Treatment Interruption after Pregnancy: Effects on Disease Progression and Laboratory Findings

Objective. To assess clinical progression and inflammatory markers among women stopping or continuing antiretroviral therapy (ART) after pregnancy. Methods. ART-naïve women with CD4+ lymphocyte counts >350 cells/uL initiating ART during pregnancy had clinical events and laboratory markers compared over one year postpartum between those stopping (n = 59) or continuing (n = 147) ART. Results. Slopes in CD4 count and HIV RNA did not differ between groups overall and in subsets of ZDV or combination therapy. The hazard ratio (HR) of a new class B event was 2.09 (95% CI 0.79–5.58) among women stopping ART, 1.24 (0.31–4.95) in those stopping ZDV, and 2.93 (0.64–13.36) among those stopping combination therapy. Women stopping ART had increased immune activation. No significant differences were seen in C-reactive protein, lipids, leptin, or interleukin-6. Conclusions. While changes in CD4 and HIV RNA levels over one year were similar between women stopping or continuing ART postpartum, higher immune activation among women stopping therapy requires further study

Treatment Interruption after Pregnancy: Effects on Disease Progression and Laboratory Findings

Objective. To assess clinical progression and inflammatory markers among women stopping or continuing antiretroviral therapy (ART) after pregnancy. Methods. ART-naïve women with CD4+ lymphocyte counts >350 cells/uL initiating ART during pregnancy had clinical events and laboratory markers compared over one year postpartum between those stopping (n = 59) or continuing (n = 147) ART. Results. Slopes in CD4 count and HIV RNA did not differ between groups overall and in subsets of ZDV or combination therapy. The hazard ratio (HR) of a new class B event was 2.09 (95% CI 0.79–5.58) among women stopping ART, 1.24 (0.31–4.95) in those stopping ZDV, and 2.93 (0.64–13.36) among those stopping combination therapy. Women stopping ART had increased immune activation. No significant differences were seen in C-reactive protein, lipids, leptin, or interleukin-6. Conclusions. While changes in CD4 and HIV RNA levels over one year were similar between women stopping or continuing ART postpartum, higher immune activation among women stopping therapy requires further study

A Genome-Wide Comparative Evolutionary Analysis of Herpes Simplex Virus Type 1 and Varicella Zoster Virus

Herpes simplex virus type 1 (HSV-1) and varicella zoster virus (VZV) are closely related viruses causing lifelong infections. They are typically associated with mucocutaneous or skin lesions, but may also cause severe neurological or ophthalmic diseases, possibly due to viral- and/or host-genetic factors. Although these viruses are well characterized, genome-wide evolutionary studies have hitherto only been presented for VZV. Here, we present a genome-wide study on HSV-1. We also compared the evolutionary characteristics of HSV-1 with those for VZV. We demonstrate that, in contrast to VZV for which only a few ancient recombination events have been suggested, all HSV-1 genomes contain mosaic patterns of segments with different evolutionary origins. Thus, recombination seems to occur extremely frequent for HSV-1. We conclude by proposing a timescale for HSV-1 evolution, and by discussing putative underlying mechanisms for why these otherwise biologically similar viruses have such striking evolutionary differences

Neurocognitive Consequences of HIV Infection in Older Adults: An Evaluation of the “Cortical” Hypothesis

The incidence and prevalence of older adults living with HIV infection is increasing. Recent reports of increased neuropathologic and metabolic alterations in older HIV+ samples, including increased cortical beta-amyloid, have led some researchers to suggest that aging with HIV may produce a neuropsychological profile akin to that which is observed in “cortical” dementias (e.g., impairment in memory consolidation). To evaluate this possibility, we examined four groups classified by HIV serostatus and age (i.e., younger ≤40 years and older ≥50 years): (1) Younger HIV− (n = 24); (2) Younger HIV+ (n = 24); (3) Older HIV− (n = 20); and (4) Older HIV+ (n = 48). Main effects of aging were observed on episodic learning and memory, executive functions, and visuoconstruction, and main effects of HIV were observed on measures of verbal learning and memory. The interaction of age and HIV was observed on a measure of verbal recognition memory, which post hoc analyses showed to be exclusively attributed to the superior performance of the younger HIV seronegative group. Thus, in this sample of older HIV-infected individuals, the combined effects of HIV and aging do not appear to result in a “cortical” pattern of cognitive deficits

Impact of H1N1 on Socially Disadvantaged Populations: Systematic Review

The burden of H1N1 among socially disadvantaged populations is unclear. We aimed to synthesize hospitalization, severe illness, and mortality data associated with pandemic A/H1N1/2009 among socially disadvantaged populations.Studies were identified through searching MEDLINE, EMBASE, scanning reference lists, and contacting experts. Studies reporting hospitalization, severe illness, and mortality attributable to laboratory-confirmed 2009 H1N1 pandemic among socially disadvantaged populations (e.g., ethnic minorities, low-income or lower-middle-income economy countries [LIC/LMIC]) were included. Two independent reviewers conducted screening, data abstraction, and quality appraisal (Newcastle Ottawa Scale). Random effects meta-analysis was conducted using SAS and Review Manager.Sixty-two studies including 44,777 patients were included after screening 787 citations and 164 full-text articles. The prevalence of hospitalization for H1N1 ranged from 17-87% in high-income economy countries (HIC) and 11-45% in LIC/LMIC. Of those hospitalized, the prevalence of intensive care unit (ICU) admission and mortality was 6-76% and 1-25% in HIC; and 30% and 8-15%, in LIC/LMIC, respectively. There were significantly more hospitalizations among ethnic minorities versus non-ethnic minorities in two studies conducted in North America (1,313 patients, OR 2.26 [95% CI: 1.53-3.32]). There were no differences in ICU admissions (n = 8 studies, 15,352 patients, OR 0.84 [0.69-1.02]) or deaths (n = 6 studies, 14,757 patients, OR 0.85 [95% CI: 0.73-1.01]) among hospitalized patients in HIC. Sub-group analysis indicated that the meta-analysis results were not likely affected by confounding. Overall, the prevalence of hospitalization, severe illness, and mortality due to H1N1 was high for ethnic minorities in HIC and individuals from LIC/LMIC. However, our results suggest that there were little differences in the proportion of hospitalization, severe illness, and mortality between ethnic minorities and non-ethnic minorities living in HIC

Osteoprotegerin antibodies in the pathogenesis of osteoporosis

Osteoporosis is a common complication of many autoimmune diseases that is typically attributed to disease specific factors rather than a direct autoimmune process. This thesis arises from the investigation of a patient with severe high bone turnover osteoporosis who was identified as having autoimmune disease but whose osteoporosis deteriorated despite appropriate treatment. This presentation led to the hypothesis that neutralising autoantibodies to the bone protective cytokine osteoprotegerin (OPG) may have developed. Serum from the index patient, but not healthy controls, was able to immunoprecipitate recombinant OPG protein, demonstrating that OPG had become the target of an autoimmune response. Purified immunoglobulins from the index case were able to inhibit the function of OPG in vitro, by suppressing OPG-mediated inhibition of a luciferase reporter cell line. This represents the first description of disease associated with neutralising antibodies to OPG. Whilst the immunoprecipitation assay did identify OPG antibodies in further patients these results were difficult to quantify. A more robust enzyme linked immunosorbent assay for OPG antibodies was developed using OPG as a capture antigen, which allowed the screening of patient cohorts. Presence of OPG antibodies was defined as a titre greater than the mean plus three standard deviations of 101 healthy volunteers. A low prevalence of 14/864 (1.6%) was seen in a general population cohort and no association with bone density or turnover was seen. An association with higher vascular calcification score in this cohort requires replication. A prevalence of 37/315 (11.7%) was seen in an osteoporosis cohort though no association was seen with bone density or response to treatment. In a coeliac cohort OPG antibodies were identified in 14/282 (5.0%) patients and presence of antibody was independently associated with reduced spine bone density. Functional inhibition of OPG was shown in vitro in 3/14 (21.4%) of the positive cases. Case finding of osteoporosis in the coeliac cohort was not improved by identification of OPG antibodies. These results are consistent with OPG antibodies being pathological in a small number of patients with osteoporosis but a clinical utility of measuring OPG antibodies has not been established