Transmitted drug-resistant HIV type 1 remains prevalent and impacts virologic outcomes despite genotype-guided antiretroviral therapy.

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.

[1]  R. Kuchenbecker,et al.  Atazanavir plus ritonavir or efavirenz as part of a 3-drug regimen for initial treatment of HIV-1. , 2011, Annals of internal medicine.

[2]  D. Katzenstein,et al.  Atazanavir Plus Ritonavir or Efavirenz as Part of a 3-Drug Regimen for Initial Treatment of HIV-1 , 2011, Annals of Internal Medicine.

[3]  E. Vittinghoff,et al.  Transmitted Drug Resistance in Persons with Acute/Early HIV-1 in San Francisco, 2002-2009 , 2010, PloS one.

[4]  B. Gazzard,et al.  Efavirenz versus boosted atazanavir or zidovudine and abacavir in antiretroviral treatment-naive, HIV-infected subjects: week 48 data from the Altair study. , 2010, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[5]  W. Heneine,et al.  Prevalence of transmitted drug resistance associated mutations and HIV-1 subtypes in new HIV-1 diagnoses, U.S.–2006 , 2010, AIDS.

[6]  Yuchiao Chang,et al.  Predicting virologic failure in an HIV clinic. , 2010, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[7]  M. Poljak,et al.  Transmission of drug-resistant HIV-1 is stabilizing in Europe. , 2009, The Journal of infectious diseases.

[8]  R. Maserati,et al.  Prevalence of transmitted HIV-1 drug resistance in HIV-1-infected patients in Italy: evolution over 12 years and predictors. , 2009, The Journal of antimicrobial chemotherapy.

[9]  P. Francioli,et al.  Long-term trends of HIV type 1 drug resistance prevalence among antiretroviral treatment-experienced patients in Switzerland. , 2009, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[10]  Anne-Mieke Vandamme,et al.  Drug Resistance Mutations for Surveillance of Transmitted HIV-1 Drug-Resistance: 2009 Update , 2009, PloS one.

[11]  Gregory S Turenchalk,et al.  Low-abundance drug-resistant viral variants in chronically HIV-infected, antiretroviral treatment-naive patients significantly impact treatment outcomes. , 2009, The Journal of infectious diseases.

[12]  M. King,et al.  Geographic and Temporal Trends of Transmitted HIV-1 Drug Resistance Among Antiretroviral-Naïve Subjects Screening for Two Clinical Trials in North America and Western Europe , 2009, HIV clinical trials.

[13]  K. Metzner,et al.  Minority quasispecies of drug-resistant HIV-1 that lead to early therapy failure in treatment-naive and -adherent patients. , 2009, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[14]  Ross J. Harris,et al.  Does short-term virologic failure translate to clinical events in antiretroviral-naïve patients initiating antiretroviral therapy in clinical practice? , 2008, AIDS.

[15]  Michael Monsour,et al.  Minority HIV-1 Drug Resistance Mutations Are Present in Antiretroviral Treatment–Naïve Populations and Associate with Reduced Treatment Efficacy , 2008, PLoS medicine.

[16]  Lynne Peeples,et al.  Class-sparing regimens for initial treatment of HIV-1 infection. , 2008, The New England journal of medicine.

[17]  F. Brun-Vézinet,et al.  Prevalence of HIV-1 Drug Resistance in Treated Patients: A French Nationwide Study , 2007, Journal of acquired immune deficiency syndromes.

[18]  John T Brooks,et al.  Mortality in the Highly Active Antiretroviral Therapy Era: Changing Causes of Death and Disease in the HIV Outpatient Study , 2006, Journal of acquired immune deficiency syndromes.

[19]  D. Pillay,et al.  The impact of transmitted drug resistance on the natural history of HIV infection and response to first-line therapy , 2006, AIDS.

[20]  M. Weinstein,et al.  Should resistance testing be performed for treatment-naive HIV-infected patients? A cost-effectiveness analysis. , 2005, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[21]  A. Moorman,et al.  Factors associated with maintenance of long-term plasma human immunodeficiency virus RNA suppression. , 2003, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[22]  Elena Losina,et al.  Use of Genotypic Resistance Testing To Guide HIV Therapy: Clinical Impact and Cost-Effectiveness , 2001, Annals of Internal Medicine.

[23]  J. J. Henning,et al.  Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents, January 28, 2000 , 1998, HIV clinical trials.