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Objective: Increasingly, pregnant women with HIV (WHIV) initiate antiretroviral therapy (ART) before conception. We assessed the risk of adverse perinatal outcomes among pregnant WHIV initiating ART preconception or antenatally, compared with women without HIV or ART-naive WHIV.

Design: Systematic review and meta-analysis.

Methods: We searched PubMed, EMBASE, CINAHL, and Global Health for studies published between 1 January 1980 and 14 July 2023. We assessed the association of preconception/antenatal ART initiation with preterm birth (PTB), very PTB (VPTB), spontaneous PTB (sPTB), low birthweight (LBW), very LBW (VLBW), small for gestational age (SGA), very SGA (VSGA), stillbirth and neonatal death (NND). Data were analysed using random effects meta-analyses. Quality assessments, subgroup and sensitivity analyses were conducted. PROSPERO registration: CRD42021248987.

Results: Thirty-one cohort studies were eligible, including 199 156 women in 19 countries. WHIV with preconception ART were associated with increased risk of PTB [risk ratio (RR) 1.55; 95% confidence interval (CI) 1.27-1.90], VPTB (RR 2.14, 95% CI 1.02-4.47), LBW (RR 2.19, 95% CI 1.32-3.63), VLBW (RR 3.34, 95% CI 1.08-10.35), SGA (RR 1.92, 95% CI 1.01-3.66), and VSGA (RR 2.79, 95% CI 1.04-7.47), compared with women without HIV. WHIV with antenatal ART were associated with increased risk of PTB (RR 1.35, 95% CI 1.15-1.58), LBW (RR 2.16, 95% CI 1.39-3.34), VLBW (RR 1.97, 95% CI 1.01-3.84), SGA (RR 1.77, 95% CI 1.10-2.84), and VSGA (RR 1.21, 95% CI 1.09-1.33), compared with women without HIV. Compared to ART-naive WHIV, WHIV with preconception or antenatal ART were associated with increased risk of SGA (preconception: RR 1.40, 95% CI 1.12-1.73; antenatal: RR 1.39, 95% CI 1.11-1.74) and VSGA (preconception: RR 2.44, 95% CI 1.63-3.66; antenatal: RR 2.24, 95% CI 1.48-3.40).

Conclusion: Among WHIV, both preconception and antenatal initiation of ART are associated with increased risks of adverse perinatal outcomes, compared to women without HIV and ART-naive WHIV.

Background: HIV infection is linked to persistent inflammation despite effective antiretroviral therapy (ART). The Systemic Immune-Inflammation Index (SII) is a marker of inflammation in various conditions.

Methods: We compared SII values between PWH and PWoH. Clinical blood laboratory data were used to calculate the SII for each participant using the formula [(Platelet count × Neutrophil count)/Lymphocyte count]. Differences in SII values between the groups were analyzed using the Wilcoxon test, and the impact of potential confounders was assessed with multivariable regression models.

Results: The study included 343 PWH and 199 PWoH. Age and race did not significantly differ, but sex distribution did (83.1% male in PWH vs. 55.8% in PWoH, P  < 0.0001). Among PWH, median [IQR] nadir and current CD4 + cell counts were 199 cells/μl [50, 350] and 650 [461,858], respectively. Nearly all PWH were on ART, with 97.2% achieving viral suppression. PWH had lower SII values than PWoH (327 [224, 444] vs. 484 [335,657], P  = 1.35e-14). PWH also had lower neutrophils and platelets ( P s < 0.001) and higher lymphocyte counts ( P  = 0.001). These differences remained significant after adjusting for age, sex, and other potential confounders.

Discussion: Contrary to expectations, PWH had lower SII levels, likely due to altered hematologic parameters influenced by HIV and ART. These findings suggest that SII interpretation in PWH requires consideration of unique hematologic profiles and underscore the need for further research to understand the mechanisms and clinical implications of SII in HIV management.

Background: People with HIV (PWH) have benefited greatly from antiretroviral therapy, but face additional challenges from age-related comorbid conditions, particularly cardiovascular disease including venous thromboembolism (VTE). Little is known about the effect of HIV viremia and immunodeficiency on VTE risk in this population.

Methods: We assessed incident, centrally adjudicated VTE among 21 507 PWH in care between January 2009 and December 2019 within the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort. We examined the association of three measures of HIV viral load (baseline, current, cumulative) and current CD4 + cell count with VTE. Cumulative viral load (copy-days of viremia) was estimated with a time-weighted sum using the trapezoidal rule. We modeled the association between viral load and VTE using Cox proportional hazards models (marginal structural Cox models for cumulative), adjusted for demographic and clinical characteristics. We compared the 75 th percentile of the viral load distribution with the 25th percentile using the hazard function from the model for all PWH with a VTE and those with a pulmonary embolism.

Results: During a median of 4.8 years of follow-up, 424 PWH developed VTE. In adjusted analyses, higher cumulative viral load (75th percentile vs. 25th percentile), the strongest viral load predictor, was associated with a 1.45-fold higher risk of VTE [95% confidence interval (95% CI): 1.22-1.72]. Low CD4 + cell count less than 100 cells/μl was associated with higher VTE risk (hazard ratio: 4.03, 95% CI: 2.76-5.89) as compared to at least 500 cells/μl. Findings were similar for PWH who had a pulmonary embolism ( n  = 189).

Conclusion: Reducing HIV viral load and maintaining CD4 + cell count may help mitigate VTE risk in PWH.

Objective: The clinical and laboratory characteristics of HHV-8-associated multicentric Castleman disease (MCD) in people with HIV (PWH) overlap with those of haemophagocytic lymphohistiocytosis (HLH) disease and indeed the two diagnoses may co-exist. A risk-stratified treatment approach to MCD based on Rituximab immunotherapy for mild cases and chemo-immunotherapy for severe cases has been shown to yield excellent outcomes in PWH. In contrast, HLH disease, previously known as secondary HLH, has a dismal prognosis even when promptly treated according to guidelines.

Design: A retrospective multicentre cohort study.

Methods: Retrospective analysis of prospectively collected clinical and pathological data on patients with biopsy-proven HIV-associated MCD at the National Centre for HIV Malignancy at Chelsea and Westminster Hospital, London between 2008 and 2024 and at the Department of Infectious Diseases at St. Joseph Hospital Berlin-Tempelhof, Germany between 2020 and 2024.

Results: In our UK-German cohort, including 113 PWH with MCD, we confirmed that HLH disease secondary to MCD is common (30%), and we demonstrated that HLH disease in this context does not adversely influence survival or risk of MCD relapse.

Conclusion: We suggest that a high HScore in MCD should not lead to a change in the treatment in this specific setting.

Objective: Kaposi's sarcoma-associated herpesvirus (KSHV) infection, essential for Kaposi sarcoma development especially in people with HIV (PWH), has been proposed to be transmitted through saliva. The potential role of salivary microbiota played in the infection of KSHV is largely obscure. This study aimed to explore the association between salivary microbiota and KSHV infection among PWH.

Design: Cross-sectional study.

Methods: During May to December 2022, we conducted a cross-sectional study among PWH in Ili prefecture Xinjiang, China. Participants completed face-to-face questionnaires, plasma and saliva samples were collected to assay KSHV infection status and 16S rRNA sequencing. We distinguished demographic characteristics between groups with and without KSHV, and compared the α and β diversity of the salivary microbiota. LEfSe identified key bacterial genera for Random Forest and XGBoost models to recognize the important discriminatory features.

Results: Among 876 PWH in Xinjiang, 38.7% were KSHV seropositive. Regression models indicated that moderate drinking, absence of dental treatment history, higher CD4 counts, and higher CD4/CD8 ratios were negatively associated with KSHV seropositivity. Linear discriminant analysis effect size (LEfSe) analysis demonstrated that 14 bacterial genera were significantly enriched at the genus level in the group with or without KSHV. Machine learning analyses gave an AUC of 0.66 for Random Forest and 0.85 for XGBoost in predicting KSHV infection status. The bacterial genera, including Alloprevotella , Fusobacterium , Prevotella_7 , Porphyromonas , Rothia , and Leptotrichia , were identified as important discriminatory features.

Conclusion: This study suggests the potential role of salivary microbiota in KSHV transmission among PWH. Identified microbial genera offer promising biomarkers for monitoring and managing KSHV in PWH.

Introduction: Approximately 39 million people live with HIV globally, with 1.3 million new infections annually. Despite improved treatment, noncommunicable diseases (NCDs) such as cardiovascular disease (CVD), neurological disorders, chronic kidney disease (CKD), and cancer are now the leading causes of death among people with HIV (PWH). Osteopontin (OPN) has emerged as a notable mediator in the inflammatory response to HIV and related NCDs. Our aim is to review the current understanding of OPN's role in HIV-related inflammatory pathways to highlight potential therapeutic avenues for improved treatment and mitigation of comorbidities.

Methods: We conducted a systematic review by searching relevant literature using specific keywords related to HIV, osteopontin, cardiovascular disease, inflammation, neurological disorders, cancer, and chronic kidney disease. The collected studies were organized and categorized by key themes, followed by a comprehensive analysis to identify patterns and draw conclusions regarding OPN's role in HIV-associated comorbidities.

Results: The intricate interactions between OPN, its isoforms, and HIV-related illnesses suggest that OPN can exhibit both pro-inflammatory and anti-inflammatory roles, depending on the stage of the disease and the specific cell type involved. Its functions are diverse throughout the progression of HIV and its associated comorbidities, including CVD, CKD, cancer, and neurological disorders.

Conclusion: OPN's effects on the disease progression of HIV and related NCDs are highly variable due to its diverse functions. Therefore, further research is essential to fully understand its complex roles before considering OPN as a therapeutic target for HIV and its comorbidities.

Objectives: Posttraumatic stress disorder (PTSD) may affect antiretroviral therapy (ART) response and clinical outcomes for veterans with HIV (VWH) receiving care in the Department of Veterans Affairs (VA). Objectives are to estimate the associations between PTSD and ART nonadherence, modifications, and failure; measure effect modification by number of deployments and combat exposure; and examine how these associations vary over time.

Design: In this prospective cohort study of all VWH on ART who deployed to Iraq and Afghanistan and receive care in the VA ( n  = 3206), patients entered at ART initiation and were censored in December 2022, totaling 22 261 person-years of follow-up.

Methods: Marginal structural log-binomial and Poisson models were fitted with a time-dependent exposure, adjusted for time-independent and time-dependent confounding and informative censoring, to estimate the associations between PTSD and ART nonadherence, modifications, and failure. Marginal structural shared frailty models were fitted to examine time-varying associations.

Results: PTSD increased the risk [adjusted risk ratio, 95% confidence interval (CI)] of ART nonadherence by 6% (1.06 [1.00, 1.13]) and the rate (adjusted incidence rate ratio, 95% CI) of ART modifications by 38% (1.38 [1.19, 1.58]). Multiple deployments amplified the association with ART nonadherence by 14%; combat exposure did not modify any association examined. The association with ART modifications increased during the first decade post-PTSD-diagnosis but subsequently stabilized.

Conclusions: PTSD increased ART nonadherence and ART modifications. Providers should screen for PTSD so that it can help guide medical decisions and treatment; particular attention should be paid to Veterans with multiple combat deployments.

Objective: To examine the impact of in-utero exposure to dolutegravir (DTG)-based or efavirenz (EFV)-based antiretroviral treatment (ART) on child neurodevelopmental outcomes.

Design: Prospective cohort design, enrolling three cohorts of 2-year-olds: children HIV-negative born to mothers with HIV (CHEU) receiving either DTG-based or EFV-based three-drug ART during pregnancy, and children born to mothers without HIV (CHUU).

Methods: Primary child neurodevelopmental outcomes were assessed using the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) and compared between cohorts using generalized estimating equation models adjusted for confounders. Children were classified as having an 'adverse ND outcome' if they scored at least 1 standard deviation (SD) below the mean or were unable to complete the BSID-III.

Results: Five hundred and sixty-four participants (202 DTG-exposed, 202 EFV-exposed, 160 HIV-unexposed; mean age 25.7 months, 49% female). Mean (SD) Gross Motor scores were slightly lower among CHEU vs. CHUU [54.6 (3.6) vs. 55.6 (4.3)] and among EFV-exposed vs. DTG-exposed [54.3 (3.5) vs. 54.9 (3.6)]. CHEU were more likely to be classified as having an 'adverse' expressive language outcome [13.2 vs 7%, adjusted risk ratio (aRR) = 2.06, 95% confidence interval (CI) 1.05-4.03] than CHUU, but other neurodevelopmental outcomes were similar. DTG exposure was associated with less frequent 'adverse' classification in Cognitive (2.5 vs. 7.4%, aRR = 0.33, 95% CI 0.13-0.79) and Expressive Language domains (10.0 vs. 16.4%, aRR = 0.58, 95% CI 0.35, 0.95), compared to EFV exposure.

Conclusion: Two-year neurodevelopmental outcomes among Botswana children DTG-exposed, EFV-exposed, and HIV-unexposed were mostly comparable. Children exposed in utero to EFV-based ART had higher risk of 'adverse' cognitive and expressive language outcomes compared with children DTG-exposed.