hepatitis c viruses

Hepatitis C virus (HCV) is perhaps one of the most overlooked viral infections worldwide, despite being very common and preventable. Recently, it has become apparent that the risk of transmitting HCV during sex had been underestimated because earlier studies included mostly monogamous, heterosexual, HIV-negative couples. Outbreaks of sexually transmitted HCV among HIV-positive men who have sex with men (MSM) have been reported in many parts of the world in the past decade, proving that the risk of sexual transmission of HCV may be higher in certain groups.

HCV is a serious threat to the health and well-being of those who become infected, but recent advances in testing and treatment have greatly improved the situation for those who are at risk or diagnosed.

What Is HCV?

HCV is transmitted by contact with HCV-infected blood. It is an extremely efficient virus, meaning people who are exposed to it are very likely to become infected. The virus can live for over two weeks in a speck of dried blood! Blood-to-blood contact remains the most likely method of transmission, whether during sex or through sharing needles. The virus has also been found in semen, but it remains unknown how efficient that route of transmission is. Without treatment, HCV viral loads can increase to levels that make transmission even more likely.

In the U.S., about 3 million people have HCV, and over 80% of these cases are chronic. Fortunately, chronic HCV infection usually progresses slowly and may not lead to liver disease in many patients -- especially if the infection is acquired later in life. Approximately 20 to 30% of people who are chronically infected develop cirrhosis over 20 to 30 years. In 2007, HCV was the cause of approximately 15,000 deaths, surpassing the annual mortality rates of HIV. HCV is a common co-infection in people with HIV, but it often goes undiagnosed for many years, and 73% of deaths are in people aged 45 to 65. Chronic HCV infection is also associated with high rates of liver disease and cirrhosis, which can lead to expensive and invasive liver transplants. The average cost of HCV-related care for one person over their lifetime exceeds $100,000.

Why Should LGBT People Be Concerned About HCV?

"Past HCV prevention efforts focused on people who inject drugs. It is now widely accepted that HCV is a sexually transmitted infection, and that HIV-positive MSM are especially vulnerable."

Past HCV prevention efforts focused on people who inject drugs. Whether for recreational drugs, hormones, or cosmetic products, LGBT populations are more likely to report having used syringes than the general population. The large number of new cases of HCV among HIV-positive MSM in Europe added a new cause for concern since the vast majority of these men reported no history of injecting drugs. Studies later confirmed that there was a network of sexual transmission in several countries by showing the strains of HCV believed to be sexually acquired were not the same as those commonly passed between injection drug users. In Amsterdam, it was estimated that 1 to 4% of HIV-positive MSM were co-infected with HCV in 2000. By 2008, nearly 21% of HIV-positive MSM in one study sample were co-infected, and most of the infections happened between 2005 and 2007. Since the early 2000s, HIV-positive MSM in Belgium have experienced a 3% increase in co-infections annually. It is now widely accepted that HCV is a sexually transmitted infection, and that HIV-positive MSM are especially vulnerable.

Rapidly increasing rates of sexually transmitted HCV have now been documented in cities in Europe, Asia, and North America. In the U.S., it appears that HIV-positive MSM in New York City are experiencing the highest rates of HCV co-infection, at around 12%. North America has not yet experienced the dramatic rates of HCV that have been seen in other parts of the world. Therefore, better prevention initiatives and increased testing could help avoid such a situation from developing.

HIV/HCV co-infection is a major concern, because it can mean faster progression to serious liver problems and can increase the likelihood of death from either virus. It is important to note that HCV has been found in HIV-negative MSM who reported only sexual risk behaviors. This could mean that sexually-transmitted HCV could become a serious issue even for MSM who are HIV negative.

How Can I Protect Myself?

2 men on grass

Past recommendations for avoiding HCV were simple: don't inject drugs -- and if you do, use clean needles. Unfortunately, the ways in which HCV transmission occurs during sex are not as well understood, and may include a number of biological and behavioral factors. Several studies of HIV-positive MSM found that recent HCV infection was associated with:

  • Past or current STIs
  • Many sex partners
  • Unprotected anal sex
  • Sex practices that increase contact with blood
  • A partner with a history of injection drug use
  • Stimulant drug use
  • Sharing straws to snort drugs
  • Drug use -- especially methamphetamine -- along with sex

HCV cannot be transmitted by sweat, tears, or saliva. Ways to lower the risk of HCV transmission include:

  • Reducing or stopping drug use
  • Not sharing equipment to snort or inject drugs
  • Using condoms consistently and correctly
  • Having fewer sexual partners
  • Not combining sex and drugs
  • Avoiding sexual practices that increase of the chance of contact with blood

Some of these recommendations are vague. This is because there are not enough data to make specific statements about what behaviors carry the highest or lowest risk of HCV transmission. A few studies have found particular sexual acts to be associated with HCV transmission, but these findings remain controversial. For example, some studies looked specifically at "fisting" as a risk for HCV transmission. This is based on the idea that the act of fisting is more likely to result in contact with blood than anal sex because it can cause more trauma to tissues in the anus.

In real life, however, sex and drugs are complicated topics. It's difficult to calculate the exact risk for any one behavior when there are endless combinations of sex acts that can occur during a single encounter. The overlap between sex and drug use certainly complicates the equation. Likewise, those acts labeled as "dangerous" can be done in ways that reduce the likelihood of transmission. As with many other STIs, the overriding message is to avoid contact with bodily fluids that may carry pathogens. Condoms, medical-grade gloves, or dental dams are a good place to start if there is a chance of contact with the bodily fluids of another person.

How Do I Know If I Have It?

There are no obvious symptoms of HCV, but some people may experience chronic fatigue, jaundice (yellowing of skin), nausea, and joint pain. The majority of people with HCV will have no symptoms for many years and may go undiagnosed until the effects on liver function become more prominent. Luckily, HCV can be detected with a simple test.

A conventional HCV test requires a blood draw and, in most cases, a waiting period. However, OraSure received FDA approval for a rapid HCV test in 2010. The test requires only a finger stick to draw a drop of blood and twenty minutes for results. It is expected that the same device will be approved for testing with an oral swab in the future. As with other antibody tests, confirmatory viral load testing should be performed if the antibody test is positive, since some people can clear the virus without treatment. If a diagnosis of chronic infection is confirmed, a healthcare provider should also perform liver function tests.

Unfortunately, not many community providers have been able to add HCV testing to their services because many states do not yet have an oversight process for rapid HCV testing. Likewise, there is little funding for HCV testing or education, though this is changing. Many federal agencies have turned their attention to the issue and some pharmaceutical companies have committed to expanding existing testing efforts. The Department of Health and Human Services now encourages HCV testing and care to be added to existing Ryan White CARE Act initiatives. The CDC has also expanded its recommendations to state that all "Baby Boomers" (those born between 1945 and 1965) should receive at least one HCV test in their lifetime. Hopefully, these new guidelines will help to increase the detection of HCV infection and referrals to treatment.

What Are the Treatment Options?

pills and pill bottle

Unlike HIV, it's possible to cure HCV disease -- to completely eliminate the virus from the body. But the first HCV medications (alpha interferon and ribavirin) had cure rates well below 50% for people co-infected with HIV and HCV. Those who underwent the long and difficult treatment often had harsh side effects, so the next generation of HCV meds has been eagerly anticipated.

The first new drugs to receive FDA approval -- the protease inhibitors Incivek and Victrelis -- more than doubled the likelihood of curing HCV while shortening the treatment duration by half. These meds improved cure rates both for those who had never taken HCV treatment and for those who had experienced a prior treatment failure. Data released earlier this year showed that these drugs also improved cure rates in co-infected people, although the improvements were less than those seen in people with HCV only.

Unfortunately, treatment with these two new drugs proved to be more challenging than expected. First, clinical trials can't recreate the real-world situations of people with HCV. Studies select participants with few physical or psychosocial health issues, and provide much interaction with experts. In reality, these new drugs require very knowledgeable doctors, committed patients, and perfect adherence to even begin to replicate the successes seen in the clinical trials. In addition, the drugs must be taken with interferon, adding more side effects to this already difficult regimen. Dr Mark Nelson of London's Chelsea and Westminster Hospital told Aidsmap that the two new drugs were similar to the first-generation HIV protease inhibitors: "Incivek and Victrelis are relatively difficult to take and relatively toxic compared to the second generation. If you have minimal liver disease, probably the best option is to wait."

What's in the Pipeline?

The need for more HCV treatment options is clear, and new research offers great hope of increasing cure rates and reducing side effects. These experimental meds take a variety of approaches to clearing the body of HCV, including combinations of protease inhibitors and other classes of drugs such as polymerase inhibitors and NS5A inhibitors, often in interferon-free regimens.

"It has been widely reported that the combination of sofosbuvir and daclatasvir was very effective -- perhaps up to 100% effective for people with HCV genotype 1."

One of the most exciting interferon-free combinations is sofosbuvir (GS-7977) and daclatasvir, two drugs originally researched by Pharmasset and Bristol-Myers Squibb. Although the final data from the phase II trials have not been released, it has been widely reported that the combination was very effective -- perhaps up to 100% effective for people with HCV genotype 1 (see "My Fight for a Hepatitis C Cure" in this issue), with few side effects. Unfortunately, such revolutionary advances in treatment and the opportunity for new blockbuster HCV medications have made some drug companies wary of collaborations, slowing even bigger developments in treatment. Perhaps most notoriously, Gilead Sciences purchased sofosbuvir from Pharmasset and announced that it will not work with Bristol-Myers Squibb to further test it in combination with daclatasvir. They will instead test it with their own drugs, most likely delaying FDA approval of an interferon-free HCV regimen for at least two years.

Other combinations have also shown good results. In 2010, a Roche study of two new drugs, danoprevir and mericitabine, showed that this interferon-free combination could suppress HCV in people who did not have HIV. Viral loads fell 100,000-fold in just 13 days in one trial.

Last year, Boehringer Ingelheim studied two of its drugs without interferon -- the protease inhibitor BI 201335 and the polymerase inhibitor BI 207127 -- in people without HIV. After 16 weeks of treatment, 60% of people in the trial had an SVR (sustained viral response, meaning an undetectable HCV viral load) 12 weeks after treatment ended, which is now regarded as an indication of a cure.

A trial of the protease inhibitor asunaprevir and daclatasvir found that 90% of people who had HCV genotype 1 had an SVR after 12 weeks of treatment, in spite of failing earlier treatment with interferon.

The ASPIRE trial of the protease inhibitor simeprevir (taken with interferon) reported cure rates of over 80% in people without HIV -- both in those new to treatment and those who had failed earlier treatment.

Unfortunately, there has yet to be a single trial of an interferon-free regimen in people co-infected with both HCV and HIV. Researchers are concerned about how effective the new drugs will be without interferon in people who are immune suppressed. They also don't know how people with other complications will respond to the new meds.

Several more drugs will likely be approved for use with interferon over the next few years. The first interferon-free combinations may not hit the market for three to five years, and their approval for co-infected people will take even longer. Of course, knowledge gained from mono-infection trials and pressure from advocates could hasten that process, and any drugs approved for people with only HCV can also be prescribed for people with both HIV and HCV (although insurance reimbursement may be a problem). For comprehensive information on HCV drugs in the pipeline, click on "Hepatitis C" at natap.org, read the TAG report at pipelinereport.org, or check out "Experimental HCV Drugs" at hivandhepatitis.com.

As more experimental drugs are developed, the biggest obstacle to affordable, safe, and convenient treatments could be the lack of collaboration in the industry. Similarly, any new HCV drugs that are approved will be in high demand, meaning a high price tag.

What If I Have Both HIV and HCV?

medical professional and patient

Despite the development of new meds, treating HIV/HCV coinfection is still very difficult. There are many concerns about how new HCV meds might affect a person's ability to manage HIV infection. The specifics of any treatment regimen will vary depending on the types of HCV and HIV, a person's overall health, treatment history, liver function, and response to different medications. As additional treatments are developed, there is great hope that such complications will become less of an issue.


The next landmark in HCV treatment will be a regimen that is interferon-free, easy to take, and tolerable both for people with HIV and for those who have advanced liver disease. While the current evidence is promising that such a treatment will eventually become available, the reality is that it will take years to reach the market. In the meantime, it is crucial that efforts are made to raise awareness about sexually transmitted HCV and to encourage those at risk to get tested in order to slow its spread. HCV is a serious but preventable condition, and increasing the amount of knowledge on the topic is the first step to empowering people to reduce the risk of its transmission.

Aaron Arnold is the Data Manager of the M2M Project at Pittsburgh AIDS Task Force. Mark Milano is the editor of Achieve_._