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Pre-ART CD4% and HIV Load Tied to
Reservoir Size in Early-Treated Infants
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CROI 2020, March 8-11, 2020, Boston
Mark Mascolini
In infants treated with antiretroviral therapy (ART) soon after birth, HIV reservoirs 1 year later were higher if infants had a lower CD4% or higher viral load before starting ART [1]. These cellular proviral HIV DNA reservoirs proved slightly smaller when infants started ART within 48 hours of birth rather than later.
The impact of early ART on HIV reservoirs in infants remains incompletely understood because most studies define "early" in terms of months. Researchers working in South Africa aimed to get a better fix on how rapid ART affects these reservoirs by limiting their analysis to treatment started within 28 days of birth. They specifically set out to learn whether ART in the first 48 hours of life significantly reduced proviral DNA reservoirs in the first year of treatment.
The study group consisted of 63 neonates with confirmed intrauterine HIV infection. Health workers at a Johannesburg hospital identified these newborns through a birth testing program. All neonates began ART as soon as possible, initially with zidovudine, lamivudine, and nevirapine, and later with lopinavir/ritonavir replacing nevirapine.
When infant samples were large enough, researchers assessed the HIV reservoir with a TaqMan PCR assay that detects and measures total HIV-1 subtype C proviral DNA. The testing strategy allowed detection of 1 viral copy per 910,000 cells.
Of the 63 infants studied, 35 (56%) were girls and 30 (48%) started ART within 48 hours of birth. Among those who started later, the median starting age was 7 days (interquartile range 4 to 17). Median pre-ART viral load stood at 12,815 copies, and median CD4% at 39.5%. One quarter of mothers had not taken antiretrovirals before delivery.
In 133 samples from 63 infants, proviral DNA could not be detected in 10.5% of samples, while 3.8% of samples had 1 to 10 detectable copies per million cells, 42.1% had 11 to 400 copies, 17.3% had 401 to 1000 copies, and 26.5% had more than 1000 copies. Median detectable DNA copies stood at 302 per million cells.
Higher pre-ART HIV RNA (viral load) correlated positively and strongly with higher on-ART proviral HIV DNA (r = 0.67, P < 0.01). HIV DNA copies in these early-treated infants dropped from an average 1622 copies/million cells before ART to 417 copies/million during 0 to 4 months of ART, to 251 copies/million during treatment months 4 to 8, and to 229 copies/million during months 8 to 12. The ART-induced drop in proviral DNA reservoir size was greatest in the first 3 months of ART and tended to plateau after month 5.
An analysis adjusted for preterm birth, delivery mode, and time after ART began identified four predictors of on-ART proviral DNA. (1) Every 10-fold higher pre-ART HIV RNA meant a higher on-ART proviral DNA reservoir (coefficient 0.18, 95% confidence interval [CI] 0.04 to 0.32). (2) A pre-ART CD4% below 30% predicted a bigger proviral DNA reservoir (coefficient 0.92, 95% CI 0.45 to 1.39). (3) Having a mother not on ART lowered reservoir size (coefficient -1.10, 95% CI -1.52 to -0.67). (4) Starting ART within 48 hours of birth led to a smaller proviral DNA reservoir (coefficient -0.39, 95% CI -0.79 to 0.00).
Reference
1. Paximadis M, Da Costa Dias B, Mncube S, et al. Predictors of the persisting viral reservoir in very early treated infants. Conference on Retroviruses and Opportunistic Infections (CROI). March 8-11, 2020. Boston. Abstract 135.
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