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

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

1499 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-11-30

Study Completion Date

2018-07-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Chloroquine for Malaria in Pregnancy

NCT01443130

Malaria

COMPLETED PHASE3

Discontinuation of Trimethoprim-sulfamethoxazole Prophylaxis in Adults on Antiretroviral Therapy in Kenya

NCT01425073

HIV Infections Acquired Immunodeficiency Syndrome Disease Progression +6 more

COMPLETED NA

Influence of Chloroquine on HIV Viral Load Among Pregnant Women in Uganda

NCT00132535

Malaria in Pregnancy HIV Infections

COMPLETED NA

Establishing Effectiveness of Daily Co-trimoxazole Prophylaxis For Prevention of Malaria in Pregnancy

NCT01053325

Malaria in Pregnancy HIV Infections

COMPLETED PHASE3

Improving PRegnancy Outcomes With PReVEntive Therapy in Africa-2 (IMPROVE-2)

NCT04158713

Pregnancy; HIV; Malaria

COMPLETED PHASE3

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

HIV

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Standard of Care Prophylaxis (TS)

Standard of care prophylaxis with daily trimethoprim sulfamethoxazole (TS).

Group Type ACTIVE_COMPARATOR

Standard of Care prophylaxis

Intervention Type DRUG

Daily trimethoprim sulfamethoxazole

Chloroquine (CQ) prophylaxis

Discontinuation of standard of care TS prophylaxis and starting weekly chloroquine prophylaxis

Group Type EXPERIMENTAL

Chloroquine (CQ) prophylaxis

Intervention Type DRUG

Discontinue standard of care and start weekly CQ.

Discontinuation of standard of care

Control arm - Discontinuation of standard of care trimethoprim sulfamethoxazole.

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Standard of Care prophylaxis

Daily trimethoprim sulfamethoxazole

Intervention Type DRUG

Chloroquine (CQ) prophylaxis

Discontinue standard of care and start weekly CQ.

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Bactrim Co-trimoxazole Aralen

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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
* 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

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No