How anti-retroviral drugs work

Using anti-retroviral drugs

A person with the Human Immuno-deficiency Virus (HIV) can live healthily for a number of years. Anti-retroviral (ARV) drugs are only needed at a certain stage of the disease when a person’€™s immune system becomes too weak to fight back. Blood tests to measure the strength of a patient’€™s immune system (CD4 count) and the amount of HIV in their body (viral load) need to be done before taking ARV drugs. Doctors usually recommend ARV therapy when a person’€™s CD4 count drops to 200. ARVs cannot kill HIV, but can interfere with its life cycle by suppressing its reproduction to a point where the viral load is undetectable. This gives the body an opportunity to replenish some of its destroyed CD4 cells.

There are three main types of ARVs. All three work by inhibiting the viral enzymes, reverse transcriptase and protease, that are essential for HIV replication. There are two kinds of ARVs that inhibit reverse transcriptase group, called nucleoside and non-nucleoside analogues and one to inhibit protease. New ARVs that block HIV from entering the cells (entry inhibitors) have also been developed but are too expensive to be widely used at present.

As HIV mutates fast, the virus soon becomes resistant to one ARV drug. This is why most HIV clinicians recommend that drugs from each of the three types ‘€“ ‘€˜triple therapy’€™ ‘€“ are used. ARVs are powerful drugs that often have side-effects. Most are fairly mild and can be managed easily. However, some are severe so it is essential that a person on ARVs is well monitored by health professionals.

How ARV’s work

The Human Immuno-deficiency Virus (HIV) works by attacking our immune systems. It hijacks the CD4 cells in our body, which co-ordinate our body’€™s immune response, and makes these cells function as factories producing HIV. As our CD4 cells are depleted, our ability to fight infections is reduced.

But the breakdown of our immune system can take years, especially if we have good nutrition and a healthy lifestyle. Anti-retroviral (ARV) drugs are only needed when our immune system becomes so weak that we cannot fight common ‘€œopportunistic’€ infections. This stage of HIV infection is called Acquired Immuno-Deficiency Syndrome (AIDS).

Ideally, blood tests to measure the strength of a patient’€™s immune system (CD4 count) and the amount of HIV in their body (viral load) should be done before a person goes on to ARV drugs. When a person’€™s CD4 count drops to 200, they should start on ARV therapy.

ARVs cannot clear the body of HIV, but they can slow down its replication and   reduce its numbers until the viral load becomes ‘€œundetectable’€ in standard tests. This gives the body the chance to replenish its CD4 cells which can then fight back against opportunistic infections.

Most ARVs work by inhibiting the two viral enzymes, reverse transcriptase (RT) and protease, that are essential for HIV replication. There are two classes of ARVs that act on RT. These are called nucleoside RT inhibitors (NRTI), such as 3TC, AZT and d4T,   and non-nucleoside RT inhibitors (NNRTI), such as nevirapine and efavirenz (Stocrin).

ARVs that act against protease are called protease inhibitors. These include nelfinavir and saquinavir.

Two new classes of ARVs have also been developed. Fusion Inhibitors (FI) act to block the virus’€™s ability to fuse with the cell it is attacking. Entry Inhibitors act against HIV before it tries to enter the cells are also being developed. At present, FIs are   very expensive while EIs are largely experimental.

In order to have a sustained benefit from ARVs, a person must take a combination of three drugs ‘€“ also known as the ‘€œcocktail’€, ‘€œtriple therapy’€ or ‘€œhighly active anti-retroviral therapy’€ (HAART). Treatment with a single drug (monotherapy) as was the practice in Europe and the US in the 1980s only works for a short period before the virus outsmarts the drug and becomes resistant. Likewise, treatment with two ARVs (dual therapy) will also work for a finite, though slightly longer period, before the virus develops resistance.

The reason for resistance developing fairly rapidly is that, as HIV replicates, it makes many mistakes that results in ‘€œmutant’€ viruses. Some of these are resistant to ARVs.     If a person consistently takes their ARVs late or skips doses, the resistant mutants will multiply and become the dominant population of virus in a person’€™s body. Once resistance develops, the ARVs become ineffective. A person with resistant virus can spread their resistant HIV to anther person who has never taken ARVs before.

ARVs are powerful drugs that often have side-effects. Most side-effects are mild and dissipate a few weeks.   Some rare side-effects can be serious and life threatening.   It is essential that a person on ARVs is monitored on an ongoing basis by health professionals.

* People on ARVs seeking help can contact the Treatment Helpline Direct 082 853 0300

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