A Cellulose Sulfate Gel Study Hopes to Push Microbicide Research Further Ahead

by Chael Needle

LifeGuide/Treatment Horizons

The study, HPTN 049, is part of the groundwork being laid by microbicide researchers and study participants seeking to target the transmission of HIV. While numerous microbicide studies in various phases are being conducted, and a handful in final phases, media attention has been scant. In order for that name-recognition breakthrough to occur, “we would benefit from a ‘Jonas Salk’ of microbicides,” says Dr. Kenneth Mayer, lead investigator for the Providence, Rhode Island, site of the NIH-funded HIV Prevention Trials Network study, which is also being conducted at the University of Pennsylvania in Philadelphia, Harlem Hospital and Bronx Lebanon Hospitals in New York, and the University of Alabama in Birmingham.

HPTN 049 is a multi-site Phase I double-blind study of six-percent cellulose sulfate (CS) gel, a vaginal microbicide candidate. Dr. Mayer says this study is part of a progression of studies that first look at lower-risk women who are sexually abstinent; then lower-risk women who are sexually active; then HIV-positive women; and finally women who are at risk for acquiring HIV.

As CS has already been studied in women who are not HIV-positive, this study decided to enroll abstinent and sexually active HIV-positive women. Fifty-nine have been enrolled, and the sexually active women have had their male partners enrolled. Participants have used six-percent CS gel or the control compound intravaginally once or twice daily for fourteen consecutive days between menses. The study will assess the local and systemic toxicity of the candidate. “Early safety studies are very careful,” says Dr. Mayer, adding that, after informed consent is given, women get blood work done and receive physical exams to determine eligibility. “We screen out women with asymptomatic infections in the genital tract, abnormal liver and kidney chemistries, and then do initial colposcopies to see if there are any significant abnormalities in the genital tract mucous membranes.” A colposcopy is a technique that uses a magnified camera to examine, in this case, the mucous membranes in the genital tract. After one week and then after fourteen days on the product, the participants are examined again to see if the product was associated with any abnormalities. Participants are also asked to keep diaries to assess their experiences with the product.

The criteria for candidacy, Dr. Mayer says, are quite restrictive: women need to have had a normal Pap smear within the past six months; and HIV-positive women need to be on a stable antiretroviral regimen, or not on a regimen at all. “Changing meds is not good for this kind of study,” notes Dr. Mayer. “The meds themselves may have side effects that could be confusing—is it the microbicide or the medicine that’s causing the side effect? One of the other substudies of this trial is how this product affects genital tract HIV. The amount of virus in the blood will be decreased by effective antiretroviral therapy but also the amount of virus in the genital tract will be affected. If you want to be able to show what the product does, you want the participants to be in a steady state with their medication.”

Says Dr. Mayer, a Professor of Medicine & Community Health at Brown University and an Attending Physician in the Division of Infectious Diseases at The Miriam Hospital, “In theory, CS acts as a non-specific blocker of HIV binding. The compound itself interferes with HIV being able to attach to the mucous membranes of the cervix, the vagina, and possibly other mucous membranes.” Researchers know how CS acts in vitro, and animal data suggests that it is protective, but there’s very little human data so far. Says Mayer: “We hope that, if we find a microbicide that protects women from becoming infected with HIV, the same microbicide might protect men and women from getting infected rectally...and that a microbicide might help protect the male partners of HIV-positive women from being infected [through vaginal intercourse]. It might be something that could be used adjunctively to help decrease mother-to-child transmission. The beginning studies are very technically complex, but our hope is that we can learn an awful lot that can serve a variety of different ways to protect people against HIV transmission.”

For more information about the HPTN 049 study and enrollment in general, please log on to www.hptn.org.

Chael Needle wrote about AVR118’s potential to counter cachexia in the January issue.

February 2004