Anti-retroviral drug resistance-associated mutations among non-subtype B HIV-1-infected Kenyan children with treatment failure.
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.
Lwembe
Raphael
R
Centre for Virus Research, Kenya Medical Research Institute, Nairobi, Kenya.
Ochieng
Washingtone
W
Panikulam
Annie
A
Mongoina
Charles O
CO
Palakudy
Tresa
T
Koizumi
Yusuke
Y
Kageyama
Seiji
S
Yamamoto
Naohiko
N
Shioda
Tatsuo
T
Musoke
Rachel
R
Owens
Mary
M
Songok
Elijah M
EM
Okoth
Frederick A
FA
Ichimura
Hiroshi
H
D019380:Anti-HIV Agents / Q000627:therapeutic use; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000145:classification / Q000187:drug effects* / Q000235:genetics*; D006801:Humans; D007630:Kenya; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D012367:RNA, Viral / Q000097:blood / Q000235:genetics; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D017211:Treatment Failure
D019380:Anti-HIV Agents; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors