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1. HIV immunological non-responders are characterized by extensive immunosenescence and impaired lymphocyte cytokine production capacity

Author

Vos, Wilhelm A. J. W., primary, Navas, Adriana, additional, Meeder, Elise M. G., additional, Blaauw, Marc J. T., additional, Groenendijk, Albert L., additional, van Eekeren, Louise E., additional, Otten, Twan, additional, Vadaq, Nadira, additional, Matzaraki, Vasiliki, additional, van Cranenbroek, Bram, additional, Brinkman, Kees, additional, van Lunzen, Jan, additional, Joosten, Leo A. B., additional, Netea, Mihai G., additional, Blok, Willem L., additional, van der Ven, Andre J. A. M., additional, Koenen, Hans J. P. M., additional, and Stalenhoef, Janneke E., additional

Published
2024
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2. Liver steatosis is prevalent in lean people living with HIV and associated with exposure to antiretroviral treatment – a cross-sectional study

Author

Van Eekeren, Louise E, primary, Vadaq, Nadira, additional, Vos, Wilhelm A J W, additional, Blaauw, Marc J T, additional, Groenendijk, Albert L, additional, Van Lunzen, Jan, additional, Stalenhoef, Janneke E, additional, Berrevoets, Marvin A H, additional, Verbon, Annelies, additional, Weijers, Gert, additional, Netea, Mihai G, additional, Van Der Ven, André J A M, additional, De Mast, Quirijn, additional, Joosten, Leo A B, additional, and Tjwa, Eric T T L, additional

Published
2024
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3. Recommendations for analytical antiretroviral treatment interruptions in HIV research trials—report of a consensus meeting

Author

Julg, Boris, Dee, Lynda, Ananworanich, Jintanat, Barouch, Dan H, Bar, Katharine, Caskey, Marina, Colby, Donn J, Dawson, Liza, Dong, Krista L, Dubé, Karine, Eron, Joseph, Frater, John, Gandhi, Rajesh T, Geleziunas, Romas, Goulder, Philip, Hanna, George J, Jefferys, Richard, Johnston, Rowena, Kuritzkes, Daniel, Li, Jonathan Z, Likhitwonnawut, Udom, van Lunzen, Jan, Martinez-Picado, Javier, Miller, Veronica, Montaner, Luis J, Nixon, Douglas F, Palm, David, Pantaleo, Giuseppe, Peay, Holly, Persaud, Deborah, Salzwedel, Jessica, Salzwedel, Karl, Schacker, Timothy, Sheikh, Virginia, Søgaard, Ole S, Spudich, Serena, Stephenson, Kathryn, Sugarman, Jeremy, Taylor, Jeff, Tebas, Pablo, Tiemessen, Caroline T, Tressler, Randall, Weiss, Carol D, Zheng, Lu, Robb, Merlin L, Michael, Nelson L, Mellors, John W, Deeks, Steven G, and Walker, Bruce D

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Immunology, HIV/AIDS, Sexually Transmitted Infections, Infectious Diseases, Clinical Research, Clinical Trials and Supportive Activities, Infection, Anti-Retroviral Agents, HIV Infections, Humans, Sustained Virologic Response, Viral Load, Withholding Treatment, Medical and Health Sciences, Biomedical and clinical sciences, Health sciences
Abstract

Analytical antiretroviral treatment interruption (ATI) is an important feature of HIV research, seeking to achieve sustained viral suppression in the absence of antiretroviral therapy (ART) when the goal is to measure effects of novel therapeutic interventions on time to viral load rebound or altered viral setpoint. Trials with ATIs also intend to determine host, virological, and immunological markers that are predictive of sustained viral control off ART. Although ATI is increasingly incorporated into proof-of-concept trials, no consensus has been reached on strategies to maximise its utility and minimise its risks. In addition, differences in ATI trial designs hinder the ability to compare efficacy and safety of interventions across trials. Therefore, we held a meeting of stakeholders from many interest groups, including scientists, clinicians, ethicists, social scientists, regulators, people living with HIV, and advocacy groups, to discuss the main challenges concerning ATI studies and to formulate recommendations with an emphasis on strategies for risk mitigation and monitoring, ART resumption criteria, and ethical considerations. In this Review, we present the major points of discussion and consensus views achieved with the goal of informing the conduct of ATIs to maximise the knowledge gained and minimise the risk to participants in clinical HIV research.

Published
2019

4. Cardiometabolic Differences in People Living with HIV Receiving Integrase Strand Transfer Inhibitors Compared to Non-nucleoside Reverse Transcriptase Inhibitors: Implications for Current ART Strategies

Author

Vos, Wilhelm A. J. W., primary, Vadaq, Nadira, additional, Matzaraki, Vasiliki, additional, Otten, Twan, additional, Groenendijk, Albert L., additional, Blaauw, Marc J. T., additional, van Eekeren, Louise E., additional, Brinkman, Kees, additional, de Mast, Quirijn, additional, Riksen, Niels P., additional, Stalenhoef, Anton F. H., additional, van Lunzen, Jan, additional, van der Ven, Andre J. A. M., additional, Blok, Willem L., additional, and Stalenhoef, Janneke E., additional

Published
2024
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5. Infektionen bei Immunsuppression

Author

Burchard, Gerd-Dieter, Kobbe, Robin, van Lunzen, Jan, Suerbaum, Sebastian, editor, Burchard, Gerd-Dieter, editor, Kaufmann, Stefan H. E., editor, and Schulz, Thomas F., editor

Published
2020
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6. Cardiometabolic Differences in People Living with HIV Receiving Integrase Strand Transfer Inhibitors Compared to Non-nucleoside Reverse Transcriptase Inhibitors:Implications for Current ART Strategies

Author

Vos, Wilhelm A.J.W., Vadaq, Nadira, Matzaraki, Vasiliki, Otten, Twan, Groenendijk, Albert L., Blaauw, Marc J.T., van Eekeren, Louise E., Brinkman, Kees, de Mast, Quirijn, Riksen, Niels P., Stalenhoef, Anton F.H., van Lunzen, Jan, van der Ven, Andre J.A.M., Blok, Willem L., Stalenhoef, Janneke E., Vos, Wilhelm A.J.W., Vadaq, Nadira, Matzaraki, Vasiliki, Otten, Twan, Groenendijk, Albert L., Blaauw, Marc J.T., van Eekeren, Louise E., Brinkman, Kees, de Mast, Quirijn, Riksen, Niels P., Stalenhoef, Anton F.H., van Lunzen, Jan, van der Ven, Andre J.A.M., Blok, Willem L., and Stalenhoef, Janneke E.

Abstract

In people living with HIV (PLHIV), integrase strand transfer inhibitors (INSTIs) are part of the first-line combination antiretroviral therapy (cART), while non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens are alternatives. Distinct cART regimens may variably influence the risk for non-AIDS comorbidities. We aimed to compare the metabolome and lipidome of INSTI and NNRTI-based regimens. The 2000HIV study includes asymptomatic PLHIV (n = 1646) on long-term cART, separated into a discovery cohort with 730 INSTI and 617 NNRTI users, and a validation cohort encompassing 209 INSTI and 90 NNRTI users. Baseline plasma samples from INSTI and NNRTI users were compared using mass spectrometry-based untargeted metabolomic (n = 500) analysis. Perturbed metabolic pathways were identified using MetaboAnalyst software. Subsequently, nuclear magnetic resonance spectroscopy was used for targeted lipoprotein and lipid (n = 141) analysis. Metabolome homogeneity was observed between the different types of INSTI and NNRTI. In contrast, higher and lower levels of 59 and 45 metabolites, respectively, were found in the INSTI group compared to NNRTI users, of which 77.9% (81/104) had consistent directionality in the validation cohort. Annotated metabolites belonged mainly to ‘lipid and lipid-like molecules’, ‘organic acids and derivatives’ and ‘organoheterocyclic compounds’. In pathway analysis, perturbed ‘vitamin B1 (thiamin) metabolism’, ‘de novo fatty acid biosynthesis’, ‘bile acid biosynthesis’ and ‘pentose phosphate pathway’ were detected, among others. Lipoprotein and lipid levels in NNRTIs were heterogeneous and could not be compared as a group. INSTIs compared to individual NNRTI types showed that HDL cholesterol was lower in INSTIs compared to nevirapine but higher in INSTIs compared to doravirine. In addition, LDL size was lower in INSTIs and nevirapine compared to doravirine. NNRTIs show more heterogeneous cardiometabolic effects than INSTIs, which hampers

Published
2024

7. International AIDS Society global scientific strategy: towards an HIV cure 2016

Author

Deeks, Steven G, Lewin, Sharon R, Ross, Anna Laura, Ananworanich, Jintanat, Benkirane, Monsef, Cannon, Paula, Chomont, Nicolas, Douek, Daniel, Lifson, Jeffrey D, Lo, Ying-Ru, Kuritzkes, Daniel, Margolis, David, Mellors, John, Persaud, Deborah, Tucker, Joseph D, Barre-Sinoussi, Françoise, Alter, Galit, Auerbach, Judith, Autran, Brigitte, Barouch, Dan H, Behrens, Georg, Cavazzana, Marina, Chen, Zhiwei, Cohen, Éric A, Corbelli, Giulio Maria, Eholié, Serge, Eyal, Nir, Fidler, Sarah, Garcia, Laurindo, Grossman, Cynthia, Henderson, Gail, Henrich, Timothy J, Jefferys, Richard, Kiem, Hans-Peter, McCune, Joseph, Moodley, Keymanthri, Newman, Peter A, Nijhuis, Monique, Nsubuga, Moses Supercharger, Ott, Melanie, Palmer, Sarah, Richman, Douglas, Saez-Cirion, Asier, Sharp, Matthew, Siliciano, Janet, Silvestri, Guido, Singh, Jerome, Spire, Bruno, Taylor, Jeffrey, Tolstrup, Martin, Valente, Susana, van Lunzen, Jan, Walensky, Rochelle, Wilson, Ira, and Zack, Jerome

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Good Health and Well Being, Acquired Immunodeficiency Syndrome, Goals, HIV Infections, Humans, International Cooperation, Organizational Objectives, Research, Societies, Medical, International AIDS Society Towards a Cure Working Group, Medical and Health Sciences, Biomedical and clinical sciences, Health sciences
Abstract

Antiretroviral therapy is not curative. Given the challenges in providing lifelong therapy to a global population of more than 35 million people living with HIV, there is intense interest in developing a cure for HIV infection. The International AIDS Society convened a group of international experts to develop a scientific strategy for research towards an HIV cure. This Perspective summarizes the group's strategy.

Published
2016

9. Safety and efficacy of the peptide-based therapeutic vaccine for HIV-1, Vacc-4×: a phase 2 randomised, double-blind, placebo-controlled trial

Author

Pollard, Richard B, Rockstroh, Jürgen K, Pantaleo, Giuseppe, Asmuth, David M, Peters, Barry, Lazzarin, Adriano, Garcia, Felipe, Ellefsen, Kim, Podzamczer, Daniel, van Lunzen, Jan, Arastéh, Keikawus, Schürmann, Dirk, Clotet, Bonaventura, Hardy, W David, Mitsuyasu, Ronald, Moyle, Graeme, Plettenberg, Andreas, Fisher, Martin, Fätkenheuer, Gerd, Fischl, Margaret, Taiwo, Babafemi, Baksaas, Ingebjørg, Jolliffe, Darren, Persson, Stefan, Jelmert, Øyvind, Hovden, Arnt-Ove, Sommerfelt, Maja A, Wendel-Hansen, Vidar, and Sørensen, Birger

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Clinical Trials and Supportive Activities, HIV/AIDS, Vaccine Related, Infectious Diseases, Immunization, Clinical Research, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Infection, Good Health and Well Being, AIDS Vaccines, Adult, Anti-Retroviral Agents, CD4 Lymphocyte Count, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Cell Proliferation, Double-Blind Method, Female, HIV Infections, Humans, Immunotherapy, Active, Male, Middle Aged, Time Factors, Viral Load, Withholding Treatment, Young Adult, Clinical Sciences, Public Health and Health Services, Microbiology, Clinical sciences, Medical microbiology, Epidemiology
Abstract

BackgroundPresent combination antiretroviral therapy (cART) alone does not cure HIV infection and requires lifelong drug treatment. The potential role of HIV therapeutic vaccines as part of an HIV cure is under consideration. Our aim was to assess the efficacy, safety, and immunogenicity of Vacc-4x, a peptide-based HIV-1 therapeutic vaccine targeting conserved domains on p24(Gag), in adults infected with HIV-1.MethodsBetween July, 2008, and June, 2010, we did a multinational double-blind, randomised, phase 2 study comparing Vacc-4x with placebo. Participants were adults infected with HIV-1 who were aged 18-55 years and virologically suppressed on cART (viral load

Published
2014

10. Barriers to a cure for HIV: new ways to target and eradicate HIV-1 reservoirs

Author

Katlama, Christine, Deeks, Steven G, Autran, Brigitte, Martinez-Picado, Javier, van Lunzen, Jan, Rouzioux, Christine, Miller, Michael, Vella, Stefano, Schmitz, Joern E, Ahlers, Jeffrey, Richman, Douglas D, and Sekaly, Rafick P

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Infectious Diseases, HIV/AIDS, Aetiology, 2.2 Factors relating to the physical environment, Infection, Anti-HIV Agents, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Drug Therapy, Combination, HIV Infections, HIV-1, Humans, RNA, Viral, Receptors, CCR5, Virus Latency, Virus Replication, Medical and Health Sciences, General & Internal Medicine, Biomedical and clinical sciences, Health sciences
Abstract

Antiretroviral therapy for HIV infection needs lifelong access and strict adherence to regimens that are both expensive and associated with toxic effects. A curative intervention will be needed to fully stop the epidemic. The failure to eradicate HIV infection during long-term antiretroviral therapy shows the intrinsic stability of the viral genome in latently infected CD4T cells and other cells, and possibly a sustained low-level viral replication. Heterogeneity in latently infected cell populations and homoeostatic proliferation of infected cells might affect the dynamics of virus production and persistence. Despite potent antiretroviral therapy, chronic immune activation, inflammation, and immune dysfunction persist, and are likely to have important effects on the size and distribution of the viral reservoir. The inability of the immune system to recognise cells harbouring latent virus and to eliminate cells actively producing virus is the biggest challenge to finding a cure. We look at new approaches to unravelling the complex virus-host interactions that lead to persistent infection and latency, and discuss the rationale for combination of novel treatment strategies with available antiretroviral treatment options to cure HIV.

Published
2013

11. Measuring Recent Thymic Emigrants in Blood of Normal and HIV-1–Infected Individuals before and after Effective Therapy

Author

Zhang, Linqi, Lewin, Sharon R, Markowitz, Martin, Lin, Hsi-Hsun, Skulsky, Eva, Karanicolas, Rose, He, Yuxian, Jin, Xia, Tuttleton, Sarah, Vesanen, Mika, Spiegel, Hans, Kost, Rhonda, van Lunzen, Jan, Stellbrink, Hans-Juergen, Wolinsky, Steven, Borkowsky, William, Palumbo, Paul, Kostrikis, Leondios G, and Ho, David D

Subjects
Infectious Diseases, HIV/AIDS, Clinical Research, 2.1 Biological and endogenous factors, Aetiology, Infection, Adolescent, Adult, Aging, Anti-HIV Agents, Base Sequence, Case-Control Studies, Cell Movement, Child, DNA Primers, DNA, Circular, Gene Rearrangement, T-Lymphocyte, HIV Infections, HIV-1, Humans, Polymerase Chain Reaction, T-Lymphocytes, Medical and Health Sciences, Immunology
Abstract

The role of the thymus in HIV-1 pathogenesis remains unclear. We developed an assay to quantify the number of recent thymic emigrants in blood based on the detection of a major excisional DNA byproduct (termed alpha1 circle) of T cell receptor rearrangement. By studying 532 normal individuals, we found that alpha1 circle numbers in blood remain high for the first 10-15 yr of life, a sharp drop is seen in the late teen years, and a gradual decline occurs thereafter. Compared with age-matched uninfected control individuals, alpha1 circle numbers in HIV-1-infected adults were significantly reduced; however, there were many individuals with normal alpha1 circle numbers. In 74 individuals receiving highly active antiretroviral therapy, we found no appreciable effect on alpha1 circle numbers in those whose baseline values were already within the normal range, but significant increases were observed in those with a preexisting impairment. The increases in alpha1 circle numbers were, however, numerically insufficient to account for the rise in levels of naive T lymphocytes. Overall, it is difficult to invoke thymic regenerative failure as a generalized mechanism for CD4 lymphocyte depletion in HIV-1 infection, as alpha1 circle numbers are normal in a substantial subset of HIV-1-infected individuals.

Published
1999

13. The 2000HIV study: Design, multi-omics methods and participant characteristics

Author

Vos, Wilhelm A. J. W., primary, Groenendijk, Albert L., additional, Blaauw, Marc J. T., additional, van Eekeren, Louise E., additional, Navas, Adriana, additional, Cleophas, Maartje C. P., additional, Vadaq, Nadira, additional, Matzaraki, Vasiliki, additional, dos Santos, Jéssica C., additional, Meeder, Elise M. G., additional, Fröberg, Janeri, additional, Weijers, Gert, additional, Zhang, Yue, additional, Fu, Jingyuan, additional, ter Horst, Rob, additional, Bock, Christoph, additional, Knoll, Rainer, additional, Aschenbrenner, Anna C., additional, Schultze, Joachim, additional, Vanderkerckhove, Linos, additional, Hwandih, Talent, additional, Wonderlich, Elizabeth R., additional, Vemula, Sai V., additional, van der Kolk, Mike, additional, de Vet, Sterre C. P., additional, Blok, Willem L., additional, Brinkman, Kees, additional, Rokx, Casper, additional, Schellekens, Arnt F. A., additional, de Mast, Quirijn, additional, Joosten, Leo A. B., additional, Berrevoets, Marvin A. H., additional, Stalenhoef, Janneke E., additional, Verbon, Annelies, additional, van Lunzen, Jan, additional, Netea, Mihai G., additional, and van der Ven, Andre J. A. M., additional

Published
2022
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19. Directed evolution of a recombinase that excises the provirus of most HIV-1 primary isolates with high specificity

Author

Karpinski, Janet, Hauber, Ilona, Chemnitz, Jan, Schäfer, Carola, Paszkowski-Rogacz, Maciej, Chakraborty, Deboyoti, Beschorner, Niklas, Hofmann-Sieber, Helga, Lange, Ulrike C, Grundhoff, Adam, Hackmann, Karl, Schrock, Evelin, Abi-Ghanem, Josephine, Pisabarro, M Teresa, Surendranath, Vineeth, Schambach, Axel, Lindner, Christoph, van Lunzen, Jan, Hauber, Joachim, and Buchholz, Frank

Published
2016
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20. Isotopic fluorine-18 radiolabelling of the anti-retroviral drug dolutegravir for pet imaging

Author

Caillé, Fabien, primary, Tisseraud, Marion, additional, Goutal, Sebastien, additional, Goislard, Maud, additional, Bonasera, Thomas, additional, Naninck, Thibaut, additional, Chapon, Catherine, additional, Barrail-Tran, Aurélie, additional, Desjardins, Delphine, additional, Lebon, Vincent, additional, Legrand, Roger, additional, Van Lunzen, Jan, additional, Parry, Chris, additional, Tournier, Nicolas, additional, and Kuhnast, Bertrand, additional

Published
2022
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23. The 2000HIV study:Design, multi-omics methods and participant characteristics

Author

Vos, Wilhelm A.J.W., Groenendijk, Albert L., Blaauw, Marc J.T., van Eekeren, Louise E., Navas, Adriana, Cleophas, Maartje C.P., Vadaq, Nadira, Matzaraki, Vasiliki, dos Santos, Jéssica C., Meeder, Elise M.G., Fröberg, Janeri, Weijers, Gert, Zhang, Yue, Fu, Jingyuan, ter Horst, Rob, Bock, Christoph, Knoll, Rainer, Aschenbrenner, Anna C., Schultze, Joachim, Vanderkerckhove, Linos, Hwandih, Talent, Wonderlich, Elizabeth R., Vemula, Sai V., van der Kolk, Mike, de Vet, Sterre C.P., Blok, Willem L., Brinkman, Kees, Rokx, Casper, Schellekens, Arnt F.A., de Mast, Quirijn, Joosten, Leo A.B., Berrevoets, Marvin A.H., Stalenhoef, Janneke E., Verbon, Annelies, van Lunzen, Jan, Netea, Mihai G., van der Ven, Andre J.A.M., Vos, Wilhelm A.J.W., Groenendijk, Albert L., Blaauw, Marc J.T., van Eekeren, Louise E., Navas, Adriana, Cleophas, Maartje C.P., Vadaq, Nadira, Matzaraki, Vasiliki, dos Santos, Jéssica C., Meeder, Elise M.G., Fröberg, Janeri, Weijers, Gert, Zhang, Yue, Fu, Jingyuan, ter Horst, Rob, Bock, Christoph, Knoll, Rainer, Aschenbrenner, Anna C., Schultze, Joachim, Vanderkerckhove, Linos, Hwandih, Talent, Wonderlich, Elizabeth R., Vemula, Sai V., van der Kolk, Mike, de Vet, Sterre C.P., Blok, Willem L., Brinkman, Kees, Rokx, Casper, Schellekens, Arnt F.A., de Mast, Quirijn, Joosten, Leo A.B., Berrevoets, Marvin A.H., Stalenhoef, Janneke E., Verbon, Annelies, van Lunzen, Jan, Netea, Mihai G., and van der Ven, Andre J.A.M.

Abstract

Background: Even during long-term combination antiretroviral therapy (cART), people living with HIV (PLHIV) have a dysregulated immune system, characterized by persistent immune activation, accelerated immune ageing and increased risk of non-AIDS comorbidities. A multi-omics approach is applied to a large cohort of PLHIV to understand pathways underlying these dysregulations in order to identify new biomarkers and novel genetically validated therapeutic drugs targets. Methods: The 2000HIV study is a prospective longitudinal cohort study of PLHIV on cART. In addition, untreated HIV spontaneous controllers were recruited. In-depth multi-omics characterization will be performed, including genomics, epigenomics, transcriptomics, proteomics, metabolomics and metagenomics, functional immunological assays and extensive immunophenotyping. Furthermore, the latent viral reservoir will be assessed through cell associated HIV-1 RNA and DNA, and full-length individual proviral sequencing on a subset. Clinical measurements include an ECG, carotid intima-media thickness and plaque measurement, hepatic steatosis and fibrosis measurement as well as psychological symptoms and recreational drug questionnaires. Additionally, considering the developing pandemic, COVID-19 history and vaccination was recorded. Participants return for a two-year follow-up visit. The 2000HIV study consists of a discovery and validation cohort collected at separate sites to immediately validate any finding in an independent cohort. Results: Overall, 1895 PLHIV from four sites were included for analysis, 1559 in the discovery and 336 in the validation cohort. The study population was representative of a Western European HIV population, including 288 (15.2%) cis-women, 463 (24.4%) non-whites, and 1360 (71.8%) MSM (Men who have Sex with Men). Extreme phenotypes included 114 spontaneous controllers, 81 rapid progressors and 162 immunological non-responders. According to the Framingham score 321 (16.9%) had a

Published
2022

26. Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine

Author

Jeffrey, Jerry L., primary, St. Clair, Marty, additional, Wang, Ping, additional, Wang, Chunfu, additional, Li, Zhufang, additional, Beloor, Jagadish, additional, Talarico, Christine, additional, Fridell, Robert, additional, Krystal, Mark, additional, White, C. Thomas, additional, Griffith, Sandy, additional, D’Amico, Ronald, additional, Smith, Kimberly, additional, Van Eygen, Veerle, additional, Vingerhoets, Johan, additional, Vandermeulen, Kati, additional, Spreen, William, additional, and van Lunzen, Jan, additional

Published
2022
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37. IL-10 induces aberrant deletion of dendritic cells by natural killer cells in the context of HIV infection

Author

Alter, Galit, Kavanagh, Daniel, Rihn, Suzannah, Luteijn, Rutger, Brooks, David, Oldstone, Michael, van Lunzen, Jan, and Altfeld, Marcus

Subjects
Cellular immunity -- Research, Immune response -- Research, Interleukin-10 -- Complications and side effects -- Research, Dendritic cells -- Properties -- Research, Killer cells -- Properties -- Research, Health care industry
Abstract

Persistent levels of IL-10 play a central role in progressive immune dysfunction associated with chronic viral infections such as HIV, but the underlying mechanisms are poorly understood. Because IL-10 affects the phenotypic and functional properties of DCs, which are responsible for initiating adaptive immune responses, we investigated whether IL-10 induces changes in DC phenotype and function in the context of HIV infection. Here, we show that IL-10 treatment of immature and mature human DCs in culture induced contrasting phenotypic changes in these populations: immature DCs exhibited aberrant resistance to NK cell-mediated elimination, whereas mature DCs exhibited increased susceptibility to NKG2D-dependent NK elimination. Treatment of immature and mature DCs with HIV resulted in potent IL-10 secretion and the same phenotypic and functional changes observed in the IL-10-treated cells. Consistent with these in vitro data, LNs isolated from individuals infected with HIV exhibited aberrant accumulation of a partially 'immature' DC population. Together, these data suggest that the progressive immune dysfunction observed in chronic viral infections might be caused in part by IL-10-induced reversal of DC susceptibility to NK cell-mediated elimination, resulting in the accumulation of poorly immunogenic DCs in LNs, the sites of adaptive immune response induction., Introduction DCs serve as immunological sentinels that monitor tissues for pathogens or tumor cells (1), (2). In tissues, DCs exist as immature, highly phagocytic cells that continuously sample the extracellular [...]

Published
2010
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39. Week 48 results from a randomized clinical trial of rilpivirine/emtricitabine/tenofovir disoproxil fumarate vs. efavirenz/emtricitabine/tenofovir disoproxil fumarate in treatment-naive HIV-1-infected adults

Author

Cohen, Calvin, Wohl, David, Arribas, Jose R., Henry, Keith, Van Lunzen, Jan, Bloch, Mark, Towner, William, Wilkins, Edmund, Ebrahimi, Ramin, Porter, Danielle, White, Kirsten, Walker, Ivan, Chuck, Susan, De-Oertel, Shampa, and Fralich, Todd

Published
2014
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40. Simplification to rilpivirine/emtricitabine/tenofovir disoproxil fumarate from ritonavir-boosted protease inhibitor antiretroviral therapy in a randomized trial of HIV-1 RNA-suppressed participants

Author

Palella, Frank J., Jr, Fisher, Martin, Tebas, Pablo, Gazzard, Brian, Ruane, Peter, Van Lunzen, Jan, Shamblaw, David, Flamm, Jason, Ebrahimi, Ramin, Porter, Danielle, White, Kirsten, Hindman, Jason, Elbert, Elizabeth, De-Oertel, Shampa, and Fralich, Todd

Published
2014
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41. Sustained virological response after early antiviral treatment of acute hepatitis C virus and HIV coinfection

Author

Schulze zur Wiesch, Julian, Pieper, Dorothea, Stahmer, Ingrid, Eiermann, Thomas, Buggisch, Peter, Lohse, Ansgar, Hauber, Joachim, and van Lunzen, Jan

Subjects
Hepatitis C -- Care and treatment, Hepatitis C -- Patient outcomes, Hepatitis C -- Research, HIV infection -- Care and treatment, HIV infection -- Patient outcomes, HIV infection -- Research, Comorbidity -- Patient outcomes, Comorbidity -- Research, Diagnostic virology -- Research, Health, Health care industry
Published
2009

42. The Architecture of Circulating Immune Cells Is Dysregulated in People Living With HIV on Long Term Antiretroviral Treatment and Relates With Markers of the HIV-1 Reservoir, Cytomegalovirus, and Microbial Translocation

Author

Van de Wijer, Lisa, primary, van der Heijden, Wouter A., additional, Horst, Rob ter, additional, Jaeger, Martin, additional, Trypsteen, Wim, additional, Rutsaert, Sofie, additional, van Cranenbroek, Bram, additional, van Rijssen, Esther, additional, Joosten, Irma, additional, Joosten, Leo, additional, Vandekerckhove, Linos, additional, Schoofs, Till, additional, van Lunzen, Jan, additional, Netea, Mihai G., additional, Koenen, Hans J.P.M., additional, van der Ven, André J.A.M., additional, and de Mast, Quirijn, additional

Published
2021
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43. Exploring predictors of HIV-1 virologic failure to long-acting cabotegravir and rilpivirine: a multivariable analysis

Author

Cutrell, Amy G., primary, Schapiro, Jonathan M., additional, Perno, Carlo F., additional, Kuritzkes, Daniel R., additional, Quercia, Romina, additional, Patel, Parul, additional, Polli, Joseph W., additional, Dorey, David, additional, Wang, Yongwei, additional, Wu, Sterling, additional, Van Eygen, Veerle, additional, Crauwels, Herta, additional, Ford, Susan L., additional, Baker, Mark, additional, Talarico, Christine L., additional, Clair, Marty St, additional, Jeffrey, Jerry, additional, White, C. Thomas, additional, Vanveggel, Simon, additional, Vandermeulen, Kati, additional, Margolis, David A., additional, Aboud, Michael, additional, Spreen, William R., additional, and van Lunzen, Jan, additional

Published
2021
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44. Chronic HIV infection induces transcriptional and functional reprogramming of innate immune cells

Author

van der Heijden, Wouter A., primary, Van de Wijer, Lisa, additional, Keramati, Farid, additional, Trypsteen, Wim, additional, Rutsaert, Sofie, additional, Horst, Rob ter, additional, Jaeger, Martin, additional, Koenen, Hans J.P.M., additional, Stunnenberg, Hendrik G., additional, Joosten, Irma, additional, Verweij, Paul E., additional, van Lunzen, Jan, additional, Dinarello, Charles A., additional, Joosten, Leo A.B., additional, Vandekerckhove, Linos, additional, Netea, Mihai G., additional, van der Ven, André J.A.M., additional, and de Mast, Quirijn, additional

Published
2021
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45. Vulnerability to reservoir reseeding due to high immune activation after allogeneic hematopoietic stem cell transplantation in individuals with HIV-1

Author

Eberhard, Johanna M., Angin, Mathieu, Passaes, Caroline, Salgado, Maria, Monceaux, Valerie, Knops, Elena, Kobbe, Guido, Jensen, Bjoern, Christopeit, Maximilian, Kroeger, Nicolaus, Vandekerckhove, Linos, Badiola, Jon, Bandera, Alessandra, Raj, Kavita, van Lunzen, Jan, Huetter, Gero, Kuball, Juergen H. E., Martinez-Laperche, Carolina, Balsalobre, Pascual, Kwon, Mi, Diez-Martin, Jose L., Nijhuis, Monique, Wensing, Annemarie, Martinez-Picado, Javier, Schulze Zur Wiesch, Julian, Saez-Cirion, Asier, Eberhard, Johanna M., Angin, Mathieu, Passaes, Caroline, Salgado, Maria, Monceaux, Valerie, Knops, Elena, Kobbe, Guido, Jensen, Bjoern, Christopeit, Maximilian, Kroeger, Nicolaus, Vandekerckhove, Linos, Badiola, Jon, Bandera, Alessandra, Raj, Kavita, van Lunzen, Jan, Huetter, Gero, Kuball, Juergen H. E., Martinez-Laperche, Carolina, Balsalobre, Pascual, Kwon, Mi, Diez-Martin, Jose L., Nijhuis, Monique, Wensing, Annemarie, Martinez-Picado, Javier, Schulze Zur Wiesch, Julian, and Saez-Cirion, Asier

Abstract

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only medical intervention that has led to an HIV cure. Whereas the HIV reservoir sharply decreases after allo-HSCT, the dynamics of the T cell reconstitution has not been comprehensively described. We analyzed the activation and differentiation of CD4(+) and CD8(+)T cells, and the breadth and quality of HIV- and CMV-specific CD8(+) T cell responses in 16 patients with HIV who underwent allo-HSCT (including five individuals who received cells from CCR5432/432 donors) to treat their underlying hematological malignancy and who remained on antiretroviral therapy (ART). We found that reconstitution of the T cell compartment after allo-HSCT was slow and heterogeneous with an initial expansion of activated CD4(+)T cells that preceded the expansion of CD8(+)T cells. Although HIV-specific CD8(+)T cells disappeared immediately after allo-HSCT, weak HIV-specific CD8 T+ cell responses were detectable several weeks after transplant and could still be detected at the time of full T cell chimerism, indicating that de novo priming, and hence antigen exposure, occurred during the time of T cell expansion. These HIV-specific T cells had limited functionality compared with CMV-specific CD8(+)T cells and persisted years after allo-HSCT. In conclusion, immune reconstitution was slow, heterogeneous, and incomplete and coincided with de novo detection of weak HIV-specific T cell responses. The initial short phase of high T cell activation, in which HIV antigens were present, may constitute a window of vulnerability for the reseeding of viral reservoirs, emphasizing the importance of maintaining ART directly after allo-HSCT.

Published
2020

46. Vulnerability to reservoir reseeding due to high immune activation after allogeneic hematopoietic stem cell transplantation in individuals with HIV-1

Author

CTI Kuball, MS Hematologie, Infection & Immunity, Regenerative Medicine and Stem Cells, Cancer, MMB Research line 3a, MMB opleiding Arts microbioloog, Eberhard, Johanna M., Angin, Mathieu, Passaes, Caroline, Salgado, Maria, Monceaux, Valerie, Knops, Elena, Kobbe, Guido, Jensen, Björn, Christopeit, Maximilian, Kröger, Nicolaus, Vandekerckhove, Linos, Badiola, Jon, Bandera, Alessandra, Raj, Kavita, van Lunzen, Jan, Hütter, Gero, Kuball, Jürgen H.E., Martinez-Laperche, Carolina, Balsalobre, Pascual, Kwon, Mi, Díez-Martín, José L., Nijhuis, Monique, Wensing, Annemarie, Martinez-Picado, Javier, Schulze Zur Wiesch, Julian, Sáez-Cirión, Asier, CTI Kuball, MS Hematologie, Infection & Immunity, Regenerative Medicine and Stem Cells, Cancer, MMB Research line 3a, MMB opleiding Arts microbioloog, Eberhard, Johanna M., Angin, Mathieu, Passaes, Caroline, Salgado, Maria, Monceaux, Valerie, Knops, Elena, Kobbe, Guido, Jensen, Björn, Christopeit, Maximilian, Kröger, Nicolaus, Vandekerckhove, Linos, Badiola, Jon, Bandera, Alessandra, Raj, Kavita, van Lunzen, Jan, Hütter, Gero, Kuball, Jürgen H.E., Martinez-Laperche, Carolina, Balsalobre, Pascual, Kwon, Mi, Díez-Martín, José L., Nijhuis, Monique, Wensing, Annemarie, Martinez-Picado, Javier, Schulze Zur Wiesch, Julian, and Sáez-Cirión, Asier

Published
2020

47. Persistence of HIV-1 structural proteins and glycoproteins in lymph nodes of patients under highly active antiretroviral therapy

Author

Popovic, Mikulas, Tenner-Racz, Klara, Pelser, Colleen, Stellbrink, Hans-Jurgen, van Lunzen, Jan, Lewis, George, Kalyanaraman, Vaniambadi S., Gallo, Robert C., and Racz, Paul

Subjects
HIV (Viruses) -- Research, Glycoproteins -- Research, Lymph nodes -- Research, Science and technology
Abstract

Here we report a long-term persistence of HIV-1 structural proteins and glycoproteins in germinal centers (GCs) of lymph nodes (LNs) in the absence of detectable virus replication in patients under highly active antiretroviral therapy (HAART), The persistence of viral structural proteins and glycoproteins in GCs was accompanied by specific antibody responses to HIV-1. Seven patients during the chronic phase of HIV-1 infection were analyzed for the presence of the capsid protein (HIV-1p24), matrix protein (HIV-1p17), and envelope glycoproteins (HIV-1gp120/gp41), as well as for viral RNA (vRNA) in biopsy specimens from LNs obtained before initiation of therapy and during HAART that lasted from 5 to 13 months. In parallel, these patients were also monitored for viremia and specific anti-HIV-1 antibody responses to structural proteins and glycoproteins both before and during treatment. Before-therapy viral levels, as determined by RT-PCR, ranged from 3 x [10.sup.3] to 6.3 x [10.sup.5] copies of vRNA per ml, whereas during treatment, vRNA was under detectable levels (

Published
2005

49. Background morbidity in HIV vaccine trial participants from various geographic regions as assessed by unsolicited adverse events

Author

Schmidt, Claudia, Smith, Carol, Barin, Burc, Bakhtyari, Arash, Bart, Pierre-Alexandre, Bekker, Linda-Gail, Chomba, Elwyn, Clumeck, Nathan, Ho, David, Hoosen, Anwar, Jaoko, Walter, Kaleebu, Pontiano, Karita, Etienne, Keefer, Michael C., van Lunzen, Jan, McMichael, Andrew, Mehendale, Sanjay, Peters, Barry, Ramanathan, Vadakkuppatu D., Robinson, Andrew, Rockstroh, Juergen, Vardas, Eftyhia, Vets, Eva, Weber, Jonathan, Graham, Barney S., Than, Soe, Excler, Jean-Louis, Kochhar, Sonali, Ho, Martin, Heald, Alison, and Fast, Patricia E.

Published
2012

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