Discontinuation of antiretroviral therapy (ART) among patients with HIV has been found to lead to virologic failure, drug resistance, and onward HIV transmission. “It’s imperative that we understand how many patients in the United States discontinue treatment, why they stop, and which patients are more likely to do this,” says Alison J. Hughes, MPH. “This information can allow us to more effectively target interventions to increase treatment persistence and optimize outcomes of people living with HIV.”

New Data

For a study published in the Journal of Acquired Immune Deficiency Syndromes, Hughes and colleagues conducted interviews with, and reviewed medical records for, a nationally representative sample of HIV-infected adults receiving HIV care from 2009 to 2010. The research team examined patient characteristics of ART discontinuation—defined as not currently taking ART—based on whether discontinuation was provider- or non–provider-initiated.

“The good news was that 93% of patients in HIV care had initiated ART,” says Hughes. “However, of those who initiated ART, nearly 6% discontinued treatment, representing about 22,000 adults in the U.S.” Nearly half of patients reported that their healthcare provider had recommended treatment discontinuation. “We speculate that the high rate of provider-initiated discontinuation reflects treatment guidelines that were in place at the time, which recommended ART only for patients with a CD4 count less than 350 cells/mm3,” adds Hughes.

HIV-Discontinue-ART-Callout

The researchers also found that certain patients were more likely to stop treatment than others (Table). “Younger age, female gender, not having continuous health insurance, incarceration, injection drug use, and a high CD4 cell count were all associated with treatment discontinuation,” explains Hughes. “Unmet need for supportive services, no care in the past 3 months, and having an HIV diagnosis of 5 or more years were also linked to higher odds of discontinuing treatment.”

The strongest predictors of provider-initiated ART discontinuation were younger age and a nadir CD4 count of 200 cells/mm3 or higher. Patients who discontinued ART on their own or because of structural barriers were more likely to have unmet needs for supportive services and less likely to have had HIV care in the prior 3 months. The study also noted the following observations:

20% of patients discontinued ART because of therapy-related reasons, such as side effects or pill burden.

16% of patients cited personal reasons for discontinuing ART, such as depression or feeling healthy and not seeing the need for treatment.

12% of patients stopped taking ART because of structural barriers, such as difficulty in getting transportation to their clinic, incarceration, or health insurance issues.

Important Implications

Studies indicate that providing ART improves individual health outcomes and substantially reduces risk of HIV transmission. To that end, Hughes says physicians should be aware that the U.S. Department of Health and Human Services recommends all patients with HIV be treated with ART—regardless of their immune status. “We hope that providers will no longer recommend discontinuation of therapy for any reason,” she says. The only exceptions are clinically indicated disruptions or discontinuation, such as when patients have severe drug toxicity, intervening illness, or surgery that precludes the use of oral therapy.

With regard to non–provider-initiated discontinuation, Hughes points to prior research showing that supportive services can help increase ART adherence. For example, mental health services can benefit people with psychiatric issues by helping them increase treatment persistence. Other research has shown that food insecurity may decrease ART adherence. “When a patient who is thinking about stopping ART is encountered, providers should assess why this is being considered and then make a referral to supportive services, if necessary,” Hughes says.

Looking Ahead

According to Hughes, it will be important to understand trends in treatment discontinuation over time in the U.S., especially as new treatment guidelines are implemented nationally. “It will also be interesting to see if expanded access to care through the Affordable Care Act helps address barriers to ART persistence, like a lack of health insurance for HIV care,” she says. “Furthermore, we need new methodologies to capture HIV-infected patients who are not receiving HIV care, a population that was excluded from our study. Research that focuses on ART persistence is crucial, especially among patients who initiate therapy at a high CD4 cell count, because they might feel healthier and be more likely to stop treatment.”

Until new research emerges, providers can refer to Hughes and colleagues’ research to better understand why patients with HIV discontinue treatment and who is at higher risk. “It helps to be mindful of the predictors of discontinuation that we observed,” she says. “At the same time, it’s important to follow guidelines and obtain self-reported adherence and persistence from all patients on antiretroviral treatment.”

 

References

Hughes AJ, Mattson CL, Scheer S, Beer L, Skarbinski J. Discontinuation of antiretroviral therapy among adults receiving HIV care in the United States. J Acquir Immune Defic Syndr. 2014;66:80-89. Available at: http://journals.lww.com/jaids/pages/articleviewer.aspx?year=2014&issue=05010&article=00011&type=abstract or at: www.medscape.com/viewarticle/824391.

Beer L, Heffelfinger J, Frazier E, et al. Use of and adherence to antiretroviral therapy in a large U.S. sample of HIV-infected adults in care, 2007–2008. Open AIDS J. 2012;6:213-223.

Conway B. The role of adherence to antiretroviral therapy in the management of HIV infection. J Acquir Immune Defic Syndr. 2007;45:S14-S18.

Ray M, Logan R, Sterne JA, et al. The effect of combined antiretroviral therapy on the overall mortality of HIV-infected individuals. AIDS. 2010;24:123-137.

Barrón Y, Cole SR, Greenblatt RM, et al. Effect of discontinuing antiretroviral therapy on survival of women initiated on highly active antiretroviral therapy. AIDS. 2004;18:1579-1584.