The impact of reducing stavudine dose versus switching to tenofovir on plasma lipids, body composition and mitochondrial function in HIV-infected patients.
BACKGROUND
Stavudine (d4T)-containing regimens are associated with a potential for lipoatrophy and dyslipidaemia. We assessed the safety and efficacy of reducing the dose of stavudine compared with switching to tenofovir or maintaining the standard dose of d4T.


METHODS
Clinically stable HIV-infected patients receiving antiretroviral therapy containing stavudine 40 mg twice daily with a plasma HIV RNA < 200 copies/ml for at least 6 months were randomized to maintain stavudine 40 mg twice daily (d4T40 arm), to reduce to 30 mg twice daily (d4T30 arm), or to switch from d4T to tenofovir (TDF arm).


RESULTS
Fifty-eight (93% male) patients were included: 22 in the d4T40 arm, 19 in the d4T30 arm and 17 in TDF arm. At baseline, median time on d4T was 6 years (interquartile range [IQR] 2.6-7.1), median age 43 years (IQR 36-51) and median CD4+ T-cell count was 587/mm3 (IQR 329-892). At week 24, median limb fat changes (g) were as follows: d4T40 = -182 (95% CI: -469- -5); d4T30 = 527 (95% CI: -343-694); and TDF = 402 (95% CI: 130-835; d4T40 versus TDF, P = 0.0003). Significant differences between median values of laboratory parameters were detected: triglycerides (mg/dl): d4T40 = 19; d4T30 = -23 and TDF = -79 (d4T40 versus TDF, P = 0.03); and total cholesterol (mg/dl): d4t40 = 22, d4T30 = -4, and TDF = -28 (d4T40 versus TDF, P = 0.04). No significant difference was observed in mitochondrial function assessed in peripheral blood mononuclear cells.


CONCLUSIONS
Although both strategies were associated with a trend toward a decrease in plasma lipids and an increase in body fat, the only significant changes were observed among those who switched to tenofovir.
Milinkovic
Ana
A
Infectious Diseases Unit, Hospital Clinic Barcelona, Barcelona, Spain. anamilinkovic@hotmail.com
Martinez
Esteban
E
López
Sonia
S
de Lazzari
Elisa
E
Miró
Oscar
O
Vidal
Sergi
S
Blanco
José L
JL
Garrabou
Gloria
G
Laguno
Montserrat
M
Arnaiz
Joan A
JA
Leon
Agathe
A
Larrousse
Maria
M
Lonca
Montserrat
M
Mallolas
Josep
J
Gatell
José M
JM
D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001823:Body Composition; D002784:Cholesterol / Q000097:blood; D004334:Drug Administration Schedule; D005260:Female; D006678:HIV; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008060:Lipodystrophy / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism; D063065:Organophosphonates / Q000627:therapeutic use*; D010101:Oxygen Consumption; D018119:Stavudine / Q000009:adverse effects / Q000627:therapeutic use*; D000068698:Tenofovir; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood
D019380:Anti-HIV Agents; D063065:Organophosphonates; D014280:Triglycerides; D002784:Cholesterol; D000068698:Tenofovir; D018119:Stavudine; D000225:Adenine