From the Office of AIDS Research, National Institutes of Health, DHHS, Bethesda, MD, USA.
Correspondence to Victoria A. Cargill, MD, MSCE, Director of Minority Research and Clinical Studies, Office of AIDS Research, National Institutes of Health, DHHS, Bethesda, MD, USA.
* Some details of the case have been altered to protect the patient's privacy.
Twenty years ago in the HIV epidemic, the ravages of immunodeficiency were well known: opportunistic infections, cancers, encephalopathies and wasting. Since the advent of highly active antiretroviral therapy, people with HIV infection are living longer and overall experience an improved quality of life. With the waning impact of opportunistic infections, other diseases have come to the fore as a major cause of morbidity and mortality in this population. Hepatitis C virus (HCV) infection and its associated complications are now a significant source of morbidity and mortality in the HIV epidemic.
The numbers alone are stunning. HCV co-infection can range from 15 to 30% of HIV-infected patients; however, among certain high-risk groups, such as injection drug users, this percentage can triple [1,2]. HCV infection without concomitant HIV infection poses management challenges, but superimposed upon HIV infection, it presents a double whammy. Important medications used in the management of HIV induced immunodeficiency are primarily metabolized through the liver, the very organ that is the target of HCV infection; an organ often compromised by ongoing inflammatory change and ultimate destruction. This picture is further complicated by the differential response rates of those co-infected with HIV, compared with those who are not.
Response to therapy in the setting of HIV is markedly diminished, and the odds decrease further once race and genotype are taken into consideration . HIV infection disproportionately affects racial and ethnic minorities, and HCV infection also disproportionately impacts them. The chances of achieving a sustained virological response to treatment for HCV infection, in the setting of HIV infection, is decreased further when the genotype is genotype 1, and the race is African American . The reason for this differential response remains unclear; however, it does not appear to be explained by either treatment adherence or viral genotype.
The real burden of this co-infection must be translated into the human cost. Take as an example the case of C.J.*, an African-American woman co-infected with HIV and HCV. Her past history is significant for the use of alcohol and marijuana, which began in 1980 at the age of 20 years. She began to add cocaine to stay awake at an extra part-time job, which she needed to help support a sibling she cared for after the death of her mother. In 1995 she was arrested for drug possession, and she opted for detoxification instead of incarceration. During an admission work-up she tested positive for HIV infection, as well as HCV infection. Routine laboratory work did not indicate the need for antiretroviral therapy at the time. She opted for detoxification but declined any other treatment.
After dropping out of care approximately 6 months after release from the detoxification program, C.J. returned to a local clinic. Her testing at that time indicated a decline in her CD4 cell count to 250 cells/μl, an HIV viral load of 100 000 copies/ml and liver function tests that were 2.5 times the upper limits of normal. She agreed to the initiation of antiretroviral therapy, but expressed ambivalence about an evaluation of her hepatitis. She finally agreed to a liver biopsy.
The results of the liver biopsy confirmed the presence of significant inflammation and fibrosis. Despite that, C.J. initially declined HCV treatment after discussion of the side-effects, the chances of a sustained virological response with genotype 1 infection, HIV co-infection and African-American race. However, after 2 years of increasing fatigue and worsening liver function tests C.J. finally consented to hepatitis C therapy. Her treatment was complicated by the hematological side-effects, made only more difficult to manage by the challenges of covering the cost of supportive therapy. Despite support, C.J. ultimately made the decision to discontinue treatment after 10 weeks. She refused a second round of interferon and ribavirin, as a result of her experience with hematological and psychiatric side-effects.
One year ago, C.J. developed abdominal bloating, which progressed to abdominal bloating and pain. A detailed work-up revealed a 5 cm liver mass, and pathology was consistent with a hepatocellular carcinoma. Therapy was instituted, but C.J. died 8 months after the diagnosis, survived by two children under the age of 14 years.
This supplement contains papers that will address virtually every aspect of HIV/HCV co-infection that C.J. illustrates. How does one manage HIV/HCV co-infection in vulnerable populations that are already marginalized and clearly have difficulties accessing care and treatment? What is the impact of HCV upon neurological and neuropsychiatric processing, and how much of this impacted C.J.'s response to treatment and her desire to undergo a second round of therapy? This case demonstrates that HIV/HCV co-infection presents a formidable challenge in many ways: transmission, and its facilitation through behaviors such as illicit drug use; treatment, and the variability in treatment response based upon genotype and race; treatment side-effects, their management and the cost of managing those side-effects; and the extrahepatic manifestations of HIV/HCV co-infection, including the neuropsychological.
Ultimately, however, it comes back to the individual. The gains realized in the first two decades of the HIV epidemic have now brought us face to face with a good news–bad news story. The good news is that our patients are living longer and their quality of life is better; the bad news is that chronic hepatitis C infection has emerged as a major cause of morbidity and mortality, with cirrhosis, end-stage liver disease and death. As the HIV epidemic continues to impact a number of vulnerable communities, our treatment of the underlying HIV infection will be challenged by the concomitant HCV infection that may ultimately limit the impact of our therapies upon immune restoration, quality of life and in some cases quantity of life. Better interventions designed to prevent these co-infections are needed, as are therapies with greater effectiveness across genotypes and races. Many more C.J.s, their families, friends and caregivers are waiting for us to provide them with answers and to bring them hope.
1. Sherman KE, Rouster SD, Chung RT, Rajicic N. Hepatitis C prevalence among patients infected with human immunodeficiency virus: a cross-sectional analysis of the U.S. Adult AIDS Clinical Trials Group. Clin Infect Dis 2002; 34:831–837.
2. Sulkowski MS, Thomas DL. Perspectives on HIV/HCV infection and illicit drug use. AIDS 2005; 19(Suppl. 3):S8–S12.
3. Muir AJ, Bornstein JD, Killenberg PG. Peginterferon alfa-2b and ribavirin for the treatment of chronic hepatitis C in blacks and non-Hispanic whites. N Engl J Med 2004; 350:2265–2271.
4. Chung RT, Andersen J, Volberding P, Robbins GK, Liu T, Sherman KE, et al. Peginterferon alfa-2a plus ribavirin versus interferon alfa-2a plus ribavirin for chronic hepatitis C in HIV-coinfected persons. N Engl J Med 2004; 351:451–459.
© 2005 Lippincott Williams & Wilkins, Inc.