HIV: how to manage heavily treatment-experienced patients.

Although decreasing in prevalence, heavily treatment-experienced (HTE) persons with limited options for HIV treatment present unique complexities, even amongst experienced providers, as there is no single approach to successful management. HTE patients are described as those having two or less antiretroviral (ARV) classes available for use with limited fully active ARV agents within each class. A detailed understanding of the underlying processes that caused previous treatment failures, diagnostics to define resistance, resistance mechanisms and ARV pharmacology should all function in tandem to determine the next steps of clinical care. This narrative review provides an overview of the clinician approach to care, including diagnostics, approaches to regimen creation, relevant resources, and a broad array of both currently available and upcoming ARVs that may be used in regimens for HTE patients.

Perceptions of Long-Acting Injectable Antiretroviral Treatment Regimens in a United States Urban Academic Medical Center.

Patient acceptance of long-acting injectable antiretroviral (LAI-ARV) HIV-1 regimens will determine uptake. Although previous literature reports high satisfaction, these data stem from clinical trials subject to selection bias. This cross-sectional survey from the HIV practices of an urban academic medical center assessed perceptions and preferences using Likert scales toward overall acceptability, proposed frequencies, injection-site reaction durations, and distribution venue. 59% of surveys were completed resulting 202 respondents. 60% were male, 72% black, and the median age was 49 (IQR 36-58). 93% reported a once daily tablet frequency, 69% reported single tablet regimens, and 59% reported missing zero doses in the prior 30 days. Patients self-categorized as likely (57%) or unlikely (43%) to accept LAI-ARV. Both decreasing frequencies between injections and durations of injection-site reactions resulted higher acceptability scores. 57% of respondents preferred receiving an injectable from their clinician's office over other potential options. These data demonstrate positive LAI-ARV acceptance potential.

Impact of an Antiretroviral Stewardship Team on the Care of Patients With Human Immunodeficiency Virus Infection Admitted to an Academic Medical Center.

BACKGROUND: Interdisciplinary antiretroviral stewardship teams, comprising a human immunodeficiency virus pharmacist specialist, an infectious diseases physician, and associated learners, have the ability to assist in identification and correction of inpatient antiretroviral-related errors. METHODS: Electronic medical records of patients with antiretroviral orders admitted to our hospital were evaluated for the number of interventions made by the stewardship team, number of admissions with errors identified, risk factors for occurrence of errors, and cost savings. Risk factors were analyzed by means of multivariable logistic regression. Cost savings were estimated by the documentation system Clinical Measures. RESULTS: A total of 567 admissions were included for analysis in a 1-year study period. Forty-three percent of admissions (245 of 567) had ≥1 intervention, with 336 interventions in total. The following were identified as risk factors for error: multitablet inpatient regimen (odds ratio, 1.834; 95% confidence interval, 1.160-2.899; P = .009), admission to the intensive care unit (2.803; 1.280-6.136; P = .01), care provided by a surgery service (1.762; 1.082-2.868; P = .02), increased number of days reviewed (1.061; 1.008-1.117; P = .02), and noninstitutional outpatient provider (1.375; .972-1.946; P = .07). The 1-year cost savings were estimated to be $263 428. CONCLUSIONS: Antiretroviral stewardship teams optimize patient care through identification and correction of antiretroviral-related errors. Errors may be more common in patients with multitablet inpatient regimens, admission to the intensive care unit, care provided by a surgery service, and increased number of hospital days reviewed. Once antiretroviral-related errors are identified, the ability to correct them provides cost savings.

Mapping patient-identified barriers and facilitators to retention in HIV care and antiretroviral therapy adherence to Andersen's Behavioral Model.

Andersen's Behavioral Model (ABM) provides a framework for understanding how patient and environmental factors impact health behaviors and outcomes. We compared patient-identified barriers/facilitators to retention in care and antiretroviral therapy (ART) adherence and evaluated how they mapped to ABM. Qualitative semi-structured interviews with 51 HIV-infected adults at HIV clinics in Philadelphia, PA, in 2013 were used to explore patients' experiences with HIV care and treatment. Interview data were analyzed for themes using a grounded theory approach. Among those interviewed, 53% were male and 88% were nonwhite; 49% were retained in care, 96% were on ART, and 57% were virally suppressed. Patients discussed 18 barriers/facilitators to retention in care and ART adherence: 11 common to both behaviors (stigma, mental illness, substance abuse, social support, reminder strategies, housing, insurance, symptoms, competing life activities, colocation of services, provider factors), 3 distinct to retention (transportation, clinic experiences, appointment scheduling), and 4 distinct to adherence (medication characteristics, pharmacy services, health literacy, health beliefs). Identified barriers/facilitators mapped to all ABM domains. These data support the use of ABM as a framework for classifying factors influencing HIV-specific health behaviors and have the potential to inform the design of interventions to improve retention in care and ART adherence.

Dolutegravir versus placebo in subjects harbouring HIV-1 with integrase inhibitor resistance associated substitutions: 48-week results from VIKING-4, a randomized study.

BACKGROUND: The Phase III VIKING-3 study demonstrated that dolutegravir (DTG) 50 mg twice daily was efficacious in antiretroviral therapy (ART)-experienced subjects harbouring raltegravir- and/or elvitegravir-resistant HIV-1. VIKING-4 (ING116529) included a placebo-controlled 7-day monotherapy phase to demonstrate that short-term antiviral activity was attributable to DTG. METHODS: VIKING-4 is a Phase III randomized, double-blind study in therapy-experienced adults with integrase inhibitor (INI)-resistant virus randomized to DTG 50 mg twice daily or placebo while continuing their failing regimen (without raltegravir or elvitegravir) for 7 days (clinicaltrials.gov identifier NCT01568892). At day 8, all subjects switched to open-label DTG 50 mg twice daily and optimized background therapy including ≥1 fully active drug. The primary end point was change from baseline in plasma HIV-1 RNA at day 8. RESULTS: The study population (n=30) was highly ART-experienced with advanced HIV disease. Patients had extensive baseline resistance to all approved antiretroviral classes. Adjusted mean change in HIV-1 RNA at day 8 was -1.06 log10 copies/ml for the DTG arm and 0.10 log10 copies/ml for the placebo arm (treatment difference -1.16 log10 copies/ml [-1.52, -0.80]; P<0.001). Overall, 47% and 57% of subjects had plasma HIV-1 RNA <50 and <400 copies/ml at week 24, and 40% and 53% at week 48, respectively. No discontinuations due to drug-related adverse events occurred in the study. CONCLUSIONS: The observed day 8 antiviral activity in this highly treatment-experienced population with INI-resistant HIV-1 was attributable to DTG. Longer-term efficacy (after considering baseline ART resistance) and safety during the open-label phase were in-line with the results of the larger VIKING-3 study.

Infections in Heart and Lung Transplant Recipients.

Patients undergoing thoracic organ transplantation procedures involving the heart or lung are at increased risk for developing a wide variety of infections due to their underlying immunosuppression and/or other factors. Lung transplant recipients are at high risk for developing infections caused by bacteria, viruses, and opportunistic fungi, whereas heart transplant recipients are at risk for developing infections caused by these same microorganisms, as well as parasitic infections, including toxoplasmosis and New World trypanosomiasis. This review will highlight the various infections that thoracic organ transplant recipients may develop following their procedures.

Antiretroviral therapy 2010 update: current practices and controversies.

Over the past four years, significant advances have been made in human immunodeficiency virus (HIV) therapy. In addition to the release of two new classes of antiretrovirals, our understanding of the older antiretrovirals continues to improve. Multiple combination pills have been brought to market, simplifying the regimens for patient ease. New controversies have arisen, notably the role of antiretrovirals in the chronic inflammatory state that HIV infection produces, which may lead to excess cardiac, renal, and hepatic mortality. The optimum time to initiate antiretroviral therapy remains unknown but clinicians are treating HIV infection earlier in its course. In this article, we review these and other new issues relating to the care of the HIV patient.

Prevalence and characteristics of patients with undiagnosed HIV infection in an urban emergency department.

The Centers for Disease Control and Prevention (CDC) recommends offering HIV testing to persons admitted to emergency departments (EDs). Whether by opt-in or opt-out, many EDs (including our own) have found a seroprevalence of 0.8-1.5% when rapid testing is offered. The true seropositivity rate is unknown. We performed a retrospective chart analysis upon all patients presenting to our ED over a 2-week period in the fall of 2007 who had serum drawn as a part of their emergency care. Demographics and clinical characteristics were linked via de-identified serum, which was sent for HIV testing. Nine hundred fifty nine patients had sera available for rapid HIV testing. One hundred twenty one (13%) samples were reactive via the OraQuick(®) test (OraSure Technologies, Bethlehem, PA), a point of care rapid antibody test. Due to concerns about the appropriateness of sera as substrate for the OraQuick(®) technology, reactive samples were retested via standard enzyme immunoassay (EIA)/Western blot. One hundred twelve analyzable samples were retested-38 were positive and 27 of these were from patients who reported a history of HIV infection. The rate of undiagnosed HIV infection was 1.2% (11/914 potentially analyzable samples). Of all patients with HIV in our ED, 29% of them were presumably unaware of their diagnosis. In conclusion, HIV seroprevalence in our urban ED is high, and a large fraction of the patients appears to be unaware of the infection.

Virologic success in an urban HIV clinic: outcome at 12 months in patients who were HAART naïve.

BACKGROUND: Randomized controlled trials with highly active antiretroviral therapy (HAART) have demonstrated over 70% virologic success rates, although patients in an inner city HIV setting likely have lower virologic success. METHOD: We studied the outcome of all treatment-naive patients beginning HAART in our urban clinic in Philadelphia, Pennsylvania. The primary outcome was virologic success at 12 months for all patients who were initiated on HAART. Secondary outcomes included virologic success at 12 months for only those who remained in care and the determination of which demographics influenced virologic success. RESULTS: Between 2003 and 2005, 109 patients were initiated on HAART: 39% women, 79% African American, 17% Hispanic, median CD4+ count 120 cells/mm3, and HIV-1 RNA 4.9 log10 copies/mL. Twenty-two were lost to follow-up after HAART initiation. Of the 87 who remained in care, 41 maintained a HIV-1 RNA <400 copies/mL through 12 months on their initial HAART regimen. Emerging drug resistance was documented in 7 of 87 patients. NNRTI-based HAART was significantly associated with greater virologic failure due to emerging resistance compared to a PI-based regimen. CONCLUSION: Our retrospective study demonstrates the difficulties in administering successful HIV care to an urban population, and efforts to help patients overcome barriers to consistent medical care must be a priority.

Bacterial peritonitis caused by Kingella kingae.

Kingella kingae is a commensal of the upper respiratory tract that occasionally causes skeletal infections in children and endocarditis in children and adults. We report a case of a 55-year-old man with liver disease and tense ascites who performed a paracentesis on himself and developed K. kingae peritonitis and bacteremia.

Antiretroviral therapy 2006: pharmacology, applications, and special situations.

As we approach the completion of the first 25 years of the human immunodeficiency virus (HIV) epidemic, there have been dramatic improvements in the care of patients with HIV infection. These have prolonged life and decreased morbidity. There are twenty currently available antiretrovirals approved in the United States for the treatment of this infection. The medications, including their pharmacokinetic properties, side effects, and dosing are reviewed. In addition, the current approach to the use of these medicines is discussed. We have included a section addressing common comorbid conditions including hepatitis B and C along with tuberculosis.

AIDS related opportunistic infections, going but not gone.

It is now more than two decades since the AIDS epidemic began with a cluster of Pneumocystis carinii pneumonia (PCP) in a community of homosexual men. Since then, many other infections have been characterized as opportunistic infections secondary to HIV infection. These include, but are not limited to, infections with Toxoplasma gondii, Cytomegalovirus (CMV), Mycobacterium avium complex (MAC), and Cryptococcus neoformans. Over the last two decades, there have been dramatic improvements in diagnosis, prevention and treatment of all these infections. As a result, in North America and Western Europe the rates of opportunistic infections secondary to AIDS have decreased substantially. We will review these common opportunistic infections below.

An outbreak of mediastinitis among heart transplant recipients apparently related to a change in the united network for organ sharing guidelines.

OBJECTIVE: To describe an outbreak of mediastinitis in heart transplant recipients. DESIGN: Retrospective and contemporaneous cohort SETTING: Urban tertiary-care university hospital with a large cardiac transplantation program. PATIENTS: Heart transplant recipients. INTERVENTIONS: Modifications of donor harvest technique; procedures aimed at decreasing skin and mucosal bacterial colonization; strict aseptic technique in the intensive care unit; and aggressive policing of established infection control practices. RESULTS: In April 1999, mediastinitis rates among heart transplant recipients increased abruptly from a baseline of 6 cases per 100 procedures to sequential quarterly rates of 22, 31, and 50 cases per 100 procedures, whereas infection rates in other cardiac operations were unchanged. Bacteria causing these infections were multidrug-resistant "nosocomial" organisms. The epidemic occurred 2 months after a change in the United Network for Organ Sharing organ allocation algorithm. This change resulted in an increase in the duration of preoperative hospitalization from a median of 52 to 79 days (P = .008) and may have promoted prolonged hospitalization of patients with high illness severity. Aggressive multidisciplinary interventions were temporally associated with a return to preoperative mediastinitis rates without changing length of hospitalization prior to transplantation. CONCLUSIONS: Changes in organ allocation for transplant that prolong waiting time in the hospital and alter illness acuity may lead to increased rates of postoperative infection. Measures to limit bacterial colonization may be a helpful countervailing strategy.