Study to Evaluate Changes in Limb Fat When Switching From a Thymidine Analogue

This is a phase II, open-label, multicentre, randomised, two-arm study of 48 weeks duration. One hundred HIV infected individuals who have documented lipodystrophy at > 1 body/facial site and currently receiving zidovudine (ZDV) or stavudine (d4T) will be recruited.

Inclusion criteria

• Subjects who are male or female > 18 years of age
• Subjects who are HIV-1 infected as documented by a licensed HIV-1 antibody ELISA
• Female subjects of childbearing potential must have a negative serum pregnancy test (beta-HCG) within 28 days of trial day 1. Women of childbearing potential must agree to use a barrier method of contraception
• Female subjects must not be pregnant or lactating
• Subjects who in the opinion of the investigator have the ability to understand and provided written informed consent to participate in the trial
• Subjects who in the opinion of the investigator have clinical lipoatrophy at > 1 body/facial site
• Subjects currently receiving nucleoside analogue regimen including stavudine (d4T) or zidovudine (ZDV)
• Subjects who are stable on current therapy for >16 weeks
• Subjects with no prior exposure to tenofovir, abacavir, or adefovir
• Subjects with no known K65R, 69S mutations or 3 or more thymidine analogue mutations
• Subjects with documented viral load <50 copies/ml on 2 consecutive occasions including most recent clinic attendance

Exclusion criteria

• Subjects who in the investigator's opinion are unlikely to complete the 48 week trial period
• Currently active opportunistic disease or documented wasting syndrome
• Currently receiving chemotherapy for malignancy
• Subjects who in the opinion of the investigator are unlikely to retain viral response after switching based on treatment or transmission history
• Currently receiving an insulin sensitising agent (glitazone or metformin)
• Anabolic steroids in the last 16 weeks other than testosterone at replacement doses (<250mg/2 weekly)
• Growth hormone use in the last 16 weeks
• Statin therapy (HMG CoA reductase inhibitor) commenced in the last 16 weeks (patients stable on statins my be included)
• Current alcohol or illicit drug use which, in the opinion of the investigator, may interfere with the subjects' ability to comply with the dosing schedule and protocol evaluations
• Receiving concurrent medications that - in the opinion of the investigator and according to drug product labelling - will result in clinically significant interactions with tenofovir or abacavir
• Pregnant or breast feeding
• Previously received more than 3 months zidovudine monotherapy