Human Immunodeficiency Virus Therapy Research Articles

Advanced Therapies for Human Immunodeficiency Virus.

Human Immunodeficiency Virus (HIV) remains a significant global health challenge with approximately 38 million people currently having the virus worldwide. Despite advances in treatment development, the virus persists in the human population and still leads to new infections. The virus has a powerful ability to mutate and hide from the human immune system in reservoirs of the body. Current standard treatment with antiretroviral therapy effectively controls viral replication but requires lifelong adherence and does not eradicate the virus. This review explores the potential of Advanced Therapy Medicinal Products as novel therapeutic approaches to HIV, including cell therapy, immunisation strategies and gene therapy. Cell therapy, particularly chimeric antigen receptor T cell therapy, shows promise in preclinical studies for targeting and eliminating HIV-infected cells. Immunisation therapies, such as broadly neutralising antibodies are being investigated to control viral replication and reduce reservoirs. Despite setbacks in recent trials, vaccines remain a promising avenue for HIV therapy development. Gene therapy using technologies like CRISPR/Cas9 aims to modify cells to resist HIV infection or eliminate infected cells. Challenges such as off-target effects, delivery efficiency and ethical considerations persist in gene therapy for HIV. Future directions require further research to assess the safety and efficacy of emerging therapies in clinical trials. Combined approaches may be necessary to achieve complete elimination of the HIV reservoir. Overall, advanced therapies offer new hope for advancing HIV treatment and moving closer to a cure.

Antiviral potential of spirulina in individuals with human immunodeficiency virus or Hepatis C virus infections: A systematic review and meta-analysis

BackgroundSpirulina, a cyanobacterium or blue-green algae that contains phycocyanin, nutritional supplementation has been evaluated in patients living with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) due to its antiviral properties. This supplementation may be beneficial in low resource settings when awaiting antiretroviral therapy (ART) for HIV. This review aimed to evaluate the effectiveness of Spirulina supplement in antiviral-naïve HIV- and HCV-infected patients by assessing its immunological effect (Cluster of Differentiation 4 or CD-4 T-cell count) and disease progression (viral load). MethodsWe searched PubMed, Cochrane Library, Scopus, and Web of Science from inception through January 23, 2024. Two authors independently performed the study selection, data extraction, and risk of bias assessment. We pooled data by using a random-effects model and evaluated publication bias by a funnel plot. ResultsWe identified 5552 articles, 5509 excluded at the title and abstract stage with 44 studies making it to the full text review. Of these 6 studies met the eligibility for inclusion in the final analysis as follows:4 randomized controlled trials (RCTs) and 2 non-RCTs. The pooled results of the Spirulina intervention found significant improvements in biomarkers of clinical outcomes, viral load (VL) and CD4 T-cell (CD4) counts, in participants of the treatment group compared to controls; the VL had an overall Cohen’s d effect size decrease of -2.49 (-4.80, -0.18) and CD4 had an overall effect size increase of 4.09 (0.75, 7.43). [Cohen’s d benchmark: 0.2 = small effect; 0.5 = medium effect; 0.8 = large effect]. ConclusionsFindings from this systematic review showed a potential beneficial effect of Spirulina supplementation in HIV- and HCV-infected patients by increasing CD4 counts and decreasing viral load. However, further research in larger controlled clinical trials is needed to fully investigate the effect of this nutritional supplement on clinically relevant outcomes, opportunities for intervention, optimal dose, and cost-benefit of Spirulina supplementation.

Efficacy and Toxicity of (Chemo)Radiation Therapy in HIV+ Patients with Squamous Cell Anal Cancer, a Subgroup Analysis of the National Multicenter Cohort FFCD-ANABASE

The influence of human immunodeficiency virus (HIV) infection on clinical outcomes in patients receiving (chemo)radiation therapy (RT) for squamous cell carcinoma of the anus (SCCA) is debated. The objective of this study was to compare efficacy and safety according to HIV status in patients with SCCA treated with C/RT. Between January 2015 and April 2020, 488 patients with a known HIV status (17.6% HIV+) were treated with radiation therapy for SCCA and included in the FFCD-ANABASE multicentric prospective cohort. Clinical outcomes including overall survival (OS), locoregional recurrence-free survival, colostomy-free survival, response rate at 4 to 6 months, cancer-specific survival, relapse-free survival, and severe acute and late toxicity were compared between HIV+ and HIV- patients. The median follow-up was 35.8 months. HIV+ patients were younger (P < .01) and predominantly male (P < .01). Intensity modulated radiation therapy was performed in 80.7% of patients, and 80.9% received concurrent chemotherapy. A higher proportion of HIV+ patients received induction chemotherapy compared with HIV- patients. No statistically significant difference in overall treatment time or severe acute and late toxicities was found between HIV+ and HIV- patients. In univariate analyses, OS (HR = 2.1 [CI 95% 1.2;3.5], P = .007), locoregional recurrence-free survival (HR = 1.7 [1.1;2.7], P = .02), and colostomy-free survival (HR = 1.7 [1.1;2.6], P = .01) were significantly shorter in HIV+ patients than in HIV- patients. Response rate, cancer-specific survival, and relapse-free survival were not significantly different. The recurrence site was significantly different according to HIV status. In the multivariate analysis, prognostic factors for OS were a World Health Organization performance status of ≥1 for the whole population, as well as HIV+ status for the subgroup of women. HIV+ patients treated with chemo-RT for SCCA have poorer clinical outcomes, especially women. No difference was found in toxicity according to HIV status with intensity modulated radiation therapy technique.

Flt3 agonist enhances immunogenicity of arenavirus vector-based simian immunodeficiency virus vaccine in macaques.

Arenaviral vaccine vectors encoding simian immunodeficiency virus (SIV) immunogens are capable of inducing efficacious humoral and cellular immune responses in nonhuman primates. Several studies have evaluated the use of immune modulators to further enhance vaccine-induced T-cell responses. The hematopoietic growth factor Flt3L drives the expansion of various bone marrow progenitor populations, and administration of Flt3L was shown to promote expansion of dendritic cell populations in spleen and blood, which are targets of arenaviral vectors. Therefore, we evaluated the potential of Flt3 signaling to enhance the immunogenicity of arenaviral vaccines encoding SIV immunogens (SIVSME543 Gag, Env, and Pol) in rhesus macaques, with a rhesus-specific engineered Flt3L-Fc fusion protein. In healthy animals, administration of Flt3L-Fc led to a 10- to 100-fold increase in type 1 dendritic cells 7 days after dosing, with no antidrug antibody (ADA) generation after repeated dosing. We observed that administration of Flt3L-Fc fusion protein 7 days before arenaviral vaccine increased the frequency and activation of innate immune cells and enhanced T-cell activation with no treatment-related adverse events. Flt3L-Fc administration induced early innate immune activation, leading to a significant enhancement in magnitude, breadth, and polyfunctionality of vaccine-induced T-cell responses. The Flt3L-Fc enhancement in vaccine immunogenicity was comparable to a combination with αCTLA-4 and supports the use of safe and effective variants of Flt3L to augment therapeutic vaccine-induced T-cell responses.IMPORTANCEInduction of a robust human immunodeficiency virus (HIV)-specific CD4+ and CD8+ T-cell response through therapeutic vaccination is considered essential for HIV cure. Arenaviral vaccine vectors encoding simian immunodeficiency virus (SIV) immunogens have demonstrated strong immunogenicity and efficacy in nonhuman primates. Here, we demonstrate that the immunogenicity of arenaviral vectors encoding SIV immunogens can be enhanced by administration of Flt3L-Fc fusion protein 7 days before vaccination. Flt3L-Fc-mediated increase in dendritic cells led to robust improvements in vaccine-induced T- and B-cell responses compared with vaccine alone, and Flt3L-Fc dosing was not associated with any treatment-related adverse events. Importantly, immune modulation by either Flt3L-Fc or αCTLA-4 led to comparable enhancement in vaccine response. These results indicate that the addition of Flt3L-Fc fusion protein before vaccine administration can significantly enhance vaccine immunogenicity. Thus, safe and effective Flt3L variants could be utilized as part of a combination therapy for HIV cure.

Nucleoside Reverse Transcriptase Inhibitor Exposure Is Associated with Lower Alzheimer's Disease Risk: A Retrospective Cohort Proof-of-Concept Study.

Brain somatic gene recombination (SGR) and the endogenous reverse transcriptases (RTs) that produce it have been implicated in the etiology of Alzheimer's disease (AD), suggesting RT inhibitors as novel prophylactics or therapeutics. This retrospective, proof-of-concept study evaluated the incidence of AD in people with human immunodeficiency virus (HIV) with or without exposure to nucleoside RT inhibitors (NRTIs) using de-identified medical claims data. Eligible participants were aged ≥60 years, without pre-existing AD diagnoses, and pursued medical services in the United States from October 2015 to September 2016. Cohorts 1 (N = 46,218) and 2 (N = 32,923) had HIV. Cohort 1 had prescription claims for at least one NRTI within the exposure period; Cohort 2 did not. Cohort 3 (N = 150,819) had medical claims for the common cold without evidence of HIV or antiretroviral therapy. The cumulative incidence of new AD cases over the ensuing 2.75-year observation period was lowest in patients with NRTI exposure and highest in controls. Age- and sex-adjusted hazard ratios showed a significantly decreased risk for AD in Cohort 1 compared with Cohorts 2 (HR 0.88, p < 0.05) and 3 (HR 0.84, p < 0.05). Sub-grouping identified a decreased AD risk in patients with NRTI exposure but without protease inhibitor (PI) exposure. Prospective clinical trials and the development of next-generation agents targeting brain RTs are warranted.

Validation of spectrophotometric and colorimetric methods for determination of efavirenz in various biological matrices: Application to the development of dissolvable microneedle-based efavirenz complex inclusion for vaginal delivery

One of the antiretroviral treatments (ART) used to treat Human Immunodeficiency Virus (HIV) disease is efavirenz (EFV). EFV itself has bioavailability issues during oral therapy due to its poor solubility. When injected, administration issues arise. Hence, creating medication delivery methods was crucial to creating EFV delivery. HIV therapy benefits from the vaginal medication delivery system's ease of use, higher bioavailability, and quick systemic absorption in the surface folds. In this study, an inclusion complex (IC) was added to the EFV formulation to increase solubility, and dissolving microneedles (DMN) was used for delivery to increase penetration. Here, in support of this formulation creation process, we carried out validation utilizing spectrophotometric and colorimetric techniques. The amount of EFV was determined by validating ethanol and artificial vaginal fluid (AVF) using UV–Vis spectrophotometry. Vaginal tissue and plasma were also validated using colorimetric with the β-naphthol reagent. The International Council for Harmonization (ICH) and US Food and Drug Administration (FDA) requirements were adhered to in verifying the creation of analytical procedures. The outcomes demonstrated a linear correlation value of ≥0.9998. The LLOQ levels were 0.99 g/mL, 0.97 g/mL, 0.66 g/mL, 0.74 g/mL, and 0.74 g/mL in ethanol, AVF, porcine vaginal tissue, rat vaginal tissue, and vaginal plasma, respectively. The developed precision and accuracy were confirmed. The approach was successfully used to determine the amount of EFV in inclusion complex integration and DMN platform. The outcomes demonstrated high IC-EFV incorporation release and penetration profiles, permeation and high drug retention andex vivokinetics in the vagina and enhanced bioavailability fromin vivostudy pharmacokinetic profiles of DMN-IC-EFV.

Transfusion Therapy in HIV: Risk Mitigation and Benefits for Improved Patient Outcomes

Transfusion therapy is a pivotal aspect of healthcare, especially for individuals living with Human Immunodeficiency Virus (HIV). This comprehensive review aims to dissect the intricate landscape of transfusion therapy in HIV patients, emphasizing the delicate balance between risks and benefits to achieve enhanced patient outcomes. With advancements in blood safety measures and antiretroviral therapy (ART), navigating the complexities of transfusion therapy in HIV management becomes paramount for healthcare professionals. The review consolidates current knowledge and emerging trends, encompassing challenges, benefits, risks, and strategies to optimize transfusion therapy for improved patient care. The paper delineates key areas, including blood safety measures such as nucleic acid testing (NAT) and pathogen reduction technologies, emphasizing their role in ensuring safer blood products for transfusion in HIV patients. Furthermore, it explores the impact of HIV on hematological disorders, delving into transfusion-transmitted infections and strategies to mitigate these risks. Additionally, it scrutinizes the therapeutic benefits of transfusion therapy in managing hematologic complications in HIV, while addressing potential risks, including immune reactions and adverse effects. Optimizing transfusion therapy in HIV necessitates personalized approaches, considering the individual patient's HIV status, comorbidities, and specific transfusion needs. The role of ART in reducing transfusion requirements and associated risks is highlighted, alongside emerging trends like novel therapies and alternative transfusion practices. Keywords: Transfusion therapy, HIV, blood safety, antiretroviral therapy, risks, benefits, patient outcomes, transfusion-transmitted infections, personalized treatment, hematology, blood products

THE EFFECT OF HUMAN IMMUNODEFICIENCY VIRUS (HIV) AND ANTIRETROVIRAL THERAPY ON THE RISK OF PRE-ECLAMPSIA : A TEN YEARS SYSTEMATIC REVIEW

Background: Human immunodeficiency virus (HIV) infection affects 25 of the US population, with women being the most likely to receive a diagnosis during their reproductive years. Pregnant HIV-infected women are recommended to start antiretroviral therapy (ART) during pregnancy, regardless of CD4 cell count. Research suggests that HIV infection may reduce the risk of pre-eclampsia (PE). Despite PE being the cause of 42,000 maternal fatalities annually, pregnant women living with HIV are less likely to develop pregnancy hypertensive problems. The aim: This study aims to determine the effect of HIV and antiretroviral therapy on the risk of PE. Methods: This work demonstrated compliance with all standards by means of a comparison with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) 2020 guidelines. Consequently, experts were able to guarantee that the study was as current as feasible. Publications released in the years 2014–2024 were considered for this search strategy. To do this, a variety of internet reference sites were used, including ScienceDirect and PubMed. Review articles, previously published works, and partially completed works were all selected not to be considered. Results: When we searched the PubMed database, we found 33 papers, but when we searched ScienceDirect, we found 92 publications. Title screening produced a total of 14 articles for PubMed and 23 articles for ScienceDirect in the search results. Eight papers from PubMed and ten from ScienceDirect made up the total of the papers we compiled. Four reviews, four duplicates, and one with insufficient results were all excluded. Nine studies that satisfied the requirements were finally included. Conclusion: This systematic review found that maternal HIV infection and not using antiretroviral therapy reduced the risk of PE. However, further investigations with more well-designed studies with larger sample sizes are still needed.

HIV-TB Coinfection: Current Therapeutic Approaches and Drug Interactions.

The co-occurrence of human immunodeficiency virus (HIV) and tuberculosis (TB) infection poses a significant global health challenge. Treatment of HIV and TB co-infection often necessitates combination therapy involving antiretroviral therapy (ART) for HIV and anti-TB medications, which introduces the potential for drug-drug interactions (DDIs). These interactions can significantly impact treatment outcomes, the efficacy of treatment, safety, and overall patient well-being. This review aims to provide a comprehensive analysis of the DDIs between anti-HIV and anti-TB drugs as well as potential adverse effects resulting from the concomitant use of these medications. Furthermore, such findings may be used to develop personalized therapeutic strategies, dose adjustments, or alternative drug choices to minimize the risk of adverse outcomes and ensure the effective management of HIV and TB co-infection.

Bibliometric Insights Into the Evolving Landscape of Antibiotic Resistance Research: Trends, Collaborations, and Key Foci (1965-2023).

Conducted on randomized clinical trials (RCTs) addressing antibiotic resistance in the PubMed database, this bibliometric analysis explores relevant sources, keyword co-occurrence, institutional co-authorship, global collaboration patterns, and evolving research trends. Utilizing an electronic search on January 13, 2024, employing the term "antibiotic resistance," 252,657 results were retrieved, of which 2,962 RCTs were analyzed. The dissemination of RCTs exhibited a variable distribution from 1965 to 2023, with a peak in 2014, noteworthy peaks in 1993-1994 and 2002-2003, contrasting declines in 1990-1991 and 2007-2008, and a consistent decrease post 2018. The University of California emerged as a predominant institution, and the journal "Antimicrobial Agents and Chemotherapy" substantially contributed. The annual growth rate stood at 1.2%, with 97 single-authored documents, an average of 8.76 co-authors per document, and 8.89% international co-authorships. Co-occurrence analysis highlighted prevalent themes, including double-blind clinical trials and significant keywords like human immunodeficiency virus (HIV) infections, Helicobacter infections, metronidazole, and amoxicillin. Trend analysis revealed a chronological shift from penicillin to HIV and Helicobacter drug therapies, culminating in combination antibacterial therapy for multiple bacterial strains. The prevailing trend in antibiotic resistance publications involved single-country endeavors, with the United States leading in collaboration frequency. The findings indicate a need to foster international collaboration, promote interdisciplinary research, support emerging trends, encourage open-access publication, and address declines in research activity, particularly RCTs.

Glycemic Control in Patients Living With HIV Initiated on Integrase Inhibitor-Based Three-Drug Antiretroviral Therapy.

Background: The increased risk of cardio-metabolic disorders associated with people living with human immunodeficiency virus (HIV) is of growing importance. Given the broad adoption of integrase strand-transfer inhibitor (INSTI)-based antiretroviral therapy (ART) as first-line therapy for HIV, additional data are needed regarding the metabolic effects of these regimens. Objective: The purpose of this study is to assess glycemic control in patients started on INSTI-based 3-drug regimens over a 2-year period. Methods: A retrospective study was conducted on patients seen in the Brooklyn Hospital Center. Men and nonpregnant, nonlactating women aged 18 years or older with a diagnosis of HIV who were initiated on or switched to an ART consisting of 2 nucleoside reverse transcriptase inhibitors (NRTIs) plus an INSTI were included in the analysis. The primary endpoint is change in A1C from baseline (pre-INSTI initiation) to 2 years after initiation. Results: Two hundred fifty-one patients were eligible based on specified inclusion and exclusion criteria. Overall, a statistically significant increase in A1C was seen in all patients started on INSTI-based regimen (95% CI, 0.10-0.36; P < 0.001). Primarily patients on both elvitegravir-based and bictegravir-based regimens saw the most significant increase in A1C: 0.16% (95% CI, 0.04-0.27; P = 0.006) and 0.39% (95% CI, 0.02-0.76; P = 0.038), respectively. Conclusion and Relevance: Integrase strand-transfer inhibitor-based 3-drug ART was associated with a small but statistically significant increase in A1C over a 2-year period, requiring additional monitoring by clinicians.

Baseline Haematological Evaluation in Individuals Prior to Initiating Antiretroviral Therapy for HIV

Introduction: Human immunodeficiency virus (HIV) was discovered in 1983, while acquired immunodeficiency syndrome (AIDS) was first detected in 1981. Since then, it continues to be a public health problem. The phenomenon of HIV/AIDS is best viewed as a pandemic affecting almost all countries of the world. The first case of HIV/AIDS in Bangladesh was documented in 1989.This study was conducted to evaluate the baseline haematologicalcharacteristic in individuals prior to initiating antiretroviral therapy for HIV. Methods: This study was a cross sectional analytical study conducted among one hundred and fifty-four HIV positive patients attending at ART center, Bangabandhu Sheikh Mujib Medical University. Patients were included as per inclusion and exclusion criteria. Co-morbid conditions were excluded mostly by self-reporting and clinically relevant investigations. Result:The study revealed that HIV infected patients were predominantly middle-aged and young comprising &gt; 70% of the patients with the mean age of the patients being 35.5 ± 9.5 years (range: 20-60 years). A male preponderance was observed in the study with a male-to-female ratio being 3:1. The majority (92.2%) of patients received first-line ART. The red cell indices like Hct, MCV, MCH, and MCHC were also low at the initiation of therapy but changed to normality after treatment. Conclusion: From the findings of the study, it can be concluded that HIV infected individuals are predominantly male, middle-aged, and young. The most common haematological abnormality is anaemia which is significantly reduced in percentage after a mean treatment period of nine and a half months with ART. Bangladesh J Medicine 2024; 35(1): 26-32

HIV-Associated Lymphoma in an Urban Clinic Population: Epidemiology and Outcomes during the Antiretroviral Therapy Era

Introduction- People living with human immunodeficiency virus (HIV) infection (PLWH) are at increased risk for Hodgkin and non-Hodgkin lymphoma. Incidence of HIV-associated lymphoma fell dramatically after the introduction of combined antiretroviral therapy (cART) in the mid-1990s, and the distribution of lymphoma subtypes shifted away from those associated with severe immunosuppression. This study examines trends in the incidence and outcomes of HIV-associated lymphomas diagnosed and treated at an urban, minority-serving cancer center in the United States since 2000. Methods- A retrospective cohort of patients diagnosed with or treated for HIV-associated lymphoma at University of Maryland Medical Center in Baltimore from 2000-2021 was identified and analyzed. Data from patients diagnosed with lymphoma from 2000-2013 was previously published. Data on patients diagnosed or treated for lymphoma at UMMC from 2014-2021 was abstracted from patients' electronic medical records. Data was summarized using simple descriptive statistics. Categorical variables were compared using Chi-squared tests. Results- The previously published study noted 160 patients with HIV-associated lymphoma during 2000-2013 (P1), of whom 131 had sufficient data for analysis. We identified 51 PLWH diagnosed with or treated for lymphoma at UMMC from 2014-2021 (P2), of whom 50 had sufficient data for analysis. The majority were male (73% during P1, 60% during P2) and African American (80% in P1, 76% in P2). Median age at diagnosis was 45 years in P1 and 42 years in P2. Median CD4 count at diagnosis was 104 cells/ul during P1 and 103 cells/ul (IQ range 35-194.5) during P2. PLWH not diagnosed with HIV prior to their lymphoma diagnosis remained similar (23% P1, 26% P2). The proportion of PLWH on cART at the time of lymphoma diagnosis increased over the course of the study period, from 28/131 (21%) to 30/50 (60%) during P2 (p&amp;lt;0.0001). Median Log 10 viral load (HIV-1 RNA copies/mL) was 4.7 during P1 and 2.7 during P2. Diffuse large B-cell lymphoma (DLBCL) was the most common type of lymphoma throughout the study period, representing 54 of 131 (41%) cases during P1 and 29 of 50 (58%) of cases during P2. Hodgkin lymphoma (HL) was the 2 nd-most common lymphoma, comprising 18% of cases during P1 and 16% during P2 (Table 1). The proportion of patients receiving some lymphoma treatment was 85% during P1 and 96% during P2, including 92% who received chemotherapy and/or monoclonal antibodies. Fourteen patients during P2 died prior to, during, or within eight weeks of completing 1st-line lymphoma treatment, including four deaths due to progressive lymphoma and six deaths due to infection. 54% of evaluable patients during P2 achieved a complete response (CR) to first-line treatment. 12-month overall survival (OS) was 49% during P1 and 61% during P2 (p=0.31). 24-month OS was 41% during P1 and 50% during P2 (p=0.44). Progression free survival (PFS) in P2 was 51% at 12 months and 42% at 24 months. For PLWH with DLBCL during P2, 56% achieved a CR to 1 st-line therapy; PFS was 49% at 12 months and 46% at 24 months. OS for this group was 62% at 12 months and 53% at 24 months. For all patients with DLBCL (with and without HIV) treated at our center from 2015-2019, 77% achieved CR to 1 st-line therapy, PFS was &amp;gt;61% at 24 months, and OS was &amp;gt;69% at 24 months. Three PLWH had perinatal acquisition of HIV and a mean age of 27 years at lymphoma diagnosis. 24-month OS for this group was 33%, compared to 51% for PLWH with other routes of transmission (p=0.78). Conclusions- Patients with HIV-associated lymphoma during P2 were more likely to be on cART and had lower viral loads at time of lymphoma diagnosis than during P1, but had similarly low CD4 counts. Distribution of lymphoma subtypes was similar during the two periods, with DLBCL and HL most common. Outcomes remain poor, especially among those patients with low CD4 counts and detectable viremia at the time of diagnosis. Prolonged duration of HIV viremia or immune suppression, related to early acquisition of infection or intermittent or partial adherence to cART, may increase the risk of adverse lymphoma outcomes. Engaging and retaining patients in HIV care is essential to reducing mortality from HIV-associated lymphoma. HIV therapies that more quickly suppress viremia and promote rapid immune reconstitution might also improve lymphoma outcomes.

The role of TEMRA cell-mediated immune senescence in the development and treatment of HIV disease.

Human Immunodeficiency Virus (HIV) has plagued human society for a long time since its discovery, causing a large number of patients to suffer and costing hundreds of millions of medical services every year. Scientists have found that HIV and antiretroviral therapy accelerate immune aging by inducing mitochondrial dysfunction, and that terminal effector memory T cells (TEMRA cells) are crucial in immune aging. This specific subset of effector memory T cells has terminally differentiated properties and exhibits high cytotoxicity and proinflammatory capacity. We therefore explored and described the interplay between exhaustion features, essential markers, functions, and signaling pathways from previous studies on HIV, antiretroviral therapy, immune senescence, and TEMRA cells. Their remarkable antiviral capacity is then highlighted by elucidating phenotypic changes in TEMRA cells during HIV infection, describing changes in TEMRA cells before, during, and after antiretroviral therapy and other drug treatments. Their critical role in complications and cytomegalovirus (CMV)-HIV superinfection is highlighted. These studies demonstrate that TEMRA cells play a key role in the antiviral response and immune senescence during HIV infection. Finally, we review current therapeutic strategies targeting TEMRA cells that may be clinically beneficial, highlight their potential role in HIV-1 vaccine development, and provide perspectives and predictions for related future applications.

The safety and efficacy of PD-1 inhibitors in patients with advanced cancers and HIV/AIDS in China.

Purpose-Immunotherapy has revolutionizedcancertherapy, becoming the standardofcare for various malignancy treatments. Human immunodeficiency virus (HIV) patients, however, are an underserved group with limited access to clinical trials and cancer therapy. This study was to evaluate the safety and efficacy of programmed cell death 1 (PD - 1) inhibitors in patients with advanced cancer and HIV/acquired immunodeficiency syndrome (AIDS). Methods and Materials-We performed a prospective, open-label, nonrandomized, phase 1 single center study. Patients with advanced cancer and HIV/AIDS received the treatment of PD - 1 inhibitors (camrelizumab, 200 mg, administered intravenously every 3 weeks), along with combination antiretroviral therapy (cART) for HIV. Results-Sixteen participants (12 men and 4 women; median age, 46.5 (29 - 78) years) were enrolled; 1 had non - Hodgkin lymphoma (NHL), and 15 had non - AIDS - defining cancers. Safety was observed over 130 cycles of treatment with camrelizumab. Most treatment-emergent adverse events at least possibly attributed to camrelizumab were grade 1 or 2, including reactive cutaneous capillary endothelial proliferation (RCCEP) (9 participants), hearing loss (1 participant), hypophysitis (1 participant). 3 participants experienced hemorrhage due to poor performance status. HIV was controlled in all participants. Best tumor responses included 3 complete response, 5 partial response, 2 stable disease, and 6 progressive disease. The 2 years progression-free survival (PFS) was 67.0% (95% CI: -0.05, 0.00) and overall survival (OS) was 55.3% (95% CI: -0.05, 0.01) for the 16 patients who had received camrelizumab. Conclusions-This study demonstrates that camrelizumab treatment in patients with advanced cancers and HIV/AIDS was feasible and the clinical outcomes were acceptable.

Human immunodeficiency virus patients with low CD4 counts are more likely to have precancerous polyps identified during index colonoscopy.

Antiretroviral treatment (ART) has improved the life expectancy of patients living with human immunodeficiency virus (HIV). As these patients age, they are at increased risk for developing non-acquired immunodeficiency syndrome defining malignancies (NADMs) such as colon cancers. To determine which factors are associated with the development of precancerous polyps on screening colonoscopy in patients with HIV and to investigate whether HIV disease status, measured by viral load and CD4 count, might influence precancerous polyp development. A retrospective review of records at two urban academic medical centers was performed for HIV patients who had a screening colonoscopy between 2005-2015. Patients with a history of colorectal cancer or polyps, poor bowel preparation, or inflammatory bowel disease were excluded. Demographic data such as sex, age, race, and body mass index (BMI) as well as information regarding the HIV disease status such as CD4 count, viral load, and medication regimen were collected. Well-controlled patients were defined as those that had viral load < 50 copies, and poorly-controlled patients were those with viral load ≥ 50. Patients were also stratified based on their CD4 count, comparing those with a low CD4 count to those with a high CD4 count. Using colonoscopy reports in the medical record, the size, histology, and number of polyps were recorded for each patient. Precancerous polyps included adenomas and proximal serrated polyps. Data was analyzed using Fisher's exact tests and logistic regression through SAS 3.8 software. Two hundred and seven patients met our inclusion criteria. The mean age was 56.13 years, and 58% were males. There were no significant differences in terms of age, race or ethnicity, insurance, and smoking status between patients with CD4 counts above or below 500. BMI was lower in patients with CD4 count < 500 as compared to those with count > 500 (P = 0.0276). In patients with CD4 > 500, 53.85% of patients were female, and 70.87% of patients with CD4 < 500 were male (P = 0.0004). Only 1.92% of patients with CD4 ≥ 500 had precancerous polyps vs 10.68% of patients with CD4 < 500 (P = 0.0102). When controlled for sex, BMI, and ART use, patients with CD4 < 500 were 9.01 times more likely to have precancerous polyps [95% confidence interval (CI): 1.69-47.97; P = 0.0100]. Patients taking non-nucleoside reverse transcriptase inhibitors were also found to be 10.23 times more likely to have precancerous polyps (95%CI: 1.08-97.15; P = 0.0428). There was not a significant difference noted in precancerous polyps between those that had viral loads greater or less than 50 copies. Patients with low CD4 counts were more likely to have precancerous polyps on their screening colonoscopy although the etiology for this association is unclear. We also found an increased risk of precancerous polyps in patients taking non-nucleoside reverse transcriptase inhibitors, which is contradictory to prior literature showing ART has decreased the risk of development of NADMs. However, there have not been studies looking at colorectal cancer and ART by drug class, to our knowledge. Further prospective studies are needed to determine the effect of HIV control and therapies on polyp development.

Proton Pump Inhibitors For HIV+ Patients - A Word Of Caution.

Madam, HIV (human immunodeficiency virus) is on the rise in Pakistan. A Lancet global health modeling study reports that patient registration with the National Aids Control Program (NACP) has risen from 4500 in 2013 to 24331 in 2019 [1]. In HIV+ patients, the gastrointestinal tract is a common site of infection, often leading to anorexia, dysphagia, vomiting, weight loss, and diarrhoea. A study conducted in 2016 showed that 80% of HIV-infected adults had moderate-severe GERD (gastro-oesophageal reflux disorder) symptoms [2]. Physicians often prescribe proton pump inhibitors (PPIs) to treat GERD and stomach or duodenal ulcers. This class of drugs is the most potent inhibitor of gastric acid secretion and is ,unfortunately, prescribed excessively and often inappropriately, regardless of if the patient is HIV+. A recent study shows that 66.2% of patients in a tertiary care hospital in Karachi, Pakistan receive PPIs without proper indication [3]. However, PPIs being prescribed inappropriately pose severe health risks to individuals that are HIV+. A recent study in 2019 raised the valid concern that the use of PPIs in patients already receiving anti-retroviral (ARV) therapy in HIV+ patients could very well be related to an increased risk of acute kidney infection (AKI) [4]. This is not the only research to show the adverse effect of PPI use in HIV patients. A 2017 study shows statistically significant increased innate immune activation due to the translocation of microbial products in HIV+ patients taking PPIs [5]. This can carry serious future implications for these patients post-treatment because higher levels of innate immune activation markers are associated with immunological failure in HIV-treated patients [6]. These statistics raise a very critical question- is it safe for PPIs to be prescribed so freely without any attention to patients being HIV+ or on ARV therapy? It is suggested that existing and future ARV therapies be planned carefully if PPIs are prescribed, and close attention be paid to a patient’s virologic response. In the case of acute hospital admission, where PPIs are prescribed for preventing stress-induced or GI ulcers, medication reconciliation algorithms that acknowledge the interaction between protease inhibitors (PIs) and PPIs should be used [7]. It would be prudent to use PPIs strictly when prescribed and for lesser periods of time.

Revolutionizing pediatric HIV therapy: The latest breakthroughs in drug delivery techniques

Human Immunodeficiency Virus (HIV) is the root cause of acquired immunodeficiency syndrome (AIDS), which destroys the body's immune cells, thereby rendering the body unable to fight any infections. It is a sexually transmitted disease (STD) in adults but in children, it is passed on from an HIV-positive mother in the womb or through the birth canal, or via breastfeeding. According to a report by United Nations International Children's Emergency Fund (UNICEF) 2021, 2.73 million children have been infected with this virus globally. Current statistics for 2022–23 would be updated by July 2023. Many antiretroviral drugs (ARVs) are available in the market for preventing the vertical transmission of HIV which are not 100% effective. The regimen for treating HIV in children is of long duration and requires drug administration multiple times daily which makes it less compliant for the children as well as their parents. As a result, the children are unable to complete the regimen. Multiple new dosage forms such as microarray patches, buccal films, 3D-printed mini tablets, polymeric micelles, and food-based nanoparticles have been developed to overcome these problems. This article aims to discuss the problems with existing therapy and recent advances that have been made in HIV therapy for children along with the various clinical trials that are currently underway.

HIV-Differentiated Metabolite N-Acetyl-L-Alanine Dysregulates Human Natural Killer Cell Responses to Mycobacterium tuberculosis Infection

Mycobacterium tuberculosis (Mtb) has latently infected over two billion people worldwide (LTBI) and caused ~1.6 million deaths in 2021. Human immunodeficiency virus (HIV) co-infection with Mtb will affect the Mtb progression and increase the risk of developing active tuberculosis by 10-20 times compared with HIV- LTBI+ patients. It is crucial to understand how HIV can dysregulate immune responses in LTBI+ individuals. Plasma samples collected from healthy and HIV-infected individuals were investigated using liquid chromatography-mass spectrometry (LC-MS), and the metabolic data were analyzed using the online platform Metabo-Analyst. ELISA, surface and intracellular staining, flow cytometry, and quantitative reverse-transcription PCR (qRT-PCR) were performed using standard procedures to determine the surface markers, cytokines, and other signaling molecule expressions. Seahorse extra-cellular flux assays were used to measure mitochondrial oxidative phosphorylation and glycolysis. Six metabolites were significantly less abundant, and two were significantly higher in abundance in HIV+ individuals compared with healthy donors. One of the HIV-upregulated metabolites, N-acetyl-L-alanine (ALA), inhibits pro-inflammatory cytokine IFN-γ production by the NK cells of LTBI+ individuals. ALA inhibits the glycolysis of LTBI+ individuals' NK cells in response to Mtb. Our findings demonstrate that HIV infection enhances plasma ALA levels to inhibit NK-cell-mediated immune responses to Mtb infection, offering a new understanding of the HIV-Mtb interaction and providing insights into the implication of nutrition intervention and therapy for HIV-Mtb co-infected patients.

Direct and indirect cardiovascular and cardiometabolic sequelae of the combined anti-retroviral therapy on people living with HIV.

With reports of its emergence as far back as the early 1900s, human immunodeficiency virus (HIV) has become one of the deadliest and most difficult viruses to treat in the era of modern medicine. Although not always effective, HIV treatment has evolved and improved substantially over the past few decades. Despite the major advancements in the efficacy of HIV therapy, there are mounting concerns about the physiological, cardiovascular, and neurological sequelae of current treatments. The objective of this review is to (Blattner et al., Cancer Res., 1985, 45(9 Suppl), 4598s-601s) highlight the different forms of antiretroviral therapy, how they work, and any effects that they may have on the cardiovascular health of patients living with HIV, and to (Mann et al., J Infect Dis, 1992, 165(2), 245-50) explore the new, more common therapeutic combinations currently available and their effects on cardiovascular and neurological health. We executed a computer-based literature search using databases such as PubMed to look for relevant, original articles that were published after 1998 to current year. Articles that had relevance, in any capacity, to the field of HIV therapy and its intersection with cardiovascular and neurological health were included. Amongst currently used classes of HIV therapies, protease inhibitors (PIs) and combined anti-retroviral therapy (cART) were found to have an overall negative effect on the cardiovascular system related to increased cardiac apoptosis, reduced repair mechanisms, block hyperplasia/hypertrophy, decreased ATP production in the heart tissue, increased total cholesterol, low-density lipoproteins, triglycerides, and gross endothelial dysfunction. The review of Integrase Strand Transfer Inhibitors (INSTI), Nucleoside Reverse Transcriptase Inhibitors (NRTI), and Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI) revealed mixed results, in which both positive and negative effects on cardiovascular health were observed. In parallel, studies suggest that autonomic dysfunction caused by these drugs is a frequent and significant occurrence that needs to be closely monitored in all HIV + patients. While still a relatively nascent field, more research on the cardiovascular and neurological implications of HIV therapy is crucial to accurately evaluate patient risk.