Further evidence that HIV/hepatitis C coinfected patients have poorer immunological response to HIV therapy

Hepatitis C coinfection is associated with lower CD4 cell counts and CD4 cell percentages in HIV-positive patients who are fully adherent to their antiretroviral treatment regimens, a US study published in the May edition of Alcoholism: Clinical and Experimental Research has found. The investigators believe that their findings have important clinical implications for the timing of both anti-hepatitis C treatment and antiretroviral therapy in coinfected individuals.

A significant number of HIV-positive individuals are coinfected with hepatitis C virus, with estimates in the US ranging from 15% to 30%. The impact of hepatitis C virus on HIV disease progression is a controversial subject. Although data from the large Swiss HIV cohort indicated that coinfected individuals experienced more rapid HIV disease progression, this finding was not supported by a large US study.

Investigators therefore wished to test the hypothesis that hepatitis C infection had an adverse effect on CD4 cell count, CD4 cell percentage and HIV viral load in a cohort of HIV-positive individuals taking antiretroviral therapy who had alcohol problems. The study involved 396 patients who were assessed at baseline and then at six monthly intervals for 42 months.

Data were gathered on demographics, HIV risk behaviours, and alcohol and drug use. Patients were also asked about their adherence to antiretroviral therapy. Those who did not report 100% adherence to their treatment in the last three days were considered non-adherent. Blood samples were obtained to measure CD4 cell count, CD4 cell percentage, and HIV viral load.

At baseline, individuals were also tested for hepatitis C virus, with just over 50% (199 individuals) having evidence of hepatitis C virus infection using RNA viral load tests.

The mean age was 43 years, 75% were men, 41% were African American, median CD4 cell count was 403 cells/mm³ and median HIV viral load was a little under 1,000 copies/ml with 31% of patients having an undetectable viral load. The mean period since HIV diagnosis was nine years and individuals had been taking antiretroviral therapy for a mean of seven years.

Of the patients who were assessed as being fully adherent to antiretroviral therapy (total 185, of which 99 were coinfected), CD4 cell counts were a mean of 46 cells/mm³ lower in coinfected patients, a statistically significant difference (p = 0.03). In non-adherent patients, no significant difference was seen in CD4 cell counts those patients who were coinfected and those who were not.

The investigators also found that adherent coinfected patients had significantly lower CD4 cell percentages than patients who only had HIV and who were also fully adherent (mean difference, 2%, p

HIV viral load did not differ significantly between coinfected patients and patients only infected with HIV, irrespective of their adherence.

Alcohol consumption did not affect the investigators findings, nor did their findings change after they controlled for time since antiretroviral therapy was initiated.

“Determining whether HCV coinfection affects HIV disease progression is important for understanding the optimal timing and sequencing of therapies for these infections”, write the investigators.

They add, “the observation of a lower CD4 cell count in patients with HCV infection that were receiving and adherent to antiretroviral therapy is of particular interest” as it is consistent with the findings from the Swiss HIV cohort that found that individuals with hepatitis C infection had a blunted recovery in CD4 cell count after initiating HIV therapy compared to those without hepatitis C. The investigators speculate that hepatitis C may have a direct effect on CD4 cells.

“This study’s findings have important implications for understanding the optimal management…for coinfected patients”, and the investigators believe that they “strengthen the argument to initiate HCV therapy early in the course of HIV disease. These findings may also support the earlier induction of antiretroviral therapy in coinfected individuals to both offset the negative impact of HIV on HCV disease progression and the potentially negative impact of HCV on CD4 cell recovery.”