Search Results (1,310)

Leprosy remains a significant public health issue, particularly due to its neuropathic consequences, which affect sensory, motor, and autonomic functions, leading to severe disabilities. HIV/AIDS, another major public health concern, overlaps geographically with leprosy and is also associated with peripheral neuropathies, complicating the management of co-infected patients. Understanding how Nerve Growth Factor (NGF) is regulated in leprosy and HIV-leprosy co-infection may contribute to immunomodulatory treatments and neuroimmune response control. A cross-sectional study evaluated NGF tissue expression using immunohistochemistry in 47 HIV/leprosy co-infected patients and 61 leprosy-only patients. The co-infected group had a higher incidence of neuritis (40.4%) and a prevalence of exclusively reversal reactions. However, the occurrence of neuritis was not associated with higher expression of NGF in the tissue. Leprosy reactions were more prevalent in non-co-infected patients with multibacillary forms (50%). Multibacillary forms in both groups of patients showed higher cellular expression of NGF, with a greater tendency for higher NGF expression in non-co-infected multibacillary patients (p = 0.0021), suggesting impairment in the immune response involved in the tissue expression of neurotrophins in the co-infected group. Overall, co-infection with HIV did not influence the increase in NGF in the lesions of leprosy patients compared with patients with leprosy alone. 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

Despite advances in the understanding of Kaposi sarcoma (KS), research from resource-limited settings remains limited. This study aimed to estimate the proportion of epidemic visceral KS among Mexican people living with HIV (PLHIV) and to describe their clinical and biochemical characteristics. We included PLHIV with histopathologically confirmed KS who received care at the National Medical Center La Raza between March 2020 and February 2023. We calculated the prevalence of epidemic KS and epidemic visceral KS and analyzed clinical and biochemical variables potentially associated with visceral involvement. The prevalence of epidemic KS was 5.6%. Among these cases, 51.4% had visceral involvement, yielding an overall prevalence of 2.8%. Patients with epidemic visceral KS exhibited significantly higher rates of oral mucosal involvement and lower hemoglobin levels compared with those without visceral disease. These findings highlight the substantial burden of epidemic visceral KS in this population and should be confirmed in future studies with larger cohorts and robust designs aimed at identifying clinical and biochemical predictors of visceral involvement. Full article

The STAT (Signal Transducer and Activator of Transcription) signaling pathway plays a central role in immune regulation by mediating cytokine responses and orchestrating both innate and adaptive immunity. Although CD4+ T cell depletion is the main driver of HIV-1–induced immunodeficiency, the virus also exerts a significant and often underestimated impact by disrupting the function of STAT family members, thereby exacerbating immune imbalance and accelerating disease progression. Specifically, HIV-1 suppresses STAT1 activation, impairing the induction of antiviral genes; inhibits IL-23–driven STAT3 activation in CD4+ Th17 cells with a reduction in IL-17; alters STAT3-dependent functions in antigen-presenting cells; and imposes profound—and at times opposing—dysregulations of STAT5, including the induction of a truncated isoform that contributes to latency. Notably, pharmacological inhibition of the JAK/STAT axis, particularly with JAK2 inhibitors, has been shown to reduce integrated proviral DNA and viral replication in vitro and in early clinical studies. This review provides an updated overview of the roles of individual STAT proteins in HIV-1 infection and pathogenesis, emphasizing the intricate interplay between viral factors and host signaling, highlighting the potential therapeutic implications, and suggesting that immunological assessment in HIV-1 patients should extend beyond CD4+ T cell counts and the CD4/CD8 ratio to include functional analysis of STAT signaling for deeper insights into immune dysfunction and chronic inflammation. Full article

Castleman disease and Kaposi sarcoma (KS) are both associated with infection by human herpesvirus 8 (HHV-8), also known as Kaposi’s sarcoma-associated herpesvirus (KSHV). This virus plays a critical role in the pathogenesis of both conditions, particularly in immunocompromised individuals, such as those with HIV/AIDS. Multicentric Castleman disease (MCD) generally presents with systemic inflammatory symptoms, lymphadenopathy, and organ dysfunction, while Kaposi sarcoma typically appears as vascular tumors on the skin, with occasional involvement of mucous membranes or internal organs. We present four clinical cases, with concurrent KS and MCD, treated with chemotherapy and rituximab, with a satisfactory response. We highlighted the essential role of prompt investigation of systemic or inflammatory manifestations (fever, vital parameter alterations such as palpitation, high breath frequency, edema, and kidney impairment) as underlined in our case series, which might underscore possible complications. Multiorgan failure, opportunistic infections, or rapid clinical deterioration might occur if the diagnosis is not adequately assessed. Therefore, this paper emphasizes the importance of timely diagnosis, as it enables the prompt initiation of appropriate antiviral, immunomodulatory, or oncologic therapies—interventions that can significantly improve outcomes and may be life-saving in advanced or aggressive disease presentations. Full article

Since the first cases of AIDS, reported in 1980, this disease has become chronic over the years, and researchers have been trying to keep it under control. Despite the development and spread of mutate viruses, HIV protease remains an important pharmacological target. In the development of new HIV protease inhibitors, heterocyclic fragments have proven to be of great importance, owing to their rigid core structure, which may fit better into the enzyme’s hydrophobic pockets, and the presence of a heteroatom, which may increase the number of H-bonding interactions at the active site. According to the concept of targeting the protein backbone, different aromatic or non-aromatic heterocyclic moieties have yielded inhibitors with sufficient activity against mutant viruses. This paper provides an overview of HIV protease inhibitors developed over the last fifteen years, with a focus on the presence of heterocycles in their structure, either in the core or on the side chains, which are crucial for their activity. The rationale behind the design of these new inhibitors, as well as the key synthetic steps involved in their preparation, is also described. Full article

HIV/AIDS remains a major global health challenge, with immune dysfunction, chronic inflammation, and comorbidities sustained by latent viral reservoirs that evade antiretroviral therapy. Euclea natalensis, a medicinal plant widely used in Southern African ethnomedicine, remains underexplored for its potential against HIV. An integrative systems pharmacology and molecular modeling framework was employed, including ADME profiling, target mapping, PPI network analysis, GO and KEGG pathway enrichment, BA-TAR-PATH analysis, molecular docking, MD simulations, and MM/GBSA calculations, to investigate the mechanistic roles of E. natalensis phytochemicals in HIV pathogenesis. Sixteen phytochemicals passed ADME screening and mapped to 313 intersecting host targets, yielding top ten hub genes with GO annotations in immune-metabolic, apoptotic, and nuclear signaling pathways. KEGG analysis revealed the enrichment of HIV-relevant pathways, including Th17 cell differentiation (hsa04659), PD-L1/PD-1 checkpoint (hsa05235), IL-17 signaling (hsa04657), HIF-1 signaling pathway (hsa04066), and PI3K-Akt (hsa04151). Lead phytochemicals, diospyrin and galpinone, strongly targeted key hub proteins (NFκβ1, STAT3, MTOR, HSP90AA1, and HSP90AB1), demonstrating favorable binding affinities, conformational stability, and binding free energetics compared to reference inhibitors. E. natalensis phytochemicals may modulate Th17 differentiation, HIV latency circuits, and comorbidity-linked signaling by targeting multiple host pathways, supporting their potential as multi-target therapeutic candidates for adjunct HIV/AIDS treatment and immunotherapy. Full article

Background: Daily oral preexposure prophylaxis (PrEP) is one strategy employed to decrease HIV transmission among adolescent girls and young women (AGYW). The Determined, Resilient, Empowered, AIDS-Free, Mentored, and Safe (DREAMS) program, funded by PEPFAR/USAID and implemented by the Project HOPE Namibia (PHN)-led consortium, provided services in the Khomas, Oshikoto, Zambezi, and Oshana regions. This study assessed the one-month PrEP retention rate among AGYW 15–24 and the associated factors. Methods: The program’s target populations for PrEP included AGYW aged 15–24 years who were at substantial risk for HIV, tested HIV-negative, and resided in the regions where the PHN-led consortium was implementing the DREAMS program. Data between 2018 and 2024 were exported from DHIS2 to IBM SPSS version 29 for secondary data analysis. We analyzed the data using Chi-squared tests and binomial and multinomial logistic regression. Results: Among the 17,277 participants newly initiated on oral PrEP and included in this study, only 2466 returned on time for their one-month appointment. The one-month PrEP retention rate among AGYW was 14.3%, 95% CI (13.8–14.8%). The most common reasons for PrEP discontinuation were traveling away from home, not needing PrEP anymore, forgetfulness, and side effects. Participants from Oshakati and Onandjokwe exhibited a higher likelihood of one-month PrEP retention. Additionally, participants who were in the programs for 7–12 months or over 36 months, who attended the safe space HIV prevention sessions, who were unaware of their partners’ HIV status, and who considered themselves at risk of HIV also exhibited a lower likelihood of one-month PrEP retention. In contrast, individuals who had 1–2 children and those who were either pregnant or breastfeeding exhibited a higher likelihood of one-month PrEP retention, (COR) = 1.28, 95% CI (1.15–1.43), and COR = 2.00, 95% CI (1.62–2.46), respectively. Conclusions: Targeted, innovative, and context-specific strategies should be developed to support AGYW in identifying their HIV risk and continuing the use of daily oral PrEP during periods of heightened risk. Additionally, prioritizing the introduction of discreet, long-acting PrEP options that require less frequent administration may better align with their needs and preferences. Full article

Background. Oncological diseases are among the leading causes of death in people living with HIV (PLWH). With the introduction of antiretroviral therapy and the consequent reduction in AIDS-defining cancers (ADC), there has been a growing incidence of non-AIDS-defining cancers (NADC). Methods. A retrospective observational study (cross sectional prevalence analysis) was conducted to investigate the prevalence and spectrum of oncological diseases in patients attending the HIV/AIDS Division at the Ferrara Hospital. The sample included 534 patients evaluated between January 2023 and November 2024 (534/682 met eligibility). Demographic, clinical, and serological data were extracted from medical records. The CDC’s 2014 definition has been adopted for the ADC/NADC classification. Statistical analysis was performed using SPSS version 29 and G*Power 3.1 software. Results. The data analysis revealed 62.8% NADC vs. 37.2% ADC (44 NADCs vs. 26 ADCs). Male individuals and those aged 50 and older were more represented. Patients with ADC more often fell into C2–C3 groups, indicative of severe immunodeficiency, while NADCs were more prevalent in clinical groups A1–B3. Statistical analysis showed that viral load was more frequently under 50 copies/mL in the NADC group, while it tended to be higher in the ADC group. Conclusions. These results align with current scientific evidence regarding the global prevalence of ADCs and NADCs. The findings highlight the need to implement targeted oncological screening strategies for HIV-positive patients to promote early diagnosis and improve prognosis. Full article

Pneumonia caused by Pneumocystis jirovecii poses a serious threat, particularly to immunocompromised patients such as those with HIV/AIDS, transplant recipients, or individuals undergoing chemotherapy. Its diagnosis is challenging because current methods, such as microscopy and certain molecular tests, have limitations in sensitivity and specificity, and require specialized equipment, which delays treatment initiation. In this context, CRISPR-Cas12-based methods offer a promising alternative: they are rapid, highly specific, sensitive, and low-cost, enabling more timely and accessible detection, even in resource-limited settings. We developed a simple and rapid detection platform based on the CRISPR-Cas12 coupled with lateral flow strips. A guide RNA was designed against DHPS, β-tubulin, and mtLSU rRNA genes. The guide corresponding to β-tubulin showed high sensitivity in the detection of P. jirovecii to produce a detectable fluorescence signal within the first 20–30 min. In addition, it demonstrated high specificity for P. jirovecii when DNA from other microorganisms was used. When coupled with lateral flow strips, high sensitivity and specificity were also observed for detecting positive samples, without the need for genetic amplification. CRISPR-Cas12 successfully detected P. jirovecii infection in an initial diagnostic application, demonstrating the potential of this method for integration into public health diagnostic systems, particularly in field, due to its adaptability, speed, and ease of use. Full article

Mycobacterial spindle cell pseudotumors (MSCPs) are rare lesions characterized by the proliferation of spindle-shaped histiocytes caused by mycobacterial infections. MSCPs have been reported in the lung, lymphatic system, and skin of immunodeficient patients. We present the case of a spindle cell pseudotumor of the pancreas in a 30-year-old male with advanced human immunodeficiency virus (HIV) infection, which led to biliary stricture, splenomegaly, chronic pancreatitis, portal hypertension, compression of the hepatic artery and portal vein, and ascites. This was the patient’s third mycobacterial infection diagnosis. The MSCP was diagnosed via endoscopic biopsy after two prior non-diagnostic biopsies of the pancreatic lesion. Following 18 months of tailored antimycobacterial therapy, the pancreatic mass resolved radiographically with normalization of liver tests and sustained clinical improvement, and there has been no relapse more than 8 months after treatment completion. This case highlights the presentation of an MSCP in a unique anatomic location not previously documented and the challenges encountered with diagnosis and management. Full article

The global fight against HIV/AIDS has been significantly bolstered by the development and implementation of pre-exposure prophylaxis (PrEP), yet innovation in PrEP interventions, improved adherence and greater access are still needed to maximize its benefit. Nonhuman primate (NHP) infection with simian immunodeficiency virus (SIV) has served as an instrumental animal model in advancing HIV PrEP research. This review comprehensively examines the utility of NHP models in evaluating the efficacy, pharmacokinetics, and safety of diverse PrEP strategies, including oral, injectable, implantable, and topical formulations. It discusses the development of diverse challenge models that simulate human transmission routes and the advantages of NHPs in enabling controlled and mechanistically informative studies. It also highlights the successful translation of pivotal NHP studies evaluating tenofovir-based regimens as well the long-acting agents, cabotegravir and lenacapavir, into the clinical settings, emphasizing the consistently high predictive power of the NHP models for the HIV PrEP clinical efficacy. Finally, it underscores the importance of species-specific pharmacologic considerations and the value of NHP data in informing clinical trial design. As the global community strives to end the HIV epidemic as a public health threat in the absence of an efficacious prophylactic vaccine, NHP models make a critical contribution in the development of next-generation HIV prevention tools. Full article

The dynamics of the HIV reservoir during antiretroviral therapy (ART) exhibit variability, with a pronounced decline during the initial years of treatment. However, the identification of biomarkers and host factors associated with the decay of the different forms of HIV proviruses remains to be fully elucidated. We conducted a longitudinal study on people with HIV provided by the Spanish National HIV cohort. We assessed the HIV-DNA levels by Intact Proviral DNA Assay, and inflammatory markers using the Proximity Extension Assay, before and after ART initiation. A multivariate linear regression model was employed to identify potential predictive markers. Our results highlight the identification of novel inflammatory markers, such as ADA, DNER, CDCP1, SCF, among others, that varied significantly over ART initiation. In addition, we observed several markers associated with intact HIV-DNA before ART initiation (CD8A, CX3CL1, and ST1A1) or during undetectable viral load post-ART (IL-10). Moreover, up to five markers were able to predict the intact HIV reservoir decay over ART. The strongest predictor was Stem Cell Factor (SCF), where higher baseline levels of this marker were associated with a greater decline in the intact HIV reservoir. In conclusion, we have identified inflammatory markers associated with the size and dynamics of the HIV-DNA reservoir. These findings provide new insights that could contribute to the development of multi-targeted intervention strategies aimed at modulating or monitoring the HIV reservoir size. Full article

Background: Neurocysticercosis (NCC) and HIV co-infection frequently occur in sub-Saharan Africa, yet the accuracy of available serological tests for NCC in immunosuppressed patients is uncertain. Methodology: We performed a cross-sectional diagnostic study on 101 people living with HIV from two endemic districts in Tanzania. Participants provided serum for cysticercosis antigen ELISA and Western Blot IgG; any positive result prompted neuroimaging investigation with cerebral computed tomography. NCC was diagnosed according to the 2017 revised Del Brutto criteria based on cCT according to Del Brutto criteria modified to exclude serology. Sensitivity, specificity, and area under the receiver–operating–characteristic curve (AUC) were calculated and adjusted for CD4 count and HIV stage. Two algorithms were compared: parallel testing (“either-test-positive”) and sequential screening (Ag ELISA screen, western blot IgG confirm). Results: NCC prevalence was 23%. Western Blot IgG outperformed Ag ELISA (sensitivity 57% vs. 30%; specificity 87% vs. 86%; AUC 0.73 vs. 0.57). Western blot IgG sensitivity declined to 54% when CD4 < 500 cells µL⁻¹, while Ag ELISA remained low. Western blot IgG positivity independently predicted NCC (adjusted odds ratio 4.1, 95% CI 1.4–11.9); Ag ELISA did not. When we counted a positive if either test was positive (parallel rule), sensitivity rose to 78% and NPV to 87%. When we ran Ag ELISA only if IgG was negative (sequential rule), we saved 70% of IgG strips, kept specificity at 95%, and PPV at 69%, but sensitivity fell to 39%. Conclusions: Western blot IgG is the most reliable single serological test for NCC in PLHIV. Parallel testing increased sensitivity and NPV and may suit better primary-level facilities without routine imaging. Sequential testing achieved high specificity, PPV, and conserved test kits, making it ideal for centers with limited reagents or scanner access. Tiered use of these assays can streamline NCC diagnosis in T. solium endemic, resource-limited settings. Full article

Background: Namibia is experiencing a generalized HIV epidemic, with 7.5% of the population living with HIV. Adolescent girls and young women (AGYW) aged 15–24 account for 28.6% of new infections annually. Various factors increase AGYW’s vulnerability to HIV. To address this, Project HOPE Namibia (PHN)-led consortium implemented the PEPFAR/USAID-funded DREAMS project in Khomas, Oshikoto, and Zambezi regions from 2018 to 2023. This study estimated the AGYW population most in need of HIV prevention and assessed geographic and age-specific gaps to improve program effectiveness and efficiency. Methods: This secondary data analysis utilized the Namibia Population-Based HIV Impact Assessment (NamPHIA) 2017, the Namibia census, and service data from the DREAMS project, which includes entry points for recruitment, screening, and enrolment. We used Python to conduct unadjusted and adjusted Poisson regression and UpSet plots for data visualization. Results: Analysis of NamPHIA data revealed low HIV prevalence in 10–14-year-olds, with only Oshikoto showing a detectable rate of 2.76%, mostly attributed to perinatal HIV transmission. Of the 12 DREAMS eligibility criteria, three could be mapped to 10–14-year-olds, while all except sexually transmitted infections could be mapped for 15–19 and 20–24-year-olds. Nationally, 17.3% of 10–14-year-old AGYW, 48.0% of 15–19-year-olds, and 50% of 20–24-year-olds met at least one DREAMS eligibility criterion. Among 15–19-year-olds, a history of pregnancy, no/irregular condom use, and out-of-school status were positively associated with HIV status. For 20–24-year-olds, transactional sex was positively associated with HIV status. Overall, 62% of screened individuals were eligible, and 62% of eligible individuals enrolled. PHN screened 134% of the estimated 37,965 10–14-year-olds, 95% of the estimated 35,585 15–19-year-olds, and 57% of the 24,011 20–24-year-olds residing in the five districts where DREAMS was implemented. Conclusions: We recommend the refinement of the DREAMS eligibility criteria, particularly for AGYW 10–14, to better identify and engage those at risk of HIV acquisition through sexual transmission. For 15–19-year-olds, PHN efforts should interrogate geographic variability in entry points for recruitment and screening practices. PHN should enhance the recruitment and engagement of AGYW 20–24, with a particular focus on those engaged in transactional sex. Full article