Current HIV/AIDS Reports最新文献

Purposeof review: In the current quest for a complete cure for HIV/AIDS, the persistence of a long-lived reservoir of cells carrying replication-competent proviruses is the major challenge. Here, we describe the main elements and characteristics of several widely used assays of HIV latent reservoir detection.

Recent findings: To date, researchers have developed several different HIV latent reservoir detection assays. Among them, the in vitro quantitative viral outgrowth assay (QVOA) has been the gold standard for assessing latent HIV-1 viral load. The intact proviral DNA assay (IPDA) based on PCR also demonstrated the predominance of defective viruses. However, these assays all have some drawbacks and may still be inadequate in detecting the presence of ultralow levels of latent virus in many patients who were initially thought to have been cured, but eventually showed viral rebound. An accurate and precise measurement of the HIV reservoir is therefore needed to evaluate curative strategies, aimed to functional cure or sterilizing cure.

Purpose of review: HIV/AIDS and COVID-19 have been the major pandemics overwhelming our times. Given the enduring immune disfunction featuring people living with HIV (PLWH) despite combination antiretroviral therapy (cART), concerns for higher incidence and severity of SARS-CoV-2 infection as well as for suboptimal responses to the newly developed vaccines in this population arose early during the pandemics. Herein, we discuss the complex interplay between HIV and SARS-CoV-2, with a special focus on the immune responses to SARS-CoV-2 natural infection and vaccination in PLWH.

Recent findings: Overall, current literature shows that COVID-19 severity and outcomes may be worse and immune responses to infection or vaccination lower in PLWH with poor CD4 + T-cell counts and/or uncontrolled HIV viremia. Data regarding the risk of post-acute sequelae of SARS-CoV-2 infection (PASC) among PLWH are extremely scarce, yet they seem to suggest a higher incidence of such condition. Scarce immunovirological control appears to be the major driver of weak immune responses to SARS-CoV-2 infection/vaccination and worse COVID-19 outcomes in PLWH. Therefore, such individuals should be prioritized for vaccination and should receive additional vaccine doses. Furthermore, given the potentially higher risk of developing long-term sequelae, PLWH who experienced COVID-19 should be ensured a more careful and prolonged follow-up.

Purpose of review: With the advent of antiretroviral therapy, HIV infection has become a chronic disease in developed countries.

Recent findings: Non-HIV-driven risk factors for kidney disease, such as APOL1 risk variants and other genetic and environmental factors, have been discovered and are better described. Consequently, the field of HIV-associated kidney disease has evolved with greater attention given to traditional risk factors of CKD and antiretroviral treatment's nephrotoxicity. In this review, we explore risk factors of HIV-associated kidney disease, diagnostic tools, kidney pathology in HIV-positive individuals, and antiretroviral therapy-associated nephrotoxicity.

Purpose of review: This review describes how advances in CyTOF and high-dimensional analysis methods have furthered our understanding of HIV transmission, pathogenesis, persistence, and immunity.

Recent findings: CyTOF has generated important insight on several aspects of HIV biology: (1) the differences between cells permissive to productive vs. latent HIV infection, and the HIV-induced remodeling of infected cells; (2) factors that contribute to the persistence of the long-term HIV reservoir, in both blood and tissues; and (3) the impact of HIV on the immune system, in the context of both uncontrolled and controlled infection. CyTOF and high-dimensional analysis tools have enabled in-depth assessment of specific host antigens remodeled by HIV, and have revealed insights into the features of HIV-infected cells enabling them to survive and persist, and of the immune cells that can respond to and potentially control HIV replication. CyTOF and other related high-dimensional phenotyping approaches remain powerful tools for translational research, and applied HIV to cohort studies can inform on mechanisms of HIV pathogenesis and persistence, and potentially identify biomarkers for viral eradication or control.

Purpose of review: To synthesize recent evidence relating the gut microbiome and microbial metabolites to cardiovascular disease (CVD) in people living with HIV (PLWH).

Recent findings: A few cross-sectional studies have reported on the gut microbiome and cardiovascular outcomes in the context of HIV, with no consistent patterns emerging. The largest such study found that gut Fusobacterium was associated with carotid artery plaque. More studies have evaluated microbial metabolite trimethylamine N-oxide with CVD risk in PLWH, but results were inconsistent, with recent prospective analyses showing null effects. Studies of other microbial metabolites are scarce. Microbial translocation biomarkers (e.g., lipopolysaccharide binding protein) have been related to incident CVD in PLWH. Microbial translocation may increase CVD risk in PLWH, but there is insufficient and/or inconsistent evidence regarding specific microbial species and microbial metabolites associated with cardiovascular outcomes in PLWH. Further research is needed in large prospective studies integrating the gut microbiome, microbial translocation, and microbial metabolites with cardiovascular outcomes in PLWH.

Purpose of review: : Behaviorally acquired (non-perinatal) HIV infection during adolescence and young adulthood occurs in the midst of key brain developmental processes such as frontal lobe neuronal pruning and myelination of white matter, but we know little about the effects of new infection and therapy on the developing brain.

Recent findings: Adolescents and young adults account for a disproportionately high fraction of new HIV infections each year. Limited data exist regarding neurocognitive performance in this age group, but suggest impairment is at least as prevalent as in older adults, despite lower viremia, higher CD4 + T cell counts, and shorter durations of infection in adolescents/young adults. Neuroimaging and neuropathologic studies specific to this population are underway. The full impact of HIV on brain growth and development in youth with behaviorally acquired HIV has yet to be determined; it must be investigated further to develop future targeted treatment and mitigation strategies.

Purpose of review: Sustaining evidence-based interventions in resource-limited settings is a perennial challenge. Despite growing research on the significance of sustainability, few frameworks describe why and how to plan for sustainability in settings limited with resources. Drawing on a synthesis of the literature on sustainability, including the Dynamic Sustainability Framework, we review lessons learned from research to date, to point out a path forward for sustaining evidence-based interventions in resource-limited settings.

Recent findings: We describe PLAN or why people learning, adapting, and nurturing the core values of an intervention can enhance its sustainability over time. PLAN is a dynamic framework that simplifies the process of planning for sustainability of evidence-based interventions throughout the lifecyle of an intervention, taking into consideration the people that matter as well as the learning, adaptation, and nurturing involved with understanding and studying the interactions between interventions/innovations, practice settings, intervention fit, and the broader ecological contexts in which implementation occurs. We use case-study data from our ongoing pragmatic HIV implementation trial, the 4 Youth by Youth project, to detail the value and implications of why people learning, adapting, and nurturing HIV interventions implemented in resource-limited settings matter. PLAN is designed to further the dialogue on ways research and practice teams can critically work to ensure the sustainability of their evidence-based interventions from the onset, particularly in settings and with populations limited with resources. It also illustrates how attention to sustainability from the beginning may foster actions necessary for sustained program → sustained benefits → sustained capacity → sustained value, but in the absence of early and active planning, none of this will occur. Ultimately, we hope to accelerate the sustainability of evidence-based HIV interventions, and making a PLAN at the bare minimum may ensure that the goals of continuing and maintaining desirable features of any evidence-based interventions can be realized.

Purpose of review: In the context of the opioid epidemic, hepatitis C virus (HCV) infection prevalence is increasing among women of reproductive age. Pregnant people with HIV/HCV coinfection may be at increased risk of adverse pregnancy and neonatal outcomes, although research in this key population is lacking.

Recent findings: Treatment with directly acting antivirals (DAAs) has transformed the clinical care for most patients with HCV. However, pregnant people were excluded from trials of these medications. A recent phase I study has shown promise with excellent safety profile for ledipasvir-sofosbuvir; demonstrating no episodes of perinatal transmission, 100% sustained virologic response, and no safety concerns. Pregnancy represents a time of maximal interaction with the healthcare system and therefore an ideal window of opportunity to cure HCV. Current observational data regarding pregnant people who are co-infected with HCV and HIV suggest poor outcomes such as increased risk of preterm birth; however, there are no prospective and well-controlled studies to fully understand the impact of HIV/HCV coinfection on pregnancy. Phase 1 studies suggest that DAAs are well-tolerated and effective during pregnancy. Only through large, prospective clinical trials will we be able to understand the interaction of HCV and HIV during pregnancy and to evaluate safety and efficacy of DAAs in this key population.

Purpose of review: The burden of metabolic diseases, including type 2 diabetes mellitus (T2DM), is rising among persons with HIV (PWH) on antiretroviral therapy (ART). This increase coincides with an aging population and a greater proportion who are overweight/obese. This review summarizes the changing epidemic of T2DM on contemporary ART, the role of weight gain, and therapeutic options.

Recent findings: Recent studies confirm that PWH face an epidemic of obesity and T2DM, similar to the general population. Contemporary ART is associated with greater weight gain and may contribute to the risk of T2DM. Recent advances in medical weight loss therapy offer a way forward in the prevention and treatment of weight-associated T2DM. Weight gain is one of the biggest contributors to T2DM in PWH. Future studies on the role of adipose tissue distribution, adipose tissue function and clinical use of effective weight loss medications may change the paradigm of care for PWH.

Purpose of review: The Nyanza region of western Kenya is lauded for impressive coverage of voluntary medical male circumcision (VMMC) and remains the bedrock of the VMMC program in Kenya. We conducted literature review on programmatic successes and challenges of implementing VMMC program in the region.

Recent findings: Responsive stakeholders' engagement, robust policy environment, effective technical working groups, prompt capacity building of health facilities, government support, flexible implementation strategies, and sustained donor funding contributed to the successes of the program that saw circumcision prevalence in Nyanza reach between 75.6 and 85.3% among 15-29-year-olds by 2019. However, the lack of support for early infant circumcision, inadequate domestic financing, and slow pace of service integration into government health facilities continue to undermine the progress towards sustainability. While local ownership of the VMMC program has been demonstrated through its inclusion in county annual health workplans and progressive integration into routine health care, continued dependence on declining external funding threatens its sustainability. Furthermore, Kenya is experiencing a youth bulge with a projected high demand for VMMC which calls for increased resource inputs into the program. Strategies are therefore needed to increase domestic resource inflows into VMMC.