Impact of Antiretroviral Therapy on Metabolic, Skeletal, and Cardiovascular Parameters

A5260s is the optional, metabolic substudy of a phase III, prospective, randomized clinical
trial (A5257). For complete details about the parent study A5257, please see
ClinicalTrials.gov identifier NCT00811954.

Some participants in study A5257 were asked to participate in substudy A5260s. Not all
participants were asked since A5260s only took place at a subset of A5257 sites.
Participants who agreed to participate in substudy A5260s were enrolled at the same time as
their enrollment in A5257. No interventions were given as part of A5260s, but all A5260s
participants underwent blood draws, self-administered questionnaire responses (related to
physical activity and body image), ultrasound scans to measure the thickness of the carotid
artery in the neck and brachial artery flow mediated dilation in the arm, and computerized
topography (CT) and dual-energy x-ray absorptiometry (DEXA) scans to measure bone mineral
density and body fat.

The duration of A5260s study was between 2 and 3 years (96 and 144 weeks), depending on when
the participant enrolled. The study was designed to enroll a total of 330 participants with
at least 110 per a group; each group represented a different randomized drug combination as
defined and assigned by the main study A5257.

Cohort A: Atazanavir (ATV) + Ritonavir (RTV) + Emtricitabine/tenofovir disoproxil fumarate
(FTC/TDF)

Cohort B: Raltegravir (RAL) + FTC/TDF

Cohort C: Darunavir (DRV) + RTV + FTC/TDF

All participants were asked to return for A5260s clinic visits at weeks 4, 24, 48 96 and 144
and participated in all clinical evaluations. No clinical evaluation was restricted to a
subset of A5260s participants. If a participant chose to discontinue participation in the
substudy, the participant was able to continue in study A5257. However, a participant
discontinuing participation from A5257 was also removed from A5260s. Additionally, a
participant's decision to discontinue or switch study drugs in the main study did not impact
participation and follow-up clinic visits in A5260s.

Inclusion Criteria:

- Enrollment in A5257 and intent to enroll in A5001 (ALLRT)

- Signed informed consent

- For A5257 inclusion criteria, please see ClinicalTrials.gov identifier NCT00811954

Exclusion Criteria:

- Diabetes mellitus, (fasting plasma glucose ≥ 126 mg/dL on two occasions or on
hypoglycemic medications).

- Known cardiovascular disease (history of myocardial infarction [MI], coronary artery
bypass graft surgery, percutaneous coronary intervention, stroke, transient ischemic
attack, or peripheral arterial disease with ankle-brachial index of less than 0.9 or
claudication)

- Uncontrolled hypothyroidism or hyperthyroidism which in the opinion of the site
investigator would affect substudy participation

- Current use of statins, fish oil (greater than 2 grams per day), fibric acid
derivatives, or niacin (more than 1000 mg per day) (NOTE: Current use of fish oil and
niacin is defined as receiving treatment in the 8 weeks prior to study entry)

- Intention to start pharmacological or surgical intervention for weight loss

- Use of any ART in the 30 days before study entry

- For A5257 exclusion criteria, please see ClinicalTrials.gov identifier NCT00811954