Current HIV Research - Volume 21, Issue 5, 2023

Introduction: A "Shock and Kill" strategy has been proposed to eradicate the HIV latent viral reservoir. Effective Latency Reversal Agents (LRA) are a key requirement for this strategy. The search for LRAs with a novel mechanism of action is ongoing. This is the first study to propose aptamers for the reactivation of HIV.Objective: The purpose of this study was to identify an aptamer that potentially reactivates HIV via the NF-Κβ pathway, specifically by binding to IkB and releasing NF-Κβ.Methods: Aptamer selection was performed at Aptus Biotech (www.aptusbiotech.es), using ikB human recombinant protein with His tag bound to Ni-NTA agarose resin using the SELEX procedure. Activation of NF-Κβ was measured by SEAP Assay. HIV reactivation was measured in JLat cells using a BD FACS-Canto™ II flow cytometer. All flow cytometry data were analyzed using Kaluza analyzing software.Results: Clones that had equivalent or greater activation than the positive control in the SEAP assay were regarded as potential reactivators of the NF-Κβ pathway and were sequenced. The three ikb clones namely R6-1F, R6-2F, and R6-3F were found to potentially activate the NF-Κβ pathway. Toxicity was determined by exposing lymphocytes to serial dilutions of the aptamers; the highest concentration of the aptamers that did not decrease viability by > 20% was used for the reactivation experiments. The three novel aptamers R6-1F, R6-2F, and R6-3F resulted in 4,07%, 6,72% and 3,42% HIV reactivation, respectively, while the untreated control showed minimal (<0.18%) fluorescence detection.Conclusion: This study demonstrated the reactivation of latent HIV by aptamers that act via the NF-Κβ pathway. Although the effect was modest and unlikely to be of clinical benefit, future studies are warranted to explore ways of enhancing reactivation.

Background: The persistence of HIV mutations and the existence of multidrug resistance have produced an opportunity for an array of innovative anti-HIV medicines with a variety of structures that target HIV key enzymes.Objective: The goal of this work was to find a new class of anti-HIV drugs founded on HIV integrase inhibitor pharmacophores.Methods: A novel class of 2-hydroxy acetophenone analogs featuring substituted benzamide or N-phenylthiourea groups was designed and synthesized based on the general pharmacophore of HIV-1 integrase inhibitors (INs).Results: Most of the synthesized analogs were found to be moderately active against the virus, with EC50 values ranging from 40 to 140 μM. Additionally, it was found that most of the compounds presented no considerable cytotoxicity (CC50 > 500 μΜ). The most potent compounds substituting with 4-fluorobenzamide (compound 7) and 4-methylbenzamide (compound 9) rings inhibited the HIV-1 replication by EC50 values of 40 and 45 μΜ, respectively. Docking studies using the crystallographic data available for PFV IN indicated that the Mg2+ coordination might be the possible mechanism of the anti-viral activity.Conclusion: Our findings proved that the synthesized analogs may suggest a very good basis for the development of new anti-HIV-1 agents.

Background: Acquired immune deficiency syndrome (AIDS) is a serious worldwide public health problem and has become the focus of prevention and control in China, while the student population is the key population for AIDS prevention.Objective: The purpose of this study was to investigate the effects of cognitive behavioral therapy (CBT) on college students' AIDS-related cognitions, attitudes, and behaviors, and to find programmatic strategies for AIDS prevention in terms of changing college students' cognitions and behaviors.Methods: In a cluster randomized controlled trial, 233 undergraduate students were assigned to the CBT group (CBT-based intervention, n=92), the TAU group (treatment as usual, n=72), and the CON group (no intervention, n=59). AIDS-related knowledge, attitudes, and behaviors of participants were assessed at pre-intervention, post-intervention, and follow-up.Results: After one month of the study, AIDS-related knowledge, attitudes, and behaviors improved in both the TAU and CBT groups, while there were no significant changes in the CON group. The intervention effect was more significant and sustainable in the CBT group compared to the TAU group.Conclusions: The application of CBT in AIDS prevention among college students is feasible, acceptable, and effective. CBT can increase the level of knowledge about AIDS, improve AIDS-related attitudes, and increase willingness to use condoms. CBT is expected to replace traditional health education as an innovative tool for AIDS prevention because of its long-lasting and efficacious nature.

Introduction: Comorbidities are increasing in people living with HIV (PLHIV), and different treatment options have advantages and disadvantages. It is important to compare information from real-life treated cases. The aim of this study was to retrospectively evaluate the data on efficacy and clinical and laboratory findings during different antiretroviral therapies.Methods: Retrospective file data of 47 PLHIV using Dolutegravir and Lamivudine (3TC/DTG), Tenofovir Alafenamide Emtricitabine and Elvitegravir Cobicistat (EVG/c/TAF/FTC) and Tenofovir Disoproxil Fumarate and Emtricitabine and Efavirenz (EFV/FTC/TDF) were analyzed. Data of the patients at baseline and 12 months after antiretroviral therapy (ART) were compared.Results: About 47 PLHIV were included in the study. Of the patients, 22 (46.8%) were in the 3TC/DTG group, 19 (40.4%) in the EVG/c/TAF/FTC, and 6 (12.8%) in the EFV/FTC/TDF group. After 12 months of treatment, BMI, HIV-RNA, CD4, WBC, hemoglobin, MCV, PDW, RDW, platelet count, creatinine, eGFR, HDL, AST, glucose values of the 3TC/DTG group were significantly different (p<0.05). After 12 months of treatment, BMI, HIV-RNA, CD4 count, MCV, creatinine, eGFR, HDL, LDL, TG, TC, AST, and HOMA-IR values of the EVG/c/TAF/FTC treatment group were significantly different (p<0.05). After 12 months of treatment, HIV RNA, total bilirubin, and LDL values in the EFV/FTC/TDF treatment group were statistically different (p<0.05).Conclusion: All treatment groups showed a decrease in HIV-RNA and an increase in CD4 at the end of one year. While CD4 elevation is lower in EFV recipients than in integrase inhibitor (INSTI) recipients, weight gain is higher in INSTI recipients. While the lipid profile was more positively affected in the 3TC/DTG group, lipid profiles were more negatively affected in the EVG/c/TAF/FTC group, although liver and kidney functions were preserved.

Background: Retroviruses are described as a risk factor for chronic neuropathy. However, it is still unknown if they can work as amyotrophic lateral sclerosis triggers. Over the years, some cases of this association have been described with heterogenous disclosures.Case Representation: This study aimed to report a case of HIV and ALS-like neuropathy and briefly discuss peculiarities of clinical aspects, such as physiopathology and treatment options. The patient underwent neurological examination associated with blood tests, electromyography, analysis of cerebrospinal fluid, and imaging studies.Discussion: A non-systematic review was performed in major databases regarding the topic. The case presented mixed upper and lower motor neuron signs and was framed as a probable case of ALS following the present criteria.Conclusion: After a short follow-up and viral load cleansing, neurological stabilization was achieved.