Search Results (3,878)

This study investigated the protective efficacy of two distinct combinations of three recombinant adeno-associated virus serotype 9 (rAAV9) vectors encoding broadly neutralizing antibodies against HIV-1—CombiMab-1 and CombiMab-2—in mice humanized with primary CD4⁺ T-lymphocytes. We demonstrated that mice preventively treated with CombiMab-1 or CombiMab-2 did not develop viremia and maintained human CD4+ T-lymphocyte counts following viral challenge, in contrast to control animals. These results demonstrate the significant protective capacity of CombiMab-1 and CombiMab-2 against HIV-1 challenge. Full article

Background: After the implementations of Highly Active Antiretroviral Therapy (HAART) HIV infection became a chronic condition and the clinical focus on non-AIDS-related comorbidities such as hypertension and chronic kidney disease has increased. This study aims to investigate the prevalence and independent predictors of hypertension and albuminuria in a cohort of people with HIV (PWHIV) with high rates of viral suppression. Methods: This is a cross-sectional study of 183 HAART-experienced PWHIV. Hypertension, defined as office systolic blood pressure of ≥140 mmHg or diastolic blood pressure of ≥90 mmHg and albuminuria, was defined as a sex-based albumin–creatinine ratio (ACR) of >355 mg/g for females and >250 mg/g for males. Univariable and multivariable logistic regression was conducted to identify the association of hypertension and albuminuria with demographic, clinical, and HIV-specific factors. Results: The prevalence of hypertension was 43.9% (n = 74) and albuminuria was 22.4% (n = 41). In the multivariable analysis, factors independently associated with prevalence of HTN were older age, overweight/obesity, and diabetes mellitus. TDF-based ART was explored as a potential factor but did not reach statistical significance (aRR = 1.85, p = 0.065). For albuminuria, older age, diabetes mellitus, and duration of HAART (aRR = 1.03 per year) were revealed as independent predictors. Conclusions: The results of this study demonstrate that the development of hypertension is primarily driven by traditional metabolic risk factors. However, the progression to albuminuria appears to be influenced not only by these comorbidities but also by long-term HIV disease and HAART exposure. These findings underline the critical need for the screening and management of hypertension and other comorbidities to mitigate the risk of long-term cardiovascular and renal complications in this aging population of PWHIV. Full article

Human herpesvirus-8 (HHV-8) is a gamma herpesvirus linked to the development of Kaposi sarcoma (KS). KS is more common in persons living with HIV (PLWH), but endemic KS in HIV-negative individuals is also common in sub-Saharan Africa. HHV-8 shedding occurs in the oral mucosa and is likely responsible for transmission. The mechanistic drivers of different HHV-8 shedding patterns in infected individuals are unknown. We applied stochastic mathematical models to a longitudinal study of HHV-8 oral shedding in 295 individuals in Uganda who were monitored daily with oral swabs. Participants were divided into four groups based on whether they were HIV-negative or -positive, as well as KS-negative or -positive. In all groups, we observed a wide variance of shedding patterns, including no shedding, brief episodic low viral load shedding, prolonged episodic medium viral load shedding, and persistent high viral load shedding. Our model closely replicates patterns in individual data and attributes higher shedding rates to increased rates of viral reactivation and lower median viral load values to more rapid and effective engagement of cytolytic immune responses. Our model provides a framework for understanding different shedding patterns observed in individuals with HHV-8 infection. Full article

Chronic inflammation constitutes a significant characteristic of sustained infections caused by viral and fungal pathogens, with a strong correlation to the development of cancer, autoimmune disorders, and tissue fibrosis. Viral proteins such as HIV-1 Tat, HBV X (HBx), HPV E6/E7, and EBV LMP1 modulate the host’s immune signaling pathways, primarily through the activation of the NF-κB signaling cascade and the disruption of cytokine equilibrium. These molecular interactions result in a pro-inflammatory microenvironment that facilitates viral persistence, immune evasion, and the process of oncogenesis. Structural investigations have elucidated the mechanisms by which these viral proteins interact with host signaling complexes, thereby highlighting their potential as viable therapeutic targets. Similarly, fungal proteins, including secreted aspartyl proteases (Saps), ribotoxin Asp f1, and chitin-binding proteins, incite chronic inflammation by activating pattern recognition receptors and triggering inflammasome activation. Despite the limited structural information of these fungal proteins, emerging models and bioinformatic analyses identified conserved motifs that are crucial for host interactions. Biologic therapies, encompassing antiviral and antifungal peptides as well as monoclonal antibodies, are currently under development to disrupt these protein-host interactions and modulate inflammatory responses. This review provides structural and functional insight into viral and fungal inflammatory proteins and evaluates the potential of biologics as targeted therapeutic interventions for chronic inflammation associated with infections. We discuss the ongoing clinical trials involving neutralizing antibodies targeting HIV, peptide vaccines aimed at HPV and other promising molecules. Finally, we discuss the current limitations of biologics and possible solutions to translate these promising therapeutics into clinical practice. Full article

Background/Objectives: The objective of this retrospective, multicenter cohort study was to compare the incidence of viral load blips between two-drug and three-drug antiretroviral therapy regimens in human immunodeficiency virus (HIV) patients. Methods: A total of 121 patients were included, with 44 receiving two-drug regimens (e.g., dolutegravir/lamivudine) and 77 receiving three-drug regimens (e.g., bictegravir/tenofovir alafenamide/emtricitabine) at the time of analysis. The primary outcome was the occurrence of viral blips, defined as transient HIV-RNA elevations ≥ 50 copies/mL; a sensitivity analysis used ≥20 copies/mL. Results: Generalized estimating equation models adjusted for clinical covariates showed no significant difference in the odds of blip occurrence comparing three-drug with two-drug regimens, both for blips ≥ 50 (odds ratio [OR]: 2.64; 95% confidence interval [CI]: 0.91–7.70; p = 0.075) and ≥20 (OR: 1.76; 95% CI: 0.76–4.08; p = 0.190). In the two- and three-drug groups, the predicted probabilities of blips were 1.4% and 3.7% (p = 0.075) for blips ≥ 50, and 6.9% and 11.5% (p = 0.190) for ≥20, respectively. No virologic failure was observed. Conclusions: These findings suggest that two-drug regimens provide virologic control comparable to three-drug regimens and may be a viable clinical option due to fewer drug interactions, lower toxicity, and reduced cost. Full article

Colonoscopy remains the gold standard for colorectal cancer (CRC) screening, but its invasiveness, cost, and limited availability in resource-constrained settings pose major barriers. Stool-based methylated DNA biomarkers, such as vimentin, offer sensitive, non-invasive alternatives. Given the high burden of HIV and helminth co-infections in sub-Saharan Africa and their potential contribution to cancer susceptibility, this study investigated whether stool-derived vimentin methylation could detect early oncogenic changes in these high-risk groups. In this retrospective cross-sectional study, archived stool samples from 62 South African adults were stratified into five groups: uninfected controls, HIV-infected only, helminth-infected only, HIV-helminth co-infected, and CRC-confirmed patients. DNA was extracted, bisulfite-converted, and analyzed for vimentin methylation using a high-resolution melt assay. Fecal occult blood testing (FOBT) was also performed. Vimentin methylation differed significantly across groups (p < 0.0001). CRC cases showed 90% methylation, confirming its role as a CRC biomarker. Interestingly, vimentin methylation frequencies were also observed in HIV-only (92.9%, p < 0.0001 vs. controls), helminth-only (93.3%, p < 0.0001), and HIV-helminth co-infected (77.9%, p < 0.0001) individuals without diagnosed cancer, compared to 10% in controls. Methylation levels in infected groups were not significantly different from CRC patients (all p > 0.05), suggesting infection-induced epigenetic changes of comparable magnitude to malignancy. To support these results, DNMT1–RG108 molecular docking (PDB 4WXX, Maestro 2025-3) demonstrated stable binding (GlideScore −6.285 kcal/mol; ΔG_bind −49.61 kcal/mol) via hydrogen bonding with Glu1266 and Asn1578 and π–π stacking with Phe1145, providing a mechanistic explanation for infection-driven vimentin methylation. No significant differences were found between infected groups. FOBT was positive in 83.3% of CRC cases, with only sporadic positives in infected groups. These findings provide novel evidence that chronic HIV and helminth infections are associated with vimentin promoter methylation at levels indistinguishable from CRC. This supports the hypothesis that persistent infection-driven inflammation promotes early epigenetic reprogramming toward oncogenesis. In high-burden African settings, stool-based methylation assays could serve as early diagnostic tools to identify at-risk individuals long before clinical disease manifests, enabling targeted surveillance and prevention. Full article

Human Immunodeficiency Virus (HIV) infection is associated with a wide spectrum of urological manifestations, reflecting both the direct effects of viral infection and the indirect consequences of immunosuppression, opportunistic infections, malignancies and long-term combined antiretroviral therapy (cART). This narrative review provides a contemporary, multifaceted overview of the clinical and pathological presentations of urological conditions in people living with HIV (PLWHIV), based on articles published between 1989 and 2025. Conditions discussed include HIV-associated nephropathy (HIVAN), opportunistic genitourinary infections, malignancies such as Kaposi sarcoma and lymphoma, as well as non-infectious complications such as HIV-associated nephropathy and erectile dysfunction (ED). The review highlights the evolving epidemiology of these conditions in the cART era, with a noted decline in opportunistic infections but a rising burden of chronic kidney disease and malignancies, largely due to improved survival and ageing of the HIV-positive population. Pathological insights are explored and discussed, including mechanisms of HIV-associated renal injury, such as direct viral infection of renal epithelial cells and genetic predispositions linked to Apolipoprotein L1 (APOL1) variants. In addition, psychosocial factors, including anxiety, stress, stigma, and alcohol use, are discussed, as they may contribute to late presentation to clinical urology services. The review also considers the challenges faced in low and middle-income countries, the impact of HIV on urological services, and the important role of palliative care in advanced disease. Ultimately, this review underscores the need for early recognition, comprehensive diagnostic and surgical evaluation, and integrated social, psychological, and palliative management strategies tailored to the unique needs of PLWHIV. A deeper understanding of the interplay between HIV, cART, psychosocial determinants, and urological health is essential for improving patient outcomes and guiding future research in this evolving field. Full article

Human immunodeficiency virus (HIV), comprising two distinct types, HIV-1 and HIV-2, remains one of the most significant global health challenges, originating from multiple cross-species transmissions of simian immunodeficiency viruses (SIVs) in the early 20th century. This review traces the evolutionary trajectory of HIV from zoonotic spillover to its establishment as a global pandemic. HIV-1, the principal strain responsible for AIDS, emerged from SIVcpz in Central African chimpanzees, with phylogenetic evidence indicating initial human transmission between the 1920s and 1940s in present day Democratic Republic of Congo. The virus disseminated through colonial trade networks, reaching the Caribbean by the 1960s before establishing endemic transmission in North America and Europe. HIV’s extraordinary genetic diversity—driven by high mutation rates (~10⁻⁵ mutations per base per replication cycle) and frequent recombination events—has generated multiple groups, subtypes, and circulating recombinant forms (CRFs) with distinct epidemiological patterns. HIV-1 Group M, comprising subtypes A through L, accounts for over 95% of global infections, with subtype C predominating in sub-Saharan Africa and Asia, while subtype B dominates in Western Europe and North America. The extensive genetic heterogeneity of HIV significantly impacts diagnostic accuracy, antiretroviral therapy efficacy, and vaccine development, as subtypes exhibit differential biological properties, transmission efficiencies, and drug resistance profiles. Contemporary advances, including next-generation sequencing (NGS) for surveillance, broadly neutralizing antibodies for cross-subtype prevention and therapy, and long-acting antiretroviral formulations to improve adherence, have transformed HIV management and prevention strategies. NGS enables near real-time surveillance of drug resistance mutations and inference of transmission networks where it is available, although access and routine application remain uneven across regions. Broadly neutralizing antibodies demonstrate cross-subtype efficacy, while long-acting formulations have the potential to improve treatment adherence. This review synthesizes recent evidence and offers actionable recommendations to optimize clinical and public health responses—including the routine use of genotypic resistance testing where feasible, targeted use of phylogenetic analysis for outbreak investigation, and the development of region-specific diagnostic and treatment algorithms informed by local subtype prevalence. While the understanding of HIV’s evolutionary dynamics has substantially improved and remains essential, translating this knowledge into universally implemented intervention strategies remains a key challenge for achieving the UNAIDS 95-95-95 targets and the goal of ending AIDS as a public health threat by 2030. Full article

We previously described an increased incidence of HIV among individuals infected with Wuchereria bancrofti (WB). However, no host, parasite, or viral factors were reported as directly associated with the increase in HIV incidence in this group. To investigate this, we compared T cell phenotypes between WB+ and WB− women. Flow cytometry analysis of activation and differentiation markers on CD4 T cells, as well as HIV entry receptor CCR5 was performed on cervical and peripheral blood samples from 54 women living without HIV (WLWoH). Additionally, HPV testing was performed on their specimens and for 13 WLWH. WB infection was associated with a significantly increased frequency of CD3⁺γδ2⁺ T cells in the cervical mucosa (median 4.0% vs. 1.4%, p = 0.012). Contrary to our expectations, we found lower frequencies of CCR5 on total, memory and activated memory CD4 T cells in the WB+ group. However, differences diminished after accounting for age and site of recruitment. WB and HIV infections were associated with an increased likelihood of high-risk human papillomavirus (HR HPV) positivity. (WB status: odds ratio (OR) 4.1, p = 0.066; HIV status: OR 5.5, p = 0.068). Our findings suggest immunological mechanisms by which WB increases the risk for other infections, e.g., HIV and HR HPV, albeit independent of the CCR5 receptor. Full article

Background: Men who have sex with men (MSM) are at high risk for anal human papillomavirus (HPV) infection, with HIV-positive MSM bearing the highest disease burden. Longitudinal data on anal HPV infection among HIV-negative and HIV-positive MSM are limited. We assessed and compared the prevalence, incidence, and clearance of anal HPV infection among HIV-negative and HIV-positive MSM in Xinjiang, China. Methods: Sexually active HIV-positive and HIV-negative MSM aged 18 years and older have been enrolled in an ongoing observational cohort study of HPV since 1 September 2016, in Xinjiang, China. Participants were followed up on every 6 months with anal HPV testing and questionnaires regarding sexual behaviors. We compared HPV prevalence, incidence, and clearance between HIV-positive and HIV-negative MSM. Prevalence ratios (PRs), incidence rate ratios (IRRs), and clearance rate ratios (CRRs) for HIV-negative and HIV-positive MSM were calculated. Results: A total of 1425 MSM, including 131 HIV-positive and 1294 HIV-negative individuals, with a median age of 29 years (interquartile range [IQR]: 24 to 36), were included in our analysis. Compared with HIV-negative MSM, HIV-positive MSM demonstrated significantly higher prevalence across both individual and grouped HPV genotypes. Specifically, the prevalence of grouped HPV genotypes (any, high-risk, low-risk, 9v, 4v, HPV16/18, and HPV 6/11) was consistently elevated in HIV-positive individuals. PRs for individual HPV types 31, 45, 34, 44, 53, and 81 were 2.47 (95% CI: 1.16–5.25), 2.47 (1.10–5.54), 4.94 (1.25–19.52), 3.29 (1.08–10.06), 2.02 (1.01–4.04), and 2.66 (1.18–6.01), respectively. Furthermore, the incidence of most individual HPV genotypes were higher, while the clearance rates were lower among HIV-positive MSM. Specifically, IRRs for HPV types 31, 33, 45, 55, and 66 were 2.12 (1.19–3.75), 2.19 (1.24–3.90), 2.32 (1.17–4.59), 3.02 (1.15–7.93), and 2.44 (1.18–5.05), respectively. CRRs for HPV types 51 and 58 were 0.33 (0.21–0.52) and 0.60 (0.45–0.79), respectively. Conclusions: HPV prevalence, incidence, and clearance of anal HPV exhibited heterogeneity between HIV-positive and HIV-negative MSM. HPV vaccination and condom promotion programs should be recommended for HIV-positive MSM to mitigate the burden of HPV infection in this vulnerable population. Full article

Purpose: The COVID-19 pandemic has led to the publication of numerous primary studies and meta-analyses; however, conclusive evidence on whether HIV infection influences COVID-19 outcomes among people living with HIV (PLHIV) is still lacking. This research uses a novel technique, the exit meta-analysis, to conclusively update the evidence of HIV’s impact on COVID-19-related mortality, hospitalization, and need for Intensive Care Unit (ICU) admission in severe disease. Methods: A search of PubMed, EMBASE, Cochrane Reviews (CDSR), SCOPUS, CINAHL reviews and Google Scholar databases was conducted up to the 18 January 2024 for meta-analyses and observational studies that reported adjusted associations for the effect of HIV on COVID-19 related mortality, hospitalization, and ICU admission. Evidence from existing meta-analyses was summarized narratively, and an updated meta-analysis was carried out using a bias-adjusted inverse variance heterogeneity model. Subgroup analysis was carried out for age groups and geographical regions. Results: Of 3153 records identified, 20 meta-analyses and 56 primary studies, with a total of 27,936,428 participants, including 655,882 PLHIV, were included. A review of the meta-analyses showed conflicting results for all outcomes. In the updated synthesis, HIV was associated with higher odds of mortality (aOR 1.43, 95% CI: 1.01–1.86, I² = 90.7%) and ICU admission (aOR 1.49, 95% CI: 0.67–2.30, I² = 88.8%), but not hospitalization (aOR 1.11, 95% CI: 0.78–1.48, I² = 97.5%). The results for both ICU admission and hospitalization include the null value, leading to lower certainty. The exit meta-analysis suggested conclusive results for mortality (DAts score = −0.012) and hospitalization (DAts score = −0.014), but not for ICU admission. Conclusions: This exit meta-analysis provides conclusive evidence that HIV increases mortality in people with COVID-19; however, more studies may be required to address ICU admission and hospitalization. Full article

Chronic hepatitis B virus (HBV) and Occult HBV infection (OBI) remain a health burden in sub-Saharan Africa. This study investigated HBV prevalence, circulating genotypes, and associated risk factors with HBV exposure among HIV-positive adults on antiretroviral therapy and pregnant women in southwestern Cameroon. A total of 233 HIV patients and 190 third-trimester pregnant women were screened for HBV DNA, viral load, serological markers (HBsAg, anti-HBc, and anti-HBs), and HBV genotypes were determined by partial sequencing of the S gene. HBV DNA was detected in 10% of HIV-positive patients and 4% of pregnant women, with an overall prevalence of 7%. OBI accounted for 9% and 3%, respectively. Anti-HBc seroprevalence was high (75% in HIV, 46% in pregnant women), while self-reported vaccination coverage was low (1% and 11%). Genotypes A, B, D, and E were identified, with genotype B reported for the first time in Cameroon. Immune escape mutations and the adefovir resistance mutation rtA181V were detected. Self-reported alcohol use was associated with HBV exposure in HIV patients (aOR = 2.08; p = 0.028) and inversely associated with tertiary education in pregnant women (aOR = 0.18; p = 0.038). This study highlights a significant burden of HBV and OBI among vulnerable populations in Cameroon. Full article

Background/Objectives: The growing intersection between nyaope use and HIV infection constitutes a critical public health problem that undermines efforts to achieve universal access to HIV treatment in South Africa. Nyaope use is strongly associated with the increased risk of HIV of transmission. A significant amount of new HIV infections was linked to substance use through sharing of injectable needles. Despite significant progress made to increase public awareness and increase accessibility to HIV services, little is known about how addiction, stigma, and discrimination influence access to HIV treatment among homeless individuals who nyaope. This study explored the hurdles of accessing HIV treatment among people who use nyaope and are homeless in Mogale City, Gauteng Province. Methods: An exploratory descriptive qualitative research approach was employed among people who are homeless, living with HIV and using nyaope (PHHIVN) in Mogale City, between May and August 2024. Data were collected utilizing in- depth interviews in English, isiZulu and Setswana languages. Purposive sampling technique was followed to select participants, and a sample size of 25 participants was reached with a mean age of 32.28 and SD = ±5.54 years, of whom 21 (84%) were male, 3 (12%) were female and 1 (4%) identified as other. Audio recordings were transcribed, translated, and analyzed following inductive thematic analysis. Results: Social exclusion and fractured support system, prioritization of drug use, nyaope dependency, withdrawal symptoms, negative peer influence, socioeconomic factors and misconception about the interaction between nyaope and HIV treatment were reported as some of the main hurdles of accessing HIV treatment among PHHIVN in Mogale City, Gauteng Province. Conclusions: It is therefore concluded that access to HIV treatment among PHHIVN in Mogale City, Gauteng Province, remains a serious public health concern influenced by various hurdles. The development of tailored interventions to improve access and adherence to HIV treatment among this population group has potential to enhance the uptake of HIV treatment. Full article

Human immunodeficiency virus (HIV) remains a global public health challenge. Antiretroviral therapy (ART) improves outcomes by suppressing viral replication and enabling immune recovery, yet the early molecular mechanisms of immune-related transcriptional change after ART remain insufficiently characterized. We enrolled eight ART-naïve male patients with HIV aged 18–35. Peripheral blood mononuclear cells (PBMCs) were collected before and after 24 weeks of combination ART (TDF, 3TC, DTG) and underwent bulk RNA-seq (Illumina HiSeq 1500, Illumina, Inc., San Diego, CA, USA). Differential expression was assessed with DESeq2 (paired design); gene set enrichment analysis (GSEA), principal component analysis (PCA), hierarchical clustering, and protein–protein interaction (PPI) networks (STRING/NetworkX) explored functional patterns and transcriptomic shifts. We identified 87 differentially expressed genes, including 67 downregulated interferon-stimulated genes (e.g., IFI44L, ISG15, STAT1) and 20 upregulated transcripts, mostly pseudogenes related to ribosomal proteins. Functional enrichment revealed suppression of type I interferon and other antiviral signaling pathways. PCA and hierarchical clustering indicated a post-ART transcriptional shift. These findings suggest that early immune recovery following ART involves downregulation of chronic interferon-driven activation. This observation may correspond to partial restoration of T-cell functional capacity, reduced immune exhaustion, and a rebalanced antiviral immune environment. Full article

Cryptosporidiosis is a zoonotic disease of medical and veterinary importance caused by Cryptosporidium spp. This study conducted a systematic review to assess the occurrence and distribution of Cryptosporidium spp. in humans in Brazil, with emphasis on C. parvum. Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) protocol and using five databases, 3689 articles were screened, and 48 met the inclusion criteria. Most studies were concentrated in the Southeast Region, particularly São Paulo, while major gaps were identified in the North and Midwest Regions. The mean prevalence was 8.9% using direct methods and 52.2% using indirect methods, with the highest positivity reported in the Northeast Region. Microscopy was the most frequently employed diagnostic tool, although it showed limited ability to differentiate species. When combined with molecular approaches, C. parvum and C. hominis were identified as the predominant species. Infection was most common among children and immunocompromised individuals, especially those with HIV and kidney diseases. Overall, the findings highlight substantial research gaps regarding cryptosporidiosis in Brazil and its disproportionate impact on vulnerable populations. Expanding regional studies, integrating molecular methods for species characterization, and implementing targeted public health strategies are essential to improve epidemiological knowledge and guide prevention and control measures. Full article