AIDS Research and Therapy最新文献

Background: People living with HIV (PLWH) frequently experience non-AIDS comorbidities, driven in part by persistent intestinal barrier dysfunction and systemic inflammation. The HIV-1 envelope protein gp120 has been implicated in damaging epithelial tight junctions. However, therapeutic options for preserving intestinal integrity are limited.

Methods: A Caco-2 cell monolayer model was used to simulate HIV-1 gp120-induced intestinal barrier injury. Barrier integrity, tight junction protein expression, apoptosis, and MAPK/ERK1/2 pathway activity were evaluated in the presence or absence of Quercetin. Transcriptomic analysis and Western blotting were performed to investigate mechanisms, including the role of dual-specificity phosphatases (DUSPs) and myosin light chain kinase (MLCK).

Results: Gp120 exposure increased epithelial permeability, decreased tight junction protein expression (ZO-1, Occludin, Claudin-1), and induced apoptosis. Quercetin treatment significantly restored barrier integrity, reduced apoptosis, and enhanced tight junction expression. Mechanistically, Quercetin suppressed ERK1/2 phosphorylation, upregulated DUSP4, DUSP5, and DUSP8, and inhibited downstream MLCK/MLC activation. The MEK inhibitor U0126 produced similar protective effects, confirming ERK1/2 involvement.

Conclusions: Quercetin alleviates gp120-induced intestinal barrier disruption via inhibition of the ERK1/2-MLCK signaling pathway and restoration of tight junction proteins. These findings highlight the therapeutic potential of Quercetin as a natural compound to protect against HIV-related mucosal injury and support its further development for managing HIV-associated comorbidities.

Background: In spite of numerous advancements in HIV prevention, there are still gaps that impede reaching key populations throughout sub-Saharan Africa. Traditional approaches usually overlook personal preferences, social context and structural obstacles, often leading to subpar service uptake. Person-centred care (PCC) has emerged in recent times as an approach that shows promise; however, its implementation is still not widespread in sub-Saharan Africa.

Objective: This scoping review aimed to systematically map the landscape of Person- Centred HIV prevention services in Sub-Saharan Africa, identifying intervention models, outcomes, and implementation barriers and facilitators.

Methods: A comprehensive search of PubMed, ScienceDirect, Google Scholar, and AJOL identified studies published between 2010 and 2025. Following PRISMA-ScR guidance, 174 records were identified, 33 duplicates removed, and 141 records screened. A total of 128 records were excluded, 13 full texts were sought, and 12 studies from six countries met the inclusion criteria. Data were charted and synthesised narratively.

Results: Services included PrEP programmes, choice based models, peer-led outreach initiatives, and differentiated ART delivery systems. Essential elements of PCC included shared decision-making, decentralisation, social support, and counselling that takes into account stigma. Models that are community-based and peer-supported improved accessibility, trust, and adherence to treatment. Interventions that provided options for prevention methods and service locations consistently demonstrated improved uptake, satisfaction, and clinical outcomes. Nonetheless, implementation varied by region, with no representation from West and Central Africa and notable disparities in reach among adolescent boys, older adults, and sexual minorities.

Conclusion: Evidence from the included studies indicates that person-centred strategies can enhance engagement with HIV prevention services in several settings across sub-Saharan Africa. However, the benefits were not uniform, and gaps in geographical representation, equity, and integration of broader psychosocial needs persist. Future programmes should address structural barriers, strengthen psychological safety and community trust, and ensure more inclusive design to improve the reach and consistency of person-centred HIV prevention.

Background: As Uganda scales up integrated chronic care, understanding viral load suppression (VLS) among people living with HIV (PLHIV) with non-communicable diseases (NCDs) is critical for optimizing service delivery. This study thus determined VLS among the PLHIV with NCDs and associated factors.

Methods: We conducted a cross-sectional analysis using routine program data from 10 districts in Eastern Uganda and 18 health facilities-three general hospitals, seven health centre (HC) IVs, seven HC IIIs and one Special HIV Clinic. We included PLHIV aged 20 + who were active in care during the April-June 2025 quarter and screened for NCDs (hypertension, diabetes mellitus, anxiety/depression and alcohol abuse). VLS was defined as < 1000 copies/ml. Robust Poisson regression estimated crude and adjusted prevalence ratios (aPRs) for VLS using 95% confidence interval (CI) and p < 0.05 for statistical significance. A forest plot visualized effect sizes and confidence intervals. STATA Corp version 15 was used for the analysis.

Results: Among 8,306 PLHIV, 62.4% were female, with a mean (Standard Deviation) age of 46.7 years (13.8). Overall VLS was 94.7% (96.72% for PLHIV with NCDs and 94.53% for those without). NCD comorbidity was 8.45%, predominantly hypertension (7%). Crude analysis showed higher VLS among PLHIV with NCDs (PR = 1.023; p = 0.002), but adjusted estimates attenuated (aPR = 1.015; 95% CI 0.999-1.031; p = 0.065). Older age groups (30-39, 40-49, 50+) had significantly higher VLS than those under 30 ( aPR = 1.063; 95% CI 1.034-1.091; p < 0.001), (aPR = 1.073; 95% CI 1.044-1.102; p < 0.001), (aPR = 1.071; 95% CI 1.043-1.100; p < 0.001) respectively. Males had lower VLS than females (aPR = 0.978, 95% CI [0.968, 0.989] p < 0.001). Clients at Health Centre III had reduced VLS (aPR = 0.979 95%CI [0.961, 0.997]; p = 0.023), while Health Centre IV and hospitals showed no significant difference when compared with those in the special clinic.

Conclusion: VLS among PLHIV with NCDs was comparable to those without, suggesting integrated care may mitigate disparities. However, age, sex, and facility level remain key determinants. Targeted interventions are needed for younger clients, men, and health centre IIIs to sustain viral suppression in the era of integrated health services.

Objective: HIV care interruptions contribute to adverse outcomes among adolescents and young adults with HIV (AYWH) and may occur due to structural barriers as well as comorbidities (e.g., mental health issues). This study characterizes a cohort of AYWH, examines the frequency of care interruptions, and assesses mental health issues during and after the COVID-19 pandemic while exploring mobile health (mHealth) potential.

Methods: Using a retrospective and prospective cohort study design, we enrolled AYWH at Mbarara Regional Referral Hospital and assessed missed visits using the timeline follow-back method (24 months). Mental health was evaluated using the Centers for Epidemiological Disease Scale-Depression (CES-D; >15 considered significant) and a locally validated anxiety/psychosocial distress scale (score 0-100) at enrolment, three and six months. Access to mobile phones, smartphones and internet was also assessed.

Results: Of 86 participants (mean age 18.6 years, 51.2% male), 89.5% had a viral load of <400 copies/ml. At enrolment, 53% had depression, with mean anxiety/psychosocial distress of 36.7. AYWH missed 19.0% of clinic visits, 3.2% of ART pickup visits, and 5.1% of laboratory visits, with no clear variation by pandemic phase. Depression and anxiety decreased significantly over 6-months (β=- 0.46; 95% CI - 0.73, - 0.19; p<0.001) and (β=- 1.25; 95% CI - 1.65, - 0.86; p=0.001) respectively. Most AYWH (59%) had mobile phone access, with 67% of those owning a smartphone and 71% having daily internet access.

Discussion/conclusion: AYWH frequently missed clinic appointments, regardless of pandemic phase. Mental health symptoms were initially high, but decreased over time. Most AYWH had access to phones and the internet.

Conclusion: To ensure continuity of HIV care and mental health support even during such disruptions, mHealth interventions may offer a viable solution and warrant further research.

Human immunodeficiency virus (HIV) infection in children is usually vertically acquired from the mother, in utero, intrapartum, or via breastfeeding. In this case, we report the probable case of horizontal transmission of HIV between two siblings. Based on the available clinical and laboratory data, perinatal, sexual, and health care-related transmission are unlikely. Although rare, this method of transmission needs to be recognized, especially in the setting of direct contact with an individual with poorly suppressed HIV viral infection.

Introduction: Globally, about 2.1 million children less than 15 years old get infected, and 110,000 die due to HIV/AIDS-related causes. Approximately 50% of HIV-exposed infants (HEI) are retained in Early Infants Diagnosis (EID) services for follow-up testing within the recommended timeframe of 18 months after birth. However, the retention of exposed infants who depend on the adults along their 18-month care cascade remains unknown. This study aimed to assess the retention in care of HEIs at the critical monitoring points of their care cascade and to establish factors associated with infant and maternal factors in order to improve the retention rates.

Methods: A retrospective cohort study utilizing quantitative methods of data collection was employed. The study examined 366 records of HIV-exposed infants born in 2021 in the Teso Sub-region. Retention rate was determined for 1st, 2nd, and 3rd PCR and rapid tests at 1.5, 9, 13.5, and 18 months, respectively. The Kaplan-Meier curve was used to estimate the retention rates at different time points of follow-up. The Cox proportional regression model was used to establish the factors associated with retention of HIV exposed infants in care.

Results: The study included 366 HIV-exposed infants (HEIs). The rate of retention was highest at 1.5 months (91.3%) but declined to (89.5%) at 9 months and 13 months (82%) before stabilizing back at 85.8% by 18 months. At multivariate analysis, factors that were significantly associated with retention in care of HIV-exposed infants included district of residence, with retention being higher in Kumi (aHR:1.50 :95%CI: 1.09-2.06) and Serere district compared to Bukedea district (aHR:1.54 :95%CI: 1.14-2.09). Timely EID registration (aHR:0.33 :95%CI: 0.12-0.71) and Timely initiation of Nevirapine prophylaxis (aHR:0.86:95%CI: 0.59-0.97) significantly reduced retention in care of HEIs.

Conclusion: Retention in care showed an early peak, followed by a gradual decline during mid-follow-up, and later stabilized toward the end of the observation period. The retention in care of HIV-exposed infants was significantly higher among infants residing in Kumi and Serere districts compared to Bukedea. Timely EID registration and timely initiation of Nevirapine prophylaxis significantly reduced retention in care. These findings underscore the importance of strengthening early infant diagnosis while addressing contextual barriers to enhance continuity of care with targeted support to lower-performing districts like Bukedea.

Background: HIV and HBV frequently coexist, with an estimated 8% prevalence of chronic HBV among people living with HIV (PLWH). In profoundly immunosuppressed PLWH, initiation or reinitiation of antiretroviral therapy (ART) can trigger immune reconstitution inflammatory syndrome (IRIS). When directed against HBV, IRIS can manifest as a hepatic flare (IRIS-HF). The long-term clinical implications of IRIS-HF remain incompletely understood.

Case presentation: We describe a 42-year-old man with HIV/HBV coinfection who had discontinued ART for one year. On ART reinitiation with bictegravir/emtricitabine/tenofovir alafenamide, his CD4 count was 2.3 cells/µL and HIV RNA was 4.8 × 10⁵ copies/mL. Five weeks later, he developed a severe hepatic flare (AST 987 U/L, ALT 968 U/L). The differential diagnosis included HBV-related IRIS, opportunistic infections (CMV hepatitis, disseminated MAC, EBV-associated lymphoma), and drug-induced liver injury. A liver biopsy revealed fatty degeneration and lymphocytic infiltration, consistent with HBV-related IRIS. Transaminases normalized by week 11. He subsequently achieved HBsAg loss with anti-HBs seroconversion within 2 years after ART reinitiation.

Conclusion: This case illustrates HBV flare due to IRIS following ART reinitiation in a profoundly immunosuppressed patient. The subsequent HBsAg loss suggests that IRIS-HF may promote HBV clearance, highlighting its potential role in achieving a functional cure. Vigilant monitoring of liver function is essential during ART initiation or reinitiation in HIV/HBV coinfected individuals.

Co-infection with human immunodeficiency virus (HIV) and syphilis creates a clinical and diagnostic challenge due to overlapping transmission routes and immunosuppression secondary to HIV. We describe a case concerning possible serological rebound in syphilis, which may be attributed to delayed initiation of antiretroviral therapy (ART), although this was not confirmed by a repeat non-treponemal test. A 40-year-old man with HIV and symptomatic secondary syphilis delayed ART initiation in the setting of poor treatment adherence for three months after syphilis diagnosis. During that three-month delay, his toluidine red unheated serum test (TRUST) titer was noted to rebound from 1:32 to 1:128. After ART initiation, he achieved sustained viral suppression (< 20 cp/mL) and immune recovery (CD4 + T cell count: 577/µL) within eight months of ART initiation; however, his syphilis titer did stabilize at 1:32. There is a need for caution in evaluating whenever possible when two diseases share a diagnosis. Our case highlights may highlight possible effects of deferral of ART initiation on immunologic recovery and the serological response for syphilis, and a need for ongoing comprehensive follow-up and circumspection in evaluation of serological change overall. Interpretation was limited by the absence of parallel repeat TRUST testing and being unable to entirely rule out possible reinfection.

Objective: Women with HIV (WWH) have up to five times higher risk for cardiovascular disease compared to age-matched women without HIV, and this risk is pronounced in reproductive-aged women. Pregnancy promotes systemic inflammation, leading to remodeling of the heart's structure and changes in function during and after pregnancy; therefore, we sought to examine the association of pregnancy history and number of live births with changes in cardiac structure and function in women with and without HIV (WWoH).

Methods: Cross-sectional data from the Multicenter AIDS Cohort Study/Women's Interagency HIV Study Combined Cohort Study (MWCCS) were analyzed using univariate and multivariable logistic and linear regression models. Data from participants with echocardiograms conducted during or after their last pregnancy were included. The association between echocardiographic parameters and ever having had a live birth and number of live births was examined by HIV status.

Results: Of 1,646 women (1,156 WWH and 490 WWoH), 83% (n = 1,369) had a history of live births. Among WWH, ever having a live birth was associated with decreased left ventricular ejection fraction (β=-1.33, p = 0.014) and number of live births was associated with increased odds of diastolic dysfunction (OR = 1.14, p = 0.009). In WWoH, live births were significantly associated with increased left ventricular end-diastolic volume index (β = 0.64, p = 0.029).

Conclusion: In this study, live birth history was associated with small but significant changes in cardiac structure and function, with WWH showing greaterlikelihood of adverse echocardiographic changes. This highlights differential cardiac remodeling patterns by HIV status. Longitudinal studies are needed to assess the progression and clinical implications of these findings.