Chloroquine for Reducing Immune Activation in HIV- Infected Individuals
Condition: HIV Infections
MeSH terms: HIV Infections
Intervention: Chloroquine; Placebo
Intervention description: Taken orally, once daily, at a dose of 250 mg for 12 weeks.; Taken orally, once daily for 12 weeks.
Intervention MeSH terms: Chloroquine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 70.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  HIV-1 infected

          -  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.

          -  Ability and willingness to provide informed consent

        Additional Inclusion Criteria for Off-ART Participants:

          -  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 cell 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

          -  HIV-1 RNA viral load greater than or equal to 1,000 copies/mL obtained within 30 days
             prior to study entry

          -  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

        Additional Inclusion Criteria for On-ART Participants:

          -  Receiving ART, defined as a regimen that includes three or more antiretroviral
             medications, for at least 24 months prior to study entry

          -  Required documentation that all HIV-1 viral loads (at least two) were below 400
             copies/mL. More information on this criterion can be found in the study protocol.

          -  Screening HIV-1 RNA <200 copies/mL within 30 days prior to study entry. More
             information on this criterion can be found in the study protocol.

          -  CD4 cell count <350 cells/mm3 at screening, obtained within 30 days prior to study
             entry

        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/dL, within 30
             days prior to study entry

          -  History of retinal disease (i.e. confirmed retinopathy by ophthalmologic examination)

          -  History of neoplasm, within 5 years prior to study entry, other than treated in situ
             carcinoma or basal-cell or 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

          -  History of tinnitus (ear and/or head noise lasting more than 5 minutes that occurs
             more often than once per week) 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.

        Additional Exclusion Criteria for On-ART Participants:

        - Plans to change ART regimen with the 6 months after study entry (change in ART regimen is
        only permitted if due to toxicity)