HCV viraemia means poorer immune response to HAART

Hepatitis C virus viraemia has a role in CD4 cell response to HAART, according to an Italian study published in the June 15^th edition of Clinical Infectious Diseases (now available on-line). The investigators believe that this finding has significant implications for treatment strategies for individuals coinfected with HIV and hepatitis C virus and suggest “treatment of hepatitis C in [coinfected] patients could not only potentially eradicate hepatitis C virus, but also reduce the possible interference of hepatitis C in a patient’s response to HAART."

Some earlier studies have suggested that HIV-positive individuals coinfected with hepatitis C virus have a poorer immune response to HAART than individuals who are not infected with hepatitis C. These studies did not, however, provide any information about the impact of hepatitis C viral load or genotype on response to antiretroviral therapy. An improved knowledge of the effects of hepatitis C viraemia and genotype on HIV-positive patients taking HAART would allow for a better understanding of how the two viruses interact and help the timing of treatment in coinfected patients.

Investigators from the Italian Cohort Naïve for Antiretrovirals (I.Co.N.A) therefore evaluated whether CD4 cell response to HAART in treatment naïve individuals was different in patients coinfected with hepatitis C virus to those only infected with HIV. The investigators also assessed if response to HAART varied according to hepatitis C viral load and hepatitis C virus genotype.

The study population comprised 1219 HIV-positive individuals who were uninfected with hepatitis C virus and 284 HIV-positive patients antibody-positive for hepatitis C virus with hepatitis C viraemia.

Individuals who were not infected with hepatitis C virus were more likely to be female (p = 0.05) and less likely to be injecting drug users (p

The median pre-HAART hepatitis C viral load was 6.09 log₁₀ IU/ml. Genotypic analysis was performed on 138 of the hepatitis C virus-infected patients. Of these 49% were infected with hepatitis C virus genotype 1, 33% with genotype 3, 16% with genotype 4, and 3% with genotype 2.

Before the initiation of HAART, patients infected with genotype 1 had a median CD4 cell count of 260 cells/mm³, which was significantly lower than patients infected with genotype 3 (315 cells/mm³) or genotype 4 (305 cells/mm³, p = 0.04).

A total of 1258 patients (84%) experienced an increase in their CD4 cell count of 100 cells/mm³ or more after the initiation of HAART. Individuals who were negative for hepatitis C virus achieved this increase significantly faster than patients coinfected with hepatitis C virus (23 weeks versus 29 weeks, p = 0.001). The investigators also found that individuals with hepatitis C virus viraemia were less likely to achieve an increase in their CD4 cell count of 100 cells/mm³ (adjusted hazard ratio, 0.82, p = 0.06), although this was only of borderline statistical significance.

When the investigators undertook further analysis, they found that the presence of hepatitis C virus viraemia significantly increased the time taken to achieve an increase in CD4 cell count of 300 cells/mm³ (p = 0.01).

However, the amount of hepatitis C virus did not have a significant impact on CD4 cell response after starting HAART.

Data on hepatitis C virus genotype and CD4 cell count increase were also analysed. There was no difference between the hepatitis C virus genotypes and the chances of achieving a CD4 cell increase of 100 cells/mm³ after commencing HAART.

In further analysis, the investigators found that patients infected with hepatitis C virus genotype 3 had a reduced chance of achieving a CD4 cell count of 300 cells/mm³ compared to patients infected with hepatitis C virus genotype 1 (p = 0.02).

“We found that the chance of achieving a CD4 cell count increase of 100 cells/mm³ or more for hepatitis C virus viraemic patients was 18% less than the chance for hepatitis C virus-negative patients,” write the investigators, adding “this difference was not statistically significant…but similar effects were observed in sensitivity analyses using alternative end points…in particular, for hepatitis C virus viraemic patients the adjusted RH of achieving a CD4 cell increase of 300 cells/mm³ or more was significantly reduced by 31% after initiation of HAART (p = 0.01).

The investigators speculate that hepatitis C virus may be lymphotropic and may actively replicate in the same T cells as HIV.

They conclude that their findings suggest that not only could treatment for hepatitis C virus achieve eradication of the virus but might also improve an individual’s response to HAART. Therefore “among coinfected persons for whom antiretroviral therapy may be safely deferred, treatment for hepatitis C virus infection should be considered appropriate regardless of the extent of hepatitis C virus-associated hepatic damage and may precede initiation of HAART.”