Impact of Antiretroviral Therapy on Metabolic, Skeletal, and Cardiovascular Parameters
Impact of Antiretroviral Therapy on Metabolic, Skeletal, and Cardiovascular Parameters
The U.S. Department of Health and Human Services (HHS) guidelines recommend that HIV-infected
 people who have never received anti-HIV therapy be treated with a triple drug regimen
 (commonly called combination antiretroviral therapy, cART). Since the introduction of cART,
 morbidity and mortality among HIV-infected patients has been dramatically reduced. However,
 metabolic, skeletal, and cardiovascular diseases have been increasingly reported among
 HIV-infected patients and may be attributable, in part, to the direct effects of cART. Much
 of our understanding of the development of these diseases, risk factors, and consequences of
 these disorders has been derived from clinical studies of HIV-infected persons receiving
 older antiretroviral agents.

 A5260s was designed to examine the contributions of HIV-disease related factors and impact of
 newer antiretroviral drugs on the development of metabolic (such as blood vessels, blood
 sugar, cholesterol), skeletal, and cardiovascular diseases in people who have never received
 anti-HIV therapy. A5260s is a prospective substudy of a phase III randomized clinical trial
 A5257 (see ClinicalTrials.gov identifier: NCT00811954). A5257 was designed to look at
 different combinations of anti-HIV drugs that do not contain the medication efavirenz (EFV)
 and how well these drug combinations work to decrease the amount of HIV in the blood and to
 allow immune system recovery in people who have never received anti-HIV therapy. A5257 also
 examined drug tolerability and safety for the various drug combinations.
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