Suchergebnisse

AbstractIntroductionPrevious studies have reported better immunovirological characteristics in women compared with men after HIV seroconversion. We investigated whether differences persisted under long‐term antiretroviral therapy (ART) in individuals treated since acute and early HIV‐1 infection (AHI).MethodsData were obtained for 262 women and 1783 men enrolled between 1996 and 2017 in the French multicentre ANRS PRIMO cohort. We modelled the viral response, long‐term immune recovery and HIV DNA decay in the 143 women and 1126 men who initiated ART within the first three months of infection.ResultsThe participants were mostly white. The mean age was 37 years at AHI diagnosis. Pre‐ART viral loads were lower in women than men, 5.2 and 5.6 log10 copies/mL (p = 0.001). After ART initiation, women more rapidly achieved viral suppression than men (adjusted hazard ratio: 1.33, 95% confidence interval 1.09 to 1.69). They also experienced a faster increase in CD4+ T‐cell count and CD4:CD8 ratio during the first months of treatment. Sex‐related differences in CD4+ T‐cell counts were more pronounced with increasing age. This led to a sustained mean difference of 99 to 168 CD4+ T‐cells/µL depending on age between women and men at 150 months of ART. Moreover, CD4:CD8 ratio of women was higher than that of men by 0.31, at 150 months of ART. There was no statistically significant difference between sexes for the levels of HIV DNA over time (mean estimate at the last modelling point: 1.9 log10 copies/106 PBMCs after 70 months of ART for both sexes).ConclusionsThe high level of immune recovery and decrease in total HIV DNA levels achieved after ART initiation during AHI reinforce the importance of early diagnosis of HIV infection and immediate ART initiation. The immunological benefit of being female increased throughout prolonged ART duration, which may give women additional protection from adverse clinical events and premature ageing.

AbstractIntroductionHIV controllers (HIC) maintain viraemia at low levels without antiretroviral treatment and have small HIV reservoirs. Nevertheless, they are heterogeneous regarding their risk of infection progression. The study of reservoirs can help elucidate this control. This study aimed to explore the factors implicated in the pathogenesis of HIV infection that are potentially associated with HIV reservoirs and their dynamics in HIC.MethodsIndividuals living with HIV included in the ANRS‐CODEX cohort with at least two HIV‐DNA measurements between 2009 and 2016 were selected. The total HIV‐DNA levels had been quantified prospectively from blood samples. Mixed‐effect linear models estimated the HIV‐DNA dynamics over time.ResultsThe median (interquartile range (IQR)) HIV‐DNA level was 1.5 (1.3 to 1.9) log copies/million peripheral blood mononuclear cells at inclusion (n = 202 individuals). These low levels showed heterogeneity among HIC. Lower levels were then associated with the protective HLA‐B*27/B*57 alleles and/or lower HIV‐RNA level at inclusion, negative hepatitis C virus serology, lower HIV‐suppressive capacity of specific CD8 T cells and lower levels of immune activation and inflammation. Interestingly, mathematical modelling of the dynamics of HIV‐DNA over time (840 measurements) showed that the number of infected cells decreased in 46% of HIC (follow‐up: 47.6 months) and increased in 54% of HIC. A multivariate analysis indicated that HLA‐B*27/B*57 alleles, a low level of HIV‐RNA and a low level of HIV‐DNA at inclusion were markers independently associated with this decrease.ConclusionsThese results offer new insights into the mechanisms of long‐term control in HIC. In half of HIC, the decrease in HIV‐DNA level could be linked to tighter viral control and progressive loss of infected cells. These findings allow the identification of HIC with a low risk of progression who may not need treatment.