Increased resilience to the development of drug resistance with modern boosted protease inhibitor-based highly active antiretroviral therapy.
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 (n = 2350) initiating first HAART between August 1996 and November 2004 were followed until November 2005 (median follow-up, 4.8 years; n = 6066 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.
Lima
Viviane D
VD
British Columbia Centre for Excellence in HIV/AIDS, St. Paul's Hospital, British Columbia, Canada.
Gill
Vikram S
VS
Yip
Benita
B
Hogg
Robert S
RS
Montaner
Julio S G
JS
Harrigan
P Richard
PR
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D015331:Cohort Studies; D004334:Drug Administration Schedule; D024921:Drug Resistance, Multiple, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008297:Male; D011336:Probability; D012307:Risk Factors; D019438:Ritonavir / Q000008:administration & dosage / Q000627:therapeutic use
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D019438:Ritonavir