Comparison of nucleoside reverse transcriptase inhibitor use as part of first-line therapy in a Serbian and a UK HIV clinic.
BACKGROUND
Use of dideoxynucleoside reverse transcriptase inhibitors (dNRTIs) may lead to increased mitochondrial toxicity. We compared nucleoside reverse transcriptase inhibitor (NRTI) use as part of antiretroviral therapy (ART) in two HIV clinics: one in a low-middle income (HIV Centre Belgrade [HCB], Serbia) and one a high income (ICDC, Royal Free Hospital, London, UK) country.


METHODS
Antiretroviral naïve patients starting ART from 2003 to 2005 were included. Specific NRTIs were compared between centers, focusing on dNRTI use. Kaplan-Meier estimates of the percentage of patients making changes to their NRTI backbone (a) for any reason or (b) for mitochondrial toxicity (peripheral neuropathy, pancreatitis, lactic acidosis) were calculated.


RESULTS
Of 287 HCB patients, 89 (31.0%) received didanosine (ddI)-containing, 39 (13.6%) stavudine (d4T)-containing, and 39 (13.6%) ddI+d4T-containing regimens; for 539 ICDC patients, these were 18 (3.3%), 66 (12.2%), and 0 (0.0%), respectively (p < .0001). After 12 months, 57.5% and 52.6% at HCB and ICDC had switched their NRTI backbone. This was reduced to 34.5% at HCB after excluding changes due to drug supply interruption and to 11.2% and 1.3% at HCB and ICDC after changes were made for mitochondrial-related reasons. At 6 months, 73/80 (91.3%) and 385/488 (78.9%) had viral load below 50 copies/mL at HCB and ICDC, respectively.


CONCLUSIONS
Patients treated at HCB faced higher levels of mitochondrial-related toxicity, likely due to greater dNRTI use.
Dragovic
G J
GJ
Department of Pharmacology, Clinical Pharmacology, and Toxicology, School of Medicine, University of Belgrade, Belgrade, Serbia. gozza@beotel.net
Smith
C J
CJ
Jevtovic
D J
DJ
Johnson
M A
MA
Ranin
J
J
Salemovic
D
D
Youle
M S
MS
D000328:Adult; D016049:Didanosine / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006761:Hospitals; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000187:drug effects; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D055771:Serbia; D012959:Socioeconomic Factors; D018119:Stavudine / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome; D006113:United Kingdom
D018894:Reverse Transcriptase Inhibitors; D018119:Stavudine; D016049:Didanosine