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Daniel Boden, MD; Arlene Hurley, RN; Linqi Zhang, PhD; Yunzhen Cao, MD; Yong Guo, MS; Elizabeth Jones; John Tsay; James Ip; Charles Farthing, MD; Kay Limoli, MS; Neil Parkin, PhD; Martin Markowitz, MD

JAMA. 1999;282:1135-1141.

Context  There is concern that the widespread use of antiretroviral drugs to treat human immunodeficiency virus 1 (HIV-1) infection may result in the increased transmission of drug-resistant virus.

Objective  To determine the prevalence of drug resistance–conferring mutations and phenotypic resistance to antiretroviral agents in a cohort of individuals newly infected with HIV-1.

Design  Case series with genetic analyses of the HIV-1 plasma-derived pol gene using reverse transcriptase polymerase chain reaction followed by direct sequencing of polymerase chain reaction products. Phenotypic analysis was performed with a recombinant virus assay.

Setting and Patients  Eighty individuals referred, on average, 1.7 months after infection with HIV-1 to the Aaron Diamond AIDS Research Center between July 1995 and April 1999. Subjects were from large urban areas (65 from New York, NY; 11 from Los Angeles, Calif); 60 (75%) were white, and 75 (93.8%) were homosexual men.

Main Outcome Measures  Prevalence of known resistance-conferring genotypes and reduced susceptibility to individual antiviral agents by phenotype.

Results  Thirteen individuals (16.3%) had genotypes associated with drug resistance to any antiretroviral agent. Virus with known resistance-conferring mutations to any nucleoside reverse transcriptase inhibitors was found in 10 individuals, to any nonnucleoside reverse transcriptase inhibitors in 6 subjects, and to any protease inhibitors in 2 cases. Multidrug-resistant virus was identified in 3 individuals (3.8%). Extensive polymorphism in the protease gene was identified. Interpretation of genotypes and phenotypes was concordant in 57 (85%) of the 67 cases in which both studies were performed.

Conclusion  The prevalence of HIV-1 variants with known resistance-conferring genotypes to any antiretroviral agent in this cohort of 80 newly infected individuals is 16.3%. These data support expanded use of resistance testing in the setting of primary HIV-1 infection. Clinical trials should be initiated to establish whether therapy guided by resistance testing, compared with the use of empirical triple combination antiretroviral therapy, provides additional virological and immunological benefit when treating primary HIV-1 infection. Further efforts to expand the study of transmission of drug-resistant HIV-1 variants, particularly in cohorts with different epidemiological profiles, are indicated.

Author Affiliations: The Aaron Diamond AIDS Research Center, Rockefeller University, New York, NY (Drs Boden, Zhang, Cao, and Markowitz, Mss Hurley, Guo, and Jones, and Messrs Tsay and Ip); AIDS Healthcare Foundation, Los Angeles, Calif (Dr Farthing); and ViroLogic Inc, South San Francisco, Calif (Ms Limoli and Dr Parkin).

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