Current HIV/AIDS Reports最新文献

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.

Purpose of review: Through December 2020, the U.S. President's Emergency Plan for AIDS Relief (PEPFAR) supported more than 25 million voluntary medical male circumcisions (VMMC) as part of the combined HIV prevention strategy in 15 African countries. PEPFAR monitors defined adverse events (AEs) occurring within 30 days of VMMC through its notifiable adverse event reporting system (NAERS). All NAERS reports through December 2020 were reviewed to quantify AE type, severity, and relation to the VMMC procedure. Interventions to improve client safety based on NAERS findings are described.

Recent findings: Fourteen countries reported 446 clients with notifiable adverse events (NAEs); 394/446 (88%) were determined VMMC-related, representing approximately 18 NAE reports per million circumcisions. Fatalities comprised 56/446 (13%) with 24/56 (43%) of fatalities determined VMMC-related, representing 0.96 VMMC-related fatalities per million circumcisions. The remaining 390 NAEs were non-fatal with 370/390 (95%) VMMC-related. Multiple programmatic changes have been made based on NAERS data to improve client safety. Client safety is paramount in this surgical program designed for individual and population-level benefit. Surveillance of rare but severe complications following circumcision has identified pre-existing or new safety concerns and guided continuous programmatic improvement.

Purpose of review: Voluntary medical male circumcision (VMMC) is a surgical procedure that reduces HIV acquisition risk by almost two-thirds. However, global implementation is lagging, in part due to VMMC hesitancy. A better understanding of the mechanism(s) by which this procedure protects against HIV may increase acceptance of VMMC as an HIV risk reduction approach among health care providers and their clients.

Recent findings: HIV acquisition in the uncircumcised penis occurs preferentially across the inner foreskin tissues, due to increased susceptibility that is linked to elevated inflammatory cytokine levels in the sub-preputial space and an increased tissue density of HIV-susceptible CD4 + T cells. Inflammation can be caused by sexually transmitted infections, but is more commonly induced by specific anaerobic components of the penile microbiome. Circumcision protects by both directly removing the susceptible tissues of the inner foreskin, and by inducing a less inflammatory residual penile microbiome. VMMC reduces HIV susceptibility by removing susceptible penile tissues, and also through impacts on the penile immune and microbial milieu. Understanding these mechanisms may not only increase VMMC acceptability and reinvigorate global VMMC programs, but may also lead to non-surgical HIV prevention approaches focused on penile immunology and/or microbiota.

Purpose of review: Voluntary medical male circumcision (VMMC) reduces the risk of HIV acquisition by 60% among heterosexual men, provides protection against certain sexually transmitted infections (STI), and leads to penile microbiome composition changes associated with reduced risk of HIV infection. Intuitively, the benefits of VMMC for female sex partners in relation to STI are likely and have been evaluated. The purpose of this review is to examine emerging findings of broader sexual and reproductive health (SRH) benefits of VMMC for female sex partners.

Recent findings: Systematic reviews find strong evidence for beneficial effects of VMMC on female sex partners risk of HPV, cervical dysplasia, cervical cancer, and with likely protection against trichomoniasis and certain genital ulcerative infections. Few studies assess the direct impact of VMMC on the vaginal microbiome (VMB), though several studies demonstrate reductions in BV, which is mediated by the VMB. Studies are lacking regarding male circumcision status and outcomes associated with non-optimal VMB, such as female infertility and adverse pregnancy outcomes. VMMC has positive effects on women's perceptions of sexual function and satisfaction, and perceptions of disease risk and hygiene, without evidence of risk compensation. VMMC has consistent association with a broad range of women's SRH outcomes, highlighting the biological and non-biological interdependencies within sexual relationships, and need for couples-level approaches to optimize SRH for men and women. The paucity of information on VMMC and influence on VMB is a barrier to optimizing VMB-associated SRH outcomes in female partners.

Purpose of review: Deep tissue HIV reservoirs, especially within the central nervous system (CNS), are understudied due to the challenges of sampling brain, spinal cord, and other tissues. Understanding the cellular characteristics and viral dynamics in CNS reservoirs is critical so that HIV cure trials can address them and monitor the direct and indirect effects of interventions. The Last Gift program was developed to address these needs by enrolling altruistic people with HIV (PWH) at the end of life who agree to rapid research autopsy.

Recent findings: Recent findings from the Last Gift emphasize significant heterogeneity across CNS reservoirs, CNS compartmentalization including differential sensitivity to broadly neutralizing antibodies, and bidirectional migration of HIV across the blood-brain barrier. Our findings add support for the potential of CNS reservoirs to be a source of rebounding viruses and reseeding of systemic sites if they are not targeted by cure strategies. This review highlights important scientific, practical, and ethical lessons learned from the Last Gift program in the context of recent advances in understanding the CNS reservoirs and key knowledge gaps in current research.