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HIV Evolving to be More Aggressive in Clusters

HIV Clusters

New research reveals that natural selection may be making HIV more transmissible in United States.

When HIV is transmitted in large population clusters in the US, it is more apt to cause high viral loads — and quickly, as reported last week by NAM AIDSmap. A recent study headed by Dr. Joel Wertheim of the University of California San Diego and Dr. Walid Heneine of the Centers for Disease Control and Prevention (CDC) and published in Nature Communications led researchers to conclude that natural selection is causing HIV in the United States to become more transmittable and aggressive.

Previously HIV researchers had theorized that rapid onward transmission of HIV after primary transmission infection would tend favor the selection of HIV variants that produce higher viral load set-points — the point where viral load stabilizes after peaking during initial transmission. Without an early diagnosis and immediate antiretroviral treatment (ART), selection of these variants would lead to a shorter period of symptom-free HIV and more rapid, widespread transmission.

Early diagnosis and connection to treatment can quickly suppress the viral loads of people living with HIV, however, larger sexual networks in which more frequent transmission might occur has a tendency to counter the effects of ART. Researchers say the only way to combat such effects in these clusters would be via very early diagnosis (within the first weeks after acquiring HIV) and the ability to trace and test the exposed sexual partners of someone experiencing this type of acute HIV infection.

Using a large dataset of well-characterized HIV isolates, the team of researchers examined whether certain HIV variants were becoming more infectious and leading to higher, more rapidly acquired viral loads. They analyzed a total of 33,285 HIV samples from individuals registered in the National HIV Surveillance System database.

None of the samples, logged in the database after genotypic testing for HIV drug resistance, showed signs of drug resistance mutations. Seventy-two percent had a viral load measurement recorded within three months prior or one month after the genotyped sample was taken. Interestingly, researchers found that 37.5 percent of those who showed viral load results were also able to be genetically linked to another individual who had been sampled.

After carefully examining the viruses’ genetic signatures, researchers were able to identify closely related viruses that formed a total of 4,366 clusters of people.

Those in clusters generally had higher viral loads than those who did not acquire HIV in clusters when diagnosed after the early infection stage (the first six months after HIV acquisition). The findings also revealed that cluster size seemed to affect viral loads — people in clusters of ten or more had higher viral loads than those in smaller clusters.

The study examined the viral loads of those sampled over the period of a decade. Researchers found that viral loads increased during that period by 0.2 log10 copies/ml in people diagnosed with a CD4 count above 500 cells, though similar patterns were observed for those diagnosed with lower CD4 cell counts. Researcher also found that people were more likely to form part of a transmission cluster in the later years of the decade — the more connections they had in a specific cluster, the higher their viral loads were at the time of diagnosis.

These findings support previous research presented at the Conference on Retroviruses and Opportunistic Infections (CROI) in 2018 by some of the investigators of this study, when they found that rapidly growing transmission clusters in the U.S. tended to involve young Latino/Hispanic men who have sex with men.

The study authors concluded that public health interventions based on molecular epidemiology (which identifies clusters of infections through matching viral genotypes in recently diagnosed people) would be very beneficial in combatting this type of natural selection in terms of transmitting these more virulent strains of HIV.


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