Tenofovir DF/emtricitabine/rilpivirine as HIV post-exposure prophylaxis: results from a multicentre prospective study.

OBJECTIVES: Since 2016, French guidelines have recommended the single-tablet regimen of tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC)/rilpivirine (RPV) as HIV post-exposure prophylaxis (PEP), but few data support this usage. We evaluated the tolerability, treatment completion and occurrence of HIV seroconversion associated with this combination in occupational and non-occupational PEP. PATIENTS AND METHODS: We conducted an observational, prospective, multicentre, open-label, non-randomized study in five French HIV centres. Adults requiring PEP according to national French guidelines were prescribed TDF/FTC/RPV one pill once a day for 28 days. Clinical and biological tolerability was assessed at week 4; occurrence of HIV seroconversion was evaluated after week 16. RESULTS: From March 2016 to March 2017, 163 courses of PEP were prescribed for 150 sexual exposures (44% heterosexual and 56% MSM) and 13 non-sexual exposures. Five participants stopped PEP after a few days because the source person was HIV uninfected. Of the remaining 158 individuals, 15 (9.5%) were lost to follow-up at week 4, 7 (4.4%) prematurely discontinued PEP [patient's decision/non-adherence (n = 3) or adverse events (gastrointestinal intolerance n = 3, fatigue n = 1)] and 136 (86.1%) completed the 28 day treatment. Overall, 69.6% of participants declared at least one adverse event, mostly of mild to moderate intensity and no serious adverse events or hepatic or renal toxicity occurred. No HIV seroconversion occurred at week 16. CONCLUSIONS: The low rate of premature treatment interruption, the good tolerability and the absence of documented HIV seroconversion support the current French guidelines of a 28 day course of TDF/FTC/RPV for sexual and non-sexual PEP.

Influence of nevirapine administration on the pharmacokinetics of dolutegravir in patients infected with HIV-1.

OBJECTIVES: The metabolic pathways of dolutegravir and nevirapine suggest a potential pharmacokinetic interaction between these drugs. The objective of this study was to investigate the influence of nevirapine administration on the pharmacokinetics of dolutegravir in patients infected with HIV-1. PATIENTS AND METHODS: This study was an investigator-initiated trial registered at ClinicalTrials.gov under identifier NCT02067767. Dolutegravir (50 mg once daily) was added to the antiretroviral regimen (400 mg of nevirapine once daily + 600/300 mg of abacavir/lamivudine once daily) in 10 adult patients for 5 days. After discontinuation of nevirapine, the combination of dolutegravir + abacavir/lamivudine was continued. Full pharmacokinetic profiles were assessed on the day of nevirapine discontinuation and 2 weeks after discontinuation of nevirapine. The pharmacokinetic parameters of dolutegravir were calculated by non-compartmental analysis. The log-transformed values of these parameters were compared between periods with and without nevirapine co-administration. RESULTS: The co-administration of nevirapine led to a significant decrease (P < 0.05) in the area under the plasma concentration-time curve for dolutegravir from the time the dose was administered until the end of the dosing interval (-19%, P = 0.011), as well as decreases in trough plasma concentration (-34%, P = 0.018) and terminal half-life (-15%, P = 0.039), and a significant increase (P < 0.05) in apparent oral clearance for dolutegravir (+23%, P = 0.011). CONCLUSIONS: The decrease in dolutegravir exposure in combination with nevirapine suggests that the metabolism of dolutegravir is induced by nevirapine. According to therapeutic drug monitoring for dolutegravir, some patients may need a higher dose than 50 mg of dolutegravir once daily to maintain the therapeutic plasma concentration throughout the dosing interval.

Measles seroprevalence in human immunodeficiency virus-infected adults born in the era of measles vaccination.

OBJECTIVE: Widespread use of the measles vaccine should lead to the elimination of this disease. Here, we study the seroprevalence of measles in a cohort of adults living with HIV born after the introduction of measles vaccine in France and attempt to identify risk factors for the absence of serum measles antibody. DESIGN: In this multi-centre cross-sectional study, adult outpatients born after 1980 were screened for the presence of measles IgG antibody. Demographic and clinical data were obtained from the standardized electronic medical record system. Univariate and multivariate logistic regressions were performed to identify factors associated with the absence of measles antibodies. RESULTS: Between April 2019 and April 2020, 648 participants were enrolled. The median age was 33 years, 53.6% were born outside of France, and 74% were considered as socially deprived. Plasma HIV RNA was undetectable in 86% of patients. Among 603 evaluable patients, measles serology was positive in 87.2%. Only 81.8% of the patients with documented vaccination tested positive for measles IgG. Younger age was significantly associated with the absence of measles serum antibodies ( P  = 0.004 for each 10-year lower), as was birth in France ( P  < 0.001) and absence of social vulnerability ( P  = 0.04). CONCLUSION: The current study revealed a low seroprevalence of measles compared with that previously reported in France 6 years earlier and to the expected rate to achieve herd immunity. Checking vaccination record should be systematically carried out in patients living with HIV to fill the immunity gaps.