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Omladina JAZAS-a

What medicines, what combinations

There are 3 classes of drugs:
RTI = nucleoside or nucleotide analogues, also known as reverse transcriptase inhibitors
NNRTI = non-nucleoside reverse transcriptase inhibitors
PI = protease inhibitors

The basic principle is that any combination must contain at least three drugs. Using only one or two drugs will result in the rapid development of resistance.

Usually it contains a combination of drugs from two different classes, which means you can usually combine two RTI and NNRTI or PI. Recently, the so-called enhanced protease inhibitors (combined with ritonavir) is applied.

The results of clinical studies confirm this practice, and the U.S. and UK protocols include such recommendations for the use of antiretroviral therapy. UK protocols recommend the third drug to be NNRTI (fewer pills and does not have a lot of affect to your diet) or PI (protease inhibitor), and that includes Kaletra, which contains ritonavir in the same capsule as the original drug. There are also indinavir, saquinavir and amprenavir, which are used to separate pill ritonavir. The two new protease inhibitors (atazanavir and tipranavir) are likely to be used.

By using low doses of ritonavir with these drugs is achieved by an overall higher level of drug in the blood that is maintained for longer, reducing the risk of resistance. It also reduces the number of pills that are used, and the need for a change in diet. However, for some people even small doses of ritonavir cause nausea.

The usage of NNRTI or PI in the combination of drugs, depends on agreement with your doctor, your health and your virus resistance to medications.

What are the inhibitors of reverse transcriptase?

There are currently five nucleoside and nucleotide inhibitors of reverse transcriptase that the British protocol recommends for people who are starting their first therapy: 3TC, abacavir, AZT, ddI and tenofovir. Although d4T was previously used a lot, now is not the first recommended therapy because it causes lipoatrphy (fat loss). Also, the DDC is rarely used because it has various side effects.

Numerous combinations of the two drugs in this class can be used, but there are a few of them that are not advisable to use. For example, abacavir and tenofovir may react with each other, and it is still subject of research. You should never be using together AZT and d4T, or d4T and ddI during pregnancy.

Any combination of medication has its own advantages and disadvantages, different dosing and side effects. For example:
• AZT +3 TC were combined into one pill called Kombivir to use twice a day, regardless of diet.
• ddI and tenofovir are drugs that are used once a day, but when used together, doses of ddI is slightly reduced and the combination should be taken with food (without tenofovir, ddI is applied on an empty stomach).

If there is no reaction between the drugs in this class, they can replace one another, which mean that if adverse effects occur in a single agent, it can be replaced by another.

Which non-nucleoside inhibitor reverse transcriptase - efavirenc or nevirapine?

The difference between efavirenca and nevirapine was the subject of many discussions.

Many doctors believe that the difference in activity against HIV in these two drugs is very small, and that efavirenc may have little more effect.

Both drugs have similar side effects, including the risk of rash or hepatotoxicity (adverse effects on the liver) which can be very serious, and in some cases even fatal. That is why regular checkups are necessary.

Nevirapine can cause severe allergic reactions, Stevens-Johnson syndrome, in case of less than 1% of the people, and it can cause liver failure that can sometimes cause even death.

These reactions to nevirapine usually occur during the first two months of treatment, and in this perios controls should be performed every two weeks. Nevirapine is easily tolerated drug.

The main side effects of efavirenz are associated with his influence on the central nervous system (CNS). There are changes in mood such as anxiety, depression and sleep disorders - intense dreams and nightmares.

This occurs in more than half the people when they start using efavirenz and usually reduces the intensity of these side effects after several weeks. About 3% of people will stop using efavirenz after the occurrence of serious disorders of the CNS. Approximately 10-15% of people will stop using it because these disorders affect the quality of their lives.

The choice of protease inhibitors

New British protocols for the use of therapies recommend a use of protease inhibitors with ritonavir, which boosts their effect. Kaletra (lopinavir / ritonavir) is the only drug that contains both drugs in one pill (form).

New forms of saquinavir and nelfinavir are in development, which should reduce the daily number of pills. Because of the side effects, some people are sensitive to ritonavir and they can use a protease inhibitor without it.

Triple nucleoside combination

The combination of three nucleosides is less successful as the first choice of therapy. Therefore, this combination is not recommended as initial therapy.

Your initial therapy containing a protease inhibitor or reverse transcriptase inhibitors nenukeozidne, could be reduced over time to a triple nucleoside combination. This would reduce the side effects linked to PI or NNRTI (eg, increased levels of fats in the blood or fat deposition - lipodystrophy).

Combinations of several drugs

Some people use a combination of five, six, seven or even more drugs because of they have developed viral resistance during previous drug combination theapies.

In these so-called "Mega - HAART" combinations, a person can benefit from an already used drug in combination with new ones being introduced. Once the amount of virus in the blood remains below the level of detection, it is safe to start using fewer drugs again.