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

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.

Timeline

Start

2008-02

Primary completion

2011-07

Completion

2011-10

Publications

• Background 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Drugs

Indications