In chronic HIV, a larger HIV reservoir as measured by HIV DNA in PBMCs associates with worse cognition. We evaluated whether HIV DNA measured in PBMCs 96 weeks (wks) after ART started in acute HIV infection (AHI) associates with neuropsychiatric outcomes and examined pre-ART predictors of HIV DNA in PBMC at 96 wks.
RV254 cohort participants in Thailand initiated ART within 4 (IQR 3-5) days after AHI diagnosis and underwent neuropsychiatric (NP) assessment and blood sampling pre-ART (baseline, BL) and during follow-up. NP assessments included Patient Health Questionnaire-9 (PHQ-9) for depressive symptoms and a 4-test cognitive battery including Color Trails 1 and 2, Trail Making A and non-dominant hand grooved pegboard. Demographically adjusted Z-scores of the 4 tests were averaged to generate a composite NPZ-4 score. Total HIV DNA in PBMCs was measured by ultrasensitive LTR-gag real-time PCR at BL, wks 24, 48 and 96. Multivariable logistic regression determined factors that correlated with undetectable HIV DNA at wk 96.
124 RV254 participants had HIV DNA measurements at wk 96. 118 (95%) were male, with a median age 26. 59 (48%) presented at Fiebig stage I-II. At BL, median blood HIV RNA and HIV DNA levels were 5.6 (IQR 5-6.5) log10 cps/ml and 186 (IQR 21.5-775.5) cps/106 PBMCs, respectively. Median CD4+ and CD8+ T-cell counts were 373 (IQR 278-529) and 482 (IQR 255-784) cells/mm3. The proportion of participants with detectable HIV DNA decreased from 100% at wk 0 to 70% (66/94), 67% (62/93) and 52% (45/87) at wks 24, 48 and 96, respectively. At wk 96, median HIV DNA was 4 (IQR 0-20) cps/106 PBMCs. NPZ-4 and PHQ-9 scores at wk 96 were statistically similar between those with detectable and undetectable HIV DNA. BL factors associated with undetectable HIV DNA at wk 96 include early Fiebig stage I-II (OR 2.8, p=0.024), lower plasma HIV RNA (OR 4.69, p=0.013), and higher CD4/CD8 ratio (OR 2.86, p=0.024). Multivariable analysis revealed that lower BL plasma HIV RNA (OR 4.67, p=0.016) and higher BL CD4/CD8 ratio (OR 2.84, p=0.031) remained independently associated with higher likelihood of undetectable HIV DNA at wk 96 (Table).
Though half of individuals had undetectable HIV DNA in PBMCs 96 wks after ART initiated during AHI, this finding did not associate with neuropsychiatric outcomes. Predictors of undetectable HIV DNA in PBMC included lower pre-ART plasma HIV-1 RNA and higher CD4/CD8 ratio, confirming that early events impact the HIV reservoir trajectory.