Drastic Reduction in Time to Controlled Viral Load in People With Human Immunodeficiency Virus in France, 2009–2019: A Longitudinal Cohort Study

International audienceAbstract Background Aspirational targets to end AIDS by 2030 include having 95% of people with human immunodeficiency virus (HIV; PWH) diagnosed, 95% treated, and 95% with controlled viral load (VL). Our objective was to describe, using a large French prospective cohort, the median transition times through the cascade of care between 2009 and 2019. Methods We analyzed patients whose first HIV diagnosis was made between 1 January 2009 and 31 December 2019. Using the Kaplan–Meier method, we estimated the time to linkage to care (from HIV diagnosis to first biological assessment), to treatment (date of first antiretroviral therapy [ART] prescription), and to controlled VL (first value <200 copies/mL). Analyses were disaggregated by time periods and patients' characteristics. Censoring date was 31 December 2021. Results Among the 16 864 patients linked to care since 2009, the median [Q1; Q3] time from HIV diagnosis to controlled VL decreased from 254 [127–745] to 73 [48–132] days in 2009–2011 and 2018–2019, respectively. Transition times from linkage to care to first ART decreased from 67 [17; 414] in 2009–2011 to 13 [5; 26] days in 2018–2019, and from ART to controlled VL from 83 [35; 130] in 2009–2011 to 38 [28; 90] days in 2018–2019. Differences were observed depending on patients' characteristics. Conclusions We describe drastic reductions in transition time through the cascade of care, allowing reduction in the transmission period following each new infection. Delayed diagnosis remains the main obstacle to ending AIDS in the next decade

Low-level viral loads and virological failure in the integrase strand transfer era

International audienceObjectives To analyse the occurrence of virological failure (VF) in patients starting ART with an integrase strand transfer inhibitor (INSTI)-based regimen in recent years, in relation with previous episodes of low-level viral load (LLVL). Patients and methods Patients starting a first ART between 1 January 2015 and 31 December 2020 based on two NRTIs and one INSTI were included if after virological control (two measures of VL < 50 copies/mL) they had a minimum of two additional VL measurements. Cox models adjusted for sex, age, acquisition group, hepatitis B or C coinfection, place of birth, year of ART initiation, CD4+ T cells and VL at ART initiation, duration of known HIV infection and of ART regimen were used to assess the association between the time to VF and the occurrence of LLVL. ART regimen was evaluated as time-varying covariate. Results LLVL was described in 13.7% and VF in 11% of the 3302 patients. LLVL was associated with VF [adjusted HR (aHR) 1.76, 95% CI 1.28–2.41], as well as age (aHR 0.97/year, 95% CI 0.96–0.98), CD4+ T cell count at ART initiation (aHR 0.93, 95% CI 0.87–0.98), heterosexual transmission (aHR 1.76, 95% CI 1.30–2.37) and being born abroad (aHR 1.50, 95% CI 1.17–1.93). Conclusions LLVL was related to VF. Even in the absence of subsequent failure, LLV episodes have a cost. Thus any VL value above 50 copies/mL should lead to enhanced adherence counselling

Low-level viral loads and virological failure in the integrase strand transfer era

AbstractObjectivesTo analyse the occurrence of virological failure (VF) in patients starting ART with an integrase strand transfer inhibitor (INSTI)-based regimen in recent years, in relation with previous episodes of low-level viral load (LLVL).Patients and methodsPatients starting a first ART between 1 January 2015 and 31 December 2020 based on two NRTIs and one INSTI were included if after virological control (two measures of VL &amp;lt; 50 copies/mL) they had a minimum of two additional VL measurements. Cox models adjusted for sex, age, acquisition group, hepatitis B or C coinfection, place of birth, year of ART initiation, CD4+ T cells and VL at ART initiation, duration of known HIV infection and of ART regimen were used to assess the association between the time to VF and the occurrence of LLVL. ART regimen was evaluated as time-varying covariate.ResultsLLVL was described in 13.7% and VF in 11% of the 3302 patients. LLVL was associated with VF [adjusted HR (aHR) 1.76, 95% CI 1.28–2.41], as well as age (aHR 0.97/year, 95% CI 0.96–0.98), CD4+ T cell count at ART initiation (aHR 0.93, 95% CI 0.87–0.98), heterosexual transmission (aHR 1.76, 95% CI 1.30–2.37) and being born abroad (aHR 1.50, 95% CI 1.17–1.93).ConclusionsLLVL was related to VF. Even in the absence of subsequent failure, LLV episodes have a cost. Thus any VL value above 50 copies/mL should lead to enhanced adherence counselling.</jats:sec

Epidemiological impact of Neisseria gonorrhoeae and Chlamydia trachomatis screening in men having sex with men: a modelling study

International audienceObjectives The impact of the systematic screening of Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) in men having sex with men (MSM) on these pathogens’ epidemiology remains unclear. We conducted a modelling study to analyse this impact in French MSM. Methods We modelled NG and CT transmission using a site-specific deterministic compartmental model. We calibrated NG and CT prevalence at baseline using results from MSM enrolled in the Dat’AIDS cohort. The baseline scenario was based on 1 million MSM, 40 000 of whom were tested every 90 days and 960 000 every 200 days. Incidence rate ratios (IRRs) at steady state were simulated for NG, CT, NG and/or CT infections, for different combinations of tested sites, testing frequency and numbers of frequently tested patients. Results The observed prevalence rate was 11.0%, 10.5% and 19.1% for NG, CT and NG and/or CT infections. The baseline incidence rate was estimated at 138.2 per year per 100 individuals (/100PY), 86.8/100PY and 225.0/100PY for NG, CT and NG and/or CT infections. Systematically testing anal, pharyngeal and urethral sites at the same time reduced incidence by 14%, 23% and 18% (IRR: 0.86, 0.77 and 0.82) for NG, CT and NG and/or CT infections. Reducing the screening interval to 60 days in frequently tested patients reduced incidence by 20%, 29% and 24% (IRR: 0.80, 0.71 and 0.76) for NG, CT and NG and/or CT infections. Increasing the number of frequently tested patients to 200 000 reduced incidence by 29%, 40% and 33% (IRR: 0.71, 0.60 and 0.67) for NG, CT and NG and/or CT infections. No realistic scenario could decrease pathogens’ incidence by more than 50%. Conclusions To curb the epidemic of NG and CT in MSM, it would not only be necessary to drastically increase screening, but also to add other combined interventions

Doravirine plus lamivudine two-drug regimen as maintenance antiretroviral therapy in people living with HIV: a French observational study

International audienceBackground: Two-drug regimens based on integrase strand transfer inhibitors (INSTIs) and boosted PIs have entered recommended ART. However, INSTIs and boosted PIs may not be suitable for all patients. We aimed to report our experience with doravirine/lamivudine as maintenance therapy in people living with HIV (PLWH) followed in French HIV settings.Methods: This observational study enrolled all adults who initiated doravirine/lamivudine between 1 September 2019 and 31 October 2021, in French HIV centres participating in the Dat'AIDS cohort. The primary outcome was the rate of virological success (plasma HIV-RNA < 50 copies/mL) at Week (W)48. Secondary outcomes included: rate of treatment discontinuation for non-virological reasons, evolution of CD4 count and CD4/CD8 ratio over follow-up.Results: Fifty patients were included, with 34 (68%) men; median age: 58 years (IQR 51-62), ART duration: 20 years (13-23), duration of virological suppression: 14 years (8-19), CD4 count: 784 cells/mm3 (636-889). Prior to switching, all had plasma HIV-RNA < 50 copies/mL. All but three were naive to doravirine, and 36 (72%) came from a three-drug regimen. Median follow-up was 79 weeks (IQR 60-96). Virological success rate at W48 was 98.0% (95% CI 89.4-99.9). One virological failure occurred at W18 (HIV-RNA = 101 copies/mL) in a patient who briefly discontinued doravirine/lamivudine due to intense nightmares; there was no resistance at baseline and no resistance emergence. There were three strategy discontinuations for adverse events (digestive disorders: n = 2; insomnia: n = 1). There was no significant change in CD4/CD8 ratio, while CD4 T cell count significantly increased.Conclusions: These preliminary findings suggest that doravirine/lamivudine regimens can maintain high levels of viral suppression in highly ART-experienced PLWH with long-term viral suppression, and good CD4+ T cell count

Increased incidence of diabetes in people living with HIV treated with first‐line integrase strand transfer inhibitors: A French multicentre retrospective study

International audienceAbstract Introduction Prevention of cardiovascular disease is a major issue in the current management of people living with HIV. Concern is growing about the metabolic impact of integrase strand transfer inhibitors (INSTIs), which could lead to an increased risk of diabetes, but the data are conflicting. This is an updated version of our previous analysis, with longer follow‐up and new molecules. Methods We retrospectively evaluated the incidence of new‐onset diabetes in people living with HIV starting combined antiretroviral therapy with an INSTI compared with non‐nucleoside reverse transcriptase inhibitors and protease inhibitors. Data were collected from the Dat'AIDS cohort study, a collaboration of 30 HIV treatment centres in France. We used a propensity score‐based inverse probability of treatment weighting approach to adjust for baseline characteristics between the two groups (INSTI and non‐INSTI). Results Between 2009 and 2021, a total of 12 150 people living with HIV were included. The incidence of diabetes was higher in the INSTI group than in the non‐INSTI group (hazard ratio 1.38; 95% confidence interval 1.07–1.77; p = 0.012). Regardless of the third drug, but to a greater extent for INSTIs, we observed a peak of new‐onset diabetes in the year following initiation of combined antiretroviral therapy. Conclusions The incidence of diabetes was higher in people treated with integrase inhibitors than in those receiving other third agents. This increased risk occurred both during the first year of treatment and in the longer term