Natural selection is leading to more transmissible HIV in United States

HIV that is being transmitted in large population clusters in the United States is more likely to cause high viral load in people who acquire it, leading US researchers to conclude that natural selection is causing HIV in the United States to become more infectious and virulent. The study by Dr Joel Wertheim of the University of California San Diego, Dr Walid Heneine of the Centers for Disease Control and Prevention and colleagues is published in Nature Communications.

Scientists have previously theorised that rapid onward transmission of HIV after primary infection would tend to favour the selection of HIV variants that produce a higher viral load set-point (the level at which viral load stabilises after the early peak in viral load during primary infection).

In the absence of early diagnosis and effective antiretroviral treatment, selection of these variants through more effective transmission would lead to a shorter period of asymptomatic HIV infection but more widespread transmission.

Glossary

drug resistance

A drug-resistant HIV strain is one which is less susceptible to the effects of one or more anti-HIV drugs because of an accumulation of HIV mutations in its genotype. Resistance can be the result of a poor adherence to treatment or of transmission of an already resistant virus.

sample

Studies aim to give information that will be applicable to a large group of people (e.g. adults with diagnosed HIV in the UK). Because it is impractical to conduct a study with such a large group, only a sub-group (a sample) takes part in a study. This isn’t a problem as long as the characteristics of the sample are similar to those of the wider group (e.g. in terms of age, gender, CD4 count and years since diagnosis).

virulence

The power of bacteria or viruses to cause a disease. Different strains of the same micro-organism can vary in virulence.

 

acute infection

The very first few weeks of infection, until the body has created antibodies against the infection. During acute HIV infection, HIV is highly infectious because the virus is multiplying at a very rapid rate. The symptoms of acute HIV infection can include fever, rash, chills, headache, fatigue, nausea, diarrhoea, sore throat, night sweats, appetite loss, mouth ulcers, swollen lymph nodes, muscle and joint aches – all of them symptoms of an acute inflammation (immune reaction).

primary infection

In HIV, usually defined as the first six months of infection.

Although early diagnosis and treatment would suppress the viral loads of people diagnosed with HIV, larger sexual networks in which more frequent transmission could take place would tend to offset the effects of expanded antiretroviral treatment. Such network effects would only be limited by very early diagnosis (in the first weeks after acquiring HIV) and by tracing and testing the sexual contacts of people diagnosed in acute infection.

Researchers at the University of California San Diego and the US Centers for Disease Control and Prevention investigated whether HIV variants are becoming more infectious and leading to higher viral loads using a large dataset of well-characterised HIV isolates.

They analysed 33,285 HIV-1 subtype B samples from individuals registered in the National HIV Surveillance System database. The samples were logged in the database after genotypic testing for HIV drug resistance. This analysis was restricted to samples tested for drug resistance within three months of HIV diagnosis. None of the samples had drug resistance mutations.

Seventy-two per cent of samples had a viral load measurement recorded within three months prior or one month after the genotyped sample was taken and 37.5% of those with viral load results could be linked genetically to another individual sampled.

Looking at the genetic signature of the viruses, the researchers were able to identify closely related viruses that formed 4366 clusters of people.

People in clusters had higher viral load than non-clustered individuals when diagnosed at all HIV stages apart from early infection (within the first six months) (+0.11log; p < 0.001). The lack of association between cluster membership and early infection may have been a consequence of the small sample size – only 476 people were diagnosed with HIV in early infection in the entire dataset of 33,285, as no cases of early infection were determined prior to 2014.

Cluster size was also associated with viral load. People in clusters of ten or more individuals had higher viral loads than those in smaller clusters (p = 0.019).

Over the decade up to 2016, viral loads increased by 0.2 log10 copies/ml in individuals diagnosed with a CD4 count above 500 cells and similar patterns were seen for people diagnosed with lower CD4 cell counts.

People were also more likely to form part of a transmission cluster in the later years of the decade, and the more connections they had in a transmission cluster, the higher their viral load at the time of diagnosis.

Although the viral load changes over the decade studied are relatively small, modelling-based research published in 2008 concluded that a viral load increase of 0.3 log increased the transmission of HIV by 20%.

The authors conclude that public health interventions based on molecular epidemiology, which identifies clusters of infections through matching viral genotypes in recently diagnosed people, might counteract the selection and transmission of more virulent strains of HIV.

Previous research presented at the Conference on Retroviruses and Opportunistic Infections in 2018 by some of the investigators of this study found that rapidly growing transmission clusters in the United States especially involved young Latino/Hispanic men who have sex with men.

References

Wertheim JO et al. Natural selection favoring more transmissible HIV detected in United States molecular transmission network. Nature Communications, 10: 5788, 2019 (open access).

doi:10.1038/s41467-019-13723-z