Chloroquine for Reducing Immune Activation in HIV- Infected Individuals

• Number of CD38 molecules per cell on CD8 T lymphocytes minus the number of CD38 molecules per cell on CD8 T lymphocytes at baseline [ Time Frame: At Baseline and Week 10 or Week 12 ] [ Designated as safety issue: No ]
  

• Number of CD38 molecules per cell on CD8 T lymphocytes at the end of the 12-week period in the given arm when chloroquine treatment is given minus the number of CD38 molecules per cell on CD8 T lymphocytes at the beginning of that same period [ Time Frame: Before and after start of treatment ] [ Designated as safety issue: No ]
  
• Occurrence of a Grade 3 or higher event [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  
• RNA copies/mL at study entry and study Weeks 12 and 24 [ Time Frame: At Entry and at Weeks 12 and 24 ] [ Designated as safety issue: No ]
  
• Number of CD38 molecules per CD8 T lymphocytes at Week 24 minus the number of CD38 molecules per cell on CD8 T lymphocytes at study entry in Arm A [ Time Frame: At Entry and Week 24 ] [ Designated as safety issue: No ]
  
• Total CD4 T cell count at Week 12 minus total CD4 T cell count at study entry [ Time Frame: At Entry and Week 12 ] [ Designated as safety issue: No ]
  
• Number of CD38 molecules per CD8 T lymphocytes at Week 24 minus the number of CD38 molecules per cell on CD8 T lymphocytes at Week 12 in Arm A [ Time Frame: At Weeks 12 and 24 ] [ Designated as safety issue: No ]
  
• Proportion of CD3 CD8 T cells that express CD38 [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  
• Proportion of CD3 CD8 T cells that express CD38 and human leukocyte antigen (HLA) DR [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  
• Proportion of CD3 CD4 T cells that express CD38 and HLA DR [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  
• Bacterial 16s rDNA levels expressed as copies/mm^3 of plasma [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  
• The number of CD38 molecules per cell on CD8 T lymphocytes at Week 28 minus the number of Cd38 molecules per cell on CD8 T lymphocytes at the latest evaluation prior to receiving active chloroquine [ Time Frame: At Week 28 and most prior evaluation ] [ Designated as safety issue: No ]
  
• Fasting lipopolysaccharide LPS and bacterial 16s rDNA levels [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  
• Activation levels of pDC and mDC [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  
• The profile of gene expression in white blood cells at scheduled timepoints [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  

HIV is characterized by persistent immune system activation, and early in the course of infection the body establishes an immune activation "set point" related to the amount of HIV in the blood stream. This set point affects the rate of CD4 cell loss. Without CD4 cells, or with very low levels of CD4 cells, the body cannot fight off illness. This is known as immunodeficiency. If left untreated HIV can lead to extreme immunodeficiency and AIDS.

Immune system activation includes activating the CD8 cells. These cells attack body cells infected with viruses. Because of this, CD4 cells infected with HIV are frequently destroyed by CD8 cells. The purpose of this study is to learn how well chloroquine reduces the level of activation of CD8 cells in people infected with HIV. Increased activation of CD8 cells is thought to lead to a more severe path of disease in HIV infection.

The constant immune activation observed in HIV- infected patients has also been linked to higher levels of byproducts from certain naturally occurring bacteria found in the gut that are known to be immune stimulants. By decreasing the stimulation from these byproducts with chloroquine treatment, HIV disease may be slowed.

The purpose of this study is to learn how well chloroquine reduces the level of activation of CD8 cells and lowers the levels of bacteria byproducts in people infected with HIV. This study will also look at how well chloroquine is tolerated and its safety in HIV- infected patients.

Participants in this study will be randomly assigned to one of two treatment arms:

Arm A: Participants will receive 12 weeks of chloroquine treatment followed by 12 weeks of placebo

Arm B: Participants will receive 12 weeks of placebo followed by 12 weeks of chloroquine

Study treatment will be given once a day for a full 24 weeks. There will be an additional 4 weeks of follow-up for purposes of safety. After treatment has started, participants will be asked to come to the clinic on Weeks 4, 10, 12, 16, 22, and 24. At each visit participants will receive enough study treatment to last until the next visit. Each visit will last between 30 and 60 minutes. At most visits participants will have a physical exam, answer questions about any medications they are taking and how they are feeling, and have blood drawn for safety to assess CD4/CD8 cell counts and viral load. Some additional blood will also be stored for immunology testing. At some visits participants will be asked questions about their medication and medical history, have pupils dilated, have a hearing test, and have an electrocardiogram (EKG). Some visits will require participants to arrive fasting. Pregnancy tests may also be conducted if the participant is able to become pregnant or if pregnancy is suspected.