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Multiclass Resistance Rate--But Not All-Class Resistance--Falls in US and Canada
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XVII International HIV Drug Resistance Workshop
June 10-14, 2008, Sitges, Spain
Mark Mascolini
Multiclass resistance rates dropped sharply from 2000 to 2005 in an eight-clinic US-Canadian study [1]. But class-wide resistance to three classes remained stable over those years, and people with nonnucleoside class resistance ran a higher risk of dying within 6 years of their first genotypic test.
Steven Deeks and colleagues studied 1591 people with a viral load topping 1000 copies in the year 2000, 52% of whom had a genotypic test result. Respective numbers and percents of people with a load above 1000 copies and a genotyping result in the following years were 1597 and 58% in 2001, 1499 and 60% in 2002, 1396 and 61% in 2003, 1290 and 66% in 2004, and 1004 and 71% in 2005. Using the Stanford system to rate virus as resistant, the investigators defined antiretroviral class resistance as (1) pan-class resistance to all available drugs in a class or (2) within-class resistance to any available drug in a class.
The study group was 78% male, 51% black, and 41% white. Median viral load stood at 45,700 copies/mL (interquartile range [IQR] 5200 to 192,800 copies/mL) and median CD4 count at 154 (IQR 49 to 290).
Half of the year-2000 group had within-class resistance to two classes; that rate fell to 33% in 2005, a highly significant decline (P < 0.001). Whereas 24% of people in 2000 had within-class resistance to the first three antiretroviral classes, only 16% did in 2005, another highly significant drop (P < 0.001). The proportion of people with pan-class resistance to two classes slipped from 28% in 2000 to 16% in 2005, but the proportion with pan-class resistance to three classes did not change significantly from 2000 (9%) to 2005 (8%) (P = 0.32).
People with pan-class resistance to protease inhibitors and nucleosides had the best survival 6 years after their first genotypic test in analyses adjusted for variables including older age (P = 0.04), transmission by needle sharing (P < 0.001), lower CD4 count (P < 0.0001), and higher viral load (P < 0.01). Mortality 6 years after the first genotype was similar for people with pan-class resistance to nucleosides plus nonnucleosides, protease inhibitors plus nonnucleosides, all three classes--and no resistance mutations at virologic failure, a likely signal of poor adherence.
An earlier 5-year study in British Columbia, where antiretrovirals are free, found that resistance to any class raised the risk of death 75% and resistance to NNRTIs tripled the death risk [2].
References
1. Deeks SG for the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) of the IeDEA. The prevalence of multidrug resistance among treated patients in North America and its impact on mortality. XVII International HIV Drug Resistance Workshop. June 10-14, 2008, Sitges, Spain. Abstract 139.
2. Hogg RS, Bangsberg DR, Lima VD, et al. Emergence of drug resistance is associated with an increased risk of death among patients first starting HAART. PLoS Med. 2006;3(9):e356 (http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0030356).
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