Dataset Information

HIV-1 full-genome phylogenetics of generalized epidemics in sub-Saharan Africa: impact of missing nucleotide characters in next-generation sequences.

ABSTRACT: To characterize HIV-1 transmission dynamics in regions where the burden of HIV-1 is greatest, the 'Phylogenetics and Networks for Generalised HIV Epidemics in Africa' consortium (PANGEA-HIV) is sequencing full-genome viral isolates from across sub-Saharan Africa. We report the first 3,985 PANGEA-HIV consensus sequences from four cohort sites (Rakai Community Cohort Study, n=2,833; MRC/UVRI Uganda, n=701; Mochudi Prevention Project, n=359; Africa Health Research Institute Resistance Cohort, n=92). Next-generation sequencing success rates varied: more than 80% of the viral genome from the gag to the nef genes could be determined for all sequences from South Africa, 75% of sequences from Mochudi, 60% of sequences from MRC/UVRI Uganda, and 22% of sequences from Rakai. Partial sequencing failure was primarily associated with low viral load, increased for amplicons closer to the 3' end of the genome, was not associated with subtype diversity except HIV-1 subtype D, and remained significantly associated with sampling location after controlling for other factors. We assessed the impact of the missing data patterns in PANGEA-HIV sequences on phylogeny reconstruction in simulations. We found a threshold in terms of taxon sampling below which the patchy distribution of missing characters in next-generation sequences has an excess negative impact on the accuracy of HIV-1 phylogeny reconstruction, which is attributable to tree reconstruction artifacts that accumulate when branches in viral trees are long. The large number of PANGEA-HIV sequences provides unprecedented opportunities for evaluating HIV-1 transmission dynamics across sub-Saharan Africa and identifying prevention opportunities. Molecular epidemiological analyses of these data must proceed cautiously because sequence sampling remains below the identified threshold and a considerable negative impact of missing characters on phylogeny reconstruction is expected.

SUBMITTER: Ratmann O

PROVIDER: S-EPMC5597042 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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HIV-1 full-genome phylogenetics of generalized epidemics in sub-Saharan Africa: impact of missing nucleotide characters in next-generation sequences.

Ratmann Oliver O Wymant Chris C Colijn Caroline C Danaviah Siva S Essex M M Frost Simon D W SDW Gall Astrid A Gaiseitsiwe Simani S Grabowski Mary M Gray Ronald R Guindon Stephane S von Haeseler Arndt A Kaleebu Pontiano P Kendall Michelle M Kozlov Alexey A Manasa Justen J Minh Bui Quang BQ Moyo Sikhulile S Novitsky Vladimir V Nsubuga Rebecca R Pillay Sureshnee S Quinn Thomas C TC Serwadda David D Ssemwanga Deogratius D Stamatakis Alexandros A Trifinopoulos Jana J Wawer Maria M Leigh Brown Andrew A de Oliveira Tulio T Kellam Paul P Pillay Deenan D Fraser Christophe C

AIDS research and human retroviruses 20170525 11

To characterize HIV-1 transmission dynamics in regions where the burden of HIV-1 is greatest, the 'Phylogenetics and Networks for Generalised HIV Epidemics in Africa' consortium (PANGEA-HIV) is sequencing full-genome viral isolates from across sub-Saharan Africa. We report the first 3,985 PANGEA-HIV consensus sequences from four cohort sites (Rakai Community Cohort Study, n=2,833; MRC/UVRI Uganda, n=701; Mochudi Prevention Project, n=359; Africa Health Research Institute Resistance Cohort, n=92) ...[more]

PMID: 28540766

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Project description:BackgroundIn a given population the age pattern of mortality is an important determinant of total number of deaths, age structure, and through effects on age structure, the number of births and thereby growth. Good mortality models exist for most populations except those experiencing generalized HIV epidemics and some developing country populations. The large number of deaths concentrated at very young and adult ages in HIV-affected populations produce a unique 'humped' age pattern of mortality that is not reproduced by any existing mortality models. Both burden of disease reporting and population projection methods require age-specific mortality rates to estimate numbers of deaths and produce plausible age structures. For countries with generalized HIV epidemics these estimates should take into account the future trajectory of HIV prevalence and its effects on age-specific mortality. In this paper we present a parsimonious model of age-specific mortality for countries with generalized HIV/AIDS epidemics.Methods and findingsThe model represents a vector of age-specific mortality rates as the weighted sum of three independent age-varying components. We derive the age-varying components from a Singular Value Decomposition of the matrix of age-specific mortality rate schedules. The weights are modeled as a function of HIV prevalence and one of three possible sets of inputs: life expectancy at birth, a measure of child mortality, or child mortality with a measure of adult mortality. We calibrate the model with 320 five-year life tables for each sex from the World Population Prospects 2010 revision that come from the 40 countries of the world that have and are experiencing a generalized HIV epidemic. Cross validation shows that the model is able to outperform several existing model life table systems.ConclusionsWe present a flexible, parsimonious model of age-specific mortality for countries with generalized HIV epidemics. Combined with the outputs of existing epidemiological and demographic models, this model makes it possible to project future age-specific mortality profiles and number of deaths for countries with generalized HIV epidemics.

Dataset Information

HIV-1 full-genome phylogenetics of generalized epidemics in sub-Saharan Africa: impact of missing nucleotide characters in next-generation sequences.

Publications

HIV-1 full-genome phylogenetics of generalized epidemics in sub-Saharan Africa: impact of missing nucleotide characters in next-generation sequences.

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