Background
Despite antiretroviral therapy (ART), HIV infection is not curable in most cases due to persistent HIV-1 reservoirs. Understanding the factors associated with long-term dynamics of intact HIV-1 proviruses during suppressive ART is critical for developing HIV-1 cure strategies. In this study, we aim to evaluate the association between sex assigned at birth and HIV-1 reservoir dynamics in people with HIV (PWH) on long-term suppressive ART.
Methods
We leveraged a digital droplet PCR (ddPCR)-based platform, intact proviral DNA assay (IPDA), to measure intact and defective HIV-1 proviruses. Adult male and female participants from MWCCS cohort with ≥10 years of suppressive ART (HIV-1 viral load <50 copies/ml or contemporary level of detection) were included. Patterns of intact proviruses decline were categorized as continuous declines (D_C), decreasing initially then rising later (D_LR), and non-decline (ND). Correlation was evaluated using Spearman’s rank correlation test.
Results
Seventeen male and 18 female PWH were included, with a median follow-up duration of 12 years. Median age at ART initiation was 38 years. Median nadir CD4 cell count was 218 cells/μl. Sixteen participants demonstrated continuous decline in intact proviruses (D_C), while 8 had late increase (D_LR) and 11 had non-decline (ND) patterns (Figure 1). In the D_LR group, the inflection of proviral DNA took place approximately 10 years after viral suppression. There was no significant difference in follow-up duration, nadir intact proviral levels, and nadir CD4 cell count among the three groups. However, female sex was associated with a higher proportion of continuous decrease than male (66.7% vs. 23.5%, p=0.04). In contrast to intact proviral DNA, total and defective proviral DNA levels were not significantly different among the three groups throughout follow-up. Estradiol levels in female PWH were negatively correlated with interleukin 6 (IL6, rho=-0.53, p=0.001), and IL6 was negatively correlated to intact proviruses (rho=-0.38, p=0.01). In male PWH, D-dimer rather than IL6 was positively associated with intact proviruses (rho=-0.34, p=0.02).
Conclusions
Among PWH with long-term suppressive ART, less than half of them had sustained proviral decline. Female sex is associated with the continuous decline pattern. Different proinflammatory pathways are related to HIV-1 intact proviral levels between male and female participants.