Changes in metabolic toxicity after switching from stavudine/didanosine to tenofovir/lamivudine—a Staccato trial substudy

Objectives Stavudine is widely used in Thailand and is associated with mitochondrial toxicity. Here, we evaluated the effect of switching from stavudine/didanosine to tenofovir/lamivudine on measures of metabolic and mitochondrial toxicity in Thai patients. Methods Thirty-five Thai patients with ful...

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Bibliographic Details
Published in:	Journal of antimicrobial chemotherapy 2008-06, Vol.61 (6), p.1340-1343
Main Authors:	Ananworanich, Jintanat, Nuesch, Reto, Côté, Hélène C. F., Kerr, Stephen J., Hill, Andrew, Jupimai, Thidarat, Laopraynak, Naphassanant, Saenawat, Sukontha, Ruxrungtham, Kiat, Hirschel, Bernard
Format:	Article
Language:	eng
Subjects:	Absorptiometry, Photon Adenine - analogs & derivatives Adenine - toxicity Adult Anti-HIV Agents - administration & dosage Anti-HIV Agents - toxicity Antibiotics. Antiinfectious agents. Antiparasitic agents Antiretroviral drugs Biological and medical sciences Body Fat Distribution Comparative studies Didanosine - toxicity DNA, Mitochondrial - analysis HIV HIV Infections - drug therapy Human immunodeficiency virus Humans Lamivudine - toxicity Lipids - blood Liver Function Tests Medical sciences Mitochondrial DNA mitochondrial toxicity NRTIs Organophosphonates - toxicity Pharmacology Pharmacology. Drug treatments Ritonavir - administration & dosage RNA, Viral - blood Saquinavir - administration & dosage Side effects Stavudine - toxicity Tenofovir Thailand Toxicology
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Summary:	Objectives Stavudine is widely used in Thailand and is associated with mitochondrial toxicity. Here, we evaluated the effect of switching from stavudine/didanosine to tenofovir/lamivudine on measures of metabolic and mitochondrial toxicity in Thai patients. Methods Thirty-five Thai patients with full HIV RNA suppression were switched from stavudine/didanosine to tenofovir/lamivudine while receiving saquinavir/ritonavir 1600/100 mg once daily. Patients were assessed at the time of switch and 24 and 48 weeks after for lipids, liver enzymes, lactate, mitochondrial DNA content and limb/total fat mass by dual energy X-ray absorptiometry (DEXA) scanning. Results Forty-eight weeks after the switch, there were significant reductions in lipids and lactate, but no change in liver enzymes. There was reversal of lipoatrophy, as shown by rises in limb fat mass (+0.38 kg, P = 0.006) and total fat mass (+0.69 kg, P = 0.02) on DEXA scan. Patients perceived weight improvement, but did not report reversal of lipoatrophy of individual body parts. The mitochondrial DNA/nuclear DNA ratio rose (+1.06, P < 0.0001). Conclusions After the nucleoside reverse transcriptase inhibitor switch, reversal of mitochondrial toxicity was consistent with switch studies of mainly Caucasian patients, although the peripheral mononuclear cell mitochondrial DNA rise exceeded previous reports.
ISSN:	0305-7453 1460-2091