HIV/HCV Coinfected People May Achieve Smaller CD4 Cell Gains after Starting Antiretroviral Therapy

		SUMMARY: HIV positive people coinfected with hepatitis C virus (HCV) may experience impaired immune recovery, with smaller increases in CD4 T-cells, after starting antiretroviral therapy (ART), according to a study described in the July 31, 2010 issue of AIDS. Investigators therefore suggested that effective hepatitis C treatment might help reduce HIV disease progression as well liver disease progression.

An estimated one-third of people with HIV also have chronic hepatitis C. Considerably research has shown that coinfected individuals experience faster liver disease progression and respond less well to interferon-based hepatitis C treatment, but the effects of coinfection on HIV disease progression are less well-defined and past studies have produced conflicting data.

To shed more light on this issue, Martin Potter and fellow investigators with the Canadian Co-infection Cohort Study examined changes in CD4 T-cell counts among HIV positive people with chronic hepatitis C infection and those who spontaneously cleared HCV. About one-quarter of HCV monoinfected people clear the virus without treatment, but spontaneous HCV clearance appears to be less common among coinfected individuals.

The researchers analyzed data from 271 participants in a prospective multi-center Canadian cohort of HIV positive adults with serologic evidence of HCV infection. All were HCV antibody positive, but while most also had detectable HCV RNA, or viral load, a small proportion showed evidence of spontaneous clearance or control of viral replication, with undetectable HCV RNA.

Baseline characteristics were similar for the 35 patients who spontaneously cleared HCV and the 236 patients who did not, except that those with chronic infection had more advanced liver disease.

Investigators measured changes in CD4 cell counts over a median follow-up duration of about 18 months.

Results

	People with detectable HCV RNA -- indicating continued viral replication -- had on average 7-fold slower CD4 cell recovery on ART compared with HCV RNA negative participants (4 vs 26 cells/mm3, respectively; P < 0.001).
	Slower recovery of CD4 cells did not improve over time.
	Results were similar when looking only at the 95 participants (including 25 spontaneous clearers) who started ART for the first time.
	Looking only at participants who achieved undetectable HIV viral load on ART, the reduction in CD4 cell recovery was less evident and did not reach statistical significance.
	There was also a trend toward greater CD4 cell decline prior to starting ART among people with detectable HCV RNA compared with spontaneous clearers, but again the difference did not reach statistical significance.

Based on these findings, the study authors concluded. "We found that CD4 cell progression is negatively affected by the presence of ongoing HCV replication in coinfected individuals initiating ART which persisted throughout stable ART, suggesting active HCV infection affects immune restoration even after years of ART exposure."

Therefore, they suggested, hepatitis C treatment might not only prevent liver disease progression, but also reduce HIV disease progression.

Lead investigator affiliation: Department of Medicine, Division of Infectious Diseases, Royal Victoria Hospital, McGill University Health Centre, Montréal, Québec, Canada.

8/13/10

Reference
M Potter, A Odueyungbo, H Yang, and others (Canadian Co-infection Cohort Study Investigators). Impact of hepatitis C viral replication on CD4+ T-lymphocyte progression in HIV-HCV coinfection before and after antiretroviral therapy. AIDS 24(12): 1857-1865 (Abstract). July 31, 2010.