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.
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.


CONCLUSIONS
Our results suggest that the genetic diversity of HIV-1 does not play a major role in the development of resistance to antiretroviral drugs.
Montes
Brigitte
B
Department of Virology, University Hospital of Montpellier, Montpellier, France.
Vergne
Laurence
L
Peeters
Martine
M
Reynes
Jacques
J
Delaporte
Eric
E
Segondy
Michel
M
D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology*; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D015658:HIV Infections / Q000188:drug therapy*; D016333:HIV Protease / Q000235:genetics*; D054303:HIV Reverse Transcriptase / Q000235:genetics*; D015497:HIV-1 / Q000145:classification / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation
D019380:Anti-HIV Agents; D054303:HIV Reverse Transcriptase; D016333:HIV Protease