Switching from TDF- to TAF-containing ART associated with the development of obesity in people living with HIV

Below please find summaries of new articles that will be published in the next issue of Annals of Internal Medicine. The summaries are not intended to substitute for the full articles as a source of information. This information is under strict embargo and by taking it into possession, media representatives are committing to the terms of the embargo not only on their own behalf, but also on behalf of the organization they represent.

1. Switching from TDF- to TAF-containing ART associated with the development of obesity in people living with HIV
Abstract: https://www.acpjournals.org/doi/10.7326/M20-4853
URL goes live when the embargo lifts

Switching from antiretroviral therapy (ART) containing tenofovir disoproxil fumarate (TDF) to ART containing tenofovir alafenamide (TAF) is associated with increased risk for significant weight increases, obesity, and rising blood lipid levels in people living with HIV. In contrast to most previous studies that were performed among treatment-naive patients, the changes in weight in the present study could not be attributed to better health due to starting HIV treatment as the patients studied were already taking ART with TDF for 6 months or longer. These findings from a cohort study are published in Annals of Internal Medicine.

Tenofovir plays an important role in ART and is recommended as part of the first-line regimens in all major HIV treatment guidelines. Because TDF is associated with kidney disease and loss of bone mineral density, TAF is an attractive alternative. However, TAF has been associated with significant weight increases, rising blood lipid levels, and an increased need for lipid-lowering therapy in treatment-naive patients.

Researchers from the University Hospital of Bern used data from the Swiss HIV Cohort Study to examine changes in weight and lipid levels over 18 months among more than 3,000 adults living with HIV who initially received TDF-containing ART for at least 6 months and then switched to TAF. They then compared these changes with those of nearly 900 patients who continued the TDF-based therapy during the same period. The researchers found that switching to TAF was associated with a significant increase in weight compared to those who continued TDF. A significantly higher proportion of patients who switched to TAF became overweight or obese, and those who switched to TAF also had greater increases in levels of total cholesterol, low-density lipoprotein cholesterol, and triglycerides during the 18-month follow-up.

According to the study authors, these findings suggest that the decision to prefer TAF over TDF as a component of ART should be individualized and accompanied by the repeated assessment of cardiometabolic risk factors, including weight and lipids.

Media contacts: For an embargoed PDF, please contact Angela Collom at acollom@acponline.org.
The corresponding author, Bernard Surial, MD, can be contacted via kommunikation@insel.ch, phone: 0041 31 632 79 25.

2. Deferred initiation of ART may increase risk for AIDS-defining cancer among patients living with HIV
Abstract: https://www.acpjournals.org/doi/10.7326/M20-5226
URL goes live when the embargo lifts

Deferred antiretroviral therapy (ART) initiation in ART-naive, HIV-positive persons is associated with a small increase in risk for AIDS-defining cancer. These findings add to the evidence that early ART may reduce risk for non-AIDS-defining cancer. A multinational prospective cohort study is published in Annals of Internal Medicine.

Immediate initiation ART regardless of CD4 cell count has been recommended in all HIV-positive persons since 2015. However, only about half of HIV-positive persons in non-resource-limited settings continue to initiate ART when their CD4 count decreases below 500 cells/L, primarily because of late diagnosis. Incidence of non-AIDS-related and AIDS-related cancer is increasing in HIV-positive persons for a number of reasons and is now a leading cause of death in HIV infection. It is unclear to what extent delayed ART initiation, with its consequences of continued HIV replication and immune deterioration, contributes to the increased risk.

Researchers from University Hospital Basel and University of Basel, Basel, Switzerland studied data from D:A:D (Data collection on Adverse events of anti-HIV Drugs), a large observational database that included data from HIV-positive persons from Europe, Australia, and the United States, to estimate the 10-year risk difference for non-AIDS-defined and AIDS-defined cancer with two different ART initiation strategies - immediate or deferred. After adjusting for baseline and time-dependent confounders (CD4 cell count and viral load), the researchers found that the 10-year absolute risk of non-AIDS-defining cancer was slightly lower in the immediate ART group compared to the deferred treatment group. Strategies promoting deferral were associated with a small increase in risk for AIDS-defining cancer. More research is needed to determine the effect of early art on non-AIDS-defining cancer.

Media contacts: For an embargoed PDF, please contact Angela Collom at acollom@acponline.org.
The corresponding author, Heiner C. Bucher, MD, MPH, can be reached at heiner.bucher@usb.ch.

3. ACP releases new policy addressing Ethical Implications of Physician Employment and Health Care Business Practices
Abstract: https://www.acpjournals.org/doi/10.7326/M20-7093
URL goes live when the embargo lifts

The American College of Physicians (ACP) says that the practice of medicine should account for efficiency and productivity but must be defined by medical ethics and serving the needs of patients. In a new policy paper published in Annals of Internal Medicine, ACP lays out a framework that addresses the impact that business practices, employment terms, and contracts can have on ethics and professionalism.

The paper was developed by ACP's Ethics, Professionalism and Human Rights Committee in response to practice environment changes. Those changes have raised concerns in the areas of physician employment, practice model shifts, new regulatory requirements, physician contracts, practice ownership, clinical priority settings and physician leadership as well as greater emphasis on the business of medicine.

ACP calls for physicians to ensure that both relationships and practices are structured to support the commitments of the physician and the profession of medicine to patients and patient care. The paper further encourages physicians to be prepared to ask questions about arrangements and feel empowered to advocate for practices that promote patient health and the patient-physician relationship. If a practice or policy harms or has the potential to harm patient care, the physician should speak out and resist and if necessary, refuse to carry it out.

In the paper, ACP states that the challenges to care and to medical practice during and after the COVID-19 crisis underscore the need to reemphasize the ethical foundation of medicine. Some see in COVID-19 an important lesson that the system can be reset to better serve both patients and clinicians. Physicians should lead in ensuring business relationships explicitly recognize and support the fundamental and timeless commitments of the physician and medicine to patients. Recommendations include:

In the shift of incentives to Value-Based Care, ethics and professionalism must be emphasized and explicitly addressed in the implementation of business practices and employment relationships, including in the face of external motivators for clinicians such as financial incentives.

Contract provisions affecting practice should align with the ethical commitments of physicians and in-network referral requirements, confidentiality clauses, and restrictive covenants, for example, should recognize that and the patient's best interest.

Physicians should consider carefully whether to sign employment contracts that permit termination without cause, as abrupt terminations can interfere with patient-physician relationship continuity.

The net value of private equity investment in physician practices for patients, physicians, and medicine is unclear. Systematic studies of this trend on patients, medicine and society are needed.

Organizations and employers should recognize and appropriately value time for patient-physician encounters and engage patients and physicians in priority settings across all aspects of health care.

Media contacts: For an embargoed PDF, please contact Angela Collom at acollom@acponline.org.
To speak with someone from ACP, please contact Andrew Hachadorian at ahachatorian@acponline.org.

Also in this issue:

Clinical Practice Guidelines Registry: Toward Reducing Duplication, Improving Collaboration, and Increasing Transparency
Chen
Ideas and Opinions
Abstract: https://www.acpjournals.org/doi/10.7326/M20-7884

On the origin of Sensitivity and Specificity
Binney
History of Medicine
Abstract: https://www.acpjournals.org/doi/10.7326/M20-5028

Post-operative Delirium
Caputo
Annals Consult Guys
Abstract: https://www.acpjournals.org/doi/10.7326/W20-0019

Under-recognition of Aldosteronism in Patients with Resistant Hypertension
Centor
Annals On Call
Abstract: https://www.acpjournals.org/doi/10.7326/A20-0008

Inpatient Notes: Timely Hip Fracture Surgery
Borges
Annals for Hospitalists
Abstract: https://www.acpjournals.org/doi/10.7326/M21-0298

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