— A biological agent that causes disease or illness to its host organism. The most common pathogens to affect humans are bacteria (e.g. salmonella), viruses (e.g. influenza), protozoa (e.g. malaria), fungi (e.g. yeast), and parasites (e.g. tapeworm).
— Unlike bacteria, a virus cannot reproduce on its own. It must get inside a host cell and hijack its systems to do that. Some viruses can exist inside the body in a dormant state where it reproduces at a low level causing few clinical symptoms. The same virus can switch on to an active state marked by aggressive reproduction in the order of billions of virus copies per day. While many drugs exist to kill bacteria (antibiotics), very few antiviral drugs are known.
— The acronym for human immunodeficiency virus. Like influenza or hepatitis, it is a virus that infects humans. HIV is exceptional in three ways: (1) it mainly targets certain cells of the immune system, (2) it is lethal to the host cell and (3) it mutates very rapidly.
HIV types subtypes and CRFs
— HIV is not just one virus, it can be divided into two major types, HIV-1 and HIV-2. HIV-1 viruses may be further divided into four groups, M, N, O and P. The HIV-1 group M viruses are the most common ones, and have caused more than 90% of all known HIV infections. Group M can be further subdivided into subtypes and circulating recombinant forms (CRFs). There are nine group M subtypes and more than 50 CRFs known today. As the virus continues to spread and mutate, new subtypes and CRFs will appear.
— The human immune system has three main lines of defense: physical, innate and adaptive. Physical barriers like skin and mucous membranes keep pathogens from entering the body in the first place. They are the first line of defense. If a pathogen breaches these barriers then the innate immune system provides an immediate but nonspecific response such as inflammation and fever. If the intruder survives the innate response then the adaptive system will start to study the pathogen over the course of the infection to find its weak point and eliminate it. It will use immunological memory to identify this pathogen should it return and mount faster and stronger attacks against it.
— Many different types of cells are involved in the immune response. One group of cells that is vital to the immune system are called T-cells. T-cells are a type of lymphocyte. Lymphocytes are a type of white blood cell. There are several different types of T-cells, each playing a different role in the body’s immune response.
— A type of T-cell, also known as “Helper T-cells.” Helper T-cells regulate both the innate and adaptive immune responses and help determine which types of immune responses the body will make to a particular pathogen. These cells do not kill infected cells or pathogens directly. Instead, they are the brains of the operation, controlling the immune response by directing other cells to perform these tasks. If the CD4 cells were lost, the body would be completely vulnerable because the other systems of cells wouldn’t know what to do. HIV mainly targets CD4 cells. The virus gets inside the cell and uses it to produce more viruses before destroying its host. When HIV is active, an exponential effect takes place. It is only a matter of time before the CD4 population is rendered to such a low level that they are completely ineffectual. HIV infection leads to low levels of CD4 cells through three main mechanisms: 1) the virus killing its host cell directly; 2) increased rates of self-destruction (apoptosis) in infected cells; and 3) killing of infected CD4 cells by immune cells (CD8 lymphocytes) that recognize and kill infected cells.
— Measures the number of CD4 T-cells in the blood to gauge the strength of the immune system in the presence of HIV infection. CD4 has been the primary indicator doctors have used to monitor the overall condition of the patient’s immune system. The test is usually simple to perform and relatively cheap to administer which has lead to its widespread use. The test has two main limitations with regard to HIV management. There are many factors, other than HIV activity, that affect the amount of CD4 T-cells present in the blood at any given time. So the doctor cannot be sure if the CD4 value is caused by HIV activity or other factors. Second, it can take up to 6 months for HIV activity to be reflected in the CD4 count.
— While CD4 measures the body’s reaction to the virus, viral load measures the number of virus particles in the blood directly. Measurements are usually expressed in number of RNA copies per milliliter of blood. A low viral load is usually between 200 to 500 copies, depending on the type of test used. This result indicates that HIV is not actively reproducing and that the immediate risk of disease progression is low because the HIV is in its dormant state. A high viral load can be anywhere from 5,000 to 10,000 copies and can range as high as one million or more. This means the virus is active and the disease will progress. The viral load test is a more reliable indicator of viral activity than the CD4 test and a more reliable indicator of disease progression. Historically, the test has had one main drawback: While a mainstay of treatment in developed nations, it has been more difficult to perform in resource-limited settings — the delicate test equipment requires laboratory conditions that are uncommon in resourcelimited clinics.
— When HIV has diminished a person’s CD4 T-Cell count to less than 200 cells/µl (bringing the proportion of CD4 T-Cells to other lymphocytes below 14%) then the person’s immune system is considered to be incapable of mounting a viable defense against invading pathogens. HIV-infected people in this position are classified medically as having acquired immunodeficiency syndrome (AIDS). AIDS is the end game of HIV infection. Just as the virus kills the host CD4 cell, the disease kills the host organism by leaving it entirely vulnerable to the millions of pathogens that assail the body each day. Once the HIV patient gets to this level of immunological vulnerability, they will typically die of opportunistic infections or tumors within 9.2 months if left untreated.
— An acronym that stands for antiretroviral drugs. These are the drugs used to manage HIV infection. While there is no cure for HIV, these drugs have been successful in slowing the disease’s progression by interfering with the virus at different stages in its development. There are over twenty ARVs on the market today, but only a handful of these are available to patients in developing nations. In most of these countries, there are two main combinations of drugs given to patients, referred to as first line and second line treatment. The drugs used in second line treatment are around eight times more expensive than first line treatment — an important consideration in resource-limited environments. Today, the prevailing logic is to start first line ARV treatment as soon as HIV becomes active, which can be several years from the time of infection. To avoid creating and spreading resistant strains of HIV, it is further suggested to stop first line ARV treatment as soon as the patient stops responding to it and switch to second line. Eventually this too will fail as the virus develops resistance to second line treatment. For most patients in resource-limited settings, once this point is reached no further treatment is available to hold HIV activity at bay.
— The life cycle of HIV is about a day and a half. During that time it will enter a cell, change the host cell DNA, create copies of itself and release those copies into the blood stream to infect other cells. When the HIV is making copies of itself, it lacks a common proofreading enzyme. This encourages copying mistakes. These mistakes are called mutations. The combination of a short life cycle and high error rate causes HIV to mutate very rapidly. This results in a great genetic variance among HIV. Most of the copying errors will convey no advantage to the mutant. But some errors will result in advantages that make the mutant insensitive to the current ARVs used. This will give that mutant a survival advantage allowing it to give rise to a generation of resistant viruses.
— A vaccine is created from compounds that can help the body recognize and destroy pathogens such as bacteria or viruses. The vaccine stimulates an immune system response to the threat. No vaccine for HIV is available today, but there are several ongoing studies around the world working to find one. The possibility of ever producing a vaccine is questioned by many due to HIV’s high mutation rate.
— Infection with HIV occurs by the transfer of blood, semen, vaginal fluid, pre-ejaculate, or breast milk. Within these bodily fluids, HIV is present as both free virus particles and viruses within infected immune cells. The three major routes of transmission are unprotected sexual intercourse, contaminated needles and transmission from an infected mother to her baby at birth, or through breast milk.