HIV Infections Clinical Research Study

What is the purpose of this study?

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.

Can I participate in this study?

You may be eligible for this study if you meet the following criteria:

• Conditions: HIV Infections
• Age: Between 18 - 65 Years
• Gender: Male or Female
• +

  Inclusion Criteria:

  HIV infected

  No antiretroviral therapy (ART) for at least 6 months prior to study entry and not

  likely to start within the 6 months after study entry

  CD4 count greater than or equal to 400 cells/mm3 at screening, obtained within 30 days

  prior to study entry

  For participants with previous ART use, documentation or recall of nadir CD4 cell

  count greater than or equal to 200 cells/mm3

  Viral load greater than or equal to 20,000 copies/mL obtained within 30 days prior to

  tudy entry

  Certain specified laboratory values obtained within 30 days prior to study entry. More

  information on this criterion can be found in the study protocol.

  Documentation that pre-entry specimen for the primary immune activation endpoint

  responses has been obtained

  Female participants of reproductive potential must have a negative pregnancy test

  performed within 24 hours prior to study entry

  If engaging in sexual activity, female participants must use adequate forms of

  contraception while receiving study treatment and for 4 weeks after stopping the

  treatment. More information on this criterion can be found in the study protocol.

  No history of CDC category C AIDS-related opportunistic infections

  Karnofsky performance score greater than or equal to 70 within 30 days prior to study

  entry

  Ability and willingness to provide informed consent
• +

  Exclusion Criteria:

  Continuous use of certain specified medication for more than 3 days within 30 days

  prior to study entry. More information on this criterion can be found in the study

  protocol.

  Use of chloroquine or hydroxychloroquine within 3 months prior to study entry

  Known history of hypersensitivity to 4-aminoquinoline compounds (such as chloroquine

  or hydroxychloroquine)

  Active drug or alcohol use or dependence that, in the opinion of the investigator

  would interfere with adherence to study requirements

  Serious illness requiring systemic treatment and/or hospitalization within 30 days

  prior to study entry

  Renal insufficiency, defined as serum creatinine greater than 1.5 mg/L, within 30 days

  prior to study entry

  History of retinal disease

  History of neoplasm other than localized squamous cell carcinoma of the skin

  Glucose-6-phosphate dehydrogenase (G6PD) deficiency at screening

  History of porphyria

  History of psoriasis

  History of cirrhosis

  History of seizure disorder

  A hearing threshold more than 25 decibels at any frequency from more than 250 hertz up

  to 4,000 hertz on screening pure-tone audiogram

  History of tinnitus or history of sudden hearing loss

  History of myopathy

  History of cardiac conduction abnormality or cardiomyopathy. More information on this

  criterion can be found in the study protocol.

Detail Study 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 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.

Study Treatments

Chloroquine, Placebo

Last Updated: March 2010