Tenofovir vaginal gel safe and well tolerated

A topical gel with anti-HIV activity has been shown to be safe and well tolerated by HIV-positive and HIV-negative women. In a study published in the February 28^th edition of AIDS investigators from the United States found that a 1% tenofovir gel inserted in the vagina once or twice daily caused severe side-effects in only one individual and generally caused only very mild and transient side-effects.

They also found that the use of the gel by HIV-positive women over 14 days did not lead to the development of resistance to tenofovir (Viread).

Male condoms are a highly effective way of preventing sexual transmission of HIV. However, they need to be used properly and many women find difficulties negotiating their use. Female condoms are also useful at preventing HIV and other sexually transmitted infections, but have their own problems.

As “acceptable, affordable, female-controlled prevention methods could he helpful in halting the [HIV] epidemic” researchers have been trying to develop a safe and tolerable topical microbicide. The nucleotide analogue tenofovir has been shown in tests involving monkeys to be an effective pre- and post-exposure prophylaxis for HIV or when used in a gel and applied into the vagina.

American researchers wanted to assess how safe and tolerable a tenofovir gel was in HIV-positive and HIV-negative women and their sexual partners of the same HIV infection status.

A total of 84 women and 24 of their male sexual partners were recruited to an open-label phase 1 study dose-ranging and frequency study. The study lasted for 14 days. After a screening visit, which involved a physical examination, blood tests (including a kidney and liver function tests, and CD4 and viral load investigations for the HIV-positive women), and a pelvic examination the women were provided with a gel containing either 0.3% or 1% tenofovir and told it apply it either twice daily, one in the morning and at bed time, or once a day – at bed time only.

All participants had their cervicovaginal mucosa examined 48 – 72 hours after starting to use the gel; were evaluated after seven days and were asked about their experiences of using their gel on completion of the study. In a sub-study, a number of women had blood samples obtained on the day they first applied the tenofovir gel and on the 13^th day of its use. HIV-positive women had more intensive monitoring and provided a sample of cervicovaginal lavage at both baseline and after completion of the study.

Although 92% of women reported some side-effect associated with the use of the gel, in 87% of cases these were classified as mild, the most frequent (23%) being genital itching. No specific side-effect was associated with the use of the gel or the frequency of application. One severe side-effect which was considered to be related to the tenofovir gel occurred and involved hospitalisation due to abdominal cramping. Pelvic inflammatory disease was diagnosed and treated with antibiotics.

Tests to monitor blood levels of tenofovir were performed on 25 women. Of these, 14 (56%) had low, but detectable levels of the drug present in their blood. The median level was 3.4ng/ml, just above the testing assay’s limit of detection of 3.0ng/ml.

Blood and cervicovaginal lavage were obtained from HIV-positive women on entry to the study and then on days 7 and 14. Two women had a viral load above 400 copies/ml in their blood on entry to the study and this had increased to twelve women by day 14. HIV was only present in the cervicovaginal lavage of two women on entry to the study, but no women had a detectable viral load at this site by day 14.

No tenofovir resistance-conferring mutations emerged after using the gel.

Non-adherence was defined as three or more missed doses and the investigators classified 94% of women as being fully adherent. In addition, 94% of women said that they would use the gel if it became available for the prevention of HIV, as did 81% of their male partners.

“Tenofovir gel was well tolerated”, write the investigators, “the 1% concentration used twice-daily [being] as well tolerated as 0.3% gel used only once a day.” They add, “although mild adverse events were common, the majority of women and their male partners reported they would use the gel if it were available.”

The investigators were encouraged that none of the HIV-positive women became resistant to tenofovir even though low blood concentrations of the drug were found. However, “longer-term studies of HIV-positive women exposed to tenofovir gel will be needed to evaluate whether chronic use could select for resistance mutations.”