HIV and syphilis are sexually transmitted diseases (STDs) that share transmission routes and risks factors. Many countries face the dual challenge of HIV and syphilis epidemics. Co-infection can mutually accelerate disease progression and increase transmission risk, posing a major challenge to global public health. This retrospective study was based on a cohort of people living with HIV (PLWH). All PLWH diagnosed between 2016 and 2023 were included. The Chi-square test was used to compare demographic and clinical characteristics between groups. Factors associated with syphilis co-infection were assessed using multivariate logistic regression, with adjusted odds ratio (aOR) and 95% confidence interval (95%CI) estimated. Kaplan-Meier analysis was used to estimate the cumulative probability of immune reconstitution (IR) and virological failure (VF) in syphilis co-infection versus HIV mono-infected individuals. Multivariate Cox regression was used to evaluate adjusted hazard ratio (aHR) and 95% CI for factors associated with IR and VF. To reduce potential confounding, we used propensity score matching (PSM) to balance baseline covariates between the syphilis co-infection and HIV mono-infection groups. All statistical analyses were performed by SPSS 23.0 and R 4.3.3. Among 39,924 PLWH in Jiangsu Province (2016-2023), the prevalence of syphilis co-infection was 14.1% (5,645/39,924). Factors independently associated with higher odds of co-infection included age < 60 years, male sex, current HIV stage, single, Han ethnicity, history of STDs, and homosexual HIV transmission. In the IR analysis, 56.6% of PLWH achieved IR. After stratifying by syphilis stage, primary syphilis was associated with a higher probability of IR before matching (log rank P < 0.001), but this difference disappeared after PSM (log rank P = 0.99). Latent syphilis showed no significant association with IR. In the virological failure (VF) analysis, latent syphilis co-infection was associated with an increased risk of VF in Cox regression models both before (log rank P = 0.0011) and after PSM (log rank P = 0.0032). Primary syphilis had no significant effect on VF. Younger age at ART initiation, early HIV stage, higher baseline CD4+ T cell count, and college or higher education were protective against VF and/or promoted IR. HIV/syphilis co-infection prevalence was high among PLWH in Jiangsu. Latent syphilis co-infection independently increases the risk of VF. Younger age at ART initiation, current HIV stage, and higher education protected against VF and/or promoted IR; male, migrant, and homosexual HIV transmission were risk factors for poorer IR. Integrated screening and management of syphilis are essential to optimizing HIV treatment outcomes.
The emergence of antimicrobial resistant gonorrhoea among men who have sex with men (MSM) demands new prevention strategies. This study aims to assess the efficacy of the 4CMenB vaccine against gonorrhoea among MSM. A prospective randomised double-blind placebo-controlled trial (NCT05766904) was conducted in Hong Kong in 2023-2024. In total, 152 MSM aged between 18 and 50 years were randomised to either vaccination or control with a 1:1 ratio using permuted blocks of four. Participants received two injections at least one month apart and attended trimonthly follow-ups for two years. The primary outcome was the incidence of the first gonorrhoea episode in one first year. Gonorrhoea incidence in the two arms were comparable (control arm 0.78 (95% confidence interval [CI] 0.64-0.95); vaccine arm 0.86 (95% CI 0.77-0.96); hazard ratio 0.76, 95% CI 0.31-1.87). Participants in the vaccine arm were more likely to experience adverse effects, be less worried about acquiring gonorrhoea (adjusted odds ratio 2.10, 95% CI 1.22-3.59), and have a lower condom use rate after unblinding. The results did not show efficacy of the 4CMenB vaccine against gonorrhoea in MSM. Receipt of the vaccine may impact risk perception and behavioural practice thus affecting vaccinee's exposure risk to STIs.
Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disease, predominantly affecting elderly patients with multiple comorbidities. This multicentre retrospective cohort study aimed to characterize the clinical profile, treatment patterns, and drug-associated cases of BP in a real-world setting. The study included 156 patients newly diagnosed with BP between 2020 and 2024 in four dermatology departments in Poland. Diagnosis was based on clinical features, and immunological assessment, including direct immunofluorescence (DIF), ELISA, and BIOCHIP-based indirect immunofluorescence. The mean age at diagnosis was 75.5 ± 10.9 years, and 78.85% of patients had at least one comorbidity, most commonly arterial hypertension, type 2 diabetes mellitus, and dyslipidemia. Severe pruritus was reported in 74.14% of evaluated patients. Blisters and erosions were the predominant clinical manifestations. Topical glucocorticosteroids were the most frequently used treatment, followed by systemic glucocorticosteroids and methotrexate. New drug exposure within 6 months before disease onset was identified in 14.74% of patients and was associated with a shorter time to diagnosis. Drug-associated cases showed lower BP180 ELISA positivity, although this did not remain significant after correction for multiple testing. These findings highlight the clinical complexity of BP and the importance of medication review and direct immunofluorescence in diagnostic evaluation.
Cervical cancer is a leading cause of cancer mortality among Ghanaian women, yet screening uptake is under 5%. The Cervical Cancer Prevention and Training Centre (CCPTC) partnered with Rotary Clubs across the country to implement the first-ever nationally representative cervical precancer screening project and to demonstrate the feasibility of an integrated nationwide screening program. We conducted a cross-sectional analysis of 1,636 asymptomatic women aged 25 years and above screened at 29 government and private facilities across all 16 regions of Ghana (January-February 2025). Eligible women underwent concurrent hr-HPV genotyping (Sansure MA-6000 platform) and VIA by CCPTC-trained alumni, with immediate thermal ablation for eligible VIA-positive lesions (TZ type 1 or 2). Multivariable logistic regression (backward stepwise elimination, P < 0.25 retention threshold) identified factors associated with hr-HPV positivity and VIA positivity. Analyses were performed in Stata v17.0. Among 1,636 women, the overall hr-HPV prevalence was 26·6% (95% CI, 24·5-28·8) and the VIA 'positivity' was 4·0% (95% CI, 3·1-5·0). Predominant genotypes were HPV52 (5·3%), HPV58 (4·4%), and HPV51 (3·6%); HPV16 and HPV18 together accounted for <5% of infections. Independent factors associated with hr-HPV infection were HIV infection (aOR=5·77; 95% CI, 2·07-16·13, P = 0.001) and having a steady partner (aOR=2·02; 95% CI, 1·22-3·36, P = 0.006); being married/cohabiting (aOR=0·51; 95% CI, 0·38-0·69, P < 0.001) or widowed (aOR=0·43; 95% CI, 0·23-0·82, P = 0.011), and prior screening (aOR=0·67; 95% CI, 0·48-0·92, P = 0.014) were protective. VIA 'positivity' was independently associated with HIV infection (aOR 7.49, 95% CI 1.99-28.19, P = 0.003). Regional hr-HPV prevalence varied from 10·0% to 39·2%. Thirty-five percent of VIA-positive women received same-visit thermal ablation. This decentralized alumni-driven model integrating off-site HPV testing, task-shifted VIA, and immediate thermal ablation proved operationally feasible across Ghana's diverse health system and revealed a substantial hr-HPV burden. The approach offers a scalable blueprint for national cervical cancer control and informs Ghana's transition toward HPV-based screening.
Human papillomavirus (HPV) infection causes cervical cancer. The objective of the study is to monitor AS04-adjuvanted HPV-16/18 vaccine (Cervarix, GSK) safety in a real-world setting in China, using electronic health records from the Yinzhou Regional Health Information Platform (YRHIP). This retrospective observational cohort study included all permanent residents (males and females) aged 9-45 y with ≥12 months continuous YRHIP registration between 1 January 2010 and 31 December 2020. The study analyzed demographic information, diagnoses coded using International Classification of Diseases 10th Revision for potential immune-mediated diseases (pIMD) and pregnancy-related outcomes, and HPV vaccination records. Of 1,002,399 participants in the YRHIP, 891,463 met the eligibility criteria. In the age group 9-45 y, uptake of AS04-adjuvanted HPV-16/18 vaccine was 11.95/1000 persons. The incidence density for other spondylopathies, sarcoidosis, and pulmonary sarcoidosis was significantly higher in females vaccinated with any dose of AS04-adjuvanted HPV-16/18 vaccine compared with females who did not receive HPV vaccination during the study period (p < .01). No causal relationship could be established due to confounding factors and potential misclassification. The GSK safety database or EudraVigilance database were reviewed and no signals associated with these events were identified. For other pIMDs and adverse pregnancy-related outcomes, no increased incidence was found for vaccinated females. While certain pIMDs demonstrated an increased incidence in vaccinated individuals, no causal association was confirmed. Further research is needed to address residual confounding factors and validate findings. The overall safety profile of AS04-adjuvanted HPV-16/18 vaccination in Chinese girls and women aged 9-45 y could be considered as favorable.Clinical Trial Registration:Retrospectively registered on http://www.chinadrugtrials.org.cn/index.html, 22 March 2021, registration number CTR20210523. What is the context? Human papillomavirus (HPV) infection can cause cervical cancer, which is among the most common cancers in Chinese women.The AS04-adjuvanted HPV-16/18 vaccine (Cervarix, GSK) was the first HPV vaccine approved in China, in 2016, to help prevent cervical cancer.This study used healthcare data from Yinzhou District, China, to monitor the real-world safety of the AS04-adjuvanted HPV-16/18 vaccine in girls and women aged 9–45 y.What did this study show? Three immune-related conditions (spondylopathies, sarcoidosis, and pulmonary sarcoidosis) were found more often among women who received any dose of the AS04-adjuvanted HPV-16/18 vaccine compared with those who were unvaccinated.However, these findings could not confirm a causal link to the vaccine. The study could not fully account for factors such as lifestyle, environment, or misclassification of diagnoses, and no similar findings were observed in GSK’s or European safety databases.Women who received the AS04-adjuvanted HPV-16/18 vaccine were more likely to have a live birth and less likely to have a therapeutic abortion or elective termination compared with unvaccinated women, with no difference for other pregnancy outcomes.What is the impact? The overall safety profile of the AS04-adjuvanted HPV-16/18 vaccination in Chinese girls and women aged 9–45 y remains favorable.
Adolescent pregnancy remains a significant public health concern across Africa, with Eastern and Southern regions experiencing the highest burden. Among adolescents living with HIV(ALHIV), the challenge is intensified by socio-economic, cultural, and healthcare factors that increase vulnerability to unintended pregnancy. This systematic review examined the prevalence of unplanned pregnancy and associated factors among adolescents living with HIV in Africa. Following PRISMA guidelines and registered in PROSPERO (CRD42024564479), a search of Medline, EMBASE, and CINAHL identified relevant studies published between 2011 and 2023. Of the 550 retrieved articles, only three met the inclusion criteria. Reported prevalence rates varied widely, ranging from 18.8% in South Africa to 60.0% and 73.9% in Kenya, indicating a substantial and uneven burden across settings. Factors associated with unintended pregnancy included involvement with boyfriends or acquaintances rather than spouses, reflecting limited agency and structural vulnerabilities. Documented adverse outcomes included miscarriage, stillbirth, and abortion, although one study did not specify outcomes. Overall, the review highlights persistently high rates of unplanned pregnancy among adolescents living with HIV and underscores the need to integrate sexual and reproductive health services into HIV care, address stigma, and strengthen context-specific interventions. Les grossesses adolescentes demeurent un problème majeur de santé publique en Afrique, les régions de l'Est et du Sud étant les plus touchées. Chez les adolescentes vivant avec le VIH (AVVIH), ce défi est exacerbé par des facteurs socio-économiques, culturels et liés aux soins de santé qui accroissent leur vulnérabilité aux grossesses non désirées. Cette revue systématique a examiné la prévalence des grossesses non planifiées et les facteurs associés chez les adolescentes vivant avec le VIH en Afrique. Conformément aux directives PRISMA et enregistrée dans PROSPERO (CRD42024564479), une recherche dans Medline, EMBASE et CINAHL a permis d'identifier les études pertinentes publiées entre 2011 et 2023. Sur les 550 articles recensés, seuls trois répondaient aux critères d'inclusion. Les taux de prévalence rapportés variaient considérablement, allant de 18,8 % en Afrique du Sud à 60,0 % et 73,9 % au Kenya, ce qui témoigne d'une prévalence importante et inégale selon les contextes. Parmi les facteurs associés aux grossesses non désirées figurait le fait d'avoir des relations avec des petits amis ou des connaissances plutôt qu'avec des conjoints, reflétant un manque d'autonomie et des vulnérabilités structurelles. Les issues défavorables documentées incluaient les fausses couches, les mortinaissances et les avortements, bien qu'une étude n'ait pas précisé ces issues. Globalement, cette analyse met en évidence des taux toujours élevés de grossesses non désirées chez les adolescentes vivant avec le VIH et souligne la nécessité d'intégrer les services de santé sexuelle et reproductive aux soins du VIH, de lutter contre la stigmatisation et de renforcer les interventions adaptées au contexte.
Latently infected resting CD4+ T cells represent the principal barrier to HIV eradication. Their immunological quiescence renders them invisible to combination antiretroviral therapy (cART) and host immune surveillance, sustaining a reservoir that mandates lifelong treatment. The 'shock and kill' strategy seeks to reverse this latency using pharmacological latency-reversing agents (LRAs) so that immune effectors and cART can eliminate reactivated cells. In this narrative, structured review, we examine histone deacetylase inhibitors (HDACis) as LRAs from a medicinal chemistry perspective. The review places particular emphasis on structure-activity relationship (SAR), isoform selectivity, and the mechanistic basis of differential clinical performance, synthesizing evidence from preclinical, ex vivo, and clinical studies published between 2010 and 2026. Four structural classes of HDACis-hydroxamic acids, benzamides, cyclic depsipeptides, and short-chain fatty acids-differ substantially in isoform selectivity, potency, pharmacokinetics, and tolerability. No single agent has achieved statistically significant reservoir reduction in clinical trials, highlighting the apparent inadequacy of the 'shock' phase alone and suggesting a need for complementary 'kill' strategies. Rational design of HDACis informed by isoform-selective SAR, combined with emerging combination LRA strategies and immunological 'kill' components, represents a promising direction toward a functional HIV cure, though substantial translational hurdles remain.
National prevalence estimates of chlamydia and gonorrhoea are essential to inform public health strategies and support evidence-based policy development. The aim was to generate national prevalence chlamydia and gonorrhoea estimates in 2022/2023, identify associated risk factors and compare prevalence over time. Five years after the first survey in 2016/2017, a second national cross-sectional probability sample survey about sexual health among men and women aged 16-34 years in the Netherlands was conducted between October 2022 and March 2023. Sexually active survey participants were invited to participate in the prevalence study and received a home-based sampling kit. Returned samples were tested for chlamydia and gonorrhoea in a laboratory (ie, nucleic acid amplification test). Weighting techniques were used to correct for selective non-response. Multivariable logistic regression analyses were performed to identify risk factors of infection. Of 6277 survey participants invited for the prevalence study, 1142 (18.2%) returned a specimen. The weighted overall chlamydia prevalence was 3.5% (95% CI 2.3% to 5.4%), and prevalence was higher in younger age groups (<25 vs ≥25 years). Due to low numbers in other groups, risk factor analysis was only possible among women aged 18-24 years, where risk factors for chlamydia included being <20 years, vocational education, no steady relationship and condomless sex. As in 2016/2017, no gonorrhoea cases were detected in 2022/2023. Chlamydia prevalence and associated risk factors did not change, except for higher prevalence among university-educated individuals in 2022/2023. Chlamydia prevalence among young sexually active men and women in the Netherlands remained stable between 2016/2017 and 2022/2023, with higher prevalence observed in younger age groups in both studies. Given recent changes in chlamydia testing guidelines in the Netherlands towards more restrictive testing of asymptomatic individuals, probability sample surveys with laboratory-confirmed STI testing are crucial for monitoring prevalence trends and evaluating public health policy.
Research on cervical cancer among WLWH represents a critical area for advancing long-term prevention and clinical management strategies. Yet as the volume of published literature in this field continues to grow rapidly, synthesizing and appraising the available evidence in a comprehensive manner has become increasingly challenging. This study aims to map the global research landscape, identify leading contributors and collaborative networks, and delineate the knowledge base and emerging research priorities in HIV-associated cervical cancer through a bibliometric analysis of multiple databases. Particular attention is given to the molecular and immunological mechanisms underlying the synergistic oncogenic interaction between HIV and high-risk HPV, as well as current trends in translational clinical research. Publications on HIV and cervical cancer from January 1, 1990, to December 31, 2025 (n = 6,137) were retrieved and analyzed using bibliometric and visualization tools, including R (bibliometrix), Python, VOSviewer, and CiteSpace. Analyses encompassed publication trends, collaboration networks, keyword co-occurrence, and thematic evolution. Research output has increased steadily, led by the United States, followed by China, South Africa, India, and the United Kingdom. The most productive journals include International Journal of Cancer and AIDS, which are also among the most frequently cited. The seminal reference is "Cancer-related Inflammation." Emerging research frontiers center on cervical cancer screening, WLWH, human papillomavirus vaccination, and deep learning. Future directions will likely emphasize lifecycle vaccination strategies for WLWH, precision therapies guided by the immune microenvironment, and scalable screening approaches for low-resource settings. These findings provide evidence-based insights to inform global health policy and accelerate cervical cancer elimination efforts.
This retrospective cross-sectional study aimed to characterize HIV-1 genotypes, assess drug resistance, and analyze molecular transmission networks in Zhongwei City to inform prevention strategies. Plasma samples were collected from antiretroviral therapy (ART)-treated patients (2007-2024) with viral load ≥ 200 copies/mL. HIV-1 pol was amplified by nested PCR; successful sequences were genotyped by maximum likelihood (ML) (IQ-TREE, TVM+F+I+G4, 1000 bootstrap). Drug resistance (DR) was interpreted using Stanford HIV Drug Resistance Database (HIVDB) v9.0; detected mutations represent acquired drug resistance (ADR). Pairwise genetic distances (GD) (TN93 model) were calculated; transmission networks were constructed in Cytoscape 3.10.3. 75 sequences were obtained. Males (84.00%), and heterosexual transmission (64.00%) predominated. CRF07_BC (46.67%) and CRF01_AE (38.67%) were the major subtypes; the overall ADR rate was 40.00%, mainly NNRTIs-associated (30.67% of all participants, including 16.00% single-class NNRTIs and 14.67% dual-class NRTIs-NNRTIs). Network inclusion rate was 40.00% of the 75 sequences; CRF07_BC showed higher betweenness centrality (p = 0.028), while CRF01_AE and CRF85_BC showed higher closeness centrality (p < 0.001). Occupation significantly affected network enrollment (p ≤ 0.05). HIV-1 subtypes are diverse with high ADR. CRF07_BC may act as a transmission bridge, whereas CRF01_AE and CRF85_BC exhibit faster potential spread. Baseline DR testing and network-guided interventions are recommended.
The diversity and abundance of the brain virome is an active field of investigation. However, how the brain virome relates to the presence of viruses outside of the nervous system remains unclear. The rationale for this study is that analyses across multiple biologically linked compartments within the same individuals provide an important opportunity to evaluate virome discordance and viral burden. To characterize viral prevalence and burden across anatomical compartments, we applied the targeted viral enrichment method ViroFind to matched postmortem brain (n = 66), cerebrospinal fluid (CSF; n = 24), and peripheral samples (spleen, peripheral blood mononuclear cells, and lymph nodes; n = 66) from individuals with and without human immunodeficiency virus (HIV) infection and substance use disorder (SUD) in the National NeuroAIDS Tissue Consortium. We detected nucleic acids from 27 viruses representing 12 taxa. Several viruses, including adenovirus, torque teno virus, Epstein-Barr virus, human herpesvirus 6 and 7, cytomegalovirus, parvovirus, and JC polyomavirus, showed significant inter-compartment differences in prevalence or burden. CSF exhibited lower overall viral diversity than brain or peripheral samples, whereas peripheral samples showed the highest viral burden. CNS viral detection was more likely when the same virus was also detected in the periphery. We also detected HBV and HCV in CNS samples despite them not being classically regarded as neurotropic. Broader virome profiling showed greater peripheral viral burden and diversity in HIV-positive than HIV-negative individuals, whereas SUD was not associated with overall viral burden differences. These findings highlight important cross-compartment differences in viral detection, including occurrence of occult HBV infection within the CNS, and support the value of CNS-periphery comparisons in virome studies. These findings can contribute to improved diagnosis and management of viral infections.
Persistent high-risk human papillomavirus infection is a critical prerequisite for cervical intraepithelial neoplasia and cervical cancer, yet viral factors alone do not fully explain why most infections clear while a subset persists and progresses. Emerging longitudinal, multi-omics, and mechanistic evidence supports a plausible model in which the cervicovaginal microbiota is not a passive bystander but a functional determinant of mucosal immunity, epithelial barrier integrity, and local metabolic tone. Lactobacillus-dominant community states, particularly those enriched in Lactobacillus crispatus, are generally associated with lower pH, regulated inflammatory signaling, stronger barrier function, and a higher likelihood of HPV clearance. In contrast, anaerobe-enriched dysbiosis is linked to elevated pro-inflammatory cytokines, altered antigen presentation, immune checkpoint signatures consistent with T-cell dysfunction, and metabolic shifts involving lactate depletion and accumulation of short-chain fatty acids and other metabolites that can influence epithelial and immune-cell programs. Importantly, the interaction is bidirectional: hrHPV can remodel the microenvironment by suppressing host defense peptides and perturbing mucosal barriers, thereby reducing Lactobacillus fitness and reinforcing dysbiosis in a feed-forward loop that favors persistence and oncogenic progression. This review integrates functional ecology, longitudinal clinical evidence, immunological and metabolic mechanisms, and translational implications, highlighting opportunities for microbiome-informed risk stratification and adjunctive interventions, as well as key gaps requiring standardized longitudinal multi-omics and rigorously designed clinical trials.
Lesbian, gay, bisexual, transgender, queer, intersex, asexual, and other sexually and gender-diverse populations (LGBTQIA+) are at risk for sexually transmitted infections (STIs). This survey assessed knowledge, attitudes, and vaccinations coverage for Human Papillomavirus (HPV), hepatitis A (HAV), hepatitis B (HBV), monkeypox (Mpox) and the associated determinants among 1944 LGBTQIA+ individuals in Italy. The survey was conducted between May and July 2025, through an internet-based questionnaire. Only 14.2% correctly identified HPV, HBV, HAV, and Mpox as STIs. Those younger, with university degree, in non-monogamous relationship, men who have sex with men, those with a chronic condition, with higher number of sexual partners in the last 12 months, those who were not binary, and who received information from healthcare workers (HCWs) were more knowledgeable. Only 31.7% considered all four vaccinations very useful, and this was more likely among those with university degree, in non-monogamous relationship, in homosexual, who received information from HCWs, who did not need additional information, who knew the sexual transmission of the infections, and reported condom use every time. Only 7.4% received all four vaccinations, while 39.6% received none. Younger age, having been tested for STIs, considering all vaccinations very useful, and having received information from HCWs were associated with higher uptake. Only 46.9% were willing to receive missing vaccinations. Younger age, non-monogamous relationship status, no prior testing for STIs, considering all four vaccinations very useful, higher perceived risk of being infected, having received one to three vaccinations, and needing additional information were associated with willingness. These findings highlight the role of HCWs in delivering information and prevention recommendations to improve knowledge and vaccination uptake.
Male circumcision (MC) has been shown in studies from South Africa, Kenya, and Uganda to reduce heterosexual Human Immunodeficiency Virus (HIV) transmission among men by approximately 50-60%. Despite Namibia's adoption of voluntary medical male circumcision (VMMC) as part of national HIV prevention strategies, uptake remains suboptimal in some communities. This study assessed the knowledge, attitudes, and perceptions (KAP) of male circumcision among men aged 20-40 years in Otjiwarongo, Namibia, and examined socio-demographic factors associated with these outcomes. A community-based cross-sectional survey was conducted between March and May 2024, involving 359 participants selected through multistage sampling. Data were collected using structured, pre-tested questionnaires and analysed using STATA version 19. Descriptive statistics, chi-square tests, and binary logistic regression were used to summarise data and identify predictors of favourable KAP outcomes. Overall, 69.1% of respondents demonstrated good knowledge of male circumcision, 72.7% had positive attitudes, and 69.9% reported positive perceptions. Awareness of male circumcision was high (91.9%); however, only 69.4% of participants recognised its role in reducing HIV infection risk, and notable misconceptions persisted regarding its protective effects and procedural aspects. Multivariable analysis showed that urban residence (AOR = 1.58; 95% CI: 1.03-2.42; p = 0.035) and higher education (AOR = 4.12; 95% CI: 1.21-14.02; p = 0.024) were significant predictors of favourable KAP outcomes. In addition, good knowledge was strongly associated with positive attitudes (AOR = 3.25; 95% CI: 2.01-5.26; p < 0.001) and perceptions (AOR = 2.87; 95% CI: 1.79-4.60; p < 0.001). In conclusion, while knowledge, attitudes, and perceptions towards male circumcision were generally favourable, important gaps and misconceptions remain. Targeted, culturally appropriate health education interventions are needed, particularly among rural and less-educated populations, to improve understanding and acceptance of VMMC as part of comprehensive HIV prevention strategies.
Drug resistance testing may improve the management of people living with HIV (PLWH) in several scenarios in low- and middle-income countries (LMICs). To guide assay development, the WHO published a target product profile (TPP) outlining two priority use cases (scenarios) for genotypic resistance testing: (1) PLWH with confirmed virological failure (VF) on an integrase strand transfer inhibitor (INSTI)-based regimen, such as tenofovir (TFV) disoproxil fumarate, lamivudine (3TC), and dolutegravir (DTG) and (2) heavily treated PLWH, including infants and young children, with confirmed VF after receiving multiple regimens including a boosted protease inhibitor (PI). An additional potential scenario includes PLWH testing positive for HIV-1 while on pre-exposure prophylaxis (PrEP). To identify drug-resistance mutations (DRMs) most likely to influence clinical management of PLWH in each WHO TPP scenarios and to inform development of assays that detect individual DRMs and the interpretation of sequence-based assays, we reviewed prevalence and in vitro susceptibility data on HIV-1 DRMs in the Stanford HIV Drug Resistance Database associated with the nucleoside RT inhibitor (NRTI), nonnucleoside RT inhibitor (NNRTI), PI, and INSTI classes and the capsid inhibitor lenacapavir. In the first scenario, the most informative NRTI DRMs were K65R and M184V/I; and the most informative INSTI DRMs were G118R, N155H, Q148H/K/R, and R263K. In the second scenario, a broader spectrum of DRMs is likely to be clinically relevant, including additional NRTI DRMs, the PI DRMs associated with reduced susceptibility to darunavir, and the NNRTI DRMs associated with reduced susceptibility to etravirine and doravirine. In PLWH testing positive for HIV-1 despite PrEP, the most informative NRTI and INSTI DRMs overlap with those in the first scenario, together with the capsid DRMs reported in persons experiencing VF while receiving lenacapavir. As global ART programs increasingly rely on INSTI-based regimens, and as the number of heavily treated individuals and difficult-to-treat pediatric cases grows, many LMICs have begun introducing HIV drug resistance testing for patient management. Although sequence-based assays provide the most comprehensive information for managing individual PLWH, assays that detect individual DRMs are also likely to be highly useful in the three WHO TPP scenarios.
HIV represents a significant public health challenge, contributing to increased mortality and morbidity in developing countries, particularly Sub-Saharan Africa. While HIV testing is crucial for early treatment and prevention, the uptake of the HIV testing among the adolescent and young adults in Botswana remains low. This study aims to predict barriers to HIV testing uptake among adolescents and young adults. A quantitative cross-sectional study was conducted. Data was obtained using a questionnaire employing a simple random sampling technique to collect the survey data. Statistical analysis involved descriptive statistics and multivariable logistic regression. A total of 353 participants were recruited. The prevalence of HIV testing uptake in the preceding 12 months was (64.9%; n = 229). Determinants associated with non-uptake of HIV testing included participants in casual relationships (OR 1.776,95%CI 0.998-3.160, P < 0.049), transactional relationships (AOR 1.098, 95% CI 0.189-6.382) compared with single participants. Additional determinants included residence beyond 5 km from HIV testing centers (OR 1.825, 95% CI 1.074-3.103, P < 0.026), and cohabiting (AOR 3.45, 95% CI 0.271-43.979). Religious affiliation was also predictive, with Christians (AOR 2.347, 95% CI 0.188-29.295), Muslims (AOR 1.765, 95% CI 0.046-59.506), and adherents of African traditional religions (AOR 1.718, 95% CI 0.084-35.004) exhibiting higher odds of non-testing compared with non-believers. Participants with negative attitudes toward HIV testing were 69% less likely to forgo HIV testing (OR 0.310, 95% CI 0.1704-3.103, P = 0.026) than those with positive attitudes. This study provides critical evidence on disparities in HIV testing among adolescents and young adults in Botswana, highlighting persistent gaps in access and utilization. These findings underscore the necessity for context-specific strategies that mitigate access barriers and address behavioral, structural, and socio-cultural determinants to optimize HIV testing uptake, advancing progress toward the UNAIDS 2030 target of zero new infections.
Host genetic susceptibility to urogenital Chlamydia trachomatis (Ct) reinfection remains poorly understood. Coding variants identified in prior genome-wide association studies (GWAS) explained only a small fraction of the risk of reinfection. Our goal in this study was to characterize whether more risk would be captured by sequence variation that traditional GWAS insufficiently captures. Specifically, we evaluated the risk attributable to SNPs present in regulatory, non-coding regions; post-transcriptional regulation by microRNAs (miRNAs) that may depend on sequence variation in either the miRNA or the target mRNA; and copy number variants (CNVs). We analyzed GWAS data from African American women with or without documented urogenital Ct reinfection. Fine mapping and independent association analyses identified 30 unique index single-nucleotide polymorphisms (iSNPs), which were expanded to variants in linkage disequilibrium. Regulatory annotation was performed using HaploReg, RegulomeDB, FORGEdb, rSNPBase, and GTEx. We examined whether genes identified in the Ct reinfection GWAS are targeted by known Ct infection-associated microRNAs using curated databases. Genome-wide CNV calling was conducted using SNP intensity data, followed by stringent quality control and gene-level association testing. Functional annotation prioritized 7 SNPs with strong regulatory evidence, with stringent criteria for regulatory relevance, using HaploReg, RegulomeDB, FORGEdb, and rSNPBase. The strongest signals were observed at the CHIT1 locus, where multiple intronic variants (including rs2486963 and rs2244385) overlapped regulatory chromatin, altered transcription factor binding motifs, and acted as cis-expression quantitative trait loci for CHIT1 in whole blood. Additional regulatory variants were identified near TDRP, ERICH1, and DLGAP1, showing tissue-specific regulatory effects. MicroRNA analysis revealed extensive post-transcriptional targeting of SOCS6 and SULF1, while CHIT1 showed no curated Ct-associated miRNA interactions. CNV analysis identified 5775 high-confidence events, with nominal gene-level associations observed for ATAD3A, CARD14, TMEM240, and ZNF140. These results indicate that a greater fraction of the susceptibility to urogenital Ct reinfection may be driven by genetic variation affecting immune and epithelial pathways rather than protein-coding changes.
Protease inhibitors (PIs) remain important components of HIV-2 treatment, but resistance genotyping is frequently challenging in individuals with low or undetectable plasma viremia. Proviral DNA sequencing may provide access to archived viral variants and improve understanding of long-term resistance and clinical evolution. In this retrospective longitudinal study, 27 individuals with HIV-2, both ART-experienced and ART-naïve, followed at a hospital in Lisbon, were analyzed. The HIV-2 protease gene was amplified from peripheral blood mononuclear cell-derived proviral DNA, cloned, and sequenced (Sanger sequencing) at baseline and, for ART-treated participants, after eight years of follow-up. Resistance profiles were interpreted using the Stanford HIVdb, HIV-2EU, and Rega algorithms. Clinical data, including ART history, CD4 counts, and plasma viral load, were collected longitudinally. Amino acid diversity was assessed using Shannon entropy, and longitudinal CD4 dynamics were evaluated using mixed-effects models with time-varying ART exposure. Sensitivity analyses were performed using generalized estimating equations (GEE). A total of 222 clonal HIV-2 protease sequences clustered within group A. Major PI resistance mutations were detected in 21.4% of ART-experienced and 23.1% of ART-naïve individuals at baseline. Longitudinal resistance trajectories varied across participants, including persistence, apparent emergence, and non-detection of previously identified mutations. Mixed-effects modeling revealed substantial inter-individual variability in CD4 trajectories, with no statistically significant associations observed between CD4 evolution and ART status, time, or their interaction. GEE analyses yielded consistent results, supporting robustness across modeling frameworks. Entropy analysis identified localized sequence diversity changes restricted to a small number of protease residues, with positions 60 and 75 differing between groups at baseline and position 21 showing longitudinal variation among treated participants. This study demonstrates that proviral DNA sequencing captures archived HIV-2 protease diversity and reveals persistent and dynamic resistance patterns within the viral reservoir. While no population-level association between ART exposure and CD4 trajectory was observed, marked inter-individual variability highlights the complexity of longitudinal immune recovery in HIV-2 infection. These findings support the value of proviral sequencing as a complementary research tool for characterizing long-term viral evolution in settings where plasma-based genotyping is limited.
Background and Objectives: Head and neck squamous cell carcinoma (HNSCC) is a biologically heterogeneous malignancy with variable clinical behavior and prognosis. Human papillomavirus (HPV)-associated tumors represent a distinct subgroup; however, data from Eastern European populations remain limited. This study aimed to evaluate the association between HPV DNA status and nodal involvement in a Bulgarian HNSCC cohort and to explore whether HPV genotype distribution is related to nodal involvement and therapeutic strategy. Materials and Methods: A prospective multicenter observational study with a cross-sectional analytical endpoint was conducted. Fifty patients with histologically confirmed HNSCC were included. Clinical and pathological data were collected, and HPV detection and genotyping were performed using molecular-based methods. Associations between HPV-related variables, nodal status (N0 vs. N+), and treatment strategy were evaluated using univariate tests. HPV status reflects DNA detection only and does not confirm transcriptionally active infection. Results: HPV DNA positivity was identified in 15/50 patients (30.0%). A higher proportion of nodal involvement was observed among HPV-positive patients compared with HPV-negative patients (46.7% vs. 17.1%, p = 0.040; crude OR = 4.23); however, this finding may be influenced by anatomical site distribution. In unadjusted analysis, HPV DNA positivity showed a relationship with nodal involvement (crude OR = 4.23; p = 0.040), although this should be interpreted cautiously. Multivariable analysis was not performed due to the limited number of outcome events. Differences in treatment allocation were observed between HPV-positive and HPV-negative patients; however, this finding may be confounded by anatomical site distribution and likely reflects differences in tumor localization rather than HPV-specific effects. Genotype analysis revealed heterogeneity, including multiple HPV types. Conclusions: HPV DNA positivity was observed in relation to nodal involvement in unadjusted analysis; however, this finding may be confounded by anatomical site and should be considered exploratory.
Fixed drug eruption (FDE) is a common cutaneous adverse reaction characterized by recurrent, well-demarcated lesions appearing at the same site upon re-exposure to a causative drug. Genital involvement represents one of the most frequent mucosal localizations in men but remains poorly described in the literature, often leading to diagnostic confusion with sexually transmitted infections. We aimed to systematically review the epidemiological, clinical and etiological characteristics of male genital FDE. A systematic review was conducted according to PRISMA 2020 guidelines. Medline, Google Scholar, Embase and the Cochrane Library were searched for articles published between 1970 and 2024, using predefined keywords relating to FDE and male genital involvement. Eligible publications included case reports and case series describing genital FDE in adult male patients. Data on demographics, clinical presentation, drug triggers, diagnostic methods and extragenital involvement were extracted. Weighted medians and means were calculated when applicable. Seventy studies were included, encompassing 262 male patients. The weighted median age was 35.5 years. Genital lesions were most commonly located on the glans penis (72.9%), followed by the shaft (17.6%), foreskin (12.2%), and scrotum (4.2%). Erythema (85.9%) was the predominant clinical presentation, while erosions (36.3%), bullae (26.7%), and post-inflammatory pigmentation (26.2%) were variably reported. In 79% of cases, genital involvement was isolated. Among extragenital sites, the oral mucosa was most frequently affected (54.5%). A causative agent was identified in 93.1% of patients. The most commonly implicated drugs were trimethoprim-sulfamethoxazole (27.9%), cyclines (20.9%), and NSAIDs (12.3%). The weighted median time to onset was 48 hours. Diagnosis relied solely on clinical history in 56.1% of patients, with oral provocation tests most frequently used when further allergy workup was performed. This review represents the largest synthesis of male genital FDE to date. The condition predominantly affects the glans and is most commonly induced by antibiotics and NSAIDs. Recognizing its characteristic presentation and drug associations is essential to differentiate it from sexually transmitted infections and avoid recurrent episodes.