Microbicide safety and effectiveness: an overview of recent clinical trials.
OBJECTIVE
This review summarizes findings from recent vaginal microbicide safety and effectiveness trials and discusses the challenges associated with undertaking these trials.


RESULTS
In safety trials, there has been a focus on the development of biomarkers of genital irritation. Recent safety studies have expanded the range of genital toxicity measures to include biomarkers of mucosal immunity, detection of haemoglobin in cervicovaginal lavage specimens and microbicide-induced vaginal flora changes. Four effectiveness trials have been stopped prematurely, two due to a lower than estimated HIV incidence rate, one as a result of an interim analysis suggesting increased risk of HIV acquisition among participants receiving active product, and one as a safety precaution. One effectiveness trial was completed and showed no reduction in HIV acquisition among participants receiving active product, and one ongoing effectiveness trial was modified by discontinuing a trial arm. Methodological challenges faced by these trials have included accurately estimating HIV incidence and pregnancy rates in trial populations, and improving adherence to and measurement of study product use.


CONCLUSIONS
Validated safety and surrogate efficacy endpoints and standard ways of reporting them are being pursued. Focus has shifted to antiretrovirals containing microbicides, some of which may be used independent of coitus. Research on how to improve and measure adherence should continue.
National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, Australia.
Mary
M
Poynten
Joelle M
JM
Brown
Monica
M
Sovero
Iona Y
IY
Millwood
John M
JM
Kaldor