Background: Characterising 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).
Method: Total, 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.
Results: Integrated HIV-1 DNA load (per 10(6) 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).
Conclusions: The 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.
Keywords: 2-LTR, 2-long terminal repeats; ART, Anti-retroviral therapy; Activation; CMV, cytomegalovirus virus; CRN, Clinical Research Network; EBV, Epstein-Bar virus; ELISA, enzyme-linked immune-enzymatic assay; HIC, HIV-1 controllers; HIV-1 VL, HIV-1 viral load; HIV-1, Human Immunodeficiency Virus type 1; HLA, Human Leukocyte Antigen; Integration; LPS, lipopolysaccharide; NIHR, National Institute for Health Research; NNRTI, Non-nucleoside reverse-transcriptase inhibitors; NRTI, nucleoside/nucleotide reverse transcriptase inhibitors; PBMCs, Peripheral blood mononuclear cells; PCR, Polymerase chain reaction; PFA, paraformaldehyde; Persistence; Reservoir; Suppression; VLS, Viral Load Suppression; WHO, World Health Organisation; sCD14, soluble CD14.