First‐Line Antiretroviral Therapy in Resource‐Limited Settings: Time to Reconsider?

To the Editor—Combination treatment with lamivudine, stavudine, and the non-nucleoside reverse-transcriptase inhibitor (NNRTI) nevirapine is the first-line antiret-roviral (ART) regimen recommended by the World Health Organization for the treatment of HIV infection. This regimen is associated with a low genetic barrier to resistance. Therefore, to avoid the development of resistance, its supply must not be interrupted. Strategies have been developed by international nongovernmental organizations (NGOs) to secure the supply of ART to patients, particularly in unsecure areas [1]. Is it time, however, to consider boosted protease inhibitor (PI)– based combination therapy as the first-line regimen in certain resource-limited settings (RLS)? Supply problems lie not with delivery at the national level but in overcoming obstacles to supply at the local level. While working with an international NGO in the Democratic Republic of Congo, we experienced many obstacles to the delivery of ART supplies in an unstable RLS. Civil unrest continues , particularly in the east, where rural health care is scarce. Most patients traveling to our clinics from the villages kept their appointments. But when the patients' dependents became sick, their crops needed harvesting , or violence erupted in their region, several months sometimes passed between appointments. Urban health care is provided by state agencies, private agencies, and NGOs. The stability of the supply of medications is uncertain. On occasion, we were approached by the local teaching hospital when their stocks of essential medications ran out. During the first 2 years of the ART program sponsored by our NGO, we were the sole providers of ART in the province. A few months into program, samples of our medications appeared in pharmacies 200 km away. Lima et al. [2] demonstrated that boosted PI-based ART regimens were significantly associated with a lower emergence of resistance , compared with nonboosted PI-based regimens. This remained the case at all levels of treatment adherence [2]. This trend has also been demonstrated by other recent studies [3]. Patients who start therapy with lower CD4 ϩ cell counts and higher viral loads (which is the case for the majority of HIV-infected persons in sub-Saharan Af-rica) were also less likely to develop resistance than were those taking a nonboosted PI or an NNRTI [3, 4]. British HIV Association guidelines state that " a boosted prote-ase inhibitor is likely to be preferable for patients with a risk of poor adherence given that treatment with this type of drug is less …