A5175 Mar2008


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  • A5175 PEARLS: A Prospective Evaluation of ART in Resource-Limited Settings Overview 1. Adult AIDS Clinical Trials Group 2. AACTG International Program 3 Chronology of Development & Implementation 4. Study Design 5. Protocol Team & Research Sites 6. Challenges 7. Current Demographics Conclusions My Role: 8.5 years as a manager and senior clinical trials specialist at the ACTG Operations Center. 5 years as the senior clinical trials specialist and project manager on PEARLS.
  • A5175 Mar2008

    1. 1. PEARLS A P rospective E valuation of A nti R etroviral T reatment in R esource- L imited S ettings
    2. 2. <ul><li>ACTG A5175 </li></ul><ul><li>A Phase IV, Prospective, Randomized, </li></ul><ul><li>Open Label Evaluation of the Efficacy </li></ul><ul><li>of Once Daily Protease Inhibitor- and </li></ul><ul><li>Once Daily Non- Nucleoside Reverse </li></ul><ul><li>Transcriptase Inhibitor-Containing </li></ul><ul><li>Therapy Combinations for the </li></ul><ul><li>Initial Treatment of HIV-1 Infected Individuals from Resource-Limited Settings </li></ul>
    3. 3. “ 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.”
    4. 4. PEARLS, an ongoing voyage on uncharted seas…
    5. 5. … launched from a mature clinical trials organization
    6. 6. ACTG proposes international initiative to NIAID - 1999
    7. 7. 06/06 e The greatest burden of the epidemic is outside the U.S., especially in resource-limited settings 2.4
    8. 8. WHO-UNAIDS Data Need for treatment far exceeds access
    9. 9. Organizational, funding & pharmaceutical provisions were provided
    10. 10. Despite uncertainties the PEARLS crew maintained a single intention of purpose…
    11. 11. … meeting biweekly via teleconferences & in person whenever possible…
    12. 12. … with leadership from the Co-Captains
    13. 13. 1520 adult patients “naïve” to treatment with CD4 T-cells <300 enroll, 270 from the U.S. and 1250 from resource limited settings
    14. 14. Three types of anti-HIV medication are used Nucleoside reverse transcriptase inhibitor (NRTI) Non-NRTI (NNRTI) Protease inhibitor (PI)
    15. 15. Hypothesis 1: three-drug regimens are given once vs. twice daily provide similar anti-HIV benefit
    16. 16. 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
    17. 17. Patients are randomized open label to either 2 NRTIs + NNRTI 2x/day or 2 NRTI + PI 1x/day or 2 NRTIs + NNRTI 1x/day
    18. 18. The time from initiation of treatment until the failure of treatment is the primary study endpoint and defined as either: Death any reason Disease progression medical condition that defines AIDS Virologic failure 2 viral loads >1,000 c/mL at wk 16 or later
    19. 19. 2002 04 05 06 07 May DSMB June Full accrual n = 1520 April Protocol development began May V1.0 May Accrual began November DSMB July DSMB October V2.0 November DSMB
    20. 20. Lima Rio de Janerio* Porto Alegre Johannesburg* Durban Harare Lilongwe Blantyre Chennai* Pune* Chiang Mai Port-au-Prince 21 Sites Data Center 33 clinical research sites implement PEARLS *Genotyping labs
    21. 21. PEARLS encounters challenges and uncertainties
    22. 22. Research infrastructure was limited in certain areas & was upgraded
    23. 23. Acquisition of study drugs were at times challenging
    24. 24. Changes in HIV clinical science and differing treatment guidelines necessitates adaptation
    25. 25. Conclusions
    26. 26. The voyage continues… Photo Credits: women & boy, UNAIDS/G. Pirozzi; woman & man, UNAIDS/W. Phillips; medications, UNAIDS/O. O’Hanlon