Towards ending HIV in Zimbabwe through focusing on improving targeting of HIV testing and uptake of HIV prevention in adolescent girls and young women

In Zimbabwe HIV remains the leading cause of death. In 2016, 1 in 7 adults were living with HIV.
In order to end the HIV epidemic as a public health threat by 2030, the Joint United Nations Programme on HIV/AIDS (UNAIDS) set the targets of: (a) 95% of people living with HIV (PLWH) being diagnosed, (b) 95% of those diagnosed on antiretroviral therapy (ART), and (c) 95% of those on ART with an undetectable viral load ("suppressed"). These targets were based on the rationale that PLWH diagnosed, on ART and suppressed have near normal life-expectancy and cannot transmit the virus to others. In Zimbabwe in 2016 these were: (a) 73%, (b) 87% and (c) 86%, respectively, despite the number of HIV tests having increased by four-fold between 2007 and 2017. This is particularly low among adolescents and young people. In addition, the proportion of all HIV tests with a positive result has been declining, with a higher cost to identify each new case. For this reason, Zimbabwe is shifting to differentiated HIV testing strategies, targeting sub-populations at higher risk of HIV and using a range of testing strategies (e.g. "index testing", whereby household, family members or partners of people diagnosed with HIV are offered an HIV test; self-testing). However, the impact of this shift is unclear, as is whether it offers value for money.
Adolescent girls and young women (AGYW; aged 15-24) are disproportionately affected by HIV. The World Health Organization (WHO) recommends Pre-Exposure Prophylaxis (PrEP; use of specific antiretrovirals in people without HIV to prevent HIV infection), as an additional choice for people at substantial risk of HIV (including AGYW). In Zimbabwe PrEP roll out has started, but only 4% of current users are AGYW (not counting those reporting as selling sex). An approach to increase PrEP use among those AGYW most at risk is required. Studies evaluating the safety and efficacy of additional PrEP formulations (long-acting injectables, implants, other antiretrovirals and in combination with contraceptives) are ongoing. However, little is known about preferences of AGYW for different PrEP attributes, nor is there information on how to ensure high uptake and sufficient support among this group.
The overall aim of this fellowship is to fill these gaps. This will be achieved by:
a. working closely with the Zimbabwe Ministry of Health and Child Care and other stakeholders to identify the optimal combination of HIV testing strategies that maximise health, within the budget available, to assess its impact (in terms of HIV infections, morbidity and mortality) and whether this combination is predicted to achieve the target of 95% of PLWH being diagnosed by 2030. This will be performed using a mathematical model informed by analysis of data already collected in Zimbabwe.
b. co-developing with AGYW a PrEP implementation intervention for AGYW who need it, that attracts them to PrEP, and supports them while taking PrEP, with the potential to offer value for money. This will be achieved using qualitative and quantitative methods (survey of AGYW) and mathematical modelling.
If the PrEP implementation intervention developed has the potential to offer value for money and being affordable, it will be then evaluated in a randomised trial in Years 5-7.

The research will be led by Dr Valentina Cambiano, Lecturer in Infectious Disease Modelling and Biostatistics at University College London (UCL) and will draw together experts from UCL, the Liverpool School of Tropical Medicine and the Centre for Sexual Health and HIV/AIDS Research Zimbabwe and Zimbabwe and international policy makers.

This research is required to address questions low- and middle- income countries with a high HIV burden are facing.

The research produced through this fellowship has a number of beneficiaries. The order in which they are presented reflects when the impact will be realised.

Firstly, the academic community, including the research team and students, will benefit. This project will expand knowledge in the field of HIV testing and prevention and sexual health more broadly and be of interest for the following disciplines: public health, epidemiology, mathematical modelling for infectious diseases, health economics and social sciences. I will master my leadership skills and strengthen and widen my academic knowledge and experience to become an independent researcher leader. The researchers employed through this fellowship, who will all be based in Zimbabwe except for me (who will spend a substantial amount of time there) and my co-I Dr Copas, will have the opportunity to gain further research experience and be supervised by national and international experts so that they become highly skilled researchers for the future. University College London (UCL) will benefit, as it will allow UCL to diversify its research portfolio, strengthen collaboration with research institutions and stakeholders in Zimbabwe and produce high-quality research in a crucial area of public health. UCL students will benefit as findings from this research will be embedded into teaching, with the aim of enhancing their learning experience. This impact will be realised in the short- (during the term of the grant) and middle-term of the grant (by Years 5-7) but of course with long lasting consequences.

Secondly, the Zimbabwe Ministry of Health and Child Care (ZMoHCC), national (Zimbabwe National AIDS Council) and international health agencies (e.g. World Health Organization, Joint United Nations Programme on HIV/AIDS), donors (e.g. the Global Fund, USAID, and Bill and Melinda Gates Foundation) and implementers/research centres (Centre for Sexual Health and HIV/AIDS Research Zimbabwe) will benefit from the proposed research. This project aims to provide evidence-based answers to questions decision-makers are currently facing: which new HIV testing strategies to implement or expand and which one to scale down (if needed) and how to optimally implemented Pre-Exposure Prophylaxis (PrEP) for adolescent girl and young women in need to ensure high uptake and adherence when needed, in an affordable and cost-effective way. The involvement of the stakeholders in this project should facilitate prompt translation of this research into policies, so it is expected some of the impact on this regard will be already seen in the short-term but most will probably take place in the medium-term.

Thirdly, the communities in Zimbabwe, and in particular adolescent girls and young women, and the international society will benefit. Adolescent girls and young women will be directly involved in the research and will jointly develop with the research team a PrEP implementation intervention; therefore, some of the impact will be already realised in the short-term. Ultimately, the vision for this proposal is that the impact will be on the people whose health will be improved by utilizing health care resources in a way that maximises health. This includes people living with HIV, but also HIV negative people at risk of acquiring HIV, and in particular sexually active adolescent girls and young women, a particularly vulnerable group. This latter group will benefit if indeed the PrEP implementation intervention developed is found to offer the potential to be cost-effective and affordable and is then proven to be effective in a trial (in Year 5-7) and it is implemented. This will be in the first instance in Zimbabwe, but lessons learned could be adapted to countries in the rest of Southern Africa. The international society will benefit by the enhancement of the efficiency of UK and international aid and by gaining knowledge of these findings. This impact will be realised in the long-term.