Treatment guidelines can vary depending on what part of the world you live in. But why do they differ and whose guidelines should you follow? To help clarify, here's a walk-through of some questions surrounding treatment guidelines, based on a presentation given at IDWeek 2014 by Roy Gulick, M.D., professor of medicine and chief of the division of infectious diseases at Weill Cornell Medical College. In his talk, Gulick compared different HIV treatment guidelines from around the world.
Where Do the Different Treatment Guidelines Come From?
According to Gulick, the five most influential guidelines include:
What Are Guidelines?
Guidelines are put together by experts who gather the available scientific data and make treatment recommendations. "They all look at the same data, yet some come to different conclusions," Gulick points out. One of the fundamental questions is when to start. To make these recommendations, randomized controlled trials (RCTs), large cohorts and other clinical information are looked at and digested.
In all the published data of when to start, starting earlier was consistently better and associated with slower progression. Other benefits seen were a lowering of mortality and tuberculosis (TB) incidence.
Guidelines panels also often use common sense, sometimes as a justification for not strictly following the science, Gulick noted, emphasizing the relative convenience of treatments today, in that we have four (perhaps soon-to-be five) one-pill once-a-day regimens that are highly effective and fairly nontoxic, which influence guidelines panels.
Highlighting just how out of sync various guidelines are, Gulick pointed to a comparison chart by Kevin M. De Cock, M.D., and Wafaa M. El-Sadr, M.D., M.P.H., published in the New England Journal of Medicine. In this case, comparing U.S., EACS and WHO guidelines, panels may change their minds when more data come in and are analyzed.
When to Start
The U.S. guidelines are the easiest to review -- start everyone immediately, at any CD4 count. On the flip side, the EACS, BHIVA and WHO guidelines recommend starting treatment "for certain patients" with CD4+ cell counts between 350 and 500. However, for people with CD4+ cell counts above 500, the WHO recommends not starting treatment, while the EACS and the BHIVA guidelines recommend it only for certain patients.
[Editor's Note: In Sept. 2015, both the WHO and BHIVA guidelines were updated to recommend starting treatment immediately for all individuals living with HIV. This change was made in light of compelling data from randomized clinical trials, including the START study, which found that starting treatment immediately was significantly more beneficial than waiting for the CD4+ cell count to drop.]
These "certain" patients are usually medically more fragile, with symptoms of some sort, such as TB, neurocognitive issues, hepatitis B, hepatitis C, malignancies and cancers, among other things. "Personal reasons" (individual desires) can be taken into account. However, if a patient wants to reduce his transmission possibilities to others, the BHIVA guidelines do recommend starting treatment. Therefore, almost everyone "can be" recommended to start treatment in Europe, according to Gulick.
What's interesting to note is that sometimes national policies on when to start don't always match up with corresponding national or international guidelines, further adding to the confusion.
What to Start With
What to start with has "crystalized" in the various guidelines, according to Gulick, but the differences between guidelines can be surprising.
The U.S. has 10 recommended first-line regimens, so how do we choose? Luckily there are more head-to-head trials starting to come out that can help doctors and patients make more personalized decisions. But right now, the guidelines do not make more detailed distinctions.
The alternative recommendations are full of options. However, as Gulick suggests, some recommendations are slow to update. For example, up until 2014, the EACS guidelines still had didanosine (ddI, Videx) on its list of alternative recommendations, even though it was removed from most other guidelines in part or totally many years ago, mainly because of its adverse events profile, which includes mitochondrial damage (peripheral neuropathy and diarrhea), pancreatitis, lactic acidosis and metabolic changes.
At the same time, some guidelines get ahead of a curve. For example, the IAS-USA guidelines recommended two drugs that had not even been approved yet, atazanavir (Reyataz) with cobicistat (Tybost), and darunavir (Prezista) with cobicistat.
[Editor's note: In Jan. 2015, atazanavir coformulated with cobicistat, known as Evotaz, was approved by the U.S. Food and Drug Administration (FDA). Also in Jan. 2015, darunavir coformulated with cobicistat, known as Prezcobix, was also recently approved by the FDA.]
Interestingly, the IAS-USA guidelines also recommend easier-to-take ("light") regimens, either with no nucleoside reverse transcriptase inhibitor (NRTI) or only one NRTI. Furthermore, the EACS guidelines recommend the CCR5 inhibitor maraviroc (Selzentry, Celsentri) as an alternative regimen, while the HHS guidelines specifically recommend not using maraviroc much, highlighting how guidelines sometimes contradict each other.
When to Switch
Guidelines vary subtly, from viral load differences of 50 to 1,000 copies/mL as meaningful moments at which to change treatment, although they are all based on persistent levels and multiple readings, not just blips.
What to Switch To
There seems to be strong agreement on "at least two active agents," although Gulick notes that cost is a significant factor that guidelines take into account when making recommendations.
On the prevention side, there's a growing question as to whether to recommend pre-exposure prophylaxis (PrEP). We know PrEP works, but the question remains, given other prevention methods, which may be cheaper and equally as effective, should we recommend people take a pill every day?
The U.S. is the most straightforward: PrEP for all men who have sex with men (MSM), particularly because the U.S. has an HIV prevalence of 15% in this population.
The Europeans have no PrEP guidelines, because the European Medicines Agency (EMA) has not approved it yet, according to Gulick. This may change, after the results of two European-sponsored trials, PROUD and IPERGAY, both of which were ended early because of overwhelming success.
The WHO recommends PrEP for gay men as well as discordant couples and "others, as needed" across the world as part of a comprehensive prevention package.
"We all go by guidelines, trust what the experts say, comprehending and synthesizing and making intelligent recommendations to us, to take care of people with HIV and all infectious diseases, and then we make the best choice," Gulick concludes.
Rob Camp is a treatment activist based in Barcelona, Spain.
Follow Rob on Twitter: @Rob_Camp.
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