HIV-Specific Tests

Viral Load: Viral load tests -- measurements of the amount of HIV per milliliter of blood (copies/mL) -- are important tests for HIV-positive people. When used in combination with CD4 count results, viral load is useful in determining when to begin therapy and, more importantly, to determine how well therapy is working.

Don't look for this important test in your basic lab report; viral load tests are ordered separately by your healthcare provider and are sometimes conducted at different laboratories than those that perform CBCs. A viral load report will specify which test was used. Typically, labs use either Amplicor polymerase chain reaction (PCR) assays or Quantiplex branched DNA (bDNA) assays. Because these tests measure the amount of virus differently, it's recommended that the same test and, ideally, the same laboratory be used each time to get consistent results.

There is no "normal" range of HIV, since the virus isn't normally present in the body. The reference range on a viral load lab report usually lists the lowest amount of virus that the particular assay can detect. For example, the most commonly used version of Amplicor PCR can't accurately detect less than 50 copies of the virus in a millimeter of blood. If HIV can be detected, the results of the lab report will include the number of HIV copies found (10,000 copies/mL, for example). If HIV can't be detected, the virus is said to be "undetectable." This, however, doesn't mean that HIV is no longer present in the body or that the virus can no longer be transmitted to somebody else; less than 5% of HIV in the body is found in the blood. It's also important to keep in mind that PCR and bDNA can't detect very small amounts of HIV that may be present in the blood.

In terms of deciding when and how to treat HIV based on these results, the goal is simple: to keep the level of HIV as low as possible. If viral load doesn't become undetectable, or becomes detectable again after a period of being undetectable, this is usually a sign that treatment isn't working effectively and that it might be necessary to change the drug regimen being used.

Drug Resistance Tests: While viral load tests can help patients and healthcare providers determine whether or not a treatment is effective, drug resistance tests may help determine why a treatment or combination of treatments may not be working. Drug resistance tests may also be useful in choosing treatments.

There are two types of drug resistance tests: genotype and phenotype. Genotype tests are really nothing more than careful inspections of the HIV in someone's blood. If HIV doesn't appear to be responding to a drug or combination of drugs, the virus' genetic material (RNA) is examined to look for small changes, called "mutations," in its structure. While some mutations are harmless, others may cause HIV to become less sensitive to a drug designed to stop it from reproducing. Over time, this HIV accumulates additional mutations which prevent it from responding to the drug altogether. Genotype tests look for the key mutations associated with resistance to a particular drug. By finding out which mutations are present, it may be possible for patients and their healthcare providers to figure out which treatments they should start with and, if necessary, which treatments they should switch to.

Unlike genotype testing, phenotype testing directly measures the sensitivity of a patient's HIV to particular antiviral drugs. These tests measure the concentration of a drug required to inhibit viral reproduction in the test tube by a defined amount, such as 50% or 95%. This is called IC50 or IC95. IC stands for inhibitory concentration. In other words, a laboratory conducting a phenotype test is trying to determine the amount of drug needed to stop HIV from reproducing. If it only takes a standard amount of the drug to halt viral reproduction -- a concentration equal to those used by HIV-positive people -- HIV is not resistant to the drug. If higher amounts of the drug are needed to stop HIV from reproducing, HIV is considered to be less sensitive to the drug being tested (the higher the concentration needed, the less sensitive the virus is to the drug being tested). The concentration of drug necessary to inhibit virus replication is expressed in units called nanomoles (nM). For example, if the IC50 of drug-sensitive virus is 100nM and that of the test virus is 400nM, the test virus is considered to be fourfold resistant to the drug being tested. In other words, HIV in the patient is four times less sensitive to the drug. For some drugs, this would be a high-level of resistance. For other drugs, it might mean a low-level of resistance. Phenotype testing is more expensive and takes longer to perform than genotype testing.

In recent years, a lot more information about drug resistance tests has been generated by clinical trials, which means that many healthcare providers are now familiar with how to use them and how to interpret their results. Several studies have demonstrated that using genotype or phenotype testing can help keep viral load undetectable longer than simply reviewing a person's treatment history or switching a regimen based on "common knowledge" about each drug's resistance profile. What's more, drug resistance tests can help figure out which drug in a regimen is no longer working. In other words, it may be possible to switch only one drug instead of all three or four being used in a particular combination.

Therapeutic Drug Monitoring (TDM): At the present time, the doses of medications used to treat HIV are the same for all adults in most cases. For some people, however, it might be necessary to increase or decrease the doses of these drugs. For example, someone experiencing side effects might be able to take a lower dose without compromising the effectiveness of the drug. Similarly, some people, even though they are taking the standard dose, may not have enough of a drug in their bloodstream to keep HIV undetectable, which can lead to drug resistance. This is why researchers are now experimenting with blood tests to check the levels of anti-HIV drugs in the bloodstream, which is better known as therapeutic drug monitoring (TDM).

Drug levels in the bloodstream can vary from person to person for many reasons. Some people metabolize (break down) medications faster, while others metabolize them slower (genetics can play a role here). Someone with a low body weight may have high levels of a drug and someone with a high body weight may have low levels of a drug. Anti-HIV drugs can interact with food, nutritional supplements, and other drugs, which can either increase or decrease the amount of the anti-HIV drugs in the bloodstream. Anti-HIV drug levels can also increase or decrease in HIV-positive women who are pregnant, given hormonal changes and changes in body weight and size. Also, certain diseases that affect the kidneys and liver, such as hepatitis, can have an impact on anti-HIV drug levels in the bloodstream. For all of these -- and other -- situations, experts are interested in learning more about the usefulness of TDM for people with HIV.

TDM can be used to check levels of protease inhibitors (PIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs) in the bloodstream. TDM, in its current form, isn't able to check levels of nucleoside reverse transcriptase inhibitors (NRTIs) in the bloodstream. What matters most with NRTIs is the amount of drug inside cells, not the bloodstream, and most TDM tests don't have the ability to measure cellular levels of these drugs.

Because there are a number of lingering questions regarding how best to use TDM, these tests aren't routinely used or available in the United States (TDM is used regularly in many parts of Europe). As of April 2004, four laboratories in the U.S. are providing commercial TDM services -- in Buffalo, New York (The University of Buffalo [716/645-3635 ext. 245]); in Cocoa Beach, Florida (TDM Laboratories [312/784 2880]); in Van Nuys, California (POMG Laboratories [818/994-9714]); and in Washington, DC (Children's National Medical Center [202/884-2096]. TDM testing for anti-HIV drugs is expensive and isn't covered by private or public health insurance plans (including AIDS Drug Assistance Programs).

Urine Tests

Urine tests, usually known as urinalysis or urine culture, are most commonly used by healthcare providers to monitor kidney function and to test for infections in the urinary tract.

Various drugs -- including cidofovir, pentamidine, foscarnet, and amphotericin B -- can cause serious kidney damage. As a result, it's extremely important for patients on these and other potentially toxic drugs to have their blood and urine tested regularly. While looking for changes in a patient's blood levels of BUN and creatinine (discussed above), it will also be important to keep an eye out for proteinuria (protein in the urine) and glycosuria (glucose in the urine). If significant levels of either develop while someone is taking a drug known to cause kidney problems, the dose of the drug may need to be reduced or stopped altogether. Glycosuria may also be a sign of diabetes.

The presence of red or white blood cells in the urine is usually abnormal and may indicate disease processes such as bladder infection or kidney stones. Blood in the urine isn't usually a cause for alarm for women who are having their periods since blood can sometimes get into the urine specimen during collection. To make sure that urine does not contain blood, it might be necessary for a woman to repeat a urinalysis after her period is over.

Stool Tests

Call it what you will, stool (feces) is an important body substance examined by healthcare providers to check for the presence of disease-causing microorganisms, particularly parasites and bacteria. For the most part, labs use microbiology tests -- similar to microbiological blood tests -- to determine if disease-causing microorganisms are present.

For an HIV-positive patient with diarrhea, a stool test is often the first step. Labs routinely check for common bacterial and protozoal infections. Very often, these prove to be the cause of the diarrhea and most can be treated relatively easily. If the results of the stool test come back negative, the healthcare provider may need to specifically order stool tests to look for isosporiasis, microsporidiosis, and cryptosporidiosis, three relatively uncommon infections that can cause serious diarrhea in patients with substantially compromised immune systems.

Pap Smears

HIV-positive women may be at an increased risk of developing cervical disease, including cancer. Pap smears are more than 90 percent accurate in determining if cells around or in the cervix are normal or abnormal. HIV-positive women should have a Pap smear every 6 or 12 months. A Pap smear requires a doctor or other trained medical professional to lightly scrape the cervix and its surrounding area with a small spatula. The scraping is applied to a glass slide and sent to a pathology laboratory for examination under the microscope.

Another method of examining the cervix uses a colposcope. A colposcope is a microscope that can examine the cervix carefully for abnormal cell growth and tumors in their very early stages. Both Pap smears and colposcopy examinations can be performed at a healthcare provider's office or clinic.

Some healthcare providers also recommend anal Pap smears and/or anal colposcope to look for abnormal cell growth, including warts and pre-cancerous lesions (dysplasia), inside the anus. Men who have sex with men and women with a history of cervical dysplasia -- particularly if they are HIV-positive -- are at a higher risk of anal dysplasia caused by human papillomavirus (HPV).