Genetic variation at NNRTI resistance-associated positions in patients infected with HIV-1 subtype C

Zehava Grossman, Valery Istomin, Diana Averbuch, Margalit Lorber, Klaris Risenberg, Itzchak Levi, Michal Chowers, Michael Burke, Nimrod Bar Yaacov, Jonathan M. Schapiro

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)909-915
Number of pages7
JournalAIDS
Volume18
Issue number6
DOIs
StatePublished - 9 Apr 2004
Externally publishedYes

Keywords

  • Drug resistance
  • Genetic variation
  • HIV
  • NNRTI
  • Reverse transcriptase
  • Subtype B
  • Subtype C
  • V106M mutation

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