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Robert M. Grant, MD, MPH; Frederick M. Hecht, MD; Maria Warmerdam, BS; Lea Liu, MD, MSc; Teri Liegler, PhD; Christos J. Petropoulos, PhD; Nicholas S. Hellmann, MD; Margaret Chesney, PhD; Michael P. Busch, MD; James O. Kahn, MD

JAMA. 2002;288:181-188.

Context  Transmission of multiclass drug-resistant human immunodeficiency virus type 1 (HIV-1) may increase with wider use of antiretroviral therapy.

Objective  To determine trends in prevalence of HIV-1 drug resistance among recently infected individuals in a geographic area with a high penetration of antiviral treatment.

Design, Setting, and Patients  Consecutive case series of 225 patients referred to a San Francisco, Calif, hospital with recent HIV-1 infection from June 1996 through June 2001.

Main Outcome Measure  Time trends in the prevalence of genotypic and phenotypic primary drug resistance.

Results  Mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors (NNRTIs) steadily increased from 0% in 1996-1997 to 12 (13.2%) in 2000-2001 (P = .01). There was 1 mutation associated with protease inhibitor resistance in 1996-1997 (2.5%) and there were 7 (7.7%) in 2000-2001 (P = .25). Genotypic resistance to nucleoside reverse transcriptase inhibitors (NRTIs) initially decreased and then returned to prior levels (P = .007 for test of homogeneity). Genotypic resistance to 2 or more classes of drugs increased from 1 (2.5%) to 12 (13.2%) (P = .004), but only 1 infection (1.2%) in the latter period was resistant to all 3 classes of agents (P = .58). Primary phenotypic resistance decreased for NRTIs from 21% to 6.2% (P = .03) and increased for NNRTIs from 0 to 8 (9.9%) (P = .02). Phenotypic resistance increased for protease inhibitors from 2.6% to 6.2% (P = .32). Median time to virologic suppression (<500 copies/mL) during therapy was 12 weeks for patients with genotypic evidence of resistance compared with 5 weeks for patients with drug-sensitive infections (P = .02).

Conclusions  The frequency of primary resistance to NNRTIs is increasing, although resistance to all available classes of antiretroviral therapy remains rare. Genotypic resistance testing in recently infected persons predicts time to viral suppression during therapy.

Author Affiliations: Gladstone Institute of Virology and Immunology (Drs Grant and Liegler and Ms Warmerdam), Positive Health Program, San Francisco General Hospital (Drs Grant, Hecht, Liu, and Kahn), Center for AIDS Prevention Studies (Dr Chesney), Department of Medicine, University of California, San Francisco (Drs Grant, Hecht, Liu, Busch, and Kahn), Blood Centers of the Pacific (Dr Busch), San Francisco; and ViroLogic, South San Francisco, Calif (Drs Petropoulos and Hellmann).

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