HIV CURE RESEARCH INFRASTURE STUDIES (H-CRIS)

EDCTP grant: TMA2017SF-1955

Research Title

Identification of Novel HIV Reactivation Agents: Towards Building Translational HIV Cure Research Infrastructure in Ghana

Background and study aims

HIV continues to be a major public health problem in Africa. Although taking HIV medications has reduced HIV-associated deaths and improved lifespan, it does cure people of the infection. Patients must take medications daily for the rest of their lives and this comes with side effects, high costs, and the virus becoming resistant to some of the medication.

It is difficult to cure HIV because after infection some of the virus hides in cell that are not dividing and sleeps there until the HIV medicine is discontinued then they come out and make the person sick. One way to try and cure HIV is therefore to find compounds that can wake the virus up from sleep so that the HIV medicine can work to clear them and destroy the cells that contain them. In this study, we propose to screen several compounds for their ability to wake the sleeping virus up, select the most effective and test them in non-dividing cells taken from HIV patients whose viruses are undetectable.

Who can participate?

Adults (18years and above) living in Ghana who are HIV infected and on HIV medication. These persons must be attending clinic at the three study sites: Korle-Bu Teaching Hospital, Korle-Bu, Accra, University of Ghana Hospital, Legon, Accra and LEKMA Hospital, Teshie, Accra. The persons must willingly decide to be part of the study and must give a written, signed consent.

What does the study involve?

Each eligible person will be asked to answer questions concerning their knowledge about efforts being made to cure HIV. Every three months when they come to clinic, they will be asked about how they are doing, whether they are taking their HIV medications and whether they have any problems with the medications. Then one tube of blood (about 10ml) will be collected from them to be used to measure how much of the virus is in the blood and their white cell (CD4) counts. On some visits, their urine samples will be collected. The whole process during each visit will take about 20 minutes. We intend to follow them up for two years during this study. We will select those who have undetectable virus to partake in the studies to wake the sleeping virus up. This study will help better understand HIV in order to figure out whether it can be better treated or eventually even be cured.

What are the possible benefits and risks of participating?

Potential Risks: Participants may experience discomfort, bruising, and/or bleeding at the site of needle insertion. This will be monitored for about 5 minutes after the blood is taken to make sure you the participant is fine before leaving the clinic. Occasionally, some people experience dizziness or feel faint. The investigator is willing to discuss your concerns about any of these risks.

Benefits: The CD4 count and viral load will be measured every 3 months. The participant’s doctor will be informed if the viral load is going up or not coming down as expected even though the participant is taken their medications. Your doctor may change your medications at that point. This could be a potential benefit from the study.

Where is the study run from?

This research study is run from the Virology Department of the Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Accra.

When is the study starting and how long is it expected to run for?

The study started on May 01, 2019 and is expected to run for 5 years

Who is the main contact?

The main contact is Dr. George Boateng Kyei; the Principal Investigator of the study.

Who is funding the study?

The study is funded by the European and Developing Countries Clinical Trials Partnership (EDCTP). Grant name TMA2017SF-1955

Achievements

The infrastructure set up for drug screening at the University of Ghana has contributed to training students and technical staff. We have also initiated evaluation of herbal extracts and other compounds for HIV replication and/or reactivation.

The project is building local research capacity of Postdoctoral fellows to become independent research leaders. Also, the PI is mentoring postgraduate students in HIV translational research.

Project-related Publications

1. Bonney EY, Lamptey H, Aboagye JO, Abana CZ-Y, Boateng AT, Quansah DNK, Obo-Akwa A, Ganu VJ, Puplampu P, Kyei GB, on behalf of the H_CRS Massive Acton Team. Unwillingness of Patients in Ghana to interrupt antiretroviral therapy for HIV Cure Research. Journal of Virus Eradication 7 (2021) 100027
2. Lamptey H, Bonney EY, Adu B and Kyei GB (2021) Are Fc Gamma Receptor Polymorphisms Important in HIV-1 Infection Outcomes and Latent Reservoir Size? Front. Immunol. 12:656894. doi: 10.3389/fimmu.2021.656894

Conference Papers

George Boateng Kyei, PROGRESS TOWARDS FINDING A CURE FOR HIV INFECTION: SHOCK AND KILL VERSUS BLOCK AND LOCK (Plenary talk) African Virology Congress 3-4 November 2021, Accra Ghana

Evelyn Yayra Bonney, THIRTY-FIVE YEARS OF HIV RESEARCH IN GHANA: ACHIEVEMENTS, CHALLENGES AND PROSPECTS (Plenary talk) African Virology Congress 3-4 November 2021, Accra Ghana

Christopher Z-Y Abana Anthony T. Boateng, Araba Abaidoo-Myles, Darius N.K Quansah^, James O. Aboagye, Osbourne Quaye^, Regina Appiah Oppong^, Helena Lamptey, Evelyn Y. Bonney, George B. Kyei^. INHIBITION OF HIV REPLICATION IN VITRO BY THREE LOCAL HERBAL EXTRACTS (ORAL), African Virology Congress 3-4 November 2021, Accra Ghana

Araba Abaidoo-Myles, James O. Aboagye, Helena Lamptey, Christopher Z-Y Abana, Anthony T. Boateng, Darius N.K. Quansah, Seth Agyemang, Peter Puplampu, Gloria A. Ansa, Joseph Oliver-Commey, Vincent Ganu, Evelyn Y. Bonney, George B. Kyei. SYPHILIS CO-INFECTIONS IN A COHORT OF HIV-POSITIVE INDIVIDUALS RECEIVING ANTI-RETROVIRAL THERAPY IN GHANA (POSTER), African Virology Congress 3-4 November 2021, Accra Ghana

Helena Lamptey, Benjamin Newcomb, Evelyn Y. Bonney, James O. Aboagye, Peter Puplampu, Gloria A. Ansa, Vincent J. Ganu, Joseph Oliver-Commey, George B. Kyei. Stakeholder PERSPECTIVES ON HIV CURE RESEARCH IN GHANA (POSTER), African Virology Congress 3-4 November 2021, Accra Ghana

Anthony T. Boateng, James O. Aboagye, Helena Lamptey, Christopher Z-Y Abana, Araba Abaidoo-Myles, Darius N.K. Quansah, Seth Agyemang, Peter Puplampu, Gloria A. Ansa, Joseph Oliver-Commey, Vincent Ganu, George B. Kyei. Evelyn Y. Bonney. HIGH LEVELS OF VIRALSUPPRESSION AMONG HIVP PATIENTS TAKING ANTIRETROVIRAL THERAPY IN GHANA (ORAL), African Virology Congress 3-4 November 2021, Accra Ghana

Aim

1: To characterize a cohort of HIV patients and evaluate their knowledge and attitude towards participation in HIV cure research

2: To screen a panel of 150 epigenetic modifying compounds for ability to reactivate HIV from latency in a cell line and primary cell model of latency.

3: To evaluate top 10 lead compounds in resting CD4 T cells isolated from patients suppressed on cART for more than 6 months

4: To assemble a well-characterized HIV patient’s biobank to serve as a repository of samples for future research and student training.


Collaborating Institutions:

University of Ghana Hospital, Legon, Accra Ghana

LEKMA Hospital, Teshie, Accra Ghana

Korle-Bu Teaching Hospital, Korle - Bu, Accra Ghana

West African Centre for Cell Biology of Infectious Pathogens, University of Ghana

Washington University in St. Louis, USA

Research Progress

Ethical Issues

Ethical clearance for the study has been obtained from the ethical/institutional review boards of:

• Noguchi Memorial Institute for Medical Research, University of Ghana, Legon
• Korle -Bu Teaching Hospital Accra
• Ghana Health Service

Recruitment of project staff

The project has successfully recruited two postdoctoral fellows, one PhD student and an Mphil student and identified project nurses at the collaborating hospitals to help with the recruitment of the study cohort.

Patient Recruitment and Sample processing

A well-characterized cohort has been set up to answer the first objective. A total of three hundred and ninety patients (390), consisting 250 from the Korle-Bu Teaching Hospital, 70 from the University of Ghana hospital and 70 from LEKMA hospitals have been recruited into the study. Blood samples have been collected from the patients, processed into plasma and peripheral blood mononuclear cells and stored at -80^oC for further analysis.

Achievements

Cell passaging, expansion and freezing of cell lines; Optimization of cell cultures and other assays are ongoing.

One manuscript has been drafted on the perception of HIV has been submitted to the journal of Virus Eradication

Sponsors

This project is part of the EDCTP2 programme

supported by the European Union.