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PLoS One. 2016 Nov 28;11(11):e0166746. doi: 10.1371/journal.pone.0166746. eCollection 2016.

Deciphering Multiplicity of HIV-1C Infection: Transmission of Closely Related Multiple Viral Lineages.

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Harvard T. H. Chan School of Public Health, Boston, Massachusetts, United States of America.
Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.
Division of Medical Virology, Stellenbosch University, Tygerberg, South Africa.
Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, Massachusetts, United States of America.



A single viral variant is transmitted in the majority of HIV infections. However, about 20% of heterosexually transmitted HIV infections are caused by multiple viral variants. Detection of transmitted HIV variants is not trivial, as it involves analysis of multiple viral sequences representing intra-host HIV-1 quasispecies.


We distinguish two types of multiple virus transmission in HIV infection: (1) HIV transmission from the same source, and (2) transmission from different sources. Viral sequences representing intra-host quasispecies in a longitudinally sampled cohort of 42 individuals with primary HIV-1C infection in Botswana were generated by single-genome amplification and sequencing and spanned the V1C5 region of HIV-1C env gp120. The Maximum Likelihood phylogeny and distribution of pairwise raw distances were assessed at each sampling time point (n = 217; 42 patients; median 5 (IQR: 4-6) time points per patient, range 2-12 time points per patient).


Transmission of multiple viral variants from the same source (likely from the partner with established HIV infection) was found in 9 out of 42 individuals (21%; 95 CI 10-37%). HIV super-infection was identified in 2 patients (5%; 95% CI 1-17%) with an estimated rate of 3.9 per 100 person-years. Transmission of multiple viruses combined with HIV super-infection at a later time point was observed in one individual.


Multiple HIV lineages transmitted from the same source produce a monophyletic clade in the inferred phylogenetic tree. Such a clade has transiently distinct sub-clusters in the early stage of HIV infection, and follows a predictable evolutionary pathway. Over time, the gap between initially distinct viral lineages fills in and initially distinct sub-clusters converge. Identification of cases with transmission of multiple viral lineages from the same source needs to be taken into account in cross-sectional estimation of HIV recency in epidemiological and population studies.

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