Know Your Specialist

Dr Emily Shava is a medical doctor (MBChB from University of Zimbabwe 2004) with a Master of Science in Clinical Trials (London School of Hygiene and Tropical Medicine 2016.)

She has been involved in clinical research in Botswana through Botswana Harvard AIDS Institute Partnership, since November 2009. Thus she has had the opportunity to work with different stakeholders and communities in the country since then.

Here she tells RACHEL RADITSEBE about the ongoing AMP Study Enrolment is ongoing in the Antibody-Mediated Prevention (AMP) study.

Tell us about that. What is AMP and how exactly does it work? AMP stands for Antibody Mediated Prevention. This is a multicentre study being conducted in different countries by two global networks known as HIV Prevention Trials Network (HPTN) and HIV Vaccine Trials Network (HVTN). The AMP study in Sub-Saharan Africa is enrolling women and is also known as HVTN 703/HPTN081 Study.

Women because in Africa they are among those at highest risk of HIV infection because of their physiology and gender based imbalances. In this study broadly neutralising antibodies(Bnabs) known as VRC 01 are being studied to see to what extent they can prevent acquisition of HIV-1(efficacy) and to what extend VRC01 can be tolerated by participants (safety). This is a follow up of previous studies which showed that VRC01 is generally safe and well tolerated (HVTN 104). It is a double blind randomized placebo controlled trial. This means that participants do not choose which group they are to be on. The study has 3 groups, high dose VRC01, low dose VRC01 and a placebo group.

They will NOT know which group they are in and the clinicians consulting them will also not know which group the participants are in. Only the site pharmacy personnel are unblended - they know which product is which. This is important to prevent bias. BHP has engaged and continues to engage various stakeholders (including Ministry of Health and wellness, DHMT, clinics) and communities through the BHP community advisory board since 2015 when we were selected to take part in this important study.

The success we are talking about now would not have been possible had the different stakeholders and communities not been on board. What is your role in the Study? I am the study coordinator for the project, responsible for day to day running of the study clinic. The person with overall responsible for the study in Botswana is the site investigator Dr Joseph Makhema. Who are the participants in the study? How many people are required and how many have you enrolled so far? The participants are healthy HIV negative women at risk of acquiring HIV, aged between 18-40 years and willing to take part in the study.

They should not be pregnant or breastfeeding and should be willing to use effective contraception to prevent pregnancy since the effect of VRC01 on pregnancy is unknown. In Sub-Saharan Africa a total of 1900 participants will be enrolled from Botswana, Kenya, Malawi, Mozambique, South Africa, Tanzania and Zimbabwe. 1555 participants have been enrolled as of the end of April. From Botswana a total of 150 participants will be enrolled. In Botswana the AMP study was activated in July, 2016.

The first participant was enrolled on August 16, 2016. To date 236 participants have been screened/checked for eligibility to participate in the study and from these, 122 women have been enrolled and are on study as of May 4, 2018. Willing participants provide written informed consent after discussion of all procedures, and their risks. The informed consent forms, together with the protocol (document that explains how the study is conducted) and other pertinent documents for study conduct are submitted for approval by the Ministry of Health and Wellness, Institutional Review Board(IRB) known as Health Research and Development Committee (HRDC).

This is the committee responsible for approval of research conducted in country. What are the fundamental questions about HIV prevention that the AMP Study is designed to answer? Are people able to “tolerate” the antibody without becoming too uncomfortable? Does the antibody lower people’s chances of getting infected with HIV? If the antibody does lower people’s chances of getting infected with HIV, how much of it is needed to provide protection from HIV? When did it begin and when is it expected to end? In Botswana the study started in July 2016. Total duration of study is 5 years. Each participant stays on study for about two years. What HIV preventive care do volunteers receive and how are you ensuring the safety of study participants? Participants come for study visits monthly.

During these visits, we do what is called “history taking” from the participants to find out how they are feeling and have been feeling. We examine them and we conduct laboratory tests to ensure safety. To prevent HIV infection, we provide risk reduction counselling and HIV prevention package per Botswana Standard of care What impact will this study have in the future of HIV prevention? We generally liken HIV prevention options to a tool box. We currently have various behavioural modification options in this tool box, including abstinence, use of condoms effectively and consistently. It is therefore important to also add more biomedical interventions in this tool box. bNabs would then be an important addition if proven to be effective. This would lead to more combination prevention options.

The idea of a toolbox with more tools in it is important because we know that when people have more choices, it increases the chances that an individual will find one tool that fits their needs and circumstances. Those decisions can be influenced by many factors – cost, ease of use, availability/easy access, partner agrees to use, etc. – so having more tools will mean increasing the chance of serving more people’s needs for HIV prevention. How will the findings benefit Batswana? I would say that it is too soon to say what direct benefit there may be to Batswana. This trial is about proving the concept that bNabs can prevent HIV. More trials will be needed to find the best antibody, or combination of antibodies, how to best administer them as a public health strategy amongst other things.

We know the strides science has made in the war against HIV/AIDS. There are very effective drugs and that is great news. But what do you say to young people that would say to you that it’s no big deal to get HIV and that there are already good drugs to control the disease as if it’s diabetes? Prevention is ALWAYS better than cure. We are truly grateful for the strides that have been made in science to avail great treatments for HIV treatment. We do not yet have all the answers about the various great treatments available, time generally brings things to light.

Additionally, prevention is more cost effective than treatment or a cure. (Note that in the question, diabetes isn’t cured – it is treated as a chronic illness.) That is important to individuals, and to countries/public health systems. From your experience, do you believe that there will be an effective vaccine and/or cure for HIV in our lifetime? Is that an achievable objective you think? Please note that in AMP study, the study agent VRC01 is NOT a vaccine but broadly neutralising antibodies (bNabs).

This study could help us develop a safe and effective HIV vaccine more quickly. An HIV vaccine developed more quickly because of this study could essentially teach the body to make antibodies like VRC01 (without getting the VRC01-like antibody through an IV/drip). To develop a vaccine like that we need to understand more about how VRC01 may work, and how much is needed to “work” (to prevent HIV infection). This study should help us learn that. My answer on vaccine in our lifetime would be YES, The Thai Trial, RV144, showed us a vaccine regimen that could reduce new infections by about 32%. That wasn’t strong enough to license, but it paved the way for a great deal of additional research.

There are 2 efficacy trials currently underway in sub-Saharan Africa testing different vaccine strategies (one of which builds on the Thai results), so we have come farther than ever before. There are various international organizations with scientists whose main focus is the development of the HIV vaccine such as the HVTN, International AIDS Vaccine Initiative(IAVI) etc. I understand that the HIV virus lives not in the blood but lymph nodes and some organs.

Is there any research currently being done to try and flush out HIV from these compartments so that it can be killed by the antiretroviral drugs? To clarify, when a person is on antiretroviral therapy, the amount of virus also known as viral load in blood will reduce. Generally, if a person is not on treatment the viral load will remain high. For people on treatment with low/undetectable viral load, scientists are looking into ways of flushing out HIV from its hiding places like the lymph nodes termed the “shock and kill” strategy.

Currently I am not aware of any such study being conducted in Botswana. HIV was around for decades before it was discovered and diagnosable and infecting humans during that period. Has anything been learnt from that to prevent a recurrence with another type of retrovirus? This is a difficult question, yes human beings are capable of learning to better themselves in the future, to what extent, time will tell. What good news can you give readers of this interview who are living with HIV/AIDS? If someone knows they are living with HIV, it means they have been responsible enough to take the test and know their status. This needs to be commended.

Currently we have available in this country potent antiretroviral treatment with minimal side effects, which means that people living with HIV can have improved quality of life, including sexual reproductive health and live longer. I would also like to take the opportunity to highlight the importance of universal test and treat and for all HIV infected people to be on treatment and to take the treatment diligently. This is important because a persistently undetectable virus is not transmissible.