Biotypes of Central Nervous System Complications in People Living With Human Immunodeficiency Virus (HIV): National Institute of Mental Health Perspectives on Advancing the Future of HIV Healthcare.

Despite effective suppressive antiretroviral therapy, central nervous system (CNS) complications related to human immunodeficiency virus (HIV) remain a significant problem for people with HIV (PWH). Numerous studies have contributed data to define the mechanisms underlying HIV-associated CNS pathophysiology, but causality remains elusive, with no effective therapies to prevent, reduce, or reverse HIV-associated CNS complications. Multiple physiological, clinical, cognitive, behavioral, social, and environmental factors contribute to the observed heterogeneity of adverse CNS outcomes among PWH. The National Institute of Mental Health in collaboration with investigators engaged in research related to HIV associated CNS complications organized a series of meetings to review the state of the science and facilitate the development of biologically based measures to identify the phenotypic heterogeneity of CNS outcomes linked to pathophysiology (biotypes). In this article, we summarize the proceedings of these meetings and explore the precision medicine framework to identify critical factors linked to the etiopathogenesis of CNS outcomes in PWH.

Towards Multidisciplinary HIV-Cure Research: Integrating Social Science with Biomedical Research.

The quest for a cure for HIV remains a timely and key challenge for the HIV research community. Despite significant scientific advances, current HIV therapy regimens do not completely eliminate the negative impact of HIV on the immune system; and the economic impact of treating all people infected with HIV globally, for the duration of their lifetimes, presents significant challenges. This article discusses, from a multidisciplinary approach, critical social, behavioral, ethical, and economic issues permeating the HIV-cure research agenda. As part of a search for an HIV cure, both the perspective of patients/participants and clinical researchers should be taken into account. In addition, continued efforts should be made to involve and educate the broader community.

Integrating behavioral and biomedical research in HIV interventions: challenges and opportunities.

Recent clinical trials have demonstrated overwhelming success of biomedical tools to prevent the spread of HIV infection. However, the complex and somewhat disparate results of some of these trials have highlighted the need for effective integration of biomedical and behavioral sciences in the design and implementation of any future intervention trial. Integrating behavioral and biomedical sciences will require appropriate behavioral theories that can be used in the context of biomedical clinical trials and multidisciplinary teams working together from the earliest stages of trial design through to completion. It is also clear that integration of behavioral science will be necessary to implement prevention at the population level and reverse the HIV epidemic.

Increase of C1q biosynthesis in brain microglia and macrophages during lentivirus infection in the rhesus macaque is sensitive to antiretroviral treatment with 6-chloro-2',3'-dideoxyguanosine.

Complement activation in the brain contributes to the pathology of neuroinflammatory and neurodegenerative diseases such as neuro-AIDS. Using semiquantitative in situ hybridization and immunohistochemistry, we observed an early and sustained increase in the expression of C1q, the initial recognition subcomponent of the classical complement cascade, in the CNS during simian immunodeficiency virus (SIV) infection of rhesus macaques. Cells of the microglial/macrophage lineage were the sources for C1q protein and transcripts. C1q expression was observed in proliferating and infiltrating cells in SIV-encephalitic brains. All SIV-positive cells were also C1q-positive. Treatment with the CNS-permeant antiretroviral agent 6-chloro-2',3'-dideoxyguanosine decreased C1q synthesis along with SIV burden and focal inflammatory reactions in the brains of AIDS-symptomatic monkeys. Thus, activation of the classical complement arm of innate immunity is an early event in neuro-AIDS and a possible target for intervention.

Workshop report: The effects of psychological variables on the progression of HIV-1 disease.

The reciprocal interactions between the neuroendocrine, immune, and autonomic nervous systems are complicated, yet worthy of examination. A body of literature suggests that psychological factors such as stress, or psychiatric conditions such as major depression, may influence the immune system thereby altering host susceptibility to viral, or other types of infection. Alternately, in an attempt to limit infection and replication, the anti-viral host response, via innate and acquired immunity and subsequent release of pro-inflammatory cytokines and additional anti-viral mediators, may affect mood, cognition emotion, and possibly precipitate a psychiatric disorder. In order to address what is known regarding neuroendocrine-immune interactions in the context of HIV infection, the Center for Mental Health Research on AIDS convened a panel of scientists from diverse areas of expertise. Their primary charge was to examine whether stress-induced activation of the neuroendocrine system affects the immune system in a manner that negatively influences HIV disease progression, and whether HIV infection influences the central nervous system and behavior. The ensuing report summarizes their deliberations as they discussed the current body of information and identified outstanding critical questions in the areas of research. The group consensus was that the biological mediators of psychological status can play an important role in mediating HIV disease progression, particularly in subgroups of vulnerable patients; furthermore, they identified candidate biological mediators and mechanisms of disease progression. The Workgroup outlined the inherent challenges and limitations of such research and provided recommendations as to the future directions of research utilizing human, animal, and in vitro models of HIV-1 infection and stress.