Relationship between plasma selenium concentrations and lower genital tract levels of HIV-1 RNA and interleukin type 1beta.
ABSTRACT To examine the relationship between selenium nutritional status and intermediates of human immunodeficiency virus (HIV)-1 transmission.
Prospective cohort study.
A study clinic at Muhimbili National Hospital, Dar es Salaam, Tanzania.
A total of 340 HIV-1-infected pregnant women with gestational ages 12-27 weeks.
Women's plasma selenium concentrations were determined at enrollment and modeled as tertiles (tertile 1: <114 microg/l (reference); tertile 2: 114-131 microg/l; tertile 3: >131 microg/l). Cervicovaginal lavage specimens were obtained at 36 weeks of gestation to determine HIV-1 RNA and interleukin-1beta (IL-1beta) levels. In subgroup analyses, 123 women with genital tract infections at enrollment were excluded.
Plasma selenium concentrations >or=114 microg/l were related to increased risk of lower-genital shedding of HIV-1 RNA. Excluding women with genital tract infections strengthened the associations (relative risk (RR) tertile 2: 1.46, 95% confidence interval (CI)=1.10, 1.92; RR tertile 3: 1.39, 95% CI=1.05, 1.84). There was evidence for an association between plasma selenium concentrations >or=114 microg/l and increased HIV-1 RNA levels among the entire cohort and after excluding women with genital tract infections. There was no association between plasma selenium and IL-1beta concentrations.
High selenium status may lead to increased risk of genital HIV-1 shedding, but data from other studies indicate that the evidence is mixed. Results from ongoing selenium trials are awaited to clarify the impact of selenium on HIV-1-related transmission endpoints. Sponsorship: National Institute of Child Health and Human Development (NICHD R01 32257) and the Fogarty International Center (NIH D43 TW00004).
Conference Paper: Team/Design: an object-based system for concurrent engineering[Show abstract] [Hide abstract]
ABSTRACT: Team/Design is an object-oriented, knowledge-based software tool developed for concurrent engineering design of both complex and simple systems. It enhances design decision-making by enabling consideration of and trade off among multiple design goals, specifications and constraints, and selection among alternatives to create the total quality product. The original impetus behind the development of Team/Design was the recognition of the need to create a flexible, effective design modeling and decision support system for concurrent engineering/system engineering. The method enhances the total quality (eg., cost performance, supportability, producibility, schedule) of the resulting product while increasing the efficiency of the design process. Object-oriented user interface techniques provide a natural approach to enable systems engineers and other design engineers to model and analyze an early-stage design from the concurrent engineering viewpoint. The development of Team/Design has shown the object-oriented, methodology to be viable for concurrent engineering decision supportReliability and Maintainability Computer-Aided Engineering in Concurrent Engineering, 1990 and 1991., Combined Proceedings of the 1990 and 1991 Leesburg Workshops on; 02/1992
- [Show abstract] [Hide abstract]
ABSTRACT: Heterosexual spread of HIV remains the major risk factor for transmission worldwide. Genital secretions from the infected partner contain both cell-free and cell-associated virus. Although the exact mechanism of heterosexual transmission is unknown, genital virus plays an important role. Decreasing the genital shedding of HIV is an important step in slowing the spread of the disease. Recent studies have shown that antiretroviral penetration into the genital tract varies by class and that antiretroviral therapy significantly decreases HIV levels. Compartmentalization between the blood and genital tract is based on viral load levels, resistant variants, viral diversity, and coreceptor usage. HSV-2, lack of lactobacilli, and plasma cell endometritis increased HIV genital shedding. HSV-2 suppressive therapy significantly reduces plasma and genital tract viral load. Data are conflicting on the effect of hormonal contraception on HIV genital shedding. Further studies are needed to translate these findings into decreased spread on a population level.Current Infectious Disease Reports 12/2008; 10(6):505-11. DOI:10.1007/s11908-008-0082-z
- [Show abstract] [Hide abstract]
ABSTRACT: High levels of HIV-1 viremia exist in peripheral blood during acute and early infection; however, data on HIV-1 viral loads in female genital secretions during this period are sparse. Prospective cohort of 188 African women with primary HIV-1 infection. HIV-uninfected and infected women were followed quarterly; we tested serial plasma specimens by HIV PCR to estimate infection dates. We used the Loess procedure to estimate the magnitude and timing of viral setpoints in plasma and cervical secretions and generalized estimating equations (GEE) to identify predictors of plasma and cervical viral setpoints. We estimated the mean HIV-1 plasma setpoint to be 4.20 log10 HIV-1 RNA copies/ml [95% confidence interval (CI) 4.04-4.35] at 121 days (95% CI 91-137) from infection; an analogous mean cervical viral setpoint was 1.64 log10 HIV-1 RNA copies/swab (95% CI 1.46-1.82) at 174 days (95% CI 145-194) from infection. Cervical loads were significantly higher (0.7-1.1 log10 copies/swab) during acute infection than subsequently. Subtype D infection, pregnancy, breastfeeding, and older age at the time of infection were associated with higher plasma viral setpoint. Subtype C infection, nonviral sexually transmitted infections, having a partner spending nights away from home, recent unprotected sex, and shorter time since infection were associated with higher cervical HIV-1 loads. Hormonal contraception was not associated with either the HIV-1 plasma setpoint or cervical loads during early infection. Cervical HIV-1 viral loads were highest during acute infection and then declined up to 6 months following infection, when a 'setpoint' was attained. The prognostic value of a cervical 'setpoint' on future transmission risk remains unclear.AIDS (London, England) 02/2010; 24(4):573-82. DOI:10.1097/QAD.0b013e32833433df · 6.56 Impact Factor