Enhanced immunovirological response in women compared to men after antiretroviral therapy initiation during acute and early HIV‐1 infection: results from a longitudinal study in the French ANRS Primo cohort

INTRODUCTION: Previous 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). METHODS: Data 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. RESULTS: The 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 log(10) 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 log(10) copies/10(6) PBMCs after 70 months of ART for both sexes). CONCLUSIONS: The 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.