Search Results (186)

The human immunodeficiency virus (HIV) is a retrovirus discovered in 1983 as the causative agent of acquired immunodeficiency syndrome (AIDS). Following several zoonotic spillover events from non-human primates, the virus spread between humans for more than 60 years under the radar. HIV infects and kills CD4 T cells, the cells that coordinate adaptive immune responses. Primoinfection is associated with a flu-like symptomatology and chronic infection is clinically silent, and mostly not diagnosed, contributing to viral spread and leading to fatal long-term outcomes. HIV genome codes for a poor reading-proof reverse transcriptase, which facilitates high sequence variability, particularly in the envelope glycoprotein complex, the sole external viral protein and main target of humoral immune responses. This antigenic variability precludes the development of an efficacious vaccine despite 40 years of research. In contrast, the development of antiretroviral drugs represents a scientific and medical success which saved the lives of millions of infected people and provides today an excellent protection against AIDS, although it does not permit viral eradication. Indeed, HIV can integrate its genome in target cells and generates a pool of latently infected cells which escape eradication by both the natural immune response and treatments. In summary, the efforts to tackle HIV have been suboptimal, and the virus has infected more than 90 million people and caused 44 million deaths worldwide. In the absence of a vaccine, a better deployment of available preventative and therapeutic tools is needed, particularly in geographical areas and communities with the highest incidence of infection. Full article

Acquired Immunodeficiency Syndrome (AIDS) is caused by Human Immunodeficiency Virus (HIV), and continues to be responsible for a substantial number of deaths worldwide each year. Development of a robust and efficient HIV-1 vaccine remains a critical priority. Structural analysis of viral proteins provides a foundational approach to designing peptide-based immunogenic vaccines. In the current experiment, we used computational prediction approaches alongside molecular docking and molecular dynamics (MD) simulations to identify potential epitopes within gp120 and Nef proteins. The selected co-epitopes were fused with the HBsAg-binding protein (SBP), a 344-amino acid protein previously identified in our laboratory through screening of a human liver cDNA expression library against HBsAg, to facilitate efficient delivery to and uptake by dendritic cells (DCs), thereby enhancing antigen (Ag) presentation. Flexible linkers are used to connect B cells, Helper T Lymphocytes (HTLs), and Cytotoxic T Lymphocytes (CTLs) in a sequential manner. The assembled vaccine construct comprises 757 amino acids, corresponding to a recombinant protein of 83.64 kDa molecular weight. Structural analysis through docking studies, MD simulations, and 3D structure validation revealed that the designed protein exhibits high structural stability and potential for interaction with Toll-like receptors (TLRs). These findings support the vaccine’s ability to enhance cellular and humoral feedback, including the stimulation of T and B cells and induction of antibody (Ab) production. The results underscore the promise of this in silico designed co-epitope vaccine as a viable candidate for HIV-1 prevention and suggest that such constructs may serve as effective immunogens in future HIV-1 vaccine strategies. Full article

Background: Human Immunodeficiency Virus (HIV) is a virus that progressively impairs immune function by depleting CD4 + T-lymphocytes, ultimately leading to acquired immunodeficiency syndrome (AIDS). People living with HIV face a higher risk of developing various bone disorders, such as osteopenia, osteoporosis, and osteonecrosis. The aim of this study was to evaluate the bone mineral density (BMD) status, to determine the prevalence of osteopenia/osteoporosis and to identify the risk factors for low BMD in patients living with HIV undergoing antiretroviral treatment (ART), registered in Craiova Regional Center. Methods: A retrospective study was conducted between June 2024 and January 2025, including HIV-infected subjects aged over 18 years. Results: The study group included 106 patients. Dual-energy X-ray absorptiometry (DEXA) showed that 87 patients had low BMD, 51% having osteopenia and 31.1% having osteoporosis. We found a statistically significant correlation between low BMD and older age, higher levels HIV viremia, CD4 nadir < 200 cells/mm³, prolonged ART exposure and tenofovir disoproxil fumarate containing regimens. Conclusions: These findings support the inclusion of routine bone health monitoring in the standard care of patients with HIV, as well as the need for reevaluation. Full article

Background: With a high human immunodeficiency virus (HIV) adult prevalence, people living with HIV (PLHIV) in Botswana continue to experience a high burden of comorbid HIV and cancer. We sought to investigate the trends of acquired immunodeficiency syndrome (AIDS) defining cancers (ADCs), non-AIDS defining cancers (NADCs), and associated risk factors in PLHIV compared with those without HIV. Methods: We analyzed data from adults aged ≥18 years reported in Botswana National Cancer Registry and National Data Warehouse. The crude, age-standardized incidence rate (ASIR), standardized incidence ratios (SIRs) of cancers and time trends were computed. Risk factors were determined using the Cox-regression model. Results: Over a 30-year period, 27,726 cases of cancer were documented. Of these, 13,737 (49.5%) were PLHIV and 3505 (12.6%) were people without HIV and 10,484 (37.8%) had an unknown HIV status. Compared to the HIV-uninfected, the PLHIV had higher and increasing trends in the cancer incidence overall during the study period (from 44.2 to 1047.6 per 100,000; p-trend < 0.001) versus (from 1.4 to 27.2 per 100,000; p-trend < 0.001). The ASIRs also increased in PLHIV for overall ADCs, NADCs and other sub-types like cervical, lung, breast, and conjunctiva cancers (p-trend < 0.001). Further, PLHIV had elevated SIRs for cervical cancer, Kaposi sarcoma in males and some NADCs. The most common risk factors were HIV infection and female sex for ADCs incidence and advanced age and being HIV-uninfected for NADCs incidence. Conclusions: Increasing trends of ADCs and NADCs during ART expansion were observed among PLHIV compared to those without HIV highlighting a greater need for targeted effective prevention and screening strategies including the provision of access to timely HIV and cancer treatment. Full article

Human immunodeficiency virus (HIV) is responsible for acquired immunodeficiency syndrome (AIDS), a condition characterized by the depletion of CD4+ T lymphocytes, which predisposes individuals to opportunistic infections and, ultimately, death. Although antiretroviral therapy (ART) has substantially improved clinical outcomes, certain limitations persist. Notably, 15–30% of individuals undergoing ART achieve viral suppression but fail to restore adequate CD4+ T cell counts, being defined as immunological non-responders (INR) and remaining at increased risk of disease progression to AIDS. The impaired immune recovery in INRs is attributed to insufficient production and/or excessive destruction of CD4+ T lymphocytes, which can be modulated by autophagy process. This evolutionarily conserved mechanism is fundamental to lymphocyte development and activation as well as to programmed cell death pathways such as apoptosis, necroptosis, ferroptosis, and pyroptosis. These pathways are essential for understanding the impaired immune reconstitution observed in people living with HIV, whose inability to maintain immune homeostasis contributes to accelerated disease progression. This review explores the interplay between autophagy, HIV, and cell death mechanisms, highlighting its relevance in immunological recovery under ART and its potential as a therapeutic target. Full article

HIV-associated neurocognitive disorders (HANDs) refer to a range of cognitive deficits that afflict people living with the Human Immunodeficiency Virus (HIV). The fundamental processes of HAND include persistent inflammation, immunological activation, and direct viral impact on the central nervous system. Emerging research shows that nutritional status, especially food consumption and body weight, is critical in determining the course and severity of HAND. Malnutrition exacerbates neurocognitive impairment by increasing inflammation and oxidative stress, while obesity may contribute to HAND through the promotion of metabolic disruption, gut microbiota alterations, and systemic inflammation. Additionally, the introduction of antiretroviral treatment (ART) has substantially enhanced the prognosis of people living with HIV by lowering viral load and improving immune function. However, depending on the regimen, ART can cause changes in body weight, which may influence the progression of HAND. This emphasizes the intricate interplay between HIV, nutrition, body weight, and neurocognitive health. As a result, various dietary approaches are currently being investigated to improve the quality of life of individuals with HIV and possibly help prevent neurocognitive decline in this population. This review aims to elucidate the relationship between nutrition and neurocognitive function in individuals living with HIV, shedding light on aspects of HANDs related to diet, body weight fluctuations, and metabolic syndrome. It explores the shift from current pharmacological treatments to innovative non-pharmacological interventions, including specific dietary strategies, to support overall health and cognitive well being in HIV-positive people. Full article

Acquired immunodeficiency syndrome (AIDS) is a chronic disease condition caused by the human immunodeficiency virus (HIV). The widespread availability of highly active antiretroviral therapies has helped to control HIV. There are ten FDA-approved protease inhibitors (PIs) that are used as part of antiretroviral therapies in HIV treatment. Importantly, all these drugs are designed and developed against the protease (PR) from HIV subtype B. On the other hand, HIV-1 PR subtype C, which is the most dominant strain in countries including South Africa and India, has shown resistance to PIs due to its genetic diversity and varied mutations. The emergence of resistance is concerning because the virus continues to replicate despite treatment; hence, it is necessary to develop drugs specifically against subtype C. This review focuses on the origin, genetic diversity, and mutations associated with HIV-1 PR subtype C. Furthermore, computational studies performed on HIV-1 PR subtype C and mutations associated with its resistance to PIs are highlighted. Moreover, potential research gaps and future directions in the study of HIV-1 PR subtype C are discussed. Full article

HIV testing is crucial towards the control of the Acquired Immune Deficiency Syndrome (AIDS) epidemic. Monitoring trends of human immunodeficiency virus (HIV) testing over time may help interpret the incidence of new HIV diagnoses and effectiveness of HIV testing strategies. We started a research project aimed at assessing testing rates for HIV infection among Italian outpatients in 2018–2023. Numeric data for screening, confirmatory, and monitoring tests obtained by a national register were compared with the numbers of adult residents, newly diagnosed HIV infections, and patients undergoing treatment. The number of screening tests declined from 1,133,377 in 2018 to 889,972 in 2020 and increased to 1,096,822 in 2023. HIV-RNA tests showed a similar pattern, whereas confirmatory immunoblots did not vary significantly over time. The ratio of screening tests to adult residents was higher in North-West (2.87%) and North-East (2.31%) Italy compared to South Italy and the islands (1.47%), indicating that screening should be enhanced in the latter area. We observed differences between the ratio of screening tests and the incidence of newly diagnosed HIV infections by geographic area. Discrepancies in the number of screening and confirmatory tests needed for each new diagnosis suggest repeated testing on people already diagnosed and possible data reporting issues. The monitoring of HIV screening tests at the national and regional levels can provide essential data to interpret trends in HIV epidemiology and plan relevant testing strategies over time. Full article

Some people with Human Immunodeficiency Virus (HIV) on effective antiretroviral therapy have persistent low lymphocyte CD4 counts and remain at an increased risk of Acquired Immunodeficiency Syndrome (AIDS). We investigated whether primary drug resistance mutations (DRMs) and HIV-1 subtype could be related to immunologic reconstitution in these people. In a multicenter, observational cohort study among treatment-naïve patients, we analyzed HIV-1 subtype, primary drug resistance mutations, CD4 counts, and CD4:CD8 ratios during effective antiretroviral therapy. We compared these variables between patients with different HIV subtypes and between those with or without drug-resistance mutations up to 48 weeks post-baseline. In 156 patients, CD4 count normalization (≥500 cells/µL) was observed in 39% of patients, while CD4:CD8 ratio ≥ 1 in 27% after treatment implementation. HIV-1 subtype B was present in 75% of the patients and subtype A in 22%. Primary resistance mutations were found in 57% of the individuals. The percentage of immunological nonrespondents did not differ significantly between those with different HIV subtypes or between those with or without primary resistance mutations (p > 0.05). In conclusion, there was no significant coincidence between the HIV subtype and primary drug resistance mutations with immunological reconstitution in patients receiving effective antiretroviral therapy. Full article

The Feline Immunodeficiency Virus (FIV) is a lentivirus belonging to Retroviridae family that affects feline immune cells, causing a progressive immunosuppression by depleting CD4+ T-lymphocytes, similarly to the acquired immune deficiency syndrome (AIDS) in humans caused by human immunodeficiency virus (HIV). Diagnosis is usually performed by clinicians using rapid Enzyme-Linked Immunosorbent Assay (ELISA) or lateral flow tests that detect FIV antibodies. The aim of this work was the development of FIVCHECK Ab ELISA, a new rapid indirect assay for the detection of FIV antibodies in feline serum/plasma samples; FIVCHECK Ab ELISA was developed after a meticulous set-up and cut-off analysis through several methods, including the Youden’s index and ROC curve, to achieve the best test performance. The new kit was validated by testing 115 feline sera (38 positives and 77 negatives for FIV antibodies) against the ELISA rapid test SNAP FIV/FeLV Combo (IDEXX). Moreover, 103 sera (28 positives and 75 negatives) were also analyzed with two other rapid indirect ELISAss, INgezim FIV (Gold Standard Diagnostics) and VetLine FIV (NovaTec); FIVCHECK Ab ELISA agreed at 100% with SNAP (100% sensitivity, 95% confidence interval (CI): 88.5–100%; 100% specificity, 95% CI: 94.0–100%), 100% with INgezim FIV and 92.2% with VetLine FIV. Intra- and inter-assay accuracy and precision gave coefficients of variation lower than 10%. The new ELISA is a simple and quick test that provides reliable results for veterinary clinics and practices. Full article

Background: We report a case of an adult patient with newly diagnosed human immunodeficiency virus (HIV) infection, acquired immune deficiency syndrome (AIDS), and acute respiratory distress syndrome (ARDS) secondary to pneumocystis and cytomegalovirus pneumonia that were present on presentation, which were successfully managed with venovenous extracorporeal membrane oxygenation (VV-ECMO). Case Presentation: A 40-year-old patient with a past medical history of asthma was admitted to a local hospital due to dyspnea, cough, and wheezing, where the patient was diagnosed with HIV infection, ARDS, and combined pneumocystis and cytomegalovirus pneumonia. Their pulmonary function quickly declined, necessitating mechanical ventilation (MV). After all conventional therapies failed, the patient was transferred to a tertiary medical center for VV-ECMO therapy. The patient was successfully treated with antiretroviral therapy (ART), antibiotics, antivirals, steroids, and 48 days of VV-ECMO support, with complete resolution of their respiratory symptoms. The patient was discharged on hospital day 82. Conclusions: HIV-positive patients with ARDS that is complicated by opportunistic pulmonary infections can be successfully managed with ART, appropriate anti-infective therapies, and VV-ECMO. Full article

(1) Background: The gut microbiota plays a crucial role in chronic immune activation associated with human immunodeficiency virus (HIV) infection, acquired immune deficiency syndrome (AIDS) pathogenesis, non-AIDS-related comorbidities, and mortality among people living with HIV (PLWH). The effects of antiretroviral therapy on the microbiome remain underexplored. This study aims to map the evidence of the impact of integrase strand transfer inhibitors (INSTI) and non-nucleoside reverse transcriptase inhibitors (NNRTI) on the gut microbiota of PLWH. (2) Methods: A scoping review was conducted using PubMed, Web of Science, and Embase, with reports collected following PRISMA for Scoping Reviews (PRISMA-ScR). (3) Results: Evidence suggests that INSTI-based regimes generally promote the restoration of alpha diversity, bringing it closer to that of seronegative controls, while beta diversity remains largely unchanged. INSTI-based therapies are suggested to be associated with improvements in microbiota composition and a tendency toward reduced inflammatory markers. In contrast, NNRTI-based treatments demonstrate limited recovery of alpha diversity and are linked to an increase in proinflammatory bacteria. (4) Conclusions: Based on the review of the current literature, it is indicated that INSTI-based antiretroviral therapy (ART) therapy facilitates better recovery of the gut microbiome. Full article

Purpose: Cytomegalovirus (CMV) retinitis is a sight-threatening condition predominantly affecting immunocompromised individuals, such as those with Human Immunodeficiency Virus (HIV)/Acquired Immunodeficiency Syndrome (AIDS). We aimed to present an observational case report on CMV retinitis following Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and to review the literature on the molecular and cellular changes in CMV and SARS-CoV-2 infections and how they may influence each other. Case Description: A 32-year-old man with a history of AIDS presented with decreased vision and ocular pain exacerbated by movement, beginning a day prior. Ocular examination revealed anterior uveitis, corneal endothelial edema, and retinal necrosis in the left eye. CMV retinitis was diagnosed based on positive serologic testing and a low cluster of differentiation 4 (CD4) count, with concurrent SARS-CoV-2 infection detected. Treatment included valganciclovir and topical agents, with a focus on managing CMV complications. This case highlights the potential role of SARS-CoV-2 in reactivating dormant CMV in severely immunocompromised individuals. We also discuss the implications of this interaction for immunocompromised patients, emphasizing the need for vigilant monitoring and personalized treatment strategies. Conclusions: Our case suggests that SARS-CoV-2 may trigger reactivation of CMV infection, leading to bilateral involvement in patients with low CD4 lymphocyte counts, which can result in severe visual impairment. The review discusses the molecular and cellular interactions between CMV and SARS-CoV-2, as well as risk factors, pathophysiology, and diagnostic methods for CMV retinitis, providing recommendations based on the literature findings. Full article

Antiretroviral therapy (ART) has significantly extended the lifespan of people living with Human Immunodeficiency Virus (HIV) or Acquired Immunodeficiency Syndrome (AIDS), thereby transforming the disease into a manageable chronic condition. However, this increased longevity has led to a higher incidence of non-AIDS-defining cancers (NADCs) among this population. In this holistic review, we explore the complex interactions between HIV, ART, and cancer development, focusing on how ART influences tumor initiation and progression in people living with HIV/AIDS (PLWHA). Our findings from this reveal several critical aspects of cancer risk in PLWHA. Firstly, while ART restores immune function, it does not fully normalize it. Chronic immune activation and persistent inflammation continue to be prevalent, creating a conducive environment for oncogenesis. Additionally, PLWHA are more susceptible to persistent infections with oncogenic viruses such as human papillomavirus (HPV) and Epstein–Barr virus (EBV), further increasing cancer risk. Some ART drugs have been implicated in genotoxicity and mitochondrial dysfunction, potentially promoting tumorigenesis. ART-induced metabolic changes, including insulin resistance and dyslipidemia, are also associated with heightened cancer risk. Common NADCs in PLWHA include lung cancer, liver cancer, anal cancer, and Hodgkin lymphoma, each with distinct etiologies linked to both HIV-related and ART-related factors. The interplay between HIV infection, chronic inflammation, immune restoration via ART, and the direct effects of ART drugs creates a unique cancer risk profile in PLWHA. Although ART reduces the incidence of AIDS-defining cancers, it does not confer the same protective effect against NADCs. Persistent HIV-related inflammation and immune activation, despite viral suppression, are key factors in cancer development. Additionally, long-term exposure to ART may introduce new oncogenic risks. These insights highlight the need for integrated cancer screening and prevention strategies tailored to PLWHA. Future research is needed to focus on identifying biomarkers for early cancer detection and developing ART regimens with lower oncogenic potential. Healthcare providers should be vigilant in monitoring PLWHA for cancer and adopt comprehensive screening protocols to mitigate the increased cancer risk associated with ART. Full article

Nonhuman primate (NHP) studies that utilize simian immunodeficiency virus (SIV) to model human immunodeficiency virus (HIV-1) infection have proven to be powerful, highly informative research tools. However, there are substantial differences between SIV and HIV-1. Accordingly, there are numerous research questions for which SIV-based models are not well suited, including studies of certain aspects of basic HIV-1 biology, and pre-clinical evaluations of many proposed HIV-1 treatment, prevention, and vaccination strategies. To overcome these limitations of NHP models of HIV-1 infection, several groups have pursued the derivation of a minimally modified HIV-1 (mmHIV-1) capable of establishing pathogenic infection in macaques that authentically recapitulates key features of HIV-1 in humans. These efforts have focused on three complementary objectives: (1) engineering HIV-1 to circumvent species-specific cellular restriction factors that otherwise potently inhibit HIV-1 in macaques, (2) introduction of a C chemokine receptor type 5 (CCR5)-tropic envelope, ideally that can efficiently engage macaque CD4, and (3) correction of gene expression defects inadvertently introduced during viral genome manipulations. While some progress has been made toward development of mmHIV-1 variants for use in each of the three macaque species (pigtail, cynomolgus, and rhesus), model development progress has been most promising in pigtail macaques (PTMs), which do not express an HIV-1-restricting tripartite motif-containing protein 5 α (TRIM5α). In our work, we have derived a CCR5-tropic mmHIV-1 clone designated stHIV-A19 that comprises 94% HIV-1 genome sequence and replicates to high acute-phase titers in PTMs. In animals treated with a cell-depleting CD8α antibody at the time of infection, stHIV-A19 maintains chronically elevated plasma viral loads with progressive CD4+ T-cell loss and the development of acquired immune-deficiency syndrome (AIDS)-defining clinical endpoints. However, in the absence of CD8α+ cell depletion, no mmHIV-1 model has yet displayed high levels of chronic viremia or AIDS-like pathogenesis. Here, we review mmHIV-1 development approaches, the phenotypes, features, limitations, and potential utility of currently available mmHIV-1s, and propose future directions to further advance these models. Full article