Image: PD HIV budding off from a lymphocyte
1. Limited HIV adaptations to host immune system and limited change in HIV viral functioning from 1980’s to 2000’s.
2. Roughly 2% overall change in HIV sequence diversity from 1980’s to 2000’s.
Evidence Rating Level: 2 (Good)
Study Rundown: This study assessed how HIV sequences are adapting to host human leukocyte antigen (HLA) interaction over time, across America, and also whether genotypic changes are connected with functional changes in the virus. Using historic HIV sequences (n=358, from 1979-1989) and modern samples (n=382, from 2000-2011), researchers focused on the HIV immunogenic proteins Gag and Nef to investigate viral adaptation to host immune responses. This complex analysis used frequencies of HLA-associated polymorphisms across different cohorts (as well as differentiated by individuals with relevant HLA(s), versus those without relevant HLA(s)) to determine the spread of immune adaptive mutations within a population over time. Researchers were specifically looking at whether polymorphism frequency would increase over time among individuals lacking relevant HLA(s) because this would support the conclusion that the virus is becoming more adaptive and not losing adaptive mutations during transmission.
Results from the study found a significant increase in frequency of polymorphisms among the modern cohort lacking relevant HLA(S). However, the increase – though significant – was small compared to the overall sequence. These findings led researchers to conclude that polymorphism variation associated with host immune response is occurring at a gradual rate within North America.
In-Depth [basic science study]: HIV specimens were collected from four North American cities (New York, Boston, San Francisco, Vancouver) across both historic and modern time periods. The focus on Gag and Nef proteins was due to prior research identifying selection pressure in those proteins connected to the HLA immune response. Researchers assumed that individuals expressing relevant HLA(s) would have high levels of HLA-associated polymorphisms, whereas individuals lacking relevant HLA(s) would see very low levels of HLA-associated polymorphisms. If however individuals lacking relevant HLA(s) continued to see polymorphisms, that would support the notion that the virus was adapting over time and maintaining adaptations through transmission.
A deep dive into the results found that among the HLA lacking cohort, there was a significant increase in frequency of polymorphisms for the Gag protein (median 3.7% in modern versus 2.0% in historical; p=0.0002). For the Nef protein, the increase was similar, but not significant (median 3.4% in modern cohort versus median 2.0% in historical; 0=0.054). Researchers also concluded that there were minimal changes to the functionality of the virus based on genotypic changes.
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