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The World Health Organization (WHO) reported that by the end of 2021, roughly 75% (28.7 million) of people living with HIV were receiving antiretroviral therapies. At the same time, in helping achieve UNAIDS 2030 95-95-95 fast track targets 1. Drug resistance is more likely to develop in patients not adhering to an optimized antiretroviral therapy (ART) and failing to achieve viral load suppression. Achievement of the UNAIDS 2030 95-95-95 Fast-Track Targets includes the mitigation of emerging antiretroviral mutations that confer drug resistance.
Genotyping HIV-1, at both the individual and population level, to test drug resistance status is a key element in the global fight to end HIV.
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HIV drug resistance describes drug resistance mutations (DRMs) within the viral genome that diminish the viral susceptibility to antiretroviral (ARV) drugs, which can result in suboptimal virologic suppression and ultimate treatment failure. The mutations conferring drug resistance usually are within the viral protein that is targeted by the drugs. Some mutations only slightly impact drug efficacy (minor DRMs), while others can significantly lower drug susceptibility (major DRMs). Certain combinations of mutations act synergistically 2. Some mutations provide resistance against multiple or all drugs within the same drug class.
Drug resistance can be transmitted or emerge over time. HIVDR can result in an increase in the transmission of HIV infection and HIV-associated morbidity and mortality 1.
How does HIVDR develop?
HIV has a high mutation rate, which helps the virus to develop resistance mutations, especially in patients treated with monotherapies. Triple-drug therapies, introduced in 1995, were believed to suppress the emergence of drug resistance as the virus would need to incorporate multiple mutations simultaneously. However, HIV manages to develop multi-drug resistance to circumvent this combination therapy.
New drugs, such as the integrase inhibitor dolutegravir (DTG), are designed to have a high genetic barrier to resistance. In other words, drug resistance develops only after multiple mutations emerge in HIV 3.
The WHO emphasizes that “all antiretroviral drugs, including those from newer drug classes, are at risk of becoming partially or fully inactive due to the emergence of drug-resistant virus” 1.
Sanger sequencing
Serves as the gold-standard method for detecting HIVDR mutations of clinical relevance.
Next-generation sequencing (NGS)
Full genome sequencing to detect low-abundance drug-resistant variants.
Point mutation assays
Measures limited pre-defined mutations in a simple, low-cost format.
Educational resources
HIV Learning Guide: A Primer for Healthcare Professionals
A valuable resource that provides access to the most cutting-edge evidence-based information on HIV
Providing the latest evidence-supported information on HIV disease, epidemiology, testing, and clinical management while appreciating that this knowledge, like the pathogen itself, is constantly evolving. Offered in four modules using case studies, the valuable content is intended for diverse stakeholders including epidemiologists, public health and medical officials, healthcare advisors, scientists, laboratorians, and other health professionals who are managing and testing for HIV.
White paper: Virus surveillance
Tracking viral diversity, virus clusters, and drug resistance can reduce the impact of emerging and harmful mutations.
Infographic: Get the facts about HIV drug resistance
Build a solid understanding of HIV drug resistance—what it is, how it develops, and when and how to test for it.
Patient outreach: Answers to questions on HIV drug resistance
Written with the layperson in mind, this Q&A document is available for customization with your organization's logo in two formats.
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Free educational webinars
Part I: Understanding HIV drug resistance
This webinar, delivered by HIV clinicians, provides an overview of virologic failure, the role of drug resistance, and how ARV treatment guidelines are informed by current and emerging HIV drug resistance.
Part II: Understanding HIV drug resistance through case studies
This webinar, delivered by HIV clinicians, uses various case studies to reinforce the principles and applications of HIV drug resistance testing.
Part III: Personal stories and future perspectives on HIV drug resistance
This webinar, delivered by HIV clinicians, shares the experiences of several persons that have lived-experience with HIV drug resistance and insights on the future path of ART management.
Free podcasts
Tackling HIV drug resistance: Brazil's approach and global implications
Hear Dr. Ricardo Diaz, MD, PhD, Professor, Infectious Disease Division and head of the Retrovirology Laboratory at Paulista School of Medicine, Federal University of Sao Paulo, share Brazil's challenges and successes treating HIV as a public health concern and how the alarming scale of recent emergent HIV drug resistance in the country threats to erode the gains made in fighting the HIV epidemic.
References
- Fact sheet: HIV drug resistance. World Health Organization. https://www.who.int/news-room/fact-sheets/detail/hiv-drug-resistance. Published November 17, 2022. Accessed March 13, 2023.
- NNRTI Resistance Notes: Stanford University. https://hivdb.stanford.edu/dr-summary/resistance-notes/NNRTI. Published December 7, 2022. Accessed March 13, 2023.
- Zhao AV, Crutchley RD, et al. A clinical review of HIV integrase strand transfer inhibitors (INSTIs) for the prevention and treatment of HIV-1 infection. Retrovirology. 2022;19(1):22. Published 2022 Oct 22. doi:10.1186/s12977-022-00608-1
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