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J. Virol. doi:10.1128/JVI.02579-07
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

The Persistence of Transmitted Drug Resistance among Subjects with Primary HIV Infection

Departments of Medicine and Pathology, University of California, San Diego, San Diego, California, USA; Department of Medicine, Veterans Affairs San Francisco Healthcare System; San Francisco, California, USA; Monogram Biosciences, South San Francisco, California, USA; Veterans Affairs San Diego Healthcare System; San Diego, California, USA

^* To whom correspondence should be addressed. Email: slittle{at}ucsd.edu.

	Abstract

Background: Following interruption of antiretroviral therapy among individuals with acquired drug resistance, pre-existing drug-sensitive virus emerges relatively rapidly. In contrast, wild-type virus is not archived in individuals infected with drug-resistant HIV and thus cannot emerge rapidly in the absence of selective drug pressure.

Methods and Findings: Fourteen recently HIV-infected patients with transmitted drug-resistant virus were followed for a median of 2.1 years after the estimated date of infection (EDI) without receiving antiretroviral therapy. HIV drug resistance and pol replication capacity (RC) were assayed in longitudinal plasma samples. Resistance mutations were characterized as pure populations or mixtures. The mean time to first detection of a wild-type/drug-resistant mixture was 96 weeks (1.8 years, 95% c.i. = 48-192 weeks) after the EDI. The median time to loss of detectable drug resistance using population-based assays ranged from 4.1 years (conservative estimate) to longer than the lifetime of the individual (less conservative estimate). The transmission of drug-resistant virus was not associated with virus of reduced RC.

Conclusions: Sexual transmission of HIV selects for highly fit drug-resistant variants that persist for years. The prolonged persistence of transmitted drug resistance strongly supports routine use of HIV resistance genotyping for all newly diagnosed individuals.