No significant effect of uridine or pravastatin treatment for HIV lipoatrophy in men who have ceased thymidine analogue nucleoside reverse transcriptase inhibitor therapy: a randomized trial.
BACKGROUND
Lipoatrophy can complicate thymidine analogue nucleoside reverse transcriptase inhibitor (tNRTI)-based antiretroviral therapy (ART). Lipoatrophy may be less likely with ART including ritonavir-boosted lopinavir (LPV/r). Small, placebo-controlled studies found that uridine (in tNRTI recipients) and pravastatin improved HIV lipoatrophy over 12 weeks. Today, most patients with lipoatrophy receive non-tNRTI-based ART; the effect of uridine in such patients is unknown.


METHODS
We performed a prospective, randomized trial in lipoatrophic adults with plasma HIV RNA<50 HIV-1 RNA copies/mL on tNRTI-sparing ART including LPV/r. Patients received uridine [36 g three times a day (tid) on 10 consecutive days per month; n=10], pravastatin [40 mg every night (nocte); n=12], uridine plus pravastatin (n=11) or neither (n=12) for 24 weeks. The primary endpoint was mean change in limb fat mass as assessed by dual-energy X-ray absorptiometry (DEXA). With 20 patients per intervention, the study had 80% power to detect a mean difference between a treatment and the control of 0.5 kg, assuming a standard deviation of 0.9 and an alpha threshold equal to 5% (two-sided).


RESULTS
Of 45 participants (all men, with median age 49.5 years and median limb fat 2.6 kg), two discontinued pravastatin and one participant stopped both pravastatin and uridine. The difference between the mean changes in limb fat mass for uridine vs. no uridine was 0.03 kg [95% confidence interval (CI) -0.35, +0.28; P=0.79]. The respective difference for pravastatin was -0.03 kg (95% CI -0.29, +0.34; P=0.84). Pravastatin slightly decreased total cholesterol (0.44 mmol/L; P=0.099). Visceral adipose tissue measured by computed tomography did not change significantly.


CONCLUSIONS
In this population and at the doses used, neither uridine nor pravastatin for 24 weeks significantly increased limb fat mass.
HIV, Immunology and Infectious Diseases Unit, Centre for Applied Medical Research, St Vincent's Hospital, Sydney, Australia. acalmy@gmail.com
A
A
Calmy
M
M
Bloch
H
H
Wand
C
C
Delhumeau
R
R
Finlayson
M
M
Rafferty
R
R
Norris
B
B
Hirschel
D A
DA
Cooper
A
A
Carr
D015502:Absorptiometry, Photon; D050154:Adiposity / Q000187:drug effects; D000328:Adult; D044966:Anti-Retroviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000924:Anticholesteremic Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D015224:Dideoxynucleosides / Q000009:adverse effects; D004359:Drug Therapy, Combination; D005121:Extremities; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy; D039682:HIV-Associated Lipodystrophy Syndrome / Q000139:chemically induced / Q000188:drug therapy*; D006801:Humans; D061466:Lopinavir; D008297:Male; D008875:Middle Aged; D017035:Pravastatin / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D011744:Pyrimidinones / Q000627:therapeutic use; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects; D019438:Ritonavir / Q000627:therapeutic use; D014529:Uridine / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*
D044966:Anti-Retroviral Agents; D000924:Anticholesteremic Agents; D015224:Dideoxynucleosides; D011744:Pyrimidinones; D018894:Reverse Transcriptase Inhibitors; D061466:Lopinavir; D017035:Pravastatin; D019438:Ritonavir; D014529:Uridine