Does Your Liver Quiver?
Hepatitis C and HIV
Hepatitis C (HCV), a chronic viral illness, has a lot in common with HIV. And if you're coinfected, or chronically infected, with both HIV and HCV, there are important interactions you need to know about.
Both HIV and HCV produce astronomical amounts of virus each day. HIV produces billions of virons (virus particles) every day. HCV produces more, possibly a million times the billions that HIV produces. This is why needle sticks and other blood exposures are more likely to transmit HCV than HIV. There are just more of those critters running around.
Antibody tests are certainly helpful in screening for both infections. But these tests can give a negative reading during the acute phase of HIV or HCV, as well as at other times, particularly when one is coinfected. So if you test negative for either or both, test again every six months. Quantitative viral load tests, called PCRS, are the only certain way to be sure of accurate diagnosis for both HIV and HCV.
Nearly all infections are chronic in both diseases, over 85% in HCV and over 99% in HIV. Chronic infection means that your body is not able to rid itself of the virus and is continually trying to fight it. It also means that you can pass on the infection to someone else through a transmission route; predominantly blood-to-blood contact with HCV. Sexual transmission is documented with HCV, but this is not the major transmission route. Clearly, though, safer sex guidelines should be followed as with HIV.
With both infections, the higher the viral load the faster the disease is likely to progress if it is not treated. When someone is co-infected with both HIV and HCV, HCV viral loads, before any treatment, tend to be higher than in people who are infected only with HCV.
Some doctors believe that liver damage can progress as much as 10 times faster in people co-infected as in people with HCV alone.
When treatment is indicated for HIV or HCV, the goal is to reduce the viral load as much as possible and as quickly as possible to halt or at least slow disease progression. HCV treatment is moving in the direction of combination therapies, some to boost the immune response (e.g., interferons), and others that are actually anti-viral in action. Combinations seem to be more effective than using any single agent. Just as in HIV, we will be seeing in the next few years protease inhibitors and other inhibitors that will interfere with the life cycle of the HCV virus. These will most likely be used in combination with interferons or the currently available interferon + ribavirin combination.
Treatment for HCV usually starts with low doses of interferon injected 3 times a week for one to two years. This has proven to be effective for only 15% of patients, however. If the viral load is not below the level of detection and the liver enzymes (shown on blood tests) are not near normal levels within the first 3 months of treatment, it most likely will not succeed.
Most people will stop treatment at this point. Recently a combination of low dose interferon with oral ribavirin has shown better results; possibly up to 45% of patients treated have seemed to benefit. This treatment has been approved for 6 months of usage, but may soon be expanded to at least a year to increase the number of people whose viral loads are suppressed. It has been approved for people who relapse after trying low dose interferon alone, as well as for first use treatment. Some studies show that just using higher doses of consensus interferon alone (an interferon that is bio-engineered to match more closely naturally occurring interferons in the body) may get at least a 56% effectiveness rate after relapse.
In HIV we know that using prescribed levels of medication and sticking to regular dosing schedules is more effective over time in keeping viral loads maximally suppressed. It is also important to suppress viral load as rapidly as possible to prevent drug-resistant strains of the virus from evolving. Research shows that this is true for HCV as well. But most physicians are still suggesting low dose interferon 3 times a week. This is ineffective for the vast majority of people.
Since interferon clears from the body rapidly, this intermittent dosing often allows the virus to reproduce between interferon doses. Clearly, more interferon (higher dosing) is better; longer therapy is better; combination therapy with ribavirin is better; daily dosing is better; high dose induction (starting with a high dose for several weeks and then cutting back) is better; and, perhaps, pegalated interferon, which is in development and stays in your system longer, is better. Sadly, all of these methods lead to more side effects such as cytopenias (blood cell component problems, including anemia in the case of using ribavirin). Many of these side effects can be treated.
Reducing side effects can help you to feel better and stick with the treatment. However, this is where most gastroenterologists (stomach and bowel specialists) and hepatologists (liver specialists) still seem to be timid. They tend to reduce the dosing of the HCV medication (most likely reducing the effectiveness of treatment) instead of treating the blood toxicity problems that HIV treating physicians are more familiar with and know how to handle. State-of-the-art research suggests that we insist that our HCV-treating physicians try to treat these problems before reducing the dosage of therapy that may lead, in turn, to a reduced chance of HCV viral suppression.
Another side effect of all of these treatments can be depression, sometimes severe enough to have suicidal thoughts. Often this can be prevented or reversed by using antidepressant medication. Some people start an antidepressant two weeks before starting any HCV treatment to reduce the possibility of depression.
Choosing to go on treatment is a difficult and very individual decision. And, yes, there is evidence that interferon treatment of any level will help slow liver disease progression even if it does not fully suppress viral replication. But if you choose to go through HCV therapy, why not give it the best chance for success including possible eradication of the virus? Insist that your doctor do whatever it takes to get the most drug possible into you for the longest period of time appropriate. And if he or she is not familiar with drugs that treat hemotoxicities then tell them it's time to become familiar with them.
Now to some special problems specifically for those folks infected with HIV and HCV. Highly active HIV anti-viral treatment regimens usually include use of a protease inhibitor (PI). Strong protease inhibitors have significantly increased survival in many folks with HIV. All Pls undergo extensive hepatic metabolism, meaning that they're processed through the liver. The possibility of liver complications exist for all four of the currently available Pls. In general Crixivan (indinavir) and Norvir (ritonavir) are more hepatatoxic than Invirase/Fortovase (saquinavir) or Viracept (nelfinavir). Many coinfected individuals seem to handle their protease inhibitor just fine. Some folks get initial liver complications and then settle back down after some time and are able to remain on their protease inhibitor therapy. Other folks get an "activation" of their HCV with increasing viral loads and elevations of liver enzymes that do not settle down and cannot be tolerated.
If you are successfully using one or more Pls with minimal effect on your liver, there is no reason to change. But if you are having a problem, you may want to talk to your doctor about switching to a less hepatotoxic protease inhibitor, or to a combination therapy that does not use a protease inhibitor. Keep in mind that the non-nucleosides, Rescriptor (delavirdine), Viramune (nevirapine), and Sustiva (efavirenz) can also be hepatotoxic. Some people are successfully using three nucleosides from the list of: Retrovir (AZT), Zerit (d4T), Epivir (3TC), Videx (ddl), Hivid (ddC) and Ziagen (abacavir). Some drug companies would love you to believe that using an HIV regimen without a protease inhibitor is just as potent and durable as one with a PI. Evidence of long term durability of non-protease regimens is not yet available. But you may want to stick with the most potent regimen you are able to tolerate.
Another special problem for co-infected people is the use of ribavirin in the treatment of their HCV. Ribavirin can interfere with the action of some of those HIV nucleoside analogues listed above, particularly AZT. The levels of these drugs in your blood may decrease, leading to the chance that you could develop viral resistance. The one exception so far is in the use of Videx (ddl) which seems to be increased by ribavirin. Studies are going on now to see if combination therapy for HCV interferon + ribavirin can successfully be done with the nucleoside-containing HIV regimens. Early indications show that it can be done. If you choose to use ribavirin, make sure your doctor carefully monitors your bloodwork to check that you are not getting an increase in your HIV viral load.
Some last minute free advice (maybe that's all it's worth ?!): HCV and HIV treatments are obviously complicated for patients as well as doctors. We will probably have new information every few months. Sometimes the patients know more than the doctors, but don't bet on that all the time. Be actively involved in your own care. Use all the resources available to you; books, the internet, friends, and support groups. But do remember that your doctor is your consultant. Write your questions down before you go to see your doctor. If you do not understand something, insist that your doctor explain it to you so that you are making informed choices. If you have questions after your visit write them down and call your doctor's office to ask that he or she get back to you with answers. Sometimes, in difficult issues such as co-infection, nobody has a clear answer yet. I do not expect my doctors to know everything. I trust a doctor who honestly tells me that he doesn't know something and will either find out for me or lead me to a resource where I can get an answer, as opposed to a doctor who pretends to know. Most HIV doctors learned these lessons long ago from their patients. It's time that our gastroenterologists and hepatologists learn how to work with us too. Insist on it.
Back to the Notes from the Underground Spring 1999 Contents Page.
This article was provided by PWA Health Group. It is a part of the publication Notes From the Underground.