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. 2017 Jun 1;64(11):1471-1478.
doi: 10.1093/cid/cix192.

Human Immunodeficiency Virus Type 1 DNA Decay Dynamics With Early, Long-term Virologic Control of Perinatal Infection

Priyanka Uprety  1 , Kunjal Patel  2 , Brad Karalius  2 , Carrie Ziemniak  3 , Ya Hui Chen  3 , Sean S Brummel  2 , Suzanne Siminski  4 , Russell B Van Dyke  5 , George R Seage  2 , Deborah Persaud  3 ; Pediatric HIV/AIDS Cohort Study (PHACS)
Collaborators, Affiliations

Human Immunodeficiency Virus Type 1 DNA Decay Dynamics With Early, Long-term Virologic Control of Perinatal Infection

Priyanka Uprety et al. Clin Infect Dis. .

Erratum in

  • Erratum.
    [No authors listed] [No authors listed] Clin Infect Dis. 2017 Oct 15;65(8):1431-1433. doi: 10.1093/cid/cix563. Clin Infect Dis. 2017. PMID: 29017252 Free PMC article. No abstract available.

Abstract

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) 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.

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.

Keywords: HIV-1 DNA decay; early ART.; perinatal HIV-1 infection.

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Figures

Figure 1.
Figure 1.
Derivation of study population in the Pediatric HIV/AIDS Cohort Study (PHACS) Adolescent Master Protocol (AMP) cohort. Abbreviations: ART, antiretroviral therapy; HIV, human immunodeficiency virus; PBMC, peripheral blood mononuclear cell; VS, virologic suppression.
Figure 2.
Figure 2.
Decay of human immunodeficiency virus type 1 (HIV-1) DNA in peripheral blood mononuclear cells (PBMCs) following virologic suppression (VS) overall (11) and by age at VS (11). Piecewise linear mixed-effects model of HIV-1 DNA decay in overall study population (solid black line) and in those who achieve VS by 1 year of age (solid blue line) and by 1 to 5 years of age (solid red line). Dashed lines represent fitted locally weighted scatterplot smoothing curve. Closed circles represent DNA levels below limit of detection.
Figure 3.
Figure 3.
Decay of human immunodeficiency virus type 1 (HIV-1) DNA in peripheral blood mononuclear cells (PBMCs) following virologic suppression (VS) overall (11) and by age at VS (11), normalized for CD4 cell count. Piecewise linear mixed-effects model of HIV-1 DNA decay in overall study population (black line) and in those who achieve VS by 1 year of age (blue line) and by 1 to 5 years of age (red line). HIV-1 proviral DNA decay by PBMCs (solid lines) and CD4 percentage (dashed lines).
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