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, 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. We 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, we 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.

Condition	Intervention	Phase
HIV Malaria Diarrhea Pneumonia Opportunistic Infections	Drug: Cotrimoxazole (trimethoprim sulfamethoxazole)	Phase IV

Further Study Details: 

Primary Outcomes: 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
Secondary Outcomes: 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.
Expected Total Enrollment:  1478

We conducted this study in Kisumu, Kenya where HIV prevelance 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.

Ages Eligible for Study:  15 Years and above,  Genders Eligible for Study:  Both

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), woman 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.

Kenya
      CDC KEMRI Research Institute, Kisumu,  Kenya

Study chairs or principal investigators

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

Study ID Numbers:  CDC-NCID-3354; UR6/CCU018970-02-2; SSC#664
Last Updated:  August 29, 2005
Record first received:  August 29, 2005
ClinicalTrials.gov Identifier:  NCT00137657
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-08-30