Initiatives to reduce HIV-related deaths remain a global public health priority. These deaths are compounded by weak health systems and lack of access to essential diagnostic tests and medications in low-income and middle-income countries (LMICs). Globally, an estimated 630 000 people living with HIV died in 2022.1 The mortality risk is highest among the estimated 4·3 million people living with advanced HIV disease, defined by WHO in adolescents and adults by a CD4 count less than 200 cells per μL or WHO clinical stage 3 or 4 disease.

Ever since resistance developed against zidovudine, we have been in a race: a drug is developed and used, HIV develops resistance to it, another drug is developed and used, and so on. This largely resistance-driven process has informed HIV drug development since its inception.1 Although this phenomenon is not unique to HIV, the use of specific resistance data to guide regimen design is notable. Resistance-guided regimen design is unfortunately available and guideline-recommended mostly in resource-rich settings and less so elsewhere; even where it is available in lower-income settings, it is restricted to more limited circumstances.

Addressing the global challenge of 1·5 million yearly HIV infections requires both non-pharmaceutical and pharmaceutical interventions. Although an effective HIV vaccine is likely to remain elusive for many years to come, passive immunisation with neutralising antibodies might provide an option for long-term prevention of infection. This approach became conceivable with the isolation of rare broadly neutralising antibodies (bnAbs) from people living with HIV.1