Speaker
Description
The Antibody Mediated Prevention (AMP) trials tested the prevention efficacy of the broadly neutralizing antibody VRC01 against HIV-1 acquisition among at-risk men and transgender persons in the Americas and Europe (HVTN 704/HPTN 085) and at-risk women in sub-Saharan Africa (HVTN 703/HPTN 081). To analyze the diversity of circulating HIV-1 strains in the two trials, we conducted a phylogenetic analysis of Env sequences from 218 study participants (127 from 704/085 and 91 from 703/081) with an HIV-1 acquisition diagnosis observed by the week 104 visit.
Midpoint-rooted phylogenetic trees of the major acquired lineage for each participant revealed different topologies in the two trials. While the subtype C tree from 703/081 showed an overall radial topology, in the 704/085 tree we observed two major subclades, one representing subtype B, the other subtypes F1 and F2, and, within them, smaller clusters of sequences sampled from Lima (Peru). This was reflected in the distributions of pairwise Hamming distances (HD, number of mutations per amino acid), which was symmetric for 703/081 (mean=0.16, min=0.12, max=0.21), but skewed to the right for 704/085 (mean=0.17, min=0.01, max=0.23).
Four Peruvian participant pairs, all sampled from Lima, were strong outliers, as their inter-participant pairwise HDs fell within 0.03% percentile of the pairwise distribution. HDs between the closest sequences in each pair ranged from 0.01 to 0.02 per AA in Env. We constructed phylogenetic trees using all available Env sequences for each pair. All four trees were of the monophyletic-monophyletic type. While this topology does not exclude direct transmission, it is most frequently found in infections linked through a common source. This higher than expected frequency of linked pairs in 704/085 compared to 703/801 may reflect the presence of smaller, localized sexual networks in the at-risk male communities sampled in the 704/085 compared to the mostly heterosexual participants from 703/081.
