This report updates, expands, and replaces the previously published CDC "Guideline for Prevention of Nosocomial Pneumonia". The new guidelines are designed to reduce the incidence of pneumonia and other severe, acute lower respiratory tract infections in acute-care hospitals and in other health-care settings (e.g., ambulatory and long-term care institutions) and other facilities where health care is provided. Among the changes in the recommendations to prevent bacterial pneumonia, especially ventilator-associated pneumonia, are the preferential use of oro-tracheal rather than naso-tracheal tubes in patients who receive mechanically assisted ventilation, the use of noninvasive ventilation to reduce the need for and duration of endotracheal intubation, changing the breathing circuits of ventilators when they malfunction or are visibly contaminated, and (when feasible) the use of an endotracheal tube with a dorsal lumen to allow drainage of respiratory secretions; no recommendations were made about the use of sucralfate, histamine-2 receptor antagonists, or antacids for stress-bleeding prophylaxis. For prevention of health-care--associated Legionnaires disease, the changes include maintaining potable hot water at temperatures not suitable for amplification of Legionella spp., considering routine culturing of water samples from the potable water system of a facility's organ-transplant unit when it is done as part of the facility's comprehensive program to prevent and control health-care--associated Legionnaires disease, and initiating an investigation for the source of Legionella spp. when one definite or one possible case of laboratory-confirmed health-care--associated Legionnaires disease is identified in an inpatient hemopoietic stem-cell transplant (HSCT) recipient or in two or more HSCT recipients who had visited an outpatient HSCT unit during all or part of the 2-10 day period before illness onset. In the section on aspergillosis, the revised recommendations include the use of a room with high-efficiency particulate air filters rather than laminar airflow as the protective environment for allogeneic HSCT recipients and the use of high-efficiency respiratory-protection devices (e.g., N95 respirators) by severely immunocompromised patients when they leave their rooms when dust-generating activities are ongoing in the facility. In the respiratory syncytial virus (RSV) section, the new recommendation is to determine, on a case-by-case basis, whether to administer monoclonal antibody (palivizumab) to certain infants and children aged <24 months who were born prematurely and are at high risk for RSV infection. In the section on influenza, the new recommendations include the addition of oseltamivir (to amantadine and rimantadine) for prophylaxis of all patients without influenza illness and oseltamivir and zanamivir (to amantadine and rimantadine) as treatment for patients who are acutely ill with influenza in a unit where an influenza outbreak is recognized. In addition to the revised recommendations, the guideline contains new sections on pertussis and lower respiratory tract infections caused by adenovirus and human parainfluenza viruses and refers readers to the source of updated information about prevention and control of severe acute respiratory syndrome.

/pdf/guidelines-for-preventing-health-care-associated-pneumonia-3ebalxrxyl.pdf

Guidelines for Preventing Health-Care-- Associated Pneumonia, 2003 Recommendations of CDC and the Healthcare Infection Control Practices Advisory Committee

Importance New data and therapeutic options warrant updated recommendations for the use of antiretroviral drugs (ARVs) to treat or to prevent HIV infection in adults. Objective To provide updated recommendations for the use of antiretroviral therapy in adults (aged ≥18 years) with established HIV infection, including when to start treatment, initial regimens, and changing regimens, along with recommendations for using ARVs for preventing HIV among those at risk, including preexposure and postexposure prophylaxis. Evidence Review A panel of experts in HIV research and patient care convened by the International Antiviral Society–USA reviewed data published in peer-reviewed journals, presented by regulatory agencies, or presented as conference abstracts at peer-reviewed scientific conferences since the 2014 report, for new data or evidence that would change previous recommendations or their ratings. Comprehensive literature searches were conducted in the PubMed and EMBASE databases through April 2016. Recommendations were by consensus, and each recommendation was rated by strength and quality of the evidence. Findings Newer data support the widely accepted recommendation that antiretroviral therapy should be started in all individuals with HIV infection with detectable viremia regardless of CD4 cell count. Recommended optimal initial regimens for most patients are 2 nucleoside reverse transcriptase inhibitors (NRTIs) plus an integrase strand transfer inhibitor (InSTI). Other effective regimens include nonnucleoside reverse transcriptase inhibitors or boosted protease inhibitors with 2 NRTIs. Recommendations for special populations and in the settings of opportunistic infections and concomitant conditions are provided. Reasons for switching therapy include convenience, tolerability, simplification, anticipation of potential new drug interactions, pregnancy or plans for pregnancy, elimination of food restrictions, virologic failure, or drug toxicities. Laboratory assessments are recommended before treatment, and monitoring during treatment is recommended to assess response, adverse effects, and adherence. Approaches are recommended to improve linkage to and retention in care are provided. Daily tenofovir disoproxil fumarate/emtricitabine is recommended for use as preexposure prophylaxis to prevent HIV infection in persons at high risk. When indicated, postexposure prophylaxis should be started as soon as possible after exposure. Conclusions and Relevance Antiretroviral agents remain the cornerstone of HIV treatment and prevention. All HIV-infected individuals with detectable plasma virus should receive treatment with recommended initial regimens consisting of an InSTI plus 2 NRTIs. Preexposure prophylaxis should be considered as part of an HIV prevention strategy for at-risk individuals. When used effectively, currently available ARVs can sustain HIV suppression and can prevent new HIV infection. With these treatment regimens, survival rates among HIV-infected adults who are retained in care can approach those of uninfected adults.

/pdf/antiretroviral-drugs-for-treatment-and-prevention-of-hiv-4ztow8e871.pdf

Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults: 2016 Recommendations of the International Antiviral Society–USA Panel

Global kidney health 2017 and beyond: a roadmap for closing gaps in care, research, and policy

Summary Background The population infected with HIV is getting older and these people will increasingly develop age-related non-communicable diseases (NCDs). We aimed to quantify the scale of the change and the implications for HIV care in the Netherlands in the future. Methods We constructed an individual-based model of the ageing HIV-infected population, which followed patients on HIV treatment as they age, develop NCDs—including cardiovascular disease (hypertension, hypercholesterolaemia, myocardial infarctions, and strokes), diabetes, chronic kidney disease, osteoporosis, and non-AIDS malignancies—and start co-medication for these diseases. The model was parameterised by use of data for 10 278 patients from the national Dutch ATHENA cohort between 1996 and 2010. We made projections up to 2030. Findings Our model suggests that the median age of HIV-infected patients on combination antiretroviral therapy (ART) will increase from 43·9 years in 2010 to 56·6 in 2030, with the proportion of HIV-infected patients aged 50 years or older increasing from 28% in 2010 to 73% in 2030. In 2030, we predict that 84% of HIV-infected patients will have at least one NCD, up from 29% in 2010, with 28% of HIV-infected patients in 2030 having three or more NCDs. 54% of HIV-infected patients will be prescribed co-medications in 2030, compared with 13% in 2010, with 20% taking three or more co-medications. Most of this change will be driven by increasing prevalence of cardiovascular disease and associated drugs. Because of contraindications and drug–drug interactions, in 2030, 40% of patients could have complications with the currently recommended first-line HIV regimens. Interpretation The profile of patients in the Netherlands infected with HIV is changing, with increasing numbers of older patients with multiple morbidities. These changes mean that, in the near future, HIV care will increasingly need to draw on a wide range of medical disciplines, in addition to evidence-based screening and monitoring protocols to ensure continued high-quality care. These findings are based on a large dataset of HIV-infected patients in the Netherlands, but we believe that the overall patterns will be repeated elsewhere in Europe and North America. The implications of such a trend for care of HIV-infected patients in high-burden countries in Africa could present a particular challenge. Funding Medical Research Council, Bill & Melinda Gates Foundation, Rush Foundation, and Netherlands Ministry of Health, Welfare and Sport.

/pdf/future-challenges-for-clinical-care-of-an-ageing-population-jp12zl3rir.pdf

Future challenges for clinical care of an ageing population infected with HIV: a modelling study

Antiretroviral therapy has changed human immunodeficiency virus (HIV) infection from a near-certainly fatal illness to one that can be managed chronically. More patients are taking antiretroviral drugs (ARVs) for longer periods of time, which naturally results in more observed toxicity. Overdose with ARVs is not commonly reported. The most serious overdose outcomes have been reported in neonates who were inadvertently administered supratherapeutic doses of HIV prophylaxis medications. Typical ARV regimens include a “backbone” of two nucleoside reverse transcriptase inhibitors (NRTI) and a “base” of either a protease inhibitor (PI) or nonnucleoside reverse transcriptase inhibitor. New classes of drugs called entry inhibitors and integrase inhibitors have also emerged. Older NRTIs were associated with mitochondrial toxicity, but this is less common in the newer drugs, emtricitabine, lamivudine, and tenofovir. Mitochondrial toxicity results from NRTI inhibition of a mitochondrial DNA polymerase. Mitochondrial toxicity manifests as myopathy, neuropathy, hepatic failure, and lactic acidosis. Routine lactate assessment in asymptomatic patients is not indicated. Lactate concentration should be obtained in patients taking NRTIs who have fatigue, nausea, vomiting, or vague abdominal pain. Mitochondrial toxicity can be fatal and is treated by supportive care and discontinuing NRTIs. Metabolic cofactors like thiamine, carnitine, and riboflavin may be helpful in managing mitochondrial toxicity. Lipodystrophy describes changes in fat distribution and lipid metabolism that have been attributed to both PIs and NRTIs. Lipodystrophy consists of loss of fat around the face (lipoatrophy), increase in truncal fat, and hypertriglyceridemia. There is no specific treatment of lipodystrophy. Clinicians should be able to recognize effects of chronic toxicity of ARVs, especially mitochondrial toxicity.

/pdf/a-review-of-the-toxicity-of-hiv-medications-cmlrzul7s9.pdf

A Review of the Toxicity of HIV Medications

It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.

/pdf/clinical-practice-guideline-for-the-management-of-chronic-101oj101sc.pdf

Clinical Practice Guideline for the Management of Chronic Kidney Disease in Patients Infected With HIV: 2014 Update by the HIV Medicine Association of the Infectious Diseases Society of America

It is estimated that by 2015 more than half of all HIV-infected individuals in the United States will be 50 years of age or older. As this population ages, the frequency of non-AIDS related comorbidities increases, which includes cardiovascular, metabolic, gastrointestinal, genitourinary and psychiatric disorders. As a result, medical management of the aging HIV population can be complicated by polypharmacy and higher pill burden, leading to poorer antiretroviral therapy (ART) adherence. Adherence to ART is generally better in older populations when compared to younger populations; however, cognitive impairment in elderly patients can impair adherence, leading to worse treatment outcomes. Practical monitoring tools can improve adherence and increase rates of viral load suppression. Several antiretroviral drugs exhibit inhibitory and/or inducing effects on cytochrome P450 isoenzymes, which are responsible for the metabolism of many medications used for the treatment of comorbidities in the aging HIV population. The combination of ART with polypharmacy significantly increases the chance of potentially serious drug-drug interactions (DDIs), which can lead to drug toxicity, poorer ART adherence, loss of efficacy of the coadministered medication, or virologic breakthrough. Increasing clinicians awareness of common DDIs and the use of DDI programs can prevent coadministration of potentially harmful combinations in elderly HIV-infected individuals. Well designed ART adherence interventions and DDI studies are needed in the elderly HIV population.

/pdf/antiretroviral-therapy-adherence-and-drug-drug-interactions-4lq614a2ym.pdf

Antiretroviral therapy adherence and drug-drug interactions in the aging HIV population

In May 2011, hepatitis C virus (HCV) protease inhibitors (PIs) were approved by the US Food and Drug Administration to treat persons with genotype 1 chronic hepatitis C virus (HCV) infection, but not those dually infected with human immunodeficiency virus (HIV). Although critical safety and efficacy data are lacking, the availability of the drugs and substantial medical need justify the off-label use of HCV PIs in select HIV/HCV-coinfected persons. Pending results of ongoing investigations, this article represents provisional guidance on the use of HCV PIs in HIV-infected persons.

/pdf/provisional-guidance-on-the-use-of-hepatitis-c-virus-1y0egxyn67.pdf

Provisional Guidance on the Use of Hepatitis C Virus Protease Inhibitors for Treatment of Hepatitis C in HIV-Infected Persons

tudy Objective
To determine whether human immunodeficiency virus (HIV)-positive patients who received intravenous midazolam during an inpatient bronchoscopy procedure were more likely to experience severe prolonged sedation if they were taking antiretroviral therapy that included a protease inhibitor versus those who were not taking any antiretroviral therapy.

Design
Retrospective cohort study.

Setting
Tertiary care academic medical center.

Patients
Two hundred forty-one HIV-positive adults who received intravenous midazolam while undergoing bronchoscopy between January 1, 2003, and December 31, 2006, were analyzed; 51 patients were taking an antiretroviral regimen that included a protease inhibitor (exposed group), whereas 190 patients were not taking any antiretroviral agents (nonexposed group).

Measurements and Main Results
Patient demographics, medication administration records, and bronchoscopy data were collected from electronic databases and patient medical records. The exposed and nonexposed groups had similar demographic characteristics except that patients in the exposed group had lower HIV viral loads and were less likely to have altered mental status or respiratory distress before bronchoscopy. In addition, the exposed group had a higher proportion of males and patients with hepatitis B or C virus coinfection. The incidence of severe prolonged sedation was 9.80% in the exposed group versus 1.58% in the nonexposed group (relative risk [RR] 6.21, 95% confidence interval [CI] 1.53–25.12). Specific protease inhibitors associated with severe prolonged sedation were atazanavir-ritonavir and lopinavir-ritonavir. Length of hospital stay was approximately 3 days longer in the exposed group compared with the nonexposed group.

Conclusion
Although the interaction between intravenous midazolam and protease inhibitors is well known, this study was the first systematic evaluation, to our knowledge, of the risk of severe prolonged sedation in a cohort of hospitalized HIV-positive patients. Coadministration of protease inhibitors with intravenous midazolam was associated with severe prolonged sedation as well as increased length of hospital stay. Therefore, concomitant use of these drugs should be closely monitored, or alternative sedatives for procedural sedation should be considered.

Paul A. Pham

Papers

Clinical Practice Guideline for the Management of Chronic Kidney Disease in Patients Infected With HIV: 2014 Update by the HIV Medicine Association of the Infectious Diseases Society of America

Antiretroviral therapy adherence and drug-drug interactions in the aging HIV population

Provisional Guidance on the Use of Hepatitis C Virus Protease Inhibitors for Treatment of Hepatitis C in HIV-Infected Persons

Severe Prolonged Sedation Associated with Coadministration of Protease Inhibitors and Intravenous Midazolam During Bronchoscopy

Daptomycin, a new cyclic lipopeptide antibiotic, for the treatment of resistant gram-positive organisms