A retrospective study of 418 treatment-naive HIV-positive individuals in Newark, New Jersey, has found that antiretroviral therapy led to smaller increases in CD4 count in those with hepatitis C (HCV) co-infection, even when viral load was successfully controlled. However, many possible confounding factors were not taken into account in the analysis, so the difference may not be purely due to HCV infection itself. The study was presented to the 44th annual meeting of the Infectious Disease Society of America (IDSA) in Toronto on October 12th.
Of the 1,989 patients who first visited the New Jersey Medical School’s Infectious Disease Practice clinic between January 2000 and February 2006, the study team selected the 418 who were HIV-positive but had not received any HIV or hepatitis C treatment at the time of the first visit.
Of these 418 patients, 130 (31%) were HIV/HCV co-infected. The HCV-positive patients tended to be slightly older (44 vs. 40 years old), male (68% vs. 52%), more likely to have smoked currently or in the past (62% vs. 55%), and much more likely to have drug use as their risk factor for HIV (77% vs. 34%). The HCV co-infected individuals also had, on average, higher CD4 counts at the start of observation (410 vs. 316 cells/mm3), but viral loads were similar. The groups were also racially similar.
Follow-up information (an average of just under 17 months) was available on 305 (73%) of these patients. Out of these, 245 were started on antiretroviral therapy, and viral loads dropped to less than 400 copies/ml in 136 (55%). There was virtually no difference in the likelihood of this “successful” viral load response between the hepatitis C co-infected and the ones who were not.
However, the average increase in CD4 counts (in cells/mm3) was almost twice as high in the HCV-negative as in the HCV-positive group. To investigate the factors affecting CD4 cell responses, the investigators compared two groups: those who had CD4 cell count increases of 50 cells/mm3 or more (a group of 117 patients), and those whose counts increased by less than 50 cells/mm3 (86 patients). They found that those with hepatitis C co-infection, and those whose viral loads never went under 400 cells/mm
A great many study limitations were acknowledged: first of all, a retrospective chart review cannot prove that any of these factors caused a “blunted” treatment response: a prospective, controlled study would be required. There was some question as to whether an increase in 50 cells/mm3 was the best basis for comparison – percentage increases, or increases above a given cutoff value (e.g. 200 cells/mm3), might have yielded different results. It is possible the co-infected patients were only showing a slower response: it might simply take longer than 17 months for their CD4 cell increases to equal those of the other group.
Many “confounding” factors, which may have led to differences between the groups, were not ruled out. There were no measurements of medication adherence, and therefore no way of knowing whether adherence rates were different between the groups. (The researchers did feel that the similar viral load responses would suggest similar adherence rates.) Although the different antiretroviral treatment classes were used in similar proportions between the two groups, the use of specific antiretrovirals – some of which are known to cause less dramatic CD4 responses – were not compared. Finally, the actual degree of HCV viremia (the level of hepatitis C virus present in the bloodstream) was not taken into account.
The researchers concluded that “despite effective suppression of HIV viral load, patients with HIV/hepatitis C coinfection had an impaired CD4 recovery.” However, they acknowledged that these results were more suggestive than conclusive.
Swaminathan S et al. Impaired CD4 response despite effective HAART in patients with Human Immunodeficiency Virus (HIV) coinfected with hepatitis C (HCV). 44th Annual Meeting of the Infectious Diseases Society of America, Toronto, abstract 58, 2006.