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

HIV Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00137657
• Other study ID #: CDC-NCID-3354
• Secondary ID: UR6/CCU018970-02
• Status: Completed
• Phase: Phase 4
• First received: August 29, 2005
• Last updated: December 12, 2005
• Start date: February 2002
• Est. completion date: November 2003

Study information

• Verified date: August 2005
• Source: Centers for Disease Control and Prevention
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1478
• Est. completion date: November 2003
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 15 Years and older

Eligibility

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.

Study Design

Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Educational/Counseling/Training

Related Conditions & MeSH terms

• Diarrhea
• HIV
• Malaria
• Opportunistic Infections
• Pneumonia

Intervention

Drug:
• Cotrimoxazole (trimethoprim sulfamethoxazole)

Locations

Country	Name	City	State
Kenya	CDC KEMRI Research Institute	Kisumu

Sponsors (2)

Lead Sponsor	Collaborator
Centers for Disease Control and Prevention	Kenya Medical Research Institute

Country where clinical trial is conducted

Kenya, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Plasmodium falciparum molecular markers of antifolate resistance before and while taking daily CTX
Primary	Change in nasopharyngeal pneumococcal resistance before and while taking daily CTX, and among children living in households where adults are taking daily CTX
Primary	Change in commensal E. coli resistance before and while taking daily CTX
Secondary	To measure CTX-resistance among Salmonella and other enteric bacterial pathogens in patients with diarrhea in the study area
Secondary	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
Secondary	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
Secondary	To assess the effect of daily CTX prophylaxis on the etiology of diarrheal diseases in HIV-infected persons
Secondary	To evaluate the serotype distribution of and immune response to colonizing pneumococci
Secondary	To assess the cause of diarrheal diseases among HIV-infected persons
Secondary	To measure the change in quality of life indicators among clients receiving daily CTX