What next after microbicide trial fails?
Dec 18, 2009
PRO 2000 microbicide gel failed to protect women against HIV infection in the largest microbicide study to date, according to partners in the Microbicide Development Programme’s 301 study.
By Anne Abaho
PRO 2000 microbicide gel failed to protect women against HIV infection in the largest microbicide study to date, according to partners in the Microbicide Development Programme’s 301 study.
PRO 2000 had appeared to reduce the risk of HIV infection by around 30% in a smaller study, known as HIV Prevention Trials Network study 035, but researchers decided that this result could have been due to chance because it was just outside the bounds of statistical significance. So they did a larger MDP 301 study.
Microbicide gels that can be used by women in the vagina to protect against HIV infection have been tested in a number of studies, and so far, none has showed any evidence that they could prevent HIV infection in women.
PRO 2000
PRO 2000 is a non-antiretroviral compound which was chosen as a microbicide because it blocks entry to cells that could be infected by HIV and because it showed promise in animal models.
The HPTN 035 recruited 3,099 women and posted encouraging results. So, MDP 301 was started as a follow up. It recruited 9,385 women and was expected to produce more dependable results. However, more infections took place in the study.
After one year of microbicide use, there was no significant difference in the risk of infection between women who received PRO 2000 or the placebo gel.
There were 130 HIV infections out of 3,156 women who were given PRO 2000 gel and 123 HIV infections out of 3,112 given the placebo gel.
Unlike the recently-reported Thai study of an HIV vaccine, which showed the product was partially effective in a population at low or medium risk of HIV infection, the MDP 301 study recruited women at high risk of HIV infection.
HIV incidence in the study was moderately high (around 4.5% of women became infected in the course of a year’s follow-up), reflecting the real-world conditions in which a new prevention method is most urgently needed.
What next?
Chief Investigator Dr Sheena McCormack of the Medical Research Council expressed great disappointment, saying they had hope in PRO 2000 after earlier studies suggested it could reduce the risk of HIV infection by 30%.
“This shows clearly the need to undertake trials, which are large enough to provide definitive evidence for whether or not a product works.â€
Every trial, regardless of the result, produces new information, new science and new ideas along which to design new trials.
The world can now tune their hope to a South African study of a microbicide containing the antiretroviral drug tenofovir. That study, the CAPRISA 004 trial, is testing the use of ARV gel (tenofovir) in women in KwaZulu-Natal and the results are expected next year.
CAPRISA 004 is a pilot study and will be followed by results from the VOICE study, which is directly comparing a tenofovir gel with oral tenofovir pre-exposure prophylaxis (PrEP) in 4,200 women at 10 sites in Uganda, South Africa, Malawi, Zambia and Zimbabwe.
This sequence of studies will provide evidence about the potential for the use of ARVs in microbicides.
PRO 2000 microbicide gel failed to protect women against HIV infection in the largest microbicide study to date, according to partners in the Microbicide Development Programme’s 301 study.
PRO 2000 had appeared to reduce the risk of HIV infection by around 30% in a smaller study, known as HIV Prevention Trials Network study 035, but researchers decided that this result could have been due to chance because it was just outside the bounds of statistical significance. So they did a larger MDP 301 study.
Microbicide gels that can be used by women in the vagina to protect against HIV infection have been tested in a number of studies, and so far, none has showed any evidence that they could prevent HIV infection in women.
PRO 2000
PRO 2000 is a non-antiretroviral compound which was chosen as a microbicide because it blocks entry to cells that could be infected by HIV and because it showed promise in animal models.
The HPTN 035 recruited 3,099 women and posted encouraging results. So, MDP 301 was started as a follow up. It recruited 9,385 women and was expected to produce more dependable results. However, more infections took place in the study.
After one year of microbicide use, there was no significant difference in the risk of infection between women who received PRO 2000 or the placebo gel.
There were 130 HIV infections out of 3,156 women who were given PRO 2000 gel and 123 HIV infections out of 3,112 given the placebo gel.
Unlike the recently-reported Thai study of an HIV vaccine, which showed the product was partially effective in a population at low or medium risk of HIV infection, the MDP 301 study recruited women at high risk of HIV infection.
HIV incidence in the study was moderately high (around 4.5% of women became infected in the course of a year’s follow-up), reflecting the real-world conditions in which a new prevention method is most urgently needed.
What next?
Chief Investigator Dr Sheena McCormack of the Medical Research Council expressed great disappointment, saying they had hope in PRO 2000 after earlier studies suggested it could reduce the risk of HIV infection by 30%.
“This shows clearly the need to undertake trials, which are large enough to provide definitive evidence for whether or not a product works.â€
Every trial, regardless of the result, produces new information, new science and new ideas along which to design new trials.
The world can now tune their hope to a South African study of a microbicide containing the antiretroviral drug tenofovir. That study, the CAPRISA 004 trial, is testing the use of ARV gel (tenofovir) in women in KwaZulu-Natal and the results are expected next year.
CAPRISA 004 is a pilot study and will be followed by results from the VOICE study, which is directly comparing a tenofovir gel with oral tenofovir pre-exposure prophylaxis (PrEP) in 4,200 women at 10 sites in Uganda, South Africa, Malawi, Zambia and Zimbabwe.
This sequence of studies will provide evidence about the potential for the use of ARVs in microbicides.