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 management of male urinary tract infections (UTIs) has historically been based on a monolithic approach, under which every episode was treated as acute prostatitis, leading to prolonged antibiotic courses. To address rising bacterial resistance and promote antimicrobial stewardship, the French Infectious Diseases Society (SPILF) updated its guidelines in 2026, introducing a stratified management framework. This review outlines the scientific evidence underlying these updated recommendations. A comprehensive review of recent literature, including randomized controlled trials and large-scale retrospective cohorts, was conducted so as to evaluate antibiotic efficacy, resistance patterns, and optimal treatment durations for male cystitis, febrile UTIs (prostatitis/pyelonephritis), and acute epididymo-orchitis. Evidence validates distinguishing male cystitis from febrile UTI. For male cystitis, 7-day regimens using narrow-spectrum oral agents-such as fosfomycin trometamol, nitrofurantoin, or pivmecillinam-achieve satisfactory clinical success with minimal risk of complications. Conversely, febrile UTIs require initial parenteral third-generation cephalosporins or oral fluoroquinolones. For targeted oral step-down therapy in prostatitis, cotrimoxazole is preferred over fluoroquinolones so as to minimize ecological impact, while amoxicillin remains the drug of choice for enterococcal coverage. Although recent data show that seven days can be sufficient for selected bacteremic presentations, to prevent relapses a conventional 14-day duration remains the standard for acute prostatitis. Non-sexually transmitted orchitis and epididymitis require a 10-day course of fluoroquinolones or cotrimoxazole. The 2026 SPILF guidelines represent a paradigm shift toward a tailored, stratified approach.
Cryptococcal meningitis remains a leading cause of HIV-related mortality in sub-Saharan Africa despite expanded antiretroviral therapy coverage. Evidence on the burden of disease and inpatient mortality among people living with HIV (PLHIV) in routine care settings in Uganda remains limited. This study assessed the proportion of cryptococcal meningitis among HIV-related admissions and examined clinical factors associated with inpatient mortality. We conducted a retrospective cohort study of adult PLHIV admitted with cryptococcal meningitis between 1st/01/2017-31st/12/2022 at a national referral hospital in Uganda. Diagnosis was based on cerebrospinal fluid cryptococcal antigen or India ink positivity. Data were abstracted from medical records and analysed using descriptive statistics and multivariable logistic regression to identify factors associated with inpatient mortality. Specific antifungal treatment regimens were not consistently documented and could not be analysed. Of 3,042 HIV-related admissions, cryptococcal meningitis accounted for 21.4% (650/3,042). Medical records for 634 patients were analysed, among whom 39.3% (249/634) died during hospitalization. Factors independently associated with higher odds of inpatient mortality included convulsions, headache, vomiting, cryptococcal meningitis-associated immune reconstitution inflammatory syndrome, concurrent opportunistic infections, chronic kidney disease, anaemia, and severe immunosuppression (low CD4 cell count). Longer duration of hospitalization (≥7 days) and symptom duration of one to two weeks before admission were associated with lower odds of mortality. Cryptococcal meningitis continues to account for a substantial proportion of HIV-related hospital admissions and inpatient deaths in Uganda. Mortality is associated with identifiable clinical and health-system factors, underscoring the need for early diagnosis, risk stratification, and optimized inpatient management for PLHIV with cryptococcal meningitis in resource-limited settings.
Human papillomaviruses (HPVs) comprise more than 200 types associated with diverse clinical outcomes, ranging from benign lesions caused by low-risk types to cancers driven by high-risk types. These differences are partly driven by variation in the Long Control Region (LCR), a non-coding element that regulates viral gene expression through interactions with viral and host transcription factors (TFs). Although individual TF binding sites have been mapped in a few well-studied HPV types, the broader regulatory differences between high-risk and low-risk HPVs remain poorly defined. Here, we systematically analyzed LCR sequences from 207 HPV types using TF motif scanning and identified 104 TFs with significantly different binding site densities between risk groups. Integration with TCGA transcriptomics data showed that 50 of 69 TF enriched in high-risk types are expressed in HPV-positive head and neck tumors (HNSC) and 53 in HPV-positive cervical tumors (CESC). Analysis of published ChIP-seq datasets further confirmed LCR occupancy for seven of these TFs in HPV18-positive cells. In addition, conservation analysis across clinical isolates of HPV-16 and HPV-18 identified highly conserved TF binding sites overlapping multiple high-risk-enriched TF motifs, suggesting functional constraint on key regulatory elements. Together, these findings reveal distinct TF binding landscapes associated with HPV risk groups and identify candidate host regulators that may contribute to differences in viral transcriptional programs and oncogenic potential across HPV types.
Although the overall number of cervical cancer cases is declining worldwide, the incidence of this type of cancer is increasing in regions with low human papillomavirus (HPV) vaccination and cancer screening rates. In such regions, screening pregnant women can help improve the overall screening rate. Worldwide, cervical cancer screening is shifting from cervical cytology to HPV testing, which reduces the incidence of cervical cancer and, when negative, allows for longer screening intervals. Although HPV-based screening has been shown to be at least as effective as cytology screening for lesion detection in the general population, its performance during pregnancy remains poorly characterized due to the exclusion of pregnant women in previous clinical trials. The aim of this trial is to evaluate the effectiveness of an HPV testing protocol compared with that of a cervical cytology protocol for cervical cancer screening in pregnant women. This study is a multicenter, nonrandomized, single-arm comparative trial. In total, 5000 pregnant women aged 30 years and older in their first trimester will undergo both cervical cytology and HPV testing, with follow-up at 1 year. The primary end point is to assess the noninferiority of the HPV testing protocol compared with the cytology protocol for detecting cervical intraepithelial neoplasia grade 2 or higher, adenocarcinoma in situ, and invasive cervical cancer (CIN2+) in early pregnancy. In the cytology protocol, CIN2+ cases will be defined as those detected in cytology-positive participants. In the HPV protocol, CIN2+ cases will be defined as those detected in HPV-positive and cytology-positive participants. The primary end point analysis will use a one-sided 10% noninferiority test using the method by Tango, and with 5000 cases, the study can achieve a statistical power of at least 80%. Secondary end points will include an evaluation of the persistence of negative results post partum to determine the optimal screening interval in this population. The trial was funded in April 2024 and has already started. Data collection commenced in September 2024 and is scheduled to be completed by December 2026. As of March 2026, a total of 1906 participants have been recruited. Data analysis is currently planned to begin in December 2027, and the study findings are expected to be published in 2028. The results of this trial will clarify whether the HPV testing protocol should be adopted as the primary cervical cancer screening method for pregnant women or whether cervical cytology should remain the standard of care. DERR1-10.2196/86397.
Breast cancer (BC) is the most common cancer among women worldwide, with over 2.3 million new cases annually. Recent studies suggest that Human Papillomavirus (HPV), a known oncogenic virus, may be involved in BC development. This study investigates HPV prevalence in BC samples and its potential role in tumorigenesis. Random-effects meta-analyses were conducted to estimate raw proportions and odds ratio (OR), with 95% confidence intervals (CIs). Heterogeneity was assessed using I2. Statistical significance was set at p < 0.05. Analyses were performed in R 4.5.0 RESULTS: Our meta-analysis encompassed 82 studies and evaluated 7,683 breast cancer (BC) tissue samples to assess the presence of HPV. The overall prevalence of HPV in BC specimens was estimated at 23% (95%CI: 19%-28%). When stratified by continent, Oceania exhibited the highest regional prevalence at 38%. Comparative analysis between BC tissues and healthy controls revealed a significantly increased likelihood of HPV detection in the cancer group (OR 5.06; P < 0.001). This association remained statistically robust in both case-control (OR 6.34; P < 0.001) and cross-sectional designs (OR 2.83; P < 0.001). Among continents, South America demonstrated the most pronounced association (OR 11.66; P = 0.005). Subgroup analysis based on economic classification indicated that countries with low-income settings had the highest HPV prevalence (34%; 95%CI: 9%-73%). Evaluation by BC subtype revealed that luminal B had the highest HPV-positive rate (44%; 95%CI: 27%-61%). This meta-analysis reveals a global presence of HPV in BC and suggests a possible link. Further well-designed studies are needed to confirm its role in tumorigenesis.
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.
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.
Adolescent girls and young women who sell sex are at a heightened risk of acquiring HIV compared to those who do not. Their access to Sexual and Reproductive Health (SRH) services is also limited. This study explored the context of sex work for young female sex workers (YFSWs) and how they accessed sexual and reproductive health (SRH) services, including HIV services, to gain insights for enhancing demand for and access to these services. This study utilized an ethnographic research design involving 38 in-depth interviews and photovoice with YFSWs aged 18-24 years and six SRH program implementers. Thematic analysis was conducted with the aid of NVIVO software. Five themes emerged: (1) "Selling sex in a setting where it is illegal"; (2) Nature of SRH services available to YFSWs; (3) Stigma as a barrier to accessing services; (4) Preference for differentiated type of SRH services; and (5) Peer influencers in creating demand for SRH services. Participants reported that sex work was illegal in Tanzania and highly stigmatized. YFSWs operated discreetly for fear of police arrests, and stigma and discrimination. Stigma and discrimination hindered access to SRH services. Peers were important in influencing YFSWs' decision on whether to use or not and where and how to access the SRH services. YFSWS operate under stressful conditions and had limited access to SRH services. Peers of YFSWs played a key role in access to and use of SRH services. There is a need for differentiated care for YFSWs and building an enabling environment to motivate YFSW to access SRHs. Given the numerous challenges faced by YFSWs in accessing SRH services, interventions targeted at this group should focus on multi-level barriers: (a) at health facility level, provide differentiated SRH care/services that are friendly and trusted; (b) at community level, address stigma and social norms that promote gender inequalities; (c) at individual level, provide SRH knowledge and livelihood options and; and finally, (d) at policy level, address policies that criminalize sex work.
The second-generation integrase strand transfer inhibitors (INSTIs) are gradually replacing efavirenz (EFV) in antiretroviral therapy due to their superior efficacy and tolerability. However, there are still concerns about their long-term metabolic safety, particularly weight gain and dyslipidemia. In real-world settings, comparative evidence on the longitudinal metabolic effects of EFV, dolutegravir (DTG), and bictegravir (BIC) in the Asian population is still limited. This study evaluated the metabolic trajectories of these regimens and explored the mediating role of weight gain in hypertriglyceridemia (HTG). HIV-infected adults initiating EFV-, DTG-, or BIC-based regimens were included. Linear mixed-effects models assessed longitudinal changes in metabolic parameters. Growth mixture modeling (GMM) identified distinct BMI trajectories, and mediation analysis evaluated weight gain's role in incident HTG.The mediation analysis for incident HTG was performed in a sub-cohort of 492 participants with normal baseline triglyceride (TG) levels. In the study population, the baseline characteristics, including education, WHO clinical stage and viral load, differed significantly. Both the DTG and BIC groups exhibited significantly faster increases in BMI and FBG over time than the EFV group (P interaction < 0.05). Regarding lipids, the DTG regimen demonstrated a generalized effect of increasing TG, whereas the BIC regimen significantly accelerated TG elevation, specifically in individuals with normal baseline levels. GMM identified a distinct "BMI increasing" trajectory (17.7% of participants). Crucially, mediation analysis revealed that the risk of incident HTG associated with INSTI-based regimens was fully mediated by weight gain (indirect effects, P < 0.05), with no significant direct drug effects. Compared to EFV-based regimen, DTG- and BIC-based regimens are associated with time-dependent weight gain and hyperglycemia. The risk of incident HTG associated with these regimens is primarily driven by progressive weight gain rather than by direct drug toxicity. Monitoring dynamic BMI trajectories is essential for early identification of metabolic risk.
Community-based facilities delivering HIV services to key populations often face significant operational and financial challenges, making the quality of management in these organizations particularly important. A growing body of evidence links management quality to health facility performance. However, research on management in health facilities has focused largely on structural characteristics and formal qualifications, with less attention to the non-cognitive characteristics of managers themselves, particularly personality traits. This is a cross-sectional, quantitative analysis of 45 facilities providing HIV services to key populations in Kenya and Malawi. The analysis includes two stages. We first use k-means cluster analysis on management practice data to identify sub-groups of facilities that share similar management profiles. We then use non-linear logit regression models to predict the probability of facilities belonging to each sub-group as a function of manager personality traits, controlling for manager education, experience, and facility location characteristics. We used the Big Five Inventory to measure personality traits. We found two clusters of facilities with statistically different levels of managerial capacity. The higher-capacity cluster shows stronger financial and people management, more developed performance monitoring and target setting, better operations management, and greater community involvement in financial decisions. In the non-linear logit models, educational achievement was not statistically significant. Manager experience working with HIV key populations and higher scores on the Stability meta-trait were positively and significantly associated with the probability of belonging to the high-managerial capacity cluster. The personality traits of managers, together with their technical and cognitive skills, are relevant to the selection and support of managers in these organizations.
Dermatophilus congolensis is traditionally regarded as a zoonotic skin pathogen. Recent European reports suggest possible transmission among men who have sex with men (MSM). We describe four microbiologically confirmed cases in Stockholm, Sweden, in 2026. All occurred in MSM using HIV pre-exposure prophylaxis and without contacts with animals. Infections were probably acquired in Sweden, Japan and Spain. These findings support transmission within sexual networks and suggest that dermatophilosis may be under-recognised in sexual health settings.
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.
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.
The intersection of cannabis and sexual behaviors poses important public health concerns, particularly following Thailand's cannabis decriminalization. However, evidence on how cannabis use relates to sexual and HIV prevention behaviors among young adults in this policy context remains limited. This mixed-methods study aimed to assess cannabis use patterns and their associations with sexual behaviors and HIV prevention behaviors among young adults attending key population-led sexual health clinics in Bangkok, Thailand. A self-report survey of 200 participants aged 18-24 assessed cannabis use, sexual behaviors, and HIV prevention behaviors using study-specific questionnaires, and the Cannabis Use Disorder Identification Test-Revised. Laboratory data, including HIV and Sexually Transmitted Infections (STIs) test results were extracted from medical records. Chi-square tests and Poisson regression examined associations between cannabis use, sexual behaviors, and HIV prevention behaviors. In-depth interviews with 15 cannabis users and 15 non-users explored perceptions of cannabis use in relation to sexual behaviors and HIV prevention behaviors to complement quantitative findings. Thematic analysis was conducted. Among the 200 participants (mean age = 21.45, SD = 1.89; 35% gay men, 32% transgender women), 22% were past-month cannabis users. Cannabis use was significantly associated with sex under the influence of any substances (Prevalence Ratio (PR)=1.24, 95%CI: 1.09,1.41), and alcohol (PR = 1.12, 95%CI: 1.02,1.24). No associations were found with other sexual behaviors, PrEP adherence, HIV or any STIs test results. Many participants cited disinhibitions as a pathway to risk, whilst some cannabis users emphasized individual responsibility as a more important determinant of behavior. Cannabis use is linked to alcohol- or substance-influenced sex. Diverging views on cannabis and sexual risk suggest a need for tailored youth-centered harm reduction strategies within sexual health clinics that address risks and empower personal responsibility, particularly in the context of Thailand's evolving cannabis policy.
To assess services provided by, and barriers to, hospital-based one-stop centre (OSC) services for women survivors of sexual violence in Ethiopia. A mixed-methods study integrating quantitative service data with that from qualitative interviews. Hospital-based OSCs in Addis Ababa, Ethiopia. Hospital records of 2283 female survivors, in-depth interviews with 20 survivors and 17 key informants. Quantitative analysis of hospital records showed the majority (61.9%) of survivors seeking OSC care did so within 72 hours of experiencing sexual violence. Most received diagnostic sexually transmitted infection (STI) testing, emergency contraception and postexposure prophylaxis for HIV. Legal and psychosocial referrals were made for 93.5% and 68.4% of survivors, respectively, with 11.8% referred for antiretroviral therapy. The majority of survivors (79%) did not return for follow-up care, including for repeat STI and pregnancy testing. Qualitative findings highlighted women's experiences of gaps in psychological support, mistrust in legal systems and structural barriers to ongoing care such as work constraints, safety concerns and transport challenges. While initial diagnostic services are largely implemented, significant gaps remain in preventive, therapeutic and follow-up care for survivors of sexual violence. This underscores the need to strengthen hospital-based OSCs in Ethiopia to provide comprehensive, survivor-centred care.
South Africa has the largest HIV epidemic in the world; in KwaZulu-Natal Province, over 40.8% of adults aged 15 years and older are living with HIV. Despite this, South Africa is home to only 3% of the world's health care workers. Nurses constitute the largest group of providers in South Africa and experience high levels of burnout, which can contribute to negative patient outcomes for people living with HIV, including reduced treatment adherence. Nurse-centered interventions that offset these effects are urgently needed. This study aims to test the feasibility and acceptability of an adapted resiliency intervention (Stress Management and Resiliency Training-Relaxation Response Resiliency Program) for professional nurses who provide care for people living with HIV in South Africa. In phase 1 (Human Research Ethics Committee [Medical] of the University of the Witwatersrand [220813, Johannesburg, South Africa] and the Massachusetts General Brigham Institutional Review Board [2022P002765, Boston, Massachusetts, United States]), we conducted 3 focus group discussions to solicit feedback on the lived experiences of stress, sources of stress, impact on job functioning, coping strategies, the proposed intervention, and recruitment strategies for nurses. These data informed adaptations to the intervention. In phase 2 (Human Research Ethics Committee [240106, Johannesburg, South Africa]; Massachusetts General Brigham Institutional Review Board [2024P001407, Boston, Massachusetts, United States]), we conducted a small proof-of-concept study (N=8) with preintervention and postintervention assessments, 6 intervention sessions with a nurse interventionist, and a qualitative exit interview. Following appropriate adaptations, we conducted a pilot randomized controlled trial (N=60) in which participants were randomized to the intervention or the control condition. The control condition received a one-time, 90-minute didactic stress management session. The intervention condition consisted of two 4-hour group skills-based sessions on the relaxation response, components of stress, recuperative sleep, mindful awareness, resilience, and social support. Sessions included practice-based exercises and videos to complement the intervention materials. Baseline, posttreatment (intervention only), and follow-up assessments, as well as qualitative exit interviews (n=15, intervention only), were conducted. Primary outcomes are feasibility (number screened, eligible, and enrolled; the number of treatment sessions and assessments completed in the intervention arm; assessment duration; and reasons for declining enrollment and prematurely leaving the trial) and acceptability (Client Satisfaction Questionnaire-8 and qualitative data). The project is funded by the National Institute of Mental Health (R34MH126753; September 2022). As of October 2025, we have completed both the proof-of-concept study (n=8; February 2025) and the pilot randomized controlled trial (n=60; August 2025). Data analysis is in progress and is expected to be completed in August 2026. Structural changes are needed to ensure the well-being of health care providers; however, given that structural changes take time, money, and political capital to execute, we must develop interventions to support providers' mental health while advocating for systematic change.
Understanding the 'real-world' challenges of delivery of pre-exposure prophylaxis (PrEP) among men who have sex with men (MSM) and transgender women (TGW) provides critical insights to guide and optimise future roll-out of the PrEP in India. Between 18 December 2019 and 31 July 2023, self-identified MSM and TGW, ≥18 years, at substantial risk for HIV were followed for 12 months for PrEP acceptability, adherence, adverse events and condom use at community-based and clinic-based settings in Jalandhar (Punjab) and Pune (Maharashtra), respectively. Data were analysed for correlates of retention and adherence. Exit interviews were conducted. The median (IQR) age of the 650 participants was 26 (22, 30) years; the majority were literate and unmarried. The overall 1-year retention was 63.2%, with 84% and 41.7% in the community-based and clinic-based settings respectively. Overall, 64.8% participants had ≥80% adherence. Being from a community-based setting, having received secondary/higher secondary/graduate level education and living with family were significantly associated with ≥80% adherence. Overall, 9.7% showed grade-2 decline in creatinine clearance. Among 411 retained, condomless anal sex (CAS) with any partner, anytime in the last 6 months was 84.4% and 78.1% at baseline and 12 months respectively. Overall, seven seroconversions occurred. Daily oral PrEP was acceptable and safe among MSM and TGW. Inclusion of PrEP as an additional prevention option would be critical for controlling HIV. Baseline risk assessment is important before initiating PrEP. Recurrent condom and risk reduction counselling during oral PrEP uptake is crucial for preventing CAS. Self-risk assessment and planned usage/stoppage of PrEP observed in the study indicates a need for counselling and assessment for potential interruptions of daily oral PrEP. Additionally, adherence would be affected, with implications for evaluating the programme's success.
Our vaccine candidate for genital herpes includes three immunogens involved in virus entry and immune evasion. HSV-2 glycoprotein C (gC2) is one of the immune evasion molecules that inhibits complement activation by binding C3b, and is the focus of this manuscript. Mice were immunized with 0.25, 0.5, 1, 10, or 30 µg of gC2 lipid nano particle (LNP)-encapsulated nucleoside-modified mRNA and challenged intravaginally with HSV-2. The gC2 mRNA-LNP, even at the lowest dose, was highly protective as a single immunogen. We measured antibody responses to six gC2 epitopes. Both neutralizing and C3b binding epitopes on gC2 were targeted. We passively immunized mice with monoclonal antibodies (mAbs) to gC2 and determined that the mAbs that enhance complement activation by blocking C3b binding were protective, while the mAb that neutralizes the virus, but does not block C3b binding, failed to protect. These results highlight the importance of a vaccine immunogen that induces antibodies that block the ability of gC to inhibit complement activation.
Persistence of human papillomavirus (HPV) infection leading to cervical carcinogenesis can be attributed to the action of high-risk HPVs, but there are still some unclear factors involved in the mechanisms of either viral clearance or persistence. Although many infections may be self-limiting and cleared successfully by the immune response of the infected individuals, other infections result in persistent HPV infection. Recent studies indicate that microbiota in the gut and cervicovaginal tract modulate host immune status, mucosal inflammation, and epithelial barrier integrity. All these factors determine susceptibility to persistent infection. Inflammation, overproduction of reactive oxygen species (ROS), genomic instability, and impaired antiviral transcription pathways are associated with dysbiosis. In parallel, redox imbalance contributes to mitochondrial dysfunction, impairing mitochondrial antiviral signaling (MAVS)-dependent interferon responses and attenuating induction of interferon-stimulated genes. Additionally, extracellular vesicles (EVs) further promote immune evasion, metabolic programming, and epigenetic regulation by facilitating the intercellular exchange of viral constituents, microRNAs, and signaling molecules. Through this interconnected network of mechanisms, microbial dysbiosis, mitochondrial disruption, and EV signaling collectively shape a niche conducive to persistence. Unlike previous reviews that primarily examine microbiome alterations, oxidative stress (OS), mitochondrial dysfunction, extracellular vesicles, or immune responses as separate processes, this review integrates clinical and omics findings into a systems-based conceptual framework of HPV persistence. By emphasizing the potential interactions among these interconnected biological systems, we aim to identify points of biological convergence, generate mechanistic hypotheses, and highlight opportunities for future biomarker development and therapeutic intervention.