Current opinion in HIV and AIDS最新文献

Purpose of review: Expression of noncoding RNAs (ncRNAs) is more tissue and cell type-specific than expression of protein-coding genes. Understanding the mechanisms of action of ncRNAs and their roles in HIV replication and latency may inform targets for the latent HIV reservoir reactivation or elimination with high specificity to CD4 + T cells latently infected with HIV.

Recent findings: While the number of studies in the field of ncRNAs and HIV is limited, evidence points to complex interactions between different ncRNAs, protein-coding RNAs, and proteins. Latency-reversing agents modulate the expression of ncRNAs, with some effects being inhibitory for HIV reactivation. An important limitation of basic research on the ncRNA mechanisms of action is the reliance on cell lines. Because of cell type specificity, it is uncertain whether the ncRNAs function similarly in primary cells.

Summary: Comprehensive functional screens to uncover all ncRNAs that regulate HIV expression and the detailed exploration of their mechanisms of action in relevant cell types are needed to identify promising targets for HIV reservoir clearance. Classes of ncRNAs as a whole rather than individual ncRNAs might represent an attractive target for reservoir elimination. Compound screens for latency reversal should factor in the complexity of their effects on ncRNAs.

Purpose of review: The complex nature and distribution of the HIV reservoir in tissue of people with HIV remains one of the major obstacles to achieve the elimination of HIV persistence. Challenges include the tissue-specific states of latency and viral persistence, which translates into high levels of reservoir heterogeneity. Moreover, the best strategies to reach and eliminate these reservoirs may differ based on the intrinsic characteristics of the cellular and anatomical reservoir to reach.

Recent findings: While major focus has been undertaken for lymphoid tissues and follicular T helper cells, evidence of viral persistence in HIV and non-HIV antigen-specific CD4 + T cells and macrophages resident in multiple tissues providing long-term protection presents new challenges in the quest for an HIV cure. Considering the microenvironments where these cellular reservoirs persist opens new venues for the delivery of drugs and immunotherapies to target these niches. New tools, such as single-cell RNA sequencing, CRISPR screenings, mRNA technology or tissue organoids are quickly developing and providing detailed information about the complex nature of the tissue reservoirs.

Summary: Targeting persistence in tissue reservoirs represents a complex but essential step towards achieving HIV cure. Combinatorial strategies, particularly during the early phases of infection to impact initial reservoirs, capable of reaching and reactivating multiple long-lived reservoirs in the body may lead the path.

Purpose of review: The public health challenge of overweight and obesity increasingly affects people living with HIV (PWH). These effects have also accelerated as the prevalence of antiretroviral therapy (ART) use has increased among PWH. It is therefore also critical that we examine and understand the pathogenesis of obesity among PWH.This review will aim to summarize relevant and recent literature related to the risks of weight gain and obesity associated with HIV disease progression, cardiometabolic disease, and multimorbidity among PWH. Further, we will discuss adipose tissue changes associated with weight gain and obesity and how these changes relate to metabolic complications.

Recent findings: Several observational and experimental studies in recent years have evaluated the role of contemporary ART regimens, particularly integrase strand transfer inhibitors (INSTIs) and tenofovir alafenamide (TAF), as contributors to weight gain, obesity, and cardiometabolic disease, though the mechanisms remain unclear. Metabolic dysregulation has also been linked to ectopic fat deposition and alterations in innate and adaptive immune cell populations in adipose tissue that accompany HIV and obesity. These factors continue to contribute to an increasing burden of metabolic diseases in an aging HIV population.

Summary: Obesity accompanies an increasing burden of metabolic disease among PWH, and understanding the role of fat partitioning and HIV and ART-related adipose tissue dysfunction may guide prevention and treatment strategies.

Purpose of review: HIV epidemics are increasing in many emerging economy countries, whilst the very process of 'economic emergence' is obesogenic. Annual deaths related to obesity and overweight are now four times more than for HIV globally. We describe the intersections between HIV and obesity in emerging economies, and highlight potential mitigation options, including antiobesity medications (AOMs), which are safe and effective, but inaccessibly priced.

Recent findings: We summarize what is known about weight-change in HIV and review strategies including public health policies and clinical interventions for emerging economy countries to fight obesity. We also illustrate the landscape from a selection of 'emerging economy' countries with available data from UNAIDS, World Bank and World Obesity Federation to visualize the developing challenges faced. AOM course prices are high in many countries, but could be manufactured and sold profitably for much less. We present lessons from the early HIV/AIDS movements on how to improve access and pricing for AOMs for people with HIV with obesity in emerging economy countries.

Summary: We illustrate the complex intersectional issues that 'emerging economy countries' may experience, with a 'double burden' of increasing HIV and obesity epidemics, and explore potential mitigation options, focussing on AOM access and pricing.

Purpose of review: The introduction of dolutegravir, an oral integrase inhibitor, within public health HIV programs has been a success, with excellent sustained viral load suppression, persistence, and safety. Initial concerns around integrase-inhibitors being implicated in safety concerns around immune reconstitution inflammatory syndromes (IRIS), neural tube defects, and weight gain, have been largely laid to rest, but new concerns about cardiovascular risk have arisen, including a link between hypertension and this antiretroviral class.

Recent findings: We review the pertinent studies here, and while we find both observational and randomized controlled study associations in some but not all studies, these are often confounded by associated weight gain and aging. In addition, definitions of hypertension, as well as measurement within the studies (such as cuff size), were not consistent within studies.

Summary: Careful analysis will be needed, as with the weight-gain signal, before assigning causation, especially as plausible physiological mechanisms for this rise in blood pressure are unclear.

Purpose of review: People with HIV (PWH) on antiretroviral therapy (ART) globally are disproportionately affected by obesity, with prevalence rates highest among women with HIV. The purpose of this review is to discuss rates of obesity, factors associated with obesity, and adverse consequences of obesity among PWH.

Recent findings: Among PWH on ART, rates of obesity have increased over the last several decades and tend to be higher than the general population. Weight gain with the initiation of new ART regimens such as integrase strand transfer inhibitor (INSTI)-based regimens are thought to contribute to higher rates of obesity among PWH on ART. Other factors, such as sex and ethnicity, also are associated with obesity among PWH on ART. Higher obesity rates among PWH may contribute to heightened cardiometabolic disease risk and lower health-related quality of life.

Summary: Prospective studies which identify factors associated with increased obesity prevalence and weight gain among PWH are necessary for the development and implementation of obesity prevention and treatment strategies among PWH on ART and, in turn, reduce the prevalence of obesity in this population.

Purpose of review: With the introduction of novel and more potent antiretroviral therapies (ART), persons with HIV (PWH) are living longer lives and experiencing higher rates of age- and weight-related comorbidities, including cardiovascular and metabolic diseases. Women with HIV (WWH) experience disproportionate rates of obesity, as evidenced by longitudinal observational cohorts both in the United States and globally.

Recent findings: In this article, we aim to review major research findings regarding WWH and obesity over the past few years. Multiple studies have evaluated geographic changes in the obesity epidemic across the globe with focus on developing countries who have seen a drastic change in obesity rates. Other new data assessed the effect of antiretroviral therapy on WWH, the cardiovascular effects of obesity in women on ART including data from the recently published REPRIEVE Trial, and issues unique to women, such as pregnancy and the effect of menopause on WWH.

Summary: Comorbid cardiometabolic conditions are rapidly increasing, in correlation with the obesity epidemic among PWH. WWH may be disproportionately impacted, and experience further effects of obesity, compounded by health disparities in many areas of the world. Further research on the most effective interventions to minimize weight gains and decrease obesity among WWH are urgently needed.