Performance of a World Health Organization first-line regimen (stavudine/lamivudine/nevirapine) in antiretroviral-naïve 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-naïve 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-naïve 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.