Human Immunodeficiency Virus Type Research Articles

Prevalence of Hepatitis C Virus and Human Pegivirus Type 1 Co-Infection in Patients Infected with Human Immunodeficiency Virus Type-1

Prevalence of Hepatitis C Virus and Human Pegivirus Type 1 Co-Infection in Patients Infected with Human Immunodeficiency Virus Type-1

Evaluation of anti-HIV-1 (Retroviridae: Orthoretrovirinae: Lentivirus: Human immunodeficiency virus type 1) activity of 6HP and 3TC in vitro using MT-4 cell line variants with different replicative activity.

Chemotherapy of HIV infection remains the only means of treating the disease. The process of development new and improving previously developed drugs is therefore considered a priority. One of the preclinical stage of drug efficacy testing is research in the virus-cell model system in vitro. To evaluate the antiviral efficacy of nucleoside reverse transcriptase inhibitors (NRTIs) 6HP and 3TC during HIV-1 replication in the neoplastic MT-4 cell line. Two variants of the CD4+ T-lymphocyte MT-4 cell line (MT-4/1 and MT-4/2) transformed by Human T-lymphotropic virus type 1 (Retroviridae: Orthoretrovirinae: Deltaretrovirus: HTLV-1), with different levels of HIV-1 replication were used. Drugs ammonium-3'-azido-3'-deoxythymidine-5'-carbomoylphosphonat (6HP) and 2',3'-dideoxy-3'-thiacytidine (3TC) were used to suppress the virus. The replication activity of HIV-1 was observed to be higher in the MT-4/2 line than in the MT-4/1 line for different strains of the virus. The use of each of the substances separately showed a more significant inhibition of viral activity in MT-4/1 than in MT-4/2 cells. When used together, the inhibition level was almost the same in all cases and ranged from 87‒96% for the MT-4/1 line and 83‒89% for the MT-4/2 line. High efficacy was observed when using lower concentrations of drugs compared to individual use. The combined use of NRTIs 6НР and 3TС is promising for the treatment of HIV-infected patients at different stages of infection and with different levels of viral load.

The burden of HIV-1 and HIV-2 epidemics in Ivory Coast.

Simian immunodeficiency viruses (SIV) infecting chimpanzees (SIVcpz) and sooty mangabeys (SIVsm) are, respectively, the biological precursors of human immunodeficiency viruses (HIV) Types 1 and 2. Former French colonies in West Africa are the regions where retroviruses first jumped from primates to humans. Ivory Coast is nowadays a country of over 29 million people, being 2% (580,000) persons living with HIV (PLWH). However, one-quarter remains undiagnosed. Heterosexual transmission is by far the most frequent mechanism of HIV acquisition and women exhibit higher rates of infection than men. Despite preventive measures, HIV infection in children throughout breastfeeding remains significant. The proportion of PLWH carrying HIV-1 is rising whereas conversely HIV-2 carriers are steadily declining. A nationwide survey conducted on earlier 2024 showed that a total of 188,880 PLWH were on follow-up. HIV-1 infection was found in 163,947, HIV-2 in 5,114, and coinfection in 3,182. HIV type was not reported for 7,500. Antiretroviral therapy with tenofovir, lamivudine, and dolutegravir is by far the most frequently prescribed regimen in Ivory Coast (n = 168,543). Viral suppression is recognized in 94.3% of treated PLWH, despite one-third acknowledging unwanted treatment interruptions after failure of stock supplies. Given shared transmission routes with HIV, coinfection with other human retroviruses such as Human T-lymphotropic virus type-1 (HTLV-1) and/or hepatitis viruses B, C, and delta are frequent in Ivory Coast. Coinfections remain largely undiagnosed and poorly managed. In summary, the HIV pandemic caused by both HIV-1 and HIV-2 is a major public health challenge in Ivory Coast, where strategies for expanding diagnosis, sustain antiretroviral treatment, and manage coinfections warrant further efforts.

Pathophysiology of Adipose Tissue Macrophages indicating a potential reservoir site for HIV infection that might be troublesome to eradicate HIV-1

Human Immunodeficiency Virus Type 1 (HIV-1) is a condition that affects over 60 million people worldwide. Viral infection can be controlled using highly active antiretroviral therapy (HAART) to suppress HIV-1 replication and hinder disease progression, but viremia quickly rebounds following HAART interruption. It is highly likely that the persistence of virus occurs predominantly in latently infected CD4+ T cells, a new strategy to eradicate HIV-1. Previously it has been shown that the viral reservoir is seeded rapidly following the initial infection of rhesus macaques with SIV, even before the establishment of a systemic infection, so destroying this reservoir may be vital to the effective clearance of HIV. We reasoned that long-lived tissue macrophages contribute significantly to the SIV/HIV reservoir, such as those that may be found in adipose tissue. Mediscope 2024;11(2): 68-72

The Effects of Viral Structural Proteins on Acidic Phospholipids in Host Membranes

Enveloped viruses rely on host membranes for trafficking and assembly. A substantial body of literature published over the years supports the involvement of cellular membrane lipids in the enveloped virus assembly processes. In particular, the knowledge regarding the relationship between viral structural proteins and acidic phospholipids has been steadily increasing in recent years. In this review, we will briefly review the cellular functions of plasma membrane-associated acidic phospholipids and the mechanisms that regulate their local distribution within this membrane. We will then explore the interplay between viruses and the plasma membrane acidic phospholipids in the context of the assembly process for two enveloped viruses, the influenza A virus (IAV) and the human immunodeficiency virus type 1 (HIV-1). Among the proteins encoded by these viruses, three viral structural proteins, IAV hemagglutinin (HA), IAV matrix protein-1 (M1), and HIV-1 Gag protein, are known to interact with acidic phospholipids, phosphatidylserine and/or phosphatidylinositol (4,5)-bisphosphate. These interactions regulate the localization of the viral proteins to and/or within the plasma membrane and likely facilitate the clustering of the proteins. On the other hand, these viral proteins, via their ability to multimerize, can also alter the distribution of the lipids and may induce acidic-lipid-enriched membrane domains. We will discuss the potential significance of these interactions in the virus assembly process and the property of the progeny virions. Finally, we will outline key outstanding questions that need to be answered for a better understanding of the relationships between enveloped virus assembly and acidic phospholipids.

Novel Approaches in HIV-1 Cure: Genetic Editing and Gene Repression Techniques. Topic Review

Introduction: The worldwide challenge presented by human immunodeficiency virus type 1, affecting 39 million individuals, endures despite the highly active antiretroviral therapy. Limitations of it, including insufficiently addressing viral reservoirs leading to prolonged drug toxicity, resistance concerns, and economic burdens, have fueled exploration into alternative approaches. Gene editing and gene repression techniques have emerged as potential solutions. Objective: Conduct a comprehensive analysis of recent research following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, focusing on genetic modification and gene repression in HIV-1-infected samples. Methods: A meticulous search identified 413 articles, of which 76 met strict criteria. Inclusion criteria involved studies on gene editing and HIV-1 expression (2019–2023), emphasizing CCR5 repression. Exclusions targeted weak evidence, lacking practical efficacy, and non-relevance to HIV-1 or genetic tools. Duplicates and non-open-access articles were also excluded. Results: The identified strategies show promise in their ability to mitigate the chronicity of the infection. However, challenges such as off-target effects, ethical considerations surrounding in vivo, ex vivo, and germline editing, and variable efficacy across studies are evident. The imperative for continued evaluation, refinement of techniques, and the development of effective administration methods is underscored. Conclusions: This topic review provides a nuanced exploration of recent advancements in gene editing and gene repression techniques for managing HIV-1. While the findings suggest promising avenues, the identified challenges necessitate ongoing research and innovation in order to harness the full potential of these strategies in the quest for an effective HIV-1 solution.

A cGAS-mediated type I interferon response in human CD4+ T cells depends on productive infection and is conserved over HIV types and strains.

Human immunodeficiency virus (HIV) type 2 is known to be less pathogenic than HIV-1, possibly due to more effective immune control mechanisms. The mechanism of innate sensing of HIV-2 by T cells is at present unclear. In this study, we show that several primary isolates of HIV-2 (CBL20 and CI85) and HIV-1 (A8 and D2), similar to the molecular clone HIV-1 NL4.3-GFP-I, induce a significant type I interferon response in its main target, activated CD4+ T cells. However, they are unable to do so after shRNA-mediated knock-down of cGAS. In addition, both HIV-1- and HIV-2-induced type I interferon response in CD4+ T cells was dependent on productive infection and integration, as the presence of RT or integrase inhibitor dramatically suppressed the sensing. Our findings collectively showed that the cGAS-dependent type I interferon response of CD4+ T cells to HIV infection is conserved over HIV types and critically depends on productive infection.IMPORTANCEBy unveiling the role of cGAS in sensing Human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) across CD4+ T cells and highlighting its broader relevance that might be mirrored in other cell types, our research provides insights into the uniform mechanism of innate immune activation by different HIV isolates. By demonstrating the necessity of productive infection, we highlight the robust and specific nature of the observed cGAS-mediated innate response, dispelling concerns about contaminating plasmids triggering an immune response. Our preliminary data suggest that the lower pathogenicity of HIV-2 may not be directly correlated to superior innate immune control mediated by cGAS.

In Vivo Dynamics of HIV-1 Infection With Impaired Antibody Immunity and Three General Infection Mechanisms

In this paper we investigate two generalized human immunodeficiency virus type-1 (HIV-1) dynamics models with impaired antibody immunity. The models include both latently and actively infected cells. Three infection mechanisms are incorporated into the models, viral infection mechanism (VIM), latent cellular infection mechanism (CIM) and active CIM. The three infection rates are provided by generic nonlinear functions. The second model includes three types of distributed time delays. We find that our models are biologically feasible. The global stability analysis of equilibria are performed and found the basic reproduction ratio (R0) as a threshold parameter. Using Lyapunov method we show that, the virus-free equilibrium is globally asymptotically stable when R0≤1 and the virus-persistence equilibrium is globally asymptotically stable when R0>1. Sensitivity analysis on R0 is studied. To support our theoretical results we provide some numerical simulations. We have demonstrated that R0 is influenced by all three of the infection types, and that if one of them were ignored, R0 would be underestimated. This might lead to inadequate medication effectiveness that aims to remove HIV-1 from the body. The effects of time delay and impaired antibody immunity on HIV-1 progression are examined. According to our research, lowered immunity is a significant factor in the infection's growth. Furthermore, time delays might drastically reduce R0, which would prevent HIV-1 from replicating. The information provided by our research in this work can improve our comprehension of HIV-1 dynamics within-host and provide guidance for the creation of novel pharmacological treatments.

Current State of Therapeutics for HTLV-1

Human T cell leukaemia virus type-1 (HTLV-1) is an oncogenic retrovirus that causes lifelong infection in ~5–10 million individuals globally. It is endemic to certain First Nations populations of Northern and Central Australia, Japan, South and Central America, Africa, and the Caribbean region. HTLV-1 preferentially infects CD4+ T cells and remains in a state of reduced transcription, often being asymptomatic in the beginning of infection, with symptoms developing later in life. HTLV-1 infection is implicated in the development of adult T cell leukaemia/lymphoma (ATL) and HTLV-1-associated myelopathies (HAM), amongst other immune-related disorders. With no preventive or curative interventions, infected individuals have limited treatment options, most of which manage symptoms. The clinical burden and lack of treatment options directs the need for alternative treatment strategies for HTLV-1 infection. Recent advances have been made in the development of RNA-based antiviral therapeutics for Human Immunodeficiency Virus Type-1 (HIV-1), an analogous retrovirus that shares modes of transmission with HTLV-1. This review highlights past and ongoing efforts in the development of HTLV-1 therapeutics and vaccines, with a focus on the potential for gene therapy as a new treatment modality in light of its successes in HIV-1, as well as animal models that may help the advancement of novel antiviral and anticancer interventions.

Regulatory T cells modulate monocyte functions in immunocompetent antiretroviral therapy naive HIV-1 infected people

We previously demonstrated that the overall number of regulatory T (Treg) cells decrease proportionately with helper CD4+ T cells and their frequencies increase in antiretroviral therapy (ART)-naive human immunodeficiency virus type-1 (HIV-1) infected individuals. The question now is whether the discrepancies in Treg cell numbers and frequencies are synonymous to an impairment of their functions. To address this, we purified Treg cells and assessed their ability to modulate autologous monocytes functions. We observed that Treg cells were able to down modulate autologous monocytes activation as well as interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-α) production during stimulation with polyinosinic-polycytidylic acid stabilized with poly-L-lysine and carboxymethylcellulose (poly-ICLC). This activity of Treg cells has been shown to be influenced by immunocompetence including but not limited to helper CD4+ T cell counts, in individuals with HIV-1 infection. Compared to immunosuppressed participants (CD4 < 500 cells/µL), immunocompetent participants (CD4 ≥ 500 cells/µL) showed significantly higher levels of transforming growth factor beta (TGF-β) and IL-10 (p < 0.001 and p < 0.05, respectively), key cytokines used by Treg cells to exert their immunosuppressive functions. Our findings suggest the contribution of both TGF-β and IL-10 in the suppressive activity of Treg cells.

Comparison of At-Home Versus In-Clinic Receipt of Long-Acting Injectable Cabotegravir/Rilpivirine.

The need for frequent travel to a clinic could impair access to injectable antiretroviral therapy for persons living with human immunodeficiency virus type 1 (HIV-1) infection. We hypothesized that allowing persons receiving treatment with long-acting injectable cabotegravir plus rilpivirine (LA CAB/RPV) to receive and store the medication in their own refrigerator prior to in-home administration by a healthcare provider would be as safe and effective as receiving treatment in a clinic. Persons prescribed LA CAB/RPV in the Infectious Diseases clinic at the Medical University of South Carolina were offered enrollment in this non-randomized, observational study between August 2021 and December 2022. After in-clinic receipt of the initial LA CAB/RPV injection, participants chose to receive each subsequent injection over the following 12-months either in clinic or at home. The 33 enrolled participants were primarily Black (64%), male (73%), and had a median age of 46. Three participants stopped LA CAB/RPV and transitioned to oral antiretroviral therapy due to allergy (n = 1), loss of virologic suppression (n = 1), and visit adherence (n = 1) concerns. A comparable number of participants received treatment primarily in clinic (n = 18) relative to at home (n = 15). Injection site pain/soreness was common (52% of injections) but did not differ between groups. There were no differences in safety or efficacy between groups and both groups reported high treatment satisfaction. All participants were virologically suppressed and retained in care at the end of the study. At-home administration of LA CAB/RPV by a healthcare provider was comparably safe, effective, and associated with high participant satisfaction relative to in-clinic administration.

Study of the protective efficacy of CombiMab-2 against human immunodeficiency virus type 1 in mice humanised with CD4&lt;sup&gt;+&lt;/sup&gt; T-lymphocytes

INTRODUCTION. Despite existing treatment methods, complete eradication of human immunodeficiency virus (HIV) infection remains an unattainable goal due to the high variability of HIV type 1 (HIV-1). HIV infection necessitates life-long administration of antiretroviral medicinal products, which cause serious adverse drug reactions. The development of gene therapy products based on adeno-associated virus (AAV) vectors encoding broadly neutralising antibodies represents a promising direction for creating long-term therapies capable of countering a wide range of viral variants.AIM. This study aimed to evaluate the protective efficacy of CombiMab-2, a medicinal product consisting of a combination of three AAV vectors (AAV9-VRC07-523, AAV9-10-1074, and AAV9-PGDM1400) encoding broadly neutralising antibodies against HIV-1, in a humanised mouse model.MATERIALS AND METHODS. The study used an HIV infection model based on immunodeficient B-NDG mice humanised with human CD4+ lymphocytes (1.5×107 cells per animal) from a leukoconcentrate of a healthy donor. The experiment used two groups of mice, including a control group (3 animals) receiving saline solution and an experimental group (5 animals) receiving CombiMab-2. The medicinal product was administered into different muscles as three separate components six weeks prior to infection. The CCR5-tropic HIV-1 strain was obtained by transfecting HEK293FT cells with the pNL4-3(AD8) plasmid encoding the full-length virus. The authors monitored viral loads in the plasma of animals by reverse transcription polymerase chain reaction and CD4+ lymphocyte counts in the peripheral blood of animals by flow cytometry for four weeks after infection.RESULTS. Six weeks after CombiMab-2 administration, the levels of broadly neutralising antibodies in the serum of humanised mice ranged from 0.17 μg/mL to 4.0 μg/mL. In the control group, the viral load reached 105 copies/mL one week after HIV-1 infection and continued to rise over the next three weeks. In the treatment group, infection developed only in one mouse, which had the lowest antibody titre before infection. No viral load was detected in the remaining mice of the treatment group, which indicated that the medicinal product was effective if serum concentrations of broadly neutralising antibodies reached 0.5 μg/mL or higher.CONCLUSIONS. The tested medicinal product based on three AAV vectors (AAV9-VRC07-523, AAV9-10-1074, and AAV9-PGDM1400) exhibits protective activity against HIV-1 in humanised mice. The presented data allow the authors to consider CombiMab-2 as a promising antiviral agent that can serve as a basis for further pharmaceutical development.

Host cell glycosylation selects for infection with CCR5- versus CXCR4-tropic HIV-1.

Human immunodeficiency virus type 1 (HIV-1) infection involves a selection bottleneck that leads to transmission of one or a few variants. C-C motif chemokine receptor 5 (CCR5) or C-X-C motif chemokine receptor 4 (CXCR4) can act as coreceptors for HIV-1 viral entry. However, initial infection mostly occurs via CCR5, despite abundant expression of CXCR4 on target cells. The host factors that influence HIV-1 susceptibility and selection during transmission are unclear. Here we conduct CRISPR-Cas9 screens and identify SLC35A2 (a transporter of UDP-galactose expressed in target cells in blood and mucosa) as a potent and specific CXCR4-tropic restriction factor in primary target CD4+ T cells. SLC35A2 inactivation, which resulted in truncated glycans, not only increased CXCR4-tropic infection levels but also decreased those of CCR5-tropic strains consistently. Single-cycle infections demonstrated that the effect is cell-intrinsic. These data support a role for a host protein that influences glycan structure in regulating HIV-1 infection. Host cell glycosylation may, therefore, affect HIV-1 selection during transmission in vivo.

HIV-1 assembly - when virology meets biophysics.

Cells naturally produce vesicles that bud from different lipid membranes using dedicated molecular machineries. Enveloped RNA viruses, including human immunodeficiency virus type 1 (HIV-1), also generate particles that bud from host cell membranes by hijacking cellular factors and signaling pathways similar to those involved in the budding of extracellular vesicles. HIV-1 buds from the host cell plasma membrane mainly via the self-assembly of Gag, a structural protein. Gag is a polyprotein that forms assembly complexes containing viral genomic RNA (gRNA), host cell lipids and proteins. HIV-1 Gag binds and segregates host cell plasma membrane lipids while self-assembling simultaneously on the gRNA and the plasma membrane. This self-assembly causes membrane bending and formation of a new viral particle with the help of host cell proteins, likely including cortical actin-associated factors. However, it is unclear whether the energy of Gag self-assembly is sufficient to generate new HIV-1 particles. In this Review, we discuss these processes in the light of the past and recent virology literature, incorporating lessons from studies on the quantitative biophysics of viral self-assembly, and explore how Gag might reorganize the plasma membrane and divert host cell membrane curving proteins and cortical actin-related factors to achieve particle assembly and budding.

Epicardial fat and liver stiffness by ARFI elastography in people living with Human Immunodeficiency Virus type 1 (HIV-1) infection without liver disease.

To evaluate the association between increased epicardial fat thickness (EFT) and liver stiffness measurement (LSM), as assessed by elastography in people living with Human Immunodeficiency Virus type 1 (HIV-1) infection (PWH). 91 PWH on effective antiretroviral treatment (ART) were enrolled. EFT was measured by transthoracic echocardiography. Liver steatosis was evaluated by ultrasound Hamaguchi criteria and LSM by elastography with Acoustic Radiation Force Impulse (ARFI) Tecnique. LSM ≥8 Kpa was suggestive of clinically relevant fibrosis. Mean age was 54.3 years and 27.5% were women. EFT correlated with HIV-1 infection duration (rS 0.252, p = 0.016), age at study entry (rS 0.527, p < 0.001), BMI (rS 0.363, p < 0.001), waist circumference (rS 0.549, p < 0.001), HDL (rS -0.391, p < 0.001), triglycerides (rS 0.375, p < 0.001), Hamaguchi score (rS 0.279, p = 0.007), right lobe of the liver (rS 0.259, p = 0.014), Left ventricular mass/Body surface area (rS 0.220, p = 0.036).A LSM ≥8 Kpa was found in 20.9% of PWH, more commonly in those with EFT above the median >5.6 mm (30.4% vs 11.1%, p = 0.038). LSM significantly correlated with EFT (rS 0.274, p = 0.009), CD4+ cells (rS -0.320, p = 0.003) and nadir of CD4+ cells (rS -0.292, p = 0.007).In a subgroup (n = 53), an HOMA-IR index >2.33 identified increased EFT, (AUC 0.73, 95%CI 0.59-0.84, p = 0.001) while an HOMA-IR >3.27 predicted increased LSM (AUC 0.76, 95%CI 0.62-0.87, p = 0.005). PWH with increased EFT have worse metabolic profile and a high proportion of clinically relevant fibrosis at ARFI elastography, despite normal liver function tests. The HOMA-IR index might be used to identify PWH with increased EFT and liver fibrosis.

The Assembly of HTLV-1-How Does It Differ from HIV-1?

Retroviral assembly is a highly coordinated step in the replication cycle. The process is initiated when the newly synthesized Gag and Gag-Pol polyproteins are directed to the inner leaflet of the plasma membrane (PM), where they facilitate the budding and release of immature viral particles. Extensive research over the years has provided crucial insights into the molecular determinants of this assembly step. It is established that Gag targeting and binding to the PM is mediated by interactions of the matrix (MA) domain and acidic phospholipids such as phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2). This binding event, along with binding to viral RNA, initiates oligomerization of Gag on the PM, a process mediated by the capsid (CA) domain. Much of the previous studies have focused on human immunodeficiency virus type 1 (HIV-1). Although the general steps of retroviral replication are consistent across different retroviruses, comparative studies revealed notable differences in the structure and function of viral components. In this review, we present recent findings on the assembly mechanisms of Human T-cell leukemia virus type 1 and highlight key differences from HIV-1, focusing particularly on the molecular determinants of Gag-PM interactions and CA assembly.

The effect of sodium deoxyribonucleate with iron complex on the expression of surface markers of MT-4 cells infected with human immunodeficiency virus type 1 (HIV-1) (Retroviridae: Primate lentivirus group)

The persistence of immune dysfunction during therapy has serious consequences for the health of HIV-infected people. Therefore, an important direction is the search for drugs that can reduce the inflammatory potential of the immune system and serve as an additional component of antiviral therapy. Aim ‒ to study the effect of the immunomodulatory drug Sodium deoxyribonucleate with iron complex (DNA-Na-Fe) on the expression of activation markers in MT-4 cells infected with HIV-1. Expression levels of CD4, CD28, CD38, CD62L and HLA-DR proteins on the plasma membrane were measured in cells. To assess viral activity, the p24 protein was quantified by ELISA. The two cell variants with different replicative activity were analyzed. Control cells, cells with DNA-Na-Fe, infected cells and infected cells with DNA-Na-Fe were tested. Based on the results obtained, it can be concluded that antiviral activity of the drug in MT-4 cells infected with HIV-1 is associated with immunomodulatory activity that enhances the expression of membrane proteins CD4, CD28, CD38 and CD62L. Diversity in the effect of DNA-Na-Fe on the studied surface proteins expression in two cell lines indicates that they depend on the characteristics of the combined molecular biological processes occurring in cells. And the increased effects observed in a system with changes in replicative activity assumes its active participation in virus replication at the stages of virus penetration and budding. Studies have shown that DNA-Na-Fe has antiviral and immunomodulatory activity.

Promising Drug Delivery System for Cervical Cancer – A Future Approach

There is evidence that peptide targeting can be applied in cervical cancer therapy and for diagnosis involving the use of molecular imaging, hence developing peptide probes for this disease. Cervical cancer, which also has a high possibility of being prevented, is among the common tumors affecting women globally. Despite the occurrence being reduced greatly by screening, the illness remains fatal and its claims many lives annually, especially in the developing nations. In exercising such a perspective, specific public health efforts known to encourage physical activity, proper diet, and early detection of cervical cancer must begin to be taken seriously. When combined, doctors, health officers, and lawmakers could speed up the global deployment of such programs. California’s American Cancer Society, the present review enlists a host of pharmaceutical goods available in the market. This perspective of present-day research and manufacturing is devoted to the development of various types of nanocarriers for possible utilization in medication transport. Thus, overall cancer mortality appears to be not substantially different, though cancer incidence rates for both sexes are 50% lower in impoverished countries when compared to affluent nations. At the moment, there are new peptide probes that are developed solely for cervical cancer-perfectly suitable for targeting peptides applicable in therapeutic and diagnostic imaging. M13KE phage dodecapeptide (12-mer) peptide library was screened for recognition of human immunodeficiency virus type 1 (HIV-1) by immunofluorescence and flow cytometry; the S7 clone was identified as most suitable. A disease that affects many women is gynecologic health problems, and cervical cancer is the leading presenting complaint experienced regularly. Among these studies, QSAR, drug-likeness, PCA, dynamic cross-correlation matrix, molecular docking, molecular dynamics and quantum calculation properties can be listed. In the first literature survey, after identifying the potent antibacterial and anticancer activity of the molecule apigenin, some other promising derivatives were identified and more research has been carried out on them, focusing on their synthesized derivatives as inhibitors of DNA polymerase theta and cervical cancer caused by human papillomavirus. The results were streamlined by the use of in-silico molecular docking, which showed that all Apigenin derivatives and the targeted proteins had potential energy-binding relationships. Further validation is essential because this study used in-silico computational methodologies and produced excellent results. Applying in-silico molecular docking made the data more comprehensible, which showed the possible energy bindings of the targeted proteins and all the Apigenin variants. Due to the fact that this work utilized in-silico computational methods and obtained significant results, further validation is required. Hence, the present wet-lab experiments coupled with both in-vitro and in-vivo conditions, additional validation of the results.

Evaluating the Use of Sacran, a Polysaccharide Isolated from Aphanothece sacrum, as a Possible Microbicide for Preventing HIV-1 Infection.

Since combination antiretroviral therapy (cART) was introduced to treat human immunodeficiency virus type-1 (HIV-1)/acquired immunodeficiency syndrome (AIDS), the AIDS mortality rate has markedly decreased, and convalescence in individuals with HIV has improved drastically. However, sexual transmission has made HIV-1 a global epidemic. Sacran is a megamolecular polysaccharide extracted from cyanobacterium Aphanothece sacrum that exhibits numerous desirable characteristics for transdermic applications, such as safety as a biomaterial, a high moisture retention effect, the ability to form a film and hydrogel, and an anti-inflammatory effect. In this study, we evaluated the anti-HIV-1 effects in sacran as a barrier to HIV-1 transmission. Sacran inhibited HIV-1 infection and envelope-dependent cell-to-cell fusion. Moreover, we used a Transwell assay to confirm that sacran inhibited viral diffusion and captured viruses. The synergistic effects of sacran and other anti-HIV infection drugs were also evaluated. HIV-1 infections can be reduced through the synergistic effects of sacran and anti-HIV-1 drugs. Our study suggests using sacran gel to provide protection against HIV-1 transmission.

Virological History Predicts Non-sustained Viral Suppression With Long-Acting Cabotegravir and Rilpivirine Therapy, Independent of Pharmacokinetic Parameters

Abstract Background This study aimed to investigate factors contributing to non-sustained viral suppression, including intermittent viremia and persistent low-level viremia, during cabotegravir (CAB) plus rilpivirine (RPV) long-acting (LA) injectable therapy, with a focus on pharmacokinetics (PK). Methods A prospective cohort study was conducted on people with human immunodeficiency virus (HIV, PWH) transitioning from stable oral antiretroviral therapy (ART) to bimonthly CAB + RPV LA. Standardized follow-up included close monitoring through blood sampling for plasma human immunodeficiency virus type 1 (HIV-1) viral load (VL) and multiple plasma drug concentrations measurements to analyze the connection between PK parameters and virologic outcomes. Results Among 173 patients with a median (interquartile range [IQR]) follow-up of 11.1(7.1–13.2) months and 789 pre-dose measurements, 38.7% experienced VL ≥ 20 copies/mL, and 16.2% had levels ≥50 copies/mL. Intermittent viremia occurred in 34.7% of patients, and persistent low-level viremia in 4%. Virological failure developed in 2 cases. Predictors of non-sustained viral suppression included VL at HIV diagnosis (adjusted hazard ratio [AHR]: 1.49 per log10 VL, 95% confidence interval [CI]: 1.04–2.12, P = .027), detectable viremia on oral ART (AHR: 2.45, 95% CI: 1.29–4.65, P = .006), and the level of viral suppression at transition (AHR: 0.38, 95% CI: .19–.75, P = .004). We found a significant association between low trough concentrations of CAB and RPV and episodes of detectable viremia exceeding 50 copies/mL. However, none of the assessed PK covariates predicted non-sustained viral suppression in multivariable models. Conclusions Non-sustained viral suppression in PWH transitioning from stable oral ART to CAB + RPV LA was linked to preexisting factors before transition. Higher VL pre-ART and incomplete suppression on oral therapy increased the risk, independent of PK parameters.