Abstract
Background
To assess SARS-CoV-2 seroprevalence in healthcare workers (HCW) with sampling in June and October 2020 and April and November 2021.
Methods
Observational and prospective study in ...2455 HCW with serum sampling. Antibodies against SARS-CoV-2 nucleocapsid and occupational, social and health risk factors were assessed at each time point.
Results
Seropositivity for SARS-CoV-2 in HCW increased from 11.8% in June 2020 to 28.4% in November 2021. Of those with a positive test in June 2020, 92.1% remained with a positive test, 6.7% had an indeterminate test and 1.1% had a negative test in November 2021. Non-diagnosed carriers represented 28.6% in June 2020 and 14.6% in November 2021. Nurses and nursing assistants showed the highest prevalence of seropositivity. Close contact (at home or in the hospital) with Covid-19 cases without protection and working in the frontline were the main risk factors. A total of 88.8% HCW were vaccinated, all with a positive serological response in April 2021, but levels of antibodies decreased about 65%, and two vaccinated persons presented a negative serological test against spike protein in November 2021. Levels of spike antibodies were higher in those vaccinated with Moderna compared with Pfizer and the percentage of antibody reduction was higher with Pfizer vaccine.
Conclusions
This study shows that seroprevalence of SARS-CoV-2 antibodies among HCW doubled that of the general population and that protection both at the workplace and in the socio-familial field was associated with a lower risk of infection, which stabilized after vaccination.
Long-term combination antiretroviral therapy often results in toxicity/tolerability problems, which are one of the main reasons for switching treatment. Despite the favorable profile of raltegravir ...(RAL), data on its combination with abacavir/lamivudine (ABC/3TC) are scarce. Based on clinical data, we evaluated this regimen as a switching strategy.
Multicenter, non-controlled, retrospective study including all virologically suppressed HIV-1-infected patients who had switched to RAL+ABC/3TC.
We evaluated effectiveness (defined as maintenance of HIV-1-RNA <50 copies/mL at 48 weeks) safety, tolerability, laboratory data, and CD4+ count at week 48 of this switching strategy.
The study population comprised 467 patients. Median age was 49 years (IQR: 45-53). Males accounted for 75.4%. Median CD4+ count at baseline was 580 cells/μL (IQR, 409). The main reasons for switching were toxicity/tolerability problems (197; 42.2%) and physician's criteria (133; 28.5%). At week 48, HIV-1 RNA remained at <50 copies/mL in 371/380 (97.6%; 95%CI: 96.4-99.0) when non-virological failure was censured. Virological failure was recorded in 1.9% patients and treatment failure in 20.5% of patients (96/467 95%CI, 16.9-24.2). The main reasons for treatment failure included switch to fixed-dose combination regimens (31; 6.6%), toxicity/poor tolerability (27; 5.8%), and physician's decision (17; 3.6%). A total of 73 adverse events were detected in 64 patients (13.7%). These resolved in 43 patients (67.2%). Of the 33 cases related or likely related to treatment, 30 were Grade-1 (90.9%). CD4+ count and renal, hepatic, and lipid profiles remained clinically stable over the 48 weeks.
Our findings suggest that RAL+ABC/3TC could be an effective, safe/tolerable, and low-toxicity option for virologically suppressed HIV-1-infected patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Second-generation integrase strand transfer inhibitors (INSTIs) are preferred treatment options worldwide, and dolutegravir (DTG) is the treatment of choice in resource-limited settings. ...Nevertheless, in some resource-limited settings, these drugs are not always available. An analysis of the experience with the use of INSTIs in unselected adults living with HIV may be of help to make therapeutic decisions when second-generation INSTIs are not available. This study aimed to evaluate the real-life effectiveness and safety of dolutegravir (DTG), elvitegravir/cobicistat (EVG/c), and raltegravir (RAL) in a large Spanish cohort of HIV-1-infected patients.
Real-world study of adults living with HIV who initiated integrase INSTIs DTG, EVG/c, and RAL-based regimens in three settings (ART-naïve patients, ART-switching, and ART-salvage patients). The primary endpoint was the median time to treatment discontinuation after INSTI-based regimen initiation. Proportion of patients experiencing virological failure (VF) (defined as two consecutive viral loads (VL) ≥200 copies/mL at 24 weeks or as a single determination of VL ≥1,000 copies/mL while receiving DTG, EVG/c or RAL, and at least 3 months after INSTI initiation) and time to VF were also evaluated.
Virological effectiveness of EVG/c- and RAL-based regimens was similar to that of DTG when given as first-line and salvage therapy. Treatment switching for reasons other than virological failure was more frequent in subjects receiving EVG/c and, in particular, RAL. Naïve patients with CD4+ nadir <100 cells/μL were more likely to develop VF, particularly if they initiated RAL or EVG/c. In the ART switching population, initiation of RAL and EVG/c was associated with both VF and INSTI discontinuation. There were no differences in the time to VF and INSTI discontinuation between DTG, EVG/c and RAL. Immunological parameters improved in the three groups and for the three drugs assessed. Safety and tolerability were consistent with expected safety profiles.
Whereas second-generation INSTIs are preferred treatment options worldwide, and DTG is one of the treatment of choices in resource-limited settings, first-generation INSTIs may still provide high virological and immunological effectiveness when DTG is not available.
Based on data from clinical practice, we evaluated the effectiveness and safety of switching to abacavir/lamivudine plus rilpivirine (ABC/3TC+RPV) treatment in virologically suppressed HIV-1-infected ...patients.
We performed a multicenter, non-controlled, retrospective study of HIV-1-infected patients who switched treatment to ABC/3TC+RPV. Patients had an HIV-RNA <50 copies/mL for at least 24 weeks prior to changing treatments. The primary objective was HIV-1 RNA <50 copies/mL at week 48. Effectiveness was analyzed by intention-to-treat (ITT), missing = failure and on-treatment (OT) analyses. The secondary objectives analyzed were adverse effects changes in renal, hepatic or lipid profiles, changes in CD4+ cell count and treatment discontinuations.
Of the 205 patients included, 75.6% were men and the median age was 49. At baseline, before switching to ABC/3TC+RPV, median time since HIV diagnosis was 13.1 years, median time with undetectable HIV-1 RNA was 6.2 years and median time of previous antiretroviral regimen was 3.1 years (48.3% patients were taking efavirenz and ABC/3TC was the most frequent backbone coformulation in 69.7% of patients). The main reasons for switching were drug toxicity/poor tolerability (60.5%) and simplification (20%). At week 48, the primary objective was achieved by 187 out of 205 (91.2%) patients by ITT analysis, and 187 out of 192 (97.4%) patients by OT analysis. The CD4+ lymphocyte count and CD4+ percentage increased significantly from baseline to week 48 by a median of 48 cells/μL (-50 to 189) and 1.2% (-1.3% to 4.1%), respectively, P<0.001. Thirty-eight adverse events (AE) were detected in 32 patients. Of these, 25 had no clear association with treatment. Three patients interrupted therapy due to AE. We observed a decrease in all lipid parameters, P<0.001, and a slight improvement in the glomerular filtration rate, P<0.01. Therapy was considered to have failed in 18 patients owing to virological failure (5 2.4%), toxicity/poor tolerability (4 2%), clinical decision (3 1.5%), loss to follow-up (3 1.5%), death (1 0.5%), and no clinical data (2 1%).
The results of this study confirms that ABC/3TC+RPV is an effective, safe, and cost-effective option for the treatment of patients with virologically stable HIV-1 infection.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The objective of this study was to evaluate how much limb fat is needed to be lost for lipoatrophy to become clinically evident. Antiretroviral drug-naive patients from a randomized trial comparing ...stavudine or abacavir plus lamivudine and efavirenz, who had subjective assessment to detect clinically evident lipoatrophy (standardized questionnaire) and objective measurements of limb fat (dual X-ray absorptiometry) at baseline, 48 weeks, and 96 weeks were included. ROC curves were used to assess the sensitivity and specificity of several cut-off values of absolute and percent limb fat loss for diagnosing lipoatrophy. Of 54 patients included, 13 (24%) had subjective lipoatrophy at 96 weeks. After 96 weeks, median limb fat change was -2.3 kg (interquartile range: -5.2, +0.2) and 0.4 kg (interquartile range: -7.2, +3.4) in patients with and without lipoatrophy, respectively. Median percent limb fat change was -45.5% (interquartile range: -78.0, +3.7) and 5.5% (interquartile range: -62.8, +95.6), respectively. The cut-off values of absolute and percent limb fat loss showing the best sensitivity and specificity values were -1.5 kg (sensitivity, 77%; specificity, 76%) and -30% (sensitivity, 85%; specificity, 73%). At least 30% limb fat is needed to be lost in HIV-infected patients for lipoatrophy to become clinically evident.
Purpose
Very scarce information has been published to date with the combination of ABC/3TC/NVP but it is currently being used in clinical practice in Spain and Portugal. Our aim was to present the ...clinical experience with this regimen in a cohort of adult HIV‐infected antiretroviral (ARV)‐naïve patients.
Methods
Retrospective, multicentre, cohort study. Consecutive adult HIV‐infected ARV‐naïve HLA‐B*5701‐negative patients, who started ABC/3TC/NVP between 2005‐2013, with at least one follow‐up visit, were included. Demographic, clinical and laboratory variables were assessed at baseline, month 1, and every three–four months thereafter. The primary end point was HIV‐1 viral load (VL)<40 c/mL at 48 weeks. Data were analyzed by intent‐to‐treat (ITT) (switch=failure, and missing=failure) and on treatment (OT) analyses.
Results
78 patients were included. Median follow up was 26 (0.1‐84) months. 86% were male, median age 41 (23‐69) years, 9% had AIDS, 8% were HCV+, baseline CD4 was 275 (10‐724) cells/µL and median VL 4.58 (3.02‐6.92) log. After 48 weeks, VL was<40 c/mL in 89.8% (OT), 79.7% (M=F) and 65.4% (S=F) and at 96 weeks in 88.5%, 78.9% and 61.6%, respectively. CD4 increased +246 (p<0.001) and +292 (p<0.001) cells/uL after 48 and 96 weeks, respectively. One or more drugs of the regimen were discontinued in 33 (42.3%) patients. In 15 (19.2%) patients (13 NVP, 2 ABC/3TC) therapy was stopped due to toxicity after a median of one month (in only two cases after six months of follow up): 80% of them had rash/liver toxicity. Six (7.7%) patients discontinued ART due to virologic failure, five (6.4%) because of other reasons and seven (9%) were lost to follow‐up. ALT but not AST significantly increased (+0.07 ukat/L at 96 weeks, p=0.033). A significant increase of 25%, 26% and 42% in total cholesterol, LDLc and HDLc, respectively, and a significant decrease in TC/HDL ratio (6%, p=0.008) was observed after 96 weeks.
Conclusions
Despite a considerable proportion of patients had to stop therapy due to toxicity (most associated with NVP), those initially tolerating this regimen presented a high virologic and immunologic response after 96 weeks, as well as a favourable lipid profile. ABC/3TC/NVP may be a suitable alternative first regimen, mainly in countries with economic constraints.
Our objective was to assess the therapeutic noninferiority of dual therapy with darunavir/ritonavir and lamivudine compared to triple therapy with darunavir/ritonavir plus 2 nucleos(t)ides for ...maintenance of human immunodeficiency virus type 1 (HIV-1) suppression.
This was a multicenter, open-label, noninferiority trial (margin 12%). Patients with HIV-1 RNA <50 copies/mL for 6 months or longer on triple therapy with darunavir/ritonavir and 2 nucleos(t)ides (tenofovir disoproxil fumarate and emtricitabine or abacavir and lamivudine) and with no resistance were randomized to continue therapy (n = 128) or switch to darunavir/ritonavir and lamivudine (n = 129). The primary endpoint was the proportion of participants with HIV-RNA <50 copies/mL after 48 weeks of follow-up according to the snapshot algorithm.
A total of 249 participants received study drugs (intention-to-treat exposed). The proportion of participants with HIV-RNA <50 copies/mL in the dual- and triple-therapy arms was 88.9% (112/126) and 92.7% (114/123; difference, -3.8%; 95% confidence interval, -11.0 to 3.4), respectively. Four participants in the dual-therapy arm and 2 in the triple-therapy arm developed protocol-defined virological failure. Switching to dual therapy was associated with a significant increase in total, low-density lipoprotein, and high-density lipoprotein (HDL) cholesterol, but not in the total-to-HDL cholesterol ratio. Serious adverse events and study drug discontinuations due to adverse events occurred in 4.8% vs 4.9%P = .97) and in 0.8% (1/126) vs 1.6% P = .55) in dual therapy vs triple therapy, respectively.
Dual therapy with darunavir/ritonavir and lamivudine demonstrated noninferior therapeutic efficacy and similar tolerability compared to triple therapy.
NCT02159599.
To determine the prevalence and risk factors (RF) for methicillin-resistant Staphylococcus aureus (MRSA) during stay in 1 acute care hospital (ACH) and 4 long-term care facilities (LTCF). After ...obtaining the informed consent, nasal and skin ulcer swabs were taken and a survey was conducted to determine RF for MRSA. Six hundred and ninety nine patients were included, 413 LTCF and 286 ACH patients and MRSA prevalence were 22.5% and 7.3% respectively. MRSA was located in the nares, skin ulcers, and in both in 61.4%, 21.1%, and 17.5%. Among MRSA carriers, 81% of the ACH and 66.7% of the LTCF patients were only colonized. The multivariate analysis for the ACH revealed the following factors to be associated with MRSA: referral from an LTCF (OR 4.84), pressure ulcers (OR 4.32), a Barthel score < 60 (OR 2.60), and being male (OR 5.21). For the LTCF: urinary catheterisation (OR 3.53), pressure ulcers (OR 2.44), other skin lesions (OR 2.64), antibiotic treatment in ≤ 6 months, (OR 2.23), previous MRSA colonization (OR 2.15), and a Barthel score <20 (OR 1.28). Molecular typing identified 2 predominant clones Q, P, present in all centres. No relationship was found between clones and antibiotic susceptibility.
MRSA prevalence is high in all centres but is 3 times greater in LTCF. The risk factors most strongly associated with MRSA were pressure ulcers and a stay in an LTCF. We propose preventive isolation in these cases.
Transmission of resistance mutations to integrase strand transfer inhibitors (INSTIs) in HIV-infected patients may compromise the efficacy of first-line antiretroviral regimens currently recommended ...worldwide. Continued surveillance of transmitted drug resistance (TDR) is thus warranted.
We evaluated the rates and effects on virological outcomes of TDR in a 96 week prospective multicentre cohort study of ART-naive HIV-1-infected subjects initiating INSTI-based ART in Spain between April 2015 and December 2016.
Pre-ART plasma samples were genotyped for integrase, protease and reverse transcriptase resistance using Sanger population sequencing or MiSeq™ using a ≥ 20% mutant sensitivity cut-off. Those present at 1%-19% of the virus population were considered to be low-frequency variants.
From a total of 214 available samples, 173 (80.8%), 210 (98.1%) and 214 (100.0%) were successfully amplified for integrase, reverse transcriptase and protease genes, respectively. Using a Sanger-like cut-off, the overall prevalence of any TDR, INSTI-, NRTI-, NNRTI- and protease inhibitor (PI)-associated mutations was 13.1%, 1.7%, 3.8%, 7.1% and 0.9%, respectively. Only three (1.7%) subjects had INSTI TDR (R263K, E138K and G163R), while minority variants with integrase TDR were detected in 9.6% of subjects. There were no virological failures during 96 weeks of follow-up in subjects harbouring TDR as majority variants.
Transmitted INSTI resistance remains rare in Spain and, to date, is not associated with virological failure to first-line INSTI-based regimens.
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