Predictors of intact HIV DNA levels among children in Kenya

Author:

Neary Jillian1,Fish Carolyn S.2,Cassidy Noah A.J.2,Wamalwa Dalton3,Langat Agnes3,Ngugi Evelyn3,Benki-Nugent Sarah4,Moraa Hellen3,Richardson Barbra A.245,Njuguna Irene46,Slyker Jennifer A.14,Lehman Dara A.24,John-Stewart Grace1478

Affiliation:

1. Department of Epidemiology, University of Washington

2. Fred Hutchinson Cancer Center, Seattle, WA, USA

3. Department of Pediatrics and Child Health, University of Nairobi, Nairobi, Kenya

4. Department of Global Health

5. Department of Biostatistics, University of Washington, Seattle, WA

6. Kenyatta National Hospital, Nairobi, Kenya

7. Department of Medicine

8. Department of Pediatrics, University of Washington, Seattle, WA, USA.

Abstract

Objective: We determined predictors of both intact (estimate of replication-competent) and total (intact and defective) HIV DNA in the reservoir among children with HIV. Design: HIV DNA in the reservoir was quantified longitudinally in children who initiated antiretroviral therapy (ART) at less than 1 year of age using a novel cross-subtype intact proviral DNA assay that measures both intact and total proviruses. Quantitative PCR was used to measure pre-ART cytomegalovirus (CMV) viral load. Linear mixed effects models were used to determine predictors of intact and total HIV DNA levels (log10copies/million). Results: Among 65 children, median age at ART initiation was 5 months and median follow-up was 5.2 years; 86% of children had CMV viremia pre-ART. Lower pre-ART CD4+ percentage [adjusted relative risk (aRR): 0.87, 95% confidence intervals (95% CI): 0.79–0.97; P = 0.009] and higher HIV RNA (aRR: 1.21, 95% CI: 1.06–1.39; P = 0.004) predicted higher levels of total HIV DNA during ART. Pre-ART CD4+ percentage (aRR: 0.76, 95% CI: 0.65–0.89; P < 0.001), CMV viral load (aRR: 1.16, 95% CI: 1.01–1.34; P = 0.041), and first-line protease inhibitor-based regimens compared with nonnucleoside reverse transcriptase-based regimens (aRR: 1.36, 95% CI: 1.04–1.77; P = 0.025) predicted higher levels of intact HIV DNA. Conclusion: Pre-ART immunosuppression, first-line ART regimen, and CMV viral load may influence establishment and sustainment of intact HIV DNA in the reservoir.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Infectious Diseases,Immunology,Immunology and Allergy

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