The HIV Research Takeaway: Is Perfect Med Adherence Necessary for HIV Treatment Success?

In The HIV Research Takeaway, we provide plain talk about new data in the world of HIV-related research, and explain in straightforward terms what the results mean for people living with or affected by HIV.

David Alain Wohl, M.D.
David Alain Wohl, M.D.

The Issue

How much adherence to HIV medication is enough? If you miss a dose here and there, what are the consequences? These are questions asked by many people living with HIV who are trying their best to keep their viral loads suppressed and CD4 cell counts high. The Internet, a false oracle, may advise that something along the lines of at least 95% adherence to HIV meds is needed to keep the HIV genie in the bottle. But this is rooted in old studies that looked at people taking old medicines. Today, we have much more forgiving and easier-to-take HIV drugs. This does not mean that high levels of adherence are not needed; they are -- just not as high as near perfect.

To get a better sense of how much is enough when it comes to HIV med adherence, investigators involved in the SMART Trial looked at self-reports of adherence among people on HIV therapy with a viral load below 50 copies/mL (i.e., undetectable) and the risk of a subsequent viral load that was over 200 copies/mL. This trial was conducted over 10 years ago and tested a strategy of stopping HIV therapy in those with higher CD4 cell counts and restarting it when counts fell to around 250 to prevent bad things from happening to people. (It did not work.) The comparison group was people randomized to stay on their HIV therapies.

The study was published in the February 2016 issue of the journal HIV Medicine. The lead author is Jemma O'Connor. The study title is, "A simple self-reported adherence tool as a predictor of viral rebound in people with viral suppression on antiretroviral therapy."

The Data

During the trial, 1,986 participants were enrolled and randomized to stay on HIV medications without a break. The investigators looked at each instance where there was a viral load that was less than 50 copies/mL to see what the next viral load was and whether the adherence level the participant reported predicted whether or not the next viral load would be high (above 200 copies/mL). Altogether, there were almost 11,000 pairs of viral load pairs looked at from this group of patients. Adherence was assessed by a question that asked whether during the previous seven days the participants took "all" (level 1), "most" (level 2), "about one-half" (level 3), "very few" (level 4) or "none" (level 5) of each of their HIV meds.

Any response that was not "all" was considered "suboptimal" adherence. The good news is that almost 89% of people reported taking all their HIV meds during the prior seven days, when asked. That is a pretty high number, but it makes sense as most people entering this study were on HIV therapy and had an undetectable viral load. More good news: Of those 11,000 or so pairs of viral loads in which the first was undetectable, only in 5% was the subsequent pair above 200 copies/mL.

The meat of the analysis looked at whether suboptimal adherence was associated with this low risk for viral rebound. Guess what, it was. For those with so-called suboptimal adherence according to the seven-day recall question, the risk of their viral load jumping to above 200 copies/mL was about 9%, while for those claiming perfect adherence it was 4.2%. Not too unexpectedly, the worse adherence a person reported, the greater the risk of viral rebound -- ranging from 8% for those who said they took "most" their HIV med doses to 13% to 16% for those who reported taking "half" to "none."

The Takeaway

This analysis does not exactly get at the complicated question of how many missed doses of HIV meds are OK, but it does provide a sense of the magnitude of the risk. Here, we saw that viral rebound was pretty rare, and that even those who reported lousy adherence were hardly guaranteed to have a high viral load at their next visit. This speaks to the forgive-ability of modern day HIV therapy. True, this study is a decade old, but participants were mostly on a combination of two nucleosides and a non-nucleoside or a boosted protease inhibitor -- treatment strategies that are still in use today.

The study also shows that when people say they take all their meds, maybe they do and maybe they don't. But, if they report missing doses, they are probably not making that up. It should be appreciated that people were only asked about adherence during the prior seven days.

Overall, people living with HIV should understand that 100% adherence, while a goal, is not necessary, nor should it be expected. Most HIV clinics in the U.S. report that somewhere in the neighborhood of 80% to 90% of their patients have low viral loads, and we know that 80% to 90% of our patients take their meds without fail each day, day after day. This high rate of treatment success has a lot to do with easier-to-take HIV regimens including combination pills and once-daily dosing. Our current crop of HIV drugs also contains medications that are very potent; plus, many people have high barriers to resistance -- meaning that even if their viral load pops up it is very hard for the virus to make mutations that will impair the ability of these drugs to work when restarted.

Now, clearly, all this is not a license to play footloose with medications being used to treat a still incurable and serious viral infection. But, we need not freak out about missed doses here and missed doses there.

David Alain Wohl, M.D., is an associate professor of medicine in the Division of Infectious Diseases at the University of North Carolina (UNC).