AIDS Community Research Initiative of America (ACRIA) - Fall 2003 / Winter 2004

Accelerated Approval: The process by which the FDA rapidly approves experimental treatments for serious or life-threatening conditions.

ACTG (AIDS Clinical Trials Group): A clinical trials network of medical centers, sponsored by the National Institute of Allergy and Infectious Disease, which conducts trials of treatments for AIDS/HIV and opportunistic infections.

Antiretroviral Pregnancy Registry: A voluntary databank established by the FDA to collect and evaluate the results of exposures to antiretrovirals during pregnancy in mothers and their children.

Arm: A group of participants in a clinical trial who receive the same treatment. Participants in a controlled trial are assigned to either a "treatment arm" (people who get the drug being tested) or the "control arm" (people who get the standard treatment or a placebo).

Blinded: A method for assigning treatment regimens in a clinical trial that keeps trial participants from knowing which treatment regimen they are taking.

Combination Therapy: Using at least two drugs at the same time to treat a disease. With current HIV treatment, combination therapy usually refers to the use of at least three drugs (see HAART).

Compassionate Use: A phrase used to describe programs that provide experimental drugs on an individual basis to seriously ill people with few or no treatment options. Often, case-by-case approval must be obtained from the FDA.

Cross-Resistance: The phenomenon by which HIV (and other disease-causing organisms) that develops resistance to one drug also becomes resistant to other drugs. For example, HIV that develops resistance to one of the non-nucleoside reverse transcriptase inhibitors will also likely have resistance to other drugs in the same class.

Disease Progression: The way that a disease develops, including the specific events involved, bodily tissues or systems affected, mechanisms of damage, and the course of disease over time. HIV disease progression is usually described in terms of CD4 counts, viral load, and new or recurring opportunistic infections.

DHHS HIV Treatment Guidelines: A guidance document for the medical management of HIV disease created and periodically updated by a panel of HIV specialists, physicians, people with HIV, and community activists under the auspices of the U.S. Department of Health and Human Services (DHHS). The most recent revision to the Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents was published in July 2003. There are similar HIV guidelines that focus on pediatrics, mother-to-child transmission, and other subjects.

DNA (deoxyribonucleic acid): A double-stranded molecule that carries genetic information and that makes up the chromosomes in a cell's nucleus.

Double-Blind: A method for assigning treatment regimens in a clinical trial which keeps both trial participants and members of the research staff from knowing which participants are on which assigned treatments.

Drug Interaction: The effect that can occur when two or more drugs are used together. These include changes of absorption in the digestive tract, changes in rate of the drugs' breakdown in the liver, new or increased side effects, and changes in the drugs' activity.

DSMB (Data and Safety Monitoring Board): An independent panel of clinical research experts that reviews the results of clinical trials while they are underway. The DSMB can change or close a trial if the early results call for that.

Efficacy: The effectiveness or ability of a drug to control or cure an illness. The efficacy of an anti-HIV drug usually refers to the drugs ability to lower viral load.

Expanded Access: A program that distributes experimental drugs to people who are unable to participate in clinical trials and have few or no other treatment options.

FDA (Food and Drug Administration): The agency of the U.S. Department of Health and Human Services that regulates the testing of experimental drugs and approves new drugs and medical products based on evidence of their safety and efficacy. The FDA also regulates the safety of foods, cosmetics, and other products.

First-Line Treatment: The best starting therapy for someone who has never received therapy before. Because of the potential for the development of cross-resistance by HIV and other microbes, the choice of first-line medication(s) may affect the efficacy of later medications.

HAART (Highly Active Antiretroviral Therapy): Anti-HIV treatment that uses a combination of drugs (usually three or more) to reduce viral load to undetectable levels.

in vitro: Latin phrase for "in glass" that refers to lab experiments conducted in cell cultures grown in an artificial environment, for example in a test tube or culture plate.

in vivo: Latin phrase for "in life" that refers to studies done in humans or animals.

Lactic Acidosis: A buildup of lactic acid in the body. Lactic acid is a byproduct of the breakdown of carbohydrates. Our bodies usually clear excess lactic acid. Lactic acidosis is a rare side effect of the nucleoside analogs. Nucleoside analogs can damage the mitochondria (the power plants of cells), making them unable to clear excess lactic acid from the blood. Severe lactic acidosis can be life-threatening.

Lipids: Fats stored in the body and used for energy. Lipids include cholesterol, fatty acids, and triglycerides.

Lipoatrophy: The loss of fat stored under the skin, especially in the limbs and cheeks.

Lipodystrophy: Changes in body composition. Symptoms include fat loss in the limbs or face, excess fat in the abdomen, breasts, and upper back, increased triglycerides and cholesterol, insulin resistance, and glucose intolerance, possibly leading to a higher risk of heart disease and diabetes. There is no clear definition of lipodystrophy, and there is no one cause, although it is at least partly associated with the use of antiretroviral drugs.

Mitochondria: Structures in human cells that turn nutrients into energy for the cells. Essentially, they are the cells' "power plants."

Mitochondrial Toxicity: Damage to the mitochondria caused by factors such as heredity, aging, infections, or certain anti-HIV medications, particularly nucleoside analogs. Mitochondrial toxicity may be responsible for side effects such as muscle weakness and muscle loss, peripheral neuropathy, pancreatitis, low platelets, low levels of other blood cells, and lactic acidosis.

Monotherapy: Treatment consisting of only one drug.

Myopathy: A general term referring to any disease of muscles. Inflammation of muscle tissue, resulting in muscle weakness is a rare side effect of long-term use of Retrovir (AZT), which is also part of Combivir and Trizivir. Myopathy can also be caused by HIV disease itself.

PACTG (Pediatric AIDS Clinical Trials Group): A clinical trials network that studies treatments for infants and children with HIV and for the interruption of mother-to-child HIV transmission. The PACTG is a joint effort of the National Institute of Allergy and Infectious Diseases (NIAID) and the National Institute for Child Health and Human Development (NICHD).

Patient Assistance Program: Programs run by drug companies to provide free medications to people who have no insurance, inadequate insurance, or financial difficulties. Most programs have strict requirements, such as income no more than 300% above the federal poverty level.

Phase I Trial: The first stage in testing a new drug in humans. The studies are usually done to gather preliminary information on the chemical action and safety of the drug using healthy volunteers. Usually done without a comparison group.

Phase II Trial: The second stage in testing a new drug in humans. Performed in patients with the disease or condition being studied. The main purpose is to evaluate the activity of a drug, and to possibly provide information on how well the drug works.

Phase III Trial: The third and usually final stage in testing a new drug in humans. Used to collect information about the safety of a drug and how well it works. Once this phase is complete, the drug manufacturers may request permission from the Food and Drug Administration to market the drug.

Phase IV Trial: A large trial designed to evaluate the long-term safety and effectiveness of a drug that has been approved by the Food and Drug Administration.

Placebo: An inactive agent given as a substitute for an active agent for the purpose of comparison in a clinical trial. A placebo usually looks like the experimental treatment being studied. If a placebo is used in trials of HIV combination therapy, people taking the placebo usually get approved drugs also.

Placebo-controlled: A trial in which the effectiveness of an experimental drug is compared to that of a placebo.

Pregnancy Category: The Food and Drug Administration rates drugs in terms of their safety during pregnancy from A (safest) to X (least safe - do not use). Most medications have not been studied in pregnant women to see if they cause damage to the fetus.

• Category A - Controlled studies in women fail to demonstrate a risk to the fetus in the first trimester (and there is no evidence of a risk in later trimesters), and the possibility of fetal harm appears remote.
• Category B - Either animal studies have not shown a fetal risk but there are no controlled studies in pregnant women, or animal studies have shown an adverse effect that was not confirmed in controlled studies in women in the first trimester (and there is no evidence of a risk in later trimesters).
• Category C - Either animal studies have shown adverse effects on the fetus and there are no controlled studies in women, or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the fetus.
• Category D - There is positive evidence of human fetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (for example, if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).
• Category X - Studies in animals or human beings have demonstrated fetal abnormalities, or there is evidence of fetal risk based on human experience or both. The risk of the use of the drug in pregnant women clearly outweighs any possible benefit.

The antiretrovirals are all classified as either category B or category C drugs.

Resistance: The ability of a virus (or other germ) to become less sensitive to a drug, usually by genetic mutation. In HIV, the viral enzymes and proteins mutate, or change, so that an antiretroviral drug cannot attach to them. (see Cross-Resistance).

RNA (ribonucleic acid): A single-stranded molecule composed of nucleotides. It is similar in basic structure to half of the double-stranded DNA. In healthy cells, RNA is used to copy portions of the cell's DNA in order to produce other cell components. HIV's RNA stores the viral genes that are later converted to DNA.

Side Effect: The action or effect of a drug beyond what it is supposed to do. The term usually refers to negative effects, such as headache, nausea, or liver damage. Side effects can be expected or unexpected, desired or undesired. Experimental drugs are studied for both short- and long-term side effects. (Side effects are also referred to as adverse events.)

Statistically Significant: The probability (usually less than 5 percent) that a finding or result of a clinical trial is caused by something other than just chance.

Treatment IND (Investigational New Drug): A program that allows a drug developer to give physicians an experimental drug for people who have no other treatment options, once the drug has shown signs that it works and is safe.

Unblinded: The decision to stop the blinded or double-blinded process in a clinical trial and reveal the treatment assignment of an individual trial participant or group of participants.

Viral Load: The amount of HIV RNA per milliliter of blood. An undetectable viral load means that the number of copies of HIV RNA is less than the test is able to measure, usually less than 50 or 400 copies (depending on which test is used).

Some of these definitions are adapted from CPCRA Glossary of Medical, Statistical, and Clinical Trials Terminology by Carlton Hogan, University of Minnesota.

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