A Guide to HIV-1 Reverse Transcriptase and Protease Sequencing for Drug Resistance Studies.

HIV-1 RT and protease sequencing and drug susceptibility testing have been done in research settings for more than ten years to elucidate the genetic mechanisms of resistance to antiretroviral drugs. Retrospective studies have shown that the presence of drug resistance before starting a new drug regimen is an independent predictor of virologic response to that regimen (DeGruttola et al., 2000; Hanna and D’Aquila, 2001; Haubrich and Demeter, 2001). Prospective studies have shown that patients whose physicians have access to drug resistance data, particularly genotypic resistance data, respond better to therapy than control patients whose physicians do not have access to the same data (Baxter et al., 2000; Cohen et al., 2000; De Luca et al., 2001; Durant et al., 1999; Melnick et al., 2000; Meynard et al., 2000; Tural et al., 2000). The accumulation of retrospective and prospective data has led three expert panels to recommend the use of resistance testing in the treatment of HIV-infected patients (EuroGuidelines Group for HIV Resistance, 2001; Hirsch et al., 2000; US Department of Health and Human Services Panel on Clinical Practices for Treatment of HIV Infection, 2000) (Table 1). There have been several recent reviews on methods for assessing HIV-1 drug resistance (Demeter and Haubrich, 2001; Hanna and D’Aquila, 2001; Richman, 2000) and on the mutations associated with drug resistance (Deeks, 2001; Hammond et al., 1999; Loveday, 2001; Miller, 2001; Shafer et al., 2000b). This review will detail the use of HIV-1 genotypic resistance testing in research settings where it is used to learn about the mechanisms and clinical significance of drug resistance and in clinical settings where it is used to help guide anti-HIV treatment.