THE NEW EPIDEMIC HIV/HCV CO-INFECTION
Infection with Hepatitis C virus (HCV) is reaching epidemic proportions in the United States. Approximately one million Americans are infected with HIV, but nearly four times that number have chronic HCV; worldwide, 40 million are infected with HIV, but 200 million are infected with HCV.1 What is the true rate of HCV infection among people with HIV? A recent study at the University of Cincinnati College of Medicine analyzed two trials sponsored by the ACTG (Adult AIDS Clinical Trials Group) using the quantitative PCR test from Roche Diagnostics to detect HCV RNA.
The study found a strong relationship between HCV infection and age in people with HIV. Patients in their forties were at very high risk; more than 50% of this group tested positive for the virus. HCV infection was also associated with both the immune status and viral load of HIV- positive people. All of those whose CD4 cell count was less than 100 cells per microliter were coinfected with HCV, compared with approximately one-fourth of those with CD4 cell counts exceeding 500 cells per microliter. This study suggests that over a third of HIV-positive patients in the U.S. are probably co-infected with HCV. Kenneth Sherman, MD, the investigator, suggests that these and similar findings are a warning sign. They highlight the need for a new policy of broad-based screening for HCV in HIV-positive patients
HIV-treating physicians must become more aware of the high prevalence of HCV in HIV patients. To achieve this goal, more accurate tests for HCV also need to be developed and made available to all primary care physicians as well as HIV-treating physicians.
Getting out the word
Why are the numbers for HCV infection so high? Many recent studies indicate that part of the problem is the poor response of HIV-treating physicians and others in the medical community to the threat of hepatitis C.
Because screening for HCV is inadequate, few cases receive early or appropriate treatment. However, institutions are beginning to respond to the dramatic increase in rates of coinfection in the U.S. For example, the Consensus Statement of the National Institutes of Health (NIH) has become:
In terms of public opinion, the HCV epidemic is in several respects affected by the same problems that hampered HIV diagnosis and treatment in the 1980s, when HIV became stereotyped as a disease of male homosexuals. It took several years before physicians routinely tested for HIV in heterosexuals, women, and other populations. The same thing is happening now with HCV; the stereotype of the intravenous drug user prevents many health professionals from screening rigorously for HCV across other groups.
For several reasons, it makes more sense to use an epidemiology model like that of HIV when viewing the current community health problem posed by HCV than to look at HCV as simply another hepatitis infection.
HCV Compared with HBV
Particular features of HCV pathogenesis also contribute to the size of today’s epidemic. Several facts about the hepatitis C virus itself, and its patterns of replication, help to explain why an epidemic of chronically infected people might have been better predicted and planned for-if more attention had been focused on the problem.
HCV poses a more difficult community health problem than does hepatitis B virus (HBV). While approximately 85% of people with HBV resolve their infection, and only 15% become chronically infected, the facts are just the opposite with HCV: roughly 85% of people with HCV become chronically infected; only 15% are able to clear the infection.1
The immune system has difficulty resolving an HCV infection for several reasons. One factor that makes it difficult for the immune system to easily recognize HCV is the array of HCV genotypic variants. At least six “clades” consisting of 11 genotypes have been identified.1
In the U.S., unfortunately, the vast majority of cases of HCV are of genotype 1, which is the most difficult for the immune system to clear and the most difficult to treat. While microbiologists have identified several other genotypes of HCV, these are generally grouped together as genotype non-1 (see the accompanying sidebar “Coinfection Treatment Issues: Genotyping HCV.”).
HCV and HIV-similarities and differences
Both HCV and HIV are single-stranded RNA viruses that produce vast numbers of variants when they multiply-and both viruses replicate at alarmingly high rates. This means the viral target is always changing.
The many variants of HCV and HIV create extraordinary challenges in the development of therapeutic agents for treatment and effective vaccinations for prevention. HCV is not a retrovirus like HIV, but a flavivirus. This difference spells good news-it means that the virus does not become integrated with the host’s genome, and this in turn means that HCV can be eradicated with ideal treatment.1,3 There can be long periods in both diseases without symptoms, but individuals infected with HCV are typically without symptoms for 20 years or more. A great deal of damage to the liver can occur before blood tests even detect liver toxicities. While HCV does not destroy the immune system as HIV does, chronic infection leads to liver toxicity and finally to end-stage liver disease.
HIV viral loads may be relatively stable over time, but HCV viral loads vary. HCV viral loads are not predictive of long-term disease outcome, nor do they correlate with the degree of hepatitis. HCV viral loads do correlate with response to therapy, which in turn is related to long-term liver disease outcome.4
Progression to liver damage
Liver disease develops slowly over a period of 20 to 30 years or more, although progression can occur in 5 to 10 years among “rapid progressors” with HCV. The percentage of people with hepatocellular carcinoma, or liver cancer, is about 3%, and the annual rate of cirrhosis is 5% to 10%.
Once end-stage liver disease occurs, there is little that can be done to reverse the damage or restore the liver.
In fact, liver disease caused by chronic HCV infection is the number one cause of liver transplantation in the United States. Approximately 35% of liver transplants in this country are for end-stage liver disease caused by untreated HCV.4
Transmission
The hepatitis C virus “reaches saturation” in intravenous drug users, as David Patrick, MD described it during a presentation at the 12th World AIDS Conference.6
Although injection is the chief route of transmission for HCV, body piercing and tattooing have also become major risk factors. Since the skin is broken in both piercing and tattooing, infected blood products can be transmitted through needles and other implements. The virus can easily be spread this way.
Users of heroin and other drugs who do not inject but who snort drugs should be advised that intranasal transmission of HCV is possible and that sharing straws and other implements should be avoided.
It is generally assumed that HCV is not spread sexually. However, there is now evidence that this conventional thinking may be wrong: HCV may be transmitted sexually among people with more than one partner, and among people who have STDs or who practice anal intercourse.1 It is now recommended that partners of people with HCV be screened. It is also prudent for people to avoid sharing razor blades and toothbrushes, as an extra precaution against possible exposure due to breaking the skin.7-9