HIV/HCV coinfected patients have a poorer outcome after starting antiretrovirals than those who only have HIV

HIV-positive individuals who are coinfected with hepatitis C virus have poorer outcomes after starting potent antiretroviral therapy than patients who are only infected with HIV, according to a nationwide Danish study to be published in the May 15^th edition of Clinical Infectious Diseases (now online). The investigators established that coinfected individuals had a higher risk of dying than patients who only had HIV, and less pronounced increases in their CD4 cell counts.

Both HIV and hepatitis C share routes of transmission (notably injecting drug use) and many individuals who are infected with HIV are also infected with hepatitis C. The introduction of potent HIV therapy brought about a significant fall in the amount of illness and death caused by HIV, and since then hepatitis C virus has become an increasingly important cause of morbidity and mortality in HIV/hepatitis C coinfected patients.

Studies looking at the influence of hepatitis C coinfection on responses to antiretroviral therapy have produced conflicting results and have often been limited by the size of their sample or a short period of follow-up. Accordingly, Danish investigators conducted a prospective cohort study involving all 2734 HIV-positive patients who started antiretroviral therapy between 1995 and early 2004 at the twelve HIV treatment centres in Denmark to establish if HIV/hepatitis C coinfected patients had a poorer outcome after starting HIV therapy than individuals who only had HIV.

Outcomes assessed were the proportion of patients with a viral load below 500 copies/ml and changes in absolute CD4 cell count. Data were also gathered on death and causes of death.

Of the 2734 individuals included in the investigators analysis, 443 (16%) were coinfected with HIV and hepatitis C. A total of 12,356 person years of follow-up were available for analysis with the median duration of follow-up being 4.7 years.

Individuals who were coinfected with hepatitis C started anti-HIV therapy at a similar median CD4 cell count to patients who only had HIV. Median viral load at this point was also comparable as was prior experience of antiretroviral therapy and the proportion of patients who had been previously diagnosed with AIDS.

However, the investigators noted that coinfected patients were 34% less likely to start taking antiretroviral therapy than patients who only had HIV. They also noticed that once HIV therapy was started, patients who were coinfected with hepatitis C virus were significantly more likely to interrupt treatment for 90 days or longer (30% coinfected patients versus 14% of patients with HIV only). In addition, patients with hepatitis C were three times more likely to interrupt treatment for three months or more because of gastrointestinal problems, including liver related toxicities, than patients who only had HIV (4.5% versus 1.5%).

At all time points after the commencement of HIV treatment, fewer hepatitis C-positive patients achieved a HIV viral load below 500 copies/ml than did hepatitis C-negative patients. However, when the investigators excluded injecting drug users from their analysis, they observed that the odds of an individual with hepatitis C virus achieving a viral load below 500 copies/ml ceased to be worse than a hepatitis C-negative patient at weeks 144 and 288. In addition, the investigators noted that the increased prevalence of lengthy treatment interruptions amongst the coinfected patients appeared to be driving the poorer virological response to HIV therapy seen amongst this group of patients.

Attention was then turned to changes in CD4 cell count after the commencement of antiretroviral treatment. Once again, at all time points, coinfected patients had a poorer response to treatment than patients who only had HIV. By week 300, the median CD4 cell count in coinfected patients was approximately 350 cells/mm³ but was over 450 cells/mm³ amongst hepatitis C-negative individuals.

A total of 370 deaths occurred, the mortality rate being 63 deaths per 1000 patient years amongst coinfected patients and 28 deaths per 1000 patient years amongst individuals who only had HIV. The investigators calculated that the overall risk ration of death was 140% higher amongst coinfected patients.

The investigators then looked at causes of death. Liver-related deaths were much more common amongst hepatitis C-infected patients than hepatitis C-negative individuals (14 per 1000 patient years versus 1 per 1000 patient years). AIDS-related mortality was also higher amongst HIV/hepatitis C coinfected patients than amongst patients who only had HIV (17 per 1000 patient years versus 11 per 1000 patient years), and coinfected patients were also more likely to die with a CD4 cell count above 100 cells/mm³ (33 deaths per 1000 patient years versus 13 per 1000 patient years).

“We found that hepatitis C virus – HIV coinfected patients had a weaker response to HAART, in terms of viral load suppression and improvement of CD4 cell counts, compared to patients who only had HIV”, comment the researchers. They add, “the viral load findings are explained by differences in covariates, mainly injection drug use and compliance with therapy.”

They highlight the importance and strengths of their study writing, “to out our knowledge, this is the first study of hepatitis C virus – HIV coinfection that includes all patients initiating HAART on a national basis.”