HIV Resistance: Frequency, Testing, Mechanisms

The prevalence of antiretroviral-resistant virus in patients with newly diagnosed HIV infection according to Centers for Disease Control and Prevention (CDC) surveys is shown in Table 1. In the most recent survey, covering 2003 to 2006, 10.9% of patients exhibited resistance to any drug, with the majority having resistance to nonnucleoside analogue reverse transcriptase inhibitors (NNRTIs) and 1.9% having resistance to at least 1 drug in numerous drug classes. At one point, data for this latter period indicated a prevalence rate of approximately 15% for resistance to any drug, and it is unclear whether a peak and decline in prevalence occurred or whether prevalence has indeed been stable at around 10% for the past 4 or 5 years. It should also be noted that very few of the patients with multiclass resistance exhibit resistance to multiple drugs or all drugs within multiple classes. Data on long-term risk of developing resistance from the UK Collaborative HIV Cohort (CHIC) study in 4306 patients beginning antiretroviral therapy with 2 nucleoside analogue reverse transcriptase inhibitors (nRTIs) and a third agent show that risk of accumulating resistance mutations to any drug over 6 years was 27%, in the context of an overall treatment failure rate of 38% (Phillips et al, AIDS, 2005). As shown in Figure 1, resistance to 2 and 3 drug classes occurred in approximately 20% and 5% of patients, respectively, after 6 years. However, these data were first reported in 2004 and may reflect antiretroviral therapy practices from as early as 1998. With use of newer, better-tolerated, and more potent regimens in recent years (including fixed-dose nRTI combinations, once-daily regimens, ritonavirboosted protease inhibitors [PIs], and efavirenz-based regimens), virologic failure rates and resistance rates are likely lower than those reflected in this study. This impression is supported by some data, including those from a chart review study in the University of North Carolina HIV Cohort Study (n = 1466; Napravnik et al, Antivir Ther, 2006). Overall, 8% of patients had triple-class resistance, with independent predictors of such resistance consisting of prior use of antiretrovirals (odds ratio [OR], 1.7) and use of a nonantiretroviral regimen as the first treatment regimen (OR, 1.7). Of 24 patients with triple-class resistance whose first regimen was potent antiretroviral therapy, the regimen included an unboosted PI in 21 (87.5%) and nelfinavir in 15. These findings suggest that triple-class resistance is indeed likely to become less common in patients initiating antiretroviral therapy as currently practiced. Based in part on evidence that resistance testing before treatment is costeffective when the prevalence of resistance in untreated patients is greater Perspective HIV Resistance: Frequency, Testing, Mechanisms