Combining the HIV Drugs
It's nice to look at the HIV drugs separately, but in the real world, the meds must be taken in combination. This is more than just putting any old drugs together. Here are some treatment strategies from the world of HIV care.
First Time on Therapy
"Treatment naive" refers to people who've never taken HIV therapy before. Your first two drug regimens have the best chance to bring the level of HIV in your blood down to undetectable. These beginning combinations can be among the simplest. Combivir/Sustiva is probably the most popular. Now that there's Epzicom and Truvada on the market, they might take the place of the Combivir in that regimen.
Some doctors prefer starting people out on a protease inhibitor (PI), and Kaletra is the leader of the pack for these drugs. But Reyataz, which is taken only once a day, may soon challenge Kaletra's lead position. Reyataz also has the advantage of not raising lipid levels (cholesterol and triglycerides).
Some treatment-naive people might even be able to take Trizivir -- one pill, twice a day. But because a recent study demonstrated that twice as many people failed Trizivir as other regimens that included a PI or NNRTI, few doctors today would start with Trizivir alone. Those people already on Trizivir who have undetectable viral loads, however, need not alter their therapy.
So know your options and try to pick a regimen that you can live with (such as number of pills and potential side effects).
Treatment Experienced, or Salvage Regimens
As more drugs and drug combinations are taken, you can expect less effectiveness -- a viral load above the level of detectable. But that's not always so bad. Studies find lots of people doing well on stable, detectable viral loads (but not real high levels). Drug therapy is keeping people out of the hospital. Again, know your options.
Norvir, a PI once used to treat people with HIV, is now used to boost the drug levels of other PIs, making them more potent and durable, and allowing less pills. At the low levels prescribed for boosting, Norvir has far fewer side effects than it did in its original, six pill twice-a-day, formulation. The most powerful boosted PI today is Kaletra, which combines lopinavir with a tiny dose of Norvir.
Combination pills -- those with two or more drugs in it -- are cutting the number of pills people take. Current combo pills on the HIV market are: Combivir, Trizivir, Epzicom and Truvada. In the works is a new combo pill, one that -- for the first time -- contains two classes of HIV drugs. That's the combination of Sustiva and Truvada.
Most HIV regimens contain two (sometimes more) nucleoside analogs. This is called the "nucleoside backbone" of the combination.
Dual PI Combos
Combining two PIs can be effective in suppressing HIV, sometimes without adding nukes or a non-nuke. The idea is to use two full-dose PIs together, rather than just boosting one PI with a small dose of Norvir. A powerful combination is Kaletra and saquinavir (Invirase or Fortovase). Studies are also looking at the combination of Kaletra and Reyataz. Kaletra and Agenerase or Lexiva should be combined with caution, because the latter two drugs lower the blood levels of the lopinavir component of Kaletra. Dual PI combos are generally salvage therapies, when a person can usually no longer take simpler regimens.
There are four classes of HIV drugs on the market (five if you want to get technical -- Viread is a nucleotide instead of a nucleoside analog). Treatment usually consists of meds from two or three of the classes. The idea behind class sparing is that you have a class of drugs you've never used before, in case you need it later on. It's also used to avoid the potential side effects and toxicity associated with a particular class of drugs.
Almost no one takes three classes of drugs for their first regimen, so they're automatically "class-sparing." The newest concept in class-sparing regimens is dual PIs (see above). Nuke-only therapy is to be avoided, although Trizivir with Viread has had early success and might prove to be an effective combination.
Among the most radical approaches to pop up over the past year or so, this concept shows promise because of Kaletra's high potency and durability, and lack of drug resistance in treatment-naive people. But for now, don't try this at home. It's still in early, small studies.
The idea behind induction/maintenance is to hit the virus "hard" early with four or five anti-HIV medications from multiple classes, then back off with fewer medications later. If a person could be maintained on two medications, for example, compliance might improve and there might be fewer side effects. With such an approach, however, there is the risk of failure -- the virus might break through, becoming resistant to the lower-dose regimen.
Special thanks to Ross Slotten, M.D., for reviewing this article.
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