SUMMARY: HIV positive people coinfected with hepatitis B virus (HBV) or hepatitis C virus (HCV) in Tanzania experienced slower immunological recovery and significantly more liver toxicity after starting antiretroviral therapy (ART), but they nevertheless had a similar risk of death, researchers reported at the 17th Conference on Retroviruses & Opportunistic Infections (CROI 2010) last month in San Francisco.

By Liz Highleyman

Past research indicates that HIV/HBV and HIV/HCV coinfected individuals, especially those with low CD4 cell counts typically experience more rapid liver disease progression than those with viral hepatitis alone. Studies of the effects of HBV and HCV on HIV disease progression have produced mixed data. Few such studies, however, have been carried out in resource-limited settings where patients start ART later on average.

A U.S./Tanzania research collaboration conducted a prospective observational study looking at the impact of coinfection on response.

As background, they noted that the prevalence of HIV/HBV coinfection ranges from 4.4% to 20.4%, and that of HIV/HCV coinfection from 3.3% to 5.0%, in sub-Saharan Africa.
This analysis included nearly 5000 adult HIV positive patients enrolled at 18 MDH PEPFAR HIV Care and Treatment clinics (Harvard's HIV/AIDS program in Tanzania) between November 2004 and June 2008 who were starting first-line ART containing a NNRTI and had been tested for hepatitis B surface antigen and HCV antibodies. A majority (67%) were women.

The NNRTI nevirapine (Viramune), which is commonly used in developing countries, has been associated with liver toxicity (hepatotoxicity) in people with higher CD4 counts; this is less often the case with efavirenz (Sustiva), the most widely used NNRTI in higher-income countries.

In this study, hepatotoxicity was defined as an ALT level between 3 and 5 times the upper limit of normal (ULN) (> 40 units/L). The median follow-up time on ART was 14 months (range 1-54).

Results

	Among 4,935 patients, the prevalence of HIV/HBV coinfection was 6.5% (315 out of 4836).
	The prevalence of HIV/HCV coinfection in this group was lower, at 1.4% (60 out of 4380).
	2 patients triply infected with HIV/HBV/HCV were excluded from further analysis.
	Median baseline ALT was significantly higher among HIV/HBV coinfected patients compared to those with HIV alone (27 vs 21 units/L).
	Median baseline CD4 cell count, in contrast, was significantly lower among the HIV/HBV coinfected participants (93 vs 123 cells/mm3).
	The HIV/HBV coinfected group also showed a trend towards more advanced WHO stage HIV disease, but this did not reach statistical significance.
	CD4 cell recovery over time was significantly slower among HIV/HBV and HIV/HCV coinfected patients compared to those with only HIV.
	The risk of hepatotoxicity was significantly higher among HIV/HBV and HIV/HCV coinfected patients compared to those with HIV alone.
	Mortality, however, was similar when comparing coinfected participants and those with HIV alone:
	HIV/HBV vs HIV only: 11.11% vs 7.98%, hazard ratio (HR) 1.28; HIV/HCV vs HIV only: 6.66% vs 6.73%; HR 1.07.

Based on these findings, the researchers concluded, "A slower rate of immunologic recovery and higher risk of hepatotoxicity among this urban Tanzanian cohort of HIV/HBV+ and HIV/HCV+ patients did not seem increase risk of mortality."

They added that the impact of coinfection on HIV virological outcomes needs to be explored further.

MDH HIV/AIDS Care and Treatment Program, Dar es Salaam, Tanzania; Harvard Sch of Public Health, Boston, MA; Northwestern Univ, Chicago, IL; Muhimbili Univ of Health and Allied Sci, Dar es Salaam, Tanzania.

3/5/10

Reference
B Christian, J Okuma, Claudia Hawkins, and others. Prevalence of Hepatitis B and C Co-infection and Response to Antiretroviral Therapy among HIV-infected Patients in an Urban Setting in Tanzania. 17th Conference on Retroviruses & Opportunistic Infections (CROI 2010). San Francisco. February 16-19, 2010. Abstract 694.