Search Results (1,236)

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

This paper evaluates the Enhancing Mobile Populations’ Access to HIV and AIDS Services, Information and Support (EMPHASIS) programme implemented by CARE International across Bangladesh, India, and Nepal. Using individual-level data, we estimate the programme’s impact on HIV-related knowledge and preventive behaviours among migrant workers. Results show that participation in EMPHASIS significantly increased correct knowledge of HIV transmission, reduced misconceptions, and improved partner communication. These informational gains translated into higher condom use and fewer unsafe sexual practices, with stronger effects among women. The findings provide evidence that peer-led, information-based interventions can improve health behaviours among mobile populations. Integrating such approaches with gender empowerment and mobile health services offers a promising model for addressing HIV vulnerability in cross-border migration settings. 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), 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

The high HIV prevalence among men who have sex with men and transgender women (TW) in Peru calls for innovative HIV prevention strategies to modify social norms, increase social support and promote empowerment and community mobilization. This qualitative article presents the synergistic processes that generated community mobilization throughout Generación Actual (GA, Current Generation in English), an HIV prevention intervention with gay men (GM) and TW in Lima South based on Mpowerment, a U.S.-model intervention program. We conducted 24 interviews with GM and TW participants, informed by observations of GA and the perceptions of its implementing coordinators, and complemented by the number/types of GA activities. Four significant processes occurred throughout GA: (1) high participant engagement, community building and empowerment; (2) an effect on HIV prevention and treatment; (3) the integration of GM and TW and (4) GA’s community center becoming a safe space for socializing, support and information. These processes helped produce positive changes related to self-empowerment, personal agency and the participants’ health, suggesting an impact of GA on HIV prevention, stigma reduction and care engagement. Community mobilization strategies that ensure active community participation and involvement may constitute relevant aspects for an effective approach to HIV prevention for TW and GM in Peru. 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

Adolescent girls and young women (AGYW) in South Africa remain disproportionately affected by HIV due to a complex interplay of structural, social, and gender-based vulnerabilities. This study explored the experiences of AGYW who participated in a group-based HIV prevention intervention in three low-socio-economic communities—Soweto, Alexandra, and Orange Farm—in Gauteng Province, South Africa. The intervention integrated economic strengthening with HIV prevention education, delivered through structured, mentor-led group sessions. Using qualitative methods, in-depth interviews were conducted with 18 AGYW aged 15–24 to examine how participation empowered them to reduce HIV-related risks. The findings reveal that the intervention significantly enhanced participants’ self-awareness, assertiveness, and knowledge of Sexual and Reproductive Health (SRH), while fostering personal independence, goal setting, and agency. The group-based format also facilitated peer connection and created a safe space for challenging harmful gender norms, improving health-seeking behaviours, and navigating access to SRH services. Mentorship emerged as a critical enabler of impact, providing emotional support and trusted guidance. The study underscores the value of community group-based HIV prevention models that empower AGYW through social, economic, and gender-responsive approaches, offering practical insights for policy and programme design in resource-constrained settings. Full article

Parathyroid gland disorders, including secondary hyperparathyroidism, have emerged as significant endocrine complications in people living with HIV (PLWHIV). This narrative review synthesises recent evidence on the prevalence, mechanisms, and clinical implications of parathyroid dysfunction in PLWHIV. HIV infection, combined antiretroviral therapy (cART), and immune activation contribute to parathyroid dysfunction, with cART regimens, particularly Tenofovir Disoproxil Fumarate (TDF), exacerbating these disturbances by altering the calcium and parathyroid hormone (PTH) dynamics. Studies show that PTH levels in PLWHIV on TDF were significantly elevated compared to those on non-TDF-based cART regimens. Histopathological studies highlight a higher prevalence of parathyroid hyperplasia in PLWHIV, often linked to chronic deficiencies in calcium, magnesium, and vitamin D, as well as immune dysregulation. The dysfunction observed ranges from inappropriate elevation of PTH levels to hypoparathyroidism, leading to rapid bone density loss and an increased fracture risk. Despite the fact that HIV is a condition associated with high malignancy, parathyroid malignancy is a very rare issue. Despite the growing recognition of these complications, routine screening for PTH and bone health remains inadequate in standard clinical HIV care. This review advocates for incorporating routine monitoring of serum PTH, calcium, phosphate, and vitamin D levels, especially in those on TDF-based cART. Early detection of subclinical parathyroid dysfunction can prevent complications such as secondary hyperparathyroidism and neuromuscular symptoms. Clinicians should be aware of atypical biochemical presentations, such as elevated PTH with normal calcium, which may indicate cART-induced dysregulation, improving patient management and outcomes. Full article

Xenotransplantation using pig cells, tissues or organs may be associated with the transmission of porcine zoonotic or xenozoonotic microorganisms. Porcine endogenous retroviruses (PERVs) pose a special risk for xenotransplantation as these viruses can infect human cells and are integrated in multiple copies in the genome of all pigs and, therefore, they cannot be eliminated as other viruses can. To prevent PERV transmission to the recipient, several strategies have been developed: PERV-C-free animals, siRNA and genomic editing. Another strategy is the generation of vaccines based on neutralizing antibodies in order to protect the recipient. To investigate whether a protective vaccine is feasible in the case of PERV, the recombinant transmembrane (p15E) and the surface envelope (gp70) protein of PERV were cloned, produced, purified and used to immunize rats. For the first time, an adjuvant type that is approved for human use was used. In all cases we obtained virus binding antibodies as shown in Western blot assays and neutralizing antibodies as shown in neutralization assays, indicating the potential for a protective vaccine. The epitopes recognized by the antisera against p15E were determined using overlapping peptides. Two main epitopes were found in the sequence of p15E, one in the membrane proximal external region (MPER) and one in the fusion peptide proximal region (FPPR). The epitopes correspond to epitopes determined previously when immunizing different animal species with p15E of PERV. Antibodies against these epitopes block the conformational changes in the transmembrane envelope proteins that are required for membrane fusion, thereby inhibiting infection. The epitope in the MPER is related by sequence and location to an epitope in the transmembrane envelope protein of the human immunodeficiency virus-1 (HIV-1) recognized by a broadly neutralizing antibody from infected patients. Full article

Background: Major advances in antiretroviral therapy (ART) have transformed HIV into a chronic condition, yet drug resistance, long-term toxicities, adherence challenges, and persistent viral reservoirs continue to drive innovation. Objectives: To map and synthesize recent developments in anti-HIV drugs and delivery platforms with a focus on (i) new molecules in clinical development and (ii) novel mechanisms of action, following a scoping review framework aligned with PRISMA-ScR. Sources: We interrogated PubMed, Embase.com, Web of Science, and Scopus (January 2020–September 2025) and screened abstracts from CROI, IAS/AIDS, IDWeek, and HIV Glasgow (2023–2025). Content: The evidence base underscores capsid inhibition (lenacapavir) for multidrug-resistant HIV and its expansion into prevention, long-acting intramuscular maintenance with cabotegravir/rilpivirine, maturation inhibitors (zabofiravir), and attachment inhibition with fostemsavir. Broadly neutralizing antibodies (bNAbs) can sustain ART-free suppression in selected individuals. Ultra-long-acting delivery systems are advancing toward translational evaluation. Summary: The pipeline is diversifying toward less frequent dosing, new targets, and combination strategies. Successful and ethical implementation will require resistance-informed selection, equitable access, and reimagined healthcare delivery models that accommodate long-acting technologies. Full article

Background/Objectives: Vaccine elicitation of antibodies with high HIV-1 neutralization breadth is a long-standing goal. Recently, the induction of such antibodies has been achieved at the fusion peptide site of vulnerability. Questions remain, however, as to how much anti-fusion peptide antibodies can be improved and whether their neutralization breadth and potency are sufficient to prevent HIV-1 infection. Methods: Here, we use yeast display coupled with deep mutational screening and biochemical and structural analyses to study the improvement of the best fusion peptide-directed, vaccine-elicited antibody, DFPH_a.01, with an initial 59% breadth. Results: Yeast display identified both single and double mutations that improved recognition of HIV-1 envelope trimers. We characterized two paratope-distal light chain (LC) mutations, S10R and S59P, which together increased breadth to 63%. Biochemical analysis demonstrated DFPH-a.01_10R59P-LC, and its component mutations, to have increased affinity and stability. Cryo-EM structural analysis revealed elbow-angle influencing by S10R-LC and isosteric positioning by S59P-LC as explanations for enhanced breadth, affinity, and stability. Conclusions: These results, along with another antibody with enhanced performance (DFPH-a.01_1G10A56K-LC with 64% breadth), suggest that mutations improving DFPH_a.01 are plentiful, an important vaccine insight. Full article

Tuberculosis preventive treatment (TPT) is a mainstay for reducing the tuberculosis (TB) burden among people living with human immunodeficiency virus (PLHIV). Context-specific challenges hinder TPT uptake and completion among PLHIV. During 2022–2024, a mixed-methods design was used to evaluate the TPT cascade and explore its facilitators and barriers among PLHIV availing care from 12 PEPFAR-supported health facilities in Uganda. The quantitative component included analysis of routine programmatic data, and the qualitative component included focus group discussions and in-depth interviews with healthcare workers and PLHIV. A total of 1349 PLHIV were enrolled in the evaluation. Among PLHIV newly initiated on ART (≤3 months), 74% started TPT, and 98% of them completed it. In PLHIV already on ART, 87% had initiated TPT (76% before and 11% during this evaluation), with a treatment completion rate of 98%. The facilitators for TPT implementation included access to shorter TPT regimens, integration of services, and adherence counseling. Barriers included knowledge gaps, pill burden, TPT drug stock-outs, and documentation inconsistencies. The TPT completion rate was higher than the national target (90%), but the TPT initiation remains low. Improved access to shorter regimens, adherence counseling, better documentation, and service integration can sustain the completion rate and improve the initiation rate in Uganda and possibly elsewhere. Full article

Background: Human immunodeficiency virus (HIV) affects more than 39 million people worldwide, with Uganda ranked 10th among countries with the highest number of cases. As new preventative HIV injectables emerge, it is vital to think about how best to tailor strategies to promote these injectable drugs, like PrEP and vaccines, when available, to the different populations most in need. Discrete choice experiments (DCEs) are economics-derived methods used to determine factors that influence engagement in a certain behavior. Objective: This study used a DCE to determine the preferences for a preventative HIV injectable drugs/vaccines among people at risk of HIV acquisition in urban and peri-urban areas of Uganda. Methods: In June 2024, we implemented a cross-sectional DCE survey in three urban sites in Uganda in English and Luganda. The survey collected information on demographics, HIV risk, vaccine confidence and responses to the 13 injection product choice tasks presented to determine preferences. We used community-based, respondent-driven sampling methods to recruit participants from three key populations: (1) female sex workers; (2) people who identify as lesbian, gay, bisexual or transgender; and (3) young women (18–24 years). We collected the data on tablets using the Sawtooth Lighthouse Studio software (v. 19.15.6), taking into consideration privacy and confidentiality, given the sensitivity of the information and recent governmental policies in Uganda. Data were analyzed using a split-sample mixed logit regression analysis. The study was approved by local ethical regulatory bodies. Results: From the total of 406 participants screened for this study, 376 participants met the eligibility criteria and were included in the final analysis (85 young women, 159 female sex workers, and 132 who identified as lesbian, gay, bisexual or transgender). The average age was 23.7 (SD: 5.7). The majority of participants had received some secondary school or vocational school (202, 53.7%) The attributes that explained the preferences were primarily severe compared to mild side effects (β: −0.69, 95% CI: −0.78, −0.60), a 30% increase in vaccine/drug effectiveness (β: 0.39, 95% CI: 0.34, 0.44), and a 50,000 UGX (or USD ~13.64) increase in cost (β: −0.22, 95% CI: −0.27, −0.17). There were no significant differences between the preferences for different injectable types. The sensitivity analyses suggested potential differences in preferences by the amount of help participants received from research assistants when completing the survey, although not by income level. Conclusions: Side effects had the greatest impact on participants’ preferences for injectable HIV prevention methods, followed closely by effectiveness and cost. It is therefore essential to develop affordable or free prevention options with minimal side effects. Policymakers should focus on reducing the financial barriers to access and emphasize transparent communication about the effectiveness and safety of these injectables in health promotion campaigns to maximize adoption and improve public health outcomes. Full article

HIV remains a significant public health challenge in sub-Saharan Africa (SSA), with vulnerable communities disproportionately affected and further marginalised by the COVID-19 pandemic. HIV self-testing (HIVST) has emerged as a transformative, empowering tool to bridge testing gaps and promote health equity. This study examined post-COVID-19 strategies for leveraging HIVST to empower vulnerable populations and advance health promotion in SSA. Analysis was performed using secondary Demographic and Health Survey (DHS) data (2015–2022) collected across 24 SSA countries. In addition, qualitative interviews were conducted with female sex workers in Port Harcourt, Nigeria (18–31 May 2023). The study adopted an explanatory sequential mixed-methods design. Quantitative analysis using complex sample logistic regression revealed low awareness (16.3%) and uptake (2.5%) of HIVST among the 594,639 respondents. Key predictors of uptake included higher education (aOR, 7.36; 95% CI, 6.62–8.18), wealth (richest quintile aOR, 3.28; 95% CI, 2.95–3.65), and knowledge of HIV transmission (aOR, 33.43; 95% CI, 11.03–101.24). Thematic analysis highlighted privacy, autonomy, and convenience as key benefits, while cost, stigma, and fear of testing alone were major barriers. The participants emphasised peer-led outreach and integration of HIVST into public health systems as effective strategies. The findings were integrated interpretively, linking macro-level testing disparities with community-level experiences to inform post-pandemic policy and programme design. The study concludes that HIVST holds strong potential to empower marginalised groups and strengthen community-driven HIV prevention post-COVID-19, but success will depend on equity-driven policies and sustainable implementation frameworks, guided by affordability and community participation. Full article

Background: Vaccine hesitancy (VH) remains a major threat to global health that can reverse the progress in tackling vaccine-preventable diseases. Vaccine uptake among adolescent Girls and young women (AGYW) is often low. We assessed VH using a validated scale among AGYW in Uganda, Zambia, and South Africa. Methods: From June 2023 to February 2024, we recruited AGYW from fishing communities in Uganda, urban and peri-urban locations in Lusaka and Ndola, Zambia, and mining communities in Rustenburg, South Africa. Eligible participants were aged 15–24 years, sexually active, and HIV-negative but at risk for HIV acquisition. We collected demographic, HIV-related behavioral data, and vaccine hesitancy data using a structured questionnaire. Vaccine confidence was assessed using the 10-question Vaccine Hesitancy Scale that describes two factors, i.e., “vaccine confidence” and “risk tolerance”. Exploratory and Confirmatory Factor Analyses were performed to assess scale validity and internal consistency. Logistic regression was used to determine associations between demographics and vaccine confidence. Results: A total of 1213 AGYW participated in the study, with a mean age of 19.4 (SD ± 2.6) years. More than half (54%) were aged between 15 and 19 years. The majority of AGYW (94%) strongly believed that vaccines were important for their health and the community and that vaccination is a good way to protect them from diseases. About two-thirds of the AGYW (66%) indicated that they were concerned about the adverse effects of vaccines, while 30% responded that they did not need vaccines for diseases that were not common. We observed that 951 (78%) of the AGYW reported high vaccine confidence, while 494 (41%) reported low concerns over risks. Vaccine confidence varied across countries, with Zambia and Uganda showing lower vaccine confidence (adjusted odds ratios of 0.28 and 0.45, respectively, p < 0.005) in comparison to South Africa. Conclusions: A high level of vaccine confidence was observed among AGYW. Vaccine confidence among AGYW was driven more by the trust in vaccine safety and the need to protect communities against diseases. These findings suggest the potential for acceptance of vaccines, including future HIV vaccines, among AGYW. Despite high levels of vaccine confidence, concerns over vaccine risks remain substantial and must be addressed. Full article