Assessment of Ambiguous Base Calls in HIV-1
            <i>pol</i>
            Population Sequences as a Biomarker for Identification of Recent Infections in HIV-1 Incidence Studies

Meixenberger, Karolin; Hauser, Andrea; Jansen, Klaus; Yousef, Kaveh Pouran; Fiedler, S.; Kleist, Max von; Norley, Stephen; Somogyi, Sybille; Hamouda, Osamah; Bannert, Norbert; Bartmeyer, Barbara; Kücherer, Claudia

doi:10.1128/jcm.03289-13

Cited by 18 publications

(18 citation statements)

References 29 publications

(75 reference statements)

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“…Kouyos et al [18] showed that time since infection correlated with the fraction of polymorphic nucleotides in partial HIV-1 pol gene sequences determined by Sanger sequencing. Others have later reported similar findings [19–21]. This idea was expanded to other measures of sequence diversity, such as mean Hamming distance [6, 7, 22] and high-resolution melting (HRM) [23].…”

Section: Introductionmentioning

confidence: 87%

Estimating time of HIV-1 infection from next-generation sequence diversity

2017

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Estimating the time since infection (TI) in newly diagnosed HIV-1 patients is challenging, but important to understand the epidemiology of the infection. Here we explore the utility of virus diversity estimated by next-generation sequencing (NGS) as novel biomarker by using a recent genome-wide longitudinal dataset obtained from 11 untreated HIV-1-infected patients with known dates of infection. The results were validated on a second dataset from 31 patients. Virus diversity increased linearly with time, particularly at 3rd codon positions, with little inter-patient variation. The precision of the TI estimate improved with increasing sequencing depth, showing that diversity in NGS data yields superior estimates to the number of ambiguous sites in Sanger sequences, which is one of the alternative biomarkers. The full advantage of deep NGS was utilized with continuous diversity measures such as average pairwise distance or site entropy, rather than the fraction of polymorphic sites. The precision depended on the genomic region and codon position and was highest when 3rd codon positions in the entire pol gene were used. For these data, TI estimates had a mean absolute error of around 1 year. The error increased only slightly from around 0.6 years at a TI of 6 months to around 1.1 years at 6 years. Our results show that virus diversity determined by NGS can be used to estimate time since HIV-1 infection many years after the infection, in contrast to most alternative biomarkers. We provide the regression coefficients as well as web tool for TI estimation.

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Section: Introductionmentioning

confidence: 87%

Estimating time of HIV-1 infection from next-generation sequence diversity

2017

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“…Ethics statement. The studies were approved by the data protection officer of the RKI and the German Federal Commissioner for Data Protection and Freedom of Information (III-401/008#0016) as well as the ethical committee of the Charité University Medicine (Berlin, Germany; EA 2/105/05) (19,50).…”

Section: Methodsmentioning

confidence: 99%

Reconstruction of the Genetic History and the Current Spread of HIV-1 Subtype A in Germany

Hanke

Faria

Kühnert

et al. 2019

J Virol

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HIV-1 non-B infections have been increasing in Europe for several years. In Germany, subtype A belongs to the most abundant non-B subtypes showing an increasing prevalence of 8.3% among new infections in 2016. Here we trace the origin and examine the current spread of the German HIV-1 subtype A epidemic. Bayesian coalescence and birth-death analyses were performed with 180 German HIV-1 pol sequences and 528 related and publicly available sequences to reconstruct the population dynamics and fluctuations for each of the transmission groups. Our reconstructions indicate two distinct sources of the German subtype A epidemic, with an Eastern European and an Eastern African lineage both cocirculating in the country. A total of 13 German-origin clusters were identified; among these, 6 clusters showed recent activity. Introductions leading to further countrywide spread originated predominantly from Eastern Africa when introduced before 2005. Since 2005, however, spreading introductions have occurred exclusively within the Eastern European clade. Moreover, we observed changes in the main route of subtype A transmission. The beginning of the German epidemic (1985 to 1995) was dominated by heterosexual transmission of the Eastern African lineage. Since 2005, transmissions among German men who have sex with men (MSM) have been increasing and have been associated with the Eastern European lineage. Infections among people who inject drugs dominated between 1998 and 2005. Our findings on HIV-1 subtype A infections provide new insights into the spread of this virus and extend the understanding of the HIV epidemic in Germany. IMPORTANCE HIV-1 subtype A is the second most prevalent subtype worldwide, with a high prevalence in Eastern Africa and Eastern Europe. However, an increase of non-B infections, including subtype A infections, has been observed in Germany and other European countries. There has simultaneously been an increased flow of refugees into Europe and especially into Germany, raising the question of whether the surge in non-B infections resulted from this increased immigration or whether German transmission chains are mainly involved. This study is the first comprehensive subtype A study from a western European country analyzing in detail its phylogenetic origin, the impact of various transmission routes, and its current spread. The results and conclusions presented provide new and substantial insights for virologists, epidemiologists, and the general public health sector. In this regard, they should be useful to those authorities responsible for developing public health intervention strategies to combat the further spread of HIV/AIDS.

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“…Although not perfect, the BED test is still the STARHS method used most frequently worldwide and has performed well in several recent studies. In a recent study performed on 1,334 seroconverters from German HIV‐1 Seroconverter Cohort, the BED test thus achieved a significantly higher accuracy than the sophisticated sequence ambiguity method using a 0.5% threshold (accuracy 84.6 vs. 75.5%, P < 0.001) [Meixenberger et al, ]. In combination with high‐resolution melting diversity, which does not require sequencing, the BED test also performed well in a recent study on samples from three large cohorts in the United States [Cousins et al, ], as well as in combination with an avidity assay (with and without CD4 and viral load testing) on 5,325 samples from seven large African cohorts [Laeyendecker et al, ].…”

Section: Discussionmentioning

confidence: 99%

Longitudinal trends of recent HIV-1 infections in Slovenia (1986-2012) determined using an incidence algorithm

et al. 2015

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Resolving dilemma whether the rise in the number of HIV diagnoses represents an actual increase in HIV transmissions or is a result of improved HIV surveillance is crucial before implementing national HIV prevention strategies. Annual proportions of recent infections (RI) among newly diagnosed persons infected with HIV-1 in Slovenia during 27 years (1986-2012) were determined using an algorithm consisting of routine baseline CD4 and HIV viral load measurements and the Aware BED EIA HIV-1 Incidence Test (BED test). The study included the highest coverage of persons diagnosed with HIV during the entire duration of an HIV epidemic in a given country/region (71%). Out of 416 patients, 170 (40.9%) had a baseline CD4 cell count less than 200 cells/mm(3) and/or HIV-1 viral load less than 400 copies/ml and were characterized as having a long-standing infection (LSI). The remaining 246 patients were additionally tested using the BED test. Overall, 23% (97/416) of the patients were labeled RI. The characteristics significantly associated with RI were as follows: younger age, acute retroviral syndrome, CDC class A and other than C, no AIDS defining illnesses, HIV test performed in the past, a higher viral load, and a higher CD4 cell count. An interesting trend in the proportion of RI was observed, with a peak in 2005 (47% of RI) and the lowest point in 2008 (12%) in parallel with a rise in the numbers of new HIV diagnoses. This study could help promote the idea of introducing periodic HIV incidence monitoring using a simple and affordable algorithm.

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Assessment of Ambiguous Base Calls in HIV-1 pol Population Sequences as a Biomarker for Identification of Recent Infections in HIV-1 Incidence Studies

Cited by 18 publications

References 29 publications

Estimating time of HIV-1 infection from next-generation sequence diversity

Estimating time of HIV-1 infection from next-generation sequence diversity

Reconstruction of the Genetic History and the Current Spread of HIV-1 Subtype A in Germany

Longitudinal trends of recent HIV-1 infections in Slovenia (1986-2012) determined using an incidence algorithm

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