HIV Drug Resistance: An Emerging Global Challenge
"Understanding the rise of HIV drug resistance in low- and middle-income countries and strategies to combat it for a healthier future."
For over 15 years, the global effort to combat HIV through antiretroviral therapy (ART) has seen remarkable success. However, a significant challenge is emerging: the increasing prevalence of HIV drug resistance, particularly in low- and middle-income countries (LMICs). This resistance threatens to undermine the progress made, potentially leading to increased mortality, higher HIV incidence, and greater costs for healthcare systems.
To achieve the ambitious UNAIDS global targets for combating HIV, enhanced strategies are essential. These include improving the quality of ART services, ensuring the durability of available ART regimens, and actively working to curb the development of resistance. Strategies also include the rollout of drugs with greater efficacy and higher genetic barriers to resistance, as well as ensuring universal access to viral load monitoring, reliable drug supply chains, and patient-centered care models.
This article will examine the contemporary data on HIV drug resistance in LMICs, exploring the implications for the global HIV response. It will also highlight the potential impact and the resistance risks associated with novel ART strategies, identifying existing knowledge gaps and areas for further research.
Current Resistance Landscape
The World Health Organization reports that acquired resistance to dolutegravir (DTG), a cornerstone of recommended first- and second-line antiretroviral therapy, may be higher than anticipated. The concern is especially pronounced among people with extensive prior treatment experience. Despite this resistance, DTG remains highly effective, with more than 90% of patients achieving sustained treatment success.
Testing and Treatment Selection
Drug resistance can reduce the effectiveness of HIV medicines, even when those medicines previously worked well. NIH states that resistance testing can identify which medicines remain effective and help clinicians choose an appropriate treatment regimen. However, contemporary antiretroviral regimens have high barriers to resistance, and uncommon resistance to these therapies means careful clinical management remains necessary.
The Rising Threat of HIV Drug Resistance
The global scale-up of antiretroviral therapy (ART) has been a game-changer in the fight against HIV, averting an estimated 7.8 million deaths and preventing 30 million new infections in low- and middle-income countries (LMICs) between 2004 and 2014. Today, over 21 million people with HIV are receiving ART, representing just over half of all people infected worldwide. A significant majority – nine out of ten – of those living with HIV reside in LMICs, primarily in sub-Saharan Africa and Asia, regions that bear the brunt of the global epidemic.
- The 90-90-90 Targets: By 2020, ensure that 90% of people with HIV know their HIV status, 90% of those infected are receiving ART, and 90% of those on ART have sustained viral suppression.
- Sustained Viral Suppression: A key factor in maximizing individual health and survival, as well as reducing HIV incidence.
- Lifelong Commitment: The need to successfully maintain individuals on effective ART for life to achieve global targets.
Emerging Research Concerns
A scoping review identifies HIV drug resistance arising when PrEP is initiated during missed acute HIV infection as a particular concern. The review also notes increasing rates of transmitted antiretroviral resistance in low- and middle-income countries. These problems may be especially difficult in such settings because ART choices are likely to be limited and alternative therapies may not be available.
Regional Pretreatment Resistance
A systematic review and meta-regression analysis estimated pretreatment NNRTI resistance in 2016 across several regions. The estimates were 11.0% in southern Africa, 10.1% in eastern Africa, 7.2% in western and central Africa, and 9.4% in Latin America and the Caribbean. These figures show substantial regional variation in pretreatment resistance.
Charting a Course for the Future
Rising HIV drug resistance poses a significant threat to the achievements made in controlling the epidemic. The commitment of policymakers and national governments is crucial to achieving global HIV targets. While substantial knowledge gaps remain in addressing resistance in LMICs, a range of measures can be taken to minimize HIV drug resistance and maintain global HIV control. The rollout of fixed-dose combination therapies provides a unique opportunity to improve treatment outcomes, provided it is implemented with improved quality of services and appropriate monitoring frameworks. Through continued research, innovation, and collaboration, we can chart a course towards a future where HIV drug resistance is effectively managed, and the global HIV targets are within reach.
Managing Resistance Systemically
Research on HIV drug resistance in the era of contemporary antiretroviral therapy describes resistance mechanisms, interactions among drug-resistant mutations, and patterns of resistance to current ART. It also provides guidance on managing HIV drug resistance. The guidance includes limiting the development of resistance and managing virologic failure complicated by resistance.
Complex Cases and Care
A 2024 case report documented the combined use of lenacapavir and fostemsavir to treat multidrug-resistant HIV. The authors described it as among the first cases to document this combination. The report supports the potential use of these novel agents in managing complex HIV-resistance cases.