Several studies have investigated the role of monocytes in HIV infection, specifically in HIV-associated chronic inflammation. However, it is unclear how these immune cells correlate with measures of HIV persistence in individuals on long-term suppressive ART.
In this cross-sectional study, we determined the frequencies of classical (CD14+CD16-), intermediate (CD14+CD16+), and non-classical (CD14dimCD16+) monocytes in ACTG A5321 participants at study entry using flow cytometry. We also obtained plasma levels of pro- and anti-inflammatory markers by ELISA and multiplex assays. We measured levels of residual plasma HIV RNA and, in CD4+ T cells, HIV DNA, cell-associated HIV (CAR), and intact proviral DNA (IPD) by PCR assays. Spearman correlations were used to assess associations between continuous measures and were adjusted for age, sex, pre-ART RNA and CD4+ T cell count, and years on ART.
Participants (N=225) had median age of 49 years, median pre-ART CD4 and CD4 at study entry of 255 and 681 cells/uL, respectively, median pre-ART HIV RNA of 4.6 log10 cps/mL, and median of 7 years on suppressive ART. Median frequency of classical monocytes was 84.6% (IQR 79.1, 88), intermediate monocytes was 1.4% (0.9, 2.6), and non-classical classical monocytes was 1.3% (0.6, 2.3). After adjusting for potential confounders, none of the monocyte subset frequencies correlated with HIV DNA, CAR, or residual plasma HIV RNA (-0.08 ? r ? 0.08). Similarly, frequencies of the subsets were not associated with IPD (N=24). Frequencies of classical monocytes modestly correlated with plasma levels of pro-inflammatory markers IL-6 (0.17, p=0.01), CCL2 (r=0.30, p=0.04), and sCD163 (0.16, p=0.02), and negatively correlated with years on ART (r=-0.18, p=0.01). Higher levels of intermediate monocytes correlated with higher levels IP-10 (r=0.14, p=0.03) and sCD163 (r=0.14, p=0.04) and showed a trend for negative correlation with anti-inflammatory IL-10 levels (r=-0.26, p=0.07). None of the immunologic parameters correlated with frequencies of non-classical monocytes.
In this study of virally suppressed people with HIV on long-term ART, monocyte subsets were not associated with measured markers of HIV persistence. Classical and intermediate monocytes had modest associations with levels of inflammation and immune activation. Further studies are needed to define the role that monocyte subsets play in HIV persistence and in inflammation and immune activation.