‘Due to their resistance to treatment, many people receiving HIV therapy are dying from the disease’

Tendai Washaya is a 29 year-old PhD fellow from the University of Zimbabwe. In this interview, she explains how, through her research, she has been striving to determine the extent of prevalence of multi-resistant HIV-1 in her country and why some patients develop greater resistance to treatment than others.

Tendai is one of two recipients of a three-month research fellowship awarded this year jointly by UNESCO and the European Molecular Biology Laboratory (EMBL). She took up her fellowship this month at the EMBL’s European Bioinformatics Institute in Cambridge in the United Kingdom, where she will be pursuing her research.

The other recipient is Adwoa Padiki Nartey from the University of Ghana. Like Tendai, Adwoa’s research project is tackling resistance to medication. However, whereas Tendai’s project is focusing on the resistance of the human body to medication, Adwoa’s research is focusing on the bacteria’s resistance to the medication designed to kill them.

The need to investigate drug resistance among patients undergoing high-intensity treatment came into focus for me when my sister was severely ill with Acquired Immune Deficiency Syndrome (AIDS). She kept getting referred for enhanced adherence counselling, despite the fact that we had specifically stated that she was taking her medication on time.

She was only found to be resistant to the medication she was taking after being transferred to a non-profit hospital and tested for drug resistance. As in most resource-limited countries, testing for drug resistance in HIV patients using a method of DNA sequencing called Sanger sequencing was very costly in Zimbabwe and unavailable in the public sector. My sister passed away in 2019.

Due to their resistance to treatment, many people receiving HIV therapy are dying from the disease. This motivated me to investigate affordable drug resistance testing methods for resource-limited countries.

The latest statistics from UNAIDS state that there were approximately 1.4 m people living with HIV in Zimbabwe in 2021.

The World Health Organization has adopted three 95% targets at global level; by 2025, 95% of all people living with HIV should have a diagnosis, 95% of these people should be taking a life-saving antiretroviral treatment and 95% of those being treated should have a viral load low enough to enjoy quality of life and reduced onward transmission of the virus.

At this stage, 96% of Zimbabweans living with HIV are aware of their HIV status, 91% are on treatment and 85% are virally suppressed.

It is an almost universal observation that, as soon as a patient starts taking medication against a given pathogen, resistant-pathogen strains emerge.

This happens regardless of the drug’s high genetic barrier to resistance (such as that of the drug Dolutegravir), with resistant strains emerging mainly due to poor adherence that lead to sub-optimal therapeutic concentrations of the drug.

Without vigilant monitoring of how heavily treated patients having shown prior resistance to HIV drugs react to the new treatment, it will be inevitable that multidrug-resistant mutations develop and eventually lead to pan-resistant HIV-1.

The introduction of Dolutegravir (an integrase transfer inhibitor) as the preferred first-line drug for patients who have had prior exposure to other drugs (reverse transcriptase inhibitors and protease inhibitors) would mean that the number of people who have been exposed to all three classes of drug increases. This heightened exposure to all three classes of drug would, in turn, foster the development of pan-resistance.

My study aims to determine the prevalence of multi-resistant HIV-1 and the resistance profiles of the HIV virus, as well as to investigate novel resistance sites in the genome of the HIV virus. This information is important, as it can then be used to advise on new and future treatment needs.

My study will also help to highlight the need for vigilant monitoring of patients receiving HIV medication to check that their treatment is working, in order to reduce the transmission of multi-resistant strains and educate patients about the importance of adhering to their particular treatment. Vigilant monitoring is especially important in a country like Zimbabwe with limited resources.

Moreover, given the limited availability of testing for HIV-drug resistance in resource-limited settings, a low-cost genotyping test (assay) to detect relevant mutations in the patient’s HIV-1 integrase gene would be warranted. An HIV drug resistance test costs approximately US$ 200, which is expensive for the average person. There is also a lack of machines to perform the test in the public sector.

My training there will help me to develop expertise in next-generation gene sequencing. I will learn how to prepare sequencing libraries for approaches based on the polymerase chain reaction (PCR). Scientists use PCR to make millions of copies of a particular tiny DNA sample, to make it easier to study.

This training will also give me practical experience in bioinformatics. I shall learn how to instruct a computer to perform a given task, such as to develop a directory of gene samples, using Linux/Unix command lines. I shall also learn how to analyse output data using bioinformatics analysis with a focus on quality control of data, reference mapping and de novo assembly approaches. I shall also learn how to do downstream analyses, such as of HIV variants associated with drug resistance.

The term de novo assembly refers to a method used to construct a genome from a wide array of DNA fragments, without any prior knowledge of their sequence – a bit like getting assistance with assembling a jigsaw puzzle.

In Zimbabwe, we don’t have the machine yet that I want to use for my study. I plan on using the Illuimina MiSeq platform for next-generation gene sequencing. There is a GeneXus in Zimbabwe but the reagents are costly to use for my project.

In addition, it will be nice to learn from, and collaborate with, scientists from other countries.

I am a second-year doctoral student with the University of Zimbabwe. I hold an MSc in Biotechnology and started my career in HIV research while working towards that degree. I am interested in translational science.

I got married in 2020 and had my son, Tadiwanashe, in 2022. He is now just over a year old. I plan on travelling to Europe with my husband and son.

_{Interview by Susan Schneegans}