Vaginal Anti-HIV Gel 'Safe For Regular Use'

A vaginal gel containing the anti-HIV drug tenofovir is safe for daily use by women, a study shows.

The research was presented at Microbicides 2008, an international microbicides conference, in Delhi, India, in the last week of February 2008.

Tenofovir is one of the primary antiretroviral drugs. It targets HIV by blocking the action of a key enzyme needed for the virus to replicate.

The Microbicides Trials Network (MTN) — sponsored by the US National Institutes of Health — conducted phase II trials on tenofovir gel in India and the United States in 2007, to test whether it is safe for women to use the gel daily instead of before having sex, and whether women complied with the procedure correctly and willingly.

The six-month study compared tenofovir with a placebo in 200 sexually active, uninfected women. It found the gel was safe — with no effects liver, blood or kidney function — both when it was used daily for a period of six months and before each act of sex.

The study also found high levels of compliance — over 80 per cent — Sharon Hillier, director at the Department of Obstetrics, Gynaecology and Reproductive Sciences at the University of Pittsburgh, and principal investigator of Microbicides MTN, said at the conference.

Over 90 per cent of the women involved said they would use such a gel if it were found to be effective against HIV.

A series of trials in Africa and the United States over the next two years will study if the drug is absorbed into the foetus during pregnancy, dose absorption in women and whether the drug is more effective as an oral pill or vaginal gel.

"The oral route versus topical application (of an anti-HIV drug) is the key scientific question," Hillier said.

Between 70 and 90 per cent of HIV infections in women are due to heterosexual intercourse. Women are biologically more vulnerable to HIV infection as the cells in the lining of the female genital tract rupture more easily, making it easier for the virus to enter.

The tenofovir results will be encouraging to the microbicide research community who have faced a series of setbacks in recent years, including the early closure of trials for cellulose sulphate microbicide and the announcement this month that a microbicide gel based on a seaweed extract, Carraguard, failed to prevent HIV transmission.

Anti-HIV Gel Fails To Prevent Infection

Trials of a vaginal gel in South Africa have failed to prove conclusively that it prevents HIV transmission from men to women.

The microbicide, Carraguard, underwent phase III clinical trials in 6000 women between 2004–2007. But on 14 February 2008, The Population Council, the US-based nongovernmental organisation that ran the trials, announced that the microbicide had been found to be safe but not effective.

"With Carraguard there was not a big enough difference between the number of women who contracted HIV on the placebo and those using Carraguard to prove that the microbicide had a significant impact," Sumen Govender, clinical study manager for the Population Council in South Africa, said.

Most women enrolled on the Carraguard trial reported only using the gel before sex some of the time, which could have affected the results, say the researchers. Govender said researchers were now analysing social aspects of the Carraguard data.

Researchers will report the results of the Carraguard trial at the International Microbicide 2008 Conference in New Delhi, India, in the week of 24–27 February 2008.

But Carraguard will continue to be used in further trials. The Population Council will commence phase I safety trials of a new microbicide, PC-815 — which comprises Carraguard and an antiretroviral drug called MIV-150 — this year.

Carraguard contains carrageenan, a chemical derived from seaweed that is effective against HIV in the laboratory. The addition of an antiretroviral drug to the microbicide should also prevent the HIV from multiplying.

Research into PC-815 will begin with safety testing on 50 participants in June this year in the Dominican Republic, pending government approval.

The failure of Carraguard represents another setback to microbicide research, following the termination of trials of the microbicide cellulose sulphate in 2007.

Ayesha Kharsany, project director at the Centre for the AIDS Programme of Research in South Africa (CAPRISA) and head of a team developing a microbicide called Tenofovir, says researchers are united in their efforts to find a product that works.

Govender says a microbicide could never completely prevent infection but could reduce it by between 30–40 per cent and would be most effective when used with another preventive measure.

Safety Concerns Halt Trials Of HIV Microbicide

Clinical trials of a microbicide — a gel or cream designed to block the sexual transmission of HIV — have been terminated early for safety reasons, but scientists insist that this must not hinder research into other microbicides.

Researchers announced in January 2007 that two clinical trials for cellulose sulphate, or ushercell, had been stopped because one trial appeared to increase the risk of women becoming infected with HIV.

According to the International Herald Tribune, the study that led to stopping the trials involved 1,333 women in Benin, South Africa and Uganda. The other trial involved 1,700 women in Nigeria.

The Word Health Organization said the trial's failure was "disappointing" and an "unexpected setback" in the search for safe and effective microbicides.

Gita Ramjee, director of the HIV Prevention Research Unit of the South African Medical Research Council, said scientists were baffled by the trial's failure and are still trying to find the reason for it.

She said cellulose sulphate went through rigorous laboratory and clinical testing prior to large-scale trials and all data had indicated it was safe.

However, Ramjee insisted that research into anti-HIV microbicides must go on, as to do otherwise would mean "giving up for women all over the world".

"We should continue with research but ensure that data is reviewed more frequently, so that rapid action can be taken should there be a cause for concern," she said.

Three other microbicide compounds are currently undergoing phase III clinical trials in Africa.

In South Africa, trials of the Carraguard microbicide are nearing completion, and the end of 2007 expects results. Another product, Pro2000, is being tested in South Africa, Tanzania and Uganda. The BufferGel microbicide is being tested in Malawi, South Africa, Zambia and Zimbabwe.

HIV specialist Jonathan Weber of Imperial College London, United Kingdom, said there was no suggestion that other microbicides currently being investigated, based on different chemical compounds, have similar problems.

"There are no silver bullets in HIV prevention research. We need a package of tools to combat the HIV epidemic, and it is hoped that a safe and effective microbicide could be part of this package," he said.

Microbicides have gained both status and funding in the past few years as a way for women to protect themselves against HIV infection in situations where they have little negotiating power to persuade male partners to use condoms.