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The largest-ever study mapping genetic variants of HIV-1 around the world over the past 35 years shows that the regional distribution of different subtypes of the virus continues to evolve, posing a challenge to prevention and treatment efforts.

As of 2024, an estimated 40.8 million people are living with HIV, a virus that attacks the body’s immune system and, if left untreated, leads to Acquired Immune Deficiency Syndrome (AIDS). Although antiretroviral therapy has improved life expectancy and reduced HIV transmission, 630,000 people died from AIDS-related illnesses and 1.3 million people became newly infected in 2024Cuts to international funding in 2025 threaten to reverse gains made in recent years, heightening the need for an effective HIV vaccine that can offer universal protection.

Part of the challenge of developing such a vaccine relates to the global genetic diversity of the virus. HIV-1 is by far the most common type of HIV, and since the start of the pandemic in the early 1990s, it has spread from Central Africa to other parts of the world, diversifying into 10 different subtypes. In addition, co-infection with two or more HIV subtypes has resulted in ‘recombinant’ strains of HIV circulating in some regions. This patchwork of different HIV-1 variants has implications not just for vaccine development, but also for the efficacy of diagnostic and monitoring tests and antiretroviral treatment.

For this study published in The Lancet Infectious Diseases, researchers from the Global HIV Molecular Epidemiology Collaboration, which is led by Associate Professor Joris Hemelaar at Oxford Population Health, contributed subtyping data from nearly 1.4 million HIV-1 samples collected between 1990 and 2024 from 154 countries. These data were combined with UNAIDS estimates of the number of people living with HIV in each country to map the global distribution of HIV-1 subtypes and recombinant strains over time.

Global map of HIV-1 variants across regions.Global map of HIV-1 variants across regions.

The study authors found that HIV-1 subtype C accounted for nearly half (49%) of global infections between 2020 and 2024, dominating in Southern Africa and South AsiaSubtype A accounted for 12% of global infections, with the highest concentration in Eastern Europe and Central Asia, as well as East Africa. In Latin and North America, as well as Western and Central Europe, subtype B infections dominated, although subtype B only made up 10% of the global total. Central Africa consistently had the highest genetic diversity of HIV-1.

Over time, the global proportions of HIV-1 variants remained stable, particularly after 2000Recombinant strains increased from 21% to 24% of global infections between 2000 and 2014, but reduced to 22% by 2024. However, notable increases of HIV-1 recombinants were observed in Western and Central Europe and East Asia. The authors acknowledge that sequencing of only part of the HIV genome can miss recombinant strains meaning that those strains are probably underestimated in the study. They also note that HIV subtyping could only be performed on samples with a detectable viral load. People living with HIV who are receiving antiretroviral treatment often have undetectable viral loads.

Ayisha Khalid, first author and DPhil student at Oxford Population Health, said:

 

Our study shows the extreme genetic diversity of HIV-variants globally, and that HIV strains are differentially distributed around the world, a pattern that continues to evolve.

‘Continuous global surveillance and research to understand the evolution and global spread of HIV strains is crucial as it affects the efficacy of diagnostic and viral load assays, the emergence of drug resistance, and vaccine development.

Joris Hemelaar, senior author of the study, said 'This study demonstrates the importance of large international collaborations to address global health problems. Without the contributions of thousands of participants and the dedication of hundreds of researchers around the world, this work would not have been possible.'

 

Our immediate next focus is a detailed global analysis of HIV-1 recombinants. Future research will examine global trends in HIV-1 genetic diversity and the factors driving these trends, which will be crucial for the development of HIV vaccines and treatments tailored to specific variants.

This study was supported by an NDPH Pump-Priming award to Joris Hemelaar and an Oxford Population Health DPhil Scholarship to Ayisha Khalid.

 

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