Hepatitis C Found to Diminish Response to HAART

The average HIV positive person who uses highly active antiretroviral therapy (HAART) usually has increased CD4+ cell counts as a result. But the size of this increase may be affected by several factors, including the ability to take medications as prescribed and directed (adherence). Now researchers in Vancouver, British Columbia, have found that co-infection with hepatitis C virus (HCV) may somehow weaken the immune system's ability to rebuild itself despite the use of HAART.

Paula Braitstein and colleagues at the B.C. Centre for Excellence in HIV/AIDS studied the effect of HCV on CD4+ cell count changes among HAART users by reviewing records in the centre's database, collected between August 1996 and July 2000. Information was analysed on 1,416 people with HIV/AIDS (PHAs) who had never previously taken HAART but began to do so during the study period. The research team also found results of blood tests for antibodies against HCV in a subset of 552 subjects as follows:

• 235 people who were positive for HIV and HCV
• 317 people who were positive for HIV only

A factor the researchers took into account when later analysing the data was adherence. The research team assessed adherence in an indirect way. They checked pharmacy databases to determine whether subjects had their prescriptions filled on a regular basis. According to previous studies, the ability to fill prescriptions on a regular basis is linked to a high degree of adherence.

Before starting therapy, the profile of the 235 PHAs who were also HCV positive was as follows:

• 22% female, 78% male
• average age: 37 years
• average CD4+ cell count: 290 cells
• average viral load: more than 100,000 copies
• 10% had symptoms of AIDS
• 43% were judged to be more than 95% adherent

Results -- HIV Positive Only

Among subjects positive only for HIV and whom researchers judged to be at least 95% adherent, the average increase in the CD4+ cell count after the first 1? years of treatment was 230 extra cells. Among subjects who were less than 95% adherent, the increase was 190 extra cells.

Results -- Positive for HIV and HCV

Among co-infected subjects, results of treatment were not as promising. After 1? years of treatment, in the group whose adherence was at least 95% there was an increase of 120 extra CD4+ cells. In subjects whose adherence was less than 95%, there was an increase of only 50 extra cells.

According to the research team, these results show that after adjusting for adherence, HCV has a powerful effect on the ability of HAART to affect the immune system. It is not clear why HCV infection might have this effect. One possibility is that HCV affects the liver's ability to properly process drugs (such as protease inhibitors and non-nukes), and so levels of these drugs in the blood are not as high as they should be. But this theory needs to be tested and confirmed. The fact that the response to HAART was worse in co-infected people raises questions about the timing for initiating HIV therapy in this population. Perhaps HAART would be more effective in HCV co-infected people if taken earlier in the course of HIV disease, when their CD4+ counts are higher? Again, this is another idea that requires further study. Overall, the Vancouver study confirms results by research teams in the European Union and lays the foundation for future studies in the area of HIV/HCV co-infection.

Reference

1. Braitstein P, et al. Impact of hepatitis C virus on CD4+ response post-initiation of HAART among a population-based cohort. 2nd IAS conference on pathogenesis and treatment, 13-16 July 2003, Paris. Abstract 214.