Current HIV Research最新文献

An effective HIV-1 vaccine should elicit diverse immune responses, including broadly neutralizing antibodies (bNAbs). Such antibodies recognize regions of the viral envelope glyco-protein (Env) that are conserved among the diverse HIV-1 clades and strains. They are isolated from people living with HIV-1 to protect animals from experimental viral exposure and reduce HIV-1 acquisition in clinical settings. However, despite efforts spanning several decades, bNAbs have not been elicited through immunization. The HIV Env efficiently binds bNAbs, but not their unmutated (germline, gl) precursors. In contrast, Env readily engages the germline precursors of antibodies with no, or very narrow, cross-neutralizing activities (non-neutralizing antibodies, nnAbs). That, in part, explains why Env-based immunogens consistently elicit nnAbs, but not bNAbs. In the past decade, Env-derived proteins have been specifically designed to engage the germline precursors of diverse bNAbs. These 'germline-targeting' Env immunogens activate the corresponding naive B cells in vivo, but are unable to guide their proper maturation towards their broadly neutralizing forms. For this, immunizations with currently not well-defined heterologous Envs are required. Here, we discuss the development of germline-targeting Env immunogens, their in vivo evaluation, and the strategies currently under evaluation that aim to rapidly guide the mat-uration of germline-precursor BCRs into their broadly neutralizing forms.

Background: 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 radio-logical method, aid in diagnosing TB in HIV-positive patients, complementing TLC in assessing disease progression in limited facilities.

Objective: 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.

Methods: 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.

Results: 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, fibro-sis, 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.

Conclusion: 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.

Introduction: 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.

Objective: 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.

Method: 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.

Result: 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.

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

Background: About 10% of individuals with latent tuberculosis infection (LTBI) develop tuberculosis (TB) disease during their lifetime. People living with HIV (PLWH) have a significantly higher risk of developing tuberculosis disease from latent tuberculosis infection (LTBI) compared to those without HIV. Many HIV treatment guidelines recommend screening and treating for LTBI.

Objective: This study aimed to investigate the LTBI screening frequency of PLWH and the rates of tuberculosis disease development during their follow-up.

Methods: A total of 483 PLWH were admitted to 3 research hospitals between January 2005 and April 2020. Patients who were 18 years and older, who did not have active TB disease, and who were followed up regularly were included in the study. Demographic characteristics and laboratory results of the patients, and tuberculin skin test (TST) and/or interferon gamma releasing assay (IGRA) results were recorded. Whether TB developed during the follow-up of the patients or not was recorded.

Results: A total of 482 PLWH were enrolled in the study, and 429 (89%) of them were male. The mean age of the patients was 37±13 years. The patients were followed for an average of 27.5 months (2-180 months). The mean CD4 count was 381±246/mm3 at the time of diagnosis. A total of 331 patients (68.7%) were screened for latent infection, and 62 (18.7%) of them were diagnosed with LTBI. During the follow-up of the patients, TB disease did not develop in anyone who was not screened for LTBI, while TB disease developed in 4 people who were screened. The mean age of PLWH who developed tuberculosis disease was 54±10 years, while those who did not develop it was 37±13 years, and the difference was statistically significant (p=0.009).

Conclusion: Screening for LTBI in PLWH and treating it when positive are recommended in the EACS guidelines. However, some local HIV guidelines recommend latent TB treatment according to ethnicity, CD4 count, and antiretroviral therapy use. Although the mean follow-up period was short, it was found that there was no difference in the development of TB disease in LTBI-positive and negative individuals in our study. For countries that are not on the list of high-burden countries for TB, it may be an option to give latent TB treatment only to selected patients who have lower CD4 counts.

Background: 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.

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

Methods: The cross-sectional study was conducted on consecutive patients who visited THE re-ferral 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 be-tween MetS and HIV by the independent variables.

Results: 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).

Conclusion: 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.

Human Immunodeficiency Virus (HIV) remains a significant global health challenge, necessitating rapid, sensitive, and accessible diagnostic tools. We examined recent advancements in electrochemical sensors for HIV gene detection, focusing on various sensing strategies, nanomaterial integration, and novel platform designs. Electrochemical sensors have demonstrated remarkable progress in HIV detection, offering high sensitivity and specificity. DNA/RNA-based sensors, aptamer approaches, and nanostructured platforms have detection limits as low as attomolar concentrations. Innovative signal amplification techniques, such as branched DNA amplification and toehold strand displacement reactions, have further enhanced sensitivity. Multiplexed detection systems enable simultaneous quantification of multiple HIV targets and related biomarkers. Integration of microfluidic technologies has improved sample processing and detection efficiency. Paper-based sensors show promise for low-cost, disposable testing platforms suit-able for resource-limited settings. While challenges remain in terms of selectivity in complex biological samples and point-of-care applicability, electrochemical sensors hold great potential for revolutionizing HIV diagnostics. Future developments in recognition elements, artificial intelligence integration, and combined sensing modalities are expected to address current limitations and expand the capabilities of these sensors, ultimately contributing to improved HIV management and epidemic control strategies.

Human Immunodeficiency Virus (HIV) damages or interferes with immune cell function and remains a serious worldwide public health concern. Many researchers have studied the virus since its discovery in an effort to better understand its immunopathogenesis and neuropathogenesis. For those who have access to efficient HIV prevention, diagnosis, treatment, and care, HIV infection has now evolved into a chronic illness that can be controlled. Despite a decrease in HIV prevalence in the general population, certain subpopulations continue to exhibit higher-risk behaviors. This work aims to uncover research gaps in HIV gene expression studies, which is crucial in finding a cure. For instance, blood samples are used for most of the gene expression experiments for HIV. However, since there are very few HIV latent reservoir cells in the blood, it can be difficult to identify and quantify them. Furthermore, blood cell populations might not accurately represent the features of reservoir cells found throughout the body. Using HIV reservoir cells from distinct tissue types in gene expression research projects could help us pinpoint the main cause of the latent HIV resilience. Gene expression studies using potential repurposed drug candidates, as well as alternative experimental setups with combinations of antiretroviral therapies, can be utilized in future studies as well. Additionally, large-sample research designs that specifically investigate intestinal disruption in individuals with HIV and associated comorbidities may help us better understand the processes behind HIV.

Background: Circulating recombinant form (CRF) 01_AE and subtype C are two HIV-1 subtypes. In recent years, novel HIV-1 recombinant forms have become more and more prevalent in China; however, new HIV-1 CRF01_AE/C recombinant forms are less prevalent nationwide.

Objective: Our research study aimed to investigate new recombinant forms between different HIV-1 subtypes and evaluate their transmission risk among men who have sex with men (MSM) in Hebei, China.

Method: The near full-length genome (NFLG) of HIV-1 was identified using the analyses of the phylogenetic tree and gene breakpoints.

Results: In the present work, we have reported a novel HIV-1 recombinant form composed of CRF01_AE and subtype C. The NFLG of this CRF01_AE/C form contained eight gene subregions, with four subtype C gene segments inserted into the CRF01_AE backbone, consisting of I CRF01_AE (790-1,171 nt), Ⅱ subtype C (1,172-1,840 nt), Ⅲ CRF01_AE (1,841-5,089 nt), Ⅳ subtype C (5,090-5,666 nt), Ⅴ CRF01_AE (5,667-6,317 nt), Ⅵ subtype C (6,318-8,586 nt), Ⅶ CRF01_AE (8,587-9,246 nt), and Ⅷ subtype C (9,247-9,409 nt). This new recombinant form was named CRF140_0107.

Conclusion: The study suggested that it is important to monitor HIV-1 diversity to reduce HIV- 1 transmission in China.

Aims: In people living with human immune deficiency (PLHIV), the rates of human papillomavirus (HPV) infection, mixed types, and high-risk (HR) strains increase, while the virus clearance is prevented. Here, we report HPV genotyping in PLHIVs from Iran and the Middle East region for the first time.

Methods: HPV genotyping in referring individuals from different provinces to our laboratory was evaluated over 2023-2024. For this, the HPV types in specimens were detected through the INNO- LiPA HPV genotyping kit. Statistical analysis was conducted with a 95% confidence interval (95%CI) and P < 0.05. Accordingly, 481 subjects from various provinces participated in this study.

Results: The rate of HPV infection was 45.7%, of which 14% were HIV-infected women referred from all provinces. The most prevalent types included 6, 51, and 18, but not 16 HR types. Mixed infections in dually infected women were significantly more than in HPV-infected ones. The HPV+/HIV+ subgroup had the lowest median age. The prevalence of HPV types and mixed infection in PLHIVs was congruent with the previous reports, except for the low rate of type 16 infection, perhaps due to the healthy nature of our subjects. Only HIV+/HPV+ cases' age was similar to the previous reports, perhaps because of sample collection and study designs. Among all factors, age and gender affected the HPV type distribution notably.

Conclusion: The current study corroborated the results of many prior reports, demonstrating the considerable impact of HIV status on HPV distribution. The authors recommend implementing a national HPV vaccination and more comprehensive reports of HPV genotyping in PLHIVs.

Background/ Objective: Due to the impact of human immunodeficiency virus (HIV) infection on personal and social life, people living with HIV (PLWH) are faced with several challenges and issues. Therefore, PLWH requires psychological interventions. The study aims were to create a suitable platform for psychological structures that empower them to address their issues effectively. In this regard, we evaluated the effect of Mindfulness-based Cognitive Therapy (MBCT) and Silva-based Relaxation Therapy (SBRT) on Psychological Capital (PsyCap), Social Anxiety (SA), and CD4 count in PLWH.

Methods: This study employed an intervention-based semi-experimental design. The population consisted of 90 individuals infected with HIV. Participants were divided into two experimental groups receiving MBCT and SBRT, respectively, and one control group, selected randomly. Before and after the intervention, questionnaires and CD4+ tests were administered to the participants. Only two experimental groups received the intervention, while the control group received no training. The appropriate training for each group was conducted twice a week over eight sessions and each session lasted 90 minutes. In the intervention groups, all the people participated in all the group training sessions. No intervention was performed for the participants of the control group, and they only completed the questionnaires in the same period as the intervention groups. "Mindfulness-Based Cognitive Therapy" and "Mind Control" books were used for the implementation of MBCT and SBRT, respectively.

Results: It was revealed that a number of male participants constituted the majority with 58 (64.4%) compared to females. Regarding the means of transmission, sexual contact was the most common with 62 (68.8%) compared to other routes. The mean age of the participants was 40.5 ± 10.8 years. For the SBRT group, the mean CD4+ count was higher, with 599.5 ± 290.9 for pretest and 563.2 ± 366.7 for post-test assessments, compared to other groups. After performing the linear regression analysis, it was found that the variables had no effect on the main outcome, which is CD4 count after the intervention (p-value= 0.27). For the MBCT group, the CD4+ count variable had a p-value = 0.10 (pretest: 447.2 ± 19.5, posttest: 411.9 ± 235.9), for the SBRT group, the CD4+ count variable had a p-value = 0.05 (pretest: 599.5 ± 290.9, posttest: 549 ± 259.9), and the control group, the CD4+ count variable had a p-value = 0.5 (pretest: 445 ± 222.7, posttest: 563.2 ± 366.7).

Conclusion: MBCT and SBRT may enhance the mental well-being of PLWH. Therefore, following the interventions, the mean level of SA decreased, and PsyCap increased. Thus, strategies to improve psychological support interventions may have a significant impact on improving the health status of individuals living with HIV, including indicators of SA and PsyCap.