A5175 Mar2008
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Transcript of A5175 Mar2008
PEARLS
A Prospective Evaluation ofAntiRetroviral Treatment inResource-Limited Settings
ACTG A5175
A Phase IV, Prospective, Randomized,Open Label Evaluation of the Efficacyof Once Daily Protease Inhibitor- andOnce Daily Non- Nucleoside Reverse
Transcriptase Inhibitor-ContainingTherapy Combinations for the
Initial Treatment of HIV-1 Infected Individuals from Resource-Limited
Settings
“Men wanted for hazardous journey. Small wages, bitter cold, long months of complete darkness, constant danger, safe return doubtful. Honor and recognition in case of success.”
PEARLS, an ongoing voyage on uncharted seas…
…launched from a mature clinical trials organization
ACTG proposes international initiative to NIAID - 1999
06/06 e
The greatest burden of the epidemic is outsidethe U.S., especially in resource-limited settings
2.4
WHO-UNAIDS Data
Need for treatment far exceeds access
Organizational, funding & pharmaceutical provisions were provided
Despite uncertainties the PEARLS crew maintained a single intention of purpose…
…meeting biweekly via teleconferences & in person whenever possible…
… with leadership from the Co-Captains
1520 adult patients “naïve” to treatment with CD4 T-cells <300 enroll, 270 from the U.S. and 1250 from resource limited settings
Three types of anti-HIV medication are used
Nucleoside reverse transcriptase inhibitor (NRTI)
Non-NRTI (NNRTI)
Protease inhibitor (PI)
Hypothesis 1: three-drug regimens are given once vs. twice daily provide similar anti-HIV benefit
Hypothesis 2: a drug regimen containing a PI, given once a day, provides similar anti-HIV benefit versus a regimen containing an NNRTI given twice a day
Patients are randomized open label to either
2 NRTIs + NNRTI 2x/day or
2 NRTI + PI 1x/day or
2 NRTIs + NNRTI 1x/day
The time from initiation of treatment untilthe failure of treatment is the primary study endpoint and defined as either:
Death any reasonDisease progression medical condition that defines AIDSVirologic failure 2 viral loads >1,000 c/mL at wk 16 or later
2002 04 05 06 07
May DSMBJuneFull accrual n = 1520
April Protocol developmentbegan
MayV1.0
MayAccrual beganNovemberDSMB
July DSMB OctoberV2.0NovemberDSMB
Lima
Rio de Janerio*
Porto Alegre Johannesburg*
Durban
Harare
Lilongwe
Blantyre
Chennai*Pune*
Chiang MaiPort-au-Prince
21 Sites Data Center
33 clinical research sites implement PEARLS
*Genotyping labs
PEARLS encounters challenges and uncertainties
Research infrastructure was limited in certain areas & was upgraded
Acquisition of study drugs were at times challenging
Changes in HIV clinical science and differing treatment guidelines necessitates adaptation
Conclusions
The voyage continues…
Photo Credits: women & boy, UNAIDS/G. Pirozzi; woman & man, UNAIDS/W. Phillips; medications, UNAIDS/O. O’Hanlon