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Global Resilience 2024

HIV drug resistance to dolutegravir on the rise in low and middle-income countries

HIV virus floating with DNA background, HIV vaccine and treatment, HIV virus disease therapy concept
HIV virus floating with DNA background, HIV vaccine and treatment, HIV virus disease therapy concept
iStock / Getty Images Plus / CIPhotos

Meg C. Doherty

World Health Organization, Geneva, Switzerland

Michael R. Jordan

Tufts University School of Medicine, Boston, MA, USA

Learn about HIV viral suppression and emerging HIV drug resistance to dolutegravir.

Antiretroviral therapy (ART) has revolutionised HIV care and treatment, allowing nearly 30 million people to live healthy lives. HIV drug resistance (HIVDR) reduces the effectiveness of antiretroviral drugs for HIV treatment and prevention, leading to an increase in HIV incidence, morbidity and mortality.

In 2018, dolutegravir (DTG)-based ART became the World Health Organization’s (WHO) preferred HIV treatment for children, adolescents, and adults. By July 2023, 91% of 127 low and middle-income countries adopted DTG-based ART, which has the benefit of rapidly achieving undetectable HIV viral load levels and has a reduced risk of developing drug resistance compared to other ART drug combinations. However, with the incorrect use of DTG-based ART, there is a risk of the emergence of HIV drug resistance (HIVDR) — leaving DTG ineffective at controlling HIV.

Dolutegravir: population-level viral suppression and drug resistance outcomes

In its HIV Drug Resistance Report 2024, WHO documents high levels of viral load suppression (>90%) in populations receiving dolutegravir-containing ART. These results bring us one step closer to the goal of ending AIDS by 2030. Yet, recent observational data reveal that HIVDR to DTG is emerging at levels that are surprising to many experts, exceeding those observed in clinical trials.

Among people not achieving viral suppression, levels of dolutegravir resistance range from 3.9% to 8.6%, with levels as high as 19.6% observed among highly treatment-experienced people who transitioned to a DTG-containing ART while having high HIV viral loads. In a study in South Africa,1 DTG resistance soared from 2.7% in 2021 to 11.9% in 2022 in people with laboratory-confirmed treatment failure and DTG use.

WHO’s response to this new evidence

WHO recommends that countries routinely implement standardised surveillance of HIVDR to follow the prevalence and patterns of resistance among people not achieving suppressed viral load.

Despite massive efforts to transition to DTG-based HIV treatment since 2018, only 10 countries have finalised acquired HIVDR surveys among adults receiving DTG-based ART, and only six countries have implemented surveys of acquired HIVDR among children and adolescents receiving DTG-based ART.

To date, countries reporting HIVDR data were early adopters of DTG-based treatment and have not repeated surveys; available results may underestimate the true prevalence of DTG resistance and preclude analysis of trends over time. WHO calls on countries to routinely implement and report data from standardised surveys characterising the prevalence, risks and patterns of DTG drug resistance. Surveys inform the quality of treatment programmes and influence care and treatment guidelines.

How to support HIVDR surveillance

Greater funding and political will are required to sustain and expand global HIVDR surveillance efforts. Without steadfast commitments from international organisations, governments, programmes and funders to address challenges associated with HIVDR, we risk unnecessarily losing lives, the effectiveness of our best HIV treatment in decades, being without a replacement in sight and putting us off-track to reach UN sustainable development goals by 2030.

[1] Steegen et al., XXX International Workshop on HIV drug Resistance and Treatment Strategies. 2023. Abstract #21.

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