Currently, the highly active antiretroviral therapy (HAART) is being administered to HIV-1 infected patients. HAART utilizes three anti-HIV drugs- reverse transcriptase inhibitors (RTI’s), non-nucleoside analogue reverse transcriptase inhibitors (NNRTI’s), and protease inhibitors. Although neither of these drugs actually kills the virus, the administration of a combination of these drugs reconstitution of some naïve CD4 T cells, suppresses virus replication, and reduces the rate of opportunistic infections.

. Once the HIV virus has infected a human cell, it utilizes an enzyme, reverse transcriptase, to convert its genetic code to a form that can be incorporated into the host's DNA. The RTI drugs, including AZT, ddc, and ddl, prevent viral DNA production by incorporating themselves into the newly forming DNA (Worth and Volberding, 1994). Once the newly produced DNA chain is terminated, further viral DNA production is suppressed because the altered structure of the viral DNA is unable to be replicated.

After HIV invades a human cell, it utilizes the enzyme, reverse transcriptase, to convert its genetic code into a form that can be incorporated into the host's DNA. The NNRTI drugs, including neviraphine and loviride, block this mechanism by attaching themselves to reverse transcriptase (Connolly and Jenkins, 1994). This prevents the enzyme from interacting normally with the viral RNA to produce viral DNA. Consequently, viral DNA production is halted.

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Obtained from Fields, B.N., et al., 1996. Fundamental Virology

Protease is critical for the production of infectious, mature virus particles. It cuts new viral multi-proteins into individual internal core proteins that enable the virus to become mature infectious. The protease inhibitors bind to protease to block the active site where protein cutting occurs. Protease inhibitors irreversibly bind to protease, rendering it inactive. As a result, the immature viruses is not cut and structured correctly. The viral RNA is not properly stabilized and the viral core will not be made ready for the entry into the cell. Thus, the virion remains non-infectious (Connolly and Jenkins, 1994).

For a complete list of approved drugs for HIV/AIDS or AIDS-related conditions, please visit the Food and Drug Administration's website at http://www.fda.gov/oashi/aids/stat_app.html

With the introduction of HAART, many HIV-infected individuals have experienced a reconstitution in their immune system. However, the success of this treatment requires the adherence (or compliance) to the complicated dosing schedule. Many individuals fail to remember to take several tales at specific times of the day, sometimes with food. Each time a dose is missed or delayed, HIV has the opportunity to reproduce faster, increasing the chances of mutations to make it resistant to treatment. Consequently, the patient must take increased drug concentrations to prevent replication, IC100. Eventually, the IC100 will rise above the maximum drug concentration in the body and the drug will have no affect on viral replication (Broers, et. al, 1994). As a result, the viral load increases.

Therefore, treatment recommendations should be tailored to an individuals's assessment of their ability to manage different dosing schedules and dietary requirements for the different drugs. However, inadequate social and economic resources have made the monitoring and education of this treatment extremely difficult (Singh, et. al, 1996).

HIV infection is characterized by high rates of viral replication, resulting in a high frequency of viral mutations and different strains. The mutation rate in HIV is high because the enzyme responsible for copying the genetic code makes many errors. As a result, there is a depletion of CD4 cells and disease progression (Wei, et. al, 1995). Although some mutations may kill the virus, many others cause increased virulence, faster replication, and increased cytotoxicity or reduced sensitivity to antiviral drugs (Ho, et. al, 1995).

Resistance can develop against all anti-HIV drugs and drugs to treat opportunistic infections. The virus becomes resistant by acquiring a mutation that desensitizes it to drug action, but does not damage itself. Since HIV mutations happen frequently at random, an untreated HIV-infected individual will have a number of strains of the virus, some of which may be naturally resistant to different antiretroviral drugs (Frost, et. al, 1994).

However, before treatment is started, the mutant or resistant strains are less frequent and the natural strain predominates as it replicates more efficiently. This strain is better suited to its environment. The introduction of HAART changes this environment by inhibiting sensitive strains and giving drug-resistant mutants a competitive advantage. When a drug modifies the environment, one of the less frequent HIV strains multiply while the dominant strain is inhibited. The speed of this resistance depends on the extent of genetic variation in the virus before treatment (Kellam, et. al, 1994).

Therefore, the goal of HAART is to suppress viral replication, inhibit the number of mutations, and limit the development of resistant variants. With HAART, resistance should take longer because a virus strain resistant to one drug could be sensitive to another. The virus must acquire multiple mutations to overcome the action of two or more drugs simultaneously and this is highly unlikely to occur. Thus, the administration of HAART is the most effective treatment known to keep the viral load to a minimum (BHIVA Guidelines Co-ordinating Committee, 1997).

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