Hepatitis C has no impact on CD4 cell recovery in patients taking HIV treatment

Patients co-infected with HIV and hepatitis C virus whose HIV treatment is suppressing their viral load to undetectable levels have comparable CD4 cell count increases to those seen in patients who are only infected with HIV, investigators report in the April 15^th edition of the Journal of Acquired Immune Deficiency Syndromes.

It is estimated that there are two million HIV-positive individuals co-infected with hepatitis C virus in the European region. Earlier research has provided conflicting information on the effect of co-infection on CD4 cell recovery in individuals taking HIV treatment. Differences in adherence to HIV treatment or the potency of antiretroviral regimens were a potential limitation of these studies. Furthermore, they defined hepatitis C co-infection as the presence of antibodies to the virus and did not investigate the influence of either hepatitis C replication or genotype.

Investigators from the EuroSIDA cohort therefore designed a prospective study to assess the influence of chronic hepatitis C co-infection and genotype on CD4 cell recovery in HIV-positive patients whose HIV treatment achieved and sustained the suppression of viral load to undetectable levels (below 50 copies/ml).

Patients with antibodies to hepatitis C virus and at least two consecutive undetectable HIV viral loads after starting HIV treatment were eligible for inclusion in the study. The investigators calculated the annual change in CD4 cell count for these patients and then compared them to those observed in patients only infected with HIV whose antiretroviral therapy had suppressed viral load to undetectable levels. Further analyses were then performed to determine the impact of hepatitis C genotype and replication on CD4 cell recovery.

A total of 4208 patients were included in the investigators’ analyses. The first analysis showed that there was no significant difference in the annual CD4 cell count increase seen in the co-infected patients (36 cells/mm³, 95% CI, 27.2-43.9) and the patients only infected with HIV (38 cells/mm³, 95% CI, 34.8-41.9).

These results did not change when the investigators adjusted for hepatitis C genotype. Nor were they altered by adjusting for nucleos(t)ide combinations, third antiretroviral drug, age, time since starting antiretroviral therapy, time to initial viral suppression, or whether an individual was treatment-naive or treatment-experienced when they started combination HIV therapy.

Taking into account ongoing hepatitis C replication did not significantly affect the results. Nor did the hepatitis C genotype influence CD4 cell recovery in these patients with ongoing hepatitis C replication. Finally the investigators compared changes in CD4 cell counts according to co-infected patients’ hepatitis C viral load. This showed that although annual CD4 cell gains (43 cell/mm³) were higher amongst patients with a hepatitis C viral load below 1 million iu/ml than those with a hepatitis C viral load above this level (35 cells/mm³), the difference was not significant (p = 0.43).

“In this large prospective cohort study, we provide evidence that hepatitis C virus coinfection does not influence the CD4 cell recovery in HIV-1-infected patients who are persistently maximally HIV suppressed…compared with HIV-monoinfected patients”, write the investigators.

Nor did they find any differences in CD4 cell gain when comparing patients who were hepatitis C “viremic vs. aviremic patients with hepatitis C virus antibodies, and between distinct hepatitis C virus genotypes among viremic patients”.

They do however conclude that co-infected patients may benefit from starting HIV treatment earlier than otherwise recommended “because studies have shown that combination antiretroviral therapy may slow fibrosis progression.” They also note the benefits of hepatitis C treatment for co-infected patients as “hepatitis C virus eradication will lower the risk of hepatotoxicity induced by antiretroviral drugs and progression of liver disease.”