Adherence to a medical regimen is important for the success of the medical regimen. Regardless of whether it has to do with diabetes or heart failure or other infections besides HIV, in particular though the medical regimen for HIV needs to be adhered to closely for the best results. Part of the reason is because the ten billion virus particles that are created every day there is ample mutations going on and the end result is some of the mutations will confer the ability of the that virus particle to ward off the affects of the antiretroviral drugs. So in essence it's a battle between the mutation and the drugs. But the idea is if you keep the blood levels of the antiretroviral drugs high, at a very high level consistently then they will prevent the emergence of resistant strains for many, many years at least most of the time. The difficulty comes when there are some low levels of antiretroviral drugs in the blood stream. Low enough that the mutations that occur now have a chance to flourish, again these are all partial resistance mutations, so that is there is a low, a lag suddenly in medication use then the chances are that the mutation level will be allowed to flourish and cause resistance. For example, in the HIV particularly there is a mutation called the K103N in which one amino acid is substituted for another at the 103 position. When that happens there is resistance not to one drug that the patient may be on but to the whole class of drugs so for at least three existing members of that class can't be used. Likewise if there is a resistance called the N184V mutation there will be resistance to two very commonly used drugs. The not so bad news is that viruses that have the N184V mutation tend to be less fit viruses. So sometimes even though it's not going to be by itself a very effective tool to reduce the overall viral population continuing a drug that caused the 184 mutation can render the population of viruses to be a little less fit. There are plenty of them but they are not as strong and vigorous. So sometimes we keep that in a regimen. That's what we call salvage therapy. Sometimes we keep it as a solo regimen, solo agent in a regimen while we are waiting for other drugs to reach the marketplace. In any event, we don't want mutations if we can help it because sometimes when they occur, then whole groups of HIV drugs cannot work well. For example, the protease inhibitor class there are probably seven or eight drugs now on the market but some of them are less useful because of the mutations. Others are less useful because of side effects and that is another whole aspect of HIV therapy. People who are alive with HIV on medications can have metabolic consequences that we would have no idea could occur. They can lose fat from their limbs, have their veins all sticking out, they can gain fat on the back of their neck or upper shoulders, they can lose fat from their face and become all drawn in here, they can gain fat inside their abdomen, their blood cholesterol and triglycerides can be radically altered, for example. All these are consequences of living with HIV in the setting of aggressive modern HIV therapy. Some drugs are more likely to cause certain side effects than others. And so we have to tailor all of this to the patient and where they are. The first regimens are a little easier nowadays. The people, who fail the first now they are on the second, fail the second now they are on the third, our choices become more limited our goals sometimes no longer can be achieved in terms of complete suppression. So the best thing to do for someone who is starting HIV therapy is get themselves mentally committed to the idea they will take that medicine. And get themselves prepared so they can remember to take medicine and hopefully they will have access to the medicine without interruption wherever they are in the world. Again our problems are taking a little medicine causes resistance and if we use the analogy of penicillin around the world, over the years penicillin has not become as useful at all in certain infections. For example gonorrhea, many years ago gonorrhea could be treated with penicillin. Then it became harder to treat it had to give injections, high doses, and so forth and finally we had to give up on penicillin as a drug for gonorrhea. Part of the problem was people, including commercial sex workers, would take a little penicillin or maybe if they were a customer take a little of the penicillin until the symptoms went away and they wouldn't take all of the medicine. The end result was the few germs that were left behind became more resistant and they were then spread and became the dominant germ. Same thing has happened with pneumococcus, Streptococcus pneumonia specifically, no longer can be reliably killed with penicillin. In some areas of the world perhaps half or more of the isolates are resistant in some fashion to penicillin. So it is something that does occur in the presence of an organism that can be killed by a dose or mildly suppressed by a small dose resistance is the outcome and this has happened with HIV unfortunately. Part of the problem with HIV is that new infections in the setting of someone who has been exposed to medication who no longer has a very suppressed viral who is not acting responsibly, who is not having sex with condoms, who is not disclosing their status, what happens now is they have a resistant virus because of their medication mishaps. And when they give HIV to the next person it's already resistant so when that person sometime later comes in for medical treatment it may have a virus that looks as if they themselves have had six or eight drugs for HIV and of course they have had nothing themselves. But they caught a virus that was resistant and so we have to be careful if we look at what we can do, at least in this part of the world, we can test for these pre-resistant viruses in the newly diagnosed patients and tailor our regimens to them. But it's a problem around the world and it can become a problem eventually in developing countries.