The results of two studies are at odds regarding whether or not people coinfected with HIV and hepatitis C virus (HCV) must have high CD4 counts if they are to respond well to HCV treatment. But the new data, published by separate research teams in the January 1 issue of the Journal ofAcquired Immune Deficiency Syndromes, suggests that people with lower CD4 counts may not have to wait until HIV treatment improves their immune systems before they can safely initiate HCV treatment, a concern given the potential for more frequent and severe side effects among patients with low CD4 cell counts undergoing pegylated interferon treatment.
The first study, finding that coinfected patients with CD4 counts above 350 were more likely to respond favorably to HCV treatment, was conducted by Milos Opravil, MD, of the Division of Infectious Diseases and Hospital Epidemiology at the University Hospital Zurich, in Switzerland, and his colleagues. Opravil’s team analyzed data originally collected in the AIDS PEGASYS Ribavirin International Coinfection Trial (APRICOT), one of the largest studies of HCV treatment in people living with HIV.
The APRICOT study found that people who received pegylated interferon and ribavirin were two- to four-times as likely to achieve a sustained virologic response (SVR)—maintaining an undetectable HCV viral load for six months after completing HCV treatment—compared with people who received either pegylated interferon without ribavirin or standard interferon with ribavirin.
Opravil’s team took the original data from APRICOT and performed a second analysis, looking at the impact of a person’s CD4 count before starting HCV treatment. The team broke the study participants into three separate groups: people with fewer than 200 CD4 cells before treatment, people with 200 to 349 CD4 cells and people with CD4 counts of 350 or higher.
When the team looked at all the patients in the study, those with CD4 counts below 200 were more likely to have an SVR than those with CD4 counts of 200 or greater. When Opravil’s team looked only at people with HCV genotype 1—the most common and difficult-to-treat HCV subtype in the United States—they found that people who started pegylated interferon and ribavirin treatment with CD4 counts of 350 or greater were significantly more likely to have an SVR than those with lower CD4 counts.
The second study, headed by Laure Valerio, MD, of the Départment de Santé Publique at the Centre Hospitalier Universitaire de Nice in France, analyzed the medical records of people with HIV from hospitals in three French cities. Valerio’s team found 175 people coinfected with HIV and HCV who had received HCV treatment. Patients were categorized as having either a CD4 count of less than 350 or a CD4 count of 350 or higher, and were further divided into two groups based on HCV genotype.
Valerio’s team found that a person’s CD4 count before starting HCV treatment had no impact on whether or not he or she achieved an SVR. This was true regardless of the HCV genotype. They did find, however, that in people with HCV genotype 1, being younger, having a lower HIV viral load, and having been on antiretrovirals for less time led to a greater chance of a achieving an SVR.
Valerio’s study may also alleviate concerns regarding the use of HCV treatment in HIV-positive people with lower CD4 counts. Overall, the rate of discontinuation of HCV treatment was largely the same as that seen in other treatment trials, this held true even for people with lower CD4 counts. While the number of treatment discontinuations was somewhat higher in those with lower CD4 counts, the rate of adverse events was similar between the groups with higher CD4 counts and lower CD4 counts.
Both studies have their weaknesses. In Opravil’s study, the number of people with low CD4 counts was limited, making it difficult to draw firm conclusions. Valerio’s study, by contrast, did have a slightly higher proportion of people with lower CD4 counts, but analyses based on medical record reviews are usually less powerful than studies that are designed in advance to test a research question, such as the effect of CD4 counts on HCV treatment. Taken as a whole, these two studies demonstrate that answers regarding the impact of a person’s CD4 count on HCV treatment success are far from settled, and that further research will be needed.
