Public-health and individual approaches to antiretroviral therapy: township South Africa and Switzerland compared

Background

The provision of highly active antiretroviral therapy (HAART) in resource-limited settings follows a public health approach, which is characterised by a limited number of regimens and the standardisation of clinical and laboratory monitoring. In industrialized countries doctors prescribe from the full range of available antiretroviral drugs, supported by resistance testing and frequent laboratory monitoring. We compared virologic response, changes to first-line regimens, and mortality in HIV-infected patients starting HAART in South Africa and Switzerland.

Methods and Findings

We analysed data from the Swiss HIV Cohort Study and two HAART programmes in townships of Cape Town, South Africa. We included treatment-naïve patients aged 16 y or older who had started treatment with at least three drugs since 2001, and excluded intravenous drug users. Data from a total of 2,348 patients from South Africa and 1,016 patients from the Swiss HIV Cohort Study were analysed. Median baseline CD4⁺ T cell counts were 80 cells/μl in South Africa and 204 cells/μl in Switzerland. In South Africa, patients started with one of four first-line regimens, which was subsequently changed in 514 patients (22%). In Switzerland, 36 first-line regimens were used initially, and these were changed in 539 patients (53%). In most patients HIV-1 RNA was suppressed to 500 copies/ml or less within one year: 96% (95% confidence interval [CI] 95%–97%) in South Africa and 96% (94%–97%) in Switzerland, and 26% (22%–29%) and 27% (24%–31%), respectively, developed viral rebound within two years. Mortality was higher in South Africa than in Switzerland during the first months of HAART: adjusted hazard ratios were 5.90 (95% CI 1.81–19.2) during months 1–3 and 1.77 (0.90–3.50) during months 4–24.

Conclusions

Compared to the highly individualised approach in Switzerland, programmatic HAART in South Africa resulted in similar virologic outcomes, with relatively few changes to initial regimens. Further innovation and resources are required in South Africa to both achieve more timely access to HAART and improve the prognosis of patients who start HAART with advanced disease.     

Long-term safety and efficacy of enzyme replacement therapy for Fabry disease

Elsewhere, we reported the safety and efficacy results of a multicenter phase 3 trial of recombinant human alpha -galactosidase A (rh-alpha GalA) replacement in patients with Fabry disease. All 58 patients who were enrolled in the 20-wk phase 3 double-blind, randomized, and placebo-controlled study received subsequently 1 mg/kg of rh-alpha GalA (agalsidase beta, Fabrazyme, Genzyme Corporation) biweekly in an ongoing open-label extension study. Evidence of long-term efficacy, even in patients who developed IgG antibodies against rh- alpha GalA, included the continuously normal mean plasma globotriaosylceramide (GL-3) levels during 30 mo of the extension study and the sustained capillary endothelial GL-3 clearance in 98% (39/40) of patients who had a skin biopsy taken after treatment for 30 mo (original placebo group) or 36 mo (original enzyme-treated group). The mean serum creatinine level and estimated glomerular filtration rate also remained stable after 30-36 mo of treatment. Infusion-associated reactions decreased over time, as did anti-rh- alpha GalA IgG antibody titers. Among seroconverted patients, after 30-36 mo of treatment, seven patients tolerized (no detectable IgG antibody), and 59% had > or =4-fold reductions in antibody titers. As of 30 mo into the extension trial, three patients were withdrawn from the study because of positive serum IgE or skin tests; however, all have been rechallenged successfully at the time of this report. Thus, enzyme replacement therapy for 30-36 mo with agalsidase beta resulted in continuously decreased plasma GL-3 levels, sustained endothelial GL-3 clearance, stable kidney function, and a favorable safety profile.     

Summary statement on quantitative cytochemistry (DNA and molecular biology): Task Force 8

OBJECTIVE: To reach consensus on the application of quantitative cytochemical analysis of chromosomal and DNA aneuploidy in cervical cytopathology. CONCLUSION: The current Pap test has limited specificity to predict cancer and its truly progressive pre-malignant lesions. Infection with human papillomavirus may trigger genetic instability, hyperproliferation and immortalization of the cervical mucosa and cause cervical cancer. Several related molecular markers have been shown to be informative about this neoplastic process. Quantitative analysis of chromosomal and DNA aneuploidy has been shown to be an important tool for identifying (progression to) high grade squamous intraepithelial lesions. A high degree of standardization (material handling, calibration and quality control, measurement and interpretation of results) is required for accurate and reproducible measurements. Areas for further study are presented.     

Histological Classif ication of Gastritis and Helicobacter pylori Infection: An Agreement at Last?

An international workshop has assessed and revised the Sydney System for the reporting of gastritis. Much of the original approach was retained including division into acute , chronic and special forms, and grading of chronic inflammation, polymorph activity, atrophy, intestinal metaplasia and H. pylori density into mild, moderate and marked categories. Visual analog scales have been introduced as a simple guide to grading. The four biopsy sites have been changed to optimize detection of H. pylori , and supplemented by a fifth biopsy from the incisura angularis, the site which is most likely to yield premalignant changes. Chronic gastritis is classified into non-atrophic and atrophic forms with the latter divided into autoimmune (diffuse corpus atrophy) and multifocal . Histological reporting of gastritis should take into account the topographical pattern ( antral or corpus predominant ), and the final diagnostic term should ideally combine morphology and etiology to maximize the clinical value of gastric biopsy diagnosis.     

Implementation of Tuberculosis Intensive Case Finding,Isoniazid Preventive Therapy,and Infection Control ("Three I's") and HIV-Tuberculosis Service Integration in Lower Income Countries

SettingWorld Health Organization advocates for integration of HIV-tuberculosis (TB) services and recommends intensive case finding (ICF), isoniazid preventive therapy (IPT), and infection control (“Three I’s”) for TB prevention and control among persons living with HIV.ObjectiveTo assess the implementation of the “Three I’s” of TB-control at HIV treatment sites in lower income countries.DesignSurvey conducted between March-July, 2012 at 47 sites in 26 countries: 6 (13%) Asia Pacific, 7 (15%), Caribbean, Central and South America, 5 (10%) Central Africa, 8 (17%) East Africa, 14 (30%) Southern Africa, and 7 (15%) West Africa.ResultsICF using symptom-based screening was performed at 38% of sites; 45% of sites used symptom-screening plus additional diagnostics. IPT at enrollment or ART initiation was implemented in only 17% of sites, with 9% of sites providing IPT to tuberculin-skin-test positive patients. Infection control measures varied: 62% of sites separated smear-positive patients, and healthcare workers used masks at 57% of sites. Only 12 (26%) sites integrated HIV-TB services. Integration was not associated with implementation of TB prevention measures except for IPT provision at enrollment (42% integrated vs. 9% non-integrated; p = 0.03).ConclusionsImplementation of TB screening, IPT provision, and infection control measures was low and variable across regional HIV treatment sites, regardless of integration status.     

A New Graves Disease–Susceptibility Locus Maps To Chromosome 20q11.2

The autoimmune thyroid diseases (AITDs) include two related disorders, Graves disease (GD) and Hashimoto thyroiditis, in which perturbations of immune regulation result in an immune attack on the thyroid gland. The AITDs are multifactorial and develop in genetically susceptible individuals. However, the genes responsible for this susceptibility remain unknown. Recently, we initiated a whole-genome linkage study of patients with AITD, in order to identify their susceptibility genes. We studied a data set of 53 multiplex, multigenerational AITD families (323 individuals), using highly polymorphic and densely spaced microsatellite markers (intermarker distance <10 cM). Linkage analysis was performed by use of two-point and multipoint parametric methods (classic LOD-score analysis). While studying chromosome 20, we found a locus on chromosome 20q11.2 that was strongly linked to GD. A maximum two-point LOD score of 3.2 was obtained at marker D20S195, assuming a recessive mode of inheritance and a penetrance of.3. The maximum nonparametric LOD score was 2.4 (P=.00043); this score also was obtained at marker D20S195. Multipoint linkage analysis yielded a maximum LOD score of 3.5 for a 6-cM interval between markers D20S195 and D20S107. There was no evidence for heterogeneity in our sample. In our view, these results indicate strong evidence for linkage and suggest the presence of a major GD-susceptibility gene on chromosome 20q11.2.     

Protection of patients' rights to privacy

The following statement was agreed [upon] by the International Committee of Medical Journal Editors (the Vancouver Group) at its meeting last week in San Francisco. It is a complete revision of the initial guidelines on this subject issued in 1991.     

应用原位杂交及免疫组化检测肝活检组织中流行性出血热病毒RNA及抗原

本文应用原位杂交及免疫组化技术对25例流行性出血热(EHF)患者肝活检组织进行了病毒RNA及其囊膜G_2蛋白的定位检测,结合光镜,认为肝细胞的变性、胞浆疏松化、点状坏死是EHF病毒直接侵犯并在其胞浆内增殖表达所致,肝组织的灶状坏死则主要是肝窦狭窄、枯否氏细胞增生导致微循环障碍引起的缺血性梗死。急性脂褐素沉积是病毒侵犯肝细胞的间接证据。研究还发现,肝细胞内病毒的多少与病程关系不明确,而与临床分型有一定相关,为探讨EHF的发病机制提供了分子水平的依据。