Prevalence of drug-resistance-associated mutations in antiretroviral drug-naive Zambians infected with subtype C HIV-1.
The ability of HIV-1 to evolve resistance to antiretroviral drugs leads to treatment failure. By nucleotide sequencing of HIV-1 subtype B isolates, amino acids responsible for drug resistance have been identified. Less information is available, however, on the extent and distribution of these amino acids in HIV-1 nonsubtype B viruses circulating mainly in developing countries. More HIV-infected patients in the developing world are now using antiretroviral drugs, and hence there is a need to monitor drug resistance mutations in HIV-1 non-subtype B viruses. This study examines the prevalence of drug resistance mutations in 28 antiretroviral drug-naive HIV-1-infected Zambians. HIV-1 proviral DNA was extracted from peripheral blood mononuclear cells. The region encompassing gag p17 to env C2-V3-C3 was amplified by the polymerase chain reaction followed by direct sequencing. Sequence analyses for drug resistance-associated mutations in th e protease and reverse transcriptase genes, and HIV-1 subtyping, were done. Overall, 92.8% of the generated sequences were HIV-1 subtype C. The generated sequences revealed only secondary associated, but no primary, drug-resistance mutations The most frequent secondary mutations in the protease and RT genes were, respectively, I93L(91.7%), L89M (79.2%), M3611V (79%, 4.2%), and R211K (70.8%), S48T (62.5%). The atypical residues M41N (3.6%) and D67A (3.6%) were detected in the RT gene. This study reveals many naturally occurring polymorphisms in HIV-1 subtype C isolates from antiretroviral drug-naive individuals. Such polymorphisms could lead to rapid treatment failure and development of drug-resistant HIV-1 mutants in individuals undergoing antiretroviral therapy.
Handema
Ray
R
Department of Mircrobiology, Yamanashi Medical University, Tamaho, Japan.
Terunuma
Hiroshi
H
Kasolo
Francis
F
Kasai
Hirotake
H
Sichone
Moses
M
Yamashita
Atsuya
A
Deng
Xuewen
X
Mulundu
Georgina
G
Ichiyama
Kouji
K
Munkanta
Mwansa
M
Yokota
Tomoyuki
T
Wakasugi
Naomi
N
Tezuka
Fumiaki
F
Yamamoto
Naoki
N
Ito
Masahiko
M
D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000494:pharmacology*; D004279:DNA, Viral / Q000032:analysis; D024882:Drug Resistance, Viral / Q000235:genetics*; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000453:epidemiology* / Q000821:virology; D016333:HIV Protease / Q000235:genetics; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000145:classification / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D010802:Phylogeny; D015995:Prevalence; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D015024:Zambia / Q000453:epidemiology
D019380:Anti-HIV Agents; D004279:DNA, Viral; D054303:HIV Reverse Transcriptase; D016333:HIV Protease