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HIV DNA Set Point Remains Elevated in Untreated vs Treated Acutely Infected Thais
Jintanat Ananworanich1; Nicolas Chomont2; Leigh . Eller3; Eugène Kroon4; Meera Bose3; Marty Nau3; Suteeraporn Pinyakorn3; Nelson L. Michael5; Nittaya Phanuphak4; Merlin L. Robb3; for the RV254/SEARCH010 study groups
1Military HIV Rsr Prog, Bethesda, MD, USA;2Univ de Montréal, Montreal, QC, Canada;3US Military HIV Rsr Prog, Walter Reed Army Inst of Rsr, Silver Spring, MD, USA;4SEARCH, Bangkok, Thailand;5US Military HIV Rsr Prog, Bethesda, MD, USA
The dynamics of HIV reservoir seeding in early acute HIV infection (AHI) and the longitudinal comparison of reservoir markers in antiretroviral therapy (ART) untreated and treated AHI is poorly understood.
Total and integrated HIV DNA were measured in the peripheral blood mononuclear cells (PBMCs) from two prospective AHI protocols of untreated (RV217, n=12) and treated (RV254, n=71) Thais. HIV DNA levels were log10 transformed prior to analysis. Differences between groups were assessed using two-tailed Student’s t test.
The untreated cohort was younger (median age 23 vs. 29 years in the treated cohort). The distribution of Fiebig stages were similar: untreated: 7 (58%) FI/II and 5 (42%) FIII/IV; treated: 33 (46%) FI/II and 38 (54%) FIII/IV. Baseline HIV RNA was higher in those untreated (6.4 vs. 5.7 log10copies/ml in treated, p=0.04). Mean time to ART initiation was 2 days from enrollment in the treated cohort. Geometric mean total HIV DNA over time is shown in the figure.
Mean baseline values were higher in the untreated vs. treated cohorts for total DNA (2.8 log vs. 1.8 log10copies/106PBMC, p=0.02) and integrated DNA (1.6 vs. 0.7 log10copies/106PBMC, p=0.006). After ART, the treated cohort had a marked reduction in total and integrated HIV DNA levels whereas these changed little in those untreated. The mean values at week 48 for total HIV DNA were 2.6 vs. 0.9 log10copies/106PBMC and integrated HIV DNA were 1.5 vs. 0.1 log10copies/106PBMC for the untreated and treated cohorts, respectively.
The mean differences of total HIV DNA between the untreated vs. treated cohorts increased from 1 log10copies/106PBMC at baseline to 1.7 log10copies/106PBMC at week 48 (p<0.0001) and 2.3 log10copies/106PBMC at week 144 (p <0.0001).
Similarly, the mean differences of integrated HIV DNA between the untreated vs. treated cohorts increased from 0.9 log10copies/106PBMC at baseline to 1.4 log10copies/106PBMC at week 48 (p<0.0001) and 1.9 log10copies/106PBMC at week 144 (p <0.0001). The total and integrated HIV DNA differences between cohorts remained after adjusting for baseline HIV DNA values.
Levels of HIV DNA “set point” appears to be established early during Fiebig I-IV AHI and determines the reservoir size in chronic infection. Over three years without ART, persons with AHI have HIV DNA that is 2 logs higher than those on ART. The window of opportunity to significantly alter HIV DNA levels with ART is possibly very early.