Background:
The genetic differences among HIV-1 subtypes may be critical to clinical management and
drug resistance surveillance as antiretroviral treatment is expanded to regions of the world
where diverse non-subtype-B viruses predominate.
Methods and Findings:
To assess the impact of HIV-1 subtype and antiretroviral treatment on the distribution of
mutations in protease and reverse transcriptase, a binomial response model using subtype and
treatment as explanatory variables was used to analyze a large compiled dataset of non-
subtype-B HIV-1 sequences. Non-subtyp
e-B sequences from 3,686 persons with well
characterized antiretroviral treatment histories were analyzed in comparison to subtype B
sequences from 4,769 persons. The non-subtype-B sequences included 461 with subtype A,
1,185 with C, 331 with D, 245 with F, 293 with G, 513 with CRF01_AE, and 618 with CRF02_AG.
Each of the 55 known subtype B drug-resistance mutations occurred in at least one non-B
isolate, and 44 (80%) of these mutations were significantly associated with antiretroviral
treatment in at least one non-B subtype. Conversely, of 67 mutations found to be associated
with antiretroviral therapy in at least one non-B subtype, 61 were also associated with
antiretroviral therapy in subtype B isolates.
Conclusion:
Global surveillance and genotypic assessment of drug resistance should focus primarily on
the known subtype B drug-resistance mutations.