Current HIV Research - Volume 23, Issue 2, 2025

The increased risk of metabolic syndrome (MetS) and its subcomponents among people living with HIV/AIDS, especially in developing countries, is well documented with the global pooled prevalence of the related risk factors in this population.

This study aimed to explore the prevalence of MetS among Iranian People living with HIV according to the ATP III and Iranian criteria.

The cross-sectional study was conducted on consecutive patients who visited THE referral centre for AIDS/HIV between May to December 2023. A total of 130 participants (n=83; 63.8% male) were investigated based on the inclusion criteria, which included having a minimum age of 25 and a maximum of 65 years and following a stable ART treatment regimen for at least six months. A Chi-square test was used to determine the relationship between the categorical variables. Uni/Multi-variable linear regression analysis was used to quantify the associations between MetS and HIV by the independent variables.

The incidence of MetS according to ATP III and Iranian criteria were 42 (32.3%) and 45 (34.6%), which was higher in older patients (p=0.001) and those with more duration since HIV diagnosis (p=0.02). Around 33.1% and 16.1% were overweight and obese, respectively. Among the components of MetS, the highest prevalence (50.8%) was related to low HDL, and the lowest was related to fasting blood sugar (21.5%). The average body fat mass, protein mass, Soft lean mass, and percentage body fat were 18.54 ± 9.46 kg, 10.91 ± 2.17 kg, 51.31 ± 9.61 kg, and 24.86±10.25% that were higher in MetS group (p<0.05).

Our study points out the high prevalence of MetS in an Iranian population living with HIV, especially those suffering from the underlying disease for a longer time. Conducting multi-centric studies with larger sample sizes is needed to confirm our results and determine the most effective measures.

The rapid increase in incidences of drug resistance and off-target toxicity in the case of Human Immunodeficiency Virus (HIV) has increased the demand for drugs with fewer side effects. HIV-1 Integrase (IN) is a promising target that helps integrate viral DNA with human DNA. It acts as a target for strand transfer inhibitors. However, the emergence of resistant mutations in the proteins necessitates the exploration of potent allosteric drugs. The allosteric integrase inhibitors (ALLINI) that interrupt the association of the integrase binding domain of the lens epithelium growth factor (LEDGF/p75) and LEDGF/p75 binding site of the IN are more promising as they hinder site specificity and viral replication.

In this study, a 3D-QSAR, molecular docking, and ADMET were carried out to investigate the binding of the C2-pyrazolopyrimidine amides and amide isosteres.

The 3D-QSAR model was developed using a series of 24 C-2 substituted pyrazolopyrimidine and amide isosteres. A statistically significant model was constructed, showing the determination coefficient (r2) and five-fold cross-validation (q2) at 0.946 and 0.506, respectively. Furthermore, the contour maps of the electrostatic potential and van der Waals coefficient provided structural modifications in the features to improve the inhibitory activity.

A molecular docking study was also performed to check the binding of the compounds to the LEDGF/p75 binding site of the IN, along with ADMET evaluation.

The outcome of the study will help to prepare the potent molecules with enhanced allosteric inhibitory activity.

Tuberculosis (TB), caused by Mycobacterium tuberculosis, often becomes a comorbidity in individuals infected with Human Immunodeficiency Virus (HIV), the cause of Acquired Immunodeficiency Syndrome (AIDS). HIV-positive individuals have a 30-fold higher risk of contracting TB compared to non-HIV individuals. Assessment of HIV-TB disease progression commonly relies on measuring CD4 cell counts. However, in areas with limited access, the World Health Organization (WHO) recommends using Total Lymphocyte Count (TLC) ≤ 1200 cells/μL as an alternative. Additionally, chest X-rays, a widely accessible radiological method, aid in diagnosing TB in HIV-positive patients, complementing TLC in assessing disease progression in limited facilities.

The objective of this study was to analyze the differences in the location and characteristics of TB lesions based on HIV status and TLC levels.

A case-control study was conducted at Adam Malik Central Hospital on pulmonary TB patients from December 2021 to December 2022, meeting inclusion criteria. Evaluation of TB lesion locations and characteristics was performed by two researchers, while HIV status and TLC data were extracted from medical records.

The study involved 154 subjects, including 77 HIV-positive and 77 non-HIV individuals. The percentage of male participants was 81.8%, with a mean age of 43.4 ± 14.4 years. The significant differences in the characteristics and locations of lesions (cavities, miliary lesions, fibrosis, atelectasis, and upper and lower lung) were revealed in HIV-positive and HIV-negative patients. Similarly, significant differences in the characteristics and locations of lesions (cavities, miliary lesions, fibrosis, atelectasis, and upper and lower lung) were revealed in a patient with TLC ≤ 1200 and TLC > 1200.

The study highlights significant differences in the characteristics and locations of tuberculosis lesions about HIV status and total lymphocyte count levels among pulmonary TB patients. HIV-positive individuals exhibited distinct patterns of TB lesions compared to their HIV-negative counterparts, indicating the impact of HIV on TB disease progression. Furthermore, variations in lesion characteristics were also observed based on TLC levels, with notable differences between patients with TLC ≤ 1200 cells/μL and those with TLC > 1200 cells/μL. These findings underscore the importance of considering both HIV status and TLC in the assessment and management of TB in affected individuals. TLC can serve as an alternative to CD4 measurement in situations where access to CD4 testing is limited.

The Human Immunodeficiency Virus (HIV) is a significant global health concern that affects millions of people worldwide. This virus targets the immune system, specifically CD4 cells, weakening the body’s ability to combat infections and diseases.

Scutellaria baicalensis, a plant of the genus Lamiaceae, and its root is the main part used in medicine. Pharmacological studies have shown that Scutellaria baicalensis has various activities such as anti-inflammatory, anti-viral, anti-bacterial, anti-tumor, antioxidant effects, etc.

To investigate the anti-HIV activity of Scutellaria baicalensis against the HIV coreceptor CXCR4.

We conducted in-silico studies using bioinformatics tools like SWISS ADME, ProTox-II, PyRx, and Biovia Discovery Studio. Ligand structures were retrieved from the PubChem database, and the crystal structure of the target protein CXCR4 Chemokine receptor (PDB ID: 3ODU) with a resolution of 2.50 Å was retrieved from the Protein data bank.

From the results, we filtered out 19 compounds with the highest binding affinity compared to the native ligand (-7.9 kcal/mol), which ranges from -10.1 kcal/mol to -8.0 kcal/mol. For the 19 compounds, we conducted ADME and Toxicity studies. From the studies, Baicalin, Wogonoside, and Oroxylin A-7-O-Glucuronide possess binding affinity of -10.1 kcal/mol, -9.6 kcal/mol, and -9.2 kcal/mol, which is greater than the native ligand (-7.9 kcal/mol).

Thus, Baicalin may possess the most potential activity against HIV. Moreover, further in-vitro and in-vivo studies are needed to evaluate their biological potential, and this work may help scientists in their future studies.

Modern antiretroviral therapy (ART) prevents disease progression in people living with HIV. Due to the increasing age of people living with HIV, the detection and management of comorbidities has become more important.

In this study, we aimed to detect the prevalence of nonalcoholic fatty liver disease (NAFLD) and associated risk factors among people living with HIV followed up in our center.

This single-center, cross-sectional study included people living with HIV, on ART for ≥1 year and virologic suppression for ≥6 months, presenting for routine follow-up between October 1, 2021, and April 1, 2022. Participants with a concurrent etiology for hepatic steatosis were excluded. Transient elastography (TE) was performed. NAFLD was defined as a controlled attenuation parameter (CAP) ≥248 dB/m; significant fibrosis (≥F2) was defined as liver stiffness measurement ≥7.1 kPa.

A total of 102 people living with HIV (84% men; median age, 39 years (IQR 33-52.5)) were enrolled. The treatment regimen of all participants included a nucleos(t)ide reverse transcriptase inhibitor and an integrase strand transfer inhibitor. TE analysis indicated NAFLD in 28 (27.5%) and fibrosis in 9 (8.8%; 6 with NAFLD) participants. In multivariable analysis, type two diabetes (OR:5.7 (95% CI 1.4-22.2), p=0.013), larger waist circumference (OR:1.1 (95% CI 1.03-1.16), p=0.007), higher alanine aminotransferase (OR:1.05 (95% CI 1.01-1.09), p=0.018), and higher thyroid stimulating hormone (OR:3.1 (95% CI 1.4-6.8), p=0.005) were independently associated with NAFLD.

We observed a significant prevalence of NAFLD among people living with HIV followed up in our center. The high prevalence of NAFLD in our sample mirrors that of the general population, likely due to rising rates of metabolic dysfunction. Our findings highlight the importance of timely screening and implementation of management strategies for NAFLD in this population.

In the changing HIV treatment landscape, the focus shifts to persons living with HIV (PLH) experiencing virological non-suppression on second-line antiretroviral therapy (ART). This includes understanding viral genetic profiles, antiretroviral susceptibility, and the effectiveness of protease inhibitors (PIs) amid evolving dolutegravir-based regimen recommendations.

In this retrospective study, PLH with first-line ART failure transitioned to second-line ART (dual NRTI + ritonavir-boosted PI) between September 2015 and October 2018. Eligible patients were ≥ 13 years old, with ≥ 9 months on first-line ART, and confirmed adherence at first- line regimen failure. Conducted at a Northern Indian tertiary hospital, this 5 year follow-up examined virological outcomes and drug resistance. Follow-up included initial viral-load (VL) and CD4 testing at 6-months, subsequent VL testing every 6-12 months, clinical evaluations, and infection screenings. Data on demographics, treatment history, virological-failure (VF), and drug-resistance testing (DRT) (Viroseq HIV-1 genotyping-system) were analysed using Kaplan-Meier and Competing-risk analysis, with appropriate censoring and imputation for events like death, transfer-out, treatment discontinuation/ interruption, loss to follow-up (LTFU), or ART-regimen change.

219 PLH shifted to ritonavir-boosted PI based second-line ART after 68 (median) months (IQR: 68) of first-line ART exposure and were followed up for 57 (median) months (IQR: 48), totalling 11,548 person-months (PM) of follow-up. Virological outcomes were assessed in 201 PLH. VF cumulative-incidence (Kaplan-Meier-analysis) ranged from 6.9% at 36 months to 15.9% at 60 months. Imputation scenarios showed a potential range, with worst-case incidences of 16.2% at 36 months and 29.4% at 60 months. Cumulative-incidence function (CIF) of VF (Competing-risk-analysis) ranged from 6.5% at 36 months to 12.7% at 60 months. Among 171 PLH with complete VL data, VF incidence was 2.7 per 1000 PM (n=29), with 94.7% achieving nadir VL <1000 cp/mL. VF with PI-mutation (VF-M) analysis, including LTFU patients (n=183), showed CIF for VFM of 2.3% at 36 months and 4.9% at 60 months. DRT (n=23-sequences) revealed 17.4% lopinavir resistance, 34.8% atazanvir resistance, and darunavir (DRV) cross-resistance in three sequences. Overall, 26.1% had no significant drug-resistance mutations, 39.1% had NNRTI resistance, but no PI DRMs, and only 34.8% (of 23-PLH who underwent DRT) potentially required third-line ART.

This 5-year longitudinal study highlights the resilience of PIs in second-line ART. The incidence of VF with PI-resistance was notably low, indicating the ongoing effectiveness of PIs in managing PLH on second-line ART and the possibility of recycling PIs in subsequent ART regimens for these patients. Cross-resistance to DRV patients highlights the need for enhanced treatment monitoring.