Reply: Beyond Viral Suppression.
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ABSTRACT:
SUBMITTER: Spinner CD
PROVIDER: S-EPMC8530261 | biostudies-literature | 2021 Oct
REPOSITORIES: biostudies-literature
Publications
Reply: Beyond Viral Suppression.
Spinner Christoph D CD Wolf Eva E Boesecke Christoph C
Open forum infectious diseases 20210215 10
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Project description:AbstractSwitching dual therapy with dolutegravir (DTG) plus rilpivirine (RPV) was assessed in the SWORD-1 and SWORD-2 studies. Real-life data regarding the immunological impact of this approach on CD4+ and CD8+ T lymphocyte counts and the CD4/CD8 ratio are scarce. We evaluated this strategy on the basis of clinical practice data.A multicentric retrospective cohort study.Treatment-experienced virologically suppressed HIV-1-infected patients who were switched to DTG plus RPV were included. Using different models for paired data, we evaluated the efficacy and immune status in terms of CD4+ and CD8+ T-cell counts and CD4/CD8 ratio at 24 and 48 weeks of treatment.The study population comprised of 524 patients from 34 centers in Spain. Men accounted for 76.9% of patients, with a median age of 53 years. Patients receiving DTG plus RPV reached weeks 24 and 48 in 99.4% and 83.8% of cases, respectively, with only three (0.57%) virological failures. We found a significant decrease in CD8+ T-cell count (log OR -40) at week 24 and an increase in CD4+ T-cell count at week 48 (log OR +22.8). In acquired immunodeficiency syndrome-diagnosed patients, we found a significant increase in the CD4+ T-cell count at week 48 (log OR = 41.7, P = .0038), but no significant changes in the CD8+ T-cell count (log OR = -23.4, P = .54). No differences were found in the CD4/CD8 ratio between the acquired immunodeficiency syndrome subgroup and sex or age.In patients with controlled treatment, dual therapy with DTG plus RPV slightly improved the immune status during the first 48 weeks after switching, not only in terms of CD4+ T-cell count but also in terms of CD8+ T-cell count, with persistently high rates of viral control.
| S-EPMC9276328 | biostudies-literature
Project description: Not available
| S-EPMC7810348 | biostudies-literature
Project description:Objective: With more people living with HIV (PLHIV) ageing into their 50s and beyond in settings where antiretroviral therapy is widely available, non-AIDS comorbidities and health-related quality of life (HRQoL) are becoming major challenges. Information is needed about whether national HIV monitoring programmes have evolved to reflect the changing focus of HIV care. Methods: We created a 56-item English-language survey to assess whether health systems report on common health-related issues for people with HIV including physical and mental health comorbidities, HRQoL, psychosocial needs, and fertility desires. One expert was identified via purposive sampling in each of six countries (Estonia, Italy, the Netherlands, Slovenia, Sweden, and Turkey) and was asked to participate in the survey. Results: Three respondents reported that the current monitoring systems in their countries do not monitor any of four specified aspects of 10 comorbidities including bone loss, cardiovascular disease, and neurocognitive disorders. Two respondents stated that their countries potentially can report on leading causes of hospital admission among PLHIV, and five on leading cases of death. In three countries, respondents reported that there was the ability to report on the HRQoL of PLHIV. In two countries, respondents provided data on the percentage of PLHIV denied health services because of HIV status in the past 12 months. Conclusions: This study identified areas for potential HIV monitoring improvements in six European countries in relation to comorbidities, HRQoL, discrimination within health systems, and other issues associated with the changing nature of the HIV epidemic. It also indicated that some countries either currently monitor or have the ability to monitor some of these issues. There are opportunities for health information systems in European countries to expand the scope of their HIV monitoring in order to support decision-making about how the long-term health-related needs of PLHIV can best be met.
| S-EPMC7098908 | biostudies-literature
Project description: Not available
| S-EPMC9323349 | biostudies-literature
Project description:BackgroundWith antiretroviral therapy, more people living with HIV (PLHIV) in resource-limited settings are virally suppressed and living longer. WHO recommends differentiated service delivery (DSD) as an alternative, less resource-demanding way of expanding HIV services access. Monitoring client's health-related quality of life (HRQoL) is necessary to understand patients' perceptions of treatment and services but is understudied in sub-Saharan Africa. We assessed HRQoL among ART clients in Tanzania accessing two service models.MethodsCross-sectional survey from May-August 2019 among stable ART clients randomly sampled from clinics and clubs in the Shinyanga region providing DSD and clinic-based care. HRQoL data were collected using a validated HIV-specific instrument-Functional Assessment of HIV infection (FAHI), in addition to socio-demographic, HIV care, and service accessibility data. Descriptive analysis of HRQoL, logistic regression and a stepwise multiple linear regression were performed to examine HRQoL determinants.Results629 participants were enrolled, of which 40% accessed DSD. Similar HRQoL scores [mean (SD), p-value]; FAHI total [152.2 (22.2) vs 153.8 (20.6), p 0.687] were observed among DSD and clinic-based care participants. Accessibility factors contributed more to emotional wellbeing among DSD participants compared to the clinic-based care participants (53.4% vs 18.5%, p = < 0.001). Satisfactory (> 80% of maximum score) HRQoL scoring was associated with (OR [95% CI], p-value) being male (2.59 [1.36-4.92], p 0.004) among clinic participants and with urban residence (4.72 [1.70-13.1], p 0.001) among DSD participants.ConclusionsSimilar HRQoL was observed in DSD and clinic-based care. Our research highlights focus areas to identify supporting interventions, ultimately optimizing HRQoL among PLHIV.
| S-EPMC8800900 | biostudies-literature
Project description: Not available
| S-EPMC9034207 | biostudies-literature
Project description:ObjectiveThe proportion of people living with HIV with suppressed viral load is a key indicator of the HIV care continuum. We explored how this proportion varied depending on how it was calculated.DesignObservational cohort study.MethodsWe calculated the proportion of the Johns Hopkins HIV Clinical Cohort who were virally suppressed each year, 2010-2018, based on different denominators; thresholds for suppression (≤20, ≤50, ≤200, or ≤400 copies/ml); and strategies for summarizing multiple viral load measurements (we classified persons as suppressed if they had any lab, ≥50% of labs, last lab, or all labs below the threshold). We also calculated 5-year risk of all-cause mortality associated with each classification of viral suppression.ResultsThree thousand eleven persons contributed 60 858 viral load values to this analysis. Proportion classified as virally suppressed ranged from 51.8 to 92.5%, depending on the definition used and persons included in the calculation. Requiring more labs below the threshold; using a lower threshold; and assuming persons lost to follow-up were not suppressed (stricter definitions) resulted in a lower proportion estimated to be suppressed. Suppression by stricter definitions were associated with better 5-year survival.DiscussionThe proportion suppressed varied greatly as a function of the subset of persons in whom it was calculated, the threshold used for suppression, and the way multiple viral loads per person per year were summarized. Measures of durable viral suppression, and low-level viremia (20-400 copies/ml), should be considered in describing the health of people with HIV, in addition to the standard estimates of suppression.
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Project description: Not available
| S-EPMC9534145 | biostudies-literature
Project description:Gene therapy covers a broad spectrum of applications, from gene replacement and knockdown for genetic or acquired diseases such as cancer, to vaccination, each with different requirements for gene delivery. Viral vectors and synthetic liposomes have emerged as the vehicles of choice for many applications today, but both have limitations and risks, including complexity of production, limited packaging capacity, and unfavorable immunological features, which restrict gene therapy applications and hold back the potential for preventive gene therapy. While continuing to improve these vectors, it is important to investigate other options, particularly nonviral biological agents which include bacteria, bacteriophage, virus-like particles (VLPs), erythrocyte ghosts, and exosomes. Exploiting the natural properties of these biological entities for specific gene delivery applications will expand the repertoire of gene therapy vectors available for clinical use. Here, we review the prospects for nonviral biological delivery vehicles as gene therapy agents with focus on their unique evolved biological properties and respective limitations and potential applications. The potential of these nonviral biological entities to act as clinical gene therapy delivery vehicles has already been shown in clinical trials using bacteria-mediated gene transfer and with sufficient development, these entities will complement the established delivery techniques for gene therapy applications.
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Project description:Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disease and one of the most common inherited tumor predisposition syndromes, affecting 1 in 3000 individuals worldwide. The NF1 gene encodes neurofibromin, a large protein with RAS GTP-ase activating (RAS-GAP) activity, and loss of NF1 results in increased RAS signaling. Neurofibromin contains many other domains, and there is considerable evidence that these domains play a role in some manifestations of NF1. Investigating the role of these domains as well as the various signaling pathways that neurofibromin regulates and interacts with will provide a better understanding of how neurofibromin acts to suppress tumor development and potentially open new therapeutic avenues. In this review, we discuss what is known about the structure of neurofibromin, its interactions with other proteins and signaling pathways, its role in development and differentiation, and its function as a tumor suppressor. Finally, we discuss the latest research on potential therapeutics for neurofibromin-deficient neoplasms.
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