By Annette M. Boyle
NEW HAVEN, CT — With human immunodeficiency virus (HIV) now being treated more like diabetes, hypertension and other chronic diseases, HIV patients face some of the same issues as other veterans dealing with ongoing conditions — managing pill schedules, maintaining adherence and coping with comorbidities.
“Adherence is an issue in any chronic disease, which is what HIV is today,” said Amy Justice, MD, PhD, section chief, general internal medicine, of the VA Connecticut Healthcare System and professor of medicine at Yale University. “As we get better at treating it, I suspect adherence may be more and more problematic.”
In the past, HIV patients struggled with adherence because of the number of pills and the toxicities. “People would taper off their medications and then have viral breakthroughs,” Justice told U.S. Medicine. “Now that’s not so much of a problem, because they just take their pills once or twice a day. But the disease has become largely asymptomatic for many patients, so taking their medications seems less important.”
With better treatments also come new problems, according to David Ross, MD, PhD, director of the HIV, HCV and public pathogens programs at the VA.
“We’ve had a major paradigm shift with HIV from struggling to keep patients alive to facing geriatric issues as new drugs were developed and death rates dropped precipitously. In the VA today, more than 200,000 HIV patients are older than 80,” Ross noted. As patients live longer, however, they develop more comorbidities. “We’re talking to patients with HIV about quitting smoking and testing for prostate cancer,” he added.
The inflammation associated with HIV, even when treated appropriately, increases the risk of cardiovascular disease, liver disease and cancer. About half will have hypertension. At least 1 in 3 patients with HIV also needs to consider how to treat or manage a hepatitis C infection, Justice said.
While HCV treatment typically lasts 12-48 weeks, veterans with HIV may find themselves on longer-term medication for other conditions. “When patients start on antiretroviral therapy, they typically also start on two other medications. They go from being on a below average number of medications to above average because things will turn up in their family history, blood work or other parts of their evaluation,” Justice noted.
Single Combination Pill
Consequently, there’s a need to balance the number of pills, their interactions and the priorities for treatment. Proving once again that less is more, a recent VA study demonstrated that patients on a single combination antiretroviral pill had better adherence and fewer hospitalizations than those on a multipill regimen.
The retrospective study, presented at the Interscience Conference on Antimicrobial Agents and Chemotherapy, analyzed data on 15,602 veterans who received medications for HIV from July 1, 2006, to September 30, 2011. Patients were considered to be in the single tablet regimen (STR) arm if they were prescribed a single pill per day at any point during the study period. Patients who received a regimen of two or more tablets per day and were never given a single-pill therapy were assigned to the multiple tablet regimen (MTR).1
During the follow-up period, 75% of patients in the STR group met adherence levels of 95% (based on prescription refills) compared with 55% of those in the MTR group. On an adjusted basis, STR patients had 31% lower risk of hospitalization.
“The single-tablet therapy had better outcomes. It could be because of adherence, but we did not evaluate the effect of adherence specifically,” said presenter Scott Sutton, PharmD, of the Dorn VAMC in Columbia, SC. “We evaluated the effects of STR vs. MTR on three variables (viral load, hospitalization and mortality).”
Some of the difference in outcomes might be due to factors other than adherence, according to Justice. “The people who got STR aren’t the same patients as those on MTR. Many more of them were treatment naïve, and they always have a better response to treatment. On the other hand, does a single pill work better than multiple pills? Yes. We’ve known that for years from hypertension research.”
While more convenient for patients, combination pills have downsides, too, Justice added. “The clinical reality is that these patients are on five or six other medications. With a polypill, it’s harder to know how they’ll interact in the soup of the body.”
A number of good single pill a day regimens are now available, Ross said. “As in many chronic diseases, trials show that all the drugs are pretty much the same, but in clinical work, you still have to find the drugs that work best for each patient. Patients have variances in resistance with HIV, and some have side effects from one or more component of combination tablets.”
Meanwhile, two studies presented at the recent American Association for the Study of Liver Diseases (AASLD) Liver Meeting provide good news for HCV/HIV co-infected veterans, who tend to experience much more rapid progression of liver disease. One study showed that a regimen that combined the protease inhibitor telaprevir with rivavirin and pegylated interferon achieved sustained virologic response at 48 weeks in 83% of patients. At the same time, co-infected patients maintained suppression of HIV to less than 50 copies/mL.2
Even more encouraging are the results of a second study that showed an interferon-free regimen that combined ribavirin and sofosbuvir, a nucleotide HCV NS5B polymerase inhibitor, resulted in sustained virologic response 12 weeks after the end of treatment (SVR12) in 76% of treatment-naïve patients with genotype 1, 88% of those with genotype 2 and 67% of those with genotype 3.3
“Up to now, labels on protease inhibitors used in HCV treatment have had an explicit statement that efficacy has not been shown with HIV-infected patients, and people have been extremely reluctant to use these agents with patients on HIV treatments because of potential interactions,” Ross told U.S. Medicine.
Telaprevir is one of two options for the current triple therapy standard for treatment of HCV. Sofosbuvir is the first in a new class of direct acting agents to near approval by the Food and Drug Administration for the treatment of HCV.
1Rao GA, Sutton SS, Hardin J, Bennett CL. Impact of highly active antiretroviral therapy regimen on adherence and risk of hospitalization in veterans with HIV/AIDS. ICAAC 2013. Presentation H-1464.
2Cotte L, et al. High end-of-treatment (EOT) response rate with telaprevir-pegIFN-RBV in treatment-experienced HIV co-infected patients with HCV genotype 1: ANRS HC26 telapreVIH study. AASLD 2013. Washington, DC, November 1-5, 2013. Abstract 1108.
3MS Sulkowski, M Rodriguez-Torres, JP Lalezari, et al. All-Oral Therapy With Sofosbuvir Plus Ribavirin For the Treatment of HCV Genotype 1, 2, and 3 Infection in Patients Co-infected With HIV (PHOTON-1). AASLD 2013. Washington, DC, November 1-5, 2013. Abstract 212.