|"Simply Medical" presents information on a variety of topics in HIV/AIDS treatment and research. It is published as a service to our readers and is intended for information purposes only. Treatment decisions should always be made in consultation with physicians and other healthcare providers.|
One thing is quite clear: You don't necessarily need to take HIV drugs just because you're HIV-positive. HIV causes illness by damaging the immune system. Measuring the T4-cell count gives an idea of how the immune system is doing, and can also help you decide if anti-HIV drugs are needed. The other important indicator of how you are doing is called the viral load test, which measures the amount of HIV in a blood sample.
Measuring both the T4-cell count and the viral load can help work out if you're at risk for disease progression over the next few years. One large study, for example, found that a person who had a T4-cell count between 350 and 500 and a viral load of less than 14,000 had a very low risk of disease progression over the next three years. Starting with those test results, the risk of progressing to a diagnosis of AIDS within three years was about 5 percent, or one in twenty, and waiting a while to plan a treatment strategy would not likely pose a health risk.
In the same study, a person who started with a T4-cell count in the same range (350-500) but a viral load of over 110,000 was found to have a much greater risk of disease progression. The risk of progressing to a diagnosis of AIDS within three years for that person was close to 50 percent, or one chance out of two. Most doctors would strongly recommend treatment in that situation.
If your risk of disease progression is low, waiting to start treatment can be a good strategy for several reasons:
One argument against waiting to start treatment is that HIV may be causing ongoing immune system damage. It's clear from research studies, however, that serious illnesses are rare when a person's T4-cell count is over 200. To be on the safe side, most doctors recommend starting HIV treatment before the T4-cell count drops below 350 cells.
A drug that's been available for several years is the NRTI -- nucleoside reverse transcriptase inhibitor -- ddI (Videx). Several small studies have investigated once-daily dosing of ddI, usually at 300 or 400 mg a day, dependent on body weight. The results suggest that ddI works as well when taken once a day as it does when taken twice a day. Based on these results, some doctors are already prescribing ddI once daily, although this has not yet been officially approved by the United States Food and Drug Administration. The company that makes the drug, Bristol-Myers Squibb, is waiting for the results of a large study of once-daily ddI before asking the FDA for permission to change the currently recommended dosing.
Viramune (nevirapine) is an approved NNRTI -- non-nucleoside analog reverse transcriptate inhibitor -- drug that may work when given once a day. The standard dose is 200 mg taken once a day for two weeks, followed by 200 mg taken twice a day. A study presented at the 1998 International AIDS Conference in Geneva looked at 123 people who took Viramune at a dose of 400 mg once a day. The blood levels of Viramune in these people stayed 250 times higher than the amount needed to block 90 percent of HIV production in the test tube. This study suggests fairly strongly that nevirapine could be given once daily. As with ddI, the FDA has not yet approved once-daily dosing of nevirapine.
The twice-daily NRTI drug 3TC (Epivir) may have the potential for simpler once-daily dosing. This suggestion is based upon the length of time the drug stays inside cells in the body after each dose, as opposed to how much can be measured floating free in the blood. Two recently presented studies have used 300 mg of 3TC dosed once daily, instead of the same amount split into two 150 mg doses over the course of the day.
All in all, once-daily dosing of ddI, 3TC, and nevirapine looks very promising. It's important to bear in mind, though, that the studies were based on what was already known about these individual drugs. Sustiva (efavirenz) is a newly approved NNRTI anti-HIV drug that has been approved for once-a-dau dosing. Not all drugs can simply be switched from three-times-a-day dosing to twice a day, or from twice day to once a day. The anti-HIV drugs AZT, d4T, and abacavir, for example, cannot be dosed once a day because they don't stay in the body long enough.
Viracept is a protease inhibitor that's already approved for treating HIV. The approved dose is three pills (750 mg) taken three times a day. Several studies have now compared the approved dose to a simpler dosing schedule of five pills (1250 mg) taken twice a day. After up to 48 weeks of treatment, the studies have found that Viracept can work just as well given twice daily as it does on the thrice-a-day schedule. It's likely that the company that makes Viracept will soon ask for FDA approval of this easier dosing schedule, but at the moment twice-daily dosing of Viracept is still considered experimental.
Fortovase is the new version of the protease inhibitor saquinavir. The approved dosing of Fortovase is six pills (1,200 mg) three times a day. Early results of a study comparing that dose to a new dose of eight pills (1,600 mg) twice daily were recently presented. Both doses were given along with two NRTI anti-HIV drugs. After eight months of treatment, there was not a big difference between the doses in terms of increases in T4 counts and reduction in viral load. Eight months, however, may not be a long enough test to tell if the twice-daily dosing will work as well as the three-times-a-day schedule over the long term.
Norvir plus Fortovase is the most commonly used combination of protease inhibitors. Norvir boosts Fortovase levels and allows both drugs to be taken twice daily, at lower than normal doses. When combined, Norvir and Fortovase are usually both given at a dose of 400 mg twice a day. The Public Health Service HIV Treatment Guidelines include Norvir plus Fortovase as a reasonable first-line treatment combination. The guidelines recommend that Norvir plus Fortovase be used in combination with one or two NRTI drugs.
Other combinations of protease inhibitors that allow twice-daily dosing are also under investigation. Studies of Norvir plus Crixivan, Viracept plus Fortovase, Crixivan plus Viracept, and Norvir plus Viracept are ongoing. Clilnical trials of two new protease inhibitors that will likely be twice-a-day dosing have just opened around the country.
Not all attempts at simpler dosing have been successful. A study of the protease inhibitor Crixivan (indinavir) given twice a day was recently stopped; the twice-daily dose did not work as well as the standard dose of Crixivan, which is 800 mg every eight hours. After six months, 91 percent of people in the standard Crixivan dose group had viral loads below 400 ("undetectable" on the standard test), compared to 64 percent of people taking the experimental twice-daily Crixivan dose. Crixivan works best at the standard dose of 800 mg every eight hours. Crixivan, as well as Norvir, has been shown to increase survival, whereas the other currently approved protease inhibitors have not yet documented this.
Public Health Service guidelines recommend monitoring viral load every three to four months if you're not yet taking HIV treatments. Changes in viral load and T4-cell counts over time can help work out if your risk of disease progression is increasing.
Viral load tests aren't perfect. The test gives a rough estimate of the amount of virus in a blood sample. Results can be different, even when two viral load tests are conducted on the same blood sample. This problem is called "variability." The variability of the viral load test can be approximately three-fold. This means that a test result of 15,000 copies could come back anywhere between 5,000 (three-fold less than 15,000) and 45,000 (three-fold more than 15,000). Because of this variability, small changes in viral load test results -- from 10,000 to 15,000, for example -- don't necessarily mean that the viral load has changed.
The FDA recently approved a new viral load test that measures HIV levels down to fifty copies. This test is called the Roche Amplicor UltraSensitive test. The other currently approved viral load test measures down to 400 copies. Roche has opened a Patient Assistance Program to ensure that the new UltraSensitive test is available regardless of insurance coverage or ability to pay. The telephone number is 1-888-TEST-PCR (1-888-837-8727).
Laboratory testing, also called bloodwork, is one of the methods used to monitor for potential side effects.
In addition to regular bloodwork, if you're taking HAART combinations you should talk to your doctor about the following:
Triglycerides and Cholesterol
These are types of fats found in the blood. HAART combinations, especially combinations including protease inhibitors, have been linked to increases in these fat levels. Fat buildup in bloodvessels can cause heart disease. Heart problems, including heart attacks, have been reported in a few people taking HAART combinations in the United States and the United Kingdom. General recommendations about cholesterol levels and heart disease are that a level of less than 200 mg/dL is best, while 200 to 239 may be a little high. Cholesterol levels of 240 or greater are associated with a high risk of heart disease. The normal range for triglycerides is 40 to 150 mg/dL. HIV infection alone can sometimes cause triglycerides to be higher than normal.
High blood sugar is another potential side effect of HAART. In some cases, high blood sugar has led to diabetes. As with fat levels, this problem has most often been linked to protease inhibitors. Blood sugar levels can be monitored for any sign of trouble. Some doctors recommend the glucose tolerance test, or GTT, which also looks for signs of diabetes.
Several anti-HIV drugs can potentially cause kidney damage. If signs of kidney damage are not noticed quickly enough, the kidneys can fail, and kidney failure is life-threatening. The protease inhibitor Crixivan can cause kidney stones. These aren't always the common type of kidney stones, which are deposits chiefly of proteins; instead they are deposits of Crixivan that have formed in the kidneys. Early Crixivan studies found that about one in twenty, or 5 percent, of people taking the drug got kidney stones. A recent study in women found that 28 percent, or more than one in four, developed signs of kidney problems after a year.
Kidney problems have also been reported with the protease inhibitor ritonavir (Norvir). The experimental anti-HIV drug adefovir (Preveon) can cause a type of kidney damage. In some cases, Preveon-related kidney damage has not improved even when the drug was stopped. Researchers strongly encourage that monitoring of kidney function include measuring the creatinine levels in the blood and testing the urine regularly for signs of kidney problems when taking this or any other treatment.
Testing blood levels of uric acid can monitor for a condition called hyperuricemia. This condition can also be a sign of kidney problems. Symptoms of hyperuricemia are joint pain and arthritis, and several studies have reported these problems in people taking HAART.
Liver problems are a common side effect of many prescription drugs. The basic tests for measuring the health of the liver are called liver enzyme tests. These are usually done as a part of regular bloodwork. NRTI anti-HIV drugs (AZT, ddI, ddC, d4T, 3TC, abacavir) can -- very rarely -- cause a severe and potentially life-threatening liver problem called lactic acidosis. Symptoms of lactic acidosis are severe nausea, vomiting, and rapid breathing. A blood measurement called serum bicarbonate can also be used to help diagnose this problem. Serum bicarbonate levels often drop below normal as a result of lactic acidosis. If this problem occurs, its treatment requires stopping and replacing the offending NRTI drug or drugs.
Protease inhibitors (PIs) -- approved protease inhibitors are indinavir (Crixivan) nelfinavir (Viracept), ritonavir (Norvir), and saquinavir (Fortovase).
Ken Fornataro is Program Director of the New York City Case Management Program and Richard Jefferys is the Access Project Director at the AIDS Treatment Data Network. For more information, call (800) 734-7104.