Viral diversity from next-generation sequencing of HIV-1 samples provides precise estimates of infection recency and time since infection. Journal of Infectious Disease
To determine the accurate time of an HIV-1 infection is often very difficult respectively impossible because of a lack of negative HIV-testing, lack of symptoms of an acute retroviral syndrome or a misinterpretation of such, or a long-interval between a negative and a positive test.
In 2011, the SHCS for the first time has provided a method to estimate the date of infection based on the fraction of ambiguous nucleotides (FAN) (Kouyos et al, CID, 2011). This method was based on sanger sequencing. The current work by Carlisle et al. now presents a new method based on next generation sequencing data to estimate the time of infection and compares it to the FAN.
HIV-1 genetic diversity increases over the course of infection, and can be used to infer time since infection (TSI) and consequently also infection recency, crucial quantities for HIV-1 surveillance and the understanding of viral pathogenesis.
They considered 313 HIV-infected individuals for whom reliable estimates of infection dates and next-generation sequencing (NGS)-derived nucleotide frequency data were available. FAN obtained by population sequencing were available for 207 samples. They assessed whether average pairwise diversity (APD) calculated using NGS sequences provided a more exact prediction of TSI and classification of infection recency (<1 year post-infection) compared to FAN.
They found that NGS-derived APD classifies an infection as recent with a sensitivity of 88% and specificity of 85%. When considering only the 207 samples for which FAN were available, NGS-derived APD exhibited a higher sensitivity (90% vs 78%) and specificity (95% vs 67%) than FAN. Additionally, APD can estimate TSI with a mean absolute error of 0.84 years, compared to 1.03 years for FAN. Thus, this work clearly shows that estimates of time of infection can be improved by using NGS sequences.