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

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ClinicalTrials.gov Identifier: NCT00137657

Recruitment Status : Completed

First Posted : August 30, 2005

Last Update Posted : December 13, 2005

Sponsor:

Collaborator:

Kenya Medical Research Institute

Information provided by:

Centers for Disease Control and Prevention

Study Description

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.

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

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 Design

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Study Type :	Interventional (Clinical Trial)
Enrollment :	1478 participants
Allocation:	Non-Randomized
Intervention Model:	Parallel Assignment
Masking:	None (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
Study Start Date :	February 2002
Study Completion Date :	November 2003

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS Pneumonia

Drug Information available for: Sulfamethoxazole Trimethoprim

Genetic and Rare Diseases Information Center resources: Malaria

U.S. FDA Resources

Arms and Interventions

Outcome Measures

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

Eligibility Criteria

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Ages Eligible for Study:	15 Years and older (Child, Adult, Older Adult)
Sexes Eligible for Study:	All
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

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To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00137657

Locations

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Kenya
CDC KEMRI Research Institute
Kisumu, Kenya

Sponsors and Collaborators

Centers for Disease Control and Prevention

Kenya Medical Research Institute

Investigators

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

More Information

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ClinicalTrials.gov Identifier:	NCT00137657
Other Study ID Numbers:	CDC-NCID-3354 UR6/CCU018970-02-2 SSC#664
First Posted:	August 30, 2005 Key Record Dates
Last Update Posted:	December 13, 2005
Last Verified:	August 2005

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:

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Opportunistic Infections Malaria Pneumonia Diarrhea Infection Lung Diseases Respiratory Tract Diseases Respiratory Tract Infections Protozoan Infections Parasitic Diseases Signs and Symptoms, Digestive Virus Diseases Trimethoprim Trimethoprim, Sulfamethoxazole Drug Combination	Sulfamethoxazole Anti-Infective Agents, Urinary Anti-Infective Agents Renal Agents Antimalarials Antiprotozoal Agents Antiparasitic Agents Folic Acid Antagonists Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-Dyskinesia Agents Cytochrome P-450 CYP2C8 Inhibitors Cytochrome P-450 Enzyme Inhibitors Anti-Bacterial Agents

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