A session in the Genomics Biotech and Emerging Medical Technologies Institute track focused on HIV treatment. Steven Deeks, MD, professor of medicine at the University of California, San Francisco, provided attendees with an overview of the epidemiology of HIV, as wells as concerns and future directions for managed care in the treatment of patients with HIV.
At present in the United States there are approximately 1,200,000 people living with HIV. In 2015, approximately 39,500 individuals received a new diagnosis; new diagnoses of HIV declined by 19% from 2005 to 2014. The US subpopulations most affected by HIV in 2015 were black men who have sex with men (MSM), white MSM, Hispanic/Latino MSM, and black heterosexual women.
Dr. Deeks said that the history of the HIV epidemic in the United States is reflected in the ways affected communities view treatment and healthcare for this patient population. From the early days in the early 1980s to the early 2000s, changes led to steady progress that culminated in advances in 2007. Currently, there are simpler regimens available, many involving a single tablet, as well as effective salvage regimens, making multi-drug resistant HIV rare. Studies have demonstrated that medication adherence is improved with the use of single-tablet regimens compared with multiple-tablet regimens.
In the contemporary era of antiretroviral therapy (ART), immediate treatment is available for all newly diagnosed patients, and initiatives toward a cure are evolving. The US FDA has approved more than 25 antiretroviral drugs to date.
The US Department of Health and Human Services guidelines recommended regimens include integrase strand transfer inhibitor (INSTI)-based therapies and protease inhibitor (PI)-based therapies. Therapies based on non-nucleoside reverse transcriptase inhibitors or on atazanavir/ritonavir, once classified as recommended, are now considered alternative regimens.
Dr. Deeks reported results studies of dolutegravir, beginning with the SINGLE Study that compared dolutegravir to efavirenz in 833 treatment-naïve adults. At week 144, dolutegravir was superior to efavirenz. In the SPRING-2 trial that compared dolutegravir with raltegravir in 822 treatment-naïve adults, dolutegravir was comparable to raltegravir. The FLAMINGO study compared dolutegravir to darunavir/r in 488 treatment-naïve adults; dolutegravir was comparable to darunavir/r, but likely superior in patients with a higher viral load.
In dual therapy trials, dolutegravir and 3TC for initial therapy are being studied in ongoing phase 3 trials. The SWORD 1 & 2 trials tested simplification of treatment with a nucleoside reverse transcriptase inhibitor (NRTI)-sparing regimen; significant improvement in bone turnover markers was seen in participants who switched to dolutegravir plus rilpivirine, a non-NRTI.
The session continued with a discussion on when to initiate ART in patients with early asymptomatic HIV infection. In the START trial, 4685 HIV-positive adults were immediately started on ART (n=2326) or had ART deferred until the CD4+ count dropped to <350 cells/mm3 (n=2359). The primary endpoint was the composite outcome of any serious AIDS-related event and any serious non-AIDS-related event. At month 60, fewer patients in the immediate start arm had reached the composite endpoint.
On September 30, 2015, the World Health Organization joined the US Department of Health and Human Services and the International Viral Society-USA in recommending ART for all individuals who are HIV positive regardless of CD4 cell count. Many academic centers recommend therapy on a patient’s initial visit, or on the day HIV is diagnosed or suspected.
In summarizing the presentation, Dr. Deeks said that integrase inhibitors plus two NRTIs are standard-of-care as first-line therapy, though emerging dual therapies and long-acting injectables could change this paradigm. Treatment failure is nearly always attributed to non-adherence; incidences of drug resistance are less common.
Dr. Deeks also noted multiple limitations associated with HIV treatment, including retention in care, interruptions in therapy related to either individual circumstances or disruption in health care coverage. He also said that comorbidities are common in the HIV patient population. “HIV expertise is needed to manage both ART and comorbidities” he said.
Steven Deeks, MD. HIV Treatment: An Overview. 2017 Fall Managed Care Forum. October 27, 2017.