Comparison of drug resistance mutations and their interpretation in patients infected with non-B HIV-1 variants and matched patients infected with HIV-1 subtype B

J Acquir Immune Defic Syndr. 2004 Apr 1;35(4):329-36. doi: 10.1097/00126334-200404010-00001.

Abstract

Objective: To compare the prevalence of mutations associated with resistance to antiretroviral drugs and their interpretation in patients infected with non-B HIV-1 variants versus HIV-1subtype B-infected patients with similar treatment regimens.

Methods: The reverse transcriptase (RT) and protease genes of HIV-1 were sequenced, and subtypes were determined by phylogenetic analysis. Each sequence belonging to a non-B variant was matched with a sequence belonging to subtype B. Patterns of resistance mutations were interpreted in terms of drug resistance using the HIV db algorithm.

Results: RT mutations M41L, L210W, and, to a lesser extent, T215Y were less prevalent in patients infected with non-B variants. This lower prevalence was associated with subtypes A (A1/A2), C, F (F1/F2), and CRF06_cpx. A lower prevalence of high-level resistance to zidovudine was also observed in patients infected with these HIV-1 variants. In the protease gene, differences between patients infected with B or non-B strains were mainly observed for mutations playing a minor role in drug resistance and known to occur mainly as a natural polymorphism in non-B strains: K20R/M/I, M36I, L63P, A71V/T, and V77I. Interpretation of genotypes using the HIV db algorithm indicated that resistance to saquinavir, ritonavir, indinavir, and amprenavir was more frequently a high-level resistance for subtype B and an intermediate-level resistance for non-B variants, but this difference was only significant for amprenavir.

Conclusion: Our results suggest that the genetic diversity of HIV-1 does not play a major role in the development of resistance to antiretroviral drugs.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Anti-HIV Agents / pharmacology*
  • Drug Resistance, Viral / genetics*
  • Female
  • Genetic Variation
  • HIV Infections / drug therapy*
  • HIV Protease / genetics*
  • HIV Reverse Transcriptase / genetics*
  • HIV-1 / classification
  • HIV-1 / genetics*
  • Humans
  • Male
  • Middle Aged
  • Mutation

Substances

  • Anti-HIV Agents
  • HIV Reverse Transcriptase
  • HIV Protease