Although 18 approved medications are now available to treat HIV infection, the process of deciding how best to use them has become complex. Making decisions about whether or when to start HIV treatment -- and which drug combinations will work best for you -- presents complex challenges for both a person living with HIV and health care providers. Because there is now so much information to absorb and interpret, communication and an open mind will be the keys to a successful treatment regimen. A critical first step is to learn all that you can about the antiretroviral (ARV) drugs that are available today, and even about the ones that are likely to gain FDA approval in the near future.
Another important lesson to learn early on is that there is no cookie-cutter approach to selecting an ARV regimen. In other words, there is no right or wrong approach; you and your physician together need to select the treatment that will work best for you as an individual. Two key factors will help determine when to start therapy and which medications to use:
Routine blood tests for your viral load and T-cell count can help determine how healthy your immune system is and when you should start or switch therapy. The T-cell count may be the most critical factor to consider in deciding when to start treatment, because it provides a strong indication of how much damage HIV has caused to the immune system.
Viral load plays a less critical role in deciding when to start treatment, but it can still provide vital information for some people who have not yet started treatment. For example, if your T-cell count is 250 and your viral load is over 100,000, your T-cell count could fall below 200 before it is measured again three to six months later. This is because the higher a person's viral load is, the faster the T-cell count is likely to decline. A high viral load could mean that the T-cell count will continue downward and should be playing a role in deciding whether to start treatment.
The two sets of guidelines make somewhat different recommendations about when to start ARV therapy. However, both guidelines strongly urge therapy for people who have AIDS-related symptoms or a T-cell count between 200 and 350. Research indicates that individuals who begin ARV treatment after their T-cell counts have fallen below 200 may experience a less successful treatment course than those who begin when their T-cell counts are higher than 200.
A matter that is still controversial is whether to start ARV therapy "early," which currently is considered to be having a T-cell count higher than 350. Some experts prefer to start therapy early, before the T-cell count shows that the immune system has been seriously compromised. Others believe that starting therapy early will not produce better results and that therapy should wait until the T-cell count has fallen below 350, though not below 200.
Besides T-cell count and VL, certain non-HIV issues play important roles in determining an ARV regimen that will be effective and that you can adhere to over the long haul. Be sure to discuss with your health care provider:
An ARV drug regimen should consist of at least three drugs, usually from at least two of the four different classes of ARV drugs:
Above all, it is important that you understand exactly how and when you should take the combination of drugs you select. Here are some key questions that you should clarify with your physician:
Make sure you know the answers to these questions before starting your regimen. Fortunately, ARV regimens do not have to be difficult to take. For example, some HIV drugs need to be taken only once a day, and at least one combination involves taking just three pills, once a day (Viread, Videx-EC, and Sustiva).
To make sure your VL remains undetectable, you will need to visit your doctor's office every three to six months to have it checked. An increase in VL during ARV treatment could mean that drug resistance has developed. You should also be sure that your doctor's lab always uses the same type of VL test. This is because there are two different types of test, and test results from the different types should not be compared directly. Even when the same type of test is used regularly, you and your doctor need to interpret any changes in VL. The VL needs to change by at least a factor of three (3 times) before the change is considered meaningful. For example, an increase from 10,000 to 25,000 copies may be due only to the sensitivity of the test and may not reflect an actual change in viral load. A T-cell count should also be performed at the same time as the VL test.
Even if you are not due to have another set of lab tests done, do not hesitate to discuss with your provider any problems that you are having with your ARV regimen. If you find that you have trouble taking every dose on time or are experiencing side effects, you and your doctor may be able to find a different combination that is easier to take or has fewer side effects. Doing this sooner rather than later is crucial. Having a regimen that you can adhere to for the long run will help the treatment work best. Strict adherence to your treatment regimen will mean that resistance will take a longer time to develop and you won't have to consider new treatment regimens so soon.
In spite of best efforts to adhere to an HIV treatment regimen, nearly everyone with HIV will at some point need to switch to a different regimen. This can happen for several reasons:
Occurrence of any of these developments is called "treatment failure," which is a more harsh-sounding term that it really is. Treatment failure basically means that the anti-HIV drugs you are currently taking are no longer doing what they should. The key tool for determining whether treatment failure has occurred is a VL test to check for the amount of virus in your blood. If your viral load does not decrease significantly and stay down while you are using highly active antiretroviral therapy (HAART), your T-cell count could decrease and you could be at risk for symptoms of HIV disease progression.
If any of the following occurs, your ARV treatment may not be working the way it should:
HIV can stop responding to HAART for a number of reasons, but the good news is that you and your health care provider can control some of these:
Of course, people who have been taking HAART for some time and have an undetectable viral load can also experience serious side effects. Perhaps the best-known example of this is lipodystrophy, which many researchers believe is due at least in part to ARV therapy. Lipodystrophy refers to body-shape changes and increased levels of fats (triglycerides and cholesterol) and sugar in the blood.
Furthermore, high cholesterol or triglycerides in an HIV-positive person can be treated according to the guidelines for the general population published by the National Cholesterol Education Project (www.nhlbi.nih.gov/about/ncep/index.htm). Be sure to discuss with your doctor any changes in body shape that you feel you are experiencing -- and make sure to have a regular blood lipid screening performed.
A number of HIV mutations caused by treatment with one drug can cause your HIV to become resistant to other drugs in the same class as the one that led to that particular mutation. This is called cross-resistance, and it poses one of the biggest hurdles in switching ARV regimens. Cross-resistance is most difficult among PIs and NNRTIs. For example, if your HIV has become resistant to Sustiva (efavirenz), it is likely also fairly resistant to Viramune (nevirapine).
Not all insurance companies, Medicaid programs, and other third-party payers cover the high costs of resistance tests. This may eventually change, because both guidelines now officially recommend using them. If your viral load is increasing while on therapy, ask your doctor about having an HIV drug-resistance test. If your doctor can prove that it is medically necessary, your third-party payer may agree to cover the cost.
Like figuring out when to start therapy and what drugs to start with, deciding when to switch therapies and what drugs to switch to is a complex process. The choices of ARV regimens available to you will depend on which drugs you are now taking and those you have used in the past. This is because of the resistance patterns that your HIV might have developed to either specific drugs or whole classes of drugs.
You and your physician should consider the following federal guidelines when selecting a different treatment regimen:
One possible approach is to "recycle" drugs that you have used in previous ARV regimens. Drugs that you stopped using for reasons other than development of resistance (due, for example, to side effects) may be the best candidates for recycling. Recycling drugs to which you are resistant is much less likely to help. Before doing so, discuss with your doctor the possibility of performing an appropriate resistance test to see if you may be able to recycle any of the drugs you have used before. If you and your doctor agree on a combination of drugs to which your HIV has only low-level resistance, this type of salvage treatment may be able to reduce your VL to a low level again.
Another option is "mega-HAART," a strategy that uses a combination of up to nine anti-HIV drugs. The idea behind this approach is that, no matter how many drugs and drug combinations a person has taken, the virus in his or her body is not likely to be resistant to all of the drugs in such a complex regimen. Of course, adherence and side effects will pose serious difficulties with this strategy.
To intensify a regimen, your doctor can prescribe a fourth anti-HIV drug, often the protease inhibitor Norvir (ritonavir). Although ritonavir can have undesirable interactions with a number of other medications, it can also raise the blood levels of other PIs and some NNRTIs. These increased levels can help put additional pressure on the virus, with the goal of reducing it to an undetectable level.
In the foreseeable future, drugs that are simpler to take and drugs that do not have the same resistance patterns as the current ones will become available. Doing all that you can today will leave you in a stronger position to benefit from these upcoming developments.
Steve McGuire is a Chicago-based writer and consultant specializing in medicine, public policy, and nonprofit issues. He can be reached at: firstname.lastname@example.org.
What About Logs?
Log is short for "logarithm," which is a mathematical term used to describe a change by a factor of 10 (that is, "times 10") in the quantity of whatever is being measured. Put another way, logs are a shorthand way to express a very large number. A log is the number of times 10 must be multiplied by itself to equal a certain number.
In relation to HIV, logs are sometimes used to state a patient's total viral load. For example, a viral load of 100,000 is log5 because it equals to 10 x 10 x 10 x 10 x 10.
Most people with HIV, however, have read or heard "log" used as the way to state how much their viral load has gone up or down. For example, if the baseline viral load is 20,000 copies/ml plasma, then a 1-log increase equals a 10-fold (10 times) increase, or 200,000 copies/ml. A 2-log increase equals 2,000,000 copies/mL plasma, or a 100-fold increase. As another example, a reduction in viral load from 100,000 to 1,000 copies/ml is a 2-log (or 99 percent) reduction. However, a half-log (0.5 log) change is not a five-fold difference, but a change of 3.16-fold.
Understanding Resistance Tests
Genotype TestsIf highly active antiretroviral therapy (HAART) is no longer working well for a patient, genotypic resistance testing helps medical providers make decisions about switching to a different therapy. It does this by identifying which drug or drugs in a HAART cocktail the patient's HIV has become resistant to. Genotype tests look for specific changes, called mutations, in the genetic code of an individual's HIV that are known to be associated with resistance to particular antiretroviral drugs. A genotype test will determine the genetic code of a person's HIV by examining a sample of the virus from the patient's blood to identify any mutations in the virus. HIV that does not have any mutations is called wild type virus, which is the most common form of HIV. This usually means that antiretroviral drugs can still work against the virus.
Phenotype TestsPhenotype tests aim to see how an individual patient's HIV actually responds when it is exposed to specific antiretroviral medications. Technicians grow a sample of a patient's HIV in the lab and then expose the virus to different antiretroviral medications. The phenotype test will determine if the virus grows slower or faster when each drug is present. If the HIV sample grows faster, the virus is more "resistant" to that drug. If the sample of virus grows slower, the virus is considered "susceptible" to the medication. This means the medicine will still work for that patient.