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Long-Term Virologic Response and Genotypic Resistance Mutations in HIV-1 Infected Kenyan Children on Combination Antiretroviral Therapy

Wamalwa, Dalton C. MBChB, MMed, MPH*; Lehman, Dara A. MHS, PhD; Benki-Nugent, Sarah MS, PhD; Gasper, Melanie A. BS†,§; Gichohi, Richard MBChB*; Maleche-Obimbo, Elizabeth MBChB, MMed, MPH*; Farquhar, Carey MD, MPH; John-Stewart, Grace C. MD, MPH, PhD; Overbaugh, Julie PhD

JAIDS Journal of Acquired Immune Deficiency Syndromes: March 1st, 2013 - Volume 62 - Issue 3 - p 267–274
doi: 10.1097/QAI.0b013e31827b4ac8
Basic and Translational Science

Background: HIV-infected children may require the use of combination antiretroviral treatment (cART) into adulthood. However, regimens are limited to first line and second line in many African settings. Therefore, understanding the long-term rate of virologic failure and drug resistance during prolonged antiretroviral treatment is important for establishing treatment strategies in African pediatric cohorts.

Methods: Children aged 18 months to 12 years initiated first-line cART and were followed every 1–3 months, for up to 5.5 years. Treatment was switched to second-line cART based on clinical and immunologic criteria according to national guidelines. Virologic failure was determined retrospectively as defined by ≥2 viral loads >5000 copies per milliliter. Drug resistance was assessed during viral failure by population-based sequencing.

Results: Among 100 children on first-line cART followed for a median of 49 months, 34% children experienced virologic failure. Twenty-three (68%) of the 34 children with viral failure had detectable resistance mutations, of whom 14 (61%) had multiclass resistance. Fourteen (14%) children were switched to second-line regimens and followed for a median of 28 months. Retrospective analysis revealed that virologic failure had occurred at a median of 12 months before switching to second line. During prolonged first-line treatment in the presence of viral failure, additional resistance mutations accumulated; however, only 1 (7%) of 14 children had persistent viremia during second-line treatment.

Discussion: Virologic suppression was maintained on first-line cART in two-thirds of HIV-infected children for up to 5 years. Switch to second line based on clinical/immunologic criteria occurred ∼1 year after viral failure, but the delay did not consistently compromise second-line treatment.

*Departments of Pediatrics, University of Nairobi, Nairobi, Kenya

Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA

Department of Medicine

§Global Health, University of Washington, Seattle, WA.

Correspondence to: Dalton C. Wamalwa, MBChB, MMed, MPH, Department of Paediatrics, University of Nairobi, Box 19676 Nairobi, Kenya 00202 (e-mail: dalton@africaonline.co.ke) and Dara Lehman, MHS, PhD, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, C3-168, Seattle, WA 98109 (e-mail: dlehman@fhcrc.org).

Supported by grants from the National Institutes of Health (R01-TW007632, K24-HD054314, and AI076105) and Fogarty (D43-TW000007).

The authors D.C.W. and D.A.L. contributed equally to the article. D.C.W. and D.A.L. were joint lead authors in the development and writing of the article. All co-authors contributed to the writing and editing of the article. D.C.W. led onsite implementation of the study including recruitment and follow-up. D.A.L. and D.C.W. conducted the statistical analysis of the data. D.A.L., S.B.N., and M.A.G. conducted resistance assays for genotypic testing and interpreted the resistance data. D.W., G.C.J.S., and C.F. designed the study including all epidemiologic aspects. R.G. and E.M.O. provided clinical service to children in the cohort with E.M.O. guiding management of complicated cases. J.O. provided overall leadership for the virologic aspects of the study including viral load and resistance testing.

D.C.W. and D.L. are co-first authors.

The authors have no conflicts of interest to disclose.

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Received May 07, 2012

Accepted October 26, 2012

© 2013 Lippincott Williams & Wilkins, Inc.