Clinical trial NCT00819390
Conditions: HIV Infections
Sponsor: Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
Start date: 2009-03-01; Completion date: 2013-05-01
Enrollment: 70 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
HIV is characterized by frequent immune system activation. 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.

Evidence suggests that by decreasing the rate of immune system activation, immune deficiency progression could be prevented. The purpose of this study is to learn how well chloroquine can reduce the level of immune activation and to test the safety and tolerance of chloroquine in people infected with HIV.

Detailed description:
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 was 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, either off antiretroviral therapy (ART) (protocol version 1.0 dated December 17, 2008) or on-ART (protocol version 2.0 dated October 1, 2010). The off-ART (Arms A and B) and on-ART (Arms C and D) participants were enrolled during different time periods, and the study was designed to analyze the two study populations separately. This study also looked at how well chloroquine was tolerated and its safety in HIV- infected participants.

Off-ART participants in the study were randomized with equal probability to one of two treatment arms:

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

Arm B: Participants received 12 weeks of placebo followed by 12 weeks of chloroquine

On-ART participants in the study were randomized with equal probability to one of two treatment arms:

Arm C: Participants received 12 weeks of chloroquine treatment followed by 12 weeks of placebo

Arm D: Participants received 12 weeks of placebo followed by 12 weeks of chloroquine

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

Arms: arm 1: Participants received chloroquine treatment from Day 0 through the Week 12 study visit and then began chloroquine placebo treatment until the Week 24 study visit. arm 2: Participants received chloroquine placebo treatment from Day 0 through the Week 12 study visit and then began chloroquine treatment until the Week 24 study visit. arm 3: Participants received chloroquine treatment from Day 0 through the Week 12 study visit and then began chloroquine placebo treatment until the Week 24 study visit. arm 4: Participants received chloroquine placebo treatment from Day 0 through the Week 12 study visit and then began chloroquine treatment until the Week 24 study visit.
Interventions: intervention 1: Chloroquine intervention 2: Placebo
Intervention descriptions: intervention 1: Taken orally, once daily, at a dose of 250 mg for 12 weeks. intervention 2: Taken orally, once daily for 12 weeks.

Protocol documents: