Ask the Doc: New Treatment Guidelines and the Quad Pill
Fresh from his Q&A forum on the Johns Hopkins website is EDGE’s new resident HIV expert, Dr. Joel Gallant, associate director of the Johns Hopkins AIDS Service at the Johns Hopkins University School of Medicine. In his first column, he tackles new treatment guidelines for ART, and the benefits of the "quad pill." Send your questions on HIV healthcare to him at email@example.com
New Guidelines on When to Start ART
Q: I just read that treatment is recommended for everyone with HIV infection. Why such a radical change? My CD4 count is over 500 and my viral load is always below 20,000. Why should I start treatment when I’m doing so well without it?
A: In March, the U.S. guidelines from the Department of Health and Human Services (DHHS) were revised to recommend ART for everyone infected with HIV infection, regardless of CD4 count. One reason for this change is prevention. The HPTN 052 study showed that treating HIV-positive people reduces sexual transmission to negative partners by at least 96 percent, making treatment of HIV infection our most effective form of prevention.
But the prevention benefit alone wouldn’t have been enough to alter guidelines so dramatically. There is also growing evidence that HIV-positive people benefit from treatment at all stages and CD4 counts. Having replicating virus is bad for you: it leads to chronic inflammation and immune activation that may increase your risk of long-term complications such as heart disease, cognitive disorders and malignancies.
In the days when ART was universally toxic and difficult, it made sense to wait until you really needed it. But it’s now clear that the toxicity of the ART we use today is trivial compared to the consequences of untreated HIV infection. And in the grand scheme of things, starting treatment right away rather than waiting until your CD4 count is below 500 or even 350 doesn’t add much additional time on ART. In the context of a lifetime on treatment, the small number of additional years (one to five, depending on the CD4 count you use) seems almost inconsequential, so the new recommendations aren’t really as "radical" as they might seem.
Is there anyone who should not be treated? People who aren’t ready or willing to start ART are the obvious candidates for waiting, though we hope they’ll be ready and willing before their CD4 counts get too low. Elite controllers, those with undetectable viral loads and stable CD4 counts without ART, might benefit from treatment, but it would be very hard to prove. Other long-term non-progressors, those who maintain stable CD4 counts without ART but who still have replicating virus, should still consider starting treatment, since years of viremia, even at low levels, may have negative consequences.
In your case, you’re doing well without ART, but things could be even better with it. First, you’ll have greater peace of mind knowing that you’re extremely unlikely to give HIV to anyone else. Secondly, you’ll be suppressing viral replication, lowering inflammation and reducing immune activation. We don’t know whether that will completely eliminate any excess risk of long-term complications, but it almost certainly reduces it.
Switching to the "Quad Pill"
Q: I’m doing fine on HIV treatment. I’m undetectable and my doctor says my CD4 count is great. But I’m hearing about a "quad pill" coming out. Should I switch?
A: The "quad pill" is a four-drug, single tablet combination of elvitegravir (a new integrase inhibitor), tenofovir and emtricitabine (the components of Truvada), and cobicistat, a new non-ritonavir pharmacologic "booster." Protease inhibitors (PIs) are almost always given in combination with ritonavir (Norvir), which increases their drug levels and allows them to be given less frequently or at lower doses.
Elvitegravir also has to be boosted, but in the quad it will be boosted by cobicistat rather than ritonavir. In clinical trials, the quad was as effective as either Atripla or the combination of Truvada plus Reyataz/Norvir, with some advantages in terms of side effects. It will probably be approved later this summer.
Should you switch? You didn’t tell me what combination you’re taking now, but you said you’re doing fine. Therefore, switching might be an option, but it isn’t necessary. Let’s talk about the pros and cons of switching from the common initial regimens:
Atripla: People doing well on Atripla without side effects have no reason to switch. Both Atripla and the quad are highly effective, single tablet, once daily regimens. But some people have subtle persistent side effects from the efavirenz component of Atripla, even after months or years of taking it. These can include concentration difficulties, problems with thinking or memory, sleeping problems or depression. In such cases, a switch might be helpful. Sometimes the only way to know whether these are efavirenz side effects is to switch and see what happens. If nothing changes, you can always go back to Atripla.
Truvada plus a protease inhibitor (PI), such as Prezista/Norvir, Reyataz/Norvir, or Kaletra): Switching will allow you to take a single tablet regimen. In some cases (especially with switches from Kaletra) there may be an improvement in diarrhea or a reduction in cholesterol or triglycerides. Be careful about switching if you have resistance to the nucleoside analog class of drugs. PIs have higher "resistance barriers" than integrase inhibitors like elvitegravir. If you have drug resistance and switch from a high barrier drug to a low barrier drug, your regimen might fail. Also, missing doses of a PI-based combination is less likely to cause resistance than missing doses of a combination that includes an integrase inhibitor, such as the quad, or a non-nucleoside reverse transcriptase inhibitor (NNRTI), such as Atripla. So if you’re someone who frequently misses doses, especially consecutive doses, then stick with what you’re taking.
Truvada plus Isentress: Both regimens include an integrase inhibitor. The advantage of the quad is that it’s taken once a day as a single pill. The advantage of Isentress is that it’s been around longer and won’t have the same effect on creatinine as the quad (see below).
Any regimen containing Epzicom: Many people take Epzicom instead of Truvada because of kidney problems. The tenofovir contained in Truvada sometimes causes kidney toxicity; Epzicom does not. If your kidneys don’t function properly, then the quad may not be a good option. Not only does it include tenofovir, but also cobicistat can give the appearance of kidney toxicity by slightly raising the serum creatinine level, a test we use to measure kidney function. Although cobicistat doesn’t hurt the kidneys itself, it can change the measurement of kidney function, which may in turn cause confusion about how to measure true tenofovir toxicity. This isn’t an issue for people with normal kidney function.
In short, I can’t tell you whether to switch or not, but I would point out that there are good and bad reasons to switch therapy when you’re on a combination that’s working. Good reasons to take quad are to reduce side effects or toxicity or to simplify therapy, especially if a simpler regimen will be easier for you to take or afford. Bad reasons to take it are because it’s new, because your friends are taking it, or because you liked the magazine ad. Finally, be careful if you already have resistance or have failed previous regimens: in those situations, it’s sometimes better not to rock the boat.