Current opinion in HIV and AIDS最新文献

Purpose of review: Cognitive disorders have been described in persons with HIV since the advent of virologically suppressive antiretroviral therapy. As persons with HIV age, their demographics and risk factors for cognitive health have changed. Here, we review these changing demographics and the recent literature regarding risk factors for cognitive decline and best management strategies.

Recent findings: Rates on noninfectious comorbidities are higher in persons with HIV compared to those without HIV and specifically include high rates of mental health conditions and cardiovascular complications. The optimal management of these noninfectious comorbidities is crucial for maintaining brain health. The early initiation of antiretroviral therapy may prevent irreversible damage to brain health and modern integrase-strand-transfer-inhibitor based antiretroviral regimens appear to have a positive effect on cognitive health.

Summary: Risk factors for cognitive decline in persons with HIV have dramatically changed in recent years along with clinical management strategies. As persons with HIV globally continue to age, ongoing considerations of these risk factors and management strategies will continue to be key in maintaining brain health for the 40 million people living with HIV globally.

Purpose of review: Human immunodeficiency virus (HIV) was historically considered a terminal illness. However, medical advancements, including antiretroviral therapy (ART), have extended the lifespan of people with HIV (PWH), emphasizing the importance of maximizing quality of life (QoL) in this aging population. These populations face unique health challenges due to various structural and environmental barriers, and comorbidities. This review aims to consolidate recent data on pain management and other palliative needs in older people with HIV (OPWH).

Recent findings: Recent research developments focus on providing relief by incorporation of geriatric and palliative care (PC) principles, use of long-acting injectable-antiretroviral therapies (LAI-ARTs), cannabinoids, exercise and self-management interventions, and tailored cognitive-behavioral therapy (CBT) for older people with HIV (OPWH; ≥50 years). The potential of these novel interventions can fulfil the needs of this underserved demographic suffering from a niche subset of physical and psychosocial issues. Yet, there remains variability in access to these services, with disparities often linked to healthcare infrastructure and socioeconomic factors.

Summary: Interventions for an aging population of PWH should take a person-centered approach, balancing different priorities and exploring multiple avenues for symptom relief.

Purpose of review: This review explores the unique challenges faced by older people with HIV (PWH) in resource-limited settings, particularly in managing age-related health issues alongside HIV. It highlights gaps in healthcare systems, structural barriers, and the need for better integration of services to improve outcomes.

Recent findings: There is currently a lack of integrated healthcare services for aging PWH, resulting in delayed treatment for noncommunicable diseases. There is also limited geriatric expertise in HIV care which exacerbates challenges in diagnosing and managing age-related conditions. Women with HIV face additional barriers due to gender disparities but have limited representation in research. Furthermore, older adults acquiring HIV are often diagnosed late, leading to poorer outcomes.

Summary: This review calls for integrating aging care into HIV programs, improving healthcare training, and garnering greater consensus on assessment tools for geriatric conditions. Additionally there is a need for more targeted HIV prevention programs for older adults who remain at risk of acquiring HIV and presenting late to care.

Purpose of review: Metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent among people with HIV (PWH) and increasingly recognized as a major contributor to morbidity and mortality. The field of MASLD is rapidly evolving with adoption of a new nomenclature and approval of the first FDA-approved therapy within the past year. These developments underscore the need to consider the current state of the science specifically in the context of HIV.

Recent findings: MASLD in PWH (MASLD-HIV) follows a more aggressive clinical course compared to HIV-negative individuals. While MASLD-HIV shares common pathogenic mechanisms with MASLD in the general population, HIV-specific factors - including altered body composition, chronic immune activation, enhanced gut permeability, and antiretroviral therapy - exacerbate disease progression. Despite an expanding pipeline of MASLD therapies, a critical gap remains in evaluating these interventions specifically among PWH. Nonetheless, dedicated studies of glucagon-like peptide-1 receptor agonists and the growth hormone-releasing hormone analog tesamorelin have shown promise in MASLD-HIV.

Summary: MASLD is a key contributor to liver-related and cardiovascular-morbidity in PWH. While there have been exciting advances to improve diagnosis and management of MASLD in the general population, differences in MASLD pathophysiology demonstrate the need to tailor our approach specifically for PWH.

Purpose of review: We describe the emerging clinical outcomes for adults born with perinatally acquired HIV (PHIV), who have been living with HIV throughout their life. Whilst many comorbidities appear similar to adults with horizontally acquired HIV, they manifest at a younger chronological age. The additional impact of HIV throughout postnatal, childhood and adolescent growth and development requires further consideration.

Recent findings: There is growing evidence of an increased incidence of metabolic, cardiovascular, respiratory, bone and renal impairment as well as structural brain changes associated with impaired cognitive function, and mental health disorders; early case series data suggests a six-fold increased prevalence of psychosis for those with lifelong HIV compared with age-matched peers. Older age, prior CDC-C diagnoses and lower nadir CD4 count confer the greatest risk of PHIV complications in adulthood, but biological factors are compounded by socioeconomic deprivation, bereavement, HIV-associated stigma, discrimination and immigration. The aetiology of these increased comorbidities is yet to be fully elucidated but includes lifelong systemic inflammation and immune dysfunction despite suppressive antiretroviral therapy (ART).

Summary: Adults living with lifelong HIV experience increased risk of comorbidities at a younger chronological age despite viral suppression on ART. Exploring the aetiology and characterizing the clinical manifestations of lifelong HIV can best inform screening tools and interventions that can enhance quality of life and longevity.

Purpose of review: Osteoporosis and fragility fractures continue to be a concern for aging people living with HIV (PLWH), despite newer antiretroviral (ART) formulations that are associated with reduced bone toxicity. The aim of this review is to evaluate recent literature focusing on estimates of osteoporosis and fractures in various study populations, efficacy of current fracture risk assessment tools, and interventions to improve bone health outcomes.

Recent findings: Prevalence of low bone mineral density (BMD) remains higher among PLWH globally, with new estimates ranging from 24 to 59%. The FRAX tool underestimates rate of major osteoporotic fractures in PLWH; some studies suggest that modifications can improve accuracy. Bone quality assessments with trabecular bone score may also improve prediction of vertebral fractures in PLWH. Preexposure prophylaxis (PrEP) with TDF/FTC is generally safe for maternal and infant bone health. Denosumab treatment effectively improves bone mass in PLWH.

Summary: Despite advancements in ART, osteoporosis and fragility fractures remain common among PLWH. There is a need for continued research on development of fracture risk assessment tools including use of clinical data, imaging studies and biomarkers, and implementation of preventive and treatment strategies for at-risk subgroups.

Purpose of review: The prevalence of neurological complications among people with HIV (PWH) is expected to increase as PWH live longer due to increased access to antiretroviral treatment (ART). This review provides updates to the understanding of the neurological sequelae, including neurocognitive impairment, neuropathy, neurological opportunistic infections, and others, which are crucial for improving care and outcomes of PWH.

Recent findings: Recent literature highlights several key themes: the pathophysiology of HIV-related neuronal damage involving HIV proteins (gp120, Nef) and neuroinflammation; the role of aging in exacerbating neurological complications; the high prevalence of HIV-associated neurocognitive disorders (HAND) and Alzheimer's disease-related dementias (AD/ADRD) among PWH; the importance of neurocognitive screening tools like IHDS and MoCA; and the identification of biomarkers and neuroimaging techniques for early detection and monitoring of HAND.

Summary: The findings highlight the need for comprehensive healthcare strategies to manage neurological complications in PWH, including targeted interventions for high-risk groups, improved diagnostic tools, and tailored treatments. It is important for clinicians and researchers to develop effective approaches to mitigate the impact of HIV on brain health and improve quality of life for PWH.

Purpose of review: Traditional cardiovascular risk factors, combined with persistent systemic inflammation, contribute to the increased prevalence of atherosclerotic cardiovascular disease (ASCVD) in people with HIV (PWH). This review highlights key findings from the REPRIEVE trial on statin-based primary prevention of major adverse cardiovascular events in PWH. It explores HIV-specific immune mechanisms contributing to residual cardiovascular risk.

Recent findings: In REPRIEVE, statin therapy used for primary prevention of major adverse cardiovascular events in PWH decreased the plasma lipoprotein-associated phospholipase A2, oxidized low-density lipoprotein, and high-sensitivity C-reactive protein (hs-CRP). However, several inflammatory markers including soluble CD14 (sCD14), sCD163, interleukin (IL)-1β, interleukin (IL)-6, IL-10, and caspase 1 did not change. The HIV reservoir, dysfunctional CD4 + T cells, immunoglobulin G N-glycans, antiapolipoprotein A1 autoantibodies, trained immunity, and clonal hematopoiesis of indeterminate potential may contribute to residual inflammation.

Summary: Despite antiretroviral and statin therapy, residual ASCVD risk in PWH underscores the need for targeted interventions. Anti-inflammatory therapies, including IL-6 and IL-1β inhibitors, CCR5 antagonists (e.g., maraviroc, cenicriviroc mesylate), and immunomodulatory agents like methotrexate and colchicine, are being explored. Understanding HIV-driven immune dysregulation may lead to novel strategies to mitigate cardiovascular risk in this population.

Purpose of review: Nonhuman primate (NHP) models of HIV-1 infection provide complementary experimental pathways for assessing aspects of acute HIV-1 infection (AHI) that cannot be addressed in humans. This article reviews acute infection studies in SIV-infected or SHIV-infected macaque species over the previous 18 months.

Recent findings: Reviewed studies examined the dynamics of replication-competent viral reservoir establishment during early infection, reservoir maintenance throughout therapy, and factors influencing viral rebound after treatment cessation. Also discussed are acute infection events in the central nervous system and liver and potential links between these events and manifestations of comorbidities during chronic infection. Additional studies addressed how occurrences during acute infection impact the development of natural viral control or posttreatment control. Another report evaluated treatment during acute infection with broadly neutralizing antibodies with enhanced ability to engage innate immune cells, highlighting the ability of this early intervention to shape innate and adaptive antiviral responses.

Summary: NHP models of HIV-1 infection are a fundamental research tool for investigating AHI events. These models enable detailed pathogenesis characterization and the testing of hypothesis-driven strategies for altering disease courses through interventions during AHI, including targeting viral persistence and comorbidities that persist throughout chronic infection.