Up to 7 million people worldwide are coinfected with HIV and hepatitis C virus (HCV), which is associated with high rates of liver fibrosis, cirrhosis, hepatocellular carcinoma, and overall mortality. Although the recommended treatment for patients coinfected with HIV and HCV genotypes 1, 2, or 3 is 24 to 48 weeks of pegylated interferon and ribavirin with or without an HCV NS3/4A serine protease inhibitor, telaprevir, or boceprevir, the use of these regimens is limited due to complex dosing of the HCV NS3/4A serine protease inhibitors, poor tolerability, and drug interactions between HCV and antiretroviral therapy (ART). It is estimated that up to 70% of patients with HIV and HCV coinfection are not eligible for HCV treatment regimens that include interferon.
However, sofosbuvir, an oral nucleotide analog HCV NS5B polymerase inhibitor, has minimal to no drug interactions with a wide variety of antiretroviral drugs. Thus, researchers sought to examine the effects of sofosbuvir in this coinfected patient population [JAMA. 2014;312(4):353-361].
This multicenter, open-label, nonrandomized, uncontrolled, phase 3 trial evaluated the sustained virologic response (SVR) and adverse events in patients coinfected with HIV and HCV genotype 1, 2, or 3 who where treated with the oral regimen of sofosbuvir and ribavirin for 12 or 24 weeks. The study was conducted at 34 treatment centers in the United States and Puerto Rico between August 2012 and November 2013.
Patients were eligible for inclusion if they were ≥18 years of age and had a body mass index of ≥18 kg/m2. Patients with HCV genotype 1, 2, or 3 who had not received HCV treatment and patients with HCV genotype 2 or 3 who had been previously treated for HCV were also eligible.
Patients receiving ART were required to have been receiving a stable regimen for at least 8 weeks prior to screening, have an HIV ribonucleic acid <50 copies/mL, and have a CD4 T-lymphocyte count >200 cells/µL. Patients not receiving ART were required to have a CD4 T-lymphocyte count >500 cells/µL at screening. No more than 20% of study participants were permitted to have evidence of cirrhosis at screening as assessed.
All patients received 400 mg of sofosbuvir administered orally once daily with ribavirin administered orally twice daily. Doses were determined based on body weight: 1000 mg daily for patients with a body weight <75 kg and 1200 mg daily for patients with a body weight ≥75 kg.
Treatment-naïve patients with HCV genotype 2 or 3 were treated for 12 weeks, while treatment-naïve patients with HCV genotype 1 and treatment-experienced patients with HCV genotype 2 or 3 were treated for 24 weeks.
The primary outcome was the proportion of patients with SVR (serum HCV <25 copies/mL) 12 weeks after cessation of HCV therapy.
Of the patients screened and enrolled in the study, a total of 223 began treatment. In each treatment group, 90% to 98% of patients were taking ART.
Among the 114 treatment-naïve patients with HCV genotype 1, 76% (n=84) achieved SVR at 12 weeks post-treatment (95% confidence interval [CI], 67%-84%). Among the 26 treatment-naïve patients with HCV genotype 2, 88% (n=23) achieved SVR at 12 weeks post-treatment (95% CI, 70%-98%). Among the 42 treatment-naïve patients with HCV genotype 3, 67% (n=28) achieved SVR at 12 weeks post-treatment (95% CI, 51%-80%). Among the 24 treatment-experienced patients with HCV genotype 2, 92% (n=22) achieved SVR at 12 weeks post-treatment (95% CI, 73%-99%). Among the 17 treatment-experienced patients with HCV genotype 3, 94% (n=16) achieved SVR at 12 weeks post-treatment (95% CI, 71%-100%).
The most commonly reported adverse events were fatigue, insomnia, headache, and nausea. Seven
patients (3%) discontinued HCV treatment due to adverse events. Adverse effects on HIV or its treatment were not observed, according to the researchers.
The study’s authors noted limitations. Patients with cirrhosis (10%) and women (17%) were
underrepresented in the study population. Also, few patients with advanced HIV disease were enrolled; therefore, the safety and efficacy of sofosbuvir and ribavirin is unknown in these populations. Lastly, the absence of a control group limits the ability to draw definitive conclusions on safety and efficacy of the regimen.
Overall, the researchers concluded that more studies on this oral regimen in diverse populations of coinfected patients is needed.—Kerri Fitzgerald