A late stage of HIV infection, characterized by a deterioration of the immune system that leaves the body vulnerable to a range of infections and cancers.
Any substance or mixture of substances intended to cause positive effects in the diagnosis, improvement, treatment or prevention of a disease. In a medical product, the chemical or mixture of chemicals that demonstrate(s) biological activity.
An unwanted effect, either measured in or reported by participants in a clinical trial. This term is used whether or not the effect is believed to have been caused by the product being studied.
An unwanted effect, or side effect, detected in clinical trial participants and attributed to the product being studied in that trial. Also applies to marketed and approved products.
acquired immunodeficiency syndrome
Proteins found in the blood and other bodily fluids that are used by the immune system to identify and counteract foreign objects, such as bacteria and viruses.
A molecule recognized by the immune system. This includes molecules specifically recognized by antibodies or by T cells. Molecules known as foreign antigens are associated with toxins, bacteria, viruses, foreign blood cells and cells from transplanted organs. The unrecognized shape of these foreign molecules triggers the immune system to produce antibodies or to activate T cells, thereby fighting an infection.
A drug that attacks a retrovirus, like HIV, by inhibiting binding to and entering into a human cell or by preventing the virus from producing more copies of itself once inside the cell. ARVs reduce the spread of virally-infected cells throughout the body.
active pharmaceutical ingredient
Class of anti-HIV (ARV) drugs that prevents the virus from attaching to a healthy host cell, thereby preventing cell infection.
Also known as a B lymphocyte, B cells are infection-fighting white blood cells that develop in the bone marrow and spleen. B cells produce antibodies, which are used by the immune system to identify and counteract foreign objects like bacteria and viruses. HIV may damage the B cells’ ability to do their job.
A clinical trial in which participants are unaware of who is included in an experimental arm (given an active drug) or control arm (given the placebo) of the study. (See also double-blind study.)
A microbicide in the entry inhibitor class prevents the virus from attaching to the host cell (lymphocyte or macrophage) by blocking the ability of HIV to interact with the CCR5 receptors on the cell surface>
Receptors on the surface of the host cells to which HIV attaches. CCR5 is the receptor on lymphocytes and macrophages and is thought to be more important in sexual transmission of HIV than CXCR4.
A protein on the outside of infection-fighting white blood cells that allows HIV to bind to and enter the cells.
In the HIV life cycle, copy DNA, or complementary DNA, is made after the virus has entered the cell and is beginning the process of replicating itself to take over the healthy cell. cDNA is formed as a copy of the HIV’s genetic material, which is single-stranded ribonucleic acid, or RNA.
Civil society organizations, or CSOs, refer to a wide range of citizens’ associations that provide benefits, services or political influence to specific groups within society. CSOs include business forums, faith-based associations, labor unions, local community groups, nongovernmental organizations (NGOs) and think tanks.
A genre or grouping of drug products that all work in a similar way. Often we refer to a class of microbicide, which indicates the way that it prevents HIV infection.
Research studies that include human volunteers. Clinical trials answer specific questions about the safety, efficacy and medical effects of a specific prevention, treatment or intervention. Carefully conducted clinical trials are required to test and seek licensure for effective disease treatments and preventions. There are typically three phases of clinical trials before the filing with regulatory authorities, sometimes followed by ongoing, post-approval trials. (See also Phase I, Phase II, Phase III, and Phase IV)
IPM’s facility responsible for producing the products used in clinical trials, including the active drug and the placebo. This refers to facilities owned by IPM or to other locations/research centers owned and operated by another manufacturer.
The abbreviation for “cluster of differentiation,” referring to a set of cell-surface molecules that are used to identify the types and stages of maturity of immune cells, for example, CD4+ T cells.
An intervention that must be applied or used near the time of sexual intercourse.
Critical Quality Attribute
A property of a drug product that should be within an appropriate limit, range, or distribution to ensure the desired quality of a product.
Occurs when resistance to one drug results in resistance to similar drugs.
civil society organization
Clinical Trial Manufacturing Facility
Receptors on the surface of the host cells to which HIV attaches. CCR5 is the receptor on lymphocytes and macrophages and is thought to be more important in sexual transmission of HIV than CXCR4.
A strategy to ensure clinical trial participants are following the appropriate procedures for using the drug product (placebo or active drug). Sometimes, this means the research center staff observes the participants use the product. Other times, the participants must keep a record of their use and return unused products. In the case of some microbicides, participants may be asked to return used applicators.
A committee of independent clinical research experts who review data while a clinical trial is in progress. The DSMB ensures that participants are not exposed to undue risk and looks for any differences in effectiveness between the experimental and control groups. The DSMB may review the data in such a way that they know which group received the drug and which group did not. This group may also recommend that a trial be modified or stopped if there are safety concerns or if the trial objectives have been achieved.
A type of cell that picks up foreign substances from the bloodstream and carries them to the immune system, activating an immune response against the invading substance.
A structured, organized method for determining the relationship between factors affecting a process and the output of that process. (ref. ICH Q8)
Deoxyribonucleic acid, or DNA, is the molecules inside cells that carry genetic information and pass it from one generation to the next. To infect a human cell, HIV must convert its genetic material, RNA, into DNA using reverse transcriptase.
design of experiment
A clinical trial in which neither the study staff nor the participants know which participants are receiving the experimental drug, the placebo or another therapy. Double-blind studies are thought to produce the most reproducible, objective results, since the researcher’s and volunteer’s expectations about the experimental drug do not affect the outcome.
The final formulated product to be tested in a clinical trial and later provided to consumers. It includes the active pharmaceutical ingredient(s) along with other non-active components or excipients.
Drug Safety Monitoring Board
A product’s ability to achieve a desired effect. In the case of microbicides, efficacy refers to the ability of the product to reduce the risk of becoming infected with HIV and perhaps other pathogens.
A class or type of anti-HIV drugs designed to disrupt the ability of HIV to enter a host cell through the cell's surface.
A disease that has spread rapidly through a segment of the human population in a given geographic area.
The study of the frequency and distribution of disease in human populations.
A necessary component of a drug product other than the active ingredient. These components may include substances to make the product stable over time or resistant to heat and humidity. Excipients also are required to create the physical nature of the product. These could be fillers to make up a solid oral tablet or gel-like substances in the case of some microbicides. The excipient in a drug product is like the chocolate in a chocolate cake. To make the cake itself, there are a number of active ingredients, like flour and eggs, but without the chocolate, the chocolate cake is not a finished product.
The form in which a drug or product is tested and later supplied to consumers. Common formulations are tablets, soft-gel capsules, oral liquids, injected liquids, creams and dermal patches. Microbicides can be in created in the form of rings, gels, films, tablets or others yet to be developed.
This stage in the HIV life cycle occurs after the attachment stage. The viral envelope, which is like the shell or skin of the virus, fuses with the host cell’s membrane, or skin. As the cell and the virus fuse to become one entity, the contents of the virus are released into the cell.
Good Clinical Practice
A protein that has small units of sugar molecules bound to it, often part of the cell’s membrane. Cell-surface glycoproteins provide a mechanism for cells to be recognized by each other and are involved in the immune response that shields the body from infection.
Good Manufactoring Practice
Also referred to as GCP, Good Clinical Practice is an international quality standard issued by the International Conference on Harmonisation (ICH) for how clinical trials involving people should be conducted.
Or GMP, Good Manufacturing Practice is an international set of guidelines that serve as the standard conditions for how drugs and medical devices should be manufactured.
A type of glycoprotein on the surface of HIV that binds or links to receptors on the host cell’s surface.
A type of glycoprotein embedded in the envelope, or shell, of HIV that helps the virus fuse with the host cell.
Highly Active Antiretroviral Therapy
Amount of time needed for half of the amount of drug administered to be eliminated from the body.
A virus that causes cold sores or fever blisters on the mouth or around the eyes and that can be transmitted to the genital region. The virus can become inactive (latent), and symptoms disappear. Stress, trauma, other infections or a suppressed immune system can reactivate the virus in a body, causing the symptoms to return.
A virus that causes painful sores around the anus or genitals. The virus can become inactive (latent), and symptoms then disappear until it becomes active again in the body. HSV-2 may be transmitted either sexually or from an infected mother to her infant during birth.
The name given to treatment regimens that aggressively inhibit the spread of HIV in the body. The usual HAART regimen combines three or more anti-HIV drugs from at least two different classes.
Histology is the study of microscopic anatomy of cells and tissues in animals and plants. A histological study of cells or tissues is often used to help diagnose a disease or illness.
Human Immunodeficiency Virus. The virus that causes AIDS. Human immunodeficiency virus, or HIV, is in the retrovirus family of viruses. There are two types of HIV — HIV-1 and HIV-2. HIV-1 is responsible for most HIV infections throughout the world, whereas HIV-2 is found primarily in West Africa.
Herpes Simplex Virus 1
Herpes Simplex Virus 2
Research conducted in the laboratory with cultured, living cells or purified cellular components, i.e. in a test tube.
Research conducted in living organisms (humans or animal models). Also see preclinical research.
The number of new cases of a disease over a period of time (e.g., the annual number of new cases of HIV in a country). Incidence is often expressed as a percentage of a population. (Contrast with prevalence)
investigational new drug
An ongoing process of counseling and communication through which potential clinical trial participants learn about the risks and benefits of participating in the trial so that they can decide whether or not to participate voluntarily.
The last stage in the HIV life cycle when viral cDNA, which is created based on viral RNA, enters the host cell nucleus and becomes incorporated into the host cell’s genetic material, permanently “infecting” that cell.
An application filed by a sponsor with the FDA requesting approval to conduct clinical trials. The IND includes detailed descriptions of all trial phases, protocols, Institutional Review Board (IRB) members, and investigators.
Types of white blood cell in the immune system. Many of these cells are involved in protecting the body from infection, such as B cells, T cells and natural killer (NK) cells. T cells, or T lymphocytes, are directly involved in the HIV infection cycle.
Derived from the Greek words for “big” and “eat,” macrophages are a type of disease-fighting white blood cell that engulfs and then destroys foreign invaders, like viruses, and calls other immune system cells to action.
The way in which a drug or product works. In the case of a microbicide, it is the way in which the active ARV component protects healthy cells from HIV infection.
A natural or man-made substance that kills microbes, most often bacteria or viruses. Researchers are developing microbicides to reduce the transmission of HIV during sexual intercourse.
Microbicide products based on the same antiretroviral (ARV) drugs used successfully to treat HIV and to prevent mother-to-child-transmission (PMTCT) of HIV. The first next-generation microbicide was proven efficacious at preventing HIV infection by the CAPRISA 004 trial.
non-nucleoside reverse transcriptase inhibitor
A class of ARV-based compounds that prevents HIV infection by stopping replication of HIV’s genetic material. NNRTIs bind to the reverse transcriptase enzyme, a protein that HIV needs to convert its genetic material, RNA, into cDNA. Without the enzyme, HIV replication is impossible, and the virus cannot spread.
An intervention that can be applied or used at regular time intervals (e.g., once daily or once monthly) independent of the last time of sexual intercourse.(Contrast with coitally dependent)
Private, not-for-profit organizations that pursue activities to relieve suffering, promote the interests of the poor, protect the environment, or undertake community development.
A class of ARV-based compounds that prevents HIV infection by blocking the production of viral cDNA. Once a molecule of the NtRTI is incorporated into a growing cDNA chain, that chain is blocked, preventing the virus from producing functional cDNA to infect the cell.
product development partnership
A study of the reactions between drugs and living structures. Pharmacodynamics measures the effects that a given drug has on various systems in the body.
The study of what the body does to an administered drug over a period of time. Pharmacokinetic studies measure the absorption, distribution, metabolism, and excretion of a drug.
The study of the origin, chemistry, and uses of drugs and their effects on the body.
A closely monitored clinical trial of a product conducted in a small number of healthy volunteers. A Phase I trial is designed to determine the product’s safety in humans, any reactions it may cause within the body and any side effects associated with increasing doses.
A controlled clinical study of a product to identify common short-term side effects, risks associated with a product and, in some cases, a first measurement of potential efficacy. Phase II trials enroll volunteers who have the same characteristics as people who would be enrolled in the later Phase III trials. Phase II trials enroll up to several hundred participants and often have a number of different testing “arms,” or groups.
A controlled clinical study, sometimes known as a “proof-of-concept” trial. These trials provide valuable information on the safety and potential efficacy of an experimental product.
A large, controlled study to determine efficacy, or the ability of a product to produce a desired clinical effect (e.g., to prevent HIV). These trials also gather additional information about safety, which is needed to evaluate whether the product should be approved and distributed. Phase III trials usually include several hundred to several thousand volunteers at multiple testing centers.
Post-marketing studies conducted after a new treatment is approved by a government regulatory body. These post-approval trials have several objectives, including comparing the drug with other drugs already in the market, monitoring the drug's long-term safety and effectiveness and determining additional potential uses for the drug.
A small-scale batch of a drug product produced in preparation for a full-scale batch. Pilot scale batches help researchers develop techniques that will be required to create much larger batches needed for clinical trials and, later, manufacturing of approved products.
A substance that looks, smells and feels just like the active drug, but does not have any active ingredients (APIs) in it. In the case of microbicides, the placebo gels, rings or other formulations will look just like the active gels, rings or other formulations, but will not have the active drug substance. Placebos are required in clinical trials to serve as a comparison so that researchers can determine if the investigational product had a statistically-significant effect.
The abbreviation for prevention of mother-to-child transmission of HIV infection, also called “vertical transmission.”
Polyanion microbicides attract the positively charged HIV. It was hoped that polyanion-based microbicides would prevent HIV from binding to and entering healthy target cells. To date, no microbicides based on polyanions have been found to be efficacious against HIV.
Before any testing can be done with human volunteers, researchers must first complete a large number of tests in the laboratory (in test tubes) and in animal models. These tests are critical in determining if an experimental product is safe enough to test in humans. IPM is committed to performing only the minimum amount of animal testing necessary to meet safety requirements established by regulatory bodies. Safety information from preclinical trials is used to support an Investigational New Drug (IND) application .
The number of people in a population infected with a particular disease at a given time. Prevalence can be thought of as a snapshot of all existing cases at a specified time. (Contrast with incidence, which measures the number of new cases).
A model that brings together private sector technologies and public sector resources. IPM’s PDP model is built on successful collaboration between IPM and a number of parties, including: public and private donors, pharmaceutical companies, scientific research organizations, global policy makers and non-governmental and international organizations.
The detailed plan for a clinical trial that states all aspects of trial design, including the goals and objectives of the trial, as well as how it will be carried out.
The externally planned actions that ensure that a product being manufactured or a clinical trial being performed meets the requirements set forth by the Good Clinical Practice (GCP) guidelines and any regulatory requirement(s).
The process of assigning trial participants to either a treatment group where they receive the drug product, or a control group where they receive the placebo. A methodology is employed that applies an element of chance to determine the assignments. This method reduces bias.
A study in which the participants are assigned by chance to separate groups that compare different treatments. Neither the researchers nor the participants can choose group assignments. Using chance to assign people to groups means the treatments they receive can be compared objectively.
A molecule on the surface of a cell that serves as a recognition or binding site for antigens, antibodies, hormones or other cellular or immunologic components. When chemical messengers bind to receptors, various cellular functions are activated or inhibited. Viruses enter host cells by interacting with receptors on the cell surface, and many drugs exert their effects by binding to receptors, thereby altering cellular function.
The group or groups responsible for making sure that all laws regulating research, testing, and other stages of drug development and approval are upheld during clinical trials and research and development for a new product. Regulators also establish what will be required for each new product to be approved for use. The Food and Drug Administration (FDA) is the key regulatory body for new drug products in the United States.
The stage in the HIV life cycle when the genetic material of the virus is copied using the reverse transcriptase enzyme. This stage occurs after fusion. Once the virus has permanently integrated into the host cell, the virus can then duplicated using the cell’s own biological processes.
Some microorganisms, including viruses like HIV, adapt so they can survive and multiply in the presence of drugs that would normally weaken or kill them. A drug-resistant HIV strain can multiply in the presence of one or more ARV drugs because of its genetic make-up.
HIV and other viruses that carry their genetic material in the form of single-stranded RNA rather than the double-stranded DNA . Retroviruses also have the enzyme reverse transcriptase that can copy RNA into cDNA, leading to infection of the host cell.
An HIV enzyme used by the virus to copy its RNA into cDNA, to allow for its incorporation into the host cell DNA.
A class of microbicides that works by preventing the action of the reverse transcriptase enzyme.
The process during viral replication when the HIV enzyme reverse transcriptase converts single-stranded viral RNA into double-stranded DNA so that the HIV genetic material can be integrated into the human cell. See also viral replication.
Also called RNA, ribonuclei acid is a type of macromolecule that stores and transfers genetic information. Although DNA is the primary genetic material of mammalian cells, RNA is the genetic material for some viruses, including HIV.
A product’s safety is measured by the magnitude of its measured harmful effects when it is administered. A safe product is one that has limited harmful effects at the dose to be used in the target population.
Transition from small-scale to production of larger and larger batches of material, eventually leading to processes that support manufacturing of industrial quantities of drug product.
A term used to indicate that an individual has become infected with HIV. Biologically, it refers to the development of antibodies to HIV, which is measured by clinicians as a biomarker of HIV infection. When people develop antibodies to HIV, they “seroconvert” from antibody-negative to antibody-positive (from HIV-negative to HIV-positive).
Also referred to as expiration dating period, the shelf life is the time period during which a drug product is expected to remain effective, provided that it is stored under the conditions defined on the container label.
small inhibitory RNA
A visit held prior to participant enrollment at a research center. The purpose is to acquaint all research center personnel with the relevant aspects of the trial prior to any participant enrollment. Components of this discussion include the clinical trial protocol, case report forms, missed visits, Institutional Review Board (IRB) practices, Institutional Ethics Committee (IEC) reporting requirements, adverse event reporting, etc.
site initiation visit
Small inhibitory RNA, or siRNA, is artificially created RNA [link to “RNA” entry] that prevents naturally occurring RNA from translating into protein. siRNA can be used as an effective tool to study biological processes in the laboratory. Some researchers are exploring the potential to use siRNA for disease treatment.
These are long-term, intermediate and accelerated studies used to establish or confirm the shelf life of a drug product or to make sure the drug product is still active and potent under a number of environmental conditions.
A basic process that a health-care provider or clinical trial investigator should follow for a certain type of patient or illness.
Small, disease-fighting white blood cells (also known as T lymphocytes) involved in immune defense. T cells include CD4 cells and CD8 cells, which are both critical components of the body’s immune system. T cells are the main target of HIV in the blood, and they act as the host that the virus needs in order to replicate. Because it targets and “hijacks” immune cells, HIV is particularly destructive on the immune system.
The substance or mixture of substances in which the active ingredient in a drug product is prepared. Vehicles are typically liquids in which the active ingredient can be dissolved effectively into a homogeneous solution. Examples of vehicles are phosphate-buffered saline (PBS), sucrose-phosphate-glutamate (SPG), normal saline and hydroxyethylcellulose (HEC). HEC is a commonly used vehicle for microbicide gels.
The first stage in the HIV life cycle, in which the virus attaches to the host cell.
The stages of the HIV life cycle beginning when the genetic material of the virus is copied into DNA using the reverse transcriptase enzyme and ending with the replicated virus being released from the human cell. In the viral replication process, HIV first integrates its genetic material permanently into the host cell, then duplicates itself using the cell's own biological process.
A mature infectious virus particle existing outside a cell.