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HIV Infections | Cotrimoxazole Prophylaxis Cessation Study Among Stabilized HIV-Infected Adult Patients on HAART in Entebbe, Uganda

HIV Infections research study

What is the primary objective of this study?

According to the national guidelines in Uganda and to the World Health Organization guidelines, HIV-infected patients should receive cotrimoxazole prophylaxis indefinitely. There are, however, concerns regarding the indefinite application of cotrimoxazole prophylaxis among patients immunologically stabilized on HAART (e.g. high pill burden, drug-drug interactions, toxicity and poor adherence because of treatment fatigue). To date no empirical evidence is available regarding the safety and optimal timing for the cessation of cotrimoxazole prophylaxis among HAART patients who successfully restored immunological competence. Research question: Does morbidity significantly differ between continuation (orthodox) and cessation (experimental) of cotrimoxazole prophylaxis among immuno-competent patients stable HAART in the resource-limited setting of Uganda?

Who is eligible to participate?

Inclusion Criteria: - Consenting HIV-infected patient aged 16 years or older, - Resident within 40 kms of study clinics - Regularly attending clinics - Documented HAART intake for at least 3 months - Clinically healthy and stable - Confirmed CD4 count of 200 cells/ul more. Exclusion Criteria: - Acutely ill patients with opportunistic or other infections - Patients already enrolled in other HAART trials (e.g DART trial) - First trimester pregnancy at enrolment - Clinical and immunological evidence of HAART treatment failure - Unable to attend study clinics regularly - Hypersensitivity to cotrimoxazole

Which medical condition, disease, disorder, syndrome, illness, or injury is researched?

HIV Infections

Study Interventions

Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.

Drug:cotrimoxazolecotrimoxazole 800/160 mg once daily as indicated by the start and end times of the specified arms for continued prevention of HIV-related infections

Drug:Placebostarch, magnesium stearate, sodium lauryl sulphate

Study Arms

Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.

1It will comprise patients randomized to receive the placebo (stop cotrimoxazole prophylaxis) at CD4 counts of 200 or more but less than 350 cells/ul as they continue with HAART. Patients will be followed until they achieve a CD4 count of 350 cells/ul.

2It will comprise patients randomized to continue with cotrimoxazole prophylaxis and HAART at CD4 counts of 200 or more but less than 350 cells/ul. These patients will be followed until they achieve a CD4 count of 350 cells/ul and above, at which point they will be considered for the second randomization.

AThis arm will comprise patients who have achieved a CD4 count of 350 or more cells/ul either at the beginning of the study or once they have reached this threshold at the end of follow up in arms 1 and 2. They (including those previously in Arm 1) will receive the placebo (stop cotrimoxazole prophylaxis) after the second randomization but continue with HAART.

BIt will comprise patients randomized to continue or start with cotrimoxazole prophylaxis and HAART at CD4 of 350 or more cells/ul after second randomization. Some of them will have used cotrimoxazole prophylaxis whilst they were in arm 2 and others in arm 1 will restart cotrimoxazole prophylaxis at this stage.

Study Status

Unknown status

Start Date: June 2008

Completed Date: June 2011

Phase: Phase 4

Type: Interventional

Design:

Primary Outcome: all-cause morbidity such as pneumonia or malaria (presumptive and definitive diagnosis)

Secondary Outcome: sub-clinical laboratory abnormalities (such as neutropenia) and serious adverse events (such as death)

Study sponsors, principal investigator, and references

Principal Investigator: George Miiro, MSc, MBChB

Lead Sponsor: MRC/UVRI Uganda Research Unit on Aids

Collaborator: Medical Research Council

More information:https://clinicaltrials.gov/show/NCT00674921

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