Factors affecting outcomes of SARS-CoV-2 infection in people living with HIV are unclear. We assessed the factors associated with SARS-CoV-2 diagnosis and severe outcomes among people living with ...HIV.
We did a retrospective cohort study using data from the PISCIS cohort of people with HIV in Catalonia (Spain) between March 1 and Dec 15, 2020. We linked PISCIS data with integrated health-care, clinical, and surveillance registries through the Public Data Analysis for Health Research and Innovation Program of Catalonia (PADRIS) to obtain data on SARS-CoV-2 diagnosis, chronic comorbidities, as well as clinical and mortality outcomes. Participants were aged at least 16 years in care at 16 hospitals in Catalonia. Factors associated with SARS-CoV-2 diagnoses and severe outcomes were assessed using univariable and multivariable Cox regression models. We estimated the effect of immunosuppression on severe outcomes (hospital admission for >24 h with dyspnoea, tachypnoea, hypoxaemia, asphyxia, or hyperventilation; or death) using Kaplan-Meier survival analysis.
We linked 20 847 (72·8%) of 28 666 participants in the PISCIS cohort with PADRIS data; 13 142 people had HIV. 749 (5·7%) people with HIV were diagnosed with SARS-CoV-2: their median age was 43·5 years (IQR 37·0-52·7), 131 (17·5%) were female, and 618 (82·5%) were male. 103 people with HIV (13·8%) were hospitalised, seven (0·9%) admitted to intensive care, and 13 (1·7%) died. SARS-CoV-2 diagnosis was more common among migrants (adjusted hazard ratio 1·55, 95% CI 1·31-1·83), men who have sex with men (1·42, 1·09-1·86), and those with four or more chronic comorbidities (1·46, 1·09-1·97). Age at least 75 years (5·2, 1·8-15·3), non-Spanish origin (2·1, 1·3-3·4), and neuropsychiatric (1·69, 1·07-2·69), autoimmune disease (1·92, 1·14-3·23), respiratory disease (1·84, 1·09-3·09), and metabolic disease (2·59, 1·59-4·23) chronic comorbidities were associated with increased risk of severe outcomes. A Kaplan-Meier estimator showed differences in the risk of severe outcomes according to CD4 cell count in patients with detectable HIV RNA (p=0·039) but no differences were observed in patients with undetectable HIV RNA (p=0·15).
People living with HIV with detectable HIV viraemia, chronic comorbidities, and some subpopulations could be at increased risk of severe outcomes from COVID-19. These groups should be prioritised in clinical management and SARS-CoV-2 vaccination programmes.
Fundació "la Caixa".
For the Catalan, Spanish and Russian translations of the Summary see Supplementary Materials section.
Reports on the impact of some antiretrovirals against SARS-CoV-2 infection and disease severity are conflicting.
We evaluated the effect of tenofovir as either tenofovir alafenamide/emtricitabine ...(TAF/FTC) or tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) against SARS-CoV-2 infection and associated clinical outcomes among people living with HIV (PLWH).
We conducted a propensity score-matched analysis in the prospective PISCIS cohort of PLWH (n = 14 978) in Catalonia, Spain. We used adjusted Cox regression models to assess the association between tenofovir and SARS-CoV-2 outcomes.
After propensity score-matching, SARS-CoV-2 diagnosis rates were similar in TAF/FTC versus ABC/3TC recipients (11.6% versus 12.5%, P = 0.256); lower among TDF/FTC versus ABC/3TC recipients (9.6% versus 12.8%, P = 0.021); and lower among TDF/FTC versus TAF/FTC recipients (9.6% versus 12.1%, P = 0.012). In well-adjusted logistic regression models, TAF/FTC was no longer associated with reduced SARS-CoV-2 diagnosis adjusted odds ratio (aOR) 0.90; 95% confidence interval (CI), 0.78-1.04 or hospitalization (aOR 0.93; 95% CI, 0.60-1.43). When compared with ABC/3TC, TDF/FTC was not associated with reduced SARS-CoV-2 diagnosis (aOR 0.79; 95% CI, 0.60-1.04) or hospitalization (aOR 0.51; 95% CI, 0.15-1.70). TDF/FTC was not associated with reduced SARS-CoV-2 diagnosis (aOR 0.79; 95% CI, 0.60-1.04) or associated hospitalization (aOR 0.33; 95% CI, 0.10-1.07) compared with TAF/FTC.
TAF/FTC or TDF/FTC were not associated with reduced SARS-CoV-2 diagnosis rates or associated hospitalizations among PLWH. TDF/FTC users had baseline characteristics intrinsically associated with more benign SARS-CoV-2 infection outcomes. Tenofovir exposure should not modify any preventive or therapeutic SARS-CoV-2 infection management.
A percentage of hepatitis C virus (HCV)-infected patients fail direct acting antiviral (DAA)-based treatment regimens, often because of drug resistance-associated substitutions (RAS). The aim of this ...study was to characterize the resistance profile of a large cohort of patients failing DAA-based treatments, and investigate the relationship between HCV subtype and failure, as an aid to optimizing management of these patients.
A new, standardized HCV-RAS testing protocol based on deep sequencing was designed and applied to 220 previously subtyped samples from patients failing DAA treatment, collected in 39 Spanish hospitals. The majority had received DAA-based interferon (IFN) α-free regimens; 79% had failed sofosbuvir-containing therapy. Genomic regions encoding the nonstructural protein (NS) 3, NS5A, and NS5B (DAA target regions) were analyzed using subtype-specific primers.
Viral subtype distribution was as follows: genotype (G) 1, 62.7%; G3a, 21.4%; G4d, 12.3%; G2, 1.8%; and mixed infections 1.8%. Overall, 88.6% of patients carried at least 1 RAS, and 19% carried RAS at frequencies below 20% in the mutant spectrum. There were no differences in RAS selection between treatments with and without ribavirin. Regardless of the treatment received, each HCV subtype showed specific types of RAS. Of note, no RAS were detected in the target proteins of 18.6% of patients failing treatment, and 30.4% of patients had RAS in proteins that were not targets of the inhibitors they received.
HCV patients failing DAA therapy showed a high diversity of RAS. Ribavirin use did not influence the type or number of RAS at failure. The subtype-specific pattern of RAS emergence underscores the importance of accurate HCV subtyping. The frequency of “extra-target” RAS suggests the need for RAS screening in all three DAA target regions.
•At direct-acting antiviral (DAA) failure, patients carry subtype-dependent resistance-associated substitutions (RAS).•Next-generation sequencing (NGS)-based RAS testing can provide useful data for managing HCV patients failing DAAs.•RAS can appear in DAA-targeted and non-targeted regions. RAS screening should include all 3 target regions (NS3, 5A and 5B).
Mitochondrial parameters in peripheral blood mononuclear cells (PBMC) and their relationship with mitochondrially-driven PBMC apoptosis were investigated in a group of HIV-1-infected long-term ...nonprogressors (LTNP) and compared with untreated asymptomatic HIV-1 infected typical progressors (TP) and uninfected healthy controls (HC). Twenty-six LTNP, 27 TP and 31 HC were evaluated. Studies were performed in PBMCs. Mitochondrial DNA content (mtDNA) was assessed by quantitative real-time PCR. Activities of mitochondrial respiratory chain complexes (MRC) II, III and IV were determined by spectrophotometry. Caspase-3 activity was assessed by fluorimetry, and caspase-9 activation and Bcl-2 levels were assessed by immunoblotting. mtDNA abundance (p<0.05), MRC complex II (p<0.001), complex III (p<0.01) and complex IV (p=0.01) were lower in the TP group than in the HC group. In the LTNP group these parameters were similar to those of the HC group except for complex II, which was decreased (p<0.01). The PBMC of TP showed the highest overall apoptotic activation, since their caspase-3 activity was greater than that of HC (p<0.05) and LTNP. In the case of LTNP, however, the difference was non-significant. Caspase-9 and the caspase-9/Bcl-2 ratio were both over-expressed in TP compared to HC (p<0.01) and LTNP (p<0.05). Both of these measurements indicate that mitochondrially-driven apoptosis in TP is greater than in LTNP and HC. A relationship between mitochondrial damage and apoptotic activation was found in TP. Mitochondrial damage is associated with increased PBMC apoptosis in patients with active HIV-1 replication (TP). These abnormalities are slight or not present in LTNP.
Introduction
Advancements in and accessibility to effective antiretroviral therapy has improved the life expectancy of people living with HIV, increasing the proportion of people living with HIV ...reaching older age (≥60 years), making this population's health‐related quality of life (HRQoL) more relevant. Our aim was to identify the determinants of poor HRQoL in people living with HIV aged ≥60 years and compare them with those of their younger counterparts.
Methods
We used data from the ‘Vive+’ study, a cross‐sectional survey conducted between October 2019 and March 2020, nested within the PISCIS cohort of people living with HIV in Catalonia and the Balearic Islands, Spain. We used the 12‐item short‐form survey (SF‐12), divided into a physical component summary (PCS) and a mental component summary (MCS), to evaluate HRQoL. We used the least absolute shrinkage and selection operator for variable selection and used multivariable regression models to identify predictors.
Results
Of the 1060 people living with HIV (78.6% males) who participated in the study, 209 (19.7%) were aged ≥60 years. When comparing older people living with HIV (≥60 years) and their younger counterparts, older people exhibited a worse PCS (median 51.3 interquartile range {IQR} 46.0–58.1 vs. 46.43 IQR 42.5–52.7, p < 0.001) but a similar MCS (median 56.0 IQR 49.34–64.7 vs. 57.0 IQR 48.9–66.3, p = 0.476). In the multivariable analysis, cognitive function correlated with a PCS (β correlation factor β −0.18, p = 0.014), and depressive symptoms and satisfaction with social role correlated with an MCS (β 0.61 and β −0.97, respectively, p < 0.001) in people living with HIV aged ≥60 years.
Conclusion
Depressive symptoms, poor cognitive function, and lower satisfaction with social roles predict poorer HRQoL in older people living with HIV. These factors need to be considered when designing targeted interventions.
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.
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.
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%,
< .0001) but similar COVID-19 diagnoses (29.2% vs 29.4%,
= .847) compared to Spanish natives. Migrants had lower complete vaccination (78.9% vs 85.1%,
< .0001) and booster doses (63.0% vs 65.5%,
= .027). COVID-19 hospitalizations (8.1% vs 5.1%,
< .0001) and intensive care unit (ICU) admissions (2.9% vs 1.2%,
< .0001) were higher among migrants, with similar hospitalization duration (5.5 vs 4.0 days,
= .098) and mortality (3 0.2% vs 6 0.4%,
= .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.
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 aim of this study was to analyze the incidence of new cases, survival of HIV-1-infected patients with progressive multifocal leukoencephalopathy (PML), and the characteristics of PML-associated ...immune reconstitution inflammatory syndrome (IRIS).
Multicenter observational cohort study of all HIV-1-infected patients newly diagnosed of PML in 7 hospitals in Barcelona (Spain) from 2002 to 2006. The annual incidence of PML was calculated. Survival was estimated using the Kaplan-Meier method. IRIS was defined as new onset or rapid worsening of PML shortly after initiation of highly active antiretroviral therapy together with a decline in HIV-1 viral load and rising of CD4 lymphocytes.
Sixty-one new cases of PML were diagnosed. The mean survival time was 15 months 95% confidence interval (CI), 11 to 19. The Kaplan-Meier estimates of the probability of survival were 47.7% (95% CI, 35 to 59) at 6 months, 38.6% (95% CI, 25 to 51) at 12 months, 35.1% (95% CI, 22 to 48) at 24 months, and 25.1% (95% CI, 10 to 40) at 36 months. IRIS was diagnosed in 14 (23%) cases. Mortality was similar in patients with and without IRIS.
PML continues to be one of the deadliest opportunistic infections in acquired immunodeficiency syndrome patients. The development of PML-associated IRIS has no influence on prognosis.
Objectives To evaluate the virological efficacy, safety, tolerability and pharmacokinetics of a regimen containing 900/100 mg of ritonavir-boosted darunavir once daily in patients with antiretroviral ...experience but no darunavir resistance. Patients and methods An observational, prospective, multicentre study was conducted. Patients were included if 900/100 mg of darunavir/ritonavir once daily and at least one other active drug had been started due to virological failure, simplification or toxicity. Minimum follow-up was 24 weeks, or less if there was premature discontinuation of any drug or loss to follow-up. In a subgroup of patients, a complete 24 h pharmacokinetic study was performed by HPLC. Results One hundred and three patients (47 switch strategies, 56 early salvage therapies) were included. After 6 months, 85/103 (83%; 95% CI: 74%–89%) and 85/93 (91%; 95% CI: 84%–97%) patients had <50 copies/mL HIV-RNA by intention-to-treat and on-treatment analyses, respectively. The respective values were 42/47 (89%; 95% CI: 72%–96%) and 42/43 (98%; 95% CI: 88%–100%) in switch therapy, and 43/56 (77%; 95% CI: 64%–87%) and 43/50 (86%; 95% CI: 73%–94%) in salvage therapy. There was a significant increase in CD4 cell counts +73 cells/mm3 (95% CI: 43%–102%), P < 0.001. There were no interruptions due to rash or liver toxicity. Significant decreases in cholesterol and triglycerides were seen in patients with abnormal lipids at baseline. Ten patients discontinued antiretrovirals (5 were lost to follow-up and 5 due to side effects). Twenty-five patients were included in the pharmacokinetic study. All patients had trough plasma concentrations >0.05 μg/mL. Conclusions Darunavir/ritonavir at 900/100 mg once daily is highly effective, safe and well tolerated in treatment-experienced patients with no darunavir resistance, both in early salvage and switch strategies. Adequate drug plasma levels were achieved in all patients.
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