Current HIV Research最新文献

Background: Dolutegravir (DTG) is a novel yet preferential first- and -second-line treatment for persons living with HIV (PLH). Owing to its recent introduction, DTG-based regimens have not undergone a comprehensive, systematic evaluation regarding their real-world utilization and safety profile among a sizeable Indian population.

Objective: This study aimed to assess the 24 week immunovirological outcomes, anthropometric and metabolic changes, tolerability, and adverse events (AEs) of DTG-based antiretroviral (ART) regimens.

Methods: A single-centre phase-IV non-interventional observational study involving 322 ART naïve and treatment-experienced PLH initiating DTG-based-regimens until October 2022 were followed up for outcomes at 24 weeks.

Results: At 24 weeks, all PLH (n = 113) in the naïve group, all PLH (n = 67) in the first-line substitution group, 93.9% PLH (n = 46) in the first-line failure group, and 95.7% PLH (n = 89) in the second-line substitution group were virologically suppressed to plasma HIV-RNA <1000 copies/mL. Virological suppression rates to plasma HIV-RNA <200 copies/mL and <50 copies/mL were consistent among PLH who received DTG as first- or second-line ART. The mean-unadjusted weight gain observed was 3.5 kg (SE: 0.330), and it was significantly higher in PLH with poorer health at baseline (either HIV-RNA ≥ 1000 copies/ml or CD4 cell count <350 cells/μL). Overall, 27.3% PLH (n = 88) gained ≥10% of their baseline body weight, corresponding to 3.7% incidence (n = 12) of treatment-emergent clinical obesity. DTG had an overall lipid-neutral effect, with an advantageous effect being observed in PLH switching from non-nucleoside analogue reverse-transcriptase inhibitors (NNRTI) or ritonavir-boosted protease inhibitors (b/PI), especially in dyslipidemic pre-treated PLH (median change in total cholesterol: 28.5 mg/dL and triglycerides: 51 mg/dL), possibly emanating from the withdrawal of the offending ART. The incidence of DTG-specific AEs, including CNS AEs, was low. Two PLH developed proximal myopathy and one developed transaminitis, warranting DTG discontinuation. Asymptomatic serum-CPK elevation and drug-induced transaminitis were seen in 25.2% (n = 27) and 3.2% (n = 10) PLH, respectively. No apparent negative effects on renal function were detected.

Conclusion: Our results from a large Indian cohort indicate a favourable virological and metabolic response, with good tolerance of DTG-based ART at 24 weeks.

Introduction: Abacavir is among the first-line initial antiretroviral regimens for most patients living with HIV/AIDS (PLWHA). Although well tolerated, it is associated with hypersensitivity reaction (HSR), which is treatment-limiting and potentially life-threatening. HSR was shown to be associated with the class I MHC allele, HLA-B*57:01. In this study, we aimed to evaluate the prevalence of HLA-B*57:01 in PLWHA in Istanbul, Türkiye.

Material and methods: Five HIV treatment centers in Istanbul included all sequential treatmentnaïve, ≥ 18 years adult PLWHA, between December 2017- December 2021. Demographic, clinical, and laboratory data were collected at baseline and during treatment. HLA-B* 57:01 genotyping was determined with PCR-SSP.

Results: Eight hundred sixty-seven PLWHA were included (male:91%, mean age 39.6±11.1 years). 1.6% of patients were found to be HLA-B*57:01 positive. Among HLA-B*57:01 positive patients, 4 were initially given abacavir-containing treatment; they were switched to non-abacavir treatment upon the allele found to be positive.

Conclusion: Although previous studies reported the HLA-B*57:01 prevalence of PLWHA in Türkiye as 3-3.6%, we have found the prevalence to be 1.6%. The current study includes higher numbers of patients than the previous studies. Furthermore, patients from all over the country apply to the centers in Istanbul; compared to the other studies, which involve patients limited to the relevant regions. It can be assumed that the number in our cohort is more representative of the country. In conclusion, the prevalence of the HLA-B*57:01 allele in PLWHA in this study is relatively low. With evident benefit in preventing abacavir HSR, HLA-B*57:01 should be screened in planning antiretroviral therapy.

Objective: The aim of the study was to assess the clinical features of women infected with the human immunodeficiency virus (HIV) using Holter monitoring.

Methods: Thirty-five female patients infected with HIV using a Holter monitor at the Ditan Hospital were retrospectively analyzed.

Results: In terms of basic rhythms, there were 30 cases of sinus rhythm, 27 cases of ventricular premature beat, 26 cases of supraventricular premature beat, 12 cases of mild reduction of HRV, 9 cases of normal heart rate variability (HRV), 8 cases of supraventricular tachycardia, 5 cases of abnormal ST-segment changes and 2 cases of sinus bradycardia 2 cases of paroxysmal atrial fibrillation 2 cases of junctional escape rhythm. There was only one case in each of the following ECG changes: persistent atrial fibrillation, sinus tachycardia, couplet supraventricular premature beats, accelerated idioventricular rhythm, sinoatrial block, second-degree Mobitz type I atrioventricular block, second-degree Mobitz type II atrioventricular block, complete right bundle branch block, T-wave abnormality, and significant reduction of HRV.

Conclusion: The Holter monitor can show more changes in the electrocardiogram (ECG) of HIV-- positive patients, particularly significant ECG abnormalities, such as paroxysmal atrial fibrillation, and can direct early clinical treatment to serious adverse results.

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: 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.

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.

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.

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.