Evaluation of phylogenetic methods for inferring the direction of HIV transmission: HPTN 052.
Zhang Y., Wymant C., Laeyendecker O., Grabowski MK., Hall M., Hudelson S., Piwowar-Manning E., McCauley M., Gamble T., Hosseinipour MC., Kumarasamy N., Hakim JG., Kumwenda J., Mills LA., Santos BR., Grinsztejn B., Pilotto JH., Chariyalertsak S., Makhema J., Chen YQ., Cohen MS., Fraser C., Eshleman SH.
BACKGROUND: Phylogenetic analysis can be used to assess HIV transmission in populations. We inferred the direction of HIV transmission using whole-genome HIV sequences from couples with known linked infection and known transmission direction. METHODS: Complete next generation sequencing (NGS) data were obtained for 105 unique index-partner sample pairs from 32 couples enrolled in the HIV Prevention Trials Network (HPTN) 052 trial (up to two samples/person). Index samples were obtained up to 5.5 years before partner infection; partner samples were obtained near the time of seroconversion. The bioinformatics method, phyloscanner, was used to infer transmission direction. Analyses were performed using samples from individual sample pairs, samples from all couples (one sample/person; group analysis) and all available samples (multi-sample group analysis). Analysis was also performed using NGS data from defined regions of the HIV genome (gag, pol, env). RESULTS: Using whole-genome NGS data, transmission direction was inferred correctly (index to partner) for 98/105 (93.3%) of the individual sample pairs, 99/105 (94.3%) sample pairs using group analysis, and 31 (96.9%) of the 32 couples using multi-sample group analysis. There were no cases where the incorrect transmission direction (partner to index) was inferred. The accuracy of the method was higher with greater time between index and partner sample collection. Pol region sequences performed better than env or gag sequences for inferring transmission direction. CONCLUSIONS: We demonstrate the potential of a phylogenetic method to infer the direction of HIV transmission between two individuals using whole-genome and pol NGS data.