Immunovirological status in people with perinatal and adult-acquired HIV-1 infection: a multi-cohort analysis from FranceResearch in context

Summary: Background: No study has compared the virological and immunological status of young people with perinatally-acquired HIV infection (P-HIV) with that of people with HIV adulthood (A-HIV) having a similar duration of infection. Methods: 5 French cohorts of P-HIV and A-HIV patients with a known date of HIV-infection and receiving antiretroviral treatment (ART), were used to compare the following proportions of: virological failure (VF) defined as plasma HIV RNA ≥ 50 copies/mL, CD4 cell percentages and CD4:CD8 ratios, at the time of the most recent visit since 2012. The analysis was stratified on time since infection, and multivariate models were adjusted for demographics and treatment history. Findings: 310 P-HIV were compared to 1515 A-HIV (median current ages 20.9 [IQR:14.4–25.5] and 45.9 [IQR:37.9–53.5] respectively). VF at the time of the most recent evaluation was significantly higher among P-HIV (22.6%, 69/306) than A-HIV (3.3%, 50/1514); p ≤ 0.0001. The risk of VF was particularly high among the youngest children (2–5 years), adolescents (13–17 years) and young adults (18–24 years), compared to A-HIV with a similar duration of infection: adjusted Odds-Ratio (aOR) 7.0 [95% CI: 1.7; 30.0], 11.4 [4.2; 31.2] and 3.3 [1.0; 10.8] respectively. The level of CD4 cell percentages did not differ between P-HIV and A-HIV. P-HIV aged 6–12 and 13–17 were more likely than A-HIV to have a CD4:CD8 ratio ≥ 1: 84.1% vs. 58.8% (aOR = 3.5 [1.5; 8.3]), and 60.9% vs. 54.7% (aOR = 1.9 [0.9; 4.2]) respectively. Interpretation: P-HIV were at a higher risk of VF than A-HIV with a similar duration of infection, even after adjusting for treatment history, whereas they were not at a higher risk of immunological impairment. Exposure to viral replication among young patients living with HIV since birth or a very early age, probably because of lower adherence, could have an impact on health, raising major concerns about the selection of resistance mutations and the risk of HIV transmission. Funding: Inserm - ANRS MIE

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