First report of its kind describes HIV reservoir landscape in breast milk

Embargoed for release until 5:00 p.m. ET on Monday 7 October 2024  

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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.       
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1. First report of its kind describes HIV reservoir landscape in breast milk

Abstract: https://www.acpjournals.org/doi/10.7326/ANNALS-24-00085

Editorial: https://www.acpjournals.org/doi/10.7326/ANNALS-24-02186

URL goes live when the embargo lifts   

In the first report of its kind, researcher from the University of Buenos Aires evaluated the HIV reservoir in the breast milk cells of two women living with HIV (WLWH) who had been on successful long-term treatment. While the researchers did not find any signs of intact or active HIV that could potentially cause infection in others, the risk for transmission in breast milk could not be entirely ruled out. According to the researchers, studies like this one are increasingly important as infant feeding guidelines for people LWH continue to change. The brief research report is published in Annals of Internal Medicine.

The idea that "Undetectable = Untransmittable" (U=U) means people with HIV who have an undetectable viral load can’t pass on the virus. However, this principle hasn't yet been proven for breastfeeding, as there's still a very small risk of transmission. For many years, guidelines in wealthy countries focused on avoiding any risk, even tiny ones, by discouraging breastfeeding for people with HIV. Recently, guidelines like the Swiss guidelines and those in the U.S. have started to consider the importance of making informed, shared decisions between patients and doctors.

The researchers evaluated free virus and cell-associated HIV DNA in breast milk over the first 7 weeks of lactation from an exceptional elite controller (the “Esperanza” patient) with 9 years of spontaneous viral control, from a WLWH receiving ART (abacavir– lamivudine–dolutegravir) with undetectable viral loads for more than 5 years, and a control patient. Very low levels of cellular HIV DNA (0.08 to 0.74 HIV DNA copies per million cells) were detected in the women with HIV; after analyzing 14 million cells from the elite controller, the researchers detected no HIV provirus by full-length individual proviral sequencing, and in 11 million cells from the woman receiving long-term dolutegravir, they detected only 4 defective HIV copies with large internal deletions. According to the authors, these data are reassuring and support the revised recommendations on infant feeding by PLWH in high resource settings.

Media contacts: For an embargoed PDF, please contact Angela Collom at acollom@acponline.org.  To speak with corresponding author Natalia Laufer, MD, PhD, please e-mail nlaufer@fmed.uba.ar.

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2. School mask mandate study highlights challenges of using observational data to study effects of public health interventions

Abstract: https://www.acpjournals.org/doi/10.7326/M23-2907     

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A re-examination of an influential and widely cited study which claimed that school mask mandates led to significantly reduced COVID-19 cases among students and staff in Massachusetts suggests that the conclusion may be flawed due to challenges inherent in the study methodology. This analysis is important because it shows that results of observational studies can be misleading and may lead to inappropriate health policy recommendations. The paper is published in Annals of Internal Medicine. 

A study of Boston-area school districts by Cowger and colleagues found that lifting mask mandates led to an additional 44.9 COVID-19 cases per 1000 students and staff over a 15-week period. However, sampling bias and confounding may have muddied the findings. Researchers from the Massachusetts Institute of Technology, the University of Toronto, Stanford, University of California-San Francisco and the United Kingdom’s Health Security Agency studied publicly available data of district case rates among students and staff in 72 Boston-area school districts originally studied by Cowger and colleagues. They then added 3 alternative control groups in Massachusetts to assess changes in COVID-19 case rates in greater Boston area school districts that did and did not lift mask mandates during the 2021-to-2022 academic year. The goal was to identify shortcomings of the difference-in-difference (DiD) methodology the original study used to estimate the effects of the mask mandate. Using both alternative statistical methods and comparison groups, the authors failed to find consistent evidence in support of the Cowger and colleagues paper conclusions. The researchers found that the data showed an inconclusive association of school mask mandates with case rates.  These findings demonstrate how the reported effectiveness of an intervention based on ecological data can be highly dependent on choice of comparison group, time period, or statistical method.

Media contacts: For an embargoed PDF, please contact Angela Collom at acollom@acponline.org. To speak with corresponding author Tracy Beth Høeg, MD, PhD, please e-mail Casey Bayer at bayerc@mit.edu. To speak with Ambarish Chandra, PhD, please email media.relations@utoronto.ca. 

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3. Metabolic risk factors among people with HIV contributed to new-onset diabetes seen in the REPRIEVE cardiovascular disease prevention trial

Data highlight need for comprehensive risk reduction strategies for people with HIV and diabetes risk factors, including diet and exercise interventions

Abstract: https://www.acpjournals.org/doi/10.7326/ANNALS-24-00944  

URL goes live when the embargo lifts        

An analysis of data from the REPRIEVE statin trial found that metabolic risk factors strongly contributed to the increased cases of new-onset diabetes among people with HIV (PWH). Metabolic factors contributed to increased diabetes risk in both those treated with pitavastatin and those treated with placebo. According to the study authors, these data highlight the need for comprehensive risk reduction strategies for PWH who have significant diabetes risk factors, including diet and exercise interventions. The findings are published in Annals of Internal Medicine. 

The global trial, REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV) showed that the statin, pitavastatin calcium, prevented major adverse cardiovascular events (MACE) among PWH but was associated with a modest increase in new-onset diabetes. Diabetes is an important consideration for PWH, who may have unique risk mechanisms related to antiretroviral therapy and other factors.

Researchers from Massachusetts General Hospital studied REPRIEVE data to determine the contribution of known diabetes risk factors to excess risk for diabetes with pitavastatin. New-onset diabetes was defined as a clinical diagnosis requiring initiation of medication for diabetes and was assessed in relation to predefined demographic and metabolic risk factors, stratified by treatment group. The researchers found that metabolic risk factors, including prediabetes and obesity, contributed to new-onset diabetes in statin- and placebo-treated participants. While key risk factors for developing diabetes were seen in both groups, the effects of pitavastatin on diabetes varied by race and global region, but an increased risk was only found in people who already had multiple risk factors for diabetes at the start of the study. Data from REPRIEVE demonstrate statins can be given safely to PWH and lead to an overall reduction in MACE, including among those with metabolic risk of developing diabetes.  These findings highlight the need for comprehensive strategies to reduce diabetes risk in PWH, especially for those in regions and racial groups at higher risk. Interventions like healthy eating and regular exercise are particularly important. For PWH who are at a healthy weight and don't have prediabetes, the overall risk of developing diabetes—whether in general or from statin use—is very low and unlikely to be a major clinical concern. According to the authors, these findings can guide the use of statins for preventing heart disease in PWH, while also addressing diabetes risk in those who are more vulnerable.

Media contacts: For an embargoed PDF, please contact Angela Collom at acollom@acponline.org. To speak with corresponding author Steven K. Grinspoon, MD, please e-mail Noah Brown at nbrown9@mgb.org.

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4. Experts debate pharmacologic management of a patient with obesity

This ‘Beyond the Guidelines’ feature is based on a discussion held at Internal Medicine 2024, the annual meeting of the American College of Physicians

Abstract: https://www.acpjournals.org/doi/10.7326/ANNALS-24-01740   

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In a new Annals “Beyond the Guidelines” feature, two internal medicine physicians discuss treatment for a patient with obesity and prediabetes in the context of American Gastroenterological Association (AGA) evidence-based recommendations for the pharmacologic management of obesity in adults. Currently, 1 in 8 adults worldwide has obesity and minority populations are disproportionately affected. New pharmacologic options have shown effectiveness for weight loss in clinical trials, but adverse effects, adherence, and cost are strong considerations. As such, asking “How would you treat this patient with obesity?” is an important clinical question. 

They reviewed the case of an adult female patient with obesity. At her most recent doctor's visit, the patient's blood pressure was 115/82 mm Hg, weight was 171 pounds, BMI was 31.2 kg/m2, and her blood work showed prediabetes. The patient reported struggling with her weight since having children and sought advice for losing about 25 lbs.

The first discussant, Anne N. Thorndike, MD, MPH, is a member of the Division of General Internal Medicine at Massachusetts General Hospital and an Associate Professor of Medicine at Harvard Medical School, Boston, Massachusetts. She noted that lifestyle modification is the foundation for obesity management, that moderate- to high-intensity multicomponent behavioral interventions can produce 5% to 10% body weight loss, and that weight loss from lifestyle interventions improves numerous health outcomes. While the patient had expressed an interest in losing about 25% of her body weight, Dr. Thorndike pointed out that even 5% weight loss can result in positive health changes. Given the potential benefit and limited harms, she would advocate intensive lifestyle modification before moving on to pharmacologic therapy. 

The second discussant, Melanie R. Jay, MD, MS. is a member of the Division of General Internal Medicine and the Department of Population Health and an Associate Professor at the NYU Grossman School of Medicine. She is also a staff physician at the New York Harbor Veterans Affairs. Dr. Jay agrees that lifestyle modification is paramount in obesity management, but if the patient has coverage and access, Dr. Jay believes that the patient’s weight and metabolic risk factors warrant treatment with a GLP-1RA. If not, she would recommend phentermine-topiramate (barring contraindications) or metformin as the patient has prediabetes and it can decrease the risk for progression to type 2 diabetes. Both discussants noted that obesity is a chronic disease requiring a lifelong commitment to follow-up and treatment.

All “Beyond the Guidelines” features are based on selected clinical conferences at Beth Israel Deaconess Medical Center (BIDMC) and include multimedia components published in the Annals of Internal Medicine.

Media contacts: For an embargoed PDF, please contact Angela Collom at acollom@acponline.org. To speak with one of the discussants, please contact Kendra McKinnon at Kmckinn1@bidmc.harvard.edu.  

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Also new in this issue:

Abortion

Cynthia H. Chuang, MD, MSc; Sarah Horvath, MD, MSHP

Annals In the Clinic

Abstract: https://www.acpjournals.org/doi/10.7326/ANNALS-24-01868   

Modernizing Medical Device Regulation: Challenges and Opportunities for the 510(k) Clearance Process

Kushal T. Kadakia, MSc; Vinay K. Rathi, MD, MBA; Sanket S. Dhruva, MD, MHS; Joseph S. Ross, MD, MHS; and Harlan M. Krumholz, MD, SM

Medicine and Public Issues

Abstract: https://www.acpjournals.org/doi/10.7326/ANNALS-24-00728

Target Trial Emulation for Evaluating Health Policy

Nicholas J. Seewald, PhD; Emma E. McGinty, PhD; and Elizabeth A. Stuart, PhD

Research and Reporting Methods

Abstract: https://www.acpjournals.org/doi/10.7326/M23-2440