HIV prevention research: A bimonthly injection to keep HIV away?

Shobha Shukla, CNS (Citizen News Service)
Dr Suwat Chariyalertsak, Director, RIHES, CMU
Pre-exposure prophylaxis or PrEP, is a relatively new concept of "treatment as prevention" against HIV for those HIV uninfected persons who might be at risk of contracting the virus. Currently, only Truvada, a two-drug (Tenofovir Disoproxil Fumarate/ Emtricitabine - TDF/FTC) combination pill, is available to be taken for PrEP.  Approved by US FDA in July 2012, Truvada is 100% effective in preventing HIV in those who take this once a day pill at least 4 or more days a week.

But studies have revealed that many find it difficult to comply with a daily pill regimen.The development of alternatives for daily PrEP, and more adherence-friendly schedules, could increase prevention choices and increase acceptability. Because of the potential issue of adherence to a daily regimen, as well as the stigma issues around a daily pill regimen, an injection shot given once every two months, that would reduce a person’s risk of acquiring HIV by more than 90%, might present the future of HIV prevention

HPTN 083

HPTN 083 is a phase 2b/3 double blind randomised safety and efficacy study being done to evaluate the efficacy of the long-acting injectable agent, cabotegravir (CAB LA), compared to daily oral Truvada, for PrEP in HIV-uninfected men who have sex with men (MSM) and transgender women (TGW). This soon to begin study aims to enrol around 4500 HIV-uninfected MSM and TGW at risk for acquiring HIV infection, aged 18 or older, across 40 sites in the Americas, Asia, and South Africa.

In an exclusive interview given to CNS (Citizen News Service), Dr Suwat Chariyalertsak, Director Research Institute for Health Sciences (RIHES), Chiang Mai University, informed that preparations ,were on to carry out this study at 3 sites in Thailand: 1 in Chiang Mai and 2 in Bangkok. Each of these 3 sites will enroll close to 180 participants: a total of 540 participants in Thailand. Dr Suwat would be supervising the study at the Chiang Mai site.

“There will be a training by USAID in December 2016. Hopefully recruitment will start in the 1st quarter of 2017. We want to learn how one compares with the other and we also want to learn what is the participants’ preference. While for most the injection may be a better option, this new regimen is also likely to reduce the stigma around the daily PrEP”, Dr Suwat informed.

Meanwhile a demonstration project to test feasibility and acceptability of daily PrEP among MSM and TWG is already underway at the PIMAN clinic operating under RIHES. PIMAN Clinic is a multipurpose venue for research on MSM, and a drop-in social hangout for MSMs. It provides free of charge HIV testing, counselling and STI services to MSMs, bisexual men and transgenders.

Participants of this one year long project, which began in January 2016, are given free daily oral PrEP medication along with standard HIV prevention methods. They also get regular HIV testing and STI counselling and free STIs treatment/referral if STIs diagnosed.

Dr Suwat told CNS that RIHES is conducting this one year long demonstration project to:
  • (i) find the feasibility and acceptance of daily oral PrEP among MSM and TGW 
  • (ii) study the factors that influence the decision of taking daily oral PrEP and 
  • (iii) assess adherence to PrEP among its users. 

This project would also provide valuable insight for future Thai national PrEP programme, as PrEP is not yet part of the Thai National Health Insurance System.

Enrolment of 200 participants (MSM or TGW over 18years of age) has begun and 60 are already on daily PrEP. Participants make their own decision about PrEP initiation and are free to change their decision at any time during the study period. As most of the MSMs who come to PIMAN are sexually active young university students who often have more than 1 partner, daily PrEP may be a better option than condoms for them, felt Suwat.

Dr Suwat said that, “We started this project in January 2016. As of now (early September 2016) we have 60 MSMs taking PrEP from this clinic. About 5-10% of those who had started on PrEP, are not taking it currently as they have separated from their partner and have yet to find a new one. So they will start again when they get a new partner.  Stopping of the drug is mostly related to their risk perception.”

Stigma around use of PrEP

According to Dr Suwat, there are many stigma issues related with taking PrEP: “Your partner might misunderstand that you are taking this drug for being HIV positive. If you say you are taking it for prevention he/she might think you are at high risk of HIV due to having multiple partners. This mistrust could end or complicate the relationship. Users of PrEP must tell their partner that they are taking it to protect themselves from HIV, and ask the partner also to take it.There has to be more awareness and knowledge about PrEP. Proper counselling for correct understanding of PrEP is essential”.

Preparations are also afoot in Thailand at the national level, to soon roll out a one year long pilot demonstration project for PrEP use in 6 provinces initially. RIHES will provide training for counselling and monitoring of this national project. Results of these two projects would provide valuable insight for future Thai national PrEP programme.

“People need to know that PrEP is for prevention and not for treatment. Right now most people do not know much about this drug. Even those who know, they think that they do not need it —they think condoms are good enough. Also, even if they want to use it, they cannot just go and buy it over the counter from a pharmacy. They first have to be screened for HIV, and get tested for some health parameters. Only if they are found eligible do they get a hospital prescription to buy it”, said Suwat.

Basic structure of HPTN 083 study

At each study site, participants will be divided into two randomised arms: A and B. In the 1st phase of the study, lasting for 5 weeks, every participant will take the daily PrEP pill—Arm A will be given daily oral CAB pill and oral TDF/FTC placebo; while Arm B will be on daily oral TDF/FTC pill and oral CAB placebo. This is to see if participants have any serious side effects to the study drugs before they start getting the injections.

In the 2nd phase of the study every participant will take the oral pill as well as the injection: Arm A will get active CAB injection at two time points 4 weeks apart, and every 8 weeks thereafter, and daily oral TDF/FTC placebo; while Arm B will get daily oral active TDF/FTC pills and CAB injection placebo at two time points 4 weeks apart, and every 8 weeks thereafter. This step will continue until the required number of endpoints is reached.

In the last phase all participants will get the active oral PrEP everyday for about one year. Participants will then transition to locally-available HIV prevention services, including services for PrEP, if available.

Let us not forget that in 2015 there were 2.1 million new HIV infections worldwide, adding up to a total of 36.7 million people living with HIV globally. Only an estimated 18.2 million of them were accessing life-saving antiretroviral medicines as of June 2016.

The development of alternative agents, and more adherence-friendly schedules for PrEP, could increase prevention choices and increase acceptability. Long-acting injectable agents have the potential to prevent HIV acquisition without relying on adherence to a daily oral regimen. Thailand is indeed taking small but steady steps to move forward with the usage of PrEP in high risk populations— not only at the local country level, but also in the larger global interest, by taking part in the HPTN 083 study.

Shobha Shukla, CNS (Citizen News Service)
1 December 2016