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

Sponsor

University of Washington (Other)

Overall Status

Completed

CT.gov ID

NCT01425073

Collaborator

Kenya Medical Research Institute (Other)

500

Enrollment

Locations

Arms

Duration (Months)

250

Patients Per Site

12.5

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
HIV Infections Acquired Immunodeficiency Syndrome Disease Progression Immune System Diseases Malaria Parasitic Diseases Pneumonia Diarrhea Infectious Disorder of Immune System	Other: Discontinue TMP/SMZ prophylaxis	N/A

Detailed Description

Please see summary above.

Study Design

Study Type:

Interventional

Actual Enrollment :

500 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Feb 1, 2012

Actual Primary Completion Date :

Oct 1, 2013

Actual Study Completion Date :

Oct 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Stop TMP/SMZ 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 Subjects in the intervention arm will discontinue use of daily TMP/SMZ for the duration of the study Other Names: Septrin Septra Cotrimoxazole Bactrim
No Intervention: Standard of care TMP/SMZ prophylaxis Arm 2 will continue standard of care treatment with trimethoprim-sulfamethoxazole (TMP/SMZ) prophylaxis.

Arm

Intervention/Treatment

Experimental: Stop TMP/SMZ

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

Subjects in the intervention arm will discontinue use of daily TMP/SMZ for the duration of the study

Other Names:

Septrin

Septra

Cotrimoxazole

Bactrim

No Intervention: Standard of care TMP/SMZ prophylaxis

Arm 2 will continue standard of care treatment with trimethoprim-sulfamethoxazole (TMP/SMZ) prophylaxis.

Outcome Measures

Primary Outcome Measures

Incidence of severe infectious morbidity (malaria, pneumonia, diarrhea) [12 months]
A combined outcome of malaria, pneumonia or severe diarrhea.

Secondary Outcome Measures

CD4 count increase [12 months]
CD4 count increase
Rate of ART treatment failure [12 months]
Rate of ART treatment failure

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.