During Stably Suppressive Antiretroviral Therapy Integrated HIV-1 DNA Load in Peripheral Blood is Associated with the Frequency of CD8 Cells Expressing HLA-DR/DP/DQ

• Data from a homogenously treated population with consistent virological suppression
• Integrated HIV-1 DNA load did not vary significantly by duration of therapy
• Integrated HIV-1 DNA load was not associated with markers of recent virus replication
• Integrated HIV-1 DNA load and CD8+HLA-DR/DP/DQ+ frequency were positively associated
• Subjects with top quartile integrated HIV-1 DNA load showed high sCD14 levelsIntegrated HIV-1 DNA load remains constant in the peripheral blood of individuals receiving long-term suppressive antiretroviral therapy (ART). However, the mechanisms preventing decay of the reservoir remain unclear. We studied a cross-sectional population, defined by the duration of suppressive ART. Integrated HIV-1 DNA load did not differ significantly according to the duration of suppressive ART, and showed no association with direct or indirect markers of ongoing virus replication. Rather, there was an independent, positive association between integrated HIV-1 DNA load and the frequency of CD8 cells expressing the activation marker HLA-DR/DP/DQ. These cells appear to have important regulatory and effector function. Our findings add to growing evidence that immune activation sustains the HIV-1 reservoir during long-term suppressive ART.

BackgroundCharacterising the correlates of HIV persistence improves understanding of disease pathogenesis and guides the design of curative strategies. This study investigated factors associated with integrated HIV-1 DNA load during consistently suppressive first-line antiretroviral therapy (ART).MethodTotal, integrated, and 2-long terminal repeats (LTR) circular HIV-1 DNA, residual plasma HIV-1 RNA, T-cell activation markers, and soluble CD14 (sCD14) were measured in peripheral blood of 50 patients that had received 1–14 years of efavirenz-based or nevirapine-based therapy.ResultsIntegrated HIV-1 DNA load (per 106 peripheral blood mononuclear cells) was median 1.9 log10 copies (interquartile range 1.7–2.2) and showed a mean difference of 0.2 log10 copies per 10 years of suppressive ART (95% confidence interval − 0.2, 0.6; p = 0.28). It was positively correlated with total HIV-1 DNA load and frequency of CD8+HLA-DR/DP/DQ+ cells, and was also higher in subjects with higher sCD14 levels, but showed no correlation with levels of 2-LTR circular HIV-1 DNA and residual plasma HIV-1 RNA, or the frequency of CD4+CD38+ and CD8+CD38+ cells. Adjusting for pre-ART viral load, duration of suppressive ART, CD4 cell counts, residual plasma HIV-1 RNA levels, and sCD14 levels, integrated HIV-1 DNA load was mean 0.5 log10 copies higher for each 50% higher frequency of CD8+HLA-DR/DP/DQ+ cells (95% confidence interval 0.2, 0.9; p = 0.01).ConclusionsThe observed positive association between integrated HIV-1 DNA load and frequency of CD8+DR/DP/DQ+ cells indicates that a close correlation between HIV persistence and immune activation continues during consistently suppressive therapy. The inducers of the distinct activation profile warrant further investigation.