HIV Genotyping of Chronically Infected Patients
By Dean L. Winslow, MD, FACP, Chief, Division of AIDS Medicine, Santa Clara Valley Medical Center; Clinical Professor of Medicine, Stanford University School of Medicine, Section Editor, HIV, is Associate Editor for Infectious Disease Alert.
Dr. Winslow is a consultant for Bayer Diagnostics, and on the speaker's bureau for GlaxoSmithKline and Pfizer.
Source: Smith D, et al. Clinical Utility of HIV Standard Genotyping Among Antiretroviral-Naive Individuals with Unknown Duration of Infection. Clinical Infect Dis. 2007;44:456-458.
This article originally appeared in the March 2007 issue of Infectious Disease Alert.
Synopsis: A total of 103 antiretroviral-naïve patients with HIV infection in San Diego County underwent genotyping between January and December 2005. Of the patients, 25% showed evidence of resistance to at least one drug class.
This study from the excellent group at University of California in San Diego had standard population-based HIV genotyping performed on plasma obtained from all antiretroviral (ARV)-naïve patients who received care in publicly funded clinics in San Diego County during the 2005 calendar year. Of the 103 patients who were studied, 26 (25%) had resistance-associated substitutions detected for at least one class of ARV agent; 18% had resistance demonstrated to one drug class, 6% to 2 classes, and 1% demonstrated 3 drug class resistance.
Studies of recently infected cohorts of HIV patients have shown the prevalence of transmitted ARV resistance to range from 8.3%-20%. Routine drug resistance testing of populations before initiation of ARV therapy has been estimated to be cost effective when the prevalence of drug resistance is 8%-10%.1 There have been few studies evaluating the prevalence of ARV resistance in chronically infected antiretroviral naïve HIV patients, so this paper is an important contribution to the literature. It is likely that the resistance observed in this study is due to both de novo infection with ARV-resistant virus and to casual use of antiretrovirals not disclosed to the patients' provider. Not surprisingly nnRTI substitutions (K103N in 12 patients and Y181C/I in 4 cases) were common as were NRTI substitutions (including TAMs and M184V). Probably due to reduced fitness in the absence of selective pressure of ARVs, PI substitutions were much rarer with resistance associated substitutions seen in only a few cases.
Due to the high cost of newer ARV agents and the potential for limiting future treatment options in patients placed on sub-suppressive regimens, it seems clear that obtaining baseline genotypic testing of all patients before initiating ARV therapy is now appropriate. While good data on timing of resistance testing in this population are not available, it makes sense to consider obtaining a baseline genotype on ARV-naïve patients when they first come into care and not waiting until just before placing the patient on ARV therapy is contemplated. This is due to the known instability in plasma of many resistance-associated substitutions in the absence of ARV-selective pressure, although "archival" resistant variants may exist as proviral DNA and re-emerge under selective pressure of ARV therapy.
- Weinstein MC, et al. Use of Genotypic Resistance Testing to Guide HIV Therapy: Clinical Impact and Cost-Effectiveness. Ann Int Med. 2001;134:440-450.