Background. Little is known about temporal trends in frequencies of clinically relevant ARV resistance mutations in HIV strains from U.S. patients undergoing genotypic testing (GT) in routine HIV care. Methods. We analyzed cumulative frequency of HIV resistance among patients in the HIV Outpatient Study (HOPS) who, during 1999–2008 and while prescribed antiretrovirals, underwent GT with plasma HIV RNA >1,000 copies/mL. Exposure ≥4 months to each of three major antiretroviral classes (NRTI, NNRTI and PI) was defined as triple-class exposure (TCE). Results. 906 patients contributed 1,570 GT results. The annual frequency of any major resistance mutations decreased during 1999–2008 (88% to 79%, ). Resistance to PIs decreased among PI-exposed patients (71% to 46%, ) as exposure to ritonavir-boosted PIs increased (6% to 81%, ). Non-significant declines were observed in resistance to NRTIs among NRTI-exposed (82% to 67%), and triple-class-resistance among TCE patients (66% to 41%), but not to NNRTIs among NNRTI-exposed. Conclusions. HIV resistance was common but declined in HIV isolates from subgroups of ARV-experienced HOPS patients during 1999–2008. Resistance to PIs among PI-exposed patients decreased, possibly due to increased representation of patients whose only PI exposures were to boosted PIs. 1. Introduction Highly active combination antiretroviral therapy (cART) has significantly improved survival and reduced the rates of AIDS-related complications among HIV-infected persons [1–3]. Emergence of HIV variants with reduced susceptibility to antiretroviral (ARV) medications can significantly limit the effectiveness and durability of treatment [3–8]. Use of ARV resistance testing to optimize cART selection has been associated with better virologic and clinical outcomes [9–11] and improved survival , and resistance testing is now generally recommended in the clinical management of HIV infection [13–15]. We have previously shown that use of genotypic and phenotypic testing increased in the HIV Outpatient Study (HOPS) during 1999–2006 and that the likelihood of testing varied by HIV disease severity and demographic characteristics . Recent European and Canadian studies have suggested that both the prevalence [17, 18] and incidence [19, 20] of ARV resistance among HIV-infected persons have declined, due predominately to a decrease in the proportion of patients with pre-cART mono- or dual-ARV experience, and the increasing use and effectiveness of more tolerable and potent cART regimens that appear less likely to result in resistance mutations [18–22].
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