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Different Predictors of ART Switches in IDUs and non-IDUs
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7th IAS Conference on HIV Pathogenesis, Treatment and Prevention, June 30-July 3, 2013, Kuala Lumpur
"A total of 1250 (46%) patients reported having a history of IDU, and were more likely to have switched therapy at least 3 times during follow-up.....Patients with a history of IDU experienced more therapeutic switches during their treatment, regardless of which antiretroviral class they started HAART on......HAART regimens containing boosted PIs were more resilient than regimens containing NNRTIs when it relates t o therapeutic switches related to virologic failure among patients without a history of IDU"
Mark Mascolini
Among people starting antiretroviral therapy (ART) in British Columbia, those who were not injection drug users (non-IDUs) switched regimens more often for virologic failure if they started with a nonnucleoside than if they started with a ritonavir-boosted protease inhibitor (PI) [1]. IDUs had more virologic failure-based regimen changes than non-IDUs, but the first-line agent did not affect switching in IDUs.
Antiretroviral regimens have become more durable in recent years, but some patients still must switch one or more drugs in their regimen because of tolerability, toxicity, or virologic failure. Researchers at the British Columbia Centre for Excellence in HIV/AIDS conducted this study to identify variables that explain the number of failure-driven regimen switches in previously untreated people starting the most common antiretroviral combinations.
Study participants were at least 19 years old, antiretroviral-naive, and starting a boosted PI (atazanavir or lopinavir) or a nonnucleoside (efavirenz or nevirapine) between January 2000 and June 2011. Follow-up continued through June 2012. The researchers recorded regimen changes resulting from virologic failure (consecutive viral loads above 50 copies) every 6 months. Statistical analyses to identify factors affecting regimen switching were figured separately for non-IDUs and for people with a history of injection drug use with adjustment for age, sex, first antiretroviral regimen, and time-varying CD4 count and viral load (figured as area under the curve, AUC).
The study included 1453 non-IDUs and 1250 IDUs. There were 200 women in the non-IDU group (14%) and 373 in the IDU group (30%). Among non-IDUs, 679 people (47%) started ART with a nonnucleoside and 774 (53%) with a boosted PI. Among IDUs, those numbers were 641 (51%) and 609 (49%). Pretreatment CD4 count was higher in non-IDUs than IDUs (210 versus 180, P < 0.0001), and pretreatment viral load was slightly but significantly higher in non-IDUs (4.96 versus 4.90 log, P = 0.0094).
Through a median follow-up of 4.7 years in both non-IDUs and IDUs, 932 non-IDUs (64% of 1453) and 692 IDUs (55% of 1250) never switched regimens. Numbers of non-IDUs and IDUs with one switch were 247 (17%) and 236 (19%), with two switches 165 (11%) and 149 (12%), and with three or more switches 109 (8%) and 173 (14%).
A multivariate model including only IDUs determined that higher time-varying viral load AUC raised the rate of regimen switching, while higher time-varying CD4 count AUC lowered the rate. For viral load every higher log10 copy-years/mL raised the switching rate 1%, and for CD4 count every higher log cell-years/mm(3) lowered the rate 9%. Gender, age, and starting with a nonnucleoside versus a boosted PI did not affect switching chances in this analysis.
Multivariate analysis including only non-IDUs determined that every log10 copy-years/mL time-varying viral load upped the switching rate 2%, while every log cell-years/mm(3) time-varying CD4 count cut the rate 16%. Starting treatment with a nonnucleoside rather than a boosted PI raised the switching rate 34%. Compared with non-IDU women, non-IDU men had a 28% lower switching rate. As with IDUs, age did not affect how often non-IDUs switched regimens.
The British Columbia investigators concluded that most IDUs and non-IDUs stayed with their initial regimen for several years. Initial regimens containing a boosted PI "were more resilient than regimens containing nonnucleosides when it relates to therapeutic switching related to virologic failure among patients without a history of injection drug use." Compared with non-IDUs, IDUs revamped their regimen more often, regardless of whether they started with a nonnucleoside or a boosted PI.
The researchers urged close monitoring of viral load in people taking combination ART to lower the risk of virologic failure and to preserve therapeutic options.
Reference
1. Lima VD, Chen Y, Kozai T, Hogg R, Montaner J. The choice of first-line regimen influences the likelihood of therapy switches and disease progression. 7th IAS Conference on HIV Pathogenesis, Treatment and Prevention, June 30-July 3, 2013, Kuala Lumpur. Abstract TUPE304.
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The choice of first-line regimen influences the likelihood of therapy switches and disease progression
Viviane Dias Lima, Yalin Chen, Tsubasa Kozai, Robert Hogg, Julio Montaner
British Columbia Centre for Excellence in HIV/AIDS, Vancouver, British Columbia, Canada
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