Primary, or transmitted, drug resistance is common among treatment naive patients recently infected with HIV-1, and impairs response to anti-retroviral therapy. We previously observed that patients with secondary resistance (developed in response to anti-retroviral treatment) who chose to stop an anti-retroviral regimen experience rapid overgrowth of drug resistant viruses by wild-type virus of higher pol replication capacity. We sought to determine if primary drug resistance would be lost at a rapid rate, and viral pol replication capacity would increase, in the absence of treatment.
We tracked drug resistance phenotype, genotype, viral pol replication capacity (single cycle recombinant assay incorporating a segment of the patient pol gene [pol RC]), plasma HIV-1 RNA, and CD4 T cell counts in the absence of treatment among patients in early HIV-1 infection.
Six of 22 patients had evidence of primary drug resistance to at least one class of drug; three resistant to protease inhibitors, three resistant to non-nucleoside reverse transcriptase inhibitors, and four resistant to nucleoside reverse transcriptase inhibitors. All six patients maintained evidence of drug resistance for the period of observation. Among patients with baseline primary drug resistance pol RC did not increase over time.
The selection environment of early infection is determined by immune pressure, and stochastic events, not viral pol replication capacity. In contrast to secondary resistant infections that are rapidly overgrown when therapy is stopped, primary drug resistance persists over time. Surveillance and clinical detection of primary resistance is feasible in the first year of infection.
From the aGladstone Institute of Virology and Immunology, San Francisco, the bCenter for Bioinformatics and Molecular Biostatistics, University of California, the cProgram in Biological and Medical Informatics, Department of Biopharmaceutical Sciences, School of Pharmacy, University of California, the dDepartment of Medicine, University of California, San Francisco and San Francisco General Hospital, San Francisco, eViroLogic, Inc., South San Francisco, fBlood Centers of the Pacific, Blood Systems, Inc., San Francisco, and the gDepartment of Laboratory Medicine, University of California, San Francisco, California, USA.
Correspondence to R. M. Grant, Gladstone Institute of Virology and Immunology, PO Box 419100, San Francisco, CA 94141-9100, USA.
Received: 26 January 2004; revised: 7 April 2004; accepted: 7 May 2004.