For those coinfected with HIV and the Hepatitis C virus (HCV), having a higher CD4 cell count when you start HCV treatment with pegylated interferon plus ribavirin does not improve the probability of treatment success, according to a French study published in the January 1st edition of the Journal of Acquired Immune Deficiency Syndromes.
The combination of pegylated interferon plus ribavirin has been shown to be superior to other treatments for HCV, in patients also infected with HIV. For this reason, it is the recommended HCV treatment by the British HIV Association (BHIVA). While doctors are confident about which HCV treatment to use, the optimum time to start treatment in HIV/HCV–coinfected patients is less clear.
Early treatment of HCV is encouraged to avoid liver damage and to increase the chances of success, but current guidelines recommend delaying treatment if CD4 cell counts are low, in order that immune reconstitution can occur on antiretroviral treatment.
With little clear evidence to suggest a relationship between CD4 cell count and response to HCV therapy, French scientists analysed a database of patients to look for a connection. Their objective was to determine if a higher baseline CD4 count predicted a greater chance of success with pegylated interferon plus ribavirin treatment. The success of HCV therapy was assessed by the presence of a sustained viral response (SVR). SVR was recorded when HCV genetic material (RNA) was consistently undetectable in blood plasma, 24 weeks after treatment.
The researchers conducted this retrospective study using data from HIV/HCV- coinfected patients treated for HIV in hospitals in Nice, Tourcoing, and Marseille since 2000 (n=175). All the HIV/HCV-coinfected patients in these cities who began pegylated interferon plus ribavirin therapy before June 2004 were included. This included patients on and off antiretroviral therapy for HIV.
The CD4 cell count at the start of the study was measured in the six months before HCV treatment began and data was divided into two groups: those with CD4 cell counts below 350 cells/mm3 and those with counts of 350 or higher (≥350 cells/mm3). Follow-up lasted from HCV therapy initiation to 24 weeks after treatment. As patients with different genotypes of HCV respond differently to treatment, the relationship between CD4 cell count and SVR was examined separately for patients with HCV genotype 1 (the most common form in Europe) or non-1 (other HCV genotypes).
Other variables recorded included: age, gender, body mass index, hepatitis B virus coinfection, HCV genotype, liver damage (METAVIR score), mode of HVC infection (such as sexual transmission or intravenous drug use), pegylated interferon dose, previous HCV treatment, presence of antiretroviral therapy, historical nadir (lowest ever) CD4 cell count, and HIV viral load.
Data for 175 HIV/HCV-coinfected patients were analysed from April 2000 to May 2004. Sixty-nine percent of the patients were men and the average (median) age was 40 years. Injection drug use was the most common way of contracting HCV accounting for 81% of the cases in this study. The majority (86%) of patients were taking antiretroviral therapy to manage their HIV infection when they started HCV treatment.
HCV treatment was successful (i.e. achieved a sustained viral response/SVR) in 29% of patients overall. When broken down into different HCV genotypes, 13% achieved SVR in patients with HCV genotype 1, 46% in patients with genotype 2 or 3, and 42% in patients with genotype 4. One patient had genotype 6 and had a SVR.
The researchers found no clear relationship between CD4 cell count at the start of HCV treatment and treatment success, as assessed by SVR. In patients with HCV genotype 1 and in patients with HCV genotype non-1, a baseline CD4 count of ≥350 cells/mm3 was not associated with SVR.
In the 91 patients with HCV genotype 1, there was no significant difference in baseline characteristics between patients with a CD4 count less than 350 cells/mm3 or ≥350 cells/mm3, except for nadir (lowest ever) CD4 cell count. In otherwords, lowest ever CD4 cell count was the only significant difference between these groups of patients at the start of the study. The same was true for the 84 patients with HCV genotype non-1. For patients with HCV genotype 1, predictors of treatment success were younger age, shorter HCV infection duration, and lower HIV viral load.
The authors suggested their results show that initiation of anti-HCV therapy with pegylated interferon plus ribavirin in HIV/HCV-coinfected patients is possible without waiting for the patients to reach a high CD4 cell count on antiretroviral therapy.
“A higher CD4 cell count at treatment initiation with pegylated interferon plus ribavirin did not improve treatment success probability, regardless of HCV genotype,” they concluded.