Study on vaginal gel to prevent HIV in women shows promising results

An investigational vaginal gel intended to prevent HIV infection in
women has demonstrated encouraging signs of success in a clinical
trial conducted in Africa and the United States. Findings of the
recently concluded study, funded by the National Institute of Allergy
and Infectious Diseases (NIAID), part of the NIH, were presented at
the Conference on Retroviruses and Opportunistic Infections in
Montreal.

The study investigators found the microbicide gel — known as PRO 2000
(Indevus Pharmaceuticals, Inc., Lexington, Mass.) — to be safe and
approximately 30 per cent effective (33 per cent effectiveness would
have been considered statistically significant). This is the first
human clinical study to suggest that a microbicide — a gel, foam or
cream intended to prevent the sexual transmission of HIV and other
sexually transmitted infections when applied topically inside the
vagina or rectum — may prevent male-to-female sexual transmission of
HIV infection.

“Although more data are needed to conclusively determine whether PRO
2000 protects women from HIV infection, the results of this study are
encouraging,” says NIAID director Anthony S. Fauci, M.D.

The phase II/IIb clinical trial, which enrolled more than 3,000 women,
is NIH’s first large clinical study of a microbicide.

“An effective microbicide would be a valuable tool that women could
use to protect themselves against HIV and one that could substantially
reduce the number of new HIV infections worldwide,” Dr. Fauci adds.

“The study, while not conclusive, provides a glimmer of hope to
millions of women at risk for HIV, especially young women in Africa,”
adds lead investigator Salim S. Abdool Karim, MBChB, Ph.D., from the
Center for the AIDS Program of Research in South Africa, who presented
the findings at CROI. “It provides the first signal that a microbicide
gel may be able to protect women from HIV infection.”

Currently, women make up half of all people worldwide living with HIV.
In sub-Saharan Africa, women represent nearly 60 percent of adults
living with HIV, and in several southern African countries young women
are at least three times more likely to be HIV-positive than young
men. In most cases, women become infected with HIV through sexual
intercourse with an infected male partner. An effective microbicide
could provide women with an HIV prevention method they initiate. This
would be particularly helpful in situations where it is difficult or
impossible for women to refuse sex or negotiate condom use with their
male partners.

The study, known as HPTN 035, began in 2005 and enrolled 3,099 women
at six sites in Africa and one in the United States. The clinical
trial tested two candidate microbicide gels for safety and their
ability to prevent HIV infection: PRO 2000 (0.5 per cent dose), and
BufferGel (ReProtect Inc., Baltimore). The US Agency for International
Development provided funding to manufacture BufferGel for the HPTN 035
study. PRO 2000 inhibits the entry of HIV into cells; BufferGel boosts
the natural acidity of the vagina in the presence of seminal fluid,
which can help to inactivate HIV and other pathogens.

The volunteers in HPTN 035 were divided at random into four
equal-sized groups: Those using BufferGel prior to engaging in sexual
intercourse; Those using PRO 2000 before engaging in sexual
intercourse; Women using placebo gel prior to engaging in sexual
intercourse; Those who did not use gel before engaging in sexual
intercourse

All participants received detailed information about the possible
risks and benefits of trial participation before enrolment and were
monitored monthly while in the study, which averaged 20 months. In
addition, all the women were counselled on safe sex practices, given
condoms, and tested and treated for sexually transmitted infections
throughout the study.

Participants reported regular use of the investigational gels (81 per
cent of sex acts) and nearly all (99 per cent) said they would use the
products if approved for HIV prevention. Condom usage was also high
throughout the course of the trial (74 per cent).

In the final analysis, 194 women in the study became infected with
HIV. Of these infections, 36 occurred in the PRO 2000 group, 54 in the
BufferGel group, 51 in the placebo group and 53 in those who did not
use gel. Based on these data, PRO 2000 was 30 percent effective, while
BufferGel had no detectable preventive effect on HIV infection. Both
PRO 2000 and BufferGel were found to be safe.

HPTN 035 was conducted by the Microbicide Trials Network (MTN), an
HIV/AIDS clinical trials network established in 2006 by NIAID with
co-funding by the Eunice Kennedy Shriver National Institute of Child
Health and Human Development and the National Institute of Mental
Health, all components of the NIH. Prior to the establishment of the
MTN, the study was led by the NIAID-funded HIV Prevention Trials
Network (HPTN), from which the study gets its name.

Roberta J. Black, Ph.D., chief of the Microbicide Research Branch in
NIAID’s Division of AIDS, says, “Although a statistically significant
protective effect was not observed, HPTN 035 successfully met its goal
of determining whether either of the two candidate microbicides had
sufficient promise to be considered for testing in a larger phase III
clinical study.”

Study participants are being informed of the findings and counselled
on the continued need to follow safe sex practices in order to avoid
possible HIV exposure. Women who became infected with HIV during the
trial were counselled and referred to appropriate medical care and
support, including antiretroviral therapy. These same women were also
given the opportunity to participate in MTN 015, a clinical study
examining the nature of HIV progression and treatment response in
HIV-infected women who were using topical microbicides or oral
antiretrovirals as an HIV preventive measure when they acquired HIV
infection.

A separate clinical study sponsored by the Medical Research Council
(MRC) and the Department for International Development of the United
Kingdom that is currently testing PRO 2000 (0.5 percent dose) in
preventing HIV infection among women in Africa could provide further
insight into the microbicide’s effectiveness. That pase III study
involving nearly 9,400 women is set to conclude in August 2009.



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