Treatment With Combinations of Several Antiviral Drugs in Infants and Young Children With HIV Infection
Condition: HIV Infections
MeSH terms: Infections; HIV Infections; Acquired Immunodeficiency Syndrome
Study type: Interventional
Phase: Phase 2

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.]
    

Intervention name(s): Abacavir sulfate; Nelfinavir mesylate; Nevirapine; Lamivudine; Stavudine; Zidovudine
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug
Intervention MeSH terms: Lamivudine; Zidovudine; Nevirapine; Abacavir; Stavudine; Nelfinavir
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
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