HIV-1 and hepatitis C virus selection bottleneck in Chinese people who inject drugs

Abstract

Objectives: For both HIV-1 and hepatitis C virus (HCV), assessing the stringency of the transmission process is a scientific priority. Enumerations of transmitted/founder (TF) viruses have shown a strict transmission bottleneck in sexual transmission of HIV-1 and a wide range in the multiplicity of infection in HCV. Here, we aim to determine the stringency of parenteral transmission for HIV-1 and HCV in people who inject drugs (PWID).

Design: We used molecular sequencing and several complementary analyses to enumerate the TF HIV-1 and HCV variants in a well described cohort of PWID in Xinjiang, China.

Methods: We performed single genome sequencing of HIV-1 env and 5' half HCV genomes, then applied phylogenetic analysis and validated models of early virus diversification to enumerate TF viruses in 60 PWID. We used multivariate analysis to determine correlates of multivariant transmission (MVT).

Results: We generated 1070 env region sequences from 33 HIV-1 early infected individuals and 773 5' half region sequences from 27 HCV early infected individuals. We found rates of MVT of 39 and 54%, respectively, for HIV-1 and HCV, with a limited range in the number of TF viruses in both infections. Behavioural characteristics suggested high-risk injection practices and lower risk sexual practices; we did not find an association between any specific behaviours and MVT.

Conclusion: MVT is frequent in parenteral transmission of both HIV-1 and HCV in Xinjiang PWID, indicating a less stringent transmission process than sexual transmission.

Figure 1. Highlighter plot, NJ phylogenetic tree, and MCC tree depictions of HIV-1 env sequences

The left column displays Highlighter plots, in which nucleotide polymorphisms are displayed as colored tics (T: red, A: green, C: blue, G: yellow) compared to the master sequence (denoted with (m) on top line of alignment). The center column depicts NJ phylogenies, with genetic distance shown by scale bar. The right column depicts MCC trees, based on Bayesian modeling, with the root of the tree representing the tMRCA, and the blue line representing the maximum time to infection as determined by sampling dates and clinical staging. A. Participant 33.12, sampled at Fiebig stage II, demonstrated a single low-diversity lineage in Highlighter and NJ tree with a maximum time to infection preceding the estimated tMRCA by MCC tree. B. Participant 33.18, sampled at Fiebig stage V, similarly displayed a single low-diversity lineage with MCC tree indicating a tMRCA after the time of infection. In this subject with later sampling, several polymorphisms that are shared between sequences are consistent with immune escape mutations ^5,42. C. Participant 58.10, sampled in Fiebig stage II, demonstrated multiple low-diversity lineages, with maximum infection time far after the MCC estimate of tMRCA. D. Participant 33.03, sampled at Fiebig stage VI, with two low-diversity lineages by Highlighter plot and NJ tree, and the maximum infection time intersecting with two lineages in the MCC tree.

Figure 2. Highlighter plot, NJ phylogenetic tree, and MCC tree depictions of HCV 5′ half sequences

Participants 33.28 (A) and 58.15 (B), both sampled in acute infection, demonstrate a single low diversity lineage and MCC estimated tMRCAs after maximum infection times, consistent with infection by a single virus. Participants 58.19 (C) and 58.16 (D), sampled post- and pre-seroconversion, respectively, demonstrate multiple low-diversity lineages by Highlighter plot and NJ tree, and maximum times to infection that substantially precede estimated tMRCAs.