pain control with anti-inflammatory drugs, celecoxib may be safer with regards to GI toxicity than NS-NSAIDs.

Antiviral activity of low-dose alovudine in antiretroviral-experienced patients: results from a 4-week randomized, double-blind, placebo-controlled dose-ranging trial.

BACKGROUND: Alovudine inhibits replication of highly nucleoside reverse transcriptase inhibitor (NRTI)-resistant HIV strains in vitro. However, dose-dependent safety concerns resulted in its initial development being halted. Recently, a 4-week course of alovudine 7.5 mg/day added to a stavudine-free failing regimen yielded a significant decrease in viral load by -1.88 log(10) HIV-1 RNA copies/mL. The magnitude of the reduction in viral load suggested that lower doses might still be effective while offering adequate safety during long-term use. OBJECTIVE: To determine whether lower dosages of alovudine still provide significant antiviral activity in patients with broad NRTI resistance. METHODS: A randomized, double-blind, placebo-controlled trial investigating three doses of alovudine (0.5, 1 and 2 mg) or placebo added for 4 weeks to a failing regimen in patients with evidence of NRTI-resistant HIV strains [>or=2 thymidine-associated mutations (TAMs)]. The primary endpoint was the mean viral load reduction between baseline and week 4. RESULTS: Seventy-two patients were enrolled in the study: 21, 13, 18 and 20 in the placebo and 0.5, 1 and 2 mg arms, respectively. Baseline median CD4 count and viral load were 298 cells/microL (range 44-692 cells/microL) and 3.9 log(10) copies/mL (range 2.5-5.2 log(10) copies/mL), respectively. Baseline viral isolates harboured a median of four TAMs. Alovudine was added to a median four-drug failing regimen. At week 4, compared with placebo, mean viral load changes were -0.42 log(10) [95% confidence interval (CI) -0.67 to -0.18] and -0.30 log(10) (-0.55 to -0.06) in the 2 and 1 mg arms, respectively. There was no significant change in CD4 cell count. Alovudine was well tolerated. CONCLUSION: A 4-week course of alovudine 2 mg/day provided a modest but significant viral load reduction in patients harbouring viruses with a median of four TAMs.