Anti-retroviral drug resistance-associated mutations among non-subtype B HIV-1-infected Kenyan children with treatment failure
✍ Scribed by Raphael Lwembe; Washingtone Ochieng; Annie Panikulam; Charles O. Mongoina; Tresa Palakudy; Yusuke Koizumi; Seiji Kageyama; Naohiko Yamamoto; Tatsuo Shioda; Rachel Musoke; Mary Owens; Elijah M. Songok; Frederick A. Okoth; Hiroshi Ichimura
- Publisher
- John Wiley and Sons
- Year
- 2007
- Tongue
- English
- Weight
- 120 KB
- Volume
- 79
- Category
- Article
- ISSN
- 0146-6615
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✦ Synopsis
Abstract
Recently increased availability of anti‐retroviral therapy (ART) has mitigated HIV‐1/AIDS prognoses especially in resource poor settings. The emergence of ART resistance‐associated mutations from non‐suppressive ART has been implicated as a major cause of ART failure. Reverse transcriptase inhibitor (RTI)‐resistance mutations among 12 non‐subtype B HIV‐1‐infected children with treatment failure were evaluated by genotypically analyzing HIV‐1 strains isolated from plasma obtained between 2001 and 2004. A region of pol‐RT gene was amplified and at least five clones per sample were analyzed. Phylogenetic analysis revealed HIV‐1 subtype A1 (n = 7), subtype C (n = 1), subtype D (n = 3), and CRF02_AG (n = 1). Before treatment, 4 of 12 (33.3%) children had primary RTI‐resistance mutations, K103N (n = 3, ages 5–7 years) and Y181C (n = 1, age 1 year). In one child, K103N was found as a minor population (1/5 clones) before treatment and became major (7/7 clones) 8 months after RTI treatment. In 7 of 12 children, M184V appeared with one thymidine‐analogue‐associated mutation (TAM) as the first mutation, while the remaining 5 children had only TAMs appearing either individually (n = 2), or as TAMs 1 (M41L, L210W, and T215Y) and 2 (D67N, K70R, and K219Q/E/R) appearing together (n = 3). These results suggest that “vertically transmitted” primary RTI‐resistance mutations, K103N and Y181C, can persist over the years even in the absence of drug pressure and impact RTI treatment negatively, and that appearing patterns of RTI‐resistance mutations among non‐subtype B HIV‐1‐infected children could possibly be different from those reported in subtype B‐infected children. J. Med. Virol. 79:865–872, 2007. © 2007 Wiley‐Liss, Inc.