HUMAN IMMUNODEFICIENCY VIRUS (HIV)

The Human Immunodeficiency Virus (HIV) belongs to a class of viruses known as the retroviruses. These viruses are known as RNA viruses because they have RNA as their basic genetic material instead of DNA. The retroviruses are unable to replicate outside of living host cells, because they contain only RNA. However, they have the enzyme reverse transcriptase that can make DNA from the RNA and allow them to integrate into the host cell genome. The retroviruses are composed of three subgroups, two of which are pathogenic to humans. They are the oncarnovirus subgroup and the lentivirus (meaning, slow virus) subgroup. The Human Immunodeficiency Virus, which belongs to the lentivirus subgroup, is further divided into two types based on the diseases they produce. The HIV-1 produces the acquired immunodeficiency syndrome (AIDS), while the HIV-2 produces a similar disease that is at present, largely restricted to West Africa.

The genetic material of the HIV virus consists of two short strands of RNA about 9,200 nucleotides long, enclosed in an outer lipid envelope. A viral glycoprotein (gp120) is displayed on the surface of the envelope. This protein recognizes and binds to the CD4 receptor on T-helper cells. The HIV genome contains a long terminal repeat (LTR) and the gag, pol, env, and tax/rex genes. The LTR helps in the integration of the virus into the host cell DNA. The gag gene codes for the proteins that make up the outer core or capsid while the env gene codes for the envelope glycoprotein including the outer envelope glycoprotein (gp 120) and the transmembrane glycoprotein (gp141). The major proteins coded by the pol gene are the reverse transcriptase, protease, and the integrase. The tax/rex gene codes for certain factors that have a regulatory role.

The HIV infects cells that have the CD4 receptor molecule on their surface. In macrophages and cells lacking this molecule, an alternate receptor molecule (such as the Fc receptor, or the complement receptor site) may be used for entry of HIV. The immune cells such as the blood monocytes, macrophages, T cells, B cells, natural killer (NK) cells, dendritic cells, hematopoietic stem cells, etc are the primary targets of HIV infection.

After entering the body, the virus attaches itself by fusion to a cell with the appropriate CD4 receptor molecule. On gaining entry into the cell, the viral particle uncoats from its envelope and releases the RNA. The reverse transcriptase encoded by the pol gene, reverse transcribes the viral RNA into DNA, and the integrase enzyme (also coded by the pol gene) inserts the HIV proviral DNA into the genomic DNA of the host cell. The HIV provirus is replicated by the host cell and transcribed to produce new progeny RNA molecules. The infected host cells either release the new HIV virions by lysis, or the viruses can escape by surface budding. These go on to infect additional host cells.

The primary target of the HIV is the immune system itself, with a special affinity for CD4 (T-helper) cells. Following infection, there is a latent phase during which the viral replication continues actively, accompanied with a progressive destruction of the CD4 cells. During latency, there are enough immune cells remaining to provide an immune response and fight infections. Eventually, when a significant number of T cells are destroyed, and the rate of production of the cells cannot match the rate of destruction, there is a loss of both cell-mediated and humoral immunity. This failure of the immune system leads to the appearance of clinical AIDS. The patients generally die of secondary causes such as Kaposi's sarcoma (a rare form of cancer that occurs in HIV-infected individuals) or bacterial and fungal infections.

Primary HIV infection may go undetected in more than half the cases, because the symptoms produced are mild and they subside quickly. This is followed by a clinical latent period, which could last on an average 8–11 years. The latency period varies from person to person and depends on a variety of factors including the person's health status and life style. In cases of acute HIV infection, the most common symptoms are fever, swelling of the lymph glands, a red, diffuse rash all over the body, sore throat or upper respiratory infection, muscle ache, diarrhea, and headache. These symptoms subside in a couple of months. Within three months of infection, the body mounts an additional immune response to the virus, and detectable levels of antibodies are seen. Both humoral and cell-mediated immune responses play a role. There is a decline in the viral counts and the levels of CD4 T-helper cells increase. In rare cases, it may take as long as six months for the immune response to develop. Therefore, the Centers for Disease Control (CDC) recommends testing for HIV at six months after the last possible exposure to the virus (through unprotected sex or sharing needles).

HIV is primarily spread as a sexually transmitted disease. However, one can also acquire the virus through either intravenous drug use or transfusions. The virus can be present in a variety of body fluids and secretions, but the presence of HIV in blood, and genital secretions, and to a lesser extent breast milk, is significant for the spread of HIV. In addition, HIV infection can be acquired as a congenital infection during birth or in infancy. Mothers with HIV infection can pass the virus either transplacentally at the time of delivery through the birth canal or through breast milk. The diagnosis of clinical AIDS often occurs because of the presence of rare diseases such as Kaposi's sarcoma, pneumonia, or other serious recurrent infections. The patient's lifestyle, and medical history could also provide clues. Laboratory diagnosis of the infection is based on serology, measuring the antibodies to HIV using ELISA. Positive results are further confirmed with another test known as a Western Blot. Together, the two tests are more than 99.9% accurate.

No vaccines are currently available to prevent infection by HIV. However, scientists and researchers the world over are working on making a vaccine to HIV and have some interesting leads. The drugs used to treat HIV fall into three categories: the nucleosides, non-nucleosides, and the protease inhibitors. The nucleoside and non-nucleoside inhibit the reverse transcriptase enzyme, while the third category of drugs inhibits the enzyme protease. These drugs are given in combinations of two or three to attack the HIV in different ways.