Coinfection with HIV and HCV presents a problem: many of the drugs used routinely to treat HIV have adverse interactions with the newer, and older, treatments for HCV.
The Centers for Disease Control and Prevention (CDC) estimate that 3.2 million Americans are infected with the hepatitis C virus (HCV), a number 3 times greater than the number of Americans infected with HIV. A smaller number of people are coinfected with HCV and HIV-an estimated 25% of all persons infected with HIV carry HCV-but these people require highly specialized care provided by a physician or group with extensive experience in the management of both types of infection. Even in the care of specialists, however, the most important question the HIV-infected person with concomitant HCV infection and a provider face today is whether to initiate therapy within a few months from now or to wait for the availability (a few years perhaps) of what will most likely be better-tolerated and more efficacious treatment regimens. Here I offer an overview of the factors to be considered when deciding to begin HCV therapy in an HIV-infected patient.
HIV and HCV share a number of similarities, at least epidemiologically. Risk factors for being infected with HCV include:
1. Having received a blood transfusion or organ transplant before 1992, the year that better testing for HCV became available (compared with 1985 for HIV).
2. Having received clotting factor concentrates (treatment for hemophilia) made before 1987.
3. Current or former injection drug use.
4. Having sustained a needle stick injury (as a health care worker) involving contact with HCV-contaminated blood.
Unlike HIV, however, HCV appears only rarely to be transmitted through heterosexual sex.
There are a number of other important differences between HIV and HCV, many of which have made treating HCV more challenging than treating HIV, despite the much larger HCV-infected population. First, HCV can be quiescent for many decades, whereas HIV typically manifests within 7 to 12 years of infection. Thus, many individuals who are infected with HCV are unaware of their status. Early awareness of HCV infection is important, because chronic liver disease will develop in 60% to 70% of those infected with HCV, cirrhosis will develop in up to 20% after 2 to 3 decades, and as many as 5% will die of consequences of HCV infection (cirrhosis or liver cancer).1 A second difference between the two infections is that in approximately 15% of those infected with HCV, the infection will spontaneously clear; spontaneous clearance of HIV never happens. In other words, a positive antibody test for HCV does not necessarily indicate chronic HCV infection or ongoing viremia. A third difference between HIV and HCV is that many of the newer drugs that have shown improved efficacy against HCV are “genotype-specific.” There are at least 6 distinct genotypes of HCV, and more than 50 subtypes have been discovered. Genotype 1 is the most common genotype in the United States and, unfortunately, has been the one most refractory to treatment. Indeed, in persons with HCV genotype 1, combination therapy (with alpha interferon and ribavirin) is recommended for twice as long as in those found to have other genotypes.
Until recently, individuals coinfected with HIV and HCV genotype 1 have had only about a 20% chance of a sustained response, even with the longer duration of therapy. On the other hand, most of the newer drugs for the treatment of HCV (eg, boceprevir, an HCV protease inhibitor) were developed because they have impressive activity against genotype 1. When bocepravir was added to a 1-year regimen of alpha interferon and ribavirin, the sustained response rate increased to 60% in HIV/HCV coinfected persons.2 Unfortunately, alpha interferon requires weekly injections and is associated with a high rate of “flu-like” symptoms, and ribavirin also has unpleasant adverse effects (eg, anemia).
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Treatment of HIV/HCV Coinfection: Patient Selection
How is the decision made on when-or whether-to begin HCV treatment in an HIV/HCV coinfected person? This is a difficult question to answer with confidence and must account for many factors. A primary problem is that many of the drugs used routinely to treat HIV have adverse interactions with the newer (and even older) treatments for HCV. For instance, among the many drugs used in combination to treat HIV, efavirenz cannot be used with boceprevir, and the only HIV protease inhibitor considered safe to use is atazanavir (with or without ritonavir). In the future, successful combination therapy used to treat HCV in HIV/HCV coinfected persons likely will not include alpha interferon, and will likely be reasonably safe in persons taking a variety of commonly prescribed antiretrovirals. However, these treatments are likely 3 to 4 years away from routine clinical use.
As would be true in a person without HIV who is infected with HCV, it is important to know the status of HCV infection before making decisions about when to initiate treatment. Specifically, knowing the patient’s HCV RNA level (viral load) is essential, primarily to exclude the possibility of previous spontaneous clearance of the virus. Next, a “detectable” viral load requires genotyping of the virus. In the case of non-genotype 1 infection, combination treatment with alpha interferon and ribavirin will result in a cure in 60% to 80% of coinfected persons. It is unlikely that future therapies will substantially improve on these numbers (for non-genotype 1 infections), and rapid responses to treatment after 1 month can be used to predict the likelihood of success at the completion of therapy. In other words, it does not take long to know whether the treatment is likely to result in a sustained virologic response at the completion of the full course of treatment. This is often useful information when dealing with adverse effects of the treatment regimen and deciding whether or not to continue.
Finally, it is critical to know the current extent of fibrosis (scarring) of the liver, especially for those with HCV genotype 1 who are trying to decide whether to start therapy now or wait several more years. Previously, this information required a liver biopsy specimen submitted to a pathologist for a “score.” Recently (April 2013), the FDA approved a noninvasive machine for determination of the extent of fibrosis. An alternative to the use of this machine, which is not widely available in the United States, is a blood test that provides a score that has been shown to correlate well with results from liver biopsies. Results from either the machine or the blood test will allow determination of the current extent of liver damage. While those individuals with the least amount of damage have been shown to have the best responses to therapy with alpha interferon and ribavirin, these same individuals have the “luxury of time” to wait for newer therapies, since their liver damage is not likely to progress substantially over the next several years.
The decision to treat the HCV genotype 1 individual coinfected with HIV now or later is best made after all of the information discussed above is available, and after extensive discussion with health care providers experienced in this area. In addition, it is extremely important for anyone infected with HCV to avoid alcohol, because any amount of alcohol consumed increases the risk for progression of fibrosis and cirrhosis. In summary, it is likely that a true cure for HCV, even in those coinfected with HIV, will be achieved in at least 70% of individuals with therapies available now or in the next several years.
1. Centers for Disease Control and Prevention. Hepatitis C information for health professionals. http://www.cdc.gov/hepatitis/hcv/hcvfaq.htm. Accessed August 11, 2013.
2. MallMallolas J, Pol S, Rivero A, et al. Boceprevir plus peginterferon/ribavirin for the treatment of HCV/HIV co-infected patients. End of treatment (week 48) interim results. Presented at: 47th Annual Meeting of the European Association for the Study of the Liver (EASL 2012); April 18–22, 2012; Barcelona, Spain. Abstract 50.