HIV/HCV coinfected patients have poorer immunologic response to HIV treatment

HIV-positive patients who are coinfected with hepatitis C virus appear to have a less favourable immunological response to potent antiretroviral therapy than individuals who are only infected with HIV, according to a Canadian study published in the January 15^th edition of the Journal of Infectious Diseases. The researchers, from British Columbia, found that coinfected individuals had significantly smaller increases in their CD4 cell count and lower gains in their CD4 cell percentage during the first year of anti-HIV therapy than patients who were only infected with HIV.

A significant proportion of HIV-positive individuals are coinfected with hepatitis C virus. There have been numerous studies looking at the impact of hepatitis C coinfection on the changes in viral load after HIV treatment has started which have found that coinfection does not affect the virological response to potent antiretroviral therapy. Studies looking at changes in immune function in coinfected patients who started HIV therapy have, however, yielded inconsistent results.

Investigators from British Columbia therefore designed a study to look at changes in CD4 cell count and CD4 cell percentage during the first year of HIV therapy in HIV-positive patients known to be either positive or negative for antibodies to hepatitis C virus. The study outcomes were an increase in CD4 cell count of 75 cells/mm³ and an increase of 10% in CD4 cell count percentage.

The study involved 1186 antiretroviral-naive individuals who started treatment with therapy containing two nucleoside analogues with a non-nucleoside or a protease inhibitor. A total of 606 (51%) of these patients were infected with hepatitis C.

Individuals who were uninfected with hepatitis C achieved an increase in their CD4 cell count of 75 cells/mm³ after starting HIV therapy significantly faster than patients who were infected with hepatitis C (median 69 days versus 84 days, p = 0.05), In addition, hepatitis C virus-uninfected patients achieved an increase of 10% in their CD4 cell percentage faster than hepatitis C virus-infected patients (median 90 days versus 151 days, p = 0.05).

Further analysis of these results was then conducted by the investigators. First they looked to see if CD4 cell increases in both hepatitis C-positive and hepatitis C-negative patients was affected by CD4 cell count before anti-HIV therapy was started. They found that regardless of baseline CD4 cell count, individuals who were hepatitis C-uninfected achieved an increase in their CD4 cell faster than patients who were infected with hepatitis C (p

The investigators then carried out an analysis controlling for factors including age, sex, AIDS diagnosis, baseline CD4 cell count, baseline viral load, adherence to antiretroviral therapy and type of anti-HIV therapy used (protease inhibitor-based versus non-nucleoside-based). The investigators did not provide any information regarding the use of anti-hepatitis C therapy. They found that hepatitis C-infected patients were significantly less likely to have an increase in their CD4 cell count of 75 cells/mm³ (adjusted hazard ratio 0.84, p = 0.03), and ‘somewhat’ less likely to have an increase in their CD4 cell percentage of 10% (adjusted hazard ratio, 0.89, p =0.36, non-significant).

The investigators carried out ‘multivariate’ analysis and looked at CD4 increases in patients who had adherence of 95% or more. They found that the average increase in CD4 cell count was 104 cells/mm³ in hepatitis C-uninfected patients compared to only 70 cells/mm³ in hepatitis C-infected individuals. They also found that adherent uninfected patients had a larger increase in their CD4 cell percentage (4% versus 2%).

“”Our results show that hepatitis C virus infection has an independent effect on immunologic response to antiretroviral therapy over time”, write the investigators.

The suggest that the “blunted immune response in HIV/hepatitis C coinfected patients may be due the nonspecific immune stimulation driven by chronic hepatitis C virus infection, or it could be that infection of immune cells by hepatitis C could favour the depletion of CD4 cells.”