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Daily Trimethoprim-sulfamethoxazole or Weekly Chloroquine Among Adults on ART in Malawi (TSCQ)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01650558
Recruitment Status : Completed
First Posted : July 26, 2012
Last Update Posted : March 29, 2019
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party):
Miriam Laufer, University of Maryland

Brief Summary:

The purpose of this study is to determine if there is a benefit to taking trimethoprim-sulfamethoxazole (TS) as prophylaxis among HIV positive adults who have viral load suppression and a good clinical response on anti-retroviral therapy (ART). If there is a benefit, then is it due to antimalarial or antibacterial properties.

The investigators hypothesize that there will be a long-term benefit on survival and disease control in the context of prophylaxis and that the benefit will largely be attributed to prevention of malaria. The main study hypothesis is that 1)TS and chloroquine (CQ) will decrease the rates of morbidity and mortality among adults after 6 or more months of ART and 2) CQ prophylaxis will be associated with more prolonged viral suppression and higher CD4 cell counts than TS prophylaxis or no prophylaxis.

Condition or disease Intervention/treatment Phase
HIV Drug: Standard of Care prophylaxis Drug: Chloroquine (CQ) prophylaxis Not Applicable

Detailed Description:

This is a randomized, controlled, open-label, phase III trial of standard of care TS prophylaxis and CQ prophylaxis compared to no prophylaxis in adults receiving ART. Adults who have been receiving ART for at least six months with a good clinical response and provide informed consent and fulfill the eligibility criteria will be randomized to one of three arms: (1) to continue standard of care trimethoprim-sulfamethoxazole (TS) prophylaxis, (2) discontinue standard of care TS prophylaxis and begin weekly CQ prophylaxis or (3) discontinue standard of care TS prophylaxis. Participants will be asked to return to the research clinic every four weeks for the first 24 weeks then every 12 weeks thereafter, and any time they are ill to facilitate both active and passive follow-up of the study endpoints. Participation will last for 32 to approximately 66 months. Participants who develop a WHO clinical stage 3 or 4 illness, experience a sustained decline in their CD4 count below 200 cells/mm3, or who experience ART failure will be placed on standard of care TS prophylaxis. Those with confirmed ART failure will be evaluated for second-line therapy according to the Malawi Ministry of Health guidelines.

The study population will include up to 1500 Malawian adults aged 18 years or older living with HIV in or near Blantyre or Zomba, Malawi, Central Africa who have been receiving antiretroviral therapy for at least 6 months with good clinical response to ART, have an undetectable HIV viral load and a CD4 count >250/mm3.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1499 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Randomized, Open-label Controlled Trial of Daily Trimethoprim-sulfamethoxazole or Weekly Chloroquine Among Adults on Anti-retroviral Therapy in Malawi
Study Start Date : November 2012
Actual Primary Completion Date : July 31, 2018
Actual Study Completion Date : July 31, 2018

Arm Intervention/treatment
Active Comparator: Standard of Care Prophylaxis (TS)
Standard of care prophylaxis with daily trimethoprim sulfamethoxazole (TS).
Drug: Standard of Care prophylaxis
Daily trimethoprim sulfamethoxazole
Other Names:
  • Bactrim
  • Co-trimoxazole

Experimental: Chloroquine (CQ) prophylaxis
Discontinuation of standard of care TS prophylaxis and starting weekly chloroquine prophylaxis
Drug: Chloroquine (CQ) prophylaxis
Discontinue standard of care and start weekly CQ.
Other Name: Aralen

No Intervention: Discontinuation of standard of care
Control arm - Discontinuation of standard of care trimethoprim sulfamethoxazole.

Primary Outcome Measures :
  1. Severe events [ Time Frame: 32-66 months ]
    Incidence of severe events (composite of death and WHO stage 3 and 4 illness)

Secondary Outcome Measures :
  1. HIV viral load [ Time Frame: Every 6 months for 32-66 months ]
    Incidence of detectable viral load (>400 copies/ml)

  2. CD4 cell count [ Time Frame: Every 6 months for 32-66 months ]
    CD4 cell counts compared among those on prophylaxis with TS or CQ versus no prophylaxis

  3. WHO HIV stage 2, 3, 4 illness [ Time Frame: 32-66 months ]
    Incidence of any WHO HIV stage 2, 3, or 4 illness

  4. Bacterial infections and malaria [ Time Frame: 32-66 months ]
    Incidence of bacterial infections and malaria

  5. Adverse events greater than or equal to Grade 3 that are related to the study product [ Time Frame: 32-66 months ]
    Occurrence of adverse events that are greater than or equal to Grade 3 that require discontinuation of TS or CQ prophylaxis

Other Outcome Measures:
  1. Bacterial or malaria infection with CQ or TS resistant organism [ Time Frame: 32-66 months ]
    Occurrence of bacterial or malaria infection with CQ or TS resistant organism

  2. Clinical and parasitological response to antimalarial therapy [ Time Frame: 32-66 months ]
    Clinical and parasitological response to antimalarial therapy in cases of uncomplicated malaria

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Age 18 years or older
  • Documented HIV-1 infection
  • Initiation of ART through a government-sponsored ART program at least six months prior
  • Undetectable HIV viral load (< 400 copies/mL)
  • CD4 count > 250/mm3
  • TS prophylaxis prescribed for at least the previous 2 months
  • Intention to remain in the study area until the end of the study period
  • Informed consent from participant
  • Female study volunteers of reproductive potential must have a negative urine pregnancy test performed within 20 days before randomization.
  • Female study volunteers of reproductive potential who participate in sexual activity that could lead to pregnancy must use contraception (male or female condoms, diaphragm or cervical cap with spermicide, intrauterine device, or hormone-based contraceptive) while receiving their assigned study drug and for one month after stopping the medications.

Exclusion Criteria:

  • Severe acute illness (defined as requiring hospitalization at the time of screening or other conditions such as laboratory abnormalities as determined by the investigators)
  • Chronic treatment (requiring therapy for > 14 days) or secondary prophylaxis (for toxoplasmosis, Pneumocystis pneumonia, or tuberculosis for example) with any drug with antimalarial or antibacterial activity
  • History of hypersensitivity to antifolate drugs or CQ
  • Laboratory exclusion criteria
  • Hemoglobin < 8.0 gm/dL
  • Platelet count < 50,000/mm3
  • Absolute granulocyte count < 500/mm3
  • Serum alanine aminotransferase (ALT) concentration > 210 U/L for men, >160 U/L for women
  • Serum creatinine concentration > 3.3mg/dl (291.7µmol/L) for men, and > 2.7mg/dl (238.7µmol/L) for women)
  • History of visual field or retinal changes
  • History of preexisting auditory damage
  • History of porphyria
  • History of psoriasis
  • History of liver disease
  • History of seizure disorder
  • History of glucose-6-phosphate dehydrogenase (G6PD) deficiency
  • History of ECG and cardiac conduction abnormality or cardiomyopathy
  • History of myopathy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01650558

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Blantyre Malaria Project Research Clinic
Blantyre, Malawi
Tisungane Clinic
Zomba, Malawi
Sponsors and Collaborators
University of Maryland
National Institute of Allergy and Infectious Diseases (NIAID)
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Principal Investigator: Miriam K Laufer, MD, MPH University of Maryland

Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Miriam Laufer, Associate Professor of Pediatrics, University of Maryland Identifier: NCT01650558     History of Changes
Other Study ID Numbers: HP-00043360; DAIDS ES-10822
U01AI089342-01A1 ( U.S. NIH Grant/Contract )
First Posted: July 26, 2012    Key Record Dates
Last Update Posted: March 29, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Miriam Laufer, University of Maryland:
Antiretroviral therapy

Additional relevant MeSH terms:
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Chloroquine diphosphate
Trimethoprim, Sulfamethoxazole Drug Combination
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Antirheumatic Agents
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antinematodal Agents
Anti-Infective Agents, Urinary
Renal Agents
Folic Acid Antagonists
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Dyskinesia Agents
Cytochrome P-450 CYP2C8 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Anti-Bacterial Agents