HIVTSCQNCT01650558
Daily Trimethoprim-sulfamethoxazole or Weekly Chloroquine Among Adults on ART in Malawi
A study testing Chloroquine (CQ) prophylaxis in people with HIV, run by University of Maryland, Baltimore at 2 sites in Malawi.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV
- What is being tested?
- Chloroquine (CQ) prophylaxis
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,499 participants
- Where
- 2 sitesMalawi
- Study dates
- Nov 2012to 31 Jul 2018
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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
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- 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
Trial locations and contacts
2 sites in 1 country.
Malawi2 sites
Blantyre Malaria Project Research Clinic
Blantyre
Tisungane Clinic
Zomba
About this study
Official title: Randomized, Open-label Controlled Trial of Daily Trimethoprim-sulfamethoxazole or Weekly Chloroquine Among Adults on Anti-retroviral Therapy in Malawi
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.
Read the 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.
- Conditions
- HIV
- Being tested
- Standard of Care prophylaxis, Chloroquine (CQ) prophylaxis
- Keywords
- Malaria, HIV, Prophylaxis, Antiretroviral therapy
- Medical subject headings
- Malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Standard of Care prophylaxisDrug
Also called Bactrim, Co-trimoxazole
Daily trimethoprim sulfamethoxazole
Chloroquine (CQ) prophylaxisDrug
Also called Aralen
Discontinue standard of care and start weekly CQ.
| Study group | Role | What they receive |
|---|---|---|
| Standard of Care Prophylaxis (TS) | Active comparator | Standard of care prophylaxis with daily trimethoprim sulfamethoxazole (TS). Receives: Drug: Standard of Care prophylaxis |
| Chloroquine (CQ) prophylaxis | Experimental | Discontinuation of standard of care TS prophylaxis and starting weekly chloroquine prophylaxis Receives: Drug: Chloroquine (CQ) prophylaxis |
| Discontinuation of standard of care | No intervention | Control arm - Discontinuation of standard of care trimethoprim sulfamethoxazole. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Severe Events
Incidence of severe events (composite of death and WHO stage 3 and 4 illness)
Measured: 22-66 months
Secondary outcomes (5)
Number of Participants With at Least One Detectable HIV Viral Load
Number of participants who ever have a detectable viral load (>400 copies/ml).
Measured: Throughout study participation, measured every six months (2-5.5 years).
CD4 Cell Count
Number of Participants with at Least One CD4 Count <200
Measured: Every 6 months for 22-66 months
WHO HIV Stage 2, 3, 4 Illness
Incidence of any WHO HIV stage 2, 3, or 4 illness
Measured: 32-66 months
Bacterial Infections and Malaria
Incidence of bacterial infections and malaria
Measured: 32-66 months
Adverse Events Greater Than or Equal to Grade 3 That Are Related to the Study Product
Occurrence of adverse events that are greater than or equal to Grade 3 that require discontinuation of TS or CQ prophylaxis
Measured: 32-66 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jul 2012 (estimated)
- Study startNov 2012
- Primary completion31 Jul 2018
- Study completion31 Jul 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for HIVStudies of the same condition, open and under way.
- More trials run by University of Maryland, BaltimoreThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Enrolment
- 1,499 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Maryland, Baltimore
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Miriam Laufer, University of Maryland, Baltimore
- Investigators
- Miriam K Laufer, MD, MPH, Principal investigator, University of Maryland, Baltimore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01650558
- Sponsor's protocol ID
- HP-00043360; DAIDS ES-10822
- Other IDs
- U01AI089342-01A1
- Acronym
- TSCQ
- Status last verified
- Jul 2022
- First submitted
- 6 Jul 2012
- Last updated
- 28 Jul 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 33744963Mungwira 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.
PubMed 35848575Laurens 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.
PubMed 27431995
Study at a glance
From the registry record, last updated by the sponsor on 28 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized, Open-label Controlled Trial of Daily Trimethoprim-sulfamethoxazole or Weekly Chloroquine Among Adults on Anti-retroviral Therapy in Malawi
- ClinicalTrials.gov ID
- NCT01650558
- Acronym / sponsor ID
- TSCQ / HP-00043360; DAIDS ES-10822
- Conditions
- HIV
- Keywords
- Malaria, HIV, Prophylaxis, Antiretroviral therapy
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,499 participants (actual)
- Lead sponsor
- University of Maryland, BaltimoreUniversity, hospital or other
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID)
- Study start
- Nov 2012
- Primary completion
- 31 Jul 2018 (actual)
- Study completion
- 31 Jul 2018 (actual)
- First posted
- 26 Jul 2012 (estimated)
- Results
- Posted 19 May 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Standard of Care Prophylaxis (TS) | Active comparator | Drug: Standard of Care prophylaxisStandard of care prophylaxis with daily trimethoprim sulfamethoxazole (TS). |
| Chloroquine (CQ) prophylaxis | Experimental | Drug: Chloroquine (CQ) prophylaxisDiscontinuation of standard of care TS prophylaxis and starting weekly chloroquine prophylaxis |
| Discontinuation of standard of care | No intervention | –Control arm - Discontinuation of standard of care trimethoprim sulfamethoxazole. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Standard of Care prophylaxisAlso: Bactrim, Co-trimoxazoleDaily trimethoprim sulfamethoxazole | Drug | Standard of Care Prophylaxis (TS) |
| Chloroquine (CQ) prophylaxisAlso: AralenDiscontinue standard of care and start weekly CQ. | Drug | Chloroquine (CQ) prophylaxis |
Primary outcome
Severe Events
Time frame: 22-66 months
Incidence of severe events (composite of death and WHO stage 3 and 4 illness)
5 secondary outcomes
Number of Participants With at Least One Detectable HIV Viral Load
Time frame: Throughout study participation, measured every six months (2-5.5 years).
CD4 Cell Count
Time frame: Every 6 months for 22-66 months
WHO HIV Stage 2, 3, 4 Illness
Time frame: 32-66 months
Bacterial Infections and Malaria
Time frame: 32-66 months
Adverse Events Greater Than or Equal to Grade 3 That Are Related to the Study Product
Time frame: 32-66 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jul 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 33744963Laurens 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.
- Derived from this study: PubMed 35848575Mungwira 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.
- Derived from this study: PubMed 27431995Laurens 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Miriam K Laufer, MD, MPH principal investigator
University of Maryland, Baltimore
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Chloroquine (CQ) prophylaxis in people with HIV, run by University of Maryland, Baltimore at 2 sites in Malawi.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Malawi. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 May 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Severe Events (time frame: 22-66 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01650558, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jul 2022.