Current ARTs, Virologic Failure, and Implications for AIDS Management: A Systematic Review.

Antiretroviral therapies (ARTs) have revolutionized the management of human immunodeficiency virus (HIV) infection, significantly improved patient outcomes, and reduced the mortality rate and incidence of acquired immunodeficiency syndrome (AIDS). However, despite the remarkable efficacy of ART, virologic failure remains a challenge in the long-term management of HIV-infected individuals. Virologic failure refers to the persistent detectable viral load in patients receiving ART, indicating an incomplete suppression of HIV replication. It can occur due to various factors, including poor medication adherence, drug resistance, suboptimal drug concentrations, drug interactions, and viral factors such as the emergence of drug-resistant strains. In recent years, extensive efforts have been made to understand and address virologic failure in order to optimize treatment outcomes. Strategies to prevent and manage virologic failure include improving treatment adherence through patient education, counselling, and supportive interventions. In addition, the regular monitoring of viral load and resistance testing enables the early detection of treatment failure and facilitates timely adjustments in ART regimens. Thus, the development of novel antiretroviral agents with improved potency, tolerability, and resistance profiles offers new options for patients experiencing virologic failure. However, new treatment options would also face virologic failure if not managed appropriately. A solution to virologic failure requires a comprehensive approach that combines individualized patient care, robust monitoring, and access to a range of antiretroviral drugs.

Next-Generation Vaccines: Nanovaccines in the Fight against SARS-CoV-2 Virus and beyond SARS-CoV-2.

The virus responsible for the coronavirus viral pandemic is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Emerging SARS-CoV-2 variants caused by distinctive mutations within the viral spike glycoprotein of SARS-CoV-2 are considered the cause for the rapid spread of the disease and make it challenging to treat SARS-CoV-2. The manufacturing of appropriate efficient vaccines and therapeutics is the only option to combat this pandemic. Nanomedicine has enabled the delivery of nucleic acids and protein-based vaccines to antigen-presenting cells to produce protective immunity against the coronavirus. Nucleic acid-based vaccines, particularly mRNA nanotechnology vaccines, are the best prevention option against the SARS-CoV-2 pandemic worldwide, and they are effective against the novel coronavirus and its multiple variants. This review will report on progress made thus far with SARS-CoV-2 vaccines and beyond employing nanotechnology-based nucleic acid vaccine approaches.

Potential of Azadirachta indica as a Capping Agent for Antiviral Nanoparticles against SARS-CoV-2.

A rare type of pneumonia later on referred to as COVID-19 was reported in China in December 2019. Investigations revealed that this disease is caused by a coronavirus previously identified as SARS-CoV-2, and since then, it has become a global pandemic with new strains emerging rapidly as a result of genetic mutations. Various therapeutic options are being explored in order to eradicate this pandemic even though approved vaccine candidates are being currently rolled out globally. Most medicinal plant extracts have astonishing properties, and they can therefore be used in the biosynthesis of effective antiviral nanoparticles. In this systematic review, we aimed to highlight the specific attributes that make Azadirachta indica (neem plant) a suitable candidate for the biosynthesis of anti-SARS-CoV-2 nanoparticles. A systematic investigation was therefore carried out in PubMed, Scopus, Web of Science, and AJOL databases with the keywords "Nanoparticles," "Biosynthesis," "Antivirals," "SARS-CoV-2," and "Azadirachta indica." 1216 articles were retrieved by the 21st of February 2022, but we screened studies that reported data on biomedical and antimicrobial assessment of Azadirachta indica extracts. We also screened studies that were reporting nanoparticles possessing antiviral properties against SARS-C0V-2, narrowing our results to 98 reports. Herein, the SARS-CoV-2 viral structure is briefly discussed with nanoparticles of biomedical importance in the design of SARS-CoV-2 antivirals. Most importantly, we focused on the biomedical and antiviral properties of Azadirachta indica extracts that could be of importance in the design of potential anti-SARS-CoV-2 nanoformulations.

Seroprevalence and characterisation of herpes simplex virus from human immunodeficiency virus in samples collected from two provinces in South Africa: a retrospective study.

Background: Herpes simplex virus (HSV) is a widely distributed human pathogen that is known for its ulcerative lesions at the infection site. HSV can cause persistent infection in the host that is often followed by a period of latency within the neurons. Considering the high rate of HIV infection in South Africa, it is important to assess the seroprevalence of HSV with a focus to determine the epidemiological association between HSV-DNA and HIV-1 in the population. Methods: A total of 44 sera samples were screened for HSV and HIV-1 using the highly sensitive enzyme-linked immunosorbent assay (ELISA). The ELISA positive samples were characterized using polymerase chain reaction (PCR) to confirm the positivity of both viruses and to further differentiate HSV into HSV-1 and -2. Thereafter, the samples were analysed for relatedness using phylogenetic analysis. Results: Of the 44 samples, 36 (81.8%) were positive for HIV-1, while 35 (79.5%) were positive for HSV when screened with ELISA kits. The PCR results, with the use of type specific primers, showed that 4/35 (11.4%) samples were specific for HSV-1 while 30/35 (85.7%) were specific for HSV-2. Statistical analysis performed using the chi-squared goodness-of-fit test showed that there is a significant relationship between HSV-2 and HIV-1 transmission. Conclusions: The prevalence of HSV in the population is high with an increased HSV-2 infection in women. Our study shows that some of the HSV-2 isolates are not related to the clinical isolate SD90e from South Africa, suggesting diversity in HSV-2 viral transmission.

UCLA1 aptamer inhibition of human immunodeficiency virus type 1 subtype C primary isolates in macrophages and selection of resistance.

We have previously shown that the aptamer, UCLA1, is able to inhibit HIV-1 replication in peripheral blood mononuclear cells (PBMCs) by binding to residues in gp120. In this study we examined whether UCLA1 was effective against HIV-1 subtype C isolates in monocyte-derived macrophages (MDMs). Of 4 macrophage-tropic isolates tested, 3 were inhibited by UCLA1 in the low nanomolar range (IC80<29 nM). One isolate that showed reduced susceptibility (<50 nM) to UCLA1 contained mutations in the α5 helix next to the CD4 and co-receptor (CoR) binding complex. To further evaluate aptamer resistance, two primary viruses were subjected to increasing concentrations of UCLA1 over a period of 84 days in PBMCs. One isolate showed a 7-fold increase in IC80 (351 nM) associated with genetic changes, some of which were previously implicated in resistance. This included F223Y in the C2 region and P369L within the CD4 and CoR binding complex. A second isolate showed a 3-fold increase in IC80 (118 nM) but failed to show any genetic changes. Collectively, these data show that UCLA1 can efficiently block HIV-1 infection in MDMs and PBMCs with escape mutations arising in some isolates after prolonged exposure to the aptamer. This supports the further development of the UCLA1 aptamer as a HIV-1 entry inhibitor.