Current Opinion in HIV and AIDS最新文献

Purpose of review: To provide an overview of studies to date that have identified posttreatment controllers (PTCs) and to explore current evidence around clinical characteristics, immune effector function, and inflammatory and viral reservoir characteristics that may underlie the control mechanism.

Recent findings: PTCs are broadly defined as individuals capable of maintaining control of HIV replication after cessation of antiretroviral therapy (ART). While starting ART early after HIV infection is associated with PTC, genetic disposition or CD8+ T-cell function do not appear to explain this phenomenon, but these features have not been exhaustively analyzed in PTCs. A lower frequency of latently infected cells prior to stopping ART has been associated with achieving PTC, including a lower level of intact HIV DNA, but more studies are needed to map the genetic location, epigenetic characteristics, and tissue distribution of the intact HIV reservoir in PTCs.

Summary: Current studies are small and heterogeneous and there is a significant need to agree on a uniform definition of PTC. Many aspects of PTC are still unexplored including whether specific features of genetic disposition, immune effector functions, and/or viral reservoir characteristics play a role in PTC. A large multisite international cohort study could aide in providing the important insights needed to fully understand PTC.

Purpose of review: The exosomes play a critical role in HIV infection, which constitute a pathway to release intracellular material and exchange material and information between cells. Exosomes have become a hotspot in the field of AIDS research. This review introduces the formation process of HIV particles and exosomes, and summarizes the role of exosomes in the progression of HIV disease from multiple aspects.

Recent findings: Many components of the exosomes involved in HIV transfer and replication affect the occurrence, development, and outcome of AIDS, and are closely related to HIV infection. Exosomes can have a dual impact on HIV infection, and play an important role in activating the latent reservoir of HIV and affecting the chronic inflammation of HIV. The biological information carried by exosomes is also of great significance for the prediction of HIV disease.

Summary: The present review summarizes the role of exosomes in HIV disease progression in various aspects in order to further understand the underlying mechanism affecting the infection and providing a new idea for the clinical diagnosis and treatment of AIDS.

Purpose of review: HIV-1 elite controllers encompass small populations of people infected with HIV-1 who can spontaneously control plasma viral loads below the limit of detection, in the absence of antiretroviral treatment. Antiviral immune responses are likely to contribute to such an impressive HIV-1 disease outcome. In this review, we discuss recent novel findings regarding antiviral innate and adaptive immune responses in elite controllers.

Recent findings: Elite controllers maintain a pool of infected cells in which intact HIV-1 proviruses are more frequently integrated into noncoding regions of the host genome, likely conferring a state of deep latency. This atypical viral reservoir configuration is best explained by potent antiviral immune responses that can successfully eliminate virally infected cells in which proviruses are integrated into permissive chromatin. However, identifying the specific type and nature of this immune selection pressure represents a formidable challenge. Recent studies continue to support the role of HIV-1-specific CD8+ T cells as the main driver of elite immune control of HIV-1, however, increasing evidence suggests that their role is complemented by a fine-tuned interplay with innate immune cell subsets. Therefore, the combination of different immune effector mechanisms may shape antiviral immunity in elite controllers.

Summary: Understanding the complex immune mechanisms responsible for natural, drug-free HIV-1 control represents a premier avenue to find and develop interventions for a cure of HIV-1 infection. Future single-cell assays designed to uncover the full genetic, epigenetic, transcriptional and functional complexity of antiviral immune responses in elite controllers may allow us to define correlates of antiviral immune protection in greater detail.

Purpose of review: This multicentre, cross-sectional study was carried out in the South of France to assess the association between frailty phenotype and antiretroviral therapy (ART) in older persons living with HIV (PLWHIV). Sociodemographic and HIV data, geriatric assessment, comorbidities, behavioral and age-related variables and the five frailty markers of Fried were recorded. Exposure to any pharmacological class of ART and all regimens were retrieved from medical records.

Recent findings: The 509 PLWHIV analysed (72.7% male) received a mean of 6.01 ART regimens and 12.5 years exposure to ART. The prevalence of at least one frailty marker [frail and prefrail phenotype (FPFP)] was 66.4%. Duration of exposure to protease inhibitors and reverse transcriptase inhibitors, number of ART regimens and comorbidities, dyslipidaemia, cancer, depression, falls, disability and pain were significantly associated with FPFP by univariate analysis. In logistic regression multivariable analysis, independent predictors for FPFP were a large number of ART regimens, presence of cancer and pain. No significant association was found with HIV-related parameters neither with ART class and duration.

Summary: A significant association was found between FPFP and a large number of different ART regimens among older PLWHIV. The burden of cancer and pain in these patients shows the importance of comprehensive care.

Purpose of review: In this special issue on human immunodeficiency (HIV) cure, we review the role of therapeutic immunization in strategies aimed to eliminate HIV-infected cells and/or mediate sustained control of viral replication in the absence of antiretroviral treatment.

Recent findings: Recent data emerging from studies in simian immunodeficiency virus macaque models using broadly neutralizing antibodies, given alone or in combination with other immunomodulatory agents, as well as data from human clinical studies with novel therapeutic vaccines are showing encouraging results indicating that achieving viral remission or at least partial viral control of HIV without antiretroviral therapy is feasible.

Summary: Although it remains unclear whether current strategies will be able to awaken a sufficient large fraction of the viral reservoir and/or vaccine-boosted immunity will induce effective, long-lasting viral suppression in chronically infected HIV population, emerging results establish cure strategies that can be further improved upon.

Purpose of review: Advances in antiretroviral therapy have saved numerous lives, converting a diagnosis with human immunodeficiency virus 1 (HIV-1) from a death sentence into the possibility for a (nearly) normal life in many instances. However, the obligation for lifelong adherence, increased risk of accumulated co-morbidities, and continued lack of uniform availability around the globe underscores the need for an HIV cure. Safe and scalable HIV cure strategies remain elusive, in large part due to the presence of viral reservoirs in which caches of infected cells remain hidden from immune elimination, primarily within tissues. Herein, we summarize some of the most exciting recent advances focused on understanding, quantifying, and ultimately targeting HIV tissue viral reservoirs.

Recent findings: Current studies have underscored the differences between viral reservoirs in tissue compartments as compared to peripheral blood, in particular, the gastrointestinal (GI) tract. Additionally, several novel or modified techniques are showing promise in targeting the latent viral reservoir, including modifications in drug delivery platforms and techniques such as CRISPR.

Summary: Elimination of tissue viral reservoirs is likely the key to generation of an effective HIV cure. Exciting studies have come out recently that reveal crucial insights into topics ranging from the basic biology of reservoir seeding to effective drug targeting. However, there are still many outstanding questions in the field about the relative importance of specific reservoirs, such as the GI tract, that may alter the final strategy pursued.

Purpose of review: Older adults account for the majority of people with HIV (PWH) in high-income countries and have increasingly complex clinical profiles related to premature aging. Frailty is an important geriatric syndrome affecting a minority of PHW. Frailty negatively affects PHW's clinical status and quality of life. This review will update care providers on the current state of frailty that limits the healthspan of PWH.

Recent findings: Ongoing low-level HIV replication in treated PWH leads to immune activation and chronic inflammation contributing to the destabilization of normally autoregulated physiologic systems in response to environmental and biologic challenges characteristic of frailty. Understanding these underlying mechanisms will determine potential intervention options. Potentially reversible risk factors that promote progression to and reversion from the dynamic state of frailty are being studied and will help prevent frailty. Simple assessment tools and treatment strategies for frailty are being adapted for aging PWH.

Summary: Insight into underlying biologic mechanisms and adapting proven geriatric principles of interdisciplinary care will inform the healthy aging of PWH.

Purpose of review: The present review aims to decipher common co-morbidities faced by people living with HIV in low- to middle-income countries, and in particular the sub-Saharan region, which hosts the majority of the HIV burden worldwide.

Recent findings: Well-controlled chronic HIV disease is strongly associated with an increased risk of developing cardiovascular disease. This is partly due to the natural aging process, however recent studies show that using antiretroviral therapy as well as the HIV disease itself may be predisposing factors to the development of cardiovascular diseases, creating a new burden for healthcare facilities in the region. Furthermore, newly completed studies assessing inflammation marker albuminuria and age-related syndrome frailty have been found in a higher prevalence than in non-HIV people, with increased morbidity and mortality.

Summary: As antiretroviral medication continues to be well supplied in the region and well tolerated by patients living with HIV, this group is now reckoning with cardiovascular ailments faced by all ageing population therefore there is a need for cardiovascular care systems to be better integrated within the existing, well-performing HIV care cascade to address this burden.