Shoot for Success

'Save the best for last' is a good rule of thumb for some things in life. But not in making a choice about anti-HIV treatment. For a long time'in fact, since combination therapy for HIV was first developed just over 10 years ago'physicians and patients have focused on the importance of 'sequencing' treatments. That's the process of choosing your first therapy with an eye toward ensuring that it won't cause resistance to your second or third and beyond. Planning ahead is always good. But the 'tried-and-true' sequencing process can sometimes mean that people with HIV start treatment with weaker, less effective therapy. In the old sequencing game this was often a necessary strategy'treatment choices were few, and keeping your future options open was the name of the game. Today, the sequencing paradigm deserves a second look. A patient's first combination should be chosen with the goal of maximizing its effectiveness for as long as possible. I call this approach treating for success. Some doctors start off assuming that your first regimen will fail. They are concerned about maximizing future treatment options, so they put less emphasis on the quality of your first set of meds'effectively treating for failure. The Food and Drug Administration has approved seven new HIV therapies since 2003. They include a number of new compounds as well as the first combination pills dosed once a day. A number of these new options can help to simplify initial treatment regimens and match the potency of older drugs while keeping long-term options open. With 24 anti-HIV medications now on the market and some drug regimens causing less resistance than older options, starting with a more complex therapy or with drugs that cause excessive side effects often doesn't make sense. Overreliance on the old plan-ahead principle means that a significant number of HIV-positive people might not get the best possible start in their treatment career. In this new treatment era there are five hallmarks to look for in a good starting regimen: high potency, long half-life, good tolerability, once-daily dosing, and a favorable resistance profile. If you are thinking about starting treatment, there are some things you should know'and ask your doctor'about each. PotencyWhat You Should Know: Anti-HIV medications should have demonstrated potency in suppressing viral load and strengthening your immune system, specifically increasing CD4-cell count, to be effective. Potency over time is a major plus. What to Ask: How effective are these drugs in reducing viral load and increasing CD4 counts? How potent are they over time?' Half-lifeWhat You Should Know: Some medications stay in the blood and cells longer than others. Evidence suggests that drugs with greater staying power could help to optimize suppression of HIV and be more forgiving of the occasional missed dose. What to Ask: What are the half-lives of the drugs in this combo? If I miss a dose one day, will they continue to significantly suppress my viral load? TolerabilityWhat You Should Know: Newer medications might come with fewer serious side effects. The better you tolerate a treatment combination, the more likely you are to take it as prescribed. This level of adherence is critical for long-term success. What to Ask: What are the main side effects associated with these medications? What is the rate of lipodystrophy, anemia, nausea, diarrhea, and neuropathy? How does this regimen compare with others on patients' ability to tolerate it? DosingWhat You Should Know: Though research is ongoing, many experts believe that once-daily dosing is an important way to help patients adhere to therapy. Drugs that can be taken with or without food are also ideal. What to Ask: Is this regimen dosed once daily, and are there any food restrictions? If not, is there any way I can switch to a regimen that is taken once a day only? [See the Treatment Guide for anti-HIV meds that can be dosed once a day.] ResistanceWhat You Should Know: Not all medications are alike when it comes to resistance. Some regimens containing older medications can cause high-level cross-resistance'that is, they can potentially knock out other drugs in their class. What to Ask: Is resistance a common problem with this regimen? How fast can it emerge? If I develop resistance to a drug in this combo, will I have substantial cross-resistance to similar drugs? We've come a long way since the early days of HIV treatment. Back then we were lucky if we could find drugs with potency against the virus, never mind all the other features above. Thankfully, we can now begin treatment with success'rather than failure'in mind. And as we do we can make a lasting first impression in the fight against HIV. Cohen is the research director for Community Research Initiative of New England.