Current Opinion in HIV and AIDS最新文献

Purpose of review: The purpose of this article is to review alterations in microbiota composition, diversity, and functional features in the context of chronic inflammation and comorbidities associated with HIV infection.

Recent findings: The gut microbiome is an important mediator of host immunity, and disruption of gut homeostasis can contribute to both systemic inflammation and immune activation. Ageing and HIV share features of intestinal damage, microbial translocation and alterations in bacterial composition that contribute to a proinflammatory state and development of age-related comorbidities. One such inflammatory pathway reviewed is the nicotinamide adenine dinucleotide (NAD+) producing kynurenine pathway (KP). Kynurenine metabolites regulate many biological processes including host-microbiome communication, immunity and oxidative stress and the KP in turn is influenced by the microbiome environment. Age-associated decline in NAD+ is implicated as a driving factor in many age-associated diseases, including those seen in people with HIV (PWH). Recent studies have shown that KP can influence metabolic changes in PWH, including increased abdominal adiposity and cardiovascular disease. Furthermore, KP activity increases with age in the general population, but it is elevated in PWH at all ages compared to age-matched controls. Host or microbiome-mediated targeting of this pathway has merits to increase healthy longevity and has potential therapeutic applications in PWH.

Summary: As a growing proportion of PWH age, many face increased risks of developing age-related comorbidities. Chronic inflammation, a pillar of geroscience, the science of ageing and of age-related disease, is influenced by the gut microbiome and its metabolites. Combined, these contribute to a systemic inflammatory signature. Advances in geroscience-based approaches and therapeutics offer a novel paradigm for addressing age-related diseases and chronic inflammation in HIV infection. Whether targeted inhibition of KP activity alleviates pathological conditions or promotes successful ageing in PWH remains to be determined.

Purpose of review: This perspective paper offers some reflections on an hypothesized changing scenario of HIV comorbidities in the years to come and provides some insights on how to improve screening and management of people with HIV (PWH) in the coronavirus disease 2019 (COVID-19) era.

Recent findings: PWH may experience a higher burden of excess disease and mortality associated with noninfectious comorbidities in the COVID-19 era. HIV care must move beyond viral-immunological success to incorporate patient-centered outcomes based on the intrinsic characteristics of the individual and its environment, assessment and screening for comorbidities, evaluation of aging and geriatric syndromes and last but not least fight stigma, ageism and inequality to access to care.

Summary: COVID-19 is widening the gap between unmet needs of PWH and healthcare systems. An increasing burden of comorbidities, multimorbidity and frailty is affecting PWH which requires redesign of care delivery oriented around the diverse needs of individuals, rather than the prerequisites of providers, and must ensure health equity. In particular, any changes to care delivery must address existing disparities in access and care among PWH and fight stigma.

Purpose of review: To highlight recent publications about sleep disorders and sleep health in adult persons with HIV (PWH), with a focus on how sleep relates to comorbidities in PWH.

Recent findings: Sleep disorders are more common in PWH than in seronegative controls, especially insomnia, with four different recent studies estimating insomnia prevalence in PWH at 21-35%. Sleep apnea prevalence estimates in PWH have varied widely. Most studies suggest PWH do not have higher sleep apnea prevalence compared with controls, though definitions of sleep apnea may affect these analyses. Comorbidities recently associated with sleep in PWH include myocardial infraction (insomnia), depressive symptoms (insomnia and restless legs syndrome), and pain (insomnia). Cognition associations with sleep were inconsistent and may depend on data collection and analytic methods. Sleep health dimensions are uncommonly reported, but PWH appear to report worse sleep health dimensions and these demonstrated mixed associations with cognition and depressive symptoms in recent studies.

Summary: Sleep disorders and poor sleep health are common in PWH and are related to comorbidities. More data from longitudinal studies and clinical trials are needed. Clinical trials of insomnia interventions in PWH are especially warranted.

Purpose of review: As people living with human immunodeficiency virus (HIV, PLWH) age, aging-related comorbidities have come into focus as major challenges to their overall health. In this review, an in-depth overview of the two most commonly encountered chronic lung diseases in PLWH, chronic obstructive pulmonary disease (COPD) and lung cancer, is provided.

Recent findings: The risk for both COPD and lung cancer remains significantly higher in PLWH compared to the HIV-uninfected population, although fortunately rates of lung cancer appear to be declining over the last two decades. Outcomes for PLWH with these conditions, though, continue to be poor with worse survival rates in comparison to the general population. PLWH still face major barriers in accessing care for these conditions, including a higher likelihood of being underdiagnosed with COPD and a lower likelihood of being referred for lung cancer screening or treatment. A lack of evidence for optimal treatment strategies for both COPD and lung cancer still hampers the care of PLWH with these conditions.

Summary: COPD and lung cancer represent substantial burdens of disease in PLWH. Improved access to standard-of-care screening and treatment and greater investigation into therapeutic responses specifically in this population are recommended.

Purpose of review: To highlight advances in understanding of host factors, in particular host genetics, in the development of chronic kidney disease (CKD) in people with HIV.

Recent findings: In Black populations, the G1 and G2 variants of the apolipoprotein L1 (APOL1) gene predispose to HIV-associated nephropathy (HIVAN). The risk of HIVAN is mostly confined to individuals with two APOL1 variants (kidney-risk genotypes). APOL1 kidney-risk genotypes are present in approximately 80% of patients with HIVAN and account for nearly half the burden of end-stage CKD in people of African ancestry with HIV. Progress has been made in elucidating the mechanisms of kidney injury in APOL1 nephropathy, and several targeted molecular therapies are being investigated in clinical trials. Genome- and epigenome-wide association studies are identifying additional genes and pathways that may be involved in the pathogenesis of CKD in people with HIV.

Summary: Genetic variants of APOL1 are strongly associated with severe CKD and contribute to the high rates of CKD in Black populations with HIV. Most individuals with APOL1 kidney-risk genotypes, however, do not develop kidney disease and further studies are required to understand the role of additional genetic and environmental factors that may affect CKD risk in this population.

Purpose of review: Although multimorbidity (defined as the coexistence of multiple conditions) presents significant health challenges to people with HIV, there is currently no consensus on how it should be defined among this population. This review aimed to examine the definition of multimorbidity in existing studies among people with HIV ( n  = 22).

Recent findings: Variation in the definition of multimorbidity (in terms of the number and nature of conditions included) across studies among people with HIV was observed, with less than half (45%) reporting a selection criteria for conditions. The number of conditions considered ranged from 4 to 65. Certain conditions (e.g. stroke, myocardial infarction and chronic kidney disease) and risk factors (e.g. hypertension) were more frequently included, while other symptoms (e.g. joint pain, peripheral neuropathy and sleeping problems) and mental health conditions (e.g. anxiety and panic attacks) were rarely included in the definition of multimorbidity.

Summary: The definition of multimorbidity among people with HIV is highly variable, with certain conditions overlooked. We propose recommendations that researchers should consider when defining multimorbidity among this population to not only enable comparisons between studies/settings but also to ensure studies consider a person-centred approach that can accurately capture multimorbidity among people with HIV.

Purpose of review: Weight gain has emerged as an important problem in people with HIV (PWH). When dealing with obesity, PWH face additional challenges to those without HIV. Understanding the nature of the problem and the modern evidence is essential to optimize management and identify knowledge gaps.

Recent findings: Some PWH treated with antiretroviral therapy (ART) gain unhealthy amounts of weight and develop consequences of obesity. Newer agents have been consistently associated with excessive weight gain. Key studies are underway to inform the optimal use of specific ART in PWH dealing with obesity. For weight management, behavioral interventions fostering a healthier and active lifestyle, coupled with pharmacological therapies such as glucagon-like peptide 1 receptor agonists may be effective strategies in PWH, as recently demonstrated in those without HIV, although data in this regard is pending.

Summary: A growing body of research has come to light in recent years regarding weight gain and obesity in PWH. However, much of the knowledge that inform current practices is extrapolated from studies in people without HIV. Modern ART regimens may promote excessive weight gain in some, and more research is needed to optimize ART selection and the use of weight loss medications.

Purpose of review: Patient centered care (PCC) in human immunodeficiency virus (HIV) care systems in sub-Saharan Africa (SSA) may improve outcomes for persons with HIV (PWH). We review the progress the region has made in promoting PCC and highlight some of the implementation challenges and potential areas of research.

Recent findings: Studies show growing interest in promoting PCC across HIV care programs in SSA. Effective implementation of PCC, however, is hampered by: (1) lack of consensus on the conceptualization of PCC, including definition, frameworks, measures, and implementation strategies; (2) limited regional studies on the adoption and sustainability of PCC interventions; and (3) healthcare structural challenges including limited capital and human resources, poor provider-patient dynamics, high provider turnover, and lack of continuity in care. Recent studies in the region have focused on identifying key PCC domains addressable in resource limited settings, understanding the PCC experiences and expectations of PWH and their providers, and testing innovative interventions. We highlight the need for additional studies to address the existing gaps.

Summary: We discuss the progress and challenges of implementing PCC in HIV care settings in SSA as well as the need for additional research to ensure that proposed PCC interventions have optimal impact.