Virtual Medical Centre

Antiretroviral Therapy Anti-HIV Drugs

• What are Antiretrovirals?
• How do Antiretrovirals Work?
• Nucleoside reverse transcriptase inhibitors (NRTIs)
• Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
• Protease inhibitors (PIs)
• New Antiretrovirals
• What are Antiretrovirals used for?
• When to start Antiretroviral Therapy?

What are Antiretrovirals?

Antiretrovirals (ARVs) or anti-HIV drugs, are medications used to destroy the HIV virus. HIV is the virus that causes HIV/AIDS disease. HIV-associated illnesses and deaths have been substantially reduced in the last decade following the introduction of these drugs. As a result the quality of life and life span of HIV patients has been significantly improved. The combined use of these drugs is known as Highly Active Anti Retroviral Therapy (HAART).

How do Antiretrovirals Work?

There are different classes of ARVs and each class work differently. Generally, ARVs work by interfering with viral duplication so that they do not make many copies. The commonly available ARVs work by blocking the viral enzymes that are essential for their multiplication. There, once the virus is inside the cells and is in the process of multiplication, the ARVs bind with the viral enzymes and thus block it, as a result the viral multiplication process is halted. The HIV virus has three enzymes that are essential in the later steps of the virus's life cycle: reverse transcriptase, integrase and protease. The ARVs are generally named after the enzyme it blocks; therefore we have reverse transcriptase inhibitors and protease inhibitors (PIs). Integrase inhibitors are still under development. The reverse transcriptase inhibitors are of two groups depending on whether it has a nucleoside molecule, these are; Nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). Here is a brief description of each,

Nucleoside reverse transcriptase inhibitors (NRTIs)

Nucleoside reverse transcriptase inhibitors (NRTIs) were the first antiretroviral drugs to be used to treat HIV infection. They work by halting the multiplication of the virus by stopping the elongation of new DNA chains. Examples of NRTIs include:

• Zidovudine (AZT)
• Stavudine (d4T)
• Didanosine (DDI)
• Zalcitabine (DDC)
• Lamivudine (3TC)
• Abacavir (ABC)
• Emtricitabine (FTC)

Non-nucleoside reverse transcriptase inhibitors (NNRTIs)

The NNRTIs are structurally different from the NRTIs and work by binding directly to the reverse transcriptase enzyme, thereby interfering with its activity. Examples of NNRTIs include:

• Nevirapine (NVP)
• Efavirenz. (EFV)

The important thing to note in this class of drugs is that there is a high degree of cross resistance, i.e. resistance to one drug in this class can cause resistance to every other drug in the class. Even those drugs not used by the patient but still in the same class are affected, therefore rendering them useless to the patient.

Protease inhibitors (PIs)

Protease inhibitors work by blocking the enzyme protease which is necessary for the final processing of virions before maturing into the infectious virus. These drugs therefore stop the maturation of the virus into its infectious form. Examples of PIs include:

• Saquinavir (SQV)
• Indinavir (IDV)
• Ritonavir (RTV)
• Amprenavir (AMP)
• Lopinavir-ritonavir (LPV plus RTV)
• Atazanavir (ATV)

New Antiretrovirals

The new ARVs work by mechanism outside the cells, unlike the already available ARVs which work by mechanisms inside the infected cells. These new drugs act by stopping the entry of HIV virus into the cell, thereby halting the very first step of HIV multiplication. 3 steps are required for the entry of the virus into the cell: attachment, binding and fusion. New drugs are now under way for each of these processes. Examples include:

• CD4 and gp120 inhibitors
• CCR5 inhibitors

Fusion inhibitors - known as enfuvirtide (fuzeon - T-20) are already approved for use in USA, Canada and Europe.

What are Antiretrovirals used for?

The goals of treatment with HAART are to;

• Prolong the survival of HIV infected individuals
• Preserve, enhance, or reconstitute the immune system and therefore reduce opportunistic infections
• Suppress HIV replication and therefore prevent disease progression
• Reduce ill health and improve quality of life

ARVs are not a cure for HIV, however when used properly can tremendously improve quality of life.

When to start Antiretroviral Therapy?

HIV status needs to be confirmed before starting ARVs. Beginning HAART is not a medical emergency and therefore time should be taken to adequately prepare the individual before starting therapy. Such preparations include discussion about the drugs, the need for lifelong therapy, implications for poor adherence to treatment and the need for ongoing care and support. Before starting treatment the following tests need to be done in order to identify suitability of the individual for treatment and to monitor the progress of the treatment once started;

• Complete clinical examination
• Full blood count (hemogram)
• Chest X Ray
• Weight and height
• Viral load

HAART should be started if the individual has;

• Severe HIV symptoms or AIDS defining illness
• Asymptomatic but with CD4 count of less than 200 cells/mm3
• Asymptomatic with CD4 count of more than 350 cells/mm3 but with viral load of 100,000 copies/ml

Therapy can be postponed for those with a CD4 count of under 350 cell/mm3 and viral load of over 100,000 copies/ml ARV's regimen The recommended regimens that has shown to be highly effective are

• 1 Non-nucleoside reverse transcriptase inhibitors (NNRTI) + 2 Nucleoside reverse transcriptase inhibitors (NRTI) (i.e. EFV + AZT+ 3TC) or
• A Protein inhibitor (PI) + 2 Nucleoside reverse transcriptase inhibitors (NRTI) (i.e. LPV/RTV + AZT+3TC)