Successful Antiretroviral Therapy May Increase T-cell Response against Hepatitis C Virus in HIV-HCV Coinfected Individuals

By Liz Highleyman

Research indicates that HIV positive patients coinfected with hepatitis C virus (HCV) tend to experience more rapid liver disease progression and respond less well to interferon-based therapy relative to people with hepatitis C alone. Studies have shown that coinfected patients tend to have higher HCV RNA levels compared with HCV monoinfected individuals, but the effect of antiretroviral therapy (ART) on HCV is not well understood.

In a study presented at the recent 16th Conference on Retroviruses and Opportunistic Infections (CROI 2009) in Montreal, Janine Rohrbach and colleagues longitudinally assessed HCV-specific CD4 T-cell responses in HIV-HCV coinfected individuals to determine whether successful combination ART would restore HCV-specific T-cell responses and reduce HCV viral load.

The study included 54 HIV-HCV coinfected patients in the Swiss HIV Cohort Study. In a laboratory analysis, the investigators measured interferon-gamma (IFN-gamma) ELISpot responses to determine CD4 T-cell reactivity. HCV RNA levels were assessed by real-time polymerase chain reaction (RT-PCR).

Analyses were done at the earliest available time point after HIV infection, just before starting ART, and at 3 time points after starting successful therapy that reduced HIV viral load to < 1000 copies/mL. All time points were before initiation of anti-HCV therapy. These time points (designated 1 through 5) occurred at a median 41 months and 2 months before starting ART, and then 7, 33, and 74 months after treatment initiation.

Results

Overall, HCV-specific T-cell responses were more likely to be detected after starting ART, and the proportion of participants with detectable responses increased with longer time on therapy.

25 participants (46%) showed no anti-HCV responses at any time point.

17 patients (31%) who did not have detectable pre-treatment responses developed responses after starting ART.

7 patients (13%) demonstrated HCV-specific responses both before and after ART initiation.

5 individuals (9%) had detectable T-cell responses before ART, but lost them after starting therapy.

The proportion of patients with detectable CD4 T-cell responses was significantly lower during untreated HIV infection than after starting successful ART (P <0.001).

HCV-specific responses while on ART were detected significantly more frequently in individuals with resolved HCV infection compared to those who developed chronic hepatitis C (P = 0.1).

Median HCV viral load increased slightly during the first year on combination ART.

Thereafter, HCV RNA decreased slightly, but not to the level expected for HCV monoinfection individuals.

Based on these findings, the researchers concluded, "Successful ART can increase HCV-specific T-cell responses and is associated with a slight decrease in HCV RNA levels long-term."

This finding, they suggested, "supports consideration of earlier ART initiation in HIV-HCV coinfected individuals."

In response to a question, presenter Andi Rauch indicated that they did not have liver biopsy data to show whether anti-HCV T-cell responses were associated with any histological or functional improvement, but said they were trying to collect past biopsy data and may look at non-invasive measures of liver damage.

Univ Hosp Bern and Univ of Bern, Switzerland Univ of Oxford, UK; Murdoch Univ, Western Australia; Univ Hosp Ctr and Univ of Lausanne, Switzerland; Inst of Social and Preventive Med, Univ of Bern, Switzerland; Univ Hosp Zurich, Switzerland.

4/10/09

Reference
J Rohrbach, G Harcourt, S Gaudieri, and others. Successful ART Is Associated with Increasing HCV-specific T Cell Responses. 16th Conference on Retroviruses and Opportunistic Infections (CROI 2009). Montreal, Canada. February 8-11, 2009. Abstract 105.