Impact of Cotrimoxazole Prophylaxis for HIV-Infected Adults on Antifolate Resistance

• ClinicalTrials.gov Identifier: NCT00137657
• Recruitment Status: Completed
• First Posted: August 30, 2005
• Last Update Posted: December 13, 2005
• Sponsor: Centers for Disease Control and Prevention
• Collaborator: Kenya Medical Research Institute
• Information provided by: Centers for Disease Control and Prevention

Tracking Information

• First Submitted Date: August 29, 2005
• First Posted Date: August 30, 2005
• Last Update Posted Date: December 13, 2005
• Study Start Date: February 2002
• Primary Completion Date: Not Provided

Current Primary Outcome Measures (submitted: November 23, 2005)

• Change in Plasmodium falciparum molecular markers of antifolate resistance before and while taking daily CTX
• Change in nasopharyngeal pneumococcal resistance before and while taking daily CTX, and among children living in households where adults are taking daily CTX
• Change in commensal E. coli resistance before and while taking daily CTX

Original Primary Outcome Measures (submitted: August 29, 2005)

• Change in Plasomdium falciparum molecular markers of antifolate resistance before and while taking daily CTX
• Change in nasopharyngeal pneumococcal resistance before and while taking daily CTX, and among children living in household where adults are taking daily CTX.
• Change in commensal E. coli resistance before and while taking daily CTX

Current Secondary Outcome Measures (submitted: November 23, 2005)

• To measure CTX-resistance among Salmonella and other enteric bacterial pathogens in patients with diarrhea in the study area
• To assess the efficacy of sulfadoxine-pyrimethamine (SP) treatment of breakthrough P. falciparum parasitemia and clinical malaria among HIV-infected persons taking daily CTX prophylaxis
• To measure sulfa metabolite levels in HIV-infected persons receiving daily CTX who develop a drug reaction, to determine if differing rates of metabolism contribute to the development of adverse reactions
• To assess the effect of daily CTX prophylaxis on the etiology of diarrheal diseases in HIV-infected persons
• To evaluate the serotype distribution of and immune response to colonizing pneumococci
• To assess the cause of diarrheal diseases among HIV-infected persons
• To measure the change in quality of life indicators among clients receiving daily CTX

Original Secondary Outcome Measures (submitted: August 29, 2005)

• To measure CTX-resistance among Salmonella and other enteric bacterial pathogens in patients with diarrhea in the study area.
• To assess the efficacy of SP treatment of breakthrough P. falciparum parasitemia and clinical malaria among HIV infected persons taking daily CTX prophylaxis
• To measure sulfa metabolite levels in HIV infected persons receiving daily CTX who develop a drug reaction, to determine if differing rates of metabolism contribute to the development of adverse reactions.
• To assess the effect of daily CTX prophylaxis on the etiology of diarrheal diseases in HIV-infected persons
• To evaluate the serotype distribution of and immune response to colonizing pneumococci
• To assess the cause of diarrheal diseases among HIV infected persons.
• To measure the change in quality of life indicators among clients receiving daily CTX.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Impact of Cotrimoxazole Prophylaxis for HIV-Infected Adults on Antifolate Resistance
• Official Title: An Evaluation of the Impact of Cotrimoxazole Prophylaxis for HIV-Infected Adults on the Development of Antifolate Resistance Among Plasmodium Falciparum, Streptococcus Pneumoniae, and Escherichia Coli
• Brief Summary: At least three studies in sub-Saharan Africa have demonstrated a decrease in morbidity or mortality among HIV-infected adults who took daily cotrimoxazole (trimethoprim sulfamethoxazole) [CTX] prophylaxis. Because of the demonstrated beneficial effect, high tolerability and low cost of CTX, the United Nations Programme on HIV/AIDS (UNAIDS) recommends that HIV-infected persons with symptomatic HIV or depressed CD4 counts receive daily CTX. The effect of this recommendation on subsequent development of antimicrobial resistance to antifolates among important pathogens needs to be evaluated. The investigators measured the change in the prevalence of markers of antifolate resistance among P. falciparum, and the change in the prevalence of CTX resistance among S. pneumoniae, and E. coli in HIV-infected individuals receiving CTX daily prophylaxis. In addition, the investigators measured the change in the prevalence of naso-pharyngeal or oro-pharyngeal carriage of CTX resistant S. pneumoniae among children living in households where an HIV-infected adult was receiving CTX daily prophylaxis.
• Detailed Description: We conducted this study in Kisumu, Kenya where HIV prevalence is high and malaria is highly endemic. HIV infected and uninfected adults were assigned to receive daily CTX if CD4 cell count was <350, or daily multivitamin if CD4 cell count was >= 350 or if the client was HIV negative. All clients were then followed for a total of 6 months. At specified scheduled and sick visits, clients received a physical exam, blood smears, nasopharyngeal swabs and stool samples or rectal swabs. Samples collected at baseline and during follow-up were used to measure the change in CTX resistance among P. falciparum parasites, pneumococcus isolates, and commensal E. coli.
• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Educational/Counseling/Training

Condition

• HIV
• Malaria
• Diarrhea
• Pneumonia
• Opportunistic Infections

• Intervention: Drug: Cotrimoxazole (trimethoprim sulfamethoxazole)
• Study Arms: Not Provided
• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Enrollment (submitted: August 29, 2005): 1478
• Original Enrollment: Same as current
• Study Completion Date: November 2003
• Primary Completion Date: Not Provided

Eligibility Criteria

Inclusion Criteria:

Clients presenting to the CRC HIV counseling and testing site in Kisumu were eligible for the study if they met the following inclusion criteria:

• 15 years of age or older
• Able to make all follow-up visits (i.e. do not plan to leave Kisumu during the next 6 months, are not homebound)
• Able to understand and give informed consent.

Exclusion Criteria:

Clients were not eligible for the study if they met any of the following exclusion criteria:

• Known allergic reaction to sulfa medications (i.e. CTX, sulfadoxine- pyrimethamine)
• Women in their first trimester of pregnancy or planning to become pregnant in the next 6 months
• Clients taking daily antibiotics for treatment of a chronic illness; or prophylaxis, excluding tuberculosis treatment.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 15 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Kenya

Administrative Information

• NCT Number: NCT00137657
• Other Study ID Numbers: CDC-NCID-3354; UR6/CCU018970-02-2; SSC#664
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Not Provided
• Study Sponsor: Centers for Disease Control and Prevention
• Collaborators: Kenya Medical Research Institute

Investigators

• Principal Investigator: Mary J Hamel, M.D.; Centers for Disease Control and Prevention

• PRS Account: Centers for Disease Control and Prevention
• Verification Date: August 2005