Treating Hepatitis C Virus and HIV Coinfections in Intravenous Drug Users
Unique considerations are called for when caring for intravenous drug users with newly diagnosed HIV/HCV coinfections.
In 2016, an estimated 2.3 million people living with HIV were coinfected with chronic hepatitis C virus (HCV).1 Of the coinfected population, more than half were intravenous drug users (IVDUs).1 One meta-analysis of the HIV/HCV coinfection literature found that more than 80% of the coinfections were in IVDUs.2 Yet, while it is established that persons who inject drugs make up a large part of this HIV/ HCV coinfected population, these patients are not clearly identified in the major HIV/HCV coinfection trials. Although this can be a difficult patient population to manage, they are a high priority from a population health standpoint. Eradication of HCV, in addition to complete viral suppression of HIV, would substantially decrease overall transmission of these viruses if these high-risk behaviors continue.
Initiation of antiretroviral therapy (ART) is recommended for all patients testing positive for HIV infection. In the coinfected population, this is even more important, as untreated HCV in HIV leads to more rapid liver disease progression and increases both morbidity and mortality.1 In patients with HIV/ HCV coinfection, the choice of ART should take into consideration the potential need for concurrent HCV treatment. Other considerations include the ability to adhere to therapy, cost or insurance coverage of medications, hepatitis B virus status, and progression of liver disease or cirrhosis. Each of these factors can further dictate the medication regimen for both disease states.3 Table 1 outlines the recommended first-line and alternative direct-acting antiviral (DAA) medications for the treatment of HCV from the American Association for the Study of Liver Diseases (AASLD) and takes into consideration appropriate, as well as inappropriate, concomitant antiretroviral agents.3
Patients with HIV should always be screened and evaluated for HCV treatment. If they meet the criteria, therapy with a DAA should then be initiated based on HCV genotype and severity of disease.3 The currently available DAA regimens result in high HCV cure rates, as measured by sustained virologic response (SVR). SVR is achieved in the HIV/HCV coinfected population at a similar rate as those with HCV monoinfection.4-6 The trials investigating many of the DAA agents in the HIV/HCV coinfected population are outlined in Table 2 (available at contagionlive.com). Some of the data on glecaprevir/ pibrentasvir have been presented, but the full trial has not yet been published. No articles on the efficacy of the newest agent, sofosbuvir/velpatasvir/voxilaprevir, are available yet in this specific patient population. However, the phase 3 trials for this medication, published as the POLARIS series, have shown SVR rates comparable with those of the agents listed below in HCV monoinfected patients. In treatment-naïve patients, 8 weeks of treatment with sofosbuvir/velpatasvir/voxilaprevir resulted in an SVR of 95%. In previously treated patients without cirrhosis, the SVR was as high as 99%.7,8 Because of the high SVR in this population and the already well-established first-line agents, sofosbuvir/velpatasvir/voxilaprevir will be seen clinically primarily in patients who have failed prior therapy.
Although HIV/HCV coinfection is common in IVDUs, these patients are not commonly mentioned in clinical trials, despite making up a large portion of the real-world HIV/HCV coinfected population. In fact, IVDU is a common exclusion criterion for trials, especially those in which treatment adherence and follow-up are directly correlated to efficacy. For example, the C-EDGE and ION-4 trials list clinically relevant drug or alcohol abuse or a history of abuse within 12 months of screening as an exclusion criterion.5,4 In the PHOTON-1 trial, persons who inject drugs were not explicitly excluded, however, if any participant had a positive urine drug toxicology screening, he or she could not participate in the study.9 The ledipasvir/sofosbuvir trial, the National Institute of Allergy and Infectious Disease’s ERADICATE trial, inclusion criteria states that if patients were opioid dependent, they had to participate in supervised treatment while in the study.10 Other studies give even less detail but state generally that anything that could affect adherence should be an exclusion criterion at the principal investigator’s discretion.
When treating a person who injects drugs with newly diagnosed HIV/HCV co-infection, as with all patients, medication therapy for both infections should be initiated as soon as possible to prevent the progression of liver disease and decrease the transmission of the viruses. HIV viral load suppression should be obtained first, followed by the addition of HCV treatment. An ideal combination for a patient presenting with an HIV/HCV coinfection would be a regimen such as dolutegravir/abacavir/lamivudineand glecaprevir/ pibrentasvir. If a patient is eligible for HIV treatment with dolutegravir/abacavir/lamivudine (namely HLA-B*5701 negative and without cardiovascular disease), glecaprevir/pibrentasvir can be safely added to this regimen with minimal risk of drug—drug interactions. Furthermore, as a pan-genotypic agent, glecaprevir/ pibrentasvir has shown efficacy for all HCV infection genotypes. Perhaps most important for this patient population is that in individuals without cirrhosis, treatment is only 8 weeks, potentially increasing the likelihood of adherence.3
Starting at diagnosis and continuing with each health care encounter, it is important to address and evaluate the patient’s illicit drug use. Studies have shown that in the HIV populations, ART is equally efficacious for IVDUs and non-IDVUs when patients are not actively using drugs.11 Illicit drugs have been linked to depression and anxiety, which is a strong predictor of poor adherence and potentially poor treatment outcomes. Persons who inject drugs and have HIV have lower rates of ART if they also have additional risk factors such as recent incarceration or lack of access to rehabilitation programs. Therefore, management of substance use disorders is often necessary to successfully eradicate HCV and appropriately manage HIV.
It is important to build a relationship of trust with these patients and not only provide medical support for their HIV/ HCV infections but also assist in getting them connected for their other comorbidities that affect patient adherence to medication therapies. This primarily includes a multidisciplinary approach to treating the patient’s substance abuse disorders. In addition to medication therapy, it is prudent to stabilize these patients through treatment of psychiatric illnesses and substance abuse treatment. Further harm-reduction measures such as connecting patients with needle exchange programs and clinics to provide sexually transmitted infection screenings and free condoms are also important.
In a patient population that is commonly lost to follow-up, it is also pertinent to engage, link, and retain these patients from the community into care. This could be done through co-management of patient’s infectious diseases in substance abuse programs or methadone clinics. As this is a high-risk population for transmission of HIV and HCV, population screening should also be provided to ensure adequate treatment for all individuals.
HIV/HCV treatments can be provided only if these patients are identified. With overlapping modes of transmission and affected populations, meeting these patients in the community is the first step for control of these conditions. With new medications being developed for both HIV and HCV, as clinicians we need to remain up-to-date on safety profiles, drug interactions, and clinical pearls for each medication. Armed with this knowledge, we can treat this unique population with the most targeted and multifaceted approach.
Dr. Badowski is a clinical associate professor at the University of Illinois at Chicago (UIC), College of Pharmacy in Chicago, Illinois. She completed a PharmD at Midwestern University, Downers Grove, Illinois, an MPH at UIC, School of Public Health, and residencies at the University of Maryland Medical Center and College of Pharmacy in Baltimore. Her current practice setting is an interdisciplinary telemedicine clinic where she manages people living with HIV in the correctional setting for the state of Illinois.
Dr. Murdock is a PGY2 ambulatory care pharmacy practice resident at the University of Illinois at Chicago, College of Pharmacy (UIC) in Chicago, Illinois. She completed a PharmD at the University of Kentucky and a first-year pharmacy residency at UIC.
- HIV/AIDS. World Health Organization website. who.int/hiv/mediacentre/news/hep-hiv-coinfected/en/. Accessed February 25, 2018.
- Platt L, Easterbrook P, Gower E, et al. Prevalence and burden of HCV co-infection in people living with HIV: a global systematic review and meta-analysis. Lancet Infect Dis. 2016;16(7):797-808. doi: 10.1016/S1473-3099(15)00485-5.
- Guidelines for the use of antiretroviral agents in adults and adolescents living with HIV. AIDSinfo website. https://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf . Updated October 17, 2017. Accessed February 15, 2018.
- Naggie S, Cooper C, Saag M, et al. Ledipasvir and sofosbuvir for HCV in patients coinfected with HIV-1. N Engl J Med. 2015;373(8):705-713. doi: 10.1056/NEJMoa1501315.
- Rockstroh JK, Nelson M, Katlama C, et al. Efficacy and safety of grazoprevir (MK-5172) and elbasvir (MK-8742) in patients with hepatitis C virus and HIV co-infection (C-EDGE CO-INFECTION): a non-randomised, open-label trial. Lancet HIV. 2015;2(8):e319-e327. doi: 10.1016/S2352-3018(15)00114-9.
- Sogni P, Gilbert C, Lacombe K, et al. All-oral direct-acting antiviral regimens in HIV/hepatitis C virus-coinfected patients with cirrhosis are efficient and safe: real-life results from the prospective ANRS CO13-HEPAVIH cohort. Clin Infect Dis. 2016;63(6):763-770. doi: 10.1093/cid/ciw379.
- Bourlière M, Gordon SC, Flamm SL, et al. Sofosbuvir, velpatasvir, and voxilaprevir for previously treated HCV infection. N Engl J Med. 2017;376(22):2134-2146. doi: 10.1056/NEJMoa1613512.
- Jacobson IM, Lawitz E, Gane EJ, et al. Efficacy of 8 weeks of sofosbuvir, velpatasvir, and voxilaprevir in patients with chronic HCV infection: 2 phase 3 randomized trials. Gastroenterology. 2017;153(1):113-122. doi: 10.1053/j.gastro.2017.03.047.
- Sulkowski MS, Naggie S, Lalezari J, et al. Sofosbuvir and ribavirin for hepatitis C in patients with HIV coinfection. JAMA. 2014;312(4):353-361. doi: 10.1001/jama.2014.7734.
- Osinusi A, Townsend K, Kohli A, et al. Virologic response following combined ledipasvir and sofosbuvir administration in patients with HCV genotype 1 and HIV co-infection. JAMA. 2015;313(12):1232-1239. doi:10.001/jama.2015.1373.
- HIV and people who use illicit drugs. AIDSinfo website. aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv/22/hiv-and-people-who-use-illicit-drugs. Updated March 27, 2012. Accessed February 25, 2018.
- Molina JM , Orkin C, Iser DM, et al. Sofosbuvir plus ribavirin for treatment of hepatitis C virus in patients co-infected with HIV (PHOTON-2): a multicentre, open-label, non-randomised, phase 3 study. Lancet. 2015;385(9973):1098-1106. doi: 10.1016/S0140-6736(14)62483-1.
- Sulkowski MS, Eron JJ, Wyles D, et al. Ombitasvir, paritaprevir co-dosed with ritonavir, dasabuvir, and ribavirin for hepatitis C in patients co-infected with HIV-1 a randomized trial. JAMA. 2015 Mar 24-31;313(12):1223-31. doi: 10.1001/jama.2015.1328
- Wyles DL, Ruane PJ, Sulkowski MS, et al. Daclatasvir plus sofosbuvir for HCV in patients coinfected with HIV-1. N Engl J Med. 2015;373(8):714-725. doi: 10.1056/NEJMoa1503153.
- Wyles D, Brau N, Kottilil S, et al. Sofosbuvir and velpatasvir for the treatment of hepatitis c virus in patients coinfected with human immunodeficiency virus type 1: an open-label phase 3 study. Clin Infect Dis. 2017;65(1):6-12. doi: 10.1093/cid/cix260.
- Sulkowski M, Hezode C, Gerstoft J, et al. Efficacy and safety of 8 weeks versus 12 weeks of treatment with grazoprevir (Mk-5172) and elbasvir (MK-8742) with or without ribavirin in patients with hepatitis C virus genotype 1 mono-infection and HIV/hepatitis C virus co-infection (C-WORTHY): a randomized, open-label phase 2 trial. Lancet. 2015;385(9973):1087-1097. doi: 10.1016/S0140-6736(14)61793-1.
- Zeuzem S, Foster GR, Wang S, et al. Glecaprevir-Pibrentasvir for 8 or 12 weeks in HCV genotype 1 or 3 infection. N Engl J Med. 2018 Jan 25;378(4):354-369. doi: 10.1056/NEJMoa1702417.
- Rockstroh J. Glecaprevir/pibrentasvir in patients with HIV co-infection. Oral presentation at: European Association for the Study of the Liver (EASL) 2017, Amsterdam, The NetherlandsAbs. LB-522.