Empiric Therapy of Helminth Co-infection to Reduce HIV-1 Disease Progression - Full Text View

Sponsor:	University of Washington
Collaborators:	Centers for Disease Control and Prevention Kenya Medical Research Institute
Information provided by (Responsible Party):	Judd Walson, University of Washington
ClinicalTrials.gov Identifier:	NCT00507221

Purpose

Abstract:

Over 25 million HIV-1 infected individuals are currently living in Africa and as many as 50-90% may be co-infected with soil transmitted helminths such as roundworms, hookworms or whipworms. Helminth infection in HIV-1-infected individuals may increase HIV-1 RNA levels and increase the rate of progression of HIV-1 to AIDS. Studies have also shown that successful treatment of helminth co-infection (as documented by clearance of helminth eggs in stool) led to a significant decrease in HIV-1 plasma viral load (-0.36 log10). This change in viral load was significantly greater than that seen in those individuals without documented clearance of their helminth co-infection (+0.67 log10) (p=0.04). Studies conducted in Africa have shown an estimated 2.5-fold increased risk for sexual transmission of the HIV-1 for each log increase in plasma HIV-1 viral load. In addition to direct effects on plasma viral load, the rate of CD4 cell decline in helminth infected individuals may be directly impacted by the significant immune activation seen with such co-infection.

The investigators propose a randomized controlled trial examining the potential benefits of routine empiric helminth eradication in HIV-1 infected adults who do not yet qualify for antiretroviral (ARV) therapy in Kenya. The current standard of care of symptomatic diagnosis and treatment will be compared to a systematic empiric scheduled de-worming program for HIV infected adults. The investigators will compare markers of disease progression including rate of CD4 decline and changes in HIV-1 RNA levels between the two treatment arms.

Condition	Intervention
HIV Infections Helminthiasis	Drug: Albendazole Drug: Praziquantel Drug: Current standard of care in Kenya

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Empiric Therapy of Helminth Co-infection to Reduce HIV-1 Disease Progression

Resource links provided by NLM:

Genetics Home Reference related topics: complement factor I deficiency

MedlinePlus related topics: HIV/AIDS

Drug Information available for: Albendazole Praziquantel

U.S. FDA Resources

Further study details as provided by University of Washington:

Primary Outcome Measures:

CD4 count [ Time Frame: every 6 months for 24 months (enrollment and months 6, 12, 18, and 24 ) ] [ Designated as safety issue: Yes ]
The primary measure of efficacy for the randomized clinical trial is the time to ART eligibility and the time to CD4 counts of less than 200 and 350 cells/mm3.
HIV-1 RNA level [ Time Frame: enrollment, 12, and 24 months. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Markers of clinical disease progression as measured by WHO staging criteria [ Time Frame: Every 3 months for 24 months (enrollment, months 3, 6, 9, 12, 15, 18, 21, and 24) ] [ Designated as safety issue: Yes ]
Secondary measures of efficacy will include changes in WHO Clinical Staging, development of IRIS, time to hospitalization, time to death, time to initiation of ARVs and CD4 response to ARVs as well as the development of IRIS among those who initiate ARVs.

Enrollment:	948
Study Start Date:	February 2008
Estimated Study Completion Date:	October 2011
Primary Completion Date:	July 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 Arm 1 will receive an intensive regimen of anti-helminthic therapy consisting of albendazole every three months for two years and praziquantel at enrollment and at one year of follow up.	Drug: Albendazole Every 3 months for 24 months (enrollment 3, 6, 9, 12, 15, 18, 21, and 24 months): 400mg/day X 3 days Drug: Praziquantel At enrollment and 12 months: 25mg/kg X 1
Active Comparator: 2 Arm 2 will receive symptomatic diagnosis and treatment of helminth infection as is current standard of care in Kenya.	Drug: Current standard of care in Kenya Current standard of care for HIV patients in Kenya based on WHO guidelines.

Show Detailed Description

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Participants must not be or have been on highly active antiretroviral therapy.
Participants must have CD4 count > 350 cells/mm3 in order to be enrolled in the randomized controlled trial.
Participants must be at least 18 years of age.
Participants must be able and willing to participate and give written informed consent.
Participants must be able and willing to return for the scheduled follow-up visits.

Exclusion Criteria:

• Participants must not be pregnant at the time of enrollment (by urine HCG testing).

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00507221

Locations

Kenya
Kenya Medical Research Institute
Nairobi, Kenya

Sponsors and Collaborators

University of Washington

Centers for Disease Control and Prevention

Kenya Medical Research Institute

Investigators

Principal Investigator:

Judd L Walson, MD, MPH

University of Washington

More Information

Publications:

Fincham JE, Markus MB, Adams VJ. Could control of soil-transmitted helminthic infection influence the HIV/AIDS pandemic. Acta Trop. 2003 May;86(2-3):315-33.

Bentwich Z, Weisman Z, Moroz C, Bar-Yehuda S, Kalinkovich A. Immune dysregulation in Ethiopian immigrants in Israel: relevance to helminth infections? Clin Exp Immunol. 1996 Feb;103(2):239-43.

Kassu A, Tsegaye A, Wolday D, Petros B, Aklilu M, Sanders EJ, Fontanet AL, Van Baarle D, Hamann D, De Wit TF. Role of incidental and/or cured intestinal parasitic infections on profile of CD4+ and CD8+ T cell subsets and activation status in HIV-1 infected and uninfected adult Ethiopians. Clin Exp Immunol. 2003 Apr;132(1):113-9.

Wolday D, Mayaan S, Mariam ZG, Berhe N, Seboxa T, Britton S, Galai N, Landay A, Bentwich Z. Treatment of intestinal worms is associated with decreased HIV plasma viral load. J Acquir Immune Defic Syndr. 2002 Sep 1;31(1):56-62.

Lawn SD, Karanja DM, Mwinzia P, Andove J, Colley DG, Folks TM, Secor WE. The effect of treatment of schistosomiasis on blood plasma HIV-1 RNA concentration in coinfected individuals. AIDS. 2000 Nov 10;14(16):2437-43.

Responsible Party:	Judd Walson, Principal Investigator, University of Washington
ClinicalTrials.gov Identifier:	NCT00507221 History of Changes
Other Study ID Numbers:	32274-B, KEMRI SSC #1251; 07-6824-B 01
Study First Received:	July 24, 2007
Last Updated:	September 27, 2011
Health Authority:	United States: Institutional Review Board; Kenya: Ministry of Health

Keywords provided by University of Washington:

HIV
Helminthiasis
Co-infection
Treatment Naive

Additional relevant MeSH terms:

HIV Infections
Acquired Immunodeficiency Syndrome
Helminthiasis
Disease Progression
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Parasitic Diseases
Disease Attributes

Pathologic Processes
Albendazole
Praziquantel
Anticestodal Agents
Antiplatyhelmintic Agents
Anthelmintics
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antiprotozoal Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on February 09, 2012