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Susan J. Little, MD; Eric S. Daar, MD; Richard T. D'Aquila, MD; Philip H. Keiser, MD; Elizabeth Connick, MD; Jeannette M. Whitcomb, PhD; Nicholas S. Hellmann, MD; Christos J. Petropoulos, PhD; Lorraine Sutton; Jacqui A. Pitt, RN; Eric S. Rosenberg, MD; Richard A. Koup, MD; Bruce D. Walker, MD; Douglas D. Richman, MD

JAMA. 1999;282:1142-1149.

Context  The transmission of drug-resistant human immunodeficiency virus (HIV) has been documented, but the prevalence of such transmission is unknown.

Objective  To assess the spectrum and frequency of antiretroviral susceptibility among subjects with primary HIV infection.

Design, Setting, and Patients  Retrospective analysis of 141 subjects identified from clinical research centers in 5 major metropolitan areas, enrolled from 1989 to 1998, with HIV seroconversion within the preceding 12 months and no more than 7 days' prior antiretroviral (ARV) therapy.

Main Outcome Measures  Phenotypic and genotypic ARV susceptibility of HIV from plasma samples.

Results  The transmission of drug-resistant HIV as assessed by a greater than 10-fold reduction in ARV susceptibility to 1 or more drugs was observed in 3 (2%) of 141 subjects, including to a nonnucleoside reverse transcriptase inhibitor in 1 patient and to a nucleoside reverse transcriptase inhibitor and a protease inhibitor in 2 patients. Population-based sequence analysis of these 3 samples identified multidrug-resistance mutations in reverse transcriptase (M184V, T215Y, K219K/R) and protease (L10I/V, K20R, M36I, M46I, G48V, L63P, A71T, V77I, V82T, I84V, L90M) in the 2 latter patient samples, along with numerous polymorphisms. A reduction in susceptibility of greater than 2.5- to 10-fold to 1 or more drugs was observed in viral isolates from 36 patients (26%). Sequence analysis of these 36 samples identified well-characterized drug resistance mutation in reverse transcriptase and protease in only 1 of these patients.

Conclusions  Reductions in drug susceptibility of more than 10-fold were rare among this cohort of recently HIV-infected subjects and were distributed among each of the 3 major classes of ARV drugs tested. Reductions in susceptibility of more than 2.5- to 10-fold to certain ARV drugs of unknown clinical significance were highly prevalent among newly infected patients. Resistance testing may be warranted to monitor the frequency of drug resistance over time and to assess the potential for geographic variability.

Author Affiliations: Departments of Medicine (Drs Little and Richman) and Pathology (Dr Richman), University of California, San Diego, and the Department of Veterans Affairs Medical Center, San Diego (Dr Richman); Department of Medicine, Cedars-Sinai Burns and Allen Research Institute, and the University of California, Los Angeles (Dr Daar and Ms Pitt); Department of Medicine, University of Texas Southwestern Medical Center, Dallas (Drs Keiser and Koup); Department of Medicine, Massachusetts General Hospital, Boston (Drs D'Aquila, Rosenberg, and Walker and Ms Sutton); Department of Medicine, University of Colorado Health Sciences Center, and the Department of Veterans Affairs Medical Center, Denver (Dr Connick); and ViroLogic Inc, South San Francisco, Calif (Drs Whitcomb, Hellmann, and Petropoulos).

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