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Genetic variation at NNRTI resistance-associated positions in patients infected with HIV-1 subtype C
- Source :
- AIDS. 18:909-915
- Publication Year :
- 2004
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 2004.
-
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.
- 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
Subjects
Details
- ISSN :
- 02699370
- Volume :
- 18
- Database :
- OpenAIRE
- Journal :
- AIDS
- Accession number :
- edsair.doi.dedup.....2e087e2145fb832cfc874ff3007bc744