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Contraindicated Drugs Combos Tied to Higher Hospital Rate in HIV+ Veterans
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Contraindicated Drugs Combos Tied to Higher Hospital Rate in HIV+ Veterans
ICAAC 2015, September 17-21, 2015, San Diego
Mark Mascolini
Almost 10% of HIV-positive veterans in a two-center study took drugs contraindicated because of drug-drug interactions (XDDI), which independently raised the odds of hospital admission 60% in the first year of antiretroviral therapy (ART) [1]. Taking a protease inhibitor (PI)-based regimen rather than an integrase inhibitor combination also independently upped the odds of hospital admission.
Researchers from the Upstate NY Veterans' Healthcare Administration and the University of New Mexico who conducted this study noted that HIV populations are vulnerable to drug-drug interactions because they usually take antiretroviral combinations involving three or more drugs plus other medications for comorbidities. Because clinical outcomes of XDDIs remain poorly described, they undertook this cross-sectional study to (1) compare the frequency of XDDIs between different antiretroviral regimens, and (2) assess the relationship between XDDIs and hospital admissions in the first year of ART.
Study participants were at least 18 years old and in care between 2000 and 2013. All took a standard antiretroviral regimen including a nonnucleoside (NNRTI), a PI, or an integrase inhibitor. No regimens included two of those classes. From medical records, the investigators collected information on demographics, comorbidities, all medications, and hospital admissions in the first year of ART. They used Lexi-Interact software to identify XDDIs.
The analysis included 1329 veterans, 608 (46%) taking an NNRTI, 455 (34%) a PI, and 266 (20%) an integrase inhibitor. Veterans taking an integrase inhibitor were somewhat younger (mean 45.4 years) than those taking a PI (47.3) or an NNRTI (47.6) (P = 0.03). Only 5% taking an integrase inhibitor were black, compared with about one quarter taking a PI or an NNRTI. Almost half taking an integrase inhibitor were white, compared with 39% taking an NNRTI and 41% taking a PI.
Numbers of comorbidities averaged 5.0 in the NNRTI group, 5.4 in the PI group, and 5.5 in the integrase inhibitor group (P = 0.07). Respective median numbers of medications were 2, 3, and 3 (P < 0.001). Proportions taking 6 or more non-HIV medications were lower in the NNRTI group (17.8%) than in the PI group (21.3%) or the integrase inhibitor group (28.9%) (P = 0.001).
The researchers determined that 128 participants (9.6%) had an XDDI. XDDI rates were 5.6% in the NNRTI group, 16.1% in the PI group, and 8.0% in the integrase inhibitor group (P < 0.001). The most frequent XDDIs involved antipsychotics plus antidepressants (10.9%), PIs plus antipsychotics (7.8%), fluticasone plus ritonavir or cobicistat (7.8%), PIs plus antimicrobials (7%), selective serotonin reuptake inhibitors plus antiretrovirals (7%), and tamsulosin plus CYP3A or CYP2D6 inhibitors (7%). Most XDDIs involved an antiretroviral.
Veterans with an XDDI had a significantly higher hospital admission rate in the first year of ART than veterans without an XDDI (25.0% versus 15.2%, P = 0.004). Admissions were most frequent among veterans taking a PI (20.3%), followed by an NNRTI (15%) and an integrase inhibitor (11.4%) (P = 0.004). The most frequent reasons for hospital admission in veterans with an XDDI were psychiatric (32.3%), infectious disease (19.4%), renal (16.1%), and respiratory (9.7%).
Logistic regression analysis identified three variables independently associated with higher odds of hospital admission in the first year of ART, at the following adjusted odds ratios (aOR) and 95% confidence intervals:
-- 10 or more comorbidities: aOR 1.78 (1.19 to 2.68), P = 0.005
-- XXDI: aOR 1.60 (1.03 to 2.49), P = 0.04
-- PI vs integrase inhibitor: aOR 1.93 (1.23 to 3.02), P = 0.004
-- NNRTI vs integrase inhibitor: aOR 1.43 (0.92 to 2.23) (not significant, P = 0.11)
The researchers concluded that XDDIs are independently associated with hospital admission in the first year of antiretroviral therapy and that antiretroviral regimens differ in XDDI rates and in their impact on hospital admission.
Reference
1. Jakeman B, Nasiri M, Ruth L, Morse C, Mahatme S, Patel N. Relationship between type of ART, drug-drug interactions, and hospitalizations. ICAAC 2015, September 17-21, 2015, San Diego. Abstract H-780.
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