Current HIV Research - Volume 22, Issue 2, 2024

Human Immunodeficiency Viruses (HIV) continue to pose a significant global health threat despite the availability of antiretroviral therapy (ART). As a retrovirus, HIV persists as a stable, integrated, and replication-competent provirus within a diverse array of long-lived cells for many years, often termed “latent reservoirs” in individuals. Thus, this review aims to furnish a comprehensive overview of diverse tissue reservoirs where HIV persists, elucidating their pathogenesis and advancement in their strategies for clinical management. Understanding the mechanisms underlying HIV persistence within tissue reservoirs is of significant interest in developing effective ART for suppressing the virus in the blood. In addition, we also discussed the ongoing mRNA HIV vaccine that has shown promising results in clinical trials to elicit broadly neutralizing antibodies and effective T-cell responses against HIV.

Background: The research and development of HIV drugs is very important, but at the same time it is a long cycle and expensive system project. High-throughput drug screening systems and molecular libraries of potential hit compounds remain the main ways for the discovery of hit compounds with anti-HIV activity. Objective: The aim of this study was to screen out the hit compounds against HIV-1 in the natural product molecule library and the antiviral molecule library, and elucidate the molecular mechanism of their inhibition of HIV-1, so as to provide a new choice for AIDS drug research. Methods: In this study, a drug screening system using HIV Rev-dependent indicator cell line (Rev-A3R5-GFP reporter cells) with pseudoviruses (pNL4-3) was used. The natural drug molecule library and antiviral molecule library were screened, and preliminary drug mechanism studies were performed. Results: Ten promising hit compounds were screened. These ten molecules and their drug inhibitory IC50 were as follows: Cephaeline (0.50 μM), Yadanziolide A (8.82 μM), Bruceine D (2.48 μM), Astragaloside IV (4.30 μM), RX-3117 (1.32 μM), Harringtonine (0.63 μM), Tubercidin (0.41 μM), Theaflavine-3, 3'-digallate (0.41 μM), Ginkgetin (10.76 μM), ZK756326 (5.97 μM). The results of the Time of additions showed that except for Astragaloside IV and Theaflavine-3, 3'-digallate had a weak entry inhibition effect, and it was speculated that all ten compounds had an intracellular inhibition effect. Cephaeline, Harringtonine, Astragaloside IV, Bruceine D, and Tubercidin may have pre-reverse transcriptional inhibition. Yadanziolide A, Theaflavine-3, 3'-digallate, Ginkgetin and RX-3117 may be in the post-reverse transcriptional inhibition. The inhibitory effect of ZK 75632 may be in the reverse transcriptional process. Conclusion: A drug screening system using Rev-A3R5-GFP reporter cells with pseudoviruses (pNL4-3) is highly efficient. This study provided potential hit compounds for new HIV drug research.

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.

Background: Second-line antiretroviral therapy (ART) was introduced in Henan Province in 2009. The number of people living with human immunodeficiency virus (HIV) starting this therapy is increasing. Objective: This study aimed to investigate the survival and factors affecting mortality among this group. Methods: We conducted a retrospective cohort study of people living with HIV (PLHIV) who switched to second-line ART between May 1, 2010, and May 1, 2016, using the Kaplan-Meier method and Cox proportional hazards models. Results: We followed 3,331 PLHIV for 26,988 person-years, of whom 508 (15.3%) died. The mortality rate was 1.88/100 person-years. After adjusting for confounding factors, we found being a woman (hazard ratio (HR), 0.66; 95% confidence interval (CI) 0.55–0.79), > 50 years old (HR, 2.69; 95% CI, 2.03-3.56), single/widowed (HR, 1.26; 95% CI, 1.04-1.52), having > 6 years of education (HR, 0.78; 95% CI, 0.65-0.94), Chinese medicine (HR, 0.75; 95% CI, 0.52-0.96), liver injury (HR, 1.58; 95% CI, 1.19-2.10), and CD4+ T cell count <200 cells/μl (HR, 1.94; 95% CI, 1.47-2.55), or 200-350 cells/μl (HR, 1.37; 95% CI, 1.03-1.82) were associated with mortality risk. Conclusions: We found lower mortality among PLHIV who switched to second-line ART than most previous studies. The limitations of a retrospective cohort may, therefore, have biased the data, and prospective studies are needed to confirm the results. Moreover, Chinese medicine combined with second-line ART shows potential as a treatment for HIV.

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.

Introduction: Mpox virus is an orthopoxvirus that causes the zoonotic infectious disease known as mpox. The disease can also spread from humans to humans. It can be transmitted through contact with bodily fluids, lesions on the skin, or internal mucosal surfaces. Method: The number of mpox cases increased during the COVID-19 pandemic. Early diagnosis and prompt management of mpox are critical in people living with HIV (PLHIV). In this study, a cross-sectional survey was conducted among PLHIV followed at the outpatient clinic between 20 April–20 August 2023. A questionnaire was used to assess the knowledge and anxiety levels of patients as well as their opinions about vaccination against mpox. The severity of symptoms in the past two weeks was assessed using the Generalised Anxiety Disorder 7-item scale. A total of 203 PLHIV were interviewed for this survey study. Result: The mean age was 39.37±11.93. The majority of them were male (86.7%), and 41.4% were men who have sex with men (MSM). Only 21 of the surveyed participants (10.4%) had a “good knowledge” score about mpox. The mean knowledge score on human Mpox was 2.05 (min:0-max:8), and 107 (52.7%) had a score of 0. Conclusion: The future study should focus on continuous education, promoting awareness through programs and establishing measures to successfully overcome identified variables that contribute to mpox pandemic understanding and attitudes. Applying the lessons learned from the COVID-19 pandemic will help the management of mpox virus.

Background: The assessment of health-related quality of life among people living with HIV (PLWH) has gained increasing importance as it assesses their overall well-being, guides treatment decisions, and addresses psychosocial challenges, improving their quality of life. This study focuses on adapting and validating the Turkish version of the WHOQOL-HIV Bref, a tool developed by the World Health Organization (WHO) to measure health-related quality of life in PLWH. This adaptation is based on the generic WHOQOL-Bref Turkish and WHOQOL-HIV Bref inventory. Methods: In line with WHO guidelines, the tool was translated and tested on 189 PLWH from İstanbul şişli Hamidiye Etfal Training and Research Hospital's HIV outpatient clinic. A variety of statistical methods were employed to assess content, construct, concurrent, and known-group validity, as well as internal consistency and reliability. Results: Participants' median age was 35 years (IQR: 14), with 178(94%) being male. The Turkish WHOQOL-HIV Bref showed overall satisfactory psychometric properties. Despite limitations in the spirituality domain, it demonstrated good internal consistency (alpha coefficient: 0.93) and strong validity across several metrics, including test-retest reliability (ICC: 0.79). Conclusion: The WHOQOL-HIV BREF in Turkish is a reliable and valid instrument for assessing the quality of life in Turkish PLWH.

Background: In the post-epidemic era, Acquired Immune Deficiency Syndrome (AIDS) remains one of the most prevalent and detrimental infectious diseases worldwide. The incidence of osteonecrosis of the femoral head (ONFH) in AIDS patients is 100 times higher than that in healthy individuals. Although Total Hip Arthroplasty (THA) is ultimately necessary for most patients, there is still a dearth of evidence regarding its safety and efficacy in Chinese AIDS patients. Methods: The clinical data of 49 patients who met the inclusion and exclusion criteria were retrospectively analyzed. Simultaneously, we categorized patients whose hemoglobin and albumin met a specific threshold as the optimized group and performed group comparisons. Results: There are statistical differences in Harris score and VAS score pre- and post-operation, with a low overall complication rate. Notably, no disparities were observed between the optimized group and the partial optimized group in terms of overall conditions, laboratory examination indicators, severity of ONFH, surgical outcomes, surgical complications, pain perception or functional limitations. Furthermore, no correlation was found between CD4+ T lymphocytes and hemoglobin levels, albumin levels, white blood cell count, or platelet count. Conclusion: THA is safe and effective in Chinese AIDS patients with ONFH. However, optimal treatment has limited efficacy in AIDS patients undergoing THA for ONFH. The reconsideration and evaluation of the predictive value of CD4+ T lymphocytes for postoperative complications in joint replacement procedures is warranted.