Current HIV Research - Online First

To reveal the epidemiology of kidney disease (KD) in people living with HIV (PLWH) and to report the antiretroviral treatment (ART) management in case of kidney disease.

This multicenter, retrospective observational study identified KD under four categories: acute kidney disease (AKD), chronic kidney disease (CKD), accelerated decline of glomerular filtration rate (GFR > 60 mL/min), and asymptomatic kidney disease indicated by markers of kidney damage. Clinical characteristics and etiological causes of KD in patients were evaluated.

Among 2092 PLWH screened, 131 patients (6.26%) had at least one form of KD. All patients with KD were Caucasian; 112 (84.5%) were male, with a median age of 51 9range 21–80) years. The most common comorbidities were hyperlipidemia (43.5%), diabetes mellitus (33.6%), and hypertension (26.9%). AKD developed in 20 patients (0.95%), CKD in 35 patients (1.67%), accelerated GFR decline in 69 patients (3.29%), and asymptomatic KD in 7 patients (0.33%). Regarding the etiological causes, 39.7% of KD cases were attributed to ART-related nephrotoxicity, 21.4% to HIV-related nephropathy, 19.8% to comorbidity-associated KD, and 6.9% to non-ART drug nephrotoxicity. ART regimen modification was performed in 39 patients (29.6%) with ART-related nephropathy. Lamivudine-based ART required fewer treatment changes (9.5%) than tenofovir disoproxil fumarate (38.1%) or tenofovir alafenamide (36.4%) (P = 0.04).

ART-related nephrotoxicity and comorbidity-associated kidney diseases are emerging challenges in the epidemiology of KD among PLWH.

Lamivudine-based ART regimens appear to be favorable in cases of KD development, showing a greater likelihood of preserving the initial treatment regimen.

Human immunodeficiency virus (HIV) is a primary health concern that leads to Acquired immunodeficiency syndrome (AIDS), with more than 39.9 million people living with HIV globally. Dolutegravir sodium is a lipophilic compound with a log P value of 2.2. The current research aimed at augmenting the solubility, dissolution, and therapeutic benefits of Dolutegravir sodium through Solid lipid nanoparticles.

The solid lipid nanoparticles (SLN) of Dolutegravir sodium were developed using high-speed homogenization and probe sonication methods. The solid lipid and surfactant were scrutinized for the development of SLN. The optimization of SLN was established using the Box-Behnken design model. The effects of lipid, surfactant, and homogenization speed on particle size and entrapment efficiency were evaluated. The colloidal dispersion was lyophilized, and accelerated stability was assessed.

Fourier Transform Infrared Spectroscopy (FTIR) confirmed the interactions between the drug excipients. The thermal behavior and crystalline nature were checked with Differential Scanning Calorimetry (DSC). Among the several tested solid lipids, the highest solubility was observed in glyceryl monostearate (GMS). The colloidal dispersion was stabilized by the Tween 20.

Accordingly, the Box-Behnken design model and the analysis of variance (ANOVA) model were applied. The p-values for the particle size and entrapment efficiency were 0.0050 and 0.0010, respectively. The optimized batch D5 showed a particle size of 189 nm, zeta potential (ZP) of -24.6 mV, entrapment efficiency of 85.94%, and drug release of 87.02%. The optimized batch D5 was further lyophilized and analyzed with scanning electron microscopy (SEM), which confirmed the nanoscale range for SLN of Dolutegravir sodium.

A significant enhancement in solubility and dissolution was achieved with the solid lipid nanoparticles. The sustained delivery of 24 hours reduces the dosage frequency and minimizes the viral load for the effective therapy of HIV, thereby improving patients' comfort and compliance.

This study aims to examine neuroanatomical differences associated with depressive symptoms in people with HIV (PWH) by comparing three groups: depressed PWH (PWH Dep+), non-depressed PWH (PWH Dep−), and HIV-negative controls. The primary goal is to explore specific alterations in brain volume and cortical thickness linked to depressive symptomatology in PWH.

A total of 61 male participants (28 PWH, 33 controls) underwent psychiatric evaluation and high-resolution structural MRI scanning. Voxel-based morphometry (VBM) and cortical thickness analyses were conducted, with age and education considered as covariates. Participants were classified into PWH Dep+ and PWH Dep− based on depression scales.

The PWH Dep+ group exhibited increased gray matter volume in the left anterior cingulate cortex and decreased cortical thickness in the left frontal pole compared to controls. In contrast, PWH Dep− participants showed increased cortical thickness in the bilateral postcentral gyrus and posterior cingulate gyrus. Additionally, volume reductions in the middle occipital and middle temporal gyri distinguished PWH Dep+ from PWH Dep−.

Depression in PWH is associated with structural brain changes, particularly in frontal and occipital regions. Although causality cannot be inferred due to the cross-sectional design, these results may enhance our understanding of the neuropathological mechanisms underlying depression in PWH. The findings should be interpreted with caution, given the relatively small sample size and the exclusion of female participants.

Patients living with HIV (PLHIV) have a higher cardiovascular risk than others, which is why the early detection of atherosclerosis in this population is important. The present study reports predictive models of subclinical atherosclerosis for this population of patients, made up of variables that are easily collected in the clinic.

The study design is a cross-sectional observational study. PLHIV without established cardiovascular disease were recruited for this study. Predictive models of subclinical atherosclerosis (Doppler ultrasound) were developed by testing sociodemographic variables, pathological history, data related to HIV infection, laboratory parameters, and capillaroscopy as potential predictors. Logistic regression with internal validation (bootstrapping) and machine learning techniques were used to develop the models.

Data from 96 HIV patients were analysed, 19 (19.8%) of whom had subclinical atherosclerosis. The predictors that went into both machine learning models and the regression model were hypertension, dyslipidaemia, protease inhibitors, triglycerides, fibrinogen, and alkaline phosphatase. Age and C-reactive protein were also part of the machine learning models. The logistic regression model had an area under the receiver operating characteristic curve (AUC) of 0.91 (95% CI: 0.84-0.99), which became 0.80 after internal validation by bootstrapping. The machine learning techniques produced models with AUCs ranging from 0.73 to 0.86.

We report predictive models for subclinical atherosclerosis in PLHIV, demonstrating relevant predictive performance based on easily accessible parameters, making them potentially useful as a screening tool. However, given the study’s limitations—primarily the sample size-external validation in larger cohorts is warranted.

The effectiveness of antiretroviral therapy (ART) in treating HIV is influenced by the clinical response of patients, which, in turn, impacts the development of drug resistance. This study aimed to assess the correlation between clinical treatment response and resistance to first-line reverse transcriptase inhibitors in HIV patients receiving treatment for ≤12 and >12 months in South Sulawesi, a province in Indonesia.

In this cross-sectional study, 36 people living with HIV (PLHIV) experiencing virological failure (VF) were sampled from HIV services in the province from August 2022 to January 2023. HIV-1 viral RNAs were extracted, sequenced, and analyzed for drug sensitivity and resistance classification using the Stanford University HIV Drug Resistance Database (HIVdb) according to World Health Organization (WHO) recommendations, determining resistance levels and HIV subtypes. Phylogenetic analysis of PR-RT sequences (~1200 base pairs) was performed using the Muscle program and MEGA11 software, utilizing the neighbor-joining method with the Kimura two-parameter model.

Genotyping of plasma samples revealed that a significant proportion of patients exhibited mutations associated with resistance to both nucleoside reverse transcriptase inhibitors (NRTIs) and non-NRTIs (NNRTIs) (48.6% and 51.4%, respectively). Clinical response indicators, such as initial body mass index and occurrence of opportunistic infections, were found to correlate with specific drug resistance, highlighting the importance of monitoring treatment response. Moreover, virologic response showed strong associations with resistance to specific drugs, suggesting the need for tailored therapeutic approaches. Patient behaviors related to transmission risk factors were also found to be linked to resistance levels, underscoring the multifactorial nature of resistance development.

Overall, this study underscores the importance of considering treatment response in managing HIV and suggests implications for optimizing therapy regimens to mitigate resistance emergence.

Some HIV patients stay in an immune unresponsive state after antiretroviral therapy (ART), with a notably higher risk of AIDS-related and non-AIDS-related complications. Double-negative T cells (DNT) can compensate for immunity and prevent immune overactivation in HIV patients. Also, immune non-responders (INRs) have fewer DNT cells than immune responders (IRs). HIV infection and ART can change the dynamic function of cell mitochondria, which are crucial in ferroptosis. Ferroptosis is a form of cell death marked by the accumulation of reactive oxygen species (ROS) and iron-dependent lipid peroxidation. Yet, the changes in DNT cell function in INRs and the impact of ferroptosis on immune reconstitution remain unclear.

Our study focused on the expression level of DNT cells in HIV immune non-responders. Then, we detected markers of ferroptosis, cell activation, proliferation, killing function, and inflammatory states of DNT cells in INRs.

The study involved 88 PLHIVs who had received antiretroviral therapy for over 4 years and tested virus-negative. These patients were classified into two groups: 28 INRs (CD4 < 350/μl) and 60 IRs (CD4 ≥350/μl). Additionally, 25 sex- and age-matched HCs were included. Flow cytometry was used to detect ferroptosis markers (JC-1, Lipid ROS, lipid peroxidation), cell proliferation, and cell activation. Transmission electron microscopy (TEM) was applied to observe mitochondrial morphology. Finally, statistical analysis was performed on the detection results.

After long-term antiretroviral therapy, we found that INRs had a lower DNT cell count than IRs. Regarding proliferation and activation, our results showed higher CD38/HLA-DR co-expression and Ki67 expression in INRs' DNT cells than in IRs', indicating over-activation of DNT cells in INRs. In terms of killing function, the perforin and granzyme B levels in INRs' DNT cells were lower than those in IRs', suggesting impaired killing function of DNT cells in INRs. For ferroptosis, the proportion of DNT cells with decreased MMP in INRs was higher than in IRs and HCs. INRs' DNT cells also had higher levels of lipid ROS and lipid peroxidation compared to those in IRs and HCs. TEM revealed that the mitochondria of INRs' DNT cells had typical morphological features. Moreover, INRs' DNT cells had a greater degree of inflammation.

Our study centered on the proliferation, activation, ferroptosis, killing function, and inflammatory status of DNT cells in INRs. We found that DNT cells in INRs had more active proliferation and activation, weakened killing function, mitochondrial function with typical ferroptosis features, and increased TNF-αlevels. Correlation analysis indicated that DNT cell overactivation (Ki-67+, CD38+HLA-DR+), MMP reduction ratio, and TNF-αexpression were negatively related to immune reconstitution in PLHIVs. In contrast, the killing function (perforin+) of DNT cells was positively related to it. These findings provide a theoretical basis for targeting the functional remodeling of DNT cells. In the future, therapeutic strategies can be explored, such as regulating the mitochondrial metabolic pathway or enhancing the immunoregulatory activity of DNT cells. These strategies can thus offer innovative solutions to the dilemma of immune reconstitution in HIV-infected individuals.

The enduring presence of HIV reservoirs represents an important obstacle to clinical management. Extensive research has been conducted in this field, but there are no bibliometric analyses focusing on HIV reservoir research. Aim: This study aimed to present the current status and global trends in HIV reservoir research through bibliometric analysis.

Studies on HIV reservoirs published from 1 January 1994 to 31 December 2023 were included in the Web of Science Core Collection database, and annual publication numbers, institutions, countries, and authors were analysed using CiteSpace bibliometric software. Furthermore, popular research topics and trends were analysed using co-cited references and keywords. From 1994 to 2023, 5778 publications on HIV reservoirs were included, with the United States producing the most publications, citations, and research funding. The most productive individual author was Nicolas Chomont. Cell was the journal publishing the most publications, while Nat Med had the best total link strength. The University of California System was the institution that made the greatest contribution. Keyword clustering analysis of the extracted publications indicated that the research areas over the past three decades have primarily focused on “central nervous system,” “histone deacetylase,” “multiple Epstein‒Barr virus infection,” and “dendritic cell.”

Moreover, keyword emergence analysis indicates that “provirus” and “identification” are likely to become central themes in future research. Future investigations should prioritize elucidating the specific mechanisms underlying proviral persistence and the identification of novel biomarkers in HIV reservoirs. Additionally, exploring the role of proviral dynamics in therapeutic development and reservoir targeting could offer new insights into potential treatment strategies.

This study makes a significant contribution to the understanding of HIV reservoirs, shedding light on key characteristics and emerging trends while also pointing to future research directions.