Potential for Drug-Drug Interactions between Antiretrovirals and HCV Direct Acting Antivirals in a Large Cohort of HIV/HCV Coinfected Patients

Abstract

Objectives: Development of direct acting antivirals (DAA) offers new benefits for patients with chronic hepatitis C. The combination of these drugs with antiretroviral treatment (cART) is a real challenge in HIV/HCV coinfected patients. The aim of this study was to describe potential drug-drug interactions between DAAs and antiretroviral drugs in a cohort of HIV/HCV coinfected patients.

Methods: Cross-sectional study of all HIV/HCV coinfected patients attending at least one visit in 2012 in the multicenter French Dat'AIDS cohort. A simulation of drug-drug interactions between antiretroviral treatment and DAAs available in 2015 was performed.

Results: Of 16,634 HIV-infected patients, 2,511 had detectable anti-HCV antibodies, of whom 1,196 had a detectable HCV-RNA and were not receiving HCV treatment at the time of analysis. 97.1% of these patients were receiving cART and 81.2% had a plasma HIV RNA <50 copies/mL. cART included combinations of nucleoside reverse transcriptase inhibitors with a boosted protease inhibitor in 43.6%, a non-nucleoside reverse transcriptase inhibitor in 17.3%, an integrase inhibitor in 15.4% and various combinations or antiretroviral drugs in 23.7% of patients. A previous treatment against HCV had been administered in 64.4% of patients. Contraindicated associations/potential interactions were expected between cART and respectively sofosbuvir (0.2%/0%), sofosbuvir/ledipasvir (0.2%/67.6%), daclatasvir (0%/49.4%), ombitasvir/boosted paritaprevir (with or without dasabuvir) (34.4%/52.2%) and simeprevir (78.8%/0%).

Conclusions: Significant potential drug-drug interactions are expected between cART and the currently available DAAs in the majority of HIV/HCV coinfected patients. Sofosbuvir/ledipasvir and sofosbuvir/daclatasvir with or without ribavirin appeared the most suitable combinations in our population. A close collaboration between hepatologists and HIV/AIDS specialists appears necessary for the management of HCV treatment concomitantly to cART.

Fig 1. Flow chart of patient analysis.

Fig 2. Distribution of antiretroviral drugs received in 1161 HIV/HCV coinfected patients under cART and potential drug-drug interactions between antiretrovirals and currently available DAAs (patients not under antiretroviral treatment, patients under HCV treatment at the time of analysis and patients with HCV reinfection excluded).

Adapted from www.hep-druginteractions.org (Abbreviations: ABC abacavir; ddI didanosine; FTC emtricitabine; LAM lamivudine; TDF tenofovir; ZDV zidovudine; EFV efavirenz; ETV etravirine; NVP nevirapine; RPV rilpivirine; DLG dolutegravir; EVGc cobicistat boosted elvitegravir; MRV maraviroc; RAL raltegravir; ATV atazanavir; ATVr ritonavir boosted atazanavir; DRVr ritonavir boosted darunavir; fAPVr ritonavir boosted fosamprenavir; IDVr ritonavir boosted indinavir; LPVr ritonavir boosted lopinavir; SQVr ritonavir boosted saquinavir; TPVr ritonavir boosted tipranavir; BOC boceprevir; DCV daclatasvir; LED Ledipasvir; OBV ombitasvir; PTVr ritonavir boosted paritaprevir; DSV dasabuvir; SMV simeprevir; SOF sofosbuvir; TVR telaprevir; PegIFN Peg interferon alpha; RBV ribavirin.)