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HCV/HIV Coinfection: Yesterday, Today and Tomorrow

Issue: November 2014

ByCody A. Chastain, MD

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Hepatitis C virus infection is a significant cause of morbidity and mortality worldwide, but it is a particular concern among people living with HIV/AIDS. Coinfection with HCV occurs in 15% to 30% of patients with HIV in the United States. Liver disease, predominantly related to viral hepatitis, is a leading cause of death among these individuals, highlighting the substantial impact of HCV coinfection on this group.

HIV coinfection transforms the often-indolent natural history of HCV monoinfection into a more aggressive entity. HCV infection is more likely to result in advanced liver fibrosis and decompensated liver disease in the setting of HIV. Furthermore, fibrosis develops faster in individuals coinfected with HIV/HCV than in those with HCV alone. Indeed, cases of rapid progression from HCV infection to decompensated liver disease, even in the absence of cirrhosis, have been reported in HIV/HCV-coinfected patients.

In the past, coinfection has been a barrier to achieving sustained virologic response with traditional HCV therapies. When treated with pegylated interferon and ribavirin, HIV/HCV-coinfected patients were less likely to achieve SVR as compared with HCV-monoinfected patients. Fortunately, modern therapies that include direct-acting antivirals appear to have excellent efficacy among HIV/HCV-coinfected individuals, just as they do among HCV-monoinfected individuals.

Current Challenges

Although there are many barriers to HCV treatment, there are three particular challenges to treating HCV in the setting of HIV coinfection today: drug-drug interactions, comorbid conditions and access to new therapies.

First, drug-drug interactions with HIV antiretroviral regimens is a critical challenge for select patients. HCV NS3B/4A protease inhibitors affect the cytochrome p450 metabolism pathway and alter the metabolism of HIV antiretroviral drugs. New DAA combination therapies based on NS5B polymerase inhibitors and NS5A replication complex inhibitors may have fewer drug-drug interactions. However, proposed DAA regimens often include agents from multiple classes, increasing risk for drug-drug interactions. Also, drug-drug interaction studies may be incomplete or only include healthy volunteers. Some HIV patients are on atypical salvage antiretroviral regimens due to HIV resistance, making the selection of HCV DAA therapies more difficult, and new DAA regimens that have few drug-drug interactions will be important additions to this field. However, providers will need to be vigilant in evaluating and monitoring for drug-drug interactions in all HIV/HCV-coinfected patients.

Cody A. Chastain

Second, comorbid conditions in people living with HIV/AIDS will continue to be a barrier to HCV therapy. Besides HIV/AIDS, these patients may have hepatitis B virus infection, diabetes, and other conditions that may directly contribute to hepatic inflammation and fibrosis development. Psychiatric conditions are common in patients with HCV and HIV; these conditions may affect treatment eligibility, compliance with follow-up and adherence. Last but not least, alcohol and IV drug use may be present HIV/HCV-coinfected individuals. Alcohol use may directly affect liver disease progression, as well as treatment candidacy, while IV drug use may increase the risk for reinfection. Given the consequences of HCV in this population, we must aggressively address modifiable comorbidities, evaluate treatment candidacy and prioritize these patients for therapy.

Third, HCV therapy may be limited for HIV/HCV-coinfected patients due to provider access and financial barriers. Management of HIV/HCV-coinfected patients is often challenging for the reasons noted, and some gastroenterologists and hepatologists may prefer to defer therapy to someone with more experience treating HIV-infected individuals. While DAA therapy for HCV is similar to antiretroviral therapy for HIV in many respects, a number of HIV providers have chosen not to prescribe DAA therapy due to clinical, educational or infrastructure-related challenges. When patients have cirrhosis, it is essential that they receive appropriate screening for hepatocellular carcinoma and for esophageal varices; additionally, referral to a skilled hepatologist for liver transplant evaluation may be required. As more HIV/HCV-coinfected patients become candidates for therapy with modern DAA regimens, infectious diseases physicians may be well positioned to increase the capacity to manage these patients while partnering with the hepatology community to care for patients with advanced liver disease.

Even when patients are linked to care with a HCV provider, there are many financial barriers to obtaining DAA therapies. DAA regimens in 2014 have been expensive, with health care costs for a full course of treatment approaching or surpassing $100,000. As such, there have been restrictions instituted by payers regarding who can treat, who should be treated and which drugs should be used. These restrictions vary between payers and are frequently changing with the advent of new therapies. This changing landscape often requires an efficient and comprehensive support structure for preauthorization approvals and insurance appeals. Furthermore, many HIV/HCV-coinfected patients do not have traditional insurance coverage and may instead receive HIV services through Ryan White HIV/AIDS Program funding. These programs, although essential for HIV care, may not have sufficient budgets to cover expensive HCV therapies.

The advent of coformulated sofosbuvir and ledipasvir (Harvoni, Gilead) is anticipated to improve regimen costs as compared with the off-label use of sofosbuvir (Sovaldi, Gilead) and simeprevir (Olysio, Janssen Therapeutics), the DAA regimen most commonly used during the past year. As multiple DAA regimens are likely to come to market in the near future, the financial landscape surrounding DAA therapy will continue to shift. Regardless of these changes, cost will undoubtedly continue to be a barrier.

Available Regimens, Future Directions

As of October, the only DAA to receive FDA approval for use in HIV/HCV-coinfected patients is sofosbuvir, although telaprevir (Incivek, Vertex Pharmaceuticals), boceprevir (Victrelis, Merck) and simeprevir have been evaluated in HIV/HCV-coinfection clinical trials and have been used off-label in this population. The most recently approved DAA, ledipasvir, was approved in October and will be available coformulated with sofosbuvir. The efficacy of this coformulated therapy in HIV/HCV-coinfected patients is being assessed in a clinical trial. The clinical role of this combination in the absence of a specific FDA approval for use in HIV/HCV coinfection has yet to be determined, although it is likely to be used for patients infected with genotype 1 who are being treated with compatible HIV antiretroviral regimens. At the time of writing, the ‘3D’ regimen of ABT-450/ritonavir, ombitasvir and dasabuvir (AbbVie) is awaiting FDA approval, which is anticipated by the end of 2015. Clinical trials evaluating this regimen in HIV/HCV coinfection are underway.

Important industry-sponsored and AIDS Clinical Trials Group (ACTG) initiatives have prioritized HIV/HCV coinfection in current and future clinical trials. New information about DAA therapy in HIV/HCV coinfection is anticipated at The Liver Meeting in Boston in November and at the Conference on Retroviruses and Opportunistic Infections (CROI) in February.

Reasons for Optimism

Despite many challenges, there are also reasons for optimism. Although the medical community continues to struggle to appropriately screen and diagnose HCV-monoinfected patients and link them to care, a vast care network is already in place for HIV-infected patients.

HCV screening among this population is common, as shared risk factors for HIV and HCV acquisition have been long recognized. In the DAA era, HIV providers are in an excellent position to expand their skillset to include HCV management. Educating and engaging these providers in the exciting arena of HCV care will continue to be an important task of experts in our community. The many lessons learned regarding HIV diagnosis, linkage to care, retention and therapy may also be applied to the epidemic of young people newly infected with HCV through IV drug use.

With new DAAs, provider education, support infrastructure and further scientific study, we have a great opportunity to drastically reduce the impact of HCV on our patients living with HIV/AIDS.