Immune Reconstitution to Measles Virus of HIV Infected Children in Zambia

NCT02058927 | Completed

• 2 other identifiers: CIDRZ 1204/IRB12-0400R01AI070018
• Study Type: observational
• Target: 203
• Locations: 1 country
• Sites: 1

Brief Summary

This is an observational study of HIV-1 infected children starting antiretroviral therapy to measure the magnitude and quality of general immune reconstitution and pathogen-specific immune reconstitution to measles virus.

Conditions

Measles

Keywords

HIV; ART; children

Outcome Measures

Primary Outcomes (1)

• Memory immune responses to measles virus

  Memory immune responses to measles virus will be measured to characterize the magnitude and quality of immune reconstitution in HIV-1 infected Zambian children initiating ART and determine pathogen-specific immune reconstitution.

  0, 6, 12, 24, 30 and 36 months from start of ART

Secondary Outcomes (1)

• Humoral and cellular immune responses to measles virus before and after revaccination

  12, 15, 24, 30 and 36 months from start of ART

Study Arms (3)

HIV-1 infected children

HIV-1-infected children initiating ART

HIV-1 uninfected children

control group of HIV-1 uninfected children matched by age

HIV-1 infected children revaccinated

nested study of revaccination against measles virus of HIV-1-infected children receiving ART who lack protective antibody titers

Drug: Measles vaccine

Interventions

Measles vaccine DRUG

measles revaccination administered at 12 months from start of ART

HIV-1 infected children revaccinated

Eligibility Criteria

• Age: 9 Months - 10 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Probability Sample

Study Population

HIV-1 infected children initiating ART in public clinics within Lusaka, Zambia.

You may qualify if:

• Boys and girls 9 months to 10 years of age residing in Lusaka, Zambia are eligible for enrolment.
• initiating ART
• history of measles vaccination confirmed by examination of the Immunization Card.

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (1)

Centre for Infectious Disease Research in Zambia

Lusaka, Zambia

Location

Related Publications (45)

• Newell ML, Brahmbhatt H, Ghys PD. Child mortality and HIV infection in Africa: a review. AIDS. 2004 Jun;18 Suppl 2:S27-34. doi: 10.1097/00002030-200406002-00004.

  PMID: 15319741 BACKGROUND

• de Martino M, Tovo PA, Balducci M, Galli L, Gabiano C, Rezza G, Pezzotti P. Reduction in mortality with availability of antiretroviral therapy for children with perinatal HIV-1 infection. Italian Register for HIV Infection in Children and the Italian National AIDS Registry. JAMA. 2000 Jul 12;284(2):190-7. doi: 10.1001/jama.284.2.190.

  PMID: 10889592 BACKGROUND

• Gortmaker SL, Hughes M, Cervia J, Brady M, Johnson GM, Seage GR 3rd, Song LY, Dankner WM, Oleske JM; Pediatric AIDS Clinical Trials Group Protocol 219 Team. Effect of combination therapy including protease inhibitors on mortality among children and adolescents infected with HIV-1. N Engl J Med. 2001 Nov 22;345(21):1522-8. doi: 10.1056/NEJMoa011157.

  PMID: 11794218 BACKGROUND

• Autran B, Carcelain G, Li TS, Blanc C, Mathez D, Tubiana R, Katlama C, Debre P, Leibowitch J. Positive effects of combined antiretroviral therapy on CD4+ T cell homeostasis and function in advanced HIV disease. Science. 1997 Jul 4;277(5322):112-6. doi: 10.1126/science.277.5322.112.

  PMID: 9204894 BACKGROUND

• Pakker NG, Notermans DW, de Boer RJ, Roos MT, de Wolf F, Hill A, Leonard JM, Danner SA, Miedema F, Schellekens PT. Biphasic kinetics of peripheral blood T cells after triple combination therapy in HIV-1 infection: a composite of redistribution and proliferation. Nat Med. 1998 Feb;4(2):208-14. doi: 10.1038/nm0298-208.

  PMID: 9461195 BACKGROUND

• Gibb DM, Newberry A, Klein N, de Rossi A, Grosch-Woerner I, Babiker A. Immune repopulation after HAART in previously untreated HIV-1-infected children. Paediatric European Network for Treatment of AIDS (PENTA) Steering Committee. Lancet. 2000 Apr 15;355(9212):1331-2. doi: 10.1016/s0140-6736(00)02117-6.

  PMID: 10776748 BACKGROUND

• Vigano A, Vella S, Saresella M, Vanzulli A, Bricalli D, Di Fabio S, Ferrante P, Andreotti M, Pirillo M, Dally LG, Clerici M, Principi N. Early immune reconstitution after potent antiretroviral therapy in HIV-infected children correlates with the increase in thymus volume. AIDS. 2000 Feb 18;14(3):251-61. doi: 10.1097/00002030-200002180-00007.

  PMID: 10716501 BACKGROUND

• van Rossum AM, Scherpbier HJ, van Lochem EG, Pakker NG, Slieker WA, Wolthers KC, Roos MT, Kuijpers JH, Hooijkaas H, Hartwig NG, Geelen SP, Wolfs TF, Lange JM, Miedema F, de Groot R; Dutch Study Group for Children with HIV Infections. Therapeutic immune reconstitution in HIV-1-infected children is independent of their age and pretreatment immune status. AIDS. 2001 Nov 23;15(17):2267-75. doi: 10.1097/00002030-200111230-00008.

  PMID: 11698700 BACKGROUND

• Douek DC, Koup RA, McFarland RD, Sullivan JL, Luzuriaga K. Effect of HIV on thymic function before and after antiretroviral therapy in children. J Infect Dis. 2000 Apr;181(4):1479-82. doi: 10.1086/315398. Epub 2000 Apr 13.

  PMID: 10762580 BACKGROUND

• Chavan S, Bennuri B, Kharbanda M, Chandrasekaran A, Bakshi S, Pahwa S. Evaluation of T cell receptor gene rearrangement excision circles after antiretroviral therapy in children infected with human immunodeficiency virus. J Infect Dis. 2001 May 15;183(10):1445-54. doi: 10.1086/320197. Epub 2001 Apr 13.

  PMID: 11329124 BACKGROUND

• Johnston AM, Valentine ME, Ottinger J, Baydo R, Gryszowka V, Vavro C, Weinhold K, St Clair M, McKinney RE. Immune reconstitution in human immunodeficiency virus-infected children receiving highly active antiretroviral therapy: a cohort study. Pediatr Infect Dis J. 2001 Oct;20(10):941-6. doi: 10.1097/00006454-200110000-00006.

  PMID: 11642627 BACKGROUND

• De Rossi A, Walker AS, Klein N, De Forni D, King D, Gibb DM. Increased thymic output after initiation of antiretroviral therapy in human immunodeficiency virus type 1-infected children in the Paediatric European Network for Treatment of AIDS (PENTA) 5 Trial. J Infect Dis. 2002 Aug 1;186(3):312-20. doi: 10.1086/341657. Epub 2002 Jul 5.

  PMID: 12134227 BACKGROUND

• Resino S, Correa R, Bellon JM, Sanchez-Ramon S, Munoz-Fernandez MA. Characterizing immune reconstitution after long-term highly active antiretroviral therapy in pediatric AIDS. AIDS Res Hum Retroviruses. 2002 Dec 10;18(18):1395-406. doi: 10.1089/088922202320935474.

  PMID: 12487811 BACKGROUND

• Burgess K, Price P, James IR, Stone SF, Keane NM, Lim AY, Warmington JR, French MA. Interferon-gamma responses to Candida recover slowly or remain low in immunodeficient HIV patients responding to ART. J Clin Immunol. 2006 Mar;26(2):160-7. doi: 10.1007/s10875-006-9008-4. Epub 2006 Mar 28.

  PMID: 16568352 BACKGROUND

• Hainaut M, Ducarme M, Schandene L, Peltier CA, Marissens D, Zissis G, Mascart F, Levy J. Age-related immune reconstitution during highly active antiretroviral therapy in human immunodeficiency virus type 1-infected children. Pediatr Infect Dis J. 2003 Jan;22(1):62-9. doi: 10.1097/00006454-200301000-00016.

  PMID: 12544411 BACKGROUND

• Weinberg A, Pahwa S, Oyomopito R, Carey VJ, Zimmer B, Mofenson L, Kovacs A, Burchett SK; Pediatric AIDS Clinical Trials Group 366 Team. Antimicrobial-specific cell-mediated immune reconstitution in children with advanced human immunodeficiency virus infection receiving highly active antiretroviral therapy. Clin Infect Dis. 2004 Jul 1;39(1):107-14. doi: 10.1086/420931. Epub 2004 Jun 14.

  PMID: 15206061 BACKGROUND

• Weinberg A, Wiznia AA, LaFleur BJ, Shah S, Levin MJ. Varicella-Zoster virus-specific cell-mediated immunity in HIV-infected children receiving highly active antiretroviral therapy. J Infect Dis. 2004 Jul 15;190(2):267-70. doi: 10.1086/422011. Epub 2004 Jun 9.

  PMID: 15216460 BACKGROUND

• Weinberg A, Gona P, Nachman SA, Defechereux P, Yogev R, Hughes W, Wara D, Spector SA, Read J, Elgie C, Cooper M, Dankner W; Pediatric AIDS Clinical Trials Group 1008 Team. Antibody responses to hepatitis A virus vaccine in HIV-infected children with evidence of immunologic reconstitution while receiving highly active antiretroviral therapy. J Infect Dis. 2006 Jan 15;193(2):302-11. doi: 10.1086/498979. Epub 2005 Dec 7.

  PMID: 16362896 BACKGROUND

• Crotty S, Ahmed R. Immunological memory in humans. Semin Immunol. 2004 Jun;16(3):197-203. doi: 10.1016/j.smim.2004.02.008.

  PMID: 15130504 BACKGROUND

• Lanzavecchia A, Sallusto F. Understanding the generation and function of memory T cell subsets. Curr Opin Immunol. 2005 Jun;17(3):326-32. doi: 10.1016/j.coi.2005.04.010.

  PMID: 15886125 BACKGROUND

• Sun JC, Bevan MJ. Defective CD8 T cell memory following acute infection without CD4 T cell help. Science. 2003 Apr 11;300(5617):339-42. doi: 10.1126/science.1083317.

  PMID: 12690202 BACKGROUND

• Shedlock DJ, Shen H. Requirement for CD4 T cell help in generating functional CD8 T cell memory. Science. 2003 Apr 11;300(5617):337-9. doi: 10.1126/science.1082305.

  PMID: 12690201 BACKGROUND

• Janssen EM, Lemmens EE, Wolfe T, Christen U, von Herrath MG, Schoenberger SP. CD4+ T cells are required for secondary expansion and memory in CD8+ T lymphocytes. Nature. 2003 Feb 20;421(6925):852-6. doi: 10.1038/nature01441. Epub 2003 Feb 9.

  PMID: 12594515 BACKGROUND

• Castellino F, Huang AY, Altan-Bonnet G, Stoll S, Scheinecker C, Germain RN. Chemokines enhance immunity by guiding naive CD8+ T cells to sites of CD4+ T cell-dendritic cell interaction. Nature. 2006 Apr 13;440(7086):890-5. doi: 10.1038/nature04651.

  PMID: 16612374 BACKGROUND

• Sun JC, Williams MA, Bevan MJ. CD4+ T cells are required for the maintenance, not programming, of memory CD8+ T cells after acute infection. Nat Immunol. 2004 Sep;5(9):927-33. doi: 10.1038/ni1105. Epub 2004 Aug 8.

  PMID: 15300249 BACKGROUND

• Kaech SM, Tan JT, Wherry EJ, Konieczny BT, Surh CD, Ahmed R. Selective expression of the interleukin 7 receptor identifies effector CD8 T cells that give rise to long-lived memory cells. Nat Immunol. 2003 Dec;4(12):1191-8. doi: 10.1038/ni1009. Epub 2003 Nov 16.

  PMID: 14625547 BACKGROUND

• Madakamutil LT, Christen U, Lena CJ, Wang-Zhu Y, Attinger A, Sundarrajan M, Ellmeier W, von Herrath MG, Jensen P, Littman DR, Cheroutre H. CD8alphaalpha-mediated survival and differentiation of CD8 memory T cell precursors. Science. 2004 Apr 23;304(5670):590-3. doi: 10.1126/science.1092316.

  PMID: 15105501 BACKGROUND

• McHeyzer-Williams LJ, McHeyzer-Williams MG. Antigen-specific memory B cell development. Annu Rev Immunol. 2005;23:487-513. doi: 10.1146/annurev.immunol.23.021704.115732.

  PMID: 15771579 BACKGROUND

• Crotty S, Kersh EN, Cannons J, Schwartzberg PL, Ahmed R. SAP is required for generating long-term humoral immunity. Nature. 2003 Jan 16;421(6920):282-7. doi: 10.1038/nature01318.

  PMID: 12529646 BACKGROUND

• Vieira P, Rajewsky K. Persistence of memory B cells in mice deprived of T cell help. Int Immunol. 1990;2(6):487-94. doi: 10.1093/intimm/2.6.487.

  PMID: 2150759 BACKGROUND

• Hebeis BJ, Klenovsek K, Rohwer P, Ritter U, Schneider A, Mach M, Winkler TH. Activation of virus-specific memory B cells in the absence of T cell help. J Exp Med. 2004 Feb 16;199(4):593-602. doi: 10.1084/jem.20030091. Epub 2004 Feb 9.

  PMID: 14769849 BACKGROUND

• Bernasconi NL, Traggiai E, Lanzavecchia A. Maintenance of serological memory by polyclonal activation of human memory B cells. Science. 2002 Dec 13;298(5601):2199-202. doi: 10.1126/science.1076071.

  PMID: 12481138 BACKGROUND

• De Milito A, Morch C, Sonnerborg A, Chiodi F. Loss of memory (CD27) B lymphocytes in HIV-1 infection. AIDS. 2001 May 25;15(8):957-64. doi: 10.1097/00002030-200105250-00003.

  PMID: 11399977 BACKGROUND

• De Milito A, Nilsson A, Titanji K, Thorstensson R, Reizenstein E, Narita M, Grutzmeier S, Sonnerborg A, Chiodi F. Mechanisms of hypergammaglobulinemia and impaired antigen-specific humoral immunity in HIV-1 infection. Blood. 2004 Mar 15;103(6):2180-6. doi: 10.1182/blood-2003-07-2375. Epub 2003 Nov 6.

  PMID: 14604962 BACKGROUND

• Slifka MK. Immunological memory to viral infection. Curr Opin Immunol. 2004 Aug;16(4):443-50. doi: 10.1016/j.coi.2004.05.013.

  PMID: 15245737 BACKGROUND

• Malaspina A, Moir S, Orsega SM, Vasquez J, Miller NJ, Donoghue ET, Kottilil S, Gezmu M, Follmann D, Vodeiko GM, Levandowski RA, Mican JM, Fauci AS. Compromised B cell responses to influenza vaccination in HIV-infected individuals. J Infect Dis. 2005 May 1;191(9):1442-50. doi: 10.1086/429298. Epub 2005 Mar 24.

  PMID: 15809902 BACKGROUND

• Ovsyannikova IG, Dhiman N, Jacobson RM, Vierkant RA, Poland GA. Frequency of measles virus-specific CD4+ and CD8+ T cells in subjects seronegative or highly seropositive for measles vaccine. Clin Diagn Lab Immunol. 2003 May;10(3):411-6. doi: 10.1128/cdli.10.3.411-416.2003.

  PMID: 12738640 BACKGROUND

• Nanan R, Rauch A, Kampgen E, Niewiesk S, Kreth HW. A novel sensitive approach for frequency analysis of measles virus-specific memory T-lymphocytes in healthy adults with a childhood history of natural measles. J Gen Virol. 2000 May;81(Pt 5):1313-9. doi: 10.1099/0022-1317-81-5-1313.

  PMID: 10769074 BACKGROUND

• van Els CA, Nanan R. T cell responses in acute measles. Viral Immunol. 2002;15(3):435-50. doi: 10.1089/088282402760312322.

  PMID: 12479394 BACKGROUND

• Moss WJ, Cutts F, Griffin DE. Implications of the human immunodeficiency virus epidemic for control and eradication of measles. Clin Infect Dis. 1999 Jul;29(1):106-12. doi: 10.1086/520136.

  PMID: 10433572 BACKGROUND

• Berkelhamer S, Borock E, Elsen C, Englund J, Johnson D. Effect of highly active antiretroviral therapy on the serological response to additional measles vaccinations in human immunodeficiency virus-infected children. Clin Infect Dis. 2001 Apr 1;32(7):1090-4. doi: 10.1086/319591. Epub 2001 Mar 19.

  PMID: 11264038 BACKGROUND

• Melvin AJ, Mohan KM. Response to immunization with measles, tetanus, and Haemophilus influenzae type b vaccines in children who have human immunodeficiency virus type 1 infection and are treated with highly active antiretroviral therapy. Pediatrics. 2003 Jun;111(6 Pt 1):e641-4. doi: 10.1542/peds.111.6.e641.

  PMID: 12777579 BACKGROUND

• Gans H, Yasukawa L, Rinki M, DeHovitz R, Forghani B, Beeler J, Audet S, Maldonado Y, Arvin AM. Immune responses to measles and mumps vaccination of infants at 6, 9, and 12 months. J Infect Dis. 2001 Oct 1;184(7):817-26. doi: 10.1086/323346. Epub 2001 Aug 22.

  PMID: 11528592 BACKGROUND

• Angel JB, Walpita P, Lerch RA, Sidhu MS, Masurekar M, DeLellis RA, Noble JT, Snydman DR, Udem SA. Vaccine-associated measles pneumonitis in an adult with AIDS. Ann Intern Med. 1998 Jul 15;129(2):104-6. doi: 10.7326/0003-4819-129-2-199807150-00007. No abstract available.

  PMID: 9669968 BACKGROUND

• Moss WJ, Clements CJ, Halsey NA. Immunization of children at risk of infection with human immunodeficiency virus. Bull World Health Organ. 2003;81(1):61-70. Epub 2003 Mar 11.

  PMID: 12640478 BACKGROUND

Related Links

• University of North Carolina website

Biospecimen

Retention: SAMPLES WITH DNA

blood samples will be stored in a repository for five years beyond the end of the study period. Some samples may be exported to the Johns Hopkins Bloomberg School of Public Health when assays cannot be performed in Zambia.

MeSH Terms

Conditions

Measles

Interventions

Measles Vaccine

Condition Hierarchy (Ancestors)

Morbillivirus Infections; Paramyxoviridae Infections; Mononegavirales Infections; RNA Virus Infections; Virus Diseases; Infections

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Study Officials

• Carolyn B Moore, MD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: February 6, 2014
• First Posted: February 10, 2014
• Study Start: May 1, 2011
• Primary Completion: February 1, 2012
• Study Completion: February 1, 2012
• Last Updated: September 18, 2014

Record last verified: 2014-09

Locations

ZA (1)