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1.
J Hosp Infect ; 147: 123-132, 2024 May.
Article in English | MEDLINE | ID: mdl-38467251

ABSTRACT

BACKGROUND: Surgical site infections (SSIs), mainly caused by Staphylococcus aureus, pose a significant economic burden in Europe, leading to increased hospitalization duration, mortality, and treatment costs, particularly with drug-resistant strains such as meticillin-resistant S. aureus. AIM: To conduct a case-control study on the economic impact of S. aureus SSI in adult surgical patients across high-volume centres in France, Germany, Spain, and the UK, aiming to assess the overall and procedure-specific burden across Europe. METHODS: The SALT study is a multinational, retrospective cohort study with a nested case-control analysis focused on S. aureus SSI in Europe. The study included participants from France, Germany, Italy, Spain, and the UK who underwent invasive surgery in 2016 and employed a micro-costing approach to evaluate health economic factors, matching S. aureus SSI cases with controls. FINDINGS: In 2016, among 178,904 surgical patients in five European countries, 764 developed S. aureus SSI. Matching 744 cases to controls, the study revealed that S. aureus SSI cases incurred higher immediate hospitalization costs (€8,810), compared to controls (€6,032). Additionally, S. aureus SSI cases exhibited increased costs for readmissions within the first year post surgery (€7,961.6 versus €5,298.6), with significant differences observed. Factors associated with increased surgery-related costs included the cost of hospitalization immediately after surgery, first intensive care unit (ICU) admission within 12 months, and hospital readmission within 12 months, as identified through multivariable analysis. CONCLUSION: The higher rates of hospitalization, ICU admissions, and readmissions among S. aureus SSI cases highlight the severity of these infections and their impact on healthcare costs, emphasizing the potential benefits of evidence-based infection control measures and improved patient care to mitigate the economic burden.


Subject(s)
Staphylococcal Infections , Surgical Wound Infection , Humans , Surgical Wound Infection/economics , Surgical Wound Infection/epidemiology , Retrospective Studies , Male , Case-Control Studies , Female , Middle Aged , Staphylococcal Infections/economics , Staphylococcal Infections/epidemiology , Aged , France/epidemiology , Europe , Spain/epidemiology , United Kingdom/epidemiology , COVID-19/economics , COVID-19/epidemiology , Health Care Costs/statistics & numerical data , Adult , Germany/epidemiology , Hospitalization/economics , Hospitalization/statistics & numerical data , Staphylococcus aureus
2.
J Hosp Infect ; 142: 9-17, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37797656

ABSTRACT

BACKGROUND: The aim of this study was to estimate the incidence, associated disease burden and healthcare utilization due to Staphylococcus aureus prosthetic joint infections (SA-PJI) after primary hip and knee arthroplasty in European centres. METHODS: This study was conducted in patients who underwent primary hip and knee arthroplasty in 19 European hospitals between 2014 and 2016. The global incidence of PJI and SA-PJI was calculated. The associated disease burden was measured indirectly as infection-related mortality plus loss of function. For healthcare utilization, number and duration of hospitalizations, number and type of surgical procedures, duration of antibiotic treatments, and number of outpatient visits were collected. Subgroup and regression analyses were used to evaluate the impact of SA-PJI on healthcare utilization, controlling for confounding variables. RESULTS: The incidence of PJI caused by any micro-organism was 1.41%, and 0.40% for SA-PJI. Among SA-PJI, 20.7% were due to MRSA with substantial regional differences, and were more frequent in partial hip arthroplasty (PHA). Related deaths and loss of function occurred in 7.0% and 10.2% of SA-PJI cases, respectively, and were higher in patients with PHA. Compared with patients without PJI, patients with SA-PJI had a mean of 1.4 more readmissions, 25.1 more days of hospitalization, underwent 1.8 more surgical procedures, and had 5.4 more outpatient visits, controlling for confounding variables. Healthcare utilization was higher in patients who failed surgical treatment of SA-PJI. CONCLUSIONS: This study confirmed that the SA-PJI burden is high, especially in PHA, and provided a solid basis for planning interventions to prevent SA-PJI.


Subject(s)
Arthroplasty, Replacement, Hip , Prosthesis-Related Infections , Staphylococcal Infections , Humans , Staphylococcus aureus , Incidence , Prosthesis-Related Infections/epidemiology , Prosthesis-Related Infections/etiology , Retrospective Studies , Arthroplasty, Replacement, Hip/adverse effects , Staphylococcal Infections/epidemiology , Hospitals , Patient Acceptance of Health Care , Cost of Illness
4.
Pneumologie ; 76(12): 855-907, 2022 Dec.
Article in German | MEDLINE | ID: mdl-36479679

ABSTRACT

The German Society of Pneumology initiated 2021 the AWMF S1 guideline Long COVID/Post-COVID. In a broad interdisciplinary approach, this S1 guideline was designed based on the current state of knowledge.The clinical recommendations describe current Long COVID/Post-COVID symptoms, diagnostic approaches, and therapies.In addition to the general and consensus introduction, a subject-specific approach was taken to summarize the current state of knowledge.The guideline has an explicit practical claim and will be developed and adapted by the author team based on the current increase in knowledge.


Subject(s)
COVID-19 , Post-Acute COVID-19 Syndrome , Humans
5.
Pneumologie ; 75(9): 665-729, 2021 Sep.
Article in German | MEDLINE | ID: mdl-34198346

ABSTRACT

The present guideline provides a new and updated concept of the management of adult patients with community-acquired pneumonia. It replaces the previous guideline dating from 2016.The guideline was worked out and agreed on following the standards of methodology of a S3-guideline. This includes a systematic literature search and grading, a structured discussion of recommendations supported by the literature as well as the declaration and assessment of potential conflicts of interests.The guideline has a focus on specific clinical circumstances, an update on severity assessment, and includes recommendations for an individualized selection of antimicrobial treatment.The recommendations aim at the same time at a structured assessment of risk for adverse outcome as well as an early determination of treatment goals in order to reduce mortality in patients with curative treatment goal and to provide palliation for patients with treatment restrictions.


Subject(s)
Communicable Diseases , Emergency Medicine , Pneumonia , Pulmonary Medicine , Adult , Aged , Austria , Critical Care , Germany , Humans , Physicians, Family
6.
Pneumologie ; 75(9): 665-729, 20210701.
Article in German | BIGG - GRADE guidelines | ID: biblio-1292456

ABSTRACT

Die vorliegende Leitlinie umfasst ein aktualisiertes Konzept der Behandlung und Prävention von erwachsenen Patienten mit ambulant erworbener Pneumonie und löst die bisherige Leitlinie aus dem Jahre 2016 ab. Sie wurde entsprechend den Maßgaben zur Methodologie einer S3-Leitlinie erarbeitet und verabschiedet. Hierzu gehören eine systematische Literaturrecherche und -bewertung, die strukturierte Diskussion der aus der Literatur begründbaren Empfehlungen sowie eine Offenlegung und Bewertung möglicher Interessenskonflikte. Die Leitlinie zeichnet sich aus durch eine Zentrierung auf definierte klinische Situationen, eine aktualisierte Maßgabe der Schweregradbestimmung sowie Empfehlungen zu einer individualisierten Auswahl der initialen antimikrobiellen Therapie. Die Empfehlungen zielen gleichzeitig auf eine strukturierte Risikoevaluation als auch auf eine frühzeitige Bestimmung des Therapieziels, um einerseits bei kurativem Therapieziel die Letalität der Erkrankung zu reduzieren, andererseits bei palliativem Therapieziel eine palliative Therapie zu eröffnen.


The present guideline provides a new and updated concept of the management of adult patients with community-acquired pneumonia. It replaces the previous guideline dating from 2016.The guideline was worked out and agreed on following the standards of methodology of a S3-guideline. This includes a systematic literature search and grading, a structured discussion of recommendations supported by the literature as well as the declaration and assessment of potential conflicts of interests.The guideline has a focus on specific clinical circumstances, an update on severity assessment, and includes recommendations for an individualized selection of antimicrobial treatment.The recommendations aim at the same time at a structured assessment of risk for adverse outcome as well as an early determination of treatment goals in order to reduce mortality in patients with curative treatment goal and to provide palliation for patients with treatment restrictions.


Subject(s)
Humans , Pneumonia/drug therapy , Pneumonia/diagnosis , Anti-Infective Agents/therapeutic use
7.
Infection ; 49(3): 533-537, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33774804

ABSTRACT

To determine the most relevant pathogens for CAP in Germany, patients with radiologically confirmed pulmonary infiltrates and at least one clinical sign of lung infection were prospectively recruited within the CAPNETZ cohort from 2004 until 2016. In 990 out of 4.672 patients (21%) receiving complete diagnostics the most prominent change of pathogens was a decrease of S. pneumoniae (58% in 2004 to 37.5% in 2016; p ≤ 0.001, ρ = - 0.148) and an increase of H. influenzae (12.2% to 20.8%; p = 0.001, ρ = 0.104).


Subject(s)
Community-Acquired Infections , Pneumonia, Bacterial , Bacteria , Community-Acquired Infections/epidemiology , Haemophilus influenzae , Humans , Pneumonia, Bacterial/diagnosis , Pneumonia, Bacterial/epidemiology , Streptococcus pneumoniae
12.
Anaesthesist ; 68(11): 785-800, 2019 11.
Article in German | MEDLINE | ID: mdl-31555832

ABSTRACT

Multidrug-resistant pathogens often lead to treatment failure of antimicrobial regimens. After a period of imbalance between the occurrence/spread of resistance mechanisms and the development of new substances, some new substances have meanwhile been approved and many more are currently undergoing clinical testing. They are particularly effective against specific resistance mechanisms/pathogens and should be preserved for definitive treatment of an isolated pathogen. In the absence of alternatives reserve antibiotics, such as aztreonam and colistin have experienced a renaissance. They are again used in special infection scenarios and clinically tested in combination with new substances. Despite the introduction and development of new substances the building of resistance will at some time also render these (at least partially) ineffective. Therefore, their implementation must be carried out according to the antibiotic or infectious diseases stewardship.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Bacterial Infections/drug therapy , Drug Resistance, Multiple, Bacterial/drug effects , Aztreonam/therapeutic use , Colistin/therapeutic use , Humans , Microbial Sensitivity Tests
13.
Anaesthesist ; 68(10): 711-730, 2019 10.
Article in German | MEDLINE | ID: mdl-31555833

ABSTRACT

The increase in resistant pathogens has long been a global problem. Complicated life-threatening infections due to multidrug-resistant pathogens (MRD) meanwhile occur regularly in intensive care medicine. An important and also potentially modifiable factor of the rapid spread of resistance is the irrational use of broad spectrum antibiotics in human medicine. In addition to many other resistance mechanisms, beta-lactamases play an important role in Gram-negative pathogens. They are not uncommonly the leading reason of difficult to treat infections and the failure of known routinely used broad spectrum antibiotics, such as cephalosporins, (acylamino)penicillins and carbapenems. Strategies for containment of MRDs primaríly target the rational use of antibiotics. In this respect interdisciplinary treatment teams, e.g. antibiotic stewardship (ABS) and infectious diseases stewardship (IDS) play a major role.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Drug Resistance, Bacterial/drug effects , Carbapenems/therapeutic use , Cephalosporins/therapeutic use , Humans , Penicillins/therapeutic use
14.
Clin Microbiol Infect ; 25(7): 818-827, 2019 Jul.
Article in English | MEDLINE | ID: mdl-30928559

ABSTRACT

BACKGROUND: For patients with bacteraemia caused by methicillin-sensitive Staphylococcus aureus anti-staphylococcal penicillins (ASPs) or cefazolin are agents of choice. While ASPs are potentially nephrotoxic, cefazolin may be less effective in some S. aureus strains due to an inoculum effect. OBJECTIVES: To perform a systematic literature review and meta-analysis assessing current evidence comparing cefazolin with ASPs for patients with S. aureus bacteraemia (SAB). METHODS: We searched MEDLINE, ISI Web of Science (Science Citation Index Expanded) and the Cochrane Database as well as clinicaltrials.gov from inception to 26 June 2018. All studies investigating the effects of cefazolin versus ASP in patients with methicillin-sensitive SAB were eligible for inclusion regardless of study design, publication status or language. Additional information was requested by direct author contact. A meta-analysis to estimate relative risks (RRs) with the corresponding 95% confidence intervals (CIs) was performed. Statistical heterogeneity was estimated using I2. The primary endpoint was 90-day all-cause mortality. The Newcastle-Ottawa Scale (NOS) and Grading of Recommendations Assessment, Development and Evaluation (GRADE) were used for study and data quality assessment. RESULTS: Fourteen non-randomized studies were included. Seven reported the primary endpoint (RR 0.71 (0.50, 1.02), low quality of evidence). Cefazolin treatment may be associated with lower 30-day mortality rates (RR 0.70 (0.54, 0.91), low quality of evidence) and less nephrotoxicity (RR 0.36 (0.21, 0.59), (low quality of evidence)). We are uncertain whether cefazolin and ASP differ regarding treatment failure/relapse as the quality of the evidence has been assessed as very low (RR of 0.84 (0.59, 1.18)). For patients with endocarditis (RR 0.71 (0.12, 4.05)) or abscesses (RR 1.17 (0.30, 4.63)), cefazolin treatment may be associated with equal 30-day and 90-day mortality (low quality of evidence). CONCLUSIONS: Cefazolin seemed to be at least equally as effective as ASPs while being associated with less nephrotoxicity.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Bacteremia/drug therapy , Cefazolin/therapeutic use , Penicillins/therapeutic use , Staphylococcal Infections/drug therapy , Staphylococcus aureus/drug effects , Humans , Treatment Failure
15.
Clin Microbiol Infect ; 25(10): 1173-1179, 2019 Oct.
Article in English | MEDLINE | ID: mdl-30825674

ABSTRACT

BACKGROUND: There is an ongoing controversy on the role of the healthcare-associated pneumonia (HCAP) label in the treatment of patients with pneumonia. OBJECTIVE: To provide an update of the literature on patients meeting criteria for HCAP between 2014 and 2018. SOURCES: The review is based on a systematic literature search using PubMed-Central full-text archive of biomedical and life sciences literature at the U.S. National Institutes of Health's National Library of Medicine (NIH/NLM). CONTENT: Studies compared clinical characteristics of patients with HCAP and community-acquired pneumonia (CAP). HCAP patients were older and had a higher comorbidity. Mortality rates in HCAP varied from 5% to 33%, but seemed lower than those cited in the initial reports. Criteria behind the HCAP classification differed considerably within populations. Microbial patterns differed in that there was a higher incidence of methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa, and, to a lesser extent, enterobacteriaceae. Definitions and rates of multidrug-resistant (MDR) pneumonia also varied considerably. Broad-spectrum guideline-concordant treatment did not reduce mortality in four observational studies. The HCAP criteria performed poorly as a predictive tool to identify MDR pneumonia or pathogens not covered by treatment for CAP. A new score (Drug Resistance in Pneumonia, DRIP) outperformed HCAP in the prediction of MDR pathogens. Comorbidity and functional status, but not different microbial patterns, seem to account for increased mortality. IMPLICATIONS: HCAP should no longer be used to identify patients at risk of MDR pathogens. The use of validated predictive scores along with implementation of de-escalation strategies and careful individual assessment of comorbidity and functional status seem superior strategies for clinical management.


Subject(s)
Bacterial Infections/epidemiology , Bacterial Infections/pathology , Enterobacteriaceae/isolation & purification , Healthcare-Associated Pneumonia/diagnosis , Healthcare-Associated Pneumonia/pathology , Pseudomonas aeruginosa/isolation & purification , Staphylococcus aureus/isolation & purification , Aged , Aged, 80 and over , Bacterial Infections/microbiology , Clinical Decision Rules , Disease Management , Drug Resistance, Multiple, Bacterial , Enterobacteriaceae/classification , Enterobacteriaceae/drug effects , Female , Healthcare-Associated Pneumonia/microbiology , Healthcare-Associated Pneumonia/mortality , Humans , Incidence , Male , Pseudomonas aeruginosa/drug effects , Staphylococcus aureus/drug effects , United States
16.
Anaesthesist ; 68(Suppl 1): 40-62, 2019 02.
Article in English | MEDLINE | ID: mdl-29383395

ABSTRACT

The mortality of patients with sepsis and septic shock is still unacceptably high. An effective calculated antibiotic treatment within 1 h of recognition of sepsis is an important target of sepsis treatment. Delays lead to an increase in mortality; therefore, structured treatment concepts form a rational foundation, taking relevant diagnostic and treatment steps into consideration. In addition to the assumed infection and individual risks of each patient, local resistance patterns and specific problem pathogens must be taken into account during the selection of anti-infective treatment. Many pathophysiologic alterations influence the pharmacokinetics (PK) of antibiotics during sepsis. The principle of standard dosing should be abandoned and replaced by an individual treatment approach with stronger weighting of the pharmacokinetics/pharmacodynamics (PK/PD) index of the substance groups. Although this is not yet the clinical standard, prolonged (or continuous) infusion of ß­lactam antibiotics and therapeutic drug monitoring (TDM) can help to achieve defined PK targets. Prolonged infusion is sufficient without TDM, but for continuous infusion, TDM is generally necessary. A further argument for individual PK/PD-oriented antibiotic approaches is the increasing number of infections due to multidrug-resistant (MDR) pathogens in the intensive care unit. For effective treatment, antibiotic stewardship teams (ABS teams) are becoming more established. Interdisciplinary cooperation of the ABS team with infectious disease (ID) specialists, microbiologists, and clinical pharmacists leads not only to rational administration of antibiotics, but also has a positive influence on treatment outcome. The gold standards for pathogen identification are still culture-based detection and microbiologic resistance testing for the various antibiotic groups. Despite the rapid investigation time, novel polymerase chain reaction(PCR)-based procedures for pathogen identification and resistance determination are currently only an adjunct to routine sepsis diagnostics, due to the limited number of studies, high costs, and limited availability. In complicated septic courses with multiple anti-infective therapies or recurrent sepsis, PCR-based procedures can be used in addition to treatment monitoring and diagnostics. Novel antibiotics represent potent alternatives in the treatment of MDR infections. Due to the often defined spectrum of pathogens and the practically (still) absent resistance, they are suitable for targeted treatment of severe MDR infections (therapy escalation). (Contribution available free of charge by "Free Access" [ https://link.springer.com/article/10.1007/s00101-017-0396-z ].).


Subject(s)
Anti-Bacterial Agents/therapeutic use , Bacteremia/diagnosis , Bacteremia/drug therapy , Antimicrobial Stewardship , Biomarkers , Drug Monitoring , Humans , Intensive Care Units , Shock, Septic/drug therapy , beta-Lactams/pharmacokinetics , beta-Lactams/therapeutic use
17.
Clin Microbiol Infect ; 25(4): 462-468, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30036671

ABSTRACT

OBJECTIVES: To evaluate whether a hospital-wide infection control programme (ICP) is effective at reducing the burden of healthcare-associated infections (HAIs) and associated severe sepsis/septic shock or death (severe HAIs). METHODS: Prospective, quasi-experimental study with two surveillance periods (September 2011 to August 2012; May 2013 to August 2014). Starting October 2012, the ICP included hand hygiene promotion and bundle implementation for common HAIs. We applied segmented mixed-effects Poisson regression and multi-state models. We reported adjusted incidence rate ratios (aIRR) and adjusted hazard ratios (aHR) with 95% confidence intervals (CI). RESULTS: Overall, 62 154 patients were under surveillance, with 1568 HAIs identified in 1170 patients (4.3 per 100 admissions) in the first and 2336 HAIs identified in 1711 patients (4.9 per 100 admissions) in the second surveillance period. No differences were found in the overall HAI incidence rates between the periods in the general wards (aIRR 1.29, 95% CI 0.78-2.15) and intensive care units (ICUs) (aIRR 0.59, 95% CI 0.27-1.31). However, the HAI incidence rate was declining in the ICUs after starting the ICP (aIRR 0.98, 95% CI 0.97-1.00 per 1-week increment), in contrast to general wards (aIRR 1.01, 95% CI 1.00-1.02). A reduction in severe HAIs (aIRR 0.13, 95% CI 0.05-0.32) and a lower probability of HAI-associated in-hospital deaths (aHR 0.56, 95% CI 0.31-0.99) were observed in the second period in the ICUs. CONCLUSIONS: There was no overall reduction in HAIs after implementation of the ICP. However, there was a significant reduction in severe HAIs in ICUs. Whether this difference was a consequence of the ICP or improvement in HAI case management is not clear.


Subject(s)
Cross Infection/epidemiology , Infection Control/methods , Shock, Septic/epidemiology , Shock, Septic/mortality , Aged , Enterobacteriaceae/isolation & purification , Female , Humans , Incidence , Intensive Care Units/statistics & numerical data , Male , Methicillin-Resistant Staphylococcus aureus/isolation & purification , Middle Aged , Patients' Rooms/statistics & numerical data , Prospective Studies , Pseudomonas/isolation & purification , Vancomycin-Resistant Enterococci/isolation & purification
18.
Intensive Care Med ; 44(11): 1826-1835, 2018 Nov.
Article in English | MEDLINE | ID: mdl-30284637

ABSTRACT

PURPOSE: Sepsis contributes considerably to global morbidity and mortality, while reasons for its increasing incidence remain unclear. We assessed risk adjusted secular trends in sepsis and infection epidemiology in Germany. METHODS: Retrospective cohort study using nationwide German hospital discharge data. We assessed incidence, outcomes and trends of hospital-treated sepsis and infections between 2010 and 2015. Sepsis was identified by explicit ICD-10 sepsis codes. As sensitivity analysis, results were compared with sepsis cases identified by implicit sepsis coding (combined infection and organ dysfunction codes). RESULTS: Among 18 664 877 hospital admissions in 2015, 4 213 116 (22.6%) patients had at least one infection code. There were 320 198 patients that had explicit sepsis codes including 136 542 patients with severe sepsis and septic shock; 183 656 patients were coded as sepsis without organ dysfunction. For patients with explicitly coded sepsis (including severe sepsis), or with severe sepsis alone, mortality rates over the period 2010-2015 decreased from 26.6 to 23.5%, and from 47.8 to 41.7%, respectively. CONCLUSIONS: Sepsis and infection remain significant causes of hospital admission and death in Germany. Sepsis-related mortality is higher and has declined to a lesser degree than in other high-income countries. Although infection rates steadily increased, the observed annual increase of sepsis cases seems to result, to a considerable degree, from improved coding of sepsis.


Subject(s)
Cost of Illness , Sepsis/epidemiology , Socioeconomic Factors , Adult , Aged , Aged, 80 and over , Databases, Factual , Female , Germany/epidemiology , Hospitalization/statistics & numerical data , Humans , Incidence , Male , Middle Aged , Retrospective Studies , Sensitivity and Specificity , Sepsis/diagnosis , Sepsis/therapy , Survival Rate
20.
Infection ; 46(5): 599-605, 2018 Oct.
Article in English | MEDLINE | ID: mdl-29961209

ABSTRACT

BACKGROUND: Here, we report the case of an HIV positive patient under a dual antiretroviral drug regimen with tenofovir disoproxil and darunavir/ritonavir with stable clinical, virological, and immunological response over 126 weeks. Dual antiretroviral therapy has the advantage of reduced toxicity and lower health care costs, treatment failure and fostering drug resistance are perceived risks. Optimal drug combinations and indication criteria for dual treatment remain controversial. Nevertheless, first clinical trials indicate non-inferiority for combinations of nucleoside reverse transcriptase inhibitors and protease inhibitors. This case presents the combination of tenofovir disoproxil in combination with a protease inhibitor as a new potential dual treatment regimen. METHOD: We performed a systematic literature search and meta-analysis of trials comparing dual to triple ART. RESULTS: Literature review revealed nine studies in which dual therapy with a protease inhibitor and an NRTI was compared to triple therapy. We performed a meta-analysis of six trials that reported a 48-week follow-up. In treatment-naïve patients as well when ART switch was assessed, there was no difference in the treatment success in patients with dual ART versus triple. CONCLUSION: We conclude that dual therapy with a protease inhibitor and NRTI is safe and effective. The use of tenofovir in dual treatment as described in our case needs to be assessed in future clinical trials.


Subject(s)
HIV Infections/drug therapy , HIV Infections/virology , HIV Protease Inhibitors/therapeutic use , HIV-1/drug effects , Reverse Transcriptase Inhibitors/therapeutic use , Antiretroviral Therapy, Highly Active , CD4 Lymphocyte Count , Darunavir/administration & dosage , HIV Infections/immunology , HIV Protease Inhibitors/administration & dosage , HIV-1/immunology , Humans , Male , Middle Aged , Reverse Transcriptase Inhibitors/administration & dosage , Ritonavir/administration & dosage , Tenofovir/administration & dosage , Time Factors , Treatment Outcome , Viral Load
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