An algorithm‐based genotypic resistance score is associated with clinical outcome in HIV‐1‐infected adults on antiretroviral therapy

Abstract

The aim of this study was to evaluate the association between genotypic drug resistance and the occurrence of HIV-related diseases and death in HIV-1-infected adults on antiretroviral therapy. MethodsWe performed an observational study on patients from an out-patient clinic in a university hospital. Genotypic drug resistance analysis after virological treatment failure was performed in 141 patients receiving two or more antiretroviral drugs. All patients had follow up of at least 6 months after the resistance test. An algorithm was developed to estimate the level of genotypic drug resistance and to assign an actual resistance score (ARS) for the drugs prescribed to each patient. The patient population was divided into quartiles according to patients' ARS values. Our endpoint was the risk of developing an HIV-related disease [Centers for Disease Control and Prevention (CDC) category B or C] during the period starting 6 months prior to and ending 6 months after the genotypic resistance test, or death during the 6 months following the resistance test. ResultsThere was a significant association between the level of resistance to the drugs prescribed (ARS) and our clinical endpoint: the odds ratio for an endpoint (with 95% confidence interval) was 3.20 (1.28-7.99), adjusted for CD4 cell count and HIV RNA, in patients in the highest ARS quartile compared with patients in the other three quartiles. ConclusionsOur study indicates that patients with high-level genotypic drug resistance are at increased risk of developing an HIV-related disease. This association could not be explained by differences in CD4 cell count or HIV RNA levels.

Effect of therapy switch on time to second-line antiretroviral treatment failure in HIV-infected patients

“…The FIRST study showed that NNRTI-DRM is the strongest predictor of poor clinical outcome [27]. Furthermore in conflict to our results several studies have documented a poor clinical outcome in general among patients with DRM [13, 28] and that the association could not be explained by differences in CD4+ T-cell count or HIV RNA levels [29]. The most recent study showed slightly less steep CD4+ T-cell declines among patients with DRM however also stated it might be due to unmeasured factors such as poor adherence[30].…”

Low-Abundance Drug-Resistant Viral Variants in Chronically HIV-Infected, Antiretroviral Treatment–Naive Patients Significantly Impact Treatment Outcomes

“…Infection with drug-resistant HIV can lead to antiretroviral treatment (ART) failure and is associated with increased mortality [1][2][3][4][5]. HIV infection exists as a viral quasispecies (a "swarm" of genetically diverse virus strains).…”

Antimicrobial Resistance and Implications for the Twenty-First Century

“…Most studies have found a therapeutic advantage in terms of likelihood of viral suppression and mean virologic RNA reduction for resistance-test-guided treatments when compared to treatments based only on clinical judgment (DeGruttola et al, 2000;Durant et al, 1999;Gianotti et al, 2006;Ormaasen et al, 2004;Tural et al, 2002). Consequently, most international guidelines recommend resistance to assist the selection of therapeutic regimens following pharmacologic viral failure (DDHS, 2006Vandamme et al, 2004).…”