277 research outputs found

    Prediction-based classification for longitudinal biomarkers

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    Assessment of circulating CD4 count change over time in HIV-infected subjects on antiretroviral therapy (ART) is a central component of disease monitoring. The increasing number of HIV-infected subjects starting therapy and the limited capacity to support CD4 count testing within resource-limited settings have fueled interest in identifying correlates of CD4 count change such as total lymphocyte count, among others. The application of modeling techniques will be essential to this endeavor due to the typically nonlinear CD4 trajectory over time and the multiple input variables necessary for capturing CD4 variability. We propose a prediction-based classification approach that involves first stage modeling and subsequent classification based on clinically meaningful thresholds. This approach draws on existing analytical methods described in the receiver operating characteristic curve literature while presenting an extension for handling a continuous outcome. Application of this method to an independent test sample results in greater than 98% positive predictive value for CD4 count change. The prediction algorithm is derived based on a cohort of n=270n=270 HIV-1 infected individuals from the Royal Free Hospital, London who were followed for up to three years from initiation of ART. A test sample comprised of n=72n=72 individuals from Philadelphia and followed for a similar length of time is used for validation. Results suggest that this approach may be a useful tool for prioritizing limited laboratory resources for CD4 testing after subjects start antiretroviral therapy.Comment: Published in at http://dx.doi.org/10.1214/10-AOAS326 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

    High-Risk Contexts for Violence Against Women: Using Latent Class Analysis to Understand Structural and Contextual Drivers of Intimate Partner Violence at the National Level

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    Introduction: Intimate partner violence (IPV) affects 1 in 3 women and poses a major human rights threat and public health burden, yet there is great variation in risk globally. Whilst individual risk factors are well-studied, less research has focussed on the structural and contextual drivers of IPV and how these co-occur to create contexts of high risk. Methods: We compiled IPV drivers from freely-accessible global country-level data sources and combined gender inequality, natural disasters, conflict, colonialism, socioeconomic development and inequality, homicide and social discrimination in a latent class analysis, and identified underlying 'risk contexts' based on fit statistics and theoretical plausibility (N=5,732 country-years; 190 countries). We used multinomial regression to compare risk contexts according to: proportion of population with disability, HIV/AIDS, refugee status, and mental health disorders; proportion of men with drug use disorders; men's alcohol consumption; and population median age (N=1,654-5,725 country-years). Finally, we compared prevalence of physical and/or sexual IPV experienced by women in the past 12 months across risk contexts (N=3,175 country-years). Results: Three distinct risk contexts were identified: 1) non-patriarchal egalitarian, low rates of homicide; 2) patriarchal post-colonial, high rates of homicide; 3) patriarchal post-colonial conflict and disaster-affected. Compared to non-patriarchal egalitarian contexts, patriarchal post-colonial contexts had a younger age distribution and a higher prevalence of drug use disorders, but a lower prevalence of mental health disorders and a smaller refugee population. IPV risk was highest in the two patriarchal post-colonial contexts and associated with country income classification. Conclusions: Whilst our findings support the importance of gender norms in shaping women's risk of experiencing IPV, they also point towards an association with a history of colonialism. To effectively address IPV for women in high prevalence contexts, structural interventions and policies are needed that address not only gender norms, but also broader structural inequalities arising from colonialism

    Drug resistance outcomes of long-term ART with tenofovir disoproxil fumarate in the absence of virological monitoring

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    Objectives: The resistance profiles of patients receiving long-term ART in sub-Saharan Africa have been poorly described. This study obtained a sensitive assessment of the resistance patterns associated with long-term tenofovir-based ART in a programmatic setting where virological monitoring is yet to become part of routine care. Methods: We studied subjects who, after a median of 4.2 years of ART, replaced zidovudine or stavudine with tenofovir disoproxil fumarate while continuing lamivudine and an NNRTI. Using deep sequencing, resistance-associated mutations (RAMs) were detected in stored samples collected at tenofovir introduction (T0) and after a median of 4.0 years (T1). Results: At T0, 19/87 (21.8%) subjects showed a detectable viral load and 8/87 (9.2%) had one or more major NNRTI RAMs, whereas 82/87 (94.3%) retained full tenofovir susceptibility. At T1, 79/87 (90.8%) subjects remained on NNRTI-based ART, 5/87 (5.7%) had introduced lopinavir/ritonavir due to immunological failure, and 3/87 (3.4%) had interrupted ART. Whilst 68/87 (78.2%) subjects maintained or achieved virological suppression between T0 and T1, a detectable viral load with NNRTI RAMs at T0 predicted lack of virological suppression at T1. Each treatment interruption, usually reflecting unavailability of the dispensary, doubled the risk of T1 viraemia. Tenofovir, lamivudine and efavirenz selected for K65R, K70E/T, L74I/V and Y115F, alongside M184V and multiple NNRTI RAMs; this resistance profile was accompanied by high viral loads and low CD4 cell counts. Conclusions: Viraemia on tenofovir, lamivudine and efavirenz led to complex resistance patterns with implications for continued drug activity and risk of onward transmission

    Parental leave in European Companies

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    Adolescent parenthood and HIV-infection in South Africa—Associations with child cognitive development

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    HIV, both directly and indirectly, impacts child development outcomes. The most severe impacts are for children infected with HIV, and those exposed but uninfected are also shown to have challenges-though less severe. However, little is known regarding the development of children born to adolescent mothers affected by HIV. This study aims to examine cognitive development for children born to adolescent mothers, comparing those children living with HIV, those HIV exposed and uninfected (HEU) and those HIV unexposed (HU). Analyses utilise cross-sectional data from 920 adolescent mother (10-19 years)-first born child dyads residing in the Eastern Cape Province, South Africa. Participants completed detailed study questionnaires inclusive of validated and study specific measures relating to sociodemographic characteristics, HIV, and maternal and child health. Trained assessors administered standardised child development assessments (using the Mullen Scales of Early Learning) with all children. Chi-square tests and ANOVA tests were used to explore maternal and child characteristics according to child HIV status (HIV, HEU, HU) on cognitive development. Linear regression models were used to explore the cross-sectional associations between child HIV status and child cognitive development. 1.2% of children were living with HIV, 20.5% were classified as being HEU and, 78.3% were classified as HU. Overall, children living with HIV were found to perform lower across developmental domains compared to both HEU and HU groups (composite score of early learning: 73.0 vs 91.2 vs. 94.1, respectively: F = 6.45, p = 0.001). HEU children on average scored lower on all developmental domains compared to HU children, reaching significance on the gross motor domain (p<0.05). Exploratory analyses identified maternal education interruption as a potential risk factor for lower child cognitive development scores and, higher maternal age to be protective of child cognitive development scores. These exploratory findings address a critical evidence gap regarding the cognitive development of children born to adolescent mothers affected by HIV in South Africa. Analyses identify stepwise differences in the average scoring on child cognitive development domains according to child HIV status among children born to adolescent mothers affected by HIV; with children living with HIV performing worse overall. Young mothers and their children may benefit from adapted interventions aimed at bolstering child development outcomes. Targeted programming particularly among younger adolescent mothers and those experiencing education interruption may identify those families, particularly in need. Attention to maternal continuity of education and age of conception may be interventions to consider

    Development of a definition for Rapid Progression (RP) of renal function in HIV-positive persons: the D:A:D study

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    Background No consensus exists on how to define abnormally rapid deterioration in renal function (Rapid Progression, RP). We developed an operational definition of RP in HIV-positive persons with baseline estimated glomerular filtration rate (eGFR) >90 ml/min/1.73 m2 (using Cockcroft Gault) in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study from 2004 to 2011. Methods Two definitions were evaluated; RP definition A: An average eGFR decline (slope) ≥5 ml/min/1.73 m2/year over four years of follow-up with ≥3 eGFR measurements/year, last eGFR <90 ml/min/1.73 m2 and an absolute decline ≥5 ml/min/1.73 m2/year in two consecutive years. RP definition B: An absolute annual decline ≥5 ml/min/1.73 m2/year in each year and last eGFR <90 ml/min/1.73 m2. Sensitivity analyses were performed considering two and three years' follow-up. The percentage with and without RP who went on to subsequently develop incident chronic kidney disease (CKD; 2 consecutive eGFRs <60 ml/min/1.73 m2 and 3 months apart) was calculated. Results 22,603 individuals had baseline eGFR ≥90 ml/min/1.73 m2. 108/3655 (3.0%) individuals with ≥4 years' follow-up and ≥3 measurements/year experienced RP under definition A; similar proportions were observed when considering follow-up periods of three (n=195/6375; 3.1%) and two years (n=355/10756; 3.3%). In contrast under RP definition B, greater proportions experienced RP when considering two years (n=476/10756; 4.4%) instead of three (n=48/6375; 0.8%) or four (n=15/3655; 0.4%) years' follow-up. For RP definition A, 13 (12%) individuals who experienced RP progressed to CKD, and only (21) 0.6% of those without RP progressed to CKD (sensitivity 38.2% and specificity 97.4%); whereas for RP definition B, fewer RP individuals progressed to CKD. Conclusions Our results suggest using three years' follow-up and at least two eGFR measurements per year is most appropriate for a RP definition, as it allows inclusion of a reasonable number of individuals and is associated with the known risk factors. The definition does not necessarily identify all those that progress to incident CKD, however, it can be used alongside other renal measurements to early identify and assess those at risk of developing CKD. Future analyses will use this definition to identify other risk factors for RP, including the role of antiretrovirals

    Adolescent mothers and their children affected by HIV-An exploration of maternal mental health, and child cognitive development.

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    BACKGROUND: Some children born to adolescent mothers may have developmental challenges, while others do not. Research focusing on which children of adolescent mothers are at the highest risk for cognitive delay is still required. Both maternal HIV status and maternal mental health may affect child development. An examination of maternal mental health, especially in the presence of maternal HIV infection may be timely. This study explores the relationship between the mental health of adolescent mothers (comparing those living with and not living with HIV) and the cognitive development performance scores of their children. Additional possible risk and protective factors for poor child development are explored to identify those children born to adolescent mothers who may be at the greatest risk of poor cognitive development. METHODS: Cross-sectional data utilised within the analyses was drawn from a large cohort of adolescent mothers and their children residing in South Africa. Detailed study questionnaires were completed by adolescent mothers relating to their self and their child and, standardised cognitive assessments were completed by trained researchers for all children using in the Mullen Scales of Early Learning. Chi-square, t-tests (Kruskal Wallis tests, where appropriate), and ANOVA were used to explore sample characteristics and child cognitive development scores by maternal mental health status (operationalised as likely common mental disorder) and combined maternal mental health and HIV status. Multivariable linear regression models were used to explore the relationship between possible risk factors (including poor maternal mental health and HIV) and, child cognitive development scores. RESULTS: The study included 954 adolescent mothers; 24.1% (230/954) were living with HIV, 12.6% (120/954) were classified as experiencing likely common mental disorder. After adjusting for covariates, maternal HIV was found to be associated with reduced child gross motor scores (B = -2.90 [95%CI: -5.35, -0.44], p = 0.02), however, no other associations were identified between maternal likely common mental disorder, or maternal HIV status (including interaction terms), and child cognitive development scores. Sensitivity analyses exploring individual maternal mental health scales identified higher posttraumatic stress symptomology scores as being associated with lower child cognitive development scores. Sensitivity analyses exploring potential risk and protective factors for child cognitive development also identified increased maternal educational attainment as being protective of child development scores, and increased child age as a risk factor for lower development scores. CONCLUSIONS: This study addresses a critical evidence gap relating to the understanding of possible risk factors for the cognitive development of children born to adolescent mothers affected by HIV. This group of mothers experience a complex combination of risk factors, including HIV, likely common mental disorder, and structural challenges such as educational interruption. Targeting interventions to support the cognitive development of children of adolescent mothers most at risk may be of benefit. Clearly a basket of interventions needs to be considered, such as the integration of mental health provision within existing services, identifying multiple syndemics of risk, and addressing educational and structural challenges, all of which may boost positive outcomes for both the mother and the child

    All-cause hospitalisation among people living with HIV according to gender, mode of HIV acquisition, ethnicity, and geographical origin in Europe and North America: findings from the ART-CC cohort collaboration

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    BACKGROUND: Understanding demographic disparities in hospitalisation is crucial for the identification of vulnerable populations, interventions, and resource planning. METHODS: Data were from the Antiretroviral Therapy Cohort Collaboration (ART-CC) on people living with HIV in Europe and North America, followed up between January, 2007 and December, 2020. We investigated differences in all-cause hospitalisation according to gender and mode of HIV acquisition, ethnicity, and combined geographical origin and ethnicity, in people living with HIV on modern combination antiretroviral therapy (cART). Analyses were performed separately for European and North American cohorts. Hospitalisation rates were assessed using negative binomial multilevel regression, adjusted for age, time since cART intitiaion, and calendar year. FINDINGS: Among 23 594 people living with HIV in Europe and 9612 in North America, hospitalisation rates per 100 person-years were 16·2 (95% CI 16·0-16·4) and 13·1 (12·8-13·5). Compared with gay, bisexual, and other men who have sex with men, rates were higher for heterosexual men and women, and much higher for men and women who acquired HIV through injection drug use (adjusted incidence rate ratios ranged from 1·2 to 2·5 in Europe and from 1·2 to 3·3 in North America). In both regions, individuals with geographical origin other than the region of study generally had lower hospitalisation rates compared with those with geographical origin of the study country. In North America, Indigenous people and Black or African American individuals had higher rates than White individuals (adjusted incidence rate ratios 1·9 and 1·2), whereas Asian and Hispanic people living with HIV had somewhat lower rates. In Europe there was a lower rate in Asian individuals compared with White individuals. INTERPRETATION: Substantial disparities exist in all-cause hospitalisation between demographic groups of people living with HIV in the current cART era in high-income settings, highlighting the need for targeted support. FUNDING: Royal Free Charity and the National Institute on Alcohol Abuse and Alcoholism
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