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Background: Healthcare needs of older people with HIV (PWH) are changing given the higher incidence and earlier onset of age-related conditions compared to people without HIV (PWoH). This emphasizes a need for novel prognostic markers that allow identification of earlier stages of functional deterioration and prevent its advancement.

Methods: With this aim, we compared muscular imaging markers (whole-body MRI) and plasma biomarkers (irisin, myostatin, and coenzyme Q10) between PWH ( n  = 50) and PWoH ( n  = 25) aged 50 or older, and their associations with clinical conditions. Spearman's rank correlation coefficient was estimated and presented in correlation matrices for the most relevant groups of study variables with intramuscular fat fraction and plasma biomarkers. The distribution of plasma biomarkers and intramuscular fat fraction values was presented graphically in boxplots as a function of the functional test category. The Wilcoxon rank sum test was performed for comparisons, and P values are presented in tables. Raw and adjusted logistic models were fitted, and the estimated odds ratios are presented in tables. Adjusted variables were age, sex, and HIV status group.

Results: PWH exhibited greater deterioration, including lower autonomy, higher rates of prefrailty/frailty and malnutrition, and reduced bone mineral density. Mild to moderate dependency (Barthel) was observed only in PWH (18.4%), with 50% of PWH at risk of dependency (Barber) compared to 25% in PWoH. Prefrailty (Fried) was more prevalent in PWH (46%) than PWoH (28%), and frailty was exclusive to PWH (14%). PWH also had higher plasma myostatin and lower irisin levels. Lower intramuscular fat content was associated with malnutrition and dependency, while total intramuscular fat was positively correlated with time living with HIV and negatively with CD4 + T-cell count. Higher coenzyme Q10 levels were seen in states of poorer health, particularly frailty [Fried, Short Physical Performance Battery (SPPB)], while higher irisin levels were observed together with frailty (Fried) and dependency (Barthel, Barber). For all adjusted models, HIV status strongly influenced Fried, Barthel, and SPPB functional scores.

Conclusion: These findings underscore the need for further assessment of these biomarkers for their diagnostic and predictive potential in aging-related conditions such as frailty in PWH.

Objective: To estimate 10-year atherosclerotic cardiovascular disease (ASCVD) risk among US adults with diagnosed HIV (PWH) and number of first major adverse cardiovascular events (MACE) that are potentially preventable over a 5-year period, if US Department of Health and Human Services recommendations for statin therapy for PWH were fully implemented.

Design: Cross-sectional study of nationally representative, individual-level data on behavioral and clinical characteristics of US PWH.

Methods: Using data from standardized questionnaires and medical records abstraction collected from June 2022 to May 2023, we calculated weighted estimates of the following among PWH aged 40-75 years without documented cardiovascular disease ( N  = 2155): 10-year ASCVD risk; statin prescription by risk level; number potentially avoidable first MACE over 5 years with moderate-intensity statin treatment. We used the 2013 Pooled Cohort Equation to calculate ASCVD risk. MACE averted was estimated by applying the 5-year number needed to treat, from the REPRIEVE trial North American cohort, to the weighted number of PWH eligible for statin therapy.

Results: Among PWH eligible for therapy, 72.5% were male individuals, 42.5% were aged 50-59 years and 35.9% were Black, non-Hispanic persons. The overall median risk score was 7.1% [95% confidence interval (CI): 6.8-7.4%]. Among those with low (<5%) and moderate risk (5 to <20%), 19.8% (16.7-22.9%) and 36.9% (33.4-40.4%) were on statin therapy, respectively. An estimated 7418 (95% CI: 1116 -13 909) additional first MACE could be prevented over 5 years if eligible PWH received moderate-intensity statin therapy.

Conclusion: Fully implementing statin therapy recommendations for PWH in the United States could substantially reduce MACE among this population.

Objective: This study analyses liver stiffness (LS) dynamics in people with HIV (PWH) and advanced liver fibrosis who achieved sustained virological response (SVR) and assess factors associated with LS normalization or progression, after long-term follow-up.

Design: Prospective multicenter cohort study.

Methods: This study included individuals with HIV/HCV co-infection from the Spanish GEHEP-011 cohort, fulfilling: pretreatment LS ≥9.5 kPa; sustained virological response (SVR) with direct-acting antiviral regimen; available measurement of LS at SVR. Factors associated with LS normalization (achieving ≤7.2 kPa in two consecutive measurement) and progression (increase of >20% LS at the last measurement available) were analyzed.

Results: A total of 678 patients were included. The median follow-up was 40 (17-71) months. The repeated measures ANOVA revealed a significant main effect of time on LS. Overall, 221 (32.6%) achieved normalization. Lower probability of normalization was associated with advanced liver disease [baseline LS: sHR = 0.26 (95% CI, 0.19-0.37), P  < 0.001; liver decompensation before SVR: sHR = 0.22 (0.05-0.97), P  < 0.001; baseline MELD score: sHR = 0.81 (0.69-0.94), P  = 0.006]. LS progression occurred in 50 (7.4%). Progression was associated with higher baseline LS [sHR = 1.04 (1.01-1.07), P  = 0.007], controlled attenuation parameter (CAP) [CAP ≥ 280 dB/m: sHR = 2.94 (1.16-7.44)] and older age [sHR 1.06 (1.00-1.13), per year, P  = 0.04].

Conclusions: In PWH, LS significantly decreases after HCV cure in the long-term, achieving values of ≤7.2 kPa. In a substantial proportion of patients, LS remain stable or even increases. Older age and concomitant steatotic liver disease are associated with LS progression.

Background: Cerebral toxoplasmosis is a common opportunistic infection in people with HIV (PWH), associated with high morbidity and mortality. It is unclear how clinical characteristics, treatment response and long-term clinical outcomes in PWH with cerebral toxoplasmosis have changed due to improved treatment of HIV.

Methods: This single-centre retrospective observational cohort study of PWH with cerebral toxoplasmosis included patients over almost 25 years.

Results: Sixty-three eligible patients were identified. Most patients were late presenters presenting with headache and neurological symptoms. Overall survival was 79% over a mean follow up of 15 years. Seventy-three percent of deaths occurred within the first year after diagnosis. Almost 10% of patients experienced residual impairments.

Conclusion: An earlier diagnosis of HIV reduces the incidence of cerebral toxoplasmosis due to timely initiation of combination antiretroviral therapy (cART) and anti- Toxoplasma prophylaxis. High index of suspicion by clinicians is vital to timely start anti- Toxoplasma therapy. If treated correctly and timely, overall survival is high.

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.

Background: Dolutegravir plus lamivudine (DTG+3TC) is a recommended first-line regimen for people with HIV (PWH), based on its efficacy and safety. However, pivotal trials excluded individuals with transmitted resistance-associated mutations (tRAMs), even when these did not affect regimen activity. The impact of such mutations on DTG+3TC efficacy remains unknown.

Methods: This was a preplanned subanalysis of the D2ARLING trial, a randomized, open-label, phase IV study comparing DTG+3TC versus DTG+tenofovir disoproxil fumarate with emtricitabine or lamivudine (DTG+TDF/XTC) in antiretroviral-naïve PWH without baseline resistance test results. Per protocol, baseline genotypic resistance testing was performed on day 1 but remained blinded throughout the study and was only unblinded after completion. Participants with successfully amplified samples were included. The primary endpoint was the proportion with HIV-1 RNA <50 copies/mL at week 48 among those with baseline tRAMs, using both mITT-exposed and observed analyses.

Results: Among 211 participants (DTG+3TC: 104; DTG+TDF/XTC: 107), tRAMs were detected in 24.6%, mainly non-nucleoside reverse transcriptase inhibitors tRAMs. At week 48, viral suppression among participants with tRAMs was achieved in 85.7% (24/28) with DTG+3TC and 91.7% (22/24) with DTG+TDF/XTC (p = 0.67; mITT). In the observed analysis, suppression rates were 96.0% and 95.7%, respectively. Within the DTG+3TC arm, week-48 suppression was 96.0% in participants in whom tRAMs were detected and 98.6% in those without detected tRAMs (p = 0.45). No protocol-defined virological failures occurred in participants with tRAMs receiving DTG+3TC.

Conclusions: DTG/3TC showed high efficacy in participants with tRAMs not affecting this regimen. The detection of such tRAMs did not compromise treatment outcomes in treatment-naïve individuals in this setting.