Performance of a World Health Organization first-line regimen (stavudine/lamivudine/nevirapine) in antiretroviral-naive individuals in a Western setting.

OBJECTIVES: In 2003, the World Health Organization (WHO) and Joint United Nations Programme on HIV/AIDS (UNAIDS) introduced the '3 by 5 Initiative' to treat 3 million individuals by the end of 2005. This study evaluates the time to treatment termination, viral load suppression, and detection of drug resistance among antiretroviral-naive individuals initiating stavudine/lamivudine/nevirapine (d4T/3TC/NVP) in British Columbia, Canada, to provide a context for future programme planning. METHODS: Primary outcome was time to treatment termination. Secondary outcome was time to viral suppression. Accumulation of drug resistance mutations was followed systematically in the first 145 individuals over 30 months. Cox proportional hazard regression identified factors associated with termination and suppression. RESULTS: 312 antiretroviral-naive individuals initiated d4T/3TC/NVP between August 1996 and September 2003. Median follow-up time was 26.5 months (interquartile range [IQR] 6.8-46.5). At a median of 12.4 months (IQR 4.3-33.3), 132 (42.3%) patients switched treatment, 53 (17.0%) stopped therapy and 26 (8.3%) died. Of 308 subjects with baseline viral load >500 copies/mL, 223 (72.4%) suppressed to <or=500 copies/mL at a median of 2.0 months. Among 145 (46.5%) individuals followed longitudinally, resistance mutations to NNRTI, 3TC, or other NRTI were detected in 11 (7.6%), six (4.1%) and four (2.8%) individuals after 12 months of therapy; and in 23 (15.9%), 17 (12.0%), and six (4.1%) individuals after 30 months. CONCLUSIONS: The population requiring second-line treatment was 30% at 12 months and 40% at 24 months; 20% had detectable drug resistance mutations by 30 months. While these results are from a Western setting, they illustrate the need to consider second- and third-line approaches as antiretroviral treatment scale-up continues in the developing world.