Source: DGNews  |  Posted 3 years ago

By Ed Susman

MONTREAL -- February 10, 2009 -- An experimental vaginal gel aimed at preventing HIV transmission failed to achieve statistically significant efficacy, according to a study presented here at the 16th Conference on Retroviruses and Opportunistic Infections (CROI).

However, the study researchers contend that the 30% reduction in infections seen with use of PRO 2000/5 gel indicates progress is being made toward developing a microbicide that could prevent HIV spread.

"This study, while not conclusive, provides a glimmer of hope to millions of women at risk for HIV, especially young women in Africa," said lead investigator Salim Abdool Karim, MBChB, PhD, Center for AIDS Programs of Research, Durban, South Africa.

Dr. Karim presented the study results in an oral presentation on February 9.

The study, known as HPTN 035, began recruiting women in 2005 in Malawi, South Africa, Zambia, Zimbabwe, and the United States. The women were divided into 4 groups and were instructed to use the gel prior to engaging in sexual intercourse.

The study randomised 3,099 women who were followed for an average of 20.4 months. The rate of retention in the study was 93.6%. There were no statistically significant differences in adverse events. Adherence to gel use was 81% across gel arms.

Among women using the PRO 2000/5 gel, 36 converted from HIV-negative status to HIV-positive status during 1,336 person-years of use. While that was lower than 53 infections among the women who used no gel and accumulated during 1,318 person-years, the gel failed to reach statistical significance (P = .06).

Similarly, infections with PRO 2000/5 gel were fewer than with carbomer 974 (54 infections), another microbicide candidate, or a placebo gel (51 infections).

PRO 2000/5 is a vaginal gel that inhibits viral entry into susceptible cells. Carbomer 974 is a buffering agent that maintains normal vaginal acidity in the presence of ejaculate.

The study was powered to find statistical significance if infection rates had been reduced by 33%. Dr. Karim said the reduction of 30% meant the study failed to prove that Pro 2000/5 gel was effective. He suggested that other studies underway with the gel may provide the evidence needed to make that claim.

Women in the study were HIV-negative at the beginning of the trial, but were considering getting pregnant. Dr. Karim said about 10% to 11% of women in each of the 4 arms of the study became pregnant during follow-up.

Despite its technical failure, Dr. Karim argued that the results showed promise for "women with no other [prevention] options."

The study did show some positive aspects, commented Sharon Hillier, PhD, Family Affairs and Reproductive Infections Disease Research, University of Pittsburgh, Pittsburgh, Pennsylvania.

"This is the first good news we have had in this area of preventing HIV infection in the last 10 years," Dr. Hillier said.

"The study had shown that women will use a gel to prevent HIV transmission. There is also some indication of effectiveness," said Dr. Hillier, who chaired a press briefing at the CROI meeting.

She suggested that further use of PRO 2000/5 or another microbicide would depend on the level of effectiveness that is deemed necessary to approve such agents for general use, particularly in areas where HIV infection is rampant.

While the results were self-reported, Dr. Karim said 81% of the women said they used the gels as instructed.

[Presentation title: Safety and Effectiveness of Vaginal Microbicides BufferGel and 0.5% PRO 2000/5 Gel for the Prevention of HIV Infection in Women: Results of the HPTN 035 Trial. Abstract 48LB]