Short and long term retention in antiretroviral care in health facilities in rural Malawi and Zimbabwe.

Despite the successful scale-up of ART services over the past years, long term retention in ART care remains a major challenge, especially in high HIV prevalence and resource-limited settings. This study analysed the short (<12 months) and long (>12 months) term retention on ART in two ART programmes in Malawi (Thyolo district) and Zimbabwe (Buhera district)

Assessment of BED HIV-1 Incidence Assay in Seroconverter Cohorts: Effect of Individuals with Long-Term Infection and Importance of Stable Incidence

BACKGROUND: Performance of the BED assay in estimating HIV-1 incidence has previously been evaluated by using longitudinal specimens from persons with incident HIV infections, but questions remain about its accuracy. We sought to assess its performance in three longitudinal cohorts from Thailand where HIV-1 CRF01_AE and subtype B' dominate the epidemic. DESIGN: BED testing was conducted in two longitudinal cohorts with only incident infections (a military conscript cohort and an injection drug user cohort) and in one longitudinal cohort (an HIV-1 vaccine efficacy trial cohort) that also included long-term infections. METHODS: Incidence estimates were generated conventionally (based on the number of annual serocoversions) and by using BED test results in the three cohorts. Adjusted incidence was calculated where appropriate. RESULTS: For each longitudinal cohort the BED incidence estimates and the conventional incidence estimates were similar when only newly infected persons were tested, whether infected with CRF01_AE or subtype B'. When the analysis included persons with long-term infections (to mimic a true cross-sectional cohort), BED incidence estimates were higher, although not significantly, than the conventional incidence estimates. After adjustment, the BED incidence estimates were closer to the conventional incidence estimates. When the conventional incidence varied over time, as in the early phase of the injection drug user cohort, the difference between the two estimates increased, but not significantly. CONCLUSIONS: Evaluation of the performance of incidence assays requires the inclusion of a substantial number of cohort-derived specimens from individuals with long-term HIV infection and, ideally, the use of cohorts in which incidence remained stable. Appropriate adjustments of the BED incidence estimates generate estimates similar to those generated conventionally

HIV Incidence in Rural South Africa: Comparison of Estimates from Longitudinal Surveillance and Cross-Sectional cBED Assay Testing

The original publication is available at http:/www.plosone.orgBackground: The BED IgG-Capture Enzyme Immunoassay (cBED assay), a test of recent HIV infection, has been used to estimate HIV incidence in cross-sectional HIV surveys. However, there has been concern that the assay overestimates HIV incidence to an unknown extent because it falsely classifies some individuals with non-recent HIV infections as recently infected. We used data from a longitudinal HIV surveillance in rural South Africa to measure the fraction of people with nonrecent HIV infection who are falsely classified as recently HIV-infected by the cBED assay (the long-term false-positive ratio (FPR)) and compared cBED assay-based HIV incidence estimates to longitudinally measured HIV incidence. Methodology/Principal Findings: We measured the long-term FPR in individuals with two positive HIV tests (in the HIV surveillance, 2003-2006) more than 306 days apart (sample size n = 1,065). We implemented four different formulae to calculate HIV incidence using cBED assay testing (n = 11,755) and obtained confidence intervals (CIs) by directly calculating the central 95th percentile of incidence values. We observed 4,869 individuals over 7,685 person-years for longitudinal HIV incidence estimation. The long-term FPR was 0.0169 (95% CI 0.0100-0.0266). Using this FPR, the cross-sectional cBED-based HIV incidence estimates (per 100 people per year) varied between 3.03 (95% CI 2.44-3.63) and 3.19 (95% CI 2.57-3.82), depending on the incidence formula. Using a long-term FPR of 0.0560 based on previous studies, HIV incidence estimates varied between 0.65 (95% CI 0.00-1.32) and 0.71 (95% CI 0.00-1.43). The longitudinally measured HIV incidence was 3.09 per 100 people per year (95% CI 2.69-3.52), after adjustment to the sex-age distribution of the sample used in cBED assay-based estimation. Conclusions/Significance: In a rural community in South Africa with high HIV prevalence, the long-term FPR of the cBED assay is substantially lower than previous estimates. The cBED assay performs well in HIV incidence estimation if the locally measured long-term FPR is used, but significantly underestimates incidence when a FPR estimate based on previous studies in other settings is used. © 2008 Bärnighausen et al.Publishers' Versio

Global Patterns in Seasonal Activity of Influenza A/H3N2, A/H1N1, and B from 1997 to 2005: Viral Coexistence and Latitudinal Gradients

Despite a mass of research on the epidemiology of seasonal influenza, overall patterns of infection have not been fully described on broad geographic scales and for specific types and subtypes of the influenza virus. Here we provide a descriptive analysis of laboratory-confirmed influenza surveillance data by type and subtype (A/H3N2, A/H1N1, and B) for 19 temperate countries in the Northern and Southern hemispheres from 1997 to 2005, compiled from a public database maintained by WHO (FluNet). Key findings include patterns of large scale co-occurrence of influenza type A and B, interhemispheric synchrony for subtype A/H3N2, and latitudinal gradients in epidemic timing for type A. These findings highlight the need for more countries to conduct year-round viral surveillance and report reliable incidence data at the type and subtype level, especially in the Tropics

High HIV Incidence and Sexual Behavior Change among Pregnant Women in Lilongwe, Malawi: Implications for the Risk of HIV Acquisition

HIV incidence is higher among pregnant women than their non-pregnant counterparts in some sub-Saharan African settings. Our aims were (1) to estimate HIV incidence during pregnancy and (2) to compare sexual activity between pregnant, postpartum, and non-pregnant women.We examined a retrospective cohort of 1087 women to identify seroconverters using antenatal and labor ward HIV test results. We also conducted a cross-sectional survey, including a quantitative questionnaire (n = 200) and in-depth interviews (n = 20) among women in early pregnancy, late pregnancy, postpartum, and non-pregnancy. Outcomes included measures of sexual activity, reported spouse's risky behavior, and beliefs about abstinence.11 of 1087 women seroconverted during pregnancy yielding a 1% seroconversion risk and an incidence rate of 4.0/100 person years (95% CI 2.2-7.2). The reported sexual activity of the early pregnancy and non-pregnancy groups was similar, but significantly higher than the late pregnancy and postpartum groups (p<0.001). During pregnancy, sex acts decreased as gestation increased (p = 0.001). There was no reported difference in the spouse's risky behavior. Most women believed that sex should cease between the 6(th) and 8(th) month of pregnancy and should not resume until 6 months postpartum. Some talked about conflict between their cultural obligation to abstain and fear of HIV infection if their spouses find other partners.HIV incidence is high among pregnant women in Malawi, and sexual activity decreases during pregnancy and postpartum. Pregnant women need to be informed of their increased risk for HIV and the importance of using condoms throughout pregnancy and the postpartum period

Population-Level Reduction in Adult Mortality after Extension of Free Anti-Retroviral Therapy Provision into Rural Areas in Northern Malawi

BACKGROUND: Four studies from sub-Saharan Africa have found a substantial population-level effect of ART provision on adult mortality. It is important to see if the impact changes with time since the start of treatment scale-up, and as treatment moves to smaller clinics. METHODS AND FINDINGS: During 2002-4 a demographic surveillance site (DSS) was established in Karonga district, northern Malawi. Information on births and deaths is collected monthly, with verbal autopsies conducted for all deaths; migrations are updated annually. We analysed mortality trends by comparing three time periods: pre-ART roll-out in the district (August 2002-June 2005), ART period 1 (July 2005-September 2006) when ART was available only in a town 70 km away, and ART period 2 (October 2006-September 2008), when ART was available at a clinic within the DSS area. HIV prevalence and ART uptake were estimated from a sero-survey conducted in 2007/2008. The all-cause mortality rate among 15-59 year olds was 10.2 per 1000 person-years in the pre-ART period (288 deaths/28285 person-years). It fell by 16% in ART period 1 and by 32% in ART period 2 (95% CI 18%-43%), compared with the pre-ART period. The AIDS mortality rate fell from 6.4 to 4.6 to 2.7 per 1000 person-years in the pre-ART period, period 1 and period 2 respectively (rate ratio for period 2 = 0.43, 95% CI 0.33-0.56). There was little change in non-AIDS mortality. Treatment coverage among individuals eligible to start ART was around 70% in 2008. CONCLUSIONS: ART can have a dramatic effect on mortality in a resource-constrained setting in Africa, at least in the early years of treatment provision. Our findings support the decentralised delivery of ART from peripheral health centres with unsophisticated facilities. Continued funding to maintain and further scale-up treatment provision will bring large benefits in terms of saving lives

Association of Age with Mortality and Virological and Immunological Response to Antiretroviral Therapy in Rural South African Adults

OBJECTIVE: To assess whether treatment outcomes vary with age for adults receiving antiretroviral therapy (ART) in a large rural HIV treatment cohort. DESIGN: Retrospective cohort analysis using data from a public HIV Treatment & Care Programme. METHODS: Adults initiating ART 1(st) August 2004-31(st) October 2009 were stratified by age at initiation: young adults (16-24 years) mid-age adults (25-49 years) and older (≥50 years) adults. Kaplan-Meier survival analysis was used to estimate mortality rates and age and person-time stratified Cox regression to determine factors associated with mortality. Changes in CD4 cell counts were quantified using a piecewise linear model based on follow-up CD4 cell counts measured at six-monthly time points. RESULTS: 8846 adults were included, 808 (9.1%) young adults; 7119 (80.5%) mid-age adults and 919 (10.4%) older adults, with 997 deaths over 14,778 person-years of follow-up. Adjusting for baseline characteristics, older adults had 32% excess mortality (p = 0.004) compared to those aged 25-49 years. Overall mortality rates (MR) per 100 person-years were 6.18 (95% CI 4.90-7.78); 6.55 (95% CI 6.11-7.02) and 8.69 (95% CI 7.34-10.28) for young, mid-age and older adults respectively. In the first year on ART, for older compared to both young and mid-aged adults, MR per 100 person-years were significantly higher; 0-3 months (MR: 27.1 vs 17.17 and 21.36) and 3-12 months (MR: 9.5 vs 4.02 and 6.02) respectively. CD4 count reconstitution was lower, despite better virological response in the older adults. There were no significant differences in MR after 1 year of ART. Baseline markers of advanced disease were independently associated with very early mortality (0-3 months) whilst immunological and virological responses were associated with mortality after 12 months. CONCLUSIONS: Early ART initiation and improving clinical care of older adults are required to reduce high early mortality and enhance immunologic recovery, particularly in the initial phases of ART

Environmental Factors Influence Language Development in Children with Autism Spectrum Disorders

International audienc

Estimating Loss to Follow-Up in HIV-Infected Patients on Antiretroviral Therapy: The Effect of the Competing Risk of Death in Zambia and Switzerland

BACKGROUND: Loss to follow-up (LTFU) is common in antiretroviral therapy (ART) programmes. Mortality is a competing risk (CR) for LTFU; however, it is often overlooked in cohort analyses. We examined how the CR of death affected LTFU estimates in Zambia and Switzerland. METHODS AND FINDINGS: HIV-infected patients aged ≥18 years who started ART 2004-2008 in observational cohorts in Zambia and Switzerland were included. We compared standard Kaplan-Meier curves with CR cumulative incidence. We calculated hazard ratios for LTFU across CD4 cell count strata using cause-specific Cox models, or Fine and Gray subdistribution models, adjusting for age, gender, body mass index and clinical stage. 89,339 patients from Zambia and 1,860 patients from Switzerland were included. 12,237 patients (13.7%) in Zambia and 129 patients (6.9%) in Switzerland were LTFU and 8,498 (9.5%) and 29 patients (1.6%), respectively, died. In Zambia, the probability of LTFU was overestimated in Kaplan-Meier curves: estimates at 3.5 years were 29.3% for patients starting ART with CD4 cells <100 cells/µl and 15.4% among patients starting with ≥350 cells/µL. The estimates from CR cumulative incidence were 22.9% and 13.6%, respectively. Little difference was found between naïve and CR analyses in Switzerland since only few patients died. The results from Cox and Fine and Gray models were similar: in Zambia the risk of loss to follow-up and death increased with decreasing CD4 counts at the start of ART, whereas in Switzerland there was a trend in the opposite direction, with patients with higher CD4 cell counts more likely to be lost to follow-up. CONCLUSIONS: In ART programmes in low-income settings the competing risk of death can substantially bias standard analyses of LTFU. The CD4 cell count and other prognostic factors may be differentially associated with LTFU in low-income and high-income settings

Knee stability assessment on anterior cruciate ligament injury: Clinical and biomechanical approaches

Anterior cruciate ligament (ACL) injury is common in knee joint accounting for 40% of sports injury. ACL injury leads to knee instability, therefore, understanding knee stability assessments would be useful for diagnosis of ACL injury, comparison between operation treatments and establishing return-to-sport standard. This article firstly introduces a management model for ACL injury and the contribution of knee stability assessment to the corresponding stages of the model. Secondly, standard clinical examination, intra-operative stability measurement and motion analysis for functional assessment are reviewed. Orthopaedic surgeons and scientists with related background are encouraged to understand knee biomechanics and stability assessment for ACL injury patients