In the Journals

HIV evolution bypassed immune resistance, but reduced virulence

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December 5, 2014

HIV strains that evolve to bypass human immune responses may do so at the cost of a reduced ability to replicate, according to recent study results.

Researchers primarily observed cohorts of ART-naive antenatal mothers with HIV from Gaborone, Botswana (n=514; mean age, 27.5 years), and Durban, South Africa (n=328; mean age, 27.3 years). A third maternal cohort also was enrolled from Durban (n=264), consisting of 38 ART-naive antenatal mothers and 226 postnatal mothers who had received AZT, or zidovudine (Retrovir, ViiV Healthcare) before delivery and no ART after, along with an additional Durban cohort (n=1,218) used for analysis.

Participants from Botswana showed lower viral loads (15,350 vs. 29,350; P<.0001) and lower absolute CD4 counts (mean 342 cells per mm3 vs. 397 cells per mm3; P=.007) compared with the initial Durban cohort. Viral loads were inversely correlated with CD4 counts in both of the initial Botswanan (P<.0001) and South African (P<.0001) cohorts.

HIV adaptation to HLA-B*57, a protein previously shown to have a protective effect against the virus, was greater in Botswana (P=7x10–82). While protection was absent in this population (P=.0002), the virus’ replicative capacity also was lower than was observed in South Africa (P=.03).

Researchers also examined the effect of ART on the evolution of HIV virulence. By simulating the presence and absence of ART throughout the epidemic using a mathematical model, they concluded that selective treatment of infection individuals with lower CD4 counts could accelerate the evolution of HIV variants with a lesser capacity to replicate. Researchers wrote that initially this effect would be difficult to detect, but could become more impactful over time.

“This research highlights the fact that HIV adaptation to the most effective immune responses … comes at a significant cost to its ability to replicate,” Phillip J.R. Goulder, MD, PhD, of the University of Oxford, said in a press release. “Anything we can do to increase the pressure on HIV in this way may allow scientists to reduce the destructive power of HIV over time.”

Disclosure: The researchers report no relevant financial disclosures.

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