Oliver Laeyendecker

Bio: Oliver Laeyendecker is an academic researcher from National Institutes of Health. The author has contributed to research in topics: Population & Viral load. The author has an hindex of 53, co-authored 264 publications receiving 15254 citations. Previous affiliations of Oliver Laeyendecker include Henry M. Jackson Foundation for the Advancement of Military Medicine & Makerere University.

Rates of HIV-1 Transmission per Coital Act, by Stage of HIV-1 Infection, in Rakai, Uganda

Abstract: Background. We estimated rates of human immunodeficiency virus (HIV)‐1 transmission per coital act in HIV-discordant couples by stage of infection in the index partner. Methods. We retrospectively identified 235 monogamous, HIV-discordant couples in a Ugandan populationbased cohort. HIV transmission within pairs was confirmed by sequence analysis. Rates of transmission per coital act were estimated by the index partner’s stage of infection (recent seroconversion or prevalent or late-stage infection). The adjusted rate ratio of transmission per coital act was estimated by multivariate Poisson regression. Results. The average rate of HIV transmission was 0.0082/coital act (95% confidence interval [CI], 0.0039‐ 0.0150) within ∼2.5 months after seroconversion of the index partner; 0.0015/coital act within 6‐15 months after seroconversion of the index partner (95% CI, 0.0002‐0.0055); 0.0007/coital act (95% CI, 0.0005‐0.0010) among HIV-prevalent index partners; and 0.0028/coital act (95% CI, 0.0015‐0.0041) 6‐25 months before the death of the index partner. In adjusted models, early- and late-stage infection, higher HIV load, genital ulcer disease, and younger age of the index partner were significantly associated with higher rates of transmission. Conclusions. The rate of HIV transmission per coital act was highest during early-stage infection. This has implications for HIV prevention and for projecting the effects of antiretroviral treatment on HIV transmission. Model estimates suggest that the rate of heterosexual HIV-1 transmission per coital act follows a U-shaped curve, being highest during the postseroconversion period, lower during latency, and increasing with advancing disease [1‐4]. This is supported by findings that blood HIV load, which is higher during the postseroconversion period and during advanced disease, is the principal predictor of heterosexual transmission [5‐

Variation in False-Negative Rate of Reverse Transcriptase Polymerase Chain Reaction-Based SARS-CoV-2 Tests by Time Since Exposure.

Abstract: Background Tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) based on reverse transcriptase polymerase chain reaction (RT-PCR) are being used to "rule out" infection among high-risk persons, such as exposed inpatients and health care workers. It is critical to understand how the predictive value of the test varies with time from exposure and symptom onset to avoid being falsely reassured by negative test results. Objective To estimate the false-negative rate by day since infection. Design Literature review and pooled analysis. Setting 7 previously published studies providing data on RT-PCR performance by time since symptom onset or SARS-CoV-2 exposure using samples from the upper respiratory tract (n = 1330). Patients A mix of inpatients and outpatients with SARS-CoV-2 infection. Measurements A Bayesian hierarchical model was fitted to estimate the false-negative rate by day since exposure and symptom onset. Results Over the 4 days of infection before the typical time of symptom onset (day 5), the probability of a false-negative result in an infected person decreases from 100% (95% CI, 100% to 100%) on day 1 to 67% (CI, 27% to 94%) on day 4. On the day of symptom onset, the median false-negative rate was 38% (CI, 18% to 65%). This decreased to 20% (CI, 12% to 30%) on day 8 (3 days after symptom onset) then began to increase again, from 21% (CI, 13% to 31%) on day 9 to 66% (CI, 54% to 77%) on day 21. Limitation Imprecise estimates due to heterogeneity in the design of studies on which results were based. Conclusion Care must be taken in interpreting RT-PCR tests for SARS-CoV-2 infection-particularly early in the course of infection-when using these results as a basis for removing precautions intended to prevent onward transmission. If clinical suspicion is high, infection should not be ruled out on the basis of RT-PCR alone, and the clinical and epidemiologic situation should be carefully considered. Primary funding source National Institute of Allergy and Infectious Diseases, Johns Hopkins Health System, and U.S. Centers for Disease Control and Prevention.

The Natural History of Hepatitis C Virus Infection: Host, Viral, and Environmental Factors

Abstract: Context Hepatitis C virus (HCV) infection may resolve (viral clearance), persist without complications, or cause end-stage liver disease (ESLD). The frequency and determinants of these outcomes are poorly understood. Objective To assess the incidence and determinants of viral clearance and ESLD among persons who acquired HCV infection from injection drug use. Design and setting Community-based prospective cohort study with enrollment in 1988-1989 and a median follow-up of 8.8 years. Subjects A total of 1667 persons aged 17 years or older with a history of injection drug use and an HCV antibody-positive test result during follow-up. Main outcome measures Viral clearance was assessed in a subset of 919 patients and defined as failure to detect HCV RNA in at least 2 consecutive samples collected 5 or more months apart. End-stage liver disease was assessed at semiannual visits and by review of medical records and death certificates and defined by the presence of ascites, esophageal varices, or hepatic encephalopathy, or when ESLD was stated as a cause of death. Results Viral clearance was observed in 90 persons who were compared with 722 with persistent viremia, while the viremia of 107 was not resolved. Viral clearance occurred more often in nonblacks (adjusted odds ratio [OR], 5.15; 95% confidence interval [CI], 2.60-10.17) and those not infected with human immunodeficiency virus (HIV) (adjusted OR, 2.19; 95% CI, 1.26-3.47). Forty cases of ESLD were observed throughout follow-up (incidence, 3.1 per 1000 person-years). In a multivariate model, risk of ESLD was higher for persons aged 38 years or older at enrollment (adjusted relative incidence, 3.67; 95% CI, 1.96-6.88) and who reported ingestion of more than 260 g of alcohol per week (adjusted relative incidence, 3.60; 95% CI, 1.73-7.52). Of 210 patients without ESLD randomly selected for biopsy, only 2 had cirrhosis. Conclusions Our results indicate that although HCV infection can be self-limited or associated with ESLD, the majority of adults have persistent viremia without clinically demonstrable liver disease. Further research is needed to explain the less frequent clearance of HCV infection among black persons and to improve utilization of treatment for those infected in the context of injection drug use. JAMA. 2000;284:450-456

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

SPAdes, a new genome assembly algorithm and its applications to single-cell sequencing ( 7th Annual SFAF Meeting, 2012)

Abstract: The lion's share of bacteria in various environments cannot be cloned in the laboratory and thus cannot be sequenced using existing technologies. A major goal of single-cell genomics is to complement gene-centric metagenomic data with whole-genome assemblies of uncultivated organisms. Assembly of single-cell data is challenging because of highly non-uniform read coverage as well as elevated levels of sequencing errors and chimeric reads. We describe SPAdes, a new assembler for both single-cell and standard (multicell) assembly, and demonstrate that it improves on the recently released E+V-SC assembler (specialized for single-cell data) and on popular assemblers Velvet and SoapDeNovo (for multicell data). SPAdes generates single-cell assemblies, providing information about genomes of uncultivatable bacteria that vastly exceeds what may be obtained via traditional metagenomics studies. SPAdes is available online ( http://bioinf.spbau.ru/spades ). It is distributed as open source software.

Human biochemical genetics

Abstract: So far in this course we have dealt entirely with the evolution of characters that are controlled by simple Mendelian inheritance at a single locus. There are notes on the course website about gametic disequilibrium and how allele frequencies change at two loci simultaneously, but we didn’t discuss them. In every example we’ve considered we’ve imagined that we could understand something about evolution by examining the evolution of a single gene. That’s the domain of classical population genetics. For the next few weeks we’re going to be exploring a field that’s actually older than classical population genetics, although the approach we’ll be taking to it involves the use of population genetic machinery. If you know a little about the history of evolutionary biology, you may know that after the rediscovery of Mendel’s work in 1900 there was a heated debate between the “biometricians” (e.g., Galton and Pearson) and the “Mendelians” (e.g., de Vries, Correns, Bateson, and Morgan). Biometricians asserted that the really important variation in evolution didn’t follow Mendelian rules. Height, weight, skin color, and similar traits seemed to

Prevention of HIV-1 Infection with Early Antiretroviral Therapy

Abstract: Background Antiretroviral therapy that reduces viral replication could limit the transmission of human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples. Methods In nine countries, we...

Preexposure Chemoprophylaxis for HIV Prevention in Men Who Have Sex with Men

Abstract: The study subjects were followed for 3324 person-years (median, 1.2 years; maximum, 2.8 years). Of these subjects, 10 were found to have been infected with HIV at en rollment, and 100 became infected during follow-up (36 in the FTC–TDF group and 64 in the placebo group), indicating a 44% reduction in the incidence of HIV (95% confidence interval, 15 to 63; P = 0.005). In the FTC–TDF group, the study drug was detected in 22 of 43 of seronegative subjects (51%) and in 3 of 34 HIV-infected subjects (9%) (P<0.001). Nausea was reported more frequently during the first 4 weeks in the FTC–TDF group than in the placebo group (P<0.001). The two groups had similar rates of serious adverse events (P = 0.57). Conclusions Oral FTC–TDF provided protection against the acquisition of HIV infection among the subjects. Detectable blood levels strongly correlated with the prophylactic effect. (Funded by the National Institutes of Health and the Bill and Melinda Gates Foun dation; ClinicalTrials.gov number, NCT00458393.)