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Higher GI Disorder Risk When Switching to RAL or DRV Versus DTG
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10th IAS Conference on HIV Science (IAS 2019), July 21-24, 2019, Mexico City
Mark Mascolini
An 11,000-person analysis linked switching to the integrase inhibitor raltegravir (RAL) or the protease inhibitor darunavir (DRV) to a higher risk of early gastrointestinal (GI) problems, when compared with switching to dolutegravir (DTG) [1]. When 4700 antiretroviral-naive people started one of these three drugs or the integrase inhibitor elvitegravir, they did not differ significantly in GI disorder risk in the first 6 months of treatment.
Researchers from Philadelphia FIGHT, Epividian, ViiV Healthcare (maker of dolutegravir), and other centers compared the onset of new GI problems in (1) people starting their first antiretroviral regimen including dolutegravir, elvitegravir, raltegravir, or darunavir or (2) antiretroviral-experienced people switching to one of the four study drugs. Everyone started or switched to one of these antiretrovirals between August 1, 2013 and December 31, 2016.
Study participants were 13 or older. GI disorders could include GI symptoms, diagnoses, or medications. Risk of a new GI disorder was estimated by Cox proportional hazards models adjusted for baseline age, sex, race, nadir CD4 count, AIDS history, opioid use, and nonsteroidal antiinflammatory use.
The study population came from from the OPERA Longitudinal Cohort [2] and included 4700 antiretroviral-naive people (1653 starting dolutegravir, 2288 starting elvitegravir, 109 starting raltegravir, and 650 starting darunavir) and 11,047 with antiretroviral experience (3958 switching to dolutegravir, 4916 switching to elvitegravir, 549 switching to raltegravir, and 1624 switching to darunavir). OPERA is a longitudinal database embracing 85 clinical sites across the United States at the time of this study.
Median age ranged from 30 to 39 in the four naive groups and from 38 to 48 in the four experienced groups. Respective proportions of women ranged from 11.7% to 25.7% and from 14.1% to 23.3%). And respective proportions of African Americans ranged from 45.4% to 53.2% and from 35.0% to 47.5%.
Among antiretroviral-naive people, proportions with a history of any GI disorder were 6% for the dolutegravir group, 4% for raltegravir, 5% for elvitegravir, and 8% for darunavir. Among antiretroviral-experienced people, proportions with a history of any GI disorder were 19% for the dolutegravir group, 12% for raltegravir, 20% for elvitegravir, and 15% for darunavir (P < 0.017 for raltegravir or darunavir versus dolutegravir).
In antiretroviral-naive participants, Cox modeling linked starting raltegravir or darunavir to a nonsignificantly higher risk (adjusted hazard ratio, aHR) of new GI disorder in the first 6 months of follow-up compared with starting dolutegravir. Among antiretroviral-experienced people, those associations became statistically significant: Switching to raltegravir inflated the risk of a new GI disorder 61% in the first 6 months of follow-up (aHR 1.61, 95% confidence interval [CI] 1.05 to 2.47), and switching to darunavir boosted the risk 46% (aHR 1.46, 95% CI 1.09 to 1.96). In an analysis including all follow-up (rather than the first 6 months), antiretroviral-naive people starting raltegravir (versus dolutegravir) ran a 90% higher risk of a new GI disorder (aHR 1.90, 95% CI 1.01 to 3.57), while antiretroviral experienced people starting darunavir (versus dolutegravir) ran a 37% higher risk (aHR 1.37, 95% CI 1.07 to 1.76).
The researchers noted that their analysis is limited by the low number of treatment-naive people starting raltegravir, lack of statistical adjustment for other antiretrovirals in the regimen, and differences in demographics and clinical characteristics in the raltegravir and darunavir groups versus the dolutegravir group.
References
1. Mounzer K, Brunet L , Fusco J, et al. Gastrointestinal disorders following initiation of dolutegravir, elvitegravir, raltegravir or darunavir. 10th IAS Conference on HIV Science (IAS 2019), July 21-24, 2019, Mexico City. Abstract TUPEB221. For e-poster: https://programme.ias2019.org//PAGMaterial/eposters/1373.pdf
2. Epividian. OPERA. Observational Pharmaco-Epidemiology Research & Analysis. https://www.epividian.com/products/opera/
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