Biomedical subjects

Daniela Bezemer

Publications and source records attributed to Daniela Bezemer.

4 recordsLinked to original sources

PubMed2025

HIV-phyloTSI: subtype-independent estimation of time since HIV-1 infection for cross-sectional measures of population incidence using deep sequence data.

BACKGROUND: Estimating the time since HIV infection (TSI) at population level is essential for tracking changes in the global HIV epidemic. Most methods for determining TSI give a binary classification of infections as recent or non-recent within a window of several months, and cannot assess the cumulative impact of an intervention. RESULTS: We developed a Random Forest Regression model, HIV-phyloTSI, which combines measures of within-host diversity and divergence to generate continuous TSI estimates directly from viral deep-sequencing data, with no need for additional variables. HIV-phyloTSI provides a continuous measure of TSI up to 9 years, with a mean absolute error of less than 12 months overall and less than 5 months for infections with a TSI of up to a year. It performs equally well for all major HIV subtypes based on data from African and European cohorts. CONCLUSIONS: We demonstrate how HIV-phyloTSI can be used for incidence estimates on a population level.

HIV Infections↗

PubMed2006

Evolution of transmitted HIV-1 with drug-resistance mutations in the absence of therapy: effects on CD4+ T-cell count and HIV-1 RNA load.

Sequence analysis of HIV-1 from 440 therapy-naive individuals included within the CASCADE study, who seroconverted within 18 months of the last negative test, identified 65 persons infected with a strain carrying resistance-associated mutations. Population-based sequencing was performed for 20 of these individuals during the therapy-free follow-up period. The median time of follow-up was 15 months (interquartile range from 10 to 23 months). Of these individuals, 12 showed subsequent evolution at the resistance positions, whereas the virus of 8 people was stable during this period. In the reverse transcriptase (RT) gene, the drug-resistant 215Y or 215F codons evolved to alternative codons in all six cases, 70R reverted to the wild-type 70K in 3 of the 4 individuals, 67N evolved only in 1 of 4 patients to a wild-type 67D, 215S evolved to wild-type 215T in 1 of 3 patients, 219N evolved to 219K in 1 of 2 patients, and one patient with 184V reversed to the wild-type 184M. The 181C variant evolved to the wild-type 181Y in 1 of 2 individuals. These codon changes were caused by single nucleotide mutations. No evolution was observed for other RT mutations: 41L, 69D, 69N, 190S, 210W, 215L, 215C, 215E and 219Q. In the protease gene, resistance mutations 84V and 90M were stable in 2 individuals. Comparing the CD4+ T-cell count of the 12 evolving versus the 8 stable cases revealed no statistically significant difference at the date of the first sequence following seroconversion. Interestingly, a lower CD4+ T-cell count was observed in the group without evolution at the second sequence time point (P = 0.043). No difference in HIV-1 RNA load was observed. These results, together with the apparent pressure to mutate at the resistance-associated positions exemplify the decreased fitness of viruses carrying 21 5Y/F, 70R or 184V.

Anti-HIV Agents↗

PubMed2004

Declining trend in transmission of drug-resistant HIV-1 in Amsterdam.

OBJECTIVE: Symptomatic primary HIV infections are over-represented in the mainly hospital-based studies on transmission of resistant HIV-1. We examined a more general population for the prevalence of resistant HIV-1 strains among primary infections. DESIGN: From 1994 to 2002 primary infections were identified within the Amsterdam Cohort Studies (ACS) among homosexual men and drug users, and at the Academic Medical Center (AMC). Whereas primary HIV-1-infected AMC patients, often presented with symptoms of acute retroviral syndrome, ACS participants largely seroconverted during follow-up and thus brought also asymptomatic primary infections to our study. METHODS: Reverse transcriptase (RT) and protease sequences were obtained by population-based nucleotide sequence analysis of the first HIV RNA-positive sample available. Subtypes were identified by phylogenetic analysis. Mutations were identified based on the IAS-USA resistance table. RESULTS: A total of 100 primary HIV-1 infections were identified (32 AMC and 68 ACS). Transmission of drug-resistant strains decreased over calendar time, with 20% [95% confidence interval (CI), 10-34%] of infections bearing drug-resistant mutations before 1998 versus only 6% (95% CI, 1-17%) after 1998. No multi-drug resistance pattern was observed. The median plasma HIV-1 RNA level of the first RNA positive sample was significantly lower for the individuals infected with a resistant strain versus those infected with wild-type, suggesting a fitness-cost to resistance. Four of seven non-B subtypes corresponded with the prevalent subtype in the presumed country of infection, and none showed resistance mutations. CONCLUSIONS: The transmission of drug-resistant HIV-1 strains in Amsterdam has decreased over time. Monitoring should be continued as this trend might change.

Adult↗

PubMed2003

Selection on coding regions determined Hox7 genes evolution.

The important role of Hox genes in determining the regionalization of the body plan of the vertebrates makes them invaluable candidates for evolutionary analyses regarding functional and morphological innovation. Gene duplication and gene loss led to a variable number of Hox genes in different vertebrate lineages. The evolutionary forces determining the conservation or loss of Hox genes are poorly understood. In this study, we show that variable selective pressures acted on Hox7 genes in different evolutionary lineages, with episodes of positive selection occurring after gene duplications. Tests for functional divergence in paralogs detected significant differentiation in a region known to modulate HOX7 protein activity. Our results show that both positive and negative selection on coding regions are influencing Hox7 genes evolution.

Amino Acid Sequence↗