Free Online Clinical Support Tool Helps Clinicians Prescribe
More than 30 therapeutic agents in more than 2,000 possible combinations are used to treat HIV today. To help providers sort through the overwhelming number of options and select the best combination of therapies for each patient, an international team of researchers and clinicians collaborated on developing a free online clinical support tool. It is especially useful with patients who have not had adequate response to previous treatment, which is a growing issue in HIV treatment.
SAN FRANCISCO — As COVID-19 clocks through its second year, more than 300 vaccines are in development and 11 are being used around the world. Three have emergency authorization from the U.S. Food and Drug Administration, and one or two others seem likely to follow suit in the coming months. At the same time, the therapeutic front looks surprisingly barren. Clinical trials have knocked back early hope for repurposing of dozens of existing molecules, leaving only a handful of treatment options for individuals infected with SARS-CoV-2.
Another ongoing pandemic faces the reverse situation. Vaccines have proved frustratingly elusive, but effective treatment options abound for individuals infected with the human immunodeficiency virus (HIV). . For many healthcare providers, the biggest challenge is choosing the best therapeutic combination for each patient over the decades most will need to manage their disease.
In 1987, the first treatment to combat HIV, azidothymidine, hit the market. Mortality from acquired immunodeficiency syndrome (AIDS) continued to climb until 1995, when more than 50,000 people in the U.S. died of the disease. The adoption of a remarkably effective combination of drugs in 1997 cut the death rate in half.
Today, more than 30 therapeutic agents in more than 2,000 possible combinations are used to treat HIV. The plethora of powerful drugs has transformed the HIV infection from a death sentence to a chronic condition and cut HIV-related deaths to about 5,000 annually, according to the U.S. Centers for Disease Control and Prevention.
As concerns such as managing diabetes, quitting smoking and aging rise in importance, primary care providers have emerged as the physicians responsible for managing the health of individuals with HIV. At the same time, many clinicians with expertise in the field have retired, and fewer new providers are choosing to specialize in HIV care.
Still, each year nearly 40,000 Americans are newly diagnosed with HIV, creating ongoing demand for customized therapies. In the VA alone, more than 30,000 veterans receive care for it.
To help providers sort through the overwhelming number of options and select the best combination of therapies for each patient, an international team of researchers and clinicians collaborated on developing HIV-ASSIST, a free online clinical support tool. Especially useful with patients who have not had adequate response to previous treatment, HIV-ASSIST was initially validated at four large academic centers with a total of 17 experienced HIV providers using 10 scenarios.1
According to the team, “HIV-ASSIST synthesizes patient and virus-specific attributes to rank ARV combinations based upon a composite objective of achieving viral suppression and maximizing tolerability.” The tool’s algorithm factors in a patient’s comorbidities, other medications, genetic information, disease burden, previous therapies and viral resistance. It also weighs characteristics of a therapeutic combination such as number of pills and interactions to come up with a ranked list of options along with the rationale for each option and educational material its advantages and disadvantages.
From Theory to Practice
Harry Lampiris, MD, an infectious disease specialist at the San Francisco VAMC, and several of the developers of HIV-ASSIST, tested the clinical decision support tool in two real-world settings, the San Francisco VA HIV Clinic and the Johns Hopkins Bartlett HIV Clinic. 2
“There is a pressing need to address the changing landscape of HIV medicine, particularly with consideration of the projected decline in trained HIV clinical experts,” the investigators said. If the tool aligned well with the recommendations of experienced HIV clinicians, it could help primary care providers identify or validate their clinical decisions.
The researchers compared provider prescribed regimens for 106 patients to the HIV-ASSIST weighted score for that regimen, its ranking within the algorithm’s recommendations and concordance with the top five recommendations. The weighted scoring uses a scale of 0 to 10, with scores less than 2.0 preferred.
The prescriber prescriptions and HIV-ASSIST recommendations perfectly matched for the 23 antiretroviral (ARV)-naive patients, with a median rank of 1.0 and a median weighted score of 1.1. For the 18 ARV-experienced patients with viremia, the prescribed regimen and the HIV-ASSIST recommended regimen had a concordance of 89%, with a median rank of 2 and median weighted score of 1. The concordance was 88% for the 65 patients for whom their current ARV regimen suppressed the virus. The median rank was 1.0, and the median weighted score for these patients was 1.1. The prescribed regimen was considered “less preferred” by HIV-ASSIST in 18% of cases compared to other options.
“Our study provides additional evidence that HIV-ASSIST provides expert guidance consistent with HIV clinicians at two major academic medical centers across a wide range of patient situations,” the authors concluded. “Our descriptive analyses also suggest that there may be applications for usage of such a tool not only for decision support, but also for quality assurance to identify situations in which provider ARV selection could benefit from additional review.”
Drug Resistance
One of the reasons prescribing is so complicated is the growing problem of HIV drug resistance, according to the World Health Organization, which points out that, in 2019, of an estimated 67% of people living with HIV globally who received antiretroviral (ART) treatment, 26% of patients initiating treatment are infected with a virus carrying resistance to first-line drugs (such as efavirenz).
Especially prone to drug resistance are HIV medications belonging to the NNRTI class or first-generation integrase inhibitors class, WHO noted.
One result can be virologic failure and the need to alter drug regimens. Virologic failure occurs when ART doesn’t suppress and sustain a patient’s viral load to less than 200 copies/mL. A variety of factors can contribute to the situation including drug resistance, drug toxicity and poor adherence to ART.
- Maddali MV, Mehtani NJ, Converse C, Kapoor S, Pham P, Li JZ, Shah M. Development and Validation of HIV-ASSIST, an Online, Educational, Clinical Decision Support Tool to Guide Patient-Centered ARV Regimen Selection. J Acquir Immune Defic Syndr. 2019 Oct 1;82(2):188-194. doi: 10.1097/QAI.0000000000002118. PMID: 31513553.
- Ramirez JA, Maddali MV, Budak JZ, Li JZ, Lampiris H, Shah M. Evaluating the Concordance of Clinician Antiretroviral Prescribing Practices and HIV-ASSIST, an Online Clinical Decision Support Tool. J Gen Intern Med. 2020 May;35(5):1498-1503. doi: 10.1007/s11606-019-05531-4. Epub 2019 Dec 2. PMID: 31792870; PMCID: PMC7210320.