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Characterizing the multiplicity of HIV founder variants during sexual transmission among MSM.

ABSTRACT: Transmission of multiple founder variants has been associated with faster HIV disease progression. Many studies have attempted to determine the number of founder variants, mainly by analysis of sequence diversity and/or tree topology from acutely HIV-infected individuals. We hypothesized that adding sequence data collected from source partners might improve resolution and characterization of transmission events. Blood plasma samples were collected from both the source and recipient in thirty epidemiologically- and phylogenetically linked transmission pairs. All were men who have sex with men, sampled on average 70 days (range 11-170) after the recipient's estimated date of infection. Next generation sequencing (454 FLX, Roche) of HIV-1 env (C2-V3) was performed for all samples. Inspection of sequence alignments, highlighter plots, phylogenetic tree topologies and sequence diversity were used to determine the multiplicity of founder viruses with and without the inclusion of source data. Using only recipient sequence data, we were able to resolve multiplicity in twenty-six of the thirty transmission pairs (87 percent). Among them, five presented with a high viral diversity at baseline (>0.10 subst/site), consistent with multiple founders. By incorporating sequence data collected from the source partner, we were able to characterize all thirty transmission pairs. Overall, sixteen transmission events (53.3 percent) involved multiple founders. Results obtained by combining sequence data from recipient and source were congruent for nineteen of the twenty-six (73 percent) cases where conclusions were made using only recipient sequence data. The multiplicity of founders was associated with significantly higher HIV RNA levels (P?=?0.04). To further evaluate the transmission bottleneck, we focused on single founder transmissions (fourteen of the thirty), and identified four recipients (28.6 percent) that had founder variants that were inferred to arise from minority viral populations in the source. These source clades ranged from 1.0 to 5.4 percent of the sampled population. Incorporating sequence data from the source increased of the ability to determine the multiplicity of founder variants, reduced misclassification, and allowed us to infer the transmission of minority variants.

SUBMITTER: Chaillon A

PROVIDER: S-EPMC6118227 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Characterizing the multiplicity of HIV founder variants during sexual transmission among MSM.

Chaillon Antoine A Gianella Sara S Little Susan J SJ Caballero Gemma G Barin Francis F Kosakovsky Pond Sergei S Richman Douglas D DD Smith Davey M DM Mehta Sanjay R SR

Virus evolution 20160101 1

Transmission of multiple founder variants has been associated with faster HIV disease progression. Many studies have attempted to determine the number of founder variants, mainly by analysis of sequence diversity and/or tree topology from acutely HIV-infected individuals. We hypothesized that adding sequence data collected from source partners might improve resolution and characterization of transmission events. Blood plasma samples were collected from both the source and recipient in thirty epi ...[more]

PMID: 30186625

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Project description:BackgroundA 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.MethodologyWe 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).ResultsTransmission 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.ConclusionsMultiple 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.

Project description:BackgroundBehavioural data from MSM are usually collected in non-representative convenience samples, increasingly on the internet. Epidemiological data from such samples might be useful for comparisons between countries, but are subject to unknown participation biases.MethodsSelf-reported HIV diagnoses from participants of the European MSM Internet Survey (EMIS) living in the Czech Republic, Germany, The Netherlands, Portugal, Sweden and the United Kingdom were compared with surveillance data, for both the overall diagnosed prevalence and for new diagnoses made in 2009. Country level prevalence and new diagnoses rates per 100 MSM were calculated based on an assumed MSM population size of 3% of the adult male population. Survey-surveillance discrepancies (SSD) for survey participation, diagnosed HIV prevalence and new HIV diagnoses were determined as ratios of proportions. Results are calculated and presented by 5-year age groups for MSM aged 15-64.ResultsSurveillance derived estimates of diagnosed HIV prevalence among MSM aged 15-64 ranged from 0.63% in the Czech Republic to 4.93% in The Netherlands. New HIV diagnoses rates ranged between 0.10 per 100 MSM in the Czech Republic and 0.48 per 100 in The Netherlands. Self-reported rates from EMIS were consistently higher, with prevalence ranging from 2.68% in the Czech Republic to 12.72% in The Netherlands, and new HIV diagnoses rates from 0.36 per 100 in Sweden to 1.44 per 100 in The Netherlands. Across age groups, the survey surveillance discrepancies (SSD) for new HIV diagnoses were between 1.93 in UK and 5.95 in the Czech Republic, and for diagnosed prevalence between 1.80 in Germany and 4.26 in the Czech Republic.Internet samples of MSM were skewed towards younger age groups when compared to an age distribution of the general adult male population. Survey-surveillance discrepancies (SSD) for EMIS participation were inverse u-shaped across the age range. The two HIV-related SSD were u- or j-shaped with higher values for the very young and for older MSM. The highest discrepancies between survey and surveillance data regarding HIV-prevalence were observed in the oldest age group in Sweden and the youngest age group in Portugal.ConclusionInternet samples are biased towards a lower median age because younger men are over-represented on MSM dating websites and therefore may be more likely to be recruited into surveys. Men diagnosed with HIV were over-represented in the internet survey, and increasingly so in the older age groups. A similar effect was observed in the age groups younger than 25 years. Self-reported peak prevalence and peak HIV diagnoses rates are often shifted to higher age groups in internet samples compared to surveillance data. Adjustment for age-effects on online accessibility should be considered when linking data from internet surveys with surveillance data.

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Characterizing the multiplicity of HIV founder variants during sexual transmission among MSM.

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Characterizing the multiplicity of HIV founder variants during sexual transmission among MSM.

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