Mitochondrial Haplogroups and Weight Gain After Initiating ART in Patients With HIV.

We studied the association of mitochondrial DNA (mtDNA) haplogroups with weight and body mass index (BMI) gain at 96 weeks in 1019 treatment-naive persons with HIV (PWH) who initiated first-line antiretroviral therapy (ART) since 2014. The mean increase in weight and BMI over the study period was 2.90 kg and 0.98 kg/m2, respectively. We found a significant adjusted association between the major UK mtDNA haplogroup and lower weight and BMI increase at 96 weeks after ART initiation. Our findings reveal a potential role for mitochondrial genetics in the complex phenomenon of weight gain after initial ART in PWH.

Multiomics plasma effects of switching from triple antiretroviral regimens to dolutegravir plus lamivudine.

INTRODUCTION: The DOLAM trial revealed that switching from triple antiretroviral therapy (three-drug regimen; 3DR) to dolutegravir plus lamivudine (two-drug regimen; 2DR) was virologically non-inferior to continuing 3DR after 48 weeks of follow-up. Weight increased with 2DR relative to 3DR but it did not impact on metabolic parameters. METHODS: Multiomics plasma profile was performed to gain further insight into whether this therapy switch might affect specific biological pathways. DOLAM (EudraCT 201500027435) is a Phase 4, randomized, open-label, non-inferiority trial in which virologically suppressed persons with HIV treated with 3DR were assigned (1:1) to switch to 2DR or to continue 3DR for 48 weeks. Untargeted proteomics, metabolomics and lipidomics analyses were performed at baseline and at 48 weeks. Univariate and multivariate analyses were performed to identify changes in key molecules between both therapy arms. RESULTS: Switching from 3DR to 2DR showed a multiomic impact on circulating plasma concentration of N-acetylmuramoyl-L-alanine amidase (Q96PD5), insulin-like growth factor-binding protein 3 (A6XND0), alanine and triglyceride (TG) (48:0). Correlation analyses identified an association among the up-regulation of these four molecules in persons treated with 2DR. CONCLUSIONS: Untargeted multiomics profiling studies identified molecular changes potentially associated with inflammation immune pathways, and with lipid and glucose metabolism. Although these changes could be associated with potential metabolic or cardiovascular consequences, their clinical significance remains uncertain. Further work is needed to confirm these findings and to assess their long-term clinical consequences.

CD66b+/CD68+ circulating extracellular vesicles, lactate dehydrogenase and neutrophil-to-lymphocyte ratio can differentiate coronavirus disease 2019 severity during and after infection.

Coronavirus disease 2019 (COVID-19) has been a major public health burden. We hypothesised that circulating extracellular vesicles (cEVs), key players in health and disease, could trace the cell changes during COVID-19 infection and recovery. Therefore, we studied the temporal trend of cEV and inflammatory marker levels in plasma samples of COVID-19 patients that were collected within 24 h of patient admission (baseline, n = 80) and after hospital discharge at day-90 post-admission (n = 59). Inflammatory markers were measured by standard biochemical methods. cEVs were quantitatively and phenotypically characterized by high-sensitivity nano flow cytometry. In patients recovered from COVID-19 lower levels of inflammatory markers were detected. cEVs from vascular (endothelial cells) and blood (platelets, distinct immune subsets) cells were significantly reduced at day-90 compared to admission levels, a pattern also observed for cEVs from progenitor, perivascular and epithelial cells. The best discriminatory power for COVID-19 severity was found for inflammatory markers lactate dehydrogenase and neutrophil-to-lymphocyte ratio and for granulocyte/macrophage-released CD66b+/CD68+-cEVs. Albeit inflammatory markers were good indicators of systemic inflammatory response and discriminators of COVID-19 remission, they do not completely reveal cell stress and organ damage states. cEVs reaching baseline pre-infection levels at 90 days post-infection in recovered patients discriminate parental cells affected by disease.

Disparities in Coronavirus Disease 2019 Clinical Outcomes and Vaccination Coverage Among Migrants With Human Immunodeficiency Virus in the PISCIS Cohort: A Population-Based Propensity Score-Matched Analysis.

Background: Coronavirus disease 2019 (COVID-19) disproportionately affects migrants and ethnic minorities, including those with human immunodeficiency virus (HIV). Comprehensive studies are needed to understand the impact and risk factors. Methods: Using data from the PISCIS cohort of people with HIV (PWH) in Catalonia, Spain, we investigated COVID-19 outcomes and vaccination coverage. Among 10 640 PWH we compared migrants and non-migrants assessing rates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing, diagnosis, and associated clinical outcomes through propensity score matching and multivariable Cox regression. Results: The cohort (mean age, 43 years; 83.5% male) included 57.4% (3053) Latin American migrants. Migrants with HIV (MWH) had fewer SARS-CoV-2 tests (67.8% vs 72.1%, P < .0001) but similar COVID-19 diagnoses (29.2% vs 29.4%, P = .847) compared to Spanish natives. Migrants had lower complete vaccination (78.9% vs 85.1%, P < .0001) and booster doses (63.0% vs 65.5%, P = .027). COVID-19 hospitalizations (8.1% vs 5.1%, P < .0001) and intensive care unit (ICU) admissions (2.9% vs 1.2%, P < .0001) were higher among migrants, with similar hospitalization duration (5.5 vs 4.0 days, P = .098) and mortality (3 [0.2%] vs 6 [0.4%], P = .510). Age ≥40 years, CD4 counts <200 cells/µL, ≥2 comorbidities, and incomplete/nonreception of the SARS-CoV-2 vaccine increased the risk of severe COVID-19 among migrants. Conclusions: MWH had lower rates of SARS-CoV-2 testing and vaccination coverage, although the rates of COVID-19 diagnosis were similar between migrants and non-migrants. Rates of COVID-19-associated hospitalizations and ICU admissions were higher among migrants in comparison with non-migrants, with similar hospitalization duration and mortality. These findings can inform policies to address disparities in future pandemic responses for MWH.

The impact of the COVID-19 pandemic on healthcare services utilization among people living with HIV in Catalonia, Spain: A population-based cohort study.

BACKGROUND: The COVID-19 pandemic disrupted healthcare services usage. We estimated the impact of the COVID-19 pandemic on healthcare services utilization among people living with HIV (PLWH) in Catalonia, Spain. METHODS: We accessed public healthcare usage in HIV units, primary care, hospitals, and emergency departments among 17,738 PLWH in the PISCIS cohort from January 1, 2017, to December 31, 2020. We performed an interrupted time series analysis using the autoregressive integrated moving average to estimate the effect of COVID-19 on medical visits and HIV monitoring among PLWH. RESULTS: A non-significant decrease of 17.1% (95% CI: [-29.4, 0.4]) in overall medical visits was observed during the lockdown, followed by a steady resumption until the end of 2020. Three health facilities presented statistically significant declines in visits during the lockdown: HIV units (-44.8% [-56.7, -23.6]), hospitals (-40.4% [-52.8, -18.1]), and emergency departments (-36.9% [-47.0, -21.9]); thereafter, the visits have begun to increase steadily but not to previous levels as of December 2020. In contrast, primary care visits remained unchanged during the lockdown by 1.9% (95% CI: -13.5, 23.9). CD4 cell (54.2% [95% CI: -64.4, -36.0]) and HIV RNA viral load (53.1% [95% CI: -62.9, -36.1]) laboratory monitoring reduced significantly during the lockdown. CONCLUSION: COVID-19 lockdowns significantly disrupted in-person healthcare services usage among PLWH. The reduction in healthcare utilization however did not affect primary care services. Despite services gradually rebounding to pre-pandemic levels, it is imperative to effectively prepare for future pandemics and implement measures to ensure continuous provision of care to PLWH during pandemic lockdowns.

Evolving trends in neuropsychological profiles of post COVID-19 condition: A 1-year follow-up in individuals with cognitive complaints.

Cognitive difficulties are reported as lasting sequelae within post COVID-19 condition. However, the chronicity of these difficulties and related factors of fatigue, mood, and perceived health have yet to be fully determined. To address this, the current longitudinal study aimed to clarify the trends of cognitive test performance and cognitive domain impairment following COVID-19 onset, and whether hospitalization influences outcomes. 57 participants who reported subjective cognitive difficulties after confirmed COVID-19 infection were assessed at baseline (~6 months post COVID-19) and follow-up (~15 months later) visits. Assessments included measures across multiple cognitive domains and self-report questionnaires of fatigue, mood, and overall health. Analyses were conducted in three stages: at the test score level (raw and adjusted scores), at the cognitive domain level, and stratified by hospitalization status during infection. Results at the test-score level indicate that cognitive performance remains relatively stable across assessments at the group level, with no significant improvements in any adjusted test scores at follow-up. Cognitive domain analyses indicate significant reductions in attention and executive functioning impairment, while memory impairment is slower to resolve. On self-report measures, there was a significant improvement in overall health ratings at follow-up. Finally, those hospitalized during infection performed worse on timed cognitive measures across visits and accounted for a larger proportion of cases with short-term and working memory impairment at follow-up. Overall, our findings indicate that cognitive difficulties persist both at test score and cognitive domain levels in many cases of post COVID-19 condition, but evidence suggests some improvement in global measures of attention, executive functioning and overall self-rated health. Furthermore, an effect of hospitalization on cognitive symptoms post COVID-19 may be more discernible over time.

Evolving AIDS- and non-AIDS Mortality and Predictors in the PISCIS Cohort of People Living With HIV in Catalonia and the Balearic Islands (Spain), 1998-2020.

Background: Effective antiretroviral therapy (ART) has substantially reduced acquired immunodeficiency syndrome (AIDS)-related deaths, shifting the focus to non-AIDS conditions in people living with human immunodeficiency virus (HIV) (PLWH). We examined mortality trends and predictors of AIDS- and non-AIDS mortality in the Population HIV Cohort from Catalonia and Balearic Islands (PISCIS) cohort of PLWH from 1998 to 2020. Methods: We used a modified Coding Causes of Death in HIV protocol, which has been widely adopted by various HIV cohorts to classify mortality causes. We applied standardized mortality rates (SMR) to compare with the general population and used competing risks models to determine AIDS-related and non-AIDS-related mortality predictors. Results: Among 30 394 PLWH (81.5% male, median age at death 47.3), crude mortality was 14.2 per 1000 person-years. All-cause standardized mortality rates dropped from 9.6 (95% confidence interval [CI], 8.45-10.90) in 1998 through 2003 to 3.33 (95% CI, 3.14-3.53) in 2015 through 2020, P for trend = .0001. Major causes were AIDS, non-AIDS cancers, cardiovascular disease, AIDS-defining cancers, viral hepatitis, and nonhepatitis liver disease. Predictors for AIDS-related mortality included being aged ≥40 years, not being a man who have sex with men, history of AIDS-defining illnesses, CD4 < 200 cells/µL, ≥2 comorbidities, and nonreceipt of ART. Non-AIDS mortality increased with age, injection drug use, heterosexual men, socioeconomic deprivation, CD4 200 to 349 cells/µL, nonreceipt of ART, and comorbidities, but migrants had lower risk (adjusted hazard risk, 0.69 [95% CI, .57-.83]). Conclusions: Mortality rates among PLWH have significantly decreased over the past 2 decades, with a notable shift toward non-AIDS-related causes. Continuous monitoring and effective management of these non-AIDS conditions are essential to enhance overall health outcomes.

Major cardiovascular events after COVID-19 in people with HIV.

OBJECTIVES: To assess the effect of COVID-19 on the postacute risk of cardiovascular events (CVEs) among people with HIV (PWH). METHODS: Population-based matched cohort, including all PWH ≥16 years in the Catalan PISCIS HIV cohort. We estimated the incidence rate of the first CVE after COVID-19, analysed it a composite outcome (2020-2022). We adjusted for baseline differences using inverse probability weighting and used competing risk analysis. RESULTS: We included 4199 PWH with and 14 004 PWH without COVID-19. The median follow-up was 243 days (interquartile range [IQR]: 93-455), 82% (14 941/18 203) were men, with a median age of 47 years. Overall, 211 PWH with COVID-19 and 621 without developed CVE, with an incidence rate of 70.2 and 56.8/1000 person-years, respectively. During COVID-19 infection, 7.6% (320/4199) required hospitalization and 0.6% (25/4199) intensive care unit admission, 97% (4079/4199) had CD4+T-cell ≥200 cells/µL, 90% (3791/4199) had HIV-RNA<50 copies/mL and 11.8% (496/4199) had previous CVE at baseline. The cumulative CVE incidence was higher among PWH after COVID-19 compared with PWH without COVID-19 during the first year (log-rank p=0.011). The multivariable analysis identified significantly increased CVE risk with age, heterosexual men, previous cardiovascular disease (CVD), and chronic kidney or liver disease. COVID-19 was associated with increased subsequent risk of CVE (adjusted hazard ratio 1.30 [95% CI, 1.09-1.55]), also when only including individuals without previous CVD (1.60 [95% CI, 1.11-2.29]) or nonhospitalized patients (1.34 [95% CI, 1.11-1.62]). DISCUSSION: COVID-19 was associated with a 30% increased risk of major CVE in PWH during the subsequent year, suggesting that COVID-19 should be considered an additional CVD risk in PWH in the short term.

Identifying risk factors for anal cancer in people with HIV in Spain: a multicentre retrospective cohort study nested in the PISCIS cohort.

BACKGROUND: People with HIV have a substantially higher risk of anal cancer than the general population. We aimed to identify risk factors associated with the development of anal cancer among people with HIV to implement more effective and targeted screening strategies. METHODS: We conducted a multicentre retrospective cohort study in 16 hospitals across Catalonia and the Balearic Islands, Spain, between Jan 1, 1998, and Dec 31, 2022. Treatment-naive people with HIV nested in the PISCIS cohort aged 16 years and older with biopsy-proven squamous cell carcinoma of the anus or anal canal were eligible for inclusion. Data were retrieved from every hospital registry and were centrally validated in the PISCIS cohort and the Public Data Analysis for Health Research and Innovation Program. The primary outcome was the incidence rate (IR) of histologically confirmed anal cancer. We used Poisson regression to examine the association between the following risk factors and incidence of anal cancer: age, mode of HIV transmission, nadir CD4 cell count, and time period of HIV diagnosis. FINDINGS: Among 14 238 people with HIV, 107 (0·8%) developed anal cancer, with an overall IR of 72·5 cases per 100 000 person-years (95% CI 59·4-87·6) and median follow-up of 9·5 years (IQR 4·4-15·7). Of these patients with anal cancer, 37 (34·6%) died, of which 24 (64·9%) deaths were related to anal cancer. Incidence was highest among people with HIV with historical nadir CD4 counts of less than 200 cells per µL (IR 105·0 person-years, 95% CI 82·0-132·5) and lowest among those with counts of more than 350 cells per µL (2·9 person-years, 0·1-16·0). Among men who have sex with men (MSM), the IR was 211·5 person-years (95% CI 151·1-211·7) among those with a CD4 count of less than 200 cells per µL, 37·6 person-years (16·2-74·1) among those with a count of 200-350 cells per µL, and 4·8 person-years (0·1-26·9) among those with a count of more than 350 cells per µL. Among people with HIV younger than 30 years, there were no cases of anal cancer among women or men who do not have sex with men, and one case among MSM with a nadir CD4 count of more than 350 cells per µL (IR 4·8 person-years, 95% CI 0·1-26·9). In the multivariable analysis, people with HIV with nadir CD4 counts of more than 350 cells per µL had the lowest risk of developing anal cancer, compared with people with HIV with counts of less than 200 cells per µL (adjusted IR ratio 0·03, 95% CI 0·00-0·25; p=0·0010) or 200-350 cells per µL (0·30, 0·17-0·55; p<0·0001). Compared with people with HIV younger than 30 years, people with HIV aged 60 years and older had an adjusted IR ratio of 27·6 (3·7-206·9; p=0·0010) and people with HIV aged 45-59 years of 21·6 (3·0-156·4; p=0·0020). Compared with individuals diagnosed after 2015, a diagnosis of HIV before 1998 had an adjusted IR ratio of 33·0 (7·9-137·5; p<0·0001). INTERPRETATION: A nadir CD4 count threshold below 350 cells per µL, particularly less than 200 cells per µL, has the potential to identify people with HIV at heightened risk of developing anal cancer. Customised screening strategies that prioritise screening for individuals at high risk with this surrogate marker could maximise available resources. External validation of these data with other cohorts is required before screening recommendations can be updated. FUNDING: Catalan Health Department, Generalitat de Catalunya.

Discrimination of the Veterans Aging Cohort Study Index 2.0 for Predicting Cause-specific Mortality Among Persons With HIV in Europe and North America.

Background: Predicting cause-specific mortality among people with HIV (PWH) could facilitate targeted care to improve survival. We assessed discrimination of the Veterans Aging Cohort Study (VACS) Index 2.0 in predicting cause-specific mortality among PWH on antiretroviral therapy (ART). Methods: Using Antiretroviral Therapy Cohort Collaboration data for PWH who initiated ART between 2000 and 2018, VACS Index 2.0 scores (higher scores indicate worse prognosis) were calculated around a randomly selected visit date at least 1 year after ART initiation. Missingness in VACS Index 2.0 variables was addressed through multiple imputation. Cox models estimated associations between VACS Index 2.0 and causes of death, with discrimination evaluated using Harrell's C-statistic. Absolute mortality risk was modelled using flexible parametric survival models. Results: Of 59 741 PWH (mean age: 43 years; 80% male), the mean VACS Index 2.0 at baseline was 41 (range: 0-129). For 2425 deaths over 168 162 person-years follow-up (median: 2.6 years/person), AIDS (n = 455) and non-AIDS-defining cancers (n = 452) were the most common causes. Predicted 5-year mortality for PWH with a mean VACS Index 2.0 score of 38 at baseline was 1% and approximately doubled for every 10-unit increase. The 5-year all-cause mortality C-statistic was .83. Discrimination with the VACS Index 2.0 was highest for deaths resulting from AIDS (0.91), liver-related (0.91), respiratory-related (0.89), non-AIDS infections (0.87), and non-AIDS-defining cancers (0.83), and lowest for suicides/accidental deaths (0.65). Conclusions: For deaths among PWH, discrimination with the VACS Index 2.0 was highest for deaths with measurable physiological causes and was lowest for suicide/accidental deaths.

Psychopathology and psychosocial adjustment in patients with HIV-associated lipodystrophy

OBJECTIVE: To study whether patients with HIV-1 associated lipodystrophy (LD) on highly active antiretroviral treatment (HAART) have more psychopathology and worse psychosocial adjustment than a similar group without this syndrome. METHODS: In a cross-sectional, observational study we compared 47 HIV-1 infected patients with LD (LD group) with 39 HIV-1 infected patients without LD (non-LD group). All participants were on HAART. The Beck Depression Inventory (BDI), the State and Trait Anxiety Inventory (STAI) and the Goldberg Health Questionnaire (GHQ-60) were administered. Levels of familial, work and social adjustment and adjustment to stressful events were evaluated in a semi-structured interview. Clinical information was extracted from the clinical records. RESULTS: In the univariate analysis patients with LD showed higher state anxiety scores (p = 0.009) and worse work adjustment (p = 0.019) than those without LD. A total of 45.3% of LD patients scored above the cut-off point on the trait anxiety scale, and over 33.3% scored above the cut-off point on the BDI, GHQ and state anxiety scales. However, in multivariate analyses LD was not independently associated with psychopathology or with worse adjustment in the studied areas. CONCLUSIONS: The finding that LD was not a predictor of greater psychopathology or worse psychosocial adjustment in HIV-1 infected patients, despite the high scores found, suggests that factors not taken into account in this study, such as LD severity and self-perception should have been included in the analysis. Further studies including a greater number of variables and a larger sample size will advance our understanding of this complex condition.