Antiretroviral Therapy in the Treatment of HIV and AIDS

In the battle against AIDS, the best tactic for the treatment of HIV is antiretroviral therapy (ART).

A combination of several antiretroviral medicines used together to slow down the rate at which Human Immunodeficiency Virus (HIV) can make copies of itself.

The Human Immunodeficiency Virus (HIV) Life Cycle

To understand how antiretroviral treatment works, we need to understand the life cycle of the Human Immunodeficiency Virus.

Upon contracting HIV, there are several steps to its life cycle.

Firstly, the free virus circulates in the bloodstream until it attaches to a cell where it empties its contents. The genetic material (RNA) in the HIV is then used by the reverse transcriptase enzyme to build HIV DNA.

This HIV DNA is inserted into the cell’s chromosome by the HIV integrase enzyme – and the HIV infection is now established in the cell. When that cell reproduces it activates the HIV DNA making the raw material needed for new HIV viruses.

The immature virus then breaks out of the cell, matures and begins the process again by attacking other cells.

HIV specifically targets and destroys CD4 cells, a type of white blood cell that is important to a well-functioning immune system. As more and more CD4 cells are destroyed by the virus, the immune system weakens – often this can take as long as ten years.

Antiretroviral Therapy in the Treatment of HIV and AIDS

(CC) NIAID 2016, Antiretroviral drugs to treat HIV infection spill out of a pill bottle.

The aim of antiretroviral therapy is to stop the HIV life cycle in its tracks and prevent its multiplication and eventual progression to Acquired Immune Deficiency Syndrome

Up to now, antiretroviral treatment has offered the best chance of preventing HIV from replicating within the body and enabling the immune system to stay healthy. The eventual aim is for the treatment to reduce the amount of viral load in the body to an undetectable level.

Antiretroviral Medicines

There are six classes of antiretroviral medicines used. These are:

  1. Nucleoside/nucleotide reverse transcriptase inhibitors (NTRI/NtRTIs); e.g. didanosine
  2. Non-nucleoside reverse transcriptase inhibitors (NNRTIs); e.g. efavirenz
  3. Protease inhibitors; e.g. indinavir
  4. Integrase inhibitors; e.g. raltegravir
  5. Fusion inhibitors; e.g. enfuvirtide
  6. Chemokine receptor 5 inhibitors; e.g. maraviroc

It’s now recognised that the most effective way to treat HIV is by combining these different classes of medicines rather than adopting a monotherapy approach. It’s therefore standard practice to start patients on a combination of at least three options from a minimum of two of the six classes – commonly known as an ‘HIV cocktail’.

Although this approach has demonstrated its effectiveness, there are some problems that can prevent antiretroviral treatment from eradicating HIV completely and additionally, these substances have their own range of adverse reactions and drug-to-drug interactions.

Complications

There are complications arising from the virus itself that can prevent successful treatment from antiretroviral therapy

The risk of mutation is high thanks to the virus’s speed of replication 1010 copies per day from the time of transmission. This high rate makes it probable that mutation will occur leading to multiple strains and resistance to medicines.

A recent meta-analysis by University College London has found that HIV medicine resistance is approaching and exceeding 10% in patients about to start or reinitiate antiretroviral therapy.

In addition to this, the virus often remains detectable in seminal fluid in what we call ‘reservoirs’ and tend to be medicine-resistant variants. This means that ART must be a lifelong treatment or relapse is likely to occur.

As with any treatment regimen, there are also patient-related factors that can prevent therapy from being effective.

Pre-existing risk factors like obesity, psychiatric disorders, fatty liver and abnormal liver, and renal functions, are more likely to cause adverse medicine reactions and provoke a withdrawal of therapy (Desai et al, 2012).

Gender and age also have an impact – not only because research has primarily involved male patients, but because many antiretroviral medicines are contraindicated for pregnant women and children. In fact, the safety and correct dosing of key antiretroviral medicines haven’t yet been established for young children and there’s a limited number of approved paediatric medicines available in any case.

Compliance with treatment is essential and requires deep understanding and co-operation from HIV patients and their family members. Consistent counselling and follow-ups are crucial in ensuring that adherence.

Alternatives to Antiretroviral Therapy?

With antiretroviral medicine resistance becoming an increasing problem – are there any alternatives to this form of treatment?

Whilst there aren’t any other alternatives currently available, there is ongoing research into new and different HIV treatments. Gene therapy is one such approach.

Gene therapy is the process of manipulating human genetic material in order to slow and stop a virus from interfering with disease processes. It’s hoped that gene therapy may lead to a ‘functional HIV cure’ that modifies part of the body’s own genetic code to make cells resistant to the virus. This could negate the need for antiretroviral therapy completely.

Another potential functional cure is bone marrow transplantation.

Although there has only been one successful case where a bone marrow transplant appears to have completely replaced the CD4 cells of the patient with those from the transplanted marrow and the HIV remained undetectable 285 days after treatment. It’s a potential treatment avenue that has been explored since the 1980s.

At the moment, most research is focused on preventing HIV through vaccination rather than attempting to find a cure.

As developing countries can seldom afford effective antiretroviral medicines and lifelong adherence to therapy is essential, the only perceived way to eradicate the virus completely is to remove its ability to be transmitted in the first place.

So far, B-cell vaccines that completely block onward infection of cells by HIV have been shown to be successful but short-lived – they lose efficacy quickly as the virus is able to develop resistance through mutation.

Another vaccine approach that stimulates the cellular immune response of cells to HIV could generate a longer-lasting response, but studies so far have shown a weak and narrow response in humans (though better results when trialled on monkeys).

Unfortunately, it looks like antiretroviral therapy remains our only effective treatment for HIV at our disposal, and increasing resistance could mean we start losing the battle with the virus in the years ahead.

As nurses and healthcare professionals, we need to continue to support our patients with HIV and ensure that compliance with treatment is maintained at all times.

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