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

This study has been completed.
Sponsor:
Collaborator:
Kenya Medical Research Institute
Information provided by:
Centers for Disease Control and Prevention
ClinicalTrials.gov Identifier:
NCT00137657
First received: August 29, 2005
Last updated: December 12, 2005
Last verified: August 2005
  Purpose

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.


Condition Intervention Phase
HIV
Malaria
Diarrhea
Pneumonia
Opportunistic Infections
Drug: Cotrimoxazole (trimethoprim sulfamethoxazole)
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Educational/Counseling/Training
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

Resource links provided by NLM:


Further study details as provided by Centers for Disease Control and Prevention:

Primary Outcome Measures:
  • 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

Secondary Outcome Measures:
  • 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

Estimated Enrollment: 1478
Study Start Date: February 2002
Estimated Study Completion Date: November 2003
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

Ages Eligible for Study:   15 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00137657

Locations
Kenya
CDC KEMRI Research Institute
Kisumu, Kenya
Sponsors and Collaborators
Kenya Medical Research Institute
Investigators
Principal Investigator: Mary J Hamel, M.D. Centers for Disease Control and Prevention
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00137657     History of Changes
Other Study ID Numbers: CDC-NCID-3354, UR6/CCU018970-02-2, SSC#664
Study First Received: August 29, 2005
Last Updated: December 12, 2005
Health Authority: United States: Federal Government

Keywords provided by Centers for Disease Control and Prevention:
HIV
malaria
E. Coli
S. pneumoniae
drug resistance
antifolate
opportunistic infections
Africa
Kenya
East Africa

Additional relevant MeSH terms:
Diarrhea
Malaria
Opportunistic Infections
Pneumonia
Signs and Symptoms, Digestive
Signs and Symptoms
Protozoan Infections
Parasitic Diseases
Infection
Virus Diseases
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Folic Acid Antagonists
Trimethoprim
Sulfamethoxazole
Trimethoprim-Sulfamethoxazole Combination
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Infective Agents
Therapeutic Uses
Anti-Infective Agents, Urinary
Renal Agents
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents

ClinicalTrials.gov processed this record on July 26, 2014