Transmitted Drug-Resistant HIV Type 1 Remains Prevalent and Impacts Virologic Outcomes Despite Genotype-Guided Antiretroviral Therapy

Abstract

Trends in transmitted drug resistance-associated mutations (TDRM) in HIV-1infection vary depending on geographic and cohort characteristics. The impact of TDRM among patients receiving fully active combination antiretroviral therapy (cART) is poorly characterized. This was a retrospective study of 801 HIV-1-infected treatment-naive patients from 2001 to 2009 who had pre-cART genotype resistance test results available. The prevalence of TDRM was compared for each year strata. Multivariate Cox proportional hazards regression models were used to assess factors associated with virologic failure at 48 weeks. TDRM was detected in 136 (17%) patients with ‡ 2 class TDRM in 20 patients. K103N/S was the most frequent (n = 77). There were no changes in the prevalence of mutations over time (P trend = 0.67). Six hundred and eleven patients were started on cART. Virologic failure occurred in 38% of those with TDRM and 24% of those without ( p < 0.01). In multivariate analysis, nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance was associated with a 1.5-fold increased risk of virologic failure. TDRM remains common among treatment-naive HIV-1-infected patients, affecting one in six patients. Transmission of NNRTI drug resistance was associated with risk of virologic failure despite initiation of genotype-guided cART.

Human immunodeficiency virus (HIV) in Washington, D.C.: Prevalence of antiretroviral resistance in treatment nave patients from 2007 to 2010

“…In addition, our rate of 15% NNRTI mutations contributing to NNRTI resistance was higher than what was typically reported for this drug class (Castor et al, 2012;Huaman et al, 2011;Hurt et al, 2009;Little et al, 2002;MacVeigh et al, 2013;Readhead et al, 2012;Ross et al, 2007;Taniguchi et al, 2012;Truong et al, 2011;Weinstock et al, 2000;Weinstock et al, 2004;Wheeler et al, 2010;Yanik et al, 2012;Youmans et al, 2011). The increase in TDR was primarily due to NNRTI mutations and occurred during the 4-year study period in a trend similar to other studies in the United States (Grant et al, 2002;Ross et al, 2008;Shet et al, 2006;Simon et al, 2002).…”

“…We observed low rates of individual major Pr mutations, all below 1%; our overall rate of 2% major Pr mutations is slightly less than many other studies in the United States (Castor et al, 2012;Huaman et al, 2011;Hurt et al, 2009;Little et al, 2002;MacVeigh et al, 2013;Readhead et al, 2012;Ross et al, 2007;Taniguchi et al, 2012;Truong et al, 2011;Weinstock et al, 2000;Weinstock et al, 2004;Wheeler et al, 2010;Yanik et al, 2012;Youmans et al, 2011). Although in the minority, persons with dual and triple class ARV resistance mutations were seen in 2% (8 patients) and 0.7% (3 patients), respectively.…”

“…The most commonly detected RT mutations in our study were M41L for NRTIs and K103N for NNRTIs, which are among the most frequently reported in many studies (Castor et al, 2012;Huaman et al, 2011;Hurt et al, 2009;Little et al, 2002;MacVeigh et al, 2013;Readhead et al, 2012;Ross et al, 2007;Taniguchi et al, 2012;Truong et al, 2011;Weinstock et al, 2004;Wheeler et al, 2010;Yanik et al, 2012;Youmans et al, 2011). We observed low rates of individual major Pr mutations, all below 1%; our overall rate of 2% major Pr mutations is slightly less than many other studies in the United States (Castor et al, 2012;Huaman et al, 2011;Hurt et al, 2009;Little et al, 2002;MacVeigh et al, 2013;Readhead et al, 2012;Ross et al, 2007;Taniguchi et al, 2012;Truong et al, 2011;Weinstock et al, 2000;Weinstock et al, 2004;Wheeler et al, 2010;Yanik et al, 2012;Youmans et al, 2011).…”

“…Based on United States Department of Health and Human Services (DHHS) guidelines, genotypic antiretroviral resistance testing (GART) was initially given CIII and DIII recommendations in 2000 for acutely-infected and chronically-infected treatment-naïve patients, (DHHS, 2007). For ARV treatment naïve individuals in the U.S., TDR mutation rates have ranged from about 5% to as high as 25% (Castor et al, 2012;Huaman et al, 2011;Hurt et al, 2009;Little et al, 1999;Little et al, 2002;MacVeigh et al, 2013;Readhead et al, 2012;Ross et al, 2007;Taniguchi et al, 2012;Truong et al, 2011;Weinstock et al, 2000;Weinstock et al, 2004;Wheeler et al, 2010;Yanik et al, 2012;Youmans et al, 2011). TDR has several important implications.…”

“…TDR has been demonstrated to increase the risk of poor outcomes, including an increase in time to achieve virologic suppression, risk of virologic failure, and a more rapid decline in CD4 counts in the first year after diagnosis. (Grant et al, 2002;Little et al, 2002;Pillay et al, 2006;Taniguchi et al, 2012;Wittkop et al, 2011). Knowledge about TDR is particularly important in Washington, D.C., which has one of the highest HIV prevalence rates in the United States (DC HAHSTA, 2010;CDC Surveillance, 2011).…”