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Background  Rapid scale-up of antiretroviral therapy (ART) and limited access to genotyping assays in low-resource settings (LRS) are inevitably accompanied by an increasing risk of HIV drug resistance (HIVDR). The current study aims to evaluate early warning indicators (EWI) as an efficient strategy to limit the development and spread of preventable HIVDR in these settings, in order to sustain the performance of national antiretroviral therapy (ART) rollout programmes.    Methods  Surveys were conducted in 2008, 2009 and 2010 within 10 Cameroonian ART clinics, based on five HIVDR EWIs: (1) Good prescribing practices; (2) Patient lost to follow-up; (3) Patient retention on first line ART; (4) On-time drug pick-up; (5) Continuous drug supply. Analysis was performed as per the World Health Organisation (WHO) protocol.    Results  An overall decreasing performance of the national ART programme was observed from 2008 to 2010: EWI 1  (100% to 70%); EWI 2  (40% to 20%); EWI 3  (70% to 0%); EWI 4  (0% throughout); EWI 5  (90% to 40%). Thus, prescribing practices (EWI 1 ) were in conformity with national guidelines, while patient adherence (EWI 2 , EWI 3 , and EWI 4 ) and drug supply (EWI 5 ) were lower overtime; with a heavy workload (median ratio ≈1/64 staff/patients) and community disengagement observed all over the study sites.    Conclusions  In order to limit risks of HIVDR emergence in poor settings like Cameroon, continuous drug supply, community empowerment to support adherence, and probably a reduction in workload by task shifting, are the potential urgent measures to be undertaken. Such evidence-based interventions, rapidly generated and less costly, would be relevant in limiting the spread of preventable HIVDR and in sustaining the performance of ART programmes in LRS.

Declining trends in early warning indicators for HIV drug resistance in Cameroon from 2008–2010: lessons and challenges for low-resource settings