Treatment limitations imposed by antiretroviral drug resistance mutations: implication for choices of first line regimens in resource-limited settings.

BACKGROUND

Recent studies have suggested that failing nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens may have greater potential to induce the development of resistance mutations, which may limit options for second-line therapy.

METHODS

Antiretroviral therapy (ART)-naïve individuals aged ≥18 years who initiated triple combination ART between January 2000 and June 2006 in British Columbia, Canada were enrolled in the study. We compared genotypic sensitivity scores (GSSs) derived from the development of resistance mutations between participants who initiated ART with ritonavir-boosted protease inhibitors (PIs) with those who initiated ART with NNRTIs, and determined the effects of these mutations on remaining active drugs.

RESULTS

A total of 1666 participants initiated ART, 818 (49.1%) with NNRTI-based regimens and 848 (50.9%) with boosted PI-based regimens. Among participants who developed resistance mutations, those who initiated NNRTI-based regimens had a lower median GSS than those on boosted PI-based regimens (9.8 vs. 11.0, respectively; P<0.001). Participants on boosted PI-based regimens [adjusted odds ratio (AOR) 3.68; 95% confidence interval (CI) 2.25, 6.01], those with ≥95% adherence to highly active antiretroviral therapy (HAART) (AOR 1.84; 95% CI 1.16, 2.92) and those with baseline CD4 count >200 cells/μL (AOR 3.44; 95% CI 1.73, 6.84) were more likely to have the maximum number of drug options.

CONCLUSION

The use of NNRTI-based first-line ART regimens may limit the options for second-line treatment when the number of available drugs is limited.