Current HIV/AIDS Reports最新文献

Purpose of review: This review highlights the difficulties in diagnosing and treating persons with a prior history of cryptococcal meningitis who improve but suffer from a recurrence of symptoms. This scenario is well known to those who frequently care for patients with cryptococcal meningitis but is not well understood. We highlight major gaps in knowledge.

Recent findings: We recently summarized our experience with 28 persons with paradoxical immune reconstitution inflammatory syndrome (IRIS) and 81 persons with microbiological relapse. CD4 count and cerebrospinal fluid white blood cell count were higher in IRIS than relapse but neither was reliable enough to routinely differentiate these conditions. Second-episode cryptococcal meningitis remains a difficult clinical scenario as cryptococcal antigen, while excellent for initial diagnosis has no value in differentiating relapse of infection from other causes of recurrent symptoms. Updated research definitions are proposed and rapid, accurate diagnostic tests are urgently needed.

Purpose of review: HIV reservoirs are the main barrier to cure. CD4+ T cells have been extensively studied as the primary HIV-1 reservoir. However, there is substantial evidence that HIV-1-infected myeloid cells (monocytes/macrophages) also contribute to viral persistence and pathogenesis.

Recent findings: Recent studies in animal models and people with HIV-1 demonstrate that myeloid cells are cellular reservoirs of HIV-1. HIV-1 genomes and viral RNA have been reported in circulating monocytes and tissue-resident macrophages from the brain, urethra, gut, liver, and spleen. Importantly, viral outgrowth assays have quantified persistent infectious virus from monocyte-derived macrophages and tissue-resident macrophages. The myeloid cell compartment represents an important target of HIV-1 infection. While myeloid reservoirs may be more difficult to measure than CD4+ T cell reservoirs, they are long-lived, contribute to viral persistence, and, unless specifically targeted, will prevent an HIV-1 cure.

Purpose of review: Despite highly effective biomedical HIV pre-exposure prophylaxis (PrEP) options, suboptimal PrEP uptake impedes progress towards ending the epidemic in the United States of America (USA). Implementation science bridges what we know works in controlled clinical trial settings to the context and environment in which efficacious tools are intended to be deployed. In this review, we focus on strategies that target PrEP use barriers at the system or structural level, exploring the implications and opportunities in the context of the fragmented USA healthcare system.

Recent findings: Task shifting could increase PrEP prescribers, but effectiveness evidence is scarce in the USA, and generally focused in urban settings. Integration of PrEP within existing healthcare infrastructure concentrates related resources, but demonstration projects rarely present the resource implications of redirecting staff. Changing the site of service via expanded telehealth could improve access to more rural populations, though internet connectivity, technology access, and challenges associated with determining biomedical eligibility remain logistical barriers for some of the highest burden communities in the USA. Finally, a tailored care navigation and coordination approach has emerged as a highly effective component of PrEP service provision, attempting to directly modify the system-level determinants of PrEP use experienced by the individual. We highlight recent advances and evidence surrounding task shifting, integration, service delivery, and tailoring. With the exception of tailored care navigation, evidence is mixed, and the downstream impact and sustainability of task shifting and care integration require further attention. To maximize PrEP outcomes, research will need to continue to examine the interplay between individuals, clinics, and the healthcare system and associated policies within which they operate.

Purpose of Review

Despite continuous innovations and federal investment to create digital interventions addressing the HIV prevention and care continua, these interventions have not reached people in the U.S. at scale. This article reviews what is known about U.S. implementation of digital HIV interventions and presents a strategy to cross the research-to-practice chasm for these types of interventions.

Recent Findings

We conducted a narrative review of U.S.-based original research on implementation of digital HIV interventions and identified few studies reporting on implementation determinants, strategies, processes, or outcomes, particularly outside the context of effectiveness trials. To supplement the literature, in 2023, we surveyed 47 investigators representing 64 unique interventions about their experiences with implementation after their research trials. Respondents placed high importance on intervention implementation, but major barriers included lack of funding and clear implementation models, technology costs, and difficulty identifying partners equipped to deliver digital interventions. They felt that responsibility for implementation should be shared between intervention developers, deliverers (e.g., clinics), and a government entity. If an implementation center were to exist, most respondents wanted to be available for guidance or technical assistance but largely wanted less involvement.

Summary

Numerous evidence-based, effective digital interventions exist to address HIV prevention and care. However, they remain “on the shelf” absent a concrete and sustainable model for real-world dissemination and implementation. Based on our findings, we call for the creation of national implementation centers, analogous to those in other health systems, to facilitate digital HIV intervention delivery and accelerate progress toward ending the U.S. epidemic.

Purpose of review: Selection of antiretroviral therapy during pregnancy must consider maternal physiology and resulting pharmacokinetic changes in pregnancy, resistance and efficacy profiles, tolerability and frequency of adverse effects, teratogenicity, and maternal, neonatal, and pregnancy outcomes. The objective of this review is to summarize the underlying data that informs the current clinical perinatal guidelines in the USA.

Recent findings: Data now supports the use of dolutegravir at all stages of pregnancy with no significant increase in neural tube defects. Safety and pharmacokinetic data on newer antiretroviral medications in pregnancy continue to lag behind the general population. While there are multiple safety and tolerability concerns with older regimens, there are now multiple options of regimens that are highly efficacious and have good safety data in pregnancy. Most pregnant patients who are virally suppressed on a well-tolerated regimen are able to safely continue those medications during pregnancy.

Purpose of review: An HIV cure that eliminates the viral reservoir or provides viral control without antiretroviral therapy (ART) is an urgent need in children as they face unique challenges, including lifelong ART adherence and the deleterious effects of chronic immune activation. This review highlights the importance of nonhuman primate (NHP) models in developing an HIV cure for children as these models recapitulate the viral pathogenesis and persistence.

Recent findings: Several cure approaches have been explored in infant NHPs, although knowledge gaps remain. Broadly neutralizing antibodies (bNAbs) show promise for controlling viremia and delaying viral rebound after ART interruption but face administration challenges. Adeno-associated virus (AAV) vectors hold the potential for sustained bNAb expression. Therapeutic vaccination induces immune responses against simian retroviruses but has yet to impact the viral reservoir. Combining immunotherapies with latency reversal agents (LRAs) that enhance viral antigen expression should be explored. Current and future cure approaches will require adaptation for the pediatric immune system and unique features of virus persistence, for which NHP models are fundamental to assess their efficacy.

Purpose of Review

The prevalence of HIV-1 in Indonesia is on a concerning upward trajectory, with a concurrent rise in the development of drug-resistant strains, challenging the efficacy of antiretroviral therapy (ART). Many mutations have been found in the pol gene that makes HIV resistant to ART. We aim to review the major drug resistance mutations (DRMs) of reverse transcriptase (RT) of pol gene in HIV-1 cases in Indonesia.

Recent Findings

A total of eleven articles reporting DRMs in HIV-1 subjects from various regions between 2015–2020 in Indonesia are included. The prevalence of major DRMs on the RT gene in studies included varies from 3.4% to 34%. The CRF01_AE subtype stands out as the predominant variant. Notably, the prevalence of major DRMs in ART-experienced individuals is 22.1%, while ART-naïve individuals show a lower rate of 4.4%. Among the RT gene mutations, M184I/V emerges as the most prevalent (10.5%) within the nucleos(t)ide reverse transcriptase inhibitors (NRTI) group, while K103N leads among the non-NRTI (NNRTI) group, with a frequency of 6.4%. Regionally, North Sulawesi records the highest prevalence of major DRMs in the RT gene at 21.1%, whereas Riau and Central Papua exhibit the lowest rates at 3.4%.

Summary

Significant variations in drug resistance mutations within the RT gene across Indonesian regions highlight the importance of closely monitoring and evaluating the effectiveness of current antiretroviral therapy (ART) regimens. Considerably, more studies are needed to understand better and overcome the emergence of DRMs on HIV-1 patients in Indonesia.

Purpose of review: Recent advances in digital technologies can be leveraged to adapt HIV prevention and treatment services to the rapidly changing needs of individuals in everyday life. However, to fully take advantage of these technologies, it is critical to effectively integrate them with human-delivered components. Here, we introduce a new experimental approach for optimizing the integration and adaptation of digital and human-delivered behavioral intervention components for HIV prevention and treatment.

Recent findings: Typically, human-delivered components can be adapted on a relatively slow timescale (e.g., every few months or weeks), while digital components can be adapted much faster (e.g., every few days or hours). Thus, the systematic integration of these components requires an experimental approach that involves sequential randomizations on multiple timescales. Selecting an experimental approach should be motivated by the type of adaptive intervention investigators would like to develop, and the scientific questions they have about its construction.

Purpose of review: Although pre-exposure prophylaxis (PrEP) is effective for reducing risk of HIV transmission, stigma persists as a barrier to HIV prevention. Digital technologies present opportunities to access hard-to-reach populations and increase the efficiency of established interventions. This review examines current digital interventions addressing stigma to improve PrEP-related outcomes.

Recent findings: Digital technologies are increasingly used for HIV prevention and include a wide range of formats. Recent interventions focused on stigma and PrEP tend to engage mobile phone-related technology and focus on younger populations with particular attention to men who have sex with men and transgender women. Digital interventions that address stigma are promising for improving PrEP-related outcomes. No single technology currently demonstrates consistent superiority. Limited access to PrEP and heightened stigma in under-resourced countries present challenges for interventions supporting diverse communities. Further research should examine how digital interventions can reduce stigma beyond the individual level to enhance PrEP use and explore opportunities to improve and integrate approaches to stigma measurement.