Transmission fitness of drug-resistant HIV revealed in a surveillance system transmission network

Test-and-treat programs are central to the global control of HIV, but transmitted drug resistance threatens the effectiveness of these programs. HIV mutations conferring resistance to antiretroviral drugs reduce replicative fitness in vitro, but their effect on propagation in vivo is less understood. Here, we estimate transmission fitness of these mutations in antiretroviral naive populations in the U.S. National HIV Surveillance System by comparing their frequency of clustering in a genetic transmission network relative with wild-type viruses. The large dataset (66,221 persons), comprising 30,196 antiretroviral naive persons, permitted the evaluation of sixty-nine resistance mutations. Decreased transmission fitness was demonstrated for twenty-three mutations, including M184V. In contrast, many high prevalence mutations (e.g. K103N, Y181C, and L90M) had transmission fitness that was indistinguishable from or exceeded wild-type fitness, permitting the establishment of large, self-sustaining drug resistance reservoirs. We highlight implications of these findings on strategies to preserve global treatment effectiveness.