Liver enzymes elevation and immune reconstitution among treatment-naïve HIV-infected patients instituting antiretroviral therapy.
OBJECTIVE
Because liver enzymes elevation (LEE) complicates antiretroviral (ARV) therapy, and because the strongest risk factor for ARV-related LEE is HBV/HCV coinfection, it is speculated that ARV-related LEE may be a form of immune reconstitution disease. This study summarizes the relation between immune reconstitution, ARV-induced LEE, and HBV/HCV coinfection.


METHODS
Medical records of ARV-naïve HIV-infected patients initiating ARV were reviewed for hepatitis coinfection, LEE (grade > or =2 AST/ALT) and changes in CD4 T-cell counts over time in an urban HIV clinic. Risk factors for LEE were statistically evaluated, and changes in CD4 T-cell counts were estimated by a mixed-effects linear model.


RESULTS
Predictors of LEE included HBV/HCV coinfection (OR = 6.44) and stavudine use (OR = 2.33). Nelfinavir use was protective (OR = 0.45). The mean rate of change in CD4 T-cell counts was higher in HBV/HCV coinfected subjects who developed LEE (99 cells/microL per month) compared with non-coinfected subjects who did not develop LEE (59 cells/microL per month, P = 0.03), non-coinfected subjects who developed LEE (36 cells/microL per month, P =0.01), and coinfected subjects who did not develop LEE, 38% higher (62 cells/microL per month; P =0.11)


CONCLUSIONS
A more robust immune restoration was observed among HBV/HCV coinfected subjects who developed liver enzyme elevation after antiretroviral initiation compared with other groups. This finding suggests that ARV-related liver enzyme elevation may be related in part to immune reconstitution, as measured by changes in CD4 T-cell counts.
Ofotokun
Ighovwerha
I
Division of Infectious Disease, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia 30303, USA. iofotok@emory.edu
Smithson
Sarah E
SE
Lu
Chengxing
C
Easley
Kirk A
KA
Lennox
Jeffrey L
JL
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood*; D000480:Alkynes; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use; D044966:Anti-Retroviral Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001219:Aspartate Aminotransferases / Q000097:blood*; D048588:Benzoxazines / Q000009:adverse effects; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology; D003521:Cyclopropanes; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000201:enzymology; D006509:Hepatitis B / Q000097:blood / Q000150:complications / Q000473:pathology; D006526:Hepatitis C / Q000097:blood / Q000150:complications / Q000473:pathology; D006801:Humans; D054019:Immune Reconstitution Inflammatory Syndrome / Q000097:blood / Q000139:chemically induced* / Q000473:pathology; D019259:Lamivudine / Q000009:adverse effects / Q000627:therapeutic use; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D012189:Retrospective Studies; D012307:Risk Factors; D018119:Stavudine / Q000009:adverse effects / Q000627:therapeutic use; D015215:Zidovudine / Q000009:adverse effects / Q000627:therapeutic use
D000480:Alkynes; D019380:Anti-HIV Agents; D044966:Anti-Retroviral Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D019259:Lamivudine; D015215:Zidovudine; D018119:Stavudine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C098320:efavirenz