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

Abnormal responses of myeloid progenitor cells to granulocyte-macrophage colony-stimulating factor in human cyclic neutropenia.

Granulocyte-macrophage progenitors (CFU-GM) from four patients with childhood onset cyclic neutropenia demonstrated abnormal in vitro proliferative responses to purified, recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) when examined in detailed dose-response studies. Marrow aspirate specimens were obtained for these studies from cyclic neutropenia patients (both during neutropenic nadirs and during recovery phases of cycles), from leukemia patients in remission who had received myelosuppressive chemotherapy, and from healthy normal volunteers. Nucleated marrow cells were then isolated by density-gradient centrifugation and cryopreserved to permit studies of CFU-GM from patients and controls to be carried out at the same time and in replicate. Maximum clonal growth of CFU-GM from normal subjects and from individuals recovering from drug-induced myelosuppression was elicited by 20-100 pmol/liter rhGM-CSF, and the CSF concentrations that induced half-maximal responses (ED50) were between 1.0 and 3.0 pmol/liter. In contrast, maximum growth of CFU-GM from the cyclic neutropenia patients required greater than or equal to 1.0 nmol/liter rhGM-CSF and ED50's were greater than 30.0 pmol/liter. These abnormalities in the GM-CSF responsive growth of myeloid progenitors were independent of cycle time and were most apparent with the predominantly neutrophilic 7-d CFU-GM. Moreover, differences in the growth of 14-d CFU-GM could be attributed mostly if not entirely to differences in the generation of neutrophilic colonies. These findings indicate that childhood onset cyclic neutropenia is associated with an underlying disturbance in the GM-CSF responsive growth of myeloid progenitors committed to neutrophilic differentiation

Case Report of Subcutaneous Nodules and Sterile Abscesses Due to Delayed Type Hypersensitivity to Aluminum-Containing Vaccines

Routine childhood immunizations have resulted in great reductions in vaccine-preventable infectious diseases. Vaccine-related adverse events, albeit rare, can be of significant consequence. Although anaphylaxis, or type I hypersensitivity, is recognized as a potential reaction after vaccination, delayed type hypersensitivity or type IV reactions are less so. We present a case of persistent subcutaneous nodules and sterile abscesses in the setting of delayed type hypersensitivity to aluminum, confirmed by patch testing and recurrence on re-exposure. We review sources of aluminum in common immunizations, principles for treatment, and strategies for management of future vaccinations for this patient.</jats:p