HCV viraemia means poorer immune response to HAART Michael Carter, Wednesday, May 18,  2005 Hepatitis C virus viraemia has a role in CD4 cell response to HAART,  according to an Italian study published in the June 15th 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  < 0.001). ALT levels were significantly higher at baseline amongst patients  with hepatitis C viraemia compared to hepatitis C virus-negative individuals (p  < 0.001). 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.” Reference  Antonucci G et al. Role of hepatitis C virus viraemia and hepatitis C  virus genotype in the immune recovery from highly active antiretroviral therapy  in a cohort of antiretroviral-naïve HIV-infected individuals. Clin Infect  Dis 40 (online edition), 2005.