The purpose of this study is to look at two different antiretroviral treatment options in individuals who are about to commence their second antiretroviral treatment.

This study will assess important clinical and laboratory differences between these two therapeutic options. Potential differences include: differences in body fat distribution, in lipid parameters, in adherence and in neurocognitive (brain) function. This study is looking to show differences in body fat distribution between the two study treatment arms. Differences in lipids, viral load, adherence, cardiac and bone biomarkers and neurocognitive function will also be assessed. There is also a lumbar puncture sub study participants can also take part in.

The total duration of involvement in the trial will be up to 96 weeks (approximately 2 years) plus a screening visit 1 - 4 weeks prior to the start of the study. Including visit the clinic on 12 occasions (screening visit, baseline visit, weeks 2, 4, 8, 12, 24, 36, 48, 64, 80 and 96)

Inclusion Criteria:

• HIV-1 infected males or females
• over 18 years of age
• signed informed consent
• currently receiving a stable antiretroviral regimen comprising of:
• two or more licensed NRTIs
• one licensed NNRTI or boosted protease inhibitor
• no previous protease inhibitor resistance documented on HIV-1 genotypic resistance testing
• failure of current antiretroviral regimen due to:
• toxicity, intolerance or virological failure if receiving an NNRTI containing regimen at screening
• toxicity or intolerance if receiving a boosted-protease inhibitor regimen at screening (with plasma HIV RNA < 400 copies/mL at screening)
• willing to modify antiretroviral therapy, in accordance with the randomisation assignment
• no previous exposure to etravirine
• subjects in good health upon medical history, physical exam, and laboratory testing in the opinion of the investigator
• have no serologic evidence of active HBV infection evidenced by negative hepatitis B surface antigen
• female subjects who are heterosexually active and of childbearing potential (i.e., not surgically sterile or at least two years post menopausal) must practice contraception as follows from screening through completion of the study:
• barrier contraceptives (condom, diaphragm with spermicide)
• IUD or Depo PLUS a barrier contraceptive
• female subjects of childbearing potential must have a negative pregnancy test.

Exclusion Criteria:

• current alcohol abuse or drug dependence
• pregnancy
• active opportunistic infection or significant co-morbidities
• current prohibited concomitant medication
• a likelihood of diminished response to any of the study treatment arms, in the opinion of the investigator, based on HIV genotypic resistance testing