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

NCT01650558 | Completed Results DMC

• 2 other identifiers: HP-00043360; DAIDS ES-10822U01AI089342-01A1
• Study Type: interventional
• Target: 1,499
• Locations: 1 country
• Sites: 2

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.

Conditions

HIV

Keywords

Malaria; HIV; Prophylaxis; Antiretroviral therapy

Outcome Measures

Primary Outcomes (1)

• Severe Events

  Incidence of severe events (composite of death and WHO stage 3 and 4 illness)

  22-66 months

Secondary Outcomes (5)

• Number of Participants With at Least One Detectable HIV Viral Load

  Throughout study participation, measured every six months (2-5.5 years).

• CD4 Cell Count

  Every 6 months for 22-66 months

• WHO HIV Stage 2, 3, 4 Illness

  32-66 months

• Bacterial Infections and Malaria

  32-66 months

• Adverse Events Greater Than or Equal to Grade 3 That Are Related to the Study Product

  32-66 months

Other Outcomes (2)

• Bacterial or Malaria Infection With CQ or TS Resistant Organism

  32-66 months

• Clinical and Parasitological Response to Antimalarial Therapy

  32-66 months

Study Arms (3)

Standard of Care Prophylaxis (TS)

ACTIVE COMPARATOR

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

Drug: Standard of Care prophylaxis

Chloroquine (CQ) prophylaxis

EXPERIMENTAL

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

Drug: Chloroquine (CQ) prophylaxis

Discontinuation of standard of care

NO INTERVENTION

Control arm - Discontinuation of standard of care trimethoprim sulfamethoxazole.

Interventions

Standard of Care prophylaxis DRUG

Daily trimethoprim sulfamethoxazole

Also known as: Bactrim, Co-trimoxazole

Standard of Care Prophylaxis (TS)

Chloroquine (CQ) prophylaxis DRUG

Discontinue standard of care and start weekly CQ.

Also known as: Aralen

Chloroquine (CQ) prophylaxis

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Maryland, Baltimore: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (2)

Blantyre Malaria Project Research Clinic

Blantyre, Malawi

Location

Tisungane Clinic

Zomba, Malawi

Location

Related Publications (3)

• Laurens MB, Mungwira RG, Nampota N, Nyirenda OM, Divala TH, Kanjala M, Mkandawire FA, Galileya LT, Nyangulu W, Mwinjiwa E, Downs M, Tillman A, Taylor TE, Mallewa J, Plowe CV, van Oosterhout JJ, Laufer MK. Revisiting Co-trimoxazole Prophylaxis for African Adults in the Era of Antiretroviral Therapy: A Randomized Controlled Clinical Trial. Clin Infect Dis. 2021 Sep 15;73(6):1058-1065. doi: 10.1093/cid/ciab252.

  PMID: 33744963 BACKGROUND

• Mungwira RG, Laurens MB, Nyangulu W, Divala TH, Nampota-Nkomba N, Buchwald AG, Nyirenda OM, Mwinjiwa E, Kanjala M, Galileya LT, Earland DE, Adams M, Plowe CV, Taylor TE, Mallewa J, van Oosterhout JJ, Laufer MK; TSCQ Study Team. High burden of malaria among Malawian adults on antiretroviral therapy after discontinuing prophylaxis. AIDS. 2022 Oct 1;36(12):1675-1682. doi: 10.1097/QAD.0000000000003317. Epub 2022 Jul 15.

  PMID: 35848575 DERIVED

• Laurens MB, Mungwira RG, Nyirenda OM, Divala TH, Kanjala M, Muwalo F, Mkandawire FA, Tsirizani L, Nyangulu W, Mwinjiwa E, Taylor TE, Mallewa J, Blackwelder WC, Plowe CV, Laufer MK, van Oosterhout JJ. TSCQ study: a randomized, controlled, open-label trial of daily trimethoprim-sulfamethoxazole or weekly chloroquine among adults on antiretroviral therapy in Malawi: study protocol for a randomized controlled trial. Trials. 2016 Jul 18;17(1):322. doi: 10.1186/s13063-016-1392-3.

  PMID: 27431995 DERIVED

MeSH Terms

Conditions

Malaria

Interventions

Trimethoprim, Sulfamethoxazole Drug Combination; Chloroquine

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Sulfamethoxazole; Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Sulfanilamides; Aniline Compounds; Amines; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Trimethoprim; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Drug Combinations; Pharmaceutical Preparations; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Miriam K. Laufer, M.D., M.P.H.
• Organization: University of Maryland School of Medicine

mlaufer@som.umaryland.edu

410-706-5333

Study Officials

• Miriam K Laufer, MD, MPH

  University of Maryland, Baltimore

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Pediatrics

Study Record Dates

• First Submitted: July 6, 2012
• First Posted: July 26, 2012
• Study Start: November 1, 2012
• Primary Completion: July 31, 2018
• Study Completion: July 31, 2018
• Last Updated: July 28, 2022
• Results First Posted: May 19, 2021

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

MA (2)