Current opinion in HIV and AIDS最新文献

Purpose of review: To summarize the heterogeneity in the elite controllers population with the aim to identify a compatible profile with a persistent HIV remission, making distinction between persistent elite controllers, people with HIV (PWHIV) who permanently maintain virological control in the absence of antiretroviral treatment (ART), and transient elite controllers, PWHIV who eventually lose virological control. For this purpose, it is important to consider the mechanisms and biomarkers that have previously been associated with the maintenance and loss of the natural virological control.

Recent findings: Transient elite controllers, before losing virological control, exhibit a distinct metabolomic, proteomic, microRNAs (miRNA), immunological and virological profile compared to persistent elite controllers. In addition to a reduced and less polyfunctional HIV-specific T-cell response, transient elite controllers show a greater proportion of intact proviruses integrated into genic regions. In contrast, persistent elite controllers display a privileged HIV-1 reservoir profile with absence of detected intact proviruses or low proportion of clonal intact proviruses preferentially integrated into genomic features associated with HIV-1 transcriptional repression.

Summary: According to previous studies, the comprehensive characterization of persistent elite controllers might be crucial to identify other PWHIV with this distinct profile as spontaneously cured.

Purpose of review: Women are underrepresented in HIV infection and prevention research despite making up half of people living with HIV. The female genital tract (FGT) serves as a primary site of HIV acquisition, but gaps in knowledge remain regarding protective innate immune mechanisms. Innate lymphoid cells are tissue-resident cells involved in mucosal barrier maintenance and protection, and innate lymphoid cells (ILCs) are altered during chronic HIV infection. However, ILCs role in mucosal HIV pathogenesis is unclear and they are poorly characterized in the FGT.

Recent findings: Human ILCs differ from their mouse counterparts and plastically adjust to their tissue of residency. Human ILC characterization is difficult due to tissue-specific adaptations and transition between subsets. While evidence for ILC involvement in antiviral activity and barrier maintenance is provided in mouse models, human ILC role in mucosal immunity remain understudied, particularly in the FGT. In chronic HIV/simian immunodeficiency virus (SIV) infection, ILCs are altered in a tissue-specific manner, and SIV models indicate potential for antiviral responses.

Summary: ILCs are tissue-resident plastic cells that provide barrier protection at mucosal surfaces and display antiviral capacity. Considering that HIV is primarily transmitted through mucosal exposure, more research is needed to understand ILC contribution to HIV pathogenesis in human mucosal surfaces relevant for HIV acquisition.

Purpose of review: Condomless receptive anal intercourse stands out as the sexual practice with highest risk of HIV-1 infection. Recent studies have suggested that the gut microbiome influences susceptibility to HIV transmission. This review explores recent research on host risk factors, the rectal microbiome composition, local inflammation, and bacteria-derived mediators that may affect HIV transmission.

Recent findings: Constitutive host factors such as rectal mucosal structure and immune cell populations in the rectum contribute to increased susceptibility. Changes in the composition of the rectal microbiota, influenced by sexual practices and HIV infection modulate immune activation and inflammation, impacting HIV susceptibility. Bacteria-derived mediators may further influence immune responses and HIV replication in the rectal mucosa.

Summary: Understanding the role of the rectal microbiome in HIV transmission has important clinical implications. Targeted interventions that modulate the microbiome may reduce susceptibility to HIV transmission by regulating immune responses and inflammation. Further research into the host-microbiome interactions could lead to novel preventive and therapeutic strategies to mitigate HIV transmission.

Purpose of review: This review explores the intersection of Mpox and HIV, highlighting clinical manifestations, immune evasion mechanisms, epidemiological challenges, and prevention strategies. People with HIV (PWH), particularly those with low CD4+ cell count, face severe Mpox outcomes. Prevention relies on education, vaccination, and early detection. Integrating Mpox management into HIV care systems is vital.

Recent findings: Since May 2022, Mpox caused by Orthopoxvirus monkeypox (MPV) Clade IIb, has affected 126 countries. In 2024, Clade Ib emerged in the Democratic Republic of Congo, leading to its declaration as a Public Health Emergency of International Concern (PHEIC). Research on MPV-HIV co-infections has provided genomic insights and protective strategies for PWH. Antivirals like tecovirimat show promise despite emerging resistance concerns.

Summary: The global Mpox outbreak caused by Clade IIb and the emergence of Clade Ib underscores its growing threat. Mpox disproportionately impacts PWH, leading to severe outcomes and higher fatality rates. This review emphasizes clinical challenges, genomic advances, and prevention strategies. Enhanced surveillance, vaccination, and tailored therapies are essential to addressing this evolving health crisis.

Purpose of review: The earliest months of HIV infection are characterized by high viral loads and elevated transmissibility, particularly during the acute (preseroconversion) phase. Transmission prevention during early HIV requires diagnostic tools that narrow the window between viral acquisition and reactive test, followed by rapid linkage to effective antiretroviral therapy (ART). Here, we review recent advances related to diagnosing and treating persons during early HIV, with a particular focus on acute HIV infection (AHI).

Recent findings: Point-of-care (POC) fourth-generation antigen/antibody tests have mixed performance, often dependent on the pretest probability of early infection within the screened population. Risk score algorithms demonstrate the potential for prioritizing resource-intensive tests, such as POC HIV RNA, to those most likely to have AHI, but their predictive performance varies across populations, complicating implementation. Emerging and re-emerging infections, including SARS-CoV-2 and mpox, present opportunities for and challenges to symptom-driven AHI screening. Daily oral ART with standard first-line regimens quickly suppresses viremia during AHI, but long-acting injectable drugs are yet to be explored for this indication.

Summary: Few practice-changing results related to diagnosing or treating persons with early HIV have been released in the last 18 months. Accurate POC HIV RNA tests could leapfrog fourth-generation POC assays, but they remain unavailable for routine use. Implementation science approaches are needed to guide use of evidence-based strategies for early HIV screening, and additional research on same-day ART linkage, including injectable ART, could produce dramatic impacts on forward transmission during this period.

Purpose of review: Rare persons who achieve disease-control despite high viral loads (viraemic nonprogressors) or maintain virologic control in the absence of antiretroviral therapy (ART) (elite controllers) or following ART interruption (posttreatment controllers) possess protective factors that can be harnessed for interventions to achieve ART-free remission. This review broadly summarizes these phenotypes in adults and children, and updates on findings important in informing strategies for ART-free remission in children with HIV.

Recent findings: To date, only a few individual cases of posttreatment control have been described in children. Smaller HIV reservoir size with very early ART initiation in neonates with in-utero acquired HIV associates with improved virological and immunological outcomes. Nine new cases of ART-free remission in children were recently described - 4 from the P1115 trial, and 5 males from the Ucwaningo Lwabantwana study in South Africa. A striking reduction in the decay of intact proviruses was observed over three decades on suppressive ART in two early-treated twins with HIV.

Summary: The unique environment of perinatal HIV infection favours effective restriction and decay of the HIV-1 reservoir with suppressive ART initiated very early. Sex and population differences require consideration in ongoing studies to inform ART-free remission.

Purpose of review: Tests for HIV may perform differently in some circumstances such as with preexposure prophylaxis (PrEP) or other HIV prevention agents. Testing algorithms may not account for this, with a risk of false negative or positive HIV results. In this review we have explored the challenges of HIV testing in these special circumstances.

Recent findings: Long-acting injectable PrEP using cabotegravir or lenacapavir has been studied in large randomized controlled trials (HPTN083/084 and PURPOSE1/2 respectively). Injectable PrEP was significantly more efficacious than oral PrEP, but infections still occurred risking the emergence of HIV drug-resistance. HIV diagnostic test results were atypical in those receiving injectable PrEP, with low or undetectable HIV viral loads, delayed or diminished antibody, and HIV detection assays reverting from reactive to unreactive; so-called long acting early viral inhibition (LEVI) syndrome. In these cases, missed or delayed HIV diagnoses could be reduced with the use of HIV nucleic acid amplification tests in addition to routine testing, but this remains unfeasible in many settings.

Summary: Finding HIV testing strategies that are affordable and practical in low- and middle-income countries that can accurately diagnose HIV in the context of HIV prevention is of high importance, but more research is needed in this area.

Purpose of review: This review summarizes recent research literature relevant to mucosal immunity and acute/early HIV infection.

Recent findings: Recent findings include new insights on the HIV transmission "bottleneck" at mucosal surfaces, the impact of acute HIV on germinal centers and mucosal B-cell function, the expression of cytotoxic effector molecules by mucosal CD8+ T-cells, and an enhanced understanding of the impact of acute HIV on innate cell-mediated defenses including mucosa-associated invariant T-cells invarant natural killer T-cells and natural killer cells.

Summary: Now more than 40 years since the beginning of the HIV/AIDS pandemic, extensive research has elucidated the dynamics of HIV replication and the corresponding host response. However, the vast majority of HIV-related immunopathogenesis studies have focused on innate and adaptive immune responses in peripheral blood. Mucosal tissues serve as the primary portals of entry for HIV and house the majority of the body's lymphocytes. Innate and adaptive immune responses in mucosal tissues are of particular relevance during the acute phase of HIV disease, as successful defenses can both limit viral dissemination within the host and prevent transmission to a new host, yet until recently these responses were poorly understood.

Purpose of review: The aim of this review was to describe future options for long-acting HIV treatment and preexposure prophylaxis (PrEP) regimens featuring both innovations with currently approved antiretrovirals and a profile of investigational agents in the pipeline.

Recent findings: Newer formulations and modes of delivery for existing antiretroviral drugs and a number of investigational agents are under study for long-acting HIV treatment and PrEP. Regimens with weekly oral dosing for HIV treatment, monthly oral dosing for HIV PrEP, and injectable agents with longer dosing intervals (every 3 months or longer) for treatment and PrEP are in clinical development. Newer agents with novel mechanisms of action and newer modes of administration including vaginal rings, implants, patches, and rectal douches also are under investigation.

Summary: Despite the success of current antiretroviral therapy and PrEP with one-pill, once-daily regimens, there is a continuing need for new formulations, investigational agents, and novel modes of delivery to overcome barriers to implementation and ensure real-world effectiveness. Newer long-acting antiretroviral regimens for HIV treatment and PrEP using novel preparations and strategies will offer choice, enhance adherence, decrease toxicity, and improve patient and provider satisfaction.

Purpose of review: Recent research on efficacy and safety of long-acting preexposure prophylaxis (PrEP) holds the promise to transform HIV prevention in high HIV burden settings. We review emerging findings regarding early end-user acceptability of long-acting PrEP modalities, feasibility of integrating long-acting PrEP into health systems, and considerations regarding drug resistance and cost.

Recent findings: Long-acting PrEP, particularly injectables, was found to be highly acceptable among individuals across key populations in high HIV burden settings. Concerns around use of long-acting PrEP highlight the importance of choice and ability to switch methods. Existing provider-level barriers to oral PrEP implementation (e.g., overburdened staff, training gaps) may impact long-acting PrEP rollout - however, utilization of PrEP implementation strategies such as task-shifting, timely PrEP training for all providers, differentiated service delivery, and integration with sexual health services, may mitigate barriers. Studies modeling injectable PrEP scale-up demonstrate substantial benefits in HIV mortality reduction, outweighing risks of increased integrase inhibitor resistance, but also highlight the urgency of pricing long-acting PrEP to ensure access and affordability.

Summary: Long-acting PrEP could be a game changer in HIV prevention in high burden settings. There is an urgent need for rapid scale production and price reductions to ensure access in high HIV burden settings. Implementation strategies are needed to address individual and provider-level barriers.