Incidence and factors associated with PrEP discontinuation in France.

OBJECTIVES: HIV pre-exposure prophylaxis (PrEP) is effective in preventing HIV, but some seroconversions occur due to poor adherence or PrEP discontinuation. Our objective was to estimate the incidence of PrEP discontinuation and describe the reasons and factors associated with discontinuations. METHODS: A retrospective cohort was conducted in three French hospitals between January 2016 and June 2022. PrEP users who attended at least twice within 6 months during study period were included and followed up until December 2022. The incidence rate of PrEP discontinuation was estimated by censoring lost to follow up individuals. Factors associated with PrEP discontinuations were identified using a multivariate Cox model. RESULTS: A total of 2785 PrEP users were included, with 94% men and 5% transgender people. Median age was 35 years. By December 2022, 653 users had stopped PrEP (24%). The incidence rate was 10.8 PrEP discontinuations for 100 person-years (PY). The main causes of discontinuation were being in a stable relationship (32%), and not judging the treatment useful anymore (12%). Individuals who discontinued PrEP were younger [<29, HR = 1.45 (1.17-1.80)], and more likely to be women [HR = 2.44 (1.50-3.96)] or sex workers [HR = 1.53 (0.96-2.44)]. They were more likely to report PrEP side effects [HR = 2.25 (1.83-2.77)] or ≥2 sexually transmitted infections [HR = 1.87 (1.53-2.27)] during the last year. CONCLUSION: The incidence of PrEP discontinuations was quite low compared to rates observed in other cohorts. Users who stopped PrEP were sometimes still exposed to HIV, emphasizing the need for targeted interventions to prepare and support PrEP discontinuations and limit seroconversion risk.

High proportion of post-migration HIV acquisition in migrant men who have sex with men receiving HIV care in the Paris region, and associations with social disadvantage and sexual behaviours: results of the ANRS-MIE GANYMEDE study, France, 2021 to 2022.

BackgroundSome migrant men who have sex with men (MSM) acquire HIV in France.AimsWe investigated, in migrant MSM receiving HIV care in France, the (i) rate of post-migration-HIV acquisition in France, (ii) delay between arrival and HIV acquisition and (iii) factors affecting HIV acquisition within 1 year after migration.MethodsThis cross-sectional study focused on ≥ 18-year-old MSM born outside France, receiving HIV care in the Paris region. Information on migration history, socioeconomic condition, sexual activity, and health was collected in May 2021-June 2022 through self-administered questionnaires and medical records. Post-migration-HIV-acquisition rate and delay between arrival in France and HIV acquisition were estimated from biographical data and CD4+ T-cell counts. Predictors of HIV acquisition within 1 year after migration were determined using logistic regression.ResultsOverall post-migration HIV-acquisition rate was 61.7% (715/1,159; 95%CI: 61.2-62.2), ranging from 40.5% (95%CI: 39.6-41.6) to 85.4% (95%CI: 83.9-86.0) in participants from Latin America and North Africa. Among post-migration-HIV acquisitions, those within 1 year after migration represented 13.1% overall (95%CI: 11.6-14.6), being highest in participants from sub-Saharan Africa (25%; 95%CI: 21.5-28.3). Participants ≥ 15-years old at migration, with post-migration-acquired HIV, had a 7.5-year median interval from arrival in France to HIV acquisition (interquartile range (IQR): 3.50-14.75). Older age at arrival, region of origin (sub-Saharan Africa and Asia), degree of social disadvantage and numbers of sexual partners were independently associated with acquiring HIV within 1 year in France.ConclusionOur findings may guide HIV prevention policies for most vulnerable migrants to Europe.

Fostemsavir in Adults with Multidrug-Resistant HIV-1 Infection.

BACKGROUND: Among some patients with human immunodeficiency virus type 1 (HIV-1) infection who have undergone multiple antiretroviral therapies and have limited options for treatment, new classes of antiretroviral drugs with novel mechanisms of action are needed. Fostemsavir is the prodrug of temsavir, a first-in-class investigational HIV-1 attachment inhibitor. METHODS: In this ongoing phase 3 trial in 23 countries, we enrolled patients with multidrug-resistant HIV-1 infection in two cohorts, according to their remaining treatment options. In the first cohort, we assigned (in a 3:1 ratio) patients who had the option of using at least one fully active, approved antiretroviral drug in at least one but no more than two antiretroviral classes to add either fostemsavir (at a dose of 600 mg twice daily) or placebo to their failing regimen for 8 days, followed by open-label fostemsavir plus optimized background therapy (randomized cohort). In the second cohort, patients who had no remaining antiretroviral options were started on open-label fostemsavir plus optimized background therapy on day 1 (nonrandomized cohort). The primary end point was the mean change in the HIV-1 RNA level from day 1 through day 8 in the randomized cohort. RESULTS: A total of 371 patients were treated, including 272 in the randomized cohort and 99 in the nonrandomized cohort. At day 8, the mean decrease in the HIV-1 RNA level was 0.79 log10 copies per milliliter in the fostemsavir group and 0.17 log10 copies in the placebo group (P<0.001). At week 48, a virologic response (HIV-1 RNA level, <40 copies per milliliter) had occurred in 54% of the patients in the randomized cohort and in 38% of those in the nonrandomized cohort; the mean increase in the CD4+ T-cell count was 139 cells per cubic millimeter and 64 cells per cubic millimeter, respectively. Adverse events led to the discontinuation of fostemsavir in 7% of the patients. In the randomized cohort, glycoprotein 120 (gp120) substitutions were found in 20 of 47 patients (43%) with virologic failure. CONCLUSIONS: In patients with multidrug-resistant HIV-1 infection with limited therapy options, those who received fostemsavir had a significantly greater decrease in the HIV-1 RNA level than those who received placebo during the first 8 days. Efficacy was sustained through 48 weeks. (Funded by Bristol-Myers Squibb and GSK/ViiV Healthcare; BRIGHTE ClinicalTrials.gov number, NCT02362503.).

Missed opportunities for HIV pre-exposure prophylaxis among people with recent HIV infection: The French ANRS 95041 OMaPrEP study.

OBJECTIVES: Our objective was to identify missed opportunities for the use of pre-exposure prophylaxis (PrEP) in people with recently acquired HIV, factors associated with PrEP knowledge, and reasons for not using PrEP. DESIGN: This was a French national cross-sectional multicentre study enrolling people diagnosed with recent HIV (incomplete Western blot or negative HIV test in the previous 6 months) in 28 HIV clinical centres. Data were gathered using a self-administered questionnaire (SAQ). METHOD: We analysed missed opportunities for PrEP use via a retrospective prep cascade. Factors associated with prior knowledge of PrEP and reasons for PrEP non-use among those who knew about PrEP were described using univariate and multivariate logistic regression models. RESULTS: Of the 224 eligible patients, 185 completed the SAQ and 168 (91%) were eligible for PrEP. Of these, 90% reported seeing at least one physician during the previous year, 26% received information about PrEP, and 5% used PrEP. Factors independently associated with a higher probability of knowing about PrEP were being a man who has sex with men, being aged 25-30 years (vs older), undergoing HIV screening at least once every semester (vs less often; odds ratio [OR] 4.11; 95% confidence interval [CI] 2.00-8.45), and practicing chemsex (OR 3.19; 95% CI 1.12-9.10). Fear of side effects and a low perceived risk of HIV infection were the two most common reasons for not using PrEP (N = 40 [33.33%] and N = 34 [28.3%], respectively). CONCLUSIONS: We found two gaps in the retrospective PrEP cascade: insufficient provision of PrEP information by healthcare providers (mainly general practitioners) and low PrEP acceptability by informed, eligible patients. More diverse healthcare providers need to be involved in PrEP prescription, and at-risk people need to be sensitized to the risk of HIV infection.

Hepatitis A and B vaccine uptake and immunisation among men who have sex with men seeking PrEP: a substudy of the ANRS IPERGAY trial.

Vaccination against hepatitis A virus (HAV) and hepatitis B virus (HBV) is recommended in men who have sex with men (MSM). We assessed HAV and HBV vaccine uptake in the non-immune participants and their immunisation during follow-up of the ANRS IPERGAY (Intervention Préventive de l'Exposition aux Risques avec et pour les Gays) pre-exposure prophylaxis (PrEP) trial.During the ANRS IPERGAY trial among MSM (NCT01473472), vaccination against HAV and HBV was offered free of charge to all non-immune participants at baseline. We assessed anti-HAV IgGs and anti-hepatitis B surface (HBs) antibodies (Abs) at baseline, 1-3 months after each vaccine dose and on the last follow-up visit. Vaccination uptake and immunisation were analysed in non-immune participants with at least 6 months of follow-up after the 1st vaccine dose.A total of 427 MSM with a median age of 34.8 years were analysed. Median follow-up was 2.2 years (Q1-Q3, 1.6-2.9). Absence of anti-HAV IgG at baseline (50.4%, 215/427) was associated with younger age (p=0.0001). Among HAV non-immune participants, 96.1% (197/205) received one or more vaccine doses and 91.0% (172/189) received two vaccine doses. Among HBV non-immune participants, 97.6 % (81/83) received one or more vaccine doses and 78.4% (58/74) received three doses. On the last-visit sample, anti-HAV IgG and anti-HBs Abs were respectively detected in 94.8% (95% CI 90.0% to 97.7%) and 79.6% (95% CI 66.5% to 89.4%) of participants with complete vaccination and in 80.0% (95% CI 51.9% to 95.7%) and 40.0% (95% CI 16.3% to 67.7%) of participants with incomplete vaccination.Vaccine acceptability against HAV and HBV infections was very high in MSM starting PrEP. Immunisation was high in participants with a full vaccination scheme. Physicians must consider PrEP visits as major opportunities to propose and complete HAV and HBV vaccination in at-risk non-immune subjects.

HIV-1-RNA and total HIV-1-DNA loads in the genital compartment in men receiving dolutegravir- versus darunavir-based combined ART (cART) regimens during primary HIV infection.

BACKGROUND: Dolutegravir is a widespread integrase strand-transfer inhibitor (INSTI) recommended for treatment of primary HIV infection (PHI). PHI is a high-risk stage for sexual transmission because of the high viral load in semen. Yet dolutegravir concentrations in semen are lower than in blood during chronic treatment. OBJECTIVES: To compare the kinetics of HIV-RNA and total HIV-DNA in the genital compartment in subjects receiving either tenofovir/emtricitabine/dolutegravir or tenofovir/emtricitabine/darunavir/cobicistat as a first-line combined ART (cART) at the time of PHI. PATIENTS AND METHODS: Eighteen subjects receiving tenofovir/emtricitabine/dolutegravir and 19 receiving tenofovir/emtricitabine/darunavir/cobicistat enrolled in the ANRS169 OPTIPRIM-2 trial participated in the genital substudy. RESULTS: Between week (W) 0 and W2 HIV-RNA in seminal plasma (SP) decreased by 1 log10 copies/mL. Undetectable SP HIV-RNA was achieved in similar proportions between the two regimens at each timepoint. Overall, eight patients still presented detectable HIV-RNA or HIV-DNA in semen at W48; 15.4% and 28.6% presented detectable HIV-RNA and 9.1% and 14.3% presented detectable HIV-DNA in dolutegravir- and darunavir-based cART groups, respectively, with no significant difference. CONCLUSIONS: For the first time, to the best of our knowledge, we showed that a dolutegravir-based regimen initiated as soon as PHI reduces HIV-RNA and HIV-DNA with no difference compared with a control group receiving a darunavir-based regimen. Although the viral purge in semen seems longer after treatment in PHI than CHI, due to high viral loads, early dolutegravir-based treatment initiation permits a major decay of both viral particles and infected cells in semen, efficiently reducing the high risk of transmission during PHI.

Increased risk of severe COVID-19 in hospitalized patients with SARS-CoV-2 Alpha variant infection: a multicentre matched cohort study.

BACKGROUND: The impact of the variant of concern (VOC) Alpha on the severity of COVID-19 has been debated. We report our analysis in France. METHODS: We conducted an exposed/unexposed cohort study with retrospective data collection, comparing patients infected by VOC Alpha to contemporaneous patients infected by historical lineages. Participants were matched on age (± 2.5 years), sex and region of hospitalization. The primary endpoint was the proportion of hospitalized participants with severe COVID-19, defined as a WHO-scale > 5 or by the need of a non-rebreather mask, occurring up to day 29 after admission. We used a logistic regression model stratified on each matched pair and accounting for factors known to be associated with the severity of the disease. RESULTS: We included 650 pairs of patients hospitalized between Jan 1, 2021, and Feb 28, 2021, in 47 hospitals. Median age was 70 years and 61.3% of participants were male. The proportion of participants with comorbidities was high in both groups (85.0% vs 90%, p = 0.004). Infection by VOC Alpha was associated with a higher odds of severe COVID-19 (41.7% vs 38.5%-aOR = 1.33 95% CI [1.03-1.72]). CONCLUSION: Infection by the VOC Alpha was associated with a higher odds of severe COVID-19.

High Prevalence and High Rate of Antibiotic Resistance of Mycoplasma genitalium Infections in Men Who Have Sex With Men: A Substudy of the ANRS IPERGAY Pre-exposure Prophylaxis Trial.

BACKGROUND: Mycoplasma genitalium (MG) is an emerging pathogen among men who have sex with men (MSM) with raising rates of antibiotic resistance. This study assessed the prevalence and incidence of MG infection in MSM enrolled in the open-label phase of the ANRS IPERGAY trial with on-demand tenofovir disoproxil fumarate/emtricitabine for human immunodeficiency virus prevention and the impact of doxycycline post-exposure prophylaxis (PEP). METHODS: 210 subjects were tested at baseline and at 6 months by real-time PCR assays for MG detection in urine samples and oropharyngeal and anal swabs. Resistance to azithromycin (AZM), to fluoroquinolones (FQs), and to doxycycline was investigated in the French National Reference Center of Bacterial Sexually Transmitted Infections (STIs). RESULTS: The all-site prevalence of MG at baseline was 10.5% (6.3% in urine samples, 4.3% in anal swabs, 0.5% in throat swabs) and remained unchanged at 6 months whether or not PEP was used: 9.9% overall, 10.2% with PEP, 9.6% without. The overall rate of MG resistance (prevalent and incident cases) to AZM and FQs was 67.6% and 9.1%, respectively, with no difference between arms. An in vivo mutation of the MG 16S rRNA, which could be associated with tetracycline resistance, was observed in 12.5% of specimens tested. CONCLUSIONS: The prevalence of MG infection among MSM on pre-exposure prophylaxis was high and its incidence was not decreased by doxycycline prophylaxis with a similar high rate of AZM and FQ resistance, raising challenging issues for the treatment of this STI and supporting current recommendations to avoid testing or treatment of asymptomatic MG infection.

Tenofovir disoproxil fumarate and emtricitabine maintenance strategy in virologically controlled adults with low HIV-1 DNA: 48 week results from a randomized, open-label, non-inferiority trial.

OBJECTIVES: Low HIV reservoirs may be associated with viral suppression under a lower number of antiretroviral drugs. We investigated tenofovir disoproxil fumarate/emtricitabine as a maintenance strategy in people living with HIV (PLHIV) with low HIV-DNA. METHODS: TRULIGHT (NCT02302547) was a multicentre, open-label, randomized trial comparing a simplification to tenofovir disoproxil fumarate/emtricitabine versus a triple regimen continuation (tenofovir disoproxil fumarate/emtricitabine with a third agent, control arm) in virologically suppressed adults with HIV-DNA <2.7 log10 copies/106 PBMCs and no prior virological failure (VF). The primary endpoint (non-inferiority margin 12%) was the percentage of participants with a plasma viral load (pVL) <50 copies/mL in ITT (Snapshot approach) and PP analyses at Week 48 (W48). RESULTS: Of the 326 participants screened, 223 (68%) were randomized to the tenofovir disoproxil fumarate/emtricitabine arm (n = 113) or control arm (n = 110). At W48, the tenofovir disoproxil fumarate/emtricitabine and control arms maintained a pVL < 50 copies/mL in 100/113 (88.5%) and 100/110 (90.9%) participants, respectively (ITT difference 2.4%, 95% CI -5.9 to 10.7; PP difference 3.4%, 95% CI -4.2 to 11.0). Six VFs occurred in the tenofovir disoproxil fumarate/emtricitabine arm (two with emerging mutations M184V and K65R) versus two in the control arm (ITT difference 3.5%, 95% CI -1.9 to 9.4). All VFs were resuppressed after treatment modification. CONCLUSIONS: Although non-inferiority was shown, simplification to tenofovir disoproxil fumarate/emtricitabine should not be used for most PLHIV because of a low risk of VF with resistance.

Hepatitis C virus (HCV) incidence among men who have sex with men (MSM) living with HIV: results from the French Hospital Database on HIV (ANRS CO4-FHDH) cohort study, 2014 to 2017.

BackgroundDespite the availability of highly effective direct-acting antivirals (DAAs) and the expected treatment as prevention (TasP) effect, transmission of hepatitis C virus (HCV) persists in men who have sex with men (MSM) who engage in high-risk sexual behaviours.AimWe aimed to estimate the incidence of primary HCV infection among MSM living with HIV in France when DAA was readily available.MethodsWe used data from a large French hospital cohort of persons living with HIV (ANRS CO4-FHDH) prospectively collected between 2014 and 2017. HCV incidence rates were calculated using person-time methods for HCV-negative MSM at inclusion who had serological follow-up from 1 January 2014 to 31 December 2017. Sensitivity analyses were performed by varying the main assumptions to assess their impact on the results.ResultsOf 14,273 MSM living with HIV who were initially HCV-seronegative, 330 acquired HCV during follow-up over 45,866 person-years (py), resulting in an overall estimated incidence rate of 0.72/100 py (95% CI: 0.65-0.80). HCV incidence significantly decreased from 0.98/100 py (95% CI: 0.81-1.19) in 2014 to 0.45/100 py (95% CI: 0.35-0.59) in 2017 (54% decrease; 95% CI: 36-67). This trend was confirmed by most of the sensitivity analyses.ConclusionThe primary incidence of HCV was halved for MSM living with HIV between 2014 and 2017. This decrease may be related to unrestricted DAA availability in France for individuals living with HIV. Further interventions, including risk reduction, are needed to reach HCV micro-elimination in MSM living with HIV.

Grazoprevir/elbasvir for the immediate treatment of recently acquired HCV genotype 1 or 4 infection in MSM.

BACKGROUND: In Europe, increases in HCV infection have been observed over the last two decades in MSM, making them a key population for recently acquired HCV. Alternative combinations of direct-acting antiviral agents against early HCV infection need to be assessed. PATIENTS AND METHODS: In this pilot trial, MSM with recently acquired genotype 1 or 4 HCV infection were prospectively included and received 8 weeks of oral grazoprevir 100 mg and elbasvir 50 mg in a fixed-dose combination administered once daily. The primary endpoint was sustained virological response evaluated 12 weeks after the end of treatment (EOT) (SVR12). Secondary endpoints were the virological characterization of failures, the quality of life before, during and after treatment and the rate of reinfection. RESULTS: In a 15 month period, 30 patients were enrolled, all of whom were MSM. Of the 29 patients completing follow-up, 28 (96%, 95% CI = 82%-99%) achieved SVR12. One patient interrupted follow-up (suicide) but had undetectable plasma HCV RNA at EOT. One patient with suboptimal adherence confirmed by plasma drug monitoring relapsed and developed NS3, NS5A and NS5B resistance-associated substitutions (V36M, M28V and S556G). The most common adverse events related to study drug were diarrhoea (n = 4, 13%), insomnia (n = 2, 7%) and fatigue (n = 2, 7%), although no patient discontinued treatment. No HIV RNA breakthrough was reported in the 28 patients with HIV coinfection. At Week 48, reinfection was diagnosed in three patients. CONCLUSIONS: Our data support the use of grazoprevir/elbasvir for immediate treatment against HCV in order to reduce HCV transmission in MSM.

Prevalence of tubulopathy and association with renal function loss in HIV-infected patients.

BACKGROUND: The incidence of chronic kidney disease (CKD) is 10 times higher in human immunodeficiency virus (HIV)-infected patients than in the general population. We explored the prevalence and determinants of proximal tubular dysfunction (PTD) in HIV-infected individuals, and assessed the impact of the tubulopathy on the estimated glomerular filtration rate (eGFR) outcome. METHODS: A cohort study was performed on 694 outpatients followed in a French centre to analyse the prevalence of PTD, the diagnosis performance of screening tools and the associated factors. eGFR was prospectively evaluated to analyse the predictive value of the tubulopathy on eGFR decrease. RESULTS: At inclusion, 14% of the patients presented with PTD and 5% with CKD. No individual tubular marker, including non-glomerular proteinuria, glycosuria dipstick or hypophosphataemia, registered sufficient performance to identify PTD. We found a significant interaction between tenofovir disoproxil fumarate exposure and ethnicity (P = 0.03) for tubulopathy risk. Tenofovir disoproxil fumarate exposure was associated with PTD in non-Africans [adjusted odds ratio (aOR) = 4.71, P < 10-3], but not in patients of sub-Saharan African origin (aOR = 1.17, P = 0.73). Among the 601 patients followed during a median of 4.3 years, 13% experienced an accelerated eGFR decline. Unlike microalbuminuria and glomerular proteinuria, tubulopathy was not associated with accelerated eGFR decline. CONCLUSION: PTD is not rare in HIV-infected individuals but is less frequent in sub-Saharan African patients and is associated with tenofovir disoproxil fumarate exposure only in non-Africans. Its diagnosis requires multiple biochemical testing and it is not associated with an accelerated eGFR decline.

Coverage of Sex Acts by Event-Driven Pre-exposure Prophylaxis: A Sub-Study of the ANRS IPERGAY Trial.

We assessed the coverage of sex acts by event-driven pre-exposure prophylaxis (ED-PrEP) over a 2-month period in 54 participants in the open label phase of the ANRS Ipergay trial. Participants received an electronic monitoring system device to record bottle openings. Self-questionnaires collected daily information on PrEP intake and sexual behavior. Intake was also estimated through returned pill counts. Full coverage of sex acts was defined as at least one pill taken both within 24 h before and within 48 h following sex. There was a strong correlation (r = - 0.92) between the number of bottle openings and returned pill counts. During the study, 42 participants (78%) practiced ED-PrEP and 12 (22%) daily PrEP with bottle openings at least 5 days/week whatever their sexual activity. Out of the 154 reported receptive anal sex acts, 81% were condomless: among them, PrEP coverage was hight: 97% among those practicing daily PrEP and 82% among those using ED-PrEP.

Acceptability of on-site rapid HIV/HBV/HCV testing and HBV vaccination among three at-risk populations in distinct community-healthcare outreach centres: the ANRS-SHS 154 CUBE study.

BACKGROUND: HIV, HBV and HCV infections continue to represent major health concerns, especially among key at-risk populations such as men who have sex with men (MSM), people who inject drugs (PWIDs), transgender women (TGW) and sex workers (SW). The objective of the ANRS-CUBE study was to evaluate the acceptability of a healthcare, community-based strategy offering a triple rapid HIV-HBV-HCV testing, and HBV vaccination, targeted at three priority groups (MSM, PWIDs and TGW/SWs), in three community centers, in the Paris area. METHODS: This longitudinal multicentric non-randomized study included all adult volunteers attending one of the three specialized community centers in Paris, between July 2014 and December 2015. HIV, HBV and HCV status and acceptability of HBV vaccination were evaluated. RESULTS: A total of 3662, MSM, 80 PWIDs and 72 TGW/SW were recruited in the three centers respectively. Acceptability of rapid tests was 98.5% in MSM and 14.9% in TGW/SWs, but could not be estimated in PWIDs since the number of users attending and the number of proposals were not recorded. User acceptability of HBV vaccination was weak, only 17.9% of the eligible MSM (neither vaccinated, nor infected) agreed to receive the first dose, 12.2% two doses, 5.9% had a complete vaccination. User acceptability of HBV vaccination was greater in PWIDs and TGW/SWs, but decreased for the last doses (66.7 and 53.3% respectively received a first dose, 24.4 and 26.7% a second dose and 6.7 and 0% a third dose). Fifty-three participants (49 MSM and 4 PWIDs) were discovered HIV positive, more than half with a recent infection. All but two HIV positive participants were linked to appropriate care in less than one month. CONCLUSIONS: Rapid HIV-HCV-HBV screening showed a very high level of acceptability among MSM. Efforts need to be made to improve immediate acceptability for HBV vaccination, especially among MSM, and follow-up doses compliance. Our results show the important role of community centers in reaching targets, often fragile, populations, while also suggesting the need to reinforce on-site human support in terms of testing and vaccination, especially when addressing PWIDs.

Meningococcal purpura fulminans and severe myocarditis with clinical meningitis but no meningeal inflammation: a case report.

BACKGROUND: During fulminant meningococcal septicaemia, meningococci are often observed in the cerebrospinal fluid (CSF) although the patients have frequently no meningeal symptoms. Meningococcal meningitis, by contrast, usually features clinical meningeal signs and biochemical markers of inflammation with elevated white blood cell count (pleiocytosis) in the CSF. Cases of typical symptomatic meningitis without these biochemical features are uncommon in adults. CASE PRESENTATION: A 21-year-old male presented with meningococcal purpura fulminans and disseminated intravascular coagulation (DIC) associated with multiple organ dysfunction syndrome requiring hospitalization in the Intensive Care Unit. Despite typical meningeal clinical signs, lumbar puncture showed no pleiocytosis, normal glycorachia and normal proteinorachia, whereas the lactate concentration in the CSF was high (5.8 mmol/L). CSF culture showed a high inoculum of serogroup C meningococci. On day 2, after initial improvement, a recurrence of hypotension led to the diagnosis of acute meningococcal myocarditis, which evolved favourably within a week. During the hospitalization, distal ischemic and necrotic lesions were observed, predominantly on the fingertips, which were treated with local and systemic vasodilators. CONCLUSIONS: We report a rare case of adult meningococcal disease characterized by an intermediate form of meningitis between purulent meningitis and meningeal inoculation from fulminant meningococcal septicaemia, without classical signs of biological inflammation. It highlights the diagnostic value of CSF lactate, which may warrant administration of a meningeal dosing regimen of beta-lactam antibiotics. This case also demonstrates the potential severity of meningococcal myocarditis; we discuss its pathophysiology, which is distinct from other sepsis-related cardiomyopathies. Finally, the observed effects of vasodilators on the meningococcal skin ischemia in this case encourages future studies to assess their efficacy in DIC-associated necrosis.

Silent Cerebral Small-Vessel Disease Is Twice as Prevalent in Middle-Aged Individuals With Well-Controlled, Combination Antiretroviral Therapy-Treated Human Immunodeficiency Virus (HIV) Than in HIV-Uninfected Individuals.

Background: Silent cerebral small-vessel disease (CSVD) is defined as white matter hyperintensities, silent brain infarction, or microbleeds. CSVD is responsible for future vascular events, cognitive impairment, frailty, and shorter survival. CSVD prevalence among middle-aged people living with well-controlled human immunodeficiency virus (HIV) infection (PLHIV) is unknown. Methods: The French National Agency for Research on AIDS and Viral Hepatitis (ANRS) EP51 Microvascular Brain Retina and Kidney Study (MicroBREAK; NCT02082574) is a cross-sectional study with prospective enrollment of treated PLHIV, ≥50 years old with viral load controlled for ≥12 months, and frequency age- and sex-matched HIV-uninfected controls (HUCs). It was designed to estimate CSVD prevalence on 3T magnetic resonance imaging (3D fluid-attenuated inversion recovery, transversal T2-weighted gradient-echo imaging and diffusion-weighted imaging), as diagnosed by 2 blinded neuroradiologists. A logistic regression model was used to assess the impact of HIV on CSVD after adjustment for traditional risk factors. Results: Between June 2013 and May 2016, 456 PLHIV and 154 HUCs were recruited. Median age was 56 and 58 years, respectively (P = .001), among whom 84.9% and 77.3%, respectively (P = .030), were men. CSVD was detected in 51.5% of PLHIV and 36.4% of HUCs with an adjusted odds ratio (aOR) of 2.3. The HIV impact differed according to age, with aOR values of 5.3, 3.7, and 1.0 for age groups <54, 54-60, and >60 years, respectively (P = .022). Older age, hypertension, and lower CD4 cell count nadir were independently associated with a higher risk of CSVD among PLHIV. Conclusions: HIV is an independent risk factor for CSVD. Despite sustained immunovirological control, the CSVD prevalence was twice as high among middle-aged PLHIV than HUCs. Clinical Trials Registration: NCT02082574.

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.).

Factors associated with partner notification of STIs in men who have sex with men on PrEP in France: a cross-sectional substudy of the ANRS-IPERGAY trial.

OBJECTIVES: Partner notification (PN) is a useful public health approach to enhance targeted testing of people at high risk of HIV and other STIs, and subsequent linkage to care for those diagnosed. In France, no specific PN guidelines exist and information about current practices is scarce. We used the ANRS-IPERGAY PrEP trial to investigate PN in HIV-negative men who have sex with men (MSM) reporting a bacterial STI. METHODS: This substudy included 275 participants who completed a specific online PN questionnaire during the open-label extension study of the ANRS-Intervention Préventive de l'Exposition aux Risques avec et pour les Gays (IPERGAY) trial. Variables used as proxies of at-risk practices were defined using data collected at the previous follow-up visit about participants' most recent sexual encounter and preventive behaviours. χ2 or Fisher's exact test helped select variables eligible for multiple logistic models. RESULTS: Of the 275 participants, 250 reported at least one previous STI. Among the latter, 172 (68.8%) had informed their partner(s) of their most recent STI. Of these, 138 (80.2%) and 83 (48.3%) had notified their casual and main partners, respectively. Participants were less likely to notify their main partner when their most recent sexual encounter involved unsafe anal sex with a casual partner (adjusted OR (aOR) (95% CI) 0.18 (0.06 to 0.54), P=0.02). Older participants were less likely to inform casual partners (aOR (95% CI) 0.44 (0.21 to 0.94), P=0.03), while those practising chemsex during their most recent sexual encounter were more likely to inform their casual partners (aOR (95% CI) 2.56 (1.07 to 6.09), P=0.03). CONCLUSION: Unsafe sexual encounters with people other than main partners and street drugs use were two sociobehavioural factors identified, respectively, as a barrier to main PN and a motivator for casual PN, in a sample of high-risk MSM. These results provide an insight into current PN practices regarding STI in France and might inform future decisions about how to define feasible and acceptable PN programmes.

Assessment of HIV Screening Tests for Use in Preexposure Prophylaxis Programs.

Preexposure prophylaxis programs involve frequent human immunodeficiency virus (HIV) testing. We evaluated the sensitivity of 2 antigen/antibody immunoassays (Architect and Bioplex), 2 antibody-based rapid tests (Vikia-HIV-1/2 and Autotest-VIH), and 1 antigen/antibody rapid test (Alere HIV Combo) for the diagnosis of HIV infection. Among the 31 HIV-1-infected participants in the ANRS-IPERGAY trial, HIV-1 RNA was detected alone in only 2. The sensitivities of the Architect and Bioplex assays were 83% (95% confidence interval [CI], 76%-99%) and 82% (95% CI, 63%-94%), respectively. The sensitivities of the Vikia, Autotest, and Alere tests were 54% (95% CI, 34%-72%), 50% (95% CI, 31%-69%), and 78% (95% CI, 58%-91%), respectively. Antigen/antibody tests should be preferred to avoid missing cases of acute HIV infection and to decrease the related risks of viral transmission and emergence of drug resistance.

Spatiotemporal dynamics of HIV-1 transmission in France (1999-2014) and impact of targeted prevention strategies.

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.