Short communication metabolic and mitochondrial effects of switching antiretroviral-experienced patients to enfuvirtide, tenofovir and saquinavir/ritonavir.
OBJECTIVE
Investigate the metabolic and mitochondrial effects of switching a highly active antiretroviral therapy (HAART) regimen with a high mitochondrial toxicity profile to a HAART with a theoretically low mitochondrial toxicity.


METHODS
Six consecutive HAART-experienced patients receiving at least one dideoxy-nucleoside reverse transcriptase inhibitor (NRTI) switched to enfuvirtide plus tenofovir plus saquinavir/ritonavir (T20+TDF+SQV/r). Blood samples were collected at baseline, 12 and 24 weeks after the switch, and viral load (VL) and lymphocyte CD4+ T-cell count were determined. Metabolic parameters consisted of fasting serum triglycerides, cholesterol (total and fractions), glucose, insulin, C-peptide and lactate. Mitochondrial assessment consisted on mitochondrial DNA (mtDNA) quantification, COX-II mitochondrial protein expression rate, mitochondrial respiratory chain complex III and IV activities, and oxygen consumption in peripheral blood mononuclear cells. For baseline mitochondrial comparisons, we included six HIV-infected patients naive for ART.


RESULTS
Switched patients exhibited a mean increase of 26 CD4+ T-cells/mm3 and a mean decrease of 1.1 log in VL (P = NS for both). Lactate, lipids and glycaemia remained stable during the study; only insulin levels increased significantly (P < 0.05). Switched patients exhibited, at baseline, low mitochondrial measurements, being significant only for complex III and IV activities with respect to naive patients (P < 0.05 for both). MtDNA content did not rise significantly during the study. However, we observed increases in COX-II mitochondrial protein synthesis (124%, P < 0.05), complex III activity (127%, P < 0.05), complex IV activity (86%, P = 0.37) and oxygen consumption (194%, P < 0.05).


CONCLUSIONS
Switching a HAART-containing dideoxy-NRTI to T20+TDF+SQV/r minimally alters metabolic parameters and exerts beneficial effects on mitochondrial function at 24 weeks. Mitochondrial improvement should be considered as an additional advantage of this rescue therapy.
Miró
Oscar
O
Mitochondrial Research Laboratory, Department of Internal Medicine, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Catalonia, Spain. omiro@clinic.ub.es
Garrabou
Glòria
G
López
Sònia
S
Deig
Elisabeth
E
Vidal
Immaculada
I
Infante
Anna B
AB
Cardellach
Francesc
F
Casademont
Jordi
J
Pedrol
Enric
E
D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D023241:Antiretroviral Therapy, Highly Active; D004272:DNA, Mitochondrial / Q000378:metabolism*; D014450:Electron Transport Complex III / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D000077560:Enfuvirtide; D005260:Female; D015700:HIV Envelope Protein gp41 / Q000009:adverse effects / Q000627:therapeutic use*; D023581:HIV Fusion Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D017320:HIV Protease Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007328:Insulin / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D063065:Organophosphonates / Q000009:adverse effects / Q000627:therapeutic use*; D010101:Oxygen Consumption; D010446:Peptide Fragments / Q000009:adverse effects / Q000627:therapeutic use*; D011446:Prospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D019438:Ritonavir / Q000009:adverse effects / Q000627:therapeutic use*; D019258:Saquinavir / Q000009:adverse effects / Q000627:therapeutic use*; D000068698:Tenofovir
D004272:DNA, Mitochondrial; D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; D017320:HIV Protease Inhibitors; D007328:Insulin; D063065:Organophosphonates; D010446:Peptide Fragments; D018894:Reverse Transcriptase Inhibitors; D000077560:Enfuvirtide; D000068698:Tenofovir; D003576:Electron Transport Complex IV; D014450:Electron Transport Complex III; D000225:Adenine; D019258:Saquinavir; D019438:Ritonavir