It was once thought that PRO200 vaginal gel was effective in harnessing HIV-1 transmission. However recent detailed studies published Online First at www.thelancet.com prove otherwise that this gel does not actually have an effect amongst women in Africa. On Feb 14, 2008, use was stopped on the recommendation of the Independent Data Monitoring Committee because of lack of proven successes. However, studies and analysis continued in the field. Leading the newly published research are Dr Sheena McCormack, UK Medical Research Council (MRC) Clinical Trials Unit, London associates.

The study was highly in-depth. The 301 study was a phase 3, randomised, double-blind, and parallel-group trial, conducted at 13 clinics in South Africa, Tanzania, Uganda, and Zambia. The authors assessed the transmission result and safety of 2% and .5% PRO2000 gels against vaginal transmissions. Three groups (2%, .5%, placebo) were analyzed for at least 52 weeks and in Uganda specifically, up to 104 weeks. At intervals of 12 weeks, 24 weeks, 40 weeks, and 52 weeks, HIV-1 contraction was established by rapid screenings that were later re-confirmed at a laboratory.

Dr. McCormack reviewed 9385 cases. 2591 (95%) of 2734 participants enrolled in the 2% PRO2000 group, 3156 (95%) of 3326 in the .5% PRO2000 group, and 3112 (94%) of 3325 in the placebo group were included in the efficacy analysis.

All three groups resulted in almost identical results with incidence per 100 woman-years at 4•5 for .5% PRO2000 vs. 4•3 for placebo, and at discontinuation of the gel in 2008, 4•7 for 2% PRO2000 gel, 3•9 for .5% PRO2000 gel, and 3•9 for placebo gel.

So why is this treatment failing? The authors mention that in early human studies active drug was recoverable by cervicovaginal lavage several hours after insertion, suggesting that it was released from the formulation and not overly diluted by vaginal secretions. It was curious to discover, however, that those that used the .5% gel, lower concentrations of PRO2000 were recovered after sex without a condom than were reported not having intercourse at all. How could this be?

The UK authors state:

This difference could result from drug redistribution, binding to semen, loss from leakage, or difficulty in assaying drug because of physical changes after interaction with semen.

In summary, PRO2000 is not effective.

The report definitively concludes:

Despite high rates of reported adherence, 0•5% PRO2000 and 2% PRO2000 were not effective for prevention of vaginally acquired HIV-1 infection or other sexually transmitted infections.

Dr. Sandra I. McCoy and Dr. Nancy Padian of the Institute of Business and Economic Research, University of California, Berkeley, in conjunction with Dr. Charlotte Watts at the London School of Hygiene and Tropical Medicine, discuss the results from innovative studies that were also held in sub-Saharan Africa. In addition to results from the CAPRISA 004 trial indicating that a microbicide containing 1% tenofovir, which belongs to a class of antiretroviral drugs known as nucleotide analogue reverse transcriptase inhibitors (nRTIs) that block reverse transcriptase, an enzyme crucial to viral production in HIV-infected persons, can actually in fact protect women against HIV infection. Two recent studies, the SIHR (Schooling, Income, and HIV Risk) in Malawi, and the RESPECT study in Tanzania, have found that by improving women’s financial situation in upstream prevention, risk of infection is actually reduced.

McCoy and colleagues conclude:

Although neither tenofovir microbicide gel nor conditional cash transfers will be an immediate prevention panacea, these promising approaches have the potential to greatly expand prevention options for women in sub-Saharan Africa. Along with further research on tenofovir gel and conditional cash transfers, serious investment in upstream, economic prevention approaches that respond to the realities faced by adolescent girls and women is still needed.

New innovation and techniques are always badly needed in treating this global epidemic.

“PRO2000 vaginal gel for prevention of HIV-1 infection (Microbicides Development Programme 301): a phase 3, randomised, double-blind, parallel-group trial”
Dr Sheena McCormack MSc, Prof Gita Ramjee PhD, Anatoli Kamali MSc, Prof Helen Rees MRCGP, Angela M Crook PhD, Mitzy Gafos MSc, Ute Jentsch PhD, Prof Robert Pool PhD, Maureen Chisembele MBBS, Saidi Kapiga MD, Richard Mutemwa MD, Andrew Vallely PhD, Thesla Palanee PhD, Yuki Sookrajh MBChB, Prof Charles J Lacey MD, Prof Janet Darbyshire MSc, Prof Heiner Grosskurth PhD, Albert Profy PhD, Prof Andrew Nunn MSc, Richard Hayes DSc, Prof Jonathan Weber PhD
The Lancet, Early Online Publication, 20 September 2010
doi:10.1016/S0140-6736(10)61086-0

Written by: Sy Kraft, B.A. – Journalism – California State University, Northridge (CSUN)