Comparison of New Anti-HIV Drug Combinations in HIV-Infected Children Who Have Taken Anti-HIV Drugs
Status:
Completed
Trial end date:
2001-06-01
Target enrollment:
Participant gender:
Summary
For PRAM-1: To evaluate zidovudine (ZDV) + lamivudine (3TC) vs. stavudine (d4T) + ritonavir
vs. ZDV + 3TC + ritonavir with respect to the change in plasma HIV-1 RNA copy number from
baseline to 48 weeks [AS PER AMENDMENT 1/5/98: 72 weeks; AS PER AMENDMENT 7/17/98: 48 weeks]
in stable HIV-infected children with >= 16 weeks of prior continuous antiretroviral therapy.
To evaluate the safety and tolerance of ZDV + 3TC vs. d4T + ritonavir vs. ZDV + 3TC +
ritonavir based upon laboratory and clinical toxicities.
AS PER AMENDMENT 10/20/97: For PRAM-1, Step 2: To evaluate d4T + nevirapine + ritonavir with
respect to change in plasma HIV-1 RNA copy number from baseline to 48 weeks in children who
have received at least 12 weeks of therapy on the PRAM-1 ZDV/3TC arm and have over 10,000
viral copies at weeks 12, 24, or 36. To evaluate the safety and tolerance of d4T + nevirapine
+ ritonavir based upon laboratory and clinical toxicities. [AS PER AMENDMENT 10/23/98: To
evaluate safety and tolerance of a switch from d4T + ritonavir vs. ZDV + 3TC + ritonavir to
d4T + indinavir vs. ZDV + 3TC + indinavir in stable, HIV-infected children with RNA values <=
10,000 copies/ml.] For PRAM-1: Evidence supports combination therapy with 2 or more antiviral
agents as beneficial in the long-term management of HIV. The possibility exists that
combination therapy may result in a synergistic or additive activity over a prolonged period
of time. Also hypothesized is that the development of resistance to individual agents will be
developed if viral replication is significantly decreased.
AS PER AMENDMENT 10/20/97: For PRAM-1, Step 2: Interim analysis at 12 weeks on PRAM-1
indicates that the proportion of children reaching undetectable RNA levels on the ZDV + 3TC
arm is significantly less than the other two arms. The protocol, therefore, has been modified
(Step 2) to permit children in the ZDV + 3TC arm with RNA copy number >= 10,000 the
opportunity to change to a novel therapeutic regimen (d4T + nevirapine + ritonavir).
Phase:
Phase 2
Details
Lead Sponsor:
National Institute of Allergy and Infectious Diseases (NIAID)