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Multifunctional anti-HIV Fc-fusion proteins aim to tackle HIV efficiently through multiple modes of action. Although results have been promising, these recombinant proteins are hard to produce. This study explored the production and characterization of anti-HIV Fc-fusion proteins in plant-based systems, specifically Nicotiana benthamiana plants and tobacco BY-2 cell suspension. Fc-fusion protein expression in plants was optimized by incorporating codon optimization, ER retention signals, and hydrophobin fusion elements. Successful transient protein expression was achieved in N. benthamiana, with notable improvements in expression levels achieved through N-terminal hydrophobin fusion and ER retention signals. Stable expression in tobacco BY-2 resulted in varying accumulation levels being at highest 2.2.mg/g DW. The inclusion of hydrophobin significantly enhanced accumulation, providing potential benefits for downstream processing. Mass spectrometry analysis confirmed the presence of the ER retention signal and of N-glycans. Functional characterization revealed strong binding to CD64 and CD16a receptors, the latter being important for antibody-dependent cellular cytotoxicity (ADCC). Interaction with HIV antigens indicated potential neutralization capabilities. In conclusion, this research highlights the potential of plant-based systems for producing functional anti-HIV Fc-fusion proteins, offering a promising avenue for the development of these novel HIV therapies.
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Background: People with HIV (PWH) are at elevated risk for atherosclerotic cardiovascular disease (ASCVD). Underrepresented racial and ethnic groups (UREGs) with HIV in the southern U.S. are disproportionately affected, yet whether cardiology specialist care for this at-risk group improves blood pressure and lipid control or prevents cardiovascular events is unknown. Methods: We evaluated a cohort of PWH from UREGs at elevated ASCVD risk without known cardiovascular disease who received HIV-related care from 2015-2018 at four academic medical centers in the Southern United States with follow up through 2020. Primary outcomes were blood pressure control (<140/90 mmHg) and lipid control (LDL-C ≤ 100 mg/dl) over 2 years and time to first major adverse cardiovascular (MACE) event. Statistical analyses were adjusted for cohort/site and patient factors including HIV measures and comorbidities. Results: Among 3972 included PWH (median age 47 years old, 32.6% female) without diagnosed cardiovascular disease, 276 (6.9%) had a cardiology clinic visit. Cardiology clinic visits were not significantly associated with subsequent blood pressure control (adjusted OR 0.78, 95% CI 0.49-1.24, p=0.29) or lipid control (adjusted OR 2.25, 95% CI 0.72-7.01, p=0.16). Over a median follow up of 5 years, patients who had a cardiology clinic visit had higher risk of MACE, overall mortality, and falsification endpoints (hospitalization or death from accident/trauma and pneumonia/sepsis) indicating a higher risk group overall, even after adjusting for measured risk factors. Conclusions: Among UREG PWH at elevated cardiovascular risk, a cardiology clinic visit was not associated with improved cardiovascular risk factors or reduced risk of cardiovascular events. Our study suggests that seeing a cardiologist is not alone sufficient to promote cardiovascular health or prevent cardiovascular events among PWH, but with low confidence given the higher risk among those who had a cardiology visit.
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Background: We aimed to determine the effectiveness of switching to bictegravir in maintaining an undetectable viral load (<50â copies/mL) among people with HIV (PWH) as compared with continuing dolutegravir-, efavirenz-, or raltegravir-based antiretroviral therapy using nationwide observational data from Mexico. Methods: We emulated 3 target trials comparing switching to bictegravir vs continuing with dolutegravir, efavirenz, or raltegravir. Eligibility criteria were PWH aged ≥16 years with a viral load <50â copies/mL and at least 3 months of current antiretroviral therapy (dolutegravir, efavirenz, or raltegravir) between July 2019 and September 2021. Weekly target trials were emulated during the study period, and individuals were included in every emulation if they continued to be eligible. The main outcome was the probability of an undetectable viral load at 3 months, which was estimated via an adjusted logistic regression model. Estimated probabilities were compared via differences, and 95% CIs were calculated via bootstrap. Outcomes were also ascertained at 12 months, and sensitivity analyses were performed to test our analytic choices. Results: We analyzed data from 3 028 619 PWH (63 581 unique individuals). The probability of an undetectable viral load at 3 months was 2.9% (95% CI, 1.9%-3.8%), 1.3% (95% CI, .9%-1.6%), and 1.2% (95% CI, .8%-1.7%) higher when switching to bictegravir vs continuing with dolutegravir, efavirenz, and raltegravir, respectively. Similar results were observed at 12 months and in other sensitivity analyses. Conclusions: Our findings suggest that switching to bictegravir could be more effective in maintaining viral suppression than continuing with dolutegravir, efavirenz, or raltegravir.
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Background: We estimated the predictive value of rectal (bacterial sexually transmitted infection [bSTI]) pathogen detection for future HIV seroconversion among young adult sexual and gender minorities (YSGMs) assigned male at birth (AMAB). Methods: Data were collected between March 2018 and August 2022 from RADAR, a longitudinal cohort study of YSGMs AMAB living in the Chicago metropolitan area (n = 1022). Rates of rectal bSTIs and the proportion of self-reported rectal bSTI symptoms are reported. We examined whether the presence of rectal bSTIs predicted HIV seroconversion using generalized estimating equations (GEEs). Results: Participants tested reactive for rectal Mycoplasma genitalium (MGen), Neisseria gonorrhoeae (NG), and Chlamydia trachomatis (CT) at a rate of 20.8 (95% CI, 18.4-23.5), 6.5 (95% CI, 5.0-8.2), and 8.4 (95% CI, 6.8-10.3) cases per 100 persons, respectively. There were no statistically significant pairwise differences in self-reported rectal bSTI symptoms between participants with self-collected swabs testing nonreactive vs reactive for rectal MGen (χ2 = 0.04; P = .84), NG (χ2 = 0.45; P = .37), or CT (χ2 = 0.39; P = .46). In multivariate GEE analysis, rectal NG (adjusted odds ratio, 5.11; 95% CI, 1.20-21.77) was a statistically significant predictor of HIV seroconversion after controlling for other bSTIs, demographics, and sexual risk behavior. Conclusions: Our findings provide a robust longitudinal estimation of the relationship between primarily asymptomatic rectal NG nucleic acid detection and HIV infection. These findings highlight the importance of asymptomatic screening for bSTIs and targeting biobehavioral intervention to prevent HIV infection among YSGMs with rectal bSTI agents detected.
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Background: The increasing number of people living with HIV requires a simple and easy-to-use quality of life (QoL) scale for people living with HIV (PLWH). This study aims to adapt the PozQoL scale into Turkish and assess its reliability and validity for the PLWH population in Turkey. Methods: Translation-back-translation methodology was employed, and face-to-face interviews were conducted with 130 patients using the PozQoL, socio-demographic, and clinical data questionnaire. Exploratory Factor Analysis (EFA) and Confirmatory Factor Analysis (CFA) were utilized to identify the underlying factor structure and examine the validity of the measurement model, respectively. Cronbach's alpha and intraclass correlation coefficients (ICCs) were used to assess internal consistency and test-retest reliability, respectively. Results: EFA revealed four factors with an eigenvalue of 0.88, explaining 62.1% of the cumulative variance. CFA indicated that the four-factor solution achieved good levels of fit. The total Cronbach's alpha was 0.81, indicating high internal consistency. The ICC for the total score was 0.92 (95% confidence interval (CI) [0.90-0.94]; p < 0.05), demonstrating high test-retest reliability. Conclusion: The Turkish version of the PozQoL was found to be a valid and reliable tool for assessing the health-related QoL of PLWH in Turkey.
Subject(s)
HIV Infections , Psychometrics , Quality of Life , Humans , Turkey , Quality of Life/psychology , Male , Female , HIV Infections/psychology , HIV Infections/diagnosis , Reproducibility of Results , Adult , Surveys and Questionnaires , Middle Aged , Psychometrics/methods , Cross-Cultural Comparison , Factor Analysis, Statistical , TranslationsABSTRACT
INTRODUCTION: Despite the favourable efficacy of antiretroviral therapy (ART), HIV/AIDS continues to impose significant disease burdens worldwide. This study aims to systematically review published prognostic prediction models for survival outcomes of treatment experienced people living with HIV (TE-PLHIV), to describe their characteristics, compare their performance and assess the risk of bias and real-world clinical utility. METHODS AND ANALYSIS: Studies will be identified through a comprehensive search in PubMed, EMBASE, Scopus, the Cochrane Library, and OpenGrey databases. Two reviewers will independently conduct a selection of eligible studies, data extraction and critical appraisal. Included studies will be systematically summarised using appropriate tools designed for prognostic prediction modelling studies. Where applicable, evidence will be summarised with meta-analyses. ETHICS AND DISSEMINATION: Ethical approval is not required because only available published data will be analysed. The results of this work will be published in a peer-reviewed journal. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number CRD42023412118.
Subject(s)
HIV Infections , Meta-Analysis as Topic , Research Design , Systematic Reviews as Topic , Humans , HIV Infections/drug therapy , Prognosis , Anti-HIV Agents/therapeutic useABSTRACT
Tuberculosis (TB) is a leading cause of mortality from an infectious disease. In this opinion article, we focus on accumulating scientific evidence indicating that viral infections may contribute to TB progression, possibly allowing novel preventive interventions. Viruses can remodel the mammalian immune system, potentially modulating the risk of reactivating latent microbes such as Mycobacterium tuberculosis (Mtb). Evidence is mixed regarding the impact of emergent viruses such as SARS-CoV-2 on the risk of TB. Therefore, we posit that important knowledge gaps include elucidating which viral families increase TB risk and whether these provide unique or shared immune mechanisms. We also propose potential future research to define the contribution of viruses to TB pathogenesis.
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The scintillating association between Leishmania and HIV has contributed exceptionally towards expansion of Visceral Leishmaniasis (VL) with Acquired Immunodeficiency Syndrome (AIDS). The co-infection poses a grievous threat to elimination of VL and containment of Human Immunodeficiency Virus (HIV). When coinfected, Leishmania and HIV complement each other's proliferation and survival by inducing immunesenescence, T cell fatigue and exhaustion. Antigen presentation is lost, co-stimulatory molecules are diminished whereas co-inhibitory molecules such as CTLA-4, TIGIT, LAG-3 etc. are upregulated to ensure a Th2-baised immune environment. As a consequence, Leishmania-HIV coinfection causes poor outcomes, inflates the spread of Leishmania parasites, enhances the severity of side-effects to drugs, as well as escalate the probability of treatment failure and mortality. What makes control extremely strenuous is that there are frequent episodes of VL relapse with no prognostic markers, no standard immunophenotype(s) and appearance of atypical clinical symptoms. Thus, a standard therapeutic regimen has been difficult to develop and treatment is majorly dependent upon a combination of liposomal Amphotericin B and Miltefosine, a therapy that is expensive and capable of causing drastic side-effects in recipients. As World Health Organization is committed to eliminate both VL and HIV in due course of future, the existing therapeutic interventions require advancements to grapple and overcome this hazardous co-infection. In this context, an overview of HIV-VL co-infection, immunopathology of HIV and Leishmania co-inhabitance, available therapeutic options and their limitations in the treatment of co-infection are discussed in-depth.
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Neutralizing monoclonal antibodies hold great potential for prevention of human immunodeficiency virus (HIV) acquisition. IgG is the most abundant antibody in human serum, has a long half-life, and potent effector functions, making it a prime candidate for an HIV prevention therapeutic. We combined Positron Emission Tomography imaging and fluorescent microscopy of 64Cu-labeled, photoactivatable-green fluorescent protein HIV (PA-GFP-BaL) and fluorescently labeled HGN194 IgG1 to determine whether intravenously instilled IgG influences viral interaction with mucosal barriers and viral penetration in colorectal tissue 2 h after rectal viral challenge. Our results show that IgG1 did not alter the number of virions found throughout the colon or viral penetration into the epithelium of the rectum or descending colon. A minor increase in virions was observed in the transverse colon of IgG1 treated animals. Overall, the number of viral particles found in the mesenteric lymph nodes was low. However, IgG1 administration resulted in a significant reduction of virions found in mesenteric lymph nodes. Taken together, our results show that HGN194 IgG1 does not prevent virions from penetrating into the colorectal mucosa but may perturb HIV virion access to the lymphatic system.
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Improving the therapeutic management of HIV-positive persons is a major public health issue and includes better detection of drug resistance mutations (DRMs). The aim of this study was (i) to explore DRMs in HIV-1-positive persons presenting a blood viral load (VL) < 1000 genomes copies (gc)/mL, including the analyze of cerebrospinal fluid (CSF) and HIV-DNA from peripheral blood mononuclear cells using ultradeep sequencing (UDS) and (ii), to evaluate how these DRMs could influence the clinical practices. For each patient (n = 12), including five low-VL patients (i.e., <1000 gc/mL), HIV-1 UDS targeting the protease, reverse transcriptase and integrase genes was performed on plasma, proviral DNA, and CSF when available. Sequencing discordances or failures were mostly found in samples from low-VL patients. A 5% UDS cut-off allowed to increase the sensitivity to detect DRMs in different compartments, excepted in CSF. Patients with the highest viral quasispecies heterogeneity were naïve of treatment or presented a medical history suggesting low selection pressure or virological failures. When analyzing compartmentalization and following-up patients: low-frequency variants (LFVs) were responsible for 47% (n = 8) and 76% (n = 13) of changes in drug resistance interpretation, respectively. In such cases, we conclude that UDS is a robust technique, which still could be improved by increase the RNA and/or DNA extraction in low-VL samples to detect LFVs. Further studies are needed to define the impact of LFVs on antiretroviral treatments. At last, when considering a DRM, the use of mutational load would probably be more suitable than frequencies.
Subject(s)
Drug Resistance, Viral , HIV Infections , HIV-1 , High-Throughput Nucleotide Sequencing , Proviruses , Viral Load , Humans , HIV-1/genetics , HIV-1/isolation & purification , HIV Infections/virology , HIV Infections/drug therapy , Viral Load/methods , Drug Resistance, Viral/genetics , Proviruses/genetics , High-Throughput Nucleotide Sequencing/methods , Male , Adult , Female , Middle Aged , Mutation , DNA, Viral/genetics , DNA, Viral/cerebrospinal fluid , Leukocytes, Mononuclear/virology , RNA, Viral/genetics , RNA, Viral/cerebrospinal fluidABSTRACT
It is a known fact that HIV infection remains a serious public health problem throughout the world, and the need to constantly develop new antiretroviral drugs to combat HIV emerges from the fact that repetitive mutations occurring in viral enzymes make this virus resistant to antiretroviral drugs. This resistance causes failure of treatment, and hence, for many years, extensive research has been to discover newer possibilities for fighting this disease at a molecular level, along with many long-standing and expensive clinical trials. Many scientific research programs have either been discarded or unsuccessful. However, the research has not stopped, and in the process, many heterocyclic scaffolds have been used to build up novel drug molecules to combat this disease. A literature survey reveals that many heterocycles have been explored and were found to be very useful in treating different types of viral infections. This concise and rigorous literature explains the journey and highlights the various strategies to develop new anti-HIV drug candidates.
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Knowledge of Human Polyomavirus (HPyV) infection in the anal area and its association with sexually transmitted infections such as Human Papillomavirus (HPV) and Human Immunodeficiency Virus (HIV) remains limited. Therefore, anal specimens from 150 individuals of both sexes were analyzed for screening purposes. HPV DNA was found in 50.7% of cases, with a predominance of high-risk (HR) genotypes. HPyV DNA was found in 39.3% of samples, with Merkel Cell Polyomavirus (MCPyV) being the most common, with a higher viral load than JCPyV and BKPyV. In addition, MCPyV viral load increased in people living with HIV (PLWH) with HPV infection (p < 0.0001).
Subject(s)
Coinfection , HIV Infections , Merkel cell polyomavirus , Papillomavirus Infections , Polyomavirus Infections , Viral Load , Humans , Male , Female , HIV Infections/virology , HIV Infections/complications , Papillomavirus Infections/virology , Adult , Middle Aged , Coinfection/virology , Coinfection/epidemiology , Merkel cell polyomavirus/genetics , Merkel cell polyomavirus/isolation & purification , Polyomavirus Infections/virology , Polyomavirus Infections/epidemiology , DNA, Viral/genetics , Genotype , Anal Canal/virology , Anal Canal/pathology , Aged , Young Adult , Papillomaviridae/genetics , Papillomaviridae/isolation & purification , Papillomaviridae/classification , Tumor Virus Infections/virology , Tumor Virus Infections/epidemiology , PrevalenceABSTRACT
Microbiome perturbations can have long-term effects on health. The dynamics of the gut microbiome and virome in women living with HIV (WLHIV) and their newborn infants is poorly understood. Here, we performed metagenomic sequencing analyses on longitudinal stool samples including 23 mothers (13 WLHIV, 10 HIV-negative) and 12 infants that experienced SARS-CoV-2 infection with mild disease, as well as 40 mothers (18 WLHIV, 22 HIV-negative) and 60 infants that remained SARS-CoV-2 seronegative throughout the study follow-up. Regardless of HIV or SARS-CoV-2 status, maternal bacterial and viral profiles were distinct from infants. Using linear mixed effects models, we showed that the microbiome alpha diversity trajectory was not significantly different between SARS-CoV-2 seropositive and seronegative women. However, seropositive women's positive trajectory while uninfected was abruptly reversed after SARS-CoV-2 infection (p = 0.015). Gut virome signatures of women were not associated with SARS-CoV-2. Alterations in infant microbiome and virome diversities were generally not impacted by SARS-CoV-2 but were rather driven by development. We did not find statistically significant interactions between HIV and SARS-CoV-2 on the gut microbiome and virome. Overall, our study provides insights into the complex interplay between maternal and infant bacterial microbiome, virome, and the influence of SARS-CoV-2 and HIV status.
Subject(s)
COVID-19 , Feces , Gastrointestinal Microbiome , HIV Infections , SARS-CoV-2 , Virome , Humans , Female , COVID-19/microbiology , COVID-19/virology , HIV Infections/microbiology , HIV Infections/virology , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Adult , Infant, Newborn , Feces/microbiology , Feces/virology , Infant , Bacteria/classification , Bacteria/isolation & purification , Bacteria/genetics , Longitudinal StudiesABSTRACT
Antiretroviral therapy roll-out has dramatically reduced HIV related-mortality; more women are living to reach menopause. Menopausal estrogen loss causes bone loss, as does HIV and some of its treatments. However, data describing HIV's impact on osteoporosis prevalence and fracture risk are scarce in southern Africa. A cross-sectional study of women aged 40-60 years (49% women living with HIV (WLH)) was conducted in Harare, Zimbabwe. Menopause, fracture and HIV history were collected, and anthropometry and bone mineral density (BMD, by dual-energy x-ray absorptiometry (DXA)) measured, and FRAX® 10-year fracture probabilities quantified. The FRAX® probability of a major osteoporotic fracture (MOF) included HIV as a risk factor for secondary osteoporosis. Linear and Poisson regression determined the relationships between clinical risk factors and both femoral neck (FN) BMD and the 10-year FRAX® probability of MOF respectively. The 393 participants had mean(SD) age of 49.6(SD = 5.8) years and mean(SD) BMI 29.1(6) kg/m2. 95% of WLH were ART established (85% TDF) and 81% had a viral load <50 copies/mL. A BMD T-Score ≤ -2.5 was more common in WLH than those without, at both FN and lumbar spine (LS) (FN 22[11.4%] vs 5[2.5%], LS 40[20.8%] vs 9[4.5%]; respectively). Prior fracture was more prevalent in WLH: any fracture type (27[14%] vs. 14[7%]); MOF (14[7.3%] vs. 5[2.5%]). WLH had a higher 10-year MOF probability [median 1.2%; IQR: 0.9-1.8] compared with those without HIV [1.0%; IQR: 0.9-1.5] (P<.001), although probabilities were low. Older age, low weight, and HIV infection were strongly associated with lower FN BMD. Higher probability of MOF was associated with older age, HIV infection, parental hip fracture and prior fracture, though adjustment attenuated the association with HIV. No woman reported anti-osteoporosis medication use. While osteoporosis and previous fractures were common and untreated in this relatively young population, particularly in WLH, the FRAX® predicted 10-year MOF risk was low. Clinical risk factors considered in fracture risk prediction tools in Zimbabwe may need contextual modification.
Improved access to treatment for HIV now means women living with HIV are able to live well into older adulthood; however, this puts them at risk of age-related diseases such as osteoporosis. HIV and some of its treatments are known to cause bone loss, as does menopause, but studies on osteoporosis and fracture risk are scarce in southern Africa, where most people with HIV live. In this study in Zimbabwe, we found women with HIV were more likely to have osteoporosis and to have had a fracture, and a higher risk of having a major osteoporotic fracture over the next 10 years, compared with women without HIV (calculated using FRAX®: a fracture risk prediction tool), although the risk was surprisingly low. Older age, being underweight, and having HIV were strongly related to lower bone density at hip (an important site for fractures). Higher risk of future fracture was associated with older age, previous fracture, having HIV, and having a parent who had a hip fracture. Despite these findings, no woman had ever been offered any anti-osteoporosis medication. Our findings suggest that osteoporosis is under-recognized and undertreated in Zimbabwe, where clinical fracture risk prediction tools need to be modified for the specific context.
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Prurigo nodularis is a chronic dermatologic condition typically presenting as firm, dome-shaped pruritic nodules of various sizes that are often symmetrically distributed on extensor surfaces of the extremities. The diagnosis is clinical and based on a history of chronic, severe pruritis in the setting of characteristic, excoriated lesions. Treatment is difficult and aimed at reducing skin irritation and pruritus. Quality of life is impacted due to the chronic, intractable, and relapsing nature of the disease. Here, we report a case of prurigo nodularis diagnosed in the outpatient clinic setting. This paper aims to report the patient's clinical history, presentation, and histopathologic findings, as well as present a literature review to determine the significance of this case and the approach to ongoing management.
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Background: Viral causes of lower respiratory tract infections (LRTIs) are associated with increased mortality in children aged <5 years (U5). Human adenovirus (HAdV) has been associated with severe LRTI; however, its relationship with HIV and malnutrition in South Africa (SA) is not understood. Objectives: To identify the prevalence of and factors associated with HAdV LRTIs in hospitalised U5 childen. Methods: Clinical and viral data on U5 children hospitalised with severe LRTI from January 2018 to June 2020 at King Edward VIII Hospital, Durban, SA, including results of a multiplex polymerase chain reaction (PCR) panel assay for respiratory viruses, were retrieved from inpatient files and laboratory databases and retrospectively analysed. Standard descriptive statistics and Pearson's χ², Fisher's exact and Mann-Whitney tests were used to determine significant associations with HAdV LRTI. Results: Among the 206 viral assays analysed (15.6% of all LRTI admissions), HAdV was the most common virus identified. The cohort had a median (interquartile range) age of 5 (2 - 13) months, 47.3% had perinatal HIV exposure, and 34.5% had severe acute malnutrition (SAM). No seasonal pattern with HAdV could be demonstrated. SAM and prematurity were significant risk factors for readmission, and perinatal HIV exposure was a significant risk factor for presence of multiple viruses on analysis of a respiratory specimen. Detection of HAdV was not associated with an increased risk of requiring oxygen or ventilatory support. Conclusion: HAdV was the most common virus found on analysis of multiplex PCR panel results in children hospitalised with severe LRTI in SA, where high rates of HIV exposure may result in increased susceptibility to viral co-infections. The role of HAdV as a cause of severe LRTI in SA infants, who have high rates of HIV exposure, requires greater scrutiny. Study synopsis: What the study adds. This study provides retrospective data identifying human adenovirus (HAdV) as the most common cause of severe lower respiratory tract infection (LRTI) in children aged <5 years (U5). The impact of respiratory syncytial virus as a common pathogen in children is well established. The study confirms anecdotal evidence that HAdV is an important disease-causing pathogen associated with LRTI. Children with perinatal HIV exposure and severe acute malnutrition (SAM) may be particularly susceptible.Implications of the findings. HAdV must be considered a major cause of severe LRTI in U5 children. Children with LRTI who had perinatal HIV exposure and those with SAM need to be tested for HAdV and to be monitored for severe disease.
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Applied behaviour science's focus on individual-level behaviours has led to overestimation of and reliance on biases and heuristics in understanding behaviour and behaviour change. Behaviour-change interventions experience difficulties such as effect sizes, validity, scale-up, and long-term sustainability. One such area where we need to re-examine underlying assumptions for behavioural interventions in Human Immunodeficiency Virus (HIV) and Tuberculosis (TB) prevention, which seek population-level benefits and sustained, measurable impact. This requires taking a "Big Leap." In our view, taking the big leap refers to using a behavioural science-informed approach to overcome the chasms due to misaligned assumptions, tunnel focus, and overweighting immediate benefits, which can limit the effectiveness and efficiency of public health programmes and interventions. Crossing these chasms means that decision-makers should develop a system of interventions, promote end-user agency, build choice infrastructure, embrace heterogeneity, recognise social and temporal dynamics, and champion sustainability. Taking the big leap toward a more holistic approach means that policymakers, programme planners, and funding bodies should "Ask" pertinent questions to evaluate interventions to ensure they are well informed and designed.
Subject(s)
Behavioral Sciences , HIV Infections , Humans , HIV Infections/prevention & control , Tuberculosis/prevention & control , Public HealthABSTRACT
To investigate the impact of different 5' untranslated regions (UTRs) on mRNA vaccine translation efficiency, five dual-reporter gene expression plasmids with different 5'UTRs were constructed. The corresponding mRNA transcripts were transcribed and capped in vitro. By comparing the expression levels of reporter genes with different 5'UTRs, we identified the 5'UTR associated with the highest expression level. Subsequently, HIVgp145 mRNA vaccines containing various 5'UTRs were constructed and verified. The results demonstrated that mRNA 3 (ß-globin 5'UTR) displayed the greatest number of green fluorescence-positive cells and the highest luciferase fluorescence intensity in the reporter gene expression system. Further, among the HIVgp145 mRNA vaccines with different 5'UTRs, mRNA 7 (ß-globin 5'UTR) exhibited the highest level of expression. These findings indicate that it is feasible to use the 5'UTR of ß-globin in an mRNA vaccine, laying the foundation for animal immunogenicity testing.
Subject(s)
5' Untranslated Regions , Genes, Reporter , mRNA Vaccines , Humans , RNA, Messenger/genetics , beta-Globins/genetics , Animals , HEK293 CellsABSTRACT
INTRODUCTION: Individuals with human immunodeficiency virus (HIV) infection now have life expectancies similar to non-infected people but face increased obesity prevalence. The long-term effects of bariatric surgery (BS) and conservative weight therapy (CWT) in patients living with HIV (PLWH) remain unexplored. METHODS: A retrospective review (2012-2018) at a Tertiary Centre for Bariatric Surgery and National Centre for HIV care examined the outcomes of BS and CWT. Parameters evaluated included weight loss and HIV metrics such as viral load and CD4 count. RESULTS: The study included 24 chronic HIV patients, with 10 undergoing BS (5 laparoscopic adjustable gastric banding (LAGB), 3 laparoscopic sleeve gastrectomy (LSG), 2 Roux-en-Y gastric bypass (LRYGB) and 14 in CWT. The BS group showed significant BMI reduction (- 7.07, - 6.55, - 7.81 kg/m2 at 1, 3, and 5 years). The CWT group's BMI reduction was non-significant. The BS group's %TWL was 16%, 17.8%, and 15% at 1, 3, and 5 years, respectively; however, stapled procedures were more effective, at 1 year, %TWL was 17% LSG and 25% RYGB, at 3 years, 23% LSG, 30% RYGB and at 5 years 21% with LSG and 28% with RYGB. HIV outcomes remained stable with undetectable viral loads in the BS group. DISCUSSION: BS appears to be a safe and effective medium-term treatment for obesity in PLWH, providing significant weight loss whilst maintaining the efficacy of HIV treatments. Although CWT has shown modest benefits, the outcomes from BS indicate that it could be a preferable option for managing obesity in PLWH based on this limited dataset.
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The greatest obstacle for scientists is to develop an effective HIV vaccine. An effective vaccine represents the last hope for halting the unstoppable global spread of HIV and its catastrophic clinical consequences. Creating this vaccine has been challenging due to the virus's extensive genetic variability and the unique role of cytotoxic T lymphocytes (CTL) in containing it. Innovative methods to stimulate CTL have demonstrated significant therapeutic advantages in nonhuman primate model systems, unlike traditional vaccination techniques that are not expected to provide safe and efficient protection against HIV. Human clinical trials are currently evaluating these vaccination strategies, which involve plasmid DNA and live recombinant vectors. This review article covers the existing vaccines and ongoing trial vaccines. It also explores the different approaches used in developing HIV vaccines, including their molecular mechanisms, target site effectiveness, and potential side effects.