Swiss researchers have reported that hepatitis C co-infection significantly reduces the likelihood of a good CD4+ cell increase after starting HAART, although there was no difference between HCV-positive and HCV-negative patients in their virological responses to HAART and likelihood of achieving and maintaining undetectable viral laod. Poor responders were seven times more likely to have HCV genotype 3a.
The study, published today in The Lancet, looked at responses to therapy in 3111 Swiss patients, one of the world's largest cohorts available for systematic study. 1157 were HCV-positive, of whom 87.7% had a history of intravenous drug use
HCV-positive individuals were significantly more likely to die after starting therapy, but deaths related to intravenous drug use accounted for the excess of deaths in the HCV-positive group. They were also more likely to develop AIDS-defining opportunistic infections after starting HAART (7.5% vs 4.7%, p=0.001). Statistical analysis showed that HCV-positive individuals were twice as likely to experience disease progression after starting HAART, and in HCV-positive individuals with viral load suppressed below the limit of detection the likelihood was even higher (hazard ratio 3.54).
This difference is largely explained by inferior immune reconstitution in HCV-positive individuals at six months, 12 months, 24 months and 36 months after starting HAART. A sub-study which looked at HCV viral load and CD4 cell recovery in 56 patients with HIV-1 RNA below the limit of detection found no relationship between HCV viral load and CD4 cell recovery. In fact, 25% of those with impaired CD4 cell recovery had undetectable HCV viral load. However, there was a significant relationship between HCV genotype and CD4 cell recovery. Genotype 3a was significantly more prevalent in the poor responders (p=0.008, OR 7.7).
A CD4 cell increase of more than 50 cells in the first six months was significantly less likely in the HCV-positive group, suggesting that the rate of immune reconstitution, as well as the extent of reconstitution, is impaired in HCV-positive individuals.
HCV has been shown to impair lymphocyte proliferation in the test tube, and the authors suggest that this may be the mechanism which affects CD4 cell recovery on HAART.
The researchers reported that the overall efficacy of HAART did not appear to have been compromised by treatment discontinuations in HCV-positive individuals unable to tolerate certain hepatotoxic drugs. HCV-positivity was not associated with the likelihood of changing treatment, unlike baseline viral load, AIDS diagnosis or female sex.
In conclusion, the authors suggest that it may be worth considering whether to treat HCV earlier, with the aim of reducing the risk of a poor response to HAART, and because of the poorer responses to HCV treatment seen in patients with advanced immunodeficiency. The authors define `early' as a CD4 cell count greater than 500.
Further information about hepatitis C and summaries of the key research on the impact of HIV/HCV coinfection can be found on aidsmap.com
Reference
Greub G et al. Clinical progression, survival and immune recovery during antiretroviral therapy in patients with HIV-1 and hepatitis C virus coinfection: the Swiss HIV Cohort study. The Lancet 356: 1800-05, 2000.