HIV Care Research Programme / COSTOP trial

Lead Research Organisation: MRC/UVRI Uganda Research Unit on AIDS

Abstract

Various studies have shown that HIV infected patients benefit from daily prophylactic intake of cotrimoxazole tablets. This antibiotic drug has the effect of decreasing the death rate and the frequency of illnesses due to bacteria (so-called opportunistic infections) that are often seen in HIV patients. The drug has also some protective effect against malaria in such patients. However, all studies showing this effect have been conducted among HIV infected patients before the era of anti-retroviral therapy (ART). It is not known whether patients who receive ART and who have regained their immune competence (that is the ability to for example fight opportunistic infections) still need this prophylaxis, and whether it may be safely discontinued. If it were safe to discontinue the drug, patients would be less exposed to side effects of cotrimoxazole, the burden of pills they have to take would be reduced and the health system (and/or the patient) would save money. We will conduct a study in Uganda that will investigate whether cotrimoxazole can be safely discontinued. This trial will be conducted in 2000 patients who have taken ART for some time, and whose CD4 immune cells have increased to at least 250 cells. The study will begin in 2010 and take 4 years.

Technical Summary

The COSTOP trial is a randomised double blind placebo controlled non-inferiority trial to evaluate whether long-term primary and secondary prophylaxis with cotrimoxazole can be safely discontinued among Ugandan adults on antiretroviral therapy who have achieved sustained immune restoration (measured as a confirmed increase in CD4 count to 250 or more cells/mm3). Two thousand eligible patients will be randomised 1:1 to the experimental or control group. Patients in the experimental group will receive one oral tablet of placebo CTX daily, whilst patients in the control group will continue to take one oral tablet of 960 mg of CTX daily. All patients will continue to take their ART. There are two co-primary outcome measures, one for efficacy and one for safety. The efficacy outcome measure is defined as the time to the occurrence of the first clinical event (pre-defined CTX-preventable opportunistic clinical event or death). The safety outcome measure is the time to the occurrence of the first grade 3 or 4 haematological adverse event. Secondary outcome measures will include the incidence of all CTX preventable events, all cause mortality, the incidence of all clinical events and related events requiring hospitalisation, the incidence of all confirmed malaria episodes (asymptomatic and symptomatic), severity and outcome of all confirmed malaria episodes, the incidence of grade 3 or grade 4 adverse events, and others. COSTOP is a three year trial, recruitment into the trial will take place over 18 months and patients will be followed for a minimum of 18 and a maximum of 36 months. The project will begin on July 1, 2010 and end after 4 years. It is funded by the MRC (UK) and will be conducted by the MRC/UVRI Uganda Research Unit on AIDS at two research clinics in Entebbe and Masaka districts.
 
Description Uganda Ministry of Health - HIV Clinical Care Commitee
Geographic Reach Africa 
Policy Influence Type Participation in a national consultation
Impact Development and revision of National antiretroviral therapy guidelines based on data from a research cohort in Uganda
 
Description Partnership with The AIDS Support Organisation (TASO) 
Organisation The AIDS Support Organization (TASO)
Country Uganda 
Sector Charity/Non Profit 
PI Contribution MRC funded clinicians supplement patient care of TASO's HIV care clinic in Entebbe.
Collaborator Contribution Source of participants in clinical research. Contribution of ongoing pyschosocial support to people affected by HIV/AIDS who are also MRC research participants. Access to broad community outreach network for dissemination of information on research objectives and research outputs
Impact Overall enhancement of quality of HIV patient care in the Entebbe community as well as developing research capacity
 
Description Partnership with The AIDS Support Organisation (TASO), Entebbe Branch 
Organisation The AIDS Support Organization (TASO)
Country Uganda 
Sector Charity/Non Profit 
PI Contribution Joint provision of HIV clinical care services. Joint development, consultation, training on antiretroviral therapy provision
Collaborator Contribution Source of research participants from the organisations' membership. Contribution of pyschosocial support services to research participants. Contribution of community outreach networks for dissemination of research information and research results
Impact Acceptance and imbedding of MRC research teams and projects in the community. Facilitated communication with community members on MRC clinical research objectives and results
 
Description Uganda National Council of Science and Technology 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? Yes
Geographic Reach Local
Primary Audience Policymakers/politicians
Results and Impact National consultative meeting of research and medicines regulators to discuss ethical appropriateness of further trials on cotrimoxazole prophylaxis among HIV infected patients on antiretroviral therapy. We provided data on effect of Cotrimoxazole on haematologic parameters of untreated HIV infected adults.

A call was made for further studies evaluating continued prophylactic treatment with Cotrimoxazole for HIV infected patients on antiretroviral therapy
Year(s) Of Engagement Activity 2008