The World Health Organization’s Response to Emerging Human Immunodeficiency Virus Drug Resistance and a Call for Global Action

The global community, including the World Health Organization (WHO), has committed to ending the AIDS epidemic and to ensuring that 90% of people living with human immunodeficiency virus (HIV) are diagnosed, 90% start treatment, and 90% achieve and maintain virological suppression. The emergence of HIV drug resistance (HIVDR) as antiretroviral treatment programs expand could preclude the 90-90-90 targets adopted by the United Nations General Assembly at the High-Level Meeting on Ending AIDS from being achieved. The Global Action Plan on HIVDR is a call for collective action grounded on normative guidance providing a standardized and robust approach to monitoring, preventing, and responding to HIVDR over the next 5 years (2017–2021). WHO is committed to supporting country, global, regional, and national partners to implement and monitor the progress of the Global Action Plan. This article outlines the key components of WHO’s strategy to tackle HIVDR and the role the organization takes in leading the global response to HIVDR.

In 2016 the United Nations’ High-Level Meeting on Ending AIDS [1] committed to “establishing an effective system to monitor, prevent and respond to the emergence of drug resistance strains of HIV in populations and antimicrobial resistance among people living with HIV.” As the world transitions to a “treat all” approach in the global response to the human immunodeficiency virus (HIV) epidemic, it is vital that population levels of HIV drug resistance (HIVDR) be routinely monitored and that countries respond appropriately when HIVDR reaches levels that can lead to unacceptably high rates of virological failure, a reversal of HIV-associated morbidity and mortality, increasing incidence of HIV, and higher overall costs of providing antiretroviral therapy (ART) [2].

Despite the progress made by the global HIV community in achieving the Millennium Development Goals [3], which resulted in 19.5 million people initiating ART by the end of 2016 and reductions in the morbidity and mortality of people living with HIV [4], the next 10 years will be a time of continued expansion in HIV programs, particularly in countries identified as “Fast Track” for focused support. The potential emergence and transmission of HIVDR must be considered a priority in conjunction with the development of quality HIV treatment and care services to ensure that highly effective drug regimens are available to all those who are diagnosed and that antiretroviral (ARV) medicines used for pre-exposure (PrEP) and post-exposure prophylaxis (PEP) remain effective.

At an individual level, the presence of pretreatment drug resistance when starting ART (or pretreatment HIV drug resistance [PDR]) increases the risk of virological failure in adults and children [5–23], the need to switch to a more costly regimen [24], treatment discontinuation [5,16,25], and accumulation of additional drug-resistance mutations [11, 12]. At a population level, the cost of inaction has both human and financial consequences. Modeling predicts that levels of PDR >10% will result in an additional 890000 deaths, 450000 new infections, and an ART program cost of $6.5 billion over the next 15 years in sub-Saharan Africa alone if current first-line ART remains unchanged [2]. The same model predicts increasing negative impact on mortality, HIV incidence, and viral load suppression (VLS) resulting from the rising prevalence of PDR and indicates that interventions such as the introduction of pretreatment HIVDR testing or, even more, a shift to dolutegravir-based ART in first-line regimens can result in more favorable health outcomes [26]. The 2017 World Health Organization (WHO) HIVDR report highlights that levels of PDR to efavirenz or nevirapine, the commonly used ARVs in first-line ART, exceed 10% in several low- and middle-income countries [27].

In its role as global convener, the WHO has led the development of a Global Action Plan (GAP) on HIV drug resistance (2017–2021) with the overarching goal to preventing HIVDR from undermining the attainment of global targets on health and HIV and enabling the most effective treatment to be provided to all people living with HIV [28]. The 5 strategic objectives of the action plan highlight the importance of effective prevention and response to HIVDR and the need to strengthen monitoring and surveillance of HIVDR, invest in innovative research, strengthen laboratory capacity, and establish enabling financial, governance, and advocacy mechanisms to achieve tangible results (Figure 1). All stakeholders with a role in the global response to HIV are called on to support implementation of the plan and to act collectively to respond to the potential threat that HIVDR poses to the global elimination of AIDS.

The Global Action Plan on HIVDR aligns itself with the broader Global Action Plan on antimicrobial resistance and calls for a comprehensive, coordinated, innovative, and integrated action to tackle HIVDR and broader antimicrobial challenges [29, 30], therefore providing an opportunity for strengthening synergy and collaboration between all allied programs at country, regional, and global levels. Collective action, including opportunities to leverage resources, can combat the threat of resistant microbes and viruses to population health in diseases of significant public health burden.

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