Human Immunodeficiency Virus Type 1 DNA Decay Dynamics With Early, Long-term Virologic Control of Perinatal Infection.
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.
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.
In the first 2 years following VS, HIV-1 DNA levels decreased by -0.25 (95% confidence interval [CI], -.36 to -.13) log10 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 log10 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) log10 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.
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.
W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
Priyanka
P
Uprety
Department of Epidemiology/Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
Kunjal
K
Patel
Department of Epidemiology/Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
Brad
B
Karalius
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Carrie
C
Ziemniak
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Ya Hui
YH
Chen
Department of Epidemiology/Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
Sean S
SS
Brummel
Frontier Science, Amherst, New York; and.
Suzanne
S
Siminski
Department of Pediatrics, Tulane University School of Medicine, New Orleans, Louisiana.
Russell B
RB
Van Dyke
Department of Epidemiology/Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
George R
GR
Seage
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Deborah
D
Persaud
D000293:Adolescent; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D002675:Child, Preschool; D015331:Cohort Studies; D004279:DNA, Viral / Q000097:blood / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000517:prevention & control / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000821:virology*; D016014:Linear Models; D008137:Longitudinal Studies; D008297:Male; D011533:Proviruses / Q000235:genetics; D019562:Viral Load / Q000187:drug effects
D019380:Anti-HIV Agents; D004279:DNA, Viral
HIV-1 DNA decay; early ART.; perinatal HIV-1 infection