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Parsons M.S.,University of Melbourne | Loh L.,University of Melbourne | Gooneratne S.,University of Melbourne | Center R.J.,University of Melbourne | And 3 more authors.
AIDS | Year: 2014

Antibody-dependent activation of natural killer (NK) cells might facilitate protective outcomes in the context of HIV exposure or infection. Antibody- dependent activation is heightened in NK cells educated by interactions between killer immunoglobulin-like receptors (KIRs) and their major histocompatibility complex class I ligands during ontogeny. Differentiated NK cells, defined as CD57+, also exhibit enhanced antibody-dependent responsiveness. Although KIRs are more frequently expressed on CD57+ NK cells, the presented data suggest education and differentiation make independent contributions to NK cell anti- HIV envelope antibody-dependent activation. © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins. Source

Lifson A.R.,University of Minnesota | Neuhaus J.,University of Minnesota | Arribas J.R.,Hospital Universitario La Paz | Van Berg-Wolf M.D.,Temple University | And 2 more authors.
American Journal of Public Health | Year: 2010

Objectives. We sought to determine smoklng-related hazard ratios (HRs) and population-attributable risk percentage (PAR%) for serious clinical events and death among HIV-positive persons, whose smoking prevalence is higher than In the generai population. Methods. For 5472 HIV-infected persons enrolled from 33 countries in the Strategies for Management of Antiretroviral Therapy clinical trial, we evaluated the relationship between baseline smoking status and development of AIDSrelated or serious non-AIDS events and overall mortality. Results. Among all participants, 40.5% were current smokers and 24.8% were former smokers. Adjusted HRs were higher for current than for never smokers for overall mortality (2.4; P<.001), major cardiovascular disease (2.0; P=,002), non-AIDS cancer (1.8; P= .008), and bacterial pneumonia (2.3; P<.001). Adjusted HRs also were significantly higher for these outcomes among current than among former smokers. The PAR% for current versus former and never smokers combined was 24.3% for overall mortality, 25.3% for major cardiovascular disease, 30.6% for non-AIDS cancer, and 25.4% for bacterial pneumonia. Conclusions. Smoking contributes to substantial morbidity and mortality in this HIV-infected population. Providers should routinely integrate smoking cessation programs into HIV health care. Source

Machalek D.A.,University of New South Wales | Poynten M.,University of New South Wales | Jin F.,University of New South Wales | Fairley C.K.,Melbourne Sexual Health Center | And 13 more authors.
The Lancet Oncology | Year: 2012

Background: Men who have sex with men (MSM) are at greatly increased risk of human papillomavirus (HPV)-associated anal cancer. Screening for the presumed cancer precursor, high-grade anal intraepithelial neoplasia (AIN), followed by treatment in a manner analogous to cervical screening, has been proposed. We aimed to assess available data for anal HPV disease that can inform pre-cancer screening programmes. Methods: We searched PubMed, OVID Medline, and Embase for all studies published before Nov 1, 2011, that reported prevalence and incidence of anal HPV detection, AIN, and anal cancer in MSM. We calculated summary estimates using random-effects meta-analysis. Findings: 53 studies met the inclusion criteria, including 31 estimates of HPV prevalence, 19 estimates of cytological abnormalities, eight estimates of histological abnormalities, and nine estimates of anal cancer incidence. Data for incident HPV and high-grade AIN were scarce. In HIV-positive men, the pooled prevalence of anal HPV-16 was 35·4% (95% CI 32·9-37·9). In the only published estimate, incidence of anal HPV-16 was 13·0% (9·6-17·6), and clearance occurred in 14·6% (10·2-21·2) of men per year. The pooled prevalence of histological high-grade AIN was 29·1% (22·8-35·4) with incidences of 8·5% (6·9-10·4) and 15·4% (11·8-19·8) per year in two estimates. The pooled anal cancer incidence was 45·9 per 100 000 men (31·2-60·3). In HIV-negative men, the pooled prevalence of anal HPV-16 was 12·5% (9·8-15·4). Incidence of HPV-16 was 11·8% (9·2-14·9) and 5·8% (1·9-13·5) of men per year in two estimates. The pooled prevalence of histological high-grade AIN was 21·5% (13·7-29·3), with incidence of 3·3% (2·2-4·7) and 6·0% (4·2-8·1) per year in two estimates. Anal cancer incidence was 5·1 per 100 000 men (0-11·5; based on two estimates). There were no published estimates of high-grade AIN regression. Interpretation: Anal HPV and anal cancer precursors were very common in MSM. However, on the basis of restricted data, rates of progression to cancer seem to be substantially lower than they are for cervical pre-cancerous lesions. Large, good-quality prospective studies are needed to inform the development of anal cancer screening guidelines for MSM. Funding: Australian Government Department of Health and Ageing. © 2012 Elsevier Ltd. Source

Callander D.,University of New South Wales | Baker D.,East Sydney Doctors | Chen M.,University of Melbourne | Chen M.,Melbourne Sexual Health Center | Guy R.,University of New South Wales
Sexually Transmitted Diseases | Year: 2013

Opt-out syphilis testing routinely conducted during HIV management checks increased testing rates for gay men with HIV in a primary care setting. Although successfully increasing testing rates, this strategy failed to meet quarterly testing guidelines, which could point to the need for additional strategies and guideline revaluation. Copyright © 2013 American Sexually Transmitted Diseases Association. Source

Gooneratne S.L.,University of Melbourne | Richard J.,University of Montreal | Lee W.S.,University of Melbourne | Finzi A.,University of Montreal | And 3 more authors.
Journal of Virology | Year: 2015

Many attempts to design prophylactic human immunodeficiency virus type 1 (HIV-1) vaccines have focused on the induction of neutralizing antibodies (Abs) that block infection by free virions. Despite the focus on viral particles, virus-infected cells, which can be found within mucosal secretions, are more infectious than free virus both in vitro and in vivo. Furthermore, assessment of human transmission couples suggests infected seminal lymphocytes might be responsible for a proportion of HIV-1 transmissions. Although vaccines that induce neutralizing Abs are sought, only some broadly neutralizing Abs efficiently block cell-tocell transmission of HIV-1. As HIV-1 vaccines need to elicit immune responses capable of controlling both free and cell-associated virus, we evaluated the potential of natural killer (NK) cells to respond in an Ab-dependent manner to allogeneic T cells bearing HIV-1 antigens. This study presents data measuring Ab-dependent anti-HIV-1 NK cell responses to primary and transformed allogeneic T-cell targets. We found that NK cells are robustly activated in an anti-HIV-1 Ab-dependent manner against allogeneic targets and that tested target cells are subject to Ab-dependent cytolysis. Furthermore, the educated KIR3DL1+ NK cell subset from HLA-Bw4+ individuals exhibits an activation advantage over the KIR3DL1- subset that contains both NK cells educated through other receptor/ligand combinations and uneducated NK cells. These results are intriguing and important for understanding the regulation of Ab-dependent NK cell responses and are potentially valuable for designing Ab-dependent therapies and/or vaccines. © 2015, American Society for Microbiology. Source

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