Thursday, July 22, 2010

Making Microbicides, Making History

The CAPRISA 004 Study results are out. The results showed a 1% tenofovir gel in 39% in preventing HIV infection and 51% effectiveness in preventing HSV-2 infection, was the highlight of the 18th World AIDS conference in Vienna, Austria.

The study, conducted by the Centre for the Aids Programme of Research in South Africa (Caprisa 004), tested the safety and effectiveness of using 1 percent tenofovir gel tested in 889 women for up to two-and-a-half years in two South African communities, one rural and one urban. Half of the women were randomly assigned to use a gel containing an antiretroviral drug, the other half were given a placebo gel. All were instructed to apply the gel within 12 hours before and 12 hours after intercourse.

The result is outstanding with evidence of high scientific and ethical integrity. No matter how the data is analysed, the analysis consistently showed statistically significant results.

The study showed two things:
1. ARVs can indeed be used as a prophylaxis
2. Microbicides (topical application of a substance in the vagina) is indeed a possible modality for HIV prevention and that women like it.

Futher results show that the observed result was due to high concentration of the tenofovir gel in the vagina and cervical tissues of study participants who remained HIV negative throughout the study. Of significance also is evidence that the higher the level of the tenofovir in the cervico-vaginal fluid, the less the HIV infection and HSV-2 infection observed. Plasma concentration (blood level of tenofovir that could result from systemic absorption of the gel from the vagina) of tenofovir and its metabolite was negligible thereby possibly explaining the absence of resistance in the study.

The result is indeed a proof of concept and exciting for the following reasons:
(i). shows that not only does topical application of 1% tenofovir prevents HIV infection, but that the gel can also prevent HSV infection (thus providing two possible synergistic mechanisms for HIV prevention)
(ii). this is demonstrated consistently across all types of analysis
(iii). consistent with prior results from ARV based prevention studies like the PMTCT study
(iv). has animal studies to support the finding.

Co-chair of the Voice Study, Zimbabwe's CAPRISA equivalent, Prof Mike Chirenje siad, "It is gratifying that we are a step closer to identifying a safe and effective HIV prevention method for women. But to know for certain that tenofovir gel is effective, additional studies must be performed, because we can’t be sure that what worked for the women in Caprisa 004 will be the same for women elsewhere."

However, this finding - as exciting as it may be - is not enough to roll out the product, other studies also need to be conducted - including studying the efficacy of intermittent ARV gel dosing for HIV prevention, rectal safety and efffectiveness and how long an interval between HIV testing will be unacceptable risk for resistance.