Increased Resilience to the Development of Drug Resistance with Modern Boosted Protease Inhibitor–Based Highly Active Antiretroviral Therapy
1British Columbia Centre for Excellence in HIV/AIDS, St. Paul’s Hospital, and 2Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, and 3Faculty of Health Sciences, Simon Fraser University, Burnaby, British Columbia, Canada
Background.
We explore the temporal and regimen‐specific changes of HIV‐1 drug resistance in a large cohort of antiretroviral‐naive individuals starting highly active antiretroviral therapy (HAART).
Methods.Individuals (
) initiating first HAART between August 1996 and November 2004 were followed until November 2005 (median follow‐up, 4.8 years; 
tests). A logistic regression model was used to predict the probability of the emergence of resistance, adjusting for baseline predictors.
Results.The cohort included 991 individuals initiating nonboosted protease inhibitor (PI)–based regimens, 475 initiating ritonavir‐boosted PI–based regimens, and 884 initiating nonnucleoside reverse‐transcriptase inhibitor (NNRTI)–based regimens. There was no difference in the development of resistance between nonboosted PI–based regimens (reference group) and NNRTI‐based HAART regimens (odds ratio [OR], 1.09 [95% confidence interval {CI}, 0.84–1.42]), but there were greatly reduced odds for boosted PI–based regimens (OR, 0.42 [95% CI, 0.28–0.62]). Individuals initiating HAART more recently (2002–2004) were at a reduced risk of resistance, compared with those who started HAART between 1996 and 1998 (OR, 0.43 [95% CI, 0.30–0.61]).
Conclusions.Individuals initiating first HAART with a boosted PI–based regimen had a 2.4‐fold lower OR for developing HIV drug resistance than did those starting nonboosted PI–based or NNRTI‐based HAART, at all adherence levels. The data demonstrate marked temporal improvement in the likelihood of the development of drug resistance for those initiating more recent HAART regimens.
Received 21 August 2007; accepted 13 December 2007; electronically published 22 May 2008.
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Potential conflicts of interest: R.S.H., P.R.H., and J.S.G.M. have received honoraria, travel grants to attend conferences, and research grants from pharmaceutical and diagnostic companies working in the area of HIV/AIDS.
Presented in part: 14th Conference on Retroviruses and Opportunistic Infections, Los Angeles, 25–28 February 2007 (abstract M-195 and poster 614).
Financial support: Michael Smith Foundation for Health Research (Senior Scholar Award to R.S.H.); Canadian Institutes of Health Research (fellowship to V.D.L.).