title: Long-term effectiveness of initiating non-nucleoside reverse transcriptase inhibitor- versus ritonavir-boosted protease inhibitor-based antiretroviral therapy: implications for first-line therapy choice in resource-limited settings.
abstract: In many resource-limited settings, combination antiretroviral therapy (cART) failure is diagnosed clinically or immunologically. As such, there is a high likelihood that patients may stay on a virologically failing regimen for a substantial period of time. Here, we compared the long-term impact of initiating non-nucleoside reverse transcriptase inhibitor (NNRTI)- versus boosted protease inhibitor (bPI)-based cART in British Columbia (BC), Canada.
  
  
  
  We followed prospectively 3925 ART-naïve patients who started NNRTIs (N=1963, 50%) or bPIs (N=1962; 50%) from 1 January 2000 until 30 June 2013 in BC. At six months, we assessed whether patients virologically failed therapy (a plasma viral load (pVL) >50 copies/mL), and we stratified them based on the pVL at the time of failure ≤500 versus >500 copies/mL. We then followed these patients for another six months and calculated their probability of achieving subsequent viral suppression (pVL <50 copies/mL twice consecutively) and of developing drug resistance. These probabilities were adjusted for fixed and time-varying factors, including cART adherence.
  
  
  
  At six months, virologic failure rates were 9.5 and 14.3 cases per 100 person-months for NNRTI and bPI initiators, respectively. NNRTI initiators who failed with a pVL ≤500 copies/mL had a 16% higher probability of achieving subsequent suppression at 12 months than bPI initiators (0.81 (25th-75th percentile 0.75-0.83) vs. 0.72 (0.61-0.75)). However, if failing NNRTI initiators had a pVL >500 copies/mL, they had a 20% lower probability of suppressing at 12 months than pVL-matched bPI initiators (0.37 (0.29-0.45) vs. 0.46 (0.38-0.54)). In terms of evolving HIV drug resistance, those who failed on NNRTI performed worse than bPI in all scenarios, especially if they failed with a viral load >500 copies/mL.
  
  
  
  Our results show that patients who virologically failed at six months on NNRTI and continued on the same regimen had a lower probability of subsequently achieving viral suppression and a higher chance of evolving HIV drug resistance. These results suggest that improving access to regular virologic monitoring is critically important, especially if NNRTI-based cART is to remain a preferred choice for first-line therapy in resource-limited settings.
authors: British Columbia Centre for Excellence in HIV/AIDS, Vancouver, British Columbia, Canada.|Division of AIDS, Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada; vlima@cfenet.ubc.ca.
authors: Viviane D
authors: VD
authors: Lima
authors: British Columbia Centre for Excellence in HIV/AIDS, Vancouver, British Columbia, Canada.|Division of AIDS, Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
authors: Mark
authors: M
authors: Hull
authors: Public Health & Preventative Medicine Residency Program, University of British Columbia, Vancouver, British Columbia, Canada.
authors: David
authors: D
authors: McVea
authors: British Columbia Centre for Excellence in HIV/AIDS, Vancouver, British Columbia, Canada.
authors: William
authors: W
authors: Chau
authors: British Columbia Centre for Excellence in HIV/AIDS, Vancouver, British Columbia, Canada.|Division of AIDS, Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
authors: P Richard
authors: PR
authors: Harrigan
authors: British Columbia Centre for Excellence in HIV/AIDS, Vancouver, British Columbia, Canada.|Division of AIDS, Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
authors: Julio Sg
authors: JS
authors: Montaner
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D019438:Ritonavir / Q000627:therapeutic use*; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors; D019438:Ritonavir
keywords: British Columbia; NNRTI boosted PI; antiretroviral therapy; cohort study; resistance; viral failure; viral suppression