Optimizing Pediatric HIV-1 Treatment, Nairobi, Kenya

NCT00428116 | Terminated Results DMC

• 2 other identifiers: STUDY00001675R01HD023412
• Study Type: interventional
• Target: 140
• Locations: 0 countries
• Sites: N/A

Brief Summary

Given the high mortality associated with infant HIV-1 and the fact that surrogate markers are poorly predictive of mortality risk,empiric highly active antiretroviral therapy (HAART) initiation is started in infants younger than 12 months. A problem with this approach is that it obligates infants to life-long therapy, which may be associated with cumulative drug toxicity, poor adherence, and treatment failure. Early HAART for prevention of mortality during the first 2 years of life has potential to salvage immune function and alter viral set-point, allowing withdrawal of therapy, perhaps for several years, until subsequent CD4% decline requires it. This untested approach is attractive because it combines the survival benefits of early pediatric HAART therapy with the benefits of antiretroviral deferral. One hundred and fifty infants who initiated HAART at \<13 months of age will be treated with HAART regimen for 24 months after which those who have immune reconstitution and adequate growth (\~100) will be randomized to continued versus deferred therapy. Clinical outcomes, growth, and toxicity will be compared in these children to determine if interruption is a safe and beneficial strategy. Follow-up in this studies will be closely monitored by an external Data Safety and Monitoring Board (DSMB).

Conditions

HIV Infections

Keywords

HIV-1; Pediatric; HAART; Treatment Naive

Outcome Measures

Primary Outcomes (1)

• Growth at 18 Months Post-randomization

  Weight and height will be transformed to the weight-for-age Z-score (i.e., WAZ) and height-for-age Z-score (i.e., HAZ) using World Health Organization Child Growth Standards, taking into account the infant's age and gender.

  18 months of post-randomization follow-up

Secondary Outcomes (1)

• Morbidity

  18 months post-randomization

Study Arms (2)

Interrupted HAART

NO INTERVENTION

After 24 months of treatment with HAART, half the eligible infants will be randomized to interrupted treatment and followed for 18 months.

Continued HAART

ACTIVE COMPARATOR

After 24 months of treatment with HAART, half the eligible infants will be randomized to continued treatment with HAART for 18 months.

Drug: HAART

Interventions

HAART DRUG

Combination first line antiretrovirals as previously described.

Continued HAART

Eligibility Criteria

• Age: Up to 54 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• A. Infants newly initiating HAART
• Less than 13 months of age
• HIV-1 DNA detection with confirmation (positive on two HIV-1 DNA filter paper tests)
• Caregiver of infant plans to reside in Nairobi for at least 3 years (reported by caregiver)
• Caregiver is able to provide sufficient location information
• B. Infants already receiving HAART
• Initiated HAART at \<13 months of age
• Records confirming HIV positive status
• Documentation of CD4% and weight prior to HAART initiation
• Must be on 1st line drug regimen
• Eligibility for randomization:
• Completed 24 months of treatment with HAART
• Normalized growth: weight for height z-score (WHZ) \> -0.5; Child's weight must be above the 5th weight-for-age percentile and the weight curve must not be flat or falling (i.e. cross 2 major percentile lines or more over the past 3 months)
• CD4% \> 25
• Children who recently initiated or who require anti-tuberculosis treatment at the time of randomization will be ineligible for randomization.

Sponsors & Collaborators

• University of Washington: lead
• Fred Hutchinson Cancer Center: collaborator
• University of Nairobi: collaborator
• National Institutes of Health (NIH): collaborator
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Related Publications (10)

• Wamalwa D, Benki-Nugent S, Langat A, Tapia K, Ngugi E, Moraa H, Maleche-Obimbo E, Otieno V, Inwani I, Richardson BA, Chohan B, Overbaugh J, John-Stewart GC. Treatment interruption after 2-year antiretroviral treatment initiated during acute/early HIV in infancy. AIDS. 2016 Sep 24;30(15):2303-13. doi: 10.1097/QAD.0000000000001158.

  PMID: 27177316 RESULT

• Njuguna IN, Wagner AD, Cranmer LM, Otieno VO, Onyango JA, Chebet DJ, Okinyi HM, Benki-Nugent S, Maleche-Obimbo E, Slyker JA, John-Stewart GC, Wamalwa DC. Hospitalized Children Reveal Health Systems Gaps in the Mother-Child HIV Care Cascade in Kenya. AIDS Patient Care STDS. 2016 Mar;30(3):119-24. doi: 10.1089/apc.2015.0239.

  PMID: 27308805 RESULT

• Sridharan G, Wamalwa D, John-Stewart G, Tapia K, Langat A, Moraa Okinyi H, Adhiambo J, Chebet D, Maleche-Obimbo E, Karr CJ, Benki-Nugent S. High Viremia and Wasting Before Antiretroviral Therapy Are Associated With Pneumonia in Early-Treated HIV-Infected Kenyan Infants. J Pediatric Infect Dis Soc. 2017 Sep 1;6(3):245-252. doi: 10.1093/jpids/piw038.

  PMID: 27481854 RESULT

• Asbjornsdottir KH, Hughes JP, Wamalwa D, Langat A, Slyker JA, Okinyi HM, Overbaugh J, Benki-Nugent S, Tapia K, Maleche-Obimbo E, Rowhani-Rahbar A, John-Stewart G. Differences in virologic and immunologic response to antiretroviral therapy among HIV-1-infected infants and children. AIDS. 2016 Nov 28;30(18):2835-2843. doi: 10.1097/QAD.0000000000001244.

  PMID: 27603293 RESULT

• Wagner A, Slyker J, Langat A, Inwani I, Adhiambo J, Benki-Nugent S, Tapia K, Njuguna I, Wamalwa D, John-Stewart G. High mortality in HIV-infected children diagnosed in hospital underscores need for faster diagnostic turnaround time in prevention of mother-to-child transmission of HIV (PMTCT) programs. BMC Pediatr. 2015 Feb 15;15:10. doi: 10.1186/s12887-015-0325-8.

  PMID: 25886564 RESULT

• Benki-Nugent S, Eshelman C, Wamalwa D, Langat A, Tapia K, Okinyi HM, John-Stewart G. Correlates of age at attainment of developmental milestones in HIV-infected infants receiving early antiretroviral therapy. Pediatr Infect Dis J. 2015 Jan;34(1):55-61. doi: 10.1097/INF.0000000000000526.

  PMID: 25144793 RESULT

• Slyker JA, Casper C, Tapia K, Richardson B, Bunts L, Huang ML, Wamalwa D, Benki-Nugent S, John-Stewart G. Accelerated suppression of primary Epstein-Barr virus infection in HIV-infected infants initiating lopinavir/ritonavir-based versus nevirapine-based combination antiretroviral therapy. Clin Infect Dis. 2014 May;58(9):1333-7. doi: 10.1093/cid/ciu088. Epub 2014 Feb 18.

  PMID: 24550373 RESULT

• Langat A, Benki-Nugent S, Wamalwa D, Tapia K, Ngugi E, Diener L, Richardson BA, Melvin A, John-Stewart GC. Lipid changes in Kenyan HIV-1-infected infants initiating highly active antiretroviral therapy by 1 year of age. Pediatr Infect Dis J. 2013 Jul;32(7):e298-304. doi: 10.1097/INF.0b013e31828afb2a.

  PMID: 23385950 RESULT

• Benki-Nugent SF, Martopullo I, Laboso T, Tamasha N, Wamalwa DC, Tapia K, Langat A, Maleche-Obimbo E, Marra CM, Bangirana P, Boivin MJ, John-Stewart GC. High Plasma Soluble CD163 During Infancy Is a Marker for Neurocognitive Outcomes in Early-Treated HIV-Infected Children. J Acquir Immune Defic Syndr. 2019 May 1;81(1):102-109. doi: 10.1097/QAI.0000000000001979.

  PMID: 30768490 DERIVED

• Benki-Nugent S, Wamalwa D, Langat A, Tapia K, Adhiambo J, Chebet D, Okinyi HM, John-Stewart G. Comparison of developmental milestone attainment in early treated HIV-infected infants versus HIV-unexposed infants: a prospective cohort study. BMC Pediatr. 2017 Jan 17;17(1):24. doi: 10.1186/s12887-017-0776-1.

  PMID: 28095807 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

Antiretroviral Therapy, Highly Active

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

Intervention Hierarchy (Ancestors)

Drug Therapy, Combination; Drug Therapy; Therapeutics

Results Point of Contact

• Title: Grace John-Stewart
• Organization: University of Washington

gjohn@uw.edu

206 543 4278

Study Officials

• Dalton Wamalwa, MMed, MPH

  Department of Paediatrics and Child Health, Kenyatta National Hospital, University of Nairobi

  PRINCIPAL INVESTIGATOR

• Grace C John-Stewart, MD, PhD

  University of Washington

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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: Professor

Study Record Dates

• First Submitted: January 22, 2007
• First Posted: January 29, 2007
• Study Start: September 1, 2007
• Primary Completion: July 1, 2013
• Study Completion: December 1, 2014
• Last Updated: July 26, 2018
• Results First Posted: August 20, 2015

Record last verified: 2018-06