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

NCT00507221 | Completed DMC

• 2 other identifiers: 32274-BKEMRI SSC #1251; 07-6824-B 01
• Study Type: interventional
• Target: 948
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

HIV Infections; Helminthiasis

Keywords

HIV; Helminthiasis; Co-infection; Treatment Naive

Outcome Measures

Primary Outcomes (2)

• CD4 count

  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.

  every 6 months for 24 months (enrollment and months 6, 12, 18, and 24 )

• HIV-1 RNA level

  enrollment, 12, and 24 months.

Secondary Outcomes (1)

• Markers of clinical disease progression as measured by WHO staging criteria

  Every 3 months for 24 months (enrollment, months 3, 6, 9, 12, 15, 18, 21, and 24)

Study Arms (2)

1

EXPERIMENTAL

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; Drug: Praziquantel

2

ACTIVE COMPARATOR

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

Interventions

Albendazole DRUG

Every 3 months for 24 months (enrollment 3, 6, 9, 12, 15, 18, 21, and 24 months): 400mg/day X 3 days

1

Praziquantel DRUG

At enrollment and 12 months: 25mg/kg X 1

1

Current standard of care in Kenya DRUG

Current standard of care for HIV patients in Kenya based on WHO guidelines.

2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• University of Washington: lead
• Centers for Disease Control and Prevention: collaborator
• Kenya Medical Research Institute: collaborator

Study Sites (1)

Kenya Medical Research Institute

Nairobi, Kenya

Location

Related Publications (8)

• 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. doi: 10.1016/s0001-706x(03)00063-9.

  PMID: 12745148 BACKGROUND

• 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. doi: 10.1046/j.1365-2249.1996.d01-612.x.

  PMID: 8565306 BACKGROUND

• 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. doi: 10.1046/j.1365-2249.2003.02106.x.

  PMID: 12653845 BACKGROUND

• 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. doi: 10.1097/00126334-200209010-00008.

  PMID: 12352151 BACKGROUND

• 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. doi: 10.1097/00002030-200011100-00004.

  PMID: 11101053 BACKGROUND

• Means AR, van Lieshout L, Brienen E, Yuhas K, Hughes JP, Ndungu P, Singa B, Walson JL. Combined effectiveness of anthelmintic chemotherapy and WASH among HIV-infected adults. PLoS Negl Trop Dis. 2018 Jan 18;12(1):e0005955. doi: 10.1371/journal.pntd.0005955. eCollection 2018 Jan.

  PMID: 29346385 DERIVED

• Gerns Storey HL, Richardson BA, Singa B, Naulikha J, Prindle VC, Diaz-Ochoa VE, Felgner PL, Camerini D, Horton H, John-Stewart G, Walson JL. Use of principal components analysis and protein microarray to explore the association of HIV-1-specific IgG responses with disease progression. AIDS Res Hum Retroviruses. 2014 Jan;30(1):37-44. doi: 10.1089/AID.2013.0088. Epub 2013 Dec 9.

  PMID: 24134221 DERIVED

• Walson J, Singa B, Sangare L, Naulikha J, Piper B, Richardson B, Otieno PA, Mbogo LW, Berkley JA, John-Stewart G. Empiric deworming to delay HIV disease progression in adults with HIV who are ineligible for initiation of antiretroviral treatment (the HEAT study): a multi-site, randomised trial. Lancet Infect Dis. 2012 Dec;12(12):925-32. doi: 10.1016/S1473-3099(12)70207-4. Epub 2012 Sep 10.

  PMID: 22971323 DERIVED

MeSH Terms

Conditions

HIV Infections; Helminthiasis; Coinfection

Interventions

Albendazole; Praziquantel

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Parasitic Diseases

Intervention Hierarchy (Ancestors)

Carbamates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Isoquinolines

Study Officials

• Judd L Walson, MD, MPH

  University of Washington

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 24, 2007
• First Posted: July 26, 2007
• Study Start: February 1, 2008
• Primary Completion: July 1, 2011
• Study Completion: October 1, 2011
• Last Updated: November 20, 2014

Record last verified: 2014-11

Locations

KE (1)