HIV disease is associated with chronic inflammation and activation of the innate immune system. This state, as measured using plasma markers of inflammation, persists following suppression of HIV viremia using antiretroviral therapy, and may increase risk of non-AIDS co-morbidities. The causes of innate immune activation in the setting of virological suppression are unclear. Natural killer (NK) cells are innate immune cells that kill virus-infected and transformed cells without prior sensitization. We have shown that NK cells are activated both phenotypically (elevated expression of HLA-DR) and functionally (increased spontaneous degranulation measured by CD107a surface expression) in virologically suppressed (VS) HIV+ individuals. NK cells also lose expression of CD16, the receptor which mediates antibody-dependent cellular cytotoxicity.
In multivariable analysis, activation of NK cells was not associated with HIV viremia or with CD4 counts but was associated with markers of inflammation (soluble CD14, neopterin and plasma LPS)1. We have identified a novel NK cell population (ΔγNK) in HIV+ patients. ΔγNKs switch off expression of the CD16 signaling adaptor molecule FcRγ, but have normal expression of the alternate signaling molecule TCRζ. ΔγNKs are retained in VS HIV+ individuals, where they account for up to 90% of total NK cells, but are not present in CMV seronegative HIV+ patients. ΔγNKs have recently been described as being generated specifically in response to CMV infection or reactivation2. In HIV-/CMV+ individuals ΔγNK cells have increased antibody- dependent killing activity and cytokine production but decreased natural cytotoxicity, and are thought to be specialized for antibody-dependent activation2. How HIV co-infection impacts ΔγNK function is unclear. We are currently studying the properties of ΔγNK cells in HIV+ individuals to understand the significance of such a dramatic skewing of the NK cell population to anti HIV NK cell activity.
1. Lichtfuss et al (2012) “Virologically Suppressed HIV Patients Show Activation of NK Cells and Persistent Innate Immune Activation” The Journal of Immunology 189, 1491–1499
2. Zhang et al (2013) “Cutting Edge: Antibody-Dependent Memory-like NK Cells Distinguished by FcRγ Deficiency” The Journal of Immunology 190, 1402–1406
Adherence to combination antiretroviral therapy (cART ) plays an important role on treatment outcomes. The TREAT Asia Studies to Evaluate Resistance – Monitoring Cohort Study (TASER-M) collects patients’ adherence based on a Visual Analogue Scale. The aim of this analysis was to assess the rates of, and factors associated with, suboptimal adherence in the first 24 months of initial cART in Asian patients.
REACH was a collaborative research and practice initiative to develop evidence building frameworks, capacity, tools and resources with the Victorian HIV community partnership.
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HIV-associated leishmaniasis, endemic in the Mediterranean basin is a growing problem in India, Brazil and East Africa. Despite surviving for than 20 years, the clinical course of our visceral-leishmania (VL)-HIV co-infected patient illustrates several management challenges including diagnosis, speciation and drug resistance; monitoring burden of disease; access to and use of VL-treatments; end-organ toxicity and the combined immunosuppressive effects of HIV-VL.
Early first sexual intercourse has been proposed as an important marker of later sexual and reproductive health. Discussions of what constitutes early sexual debut in this context, however, have been limited.
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