Resisting Drug Resistance in Resource-Constrained Settings
Improving access to virologic monitoring in such settings is essential to maximizing HIV treatment outcomes.
Expanded availability of antiretroviral therapy (ART) in resource-limited settings has led to improved outcomes among HIV-infected people — but also to more failures of initial treatment regimens, caused by adherence problems or transmitted resistance. Understanding the resistance consequences of first-line treatment failure is critical to planning management strategies for second-line therapy. Investigators recently reviewed data from resource-limited settings on the emergence of HIV drug resistance among individuals for whom first-line therapy has failed, as well as on clinical and resistance outcomes of those treated with second-line ART.
Most first-line ART regimens consisted of a nonnucleoside reverse transcriptase inhibitor (NNRTI) plus two nucleoside reverse transcriptase inhibitors (NRTIs). Overall, 76% to 90% of individuals receiving such regimens achieved HIV suppression within 12 months. Among those with detectable HIV RNA at 12 months, 60% to 72% had virus with resistance mutations identified — most often M184V, K103N, or both. When clinical or immunologic parameters (CD4-cell counts) rather than viral load were used to determine treatment failure, resistance-mutation patterns were often more varied and complex because of longer duration of viral replication on a failing regimen. One study of patients treated with AZT/3TC + nevirapine showed an average of 2.89 thymidine-associated mutations arising during the second year of nonsuppressive ART, reinforcing the value of earlier switch from a virologically failing regimen. Second-line regimens (usually involving HIV protease inhibitors) were generally effective, but did not suppress virus in about 22% of those receiving them, most often due to poor adherence.
CITATION(S):
Hosseinipour MC et al. Emergence of HIV drug resistance during first- and second-line antiretroviral therapy in resource-limited settings. J Infect Dis 2013 Jun 15; 207:suppl 2:S49.
