title: Lack of recurrence of hyperlactatemia in HIV-infected patients switched from stavudine to abacavir or zidovudine.
abstract: Stavudine (d4T) has been observed in clinical trials and cohort studies to be more often implicated in cases of hyperlactatemia than other nucleoside reverse transcriptase inhibitors, possibly because of its relatively greater propensity to induce mitochondrial toxicity. The ESS40010 study was a 48-week, open-label, switch study that assessed changes in serum lactate levels and signs/symptoms of hyperlactatemia after substitution of abacavir (n = 86) or zidovudine (n = 32) for d4T in 118 virologically suppressed HIV-infected patients (HIV-1 RNA <400 copies/mL) who had developed serum lactate concentrations > or =2.2 mmol/L (n = 16) or had remained normolactatemic (n = 102) after receiving > or =6 months of d4T-based treatment. Median serum lactate decreased significantly below baseline at week 24 (-0.15 mmol/L, P = 0.0002) and week 48 (-0.15 mmol/L, P = 0.0015). In 10 hyperlactatemic patients in whom d4T was discontinued, serum HIV-1 RNA levels rebounded over the ensuing 31 days, but virologic suppression (HIV-1 RNA <400 copies/mL) was regained when treatment using abacavir or zidovudine was subsequently instituted. In the group with elevated lactate at baseline, symptoms of hyperlactatemia improved in 8% to 23% of patients, did not change in 69%, and worsened in 8%. Serum transaminases, which had been elevated while patients received d4T, normalized after d4T discontinuation and remained in the normal range after the switch to abacavir or zidovudine. Overall, in patients with d4T-associated hyperlactatemia, stopping d4T results in normalization of lactate and a rebound in viral load; restarting treatment using abacavir or zidovudine subsequently maintains normal lactate levels and rapidly leads to a return of virologic suppression.
authors.affiliation: Department of Medicine, Owen Clinic/University of California at San Diego Medical Center, 92103, USA. tlonergan@ucsd.edu
authors.forename: J Tyler
authors.initials: JT
authors.lastname: Lonergan
authors.forename: Grace A
authors.initials: GA
authors.lastname: McComsey
authors.forename: Robin L
authors.initials: RL
authors.lastname: Fisher
authors.forename: Peter
authors.initials: P
authors.lastname: Shalit
authors.forename: Thomas M
authors.initials: TM
authors.lastname: File
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Ward
authors.forename: Vanessa C
authors.initials: VC
authors.lastname: Williams
authors.forename: Siegrid M
authors.initials: SM
authors.lastname: Hessenthaler
authors.forename: Laura
authors.initials: L
authors.lastname: Lindsey
authors.forename: Jaime E
authors.initials: JE
authors.lastname: Hernandez
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D015224:Dideoxynucleosides / Q000627:therapeutic use*; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy*; D015497:HIV-1; D006801:Humans; D007773:Lactates / Q000097:blood*; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D018119:Stavudine / Q000627:therapeutic use*; D016896:Treatment Outcome; D019562:Viral Load; D015215:Zidovudine / Q000627:therapeutic use*; D000099227:Abacavir
chemical_list: D019380:Anti-HIV Agents; D015224:Dideoxynucleosides; D007773:Lactates; D018119:Stavudine; D015215:Zidovudine; D000099227:Abacavir