Setting: Malawi has an extensive national antiretroviral treatment (ART) program, and although less than 2% of all patients receive second-line ART, there are increasingly more patients failing on these regimens.Objective: To establish a virtual ART committee using limited available local facilities and expertise to recommend third-line regimens based on genotype resistance of samples sent abroad.Design: A secretariat and a laboratory sample hub were established. The committee started work after locally organizing training courses. Decisions about ART regimens were mainly based on a relatively simple, previously described algorithm, which allowed decisions to be taken without extensive expert knowledge.Results: Of the 25 applications assessed, 23 samples were sent for resistance testing from June 2017 to April 2018. Major protease inhibitor (PI) resistance was detected in 65% of the samples. PI resistance was found even in patients exposed to PIs for short periods. In particular, patients who received co-administration of PIs and rifampicin frequently showed resistance mutations.Conclusion: Third-line ART using genotypic resistance testing and algorithm-based treatment regimens are feasible in low-resource settings. Our model can serve as a base for similar programs initiating programmatic third-line ART in other African countries.