For participants with HIV taking either lopinavir or fosamprenavir who have elevated triglycerides, this trial will study the change in triglycerides after switching protease inhibitors.

This Phase IV trial will look at lipid and virologic responses after a switch to a more lipid-friendly antiretroviral regimen. Participants will be randomized to receive either boosted atazanavir or boosted darunavir given once daily, along with background NRTIs. This 24-week study will require 4 visits after randomization for evaluation, monitoring, and lab studies.

Inclusion Criteria:

• Currently receiving Antiretroviral Therapy (ART) regimen including LPV/r or FPV/r and > or equal to 2 Nucleoside Reverse Transcriptase Inhibitors (NRTIs). Patient must be on a stable regimen containing LPV/r or FPV/r for at least 12 weeks prior to screening.
• Documentation of an undetectable Human Immunodeficiency Virus (HIV) viral load (VL<400 copies/ml) using an FDA approved assay for a minimum of twelve weeks prior to screening AND undetectable HIV viral load using an FDA approved ultrasensitive assay at screening.
• No evidence of HIV protease resistance as defined by the Stanford HIV database
• Currently receiving first protease inhibitor unless switch to LPV/r or FPV/r was for non-virologic reasons
• Fasting triglycerides > 200 mg/dL
• No ongoing issues that in the opinion of the investigator would lead to decreased ability to comply with the study procedures
• If currently receiving a proton pump inhibitor, the dose is < omeprazole 20 mg or the equivalent dose of another proton pump inhibitor
• If patient is receiving another lipid lowering medication, it must be at a stable dose

Exclusion Criteria:

• Currently receiving an ART regimen other than > or equal to two NRTIs and either LPV/r or FPV/r

• Prior use of darunavir or atazanavir

• CDC Class C Illness diagnosed within 30 days of screening

• Patient is currently receiving the following Hydroxamethylglutaryl-coA (HMGCoA) reductase inhibitor medications (statins): pravastatin, lovastatin, simvastatin

• Patient is currently receiving a bile acid sequestrant (cholestyramine, colestipol, and colesevelam)

• Grade 3 or 4 Laboratory abnormalities as defined by a standardized grading scheme based on the DAIDS table with the following exceptions:

  1. Pre-existing diabetes mellitus with asymptomatic, nonfasting glucose grade 3 elevations
  2. Subjects with asymptomatic grade 3 fasting triglyceride or cholesterol elevations

• Clinical or laboratory evidence of clinically significant liver impairment/dysfunction disease or cirrhosis

• Note: Individuals co-infected with chronic hepatitis B or C viruses will be allowed to enter the trial if their condition is clinically stable and they will not require therapy during the course of the study. Individuals diagnosed with acute viral hepatitis at screening will not be allowed to enroll during acute phase

• Active substance abuse or significant psychiatric illness that in the opinion of the investigator might interfere with study compliance

• Use of any investigational agents 30 days prior to screening

• Life expectancy < 6 months in the opinion of the investigator

• Pregnancy or breast feeding

• Female subject of childbearing potential (i.e., heterosexually active, and not surgically sterile or at least two years post-menopausal) not using effective non-hormonal birth control methods or not willing to continue practicing these birth control methods from screening until the last trial related activity