Daily Trimethoprim-sulfamethoxazole or Weekly Chloroquine Among Adults on ART in Blantyre, Malawi (TSCQ)
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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Factorial Assignment
Masking: 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 Blantyre, Malawi|
- Severe events [ Time Frame: 2 to 3.5 years ] [ Designated as safety issue: No ]Incidence of severe events (composite of death and WHO stage 3 and 4 illness)
- HIV viral load [ Time Frame: Every 6 months for 2-3.5 years ] [ Designated as safety issue: No ]Incidence of detectable viral load (>400 copies/ml)
- CD4 cell count [ Time Frame: Every 6 months for 2-3.5 years ] [ Designated as safety issue: No ]CD4 cell counts compared among those on prophylaxis with TS or CQ versus no prophylaxis
- WHO HIV stage 2, 3, 4 illness [ Time Frame: 2 to 3.5 years ] [ Designated as safety issue: No ]Incidence of any WHO HIV stage 2, 3, or 4 illness
- Bacterial infections and malaria [ Time Frame: 2 to 3.5 years ] [ Designated as safety issue: No ]Incidence of bacterial infections and malaria
- Adverse events greater than or equal to Grade 3 that are related to the study product [ Time Frame: 2 to 3.5 years ] [ Designated as safety issue: Yes ]Occurrence of adverse events that are greater than or equal to Grade 3 that require discontinuation of TS or CQ prophylaxis
- Bacterial or malaria infection with CQ or TS resistant organism [ Time Frame: 2 to 3.5 years ] [ Designated as safety issue: No ]Occurrence of bacterial or malaria infection with CQ or TS resistant organism
- Clinical and parasitological response to antimalarial therapy [ Time Frame: 2 to 3.5 years ] [ Designated as safety issue: No ]Clinical and parasitological response to antimalarial therapy in cases of uncomplicated malaria
|Study Start Date:||November 2012|
|Estimated Study Completion Date:||April 2016|
|Estimated Primary Completion Date:||April 2016 (Final data collection date for primary outcome measure)|
Active Comparator: Standard of Care Prophylaxis (TS)
Standard of care prophylaxis with daily trimethoprim sulfamethoxazole (TS).
Drug: Standard of Care prophylaxis
Daily trimethoprim sulfamethoxazole
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.
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 and any time they are ill to facilitate both active and passive follow-up of the study endpoints. Participation will last for 24 to approximately 42 months. Participants who develop a WHO clinical stage 3 or 4 illness (see Appendix A for a complete listing), 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 900 Malawian adults aged 18 years or older living with HIV in or near Blantyre, 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. Participants must intend to stay in Blantyre for the entire study period.
|Blantyre Malaria Project Research Clinic||Recruiting|
|Contact: Randy Mungwira, MD +265-1-875-021 email@example.com|
|Contact: Jane Mallewa, MD +265 1-874-628 firstname.lastname@example.org|
|Sub-Investigator: Joep JG van Oosterhout, MD|
|Sub-Investigator: Matthew B Laurens, MD, MPH|
|Sub-Investigator: Terrie E Taylor, DO|
|Principal Investigator:||Miriam K Laufer, MD, MPH||University of Maryland, Baltimore County|