Viral Reservoir in Early-Treated Human Immunodeficiency Virus-Infected Children and Markers for Sustained Viral Suppression.

BACKGROUND: The impact of very early infant treatment on human immunodeficiency virus (HIV) reservoir, and markers for treatment success, require study. METHODS: The Early Infant Treatment Study (EIT) enrolled 40 children living with HIV started on antiretroviral treatment (ART) at <7 days of age, with 23 who had started treatment between 30-365 days to serve as controls. Quantitative HIV DNA was evaluated every 1-3 months in peripheral blood mononuclear cells. 84-week repeat qualitative whole blood DNA polymerase chain reaction and dual enzyme immunosorbent assay were performed. RESULTS: Median quantitative cell-associated DNA after at least 84 weeks was significantly lower among the first 27 EIT children tested than among 10 controls (40.8 vs 981.4 copies/million cells; P < .001) and correlated with pre-ART DNA. Median DNA after 84 weeks did not differ significantly by negative or positive serostatus at 84 weeks (P = .94), and appeared unaffected by periods of unsuppressed plasma RNA from 24-84 weeks (P = .70). However, negative 84-week serostatus was 67% predictive for sustained RNA suppression, and positive serostatus was 100% predictive for viremia. Loss of qualitative DNA positivity at 84 weeks was 73% predictive for sustained suppression, and persistent positivity was 77% predictive for viremia. CONCLUSIONS: Lower viral reservoir was associated with starting ART at <1 week. Negative serostatus and qualitative DNA were useful markers of sustained viral suppression from 24-84 weeks.

HIV diagnostic algorithm requires confirmatory testing for initial indeterminate or positive screens in the first week of life.

BACKGROUND: Risk for nondiagnostic and false-positive HIV testing has not been quantified for neonates. METHODS: From April 2015 to July 2018, we screened HIV-exposed infants in Botswana less than 96 h from birth by qualitative DNA PCR. Repeat blood draws for DNA and RNA PCR testing occurred for initial positive and indeterminate results to establish final diagnosis. We compared screening DNA PCR cycle threshold values with final HIV status of the child. RESULTS: Of 10 622 HIV-exposed infants, 10 549 (99.3%) had no HIV DNA detected (negative), 42 (0.4%) had HIV DNA detected (positive), and 31 (0.3%) tested indeterminate at first HIV screen. Repeat testing identified 2 (5.0%) of 40 positive screens (2 declined additional testing) as false positives and confirmed 2 (6.5%) of 31 indeterminate screens as infected. Median cycle threshold value at screening was 28.1 (IQR 19.8--34.8) for children with final positive status, and 35.5 (IQR 32.8--41.4) for indeterminates who were ultimately negative. Six (15%) of 40 infants with final positive status had cycle threshold value greater than 33 at first screen, whereas 3 (9.7%) of 31 indeterminates with final negative status had cycle threshold value 33 or less at first screen. This threshold resulted in a negative predictive value of 82% and a positive predictive value of 92% for a single screen. CONCLUSION: Although a DNA PCR cycle threshold value of 33 was predictive of the final HIV status in newborns, overlap occurred for true positives, false positives, and initial indeterminates. Testing additional samples should be standard practice for positive and indeterminate HIV DNA PCR tests in the first week of life.