Discontinuation of Trimethoprim-sulfamethoxazole Prophylaxis in Adults on Antiretroviral Therapy in Kenya

Study Overview
=================
Brief Summary
-----------------
Both antiretroviral therapy (ART) and prevention of opportunistic infections (OIs) have been associated with significantly decreased mortality in HIV-infected individuals. Trimethoprim-sulfamethoxazole (TMP/SMZ), also known as bactrim, is a common antibiotic and used as prophylaxis for OIs. For countries with high prevalence of HIV and limited health infrastructure, the WHO endorses universal TMP/SMZ for all HIV-infected individuals. Notably, these guidelines were created prior to the scale-up of ARTs. Following ART and subsequent immune recovery, TMP/SMZ may no longer be required. In the US and Europe, for example, TMP/SMZ is discontinued after patients show evidence of immune recovery. Therefore, we propose a prospective randomized trial among HIV infected individuals on ART with evidence of immune recovery (ART for > 18mo and CD4 >350 cells/mm3) to determine whether continued TMP/SMZ prophylaxis confers benefits in decreasing morbidity (malaria, pneumonia, diarrhea), mortality, CD4 count maintenance, ART treatment failure and malaria immune responses.

Detailed Description
-----------------
Please see summary above.

Official Title
-----------------
Discontinuation of Trimethoprim-sulfamethoxazole Prophylaxis in Adults on Antiretroviral Therapy in Kenya: a Randomized Trial

Conditions
-----------------
HIV Infections, Acquired Immunodeficiency Syndrome, Disease Progression, Immune System Diseases, Malaria, Parasitic Diseases, Pneumonia, Diarrhea, Infectious Disorder of Immune System

Intervention / Treatment
-----------------
* Other: Discontinue TMP/SMZ prophylaxis


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Participants must be at least 18 years of age. Participants must be willing to participate and give written informed consent. Participants must be willing and able to return for the scheduled follow-up visits. Participants must have been on ART for > 18 months. Participants must have a CD4 count of > 350 cells/mm3. Participants must not be suspected of ART treatment failure. Exclusion Criteria: Participants must not be pregnant at enrollment (by urine HCG testing). Participants must not be breastfeeding at the time of enrollment. Participants must be on first-line ART therapy as defined by Kenyan National Guidelines.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Stop TMP/SMZ<br>Arm 1 will have patients discontinue trimethoprim-sulfamethoxazole (TMP/SMZ) prophylaxis; patients will follow up every 3 months with study staff. | Other: Discontinue TMP/SMZ prophylaxis<br>* Subjects in the intervention arm will discontinue use of daily TMP/SMZ for the duration of the study<br>* Other names: Bactrim;|
| No Intervention: Standard of care TMP/SMZ prophylaxis<br>Arm 2 will continue standard of care treatment with trimethoprim-sulfamethoxazole (TMP/SMZ) prophylaxis. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of severe infectious morbidity (malaria, pneumonia, diarrhea) | A combined outcome of malaria, pneumonia or severe diarrhea. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CD4 count increase | CD4 count increase | 12 months | 
| Rate of ART treatment failure | Rate of ART treatment failure | 12 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
HIV, Co-Infections, Malaria, Pneumonia, Diarrhea