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HPTN 020 SAFETY & TOLERABILITY OF VAGINAL PRO 2000 GEL

HPTN 020 SAFETY & TOLERABILITY OF VAGINAL PRO 2000 GEL LESSONS LEARNED. PRO 2000 GEL. SYNTHETIC NAPHTHALENE SULFONATE POLYMER AQUEOUS GEL WITH CARBOMER, pH 4.5 BUFFER, PARABEN PRESERVATIVES

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HPTN 020 SAFETY & TOLERABILITY OF VAGINAL PRO 2000 GEL

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  1. HPTN 020 SAFETY & TOLERABILITY OF VAGINAL PRO 2000 GEL LESSONS LEARNED

  2. PRO 2000 GEL • SYNTHETIC NAPHTHALENE SULFONATE POLYMER • AQUEOUS GEL WITH CARBOMER, pH 4.5 BUFFER, PARABEN PRESERVATIVES • BINDS GP 120, INTERFERES WITH CD4 BINDING AND V3 LOOP-ASSOCIATED CELL FUSION (INTERNEURON PHARMACEUTICALS)

  3. PRO 2000 Activity In Vitro

  4. PRIOR DATA: PRO 2000 GEL • CERVICAL EXPLANT AND MACAQUE MODELS: PROTECTION AT 0.5-4% • 73 SEXUALLY ABSTINENT WOMEN FROM LONDON AND ANTWERP • APPLIED PLACEBO, 0.5%, OR 4% GEL INTRAVAGINALLY QD X 14D • NO SAE OR ABSORPTION CV BIOPSIES: NO INFLAMMATION (VAN DAMME, 2000)

  5. HPTN 020: PARTICIPANTS AND TRIAL DESIGN HIV- HIV+ • PHILADELPHIA 10 3 • PROVIDENCE 14 3 • DURBAN 13 3 • JOHANNESBURG 13 4 • COHORTS: A1: 2% QD A2: 2% BID A3: 4% QD A4: 4% BID B1: 4%BID

  6. HPTN 020: DEMOGRAPHICS • MEAN AGE: 30.3, RANGE: 18-45 Y.O. • US: 2/3 CAUCASIAN; 10% AFRICAN-AM. • SA: 55% INDIAN; 39% BLACK. • HIV+ WOMEN: MEDIAN CD4: 608 MEDIAN PVL: 3, 413 4 WOMEN ON HAART

  7. HPTN 020: CLINICAL COURSE • 95% COMPLETED COURSE AND WERE ADHERENT • 24/24 COMPLETED 2% AND 4% QD • 1/13 IN 2 % BID COHORT D/C: HSV • 1/13 IN 4% BID D/C B/C EPITHELIAL LESIONS (?ABUSE) • 1/13 HIV+ WOMAN BECAME PREGNANT

  8. CLINICAL EVENTS: HPTN 020 • OVER 90% REPORTED AT LEAST ONE AE; 0 SAE MAINLY MILD, TRANSIENT VAGINAL SXS: • DISCHARGE: 27% BLEEDING: 25% PAIN: 19% PRURITUS: 17% BURNING: 16% IRRITATION: 14% EROSIONS: VAGINAL OR VULVAR: 8% CERVICAL: 6% UTERINE OR CERVICAL BLEEDING: 10%

  9. COLPOSCOPIC ADVERSE EVENTS: HPTN O2O EXTERNAL GENITAL TRACT ABRASION: 10% EXTERNAL OR CERVICAL ERYTHEMA: 8% CERVICAL ULCERATION: 8% OF 15 WOMEN WITH EPITHELIAL DISRUPTION: APPLICATOR TRAUMA 4 SPECULUM TRAUMA 2 HSV INFECTION 2 SHAVING CUT OR PHYSICAL TRAUMA 2 REMOVAL OF CONDOM FRAGMENT 1

  10. GENITAL TRACT INFECTIONS 3 PTS DEVELOPED HSV 3 PTS DEVELOPED UTI I PT DEVELOPED CLINICAL BV OF 5 PTS WITH 3/4 AMSEL’S CRITERIA PRE-TRIAL, NO CLINICAL BV, BUT 2 STILL HAD 3/4 (+) AMSEL SOME DECREASE IN LACTOBACILLI (?DILUTION) NO CLINICAL CANDIDIASIS IN THE TRIAL. MEDIAN pH: 5.0 AFTER 2 WEEKS (MAX: 6.0)

  11. REGIMEN & CLINICAL FINDINGS • NO CORRELATION OF MUCOSAL ABNORMALITIES BY GEOGRAPHIC SITE, FREQUENCY OR DOSE. • HIV+ WOMEN HAD MORE EPITHELIAL EVENTS. • WOMEN WHO USED 4% PRO 2000 BID HAD MORE SYMPTOMS. • INCREASED SEXUAL ACTIVITY AND FEWER AE? (p=0.08). ?RELATIONSHIP

  12. ACCEPTABILITY: HPTN 020 “IF YOU HAD REASON TO BE WORRIED ABOUT HIV AND PRO 2000 GEL WERE AVAILABLE OTC….WOULD YOU USE IT? 100% YES “WOULD YOU RECOMMEND THE PRODUCT TO OTHER WOMEN?” 100% YES

  13. SUMMARY OF HPTN 020 GENERALLY SAFE, WELL TOLERATED, AND ACCEPTABLE TO LOW RISK HIV- SEXUALLY ACTIVE AND ABSTINENT HIV+ WOMEN SUGGESTION OF INCREASED SYMPTOMS AND MUCOSAL EVENTS WITH INCREASED CONCENTRATION AND FREQUENCY, BUT N’S ARE SMALL REASONABLE TO GO FORWARD WITH EFFICACY TRIAL.

  14. ISSUES TO CONSIDER • PRO 2000: WELL-TOLERATED IN 136 WOMEN WHEN USED QD AND BID FOR UP TO 14 DAYS • ? MORE MUCOSAL EVENTS AND SXS IN HIGHER CONCENTRATION, AND HIV+ WOMEN. • MACAQUE MODELS- PROTECTION AT 0.5%. INCREASED FINDINGS AT 2% AND 4%, NONE AT 0.5% (PATTON, 2001). • NEED FOR PLACEBO AND OBSERVATIONAL ARMS B/C INTENSIVE EVALUATIONS.

  15. Roberta Black Margaret Chesney Cynthia Clark Anne Coletti Amy Cooper Paulette Corey Michelle Culp Jennifer Day Diane Dean Anne Emans Lynda Emel Alice Fisher Tom Fleming Jorges Flores Salim Karim Quarraisha Karim Cliff Kelly Laurie Kunches Dale Lawrence HPTN 020 PROTOCOL TEAM

  16. Craig Magaret Lisa Maslankowski Kenneth Mayer James McIntyre Linda McNeil David Metzger Paolo Miotti Neetha Morar Jeffrey Peipert Scott Plusquellec Al Profy Gita Ramjee Helen Rees Barbra Richardson Zeda Rosenberg Hayes Sheppard Mark Vajaranant Julia Welch HPTN 020 PROTOCOL TEAM

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