AIDS最新文献

Objective: People with HIV (PWH) have high burden of cardiovascular diseases, with cytomegalovirus (CMV) suggested to contribute to the cardiovascular disease (CVD) pathogenesis. However, research on CMV and hypertension in PWH is limited. We investigated whether CMV immunoglobulin G (IgG) seropositivity and concentrations are associated with prevalent and de novo hypertension in PWH.

Design: Longitudinal study of PWH from the Copenhagen Comorbidity in HIV Infection (COCOMO) study.

Methods: Participants with available CMV IgG concentrations, blood pressure, and data on use of antihypertensives were included. Associations between CMV IgG seropositivity and high CMV IgG concentrations (>180 U/ml) with prevalent and de novo hypertension at two-year follow-up were analyzed using logistic regression adjusted for age, sex, ethnic origin, body mass index, smoking, and CD4 + T-cell nadir.

Results: We included 1036 PWH, 95% were CMV IgG seropositive, and 41% had prevalent hypertension. Median CMV IgG concentration was higher among those with hypertension [159 U/ml, interquartile range (IQR) 124-501] than those without (147 U/ml, IQR 114-455) ( P  = 0.001). The incidence rate of de novo hypertension was 8.3 cases per 100 person-years. CMV IgG seropositivity [adjusted odds ratio (aOR) 0.61 [95% confidence interval (CI): 0.32-1.16], P  = 0.13] and high CMV IgG concentrations (aOR 1.09 [95% CI: 0.80-1.50], P  = 0.58) were not associated with prevalent hypertension. Likewise, no associations were observed between CMV IgG seropositivity (aOR 1.75 [95% CI: 0.61-7.40], P  = 0.36) or high CMV IgG concentrations (aOR 1.20 [95% CI: 0.74-1.93], P  = 0.46) and de novo hypertension.

Conclusions: We found no association between CMV IgG serostatus or concentrations and prevalent or de novo hypertension in PWH.

Chronic systemic inflammation may affect linear growth and neurodevelopment in children who are HIV-exposed but uninfected (cHEU). We examined plasma concentrations of neutrophil activation marker chitinase-3-like protein 1 (CHI3L1) levels in 153 Ugandan cHEU. At 18 months of age, CHI3L1 levels were inversely correlated with height-for-age z scores (τB = -0.17, P = 0.0035) and a normalized developmental score (τB = -0.20, P = 0.00027). CHI3L1 appears to be a marker of adverse growth and development in cHEU.

Background: People with HIV experience conventional and HIV-specific risk factors for increased blood pressure and may have different trajectories than people without HIV. Using data from the Multicenter AIDS Cohort Study (MACS) and Women's Interagency HIV Study (WIHS), we describe longitudinal patterns in blood pressure, hypertension, and vital status for people with HIV and without HIV.

Methods: We estimated longitudinal trajectories of systolic and diastolic blood pressure, pulse pressure, and mean arterial pressure using generalized estimating equations. Using multinomial logistic regression and Kaplan-Meier curves, we estimated the proportion of participants in four states corresponding to vital and hypertensive status.

Results: We included men and women with HIV who reported antiretroviral therapy use (MACS: n  = 1555; WIHS: n  = 2765) and men and women without HIV (MACS: n  = 1671; WIHS: n  = 1145) between ages 20 and 70 from 1998 to 2019. Trajectory shapes were similar between people with and without HIV within cohorts. Men with and without HIV had similar blood pressure across ages. Women with HIV had lower blood pressure than those without HIV (average systolic difference -4.7 mmHg; 95% CI: -5.6, -3.8). Despite comparable average time alive without hypertension, people with HIV experienced higher mortality than those without HIV (risk at age 50, MACS: 13.1% vs. 8.1%; WIHS 33.3% vs. 9.6%).

Conclusion: Blood pressure trajectories were similar between people with and without HIV, although blood pressure was slightly lower for women with HIV. High mortality among people with HIV (vs. without) may have resulted in a lower proportion of people with hypertension at older ages.

Objective: Antiretroviral therapy (ART) decreases HIV viral replication leading to CD4+ recovery, decreased CD8+ expansion and CD4+/CD8+ ratio recovery. We investigated factors associated with impaired recovery of CD4+ and CD4+/CD8+ ratios among people with HIV (PWH) maintaining HIV viral suppression.

Design/methods: PWH ≥18 years accessing the Southern Alberta Clinic between 01/01/1998-01/06/2022 entered the study at time of HIV viral suppression (<200 copies/mL). Continuous time-to-event Cox proportional hazard models estimated crude and adjusted hazards ratios (aHR) and 95% confidence intervals for factors associated with recovery of CD4+ count (≥500 cells/mm3) and CD4+/CD8+ ratio (≥1) at 10 years.

Results: Over 10 years, 83% of PWH reached a CD4+ count of ≥500 cells/mm3 but only 54% reached a CD4+/CD8+ ratio of ≥1. CD4+ recovery was less common among people diagnosed with HIV >50 years old vs. <30 years old (aHR: 0.59 [0.46-0.77]). Females were more likely to recover both CD4+ (aHR: 1.42[1.18-1.71]) and CD4+/CD8+ ratios (aHR: 1.56[1.25-1.95]) compared with males. Both higher baseline CD4+ counts and CD4+/CD8+ ratios were associated with greater immune recovery. ART regimen at study entry impacted CD4+ but not CD4+/CD8+ ratio recovery. CMV coinfection was associated with reduced CD4+/CD8+ ratio recovery (aHR: 0.47 [0.37-0.62]).

Conclusions: While most PWH with ongoing viral suppression will recover their CD4+ cell counts, recovery of CD4+/CD8+ ratio recovery is less common, indicating ongoing immune dysfunction. Several demographic and clinical factors are associated with impaired immune recovery. Further characterization and understanding of the long-term impact of impaired immune recovery is needed.

Objective: The lung is commonly involved in advanced Kaposi sarcoma (KS) but diagnosis of pulmonary KS in low-resource settings is difficult. Clinical assessments were evaluated to improve screening for pulmonary KS in a low-resource setting.

Methods: A longitudinal cohort of Africans with HIV-associated KS in the Parirenyatwa Hospital KS clinic, Harare, Zimbabwe, was followed from 2016-2018. Assessments included physical exam, chest x-ray, pulmonary function tests, and bronchoscopy with bacterial, fungal and TB cultures. Prevalence of pulmonary KS, TB and bacterial or fungal pneumonia were estimated with confidence intervals (CI). Collective diagnostic performance of combinations of 95 clinical assessments was evaluated by training iterative machine learning models using all available data. Assessments with high importance by cross-validated Shapley value analysis were included in the next iteration. Model performance was evaluated by Area Under Receiver-Operator Characteristic curves (AUROC).

Results: Among 181 participants with cutaneous KS, 113 had KS lesions in the lower respiratory tract (median 3 anatomic sites; range 1-11 sites). Pulmonary KS prevalence by bronchoscopy was 62.4% (95% CI 55.3, 69.6%). Prevalence of TB and fungal/bacterial pneumonia were 9.4% (95% CI 5.3-13.5%) and 9.4% (95% CI 5.1-13.7%), respectively. A converged set of seven clinical assessments retained in the final model had improved specificity and sensitivity for predicting pulmonary KS compared to individual assessments (AUROC 0.70; 95% CI 0.63-0.78).

Conclusion: Pulmonary KS burden remains high in Zimbabwe, despite increased access to antiretroviral therapy. A constellation of clinical assessments was identified to improve screening for pulmonary KS in low-resource settings.

Objectives: To compare changes in inflammatory biomarkers among youth with perinatally-acquired HIV (PHIV) and perinatal HIV-exposure without infection (PHEU), and to examine their associations with antiretroviral therapy (ART) and HIV disease status.

Design: A substudy within a longitudinal cohort study conducted across 14 U.S. sites.

Methods: We measured inflammatory biomarkers at baseline and ∼11 years later in 99 PHIV participants receiving ART and 59 PHEU participants. Univariable and multivariable linear regression models evaluated changes within and between groups and associations between biomarker concentrations at follow-up and ART regimens, CD4 counts, and viral loads (VL).

Results: At baseline, the median ages of PHIV and PHEU were 13 and 10 years. Median baseline concentrations of IL-18 and TNF-α were significantly higher in PHIV than PHEU. At follow-up, only the median sTNF-R2 concentration was significantly higher in PHIV than PHEU. In both groups, median biomarker concentrations decreased from baseline to follow-up except for TNF-α (increased in PHEU) and hsCRP (increased in both). A greater decrease in IL-10 in PHIV than PHEU was the only significant difference between groups. At follow-up, a nadir CD4 <15% was associated with lower IL-8 concentrations; CD4 count ≤500 cells/mm3 was associated with higher IL-18 concentrations; and VL ≥400 copies/mL was associated with higher sTNF-R2 concentrations. Longer duration of integrase inhibitor (INSTI) use was associated with increases in IL-6, IL-8, and IL-10.

Conclusions: Among PHIV on ART, inflammation decreases over time, associated with better HIV disease control, and likely reduces the risk of HIV-related comorbidities. However, inflammation may increase with INSTI exposure.

Objective: HIV has been shown to persist in cerebrospinal fluid (CSF) in persons on antiretroviral therapy (ART), which may be linked with inadequate ART exposure, potentially contributing to neurocognitive dysfunction. Our objective was to compare ART regimen inhibitory activity in CSF with participant outcomes.

Methods: A5321 is a prospective study of HIV reservoirs among persons with HIV on long-term ART with documented suppressed viremia; 44 participants who underwent lumbar puncture were evaluated. CSF trough concentrations were determined and inhibitory quotients (IQs) calculated for each antiretroviral (ARV) in a participant's regimen as the ratio of CSF concentration to literature values for in vitro HIV IC50or90. The geometric mean (GM) of CSF IQs of all drugs in each participant's ART regimen was calculated (CSF ART-IQGM). Statistical analyses evaluated associations among ART-IQGM and CSF HIV DNA, biomarkers and global deficit score (GDS).

Results: The median (Q1, Q3) CSF ART-IQGM was higher in those with undetectable vs detectable CSF HIV DNA: 0.9 (0.5, 1.6) vs 0.5 (0.3, 0.9), p = 0.027. Higher ART-IQGM was associated with lower GDS (i.e., better global cognitive function, Spearman: -0.30, p = 0.05). There was no association between CSF inflammatory biomarkers and ART-IQGM.

Conclusions: The CSF ART-IQGM is a novel approach to assess ART regimen activity. This metric was associated with lack of CSF HIV DNA detection and better GDS, which suggests ART regimen activity affects HIV persistence in CSF. This tool motivates further investigations of relationships between regimen activity and biomarkers of HIV persistence in CSF and in other anatomic HIV reservoirs.

Background: Some female sex workers (FSW) are initiated into sex work underage (<18 years) and/or through coercion, potentially increasing vulnerability. We estimated the contribution of these factors to HIV transmission in Tijuana, Mexico.

Methods: Using data from three bio-behavioural studies among adult FSWs in Tijuana (2003-2015), regression analysis assessed associations between underage or coerced entry into sex work and increased sexual or injecting risk behaviours. A dynamic HIV transmission model projected the proportion of new HIV infections prevented among FSWs over 2025-2034 from removing any additional risk behaviours associated with underage or coerced entry into sex work.

Results: Across studies (881 FSW), 10.1-39.0% of FSW reported initiating sex work underage, which was associated with client volume (adjusted rate ratio: 1.33; 95%CI:1.15-1.54), recent injecting drug use (IDU last 6 months) (adjusted odds ratio [aOR]: 1.74; 95%CI:1.08-2.79) and decreased odds of always using condoms (aOR: 0.75; 95%CI:0.53-1.06). Additionally, 19.0-20.7% reported coerced entry into sex work, which was marginally associated with recent IDU (aOR: 1.50; 95%CI:0.97-2.31).Removing the additional risks associated with underage or coerced entry into sex work from 2025 could prevent 33.0% (95%CrI:23.8-40.8%) of HIV infections amongst FSWs that started underage, 18.5% (95%CrI:11.3-28.3%) among FSW that were coerced, and 10.3% (95%CrI:6.8-14.5%) among all FSWs. If underage and coerced entry into sex work could also be stopped, then 22.3% (95%CrI:18.4-26.9) of HIV infections could be prevented among all FSWs.

Conclusions: Underage and coerced entry into sex work could be important drivers of HIV transmission among FSWs in Tijuana.

Objective: Primary 48-week analyses of the WISARD trial showed maintenance of virological suppression in most participants with K103N mutation when switched from standard regimens to dolutegravir plus rilpivirine (DTG/RPV). In this proof-of-concept pilot study we evaluate 96-week efficacy and safety of DTG/RPV.

Design: Open-label, parallel, two-arm, randomised trial across 32 sites in seven European countries.

Methods: Treatment-experienced HIV-1 participants with HIV RNA <50 copies/mL and documented prior K103N mutation, switched to DTG/RPV either immediately (DTG/RPV-I) or deferred after week 48 (DTG/RPV-D [control]; randomised 2:1). Endpoints were confirmed virological failure (CVF), virological suppression, safety, and changes in patient-reported outcomes from baseline to weeks 48/96.

Results: Of 140 randomised participants (95 DTG/RPV-I, 45 control), 4 had CVF by week 48 (3 DTG/RPV-I, 1 control) and 4 further patients had CVFs by week 96 (2 in each arm). Of the total 8 CVFs through week 96, HIV-1 RNA was ≥400 copies/mL in 4; only one sample amplified with no emergent DTG- or RPV-associated resistance mutations. The other three samples did not amplify due to insufficient sample. The week 96 proportion of subjects with virological suppression was 84.2% for DTG/RPV-I and 73.3% for DTG/RPV-D groups (difference +10.9%, 95% confidence interval -4 to +25.8; p=0.168). Serious adverse events were infrequent in both groups, and none were considered related to study medication. HRQoL, participant satisfaction, and sleep quality were stable over time and similar in both groups.

Conclusions: Week 96 data confirm that switching to DTG/RPV maintains virological suppression and is safe in most participants with a history of K103N.

Background: People with HIV (PWH) remain underrepresented in molecular studies and clinical trials of diffuse large B-cell lymphoma (DLBCL), despite DLBCL being a leading cause of cancer-related death in this population.

Methods: We performed whole-exome sequencing on 30 DLBCL tumors (24 with paired germline) from a Malawian cohort including both HIV-positive (HIV+) and HIV-negative (HIV-) individuals.

Results: KMT2D , BIRC6 , TP53 , and ARID1A were among the most frequently mutated genes. Compared to HIV- DLBCL, the HIV+ DLBCL tumors in this cohort were enriched for mutations in KMT2D , among others, and prior antiretroviral therapy associated with increased tumor mutational burden (TMB) and neoantigen load. Five HIV+ DLBCL tumors exhibited microsatellite instability (MSI), each with strong contributions from mutational signatures related to DNA repair. Furthermore, ARID1A mutations were observed in several MSI samples and in tumors with MSH2 loss. Integration with a published HIV+ DLBCL dataset revealed recurrent driver mutations including LILRB1 p.R30S, MYD88 p.S206C and p.S238N, and NRAS p.Q61K, as well as PTEN mutation as negatively prognostic.

Conclusions: Together, these results highlight distinct tumorigenic mechanisms in HIV+ DLBCL and underscore the need for mutational profiling of HIV+ DLBCL cohorts worldwide to identify biomarkers and therapeutic targets.