A ground-breaking study issued in 2010 indicated a vaginal gel containing an HIV drug can sharply reduce infections in women who use it before and after sex.
"Women did not use consistently any of the products. Adherence was very low," said Marrazzo, part of the project known as the Vaginal and Oral Interventions to Control the Epidemic (VOICE).
HIV/AIDS experts said the results showed how important a factor human behavior is when devising ways to prevent HIV.
Experts have been searching for years for inexpensive, safe and simple medications to decrease the risk of transmission among a population that is largely destitute and with little access to quality health care.
The study also found the group most likely to contract HIV - unmarried women under 25 - was also the most likely not to use any of the medicines. The results were presented at a Conference on Retroviruses and Opportunistic Infections in Atlanta.
The three-year study that started in September 2009 tested a daily tablet called Truvada, which was approved for HIV prevention in July 2012 by the U.S. Food and Drug Administration after it was shown to significantly reduce the risk of HIV infection when used as a preventative measure.
Researchers have been trying for years to formulate a microbicide - a gel, cream, ring or tablet inserted into the vagina or rectum before sex to prevent transmission of the human immunodeficiency virus (HIV) that causes AIDS.
"We need to rethink the design of these intervention trials ... in healthy people because it is difficult for anybody to take a pill or anything every day, particularly when you are healthy and do not feel that you need a drug," said Marrazzo.
Truvada is made by Gilead Sciences, which also developed tenofovir. In 2006, Gilead assigned a royalty-free license for tenofovir gel to CONRAD.
Jonathan Mermin, an HIV/AIDS prevention expert at the U.S. Centers for Disease Control and Prevention (CDC) said these trial results underscored the complexities of getting healthy people to use preventative measures against HIV.
"Clinicians and public health professionals will have to further assess and better understand how to promote and support the high levels of adherence necessary," he said.
(Additional reporting by Kate Kelland in London; Editing by Louise Ireland and Michael Roddy)