Current opinion in HIV and AIDS最新文献

{"title":"Natural killer cells in pediatric HIV cure strategies: from viral control to immunotherapeutics.","authors":"Nicola Cotugno, Lesley de Armas, Paolo Palma","doi":"10.1097/COH.0000000000001034","DOIUrl":"10.1097/COH.0000000000001034","url":null,"abstract":"<p><strong>Purpose of review: </strong>Perinatal HIV infection occurs during a critical window of immune development, in a predominantly naïve immune system, resulting in distinct and unique virologic and immunologic outcomes compared with adult-acquired infection. Innate immunity and specifically natural killer (NK) cells play a role in early viral control and critically shape both size and composition of the HIV reservoir established in infancy. This review examines how NK cell function during acute infection and treatment interruption may contribute to virological outcomes.</p><p><strong>Recent findings: </strong>Emerging data show that NK cell phenotypic and functional diversity associates with reservoir size and persistence. Immune-genetic factors, including HLA and KIR interactions and sex-specific differences, can significantly modulate NK-mediated HIV control. Studies also highlight how perinatal HIV exposure and co-infections alter innate immune networks involving monocytes and CD8 T cells, further influencing reservoir dynamics.</p><p><strong>Summary: </strong>Insights into pediatric NK cell immunity reveal unique mechanisms of early HIV control and reservoir shaping that differ from adults. Understanding how NK cell function influences virological outcomes during acute infection and analytic treatment interruption (ATI) provides a critical foundation for designing cure strategies tailored to children. These include leveraging antibody-based interventions and emerging NK-directed immunotherapies to enhance reservoir clearance and support safer, more effective ATI-informed cure approaches.</p>","PeriodicalId":93966,"journal":{"name":"Current opinion in HIV and AIDS","volume":" ","pages":"312-319"},"PeriodicalIF":4.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13258098/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147950437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Paediatric HIV cure section in Current Opinion in HIV and AIDS.","authors":"Philip J R Goulder, Carlo Giaquinto, Paolo Rossi","doi":"10.1097/COH.0000000000001043","DOIUrl":"10.1097/COH.0000000000001043","url":null,"abstract":"","PeriodicalId":93966,"journal":{"name":"Current opinion in HIV and AIDS","volume":"21 4","pages":"309-311"},"PeriodicalIF":4.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148159757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HIV broadly neutralizing antibodies for children: implementation barriers in low-income settings.","authors":"Arantza Cobela-García, Alfredo Tagarro, Pablo Rojo","doi":"10.1097/COH.0000000000001033","DOIUrl":"10.1097/COH.0000000000001033","url":null,"abstract":"<p><strong>Purpose of review: </strong>Broadly neutralizing monoclonal antibodies (bNAbs) represent a transformative frontier for the prevention, treatment, and potential remission of HIV in children. Given that over 95% of the pediatric population living with or at risk for HIV resides in low-income and middle-income countries (LMICs), prioritizing trials and implementation in these regions is an ethical and clinical imperative. This review identifies the primary structural, biological, and regulatory barriers that must be addressed to ensure equitable global access to bNAb-based interventions.</p><p><strong>Recent findings: </strong>Recent trials in Africa suggest that dual-bNAb combinations can maintain viral suppression in children during ART interruptions and restrict the viral reservoir. While the lower weight-based dosing requirements in neonates and infants present a cost-effective advantage for pediatric HIV management, several scientific and implementation challenges persist. Biological barriers, such as substantial pre-existing resistance to specific bNAbs within HIV-1 Clade C isolates, necessitate region-specific combination therapies, which in turn increase manufacturing and programmatic complexity. Furthermore, pharmacokinetic modeling indicates that elevated viral loads accelerate bNAb clearance, directly influencing optimal dosing strategies and highlighting a critical implementation gap in settings with limited viral load monitoring. Current trials in children are notably behind those in adults, with a lack of confirmatory efficacy data. These biological and clinical challenges are further limited by operational challenges, including climate-driven issues and infrastructure deficits that threaten the cold-chain logistics essential for biologic distribution, posing significant barriers to equitable global access.</p><p><strong>Summary: </strong>While bNAbs offer a promising path toward HIV remission and simplified prevention, their success in LMICs depends on overcoming specific implementation barriers. Addressing these challenges is essential to prevent a delayed and inequitable deployment of these therapies to children in need. All stakeholders within the process from discovery to final implementation need to be involved for an appropriate implementation.</p>","PeriodicalId":93966,"journal":{"name":"Current opinion in HIV and AIDS","volume":" ","pages":"320-327"},"PeriodicalIF":4.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147847772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How nonhuman primate infant and mother-infant models can inform pediatric HIV-1 cure research.","authors":"Claire-Maëlle Fovet, Nabila Seddiki","doi":"10.1097/COH.0000000000001035","DOIUrl":"10.1097/COH.0000000000001035","url":null,"abstract":"<p><strong>Purpose of review: </strong>An estimated 1.4 million children live with HIV-1, yet major gaps remain in understanding neonatal pathogenesis and curative strategies. Nonhuman primate (NHP) infant and mother-infant models provide a critical platform to investigate immune development, elucidate age-specific mechanisms of infection, and evaluate treatment responses, aspects that cannot be directly studied in humans.</p><p><strong>Recent findings: </strong>Newborn macaques exhibit exaggerated gut and lymph nodes seeding, absent interferon-I responses, and accelerated progression compared to juveniles, while ultra-early antiretroviral treatment (ART, day 3) achieves 80% postanalytical treatment interruption (ATI) control that collapses by day 5 due to rapid reservoir fixation. Immunotherapies reveal mechanistic constraints: interleukin-15 agonists paradoxically prolong infected cell survival, whereas CD4-mimetics and BCL-2 inhibitors reduce proviral loads. Germline-targeting SOSIP vaccines elicit superior broadly neutralizing antibodies (bNAb) precursors in infants versus adults, though maternal antibody transfer remains inefficient. Neonatal AAV-delivered bNAbs exploit immune tolerance to confer multiyear protection against SHIV challenges.</p><p><strong>Summary: </strong>NHP models, via timed infections, longitudinal and multitissue sampling, and safe ATI, dissect therapeutic windows guiding clinical translation. Advancing mother-infant NHP research is therefore essential to support the development of pediatric strategies for ART-free remission, a goal that remains challenging to achieve.</p>","PeriodicalId":93966,"journal":{"name":"Current opinion in HIV and AIDS","volume":" ","pages":"337-344"},"PeriodicalIF":4.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147847826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The place to be: HIV persistence within tissue reservoirs.","authors":"Thibaut Dagand, Julien Paul Gigan, Rémi Fromentin, Nicolas Chomont","doi":"10.1097/COH.0000000000001037","DOIUrl":"10.1097/COH.0000000000001037","url":null,"abstract":"<p><strong>Purpose of review: </strong>HIV persists despite effective antiretroviral therapy (ART) due to long-lived reservoirs that resist immune clearance. In people with HIV (PWH) on ART, most infected cells reside in tissues rather than in circulation. Understanding how tissue environments shape HIV persistence and immune control has therefore become central to the development of curative strategies. This review summarizes recent advances in the anatomical, cellular, and immunological mechanisms that contribute to HIV persistence in tissues during ART.</p><p><strong>Recent findings: </strong>Studies combining human tissues, non-human primate models, and single-cell and spatial technologies have revealed that HIV reservoirs are widely distributed across lymphoid and non-lymphoid tissues. Tissue-resident CD4 + T cell populations, including Th17 and T follicular helper cells, represent major cellular reservoirs. Tissue microenvironments influence HIV transcription and may support transcriptionally active reservoirs capable of contributing to viral rebound following treatment interruption. In parallel, HIV-specific CD8 + T cells persist during ART and may sense residual antigen production, but their ability to control infection in tissues can be limited by local immunoregulatory niches and intrinsic resistance mechanisms in reservoir cells.</p><p><strong>Summary: </strong>These findings highlight tissues as key sites governing HIV persistence and immune control, underscoring the need for therapeutic strategies that target tissue reservoirs to achieve durable HIV remission.</p>","PeriodicalId":93966,"journal":{"name":"Current opinion in HIV and AIDS","volume":" ","pages":"296-301"},"PeriodicalIF":4.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147847807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early intervention, lasting impact: benefits of early antiretroviral therapy and implications for posttreatment control.","authors":"Dita C Bolluyt, Godelieve J de Bree, Alexander O Pasternak","doi":"10.1097/COH.0000000000001040","DOIUrl":"10.1097/COH.0000000000001040","url":null,"abstract":"<p><strong>Purpose of review: </strong>Over the past few years, it has become increasingly clear that starting antiretroviral therapy (ART) during acute HIV infection (AHI) leads to a faster viral reservoir decay and partial preservation of the immune system. Here, we review the benefits of treating AHI for the reservoir composition and the adaptive immune function, as well as implications for HIV cure studies.</p><p><strong>Recent findings: </strong>AHI is most commonly defined as the first 6 months following infection. During this early infection stage of infection, HIV viremia reaches its peak, concurrently with the development of the HIV-specific immune response. Early ART limits the size of the viral reservoir, and a smaller reservoir is associated with of longer time to viral rebound posttreatment interruption and, in some cases, posttreatment control (PTC). Moreover, initiating ART during AHI partially preserves the function of T and B cells, leading to improved control of the viral reservoir, and potentially creating windows for HIV cure strategies.</p><p><strong>Summary: </strong>Recent cure studies show that both CD8 + T-cell and antibody responses provide important clues for predicting PTC, as individuals with robust, functional immune profiles are more likely to maintain viral suppression after stopping ART. However, while early ART initiation lowers the viral reservoir and preserves immune function, these factors alone are not sufficient for PTC, highlighting the need for a comprehensive molecular profile that integrates viral and host biomarkers to reliably predict PTC.</p>","PeriodicalId":93966,"journal":{"name":"Current opinion in HIV and AIDS","volume":" ","pages":"271-278"},"PeriodicalIF":4.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13258203/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147950494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of sex differences in adult and paediatric HIV-1 cure.","authors":"Maximilian Muenchhoff, Nomonde Bengu, Philip J R Goulder","doi":"10.1097/COH.0000000000001038","DOIUrl":"10.1097/COH.0000000000001038","url":null,"abstract":"<p><p>Stronger type I interferon responses in females compared to males, starting from intrauterine life, underpin the sex differences observed in HIV-1 cure/remission outcomes in children and adults. In adults these innate immune sex differences favour females achieving HIV-1 cure/remission over males. Recent studies of the adult viral reservoir reflect the ability of innate immune responses in females, including natural killer (NK) cell activity, to remove cells harbouring intact proviral DNA more effectively than males. In children, the situation is more complex. Initially, in the first years of life, males have a higher propensity to achieve HIV-1 cure/remission, at this stage benefiting from the effects of having weaker interferon (IFN)-I responses, including low baseline HIV-1 DNA loads and being recipients of an IFN-I sensitive transmitted founder virus. By mid-childhood, the picture is mixed, with the impact of stronger innate immunity in females combined with the development of more effective HIV-specific CD8 + T-cell response via immune ontogeny tending to favour females beyond the age of 5-10 years. In children, therefore, the double-edged sword effects of IFN-I in the setting of vertical transmission and immune ontogeny results in distinct, dynamic sex advantages through childhood.</p>","PeriodicalId":93966,"journal":{"name":"Current opinion in HIV and AIDS","volume":" ","pages":"287-295"},"PeriodicalIF":4.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13258085/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147950514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Innate immune mechanisms in HIV elite controllers.","authors":"Celia Sánchez-Campaña, Maria J Buzón","doi":"10.1097/COH.0000000000001020","DOIUrl":"10.1097/COH.0000000000001020","url":null,"abstract":"<p><strong>Purpose of review: </strong>To synthesize current evidence on how innate immune mechanisms, including natural killer (NK) cells, dendritic cells (DCs), monocytes, and the cytokine milieu, contribute to durable HIV control in elite controllers (ECs), to highlight key gaps in our understanding of these pathways, and to discuss how EC-informed innate signatures can be harnessed to guide the design of cure-directed interventions.</p><p><strong>Recent findings: </strong>Recent high-dimensional and functional studies have refined the innate immune signatures associated with spontaneous HIV control. NK cells in ECs exhibit distinctive phenotypes, including enrichment of CD69 + subsets, adaptive-like NKG2C + CD57 + populations, and unusual NKG2A/NKG2C co-expression, together with epigenetic remodeling suggestive of specialized antiviral programming. Parallel work has revealed substantial but heterogeneous alterations in monocyte homeostasis, with cohort-dependent shifts in classical and intermediate subsets and evidence of perturbed inflammatory potential. Dendritic-cell studies have identified enhanced intrinsic antiviral programs in ECs, including cooperative activation of cGAS-STING and RIG-I pathways and metabolically reinforced cDC maturation, pointing to improved sensing and antigen-presenting capacity. At the soluble level, newly generated data demonstrate that ECs maintain low circulating interferon alpha (IFN-α) and minimal cellular perturbation, supporting the model of a tightly regulated and spatially constrained IFN-I response.</p><p><strong>Summary: </strong>Elite controllers provide a human model in which innate immunity, through specialized innate cell programs, contributes to durable HIV suppression alongside adaptive responses. However, our view of these pathways is fragmentary, particularly in tissues and over time. Defining which innate mechanisms are necessary, sufficient and safely targetable will be crucial for translating EC biology into rational, combination strategies aimed at achieving ART-free HIV remission.</p>","PeriodicalId":93966,"journal":{"name":"Current opinion in HIV and AIDS","volume":"21 3","pages":"232-239"},"PeriodicalIF":4.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147583367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The elite controller phenotype.","authors":"Nicolas Noel, Olivier Lambotte","doi":"10.1097/COH.0000000000001027","DOIUrl":"10.1097/COH.0000000000001027","url":null,"abstract":"<p><strong>Purpose of review: </strong>Achieving a functional cure for HIV remains a major challenge. In this context, elite controllers (ECs) - rare people living with HIV who maintain durable virological suppression without antiretroviral therapy - represent a unique and highly informative model. Recent years have seen major advances in the characterization of EC phenotypes across diverse geographic settings, as well as renewed interest in their relevance for HIV cure strategies. This review is considering emerging data refining EC heterogeneity, and the unresolved question of antiretroviral treatment indications in this population.</p><p><strong>Recent findings: </strong>Recent studies highlight the marked heterogeneity among ECs, ranging from persistent controllers with long-term undetectable viral loads to transient or viremic controllers at risk of losing control. Key advances concern the quantitative and qualitative features of the HIV reservoir and the role of both adaptive and innate immune responses. Longitudinal cohorts have also clarified the dynamics of loss of control, and the generally low but nonnegligible burden of non-AIDS-defining comorbidities.</p><p><strong>Summary: </strong>Elite controllers provide critical insights into mechanisms of durable HIV remission and inform cure-oriented research. Improved stratification of EC phenotypes may help identify individuals approaching spontaneous functional cure. Antiretroviral therapy should be individualized, balancing virological stability, immune activation, comorbidities, and patient preference, while ongoing research aims to translate lessons from ECs into scalable HIV cure strategies.</p>","PeriodicalId":93966,"journal":{"name":"Current opinion in HIV and AIDS","volume":" ","pages":"212-217"},"PeriodicalIF":4.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13048319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147313673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic determinants of HIV-1 elite control.","authors":"Barry Ryan, Jacques Fellay, Christian W Thorball","doi":"10.1097/COH.0000000000001019","DOIUrl":"10.1097/COH.0000000000001019","url":null,"abstract":"<p><strong>Purpose of review: </strong>Elite controllers, rare individuals who maintain undetectable HIV-1 viremia without antiretroviral therapy, represent a human model of a functional cure. Understanding the host genetic factors that enable this spontaneous viral control is a key goal of HIV-1 research. This review synthesizes recent findings that are challenging and expanding the classic, human leucocyte antigen (HLA)-centric view of elite control.</p><p><strong>Recent findings: </strong>While the dominant association of specific HLA class I alleles (e.g., HLA-B*57, HLA-B*27) with low set-point viral load remains the cornerstone of the field, recent research has highlighted three emerging themes. First, the discovery of a large-effect, Africa-specific genetic association near the CHD1L locus has underscored the critical importance of studying genetically diverse populations. Second, novel approaches have highlighted a multilayered cellular response to HIV-1, suggesting more complex mechanisms of control beyond genetics alone. Third, a central paradox has emerged: the host genetic factors that strongly impact viral load do not show any association with the size or decay rate of the latent viral reservoir in treated individuals, complicating the path from \"control\" to \"cure.\"</p><p><strong>Summary: </strong>The genetic architecture of HIV-1 elite control is more complex than previously appreciated. The field has moved beyond HLA to uncover new, ancestry-specific pathways, explore multiple biological variables, and confront the critical disconnect between controlling viremia and eliminating the latent reservoir.</p>","PeriodicalId":93966,"journal":{"name":"Current opinion in HIV and AIDS","volume":"21 3","pages":"218-223"},"PeriodicalIF":4.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147583365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}