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Drawing on lessons learned from community experiences in concentrated epidemics, this paper explores three imperatives in the effort to reduce the sexual transmission of HIV: combat prevention fatigue, diversify HIV testing and combat stigma and discrimination. The paper argues for a non‐judgmental harm reduction approach to the prevention of sexual transmission of HIV that takes into account the interpretation of risk by diverse individuals and communities in the era of antiretroviral therapy. This approach requires greater attention to increasing access to opportunities to know one's serostatus, especially among key populations at greater risk. Novel approaches to diversifying HIV testing approaches at community level are needed. Finally, the paper makes a plea for bold measures to combat stigma and discrimination, which continues to represent a formidable barrier for access to services for affected populations and may contribute to HIV‐related risk behaviours. A "triple therapy" approach to address stigma and discrimination is discussed, which includes greater acceptance of people living with HIV and AIDS (PLWHA), improving relevant laws and policies, and involving prevention users‐ working with people rather than for people‐.Note: this paper corresponds to the plenary talk of Bruno Spire at the XVIIth World AIDS Conference, August 8th, Mexico city: http://www.kaisernetwork.org/health_cast/player.cfm?id=4383

Combination antiretroviral therapy (cART) has led to a major reduction in HIV‐related mortality and morbidity. However, HIV still cannot be cured. With the absence of an effective prophylactic or therapeutic vaccine, increasing numbers of infected people, emerging new toxicities secondary to cART and the need for life‐long treatment, there is now a real urgency to find a cure for HIV.There are currently multiple barriers to curing HIV. The most significant barrier is the establishment of a latent or "silent" infection in resting CD4+ T cells. In latent HIV infection, the virus is able to integrate into the host cell genome, but does not proceed to active replication. As a consequence, antiviral agents, as well as the immune system, are unable to eliminate these long‐lived, latently infected cells. Reactivation of latently infected resting CD4+ T cells can then re‐establish infection once cART is stopped. Other significant barriers to cure include residual viral replication in patients receiving cART, even when the virus is not detectable by conventional assays. In addition, HIV can be sequestered in anatomical reservoirs, such as the brain, gastrointestinal tract and genitourinary tract.Achieving either a functional cure (long‐term control of HIV in the absence of cART) or a sterilizing cure (elimination of all HIV‐infected cells) remains a major challenge. Several studies have now demonstrated that treatment intensification appears to have little impact on latent reservoirs. Some potential and promising approaches that may reduce the latent reservoir include very early initiation of cART and the use of agents that could potentially reverse latent infection.Agents that reverse latent infection will promote viral production; however, simultaneous administration of cART will prevent subsequent rounds of viral replication. Such drugs as histone deacetylase inhibitors, currently used and licensed for the treatment of some cancers, or activating latently infected resting cells with cytokines, such as IL‐7 or prostratin, show promising results in reversing latency in vitro when used either alone or in combination. In order to move forward toward clinical trials that target eradication, there needs to be careful consideration of the risks and benefits of these approaches, agreement on the most informative endpoints for eradication studies and greater engagement of the infected community.

International audience ; AbstractBackgroundCocaine use is frequent in patients receiving methadone maintenance treatment (MMT) and can jeopardize their treatment response. Identifying clinical predictors of cocaine use during methadone treatment can potentially improve clinical management. We used longitudinal data from the ANRS Methaville trial both to describe self-reported occasional and regular cocaine use during MMT and to identify clinical predictors.MethodsWe selected 183 patients who had data on cocaine (or crack) use at months 0 (M0), M6, and/or M12, accounting for 483 visits. The outcome was "cocaine use" in three categories: "no," "occasional," and "regular" use. To identify factors associated with the outcome over time, we performed a mixed multinomial logistic regression.ResultsTime on methadone was significantly associated with a decrease in occasional but not in regular cocaine use from 14.7 % at M0 to 7.1 % at M12, and from 10.7 % at baseline to 6.5 % at M12, respectively. After multiple adjustments, opiate injection, individuals screening positive for attention deficit hyperactivity disorder (ADHD) symptoms, and those presenting depressive symptoms were more likely to regularly use cocaine.ConclusionsAlthough time on MMT had a positive impact on occasional cocaine use, it had no impact on regular cocaine use. Moreover, regular cocaine users were more likely to report opiate injection and to present ADHD and depressive symptoms. Early screening of these disorders and prompt tailored pharmacological and behavioral interventions can potentially reduce cocaine use and improve response to MMT.Trial registrationThe trial is registered with the French Agency of Pharmaceutical Products (AFSSAPS) under the number 2008-A0277-48, the European Union Drug Regulating Authorities Clinical Trials, number Eudract 2008-001338-28, the ClinicalTrials.gov Identifier: NCT00657397, and the International Standard Randomised Controlled Trial Number Register ISRCTN31125511.

International audience ; AbstractBackgroundCocaine use is frequent in patients receiving methadone maintenance treatment (MMT) and can jeopardize their treatment response. Identifying clinical predictors of cocaine use during methadone treatment can potentially improve clinical management. We used longitudinal data from the ANRS Methaville trial both to describe self-reported occasional and regular cocaine use during MMT and to identify clinical predictors.MethodsWe selected 183 patients who had data on cocaine (or crack) use at months 0 (M0), M6, and/or M12, accounting for 483 visits. The outcome was "cocaine use" in three categories: "no," "occasional," and "regular" use. To identify factors associated with the outcome over time, we performed a mixed multinomial logistic regression.ResultsTime on methadone was significantly associated with a decrease in occasional but not in regular cocaine use from 14.7 % at M0 to 7.1 % at M12, and from 10.7 % at baseline to 6.5 % at M12, respectively. After multiple adjustments, opiate injection, individuals screening positive for attention deficit hyperactivity disorder (ADHD) symptoms, and those presenting depressive symptoms were more likely to regularly use cocaine.ConclusionsAlthough time on MMT had a positive impact on occasional cocaine use, it had no impact on regular cocaine use. Moreover, regular cocaine users were more likely to report opiate injection and to present ADHD and depressive symptoms. Early screening of these disorders and prompt tailored pharmacological and behavioral interventions can potentially reduce cocaine use and improve response to MMT.Trial registrationThe trial is registered with the French Agency of Pharmaceutical Products (AFSSAPS) under the number 2008-A0277-48, the European Union Drug Regulating Authorities Clinical Trials, number Eudract 2008-001338-28, the ClinicalTrials.gov Identifier: NCT00657397, and the International Standard Randomised Controlled Trial Number Register ISRCTN31125511.

International audience ; AbstractBackgroundCocaine use is frequent in patients receiving methadone maintenance treatment (MMT) and can jeopardize their treatment response. Identifying clinical predictors of cocaine use during methadone treatment can potentially improve clinical management. We used longitudinal data from the ANRS Methaville trial both to describe self-reported occasional and regular cocaine use during MMT and to identify clinical predictors.MethodsWe selected 183 patients who had data on cocaine (or crack) use at months 0 (M0), M6, and/or M12, accounting for 483 visits. The outcome was "cocaine use" in three categories: "no," "occasional," and "regular" use. To identify factors associated with the outcome over time, we performed a mixed multinomial logistic regression.ResultsTime on methadone was significantly associated with a decrease in occasional but not in regular cocaine use from 14.7 % at M0 to 7.1 % at M12, and from 10.7 % at baseline to 6.5 % at M12, respectively. After multiple adjustments, opiate injection, individuals screening positive for attention deficit hyperactivity disorder (ADHD) symptoms, and those presenting depressive symptoms were more likely to regularly use cocaine.ConclusionsAlthough time on MMT had a positive impact on occasional cocaine use, it had no impact on regular cocaine use. Moreover, regular cocaine users were more likely to report opiate injection and to present ADHD and depressive symptoms. Early screening of these disorders and prompt tailored pharmacological and behavioral interventions can potentially reduce cocaine use and improve response to MMT.Trial registrationThe trial is registered with the French Agency of Pharmaceutical Products (AFSSAPS) under the number 2008-A0277-48, the European Union Drug Regulating Authorities Clinical Trials, number Eudract 2008-001338-28, the ClinicalTrials.gov Identifier: NCT00657397, and the International Standard Randomised Controlled Trial Number Register ISRCTN31125511.

International audience ; AbstractBackgroundCocaine use is frequent in patients receiving methadone maintenance treatment (MMT) and can jeopardize their treatment response. Identifying clinical predictors of cocaine use during methadone treatment can potentially improve clinical management. We used longitudinal data from the ANRS Methaville trial both to describe self-reported occasional and regular cocaine use during MMT and to identify clinical predictors.MethodsWe selected 183 patients who had data on cocaine (or crack) use at months 0 (M0), M6, and/or M12, accounting for 483 visits. The outcome was "cocaine use" in three categories: "no," "occasional," and "regular" use. To identify factors associated with the outcome over time, we performed a mixed multinomial logistic regression.ResultsTime on methadone was significantly associated with a decrease in occasional but not in regular cocaine use from 14.7 % at M0 to 7.1 % at M12, and from 10.7 % at baseline to 6.5 % at M12, respectively. After multiple adjustments, opiate injection, individuals screening positive for attention deficit hyperactivity disorder (ADHD) symptoms, and those presenting depressive symptoms were more likely to regularly use cocaine.ConclusionsAlthough time on MMT had a positive impact on occasional cocaine use, it had no impact on regular cocaine use. Moreover, regular cocaine users were more likely to report opiate injection and to present ADHD and depressive symptoms. Early screening of these disorders and prompt tailored pharmacological and behavioral interventions can potentially reduce cocaine use and improve response to MMT.Trial registrationThe trial is registered with the French Agency of Pharmaceutical Products (AFSSAPS) under the number 2008-A0277-48, the European Union Drug Regulating Authorities Clinical Trials, number Eudract 2008-001338-28, the ClinicalTrials.gov Identifier: NCT00657397, and the International Standard Randomised Controlled Trial Number Register ISRCTN31125511.

International audience ; AbstractBackgroundCocaine use is frequent in patients receiving methadone maintenance treatment (MMT) and can jeopardize their treatment response. Identifying clinical predictors of cocaine use during methadone treatment can potentially improve clinical management. We used longitudinal data from the ANRS Methaville trial both to describe self-reported occasional and regular cocaine use during MMT and to identify clinical predictors.MethodsWe selected 183 patients who had data on cocaine (or crack) use at months 0 (M0), M6, and/or M12, accounting for 483 visits. The outcome was "cocaine use" in three categories: "no," "occasional," and "regular" use. To identify factors associated with the outcome over time, we performed a mixed multinomial logistic regression.ResultsTime on methadone was significantly associated with a decrease in occasional but not in regular cocaine use from 14.7 % at M0 to 7.1 % at M12, and from 10.7 % at baseline to 6.5 % at M12, respectively. After multiple adjustments, opiate injection, individuals screening positive for attention deficit hyperactivity disorder (ADHD) symptoms, and those presenting depressive symptoms were more likely to regularly use cocaine.ConclusionsAlthough time on MMT had a positive impact on occasional cocaine use, it had no impact on regular cocaine use. Moreover, regular cocaine users were more likely to report opiate injection and to present ADHD and depressive symptoms. Early screening of these disorders and prompt tailored pharmacological and behavioral interventions can potentially reduce cocaine use and improve response to MMT.Trial registrationThe trial is registered with the French Agency of Pharmaceutical Products (AFSSAPS) under the number 2008-A0277-48, the European Union Drug Regulating Authorities Clinical Trials, number Eudract 2008-001338-28, the ClinicalTrials.gov Identifier: NCT00657397, and the International Standard Randomised Controlled Trial Number Register ISRCTN31125511.

International audience ; BACKGROUND: In France, the rapid scale-up of buprenorphine, an opioid maintenance treatment (OMT), in primary care for drug users has led to an impressive reduction in HIV prevalence among injecting drug users (IDU) but has had no major effect on Hepatitis C incidence. To date, patients willing to start methadone can only do so in a methadone clinic (a medical centre for drug and alcohol dependence (CSAPA) or a hospital setting) and are referred to primary care physicians after dose stabilization. This study aims to assess the effectiveness of methadone in patients who initiated treatment in primary care compared with those who initiated it in a CSAPA, by measuring abstinence from street opioid use after one year of treatment. METHODS/DESIGN: The ANRS-Methaville study is a randomized multicenter non-inferiority control trial comparing methadone induction (lasting approximately 2 weeks) in primary care and in CSAPA. The model of care chosen for methadone induction in primary care was based on study-specific pre-training of all physicians, exclusion criteria and daily supervision of methadone during the initiation phase. Between January 2009 and January 2011, 10 sites each having one CSAPA and several primary care physicians, were identified to recruit patients to be randomized into two groups, one starting methadone in primary care (n = 147), the other in CSAPA (n = 48). The primary outcome of the study is the proportion of participants abstinent from street opioids after 1 year of treatment i.e. non-inferiority of primary care model in terms of the proportion of patients not using street opioids compared with the proportion observed in those starting methadone in a CSAPA. DISCUSSION: The ANRS-Methaville study is the first in France to use an interventional trial to improve access to OMT for drug users. Once the non-inferiority results become available, the Ministry of Health and agency for the safety of health products may change the the New Drug Application (NDA) of methadone and make methadone induction by trained primary care physicians possible.The trial is registered with the French Agency of Pharmaceutical Products (AFSSAPS) under the number 2008-A0277-48, the European Union Drug Regulating Authorities Clinical Trials.Number Eudract 2008-001338-28, the ClinicalTrials.gov Identifier: NCT00657397 and the International Standard Randomised Controlled Trial Number Register ISRCTN31125511.

IntroductionPeople living with HIV (PLHIV) on antiretroviral therapy (ART), with sustained undetectable viral load (sUVL) and no history of sexually transmitted infections for at least six months, are considered to have a low risk of HIV transmission (LRT). We aimed to characterize, in a representative sample of French PLHIV, the sexual behaviour of LRT PLHIV compared with non‐LRT PLHIV.MethodsThe cross‐sectional ANRS‐VESPA2 survey was conducted on adult PLHIV attending French hospitals in 2011. The LRT PLHIV group included participants with sUVL and no sexually transmitted infection for at least 12 months. Socio‐behavioural and medical data were collected. Chi‐square tests helped compare sexual risk indicators between LRT and non‐LRT PLHIV. The survey's retrospective nature allowed us to perform complementary category‐based analyses of LRT PLHIV according to whether they had sUVL for at least 18, 24 or 36 months in three socio‐epidemiological groups: men who have sex with men (MSM), other men and women.ResultsAnalysis included 2638 PLHIV diagnosed >12 months with available viral load data. The proportion of LRT PLHIV varied from 58% (≥12 months sUVL) to 38% (≥36 months sUVL). Irrespective of sUVL duration, we found the following: 1) LRT men (MSM and other men) were more likely to report having no sexual partner than their non‐LRT counterparts. Among men having sexual partners in the previous 12 months, no significant difference was seen between LRT and non‐LRT men in the number of sexual partners. LRT women were less likely to report having more than one sexual partner than non‐LRT women; 2) LRT MSM were more likely to report being in sexually inactive couples than their non‐LRT counterparts; 3) among sexually active participants, no difference was observed between LRT and non‐LRT PLHIV concerning condom use with their serodiscordant steady partner or with their most recent casual sexual partners.ConclusionsLRT PLHIV with sUVL ≥12 months did not report more sexual risk behaviours than their non‐LRT counterparts. Because the same result was obtained for those having a sUVL ≥36 months, the hypothesis of increased sexual risk behaviour over time in PLHIV meeting non‐transmission biomedical criteria is not supported.

AbstractIntroductionIn a context of declining condom use and high sexually transmitted infection (STI) incidence, the diffusion of "treatment as prevention" (Tasp) and more recently pre‐exposure prophylaxis (PrEP) may have changed the sexual behaviour of newly diagnosed men who have sex with men (MSM) with HIV.MethodsSix hundred and nine MSM were enrolled and followed annually between 2014 and 2021 in the ANRS PRIMO Cohort (ClinicalTrials.gov:NCT03148964) from the time of HIV seroconversion. We studied changes over calendar time in sexual behaviour before and after HIV diagnosis. Factors associated with inconsistent condom use (ICU) after HIV diagnosis, PrEP use by partner(s) and bacterial STI acquisition were studied in random‐effects models.ResultsIn the 6 months preceding HIV diagnosis, the number of sexual partners decreased from a median of 10 (IQR: 4−19) in 2014 to 6 (3−11) in 2021. After HIV diagnosis, ICU increased from 57.1% (16/28) of visits in 2014 up to 84.2% (229/272) in 2020−2021. Up to 25% (63/229) of MSM with HIV in recent years reported the use of PrEP by their partner(s) as the reason for ICU; these MSM were less frequently in a stable relationship, had a higher number of sexual partners and higher education level than those who did not report the use of PrEP by their partner(s). STI incidence after HIV diagnosis increased between 2014 and 2016 and remained high afterwards. STI risk was no longer associated with PrEP use by partners after adjustment for the number of partners and calendar period. ICU, age below 35 years, not being in a stable relationship, higher number of sexual partners were independently associated with an increased risk of STI.ConclusionsImplementation of TasP and more recently PrEP has led to major changes in the sexual behaviour of MSM with HIV. ICU has become overwhelmingly prevalent, PrEP use by the partner increasingly being the reported reason for ICU, behind TasP, which remains the main reason. Characteristics of MSM at the time of diagnosis of HIV have changed, with fewer number of sexual partners today than in 2014, which must lead to broaden the indications for PrEP prescription. STIs incidence remains high in MSM with HIV and requires improvements in screening and prevention methods such as pre‐ or post‐exposition antibiotics or vaccines.

AbstractIntroductionDespite the advent of HIV cure‐related clinical trials (HCRCT) for people living with HIV (PLWH), the risks and uncertainty involved raise ethical issues. Although research has provided insights into the levers and barriers to PLWH and physicians' participation in these trials, no information exists about stakeholders' preferences for HCRCT attributes, about the different ways PLWH and physicians value future HCRCT, or about how personal characteristics affect these preferences. The results from the present study will inform researchers' decisions about the most suitable HCRCT strategies to implement, and help them ensure ethical recruitment and well‐designed informed consent.MethodsBetween October 2016 and March 2017, a discrete choice experiment was conducted among 195 virally controlled PLWH and 160 physicians from 24 French HIV centres. Profiles within each group, based on individual characteristics, were obtained using hierarchical clustering. Trade‐offs between five HCRCT attributes (trial duration, consultation frequency, moderate (digestive disorders, flu‐type syndrome, fatigue) and severe (allergy, infections, risk of cancer) side effects (SE), outcomes) and utilities associated with four HCRCT candidates (latency reactivation, immunotherapy, gene therapy and a combination of latency reactivation and immunotherapy), were estimated using a mixed logit model.ResultsApart from severe SE – the most decisive attribute in both groups – PLWH and physicians made different trade‐offs between HCRCT attributes, the latter being more concerned about outcomes, the former about the burden of participation (consultation frequency and moderate SE). These different trades‐offs resulted in differences in preferences regarding the four candidate HCRCT. PLWH significantly preferred immunotherapy, whereas physicians preferred immunotherapy and combined therapy. Despite the heterogeneity of characteristics within the PLWH and physician profiles, results show some homogeneity in trade‐offs and utilities regarding HCRCT.ConclusionsSevere SE, not outcomes, was the most decisive attribute determining future HCRCT participation. Particular attention should be paid to providing clear information, in particular on severe SE, to potential participants. Immunotherapy would appear to be the best HCRCT candidate for both PLWH and physicians. However, if the risk of cancer could be avoided, gene therapy would become the preferred strategy for the latter and the second choice for the former.