“There is clearly an epidemic of HIV in MSM and transgender community not only in Asian countries but also in the United States. MSM people of colour or those from African-American or Latino-American backgrounds, have the highest risk of HIV among the MSM community in US. In some of the major American cities rates are extremely high. That kind of situation is mirrored in Asia too. We see at varying degrees that some countries have higher rates than others, but we do see HIV increasing in MSM communities throughout South-East Asia and East Asia in general” said Dr Timothy H Holtz, Director, HIV/STD Research Programme, Thailand Ministry of Public Health (MOPH) - US Centre for Disease Control and Prevention (CDC) Collaboration, Bangkok, Thailand.
PUSH RESEARCH AGENDA FORWARD
Added Dr Holtz: “We need to push the research agenda forward trying to find prevention methodologies that will work, will be compatible with and acceptable to MSM and transgender community, as well as press forward the interventions that we already know work: emphasis on safe sex, distribution and promotion of condom use, Pre-Exposure Prophylaxis (PrEP) among others.”
According to CDC, PrEP is a new HIV prevention method which was approved by the US Food and Drug Administration in July 2012. When used consistently, PrEP has been shown to be effective in MSM and heterosexually-active men and women.
“Young MSM people in Thailand have possibly the highest rate of HIV incidence that we have been able to measure in our community. I think it is important to have HIV prevention methods that are acceptable, compatible and also of interest to people who are at risk” said Dr Holtz.
One of the most promising researches taking place on new HIV prevention technologies for MSM and transgender people is on rectal microbicides.
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 as the rectal lining is only one-cell thick, the virus can more easily reach immune cells to infect.
MTN017 and THAILAND
For the first time ever, rectal microbicides research is moving to Phase II clinical studies involving MSM and transgender people as participants in US and other countries, including Thailand. Thailand research site, where Dr Holtz works, is also important because only two out of eight research sites for Phase II rectal microbicide study (formally called MTN017) will do ‘tissue explant’ and live HIV challenge (tissue biopsies will be done and these tissue samples will be exposed to HIV virus in laboratory conditions). These two sites, which are gearing up to do tissue explants and live HIV challenge, are University of Pittsburgh in US and Thailand MOPH – US CDC site in Bangkok.
INNOVATIVE MTN017 STUDY DESIGN
"The MTN017 study design is not typical and pretty innovative – it has three periods and six cross over groups" said Dr Holtz. It is making sure that everybody gets exposed to the same duration of study products, no matter which of the three study arms the study participant is randomized into at the beginning. Everybody is going to have the same exposure to all three regimens: oral Truvada/PrEP for eight weeks, rectal gel (reduced glycerin and tenofovir gel) daily for eight weeks, and sex dependent rectal gel for eight weeks. There is no placebo arm.
HOW THAILAND SITE WAS SELECTED
“This is the first phase II rectal microbicides clinical study outside of US. We were already in process of doing an oral PrEP study with HIV Prevention Trial Network (HPTN). We wanted to work together with our colleagues in development of rectal microbicides as well. We invited Dr Ian McGowan [Dr McGowan is the co-Principal Investigator at Microbicide Trials Network - MTN] and other MTN colleagues to come and visit our site. We have been operating a MSM-centred clinic in downtown Bangkok for over six years now and we are very proud of our facility. We think it is a very MSM-friendly, warm and inviting clinic space that respects confidentiality, also provides services to those who might opt to stay anonymous, and is one of the very few MSM-friendly clinics in the city. We also have a long history of running clinical studies as part of our programme with about 17 years-worth of experience doing clinical studies, with high retention rates” said Dr Holtz.
Research studies in Thailand have shown commendable retention rates owing to genuine community engagement as science progresses. Another MTN017 rectal microbicide site in Thailand is in Chiang Mai, where the key researcher - Dr Suwat Chariyalertsak, Director, Research Institute for Health Sciences (RIHES), Chiang Mai University, Thailand - had received a global award in the past year for best retention of clinical study participants in the HPTN-052 study. High retention rates in Bangkok site in previous studies and appreciable community engagement certainly gives hope for better adherence in MTN017.
MSM and transgender communities in particular were involved at MTN017 study sites right from the beginning. The study is yet to begin, but community consultations were held from very early on to feed into the research process as it progresses ahead. “We had a community consultation in January 2012 when Dr Ian McGowan and Dr Ross Cranston [Dr Cranston is the Protocol Chair of MTN017 study and co-investigator at MTN] and other MTN colleagues came over – we engaged members from MSM and transgender community in this consultation too” said Dr Holtz.
Recollecting some of the questions that came up from the MSM and transgender community during this consultation Dr Holtz said: “There were questions about anal sex, because it is about a part of the body that we usually don’t get to see. So there were questions about what happens in the male and female rectum during anal sex, questions about constitution or makeup of lubricants, questions related to the whole issue of ‘osmolarity’ which we have to consider before putting anything inside our body, and questions about hormone use by transgender women as there is a fair amount of hormone use (as well as the use of surgical intervention) among the transgender community. There was a great deal of interest in participating in any further clinical studies, I think the community here is pretty engaged and they want to see the research agenda to move forward, and in general there is lot of support from the community.”
TISSUE EXPLANT AND LIVE HIV CHALLENGE
Speaking to Citizen News Service – CNS about ‘tissue explant and live HIV challenge’ component that will be performed only in two sites (including the Bangkok site), Dr Holtz shared that “there were lot of questions from MTN laboratory group about our capacity, staff, about training and other issues-- whether or not we will be able to conduct all procedures properly. There will always be challenges when we are trying to do tissue culture, medical procedures such as biopsies of tissues, keeping the tissue viable in a laboratory and challenge the tissue with HIV virus. This is not something we have ever done before but we have been preparing our laboratory for this.”
Dr Holtz's team overcame challenges that came up one by one. The first challenge was how to make sure that the tissue explant from biopsy reaches the laboratory within 30 minutes from the clinic. “Our clinic site is located 20 km away from main laboratory. Our clinic in Bangkok downtown is our main clinic site, and is in middle of a very busy commercial centre, and at times it is difficult to get to a highway (freeway or toll-way), and to get back up to MOPH campus where our offices and laboratories are co-located in Department of Disease Control, MOPH. We had recognized that getting biopsy samples from our clinic to laboratories within 30 minutes would be a challenge, so we have actually changed the location of where we are going to do our biopsy specimens at an infectious disease institute located in MOPH campus. So all the medical procedures like sigmoidoscopy or biopsies will be done literally at a centre 5 minutes away from our laboratories. So as soon as biopsy specimens are taken we will be able to take them to our laboratories within 5-10 minutes where they will be processed immediately.”
Another challenge was related to ensuring that study participants are well educated and motivated to adhere to study regimens as required. “Taking the study products for long periods of time will be challenging in terms of adherence as study participants have to be on each of the three study products for two months at a time. We are trying to make sure we have enough adherence counsellors and support staff to help the study participants to get through the study regimens. There will be extensive screening and education in informed consent process, to make sure that the people understand that this is a fairly rigorous study” said Dr Holtz.
Earlier, in an attempt to advance the research agenda (in terms of collecting enough evidence) of getting to the phase III of rectal microbicides research, this MTN017 study was expanded to eight sites and the length of time was increased too.
WHEN WILL THIS STUDY BEGIN?
Right now the Thai site is in middle of getting approvals from the CDC Institutional Review Board (IRB) and Thai Ethics committee. Both of the committees have reviewed MTN017 protocol and have given some questions to answer which is routine. “As soon as we get responses to these questions back to the committees and get their approvals, then only we will be able to start the scheduling for the training” said Dr Holtz. “MTN will come to train our staff, as well as the site in Chiang Mai – we are trying to keep our sites coordinated as much as possible. Recently there has been some talk about doing real time pharmacokinetics studies and so now there is a letter of amendment that is being drafted for the study. Study can only begin when letter of amendment has been approved at each site. Adherence to the product is one of the most important factors in the study. We would not be able to get any safety data unless people are adhering to the regimen – having real time pharmacokinetic data is going to be important for us. We were hoping that the study starts in first half of 2013 (May or June) perhaps.”
RESEARCH ON DELIVERY METHODS
Dr Holtz and team is also considering studying different kinds of longer acting PrEP delivery methods to have higher drug concentrations in that part of body locally, such as injectables or rings (vaginal ring, or ring that can be inserted into a rectum or colon). Some researchers are also looking at other kind of drugs that can be used and more information and research updates might come up in the forthcoming MTN Annual Meeting next month in US.
It is vital that people have options to protect themselves from HIV and other STIs that are safe, effective, accessible, affordable and work in their unique contexts. Let us hope that the range of HIV prevention options continues to expand to meet different and unique needs and contexts of people around the world. More updates on research studies might come from the forthcoming MTN Annual Meeting, so remain tuned to CNS for further updates.
Bobby Ramakant, Citizen News Service - CNS
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