Implementation of the HIVQUANT™ Pilot Trial underway in Southern Malawi

January,  2024

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There are 38 million people currently living with HIV-1 (PLHIV) worldwide with approximately 1 million deaths each year.  The current HIV prevalence among adults between 15 to 49 years of age in Malawi is approximately 8.9 percent. Over 1.5 million people have died of HIV-related illnesses in the country, and over 1 million people are living with HIV (AVERT, 2017). Despite readily available anti-retroviral therapy (ART), the country registered 21,000 new infections in 2020 alone with the adult prevalence at 8.1% (Beintheknow, 2020). Among AGYW, 2 young women are infected with HIV every hour, with the prevalence among adolescent girls at 12.9 percent, compared to the country’s national average of 8.9 percent. In Zomba District where the project will be implemented, the HIV prevalence among young women is 16.8%, compared with 9.3% among men of the same age (Peterson et al, 2020). In the most recent WHO HIV-1 drug resistance report, a surveillance study found Malawi has the worst first-line drug resistance rates (68%) in infants born to HIV-1-positive mothers (Malisa et al, 2023).

HIV-1 suppression to “undetectable” viral load levels (i.e., below 50 copies/ml in plasma) following initiation of combination antiretroviral therapy (cART) is significantly associated with longevity and improved quality of life. The dissemination and use of low-cost generic first-line cART have made treatment widely available.  In East and Southern Africa, approximately 80% of HIV-1 positive people know their status and are on cART but less than 45% have access to a viral-load test.  This is driving the emergence of drug resistance isolates.  Up to 26% of people who initiate treatment worldwide have first-line drug resistance to HIV-1.  Up to 10% of adults starting HIV treatment can have drug resistance to the non-nucleoside reverse transcriptase inhibitors (NNRTI) drug class. Pretreatment NNRTI resistance is up to 3 times more common in people with previous exposure to antiretroviral drugs. The prevalence of drug-resistant HIV is high in children under 18 months of age and newly diagnosed with HIV. Based on surveys conducted in 10 countries in sub-Saharan Africa (2012–2020), nearly half of the infants newly diagnosed with HIV have an NNRTI-resistant virus before initiating treatment. In the worst-affected areas of sub-Saharan Africa however, up to 69% of infants born to HIV-1 positive mothers, carry first-line cART-resistant strains to the only drugs that are cheaply available in these areas. This is a huge public health concern.  

Viral load tests cost approximately £50 to £100 each and require a cold chain, specialized equipment, and specially trained staff.  Cheaper (~£12 per test), alternative, point-of-care tests such as the GeneXpert® HIV-1 viral load test (Cepheid) have been developed and are being disseminated to secondary and tertiary clinical centers but are limited in the number of samples that can be processed within two hours.  Moreover, they still require specialized equipment and a reliable power source. Laboratory-developed assays (LDAs) such as the one developed by Kibirige et al. provide an improved and efficient tool for large-scale patient screening because they can be tailored to the available specimens and run at a lower cost. They provide a more viable treatment monitoring option for resource-constrained settings.

Kibirige C. et al., developed, patented, and published a sensitive HIV-1 LDA in January 2022. Validation studies following US FDA guidelines demonstrated the assay to have a limit of quantification of 88 copies of HIV-1 RNA per ml of plasma or the equivalent of 1 infected cell with 95% efficiency. It is 95.75% accurate, 100% sensitive, and 93.24% specific for HIV-1. It showed a 99.2% detection rate on an accredited panel of 127 diverse global HIV-1 isolates. Dr. Kibirige has further developed the assay into a cost-effective qPCR kit that does not require a cold chain or special equipment.

This pilot study will investigate the use of the HIVQuant® assay for quantification of plasma HIV-1 RNA viral load alongside quantification of intracellular HIV-1 DNA from peripheral blood mononuclear cells or crude whole blood lysates as alternative point-of-care protocols for treatment monitoring in resource-constrained clinics, and establish correlations relative to the measures obtained by current standard plasma viral load assays. The study will provide an exploratory analysis of the procedures and methods to guide the development of a subsequent larger clinical trial for a more efficient approach to large-scale patient treatment monitoring in resource-constrained settings.

CenRID is collaborating with Imperial College, London, to conduct the HIVQuant™ study at the Zomba Central Hospital in Southern Malawi.

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