Safety, tolerability, and systemic absorption of dapivirine vaginal microbicide gel in healthy, HIV-negative women

被引:74
作者
Nel, Annalene A. [1 ]
Coplan, Paul [2 ]
van de Wijgert, Janneke H. [3 ,4 ]
Kapiga, Saidi H. [5 ,6 ]
von Mollendorf, Claire [7 ]
Geubbels, Eveline [3 ,4 ]
Vyankandondera, Joseph [3 ,8 ]
Rees, Helen V. [7 ]
Masenga, Gileard [5 ]
Kiwelu, Ireen [9 ]
Moyes, Jocelyn [7 ]
Smythe, Shanique C. [1 ]
机构
[1] Int Partnership Microbicides, Silver Spring, MD 20910 USA
[2] Wyeth Res, Collegeville, PA USA
[3] Projet Ubuzima, Kigali, Rwanda
[4] Ctr Poverty Related Communicable Dis, Acad Med Ctr, Amsterdam, Netherlands
[5] Kilimanjaro Reprod Hlth Program, Moshi, Tanzania
[6] London Sch Hyg & Trop Med, London WC1, England
[7] Univ Witwatersrand, Reprod Hlth & HIV Res Unit, Johannesburg, South Africa
[8] Kigali Teaching Hosp, Kigali, Rwanda
[9] Kilimanjaro Reprod Hlth Program, KCMC Biotechnol Lab, Moshi, Tanzania
关键词
dapivirine; HIV; HIV prevention; microbicide; vaginal gel; ACCEPTABILITY; TMC120;
D O I
10.1097/QAD.0b013e32832c413d
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Objectives: To assess the local and systemic safety of dapivirine vaginal gel vs. placebo gel as well as the systemic absorption of dapivirine in healthy, HIV-negative women. Methods: Two prospective, randomized, double-blind, placebo-controlled phase I/II studies were conducted at five research centers, four in Africa and one in Belgium. A total of 119 women used dapivirine gel (concentrations of 0.001, 0.002, 0.005, or 0.021%,), and 28 used placebo gel twice daily for 42 clays. The primary endpoints were colposcopic findings, adverse events, Division of AIDS grade 3 or grade 4 laboratory values, and plasma levels of dapivirine. Results: Safety data were similar for the dapivirine and placebo gels. None of the adverse events with incidence more than 5% occurred with greater frequency in the dapivirine than placebo groups. Similar percentages of placebo and dapivirine gel users had adverse events that were considered by the investigator to be related to study gel. A total of five serious adverse events occurred in the two studies, and none was assessed as related to study gel. Mean plasma concentrations of dapivirine were approximately dose proportional, and, within each dose group, mean concentrations were similar on days 7, 28, and 42. The maximum observed mean concentration was 474 pg/ml in the 0.02%. gel group on clay 28. Two weeks after the final application of study gel, mean concentrations decreased to 5 pg/ml or less. Conclusion: Twice daily administration of dapivirine vaginal gel for 42 days was safe and well tolerated with low systemic absorption in healthy, HIV-negative women Suggesting that continued development is warranted. (C) 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
引用
收藏
页码:1531 / 1538
页数:8
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