Current treatment guidelines recommend switching patients to at least 2 active antiretroviral agents at the earliest evidence of detectable viremia related to decreased drug susceptibility.[1,5] This approach is appealing if a new regimen is available, well tolerated, and succeeds in limiting HIV replication to undetectable levels, thereby minimizing the probability of acquiring additional resistance. The aggressiveness with which to approach virologic failure, however, must be balanced by the risks associated with exposing patients to additional antiretroviral agents. Our findings demonstrate a relatively slow rate of resistance evolution in patients with HIV-1 subtype B, especially among individuals with multiple mutations, who have stable HIV RNA levels in plasma over time, and who maintain HIV RNA levels <1000 copies/mL. These data suggest that maintaining specific patients on a failing regimen results in relatively slow resistance evolution with limited reduction in antiretroviral drug susceptibility. However, this must be tempered by the specific regimen and prior resistance profile of the patient, because acquiring even a single mutation may cause resistance to all NNRTIs and the M184V mutation leads to resistance to lamivudine and emtricitabine.
Many patients maintained on an incompletely suppressive regimen continue to derive immunologic, virologic, and clinical benefit, possibly due to the reduced replication capacity of mutant HIV variants, enhanced HIV-specific immune responses, and residual drug activity.[3,6,29,30] Therefore, delaying switching of suboptimal regimens may be indicated in some patients. However, patients with HIV-1, with limited resistance, especially those with plasma HIV RNA >1000 copies/mL, are at risk for emergence of increasingly resistant virus. Further studies monitoring resistance evolution over time are needed, and combined analyses across observational clinical cohorts would strengthen our initial observations.