Chronic hepatitis C infection blunts CD4 gains after start of HIV treatment

Michael Carter
Published: 10 August 2010

Ongoing hepatitis C replication inhibits improvements in the CD4 cell counts of HIV-positive patients taking antiretroviral therapy, Canadian investigators report in the July 31st edition of AIDS.

Researchers monitored changes in the CD4 cell counts of HIV-positive patients who had antibodies to hepatitis C virus. Falls in CD4 cell counts before HIV treatment was started, and increases in such counts after the initiation of antiretroviral therapy were compared between individuals who had spontaneously cleared hepatitis C, and those who had chronic infection with the virus.

Ongoing hepatitis C replication was associated with slightly higher CD4 cell count loss prior to starting HIV treatment. There was also clear evidence that individuals with chronic hepatitis C had blunted CD4 cell responses to antiretroviral therapy.

“Spontaneous clearance of HCV [hepatitis C virus] is independently associated with a better rate of CD4 cell recovery once ART [antiretroviral therapy] is introduced”, comment the investigators, who stress that their “findings were robust.”

Investigators from the Canadian Coinfection Cohort Study performed their research because there is uncertainty about the impact of hepatitis C co-infection on HIV disease progression. Moreover, they were concerned that earlier research exploring this question may have been limited because antibody status was used to define hepatitis C infection. A significant proportion of patients infected with hepatitis C spontaneously clear the infection, leading the researchers to postulate that the results of some studies could have been confounded because some individuals in the hepatitis C arm were in fact free from the infection.

Their study population included 271 patients. All were infected with HIV, and all had antibodies to hepatitis C.

However, they divided the patients into two groups. The first involved 236 with chronic hepatitis C infection (and therefore ongoing replication of the virus), the other, those who had spontaneously cleared the infection.

Changes in the CD4 cell counts of these two groups were then compared before and after the initiation of antiretroviral therapy.

A total of 95 patients, 25 of whom had spontaneously cleared hepatitis C, were naïve to HIV treatment on recruitment to the study.

CD4 cell counts fell by a non-significant average of 44 cells/mm3 per year amongst the patients who had cleared hepatitis C, and by an average of 84 cells/mm3 each year in those with ongoing replication of the virus. However, after adjustment for follow-up time the association between chronic hepatitis C infection and greater loss of CD4 cells was not significant.

Information on CD4 cell count increases after the initiation of antiretroviral therapy was available for 226 individuals. Once again, 25 patients had spontaneously cleared their hepatitis C infection. The median duration of follow-up was 18 months for those with chronic hepatitis C and 15 months for those who had cleared the infection.

Average annual CD4 cell count increases were seven-fold higher for patients who had cleared hepatitis C infection than for those with ongoing hepatitis C replication (4 vs. 24 cells/mm3 p < 0.001).

The association between spontaneous clearance of hepatitis C virus and more robust increases in CD4 cell count during HIV therapy remained significant after the investigators adjusted their results to take into account potentially confounding factors.

Moreover, the researchers also founded that the blunted CD4 cell response seen in the patients with chronic hepatitis C did not improve over time.

Limiting analysis to patients who started HIV treatment for the first time after entry to the study cohort did not affect the results.

However, when the researchers restricted their analysis to patients who maintained an undetectable HIV viral load throughout follow-up, the impact of chronic hepatitis C virus infection on CD4 cell count recovery was attenuated. CD4 cell counts still increased more slowly in those with ongoing replication of hepatitis C, but the interaction between chronic infection and CD4 cell gain ceased to be statistically significant.

“We found that CD4 cell progression is negatively affected by the presence of ongoing HCV replication in coinfected individuals taking ART”, write the investigators. They add, “elucidating the mechanisms by which this difference occurs and investigating the impact of HCV treatment on CD4 cell progression should be prioritised.”

The study’s authors conclude, “when successful, HCV treatment might have an important role not only in improving HCV related outcomes, but for HIV-related prognosis as well”.

Reference

Potter M et al. Impact of hepatitis C viral replication on CD4 T-lymphocyte progression in HIV – HCV coinfection before and after antiretroviral therapy. AIDS 24: 1857-65, 2010. 

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