Treatment Of Acquired Immunodeficiency Syndrome Research Articles

Design of Novel HIV-1 Protease Inhibitors with Favorable Oral Properties using a Molecular Modelling Approach

Acquired immunodeficiency syndrome (AIDS) is a chronic and potentially fatal transmissible disease caused by the Human Immunodeficiency Virus (HIV). Since its discovery in 1981, an estimated 85 million cases and 40 million AIDS related deaths have occurred worldwide. Among the two types of HIV, HIV-1 accounts for over 90% of reported cases. Throughout the years, multiple drugs have been approved for the treatment of AIDS. However, these drugs face many drawbacks such as toxic side effects, non-optimal pharmacodynamic profile and drug resistance due to virus mutation. This study aims to design novel potent HIV-1 protease inhibitors that overcome these drawbacks through molecular modelling methods. Pubchem database was screened for potential lead compounds. Results were filtered through two phases of ADMET and docking studies. Finally, the chosen lead compound was optimized through fragment replacement to obtain the novel inhibitors.

A Systematic Review of Gene Editing Therapy for Acquired Immunodeficiency Syndrome

Acquired immunodeficiency syndrome (AIDS) is a deadly immunological disease that affects the immune system and becomes more common in recent years, which is brought on by the inflection of human immunodeficiency (HIV). The treatment of AIDS has always been a major challenge for the medical community to overcome because the existing treatment methods are not universal. At present, the scientific community is focusing on gene editing therapy, and the feasible tools are zinc finger nucleases (ZFNs), transcription activator-like nucleases (TALENs), and clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9). Since gene editing technology has advanced so quickly, gene editing therapy is now thought to be one of the most promising AIDS treatment. Though these systems are powerful and efficient, there are still several serious challenges that scientists should face. The clinical safety issues have always existed and been controversial, especially after He Jiankui’s case that editing AIDS-resistance human embryos coming to the light. And the legal regulations were strongly criticized due to gaps in the bottom line of scientific research. This review summarizes existing applications of gene editing in AIDS with the safety and ethical issues of clinical application, searching for the relevant solutions to the current challenges.

B-266 Analytical Performance Comparison of Two Genotyping Assays for HIV-1 Drug Resistance Using Sanger Sequencing

Abstract Background The first case of Acquired Immunodeficiency Syndrome (AIDS) was registered in the United States in early 1980. Two years later, was identified the Human Immunodeficiency Virus (HIV-1), which causes AIDS. Compared to other diseases, the treatment of AIDS achieved an important advance in just over 30 years, in which several drugs were used and replaced. However, resistance to antiretrovirals (ARVs) remains a problem in clinical practice. There are about 20 approved HIV-1 treatment drugs belonging to four different classes: Protease Inhibitors (PI), Nucleoside Reverse Transcriptase Inhibitors (NRTI), Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI), and Integrase Strand Transfer Inhibitor (INSTI). ARVs resistance is caused by mutations in molecular targets of these drugs: protease, reverse transcriptase, and integrase enzymes. Virus genotyping that includes these regions is extremely important to identify the resistance mutations to ARVs therapies, being able to direct treatments. Thus, this study aimed to evaluate the analytical performance of the Applied Biosystems HIV-1 Genotyping Kit with Integrase compared to in-house Sanger genotyping method. Methods Viral RNA isolation from 20 individuals was performed by QIAamp Viral RNA Kit (Qiagen), according to the manufacturer’s instructions. HIV-1 genotyping was performed using both methods: in-house Sanger genotyping and Applied Biosystems HIV-1 Genotyping Kit with Integrase (Thermo Fisher), according to the manufacturer’s instructions. All results were submitted to SeqScape software to evaluate sequencing metrics. The consensus sequence was generated for each sample and analyzed at the online Stanford HIVdb Program (version 9.4) for drug resistance evaluation. Results The 54 mutations analyzed were distributed among the targets: PI (27.8%; 15/54), NRTI (24.1%; 13/54), NNRTI (22.2%; 12/54), and INSTI (25.9%; 14/54). The in-house method evaluated the susceptibility to PI drugs (ATV, DRV, FPV, IDV, LPV, NFV, SQV, and TPV), NRTI (ABC, AZT, D4T, DDI, FTC, 3TC, and TDF), and NNRTI (DOR, EFV, ETR, NVP, and RPV). In addition to protease and reverse transcriptase targets, the commercial kit also evaluated INSTI (BIC, CAB, DTG, EVG, and RAL) drugs. Four of 20 individuals evaluated had viral loads below 1000 copies/mL and have no results in both methods, as expected due to the detection limit of both assays. Furthermore, due to sequencing limitations using the in-house methodology, three samples were not included in the analysis as it didn't show any results. It was observed 92.3% agreement (n = 12/13) in the analyzed samples. A sensitivity of 100% and precision of 99% were found in the commercial kit using the in-house kit as a reference. The evaluation of the intra-assay (repeatability) and inter-assay (reproducibility) indicated 100% of agreement. Conclusions The Applied Biosystems HIV-1 Genotyping Kit with Integrase showed satisfactory performance in the detection of the main antiretroviral resistance mutations.

Multi-Clinical Factors Combined with an Artificial Intelligence Algorithm Diagnosis Model for HIV-Infected People with Bloodstream Infection.

Although highly active antiretroviral therapy (HA-ART) can effectively suppress the disease process in patients with acquired immunodeficiency syndrome (AIDS), opportunistic infections, mainly bloodstream infections (BSI), are still the main cause of death in people living with HIV. There is no effective diagnostic strategy for HIV-infected people with BSI. This study aimed to develop an AI diagnostic model with high sensitivity to improve the early detection of HIV-infected people with BSI. This study retrospectively analyzed the 40 clinical factors of 498 HIV-infected people (171 with BSI positive and 327 with BSI negative) who admitted to Wenzhou Central Hospital from September 2014 to July 2021. This study used the hospital information management system to collect the clinical characteristics, laboratory and imaging examination results, and clinical diagnosis of the two groups. The diagnostic results of all patients were in line with the diagnostic criteria of the Chinese Guidelines for the Diagnosis and Treatment of AIDS (2021 Edition), and the BSI diagnosis was in line with the diagnostic criteria of sepsis and bacteremia in Practical Internal Medicine (13th Edition). On this basis, various risk prediction models were established by combining 8 artificial intelligence (AI) algorithms in the training set and validating the diagnosis performance in the testing set. The model with the best diagnostic performance was selected as the final diagnostic model. The clinical characteristics of HIV-infected people with BSI are atypical, and the pathogens in this area are mainly fungi. Ten risk factors were selected: low level of hemoglobin, CD4+T cell and platelets, high level of lactate dehydrogenase and blood urea nitrogen, splenomegaly, without ART treatment, strip shadow, nodular shadow, and shock. The combination of the ten risk factors, age, gender and the "svmRadial" model can identify the HIV-infected people with BSI from the HIV-infected people without BSI with an area under the curve of 0.916 and a sensitivity and specificity of 0.824 and 0.855, respectively. The model showed excellent performance in diagnosing HIV-infected people with BSI. Internal and external validation showed that the diagnosis model had high clinical application value.

The Use of Zidovudine Pharmacophore in Multi-Target-Directed Ligands for AIDS Therapy

The concept of polypharmacology embraces multiple drugs combined in a therapeutic regimen (drug combination or cocktail), fixed dose combinations (FDCs), and a single drug that binds to different targets (multi-target drug). A polypharmacology approach is widely applied in the treatment of acquired immunodeficiency syndrome (AIDS), providing life-saving therapies for millions of people living with HIV. Despite the success in viral load suppression and patient survival of combined antiretroviral therapy (cART), the development of new drugs has become imperative, owing to the emergence of resistant strains and poor adherence to cART. 3'-azido-2',3'-dideoxythymidine, also known as azidothymidine or zidovudine (AZT), is a widely applied starting scaffold in the search for new compounds, due to its good antiretroviral activity. Through the medicinal chemistry tool of molecular hybridization, AZT has been included in the structure of several compounds allowing for the development of multi-target-directed ligands (MTDLs) as antiretrovirals. This review aims to systematically explore and critically discuss AZT-based compounds as potential MTDLs for the treatment of AIDS. The review findings allowed us to conclude that: (i) AZT hybrids are still worth exploring, as they may provide highly active compounds targeting different steps of the HIV-1 replication cycle; (ii) AZT is a good starting point for the preparation of co-drugs with enhanced cell permeability.

Study on the Mechanism of Improving HIV/AIDS Immune Function with Jian Aikang Concentrated Pill Based on Network Pharmacology Combined with Experimental Validation.

PurposeThis study was the first to screen the active compounds of Jian Aikang Concentrated Pill (JAKCP) with network pharmacology, predict its potential targets, screen the signaling pathways, and combine with cellular experimental validation to explore the potential mechanism of JAKCP for the treatment of acquired immunodeficiency syndrome (AIDS).MethodsThe main compounds and targets of Chinese herbs in JAKCP were identified by TCMSP; the targets of AIDS were collected from Genecards, Online Mendelian Inheritance in Man (OMIM), Disgenet, Therapeutic Target Database (TTD) and Drugbank; the network of “Chinese herbs-active compounds-targets” for JAKCP was constructed by Cytoscape, and protein–protein interaction (PPI) network was constructed using STRING to generate the intersection targets, Metascape was conducted to analyze the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), and the network of “main active compounds-core targets-pathways” was constructed by Cytoscape. Finally, the effect of JAKCP on the survival rate of HIV pseudovirus-infected MT-4 cells was investigated by CCK-8 assay, and the predicted targets were verified by ELISA, qPCR and Western blot.ResultsA total of 147 active compounds of JAKCP were screened covering 351 targets and 416 AIDS disease targets were obtained, besides 140 intersection targets and 321 KEGG pathways were collected. Ultimately, quercetin, kaempferol, stigmasterol, beta-sitosterol, epigallocatechin gallate were identified as the important compounds, the core targets are HSP90AA1, IL-10, IL-6, TNF, IL-1β, TP53, and IL-1ɑ, and the biological pathways and processes mainly include T cell activation, regulation of DNA-binding transcription factor activity and apoptotic signaling pathway. Experiments on the targets of “T cell activation” demonstrated that JAKCP promotes the survival of HIV pseudovirus-infected MT-4 cells. Also, JAKCP down-regulated mRNA and protein levels of IL-1ɑ, IL-1β, and IL-6 while up-regulated mRNA and protein levels of IL-2, IL-6ST, and IL-10 in vitro.ConclusionJAKCP exerted regulatory immune functions through multi-component, multi-target and multi-pathway, thereby providing novel ideas and clues for the treatment of AIDS.

Recent Advances in Computer-aided Antiviral Drug Design Targeting HIV-1 Integrase and Reverse Transcriptase Associated Ribonuclease H

Acquired immunodeficiency syndrome (AIDS) has been a chronic, life-threatening disease for a long time. Though, a broad range of antiretroviral drug regimens is applicable for the successful suppression of virus replication in human immunodeficiency virus type 1 (HIV-1) infected people. The mutation-induced drug resistance problems during the treatment of AIDS forced people to continuously look for new antiviral agents. HIV-1 integrase (IN) and reverse transcriptase associated ribonuclease (RT-RNase H), two pivotal enzymes in HIV-1 replication progress, have gained popularity as druggable targets for designing novel HIV-1 antiviral drugs. During the development of HIV-1 IN and/or RT-RNase H inhibitors, computer-aided drug design (CADD), including homology modeling, pharmacophore, docking, molecular dynamics (MD) simulation and binding free energy calculation, represent a significant tool to accelerate the discovery of new drug candidates and reduce costs in antiviral drug development. In this review, we summarized the recent advances in the design of single- and dual-target inhibitors against HIV-1 IN or/and RT-RNase H as well as the prediction of mutation-induced drug resistance based on computational methods. We highlighted the results of the reported literatures and proposed some perspectives on the design of novel and more effective antiviral drugs in the future.

POSB118 Cost-Effectiveness of Elvitegravir, Cobicistat, Emtricitabine and Tenofovir Alafenamide Fumarate Tablets in Acquired Immunodeficiency Syndrome from the Chinese Payer Perspective

In China, long-term use of conventional drugs treating acquired immunodeficiency syndrome (AIDS) is associated with toxicity, adverse effects (AEs), and poor compliance. On January 1, 2020, elvitegravir, cobicistat/emtricitabine/tenofovir alafenamide fumarate tablets (E/C/F/TAF) were included in the Chinese National Medical Insurance list. E/C/F/TAF is a fixed-dose-combination tablet for once-daily administration. This study assessed the cost-effectiveness of E/C/F/TAF vs other combination regimens for the treatment of AIDS from the Chinese payer perspective.

Chinese guidelines for diagnosis and treatment of HIV/AIDS (2021 edition)

Acquired immunodeficiency syndrome(AIDS) is an important public health problem in China. In 2005, the first edition of the guidelines for the diagnosis and treatment of AIDS was formulated by the AIDS Professional Group of Society of Infectious Diseases of Chinese Medical Association, which was updated in 2011, 2015, and 2018, respectively. The 2021 edition of the guidelines was revised on the basis of the 2018 edition and updated according to national clinical practice and the latest research results. The new research progress in opportunistic infections, antiretroviral therapy, post-exposure prophylaxis (PEP), pre-exposure prophylaxis (PrEP), whole course management of human immunodeficiency virus(HIV) infection, and prevention of mother to child transmission was updated in this guidelines. In the 2021 edition, the indications, medication regimen, follow-up and monitoring, and precautions of PrEP were introduced in detail.

Voltammetric Methods Used in the Determination of Nucleoside Reverse Transcriptase Inhibitors

Background: The Human Immunodeficiency Virus (HIV) has now been established as the causative agent of the Acquired Immunodeficiency Syndrome (AIDS) and exactly 25 antiretroviral drugs have been formally approved for clinical use in the treatment of AIDS. The life quality and duration of HIV-positive patients have increased with the usage of antiretroviral drugs in the treatment of AIDS. Nucleoside Reverse Transcriptase Inhibitors (NRTIs) are one of the subgroups of antiretroviral. Objective: The quantification of drugs is important, as they make positive contributions to dose adjustments in practice. Voltammetric methods are very powerful analytical methods used in the pharmaceutical industry because of the determination of therapeutic agents and/or their metabolites in clinical samples at extremely low concentrations (10-50 ng/ml). Methods: This review mainly includes the pharmacological properties and recent determination studies by voltammetric methods from pharmaceutical dosage forms and biological samples of eight NRTIs group antiretroviral drugs (zidovudine, abacavir, adefovir, entecavir, zalcitabine, didanosine, emtricitabine, lamivudine) that are used in the clinic and show electroactive properties, were performed. Conclusion: Due to the variety of working electrodes in voltammetric methods, it is possible to choose the electrode that best responds. In this way, the analysis of NRTIs was possible at lower concentrations in pharmaceuticals and biological samples with voltammetric methods in these studies without the necessity for the sample pre-treatment or time-consuming extraction steps. The voltammetric methods provide good stability, repeatability, reproducibility and high recovery for the analysis of the analyte. They could be used for the pharmacokinetic studies as well as for quality control laboratory studies.

Treating older patients with AIDS using Traditional Chinese Medicine Combined with Conventional Western Medicine in China.

Acquired immunodeficiency syndrome (AIDS) is a chronic and incurable disease. People with human immunodeficiency virus (HIV) require lifelong care. Traditional Chinese Medicine (TCM) has played an important role in AIDS treatment since the year 2004. TCM offers many advantages including a rich resource of Chinese herbs, lower cost and fewer side effects. In addition to the widespread use of antiviral therapy, TCM offers unique humanistic care and holistic adjustment of the body system. To date, more and more patients are benefiting from TCM not only in China. In this article, we describe the feasibility of treating AIDS with TCM.

Comparative evaluation of the applicability of fixed-dose combined drugs in HIV therapy

The principal global pandemic is Acquired Immunodeficiency Syndrome (AIDS), the early diagnosis and the premature treatment is the main current strategies in combating the development and spread of the disease. Antiretroviral therapy is effective and safe, what is sought nowadays is compliance and convenience for the patient. Different countries adopt different combinations of antiretroviral drugs when using the fixed-dose combination (FDC). The study design was a meta-analysis with clinical trials, patients experienced and naïve of treatment. The Pubmed, Scopus, Embase, Web of Science and Cochrane databases were searched for studies reporting AIDS treatment. The primary outcome was viral load and another outcome is adverse events. The results of the main analysis included 5224 patients. Since there was significant heterogeneity between studies, random effects were selected, and they showed an event rate of 0.67 (95%CI from 0.57 to 0.77). The exploratory analysis showed the general drug effects are not consistently significant along time, and treatments of longer times are more efficient. Specifically, the random analyses of 6 months and 1 year did not show significant drug effects on viral load, while a significant effect of 71% (95% CI from 0.61 to 0.80) in a very heterogeneous analyses (I2>96%). First, d4T-3TC-NVP showed a mean rate of only 21% efficacy and the second, EFV-TDF-FTC did not reach statistical significance (p=0.07). This meta-analysis shows that fixed-dose combination therapy is tolerability, safety and effective, occurred viral load suppression between patients on FDC.

Prolonged Release of Anti-Retroviral Efavirenz From System Using ZIF-8 as Carrier.

Acquired Immunodeficiency Syndrome (AIDS) is a major public health problem in the world. One of the highly effective drugs in anti-HIV therapy is efavirenz (EFZ), which is classified as Class II according to the Classification System of Biopharmaceuticals, presenting low solubility and high permeability, this being an obstacle related to the drug. This study aimed to obtain an innovative system based on EFZ and the Zeolitic Imidazolate Framework (ZIF-8) to use in the development of prolonged-release pharmaceutical forms that can circumvent this problem. The EFZ: ZIF-8 system was obtained by a selected ex-situ method due to its higher incorporation efficiency. Different characterization techniques corroborated the obtainment of the system, and drug release was analyzed by dissolution testing under sink conditions, the profiles being adjusted to some kinetic models. At pH 1.2, the structure of ZIF-8 breaks down rapidly, releasing a large amount of drug within either 3h or short time. In the pH 4.5 and 6.8 medium, the EFZ release from the EFZ: ZIF-8 system obtained in ethanol was prolonged, releasing 95% of the drug in 24h at pH 4.5 and 75% medium at pH 6.8. It is evident that a promising pH-sensitive system was obtained using ZIF-8 as a novel carrier of EFZ intended for the alternative treatment of AIDS.

Docking Study on Anti-HIV-1 Activity of Secondary Metabolites from Zingiberaceae Plants.

ABSTRACTIntroduction:Human immunodeficiency virus type-1 (HIV-1) that causes acquired immunodeficiency syndrome (AIDS) has become a worldwide health problem today. There are approximately 30 anti-HIV-1 drugs that have been used in the treatment of AIDS. However, effective anti HIV-1 agents with less side affect and high inhibition potency are still in demand.Objective:The objective of this study was to identify the potential compounds from Zingiberaceae plants that might be active as anti-HIV-1 by molecular docking.Materials and Methods:Molecular docking simulation was performed by using AutoDock 4.2 on Linux operation system. Docking protocol was validated by using root mean square deviation (RMSD) value using redocking and cross-docking methods. The reported metabolites from Zingiberaceae plants were docked on HIV-1 protease, integrase, and reverse transcriptase protein enzymes.Results:The docking result showed that the genera of Zingiber, Etlingera, Alpinia, Hedychium, and Boesenbergia have potential metabolites that inhibit HIV protease, integrase, and reverse transcriptase enzymes by possessing lower docking energy than native ligand of amprenavir, raltegravir, and nevirapine. Among the metabolites, noralpindenoside B and alpindenoside A from Alpinia densespicata inhibited protease enzymes with the lowest docking energy of -18.02 and -17.90 kcal/mol, respectively. Meanwhile, panduratin E from Boesenbergia pandurata Roxb. and 5α,8α-epidioxyergosta-6,22-dien-3β-ol from Etlingera elatior showed the lowest docking energy on integrase protein with docking energy of -11.97 and -11.41 kcal/mol, respectively. Pahangensin A from Alpinia pahangensis Ridley showed the lowest docking energy on reverse transcriptase enzyme with docking energy of -13.76 kcal/mol.Conclusion:The docking molecular study has identified the possible potential compounds from Zingiberaceae plants that might be used for anti-HIV-1 treatment. So, this study suggested further isolation and purification of the predicted compounds.

Novel Thiazolidin-4-ones as Potential Non-nucleoside Inhibitors of HIV-1 Reverse Transcriptase.

Background: HIV is the causative agent of Acquired Immunodeficiency Syndrome (AIDS), an infectious disease with increasing incidence worldwide. Non-nucleoside reverse transcriptase inhibitors (NNRTIs) play an important role in the treatment of AIDS. Although, many compounds are already being used as anti-HIV drugs, research for the development of new inhibitors continues as the virus develops resistant strains. Methods: The best features of available NNRTIs were taken into account for the design of novel inhibitors. PASS (Prediction of activity spectra for substances) prediction program and molecular docking studies for the selection of designed compounds were used for the synthesis. Compounds were synthesized using conventional and microwave irradiation methods and HIV RT inhibitory action was evaluated by colorimetric photometric immunoassay. Results: The evaluation of HIV-1 RT inhibitory activity revealed that seven compounds have significantly lower ΙC50 values than nevirapine (0.3 μΜ). It was observed that the activity of compounds depends not only on the nature of substituent and it position in benzothiazole ring but also on the nature and position of substituents in benzene ring. Conclusion: Twenty four of the tested compounds exhibited inhibitory action lower than 4 μΜ. Seven of them showed better activity than nevirapine, while three of the compounds exhibited IC50 values lower than 5 nM. Two compounds 9 and 10 exhibited very good inhibitory activity with IC50 1 nM.

Protease Inhibitors for the Treatment of HIV/AIDS: Recent Advances and Future Challenges.

Acquired Immunodeficiency Syndrome (AIDS) is a chronic disease characterized by multiple life-threatening illnesses caused by a retro-virus, Human Immunodeficiency Virus (HIV). HIV infection slowly destroys the immune system and increases the risk of various other infections and diseases. Although, there is no immediate cure for HIV infection/AIDS, several drugs targeting various cruxes of HIV infection are used to slow down the progress of the disease and to boost the immune system. One of the key therapeutic strategies is Highly Active Antiretroviral Therapy (HAART) or ' AIDS cocktail' in a general sense, which is a customized combination of anti-retroviral drugs designed to combat the HIV infection. Since HAART's inception in 1995, this treatment was found to be effective in improving the life expectancy of HIV patients over two decades. Among various classes of HAART treatment regimen, Protease Inhibitors (PIs) are known to be widely used as a major component and found to be effective in treating HIV infection/AIDS. For the past several years, a variety of protease inhibitors have been reported. This review outlines the drug design strategies of PIs, chemical and pharmacological characteristics of some mechanism-based inhibitors, summarizes the recent developments in small molecule based drug discovery with HIV protease as a drug target. Further discussed are the pharmacology, PI drug resistance on HIV PR, adverse effects of HIV PIs and challenges/impediments in the successful application of HIV PIs as an important class of drugs in HAART regimen for the effective treatment of AIDS.

Research Progress of Glycyrrhizic Acid on Antiviral Activity

Glycyrrhizic acid (GA), a triterpene isolated from the roots and rhizomes of licorice, named Glycyrrhiza glabra, is the principal bioactive ingredient of anti-viral, anti-inflammatory and hepatoprotective effects. GA has been used in the clinical treatment of hepatitis, bronchitis, gastric ulcer, AIDS (acquired immunodeficiency syndrome), certain cancers and skin diseases. It has a direct effect on anti-HBV (hepatitis B virus) via affecting the HBsAg (hepatitis B surface antigen) to extracellular secretion, improving liver dysfunction in patients with chronic hepatitis B, and ultimately improving the immune status of HBV. GA can significantly inhibit the proliferation of HIV, showing an immune activation. The clinical application of GA on the prevention and treatments of various diseases may derive from its numerous pharmacological properties. This review provides the summary of the antiviral effects of GA on research progress and mechanism in recent years.

The 2018 Clinical Guidelines for the Diagnosis and Treatment of HIV/AIDS in HIV-Infected Koreans.

Since the establishment of the Committee for Clinical Guidelines for the Diagnosis and Treatment of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) by the Korean Society for AIDS in 2010, clinical guidelines have been prepared in 2011, 2013, and 2015. As new research findings on the epidemiology, diagnosis, and treatment of AIDS have been published in and outside of Korea along with the development and introduction of new antiretroviral medications, a need has arisen to revise the clinical guidelines by analyzing such new data. The clinical guidelines address the initial evaluation of patients diagnosed with HIV/AIDS, follow-up tests, appropriate timing of medication, appropriate antiretroviral medications, treatment strategies for patients who have concurrent infections with hepatitis B or C virus, and treatment in pregnant women. Through these clinical guidelines, the Korean Society for AIDS and the Committee for Clinical Guidelines for the Diagnosis and Treatment of HIV/AIDS would like to contribute to overcoming AIDS by delivering the latest data and treatment strategies to healthcare professionals who treat AIDS in the clinic.

Permeability and in vivo distribution of poly(Ɛ-caprolactone) nanoparticles loaded with zidovudine

Zidovudine (AZT) is one of first choice drugs for the treatment of acquired immunodeficiency syndrome (AIDS). Despite its efficacy to control virus replication, the extent of adverse effects and the therapeutic regimen are directly related to patients’ non-compliance. In this work, we evaluated the permeability and in vivo distribution of AZT incorporated into poly(Ɛ-caprolactone), PCL, nanoparticles (AZT-NP) aiming to reduce the normally observed side effects and increase the drug bioavailability. AZT-NP were obtained by interfacial deposition of preformed polymer. The mean diameter of the nanoparticles was 283.4 nm ± 17.0 with a polydispersity index of 0.232 ± 0.073. The nanoparticles presented a zeta potential of − 32.4 mV ± 3.3, entrapment rate of 53.11% ± 9.25, and were stable for at least 7 days. The drug and the polymer showed no incompatibility in thermal analysis. The permeability of AZT across Caco-2 cells was 22-fold higher for AZT-NP compared to the drug solution. The nanoparticles were able to release AZT in vivo after oral administration in mice, and the plasma levels of labeled AZT-NP were higher and more constant when compared to free labeled AZT. Thus, AZT-NP demonstrated superior performance compared to the drug solution in vivo and in vitro, showing the potential of this system for the treatment of AIDS.

Evolution of HIV/AIDS response in Brazil: Policy innovations and challenges in the fourth decade of the epidemic.

Brazil was the first low- and middle-income country to provide universal treatment access to people living with the acquired immunodeficiency syndrome (AIDS), becoming a widely acclaimed model for best practice to managing this epidemic. However, we know little about important challenges to the key pillars of Brazil's response. This article discusses how the evolution of the country's health system institutions and international advancements in AIDS treatment and prevention affected the national response. Decentralization of health system resources and policy making brought fresh challenges to the centralized governance of the national AIDS program and to civil society, weakening their coordination and advocacy capacity. Regardless, AIDS treatment and prevention strategies in Brazil remain aligned with the current international protocols, but unfortunately have been restricted in some geographic areas and/or populations.