1. Genetic variation at NNRTI resistance-associated positions in patients infected with HIV-1 subtype C
- Author
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Diana Averbuch, Michael Burke, Nimrod Bar Yaacov, Michal Chowers, Itzchak Levi, Zehava Grossman, Margalit Lorber, Klaris Risenberg, Jonathan M. Schapiro, and Valery Istomin
- Subjects
Adult ,Cyclopropanes ,Male ,Efavirenz ,Nevirapine ,Immunology ,HIV Infections ,Drug resistance ,Biology ,chemistry.chemical_compound ,Drug Resistance, Viral ,Oxazines ,Genetic variation ,medicine ,Humans ,Immunology and Allergy ,Sida ,Polymorphism, Genetic ,Reverse-transcriptase inhibitor ,Genetic Variation ,virus diseases ,Nucleosides ,Resistance mutation ,biology.organism_classification ,Virology ,Reverse transcriptase ,Benzoxazines ,Infectious Diseases ,chemistry ,Alkynes ,Mutation ,HIV-1 ,RNA, Viral ,Reverse Transcriptase Inhibitors ,Female ,medicine.drug - Abstract
OBJECTIVE Genetic differences between subtypes of HIV-1, even when not associated with key resistance mutations, are known to affect baseline susceptibility to specific antiretroviral drugs and resistance-development pathways. We studied the prevalence and patterns of non-nucleoside reverse transcriptase inhibitor (NNRTI)-associated mutations in HIV-1 subtype C-infected patients. METHOD We analysed the genetic variation at sites associated with NNRTI and nucleoside reverse transcriptase inhibitor resistance in subtype C- versus B-infected patients, both drug-naive and -experienced. We extended the comparison to subtype B records from the Stanford database. RESULTS A total of 150 subtype B and 341 subtype C-infected patients were studied. No significant differences were found in treatment and clinical parameters between the groups. In NNRTI-naive patients, changes in NNRTI positions were present in 9.3% of subtype B- versus 33.1% of subtype C-infected patients (P < 0.001). Differences were seen in both drug-naive (subtype B, 10.0% versus subtype C, 50.1%; P < 0.021) and drug-experienced NNRTI-naive patients (subtype B, 9.0% versus subtype C, 23.8%; P < 0.001). In NNRTI experienced patients, the number of A98G/S changes was significantly higher in subtype C patients treated with either efavirenz or nevirapine (P < 0.0001), and V106M was higher in efavirenz-treated subtype C-infected patients (P < 0.0001). The average mutation rates were 1.26 and 1.67 per patient for subtypes B and C, respectively (P = 0.036). The frequency of nucleoside associated mutations, but not M184V, in treated patients was significantly higher in subgroup B-infected patients (P = 0.028). CONCLUSION Collectively, these data indicate that genetic variation at NNRTI resistance-associated positions such as V106M and A98S is substantially greater in subtype C-infected patients than in subtype B-infected patients. The natural structure of each subtype probably affects the frequency and pattern of drug resistance mutations selected under treatment.
- Published
- 2004