Current HIV Research最新文献

Introduction: People living with HIV (PLWH) are more susceptible to acquiring and having serious consequences from COVID-19. The objective of this study was to examine the correlation between COVID-19 infection and other risk factors in these patients.

Methods: This is a descriptive-analytical study recruiting 160 PLWH referred to the Behavioral Disease Counselling Centre of Imam Khomeini Hospital in Tehran in 2021. The patients were selected through convenient sampling. A checklist was used to collect the necessary data. Descriptive statistical tests, such as mean and standard deviation, were employed alongside inferential statistics, including chi-square, Fisher, independent t-tests, and logistic regression, all evaluated at a significance level of p<0.05 using the R software.

Results: The patients' average age was 43.15 ± 11.23. Forty-four women and 116 men were present. A notable association was observed between the incidence of COVID-19 and variables such as hepatitis C and the duration of time since HIV diagnosis (p<0.001). Moreover, a strong correlation was found between the amount of COVID-19 vaccination doses given to patients and their probability of acquiring the disease. The first vaccination dose was linked to a 5.45 percent increase in COVID-19 incidence in patients, whereas the second and third doses (t=2.95, t=7.57) reduced the risk of getting COVID-19. Furthermore, no discernible link (p>0.05) was found between the use of various antiretroviral medications and COVID-19 infection.

Conclusion: This study finds that vaccine type does not impact COVID-19 outcomes in HIV-positive patients, but receiving more doses decreases the probability of occurrence of COVID-19, advocating for multiple vaccinations. However, PLWH, especially those non-compliant with antiretrovirals, need strict adherence to health protocols due to heightened vulnerability to viral illnesses.

The aim of the present investigation is to identify effective anti-HIV drugs through the in-silico virtual screening of the coumarin pharmacophore with or without substituents. Virtual screening started with target identification through computation docking and interactions, binding affinity through molecular dynamics, and the ADMET profile through the use of various enzymes. The target study suggests that the target is involved in various stages of HIV replication and in determining the ways in which non-nucleoside reverse transcriptase inhibitors (RTIs) influence it. The interaction pattern and simulation study conclude the specific affinity of coumarin pharmacophore to the HIV's reverse transcriptase enzyme, especially 3HVT. Moreover, the amide linkage worked as a synergistic bridge to provide more interaction to the pharmacophore. The initial results led to the determination of 83 virtual amide-like molecules, which were screened through docking and MD studies (100 ns) on the best-suited enzyme HIV's reverse transcriptase enzyme, such as PDB ID "3HVT". The virtual screening study revealed the high affinity of compounds 7d and 7e with the lowest IC₅₀ values of 0.729 and 0.658 μM; moreover, their metabolism pattern study, toxicity, and QED values in a range of 0.31-0.40 support a good drug candidate. The two compounds were also synthesized and characterized for future in vitro and in vivo studies. The in silico-based descriptor of compounds 7d and 7e indicates the potential future and provides the best two molecules and their synthetic route for the development of a more effective drug to combat HIV/AIDS epidemics.

Introduction: The prevalence of sleep disorders in people living with HIV (PLWH) is higher than in the general population. Even if viral suppression is achieved with Antiretroviral Therapy (ART), the chronic immune activation and increased inflammation due to immune reconstitution persist. The aim of our study was to determine the prevalence of poor quality of sleep (QoS) and associated risk factors in PLWH and to investigate the relationship between poor QoS and CD4 T lymphocyte count and CD4 reconstitution.

Methods: PLWH ≥18 years old, attending for routine HIV monitoring were recruited. PLWH with conditions that may affect their QoS (pregnant, hospitalized, malignancy, substance-alcohol abuse, psychiatric disease or treatment, sleeping pill) were excluded. Pittsburgh Sleep Quality Index (PSQI, score ≥5 indicates poor QoS), Epworth Sleepiness Scale (ESS, score ≥11 indicates daytime sleepiness), and Beck Depression Scale (BDS, score ≥10 indicates clinical depression) were applied. CD4+ T lymphocyte reconstitution (current-baseline CD4+ count) and CD4+ T lymphocyte reconstitution rate [(current-baseline CD4+ count)/duration of HIV infection in years] were calculated for PLWH on ART. Student t-test and Pearson's chi-squared test were used for analysing the data, and p<0.05 was considered significant.

Results: A total of 131 (15 newly diagnosed, 116 on ART for at least six months) PLWH were enrolled. Poor QoS was detected in 60.3% of PLWH. When compared, the ratio was higher in newly diagnosed PLWH (vs PLWH on ART, p>0,05). Daytime sleepiness in PLWH with poor Qos (p=0.04) was significantly increased (vs good QoS). Clinical depression (p=0.001) was significantly more common in PLWH with poor QoS (vs good QoS). Although statistically nonsignificant (p>0,05), younger age, female sex, being single, homosexüel sexual preference, high income and living with the family were associated with poor QoS. No association was found between the ART regime and QoS. PLWH with poor QoS had a higher CD4+ T lymphocyte count (p>0,05), a higher number of CD4+ T lymphocyte reconstitution (p<0.05), and a higher reconstitution rate than PLWH with good QoS (p<0.05).

Conclusion: Prevalence of poor QoS was high in our cohort. Poor QoS was associated with CD4+ T lymphocyte reconstitution and reconstitution rate.

Introduction: Tuberculosis is an opportunist infection that is fatal and most frequently seen in HIV-positive patients due to immunosuppression. Endobronchial lesions can portray symptoms in different ways. Endobronchial Tuberculosis is one of these lesions.

Case report: An HIV-positive, untreated 26-year-old patient with fever, cough, and dyspnea consulted our clinic. In the chest X-ray taken, effusion on the right side and non-homogeneous density increase in the middle and upper lobes, bilaterally more prominent on the right side, were observed. Therefore, the patient underwent bronchoscopy because the CT (computerized tomography) showed mediastinal lymphadenopathy (LAP) and an endobronchial lesion in the left main bronchus. During bronchoscopy, a vegetative endobronchial lesion that causes obstruction in the left main bronchus was monitored. With the help of Pathology and PCR results, endobronchial tuberculosis was diagnosed.

Conclusion: Even if Acid-alcohol-resistant Bacillus (ARB) is detected negative in patients who stop responding to antimicrobial treatment and are being monitored under radiological scanning, a distinctive diagnosis of endobronchial tuberculosis should be kept in mind while performing bronchoscopy.

Background: Human immunodeficiency virus-1 infection still remains a global health threat. While antiretroviral therapy is the primary treatment option, concerns about the emergence of drug-resistance mutations and treatment failure in HIV-infected patients persist.

Objective: In this study, we investigated the development of drug resistance in HIV-1-infected individuals receiving antiretroviral therapy for 6-10 years.

Methods: In this cross-sectional study, we evaluated 144 people living with HIV-1 who had received antiretroviral therapy for at least 6 years. Plasma specimens were collected, and the HIV-1 viral load and drug-resistance mutations were assessed using molecular techniques.

Results: The demographic and epidemiological characteristics of the participants were also analyzed: Twelve [8.3%) of the studied patients showed a viral load over 1000 copies per/mL, which indicates the suboptimal response to antiretroviral therapy. Significant correlations were found between viral load and CD4 count, as well as epidemiological factors, such as vertical transmission, history of imprisonment, and needle stick injuries. Drug resistance mutations were detected in 10 (83.3%) of patients who failed on antiretroviral therapy, with the most common mutations observed against nucleoside reverse transcriptase inhibitors (5 (41.7%)) and non-nucleoside reverse transcriptase inhibitors (9 (75%)). Phylogenetic analysis revealed that 12 patients who failed treatment were infected with CRF35_AD.

Conclusion: Our study provides important insights into the characteristics and development of drug resistance in HIV-1-infected individuals receiving long-term antiretroviral therapy in Iran. The findings underline the need for regular viral load monitoring, individualized treatment selection, and targeted interventions to optimize treatment outcomes and prevent the further spread of drug-resistant strains.

Background: The interaction of human immunodeficiency virus (HIV), host and antiretroviral therapy (ART) causes a range of metabolic disorders that can be characterized as a metabolic syndrome (MetS) that increases the cardiovascular risk. MetS involves central obesity, which can be detected using different anthropometric parameters.

Objective: To assess the abilities of different anthropometric parameters in the prediction of MetS in HIV-infected men on ART.

Method: The study involved 92 male participants (mean age 44.46±10.38 years), divided into two groups: with and without MetS. All subjects underwent biochemical evaluation (triglycerides, HDL-cholesterol, fasting glucose), blood pressure measurement and anthropometric assessment: body mass, body height, body mass index (BMI), body fat mass, body circumferences (chest, upper arm, forearm, waist, hip, proximal and middle thigh and calf), sagittal abdominal diameter (SAD), skinfold thicknesses (subscapular, anterior and posterior upper arm, anterior and lateral forearm, abdominal, supraspinal, thigh and calf), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), waist-to-thigh ratio (WTR), sagittal abdominal diameter-to-body height ratio (SADH), body adiposity index (BAI) and conicity index. MetS was specified according to IDF criteria.

Results: Subjects with MetS had statistically significant higher values of all anthropometric parameters except middle thigh circumference, calf skinfold and body height. According to ROC analysis and Binary Logistic Regression, SAD has been shown as the best predictor of MetS with a predictive value of 21.40 cm (AUC:0.91), followed by WHR with a predictive value of 0.93.

Conclusion: Sagittal abdominal diameter is the strongest anthropometric indicator of MetS in HIV-infected patients on ART.

HIV/ AIDS is a global pandemic, one of the most challenging; with no cure for the disease, various therapies available in the form of regimens as Highly Active Anti-Retroviral Therapy (HAART) or simply Anti-Retroviral Therapy (ART) are the only way to manage the disease. The Fixed Dose Combinations (FDCs) concept has been a well-recognised improvement in pharmacotherapy for the treatment of a variety of chronic maladies like hypertension, diabetes, HIV/AIDS, and several FDC products consisting of HIV drugs are approved. These single-tablet regimens have been essential in streamlining ART, lowering pill burden and increasing adherence. Adherence to HAART is the most vital factor to ensure medication success and virologic suppression. However, adherence is faced with several barriers including adverse effects of drugs, the complexity of ART, social-cultural factors, and pill burden among others. This writing reviews the concept of adherence to ART, and its barriers while stressing pill burden as a significant one which we suggest would be solved by using Fixed Dose Combinations (FDCs).

Introduction: The C-C chemokine receptor type 5 (CCR5) is a major co-receptor for human immunodeficiency virus (HIV). Some individuals carry the CCR5 delta-32 genetic polymorphism. People with homozygous CCR5 delta-32 gene are nearly completely resistant to HIV-1 infection. High-resolution melting curve (HRM) analysis is a post-PCR technique utilized for identifying genetic variations in a quick, affordable, and closed-tube assay. The objective of this study was to develop an HRM assay for easy detection of delta-32 mutations.

Materials and methods: DNA was extracted from peripheral blood mononuclear cells. HRM was performed to detect delta-32 mutation. The study investigated the impact of various factors, including annealing temperature, template concentration, touchdown PCR, additives, amplicon size, and program settings, on HRM Tm differentiation.

Results: It was expected that there would be a 4°C Tm difference between amplicons with and without delta-32 mutation, but the test showed a difference of only 2.3°C. In attempts to identify heterozygote delta-32 variants, a Tm difference of only 0.4°C could be achieved. Various modifications were applied, such as adjusting the template concentration, using touchdown PCR, and adding DMSO and glycerol. However, none of these changes helped to differentiate the Tm effectively, especially in delta-32 heterozygote samples.

Conclusion: The HRM test identified four samples with heterozygote mutations in each HIV-infected (8.89%) and control (5.72%) groups. More importantly, this study showed that identifying the delta-32 mutation of the CCR5 gene using HRM assay is not as straightforward as previously suggested in some literature, and it requires special setup conditions.

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.