Although second-line generic antiretroviral drugs are of great value in developing countries, there are concerns regarding their quality. We studied a generic Lopinavir/ritonavir (200/50 mg; Arga-L, India) marketed in the Republic of Congo but not prequalified by WHO. Despite adequate quantitative and qualitative drug content, Arga-L had a bio-availablility of 10% compared with Kaletra. To avoid selection of drug-resistant HIV, rigorous pharmacological monitoring of generic drugs not prequalified by WHO must be a priority.