{"title":"HIV-1 reservoir landscape of post-treatment control.","authors":"Caroline Charre, Yanis Merad, Véronique Avettand-Fenoel","doi":"10.1097/COH.0000000000000891","DOIUrl":"https://doi.org/10.1097/COH.0000000000000891","url":null,"abstract":"<p><strong>Purpose of review: </strong>This review explores the viral reservoir landscape in individuals who control viral replication after treatment interruption (TI), designated as post-treatment controllers (PTCs). Identifying their virologic features is crucial to inform drug-free HIV remission strategies.</p><p><strong>Recent findings: </strong>Traditionally characterized as small, likely due to early treatment, the viral reservoir of PTCs, after TI, exhibits limited transcriptional activity, residual viral replication and subsequent proviral diversity. Intact proviruses are found to be restricted. In nonhuman primate PTCs, this depletion of intact proviruses is already observed in lymph nodes before TI, suggesting that control mechanisms begin during antiretroviral therapy. Furthermore, recent studies suggest immune-driven proviral deep latency associated with repressive epigenetic features and integration sites in PTCs. While molecular mapping of virological features of PTCs is increasingly precise and coupled with in-depth immunologic assays, robust predictive biomarkers of PTCs are still lacking.</p><p><strong>Summary: </strong>Despite limited sample sizes and heterogeneous definitions, common virologic features of PTCs include restricted reservoir size and transcriptional activity, fewer intact proviruses and deep proviral latency. Ongoing research using innovative technologies will further elucidate the mechanisms underlying post-treatment control, paving the way for successful HIV cure interventions.</p>","PeriodicalId":93966,"journal":{"name":"Current opinion in HIV and AIDS","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142559839","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":"Stem cell transplantation and allogeneic immunity: post treatment control or HIV cure?","authors":"Megan Cleary, Lishomwa C Ndhlovu, Jonah B Sacha","doi":"10.1097/COH.0000000000000892","DOIUrl":"https://doi.org/10.1097/COH.0000000000000892","url":null,"abstract":"<p><strong>Purpose of review: </strong>Long-lasting HIV remission has been reported in a small group of people with HIV (PWH) following allogenic hematopoietic stem cell transplants (HSCT) for the treatment of hematologic malignancies. While the mechanisms of HIV remission following release from antiretroviral therapy (ART) were not initially known, subsequent findings from clinical cases and preclinical nonhuman primate studies have implicated mechanisms of clearance. Here, we review the six currently published human cases of long-term ART-free HIV remission.</p><p><strong>Recent findings: </strong>Since the first report of ART-free HIV remission following HSCT, five subsequent cases of HSCT-induced sustained HIV remission have been published. While the pre- and posttransplant treatment conditions vary greatly, all but one received cells from donors homozygous for a 32 bp deletion in the gene that encodes CCR5 (ccr5Δ32), the major HIV coreceptor. Studies in nonhuman primates and the newest published individual suggest that while CCR5 deficiency can protect donor cells from infection early posttransplant, it is not required for long term remission, as ablation of the viral reservoir is likely due to allogeneic immunity mediating a graft-versus-reservoir response.</p><p><strong>Summary: </strong>Studies of HSCT in PLWH and simian immunodeficiency virus (SIV)-infected monkeys show that those with durable remission are likely cured, demonstrated by complete ablation of the replication-competent HIV reservoir, gradual loss of anti-HIV immunity, and greater than 5 years of aviremia.</p>","PeriodicalId":93966,"journal":{"name":"Current opinion in HIV and AIDS","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142559840","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}
Demi A Sandel, Rachel L Rutishauser, Michael J Peluso
{"title":"Post-intervention control in HIV immunotherapy trials.","authors":"Demi A Sandel, Rachel L Rutishauser, Michael J Peluso","doi":"10.1097/COH.0000000000000890","DOIUrl":"https://doi.org/10.1097/COH.0000000000000890","url":null,"abstract":"<p><strong>Purpose of review: </strong>While post-treatment control following interruption of standard-of-care antiretroviral therapy (ART) is well described, post-intervention control following immunotherapy in HIV cure-related clinical trials is less well understood. We provide an overview of recent studies that have identified post-intervention controllers and review the mechanisms that may drive this biologically important phenotype.</p><p><strong>Recent findings: </strong>Post-intervention controllers have been identified in recent immunotherapy trials testing broadly neutralizing antibodies, immune modulators, modified T cells, checkpoint inhibitors, and gene therapy administered individually or in combination. Currently, there is substantial variability in how each trial defines post-intervention control, as well as in how the mechanisms underlying such control are evaluated. Such mechanisms include ongoing activity of both exogenous and autologous antibodies, as well as changes in HIV-specific T cell function.</p><p><strong>Summary: </strong>While no therapeutic strategy to date has succeeded in definitively inducing HIV control, many studies have identified at least a small number of post-intervention controllers. The field would benefit from a standardized approach to defining and reporting this phenotype, as well as standardization in the approach to assessment of how it is achieved. Such efforts would allow for comparisons across clinical trials and could help accelerate efforts toward an HIV cure.</p>","PeriodicalId":93966,"journal":{"name":"Current opinion in HIV and AIDS","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142570696","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}
Leila B Giron, Alexander O Pasternak, Mohamed Abdel-Mohsen
{"title":"Soluble markers of viral rebound and post-treatment HIV control.","authors":"Leila B Giron, Alexander O Pasternak, Mohamed Abdel-Mohsen","doi":"10.1097/COH.0000000000000889","DOIUrl":"10.1097/COH.0000000000000889","url":null,"abstract":"<p><strong>Purpose of review: </strong>We focus on the different classes of biological molecules measurable in easily accessible bodily fluids that have the potential to serve as biomarkers for the HIV post-treatment controller (PTC) phenotype and/or the timing of viral rebound after stopping antiretroviral therapy (ART).</p><p><strong>Recent findings: </strong>Various viral components and host factors measurable in body fluids can play crucial roles in understanding and predicting the PTC phenotype. We review recent findings linking viral components, the quantitative and qualitative features of antibodies (including autologous HIV-specific antibodies), markers of inflammation and tissue damage, other host proteins (including hormones such as sex hormones), as well as metabolites, extracellular vesicles, and cell-free DNA to HIV control post-ART interruption. Several of these molecules can or have the potential to predict the time and probability of viral rebound after stopping ART and are biologically active molecules that can directly or indirectly (by modulating immune pressures) impact the size and activity of HIV reservoirs during and post-ART interruption.</p><p><strong>Summary: </strong>A comprehensive model combining multiple markers is needed to predict the PTC phenotype. This model can be leveraged to predict and understand the PTC phenotype, which can guide novel curative interventions to replicate this phenotype in post-treatment non-controllers.</p>","PeriodicalId":93966,"journal":{"name":"Current opinion in HIV and AIDS","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142402442","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":"Pediatric perspective: the microbiome in vertical HIV-infection: unravelling gaps, challenges, and therapeutic potential.","authors":"Talía Sainz, Grace Aldrovandi","doi":"10.1097/COH.0000000000000875","DOIUrl":"https://doi.org/10.1097/COH.0000000000000875","url":null,"abstract":"<p><strong>Purpose of review: </strong>The intricate interplay between HIV and the host microbiota has emerged as a significant area of investigation with therapeutic potential. Despite numerous studies on this complex interaction in adults, vertically acquired infections, which have distinct immunological and virological characteristics, remain relatively understudied.</p><p><strong>Recent findings: </strong>Disturbances, including prolonged exposure to HIV and antiretroviral therapy, significantly impact the gut microbiome, though isolating these effects from other influencing factors is challenging. Children and adolescents living with HIV exhibit reduced microbiome diversity and potential imbalances between beneficial and pathogenic taxa. However, most available data focus on microbiome composition rather than function. The observed variations in specific microbial phyla are intriguing, but their health effects are unknown. Although modulating the microbiota may be theoretically easier during childhood, few interventional trials have included children.</p><p><strong>Summary: </strong>Therapeutic interventions aimed at modulating the gut microbiome in children with HIV have shown limited impact, and their ability to induce long-term microbiome changes remains uncertain. A more functional, longitudinal approach, along with an ecological perspective, is needed to understand the complex interplay between the microbiome and the host. This will help clarify the relevance of microbiota alterations and their potential implications for clinical outcomes, such as inflammation and immune reconstitution in pediatric HIV.</p>","PeriodicalId":93966,"journal":{"name":"Current opinion in HIV and AIDS","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141899216","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}
Ricky A Lippincott, John O'Connor, Charles P Neff, Catherine Lozupone, Brent E Palmer
{"title":"Deciphering HIV-associated inflammation: microbiome's influence and experimental insights.","authors":"Ricky A Lippincott, John O'Connor, Charles P Neff, Catherine Lozupone, Brent E Palmer","doi":"10.1097/COH.0000000000000866","DOIUrl":"10.1097/COH.0000000000000866","url":null,"abstract":"<p><strong>Purpose of review: </strong>To review novel experimental approaches for studying host:microbe interactions and their role in intestinal and systemic inflammation in people living with HIV (PLWH).</p><p><strong>Recent findings: </strong>Inflammation in PLWH is impacted by interactions between the microbiome, the intestinal epithelium, and immune cells. This complex interplay is not fully understood and requires a variety of analytical techniques to study. Using a multiomic systems biology approach provides hypothesis generating data on host:microbe interactions that can be used to guide further investigation. The direct interactions between host cells and microbes can be elucidated using peripheral blood mononuclear cells (PBMCs), lamina propria mononuclear cells (LPMC's) or human intestinal organoids (HIO). Additionally, the broader relationship between the host and the microbiome can be explored using animal models such as nonhuman primates and germ-free and double humanized mice.</p><p><strong>Summary: </strong>To explore complex host:microbe relationships, hypotheses are generated and investigations are guided by multiomic data, while causal components are identified using in-vitro and in-vivo assays.</p>","PeriodicalId":93966,"journal":{"name":"Current opinion in HIV and AIDS","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11305906/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141332678","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":"Penile microbiome: decoding its impact on HIV risk.","authors":"Sydney G Nelson, Cindy M Liu","doi":"10.1097/COH.0000000000000865","DOIUrl":"10.1097/COH.0000000000000865","url":null,"abstract":"<p><strong>Purpose of review: </strong>The penile microbiome has been linked to local inflammation and increased risk for sexually transmitted infections, including HIV. This review explores recent studies of this emerging area of HIV research.</p><p><strong>Recent findings: </strong>The male urogenital tract supports multiple distinct niches, where their associated microbiome are shaped by abiotic (e.g., oxygen, moisture) and biotic (e.g., host immunity) environmental factors and host behaviors, particularly sexual activity. In addition, male circumcision is a significant drivers of male genital microbiome in both children and adults. Recent sexual partner studies provide new insight into the exchange of genital bacteria and concurrent local immune changes that may impact HIV risk.</p><p><strong>Summary: </strong>The male genital microbiome is shaped by the local microenvironment and host behaviors including sexual activity. Improving our understanding of the connection between the male genital microbiome, local inflammation, and HIV susceptibility, as well as how pro-inflammatory genital bacteria are transmitted between sexual partners may inform new strategies to prevent HIV transmission.</p>","PeriodicalId":93966,"journal":{"name":"Current opinion in HIV and AIDS","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11305963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141461341","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":"Therapeutic microbiome modulation: new frontiers in HIV treatment.","authors":"Rene Bulnes, Netanya S Utay","doi":"10.1097/COH.0000000000000864","DOIUrl":"10.1097/COH.0000000000000864","url":null,"abstract":"<p><strong>Purpose of review: </strong>Dysbiosis may be a key driver of systemic inflammation, which increases the risk of non-AIDS events in people living with HIV (PLWH). Modulation of the microbiome to reverse this dysbiosis may be a novel approach to decrease inflammation and therefore morbidity and mortality in PLWH.</p><p><strong>Recent findings: </strong>Fecal microbiota transplantation (FMT), probiotics, prebiotics, synbiotics, postbiotics, and dietary modifications have the potential to modulate the microbiome. These interventions have been well tolerated in clinical trials to date. However, these interventions have not resulted in consistent or lasting changes to the microbiome or consistent changes in biomarkers of intestinal permeability, microbial translocation, inflammation, immune activation, or CD4 + T cell counts. Sustained engraftment may require prebiotics and/or dietary modifications added to either probiotics or FMT.</p><p><strong>Summary: </strong>Adequately powered randomized controlled trials are needed to elucidate whether microbiome modulation can be achieved and impact systemic inflammation in PLWH.</p>","PeriodicalId":93966,"journal":{"name":"Current opinion in HIV and AIDS","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141319339","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":"Elite controllers microbiome: unraveling the mystery of association and causation.","authors":"Xiangning Bai, Anders Sönnerborg, Piotr Nowak","doi":"10.1097/COH.0000000000000867","DOIUrl":"10.1097/COH.0000000000000867","url":null,"abstract":"<p><strong>Purpose of review: </strong>To unravel the current knowledge and possible link between the gut microbiome and HIV-1 virological control in elite controllers (EC), who can suppress viral replication in the absence of antiretroviral therapy. In addition, to discuss the limitations of current research and propose future research directions.</p><p><strong>Recent findings: </strong>EC possess a different gut bacterial microbiota profile in composition and functionality from that of treatment-naive HIV-1 viremic progressors (VP). Specifically, EC have a richer bacterial microbiota as compared to VP, which closely resembles the microbiota in HIV-1 negative healthy controls (HC). Differentially abundant bacteria are found between EC and VP or HC, though results vary among the few existing studies. These data imply that the gut microbiome could contribute to the natural suppression of HIV-1 infection.</p><p><strong>Summary: </strong>An association between the gut microbiome and HIV-1 virological control is evidenced by recent studies. Yet, there are substantial knowledge gaps, and the underlying mechanism of how the microbiome influences the EC phenotype is far from clarified. Future research should consider diverse microbial communities, the complex microbe-host interactions, as well as yet-unidentified causal links between microbiome alterations and HIV-1 disease progression.</p>","PeriodicalId":93966,"journal":{"name":"Current opinion in HIV and AIDS","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141319338","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}
Emily M Cherenack, Courtney A Broedlow, Nichole R Klatt
{"title":"The vaginal microbiome and HIV transmission dynamics.","authors":"Emily M Cherenack, Courtney A Broedlow, Nichole R Klatt","doi":"10.1097/COH.0000000000000869","DOIUrl":"10.1097/COH.0000000000000869","url":null,"abstract":"<p><strong>Purpose of review: </strong>Among women, having a nonoptimal, highly diverse vaginal microbiome dominated by bacteria other than optimal Lactobacillus species such as L. crispatus or L. jensenii predicts HIV transmission. Reducing HIV acquisition among women requires a better understanding of the mechanisms through which the vaginal microbiome impacts HIV transmission dynamics and how to more effectively treat and intervene. Technological advancements are improving the ability of researchers to fully characterize interacting host-bacteria mechanisms. Consequently, the purpose of this review was to summarize the most innovative research on the vaginal microbiome and its role in HIV transmission in the past year.</p><p><strong>Recent findings: </strong>Studies combining multiomics, experimental, and translational approaches highlight the associations of a nonoptimal microbiome with maladaptive alterations in immune cell functioning, vaginal metabolites, host cell transcription, mucosal immunity, and epithelial barrier integrity. While there are multiple mechanisms proposed to increase HIV acquisition risk, there are virtually zero acceptable and effective treatments to improve the vaginal microbiome and immunity.</p><p><strong>Summary: </strong>Women-centered solutions to modify the vaginal microbiome and bacterial metabolites should continue to be explored as a mechanism to reduce HIV acquisition.</p>","PeriodicalId":93966,"journal":{"name":"Current opinion in HIV and AIDS","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141461343","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}