A Randomized Trial of Dolutegravir Plus Darunavir/Cobicistat as a Switch Strategy in HIV-1-Infected Patients With Resistance to at Least 2 Antiretroviral Classes.

Background: Suppressed patients with drug-resistant HIV-1 require effective and simple antiretroviral therapy to maintain treatment adherence and viral suppression. Methods: This randomized, open-label, noninferiority, multicenter pilot study involved HIV-infected adults who met the following criteria: confirmed HIV-1 RNA <50 copies/mL for ≥6 months preceding the study randomization, treatment with at least 3 antiretroviral drugs, and a history of drug resistance mutations against at least 2 antiretroviral classes but remaining fully susceptible to darunavir (DRV) and integrase inhibitors. Participants were randomized 1:1 to switch to dolutegravir (DTG; 50 mg once per day) plus DRV boosted with cobicistat (DRV/c; 800/150 mg once per day; 2D group) or continue with their baseline regimen (standard-of-care [SOC] group). The primary endpoint was the proportion of patients with HIV-1 RNA <50 copies/mL at week 48 relative to time to loss of virologic response, with a noninferiority margin set at -12.5%. Virologic failure was defined as confirmed HIV-1 RNA ≥50 copies/mL or a single determination of HIV-1 RNA >50 copies/mL followed by antiretroviral therapy discontinuation. Results: Forty-five participants were assigned to the 2D group and 44 to the SOC group. Time to loss of virologic response showed no difference in the proportion maintaining HIV-1 RNA <50 copies/mL at week 48: 39 of 45 (86.7%; 95% CI, 73.21%-94.95%) in the 2D group vs 42 of 44 (95.4%; 95% CI, 84.53%-99.44%) in the SOC group (log-rank P = .159) with an estimated difference of -8.7 (95% CI, -22.72 to 5.14). Only 2 (4.5%) in the SOC group experienced virologic failure, and 3 participants from the 2D group experienced adverse events leading to treatment discontinuation. Conclusions: In suppressed patients with at least 2 resistant antiretroviral classes, noninferiority could not be demonstrated by fully active DRV/c plus DTG. Nevertheless, there were no unexpected adverse events or virologic failure. DRV/c plus DTG may be considered a once-daily therapy option only for well-selected patients. Clinical Trials Registration. ClinicalTrials.gov (NCT03683524).

Reinforcement of the Standard Therapy with Two Infusions of Convalescent Plasma for Patients with COVID-19: A Randomized Clinical Trial.

BACKGROUND: The aim was to evaluate the reinforcement of the standard therapy with hyperimmune plasma (HP) in Coronavirus-19 disease (COVID-19) patients. METHODS: Open-label, multicenter, randomized clinical trial performed in three hospitals in the Balearic Islands. Non-severe COVID-19 hospitalized patients with clinical time evolution equal to/less than 7 days were included, and randomized in: plasma group (PG) (n = 37), receiving 600 mL divided into two doses from convalescent plasma donor, administered on days 1 and 2 after the enrollment; and control group (CG) (n = 17). Primary outcome was the time for clinical improvement within 21 days, defined as patient achievement of categories 8, 7, and 6 in the Adaptive COVID-19 Treatment Trial scale (ACTT). The trial was terminated early due to the impossibility of recruitment due to the pandemic. RESULTS: PG presented better scores on the ACTT scale at 7 days after HP infusion, whereas CG was needed 14 days to achieve similar results. The plasma infusion was safe. CONCLUSIONS: Despite the tendency observed in the plasma group to achieve slightly earlier better physical condition compared with the standard treatment alone. The administration of HP has been shown to be a safe therapy. No robust evidence was found to affirm a therapeutic effect of the early administration of two infusions of HP for non-severe COVID-19 infected patients. The interpretation is limited by the early termination of the trial, which resulted in a small sample size.

DOLAVI Real-Life Study of Dolutegravir Plus Lamivudine in Naive HIV-1 Patients (48 Weeks).

Brief: Real-world data in naïve HIV-1 patients demonstrate that dolutegravir plus lamivudine in a multiple tablet regimen is effective, safe, and satisfactory; it causes moderately increasing weight and abdominal circumference and is administrable on a test-and-treat strategy. Background: Our objectives were to determine the real-life effectiveness and safety of DT with dolutegravir (50 mg/QD) plus lamivudine (300 mg/QD) in a multiple-tablet regimen (MTR) in naïve PLHIV followed up for 48 weeks and to evaluate the compliance and satisfaction of patients. Material and methods: An open, single-arm, multicenter, non-randomized clinical trial from May 2019 through September 2020 with a 48-week follow-up. Results: The study included 88 PLHIV patients (87.5% male) with a mean age of 35.9 years; 76.1% were MSM patients. The mean baseline CD4 was 516.4 cells/uL, with a viral load (VL) of 4.49 log10, and 11.4% were in the AIDS stage. DT started within 7 days of first specialist consultation in all patients and the same day in 84.1%; 3.4% had baseline resistance mutations (K103N, V106I + E138A, and V108I); 12.5% were lost to follow-up. At week 48, 86.3% had VL < 50 cop/uL by intention-to-treat analysis and 98.7% by per-protocol (PP) analysis. Virological failure (VF) was recorded in 1.1%, with no resistance mutation. One blip was detected in 5.2% without VF. Three reported anxiety, dizziness, and cephalgia, respectively, at week 4 and one reported insomnia at week 24; none reported adverse events at week 48. The mean weight was 4 kg higher at 48 weeks (p = 0.0001) and abdominal circumference 3 cm larger at 24 weeks (p = 0.022). No forgetfulness occurred in 98.7% of patients. Patient satisfaction was 90/100 at 4, 24, and 48 weeks. Conclusion: Real-world data demonstrate that dolutegravir plus lamivudine in MTR is effective, safe, and satisfactory, moderately increasing weight and abdominal circumference and administrable on a test-and-treat strategy.

Seroprevalence of SARS-CoV-2 antibody among healthcare workers in a university hospital in Mallorca, Spain, during the first wave of the COVID-19 pandemic.

OBJECTIVE: To estimate the SARS-CoV-2 antibody seroprevalence in healthcare workers (HCWs) at a university hospital in Mallorca, Spain. METHODS: All HCWs received an e-mail inviting them to take part in the study. Participants had a nasopharyngeal swab test performed for reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) and serological tests to detect SARS-CoV-2 antibodies (primary study). Additionally, they were invited to complete a questionnaire on their exposure to COVID-19 individuals and their COVID-19-related symptoms (secondary study). Prevalence of antibodies (IgG, IgM, or both) and 95% confidence intervals (CIs) were calculated. RESULTS: Seventy-nine percent of the hospital's HCWs (N = 2210) took part in the primary study. Antibodies were detected in 61 participants, a prevalence of 2.8% (95% CI: 2.5-3.1). The prevalence was slightly higher in nurses (3.4%), registrars (3.9%), and wardens (3.4%). Thirty-nine percent of the primary study participants completed the secondary study questionnaire. Those with positive antibody test results had closer contact with COVID-19 individuals (60% vs. 92%; p < 0.001). CONCLUSION: After the first wave of the COVID-19 pandemic in Spain, the seroprevalence of SARS-CoV-2 antibodies in our university hospital HCWs was around 2.8%, which is slightly higher than the seroprevalence in the general population in our region. We believe it would be advisable to perform additional seroprevalence studies during the second wave of the epidemic.

Challenges in understanding host genetics and severity of community-acquired pneumonia.

This study found no association of the top two associated FER variants with severity of community-acquired pneumonia. Precise characterisation of phenotypes may be required in order to unravel the genetic mechanisms predisposing to poor outcome in sepsis. https://bit.ly/3jc9SmR.

Evolution, Clinical and Microbiological Characteristics of Invasive Pneumococcal Disease since the Introduction of the Pneumococcal Conjugate Vaccine 13-Valent in Adults over 18 Years Old.

Invasive pneumococcal disease (IPD) presents high mortality in the population at risk. The aim of this work is to know the evolution, clinical and microbiological characteristics of IPD in the adult population of Majorca, since the introduction of a public funded program for pneumococcal conjugate vaccine (PCV-13) in the pediatric population in the Balearic Islands in 2016. For this purpose, a retrospective multicenter study was carried out in which all episodes of IPD in adult patients from the four hospitals of the public health system of Majorca were included, comparing the periods between 2012 and 2015 and between 2016 and 2019. Clinical variables, serotypes and antibiotic sensitivity were collected. There were 498 cases of IPD; 56.8% were male with a mean age of 67 (standard deviation: 16). Most infections were bacterial pneumonias (73.7%). Of the total cases, 264 (53%) presented complications. Of the 498 cases, 351 strains were obtained, of which 145 (41.3%) belong to vaccinal serotypes (included in the PCV-13 vaccine) and 206 (58.7%) to non-vaccinal serotypes (not included in the PCV-13 vaccine). The percentage of IPD caused by vaccinal serotypes was lower in the second period (47.8% vs. 34.5%; p = 0.012).

Low Albumin Levels Are Associated with Poorer Outcomes in a Case Series of COVID-19 Patients in Spain: A Retrospective Cohort Study.

There is limited information available describing the clinical and epidemiological features of Spanish patients requiring hospitalization for coronavirus disease 2019 (COVID-19). In this observational study, we aimed to describe the clinical characteristics and epidemiological features of severe (non-ICU) and critically patients (ICU) with COVID-19 at triage, prior to hospitalization. Forty-eight patients (27 non-ICU and 21 ICU) with positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were analyzed (mean age, 66 years, [range, 33-88 years]; 67% males). There were no differences in age or sex among groups. Initial symptoms included fever (100%), coughing (85%), dyspnea (76%), diarrhea (42%) and asthenia (21%). ICU patients had a higher prevalence of dyspnea compared to non-ICU patients (95% vs. 61%, p = 0.022). ICU-patients had lymphopenia as well as hypoalbuminemia. Lactate dehydrogenase (LDH), C-reactive protein (CRP), and procalcitonin were significantly higher in ICU patients compared to non-ICU (p < 0.001). Lower albumin levels were associated with poor prognosis measured as longer hospital length (r = -0.472, p < 0.001) and mortality (r = -0.424, p = 0.003). As of 28 April 2020, 10 patients (8 ICU and 2 non-ICU) have died (21% mortality), and while 100% of the non-ICU patients have been discharged, 33% of the ICU patients still remained hospitalized (5 in ICU and 2 had been transferred to ward). Critically ill patients with COVID-19 present lymphopenia, hypoalbuminemia and high levels of inflammation.

Should MASP-2 Deficiency Be Considered a Primary Immunodeficiency? Relevance of the Lectin Pathway.

Mannose-binding lectin (MBL)-associated serine protease-2 (MASP-2) is an indispensable enzyme for the activation of the lectin pathway of complement. Its deficiency is classified as a primary immunodeficiency associated to pyogenic bacterial infections, inflammatory lung disease, and autoimmunity. In Europeans, MASP-2 deficiency, due to homozygosity for c.359A > G (p.D120G), occurs in 7 to 14/10,000 individuals. We analyzed the presence of the p.D120G mutation in adults (increasing the sample size of our previous studies) and children. Different groups of patients (1495 adults hospitalized with community-acquired pneumonia, 186 adults with systemic lupus erythematosus, 103 pediatric patients with invasive pneumococcal disease) and control individuals (1119 healthy adult volunteers, 520 adult patients without history of relevant infectious diseases, and a pediatric control group of 311 individuals) were studied. Besides our previously reported MASP-2-deficient healthy adults, we found a new p.D120G homozygous individual from the pediatric control group. We also reviewed p.D120G homozygous individuals reported so far: a total of eleven patients with a highly heterogeneous range of disorders and nine healthy controls (including our four MASP-2-deficient individuals) have been identified by chance in association studies. Individuals with complete deficiencies of several pattern recognition molecules of the lectin pathway (MBL, collectin-10 and collectin-11, and ficolin-3) as well as of MASP-1 and MASP-3 have also been reviewed. Cumulative evidence suggests that MASP-2, and even other components of the LP, are largely redundant in human defenses and that individuals with MASP-2 deficiency do not seem to be particularly prone to infectious or autoimmune diseases.

Factors associated with the number of drugs in darunavir/cobicistat regimens.

BACKGROUND: Darunavir/cobicistat can be used as mono, dual, triple or more than triple therapy. OBJECTIVES: To assess factors associated with the number of drugs in darunavir/cobicistat regimens. METHODS: A nationwide retrospective cohort study of consecutive HIV-infected patients initiating darunavir/cobicistat in Spain from July 2015 to May 2017. Baseline characteristics, efficacy and safety at 48 weeks were compared according to the number of drugs used. RESULTS: There were 761 patients (75% men, 98% were antiretroviral-experienced, 32% had prior AIDS, 84% had HIV RNA <50 copies/mL and 88% had ≥200 CD4 cells/mm3) who initiated darunavir/cobicistat as mono (n=308, 40%), dual (n=173, 23%), triple (n=253, 33%) or four-drug (n=27, 4%) therapy. Relative to monotherapy, triple therapy was more common in men aged <50 years, with prior AIDS and darunavir plus ritonavir use, and with CD4 cells <200/mm3 and with detectable viral load at initiation of darunavir/cobicistat; dual therapy was more common with previous intravenous drug use, detectable viral load at initiation of darunavir/cobicistat and no prior darunavir plus ritonavir; and four-drug therapy was more common with prior AIDS and detectable viral load at initiation of darunavir/cobicistat. Monotherapy and dual therapy showed a trend to better virological responses than triple therapy. CD4 responses and adverse effects did not differ among regimens. DISCUSSION: Darunavir/cobicistat use in Spain has been tailored according to clinical characteristics of HIV-infected patients. Monotherapy and dual therapy have been common and preferentially addressed to older patients with a better HIV status, suggesting that health issues other than HIV infection may have been strong determinants of its prescription.

Afectación osteoarticular por Streptococcus pneumoniae tras la autorización de las vacunas conjugadas / Osteoarticular infections caused by Streptococcus pneumoniae since authorization of conjugate vaccines

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Polyserositis: a diagnostic challenge.

BACKGROUND: Polyserositis (PS) is the inflammation, with effusion, of different serous membranes. It has been associated with different aetiologies, but the aetiology of PS remains unknown in a high percentage of patients. AIMS: The general objective of this retrospective study was to analyse the aetiology of PS cases seen at Son Llàtzer Hospital in an 11-year period. Other objectives were to determine the epidemiological, clinical and analytical characteristics of these patients. METHODS: An observational, descriptive and retrospective study to analyse the aetiology of PS cases seen at Son Llàtzer Hospital. The inflammation of two or more serous membranes confirmed by an imaging test was required and at least one of the serous fluid should be an exudate. RESULTS: A total of 92 patients was included in the study. The most common diagnosis was neoplasm (nearly one-third of cases) followed by infectious and autoimmune diseases. PS aetiology was unknown in more than one-third. Pleura and pericardium were the most common sites of serosal involvement (83%). Antinuclear antibodies' positivity in serum and increased levels of adenosine deaminase in pleural effusion were significantly associated with a final diagnosis of autoimmune disease. Increased pleural lactate dehydrogenase levels were significantly associated with a final diagnosis of neoplasm. In 9 of 14 patients with a previous cancer, PS represented a recurrence of their cancer. Cases of unknown aetiology presented most frequently as pleural and pericardial involvement, and the majority resolved. In very few patients, an infectious aetiology could be proven. CONCLUSION: PS is a frequent clinical entity that is associated with different diseases and its diagnosis could be challenging, with a high rate of unknown aetiologies.

Genetic susceptibility to invasive pneumococcal disease.

BACKGROUND: The pathogenesis of IPD remains unknown, especially among middle-aged individuals without risk factors (WRF). OBJECTIVES: The aim of the present study was to investigate the role of single nucleotide polymorphisms (SNP) within key genes involved in innate immune response on IPD susceptibility. METHODS: Forty-three SNPs within 10 immunological genes were investigated in a cohort of 144 Caucasian IPD patients and 280 ethnically matched controls. RESULTS: The allele distribution of the NFKBIA rs1050851 and NFKBIE rs2282151 variants were associated with IPD susceptibility (χ2 = 4.23, p = 0.04 and χ2 = 5.13, p = 0.02, respectively). Additionally, the genotype distribution of NFKBIZ rs645781 (χ2 = 8.25, p = 0.02) and IL1R1 rs3917254 (χ2 = 6.70, p = 0.04) were also associated with IPD risk. When only IPD-WRF patients were considered; the allele distribution of IL1R1 rs2160227 (χ2 = 5.62, p = 0.03), rs13020778 (χ2 = 5.73, p = 0.02), rs3917267 (χ2 = 3.72, p = 0.05) and IL4 rs2227284 (χ2 = 3.76, p = 0.05) and the genotype distribution of IL10 rs3024509 (χ2 = 7.70, p = 0.02), IL1R1 rs3917254 (χ2 = 13.40, p = 0.001), NFKBIZ rs645781 (χ2 = 13.86, p = 0.001) and rs677011 (χ2 = 9.06, p = 0.01) variants were associated with IPD risk. CONCLUSIONS: We found several associations between variants in the IL1R1, IL4, IL10, NFKBIE, NFKBIA, and NFKBIZ genes and risk of IPD. If validated, these biomarkers may help to identify people with higher risk of IPD.

QuantiFERON-TB Gold In-Tube as a Confirmatory Test for Tuberculin Skin Test in Tuberculosis Contact Tracing: A Noninferiority Clinical Trial.

Background: Screening strategies based on interferon-γ release assays in tuberculosis contact tracing may reduce the need for preventive therapy without increasing subsequent active disease. Methods: We conducted an open-label, randomized trial to test the noninferiority of a 2-step strategy with the tuberculin skin test (TST) followed by QuantiFERON-TB Gold In-Tube (QFT-GIT) as a confirmatory test (the TST/QFT arm) to the standard TST-alone strategy (TST arm) for targeting preventive therapy in household contacts of patients with tuberculosis. Participants were followed for 24 months after randomization. The primary endpoint was the development of tuberculosis, with a noninferiority margin of 1.5 percentage points. Results: A total of 871 contacts were randomized. Four contacts in the TST arm and 2 in the TST/QFT arm developed tuberculosis. In the modified intention-to-treat analysis, this accounted for 0.99% in the TST arm and 0.51% in the TST/QFT arm (-0.48% difference; 97.5% confidence interval [CI], -1.86% to 0.90%); in the per-protocol analysis, the corresponding rates were 1.67% and 0.82% in the TST and TST/QFT arms, respectively (-0.85% difference; 97.5% CI, -3.14% to 1.43%). Of the 792 contacts analyzed, 65.3% in the TST arm and 42.2% in the TST/QFT arm were diagnosed with tuberculosis infection (23.1% difference; 95% CI, 16.4% to 30.0%). Conclusions: In low-incidence settings, screening household contacts with the TST and using QFT-GIT as a confirmatory test is not inferior to TST-alone for preventing active tuberculosis, allowing a safe reduction of preventive treatments. Clinical Trials Registration: NCT01223534.

Dual Therapy With Darunavir and Ritonavir Plus Lamivudine vs Triple Therapy With Darunavir and Ritonavir Plus Tenofovir Disoproxil Fumarate and Emtricitabine or Abacavir and Lamivudine for Maintenance of Human Immunodeficiency Virus Type 1 Viral Suppression: Randomized, Open-Label, Noninferiority DUAL-GESIDA 8014-RIS-EST45 Trial.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Dual therapy with darunavir/ritonavir and lamivudine demonstrated noninferior therapeutic efficacy and similar tolerability compared to triple therapy. CLINICAL TRIALS REGISTRATION: NCT02159599.

Pneumococcal infections in elderly patients attending hospital since PCV-13 authorization in Spain.

OBJECTIVES: To study the characteristics and outcomes of pneumococcal infections in patients aged ≥65 years since the authorization of the 13-valent pneumococcal conjugate vaccine (PCV-13) in Spain. METHODS: All pneumococcal pneumonias, empyemas or primary bacteraemias treated at two hospitals in Majorca from 2010 to 2015 were included. Clinical variables, serotypes, and antibiotic susceptibility were collected. RESULTS: Two hundred and forty-nine pneumonias, 11 primary bacteraemias, and 2 empyemas in 243 patients were studied; 181 (69.1%) men, median age 76 years (range: 66-99). Seven (2.6%) were pneumococcal-vaccinated. Bacteraemia was present in 127 (61.9%) cases and related to a higher severity, p= 0.02, and not having chronic lung disease, p = 0.002. Ninety-seven (37%) episodes involved complications and 30 (11.5%) patients died. Mortality was related with the presence of complications at admission, p < 0.001. Only septic shock was more frequent in patients ≥65 years during the period 2010-2015 compared to the period 2006-2010: 38 of 262 (14.5%) vs. 17 of 212 (8%), p = 0.02. Most infections (57.6%) were due to PCV-13 serotypes but were not related to a worse prognosis. The proportion of PCV-13 serotypes tended to decrease from 61% (non-invasive) and 80% (invasive) in 2010-2011 to 33% and 47% in 2014-2015. The antibiotic susceptibility remained stable. CONCLUSIONS: Rates of pneumococcal vaccination in elderly patients with pneumococcal infections were very low. Except for septic shock, the main outcome variables (including mortality) were similar to the ones observed in the period preceding PCV-13 authorization. PCV-13 serotypes were responsible for most infections although they showed a decreasing trend.

Vacuna neumocócica: «El camino del progreso no es ni rápido ni fácil» / Neumococcal vaccine: «the road to progress is neither fast nor easy»

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Withdrawing inactive NRTIs in HIV-1 subjects with suppressed viraemia: a randomized trial.

BACKGROUND: Extensively pretreated subjects with virological failure (VF) may receive salvage regimens containing NRTIs with only residual or no activity. Once virological suppression is achieved, their contribution remains elusive. METHODS: This was a multicentre, randomized, prospective study. Subjects with at least one prior VF, HIV-1 RNA <50 copies/mL for ≥6 months and receiving a regimen with at least two active drugs (one of them a boosted PI) were randomized 1:1 to stop (experimental arm) or maintain (control arm) NRTIs. EudraCT: 2012-000198-21. RESULTS: Ninety subjects were randomized (experimental, n = 45; and control, n = 45). The mean age was 50 years, 80% were male, the mean CD4+ cell count was 542 cells/mm(3) and the median number of prior VFs was 3. Seventy-four subjects (82%) harboured the mutation M184V/I and the median number of thymidine-associated mutations was 3 (IQR: 0-4). In the experimental arm, thirty-two (71%) subjects removed one NRTI and 13 (29%) subjects removed two. Twenty-two of 45 (49%) discontinued tenofovir disoproxil fumarate. Forty-one of 45 (91.1%, experimental arm) and 44 of 45 (97.8%, control arm) had HIV-1 RNA <50 copies/mL at 48 weeks (difference: -6.7%; 95% CI: -17.4, 4.1). In a post-hoc analysis allowing NRTI reintroduction, efficacy rates were 95.6% and 97.8%, respectively (difference: -2.2%; 95% CI: -7.2, 2.7). Rates of discontinuation at 48 weeks were 2% in both arms. One subject developed a late VF with resistance selection. CONCLUSIONS: In patients receiving a successful multidrug salvage regimen with at least two active drugs (one a boosted PI), the withdrawal of inactive NRTIs was safe, rates of VF were low and drug resistance was uncommon at 48 weeks in this small study. This strategy could potentially prevent long-term toxicities, reduce the number of drugs and reduce costs if non-inferiority was met in a fully powered trial.

Evolution of pneumococcal infections in adult patients during a four-year period after vaccination of a pediatric population with 13-valent pneumococcal conjugate vaccine.

OBJECTIVES: To describe the distribution of vaccine and non-vaccine pneumococcal serotypes from adult patients for different clinical scenarios, after the introduction of the 13-valent pneumococcal conjugate vaccine (PCV-13) for children. METHODS: This was a prospective study of pneumococcal infections in adult patients (January 2010 to April 2014) in Hospital Son Llàtzer, Mallorca (Spain). Two different periods of time were compared, the first before (first period) and the second after (second period) the introduction of PCV-13. Information related to clinical characteristics, outcomes of infection, pneumococcal serotypes, and antibiotic susceptibility was collected. RESULTS: We studied 407 episodes (371 patients), 201 in the first period and 206 in the second period. The majority of patients were male; the median patient age was 68 (range 15-99) years. Infections due to PCV-13 serotypes decreased from 59.7% to 47.6% (p=0.014), mainly serotypes 3, 7, 18C, 19F, and 23F. In the second period, PCV-13 serotypes were the cause of pneumonia in 58.2% of cases and in 40.8% of invasive infections, but these serotypes were not related with any outcome variable. No differences in hospital or intensive care unit admission, severity, or mortality were observed between the two periods. Susceptibility to penicillin (98.2% vs. 95.1%, p=0.03) and amoxicillin (96.5% vs. 91%, p=0.007) was slightly higher in the first period. CONCLUSIONS: Although a reduction in infections due to vaccine serotypes was observed, close to half of infections in adult patients were caused by PCV-13 serotypes. Even after pediatric vaccination with PCV-13, vaccine serotypes were still responsible for most pneumonia and invasive disease, underscoring the importance of implementing current guidelines and extending vaccination to other risk groups.