a5175 mar2008
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PEARLS
A Prospective Evaluation ofAntiRetroviral Treatment inResource-Limited Settings
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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
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“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.”
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PEARLS, an ongoing voyage on uncharted seas…
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…launched from a mature clinical trials organization
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ACTG proposes international initiative to NIAID - 1999
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06/06 e
The greatest burden of the epidemic is outsidethe U.S., especially in resource-limited settings
2.4
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WHO-UNAIDS Data
Need for treatment far exceeds access
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Organizational, funding & pharmaceutical provisions were provided
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Despite uncertainties the PEARLS crew maintained a single intention of purpose…
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…meeting biweekly via teleconferences & in person whenever possible…
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… with leadership from the Co-Captains
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1520 adult patients “naïve” to treatment with CD4 T-cells <300 enroll, 270 from the U.S. and 1250 from resource limited settings
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Three types of anti-HIV medication are used
Nucleoside reverse transcriptase inhibitor (NRTI)
Non-NRTI (NNRTI)
Protease inhibitor (PI)
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Hypothesis 1: three-drug regimens are given once vs. twice daily provide similar anti-HIV benefit
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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
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Patients are randomized open label to either
2 NRTIs + NNRTI 2x/day or
2 NRTI + PI 1x/day or
2 NRTIs + NNRTI 1x/day
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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
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2002 04 05 06 07
May DSMBJuneFull accrual n = 1520
April Protocol developmentbegan
MayV1.0
MayAccrual beganNovemberDSMB
July DSMB OctoberV2.0NovemberDSMB
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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
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PEARLS encounters challenges and uncertainties
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Research infrastructure was limited in certain areas & was upgraded
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Acquisition of study drugs were at times challenging
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Changes in HIV clinical science and differing treatment guidelines necessitates adaptation
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Conclusions
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The voyage continues…
Photo Credits: women & boy, UNAIDS/G. Pirozzi; woman & man, UNAIDS/W. Phillips; medications, UNAIDS/O. O’Hanlon