Current HIV Research最新文献

People Living with HIV (PLHIV) experience accelerated aging, yet strategies for healthy aging in this group are not well studied. Although survival rates have improved, non-infectious comorbidities, like cardiovascular diseases, diabetes, and cancers, are increasing and tend to appear earlier and more severely in PLHIV frailty, defined as increased vulnerability to stressors, which is a growing concern among aging PLHIV, driven by factors, like chronic inflammation, antiretroviral therapy toxicity, and traditional risk factors. Key areas of focus include inactivity, sarcopenia, vitamin D deficiency, and polypharmacy. Addressing these factors is crucial to preventing functional decline and improving the quality of life of PLHIV, though more research is necessary. The aim of this article was to identify and conduct a narrative review of these factors in a pragmatic way in order to facilitate the clinicians.

Background: Heterologous combinations in vaccine design are an effective approach to promote T cell activity and antiviral effects. The goal of this study was to compare the homologous and heterologous regimens targeting the Nef-Tat fusion antigen to develop a human immunodeficiency virus-1 (HIV-1) therapeutic vaccine candidate.

Methods: At first, the DNA and protein constructs harboring HIV-1 Nef and the first exon of Tat as linked form (pcDNA-nef-tat and Nef-Tat protein) were prepared in large scale and high purity. The generation of the Nef-Tat protein was performed in the E. coli expression system using an IPTG inducer. Then, we evaluated and compared immune responses of homologous DNA prime/ DNA boost, homologous protein prime/ protein boost, and heterologous DNA prime/protein boost regimens in BALB/c mice. Finally, the ability of mice splenocytes to secret cytokines after exposure to single-cycle replicable (SCR) HIV-1 was compared between immunized and control groups in vitro.

Results: The nef-tat gene was successfully subcloned in eukaryotic pcDNA3.1 (-) and prokaryotic pET-24a (+) expression vectors. The recombinant Nef-Tat protein was generated in the E. coli Rosetta strain under optimized conditions as a clear band of ~ 35 kDa detected on SDS-PAGE. Moreover, transfection of pcDNA-nef-tat into HEK-293T cells was successfully performed using Lipofectamine 2000, as confirmed by western blotting. The immunization studies showed that heterologous DNA prime/protein boost regimen could significantly elicit the highest levels of Ig- G2a, IFN-γ, and Granzyme B in mice as compared to homologous DNA/DNA and protein/protein regimens. Moreover, the secretion of IFN-γ was higher in DNA/protein regimens than in DNA/DNA and protein/protein regimens after exposure of mice splenocytes to SCR HIV-1 in vitro.

Conclusion: The chimeric HIV-1 Nef-Tat antigen was highly immunogenic, especially when applied in a heterologous prime/ boost regimen. This regimen could direct immune response toward cellular immunity (Th1 and CTL activity) and increase IFN-γ secretion after virus exposure.

Background: The study was conducted to analyze HIV dynamics across blood-retinal barrier (BRB) and the relevant risk factors for HIV-associated ocular complications.

Methods: This study included a case series of 40 HIV-positive patients with ocular lesions, which were studied retrospectively. Clinical and laboratory examinations included plasma and intraocular viral load (VL).

Results: HIV VL on paired aqueous/plasma samples was available for 40 patients. Aqueous VL was negatively associated with antiretroviral treatment (ART) duration (p = 0.02 and p < 0.05), and plasma VL was independent of ART duration (p = 0.53). An aqueous/plasma discordance was found in 19/40 (47.5%) patients, eight of whom (20%) had detectable aqueous VL despite a suppressed plasma VL (escape). There were significant differences in CD4+ T-lymphocyte levels (p = 0.011 and p < 0.05) and ART duration (p = 0.007 and p < 0.05) between the patients with HIV-associated ocular complications and the patients without.

Conclusion: This study provides a rationale for initiating ART early in the course of infection to reduce HIV VL in the aqueous humor, and raises the possibility of the ocular sanctuary where HIV replicates. Meanwhile, early and standard ART would be an optimal option to protect against ocular opportunistic infection.

Background: HIV-associated pulmonary arterial hypertension (HIV-PAH), a rare and fatal condition within the pulmonary arterial hypertension spectrum, is linked to HIV infection. While ferroptosis, an iron-dependent cell death form, is implicated in various lung diseases, its role in HIVPAH development remains unclear.

Methods: Leveraging Gene Expression Omnibus data, we identified differentially expressed genes (DEGs) in pulmonary arterial smooth muscle cells, including HIV-related DEGs (HIV-DEGs) and ferroptosis-related HIV-DEGs (FR-HIV-DEGs). PPI network analysis of FR-HIV-DEGs using CytoHubba in Cytoscape identified hub genes. We conducted functional and pathway enrichment analyses for FR-HIV-DEGs, HIV-DEGs, and hub genes. Diagnostic value assessment of hub genes utilized ROC curve analysis. Key genes were further screened, and external validation was performed. Additionally, we predicted a potential ceRNA regulatory network for key genes.

Results: 1372 DEGs were found, of which 228 were HIV-DEGs, and 20 were FR-HIV-DEGs. TP53, IL6, PTGS2, IL1B (downregulated), and PPARG (upregulated) were the five hub genes that were screened. TP53, IL6, and IL1B act as ferroptosis drivers, PTGS2 as a ferroptosis marker, and PPARG as a ferroptosis inhibitor. Enrichment analysis indicated biological processes enriched in "response to oxidative stress" and pathways enriched in "human cytomegalovirus infection." Key genes IL6 and PTGS2 exhibited strong predictive value via ROC curve analysis and external validation. The predicted ceRNA regulatory network identified miRNAs (has-mir-335-5p, has-mir-124-3p) targeting key genes and lncRNAs (XIST, NEAT1) targeting these miRNAs.

Conclusion: This study advances our understanding of potential mechanisms in HIV-PAH pathogenesis, emphasizing the involvement of ferroptosis. The findings offer valuable insights for future research in HIV-PAH.

Background: Eastern African countries are among the countries with a very high HIV/AIDS prevalence rate. High HIV/AIDS prevalence is a problem that has a detrimental effect on the economic development of these countries. Previous studies have generally examined the relationship of HIV/AIDS with life expectancy or economic growth. In this study, three different models have been established and the relationship of HIV/AIDS with economic growth, health expenditures, and life expectancy has been analyzed, and current econometric methods and policy recommendations have been developed according to the results.

Objective: The aim of this study was to investigate the relationship between health expenditure, environmental degradation, life expectancy, HIV/AIDS, and economic growth.

Method: Annual data from 9 Eastern African countries for the period of 2000-2019 were used. Panel ARDL/PMG and Dumitrescu-Hurlin methods were used.

Results: HIV/AIDS negatively affects economic growth and life expectancy, and positively affects health expenditures. According to the causality results, HIV/AIDS is the cause of economic growth. In addition, a bidirectional causal relationship has been found between HIV/AIDS and life expectancy.

Conclusion: The main conclusion of the study is that HIV/AIDS plays a negative role in economic growth and life expectancy. Further steps must be taken to prevent the further spread of HIV/AIDS, which causes these factors to affect the well-being of the countries.

Background: The time elapsed since HIV infection diagnosis (TdiagHIV) affects the quality of life (QoL) and can get worse when chronic illnesses start.

Objective: The aim of this study was to analyze the impact of metabolic syndrome (MetS) and cardiovascular risk (CVR) on the QoL of people living with HIV (PLHIV).

Methods: Cross-sectional study, with 60 PLHIV followed at a Reference Center in the city of Jataí, Goiás, Brazil. Data collection involved sociodemographic, clinical, CVR, MetS, and QoL information. The data were analyzed using descriptive and inferential statistics, with the BioEstat 5.3 program adopting p<0.05.

Results: There was a predominance of men (61.7%), aged ≤38 years (53.3%), with a TdiagHIV of 97.88±85.65 months and use of antiretroviral therapy (ART) of 80.13±69.37 months. The worst domain of QoL was concern about confidentiality (40 points), and the best was medication concerns (95 points). MetS predominated at 18.3% and a moderate CVR at 11.7%. MetS was positively associated with age >38 years, the female sex, with the lowest score in QoL for general function, and the highest for TdiagHIV and the use of ART (p<0.05). A moderate CRV was positively related to higher TdiagHIV and ART use, and low HDL-c, and the lowest score for QoL was found for trust in a professional (p<0.05).

Conclusion: PLHIV who are older, have a higher TdiagHIV, and use ART are more likely to develop MetS and moderate CVR. The presence of these diseases in PLHIV causes impairment in areas of QoL.

Background: COVID-19 has inevitably influenced health systems. HIV testing rates have been reduced, and access to antiretroviral treatment has been scaled down. We evaluated the impact of COVID-19 on the management of people living with HIV (PLWH) in Türkiye.

Methods: We conducted a cross-sectional study in three tertiary care hospitals. We compared the baseline characteristics at the first visit and viral suppression rates at the 24th week of new HIV diagnoses during the pandemic with those during the previous two years. To observe the effect of the pandemic on people living with HIV who were already in care, we compared the metabolic and clinical parameters like weight, blood pressure, blood lipid levels, fasting glucose levels, and liver and renal function tests, of the same people before and during the pandemic.

Results: The first group included 380 cases (127 diagnosed during the pandemic and 253 diagnosed during the previous year). The demographic characteristics were similar. The newly diagnosed PLWH during the pandemic had significantly higher baseline HIV RNA levels (p=0.005), a lower number of clinical visits (p=0.0005), and a lower number of cases with undetectable viral loads at 24 weeks of treatment (p=0.0005) than those diagnosed during the pre-pandemic period. The second group included 261 individuals with a mean follow-up duration of 24.7 (SD± 3.5; min- max 12-144) months. The comparison of laboratory parameters revealed that in the postpandemic period, virologic suppression was maintained at 90.1%, body mass index (p=0,0001), total cholesterol (p=0,0001), and LDL levels (p=0,0001) increased significantly, and creatinine levels decreased significantly (p=0,0001).

Conclusion: Our study showed that COVID-19 deteriorated the HIV management of PLHIV. Strengthening the medical infrastructure of basic services for PLWH is critical for future crises.

HIV infection is a worldwide epidemic. Antiretroviral therapy allows people living with HIV (PLHIV) increased longevity and a better quality of life. Among the various ways of monitoring the clinical evolution of PLHIV, handgrip strength (HGS) is a promising strategy, as this test can be used to assess the health condition quickly and at a low cost. In this sense, the present study aims to describe, through a literature review, the relationship between HGS and the clinical evolution of PLHIV, especially with morbimortality. Initially, it is highlighted that aging, HIV infection, and excess body fat are related to the loss of HGS in PLHIV. Furthermore, PLHIV is more likely to present cardiometabolic diseases that can be aggravated by reduced HGS. Thus, in people without positive HIV serology, low HGS indirectly, through the presence of risk factors or cardiometabolic diseases, or directly increases the chance of mortality. In conclusion, the lack of studies on this topic for PLHIV is highlighted, and more longitudinal studies, including control groups, are needed.

Introduction: People living with HIV (PLHIV) suffer from a range of consequences related to infection, including hyperlipidemia and neurologic and sleep disorders. Supplements containing phenolic compounds with high antioxidant properties can reduce these side effects. Resveratrol is a phenolic compound that improves the symptoms of diabetes, cancer, and viral infections. This study aimed to evaluate the effects of resveratrol on hyperlipidemia and neurological problems in PLHIV in Iran.

Methods: In this double-blind, randomized clinical trial, 41 PLHIV were randomly assigned to two groups: a placebo group (n=21) and a resveratrol group (n=20). Triglyceride and cholesterol levels were determined for all the subjects before and one month after they used the medication. Additionally, standard questionnaires were used to evaluate the quality of sleep, stress, depression, and quality of life of the participants. The data were analyzed via analysis of covariance in Stata 17.0.

Results: The study population did not significantly differ in terms of age (p=0.49), sex (p=0.09), marital status (p=0.90), level of education (p=0.90), duration of HIV infection (p=0.54), or mode of HIV transmission (p=0.51). The administration of resveratrol did not affect psychological parameters or blood cholesterol (p=0.091) or triglyceride (p=0.932) levels.

Conclusion: The administration of resveratrol did not affect cholesterol or triglyceride levels or the rates of depression, anxiety, sleep quality, or quality of life in PLHIV. The resveratrol supplementation in a large-scale clinical study involving more patients for a longer course of treatment may have had more significant effects on the serum levels of lipids and psychological factors.

Background: The incorporation of anti-HIV drugs into polymer to form polymer-drug conjugates has been reported to result in improved therapeutic activity. Zidovudine, an anti-HIV drug, was explored alone and in combination with known drug molecules using polyamidoaminebased carriers.

Objective: Polymer-drug conjugates incorporated with zidovudine, cinnamic acid, and 4-aminosalicylic acid were prepared and evaluated for their potential efficacy in vitro against pseudo- HIV-1.

Methods: Aqueous Michael addition polymerization reaction was employed to prepare the conjugates. The conjugates were incorporated with zidovudine, cinnamic acid, and 4-aminosalicylic acid. They were characterized by SEM/EDX, XRD, FTIR, NMR, LC-MS, particle size analysis, in vitro analysis, computational studies, and in silico toxicity predictions.

Results: The conjugates displayed spherically shaped morphology. The in vitro findings showed that polymer-drug conjugates, T15 and T16, with a single drug were effective against pseudo- HIV-1 at high concentrations of 111.11 and 333.33 μg/mL, respectively. Molecular docking studies supported the in vitro results. Additionally, SwissADME, ProTox-II, and GUSAR (General Unrestricted Structure-Activity Relationships) analyses revealed that these compounds have promising antiviral potential.

Conclusion: The prepared polymer-drug conjugates with a single drug showed promising effects against the Pseudo-HIV-1, and the conjugates displayed features that make them potential anti- HIV therapeutics that require further studies.