Prioritizing Antiretrovirals for Second-Line Therapy in Resource-Limited Countries

Approximately 2 million people in low- to middle-income countries are currently receiving potent antiretroviral therapy (ART). Although at least 95% of these patients are on first-line regimens, many are expected to require second-line therapy by 2010. To help national program officials plan for this shift, the WHO has released recommendations from an expert panel that was convened in May 2007.

The panel determined that, in accordance with WHO guidelines, current first-line therapy in low- to middle-income countries is predominantly AZT or d4T in combination with 3TC and an NNRTI. Use of tenofovir, abacavir, PIs, and triple-NRTI regimens is limited. By 2010, second-line agents are expected to account for 90% of the cost of antiretrovirals, assuming current switch rates of 3% per year and no price reductions in medications. Because of the lack of viral-load measurement to detect virologic failure, switching is often delayed in resource-limited settings, which raises the likelihood of NRTI resistance.

The panel reviewed the antiretrovirals recommended in 2006 by the WHO for second-line therapy and evaluated each based on six domains: efficacy, simplicity, toxicity, suitability for use in special populations, potential for low cost, and compatibility with pediatric formulations. The panel deemed the following drugs to be the highest priorities for inclusion in formularies of second-line ART:

• For use in patients who previously received a thymidine analogue: tenofovir/3TC and abacavir + ddI

• For use in patients who did not receive a thymidine analogue previously: AZT/3TC, for those who experienced virologic failure on tenofovir; and AZT/3TC and tenofovir/3TC, for those who previously received abacavir

• For use in most patients: lopinavir/ritonavir and ritonavir-boosted atazanavir