Macroenzyme creatine kinase (CK) type 2 in HIV-infected patients is significantly associated with TDF and consists of ubiquitous mitochondrial CK.
OBJECTIVE
To evaluate the prevalence and origin of macroenzyme creatine kinase type 2 (Macro CK2) in HIV-1-infected patients on antiretroviral treatment.


METHODS
CK, CK-MB activity and protein weight, electrophoretic behaviour, glomerular filtration rate (GFR), aspartate aminotransferase (AST), alanine aminotransferase (ALT), bone alkaline phosphatase (AP), beta2-microglobulin serum levels and proteinuria were analysed in 468 HIV-infected outpatients. Sera with detectable Macro CK2 were further analysed using immunoblotting.


RESULTS
CK-MB isoenzyme activity and mass concentration revealed the presence of Macro CK2 in 32/408 (7.8%) outpatients. Tenofovir DF (TDF) treatment was a prominent common feature in these patients. Prospective examination of sera from 41 patients collected prior to and during TDF exposure showed Macro CK2 in 20/41 (48%) TDF-treated patients and in 0/19 control sera from patients with TDF-free regimens. Macro CK2 was not present prior to TDF exposure. Patients with Macro CK2 showed a significant elevation of serum beta2-microglobulin levels. GFR, AST/ALT ratio, bone AP and proteinuria remained unchanged. Electrophoresis and immunoblotting demonstrated that the Macro CK2 in TDF-treated patients consisted of the ubiquitous (uMtCK) and not the sarcomeric type (sMtCK) of mitochondrial CK (MtCK).


CONCLUSIONS
Macro CK2 consisting of uMtCK is associated with the use of TDF-containing regimens. Whether the appearance of uMtCK in these patients reflects mitochondrial damage remains to be clarified.
Schmid
Holger
H
Medizinische Poliklinik, Ludwig Maximilians University Munich, Germany.
Mühlbayer
Dieter
D
Röling
Jörg
J
Sternfeld
Thomas
T
Jülg
Boris
B
Schlattner
Uwe
U
Nelson
Peter J
PJ
Bogner
Johannes R
JR
Wallimann
Theo
T
Goebel
Frank D
FD
D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D015331:Cohort Studies; D052281:Creatine Kinase, Mitochondrial Form / Q000737:chemistry* / Q000378:metabolism*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000201:enzymology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000009:adverse effects* / Q000627:therapeutic use; D000068698:Tenofovir
D019380:Anti-HIV Agents; D063065:Organophosphonates; D000068698:Tenofovir; D052281:Creatine Kinase, Mitochondrial Form; D000225:Adenine