ASM Microbe

ASM Microbe

August 09, 2016
3 min read

Guest Commentary: Direct-acting antiviral ‘revolution’ improves treatment of HIV/HCV coinfection

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In this guest commentary, Michael Saag, MD, director of the Center for AIDS Research, University of Alabama at Birmingham, and Co-Editor in Chief of HCV Next, discusses the treatment of HIV/hepatitis C virus coinfection following the advent of direct-acting antivirals.

There has been a revolution in the treatment of hepatitis C virus over the last decade. What used to be a difficult to manage and cure infection that required a year of injectable interferon and oral ribavirin now can be cured readily in 12 weeks with all-oral therapy. This is important, particularly, for people who have both HIV and hepatitis C virus. Heretofore, the interferon-ribavirin combinations could only cure up to 40%, or at most 50%, of patients with HIV/HCV coinfection; now, that cure rate is approaching 95% to 98%.

Michael Saag

The revolution in direct-acting agents is rooted in the drug development for HIV. In particular, the HIV small-molecule drug pipeline was developed from the late 1980s into the 1990s, leading to drugs that included nucleoside, non-nucleoside and protease inhibitor anti-HIV drugs. In the late 1990s, an assay system based on replicase technology allowed pharmaceutical companies to begin high-throughput screening of a large number of small molecules that, ironically, also included drugs of the nucleoside, non-nucleoside and protease inhibitor variety; however, in this case, it was targeting hepatitis C enzymes rather than HIV enzymes. In addition, another area, NS5A gene product inhibitors, appeared that is of critical importance in terms of assuring cure.

In the last 5 years, many of these direct-acting agents have come to market. While these drugs were initially developed mostly for patients with HCV monoinfection, research in the last several years has evaluated these drugs in those who have HIV/HCV coinfection. The bottom line to all of the studies is that the direct-acting anti-HCV drugs work just as well in patients coinfected with HIV and HCV as they do in patients with HCV only. This is a dramatic departure from the previous era of interferon-based regimens where, uniformly, patients with HIV/HCV coinfection did not fare as well in terms of outcomes as those with HCV monoinfection. What this means is that we are now able to cure HCV in virtually every patient with HIV/HCV coinfection, provided we know who they are and we have access to the medications. The main thing we have to manage is drug-drug interactions, which HIV providers are quite adept at doing.

In many ways, access to HCV medications, ironically, is easier for the coinfected population than it is for the monoinfected population. Owing to the relatively high cost of anti-hepatitis C medicines, payers require a lot of documentation before granting payment for anti-hepatitis C drugs. However, for those patients with HIV/HCV coinfection, virtually all individuals – even those with earlier-stage disease (F0 and F1 scores) – are able to gain access because of the epidemiologic data that shows that HIV/HCV coinfected patients progress more rapidly to advanced fibrosis than those who are monoinfected. As a result, simply indicating on the prior authorization form that the patient has HIV/HCV coinfection usually will lead to approval of the medications by the payers. This is great news for our patients with HIV/HCV coinfection. 

In addition, the source of payment also is a little bit easier in the HIV/HCV coinfected space, owing to the Ryan White Care Act. Patients who are eligible for ADAP funding can gain payment for hepatitis C drugs through this program, whereas those who are monoinfected are not eligible for payment through Ryan White. Therefore, patients who have HIV/HCV coinfection gain approval through normal insurance company status and also obtain access to the Ryan White ADAP program if they have a gap in their insurance that does not provide coverage.

So, what does that mean for providers? All providers taking care of patients with HIV should screen every patient for HCV. If they determine that there is antibody positivity, they should follow this up with an HCV viral load test and genotyping; those who have detectable viral loads should have targeted therapy prescribed based on both the genotype and the fibrosis score, with adjustment for potential drug-drug interactions. Information on specific drug-drug interactions and treatment of HCV in general can readily be accessed in the HCV guidelines produced by the American Association for the Study of Liver Diseases and the Infectious Diseases Society of America and can be found at the website

Disclosure: Saag reports receiving research grants through his institution from AbbVie, Bristol Myers Squibb, Gilead Sciences, Merck and ViiV Healthcare and serving on advisory boards for Bristol Myers Squibb, Gilead Sciences and Merck.