Clinical trial NCT00137657: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: HIV
Malaria
Diarrhea
Pneumonia
Opportunistic Infections
Keywords: HIV
malaria
E. Coli
S. pneumoniae
drug resistance
antifolate
opportunistic infections
Africa
Kenya
East Africa
Lead sponsor: Centers for Disease Control and Prevention
Sponsor class: FED
Collaborators: name: Kenya Medical Research Institute
First posted: 2005-08-30
Enrollment: 1478
Sex: ALL
Minimum age (years): 15
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: ECT

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.

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.

Primary outcomes:
measure: Change in Plasmodium falciparum molecular markers of antifolate resistance before and while taking daily CTX
measure: Change in nasopharyngeal pneumococcal resistance before and while taking daily CTX, and among children living in households where adults are taking daily CTX
measure: Change in commensal E. coli resistance before and while taking daily CTX
Secondary outcomes:
measure: To measure CTX-resistance among Salmonella and other enteric bacterial pathogens in patients with diarrhea in the study area
measure: 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
measure: 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
measure: To assess the effect of daily CTX prophylaxis on the etiology of diarrheal diseases in HIV-infected persons
measure: To evaluate the serotype distribution of and immune response to colonizing pneumococci
measure: To assess the cause of diarrheal diseases among HIV-infected persons
measure: To measure the change in quality of life indicators among clients receiving daily CTX
Other outcomes:
Locations:
city: Kisumu
country: Kenya
facility: CDC KEMRI Research Institute
Study officials:
affiliation: Centers for Disease Control and Prevention
name: Mary J Hamel, M.D.
role: PRINCIPAL_INVESTIGATOR
References: