Clinical trial NCT00000872: Treatment With Combinations of Several Antiviral Drugs in Infants and Young Children With HIV Infection
Official title: Early Intensive Antiretroviral Combination Therapy in HIV-1 Infected Infants and Children
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infections
Keywords: Virus Replication
HIV-1
Drug Therapy, Combination
Zidovudine
Nevirapine
Stavudine
HIV Protease Inhibitors
CD4 Lymphocyte Count
Lamivudine
RNA, Viral
Reverse Transcriptase Inhibitors
Anti-HIV Agents
Viral Load
Nelfinavir
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2001-08-31
Enrollment: 55
Sex: ALL
Minimum age (years): 15
Maximum age (years): 2
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This trial tests the safety and effectiveness of the early use of combinations of anti-HIV drugs in HIV-infected infants and young children in an effort to block virus growth and preserve normal immune functions.

Various anti-HIV drug combinations need to be tested in order to find the best way to treat infants and children who have been infected with HIV during birth.

Detailed description: This study examines the antiretroviral activity of ZDV/3TC/NVP in vertically-infected infants and children aged 15 days up to 2 years, and ZDV/3TC/NVP/ABC in vertically-infected infants and children aged 30 days up to 2 years. This study will assess HIV-1 and CD4/CD8 T-cell kinetics, activation, and maturation. It will also test the concept that early (younger than 3 months of age) use of potent, combination antiretroviral therapy will allow the long-term control of viral replication with preservation of normal immune function. \[AS PER AMENDMENT 3/11/98: This study will also examine the antiretroviral activity of ZDV/3TC/NVP/NFV in vertically infected infants and children.\]

This is a 2-part Phase I/II, open-label trial in HIV-infected infants. Part A assesses the triple combination of ZDV, 3TC, and NVP. Four to eight patients are enrolled in each age cohort (Cohort 1: at least 15 days, no more than 3 months; Cohort 2: over 3 months, no more than 2 years). Part B assesses the quadruple combination of ZDV, 3TC, NVP, and ABC. Eight patients are enrolled in each age cohort (Cohort 3: at least 30 days, no more than 3 months; Cohort 4: over 3 months, no more than 2 years). \[AS PER AMENDMENT 3/11/98: This study is now a 3-part Phase I/II trial. Parts A and B are as above. Part C will assess the quadruple regimen of d4T, 3TC, NVP and NFV. Up to 8 patients will be enrolled in each age cohort (Cohort 5: at least 15 days, no more than 3 months; Cohort 6: over 3 months, no more than 2 years). If 3 of 4 patients in either cohort of Part B do not achieve plasma RNA less than 1,000 copies/ml after 16 weeks of quadruple therapy, enrollment of patients to that cohort will stop and enrollment of 8 patients to the corresponding cohort in Part C will begin. For Part C, patients whose RNA level is no more than 1,000 copies/ml at Week 16 will remain on assigned treatment until Week 104. If at any time between Weeks 16 and 104 a patient's RNA level increases to greater than 1,000 copies/ml, plasma RNA will be repeated within 1 week. If both RNA levels are greater than 1,000 copies/ml, the patient will discontinue study treatment and be followed every 12 weeks for 1 year.\] \[AS PER AMENDMENT 4/14/99: The study has been extended for an additional 96 weeks for children with continued suppression of viral replication (RNA less than 400 copies/ml) at Week 104. If at any time between Week 12 or 16 and Week 200 a patient's RNA level increases to greater than 1,000 copies/ml, plasma RNA will be repeated within 1 week. If both RNA levels are above 1,000 copies/ml, the patient will discontinue treatment for best available therapy and be followed every 12 weeks for 1 year following the discontinuation of study treatment.\] \[AS PER AMENDMENT 9/16/99: An additional cohort (Cohort 7) of 5 to 10 patients has been added. Cohort 7 includes patients between 15 days and 3 months of age. Cohort 7 patients who experience suppression of viral replication at Week 104 are followed through Week 200.\]

Eligibility criteria: Inclusion Criteria

Children may be eligible for this study if they:

* Are 15 days to 2 years old.
* Have consent of parent or legal guardian.
* Are HIV-positive.

Exclusion Criteria

Children will not be eligible for this study if they:

* Have certain infections which require treatment during the study.
* Have received certain medications.

Primary outcomes:
measure: Antiretroviral activity of ZDV/3TC/NVP
timeFrame: Throughout study
measure: Durability of viral suppression
timeFrame: Throughout study
measure: Immune competence and HIV-1 specific immune respones with prolonged viral suppression beyond 104 weeks
timeFrame: Throughout study
measure: Antiretroviral activity of ZDV/3TC/NVP/1592U89 regimen
timeFrame: Throughout study
measure: Antiretroviral activity of d4T/3TC/NVP/NFV regimen
timeFrame: Throughout study
measure: Tolerance and pharmacokinetic profile of NFV
timeFrame: Throughout study
Secondary outcomes:
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: Univ. of Florida College of Medicine-Dept of Peds, Div. of Immunology, Infectious Diseases & Allergy
state: Florida
city: New Orleans
country: United States
facility: Tulane/LSU Maternal/Child CRS
state: Louisiana
city: Baltimore
country: United States
facility: Univ. of Maryland Med. Ctr., Div. of Ped. Immunology & Rheumatology
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins Hosp. & Health System - Dept. of Peds., Div. of Infectious Diseases
state: Maryland
city: Boston
country: United States
facility: BMC, Div. of Ped Infectious Diseases
state: Massachusetts
city: Springfield
country: United States
facility: Baystate Health, Baystate Med. Ctr.
state: Massachusetts
city: Worcester
country: United States
facility: WNE Maternal Pediatric Adolescent AIDS CRS
state: Massachusetts
city: Detroit
country: United States
facility: Univ. of Mississippi Med. Ctr Children's Hosp.
state: Michigan
city: New York
country: United States
facility: Nyu Ny Nichd Crs
state: New York
city: Philadelphia
country: United States
facility: The Children's Hosp. of Philadelphia IMPAACT CRS
state: Pennsylvania
city: Houston
country: United States
facility: Texas Children's Hosp. CRS
state: Texas
city: Norfolk
country: United States
facility: Children's Hosp. of the King's Daughters, Infectious Disease
state: Virginia
Study officials:
name: Katherine Luzuriaga
role: STUDY_CHAIR
References:
citation: Luzuriaga K, McManus M, Britto P, Wu HL, Lindsey J, Sullivan JL. Viral kinetics and control of replication following potent early combination antiretroviral therapy of vertical HIV-1 infection. HIV Pathog Treat Conf. 1998 Mar 13-19;52 (abstract no 2024)
citation: Capparelli E, Sullivan J, Mofenson L, Smith B, Graham B, Britto P, Becker M, Luzuriaga K. Pharmacokinetics (PK) of nelfinavir and its metabolite (M8) in HIV-infected infants following BID or TID administration. 8th Conf Retro and Opportun Infect. 2001 Feb 4-8 (abstract no 729)
citation: Luzuriaga K, Wu H, McManus M, Britto P, Borkowsky W, Burchett S, Smith B, Mofenson L, Sullivan JL. Dynamics of human immunodeficiency virus type 1 replication in vertically infected infants. J Virol. 1999 Jan;73(1):362-7. doi: 10.1128/JVI.73.1.362-367.1999.
citation: Luzuriaga K, Mcmanus M, Britto P, Wu H, Lindsey J, Smith B, Mofenson L, Sullivan JL. Early combination antiretroviral therapy of vertical HIV-1 infection: viral kinetics and control of viral replication. Conf Retroviruses Opportunistic Infect. 1998 Feb 1-5;5th:225 (abstract no LB12)
citation: Capparelli EV, Sullivan JL, Mofenson L, Smith E, Graham B, Britto P, Becker MI, Holland D, Connor JD, Luzuriaga K; Pediatric ACTG 356 Investigators. Pharmacokinetics of nelfinavir in human immunodeficiency virus-infected infants. Pediatr Infect Dis J. 2001 Aug;20(8):746-51. doi: 10.1097/00006454-200108000-00006.
citation: Luzuriaga K, McManus M, Mofenson L, Britto P, Graham B, Sullivan JL; PACTG 356 Investigators. A trial of three antiretroviral regimens in HIV-1-infected children. N Engl J Med. 2004 Jun 10;350(24):2471-80. doi: 10.1056/NEJMoa032706.
citation: McManus M, Henderson J, Gautam A, Brody R, Weiss ER, Persaud D, Mick E, Luzuriaga K; PACTG 356 Investigators. Quantitative Human Immunodeficiency Virus (HIV)-1 Antibodies Correlate With Plasma HIV-1 RNA and Cell-associated DNA Levels in Children on Antiretroviral Therapy. Clin Infect Dis. 2019 May 2;68(10):1725-1732. doi: 10.1093/cid/ciy753.