Addition of genotypic resistance testing did not improve virologic response in patients with HIV virologic failure sub-Saharan Africa

1. Addition of genotypic resistance testing did not improve virologic response in patients with HIV virologic failure sub-Saharan Africa

Abstract: https://www.acpjournals.org/doi/10.7326/M21-2229  

Editorial: https://www.acpjournals.org/doi/10.7326/M21-3903

URL goes live when the embargo lifts

A randomized controlled trial found that the addition of genotypic resistance testing to routine care did not improve virologic suppression among persons whose first-line antiretroviral therapy (ART) failed in public-sector HIV clinics in Uganda and South Africa. These results reinforce the critical need for and persistent challenge of finding effective interventions for persons who have virologic failure after ART initiation in the public sector in sub-Saharan Africa. The findings are published in Annals of Internal Medicine.

Virologic failure in HIV predicts the development of drug resistance and mortality. Genotypic resistance testing where a patient's blood is analyzed for the presence of specific genetic mutations that are known to cause resistance to specific drugs, is the standard of care after virologic failure in high-income settings but is rarely implemented in sub-Saharan Africa where virologic failure in HIV is a major public health threat.

In the REVAMP (Resistance Testing Versus Adherence Support for Management of Patients with Virologic Failure of First-Line Antiretroviral Therapy in sub-Saharan Africa), researchers from Massachusetts General Hospital enrolled 840 adults in South Africa and Uganda with HIV and viral load levels of 1,000 copies/mL or higher and randomly assigned them to immediate genotypic resistance testing or standard of care, including adherence counseling sessions and repeated viral load testing. Most of the patients were receiving a regimen of tenofovir, emtricitabine, and efavirenz at enrolment. Virologic suppression was tested at 9 months. The proportion of patients with viral load levels below 200 copies/mL did not differ between the two groups.

The authors of an accompanying editorial from Weill Cornell Medicine noted that the study has significant strengths, including its real-world setting in public health ambulatory clinics. However, participants were receiving nonnucleoside reverse transcriptase inhibitor (NNRTI)–based regimens at study entry, which is no longer the standard of care. The authors suggest that future research explore the use of drug resistance testing in managing virologic failure with more contemporary antiretroviral therapy, such as integrase inhibitor–based regimens, as optimal antiretroviral management is the key to further reductions in HIV morbidity, mortality, and transmission worldwide.

Media contacts For an embargoed PDF, please contact Angela Collom at acollom@acponline.org. To speak with the lead author, Mark J. Siedner MD MPH, please contact, Michael Morrison at mdmorrison@partners.org

-------------------------------------------------

2. Treatment with belimumab after rituximab reduced disease activity and symptoms for patients with lupus

Abstract: https://www.acpjournals.org/doi/10.7326/M21-2078              

URL goes live when the embargo lifts

A randomized controlled trial found that treatment with the biologic drug belimumab after rituximab significantly reduced disease activity and symptoms for patients with lupus without increased risk for infections or other adverse effects. These results suggest that this combination could be developed as a viable treatment strategy for patients with lupus. The findings are published in Annals of Internal Medicine.

For some patients with lupus, repeated cycles of rituximab resulted in ever higher serum anti–double-stranded DNA antibody levels, which were associated with disease flares and elevated serum B-cell activating factor (BAFF) levels. Researchers from University College London Hospitals hypothesized that targeting BAFF levels would reduce the frequency of flares after rituximab. Inhibition of BAFF may also delay B-cell repopulation, which has been associated with improved clinical outcomes after rituximab.

The researchers recruited 52 participants prescribed rituximab for refractory lupus at 16 centers in England to participate in their study. After 4 to 8 weeks on the rituximab regimen, patients were randomly assigned to also receive intravenous belimumab or placebo for 52 weeks. The researchers found that compared to rituximab alone, belimumab suppressed the number of B-cells and significantly reduced disease activity and symptoms. Combination therapy also reduced severe lupus flares by 3-fold in the context of patients who had refractory active disease at the outset of the trial. According to the researchers, these findings support further exploration of belimumab after rituximab as the first combination biologic therapy for patients with lupus, at least in those whose disease is refractory to conventional therapy and/or requires high corticosteroid dosages.

Media contacts For an embargoed PDF, please contact Angela Collom at acollom@acponline.org. To speak with corresponding author, Michael R. Ehrenstein, MBBS, PhD, please contact Matt Chorley at m.chorley@ucl.ac.uk.

-------------------------------------------------

3. Large hospitals and major teaching hospitals quickly adopt hospital at home programs after CMS individual waiver

Abstract: https://www.acpjournals.org/doi/10.7326/M21-2516             

URL goes live when the embargo lifts

A brief research report found that large hospitals and major teaching hospitals were quick to adopt hospital at home programs after the Centers for Medicare and Medicare and Medicaid Services (CMS) announced its Acute Hospital Care at Home (AHCaH) individual waiver in response to COVID-19 pandemic. Few rural hospitals took advantage of the waivers and more work is needed to overcome obstacles to adoption. The findings are published in Annals of Internal Medicine.  

Hospital at home (HaH) provides acute hospital-level care in a patient's home as a substitute for traditional inpatient hospital care. CMS announced a comprehensive strategy to enhance hospital capacity, including AHCaH individual waiver. Hospitals qualifying for the individual waiver receive the full hospital-level diagnosis-related group payment for services provided at home.

Researchers from Harvard Medical School, Brigham and Women's Hospital analyzed data from the AHCaH CMS dashboard and linked hospitals holding a waiver to the American Hospital Association's 2019 Annual Survey to determine characteristics of hospitals that participated in the program. The analysis showed rapid uptake among large hospitals (8.9%) and major teaching hospitals (13.2%), but few rural hospitals (0.1%) have thus far received a waiver. The authors note that despite apparent optimism about the potential of HaH to improve disparities among rural and urban areas of the United States, limited resources to launch new care models at rural hospitals or requirements for patients to be within a certain distance of the hospital may limit effectiveness in these populations. They suggest additional research and technical assistance tailored to rural areas to improve uptake.

Media contacts For an embargoed PDF, please contact Angela Collom at acollom@acponline.org. To speak with corresponding author, David M. Levine, MD, MPH, MA, please email dmlevine@bwh.harvard.edu.

-------------------------------------------------

New COVID-19-related content this week:

COVID-19–Related Care for Hispanic Elderly Adults With Limited English Proficiency         

Steffie Woolhandler, MD, MPH; Samuel Dickman, MD; Chris Cai, MD; Danny McCormick, MD, MPH; Jessica Himmelstein, MD, MPH; David U. Himmelstein, MD

Brief Research Report

Free full text: https://www.acpjournals.org/doi/10.7326/M21-2900

Also new in this issue:

QUADAS-C: A Tool for Assessing Risk of Bias in Comparative Diagnostic Accuracy Studies

Bada Yang, MD; Sue Mallett, DPhil; Yemisi Takwoingi, DVM, PhD; Clare F. Davenport, PhD; Christopher J. Hyde, MD; Penny F. Whiting, PhD*; Jonathan J. Deeks, PhD; Mariska M.G. Leeflang, DVM, PhD; and the QUADAS-C Group

Research and Reporting Methods

Abstract: https://www.acpjournals.org/doi/10.7326/M21-2234   

Editorial: https://www.acpjournals.org/doi/10.7326/M21-3873