Overview
Over the past decade, the world has witnessed an unprecedented increase in the use of antiretroviral therapy (ART), which has saved the lives of tens of millions of people living with HIV. At the end of 2021, 28.7 million people were receiving ART globally, out of an estimated 38.4 million people living with HIV.
Increased use of HIV medicines has been accompanied by the emergence of HIV drug resistance, the levels of which have steadily increased in recent years.
HIV drug resistance is caused by changes in the genetic structure of HIV that affect the ability of medicines to block the replication of the virus. 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. If not prevented, HIV drug resistance can jeopardize the efficacy of medicines used to treat HIV, resulting in increased numbers of HIV infections and HIV-associated morbidity and mortality.
Scope of the problem
Surveillance of HIV drug resistance provides countries with evidence that can be used to optimize patient and population-level treatment outcomes. WHO recommends that countries routinely implement nationally representative HIV drug resistance surveys in different populations, including adults, children and adolescents.
WHO’s Report on HIV drug resistance 2021 shows substantial progress in the development of national action plans to prevent, monitor and respond to HIV drug resistance and the implementation of nationally representative surveys in low- and middle-income countries. As of 2021, 64% of countries with a high burden of HIV have developed national action plans. Between 2004 and 2021, 66 countries implemented surveys of HIV drug resistance using WHO-recommended standard methods, and 34 countries plan to conduct HIV drug resistance surveys within the next two years.
Pretreatment HIV drug resistance
Drug resistance can be found in some people before they begin treatment. This resistance can either be transmitted at the time of infection or acquired during previous treatments, for example in women given antiretroviral medicine to prevent mother-to-child transmission of HIV.
WHO recommends surveillance of HIV drug resistance in adults initiating or reinitiating ART and in treatment naive infants initiating ART to inform optimal selection of first-line regimens.
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 one half of infants newly diagnosed with HIV have NNRTI resistant virus before initiating treatment.
The global prevalence of NNRTI resistance in adults and infants emphasizes the need to fast-track the transition to WHO-recommended dolutegravir-based treatments.
Acquired HIV drug resistance
Viral load suppression – the goal of HIV treatment – is the prevention of HIV drug resistance. When viral load suppression is achieved and maintained, drug-resistant HIV is less likely to emerge. In 14 nationally representative surveys implemented between 2015 and 2020, the level of viral load suppression among adults receiving ART was generally high. The pooled results for viral load suppression in Africa were 94% (95% CI 92–96%) among adults receiving first-line ART and 84% (95% CI 79–88%) among adults receiving second-line ART. In the Americas, the pooled results for viral load suppression were 81% (95% CI 75–87%) among adults receiving first-line ART and 70% (95% CI 67–72%) among adults receiving second-line ART.
Despite treatment with potent medicines and even when adherence to treatment is supported, some HIV drug resistance is expected to emerge. Surveillance of acquired HIV drug resistance in populations receiving ART provides valuable information for the optimal selection and management of ART regimens. Among populations failing NNRTIs-based ART, the levels of resistance to commonly used NNRTIs ranged from 50% to 97%.
The high levels of HIV drug resistance to NNRTIs among individuals with treatment failure emphasize the need to scale up viral load testing and enhanced adherence counselling, and to promptly switch individuals with treatment failure.
Fortunately, countries are rapidly transitioning to dolutegravir-containing regimens for adults and children. Dolutegravir-based ART has been shown to be associated with very high levels of viral load suppression and does not lead to as much acquired resistance in people failing it. At present, global data remain limited regarding emergence of HIV resistance to dolutegravir.
WHO recommends that countries implement routine surveillance of acquired HIV drug resistance in adults, children and adolescents receiving ART either using a viral load laboratory-based method or an ART clinic-based method. Which method is used depends upon national viral load testing coverage and the availability of deidentified demographic information.
Pre-exposure prophylaxis for HIV prevention
Many people living in situations considered high risk for exposure to HIV take medicines daily to reduce the chance of acquiring the disease. WHO recommends oral pre-exposure prophylaxis (PrEP) be offered as an additional choice for HIV prevention.
HIV infection is infrequent among individuals taking PrEP, and particularly among those who adhere to their medications. However, among people becoming HIV infected despite the use of PrEP, the emergence of drug resistance is common. This could reduce HIV treatment options due to the overlapping resistance profiles between antiretroviral drugs used for both PrEP and treatment.
To monitoring the continuous effectiveness of HIV medicines used for both treatment and prevention, WHO recommends that countries implement nationally representative surveys to monitor the levels of HIV drug resistance among people initiating treatment, people receiving treatment and among people using PrEP who acquire HIV.
WHO response
Minimizing the emergence and spread of HIV drug resistance is a critical aspect of the broader global response to antimicrobial resistance and requires coordinated action across all government sectors and levels of society.
WHO’s Global action plan on HIV drug resistance 2017–2021, aligned with the Global action plan on antimicrobial resistance and the HIV drug resistance strategy, 2021 update outline key actions for country and global stakeholders to prevent, monitor and respond to HIV drug resistance and to protect the ongoing progress towards achieving the global targets for HIV epidemic control by 2030. The key actions are:
- Prevention and response: implement high-impact interventions to prevent and respond to HIV drug resistance, including an emphasis on dolutegravir-based antiretroviral regimens, monitoring HIV care service delivery, and strategies to ensure uninterrupted drug supplies.
- Monitoring and surveillance: obtain quality data on HIV drug resistance and HIV service delivery from periodic surveys while expanding routine viral load and HIV drug resistance testing.
- Research and innovation: encourage relevant and innovative research that will have the greatest public health impact in minimizing HIV drug resistance.
- Laboratory capacity: support and expand use of viral load testing and build capacity to monitor HIV drug resistance.
- Governance and enabling mechanisms: ensure country ownership, coordinated action, advocacy and sustainable funding are in place to support action on HIV drug resistance.