A 36-year-old bisexual male with B3 HIV disease is expected to be incarcerated for nine months. On intake, the CD4 lymphocyte cell count is 542 cells/mm (31%), up from a nadir of 240 (17%), with an HIV bDNA < 50 copies/ml. He is currently on d4T 40 mg bid, 3TC 150 mg bid, and nelfinavir 1,250 mg bid and has never had any opportunistic infections. He denies any injection drug use (IDU), but does report a remote history of brief intranasal cocaine use. He is found on screening laboratory testing to have mildly elevated liver enzymes (AST 76 and ALT 91) with normal LDH, bilirubin, albumin, prothrombin time, hematocrit, and platelet count. He reports symptoms of depression (difficulty sleeping, decreased appetite, and anhedonia) and appears depressed. The examination is otherwise normal; in particular there is no evidence of spider angioma or palmar erythema. The provider screens the patient for hepatitis; an enzyme immunoassay (EIA) shows that the patient tests positive for hepatitis C virus (HCV) antibody and hepatitis B (HBV) core and surface antibody, but negative for hepatitis A (HAV) antibody.
What would you do for this patient? Should HAART be stopped?
It is difficult to determine the cause of liver toxicity in HIV/HCV co-infected patients on HAART. Ritonavir may be the most common cause of antiretroviral-related hepatoxicity, but all antiretrovirals can damage the liver. Regardless of the etiology, HAART should be continued in this patient given the mild transaminitis and no evidence of synthetic dysfunction. Given the high rate of HBV and HCV co-infection in HIV-infected patients, and particularly among incarcerated persons, it is incumbent upon the provider to rule out an infectious etiology as was done with this patient. It is controversial whether RIBA confirmation is necessary with positive EIAs in high-risk patients, given that new-generation EIAs have high positive predictive value in high-risk patients such as this one.
What if this patient had screened EIA negative?
A recent study published in JAIDS1 reported that between 6% and 19% (depending on the HCV RNA method used) of HIV-infected HCV antibody-negative patients had HCV viremia. HCV viremia in persons without HCV antibodies was associated with HIV acquisition through sexual contact as opposed to parenteral risk factors and lower CD4 lymphocyte count. Most experts recommend follow-up HCV RNA in all HIV-infected patients who screen HCV antibody negative, but are still suspected of harboring HCV infection.
Another reason to do a follow-up HCV RNA is that up to 10% of patients infected with HCV actually clear the virus (HCV antibody positive and RNA negative) although the rate appears lower in HIV/HCV co-infected patients.
I would suggest checking the liver enzymes in one month and, if stable, checking every two to three months thereafter. Also continue to monitor his T-cell subsets, HIV RNA, kidney function, glucose and electrolytes every three months if they all remain stable. I would advise periodically monitoring a fasting lipid panel.
An important early step is to obtain HAV and HBV serologies, as was done in this case. HCV-infected persons are at higher risk of going on to fulminant hepatic failure if they contract HAV or HBV than are people who do not have HCV infection. Therefore, those who have not had prior infection should be vaccinated.
Why not just vaccinate against both hepatitis A and B and save the cost of the serologies?
That strategy would be fine for HAV, but not for HBV. HAV has no chronic carrier state, but providers must rule out chronic active hepatitis B (hepatitis B surface antigen positive). Given that this patient was negative for HAV antibodies, he was then vaccinated against HAV.
Should hepatitis C treatments be discussed next?
This patient has several other issues that need to prioritized and dealt with prior to even discussing treatment for HCV. He should be educated regarding HCV infection transmission, just as one would with someone who initially tests positive for HIV infection.
Contaminated needles associated with IDU account for the majority of HCV infections in the developed world. Since 1992, at least two-thirds of new cases of HCV infection in the United States can be attributed to IDU. Although HCV was originally presumed to not be readily transmitted by sexual contact, there is mounting evidence that HCV is transmitted via sexual contact and HCV RNA has been detected in semen, vaginal secretions, and saliva, though whether the virus is replication-competent in these sites is not known. Sharing of razors and toothbrushes should be strongly discouraged given their potential for being contaminated with blood.
The next step would be to discuss the natural history of HCV with the patient, including that he is likely to have some liver damage, the extent of which is unknown. Although most people do not go on to end-stage liver disease with cirrhosis, this patient should be warned of the hazards of alcohol abuse and HCV.
The provider should explain that HIV accelerates the progression of HCV, and that cirrhosis and mortality rates are higher in co-infected patients than they are with HCV alone.
The provider can then discuss available treatments. Co-infected patients, especially with high CD4 T-cell counts, have been shown to have similar treatment response rates compared to people with HCV only. This individual's short incarceration period does not make him a good candidate to initiate the current optimal treatment -- pegylated interferon and ribavirin for 6-12 months dependent upon HCV genotype. I would advise discussing the options available to him and would attempt to help him enter into the health care system in the community prior to his release.
This patient's co-morbid mental illness should be addressed. Incarcerated men and women have much higher rates of depression and other mental illnesses than the general population. Untreated depression is clearly correlated with poor adherence to antiretrovirals and is a relative contraindication to interferon therapy for HCV.
Case presented and discussed by Stephen Tabet, M.D., M.P.H., Assistant Professor of Medicine, University of Washington, and Director, Northwest Correctional Medicine Education Program.
A collaboration with the Northwest AIDS Education and Training Center, with Stephen Tabet, M.D., and Kate Willner.
- Journal of Acquired Immune Deficiency Syndrome. 2002 Oct 1;31(2):154-62.
Back to the HEPP Report April 2003 contents page.