Many patients infected with HIV do not achieve or maintain virologic suppression below levels of detection while on potent combination antiretroviral therapy. The likelihood of emergence of incident mutations conferring reduced antiretroviral drug susceptibility was estimated among patients maintained on a stable regimen with ongoing detectable plasma HIV RNA levels. Ninety-eight HIV-infected patients were identified who had 2 genotypic antiretroviral resistance tests available. Poisson log-linear regression models were used to identify predictors and estimate incidence rates of number of acquired antiretroviral drug resistance mutations per person-year. At the 1st resistance test, 88% of patients had evidence of at least 1 mutation. Sixty percent of patients acquired at least 1 new mutation during a median of 9.3 months between consecutive resistance tests, with an incidence rate of 1.61 acquired mutations per person-year (95% CI: 1.36-1.90). Predictors of resistance evolution included average plasma HIV RNA level, HIV RNA slope, and number of mutations detected at the 1st resistance test. The likelihood of acquiring drug resistance mutations while remaining on potent combination antiretroviral therapy that does not confer complete suppression of HIV replication is relatively low and depends on the level of viral replication and prior resistance.
From the *School of Medicine, Division of Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, NC; †School of Medicine, Duke University, Durham, NC; and ‡School of Public Health, Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC.
Received for publication February 14, 2005; accepted June 13, 2005.
Supported by the University of North Carolina at Chapel Hill, Center for AIDS Research, National Institutes of Health-funded program 9P30 AI 50410-04; the University of North Carolina, General Clinical Research Center, National Institutes of Health-funded program RR00046; the Doris Duke Clinical Research Foundation; and the Alpha Omega Alpha Carolyn L. Kuckein Student Research Fellowship.
Reprints: Sonia Napravnik, School of Medicine, Division of Infectious Diseases, The University of North Carolina at Chapel Hill, 211-A West Cameron Avenue, Chapel Hill, NC 27599-7215 (e-mail: firstname.lastname@example.org).