We describe the resistance-associated substitutions that are present in the reverse transcriptase (RT) genes of HIV-1 CRF02_AG strains infecting drug-naive villagers of Cameroon. The 11 sequences analyzed were previously subtyped as CRF02_AG in the gag, pro, and env genes, and this work revealed that most (10/11) had a concordant subtype (CRF02_AG) in the pol gene, while one sequence had discordant subtype (A1) in the pol gene. Classification of the CRF02_AG sequences was further confirmed by recombination breakpoint analysis, which revealed a mosaic composition similar to the reference strain IbNG. Analysis of the RT genes for resistance-associated substitutions revealed two sequences containing a V118I substitution. Even though no other resistance-associated substitutions were found, the presence of V118I, which is implicated in resistance to reverse transcriptase inhibitors, in CRF02_AG strains infecting drug-naive individuals should be considered when introducing these antiretrovirals in areas where CRF02_AG is the predominant subtype, such as Cameroon.