Browsing by Author "Dye, Christopher"

Now showing 1 - 6 of 6
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    Antiretroviral therapy for prevention of tuberculosis in adults with HIV : a systematic review and Meta-Analysis
    (Public Library of Science, 2012-07) Suthar, Amitabh B.; Lawn, Stephen D.; Del Amo, Julia; Getahun, Haileyesus; Dye, Christopher; Sculier, Delphine; Sterling, Timothy R.; Chaisson, Richard E.; Williams, Brian G.; Harries, Anthony D.; Granich, Reuben M.
    Background: Human immunodeficiency virus (HIV) infection is the strongest risk factor for developing tuberculosis and has fuelled its resurgence, especially in sub-Saharan Africa. In 2010, there were an estimated 1.1 million incident cases of tuberculosis among the 34 million people living with HIV worldwide. Antiretroviral therapy has substantial potential to prevent HIV-associated tuberculosis. We conducted a systematic review of studies that analysed the impact of antiretroviral therapy on the incidence of tuberculosis in adults with HIV infection. Methods and Findings: PubMed, Embase, African Index Medicus, LILACS, and clinical trial registries were systematically searched. Randomised controlled trials, prospective cohort studies, and retrospective cohort studies were included if they compared tuberculosis incidence by antiretroviral therapy status in HIV-infected adults for a median of over 6 mo in developing countries. For the meta-analyses there were four categories based on CD4 counts at antiretroviral therapy initiation: (1) less than 200 cells/ml, (2) 200 to 350 cells/ml, (3) greater than 350 cells/ml, and (4) any CD4 count. Eleven studies met the inclusion criteria. Antiretroviral therapy is strongly associated with a reduction in the incidence of tuberculosis in all baseline CD4 count categories: (1) less than 200 cells/ml (hazard ratio [HR] 0.16, 95% confidence interval [CI] 0.07 to 0.36), (2) 200 to 350 cells/ml (HR 0.34, 95% CI 0.19 to 0.60), (3) greater than 350 cells/ml (HR 0.43, 95% CI 0.30 to 0.63), and (4) any CD4 count (HR 0.35, 95% CI 0.28 to 0.44). There was no evidence of hazard ratio modification with respect to baseline CD4 count category (p = 0.20). Conclusions: Antiretroviral therapy is strongly associated with a reduction in the incidence of tuberculosis across all CD4 count strata. Earlier initiation of antiretroviral therapy may be a key component of global and national strategies to control the HIV-associated tuberculosis syndemic.
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    Clinical prognostic value of RNA viral load and CD4 cell counts during untreated HIV-1 infection : a quantitative review
    (Public Library of Science, 2009-16-07) Korenromp, Eline L.; Williams, Brian G.; Schmid, George P.; Dye, Christopher
    Background: The prognostic value of CD4 counts and RNA viral load for identifying treatment need in HIV-infected individuals depends on (a) variation within and among individuals, and (b) relative risks of clinical progression per unit CD4 or RNA difference. Methodology/Principal Findings: We reviewed these measurements across (a) 30 studies, and (b) 16 cohorts of untreated seropositive adults. Median within-population interquartile ranges were 74,000 copies/mL for RNA with no significant change during the course of infection; and 330 cells/μL for CD4, with a slight proportional increase over infection. Applying measurement and physiological fluctuations observed on chronically infected patients, we estimate that 45% of population-level variation in RNA, and 25% of variation in CD4, were due to within-patient fluctuations. Comparing a patient with RNA at upper 75th centile with a patient at median RNA, 5-year relative risks were 1.4 (95% CI 1.2-1.7) for AIDS and 1.5 (1.3-1.9) for death, without change over the course of infection. In contrast, for a patient with CD4 count at the lower 75th centile, relative risks increased from 1.0 at seroconversion to maxima of 6.3 (4.4-8.9) for AIDS and 5.5 (2.7-10.1) for death by year 6, when the population median had fallen to 300 cells/ μL. Below 300 cells/μL, prognostic power did not increase, due to a narrower CD4 range. Conclusions: Findings support the current WHO recommendation (used with clinical criteria) to start antiretroviral treatment in low-income settings at CD4 thresholds of 200-350 cells/μL, without pre-treatment RNA monitoring - while not precluding earlier treatment based on clinical, socio-demographic or public health criteria. © 2009 Korenromp et al.
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    Dynamics and control of infections on social networks of population types
    (Elsevier, 2018) Williams, Brian G.; Dye, Christopher
    Random mixing in host populations has been a convenient simplifying assumption in the study of epidemics, but neglects important differences in contact rates within and between population groups. For HIV/AIDS, the assumption of random mixing is inappropriate for epidemics that are concentrated in groups of people at high risk, including female sex workers (FSW) and their male clients (MCF), injecting drug users (IDU) and men who have sex with men (MSM). To find out who transmits infection to whom and how that affects the spread and containment of infection remains a major empirical challenge in the epidemiology of HIV/AIDS. Here we develop a technique, based on the routine sampling of infection in linked population groups (a social network of population types), which shows how an HIV/AIDS epidemic in Can Tho Province of Vietnam began in FSW, was propagated mainly by IDU, and ultimately generated most cases among the female partners of MCF (FPM). Calculation of the case reproduction numbers within and between groups, and for the whole network, provides insights into control that cannot be deduced simply from observations on the prevalence of infection. Specifically, the per capita rate of HIV transmission was highest from FSW to MCF, and most HIV infections occurred in FPM, but the number of infections in the whole network is best reduced by interrupting transmission to and from IDU. This analysis can be used to guide HIV/AIDS interventions using needle and syringe exchange, condom distribution and antiretroviral therapy. The method requires only routine data and could be applied to infections in other populations.
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    HIV treatment as prevention : debate and commentary : will early infection compromise treatment-as-prevention strategies?
    (Public Library of Science (PLOS), 2012-07) Cohen, Myron S.; Dye, Christopher; Fraser, Christophe; Miller, William C.; Powers, Kimberly A.; Williams, Brian G.
    Universal HIV testing and immediate antiretroviral therapy for infected individuals has been proposed as a way of reducing the transmission of HIV and thereby bringing the HIV epidemic under control. It is unclear whether transmission during early HIV infection—before individuals are likely to have been diagnosed with HIV and started on antiretroviral therapy—will compromise the effectiveness of treatment as prevention
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    Nutrition, diabetes and tuberculosis in the epidemiological transition
    (Public Library of Science (PLOS), 2011-06) Dye, Christopher; Trunz, Bernadette Bourdin; Lonnroth, Knut; Roglic, Gojka; Williams, Brian G.
    Background: Diabetes prevalence and body mass index reflect the nutritional profile of populations but have opposing effects on tuberculosis risk. Interactions between diabetes and BMI could help or hinder TB control in growing, aging, urbanizing populations. Methods and Findings: We compiled data describing temporal changes in BMI, diabetes prevalence and population age structure in rural and urban areas for men and women in countries with high (India) and low (Rep. Korea) TB burdens. Using published data on the risks of TB associated with these factors, we calculated expected changes in TB incidence between 1998 and 2008. In India, TB incidence cases would have increased (28% from 1.7 m to 2.1 m) faster than population size (22%) because of adverse effects of aging, urbanization, changing BMI and rising diabetes prevalence, generating an increase in TB incidence per capita of 5.5% in 10 years. In India, general nutritional improvements were offset by a fall in BMI among the majority of men who live in rural areas. The growing prevalence of diabetes in India increased the annual number of TB cases in people with diabetes by 46% between 1998 and 2008. In Korea, by contrast, the number of TB cases increased more slowly (6.1% from 40,200 to 42,800) than population size (14%) because of positive effects of urbanization, increasing BMI and falling diabetes prevalence. Consequently, TB incidence per capita fell by 7.8% in 10 years. Rapid population aging was the most significant adverse effect in Korea. Conclusions: Nutritional and demographic changes had stronger adverse effects on TB in high-incidence India than in lower-incidence Korea. The unfavourable effects in both countries can be overcome by early drug treatment but, if left unchecked, could lead to an accelerating rise in TB incidence. The prevention and management of risk factors for TB would reinforce TB control by chemotherapy. © 2011 Dye et al.
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    The potential impact of male circumcision on HIV in Sub-Saharan Africa
    (Public Library of Science -- PLoS, 2006-07) Williams, Brian G.; Lloyd-Smith, James O.; Gouws, Eleanor; Hankins, Catherine; Getz, Wayne M.; Hargrove, John; De Zoysa, Isabelle; Dye, Christopher; Auvert, Bertran
    Background A randomized controlled trial (RCT) has shown that male circumcision (MC) reduces sexual transmission of HIV from women to men by 60% (32% 76%; 95% CI) offering an intervention of proven efficacy for reducing the sexual spread of HIV. We explore the implications of this finding for the promotion of MC as a public health intervention to control HIV in sub-Saharan Africa. Methods and Findings Using dynamical simulation models we consider the impact of MC on the relative prevalence of HIV in men and women and in circumcised and uncircumcised men. Using country level data on HIV prevalence and MC, we estimate the impact of increasing MC coverage on HIV incidence, HIV prevalence, and HIV-related deaths over the next ten, twenty, and thirty years in sub-Saharan Africa. Assuming that full coverage of MC is achieved over the next ten years, we consider three scenarios in which the reduction in transmission is given by the best estimate and the upper and lower 95% confidence limits of the reduction in transmission observed in the RCT. MC could avert 2.0 (1.1 3.8) million new HIV infections and 0.3 (0.1 0.5) million deaths over the next ten years in sub-Saharan Africa. In the ten years after that, it could avert a further 3.7 (1.9 7.5) million new HIV infections and 2.7 (1.5 5.3) million deaths, with about one quarter of all the incident cases prevented and the deaths averted occurring in South Africa. We show that a) MC will increase the proportion of infected people who are women from about 52% to 58%; b) where there is homogenous mixing but not all men are circumcised, the prevalence of infection in circumcised men is likely to be about 80% of that in uncircumcised men; c) MC is equivalent to an intervention, such as a vaccine or increased condom use, that reduces transmission in both directions by 37%. Conclusions This analysis is based on the result of just one RCT, but if the results of that trial are confirmed we suggest that MC could substantially reduce the burden of HIV in Africa, especially in southern Africa where the prevalence of MC is low and the prevalence of HIV is high. While the protective benefit to HIV-negative men will be immediate, the full impact of MC on HIV-related illness and death will only be apparent in ten to twenty years.