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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 1/2009-12/2019 within the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort. We examined the association of three measures of HIV viral load (VL: baseline, current, cumulative) and current CD4 count with VTE. Cumulative VL (copy-days of viremia) was estimated with a time-weighted sum using the trapezoidal rule. We modeled the association between VL and VTE using Cox proportional hazards models (marginal structural Cox models for cumulative), adjusted for demographic and clinical characteristics. We compared the 75th percentile of the VL distribution with the 25th percentile using the hazard function from the model for all PWH with a VTE and those with a pulmonary embolism (PE).

Results: During a median of 4.8 years of follow-up, 424 PWH developed VTE. In adjusted analyses, higher cumulative VL (75th percentile vs. 25th percentile), the strongest VL predictor, was associated with a 1.45-fold higher risk of VTE (95%CI:1.22-1.72). Low CD4 cell count <100 cells/mm3 was associated with higher VTE risk (HR: 4.03, 95%CI: 2.76-5.89) as compared to ≥500 cells/mm3. Findings were similar for PWH who had a pulmonary embolism (n = 189).

Conclusions: Reducing HIV VL and maintaining CD4 cell count may help mitigate VTE risk in PWH.

Objective: The clinical and laboratory characteristics of HHV8-associated Multicentric Castleman Disease (MCD) in people living with HIV (PLWH) overlap with those of Hemophagocytic 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 PLWH. 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 PWLH 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.

Background: People living with HIV (PLHIV) often exhibit reduced CD4+ T cell counts and altered CD4/CD8 ratios, but their impact on fragility fractures remains underexplored. This study investigated the association between CD4 count, CD4/CD8 ratio, and fragility fractures in PLHIV in China.

Methods: A retrospective cohort study was conducted on PLHIV treated at Beijing Ditan Hospital from January 2011 to September 2023. Data on demographics, clinical status, and bone mineral density were collected. Fragility fractures were identified through medical records. Multivariate Cox regression was used to assess the relationship between CD4 count, CD4/CD8 ratio, and fracture risk, with restricted cubic splines (RCS) applied to explore potential nonlinear associations. Subgroup analyses evaluated the consistency of these findings.

Results: The study included 1,107 participants (median age 37 years, 92.6% male). The median CD4 count was 547 cells/μL, and the median CD4/CD8 ratio was 0.7. Fragility fractures occurred in 185 participants (16.7%). Lower CD4 counts (<200 cells/μL) were associated with a higher risk of fractures (aHR = 2.78; 95% CI: 1.66-4.65; p < 0.001), as were lower CD4/CD8 ratios (<0.5) (aHR = 3.43; 95% CI: 2.16-5.44; p < 0.001). RCS indicated a curvilinear association, with increased fracture risk at CD4/CD8 ratios below 1.16. Subgroup analyses confirmed the stability of these associations.

Conclusion: Lower CD4 counts and CD4/CD8 ratios are linked to an increased risk of fragility fractures in PLHIV, underscoring the importance of immune function in bone health.

Objective: We developed Healthy Families-PrEP to support perinatal women to use HIV prevention strategies.

Design: Single arm study to evaluate PrEP use among pregnant women exposed to the intervention.

Methods: We offered safer conception counselling including TDF/FTC as PrEP with adherence support (Healthy Families-PrEP) for women planning for pregnancy in South Africa with a partner with HIV or unknown serostatus. Women completed pregnancy and HIV testing quarterly and were followed for one year or until pregnancy end. For those initiating PrEP, electronic pillcap data and plasma were collected. We described PrEP adherence by proportion of days with pillcap openings and proportion of women with detected (≥10ng/mL) plasma tenofovir.

Results: From November 2017 to January 2020, 326 women with median age 24 (IQR: 22-27) years enrolled. Partner HIV-serostatus was unknown by 316 (97%). Over 3,204 person-months of follow-up, 56 women became pregnant. Twenty-six women used PrEP during pregnancy and opened pillcaps on a mean of 53.1% (95% CI 46.9-59.3%) of days. Plasma tenofovir was detected among 25.0%, 15.4%, and 12.5% of women providing samples during months 0-3, 4-6, and 7-9. No HIV seroconversions were observed.

Conclusions: We observed low pregnancy incidence. Counselling may have encouraged delayed pregnancy plans; some women may have exaggerated pregnancy plans to enroll. About half of pregnant women used PrEP and took over half of doses by pillcap. Fewer than 25% had tenofovir detected, likely reflecting pregnancy-related pharmacokinetics and adherence challenges. High interest in pregnancy PrEP use highlights the need to optimize adherence support and prevention choice.

Objective: The purpose of this study was to evaluate the efficacy of combination nicotine replacement therapy (c-NRT) for smoking cessation among people with HIV (PWH) in South Africa.

Design: We conducted an open label, individually randomized clinical trial.

Methods: Using a two-armed approach, PWH who smoke were randomized to receive either 1) intensive anti-smoking behavioral counseling (BC) or 2) intensive anti-smoking BC plus c-NRT (nicotine patches augmented by nicotine gum). Self-reported smoking abstinence was biochemically validated with exhaled breath carbon monoxide (CO) and urine cotinine at six months. Recruitment, provision of trial interventions, and follow-up of participants took place March 2014 through June 2016.

Results: We randomly assigned 280 participants to the BC arm and 281 participants to the BC + c-NRT arm. 438 (78%) participants were male and 123 (22%) were female. For our primary outcome of biochemically verified abstinence at six months, 41 (15%) were quit in the BC + c-NRT arm versus 28 (10%) in the BC arm, resulting in a 5% (95% CI -1%, 10%) absolute difference in relative risk and an adjusted odd ratio of 1.47 (95% CI: 0.86, 2.52) comparing the BC + c-NRT to the BC arm.

Conclusions: Although our results did not reach statistical significance, we found augmentation of BC with c-NRT to increase smoking abstinence at six months, which is consistent with performance in the general population. PWH in low-resource settings may benefit from the addition of c-NRT to existing tobacco cessation interventions.

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 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 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 (ps < 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.

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 Dec 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/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. LEfSe analysis demonstrated that 14 bacterial genera were significantly enriched at the genus level in the group with/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.

Conclusions: 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.

Objectives: To analyze weight changes associated with dolutegravir- versus efavirenz-based antiretroviral therapy (ART) in people living with HIV (PLHIV) in rural Tanzania, where undernutrition is prevalent.

Design: Longitudinal, observational study of the prospective Kilombero and Ulanga Antiretroviral Cohort (KIULARCO).

Methods: We included adult, ART-naïve, non-pregnant PLHIV initiating efavirenz-based ART 12/2016-02/2019 or dolutegravir-based ART 03/2019-12/2022. We used multivariable linear mixed-effects models to assess adjusted weight changes during 18 months after ART start and Cox regression models to assess factors associated with incident obesity, weight gain ≥10% and hypertension.

Results: Of 1,205 PLHIV at ART start (median age 40 years (IQR 32-48); 719 (59.7%) females), 166 (13.8%) individuals were underweight and 317 (26.3%) overweight/obese; 621 (51.5%) initiated efavirenz-based and 584 (48.5%) dolutegravir-based ART. After 18 months, estimated weight gain was 5.1 kg (95%CI 4.7-5.5) in the dolutegravir versus 4.0 kg (95%CI 3.7-4.4) in the efavirenz group. The weight gain difference between treatment groups was high in men (1.7 kg (95%CI 0.8-2.6; p < 0.001), in those aged 30-49 years (1.5 kg (0.8-2.1); p < 0.001) and those with CD4 counts ≥500/ul (2.5 kg (1.4 - 3.7), p < 0.001). Cumulative obesity incidence at 18 months was 10.9% (95%CI 8.3-14.0) in the dolutegravir and 5.1% (95%CI 3.6-7.1) in the efavirenz group. Associated factors were dolutegravir and a pre-ART body mass index (BMI) of 25-29 kg/m2. Dolutegravir and age, but not weight gain were associated with incident of hypertension.

Conclusions: Dolutegravir-based ART was associated with more weight gain, higher obesity and hypertension - especially in those with a higher pre-ART BMI compared to efavirenz-based regimens.

Objective: This study aimed to estimate the latent frailty trajectories and identify corresponding predictors (socio-demographic, HIV-related, comorbidities, and behavioral) among a cohort of PWH.

Design: Longitudinal observational study using latent class growth modeling.

Methods: Nine hundred seventy-six PWH aged 40 years and older with frailty measured from at least two visits within the ACTG HAILO cohort were included. Frailty components included weakness, physical activity, weight loss, exhaustion, and slowness. Latent class growth models were estimated to capture change in frailty over time; multinomial logistic regression was used to estimate associations between predictors and frailty trajectory class.

Results: At baseline, participants were M = 51.5 years old (SD = 7.5), 81% male (n = 783), 48% White non-Hispanic (n = 461), and 20% Hispanic (n = 195). Latent class growth models identified three frailty trajectories: Sustained robustness (n = 811; 83%), Worsening frailty (n = 79; 8%), and Frailty improvement (n = 86; 9%). Older age, race, sex at birth, select comorbidities (cardiovascular disease, depression, type 2 diabetes), and behavioral characteristics (physical activity, smoking, and alcohol) were associated with fluctuations in frailty trajectories over time (p < 0.05).

Conclusions: Modifiable factors such as managing comorbidities and promoting physical activity present ideal opportunities for future interventions to prevent or slow the progression of frailty.

Objective: To investigate whether psychosocial factors account for a proportion of the difference in cognitive performance between persons with and without HIV.

Design: Cross-sectional study of 273 participants (178 persons with HIV) from a low income area of Cape Town, South Africa.

Methods: Participants completed comprehensive cognitive testing (7 domains) and 12 psychosocial measures (5 current: income, occupation, assets, accommodation, depressive symptoms, 7 from childhood: assets, quality of education, exposure to childhood trauma and violence, primary caregiver occupation and highest level of education), as well as demographic measures standard in cognition studies (age, sex, years of education). We investigated the HIV association with global cognitive performance after adjustment for standard demographic variables, exploratory psychosocial variables, and balancing characteristics of those with and without HIV using propensity score modelling.

Results: Persons with HIV had significantly lower scores than persons without HIV in 8/12 psychosocial variables. Of these, 7/12 significantly predicted global T-score. In unadjusted regression, HIV status was associated with a reduction in global T-score of 3.72 units. Adjustment for standard variables, reduced the effect of HIV on global T score by 26.9% to 2.72, additional adjustment for psychosocial variables reduced by 40.3% to 2.22, and adjustment for propensity scores by 42.7% to 2.13.

Conclusions: Persons with HIV in this setting have lower psychosocial indices, both current and in childhood, which are associated with lower cognitive test performance as an adult. This is incompletely mitigated by adjustments for standard demographic variables which risks overestimation of cognitive impairment on a population level.