Resistance-associated mutations were detected in 13.8% of treatment-naive patients in three Asian countries, but most of the mutations were of questionable clinical relevance.
Given that the options for antiretroviral therapy (ART) are limited in many Asian countries, transmitted drug resistance could have a major influence on treatment outcomes. However, the prevalence of such resistance in Asia remains largely unknown.
Researchers used standard genotyping assays to test for HIV drug resistance–associated mutations (RAMs) in 682 treatment-naive patients initiating ART at any of eight sites in Hong Kong, Malaysia, and Thailand. Most patients were infected with HIV-1 subtype CRF01_AE (78%) or subtype B (16%).
Overall, 13.8% of patients had evidence of at least one mutation that is associated with resistance to nucleoside reverse transcriptase inhibitors (NRTIs), nonnucleoside reverse transcriptase inhibitors (NNRTIs), or protease inhibitors. The RAMs most commonly identified included the NRTI mutation K70R (6.5%) and the NNRTI mutations V179D (3.2%), V106I (1.9%), and V90I (0.7%).
Comment: Because the HIV epidemic in Asia is relatively young, one would expect there to be relatively low rates of exposure to sequential monotherapy. The observed rate of RAMs detected (13.8%) is therefore disturbingly high. Fortunately, most of the observed mutations are common polymorphisms and, at least when present in isolation, would not be expected to alter susceptibility to standard first-line regimens. K70R, for instance, affects several NRTIs when combined with other thymidine analogue mutations, but it has only a negligible effect when found in isolation, as was the case in most instances in this study. Similarly, while the NNRTI mutations listed above have been detected in patients failing etravirine, none of them affect the NNRTIs routinely used in Asia, namely nevirapine and efavirenz. All mutations observed in this study, however, could affect pathways to resistance and reduce secondary options in patients failing therapy. In contrast to guidelines used in Europe and the U.S., the WHO and Thai national guidelines do not recommend resistance testing at treatment initiation. These study findings suggest that resistance testing would be important, at least in patients with treatment failure.