MTN017 PHASE-II STUDY TO BEGIN SOON
"We have just received approval from the Division of AIDS, regulatory approval for protocol version 1.0 of MTN017 study before the AIDS 2012. We can now send the protocol to the research sites and they can start working with the Institutional Review Boards (IRBs), various ethics committees, among others, to go through the approval process" said Dr Ross D Cranston, Protocol Chair, Division of Infectious Diseases, University of Pittsburgh and co-investigator in the Microbicide Trials Network (MTN).
According to Jim Pickett, Chair of International Rectal Microbicides Advocates (IRMA) and Director (Advocacy), AIDS Foundation of Chicago: Rectal microbicides are products currently under research – that could take the form of gels or lubricants – being developed and tested to reduce a person’s risk of HIV or other sexually transmitted infections from anal sex. The risk of becoming infected with HIV during unprotected anal sex is 10 to 20 times greater than unprotected vaginal sex because the rectal lining is only one-cell thick, the virus can more easily reach immune cells to infect.
MTN017 is an extended safety study (in phase II now). Participants will be randomized either in daily rectal formulation of tenofovir gel, the same gel with associated rectal sex, or oral Truvada (Tenofovir - TDF/emtricitabine - FTC). "We are comparing safety profiles and also looking at acceptability between those three regimens" said Dr Cranston.
Dr Cranston is also involved with explant research on rectal microbicides. A biopsy is done after exposing the rectal tissue to microbicides and this very small quantity of tissue is kept 'alive' in a research laboratory. Then this tissue is exposed to HIV in lab conditions. This is how researchers find out whether the product under research has anti-HIV efficacy on human tissue kept alive in the laboratory or not.
"This gives us an idea of how a drug is actually working. In MTN006 study trial of rectal microbicide after 7 days of dosing, these explants showed protection from HIV" added Dr Cranston.
This MTN017 study will also look at behavioural correlates of rectal microbicides, factors associated with adherence or non-adherence to products, sexual activity and condom use, changes in sexual life with gel or Truvada use, problems participants perceive by the use of these products or whether there is any sharing of products between individuals in the three arms of this study.
Participants will be exposed to each of the three regimen in MTN017 study for 8 weeks. In previous studies the longest period of time anyone has been exposed to the rectal tenofovir products under research has been seven days. "So we are extending the duration of exposure to rectal tenofovir products significantly. Of course this will be reinforced with HIV prevention counseling and safety monitoring. I do think this is important because we found in MTN007 study that there was a time regulation of a whole number of proteins in the tenofovir arm compared to the placebo arm. The rectal tissue concentration was higher when the rectal microbicide was applied, compared to the oral dose of tenofovir" said Dr Cranston.
MTN017 study sties will be in Boston, Pittsburgh and San Francisco in USA, the Center for Disease Control and Prevention (CDC) site in Bangkok and another site in Chiang Mai in Thailand, Cape Town, South Africa and Lima, Peru.
Dr Cranston explained: "If we find that this product is safe and acceptable in the populations that we are studying which is men who have sex with men (MSM) and transgender women, hopefully we will be able to mobilize enough funding and get a green light to go into an effectiveness study." Effectiveness study is also referred to as Phase-IIb or Phase III clinical trial and is usually a large-scale multi-centric study engaging a much larger number of study participants (number of study participants is inversely proportional to HIV rates in the population).
OTHER STUDIES ON RECTAL MICROBICIDES
There are other studies going on currently in addition to MTN017 where University of Pittsburgh is involved.
PROJECT GEL: This study is engaging 140 young MSM participants. If these men will be 80% adherent to the gel under study then they will be enrolled into a tenofovir gel study at the end. This study involves high risk men – the criteria includes men who have at least one episode of unprotected anal sex in the last one year. The Phase I of this study is just about to begin.
CHARM
"Another rectal microbicide study that is happening in the Pittsburgh is called CHARM (Combination HIV Antiretroviral Rectal Microbicide). Combination antiretrovirals are more potent and more useful as rectal microbicides. The rationale behind the CHARM programme is that we need a rectal specific combination antiretroviral microbicide. CHARM phase-I is just about to start and will be comparing three formulations of tenofovir gel – the old vaginal formulation used in CAPRISA 008 study, reduced glycerin formulation of this gel, and also a rectal specific formulation" said Dr Cranston.
WAY FORWARD
The AIDS 2012 conference has certainly upped the beat on 'ending AIDS'. Ending AIDS is not possible unless we can protect every person from HIV - and meet their unique needs and contexts, and provide quality treatment, care and support services for all those living with HIV. While we scale up existing evidence-based interventions, it is also vital to accelerate research and development of new HIV prevention tools, more effective, affordable, and less toxic treatment therapies, and also address social drivers of HIV. Rectal microbicides research needs to be accelerated as well.
Bobby Ramakant - CNS
