Background
There are known sex differences in HIV infection, latency, and immune responses. Women are overrepresented in some cohorts of immune controllers of HIV, raising questions about whether sex differences in immune responses track with features like spontaneous viral control. Previous studies addressed sex differences in the CD4 T cell reservoir and report that though men and women have similar HIV DNA levels in CD4s, there are sex-based differences in latency and reactivation. Therefore, we sought to assess if there were sex-differences in latency and reactivation in the monocyte reservoir in a large cohort of people with HIV (PWH).
Methods
Viral reservoirs were assessed in 138 PWH (70% female[F], 74% Black, 98% viral load <200cp/mL). Monocytes and CD4 T cells were isolated from the same blood draw and used in cell specific intact proviral DNA (IPDA) and quantitative viral outgrowth assays (QVOA). Monocyte IPDAs were completed on 121 PWH (69%F) and monocyte-derived macrophage (MDM)-QVOAs completed on 75 PWH (49%F), 58 PWH(38%F) had cells available for both assays. A subset of participants had CD4 T cell IPDAs (n=118, 69%F) and QVOAs (n=27, 63%F) to determine if sex-based differences were specific to one cellular reservoir. T cell contamination was assessed by flow cytometry and TCRβ qPCR, and mathematically removed from the monocyte signal.
Results
92% of PWH had detectable provirus in monocytes in some form (median[md]= 42 copies[cp]/1e6) with 34% having detectable intact provirus (md=20cp/1e6). No sex differences were observed in the frequency of PWH that had detectable total or intact provirus or with the absolute quantities observed. 24% of PWH had reactivatable monocyte reservoirs as measured by MDM-QVOA. Notably, while the infectious units per million values did not differ between sexes, the frequency of reactivation was significantly lower in women compared to men with HIV (13% vs 32%, χ2=4.4, P=0.036). No sex differences were observed in HIV DNA levels or reactivation frequency in CD4 T cells.
Conclusions
Our data suggest that the monocyte reservoir is less likely to reactivate in women with HIV despite having equivalent levels of HIV DNA compared to men with HIV. Further work is needed to determine if tissue specific macrophage reservoirs are also less likely to reactivate in women or if this is specific to monocytes. This sex-related difference in HIV reactivation has significant implications for the design and measurement of curative interventions in women with HIV.