The World Health Organization Network for HIV Isolation and Characterization: summary of a pilot study.
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Biomedical subjects
Publications and source records attributed to S Osmanov.
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The World Health Organization Global Programme on AIDS (WHO/GPA) is conducting a large-scale collaborative study of human immunodeficiency virus type 1 (HIV-1) variation, based in four potential vaccine-trial site countries: Brazil, Rwanda, Thailand, and Uganda. Through the course of this study, it was crucial to keep track of certain attributes of the samples from which the viral nucleotide sequences were derived (e.g., country of origin and viral culture characterization), so that meaningful sequence comparisons could be made. Here we describe a system developed in the context of the WHO/GPA study that summarizes such critical attributes by representing them as standardized characters directly incorporated into sequence names. This nomenclature allows linkage of clinical, phenotypic, and geographic information with molecular data. We propose that other investigators involved in human immunodeficiency virus (HIV) nucleotide sequencing efforts adopt a similar standardized sequence nomenclature to facilitate cross-study sequence comparison. HIV sequence data are being generated at an ever-increasing rate; directly coupled to this increase is our deepening understanding of biological parameters that influence or result from sequence variability. A standardized sequence nomenclature that includes relevant biological information would enable researchers to better utilize the growing body of sequence data, and enhance their ability to interpret the biological implications of their own data through facilitating comparisons with previously published work.
OBJECTIVE: Accurate estimates of HIV incidence that reflect the effect of non-vaccine interventions (education, counselling, condom promotion, and possibly sexually transmitted disease treatment) and that may be provided in a Phase III vaccine efficacy trial, are needed so that vaccine trial population sample sizes can be accurately determined. In order to avoid delays in the implementation of efficacy trials, well characterized cohorts must also be developed and available to participate in such trials. We reviewed the potential study populations, the epidemiologic methods for the determination of HIV incidence (using open cohort, closed cohort, and seroprevalence data methods), and the need for the development of population cohorts in preparation for Phase III HIV vaccine efficacy trials. SETTING: Phase III trials in developed and developing countries. METHODS: Comparison of open and closed cohorts and those using seroprevalence data to estimate HIV incidence. RESULTS: Open and closed cohorts each have disadvantages and advantages. However, the open cohort may be more suitable for determining estimates of HIV incidence that reflect non-vaccine interventions and for the development of a well characterized cohort available to participate in efficacy trials. CONCLUSION: Careful preparation of research infrastructures and population cohorts will help ensure the successful conduct of scientifically and ethically sound HIV vaccine efficacy trials in the future.
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OBJECTIVES: To develop an assay for the early detection and quantification of minor human immunodeficiency virus-1 populations bearing multiple drug resistance (MDR) mutations. STUDY DESIGN/METHODS: The oligonucleotide ligation assay (OLA) is based on ligation of probe and detector oligonucleotides annealed to a polymerase chain reaction amplicon strand with detection by an enzyme immunoassay. In OLA-MDR, oligonucleotides were designed to detect MDR mutations. The method was validated with wild-type and MDR mutant clones mixed at different proportions. RESULTS: K103N mutants were detected as minor populations (5%-30%) by OLA in 6 of 18 samples from patients treated with nonnucleoside reverse transcription inhibitors and classified as wild type by sequencing. In one patient, the kinetics of the increase of MDR mutants could be followed in sequential samples, with K103N being detected earlier by OLA than by sequencing. Q151M mutants were detected as minor populations (13%-24%) by OLA but not by sequencing in 4 samples. CONCLUSIONS: Oligonucleotide ligation assay MDR exhibits higher sensitivity than sequencing for detection of minor MDR mutant populations.