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In this trial of preexposure prophylaxis with tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) in men who have sex with men, TDF-FTC was found to be effective in preventing HIV-1 infection when it was taken before sexual activity. The prevention of infection with human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) remains a major public health challenge. 1 Owing to the lack of an effective HIV vaccine, consistent condom use remains the cornerstone of prevention, but biomedical interventions such as male circumcision and the use of antiretroviral drugs for the treatment of HIV infection represent additional prevention strategies. 2 – 5 Among the promising interventions is preexposure prophylaxis, in which antiretroviral drugs are started in HIV-negative persons before potential exposure to the virus. Daily oral preexposure prophylaxis with either tenofovir disoproxil fumarate (TDF) or the combination of TDF and . . .

Early initiation of antiretroviral treatment during primary HIV infection led to negative HIV self-tests and point-of-care tests in 30% and 7%–9% of cases, respectively. These data reinforce the message that patients should never be retested after entering HIV care. Abstract We assessed the impact of early antiretroviral treatment (ART) on human immunodeficiency virus (HIV) antibody detection by rapid tests in 44 individuals after several years of successful ART. HIV self-tests and point-of-care tests were negative in 30% and 7%–9% of cases, respectively. These data reinforce the message that patients should never be retested after entering HIV care.

Increased rates of sexually transmitted infections (STIs) have been reported among men who have sex with men. We aimed to assess whether post-exposure prophylaxis (PEP) with doxycycline could reduce the incidence of STIs. All participants attending their scheduled visit in the open-label extension of the ANRS IPERGAY trial in France (men aged 18 years or older having condomless sex with men and using pre-exposure prophylaxis for HIV with tenofovir disoproxil fumarate plus emtricitabine) were eligible for inclusion in this open-label randomised study. Participants were randomly assigned (1:1) at a central site to take a single oral dose of 200 mg doxycycline PEP within 24 h after sex or no prophylaxis. The primary endpoint was the occurrence of a first STI (gonorrhoea, chlamydia, or syphilis) during the 10-month follow-up. The cumulative probability of occurrence of the primary endpoint was estimated in each group with the Kaplan-Meier method and compared with the log-rank test. The primary efficacy analysis was done on the intention-to-treat population, comprising all randomised participants. All participants received risk-reduction counselling and condoms, and were tested regularly for HIV. This trial is registered with ClinicalTrials.gov number, NCT01473472. Between July 20, 2015, and Jan 21, 2016, we randomly assigned 232 participants (n=116 in the doxycycline PEP group and n=116 in the no-PEP group) who were followed up for a median of 8·7 months (IQR 7·8–9·7). Participants in the PEP group used a median of 680 mg doxycycline per month (IQR 280–1450). 73 participants presented with a new STI during follow-up, 28 in the PEP group (9-month probability 22%, 95% CI 15–32) and 45 in the no-PEP group (42%, 33–53; log-rank test p=0·007). The occurrence of a first STI in participants taking PEP was lower than in those not taking PEP (hazard ratio [HR] 0·53; 95% CI 0·33–0·85; p=0·008). Similar results were observed for the occurrence of a first episode of chlamydia (HR 0·30; 95% CI 0·13–0·70; p=0·006) and of syphilis (0·27; 0·07–0·98; p=0·047); for a first episode of gonorrhoea the results did not differ significantly (HR 0·83; 0·47–1·47; p=0·52). No HIV seroconversion was observed, and 72 (71%) of all 102 STIs were asymptomatic. Rates of serious adverse events were similar in the two study groups. Gastrointestinal adverse events were reported in 62 (53%) participants in the PEP group and 47 (41%) in the no-PEP group (p=0·05). Doxycycline PEP reduced the occurrence of a first episode of bacterial STI in high-risk men who have sex with men. France Recherche Nord & Sud Sida-HIV Hépatites (ANRS) and Bill & Melinda Gates Foundation.

Clinical research has focused on risk factors and treatment for severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), particularly in people with a comorbidity including the human immunodeficiency virus (HIV), but little attention has been paid to the care pathway. This article aims to show how living with HIV may have been a biopsychosocial burden or boost in care pathways for Covid-19. People living with HIV (PLHIV) from 9 clinical centers were invited to participate in this qualitative study. The sampling was purposive with a maximum variation in their sociodemographic profiles. Semi-structured interviews were conducted until data saturation, then coded for thematic analysis, using an inductive general approach. We interviewed 34 PLHIV of which 20 had SARS-COV-2 once. They were 24 males, 26 born in France; median age: 55. Twenty had a CD4 number above 500, and all were on antiretroviral therapy (ART). HIV appeared as a burden when Covid-19 symptoms reminded HIV seroconversion, fear of contamination, and triggered questions about ART effectiveness. HIV was not considered relevant when diagnosing Covid-19, caused fear of disclosure when participants sought SARS-COV-2 testing, and its care in hospitals was disrupted by the pandemic. ART-pill fatigue caused avoidance for Covid-19 treatment. As a boost, living with HIV led participants to observe symptoms, to get advice from healthcare professionals, and screening access through them. Some participants could accept the result of screening or a clinical diagnosis out of resilience. Some could consider ART or another drug prescribed by their HIV specialist help them to recover from Covid-19. Living with HIV could function as a burden and/or a boost in the care pathways for Covid-19, according to patients' relationship to their HIV history, comorbidities and representation of ART. Covid-19 in PLHIV needs further qualitative study to gain a more comprehensive assessment of the pandemic's consequences on their lives and coping strategies.

Pill burden during antiretroviral treatment (ART) is associated with worse adherence and impaired virological suppression. We compared the effectiveness, tolerance, and persistence on treatment of single tablet regimens (STRs) with non-STR once-daily regimens in patients receiving first-line ART. Retrospective analysis of naïve HIV-1 infected patients prospectively enrolled in the French Dat'AIDS cohort and initiating first-line ART with STRs or once-daily non-STRs from 2004 to 2013. The primary outcome was time to treatment discontinuation defined by any change in the treatment regimen. STR and non-STR groups were compared controlling for baseline risk factors by inverse probability weighted treatment Cox analysis (IPWT) and propensity-score matching (PSM). Overall, 3212 patients (STR 499, non-STR 2713) were included. Median time to treatment discontinuation was shorter in non-STR patients than in STR patients, both in the IPWT (HR = 0.61, p<0.0001) and the PSM cohort (HR = 0.55, p<0.0001). This difference disappeared when censoring ART modification for simplification, both in the IPWT (HR = 0.97, p = 0.65) and the PSM cohort (HR = 0.91, p = 0.33). A lower rate of virological failure was observed with STRs than with non-STRs in both cohorts (HR = 0.23; p = 0.002 and HR = 0.22, p = 0.003, respectively). A lower rate of treatment modification for adverse event was observed with non-STRs in the IPWT cohort (HR = 1.46, p<0.0001), but not in the PSM cohort (HR = 1.22, p = 0.11). First-line therapy with STRs was associated with a longer time to treatment discontinuation than with non-STRs. However, when ART modification for simplification was not considered as a failure, STRs and non-STRs were similar.

Development of direct acting antivirals (DAA) offers new benefits for patients with chronic hepatitis C. The combination of these drugs with antiretroviral treatment (cART) is a real challenge in HIV/HCV coinfected patients. The aim of this study was to describe potential drug-drug interactions between DAAs and antiretroviral drugs in a cohort of HIV/HCV coinfected patients. Cross-sectional study of all HIV/HCV coinfected patients attending at least one visit in 2012 in the multicenter French Dat'AIDS cohort. A simulation of drug-drug interactions between antiretroviral treatment and DAAs available in 2015 was performed. Of 16,634 HIV-infected patients, 2,511 had detectable anti-HCV antibodies, of whom 1,196 had a detectable HCV-RNA and were not receiving HCV treatment at the time of analysis. 97.1% of these patients were receiving cART and 81.2% had a plasma HIV RNA <50 copies/mL. cART included combinations of nucleoside reverse transcriptase inhibitors with a boosted protease inhibitor in 43.6%, a non-nucleoside reverse transcriptase inhibitor in 17.3%, an integrase inhibitor in 15.4% and various combinations or antiretroviral drugs in 23.7% of patients. A previous treatment against HCV had been administered in 64.4% of patients. Contraindicated associations/potential interactions were expected between cART and respectively sofosbuvir (0.2%/0%), sofosbuvir/ledipasvir (0.2%/67.6%), daclatasvir (0%/49.4%), ombitasvir/boosted paritaprevir (with or without dasabuvir) (34.4%/52.2%) and simeprevir (78.8%/0%). Significant potential drug-drug interactions are expected between cART and the currently available DAAs in the majority of HIV/HCV coinfected patients. Sofosbuvir/ledipasvir and sofosbuvir/daclatasvir with or without ribavirin appeared the most suitable combinations in our population. A close collaboration between hepatologists and HIV/AIDS specialists appears necessary for the management of HCV treatment concomitantly to cART.

Background Characterizing HIV-1 transmission networks can be important in understanding the evolutionary patterns and geospatial spread of the epidemic. We reconstructed the broad molecular epidemiology of HIV from individuals with primary HIV-1 infection (PHI) enrolled in France in the ANRS PRIMO C06 cohort over 15 years. Results Sociodemographic, geographic, clinical, biological and pol sequence data from 1356 patients were collected between 1999 and 2014. Network analysis was performed to infer genetic relationships, i.e. clusters of transmission, between HIV-1 sequences. Bayesian coalescent-based methods were used to examine the temporal and spatial dynamics of identified clusters from different regions in France. We also evaluated the use of network information to target prevention efforts. Participants were mostly Caucasian (85.9%) and men (86.7%) who reported sex with men (MSM, 71.4%). Overall, 387 individuals (28.5%) were involved in clusters: 156 patients (11.5%) in 78 dyads and 231 participants (17%) in 42 larger clusters (median size: 4, range 3–41). Compared to individuals with single PHI (n = 969), those in clusters were more frequently men (95.9 vs 83%, p < 0.01), MSM (85.8 vs 65.6%, p < 0.01) and infected with CRF02_AG (20.4 vs 13.4%, p < 0.01). Reconstruction of viral migrations across time suggests that Paris area was the major hub of dissemination of both subtype B and CRF02_AG epidemics. By targeting clustering individuals belonging to the identified active transmission network before 2010, 60 of the 143 onward transmissions could have been prevented. Conclusion These analyses support the hypothesis of a recent and rapid rise of CRF02_AG within the French HIV-1 epidemic among MSM. Combined with a short turnaround time for sample processing, targeting prevention efforts based on phylogenetic monitoring may be an efficient way to deliver prevention interventions but would require near real time targeted interventions on the identified index cases and their partners.

Achieving functional cure of chronic HBV infection (Hepatitis B surface antigen [HBsAg] clearance, eventually followed by acquisition of anti-hepatitis B surface antigen [Anti-HBs]) in individuals with HIV and HBV infections is a rare event. In this setting, factors related to HBV cure have not yet been fully characterized. HIV-infected individuals with chronic HBV infection enrolled in the French Dat'AIDS cohort (NCT02898987), who started combined antiretroviral (cART)-anti-HBV treatment were retrospectively analyzed for HBsAg loss and Anti-HBs seroconversion. Overall, 1419 naïve-subjects received three different cART-anti-HBV treatment schedule: (1) 3TC or FTC only (n = 150), (2) TDF with or without 3TC or FTC (n = 489) and (3) 3TC or FTC as first line followed by adding/switching to TDF as second line (n = 780). Individuals were followed-up for a median of 89 months (IQR, 56-118). HBV-DNA was < 15 IU/mL in 91% of individuals at the end of the follow-up. Overall, 97 individuals cleared HBsAg (0.7/100 patient-years), of whom, 67 seroconverted for Anti-HBs (0.5/100 patient-years). A high CD4 nadir, a short delay between HBV diagnosis and treatment, a longer time on HBV therapy, an African origin and TDF-based therapy were independent predictors of HBsAg clearance (Probability of odds ratio [OR]>1, >95%) suggested by Bayesian analysis. Also, TDF-based regimen as first line (OR, 3.03) or second line (OR, 2.95) increased rates of HBsAg clearance compared to 3TC or FTC alone, with a 99% probability. HBsAg clearance rate was low in HIV-HBV co-infected cART-anti-HBV treated individuals, but was slightly improved on TDF-based regimen.

ObjectivesWe aimed to assess among men who have sex with men (MSM) risk factors for HIV infection, to identify those who require urgent pre-exposure prophylaxis (PrEP) prescription.MethodsAll participants enrolled in the placebo arm of the ANRS IPERGAY trial, or infected between screening and day 0, were included. Baseline characteristics were described and HIV incidence rate ratios (RRs) were estimated with their 95% CIs.Results203 MSM were included with a median follow-up of 9 months. During the study period, 16 participants acquired HIV infection while not receiving tenofovir disoproxil and emtricitabin (TDF/FTC) over 212.4 person-years (PYs) of follow-up (incidence rate 7.5/100 PYs, 95% CI: 4.3 to 12.2). Being enrolled in Paris was associated with a significant increased risk of HIV infection (RR: 4.1; 95% CI: 1.1 to 28.3). A high number of sexual partners in prior 2 months (≥10 vs <5) and of condomless receptive anal sex episodes in prior 12 months (>5 vs <5) were strong predictors for HIV acquisition (RR: 10.6 (2 to 260.2) and 3.3 (1.2 to 10.2), respectively). Those who reported more often or only receptive sexual practices were also at increased risk (RR: 9.8 (2.0 to 246.6)). The use of recreational drugs in prior 12 months, especially gamma hydroxybutarate/gamma butyrolactone (RR: 5.9; 95% CI: 2 to 21.7), was associated with a significantly increased risk of HIV acquisition even after adjustment for sexual practices.ConclusionsMSM who have frequent condomless receptive anal sex and multiple partners, or use recreational drugs should be targeted in priority for PrEP prescription especially if they live in an area with a high prevalence of HIV infection.

Natural‐killer (NK) cells are important immune effectors during a viral infection. Latent CMV infection is widely spread and was demonstrated to shape the NK cell repertoire through the NKG2C receptor. An expansion of NKG2C+ NK cells has been reported during primary HIV infection (PHI), but their role is not known. We previously found a correlation between the maturation state of the NK cell compartment and a lower viral load by studying patients from the ANRS 147 Optiprim trial. We investigated here extensively the NKG2C+ NK cells at the time of PHI and its evolution after 3 months of early antiretroviral therapy (combination antiretroviral therapy (cART)). Multiparametric cytometry combined with bioinformatics was used to determine subsets. NKbright NKG2C+ progenitor, NKdim NKG2C+ effector and NKdim NKG2C+CD57+ memory‐like populations were identified. Two groups of patients were unraveled according to the distribution of the NKG2C+ subsets skewed toward either progenitor/effector or memory‐like phenotype. Patients with high NKG2C+CD57+ NK cell frequencies showed lower HIV‐RNA, lower immune activation, higher pDC counts and reached more rapidly undetectable levels of HIV‐RNA at M1 under cART. NKG2C+CD57+ NK cell frequency was the only factor strongly correlated to low viral load among other clinical features. While the patients were cytomegalovirus (CMV) infected, there was no sign of reactivation of CMV during PHI suggesting that memory‐like NK cells were already present at the time of HIV infection and constituted a preexisting immune response able to contribute to natural control of HIV. This parameter appears to be a good candidate in the search of predictive markers to monitor HIV remission. HIV: Exposure to CMV offers partial immune protection Prior infection with cytomegalovirus (CMV) leaves an immune footprint that helps contain HIV in patients undergoing antiretroviral therapy. A team led by Francoise Gondois‐Rey and Daniel Olive from Aix‐Marseille University, France, studied the white blood cells of 30 patients involved in a clinical trial testing drug cocktails for limiting HIV infection during the period following initial contact with the virus. The researchers measured levels of an infection‐fighting immune cell known as a natural killer cell that, in response to prior CMV exposure, expresses a particular surface receptor called NKG2C. They showed that patients with higher levels of these cells had some degree of pre‐existing immunity that helped limit HIV viral loads. Levels of this particular immune cell subset may provide a good predictive biomarker of who is likely to achieve HIV remission.