Efficacy, safety, and effect on sexual behaviour of on-demand pre-exposure prophylaxis for HIV in men who have sex with men : an observational cohort study

Background Data for on-demand pre-exposure prophylaxis (PrEP) are scarce. We implemented a cohort study to assess its efficacy, safety, and effect on sexual behaviour. Methods We invited men and transgender women who have sex with men, previously enrolled in the randomised placebo-controlled ANRS IPERGAY trial at seven sites (six in France and one in Canada), to participate in an openlabel extension with on-demand tenofovir disoproxil fumarate (300 mg) and emtricitabine (200 mg) to be taken before and after sexual intercourse. We assessed the incidence of HIV and other sexually transmitted infections (STIs), PrEP adherence, safety, and sexual behaviour. Statistical analyses included comparisons of proportions and incidence between the randomised phase of the ANRS IPERGAY trial and the open-label phase, and all participants were included in safety analyses. ANRS IPERGAY is registered with ClinicalTrials. gov, number NCT01473472. Findings Between Nov 4, 2014, and Jan 27, 2015, we enrolled 361 participants. Median follow-up was 18.4 months (IQR 17.7-19.1). One participant who discontinued PrEP acquired HIV infection. HIV incidence was 0.19 per 100 person-years (95% CI 0.01-1.08), compared with 6.60 per 100 person-years (3.60-11.05) in the placebo group of the randomised study, indicating a relative reduction of 97% (95% CI 81-100) in the incidence of HIV with ondemand PrEP. Participants used a median of 18 pills of study drugs per month (IQR 11-25), and at the 6 month visit 240 (71%) of 336 participants had tenofovir detected in plasma. Drug-related gastrointestinal events were reported in 49 participants (14%) but were self-limited. Only four participants (1%) discontinued PrEP, three because of an increase in plasma creatinine. The proportion of participants reporting condomless sex at their last receptive anal intercourse significantly increased from 77% (136 of 176 participants) at baseline to 86% (66 of 77 participants) at 18 months' follow-up (p for trend= 0.0004). The incidence of a first bacterial STI during this open-label phase did not change significantly compared with the randomised phase (59.0 vs 49.1 per 100 person-years, respectively; p= 0.11). Interpretation On-demand oral PrEP is highly effective at preventing HIV infection among high-risk men who have sex with men and therefore represents an alternative to daily PrEP, expanding choices for HIV prevention. High rates of STIs resulting from low condom use did not undermine PrEP efficacy, but warrant frequent testing

Predictors of virological outcome and safely in primary HIV type 1-infected patients initiating quadruple antiretroviral therapy: QUEST GW PROB3005

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Clin Infect Dis

Background: New options for first-line treatment of HIV-2 infection are needed. We evaluated an integrase inhibitor (raltegravir)-containing regimen. Methods: ART-naive adults infected with HIV-2 only and history of CDC group B or C event, or a CD4 count 50 cells/muL/year over the past 3 years, or a confirmed plasma HIV-2 RNA (pVL) >/=100 copies (cp)/mL were eligible for this non-comparative trial. The composite primary endpoint was survival at 48 weeks (W48) without any of the following: CD4 gain from baseline /=40 cp/mL from W24, raltegravir permanent discontinuation, incident B or C event. HIV-2 ultrasensitive pVL (uspVL) and total DNA were assessed using "in-house" PCR assays. Results: Baseline median CD4 count of 30 enrolled individuals (67% women) was 436 cells/microL (InterQuartile Range[IQR] 314- 507); pVL was >/=40 cp/mL in 20/30 (67%); uspVL was >/=5 cp/mL in 23/25 (92%); total DNA was >6 cp/PCR in 8/25 (32%). At W48, the composite endpoint of success was reached in 12/30 (40%; 95% Confidence Interval 22.7 to 59.4). Failure was mainly due to CD4 gain 6 cp/PCR in 3/26 (12%). Median CD4 gain was +87 cells/microL (IQR +38- +213, n=28). No serious adverse reaction was reported. Conclusion: Raltegravir-containing cART is a safe option for first line treatment of HIV-2 infection, yielding a comparable success rate to protease inhibitors. UspVL and total DNA were undetectable in the vast majority of participants

Human Immunodeficiency Virus Type 1 Group O Infection in France: Clinical Features and Immunovirological Response to Antiretrovirals

International audienc

Decreased darunavir concentrations during once-daily co-administration with maraviroc and raltegravir: OPTIPRIM-ANRS 147 trial

International audienceBackgroundThe OPTIPRIM-ANRS 147 trial compared intensive combination ART (darunavir/ritonavir, tenofovir disoproxil fumarate/emtricitabine, raltegravir and maraviroc) started early during primary HIV-1 infection with standard tritherapy with darunavir/ritonavir, tenofovir disoproxil fumarate and emtricitabine. From month 6 to 18, the percentage of viral load values <50 copies/mL was lower in the pentatherapy arm than in the tritherapy arm. Here we compared antiretroviral drug concentrations between the two arms.MethodsPlasma samples were collected from 50 patients at various times after drug administration. A Bayesian approach based on published population pharmacokinetic models was used to estimate residual drug concentrations (Ctrough) and exposures (AUC) in each patient. A mixed linear regression model was then used to compare the AUC and Ctrough values of each drug used in both groups.ResultsPublished models adequately described our data and could be used to predict Ctrough and AUC. No significant difference in tenofovir disoproxil fumarate, emtricitabine and ritonavir parameters was found between the two arms. However, darunavir Ctrough and AUC were significantly lower in the pentatherapy arm than in the tritherapy arm (P = 0.03 and P = 0.04, respectively).ConclusionsAdding maraviroc and raltegravir to darunavir-based tritherapy decreased darunavir concentrations. Compliance issues, maraviroc–darunavir interaction and raltegravir–darunavir interaction were suspected and may affect the kinetics of viral decay during pentatherapy. A specific pharmacokinetic interaction study is needed to explore the interactions between darunavir and maraviroc and raltegravir

Characteristics and outcomes of an international cohort of 600 000 hospitalized patients with COVID-19

Background: We describe demographic features, treatments and clinical outcomes in the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) COVID-19 cohort, one of the world’s largest international, standardized data sets concerning hospitalized patients. Methods: The data set analysed includes COVID-19 patients hospitalized between January 2020 and January 2022 in 52 countries. We investigated how symptoms on admission, co-morbidities, risk factors and treatments varied by age, sex and other characteristics. We used Cox regression models to investigate associations between demographics, symptoms, co-morbidities and other factors with risk of death, admission to an intensive care unit (ICU) and invasive mechanical ventilation (IMV). Results: Data were available for 689 572 patients with laboratory-confirmed (91.1%) or clinically diagnosed (8.9%) SARS-CoV-2 infection from 52 countries. Age [adjusted hazard ratio per 10 years 1.49 (95% CI 1.48, 1.49)] and male sex [1.23 (1.21, 1.24)] were associated with a higher risk of death. Rates of admission to an ICU and use of IMV increased with age up to age 60 years then dropped. Symptoms, co-morbidities and treatments varied by age and had varied associations with clinical outcomes. The case-fatality ratio varied by country partly due to differences in the clinical characteristics of recruited patients and was on average 21.5%. Conclusions: Age was the strongest determinant of risk of death, with a ~30-fold difference between the oldest and youngest groups; each of the co-morbidities included was associated with up to an almost 2-fold increase in risk. Smoking and obesity were also associated with a higher risk of death. The size of our international database and the standardized data collection method make this study a comprehensive international description of COVID-19 clinical features. Our findings may inform strategies that involve prioritization of patients hospitalized with COVID-19 who have a higher risk of death