搜索结果：Current HIV research

The funding crisis for HIV services in east, central, southern, and west Africa means that innovative strategies for continuing prevention and care for HIV are needed. One such strategy is enabled self-care: the provision of free HIV self-tests, pre-exposure prophylaxis (PrEP), tenofovir-lamivudine-dolutegravir for post-exposure prophylaxis (PEP), and antiretroviral therapy (ART) provided in local pharmacies and by community-based health workers. We modelled the introduction of a policy of transition to enabled self-care compared with continuation of current service provision. We used an established individual-based model (HIV Synthesis) to simulate HIV epidemics in 1000 setting scenarios representing diversity in setting characteristics across east, central, southern, and west Africa, and uncertainty in parameter values. For each setting scenario, we simulated 100 000 people aged ≥15 years between 1989 and 2076. The model incorporates ART access informed by studies of barriers to accessing clinics. Our main outcomes included the number of adults testing for HIV in a 3-month period, PrEP and PEP use, coverage of people on ART, HIV-related deaths, HIV incidence, perinatal transmission, disability-adjusted life-years (DALYs), and costs. We chose a 50-year time horizon to capture the full effects of the policies. For each setting scenario, we performed three replicate runs for each of the two policies and for each policy took the mean across the three runs. Our model estimated that transitioning to enabled self-care would lead to increases in testing from a median of 5·0% (90% range 2·3-11·5) of adults testing per 3 months to 12·7% (6·6-21·1), an increase in PrEP and PEP use (+0·5% of adults [0·0-2·2]), and an increase in ART coverage for people with diagnosed HIV (+1% [0-3]) with enhanced benefits in those previously without access to PrEP and testing services. Enabled self-care was predicted to result in a median 18% (90% range 4-33) fewer HIV deaths, and a relative rate of 0·73 (0·52-0·94) in terms of HIV incidence per 100 person-years over 10 years. Overall, over a 50-year time horizon, enabled self-care was predicted to cut discounted programme costs by US$6·0 million (5·6-6·5; a 7% decrease), avert 34 000 (32 200 to 36 000) DALYS, and be cost-effective (at a cost-effectiveness threshold of $300 per DALY averted) in 95% of setting scenarios. The mean undiscounted annual cost per adult in the population per year across setting scenarios was $12 (median $11 [90% range 6-22]). The higher the HIV prevalence was in a setting scenario, the more cost-effective the policy was found to be (odds ratio 1·41 [95% CI 1·25-1·60] per 1% higher HIV prevalence). Introduction of community access to self-tests and antiretroviral drugs through a transition to enabled self-care is very likely to be cost-effective in most settings in east, central, southern, and west Africa; enable incidence declines to be sustained at reduced cost; and increase equity of access to HIV services. Policy makers who wish to consider such a policy will need to evaluate its feasibility in their own country settings. UCL and Gates Foundation.

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&#x2009;<&#x2009;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&#x2009;<&#x2009;0.001), but this difference disappeared after PSM (log rank P&#x2009;=&#x2009;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&#x2009;=&#x2009;0.0011) and after PSM (log rank P&#x2009;=&#x2009;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.

Despite substantial gains in the global HIV response, infants and young children continue to experience poorer outcomes across the HIV testing and care cascade. Rates of early infant diagnosis, timely antiretroviral therapy (ART) initiation, retention in care and viral suppression remain unacceptably low in paediatric populations. These disparities are compounded by systemic challenges, including fragmented service delivery, limited availability of child-friendly ART and other drug formulations, and health systems that fail to integrate HIV services within broader maternal and child health platforms. As a result, many children living with HIV are diagnosed and start treatment late and face high risks of mortality and morbidity, particularly in the first 2 years of life. In this commentary, we advocate for the urgent reimagining of paediatric HIV service delivery, emphasizing the need to centre infants and young children within models of care. We highlight four promising approaches: (1) Integrated mother-infant follow-up models that ensure continuity of care from pregnancy through the postpartum period and infancy until the infant's final HIV status is determined; (2) Family-centred models that treat the household as the unit of care; (3) Advanced HIV care strategies tailored to the needs of children with late presentation or treatment failure, including paediatric tailored ART regimens and diagnostics; and (4) Community-based interventions that leverage peer support, lay health workers, and provide stigma-free entry points to expand access and retention to care and treatment. These approaches have demonstrated that when services are designed to reflect the developmental, clinical and social needs of children and their caregivers, outcomes significantly improve. However, many of these models remain underutilized, fragmented or inadequately resourced. To close the paediatric HIV treatment gap, we must move beyond pilot projects towards national, integrated and adequately funded child-centred systems. This requires political will, strategic investment and prioritization of children in HIV policy, innovation and implementation research. A sustained and equitable HIV response must include infants and young children not as an afterthought, but as a core priority. Epidemic control cannot be achieved if the youngest children are left behind.

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.

Intimate Partner Violence (IPV) remains a significant public health concern, particularly for persons living with HIV (PLHIV) and other sexually transmitted infections (STIs). The intersection of IPV and HIV/STIs creates complex care needs requiring trauma-informed, contextually grounded responses. This study explored healthcare practitioners' perspectives on existing practices and opportunities to strengthen IPV-related care in public HIV/STI clinical settings in Trinidad and Tobago. Structured weekly consultations were conducted over seven weeks with 13 healthcare practitioners-including physicians, nurses, psychologists, social workers, and peers living with HIV-across five public HIV/STI clinics. Guided by national clinical protocols, discussions explored current practices, care gaps, and system-level challenges. Trauma-Informed Care (TIC) was examined through four core assumptions: realizing the impact of trauma, recognizing its signs, responding appropriately, and resisting re-traumatization. Practitioners also considered how TIC could be integrated along the care pathway at five key points: awareness, identification, first-line response, survivor-centered care, and inter-agency referral. Participants identified critical system-level gaps, including the lack of standardized IPV protocols, limited documentation, concerns about privacy, fragmented referral systems, and stigma related to both HIV and IPV. Time constraints and limited training were cited as barriers to consistent, high-quality care. Practitioners also highlighted the elevated vulnerability of women, youth living with HIV, and men who have sex with men to IPV. There was strong consensus on the need for structured TIC training for all levels of staff. The findings underscore urgent opportunities to enhance clinical responses to IPV through the integration of trauma-informed care along the HIV/STI service pathway. Prioritizing TIC can improve care quality, reduce re-traumatization, and strengthen engagement and resilience among populations most at risk.

HIV/AIDS remains a public health concern globally. Comorbidities add to the disease burden among people living with HIV (PLHIV) and may be associated with poorer health-related quality of life. This study aimed to assess the prevalence of comorbidities, health-related quality of life (HRQoL), and associated factors among people living with HIV in Gandaki Province, Nepal. A cross-sectional study was conducted at the antiretroviral therapy (ART) centre of Western Regional Hospital, Pokhara. PLHIV registered at the ART centre were selected using simple random sampling. A multivariable logistic regression model was used to explore factors associated with HRQoL. Adjusted odds ratios (AORs) with 95% confidence intervals (CIs) were reported. A total of 337 PLHIV participated in the study. The mean overall HRQoL score was 6.25&#x2009;&#xb1;&#x2009;1.87, and 52.2% of participants reported poor quality of life. At least one comorbidity was present in 28.2% of participants. The most frequently reported comorbidities were hypertension (36.8%), diabetes (33.7%), tuberculosis (14.9%), hepatitis B (10.6%), and hepatitis C (4.3%). PLHIV with comorbidities had higher odds of poor HRQoL compared with those without comorbidities (AOR&#x2009;=&#x2009;1.65; 95% CI: 0.98-2.78). Factors associated with comorbidities included marital status, family structure, education, occupation, current alcohol consumption, having a migrant worker spouse, CD4 count, transportation costs, perceived behaviour of healthcare workers, and HRQoL across all except the physical domain. Comorbidities were common among people living with HIV. The findings suggest a high prevalence of poor quality of life among PLHIV, with comorbidities potentially associated with poorer HRQoL. These findings underscore the need for integrated interventions that address both health and social factors, including community engagement strategies.

Since the mid-1990s, there have been major advances in diagnosing and providing antiretroviral therapy (ART) for pregnant women living with HIV (WLWH) in both resource-rich and resource-limited settings. Initial progress was based on the 1994 landmark perinatal trial, which showed 67% reduction in vertical transmission among infants born to non-breastfeeding mothers in the United States when zidovudine was given during pregnancy, at labour/delivery and for 6 weeks after birth. International perinatal trials began testing "short-course" zidovudine regimens during late pregnancy and at labour/delivery to develop cost-effective, feasible and deliverable interventions for low-resource environments. More recent research has focused on the delivery of cost-effective combination triple ART during pregnancy and breastfeeding for WLWH. The latest trial results indicate that providing lifetime maternal ART at the time of antenatal diagnosis improves overall survival and decreases morbidity, while reducing vertical transmission to <1%. Translation of clinical trial results into successful widescale programme implementation remains a major challenge, particularly in low- and middle-income countries with high HIV seroprevalence and weak maternal and child health infrastructure. Interventions recommended earlier in the global epidemic are no longer adequate, but key points of the perinatal cascade of services remain crucial to both ensure successful HIV care for WLWH and maximize reductions in vertical transmission. Notable progress made in Botswana and Uganda is valuable to highlight country-led successes. Rapid HIV testing for pregnant women whose status is unknown, followed by immediate implementation of lifetime maternal ART, and linkage to long-term HIV care/treatment are essential. Counselling on adherence, as well as the use of long-acting ART regimens and holistic support for women's care, including psychosocial support, are also needed. A current major challenge has been the sudden reduction in international donor funding, which has had a significant negative impact on continuity and effective delivery of HIV care/treatment services. Much progress has been made in advancing HIV interventions and programmes for WLWH and pregnant and breastfeeding mothers. However, several challenges persist, which compromise delivery of effective interventions on the path to eliminate perinatal HIV transmission, and care/treatment remains suboptimal for WLWH, especially in resource-limited settings.

Hypertension is a frequent comorbidity among people living with HIV (PLHIV) in sub-Saharan Africa, but analytical data from routine HIV clinics in Cameroon remain limited. This study assessed factors associated with prevalent hypertension among adults receiving antiretroviral therapy (ART) at an urban HIV clinic in Yaounde, Cameroon. We conducted a cross-sectional study at the Day Hospital of Yaounde Central Hospital between January and March 2024. The analytical dataset included 460 adults living with HIV receiving ART. Prevalent hypertension was coded as a binary outcome. Robust Poisson regression was used to estimate prevalence ratios (PRs) and adjusted prevalence ratios (aPRs) because hypertension was common. Sensitivity models were fitted to clarify the interpretation of cumulative ART duration in relation to current age. Among 460 participants, 199 (43.3%) had prevalent hypertension. The mean age was 50.5 &#xb1; 10.9 years, and 338 (73.5%) participants were women. In bivariable analysis, older age (PR per 1-year increase 1.02, 95% CI 1.01-1.03; p&#x2009;<&#x2009;0.001), longer ART duration (PR per 1-year increase 1.03, 95% CI 1.01-1.05; p&#x2009;<&#x2009;0.001), family history of hypertension (PR 2.98, 95% CI 2.40-3.71; p&#x2009;<&#x2009;0.001), HIV stage II at ART initiation (PR 1.29, 95% CI 1.03-1.60; p&#x2009;=&#x2009;0.024), and obesity (PR 1.43, 95% CI 1.10-1.87; p&#x2009;=&#x2009;0.007) were associated with hypertension. In the final multivariable model, older age (aPR 1.02, 95% CI 1.01-1.03; p&#x2009;=&#x2009;0.002), family history of hypertension (aPR 2.83, 95% CI 2.25-3.57; p&#x2009;<&#x2009;0.001), and obesity (aPR 1.29, 95% CI 1.01-1.65; p&#x2009;=&#x2009;0.045) remained independently associated with prevalent hypertension, whereas cumulative ART duration was not independently associated after adjustment (aPR 1.00, 95% CI 0.99-1.02; p&#x2009;=&#x2009;0.619). Restricted cubic spline analysis did not show evidence of an overall association or non-linearity for ART duration. In this urban HIV clinic, hypertension was frequent and was associated mainly with age, family history of hypertension, and obesity in the adjusted model. Cumulative ART duration was associated with hypertension in crude or minimally adjusted models but not after adjustment for age and cardiometabolic factors. These findings support integrating routine blood-pressure screening, weight management, lifestyle counselling, and standardized hypertension care into HIV services.

BackgroundDespite substantial global progress in HIV prevention and treatment, mother-to-child transmission (MTCT) of HIV remains a major public health challenge in sub-Saharan Africa, which accounts for approximately 65% of the world's 39.9 million people living with HIV. Vertical transmission rates vary substantially across regions and over time. We conducted a systematic review and meta-analysis to estimate the overall, temporal, regional, and country level prevalence of HIV MTCT in sub-Saharan Africa.MethodsThis research was conducted between June 2024 and May 2025, in accordance with PRISMA guidelines and a protocol registered in PROSPERO (CRD42025637989). We systematically searched six databases (MEDLINE, Embase, PubMed, ScienceDirect, Web of Science, and the Cochrane Library) for articles published in English or French. We included cross-sectional, cohort, and case-control studies involving HIV-positive pregnant women aged &#x2265;18 years that reported MTCT prevalence. Two reviewers independently screened, extracted data, and assessed study quality (Joanna Briggs Institute and Newcastle-Ottawa Scale). Pooled prevalence and 95% CI were calculated using a random-effects model in STATA 17. Heterogeneity (I2), subgroup analyses (by period, region, country), sensitivity analysis, and funnel plots for publication bias were performed.ResultsFrom 5,848 records, 48 studies (86,376 mothers; 2,875,104 infants) across 15 countries were included. The pooled MTCT prevalence was 7.0% (95% CI 5.2-9.4%; I2 = 99.1%). Temporal trends showed a decline from 26.0% (1993-2000) to 8.0% (2001-2010) and 5.0% (2011-2023). Regionally, West Africa had the highest prevalence (12.1%; 95% CI 6.5-21.6%), Southern Africa had the lowest (4.7%; 95% CI 2.6-8.1%). Approximately 9% of HIV-exposed infants were infected by 24-48 months, 6% were infected by 24 months after enrolment, and 7% tested positive at their first HIV test conducted between 1 and 12 weeks of age.ConclusionAlthough MTCT rates have declined, the current 7.0% remains above the WHO target (<5%) with noted significant regional and national disparities. However, this rate should be interpreted cautiously due to the extremely high heterogeneity (I2 = 99.1%) knowing it's a directional synthesis of available evidence rather than a precise population-level figure.

The disclosure of one's HIV-positive status is a personal decision that can play an important role in engagement in HIV treatment and care. Social network approaches situate individuals within broader webs of social connections that influence health and wellbeing and thus hold the potential to elucidate key social factors shaping the process of disclosure. As part of a larger clinical study examining how substance use and mental health shape HIV outcomes, we recruited 61 individuals newly diagnosed with HIV at two clinics in Western Kenya to participate in an egocentric social networks study. We conducted a survey that generated a visual network map to guide a subsequent qualitative interview about experiences being diagnosed and living with HIV. We thematically analyzed the qualitative data and visual network maps to examine the social contexts and patterns of HIV disclosure, with the goal of identifying supportive contexts of disclosure. The mean age was 36.7 years (range: 20-62); women were significantly younger than men and more likely to self-report a mental health issue. Typically, participants disclosed their HIV-positive status to a small number of close, trusted alters in their network, including intimate partners, siblings and other family members, and friends. The need for mental health support in the wake of a new diagnosis, especially among women, encouraged disclosure. Across nearly all stories, stigma was a powerful deterrent to sharing one's status, and multiple people noted prior disclosure to others not named in their current networks because their relationships were negatively impacted. Our study shows how the intersection of social relationships, mental health, and stigma is critical in understanding decision-making processes around disclosure. Selective disclosure typically improved participants' wellbeing while stigma precluded disclosure and exacerbated distress. Our study offers suggestions for social network interventions to support people living with HIV/AIDS.

The Kaposi Sarcoma herpesvirus (KSHV) causes Kaposi sarcoma (KS), primary effusion lymphoma, a lymphoproliferative disease (KSHV-multicentric Castleman's disease), and a cytokine inflammatory syndrome (KICS). These diseases occur more frequently, though not exclusively, among people living with HIV or other types of immune dysregulation. While limited KS can regress with immune reconstitution, such as through antiretroviral therapy (ART) in people living with HIV, there are currently no curative treatments for advanced KS. Preventive or therapeutic vaccines targeting KSHV could have a significant clinical impact; however, the development and testing of such strategies have been limited by the lack of preclinical models that faithfully recapitulate KS, including the presence of infected spindle cells and a relevant immune microenvironment. HIV/AIDS is an important cofactor for KS, and globally, the majority of individuals with KS are HIV-infected. Current evidence indicates that HIV-1 may enable KS progression through immunosuppression and promote pathogenesis by inducing inflammatory cytokines and producing secreted regulatory proteins like Tat and Nef. The design and testing of new therapeutic approaches based on pathogenesis are hampered by the lack of models that replicate KSHV oncogenesis in the context of HIV/AIDS. In the present study, we demonstrate that KSHV-infected cells can form tumors in an immunocompetent mouse model after in vivo passage in nude mice and EcoHIV infection and/or morphine treatment, both of which have immunomodulatory and pro-inflammatory effects. These tumors exhibit gene expression profiles and immune microenvironments that closely resemble those observed in human KS lesions. This novel KSHV tumor model in immunocompetent mice provides a valuable platform to test immunotherapeutic strategies for KS, including immunomodulatory agents, targeted antibody therapies, checkpoint inhibitors, and vaccines.

Background/Objectives: This study aimed to investigate the genital pathogen profile and co-infection dynamics using multiplex RT-qPCR, specifically evaluating the independent associations with age, sex, and HIV status. Methods: Data from 1217 patients who underwent a sexually transmitted infection (STI) panel study at the Microbiology Laboratory of Marmara University Pendik Training and Research Hospital between January 2024 and December 2025 were retrospectively reviewed. Pathogen detection was performed using a commercial kit (Bioeksen, Istanbul, T&#xfc;rkiye) with the multiplex RT-qPCR method. The independent effects of HIV positivity, age, and sex on pathogen frequency and co-infection were analyzed using logistic regression models; results were evaluated using adjusted odds ratio (aOR) and 95% confidence interval (CI). Results: Any-pathogen positivity was detected in 57.8% of patients, with Ureaplasma spp. (36.9%) and Gardnerella vaginalis (32.5%) being the most prevalent. While overall pathogen positivity did not differ significantly by HIV status (p = 0.158), HIV-positive patients exhibited distinct microbiological architectures. Higher positivity rates were observed in women in both groups, and a strong correlation was found between sex and the presence of infection (p < 0.001). Multivariate analysis revealed that HIV positivity was independently associated with an over fivefold increase in HSV-2 detection (aOR = 5.09, 95% CI: 1.47-17.65; p = 0.010). Furthermore, HIV-positive individuals were significantly enriched for complex polymicrobial patterns involving three or more pathogens (p = 0.008). Conversely, male sex was independently associated with a substantially lower risk of co-infection (aOR = 0.17, 95% CI: 0.12-0.22; p < 0.001), and increasing age showed an inverse relationship with co-infection frequency (aOR = 0.98 per year, 95% CI: 0.97-0.99; p = 0.001). Conclusions: This study adds to current epidemiological evidence by showing that genital pathogen distribution is shaped by age- and sex-related heterogeneity, with flora-associated co-infections predominating in women and more classical STI-related agents occurring more often in men. Our findings suggest that multiplex RT-qPCR provides value not only for broad pathogen detection but also for identifying demographic- and HIV-associated co-infection patterns that may support stratified screening and targeted clinical management.

The United States faces an unprecedented surge in methamphetamine (MA) use, with severe implications for people living with HIV (PWH) or at risk of HIV acquisition. Current detection methods, including self-report and urine testing, have significant limitations. Hair testing represents a promising alternative for quantifying longer-term substance exposure but requires validation in clinical research settings. U.S. based cohort of men with and at-risk of HIV in Los Angeles (mSTUDY). We conducted a cross-sectional validation study using data from mSTUDY. We analyzed hair samples from two groups with negative urine MA tests: individuals reporting daily/weekly MA use (n=22) and controls reporting no MA use (n=22). Hair was analyzed using liquid chromatography-tandem mass spectrometry, with MA positivity defined as concentrations >200 picograms/mg per Society of Hair Testing guidelines. Hair analysis detected MA use in 17/22 (77%) participants reporting regular use despite negative urine tests. Among controls reporting no MA use, 3 of 22 (14%) had positive hair samples. The positive likelihood ratio for detecting MA use not identified by urine testing was 6.0 (95% CI: 2.1-17.3), with sensitivity of 77.3% (95% CI: 56.6-89.9%) and specificity of 86.4% (95% CI: 66.7-95.3%). Among PWH, those reporting MA use had lower rates of virologic suppression compared to those without reported use (45% vs 82%, p=0.05). Hair testing successfully identified past-month MA use not detected by urine testing, with strong diagnostic performance. This validated biomarker provides objective measurement of longer-term MA use patterns, offering an important complement to current detection methods in substance use and HIV research.

Current antiretroviral therapies suppress HIV replication but fail to eliminate integrated proviral DNA in long-lived CD4&#x207a; cells, precluding a cure. CRISPR-Cas9 offers potential for HIV eradication but efficient and cell-specific delivery into HIV target cells remains a major hurdle. We developed CD4-directed Nanoblades (CD4-NBs), murine leukemia virus-like particles pseudotyped with anti-CD4 nanobodies and a fusogenic glycoprotein VSV Gmut, to selectively deliver Cas9-gRNA ribonucleoproteins into CD4&#x207a; cells. CD4-NBs selectively delivered cargo to CD4&#x207a; cells in vitro and in vivo, achieving efficient gene disruption in primary CD4+ cells. Dual-guide CD4-NBs targeting conserved HIV tat/rev/env regions disrupted proviral DNA, suppressing HIV infection in CD4+ cells. In HIV-infected, ART-pretreated humanized mice, CD4-NBs significantly reduced plasma viremia. While full tissue reservoir clearance was not achieved, repeated dosing did reduce viral RNA and proviral DNA in bone marrow and lungs, respectively. As such, this proof-of-concept study supports the promise of CD4-NBs as a minimally invasive, CD4&#x207a; cell-targeted gene editing strategy for HIV therapy.

In the European Union (EU), HIV disproportionately affects men who have sex with men (MSM), with prevalence rates ranging from 2.4% to 29%. Pre-exposure prophylaxis (PrEP) is highly effective in preventing HIV, yet access and uptake remain uneven. We used a stochastic agent-based model of HIV transmission among MSM to evaluate the effectiveness and cost-effectiveness of five PrEP eligibility policies across 20 EU countries, incorporating data on sexual behavior, adherence, and healthcare costs. US, CDC and Belgian guidelines, which recommend broad eligibility, achieved the highest reductions in HIV infections and deaths, whereas WHO guidelines consistently emerged as the most cost-effective option, particularly in countries with constrained budgets. Our analyses further show that lowering drug costs would expand the range of cost-effective options in settings without PrEP reimbursement. Finally, we estimated willingness-to-pay thresholds for injectable, long-acting PrEP. Long-acting injectable formulations are emerging as new PrEP options. Current prices largely exceed these thresholds, but cabotegravir could approach cost-effectiveness under WHO guidelines in some countries. Overall, broad eligibility criteria maximize effectiveness, while WHO guidelines balance affordability and impact. Expanding oral PrEP access and reducing drug costs remain essential for HIV prevention in Europe, while injectable PrEP is likely to require substantial price reductions or targeted use in selected populations to become economically attractive. Our findings highlight the need for policy adjustments to improve PrEP accessibility, inform national health strategies, and achieve sustainable HIV prevention across diverse settings.

The 2016 NICE guidelines recommend offering HIV testing alongside routine blood tests in areas of high HIV prevalence (>2 per 1000 adults aged 18-59). Despite this, implementation in primary care has been limited. A universal-offer HIV testing intervention was implemented across seven general practices in Brighton and Hove. Data were collected on all blood test appointments between June 2022 and February 2024, including demographics, whether an HIV test was offered, patient acceptance, and test results. Mixed-effects logistic regression was used to assess factors associated with test offer and uptake. An electronic survey was disseminated to staff to gather views on feasibility and acceptability. Seven sites were recruited, although only four successfully engaged and provided complete data. A total of 6105 HIV tests were conducted, with one new diagnosis identified. HIV testing was offered to 45% of eligible patients, with 74% accepting. Older adults were significantly less likely to be offered a test [aOR 71-80: 0.79 (95% CI: 0.69-0.91); 81+: 0.50 (0.42-0.60)]. Amongst those offered testing, patients aged over 50 were less likely to accept [aOR: 0.72 (0.57-0.91)], with the lowest uptake amongst those aged 81+ [aOR: 0.44 (0.32-0.61)]. Staff reported no barriers to feasibility or patient acceptability. Routine HIV testing in primary care is well-accepted and can identify new cases. However, site engagement can be challenging, with closer monitoring, support, and rigorous on-boarding processes required.

HIV (human immunodeficiency virus)/HBV (hepatitis B virus) coinfection remains a significant public health challenge. HIV infection affects the natural course of chronic HBV infection, with HIV/HBV coinfected patients experiencing higher liver-related morbidity, hospitalization rates, and mortality than those with HBV monoinfection. Surprisingly, an increasing number of studies have shown that hepatitis B surface antigen (HBsAg) clearance rates in HIV/HBV coinfection can reach over 10%, which is significantly higher than in HBV monoinfection. In this review, we summarize the predictive factors for HBsAg clearance observed in HIV/HBV coinfection, including baseline HBsAg levels, baseline HBV DNA levels, baseline CD4+T cell-counts, and immune reconstitution inflammatory syndrome-related hepatic flare. Based on current evidence, we further discuss a potential mechanism for HBsAg clearance: HIV-induced immunodeficiency, particularly the depletion of CD4+ T cells, may unexpectedly disrupt preexisting HBV-specific tolerance. After antiretroviral therapy (ART) in HIV/HBV coinfected individuals, partial immune system reconstitution occurs, and the reconstituted immune system, no longer tolerized by HBV, effectively clears HBV-infected hepatocytes, triggering transient hepatitis and ultimately achieving a functional cure through HBsAg clearance. Additionally, emerging data suggest that the underlying immunological mechanisms of HBsAg clearance in HIV/HBV coinfection may primarily involve: PD-1/PD-L1 pathway inhibition, cytokine induction promoting immune cell recruitment and an inflammatory environment, and natural killer (NK) cell functional remodeling. These collective observations highlight the important role of immune modulation in HBV clearance, providing insights that can facilitate the development of a functional HBV cure. Identifying the mechanisms involved in HBsAg loss in HIV/HBV patients may facilitate the development of drugs that mimic these anti-HBV responses.

The central nervous system (CNS) remains a relatively understudied reservoir of HIV that may have significant implications for HIV cure and the pathogenesis of cognitive disorders that persist despite viral suppression with antiretroviral therapy (ART). This review will describe our current understanding of the nature, size and composition of the CNS reservoir and the possible contribution of viral persistence in the CNS on viral replication, neuroinflammation and cognitive disease. Reservoirs of intact and defective HIV proviral DNA have recently been detected in both the brain parenchyma and cerebrospinal fluid (CSF) of ART-suppressed PWH. Moreover, viruses from these sites are transcriptionally and translationally active, with the potential to propagate infection ex vivo in the absence of ART. Ongoing viral persistence likely contributes to elevated risk of comorbid neurocognitive issues and measures of neuroinflammation support a pathological impact of HIV reservoirs on the brain. However, it is becoming clear that the sub-regions of the CNS including the brain parenchyma and CSF contain unique reservoir characteristics including cellular sources and reservoir dynamics which likely impart different effects on neuropathology. The CNS represents a heterogeneous reservoir of HIV with sub-regional differences in reservoir maintenance and cellular sources, highlighting the need to consider these nuances in HIV treatment, neuropathology and cure strategies.

The purpose of this study was to characterise physical activity promotion and explore strategies to increase physical activity promotion among HIV providers at an outpatient infectious disease clinic. We conducted a mixed-methods study with an explanatory sequential design using a questionnaire and semi-structured interviews. We recruited providers with an independent caseload of people living with HIV (PLHIV) in an outpatient HIV clinic. We administered a questionnaire asking about physical activity promotion with patients, followed by a semi-structured interview with a subsample of participants. We analysed questionnaire responses descriptively and interview transcripts were analysed using a conventional content analysis. Seventeen providers participated in the study. Questionnaire responses (n=17) indicated that 88% of providers felt that physical activity promotion was a worthwhile intervention, but 65% did not feel that there was sufficient compensation from insurance companies or clinic resources to promote physical activity. In interviews (n=8), providers reported they felt that more structured physical activity advice for patients would be most beneficial. Understanding the extent of physical activity promotion among providers, as well as barriers and facilitators of this behaviour, may inform implementation of strategies to maximise health promotion. Providers generally promoted physical activity but discussed the need for structured physical activity interventions and described the current systems-level barriers for activity promotion. The incorporation of an in-clinic specialist was proposed as a potential strategy to better facilitate initiation and sustained adherence to physical activity with PLHIV but should be explored in future studies.