Journal
CLINICAL INFECTIOUS DISEASES
Volume 64, Issue 11, Pages 1471-1478Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/cid/cix192
Keywords
perinatal HIV-1 infection; HIV-1 DNA decay; early ART
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Funding
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- National Institute on Drug Abuse
- National Institute of Allergy and Infectious Diseases (NIAID)
- Office of AIDS Research
- National Institute of Mental Health (NIMH)
- National Institute of Neurological Disorders and Stroke
- National Institute on Deafness and Other Communication Disorders
- National Heart, Lung and Blood Institute
- National Institute of Dental and Craniofacial Research
- National Institute on Alcohol Abuse and Alcoholism, through Harvard T.H. Chan School of Public Health [HD052102]
- National Institute on Alcohol Abuse and Alcoholism, through Tulane University School of Medicine [HD052104]
- NIH [RO1 HD080474]
- Johns Hopkins University Center for AIDS Research [P30AI094189]
- NIH/NIAID [UM1AI068632, UM1AI068616, UM1AI106716]
- NICHD
- NIMH
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Background. Early antiretroviral therapy (ART) limits proviral reservoirs, a goal for human immunodeficiency virus type 1 (HIV-1) remission strategies. Whether this is an immediate or long-term effect of virologic suppression (VS) in perinatal infection is unknown. Methods. We quantified HIV-1 DNA longitudinally for up to 14 years in peripheral blood mononuclear cells (PBMCs) among 61 perinatally HIV-1-infected youths in the Pediatric HIV/AIDS Cohort Study who achieved VS at different ages. Participants in group 1 (n = 13) were <1 year of age and in group 2 (n = 48) from 1 through 5 years of age at VS. Piecewise linear mixed-effects regression models assessed the effect of age at VS on HIV-1 DNA trajectories during VS. Results. In the first 2 years following VS, HIV-1 DNA levels decreased by -0.25 (95% confidence interval [ CI], -.36 to -.13) log 10 copies/million PBMCs per year and was faster with early VS by age 1 year compared with after age 1 (-0.50 and -0.15 log 10 copies/million PBMCs per year, respectively). Between years 2 and 14 from VS, HIV-1 DNA decayed by -0.05 (95% CI, -.06 to -.03) log 10 copies/million PBMCs per year and was no longer significantly different between groups. The estimated mean half-life of HIV-1 DNA from VS was 15.9 years and was shorter for group 1 compared to group 2 at 5.9 years and 18.8 years, respectively (P = .09). Adjusting for CD4 cell counts had no effect on decay estimates. Conclusions. Early effective, long-term ART initiated from infancy leads to decay of HIV-1-infected cells to exceedingly low concentrations desired for HIV-1 remission strategies.
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