In the late 1990’s, when treating HIV required taking a handful of pills several times a day, usually at specific times and often with complex food restrictions, it was common to refer to an antiretroviral regimen as a “cocktail.” Today, with most initial regimens consisting of just 1-2 pills taken once a day, a regimen is more like a shot than a cocktail. Choosing the regimen is easier than it used to be, too, since most combinations will work well in most people. Still, there are some things to consider before you start an initial regimen: 1. How important is a single-tablet regimen (STR)? Would taking two pills a day be a problem? If an STR is very important to you, there are several good choices. Current U.S. guidelines recommend three STRs: Triumeq, Genvoya, and Stribild. Triumeq, a combination of dolutegravir, abacavir, and lamivudine, is taken once a day with or without food. Before taking it, you must be tested to make sure you’re not allergic to abacavir. Also, we generally avoid abacavir (including Triumeq) in people at high risk for heart attack. Genvoya, a combination of elvitegravir, cobicistat, emtricitabine, and tenofovir AF (referred to as TAF), is taken once a day with food. One downside is that the cobicistat in Genvoya interacts with some other drugs. Stribild is similar to Genvoya, but it contains the original form of tenofovir (tenofovir DF, or TDF), which is more likely to cause bone and kidney toxicity than TAF. There’s no reason to use Stribild if you can use Genvoya. If you don’t care whether you take one or two pills, another good choice is Truvada plus Tivicay. Truvada combines emtricitabine and TDF, and will become an even more attractive option when a TAF-containing version of Truvada is approved in early 2016. Tivicay, the brand name for dolutegravir, is a potent and well-tolerated integrase inhibitor with few drug interactions. 2. Would it matter if I had to take medications with food? Several regimens should be taken with food for better absorption, including Stribild, Genvoya, and any regimen containing Reyataz, Evotaz, Prezista, or Prezcobix. Complera should be taken with a full meal. Regimens containing dolutegravir (Tivicay, Triumeq) can be taken with or without food. Regimens containing efavirenz (Sustiva, Atripla) should generally be taken on an empty stomach at bedtime, because food can increase drug levels, which causes more nervous system side effects. 3. Am I taking medications that might interact with some HIV drugs? The regimens most likely to interact with some other drugs are those containing cobicistat (Genvoya, Stribild, Evotaz, Prezcobix) or ritonavir (Norvir combined with Prezista or Reyataz, or ritonavir in the form of Kaletra). That doesn’t mean there are no interactions with other drugs, but the list is much shorter. Make sure your provider and pharmacist know all the drugs you’re taking, including over-the-counter medications and supplements. If you’re taking cobicistat or ritonavir (see the list above), avoid over-the-counter fluticasone (Flonase), one of the only over-the-counter medications you need to worry about. Ask your provider or pharmacist about alternatives. 4. Do I have any other medical conditions that might affect my choice? The choice of regimen may be affected by your other certain other conditions. For example, chronic hepatitis B or C, kidney disease, or heart disease may influence the drugs your provider chooses for you. Pregnancy (or plans for pregnancy) will also affect this decision. 5. How well will I adhere to therapy? Am I likely to miss doses or interrupt treatment? If you’ve never had to take medication every day, you may not know the answer to this question. If you’ve never finished a course of antibiotics in your life, there’s cause for concern. Missing doses, especially multiple consecutive doses, can cause the virus to mutate and become resistant to medications, which may limit your future treatment options. Some regimens, such as those that contain protease inhibitors or dolutegravir, are less prone to resistance than others. 6. What does my baseline resistance test show? Are there any drugs that my virus is resistant to? Everyone should get a baseline resistance test done before starting therapy, because it’s possible to be infected with virus that’s resistant to some drugs. Your provider should choose your regimen based on those results. In the rare cases where you can’t wait 2-3 weeks for the test results (e.g. acute infection or advanced HIV disease), a regimen containing a protease inhibitor or dolutegravir can be started. As you can see, there’s no “one size fits all” when it comes to choosing a regimen, but most people have many great options to choose from. Make sure you’re seeing an experienced provider who is familiar with the latest clinical trial results and treatment guidelines. The evidence is clear that provider experience is an important predictor of how well you do on therapy.