BackgroundPeople living with HIV (PLWH), even when viral replication is controlled through antiretroviral therapy (ART), experience persistent inflammation. This inflammation is partly attributed... Show moreBackgroundPeople living with HIV (PLWH), even when viral replication is controlled through antiretroviral therapy (ART), experience persistent inflammation. This inflammation is partly attributed to intestinal microbial dysbiosis and translocation, which may lead to non-AIDS-related aging-associated comorbidities. The extent to which living with HIV - influenced by the infection itself, ART usage, sexual orientation, or other associated factors - affects the biological age of the intestines is unclear. Furthermore, the role of microbial dysbiosis and translocation in the biological aging of PLWH remains to be elucidated. To investigate these uncertainties, we used a systems biology approach, analyzing colon and ileal biopsies, blood samples, and stool specimens from PLWH on ART and people living without HIV (PLWoH) as controls.ResultsPLWH exhibit accelerated biological aging in the colon, ileum, and blood, as measured by various epigenetic aging clocks, compared to PLWoH. Investigating the relationship between microbial translocation and biological aging, PLWH had decreased levels of tight junction proteins in the intestines, along with increased microbial translocation. This intestinal permeability correlated with faster biological aging and increased inflammation. When investigating the relationship between microbial dysbiosis and biological aging, the intestines of PLWH had higher abundance of specific pro-inflammatory bacteria, such as Catenibacterium and Prevotella. These bacteria correlated with accelerated biological aging. Conversely, the intestines of PLWH had lower abundance of bacteria known for producing the anti-inflammatory short-chain fatty acids, such as Subdoligranulum and Erysipelotrichaceae, and these bacteria were associated with slower biological aging. Correlation networks revealed significant links between specific microbial genera in the colon and ileum (but not in feces), increased aging, a rise in pro-inflammatory microbe-related metabolites (e.g., those in the tryptophan metabolism pathway), and a decrease in anti-inflammatory metabolites like hippuric acid.ConclusionsWe identified specific microbial compositions and microbiota-related metabolic pathways that are intertwined with intestinal and systemic biological aging. This microbial signature of biological aging is likely reflecting various factors including the HIV infection itself, ART usage, sexual orientation, and other aspects associated with living with HIV. A deeper understanding of the mechanisms underlying these connections could offer potential strategies to mitigate accelerated aging and its associated health complications.1fCw832AZENtKENNTh8vkGVideo AbstractConclusionsWe identified specific microbial compositions and microbiota-related metabolic pathways that are intertwined with intestinal and systemic biological aging. This microbial signature of biological aging is likely reflecting various factors including the HIV infection itself, ART usage, sexual orientation, and other aspects associated with living with HIV. A deeper understanding of the mechanisms underlying these connections could offer potential strategies to mitigate accelerated aging and its associated health complications.1fCw832AZENtKENNTh8vkGVideo Abstract Show less
Background: Digital triage tools for sexually transmitted infection (STI) testing can potentially be used as a substitute for the triage that general practitioners (GPs) perform to lower their work... Show moreBackground: Digital triage tools for sexually transmitted infection (STI) testing can potentially be used as a substitute for the triage that general practitioners (GPs) perform to lower their work pressure. The studied tool is based on medical guidelines. The same guidelines support GPs' decision-making process. However, research has shown that GPs make decisions from a holistic perspective and, therefore, do not always adhere to those guidelines. To have a high-quality digital triage tool that results in an efficient care process, it is important to learn more about GPs' decision-making process. Objective: The first objective was to identify whether the advice of the studied digital triage tool aligned with GPs' daily medical practice. The second objective was to learn which factors influence GPs' decisions regarding referral for diagnostic testing. In addition, this study provides insights into GPs' decision-making process. Methods: A qualitative vignette-based study using semistructured interviews was conducted. In total, 6 vignettes representing patient cases were discussed with the participants (GPs). The participants needed to think aloud whether they would advise an STI test for the patient and why. A thematic analysis was conducted on the transcripts of the interviews. The vignette patient cases were also passed through the digital triage tool, resulting in advice to test or not for an STI. A comparison was made between the advice of the tool and that of the participants. Results: In total, 10 interviews were conducted. Participants (GPs) had a mean age of 48.30 (SD 11.88) years. For 3 vignettes, the advice of the digital triage tool and of all participants was the same. In those vignettes, the patients' risk factors were sufficiently clear for the participants to advise the same as the digital tool. For 3 vignettes, the advice of the digital tool differed from that of the participants. Patient-related factors that influenced the participants' decision-making process were the patient's anxiety, young age, and willingness to be tested. Participants would test at a lower threshold than the triage tool because of those factors. Sometimes, participants wanted more information than was provided in the vignette or would like to conduct a physical examination. These elements were not part of the digital triage tool. Conclusions: The advice to conduct a diagnostic STI test differed between a digital triage tool and GPs. The digital triage tool considered only medical guidelines, whereas GPs were open to discussion reasoning from a holistic perspective. The GPs' decision-making process was influenced by patients' anxiety, willingness to be tested, and age. On the basis of these results, we believe that the digital triage tool for STI testing could support GPs and even replace consultations in the future. Further research must substantiate how this can be done safely. Show less
Purpose: Immediate initiation of antiretroviral treatment following HIV infection is a cornerstone of the current HIV ‘universal test and treat’ approach. Delayed progress along the HIV care... Show morePurpose: Immediate initiation of antiretroviral treatment following HIV infection is a cornerstone of the current HIV ‘universal test and treat’ approach. Delayed progress along the HIV care continuum is thus framed as a major stumbling block in effective HIV epidemic control. Through examining the HIV care trajectories of people diagnosed with HIV in Shinyanga Region, Tanzania, we offer a critical interrogation of the HIV care continuum. Methods: Data are drawn from a social science study on the uptake of a ‘treat all’ model of HIV prevention and care conducted from 2018 to 2019. Methods included interviews with participants who tested positive (n = 30) and interviews (n = 25) with health staff involved in the testing campaigns.Findings: Exploring individuals’ care trajectories, we found that most participants followed pathways to care that do not easily align with the current emphasis on rapid, linear progress from testing to treatment initiation. Instead, participants’ trajectories from diagnosis to treatment happened on a different, non-linear time scale mediated through social relations and diverse communities of care. We thus conceptualize five pathways of linkage to care - virtuous/immediate, delayed testing, repeat testing, negotiated, and ‘failed’.Conclusion: Based on our findings we propose a community-centered HIV care continuum that exposes moments of potential connection with or rupture from the health system and centers the importance of social support structures and forms of relational labor involving broader communities of care. Show less
Okere, N.E.; Meta, J.; Maokola, W.; Martelli, G.; Praag, E. van; Naniche, D.; ... ; Hermans, S. 2022
Background: Differentiated service delivery (DSD) offers benefits to people living with HIV (improved access, peer support), and the health system (clinic decongestion, efficient service delivery).... Show moreBackground: Differentiated service delivery (DSD) offers benefits to people living with HIV (improved access, peer support), and the health system (clinic decongestion, efficient service delivery). ART clubs, 15–30 clients who usually meet within the community, are one of the most common DSD options. However, evidence about the quality of care (QoC) delivered in ART clubs is still limited.Materials and methods: We conducted a concurrent triangulation mixed-methods study as part of the Test & Treat project in northwest Tanzania. We surveyed QoC among stable clients and health care workers (HCW) comparing between clinics and clubs. Using a Donabedian framework we structured the analysis into three levels of assessment: structure (staff, equipment, supplies, venue), processes (time-spent, screenings, information, HCW-attitude), and outcomes (viral load, CD4 count, retention, self-worth).Results: We surveyed 629 clients (40% in club) and conducted eight focus group discussions, while 24 HCW (25% in club) were surveyed and 22 individual interviews were conducted. Quantitative results revealed that in terms of structure, clubs fared better than clinics except for perceived adequacy of service delivery venue (94.4% vs 50.0%, p = 0.013). For processes, time spent receiving care was significantly more in clinics than clubs (119.9 vs 49.9 minutes). Regarding outcomes, retention was higher in the clubs (97.6% vs 100%), while the proportion of clients with recent viral load <50 copies/ml was higher in clinics (100% vs 94.4%). Qualitative results indicated that quality care was perceived similarly among clients in clinics and clubs but for different reasons. Clinics were generally perceived as places with expertise and clubs as efficient places with peer support and empathy. In describing QoC, HCW emphasized structure-related attributes while clients focused on processes. Outcomes-related themes such as improved client health status, self-worth, and confidentiality were similarly perceived across clients and HCW.Conclusion: We found better structure and process of care in clubs than clinics with comparable outcomes. While QoC was perceived similarly in clinics and clubs, its meaning was understood differently between clients. DSD catered to the individual needs of clients, either technical care in the clinic or proximate and social care in the club. Our findings highlight that both clinic and DSD care are required as many elements of QoC were individually perceived. Show less
Luenen, S. van; Kraaij, V.; Spinhoven, P.; Wilderjans, T.F.; Garnefski, N. 2019
Background:South-south collaboration on health and development research is a critical mechanism for social and economic progress. It allows sharing and replicating experiences to find a “southern... Show moreBackground:South-south collaboration on health and development research is a critical mechanism for social and economic progress. It allows sharing and replicating experiences to find a “southern solution” to meet shared health challenges, such as access to adequate HIV/AIDS prevention and treatment. This study aimed to generate evidence on the dynamics of south-south collaboration in HIV/AIDS research, which could ultimately inform stakeholders on the progress and nature of collaboration towards increased research capacities in low- and middle-income countries (LMIC).Methods:Bibliometric and social network analysis methods were used to assess the 10-year (2006–2015) scientific contribution of LMIC, through the analysis of scientific publications on HIV/AIDS prevention and/or treatment. Five dimensions oriented the study: knowledge production, co-authorship analysis, research themes mapping, research types classification and funding sources.Results:Publications involving LMIC have substantially increased overtime, despite small expression of south-south collaboration. Research themes mapping revealed that publication focus varied according to collaborating countries’ income categories, from diagnosis, opportunistic infections and laboratory-based research (LMIC single or LMIC-LMIC) to human behavior and healthcare, drug therapy and mother to child transmission (LMIC-HIC). The analysis of research types showed that south-south collaboration s frequently targeted social sciences issues. Funding agencies acknowledged in south-south collaboration also showed diverse focus: LMIC-based funders tended to support basic biomedical research whereas international/HIC-based funders seem to cover predominantly social sciences-oriented research.Conclusions:Although the global environment has fostered an increasing participation of LMIC in collaborative learning models, south-south collaboration on HIV/AIDS prevention and/or treatment research seemed to be lower than expected, stressing the need for strategies to foster these partnerships. The evidence presented in this study can be used to strengthen a knowledge platform to inform future policy, planning and funding decisions, contributing to the development of enhanced collaboration and a priority research agenda for LMICs. Show less
Kunze, C.; Borner, K.; Kienle, E.; Orschmann, T.; Rusha, E.; Schneider, M.; ... ; Brack-Werner, R. 2017
Astrocytes, the most abundant cells in the mammalian brain, perform key functions and are involved in several neurodegenerative diseases. The human immunodeficiency virus (HIV) can persist in... Show moreAstrocytes, the most abundant cells in the mammalian brain, perform key functions and are involved in several neurodegenerative diseases. The human immunodeficiency virus (HIV) can persist in astrocytes, contributing to the HIV burden and neurological dysfunctions in infected individuals. While a comprehensive approach to HIV cure must include the targeting of HIV-1 in astrocytes, dedicated tools for this purpose are still lacking. Here we report a novel Adeno-associated virus-based vector (AAV9P1) with a synthetic surface peptide for transduction of astrocytes. Analysis of AAV9P1 transduction efficiencies with single brain cell populations, including primary human brain cells, as well as human brain organoids demonstrated that AAV9P1 targeted terminally differentiated human astrocytes much more efficiently than neurons. We then investigated whether AAV9P1 can be used to deliver HIV-inhibitory genes to astrocytes. To this end we generated AAV9P1 vectors containing genes for HIV-1 proviral editing by CRISPR/Cas9. Latently HIV-1 infected astrocytes transduced with these vectors showed significantly diminished reactivation of proviruses, compared with untransduced cultures. Sequence analysis identified mutations/deletions in key HIV-1 transcriptional control regions. We conclude that AAV9P1 is a promising tool for gene delivery to astrocytes and may facilitate inactivation/destruction of persisting HIV-1 proviruses in astrocyte reservoirs. Show less
