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RESISTANCE TO ANTIVIRAL NON NUKES
Jun 28, 2009

Hey doc XXXX here again I was the 22yr old guy just diagnosed with CD4 of 110 you'll be glad to know its now up to 180 but the doc says it'll bounce about. Anyways the specialist came up and talked to me and my fiance who is also positive. He got the resistance tests back and said me and her are both resisant to non nukes so instead of 2 pills aday its gonna be more like 5. How does this resistance occur when ive never had it before? Is there a limit amount of nuke drugs that can be taken? What are the chances of developing resistance to the nukes? Are nukes as effective as non nukes? Also im alergic to the bactrum and dapsom that they gave me as a result I have to have IV for PCP is this as effective? Sorry bout all the questions doc must drive you nuts im just freaking out and I guess your the man to talk to. Also is there a possibilty that they would run out of drugs to give me if I take them like clockwork. Thanks Doc would be good to hear from you I know your a busy man

XXXXX

PS: Please discard first emil

Response from Dr. Frascino

Hi XXXX,

The reason your resistance test showed resistance to non-nukes is that you acquired a virus that had already developed this resistance! It is a problem because now these drugs won't be effective for you or your fiancé. (I should mention there is a new non-nuke called Intelence that remains effective against viral strains that are resistant to other non-nukes. This drug may still be an option for you.)

As for the chance of developing resistance to other drugs, such as specific nucleoside reverse transcriptase inhibitors or protease inhibitors, this is always a possibility. Whenever the virus reproduces itself there is the possible there will be a slight genetic variation that will result in the newly produced virus becoming resistant to a specific medication. That is one of the reasons we try to drive the HIV viral load (viral reproduction) down to undetectable levels as quickly as possible. This decreases the chances for development of drug resistance. Also, nonadherence to medication regimens or improper dosing can encourage the development of drug resistance, because this can lead to having a subtherapeutic level of the drug "onboard." Not having therapeutic drug levels allows the virus to reproduce in the presence of the drugs and as a result the virus is encouraged, genetically speaking, to develop resistance as it replicates. HIV reproduces itself at a tremendous pace (billions of reproductions per day!). Therefore it is essential an HIVer be on a fully suppressive regimen and take the medications exactly as directed. These two factors work in tandem to decrease the risk of developing drug resistance. As far as the efficacy of drugs, different viral strains are more or less susceptible to various antiretrovirals. That is why we run resistance tests to ascertain what the best options are for a particular person's viral strain.

Regarding your PCP, intravenous pentamadine (which is what I'm assuming you are taking) is indeed effective treatment for PCP pneumonia. It can also be used for prophylaxis. (Aerosolized pentamadine can also be used for prophylaxis but not for treatment.)

As for running out of drugs for you, hopefully not! We now have over 20 antiretrovirals in multiple different classes. Certainly some are easier to take and tolerate than others.

XXXX, continue reviewing the information on this site, in its archives and on its related links. You'll find much of the information enlightening.

I'm delighted to hear your CD4s are heading up! Now we need to get your HIV plasma viral load down and your PCP treated!

I'm here if you need me. I'll print some information below regarding PCP and its treatment.

Good luck.

Dr. Bob

Pneumocystis Pneumonia (PCP) March 19, 2009

What Is PCP?

Pneumocystis pneumonia (PCP or pneumocystis) is the most common opportunistic infection in people with HIV. Without treatment, over 85% of people with HIV would eventually develop PCP. It has been the major killer of people with HIV. Although PCP is now almost entirely preventable and treatable, it still causes death in about 10% of cases.

Currently, with strong antiretroviral therapy (ART) available, PCP rates have dropped dramatically. Unfortunately, PCP is still common in people who are infected with HIV for a long time before getting treatment. In fact, 30% to 40% of people with HIV develop PCP if they wait to get treatment until their CD4 cell counts are around 50. The best way to reduce cases of PCP is testing for HIV to identify cases sooner.

PCP is caused by a fungus. It used to be called pneumocystis carinii, but scientists now call it pneumocystis jiroveci. A healthy immune system can control the fungus. However, PCP causes illness in children and in adults with a weakened immune system.

Pneumocystis almost always affects the lungs, causing a form of pneumonia. People with CD4 cell counts (see Fact Sheet 124) under 200 have the highest risk of developing PCP. People with counts under 300 who have already had another opportunistic infection are also at risk. Most people who get PCP become much weaker, lose a lot of weight, and are likely to get PCP again.

The first signs of PCP are difficulty breathing, fever, and a dry cough. Anyone with these symptoms should see a health care provider immediately. However, everyone with CD4 counts below 300 should discuss PCP prevention with their health care provider, before they experience any symptoms.

How Is PCP Treated?

For many years, antibiotics were used to prevent PCP in cancer patients with weakened immune systems. It was not until 1985 that a small study showed that these drugs would also prevent PCP in people with AIDS.

The drugs now used to treat PCP include TMP/SMX, dapsone, pentamidine, and atovaquone.

TMP/SMX (Bactrim or Septra, see Fact Sheet 535) is the most effective anti-PCP drug. It's a combination of two antibiotics: trimethoprim (TMP) and sulfamethoxazole (SMX). Dapsone (see Fact Sheet 533) is similar to TMP/SMX. Dapsone seems to be almost as effective as TMP/SMX against PCP. Pentamidine (NebuPent, Pentam, Pentacarinat) (see Fact Sheet 537) is a drug that is inhaled in an aerosol form to prevent PCP. Pentamidine is also used intravenously (IV) to treat active PCP. Atovaquone (Mepron) (see Fact Sheet 538) is a drug used in people with mild or moderate cases of PCP who cannot take TMP/SMX or pentamidine.

Can PCP Be Prevented?

The best way to prevent PCP is to use strong ART. People who have less than 200 CD4 cells can prevent PCP by taking the same medications used for PCP treatment.

Another way to reduce the risk of PCP is not to smoke, or to stop smoking. HIV-positive smokers develop PCP two to three times faster than HIV-positive people who do not smoke. One study found that ex-smokers who stopped for at least a year developed PCP no quicker than non-smokers.

Combination ART can make your CD4 cell count go up. If it goes over 200 and stays there for 3 months, it may be safe to stop taking PCP medications. However, because PCP medications are inexpensive and have mild side effects, some researchers think they should be continued until your CD4 cell count reaches 300. Be sure to talk with your health care provider before you stop taking any of your prescribed medications.

Which Drug Is Best?

Bactrim or Septra (TMP/SMX) is the most effective drug against PCP. It is also inexpensive, costing only about $10 per month. It is taken in pill form, not more than one pill daily. Cutting back from one pill a day to three pills a week reduces the allergy problems of Bactrim and Septra, and seems to work just as well.

However, the "SMX" part is a sulfa drug and almost half of the people who take it have an allergic reaction. This usually is a skin rash, sometimes a fever. Allergic reactions can be overcome using a desensitization procedure. Patients start with a small amount of the drug and take increasing amounts until they can tolerate the full dose.

Dapsone causes fewer allergic reactions than TMP/SMX. It is also fairly inexpensive -- about $30 per month. It also is taken as a pill and, like Bactrim or Septra, not more than one pill daily.

Pentamidine involves a monthly visit to a clinic with a nebulizer, the machine that produces a very fine mist of the drug. The mist is inhaled directly into the lungs. The procedure takes about 30 to 45 minutes. You pay for the drug plus the clinic costs, between $120 and $250 per month. Patients using aerosol pentamidine get PCP more often than people taking the antibiotic pills.

The Bottom Line

PCP is now almost totally treatable and preventable. However, it is still common in people who do not know they are infected with HIV. Strong antiretroviral drugs (ARVs) can keep the CD4 cell count from dropping. If your CD4 cell count is below 300, talk to your health care provider about taking drugs to prevent PCP. Everyone whose CD4 cell count is below 200 should be taking anti-PCP medication.



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