title: Response to Therapy in Antiretroviral Therapy-Naive Patients With Isolated Nonnucleoside Reverse Transcriptase Inhibitor-Associated Transmitted Drug Resistance.
abstract: Nonnucleoside reverse transcriptase inhibitor (NNRTI)-associated transmitted drug resistance (TDR) is the most common type of TDR. Few data guide the selection of antiretroviral therapy (ART) for patients with such resistance.
  
  
  
  We reviewed treatment outcomes in a cohort of HIV-1-infected patients with isolated NNRTI TDR who initiated ART between April 2002 and May 2014. In an as-treated analysis, virological failure (VF) was defined as not reaching undetectable virus levels within 24 weeks, virological rebound, or switching regimens during viremia. In an intention-to-treat analysis, failure was defined more broadly as VF, loss to follow-up, and switching during virological suppression.
  
  
  
  Of 3245 patients, 131 (4.0%) had isolated NNRTI TDR; 122 received a standard regimen comprising 2 NRTIs plus a boosted protease inhibitor (bPI; n = 54), an integrase strand transfer inhibitor (INSTI; n = 52), or an NNRTI (n = 16). The median follow-up was 100 weeks. In the as-treated analysis, VF occurred in 15% (n = 8), 2% (n = 1), and 25% (n = 4) of patients in the bPI, INSTI, and NNRTI groups, respectively. In multivariate regression, there was a trend toward a lower risk of VF with INSTIs than with bPIs (hazard ratio: 0.14; 95% confidence interval: 0.02 to 1.1; P = 0.07). In intention-to-treat multivariate regression, INSTIs had a lower risk of failure than bPIs (hazard ratio: 0.38; 95% confidence interval: 0.18 to 0.82; P = 0.01).
  
  
  
  Patients with isolated NNRTI TDR experienced low VF rates with INSTIs and bPIs. INSTIs were noninferior to bPIs in an analysis of VF but superior to bPIs when frequency of switching and loss to follow-up were also considered.
authors: *Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA; †Department of Internal Medicine, Kaiser Permanente Northern California, San Francisco Medical Center, San Francisco, CA; ‡Division of Research, Kaiser Permanente Northern California, Oakland, CA; §Department of Infectious Diseases, Kaiser Permanente Northern California, San Leandro Medical Center, San Leandro, CA; ‖Stanford Prevention Research Center, Department of Medicine, and ¶Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA; and #Department of Statistics, Stanford University School of Humanities and Sciences, Stanford, CA.
authors: Dana S
authors: DS
authors: Clutter
authors: W Jeffrey
authors: WJ
authors: Fessel
authors: Soo-Yon
authors: SY
authors: Rhee
authors: Leo B
authors: LB
authors: Hurley
authors: Daniel B
authors: DB
authors: Klein
authors: John P A
authors: JP
authors: Ioannidis
authors: Michael J
authors: MJ
authors: Silverberg
authors: Robert W
authors: RW
authors: Shafer
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D002140:California; D024882:Drug Resistance, Viral / Q000187:drug effects*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology* / Q000627:therapeutic use; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018894:Reverse Transcriptase Inhibitors