HCV and HIV: Different Viruses, Striking Similarities

Hepatitis C virus and HIV share many of the same characteristics. The research community for HCV is already quite familiar with the patterns set by HIV; however, for other clinicians who treat HCV, the parallels may not be as apparent.

 

Both HCV and HIV are RNA viruses that are about 9 kilobase (kb) long. HCV is a flavivirus and HIV is a retrovirus. Both viruses are transmitted through blood products and through sexual activity. HCV and HIV replicate at extraordinarily high levels, about 10 billion per day for HIV and about 100 billion per day for HCV. This high rate of replication is likely related to a remarkable replication pathway that leads to errors, or mutations, in the genome as they replicate.

In addition, HCV and HIV are marked by an immune response to suppress viral replication that selects for viruses that escape. HCV and HIV can become the predominant virus in plasma because of a selective growth advantage directly related to the ability to escape.

When a person becomes infected with HCV or HIV, the immune system responds, but the viruses mutate so fast that a sort of cat-and-mouse game ensues. The virus is always one step ahead of the immune system. This has impacted the way that treatments for both HCV and HIV have developed and also why vaccines are difficult to develop.

Revolutions in Therapeutics

In 1987, azidothymidine (AZT) emerged as a major therapeutic agent for HIV. Several other analogs followed: nucleoside and nucleotide reverse transcriptase inhibitors, followed by non-nucleotide reverse transcriptase inhibitors. After that came the protease inhibitors, which interfere with the mutation of virus. Then, the integrase inhibitors appeared.

The real revolution in HIV drug development occurred between 1993 and 2005.

Treatment for HCV has followed a similar pattern with the exception of NS5A inhibitors, which are not applicable to HIV, and with the exception of integrase inhibitors, which are not applicable to HCV. Moreover, the changes in HCV therapy are happening a lot faster than that of HIV.The HCV therapy revolution will be like the revolution we experienced with HIV, except on fast forward. The main reason for this is that we learned many lessons during the history of HIV, and we are now directly applying this knowledge to the treatment of HCV. This has resulted in dramatically accelerated drug development for HCV. That said, it helps that the drugs available for HCV are curing patients in the 98% effectiveness range. It should be of no surprise that many members of the research community who worked with HIV are now working with HCV.

A key lesson we took from the HIV experience is how to develop a test for viral load. In HIV, it was difficult and time consuming to come up with the test to quantitate the amount of HIV in plasma, but the development was much faster in HCV. This allows us to determine who is chronically infected with HCV and who is a candidate for curative therapy.

Demographics and Epidemiology

Early in the days of the HIV epidemic, the majority of people with the disease were unaware of their status. The same is true today for many people with HCV. In my opinion, this is why universal testing of HCV is needed. With HIV, we focused on special populations such as men who have sex with men. In HCV, we are looking at individuals in the baby boomer birth cohort (born 1945 to 1965). Most of the people who do not know their HCV status are in this group.

It is also important to consider linkage to care. It was difficult for patients with HIV to get treatment in the early days of the epidemic.In 2010, the White House announced a national HCV strategy, but there are still access issues largely because of barriers to access to care. Once again, we should follow the precedent set by HIV and reduce barriers to care for patients with HCV.

After linking patients to care, we need to keep them there. It may be helpful to look to retention in care models set by HIV. The term cascade should be applied to HCV as it has been for HIV.

Key Differences 

Similarities aside, there are also distinct differences between HCV and HIV, including transmission, progression, treatment and how long the viruses live outside of the body.

The fundamental difference between HCV and HIV is that once HIV enters the cell, it integrates into the host genome and becomes part of the host DNA. HIV gains entry into the host nucleus. That integration is why it is almost impossible to cure HIV. In HCV, there isn't the DNA intermediary in the viral genome. The virus does not integrate into the host DNA, which is why it can be eradicated into the cytoplasm and the patient is cured of infection.

Impact on the Clinical Community

The concepts of treating HCV are comparable to those for treating HIV. Adherence is of the utmost importance because the virus is so rapidly replicating. But when the virus is treated, the viral load plummets almost immediately. Clinicians must understand, and help make patients understand, that the viral load can go from a million copies to nearly undetectable within a week or two.

Further, the clinical community should understand that resistance can develop quickly. Both HCV and HIV have a strong tendency to develop escape mutations.

The drug-drug interactions of HCV and HIV are also similar. For example, ritonavir boosts protease inhibitors for the treatment of both HCV and HIV. In addition, some of the drugs developed for HCV are metabolized by the same enzyme systems. A specialist who has treated HIV may know this information, but may not be as apparent to someone who may be treating HCV for the first time. The good news is that the new HCV therapies are easy to administer compared with lifetime therapeutic monitoring as is required for HIV. A short course of direct-acting antiviral therapy usually results in cure and the complications are relatively minor, assuming the patient does not have decompensated cirrhosis.

An important final point is that, like with HIV, there are so many people worldwide infected with HCV that there are not enough specialists available to treat everyone. Involvement from specialists in other areas, such as internal medicine and family medicine, to treat this disease may have the most impact in the future.

For more information:

Michael S. Saag, MD, is professor of medicine, Jim Straley Chair in AIDS Research and director of the Center for AIDS Research at the University of Alabama at Birmingham. He is also a co-Chief Medical Editor of HCV Next. Saag can be reached at HCV Next, 6900 Grove Road, Thorofare, NJ 08086; email: hcv@healio.com.
Disclosure: Saag reports serving as a principal investigator for several clinical trials sponsored by Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, Janssen Therapeutics, Merck and ViiV, where all funding went to his institution and he received no salary support.