Women have shown more favorable immunovirological characteristics than men around seroconversion. Here we investigated whether differences persisted under long-term antiretroviral therapy (ART) in individuals treated since acute and early HIV-1 infection (AHI).
Data was obtained for 262 women and 1783 men enrolled in the French multicenter ANRS PRIMO cohort between 1996 and 2017. We modelled the viral response, long-term immune recovery and total HIV DNA decay in the 143 women and 1126 men who initiated ART within the first three months of infection. Models were adjusted for age, geographical origin, viral load at ART initiation, time from infection to ART initiation and calendar period.
The 1269 participants were mostly white (85%). The median age at AHI diagnosis was 36 years (IQR: 29–44). The median ART duration was 62 months (IQR: 20–87). Mean pre-ART viral loads were lower in women than men, 5.2 and 5.6 log10 copies/mL respectively (P = 0.001). After ART initiation, women more rapidly achieved viral suppression (HIV RNA < 50 copies/mL) than men (age and pre-ART viral load adjusted hazard ratio: 1.33, 95% confidence interval 1.09 – 1.69). They also experienced a faster increase in CD4+ T-cell count and CD4:CD8 ratio during the first two months of treatment. Baseline 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 12.5 years of ART. CD4:CD8 ratio of women was persistently higher than that of men by a mean of 0.31. With long-term ART, women and men achieved similar levels of total HIV DNA (mean estimate at the last modelling point: 1.9 log10 copies/106 PBMCs after 70 months of ART for both sexes).
ART initiated within 3 months of AHI was associated with a larger immunological benefit in women. This benefit was sustained and more pronounced under very long-term ART, which may give women additional protection from adverse clinical outcomes and premature ageing.