Abstract
Pre-existing HIV drug resistance can jeopardize first-line antiretroviral therapy (ART) success. Changes in the prevalence of drug resistance-associated mutations (DRMs) were analyzed from HIV-infected, ART-naive, U.S. individuals seeking ART treatment from 2000 to 2009. HIV DRM data from 3,829 ART-naive subjects were analyzed by year of sample collection using International Antiviral Society-United States (IAS-USA) and World Health Organization (WHO) “surveillance” DRM definitions; minor IAS-USA-defined DRMs were excluded. IAS-USA DRM prevalence between 2000 and 2009 was 14%, beginning with 8% in 2000 and 13% in 2009. The greatest incidence was observed in 2007 (17%). Overall, IAS-USA-defined non-nucleoside reverse transcriptase inhibitor (NNRTI) DRMs were 9.5%; nucleoside reverse transcriptase inhibitor (NRTI): 4%, and major protease inhibitor (PI): 3%. The most frequently detected IAS-USA-defined DRMs by class were NNRTI: K103N/S (4%), NRTI: M41L (1.5%), and PI: L90M (1%). Overall, WHO-defined DRM prevalence was 13% (5% in 2000; 13% in 2009). By class, NNRTI prevalence was 6%, NRTI: 6%, and PI: 3.2%. The most frequent WHO-defined DRMs were NRTI: codon T215 (3.0%), NNRTI: K103N/S (4%), and PI: L90 (1%). WHO-defined NNRTI DRMs declined significantly (p = .0412) from 2007 to 2009. The overall prevalence of HIV-1 containing major IAS-USA or WHO-defined DRMs to ≥2 or ≥3 classes was 2% and <1%, respectively. The prevalence of HIV-1 with WHO-defined dual- or triple-class resistance significantly declined (p = .0461) from 2008 (4%) to 2009 (<1%). In this U.S. cohort, the prevalence of HIV-1 DRMs increased from 2000 onward, peaked between 2005 and 2007, and then declined between 2008 and 2009; the detection of WHO-defined dual- or triple-class DRM similarly decreased from 2008 to 2009.
Highlights
HIV-1 drug resistance may be acquired in response to antiretroviral (ARV) drug pressure and as the prevalence of resistance mutations among treatment-experienced, HIVinfected individuals has increased, so has the probability of transmission of drug resistance (TDR).[1]
From 2000 to 2009, 14% [551/3,829; 95% confidence interval (CI; 13.3%–15.5%)] (Table 2) of antiretroviral therapy (ART)-naive HIVinfected subjects were infected with HIV-1 containing nucleoside reverse transcriptase inhibitor (NRTI), NNRTI, or major protease inhibitor (PI) drug resistance-associated mutations (DRMs) as defined by International Antiviral Society-United States (IAS-United States (USA)) guidelines
Mutations classified as minor PI or NNRTI in the IAS-USA guidelines were not considered indicative of TDR and were not quantified for this analysis, since these polymorphisms occur in the absence of drug selection pressure and by themselves have little or no impact on drug susceptibility
Summary
HIV-1 drug resistance may be acquired in response to antiretroviral (ARV) drug pressure and as the prevalence of resistance mutations (drug resistance-associated mutations [DRMs]) among treatment-experienced, HIVinfected individuals has increased, so has the probability of transmission of drug resistance (TDR).[1] Numerous factors, including viral replication fitness and transmission fitness and individual risk behavior, can influence both the prevalence and the specific types of HIV-1 drug resistance that may be observed in therapy-naive individuals.[2,3,4,5,6] New combination antiretroviral treatment (cART) regimens have reduced morbidity and mortality for individuals infected with HIV-1.7. It has been theorized that infection with TDR containing HIV-1 establishes those drug resistance-associated variants within the patient’s viral reservoirs, making it less likely for wild-type HIV-1 to emerge in the absence of drug selection pressure and making treatment more difficult in those patients.[8,9,10,11]
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