Cytomegalovirus Infection May Contribute to the Reduced Immune Function, Growth, Development, and Health of HIV-Exposed, Uninfected African Children.

With increasing access to antiretroviral therapy (ART) in Africa, most children born to HIV-infected mothers are not themselves HIV-infected. These HIV-exposed, uninfected (HEU) children are at increased risk of mortality and have immune, growth, development, and health deficits compared to HIV-unexposed children. HEU children are known to be at higher risk than HIV-unexposed children of acquiring cytomegalovirus (CMV) infection in early life. This risk is largely unaffected by ART and is increased by breastfeeding, which itself is critically important for child health and survival. Early CMV infection, namely in utero or during early infancy, may contribute to reduced growth, altered or impaired immune functions, and sensory and cognitive deficits. We review the evidence that CMV may be responsible for the health impairments of HEU children. There are currently no ideal safe and effective interventions to reduce postnatal CMV infection. If a clinical trial showed proof of the principle that decreasing early CMV infection improved health and development of HEU children, this could provide the impetus needed for the development of better interventions to improve the health of this vulnerable population

Lessons from the failure of the adenovector HIV vaccine

The much-publicised halting of the joint Merck/HIV Vaccine Trials Network phase IIB candidate HIV-1 vaccine trial in 2007 has led to an unprecedented degree of discussion and introspection amongst the HIV research community. In this commentary, we will summarise the lessons learned from the trial and examine the current state of HIV vaccine research

Resisting Immune Exhaustion in HIV-1 Infection

Sarah Rowland-Jones and Thushan de Silva discuss a new study describing the fate of cytotoxic T lymphocytes responding to HIV-1 from very early through to chronic infection

Natural killer cells during acute HIV-1 infection: clues for HIV-1 prevention and therapy

Despite progress in preexposure prophylaxis, the number of newly diagnosed cases with HIV-1 remains high, highlighting the urgent need for preventive and therapeutic strategies to reduce HIV-1 acquisition and limit disease progression. Early immunological events, occurring during acute infection, are key determinants of the outcome and course of disease. Understanding early immune responses occurring before viral set-point is established, is critical to identify potential targets for prophylactic and therapeutic approaches. Natural killer (NK) cells represent a key cellular component of innate immunity and contribute to the early host defence against HIV-1 infection, modulating the pathogenesis of acute HIV-1 infection (AHI). Emerging studies have identified tools for harnessing NK cell responses and expanding specialized NK subpopulations with adaptive/memory features, paving the way for development of novel HIV-1 therapeutics. This review highlights the knowns and unknowns regarding the role of NK cell subsets in the containment of acute HIV-1 infection, and summarizes recent advances in selectively augmenting NK cell functions through prophylactic and therapeutic interventions

Doing God in public: an Anglican interpretation of MacIntyre’s tradition-based reasoning as a Christian praxis for a pluralist world

‘We don’t do God’, Alastair Campbell famously said of UK government policy-making. In contrast, Anglican Bishops at the 2008 Lambeth Conference committed themselves to reflect on contextualising their faith, and pursue their conclusions in public ethical discourse. This thesis proposes that the Bishops (and others) may justifiably pursue this two-fold course, through the application, reinterpretation and development of Alasdair MacIntyre's tradition-based moral reasoning. I contend that the validity of a MacIntyrean approach in contextualising Christianity is readily apparent; and can shed light on Anglican differences around human sexuality. Through distinguishing between MacIntyre’s ‘utopian’ theory and his practical requirement merely to be ‘good enough’ to ‘go on and go further’, I argue that we find effective resources for extensive moral rational engagement with other traditions, and, more surprisingly, within liberal democracy. This, I agree with Jeffrey Stout, has the potential to operate, to a useful degree, as akin to a ‘tradition’. I then outline how the Bishops can best pursue substantive, rational, ethical dialogue, first, with other communities of tradition; second, with those groupings, widespread throughout society, which, though not fully-fledged communities of tradition, nonetheless sufficiently reflect them to be able to sustain some degree of moral debate; and third, through developing MacIntyre's appropriation of Aquinas’ work on Natural Law, in circumstances that, or among those who, uphold no tradition. In each case, I argue the potential is greater than MacIntyre allows, and, importantly, is enhanced by constructive engagement, which it is therefore generally a morally rational obligation to pursue. With examples drawn primarily from the work of Dr Rowan Williams, the Archbishop of Canterbury, I point to practical ways in which my proposed MacIntyrean praxis can both strengthen the Church’s engagement in public discourse, and enhance the nature of the public space as a place for pursuing the common good

Doing God in public: an Anglican interpretation of MacIntyre’s tradition-based reasoning as a Christian praxis for a pluralist world

‘We don’t do God’, Alastair Campbell famously said of UK government policy-making. In contrast, Anglican Bishops at the 2008 Lambeth Conference committed themselves to reflect on contextualising their faith, and pursue their conclusions in public ethical discourse. This thesis proposes that the Bishops (and others) may justifiably pursue this two-fold course, through the application, reinterpretation and development of Alasdair MacIntyre's tradition-based moral reasoning. I contend that the validity of a MacIntyrean approach in contextualising Christianity is readily apparent; and can shed light on Anglican differences around human sexuality. Through distinguishing between MacIntyre’s ‘utopian’ theory and his practical requirement merely to be ‘good enough’ to ‘go on and go further’, I argue that we find effective resources for extensive moral rational engagement with other traditions, and, more surprisingly, within liberal democracy. This, I agree with Jeffrey Stout, has the potential to operate, to a useful degree, as akin to a ‘tradition’. I then outline how the Bishops can best pursue substantive, rational, ethical dialogue, first, with other communities of tradition; second, with those groupings, widespread throughout society, which, though not fully-fledged communities of tradition, nonetheless sufficiently reflect them to be able to sustain some degree of moral debate; and third, through developing MacIntyre's appropriation of Aquinas’ work on Natural Law, in circumstances that, or among those who, uphold no tradition. In each case, I argue the potential is greater than MacIntyre allows, and, importantly, is enhanced by constructive engagement, which it is therefore generally a morally rational obligation to pursue. With examples drawn primarily from the work of Dr Rowan Williams, the Archbishop of Canterbury, I point to practical ways in which my proposed MacIntyrean praxis can both strengthen the Church’s engagement in public discourse, and enhance the nature of the public space as a place for pursuing the common good

Editorial: Autoimmunity and Chronic Inflammation in Early Life

Non-communicable diseases such as cardiovascular diseases, metabolic disease and chronic inflammatory diseases are often attributed to an interplay between genetic predispositions and imprinting mechanisms early in life. In a simplified concept, the fetal development is characterized by the acquisition of immuno-tolerance towards maternal and self-antigens, whereas the neonatal period reflects the acquisition of immune-defense against potentially harmful environmental antigen. Immune development involves a complex cross talk of immune cells in various organs that is influenced by environmental antigen (1–3). During infancy and childhood, autoimmune diseases and chronic inflammation coincide with an exponential diversification of the adaptive immune system, causing potentially life-long consequences. Interestingly, the earlier hypothesis of an “immunodeficiency of immaturity” had to be partially revised since it has become clear that inflammatory states in the neonate, e.g. in the context of sepsis, represent a lack of controlling inflammation rather than a failure to mount inflammation. Thus, hyperinflammatory states can occur even in the very immature organism and can lay the ground for autoimmunity or various conditions of chronic inflammation. This knowledge may affect therapeutic approaches. In this Research Topic, we have called for publications that relate to clinical or molecular aspects of aberrant immune responses in pediatric patients. Here we briefly present the 12 contributions that comprise six Original Research articles, three (mini) reviews and three case reports. The contributions can be grouped into three sections: 1. Clinical manifestations of early autoimmune and chronic inflammatory diseases 2. From molecular mechanisms to autoimmune phenotype

Effects of HIV infection and ART on phenotype and function of circulating monocytes, natural killer, and innate lymphoid cells.

HIV infection causes upregulation of markers of inflammation, immune activation and apoptosis of host adaptive, and innate immune cells particularly monocytes, natural killer (NK) and innate lymphoid cells (ILCs). Although antiretroviral therapy (ART) restores CD4 T-cell counts, the persistent aberrant activation of monocytes, NK and ILCs observed likely contributes to the incomplete recovery of T-cell effector functions. A better understanding of the effects of HIV infection and ART on the phenotype and function of circulating monocytes, NK, and ILCs is required to guide development of novel therapeutic interventions to optimize immune recovery

Antiretroviral Therapy for HIV-2 Infection: Recommendations for Management in Low-Resource Settings

HIV-2 contributes approximately a third to the prevalence of HIV in West Africa and is present in significant amounts in several low-income countries outside of West Africa with historical ties to Portugal. It complicates HIV diagnosis, requiring more expensive and technically demanding testing algorithms. Natural polymorphisms and patterns in the development of resistance to antiretrovirals are reviewed, along with their implications for antiretroviral therapy. Nonnucleoside reverse transcriptase inhibitors, crucial in standard first-line regimens for HIV-1 in many low-income settings, have no effect on HIV-2. Nucleoside analogues alone are not sufficiently potent enough to achieve durable virologic control. Some protease inhibitors, in particular those without ritonavir boosting, are not sufficiently effective against HIV-2. Following review of the available evidence and taking the structure and challenges of antiretroviral care in West Africa into consideration, the authors make recommendations and highlight the needs of special populations