History of viral suppression on combination antiretroviral therapy as a predictor of virological failure after a treatment change*

Objectives

HIV‐infected persons experience different patterns of viral suppression after initiating combination antiretroviral therapy (cART). The relationship between such differences and risk of virological failure after starting a new antiretroviral could help with patient monitoring strategies.

Methods

A total of 1827 patients on cART starting at least one new antiretroviral from 1 January 2000 while maintaining a suppressed viral load were included in the analysis. Poisson regression analysis identified factors predictive of virological failure after baseline in addition to traditional demographic variables. Baseline was defined as the date of starting new antiretrovirals.

Results

Four hundred and fifty‐one patients (24.7%) experienced virological failure, with an incidence rate (IR) of 7.3 per 100 person‐years of follow‐up (PYFU) [95% confidence interval (CI) 6.7–8.0]. After adjustment, patients who had rebounded in the year prior to baseline had a 2.4‐times higher rate of virological failure after baseline (95% CI 1.77–3.26; P<.0001), while there was no increased incidence in patients whose last viral rebound was >3 years prior to baseline [Incidence rate ratio (IRR) 1.06; 95% CI 0.75–1.50; P=0.73] compared with patients who had never virally rebounded. Patients had an 86% (95% CI 1.36–2.55; P<.0001), 53% (95% CI 1.06–2.04; P=0.02) and 5% (95% CI 0.80–1.38; P=0.72) higher virological failure rate after baseline if they were virally suppressed <50%, 50–70% and 70–90% of the time they were on cART prior to baseline, respectively, compared with those virally suppressed >90% of the time.

Discussion

Intensive monitoring after a treatment switch is required in patients who have rebounded recently or have a low percentage of time suppressed while on cART. Consideration should be given to increasing the provision of adherence counselling.     

A comparison of the long‐term durability of nevirapine,efavirenz and lopinavir in routine clinical practice in Europe: a EuroSIDA study

Objectives

The durability of combination antiretroviral therapy (cART) regimens can be measured as time to discontinuation because of toxicity or treatment failure, development of clinical disease or serious long‐term adverse events. The aim of this analysis was to compare the durability of nevirapine, efavirenz and lopinavir regimens based on these measures.

Methods

Patients starting a nevirapine, efavirenz or lopinavir‐based cART regimen for the first time after 1 January 2000 were included in the analysis. Follow‐up started ≥3 months after initiation of treatment if viral load was <500 HIV‐1 RNA copies/mL. Durability was measured as discontinuation rate or development/worsening of clinical markers.

Results

A total of 603 patients (21%) started nevirapine‐based cART, 1465 (51%) efavirenz, and 818 (28%) lopinavir. After adjustment there was no significant difference in the risk of discontinuation for any reason between the groups on nevirapine and efavirenz (P=0.43) or lopinavir (P=0.13). Compared with the nevirapine group, those on efavirenz had a 48% (P=0.0002) and those on lopinavir a 63% (P<0.0001) lower risk of discontinuation because of treatment failure and a 31% (P=0.01) and 66% (P<.0001) higher risk, respectively, of discontinuation because of toxicities or patient/physician choice. There were no significant differences in the incidence of non‐AIDS‐related events, worsening anaemia, severe weight loss, increased aspartate aminotransferase (AST)/alanine aminotransferase (ALT) levels or increased total cholesterol. Compared with patients on nevirapine, those on lopinavir had an 80% higher incidence of high‐density lipoprotein (HDL) cholesterol decreasing below 0.9 mmol/L (P=0.003), but there was no significant difference in this variable between those on nevirapine and those on efavirenz (P=0.39).

Conclusions

The long‐term durability of nevirapine‐based cART, based on risk of all‐cause discontinuation and development of long‐term adverse events, was comparable to that of efavirenz or lopinavir, in patients in routine clinical practice across Europe who initially tolerated and virologically responded to their regimen.     

Highlights of the 2017 European AIDS Clinical Society (EACS) Guidelines for the treatment of adult HIV‐positive persons version 9.0

Background

The European AIDS Clinical Society (EACS) Guidelines have since 2005 provided multidisciplinary recommendations for the care of HIV‐positive persons in geographically diverse areas.

Guideline highlights

Major revisions have been made in all sections of the 2017 Guidelines: antiretroviral treatment (ART), comorbidities, coinfections and opportunistic diseases. Newly added are also a summary of the main changes made, and direct video links to the EACS online course on HIV Management. Recommendations on the clinical situations in which tenofovir alafenamide may be considered over tenofovir disoproxil fumarate are provided, and recommendations on which antiretrovirals can be used safely during pregnancy have been revised. Renal and bone toxicity and hepatitis C virus (HCV) treatment have been added as potential reasons for ART switches in fully virologically suppressed individuals, and dolutegravir/rilpivirine has been included as a treatment option. In contrast, dolutegravir monotherapy is not recommended. New recommendations on non‐alcoholic fatty liver disease, chronic lung disease, solid organ transplantation, and prescribing in elderly are included, and human papilloma virus (HPV) vaccination recommendations have been expanded. All drug–drug interaction tables have been updated and new tables are included. Treatment options for direct‐acting antivirals (DAAs) have been updated and include the latest combinations of sofosbuvir/velpatasvir/voxilaprevir and glecaprevir/pibrentasvir. Recommendations on management of DAA failure and acute HCV infection have been expanded. For treatment of tuberculosis (TB), it is underlined that intermittent treatment is contraindicated, and for resistant TB new data suggest that using a three‐drug combination may be as effective as a five‐drug regimen, and may reduce treatment duration from 18‐24 to 6‐10 months.

Conclusions

Version 9.0 of the EACS Guidelines provides a holistic approach to HIV care and is translated into the six most commonly spoken languages.     

Appropriateness of Medication Selection for Older Persons in an Urban Academic Emergency Department

OBJECTIVES: To determine the frequency of potentially inappropriate medication selection for older persons presenting to the ED, the most common problematic drugs, risk factors for suboptimal medication selection, and whether use of these medications is associated with worse outcomes. METHODS: The authors performed a prospective cohort study of 898 patients 65 years or older who presented to an urban academic ED in 1995 and 1996. Seventy-nine percent of the patients were African-American and 43% did not graduate from high school. Potentially inappropriate medications and adverse drug-disease interactions were identified using the 1997 Beers explicit criteria for elders. During the three months after the initial visit, revisits to the ED or hospital, death, and changes in health-related quality of life were analyzed as measured by validated questions adapted from the Medical Outcomes Study. RESULTS: Upon presentation, 10.6% of the patients were taking a potentially inappropriate medication, 3.6% were given one in the ED, and 5.6% were prescribed one upon discharge from the ED. The most frequently prescribed potentially inappropriate medications in the ED were diphenhydramine, indomethacin, meperidine, and cyclobenzaprine. Emergency physicians added potentially inappropriate medications most often to patients with discharge diagnoses of musculoskeletal disorder, back pain, gout, and allergy or urticaria. Potentially adverse drug-disease interactions were relatively uncommon at presentation (5.2%), in the ED (0.6%), and on discharge from the ED (1.2%). Potentially inappropriate medications and adverse drug-disease interactions prescribed in the ED were not associated with higher rates of revisit to the ED, hospitalization, or death, but were correlated with worse physical function and pain. However, confidence intervals were wide for analyses of revisits and death. CONCLUSIONS: Suboptimal medication selection was fairly common and was associated with worse patient-reported health-related quality of life.     

Clinical Interview Assessment of Financial Capacity in Older Adults with Mild Cognitive Impairment and Alzheimer's Disease

OBJECTIVES: To investigate financial capacity in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) using a clinician interview approach.
DESIGN: Cross-sectional.
SETTING: Tertiary care medical center.
PARTICIPANTS: Healthy older adults (n=75) and patients with amnestic MCI (n=58), mild AD (n=97), and moderate AD (n=31).
MEASUREMENTS: The investigators and five study physicians developed a conceptually based, semistructured clinical interview for evaluating seven core financial domains and overall financial capacity (Semi-Structured Clinical Interview for Financial Capacity; SCIFC). For each participant, a physician made capacity judgments (capable, marginally capable, or incapable) for each financial domain and for overall capacity.
RESULTS: Study physicians made more than 11,000 capacity judgments across the study sample (N=261). Very good interrater agreement was obtained for the SCIFC judgments. Increasing proportions of marginal and incapable judgment ratings were associated with increasing disease severity across the four study groups. For overall financial capacity, 95% of physician judgments for older controls were rated as capable, compared with 82% for patients with MCI, 26% for patients with mild AD, and 4% for patients with moderate AD.
CONCLUSION: Physicians and other clinicians can reliably evaluate financial capacity in cognitively impaired older adults using a relatively brief, semistructured clinical interview. Patients with MCI have mild impairment in financial capacity, those with mild AD have emerging global impairment, and those with moderate AD have advanced global impairment. Patients with MCI and their families should proactively engage in financial and legal planning, given these patients' risk of developing AD and accelerated loss of financial abilities.     

Does the Shoe Fit? Ethical,Legal, and Policy Considerations of Global Positioning System Shoes for Individuals with Alzheimer's Disease

As the overall incidence of Alzheimer's disease rises, the burden on caregivers and law enforcement institutions will increase to find individuals who wander. As such, technological innovations that could reduce this burden will become increasingly important. One such innovation is the GPS Shoe. As with any innovation involving the transfer of personal data to third parties, potential pitfalls with respect to loss of privacy and inadequate consent counterbalance the substantial promise of GPS shoes. To some extent, advance planning can mitigate these concerns, wherein individuals willingly elect to be monitored before their impairments progress to a stage that makes such authorization impractical. Nonetheless, tension may arise between the peace of mind of caregivers and family members and other important considerations at the intersection of autonomy, privacy, dignity, and consent. Ultimately, confronting ethical, legal, and policy considerations at the front end of product development and deployment will help ensure that new technologies are used wisely and that their lifesaving potential is realized.