Current opinion in HIV and AIDS最新文献

Purpose of review: As more women with HIV survive into older age, the menopausal transition has emerged as a critical yet underexplored determinant in HIV pathogenesis. Declining exposure to estrogens during menopause alters innate and adaptive immunity, driving inflammation, comorbidities, and viral persistence.

Recent findings: Estrogen influences both innate and adaptive immune responses. Estradiol enhances plasmacytoid dendritic cell type I interferon (IFN) production through Toll-like Receptor 7 (TLR7), promotes natural killer (NK) cell activity, and tempers monocyte/macrophage activation. Menopause reverses these effects, contributing to elevated inflammatory mediators. On the adaptive side, estrogen loss increases T-cell activation and exhaustion, impairs B-cell responses, and removes estrogen receptor (ER)-mediated suppression of HIV transcription. Together, these shifts may promote stabilization or expansion of the HIV reservoir in perimenopausal women with HIV, in contrast to the gradual decay often observed in men on antiretroviral therapy (ART).

Summary: Estrogen depletion during menopause reshapes immunity in women with HIV, fueling chronic inflammation, comorbidity risk, and HIV reservoir persistence. Integrating reproductive aging into HIV cure and comorbidity research, and testing hormone-based and anti-inflammatory interventions, will be essential to improve health outcomes for aging women with HIV.

Purpose of review: HIV infects a broad array of tissues throughout the body. Consequently, any successful HIV cure strategy will need to target tissue HIV reservoirs, in addition to peripheral blood. Here we review recent immunotherapy approaches for HIV cure, with a focus on their ability to target viral tissue reservoirs, including immune privileged sites like the central nervous system (CNS).

Recent findings: Recent clinical trials of immunotherapy for HIV cure have demonstrated viral control in a subset of participants. T cell therapies, especially chimeric antigen receptor (CAR) T cells that can be targeted to lymphoid tissue, are highly promising, as are monoclonal antibody therapies such as broadly neutralizing antibodies to suppress HIV viremia and immune checkpoint inhibitors to enhance immune function. Despite this success, the penetration of many of these agents into the CNS is limited, and this remains a barrier to more widespread success of these therapies.

Summary: Immunotherapies represent a promising path toward an HIV cure, however their ability to target viral reservoirs within tissues represents a major challenge. Combination approaches leveraging multiple immunotherapy strategies, and other agents to reduce the HIV reservoir will likely be required to achieve viral control in the absence of antiretroviral therapy.

Purpose of review: Despite effective antiretroviral therapy (ART), HIV-1 persists in latently infected cells that evade host immunity and can resume viral production upon treatment interruption. To address this challenge, the "shock and kill" strategy aims to use latency-reversing agents (LRAs) to reactivate HIV-1 expression, to allow infected cells to die from viral cytopathic effects or immune-mediated killing.

Recent findings: Several LRAs capable of reactivating HIV-1 ex vivo have been identified over the years, but most induce excessive T-cell activation and are unsuitable for in vivo use. Those advanced to clinical trials safely trigger HIV-1 transcription and modestly reduce reservoir size but have failed to achieve reservoir eradication. This limited in vivo efficacy of LRAs is thought to result from their inability to overcome posttranscriptional blocks, as well as from LRA-induced off-target effects on cellular transcription that can impair immune responses. Recent trials combining LRAs with immune modulators have shown promise in further reducing reservoir size and enhancing immunological control after treatment interruption.

Summary: Combining LRAs with immune modulators represents a promising strategy to expose viral reservoirs to immune clearance and advance toward durable, scalable ART-free remission.

Purpose of review: Persistent HIV reservoirs within lymphoid tissues represent a major obstacle to achieving an HIV cure. This review examines current and emerging assays used to visualize, characterize, and quantify these reservoirs. Recent advancements in imaging, sequencing, and single-cell technologies are providing unprecedented detail about the composition, landscape and behavior of HIV reservoirs.

Recent findings: Innovative assays, including intravital microscopy, spatial transcriptomics, next-generation sequencing, and highly multiplexed single-cell analyses, are revealing the complex interplay between the virus and the host immune system within lymphoid tissues. These methods are uncovering the heterogeneity of the latent reservoir, identifying specific cellular and molecular markers of viral persistence, and providing a more nuanced understanding of latency reversal dynamics.

Summary: Advancements in visualizing and characterizing HIV reservoirs are crucial for the development and evaluation of novel cure interventions. By providing a deeper understanding of the mechanisms underlying viral persistence, these assays can inform the design and measure the effectiveness of targeted therapies aimed at eliminating or permanently silencing the reservoir.

Purpose of review: The purpose of this review is to assess current methods for evaluating the sustainability and scalability of HIV prevention, care, and treatment programs - the maintenance, timeliness, and quality of which are priorities for global HIV epidemic control. We highlight specific opportunities to enhance methodological rigor for lasting HIV epidemic control.

Recent findings: Cost and cost-effectiveness of implementation strategies can prepare organizations for sustainability and scale-up. Organizational readiness for initial implementation and alignment with institutional structures are associated with program sustainment and scale-up capacity. Health systems capacity, including alignment between health ministries and external donors, builds capacity for sustainment. Due to limited resources and staffing instability, health systems may lack absorptive capacity to sustain programs once external funding is removed.

Summary: There is a growing body of scholarship retrospectively evaluating the durability and expansion of HIV prevention and treatment programs in practice, in addition to just in principle or theory (i.e. prospectively). To inform future decision-making and support sustained delivery across varying settings and populations, future work should prioritize longitudinal, mixed-methods approaches that assess the impact of policy changes, absorptive capacity, and integrating HIV treatment and prevention into existing health systems.

Purpose of review: This review examines recent research on the mechanisms underlying resistance to cytotoxic T lymphocyte (CTL)-mediated killing, commonly referred to as 'CTL-resistance', which contributes in the persistence of the HIV-1 reservoir and represents a major barrier to achieving an HIV-1 cure.

Recent findings: Recent discoveries have revealed that the viral reservoir in people with HIV (PWH) in long-term antiretroviral (ART) treatment is enriched within cells exhibiting a pro-survival phenotype, reduced antigen presentation capacity, or intrinsic mechanisms that may directly counteract cytotoxic responses, thereby facilitating immune-killing evasion. Among many others, overexpression of the antiapoptotic protein BCL-2, the pro-survival factor BIRC-5/SURVIVIN and its upstream regulator OX40, the histone methyltransferase EZH-2, or a quiescent metabolic profile with reduced reactive oxygen species production have been described as the most notable mechanisms of CTL-resistance.

Summary: While several advances in HIV therapeutic vaccines have demonstrated its ability to induce strong polyfunctional CTL responses associated with improved viral control, vaccine-induced responses fail to reduce reservoir levels- which might be partially due to a CTL-resistant HIV reservoir able to evade immune-mediated clearance. Strategies aimed at reversing this CTL-resistance or sensitize the HIV-1 reservoir might improve the efficacy of future immunotherapies aimed at achieving a durable ART-free control.

Purpose of review: Substance use disorders (SUDs) are common among people with HIV (PWH) and have been linked to sub-optimal HIV care outcomes. Integration of substance use services into HIV care is an implementation strategy with potential to increase uptake of substance use services and improve HIV care outcomes. This review synthesizes recent U.S.-based studies on the epidemiology of substance use and HIV and integrated care models.

Recent findings: We identified 18 studies published between January 2023 and June 2025. These studies reported high prevalence of substance use among PWH, with disparities by race/ethnicity and sexual orientation. Examples of integrated care models ranged from co-located low-barrier clinics to brief behavioral interventions. Overall, integration strategies were feasible and acceptable but demonstrated variable levels of reach and impact on HIV care outcomes. Few studies explicitly used implementation science frameworks.

Summary: Effective integration of SUD and HIV care has the potential to improve uptake of substance use services, address disparities, and aligns with federal initiatives to achieve HIV and substance use public health goals, such as Ending the HIV Epidemic and HEAL. Increased application of implementation science could guide the evaluation of these programs and hopefully enhance their reach and impact.

Purpose of review: While existing guidance supports the use of analytical treatment interruptions (ATIs) in HIV cure clinical trials, their design must be tailored to the intervention and scientific question. As immunologically based cure strategies gain prominence, understanding how ATIs interact with HIV-specific immune responses is critical for their safe and effective implementation.

Recent findings: Time to rebound ATIs evaluate how quickly HIV returns after stopping treatment and are generally safer due to limited viraemia duration. In contrast, set point ATIs measure the level at which viraemia stabilizes after rebound and may pose greater risks, as participants can experience higher viraemia before reaching a set point or demonstrating post intervention control. Shorter ATIs appear to cause only transient effects on the HIV reservoir, immune function, and inflammation. However, the long-term consequences of prolonged ATIs remain unclear due to limited data.

Summary: As HIV cure research progresses, carefully designed ATIs are essential for evaluating new therapies. Longer follow up post virological suppression should be considered, despite potential cost and logistical burdens. When collected, these data and outcomes should be reported in trial publications and shared with stakeholders.

Purpose of review: This review synthesizes literature since January 2024 on the adaptation of HIV interventions and implementation strategies. Both the enormous, but currently unfilled potential of new treatment and prevention technologies, as well as the pressing need to meet global HIV epidemic control targets amid recent HIV funding cuts, necessitate adaptation to improve intervention and implementation effectiveness, scalability, and responsiveness in diverse populations and contexts.

Recent findings: Recent literature demonstrates the application of multistep frameworks guiding adaptation and improved documentation using tools such as FRAME, and rigorous study designs that inherently support and evaluate adaptation such as MOST and SMART. Adaptation targets include enhanced cultural relevance and implementer perspectives, while amplifying community voices and leveraging technology. More rigorous evaluation of adaptation processes and outcomes is still needed.

Summary: The findings highlight the importance of adaptation in improving scalability, equity, and impact in HIV implementation. Improved transparency in adaptation documentation and etiologies can improve adaptation efficiency, mechanistic understanding, and transferability. Novel study designs support adaptation with rigorous evaluation. Prioritizing structured, participatory adaptation processes can improve equity and health impact, especially for marginalized populations.