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  20th International AIDS Conference
July 20-25, 2014
Melbourne, Australia
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Switching From First-Line ART When Suppressed Boosts Failure Chance
  20th International AIDS Conference, July 20-25, 2014, Melbourne
Mark Mascolini
Switching from first-line antiretroviral therapy (ART) with a viral load below 50 copies boosted chances of virologic failure 35%, according to analysis of a multicenter prospective Canadian cohort [1]. Switching two or more times with a sub-50-copy load proved half as likely in men as in women.
Efficacy and safety of antiretroviral regimens have improved over the years, but some people switch from their first-line combination to improve tolerability or convenience, or to avoid drug interactions, even though they have attained an undetectable viral load. In a 2002-2009 study, 40% of European and North American ART-Cohort Collaboration participants swapped their first regimen for different antiretrovirals [2].
To determine rates of switching with a sub-50 load and consequences of such switches, Canadian researchers analyzed antiretroviral-naive adults in the multisite CANOC cohort who started their first regimen from 2005 through 2012. The CANOC team determined how many people switched from their first regimen during virologic suppression, defined as two viral loads below 50 copies measured more than 1 month apart. They defined virologic failure as a viral load above 1000 copies.
Among 2807 people in the switching analysis (13% women, 12% injection drug users), 1003 (36%) switched their regimen while virologically suppressed, including 612 (22%) who switched more than once. Median time from starting to switching measured 0.8 year (interquartile range [IQR] 0.4 to 1.7), and median age at switching stood at 42 years (IQR 35 to 48). Median CD4 count was 450 (IQR 320 to 580) when people traded their first regimen for another.
People who switched once had a lower median age (38 years) than people who never switched (41 years) or people who switched more than once (42 years) (P < 0.001). Injection drug users made up 11% of never-switchers, 8% of once-time switchers, and 25% of multiple switchers (P = 0.008). Median pre-ART CD4 count measured 280 in never-switchers, 252 in one-time switchers, and 220 in multiple switchers (P < 0.001).
Logistic regression analysis identified nine independent predictors of switching once or more than once, at the following adjusted odds ratios (aOR) (and 95% confidence intervals). (An aOR below 1.0 indicates a lower chance of switching.)
Switching once
Every 10 more years of age: aOR 0.88 (0.78 to 0.99), P = 0.04
Every additional year of ART: aOR 1.45 (1.32 to 1.60), P < 0.001
Ontario versus British Columbia: aOR 2.84 (2.05 to 3.95), P < 0.001
Quebec versus British Columbia: aOR 2.86 (1.99 to 4.10), P < 0.001
Switching more than once
Men versus women: aOR 0.53 (0.39 to 0.71), P < 0.001
Starting ART before 2008: aOR 0.69 (0.49 to 0.95), P = 0.03
Every additional year of ART: aOR 1.72 (1.57 to 1.88), P < 0.001
Ontario versus British Columbia: aOR 0.32 (0.25 to 0.42), P < 0.001
Quebec versus British Columbia: aOR 0.48 (0.36 to 0.64), P < 0.001
Every 100-cell higher pre-ART CD4 count marginally raised chances of switching once (aOR 1.07, 95% CI 0.99 to 1.15, P = 0.09).
A marginal structural model to identify predictors of virologic failure considered time-varying CD4 count and six fixed factors: age, gender, injection drug use, pre-ART CD4 count, province, and year when ART began. This model determined that switching a suppressive regimen raised chances of failure 35% (aOR 1.35, 95% CI 1.18 to 1.53, P < 0.001). Injection drug use almost tripled the odds of failure (aOR 2.85, 95% CI 1.70 to 4.80, P < 0.001). And male gender lowered chances of virologic failure 65% (aOR 0.35, 95% CI 0.21 to 0.58, P < 0.001). Variables that did not affect failure risk in this analysis were age, pre-ART CD4 count, province, or year when ART began.
The researchers speculated that the higher chance of switching more than once among women and their higher chance of failure may partly reflect regimen changes around pregnancy. Switches for tolerability, they suggested, may represent specific patient characteristics related to antiretroviral intolerance as a marker of poor adherence, for example, in injection drug users.
The CANOC team proposed that "regimen switching while virologically suppressed may not be completely benign." They called for closer follow-up of people switching antiretroviral regimens for nonvirologic reasons because such switches may signal adherence challenges or worse antiretroviral tolerance (for example, among women).
1. Hull M, Cescon A, Raboud J, et al. Switching from first antiretroviral therapy regimen while virologically suppressed is associated with increased risk of subsequent virologic failure. AIDS 2014. 20th International AIDS Conference. July 20-25, 2014. Melbourne. Abstract TUAB0103.
2. Antiretroviral Therapy Cohort Collaboration (ART-CC). Durability of first ART regimen and risk factors for modification, interruption or death in HIV-positive patients starting ART in Europe and North America 2002-2009. AIDS. 2013;27:803-813. http://www.ncbi.nlm.nih.gov/pubmed/23719350