Assessing the association between changing NRTIs when initiating second-line ART and treatment outcomes.

BACKGROUND After first-line antiretroviral therapy (ART) failure, the importance of change in nucleoside reverse transcriptase inhibitor (NRTI) in second-line is uncertain due to the high potency of protease inhibitors used in second-line. SETTING We used clinical data from 6,290 adult patients in South Africa and Zambia from the International Epidemiologic Databases to Evaluate AIDS-Southern Africa cohort. METHODS We included patients who initiated on standard first-line ART and had evidence of first-line failure. We used propensity score-adjusted Cox proportional hazards models to evaluate the impact of change in NRTI on second-line failure compared to remaining on the same NRTI in second-line. In South Africa, where viral load monitoring was available, treatment failure was defined as two consecutive viral loads >1,000 copies/mL. In Zambia, it was defined as two consecutive CD4 counts <100 cells/mm. RESULTS Among patients in South Africa initiated on zidovudine, the adjusted hazard ratio for second-line virologic failure was 0.25 (95% CI: 0.11, 0.57) for those switching to tenofovir vs. remaining on zidovudine. Among patients in South Africa initiated on tenofovir, switching to zidovudine in second-line was associated with reduced second-line failure (adjusted hazard ratio = 0.35 [95% CI: 0.13, 0.96]). In Zambia where viral load monitoring was not available, results were less conclusive. CONCLUSION Changing NRTI in second-line was associated with better clinical outcomes in South Africa. Additional clinical trial research regarding second-line NRTI choices for patients initiated on tenofovir or with contraindications to specific NRTIs is needed.