Differential Persistence of Transmitted HIV-1 Drug Resistance Mutation Classes

Methods. We studied participants with acute and/or early HIV infection and TDR in 2 cohorts (San Francisco, California, and Sao Paulo, Brazil). We followed baseline mutations longitudinally and compared replacement rates between mutation classes with use of a parametric proportional hazards model. Results. Among 75 individuals with 195 TDR mutations, M184V/I became undetectable markedly faster than did nonnucleoside reverse-transcriptase inhibitor (NNRTI) mutations (hazard ratio, 77.5; 95% confidence interval [CI], 14.7-408.2; P < .0001), while protease inhibitor and NNRTI replacement rates were similar. Higher plasma HIV-1 RNA level predicted faster mutation replacement, but this was not statistically significant (hazard ratio, 1.71 log(10) copies/mL; 95% CI, .90-3.25 log(10) copies/mL; P = .11). We found substantial person-to-person variability in mutation replacement rates not accounted for by viral load or mutation class (P < .0001). Conclusions. The rapid replacement of M184V/I mutations is consistent with known fitness costs. The long-term persistence of NNRTI and protease inhibitor mutations suggests a risk for person-to-person propagation. Host and/or viral factors not accounted for by viral load or mutation class are likely influencing mutation replacement and warrant further study.

National Institutes of Health/National Institute of Allergy and Infectious Diseases (NIH)[T32AI060530]

National Institutes of Health/National Institute of Allergy and Infectious Diseases (NIH)[PO1AI071713]

National Institutes of Health/National Institute of Allergy and Infectious Diseases (NIH)[K24AI069994]

National Institutes of Health/National Institute of Allergy and Infectious Diseases (NIH)[P30 AI027763]

National Institutes of Health/National Institute of Allergy and Infectious Diseases (NIH)[UL1 RR024131]

Brazilian Programfor STD and AIDS, Ministry of Health[914/BRA/3014-UNESCO]

Sao Paulo City Health Department[2004-0.168.922-7]

Programa Nacional de Pos Doutorado / Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior[PNPD/CAPES-2496/08]

FAPESP Fundacao de Amparo a Pesquisa do Estado de Sao Paulo[04/15856-9]

FAPESP Fundacao de Amparo a Pesquisa do Estado de Sao Paulo[04/12316-3]

Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq), Brazilian Ministry of Science and Technology