Changes in metabolic toxicity after switching from stavudine/didanosine to tenofovir/lamivudine--a Staccato trial substudy.
OBJECTIVE
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.
Ananworanich
Jintanat
J
The HIV Netherlands Australia Thailand Research Collaboration, Bangkok, Thailand. jintanat.a@hivnat.org
Nuesch
Reto
R
Côté
Hélène C F
HC
Kerr
Stephen J
SJ
Hill
Andrew
A
Jupimai
Thidarat
T
Laopraynak
Naphassanant
N
Saenawat
Sukontha
S
Ruxrungtham
Kiat
K
Hirschel
Bernard
B
D015502:Absorptiometry, Photon; D000225:Adenine / Q000031:analogs & derivatives* / Q000633:toxicity; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000633:toxicity*; D050218:Body Fat Distribution; D004272:DNA, Mitochondrial / Q000032:analysis; D016049:Didanosine / Q000633:toxicity*; D015658:HIV Infections / Q000188:drug therapy; D006801:Humans; D019259:Lamivudine / Q000633:toxicity*; D008055:Lipids / Q000097:blood; D008111:Liver Function Tests; D063065:Organophosphonates / Q000633:toxicity*; D012367:RNA, Viral / Q000097:blood; D019438:Ritonavir / Q000008:administration & dosage; D019258:Saquinavir / Q000008:administration & dosage; D018119:Stavudine / Q000633:toxicity*; D000068698:Tenofovir; D013785:Thailand
D019380:Anti-HIV Agents; D004272:DNA, Mitochondrial; D008055:Lipids; D063065:Organophosphonates; D012367:RNA, Viral; D019259:Lamivudine; D000068698:Tenofovir; D018119:Stavudine; D000225:Adenine; D016049:Didanosine; D019258:Saquinavir; D019438:Ritonavir