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LOW HIV RESERVOIR AT 84 WEEKS IN VERY EARLY TREATED HIV-INFECTED CHILDREN IN BOTSWANA
Roger L. Shapiro1, Mathias Lichterfeld2, Michael D. Hughes1, Kara Bennett3, Kenneth Maswabi4, Gbolahan Ajibola4, Pilar Garcia-Broncano5, Sikhulile Moyo4, Terence Mohammed4, Patrick Jean-Philippe6, Maureen Sakoi4, Oganne Batlang4, Shahin Lockman2, Joseph Makhema4, Daniel R. Kuritzkes2
1Harvard University, Boston, MA, USA,2Brigham and Women's Hospital, Boston, MA, USA,3Bennett Statistical Consulting, Inc, New York, NY, USA,4Botswana Harvard AIDS Institute Partnership, Gabarone, Botswana,5Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA,6NIH, Rockville, MD, USA
Markers of HIV-1 reservoir size and immune responses are poorly described in HIV-infected infants treated very early in life.
The Early Infant Treatment Study (EIT) screens HIV-exposed children in Botswana by Roche TaqMan qualitative DNA PCR, and offers antiretroviral treatment (ART) for HIV-infected infants < 7 days of age. Nevirapine, zidovudine (ZDV), lamivudine (3TC) are provided as initial ART, and changed to lopinavir/ritonavir, ZDV, 3TC at 2+ weeks. Study visits and HIV RNA testing occur at enrollment, weeks 1, 2, 4, 8, 12, 24, then every 3 months. At least 1 million PBMCs for quantitative HIV DNA are collected at most visits. At 84 weeks, qualitative DNA PCR testing is repeated on PBMCs from a 3mL sample, and dual enzyme linked immunosorbent assay (ELISA) is performed (Bio-Rad GS HIV 1/2, Murex HIV 1.2.O). Children starting ART at age 30-365 days in the Botswana ART program and sampled 24-36 months of age served as controls.
Between April 2015 and September 2017, 27 HIV+ children enrolled in EIT; 9 had reached 84 weeks on ART. Among these 9 children, median age at ART start was 2 days after birth (range 1, 5), and median baseline HIV RNA was 3145 copies/mL (range < 40, > 10,000,000). By 24 weeks, 6 (67%) had HIV RNA < 40 copies/mL; 5 (56%) remained < 40 copies/mL at all subsequent visits through 84 weeks. At the 84-week visit, 8 (89%) were < 40 copies/mL. HIV ELISA was negative in 5 (56%) children at week 84 (all were children with low or undetectable HIV RNA from 24-84 weeks); indeterminate in a child with subsequent viral rebound at week 96; and positive in 3 children with high HIV RNA at ≥ 24 weeks. Qualitative HIV DNA PCR at 84 weeks had reverted to negative for 6 (67%) of the early treated children, but only 2 (12%) of 17 controls. Figure 1 shows quantitative HIV DNA levels in PBMCs from enrollment through 84 weeks, with a median of 94.5 copies/million PBMCs at enrollment and 5.3 copies/million PBMCs at the week 84 visit. In the 6 children with negative qualitative DNA PCRs, 4 (67%) had quantitative HIV DNA PCR ≤ 5 copies/million PBMCs, and 5 (83%) were ELISA negative.
Children treated in the first week of life had low HIV viral reservoir at enrollment and after 84 weeks of ART. Negative qualitative HIV DNA PCR at week 84 was accompanied by negative HIV ELISA in 5 of 6 children.