Changes in hepatitis C viral response after initiation of highly active antiretroviral therapy and control of HIV viremia in chronically co-infected individuals.
BACKGROUND
HIV seropositive individuals co-infected with hepatitis C virus (HCV) have an increased risk for liver cirrhosis. We examined the long-term effect of controlling HIV infection with highly active antiretroviral therapy (HAART) on HCV viremia among co-infected patients.


METHODS
HIV/HCV co-infected patients who initiated HAART and were able to control HIV viremia to <500 copies/mL were evaluated. HIV and HCV viremia were measured at each time point from frozen plasma samples by using bDNA methodology. Liver function tests and CD4+ and CD8+ T cell counts of all patients were obtained at each time point.


RESULTS
Seventeen co-infected patients met criteria for study from a cohort of 156 patients. Median time to achieve an HIV viral load (VL) <500 copies/mL after initiation of HAART was 28 weeks (range, 5-225 weeks). Thirteen of 17 patients had increases in HCV VL. Slope analysis of HCV VL vs. HIV VL was -0.14 (p=.0496), demonstrating a 0.14 log increase in HCV VL concomitant with control of HIV viremia. HCV viremia returned toward baseline levels in the 16 patients who maintained HIV suppression for 6 months. None cleared HCV after initiation of HAART during this time. Alkaline phosphatase, ALT, and AST levels were not significantly changed from baseline nor correlated with change in HCV VL (p>.05).


CONCLUSIONS
Control of HIV viremia may result in an early increase in HCV viremia. In this study, for every 1 log decrease of HIV VL there was a 0.14 log increase of HCV VL. The exact mechanism of this flare seen with control of HIV viremia is unknown. However, HAART alone was not able to eliminate or significantly reduce the HCV viremia in this cohort of co-infected patients.
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Skottilil@niaid.nih.gov
Shyam
S
Kottilil
Shyla
S
Jagannatha
Amy
A
Lu
Shuying
S
Liu
Mary
M
McLaughlin
Julia A
JA
Metcalf
Robin
R
Dewar
Colleen
C
Campbell
Chad
C
Koratich
Frank
F
Maldarelli
Henry
H
Masur
Michael A
MA
Polis
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D000998:Antiviral Agents / Q000097:blood / Q000627:therapeutic use; D021121:Branched DNA Signal Amplification Assay / Q000379:methods; D015704:CD4 Antigens / Q000097:blood*; D016827:CD8 Antigens / Q000097:blood*; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy*; D006526:Hepatitis C / Q000097:blood* / Q000150:complications*; D006801:Humans; D007371:Interferon-gamma / Q000097:blood / Q000627:therapeutic use; D007378:Interleukins / Q000097:blood; D008111:Liver Function Tests; D008297:Male
D000998:Antiviral Agents; D015704:CD4 Antigens; D016827:CD8 Antigens; D007378:Interleukins; D007371:Interferon-gamma