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HIV Diagnosis in Hospitalized Malawian Infants

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01388452
First Posted: July 6, 2011
Last Update Posted: May 14, 2013
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
John E. Fogarty International Center (FIC)
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party):
University of North Carolina, Chapel Hill
  Purpose

Purpose: The purpose of this research study is to learn about two HIV tests - a clinical "presumptive diagnosis" (PD) that a trained healthcare provider can quickly use to determine if a child is likely to be HIV-infected and in need of HIV medicines and an "expedited" gold standard RNA-PCR test (expedited PCR) that is done at the UNC Project lab located at the hospital and the result given within 48 hours. Both of these tests can obtain results quickly while the current test called dried blood spot DNA-PCR goes to a lab and the result may take up to one month. The performance of PD and expedited PCR will be compared to one another with respect to HIV-infected infants correctly initiating life-saving antiretroviral therapy.

Participants: Hospitalized children younger than 12 months of age who are HIV DNA-PCR eligible at Kamuzu Central Hospital (KCH), in Lilongwe, Malawi. Other participants will be patient caregivers and clinical officers who provide healthcare for children that could be HIV-infected. Clinical officers will be trained to conduct the presumptive diagnosis test.

Procedures (methods): Patients will be randomized to either standard of care (PD and dried blood spot DNA-PCR) or expedited PCR. A consultant pediatrician and a clinical officer will perform the PD. If the PD or expedited PCR test results are positive, hospital care could include HIV medicine.


Condition Intervention
HIV Infections Device: Point of care HIV RNA PCR

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Presumptive and Definitive Virologic HIV Diagnosis in Hospitalized Malawian Infants

Resource links provided by NLM:


Further study details as provided by University of North Carolina, Chapel Hill:

Primary Outcome Measures:
  • ART initiation of HIV-infected infants [ Time Frame: Participants will be followed for an expected average of 2 months, or until their HIV-status is confirmed ]
    The primary outcome will be the proportion of HIV+ children initiated on ART in the hospital. We will need a sample size of 400 infants assuming the standard of care will initiate 60% and the experimental group will initiate 85% of HIV-infected infants on ART prior to hospital discharge, respectively. These assumptions also take into consideration a predicted inpatient HIV-prevalence in HIV-exposed infants of 25% and a 5% absconding rate, using a confidence interval of 10% and confidence level of p < 0.05.


Enrollment: 300
Study Start Date: June 2011
Study Completion Date: December 2012
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Point of Care HIV RNA PCR
Patients randomized to this arm will be followed prospectively from the time of clinical evaluation in the hospital until 12 months after returning for outpatient care at the KCH HIV clinic. The counselor will collect infant blood for point of care RNA PCR testing, number the sample, and transport it to the central laboratory for processing. Patients determined to be HIV-uninfected or HIV-exposed uninfected will not continue in the study beyond virologic test result disclosure, which will occur as an inpatient at KCH for this arm. If the patient does not return for outpatient care for three months after hospitalization then the patient's participation in the study will end.
Device: Point of care HIV RNA PCR
The intervention is a HIV RNA PCR test for which UNC Project laboratory personnel will process samples in 48 hours so that patients can receive results prior to hospital discharge.
No Intervention: Standard of Care

Patients randomized to this arm will be followed prospectively from the time of clinical evaluation in the hospital until 12 months after returning for outpatient care at the KCH HIV clinic. The counselor will collect infant blood for dried blood spot DNA PCR testing, number the sample, and transport it to the central laboratory for processing. If the patient is PD positive then the patient will be offered ART initiation prior to hospital discharge.

Patients determined to be HIV-uninfected or HIV-exposed uninfected will not continue in the study beyond virologic test result disclosure, which will occur as an outpatient at KCH for this arm. If the patient does not return for outpatient care for three months after hospitalization then the patient's participation in the study will end.


  Show Detailed Description

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   up to 12 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male and female children
  • Less than 12 months of age
  • Inpatient at KCH
  • HIV DNA-PCR test eligible
  • No prior definitive PCR test result

Exclusion Criteria:

  • Caregiver does not want to be contacted by study team
  • Mother initiated on ART prior to pregnancy
  Contacts and Locations
Information from the National Library of Medicine

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): NCT01388452


Locations
Malawi
Kamuzu Central Hospital
Lilongwe, Malawi
Sponsors and Collaborators
University of North Carolina, Chapel Hill
John E. Fogarty International Center (FIC)
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
Principal Investigator: Eric D McCollum, MD UNC Project
Principal Investigator: Mina Hosseinipour, MD, MPH University of North Carolina, Chapel Hill
  More Information

Publications:
1. Joint United Nations Programme on HIV/AIDS (2008) 2008 Report on the Global AIDS Epidemic. Available: http://data.unaids.org/pub/GlobalReport/2008/JC1511_GR08_ExecutiveSummary_en.pdfAccessed 7 September 2009.
2. The United Nations Children's Fund (2008) Children and AIDS: Third Stocktaking Report, 2008. Available: http://www.unicef.org/publications/index_46585.html. Accessed 7 September 2009.
3. Ministry of Health Malawi: HIV Unit (2008) Annual Report HIV Unit 2008.
4. World Health Organization (2007) Guidance on provider-initiated HIV testing and counseling in health facilities. Available: http://whqlibdoc.who.int/publications/2007/9789241595568_eng.pdf. Accessed 26 August 2009.
Rogerson SR, Gladstone M, Callaghan M, Erhart L, Rogerson SJ, Borgstein E, Broadhead RL. HIV infection among paediatric in-patients in Blantyre, Malawi. Trans R Soc Trop Med Hyg. 2004 Sep;98(9):544-52.
6. Ministry of Health Malawi: HIV Unit (2008) Guidelines for Paediatric HIV Testing and Counseling.
Violari A, Cotton MF, Gibb DM, Babiker AG, Steyn J, Madhi SA, Jean-Philippe P, McIntyre JA; CHER Study Team. Early antiretroviral therapy and mortality among HIV-infected infants. N Engl J Med. 2008 Nov 20;359(21):2233-44. doi: 10.1056/NEJMoa0800971.
Diaz C, Hanson C, Cooper ER, Read JS, Watson J, Mendez HA, Pitt J, Rich K, Smeriglio V, Lew JF. Disease progression in a cohort of infants with vertically acquired HIV infection observed from birth: the Women and Infants Transmission Study (WITS). J Acquir Immune Defic Syndr Hum Retrovirol. 1998 Jul 1;18(3):221-8.
Tovo PA, de Martino M, Gabiano C, Cappello N, D'Elia R, Loy A, Plebani A, Zuccotti GV, Dallacasa P, Ferraris G, et al. Prognostic factors and survival in children with perinatal HIV-1 infection. The Italian Register for HIV Infections in Children. Lancet. 1992 May 23;339(8804):1249-53.
Newell ML, Coovadia H, Cortina-Borja M, Rollins N, Gaillard P, Dabis F; Ghent International AIDS Society (IAS) Working Group on HIV Infection in Women and Children. Mortality of infected and uninfected infants born to HIV-infected mothers in Africa: a pooled analysis. Lancet. 2004 Oct 2-8;364(9441):1236-43.
Chilongozi D, Wang L, Brown L, Taha T, Valentine M, Emel L, Sinkala M, Kafulafula G, Noor RA, Read JS, Brown ER, Goldenberg RL, Hoffman I; HIVNET 024 Study Team. Morbidity and mortality among a cohort of human immunodeficiency virus type 1-infected and uninfected pregnant women and their infants from Malawi, Zambia, and Tanzania. Pediatr Infect Dis J. 2008 Sep;27(9):808-14. doi: 10.1097/INF.0b013e31817109a4.
Dunn D; HIV Paediatric Prognostic Markers Collaborative Study Group. Short-term risk of disease progression in HIV-1-infected children receiving no antiretroviral therapy or zidovudine monotherapy: a meta-analysis. Lancet. 2003 Nov 15;362(9396):1605-11.
13. World Health Organization (2006) Report of the WHO Technical Reference Group, Paediatric HIV/ ART Care Guideline Group Meeting.
14. World Health Organization (2006) Antiretroviral therapy of HIV infection in infants and children in resource-limited settings: towards universal access. Available: http://www.who.int/ hiv/pub/guidelines/pmtctguidelines3.pdf. Accessed 17 November 2009.
Sherman GG, Cooper PA, Coovadia AH, Puren AJ, Jones SA, Mokhachane M, Bolton KD. Polymerase chain reaction for diagnosis of human immunodeficiency virus infection in infancy in low resource settings. Pediatr Infect Dis J. 2005 Nov;24(11):993-7.
16. United Nations Children's Fund (2008) Children and AIDS. Third Stocktaking Report, 2008. Available at: http:// www.unicef.org/publications. Accessed 17 November, 2009.
17. Ministry of Health Malawi and National AIDS Commission (2008) Treatment of AIDS: Guidelines for the Use of Antiretroviral Therapy in Malawi, Third Edition.
18. Ministry of Health Malawi and National AIDS Commission (2009) Early Infant Diagnosis Report, 24 August.
19. Kabue MM, Braun M, Aetker L, Chirwa M, Mofolo I, et al. (2009) ART initiation and increased survival of infants traced from PMTCT to pediatric HIV care: highlighting the need for program coordination in Lilongwe, Malawi. 5th Conference on HIV Pathogenesis, Treatment and Prevention. Cape Town, South Africa. Abstract WEPDD103.
Peltier CA, Omes C, Ndimubanzi PC, Ndayisaba GF, Stulac S, Arendt V, Courteille O, Muganga N, Kayumba K, Van den Ende J. Validation of 2006 WHO prediction scores for true HIV infection in children less than 18 months with a positive serological HIV test. PLoS One. 2009;4(4):e5312. doi: 10.1371/journal.pone.0005312. Epub 2009 Apr 24.
Inwani I, Mbori-Ngacha D, Nduati R, Obimbo E, Wamalwa D, John-Stewart G, Farquhar C. Performance of clinical algorithms for HIV-1 diagnosis and antiretroviral initiation among HIV-1-exposed children aged less than 18 months in Kenya. J Acquir Immune Defic Syndr. 2009 Apr 15;50(5):492-8. doi: 10.1097/QAI.0b013e318198a8a4.
Kilewo C, Karlsson K, Massawe A, Lyamuya E, Swai A, Mhalu F, Biberfeld G; Mitra Study Team. Prevention of mother-to-child transmission of HIV-1 through breast-feeding by treating infants prophylactically with lamivudine in Dar es Salaam, Tanzania: the Mitra Study. J Acquir Immune Defic Syndr. 2008 Jul 1;48(3):315-23. doi: 10.1097/QAI.0b013e31816e395c.
Kumwenda NI, Hoover DR, Mofenson LM, Thigpen MC, Kafulafula G, Li Q, Mipando L, Nkanaunena K, Mebrahtu T, Bulterys M, Fowler MG, Taha TE. Extended antiretroviral prophylaxis to reduce breast-milk HIV-1 transmission. N Engl J Med. 2008 Jul 10;359(2):119-29. doi: 10.1056/NEJMoa0801941. Epub 2008 Jun 4.
Six Week Extended-Dose Nevirapine (SWEN) Study Team, Bedri A, Gudetta B, Isehak A, Kumbi S, Lulseged S, Mengistu Y, Bhore AV, Bhosale R, Varadhrajan V, Gupte N, Sastry J, Suryavanshi N, Tripathy S, Mmiro F, Mubiru M, Onyango C, Taylor A, Musoke P, Nakabiito C, Abashawl A, Adamu R, Antelman G, Bollinger RC, Bright P, Chaudhary MA, Coberly J, Guay L, Fowler MG, Gupta A, Hassen E, Jackson JB, Moulton LH, Nayak U, Omer SB, Propper L, Ram M, Rexroad V, Ruff AJ, Shankar A, Zwerski S. Extended-dose nevirapine to 6 weeks of age for infants to prevent HIV transmission via breastfeeding in Ethiopia, India, and Uganda: an analysis of three randomised controlled trials. Lancet. 2008 Jul 26;372(9635):300-13. doi: 10.1016/S0140-6736(08)61114-9.
25. Chasela C, Hudgens M , Jamieson D , Kayira D , Hosseinipour M, et al. (2009) Both maternal HAART and daily infant nevirapine (NVP) are effective in reducing HIV-1 transmission during breastfeeding in a randomized trial in Malawi: 28 week results of the Breastfeeding, Antiretroviral and Nutrition (BAN) Study. 5th Conference on HIV Pathogenesis, Treatment and Prevention. Cape Town, South Africa. Abstract WELBC103.
26. World Health Organization (2008) World Malaria Report. Available: http://apps.who.int/malaria/wmr2008/malaria2008.pdf. Accessed 19 November 2009.

Responsible Party: University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT01388452     History of Changes
Other Study ID Numbers: 10-0441
R24TW007988 ( U.S. NIH Grant/Contract )
5P30AI050410 ( U.S. NIH Grant/Contract )
First Submitted: June 14, 2011
First Posted: July 6, 2011
Last Update Posted: May 14, 2013
Last Verified: May 2013

Keywords provided by University of North Carolina, Chapel Hill:
HIV
routine HIV testing
provider-initiated HIV testing and counseling
early infant diagnosis
Africa South of the Sahara

Additional relevant MeSH terms:
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases


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