ABSTRACT
BACKGROUND: HIV-infected patients receiving antiretroviral therapy (ART) are at risk for contraindicated drug-drug interactions (XDDIs). OBJECTIVE: This study compared the frequency of XDDIs between different types of ART regimens. METHODS: A retrospective cohort study was performed among adult HIV-infected patients receiving care at either the Upstate New York Veterans' Healthcare Administration or the University of New Mexico Truman Health Services between 2000 and 2013. The cohort consisted of patients receiving traditional ART regimens composed of 2 nucleoside reverse transcriptase inhibitors plus either a nonnucleoside reverse transcriptase inhibitor (NNRTI), a protease inhibitor (PI), or an integrase strand transfer inhibitor (INSTI). The primary outcome was the presence of XDDIs. Lexi-Interact was used to define XDDIs. RESULTS: Of the 1329 patients who met inclusion criteria, 45.7%, 34.2%, and 20.1% were receiving an NNRTI-, PI-, or INSTI- based ART regimen, respectively. Among the 128 (9.6%) patients with an XDDI, more than half (53.9%) had an interaction involving ART. The presence of XDDIs was highest for PI-based regimens (16.3%) compared with INSTI- (7.9%) and NNRTI-based (5.4%) regimens; P < 0.001. The variables independently associated with XDDIs were ART regimen type (prevalence ratio [PR] = 1.91; 95% CI = 1.51-2.40, P < 0.001), use of ≥6 non-HIV medications (PR = 5.84; 95% CI = 3.92-8.71, P < 0.001), and age ≥40 years (PR = 1.62; 95% CI = 0.92-2.86, P = 0.10). CONCLUSION: The probability of XDDIs varies as a function of ART regimen type, advanced age, and use of multiple non-HIV medications.
Subject(s)
Anti-HIV Agents , Antiretroviral Therapy, Highly Active , Drug-Related Side Effects and Adverse Reactions/epidemiology , HIV Infections/drug therapy , Reverse Transcriptase Inhibitors , Adult , Anti-HIV Agents/administration & dosage , Anti-HIV Agents/pharmacokinetics , Anti-HIV Agents/therapeutic use , Contraindications , Drug Interactions , Drug-Related Side Effects and Adverse Reactions/etiology , Female , HIV Infections/virology , Humans , Male , Middle Aged , Multivariate Analysis , New Mexico , New York , Regression Analysis , Retrospective Studies , Reverse Transcriptase Inhibitors/administration & dosage , Reverse Transcriptase Inhibitors/pharmacokinetics , Reverse Transcriptase Inhibitors/therapeutic use , Young AdultABSTRACT
There have been dramatic advancements in the treatment of chronic hepatitis C (HCV) infection. This is largely due to the approval of several direct-acting antiviral agents (DAAs) from a variety of medication classes with novel mechanisms of action. These therapies are a welcomed advancement given their improved efficacy and tolerability compared to pegylated interferon and ribavirin (RBV)-based regimens. These convenient, all-oral regimens treat a variety of genotypes and often offer high cure rates in a variety of HCV-infected populations. While there are several benefits associated with these therapies, there are also notable shortcomings. Shortcomings include diminished response or need for adjunctive RBV in difficult-to-treat populations (decompensated cirrhosis, active substance abuse patients, advanced kidney disease, etc.), activity against select genotypes, substantial drug-drug interaction potential, and high cost. Therefore, while current DAA-based therapies have several favorable attributes, each also has its limitations. The purpose of this review is to (1) identify the characteristics of an ideal HCV treatment regimen, (2) describe desirable features of existing regimens, (3) summarize limitations of existing regimens, and (4) introduce promising emerging therapies. This manuscript will serve as a guide for evaluating the caliber of future HCV treatment regimens.
