Randomized, Open-label Controlled Trial of Daily Trimethoprim-sulfamethoxazole or Weekly Chloroquine Among Adults on Anti-retroviral Therapy in Malawi
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 1,499
- 试验地点
- 2
- 主要终点
- Severe Events
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
研究组 & 干预措施
Standard of Care Prophylaxis (TS)
Standard of care prophylaxis with daily trimethoprim sulfamethoxazole (TS).
干预措施: Standard of Care prophylaxis (Drug)
Chloroquine (CQ) prophylaxis
Discontinuation of standard of care TS prophylaxis and starting weekly chloroquine prophylaxis
干预措施: Chloroquine (CQ) prophylaxis (Drug)
结局指标
主要结局
Severe Events
时间窗: 22-66 months
Incidence of severe events (composite of death and WHO stage 3 and 4 illness)
次要结局
- WHO HIV Stage 2, 3, 4 Illness(32-66 months)
- 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)
- 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)
研究者
Miriam Laufer
Associate Professor of Pediatrics
University of Maryland, Baltimore