A time lag insensitive approach for estimating HIV-1 transmission direction

摘要

Objectives: Identifying the direction of transmission in transmission pairs is important both for forensic investigations and for the monitoring of HIV epidemics, however, reliable methods are not yet available due to the long time lag between infection and sampling in most real cases. DESIGNS:: Based on bottleneck effect and coreceptor switching, we aimed at identifying an estimator from sequences of viral gp120 proteins to determine transmission direction between transmission pairs. The estimator should be changed with HIV transmission but was independent of disease progression in an individual. Methods: Here, we present a novel and reliable approach for identifying transmission direction. We derived a set of conserved patterns, called common patterns, from the sequences of viruses, which differed in their coreceptor usage. The number of unique common patterns in viral sequences decreased with transmission but remained almost constant with the progress of disease in an individual. We used this number as an estimator to determine transmission direction in 73 transmission pairs for which the transmission direction was already known. Results: Our method predicted transmission direction with an accuracy of up to 94.5%. Of greater importance, our approach was not influenced by time lags between infection and sampling, and even transmission direction for transmission pairs with long time lags ranging from 2 years to more than 18 years were correctly determined. Conclusion: Our approach for accurately determining transmission direction between transmission pairs is irrespective of the time lag between infection and sampling, which means a promising applications prospect.