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  • Oxford University Press (OUP)  (10)
  • 1
    In: Journal of Antimicrobial Chemotherapy, Oxford University Press (OUP), Vol. 75, No. 10 ( 2020-10-01), p. 3004-3014
    Abstract: We compared 48 week effectiveness and safety of first-line antiretroviral regimens. Methods We analysed HIV treatment-naive adults from the Cohort of the Spanish HIV/AIDS Research Network (CoRIS) starting the most commonly used antiretroviral regimens from 2014 to 2018. We used multivariable regression models to assess the impact of initial regimen on: (i) viral suppression (VS) (viral load & lt;50 copies/mL); (ii) change in CD4 cell count; (iii) CD4/CD8 normalization ( & gt;0.4 and & gt;1); (iv) CD4 percentage normalization ( & gt;29%); (v) multiple T-cell marker recovery (MTMR: CD4  & gt; 500 cells/mm3 plus CD4 percentage & gt;29% plus CD4/CD8  & gt; 1); (vi) lipid, creatinine and transaminase changes; and (vii) discontinuations due to adverse events (AE). Results Among 3945 individuals analysed, the most frequently prescribed regimens were ABC/3TC/DTG (34.0%), TAF/FTC/EVG/CBT (17.2%), TDF/FTC + DTG (11.9%), TDF/FTC/EVG/CBT (11.7%), TDF/FTC/RPV (11.5%), TDF/FTC + bDRV (8.3%) and TDF/FTC + RAL (5.3%). At 48 weeks, 89.7% of individuals achieved VS with no significant differences by initial regimen. CD4 mean increase was 257.8 (249.3; 266.2) cells/mm3, and it was lower with TAF/FTC/EVG/CBT and TDF/FTC/RPV compared with ABC/3TC/DTG. CD4 percentage normalization was less likely with TAF/FTC/EVG/CBT, and MTMR was less likely with TAF/FTC/EVG/CBT and TDF/FTC + RAL. The proportion of discontinuations due to AE was higher with TDF/FTC + bDRV (9.7%), followed by TDF/FTC/EVG/CBT (9.5%) and TDF/FTC + DTG (7.9%). Compared with ABC/3TC/DTG, cholesterol and LDL mean increases were higher with TAF/FTC/EVG/CBT and lower with TDF/FTC + DTG, TDF/FTC/RPV and TDF/FTC + RAL. Higher mean increases in triglycerides were significantly associated with TAF/FTC/EVG/CBT. Regimens containing DTG showed higher creatinine increases. Conclusions The significantly greater immunological response and safety of some combinations may be useful for making decisions when initiating treatment.
    Type of Medium: Online Resource
    ISSN: 0305-7453 , 1460-2091
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 1467478-6
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  • 2
    In: Clinical Infectious Diseases, Oxford University Press (OUP), ( 2024-07-03)
    Abstract: Non-AIDS defining malignancies present a growing challenge for persons with HIV (PWH), yet tailored interventions for timely cancer diagnosis are lacking. The Spanish IMPAC-Neo protocol was designed to compare two comprehensive cancer screening strategies integrated into routine HIV care. This study reports baseline data on the prevalence and types of precancerous lesions and early-stage cancer among participants at enrolment. Acceptability of the procedure was additionally assessed. Methods Cross-sectional analysis of a comprehensive screening protocol to detect precancer and cancer. The readiness of healthcare providers to implement the protocol was evaluated using a validated 4-item survey. Results Among the 1430 enrolled PWH, 1172 underwent 3181 screening tests, with positive findings in 29.4% of cases, leading to further investigation in 20.7%. Adherence to the protocol was 84%, with HIV providers expressing high acceptability (97.1%), appropriateness (91.4%), and feasibility (77.1%). A total of 145 lesions were identified in 109 participants, including 60 precancerous lesions in 35 patients (3.0%), 9 early-stage cancers in 9 patients (0.8%), and 76 low-risk lesions in 65 subjects (5.5%). Adverse events related to screening occurred in 0.8% of participants, all mild. The overall prevalence of cancer precursors or early-stage cancer was 3.8% (95% CI, 2.74%–5.01%), with highest rates observed in individuals screened for anal and colorectal cancers. Conclusions The baseline comprehensive cancer screening protocol of the IMPAC-Neo study successfully identified a significant proportion of PWH with precancerous lesions and early-stage cancer. High adherence rates and positive feedback from providers suggest effective implementation potential in real-world healthcare settings.
    Type of Medium: Online Resource
    ISSN: 1058-4838 , 1537-6591
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2024
    detail.hit.zdb_id: 2002229-3
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  • 3
    In: Journal of Antimicrobial Chemotherapy, Oxford University Press (OUP), Vol. 78, No. 6 ( 2023-06-01), p. 1423-1432
    Abstract: To assess the effectiveness and tolerability of dolutegravir (DTG)/lamivudine (3TC) among treatment-naive and virologically suppressed treatment-experienced individuals in the multicentre cohort of the Spanish HIV/AIDS Research Network (CoRIS) during the years 2018–2021. Methods We used multivariable regression models to compare viral suppression (VS) [HIV RNA viral load (VL) & lt;50 copies/mL] and the change in CD4 cell counts at 24 and 48 (±12) weeks after initiation with dolutegravir/lamivudine or other first-line ART regimens. Results We included 2160 treatment-naive subjects, among whom 401 (18.6%) started with dolutegravir/lamivudine. The remaining subjects started bictegravir (BIC)/emtricitabine (FTC)/tenofovir alafenamide (TAF) (n = 949, 43.9%), DTG + FTC/tenofovir disoproxil fumarate (TDF) (n = 282, 13.1%), DTG/3TC/abacavir (ABC) (n = 255, 11.8%), darunavir (DRV)/cobicistat(COBI)/FTC/TAF (n = 147, 6.8%) and elvitegravir (EVG)/COBI/FTC/TAF (n = 126, 5.8%). At 24 and 48 weeks after starting dolutegravir/lamivudine, 91.4% and 93.8% of the subjects, respectively, achieved VS. The probability of achieving VS with dolutegravir/lamivudine was not significantly different compared with any other regimen at 24 or 48 weeks, with the exception of a lower chance of achieving VS at 24 weeks for DRV/COBI/FTC/TAF (adjusted OR: 0.47; 95% CI: 0.30–0.74) compared with dolutegravir/lamivudine. For the analysis of treatment-experienced virally suppressed subjects we included 1456 individuals who switched to dolutegravir/lamivudine, among whom 97.4% and 95.5% maintained VS at 24 and 48 weeks, respectively. During the first 48 weeks after dolutegravir/lamivudine initiation, 1.0% of treatment-naive and 1.5% of treatment-experienced subjects discontinued dolutegravir/lamivudine due to an adverse event. Conclusions In this large multicentre cohort, effectiveness and tolerability of dolutegravir/lamivudine were high among treatment-naive and treatment-experienced subjects.
    Type of Medium: Online Resource
    ISSN: 0305-7453 , 1460-2091
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 1467478-6
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  • 4
    In: Clinical Infectious Diseases, Oxford University Press (OUP), ( 2023-06-22)
    Abstract: Evidence supporting combination treatment with a beta-lactam plus an aminoglycoside (C-BA) for endocarditis caused by viridans and gallolyticus group streptococci (VGS-GGS) with intermediate susceptibility to penicillin (PENI-I) is lacking. We assessed the clinical characteristics and outcomes of PEN-I VGS-GGS endocarditis and compared the effectiveness and safety of C-BA with third-generation cephalosporin monotherapy. Methods Retrospective analysis of prospectively collected data of a cohort of definite endocarditis caused by penicillin-susceptible and PENI-I VGS-GGS (penicillin minimum inhibitory concentration ranging from 0.25 to 2 mg/L) between 2008 and 2018 in 40 Spanish hospitals. We compared cases treated with monotherapy or with C-BA and performed multivariable analyses of risk factors for in-hospital and 1-year mortality. Results A total of 914 consecutive cases of definite endocarditis caused by VGS-GGS with complete or intermediate susceptibility to penicillin were included. A total of 688 (75.3%) were susceptible to penicillin and 226 (24.7%) were PENI-I. Monotherapy was used in 415 (45.4%) cases (cephalosporin in 331 cases) and 499 (54.6%) cases received C-BA. In-hospital mortality was 11.9%, and 190 (20.9%) patients developed acute kidney injury. Heart failure (odds ratio [OR]: 6.06; 95% confidence interval [CI] : 1.37–26.87; P = .018), central nervous system emboli (OR: 9.83; 95% CI: 2.17–44.49; P = .003) and intracardiac abscess (OR: 13.47; 95% CI: 2.24–81.08; P = .004) were independently associated with in-hospital mortality among PEN-I VGS-GGS cases, while monotherapy was not (OR: 1.01; 95% CI: .26–3.96; P = .982). Conclusions Our findings support the use of cephalosporin monotherapy in PEN-I VGS-GGS endocarditis in order to avoid nephrotoxicity without adversely affecting patient outcomes.
    Type of Medium: Online Resource
    ISSN: 1058-4838 , 1537-6591
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    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2002229-3
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  • 5
    In: Clinical Infectious Diseases, Oxford University Press (OUP), Vol. 69, No. 10 ( 2019-10-30), p. 1690-1700
    Abstract: Outpatient parenteral antibiotic treatment (OPAT) has proven efficacious for treating infective endocarditis (IE). However, the 2001 Infectious Diseases Society of America (IDSA) criteria for OPAT in IE are very restrictive. We aimed to compare the outcomes of OPAT with those of hospital-based antibiotic treatment (HBAT). Methods Retrospective analysis of data from a multicenter, prospective cohort study of 2000 consecutive IE patients in 25 Spanish hospitals (2008–2012) was performed. Results A total of 429 patients (21.5%) received OPAT, and only 21.7% fulfilled IDSA criteria. Males accounted for 70.5%, median age was 68 years (interquartile range [IQR], 56–76), and 57% had native-valve IE. The most frequent causal microorganisms were viridans group streptococci (18.6%), Staphylococcus aureus (15.6%), and coagulase-negative staphylococci (14.5%). Median length of antibiotic treatment was 42 days (IQR, 32–54), and 44% of patients underwent cardiac surgery. O ne-year mortality was 8% (42% for HBAT; P 〈 .001), 1.4% of patients relapsed, and 10.9% were readmitted during the first 3 months after discharge (no significant differences compared with HBAT). Charlson score (odds ratio [OR], 1.21; 95% confidence interval [CI] , 1.04–1.42; P = .01) and cardiac surgery (OR, 0.24; 95% CI, .09–.63; P = .04) were associated with 1-year mortality, whereas aortic valve involvement (OR, 0.47; 95% CI, .22–.98; P = .007) was the only predictor of 1-year readmission. Failing to fulfill IDSA criteria was not a risk factor for mortality or readmission. Conclusions OPAT provided excellent results despite the use of broader criteria than those recommended by IDSA. OPAT criteria should therefore be expanded.
    Type of Medium: Online Resource
    ISSN: 1058-4838 , 1537-6591
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
    detail.hit.zdb_id: 2002229-3
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  • 6
    In: Journal of Antimicrobial Chemotherapy, Oxford University Press (OUP), ( 2019-10-29)
    Abstract: To assess the attitudes and opinions about generic antiretroviral drugs (ARVs) and single-tablet regimen (STR) de-simplification among physicians prescribing HIV treatment in the cohort of the Spanish HIV/AIDS Research Network (CoRIS). Methods An online questionnaire with 27 structured questions was sent to all physicians (n = 199) who prescribed ARVs among the 45 centres participating in the cohort. Results A total of 169 (84.9%) physicians answered the questionnaire. Only 4.1% of the physicians would never prescribe generic ARVs, but 53.3% would not prescribe them if the number of pills per day increased and 89.3% would not prescribe them if the number of doses per day increased. However, 84.0% of the physicians agreed to prescribe generic ARVs if doing so would decrease costs for the public healthcare system. The percentages of physicians stating that generic ARVs (compared with branded ones) would be associated with worse adherence, more adverse effects or more probability of virological failure, provided that the number of pills and doses per day would not change, were low: 0.6%, 7.7% and 3.6%, respectively. However, these percentages were much higher if the generic ARV entailed breaking an STR: 63.9%, 18.9% and 42.0%, respectively. Most physicians stated that they needed more information about the effectiveness and safety of generic ARVs and the price difference compared with their branded equivalents. Conclusions Although most physicians were confident about prescribing generic ARVs, the majority had strong concerns about de-simplifying STR, and they also needed more information about generic drugs.
    Type of Medium: Online Resource
    ISSN: 0305-7453 , 1460-2091
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
    detail.hit.zdb_id: 1467478-6
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  • 7
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 9, No. 9 ( 2022-09-02)
    Abstract: Outpatient parenteral antibiotic treatment (OPAT) programs are increasingly used to manage infective endocarditis (IE), but current criteria for indicating OPAT are markedly conservative. We aimed to investigate whether more liberal criteria for indicating OPAT in IE can be safely used. Methods This was a prospective multicenter nationwide cohort study (2008–2018). Rates of readmission, recurrences, and 1-year mortality were compared between hospital-based antibiotic treatment (HBAT) and OPAT. Risk factors for readmission and mortality in OPAT patients were investigated by logistic regression. Patients did not fulfill OPAT-GAMES (Grupos de Apoyo al Manejo de la Endocarditis en ESpaña) criteria if they had any of the following: cirrhosis, severe central nervous system emboli, undrained abscesses, severe conditions requiring cardiac surgery in nonoperable patients, severe postsurgical complications, highly difficult-to-treat microorganisms, or intravenous drug use. Results A total of 2279 HBAT patients and 1268 OPAT patients were included. Among OPAT patients, 307 (24.2%) did not fulfill OPAT-GAMES criteria. Overall, OPAT patients presented higher rates of readmission than HBAT patients (18.2% vs 14.4%; P = .004), but no significant differences were found in the propensity analysis. Patients not fulfilling OPAT-GAMES criteria presented significantly higher rates of readmission than HBAT and OPAT-GAMES (23.8%, 14.4%, 16.4%; P  & lt; .001), whereas no significant differences were found in mortality (5.9%, 8%, 7.4%; P = .103) or recurrences (3.9%, 3.1%, 2.5%; P = .546). Not fulfilling OPAT-GAMES criteria was associated with higher risk of readmission (odds ratio [OR], 1.43; 95% CI, 1.03–1.97; P = .03), whereas cardiac surgery was associated with lower risk (OR, 0.72; 95% CI, 0.53–0.98; P = .03). Conclusions OPAT-GAMES criteria allow identification of IE patients at higher risk of long-term complications to whom OPAT cannot be safely administered.
    Type of Medium: Online Resource
    ISSN: 2328-8957
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2757767-3
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  • 8
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 8, No. 6 ( 2021-06-01)
    Abstract: Although Streptococcus anginosus group (SAG) endocarditis is considered a severe disease associated with abscess formation and embolic events, there is limited evidence to support this assumption. Methods We performed a retrospective analysis of prospectively collected data from consecutive patients with definite SAG endocarditis in 28 centers in Spain and Italy. A comparison between cases due to SAG endocarditis and viridans group streptococci (VGS) or Streptococcus gallolyticus group (SGG) was performed in a 1:2 matched analysis. Results Of 5336 consecutive cases of definite endocarditis, 72 (1.4%) were due to SAG and matched with 144 cases due to VGS/SGG. SAG endocarditis was community acquired in 64 (88.9%) cases and affected aortic native valve in 29 (40.3%). When comparing SAG and VGS/SGG endocarditis, no significant differences were found in septic shock (8.3% vs 3.5%, P = .116); valve disorder, including perforation (22.2% vs 18.1%, P = .584), pseudoaneurysm (16.7% vs 8.3%, P = .108), or prosthesis dehiscence (1.4% vs 6.3%, P = .170); paravalvular complications, including abscess (25% vs 18.8%, P = .264) and intracardiac fistula (5.6% vs 3.5%, P = .485); heart failure (34.7% vs 38.9%, P = .655); or embolic events (41.7% vs 32.6%, P = .248). Indications for surgery (70.8% vs 70.8%; P = 1) and mortality (13.9% vs 16.7%; P = .741) were similar between groups. Conclusions SAG endocarditis is an infrequent but serious condition that presents a prognosis similar to that of VGS/SGG.
    Type of Medium: Online Resource
    ISSN: 2328-8957
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2757767-3
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  • 9
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 9, No. 3 ( 2022-03-01)
    Abstract: Physical activity has anti-inflammatory effects and reduces morbidity and mortality in the general population, but its role in the clinical, CD4/CD8 ratio, and immune activation status of HIV-infected patients has been poorly studied. Methods A cross-sectional study was carried out in a cohort of 155 HIV-infected patients on stable antiretroviral therapy (ART) to compare clinical, biochemical, CD4/CD8 ratio, and immune activation status according to their physical activity in the last 2 years (sedentary/low vs moderate/intense) assessed by the iPAQ. A binary logistic regression and mixed analysis of variance were performed to evaluate the impact of levels of physical activity on CD4/CD8 ratio. Results In our series, 77 (49.7%) out of 155 patients were sedentary, and 78 (50.3%) practiced moderate/intense physical activity. Moderate/intense physical activity was associated with better metabolic control (lower body mass index, P = .024; glucose, P = .024; and triglyceride, P = .002) and CDC HIV stage (P = .046), lower CD8+ (P =  .018), CD4+CD8+ (P = .026), CD4+CD86+ (P = .045), CD4+HLA-DR+ (P = .011), CD8+HLA-DR+ (P = .048) T lymphocytes and CD16+HLA-DR+ natural killer cells (P = .026), and higher CD3+CD4+ T lymphocytes (P = .016) and CD4/CD8 ratio (P = .001). Sedentary lifestyle (odds ratio [OR], 2.12; P = .042), CD4 nadir (OR, 1.005; P  & lt; .001), and CD8+CD38+ T cells (OR, 1.27; P = .006) were independently associated with low CD4/CD8 ratio ( & lt;0.8). Earlier and more intense CD4/CD8 ratio recovery was observed in patients with higher physical activity in the 2-year follow-up with a significant interaction between these variables: F(2, 124) = 3.31; P = .049; partial η2 = 0.042. Conclusions Moderate to high physical activity is associated with beneficial health effects, improvement in metabolic profile, and reduction of chronic inflammation in patients with HIV. Although more studies and clinical trials are needed to confirm these findings, a healthy lifestyle including at least moderate physical activity should be recommended to HIV patients on stable ART.
    Type of Medium: Online Resource
    ISSN: 2328-8957
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2757767-3
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  • 10
    In: The Journal of Infectious Diseases, Oxford University Press (OUP), Vol. 224, No. 2 ( 2021-07-15), p. 229-240
    Abstract: Etiopathogenesis of the clinical variability of the coronavirus disease 2019 (COVID-19) remains mostly unknown. In this study, we investigate the role of killer cell immunoglobulin-like receptor (KIR)/human leukocyte antigen class-I (HLA-I) interactions in the susceptibility and severity of COVID-19. Methods We performed KIR and HLA-I genotyping and natural killer cell (NKc) receptors immunophenotyping in 201 symptomatic patients and 210 noninfected controls. Results The NKcs with a distinctive immunophenotype, suggestive of recent activation (KIR2DS4low CD16low CD226low CD56high TIGIThigh NKG2Ahigh), expanded in patients with severe COVID-19. This was associated with a higher frequency of the functional A-telomeric activating KIR2DS4 in severe versus mild and/or moderate patients and controls (83.7%, 55.7% and 36.2%, P  & lt; 7.7 × 10−9). In patients with mild and/or moderate infection, HLA-B*15:01 was associated with higher frequencies of activating B-telomeric KIR3DS1 compared with patients with other HLA-B*15 subtypes and noninfected controls (90.9%, 42.9%, and 47.3%; P  & lt; .002; Pc = 0.022). This strongly suggests that HLA-B*15:01 specifically presenting severe acute respiratory syndrome coronavirus 2 peptides could form a neoligand interacting with KIR3DS1. Likewise, a putative neoligand for KIR2DS4 could arise from other HLA-I molecules presenting severe acute respiratory syndrome coronavirus 2 peptides expressed on infected an/or activated lung antigen-presenting cells. Conclusions Our results support a crucial role of NKcs in the clinical variability of COVID-19 with specific KIR/ligand interactions associated with disease severity.
    Type of Medium: Online Resource
    ISSN: 0022-1899 , 1537-6613
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    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 1473843-0
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