Purpose
In recent decades, the life expectancy of HIV-infected patients has increased considerably, to the extent that the disease can now be considered chronic. In this context of progressive aging, ...HIV-infected persons have a greater prevalence of comorbid conditions. Consequently, they usually take more non-antiretroviral drugs, and their drug therapy are more complex. This supposes a greater risk of drug interactions, of hospitalization, falls, and death. In the last years, deprescribing has gained attention as a means to rationalize medication use.
Methods
Review of the different therapeutic approach that includes optimization of polypharmacy and control and reduction of potentially inappropriate prescription.
Results
There are several protocols for systematizing the deprescribing process. The most widely used tool is the
Medication Regimen Complexity Index
, an index validated in HIV-infected persons. Anticholinergic medications are the agents that have been most associated with major adverse effects so, various scales have been employed to measure it. Other tools should be employed to detect and prevent the use of potentially inappropriate drugs. Prioritization of candidates should be based, among others, on drugs that should always be avoided and drugs with no justified indication.
Conclusions
The deprescribing process shared by professionals and patients definitively would improve management of treatment in this population. Because polypharmacy in HIV-infected patients show that a considerable percentage of patients could be candidates for deprescribing, we must understand the importance of deprescribing and that HIV-infected persons should be a priority group. This process would be highly feasible and effective in HIV-infected persons.
Effective, safe, and affordable antivirals are needed for coronavirus disease 2019 (COVID-19). Several lines of research suggest that tenofovir may be effective against COVID-19, but no large-scale ...human studies with appropriate adjustment for comorbidities have been conducted.
We studied HIV-positive individuals on antiretroviral therapy (ART) in 2020 at 69 HIV clinics in Spain. We collected data on sociodemographics, ART, CD4+ cell count, HIV-RNA viral-load, comorbidities and the following outcomes: laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, COVID-19 hospitalization, intensive care unit (ICU) admission and death. We compared the 48-week risks for individuals receiving tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC), tenofovir alafenamide (TAF)/FTC, abacavir (ABC)/lamivudine (3TC), and other regimes. All estimates were adjusted for clinical and sociodemographic characteristics via inverse probability weighting.
Of 51 558 eligible individuals, 39.6% were on TAF/FTC, 11.9% on TDF/FTC, 26.6% on ABC/3TC, 21.8% on other regimes. There were 2402 documented SARS-CoV-2 infections (425 hospitalizations, 45 ICU admissions, 37 deaths). Compared with TAF/FTC, the estimated risk ratios (RR) (95% confidence interval) of hospitalization were 0.66 (0.43, 0.91) for TDF/FTC and 1.29 (1.02, 1.58) for ABC/3TC, the RRs of ICU admission were 0.28 (0.11, 0.90) for TDF/FTC and 1.39 (0.70, 2.80) for ABC/3TC, and the RRs of death were 0.37 (0.23, 1.90) for TDF/FTC and 2.02 (0.88-6.12) for ABC/3TC. The corresponding RRs of hospitalization for TDF/FTC were 0.49 (0.24, 0.81) in individuals ≥50 years and 1.15 (0.59, 1.93) in younger individuals.
Compared with other antiretrovirals, TDF/FTC lowers COVID-19 severity among HIV-positive individuals with virological control. This protective effect may be restricted to individuals aged 50 years and older.
Aims
To compare patients who acquired HIV infection through use of injected drugs (HIV‐IDU) with patients who acquired HIV by sexual transmission (HIV‐ST) in terms of late presentation (LP), delay in ...anti‐retroviral treatment (ART) initiation, virological and immunological response to ART, mortality and progression to AIDS.
Design
Prospective multi‐centre cohort study of HIV‐infected subjects naive to ART at entry (Cohort of the Spanish HIV Research Network: CoRIS).
Setting
Thirty‐one centres from the Spanish public health‐care system.
Participants
A total of 9355 patients were included (1064 HIV‐IDU and 8291 HIV‐ST) during 2004–13.
Measurements
We compared LP (defined as presentation for care with a CD4 cell count < 350/μl and/or AIDS‐defining illness), delayed ART initiation (defined as initiating treatment more than 6 months after the date when treatment was indicated by the guidelines, or not initiating treatment at all when it was indicated), virological and immunological response to ART (defined as viral load < 50 HIV‐1 RNA copies/ml and a CD4 count increase of at least 100 cells/μl, respectively, after 1 year of treatment), mortality and progression to AIDS in HIV‐IDU and HIV‐ST.
Findings
Compared with HIV‐ST, HIV‐IDU had higher risk of LP odds ratio (OR) = 1.76; 95% confidence interval (CI) = 1.41–2.18, delayed ART initiation (OR 1.87; 95% CI = 1.46–2.40) and higher mortality hazard ratio (HR) = 1.43; 95% CI = 1.03–2.01 and risk of progression to AIDS subhazard ratio (SHR) = 1.68; 95% CI = 1.29–2.18. Virological suppression due to ART was lower in HIV‐IDU than in patients with HIV‐ST only among patients without hepatitis C virus (HCV) infection adjusted OR (aOR) = 0.59; 95% CI = 0.36–0.95; among patients with HCV infection, virological suppression due to ART did not show significant differences between HIV‐IDU and HIV‐ST. There were no significant differences in immunological response after adjusting by HCV (aOR = 0.74; 95% CI = 0.52–1.06).
Conclusions
In Spain, patients who acquire HIV infection through use of injected drugs appear to have a higher risk of late presentation, delayed initiation of anti‐retroviral treatment and progression to AIDS and death than patients who acquire HIV by sexual transmission.
To study whether the association between the CD4/CD8 ratio variation over time and the development of clinical outcomes vary in late presenters (CD4 count < 350/µL or AIDS event at enrolment) or ...advanced presenters (CD4 count < 200/µL or AIDS event at enrolment).
We included ART-naïve adults from the Cohort of the Spanish HIV/AIDS Research Network (CoRIS) enrolled between January 2004 up to November 2018 and with at least 6 months of follow-up. We used extended Cox proportional hazard models to estimate the hazard ratios (HRs) for the association between CD4/CD8 ratio over time and a composite endpoint of the occurrence of the first AIDS event, first serious non-AIDS event or overall mortality occurring from 6 months after enrolment. HRs in non-late, late and advanced presenters were obtained by including an interaction term between late presentation status and CD4/CD8 ratio over time.
Of 10,018 participants, 55.6% were late presenters and 26.5% were advanced presenters. Compared with CD4/CD8 ratio > 0.4, CD4/CD8 ratio ≤ 0.4 over time was associated with an increased risk of experiencing the composite endpoint in non-late (HR 1.90; 95%CI 1.48, 2.43), late (HR 1.94; 1.46, 2.57) and advanced presenters (HR 1.72; 1.26, 2.34). Similarly, CD4/CD8 ratio ≤ 0.4 over time was associated with a higher risk of developing an AIDS event (HR 3.31; 2.23, 4.93 in non-late; HR 2.75; 1.78, 4.27 in late and HR 2.25; 1.34, 3.76 in advanced presenters) or serious non-AIDS event (HR 1.39; 0.96, 2.02 in non-late, HR 1.62; 1.10, 2.40 in late and HR 1.49; 0.97, 2.29 in advanced presenters) as well as with a higher risk of overall mortality (HR 1.49; 0.92, 2.41 in non-late, HR 1.80; 1.04, 3.11 in late and HR 1.61; 0.92, 2.83 in advanced presenters) compared to CD4/CD8 > 0.4, regardless of the late presentation status.
A low CD4/CD8 measured over time is associated with increased risk of morbidity and mortality in people living with HIV independently of their late presentation status. These data support the prognostic role of CD4/CD8 over time and can help defining a subgroup of patients who need closer monitoring to avoid comorbidities.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We estimated the incidence rate of HIV medical care interruption (MCI) and its evolution over a 16 year-period, and identified associated risk factors among HIV-positive individuals from the CoRIS ...cohort in 2004-2020.
We included antiretroviral-naive individuals aged≥18 years at enrolment, recruited between January 1, 2004, and August 30, 2019, and followed-up until November 30, 2020.
Individuals with any time interval >15 months between two visits were defined as having a MCI. We calculated the incidence rate (IR) of having at least one MCI and used multivariable Poisson regression models to identify associated risk factors.
Of 15,274 individuals, 5,481 (35.9%) had at least one MCI. Of those, 2,536 (46.3%) returned to HIV care after MCI and 3,753 (68.5%) were lost to follow-up at the end of the study period. The incidence rate (IR) of MCI was 7.2/100 person-years (95%CI: 7.0-7.4). The annual IR gradually decreased from 20.5/100 py (95%CI: 16.4-25.6) in 2004 to 4.9/100 py (95%CI: 4.4-5.5) in 2014, a slight increase was observed between 2015 and 2018, reaching 9.3/100 py (95% CI: 8.6-10.2) in 2019. Risk factors for MCI included younger age, lower educational level, having contracted HIV infection through injecting drug use or heterosexual intercourse, having been born outside of Spain, and CD4 count > 200 cell/μL, viral load <100,000 and co-infection with hepatitis C virus at enrolment.
Around a third of individuals had at least one MCI during the follow-up. Identified predictors of MCI can help health workers to target and support most vulnerable individuals.
With the purpose of reducing the well-known negative impact of late presentation (LP) on people living with HIV (PLWH), guidelines on early HIV diagnosis were published in 2014 in Spain, but since ...then no data on LP prevalence have been published. To estimate prevalence and risk factors of LP and to evaluate their impact on the development of clinical outcomes in the Cohort of the Spanish HIV/AIDS Research Network (CoRIS) during 2004-2018.
CoRIS is an open prospective multicenter cohort of PLWH, adults, naive to ART at entry. LP was defined as HIV diagnosis with CD4 count ≤350 cells/μL or an AIDS defining event (ADE). Multivariable Poisson regression models were used to estimate both prevalence ratios (PR) for the association of potential risk factors with LP and Incidence rate ratios (IRRs) for its impact on the development of the composite endpoint (first ADE, first serious non-AIDS event SNAE or overall mortality).
14,876 individuals were included. Overall, LP prevalence in 2004-2018 was 44.6%. Risk factors for LP included older age, having been infected through injection drug use or heterosexual intercourse, low educational level and originating from non-European countries. LP was associated with an increased risk of the composite endpoint (IRR: 1.34; 95%CI 1.20, 1.50), ADE (1.39; 1.18, 1.64), SNAE (1.22; 1.01, 1.47) and mortality (1.71; 1.41, 2.08).
LP remains a health problem in Spain, mainly among certain populations, and is associated with greater morbidity and mortality. Public policies should be implemented to expand screening and early diagnosis of HIV infection, for a focus on those at greatest risk of LP.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Because inflammation is associated with mortality and has been linked to HIV transcription in lymphoid tissues during ART, it is necessary to address the long-term effects of switching 3-drug (3DR) ...to 2-drug regimens (2DR) on inflammation.
Nested study in the Spanish AIDS Research Network. We selected PWH ART-naive initiating 3DR who achieved viral suppression in the first 48 weeks and either remained on 3DR or switched to 2DR (3TC+bPI; 3TC+DTG; DTG+RPV). We assessed the trajectories on inflammatory markers during ART using multivariate piecewise mixed models.
We analyzed 619 plasma samples from 148 patients (3DR, N=90; 2DR, N=58), the median follow-up was 4.6 (IQR 3.2-6.2) years. There were no significant differences in baseline characteristics between groups. After adjusting for potential confounders, patients with 3DR experienced a slow decline of IL6, hs-CRP, sCD14, sCD163, and D-dimer over time. In contrast, compared to 3DR, switching to 2DR was associated with increases in IL-6 (p=0.001), hs-CRP (p=0.003), and D-dimer (p=0.001) after year 3 from virologic suppression. 2DR was associated with a higher risk of hs-CRP quartile increase (aOR 3.3, 95%CI 1.1-10) and D-dimer quartile increase (aOR 3.7, 95%CI 1.1-13). The adjusted biomarker trajectories did not reveal a distinct pattern according to the type of 2DR used (bPI
DTG).
In this study in virally suppressed individuals, maintaining 3DR was associated with a more favorable long-term inflammatory profile than switching to 2DR. The potential clinical implications of these findings on the development of non-AIDS events deserve further investigation.
To study the impact of late presentation (CD4 <350 cells/μL or an AIDS-defining event) on effectiveness and safety of initial ART and to evaluate whether treatment response depends on first-line ART ...regimen in late presenters (LP).
ART-naïve adults from the Cohort of the Spanish HIV/AIDS Research Network (CoRIS) starting triple ART between 2010 and 2018.
We used multivariable models to assess differences in viral suppression (VS, viral load <50 copies/mL), immunological response (IR, change in CD4 count, CD4% (>29%) and CD4/CD8 normalization (>0.4 and >1) multiple T-cell marker recovery (MTMR): CD4+ >500 cells/μL plus CD4% >29% plus CD4/CD8 >1), and treatment discontinuation due to adverse events (TDAE) at 48 weeks from ART initiation.
Of 8,002 participants, 48.7% were LP. Of them 45.8% initiated ART with a NNRTI- (mostly TDF/FTC/EFV), 33.9% with a PI- (mostly TDF/FTC+boosted DRV) and 20.3% with an INI-based regimen (mostly ABC/3TC/DTG). At 48 weeks, LP had similar VS, but worse IR, than non-LP with no difference on TDAE. LP initiating with NNRTI- based regimens were more likely to achieve VS than those starting with INI-based, due to the higher chance of achieving VS observed with TDF/FTC/RPV compared to ABC/3TC/DTG. Initial treatment with NNRTI- or PI-based showed similar IR than the INI-based regimens, which showed lower rates of TDAE than NNRTI- and PI-based regimens.
Despite safety and effectiveness of initial ART in terms of VS, LP may not experience complete IR. In LP, effectiveness and safety depends on both the class and the specific first-line ART regimen.
COVID-19 pandemic has put the protocols and the capacity of our Hospitals to the test. The management of severe patients admitted to the Intensive Care Units has been a challenge for all health ...systems. To assist in this challenge, various models have been proposed to predict mortality and severity, however, there is no clear consensus for their use. In this work, we took advantage of data obtained from routine blood tests performed on all individuals on the first day of hospitalization. These data has been obtained by standardized cost-effective technique available in all the hospitals. We have analyzed the results of 1082 patients with COVID19 and using artificial intelligence we have generated a predictive model based on data from the first days of admission that predicts the risk of developing severe disease with an AUC = 0.78 and an F1-score = 0.69. Our results show the importance of immature granulocytes and their ratio with Lymphocytes in the disease and present an algorithm based on 5 parameters to identify a severe course. This work highlights the importance of studying routine analytical variables in the early stages of hospital admission and the benefits of applying AI to identify patients who may develop severe disease.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
There is little information concerning infective endocarditis (IE) in patients with bicuspid aortic valve (BAV) or mitral valve prolapse (MVP). Currently, IE antibiotic prophylaxis (IEAP) is not ...recommended for these conditions.
This study sought to describe the clinical and microbiological features of IE in patients with BAV and MVP and compare them with those of IE patients with and without IEAP indication, to determine the potential benefit of IEAP in these conditions.
This analysis involved 3,208 consecutive IE patients prospectively included in the GAMES (Grupo de Apoyo al Manejo de la Endocarditis infecciosa en España) registry at 31 Spanish hospitals. Patients were classified as high-risk IE with IEAP indication (high-risk group; n = 1,226), low- and moderate-risk IE without IEAP indication (low/moderate-risk group; n = 1,839), and IE with BAV (n = 54) or MVP (n = 89).
BAV and MVP patients had a higher incidence of viridans group streptococci IE than did high-risk group and low/moderate-risk group patients (35.2% and 39.3% vs. 12.1% and 15.0%, respectively; all p < 0.01). A similar pattern was seen for IE from suspected odontologic origin (14.8% and 18.0% vs. 5.8% and 6.0%; all p < 0.01). BAV and MVP patients had more intracardiac complications than did low/moderate-risk group (50% and 47.2% vs. 30.6%, both p < 0.01) patients and were similar to high-risk group patients.
IE in patients with BAV and MVP have higher rates of viridans group streptococci IE and IE from suspected odontologic origin than in other IE patients, with a clinical profile similar to that of high-risk IE patients. Our findings suggest that BAV and MVP should be classified as high-risk IE conditions and the case for IEAP should be reconsidered.
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