HIV Salvage Therapy: Civil Services Mentor Magazine - April + May 2014

HIV SALVAGE THERAPY

The Menace of HIV

Human Immunodeficiency Virus (HIV) which causes the condition of Acquired Immunodeficiency Syndrome (AIDS) has been a global menace for quite some time now. The main challenge faced by the scientists in checking the spread and threats, posed by this disease, is that the virus could not be successfully checked from spreading itself. No course of medicine has been able to restrict and counteract the growth of the virus. That is why, there has been much global concern regarding the HIV/AIDS.

The life Cycle of HIV can be as short as about 1.5 days from viral entry into a cell, through replication, assembly, and release of additional viruses, to infection of other cells. HIV lacks proofreading enzymes to
correct errors made when it converts its RNA into DNA via reverse transcription. Its short life-cycle and high error rate causes the virus to mutate very rapidly, resulting in a high genetic variability of HIV. As the virus mutates, many of the cells develop an ability to resist the human immune system and anti-viral drugs. This makes the development of the antivirus for HIV difficult.

The American National Institute of Health (ANIH) and other organizations recommend offering ARV treatment to all patients with AIDS. However, because of the complexity of selecting and following a regimen, the severity of the sideeffects, and the importance of compliance to prevent viral resistance, such organizations emphasize the importance of involving patients in therapy choices and recommend analyzing the risks and the potential benefits to patients with low viral loads.

History of HIV/AIDS Treatment

ARV treatment guidelines have changed over the years. Before 1987, there were no ARV drugs available, and the treatment consisted of treating complications from the immunodeficiency, while taking no steps to restrict the growth of the viral strains.

After ARV was introduced, most medical practitioners agreed to treat those with a very low CD4 count. CD4 is a component of the human immune system, that is found in the White blood cells, which help in fighting with diseases. HIV causes a rapid fall in the number of CD4 cells of the blood.

In 1995, David Ho promoted a ‘Hit Hard, Hit Early’ Approach, that had risk of increasing the side effects and developing a multidrug resistance. However, this approach was soon abandoned, as it had many side-effects and was too costly.

There were also a series of debates about when and how to initiate the therapy process. While earlier the treatment was more focused on the symptomatic conditions associated with HIV, the more recent developments have shifted their focus on the asymptomatic stage of HIV. Asymptomatic stage refers to the period when there are no external signs of the HIV/AIDS.

In recent times, the scientists have come to a consensus that the ARV therapy should never be stopped. This is because the selection pressure of incomplete suppression of viral replication in the presence of drug therapy causes the more drug sensitive strains to be selectively inhibited. This allows the drug resistant strains to become dominant, which, in turn, makes it harder to treat the infected individual as well as anyone else they infect.

The Anti-RetroViral Therapy (ARV)

Till now, the management of HIV/AIDS included the use of multiple antiretroviral (ARV) drugs, that checks the growth of the virus. ARV combination therapy defends against resistance by suppressing HIV replication as much as possible. The combinations of ARV create multiple obstacles to HIV replication to keep the number of offspring low and reduce the possibility of a superior mutation.

Since the Virus develops a resistance to the drugs, there are several classes of antiretroviral agents that are used in combinations, during the different stages of the HIV lifecycle. ARVs are given to slow down the HIV reproduction, which helps to increase the quality of life and survival. No individual ARV drug has been effective in suppressing the HIV infection for long. Thus, these drugs are necessarily taken in combination.

A common combination of ARV includes-

  1. 2 NRTIs (Nucleotide Reverse Transcritase Inhibitors) + 1 PI (Protease Inhibitors); or,
  2. 2 NRTIs + 1 NNRTI (Non- Nucleoside Reverse Transcriptase Inhibitor).

These three drug combinations are commonly known as a Triple Cocktail. Further, these combinations of ARV drugs are subject to certain positive and negative synergies, which limit the number of useful combination.
The use of multiple drugs that act on different viral targets is known as Highy Active Antiretrovial Therapy (HAART). HAART process decreases the patient’s total burden of HIV, and maintains the function of the immune system, thus preventing the opportunistic infections, that might lead to the patient’s death.

The side-effects related to ARV, if used improperly, are- the virus becomes resistant to the drug line more rapidly; improper serial use of the reverse transcriptase inhibitorszidovudine, didanosine, zalcitabine, stavudine and lamivudine can lead to the development of multi-drug resistant mutations.

Some of the mutation-kinds, that the HIV can develop, are- V75I, F77L, K103N, F116Y, Q151M and M184V mutations.

The Salvage Therapy

Salvage Therapy, also known as Third Line Therapy or Rescue Therapy, is a term describing treatment regimes for people who have few or limited anti-HIV drug options. This includes people who have failed at least two previous anti- HIV drug regimens and/or people with evidence of HIV resistance to at least one drug in each of three major classes. Thus, this therapy has been developed as a response to the needs of the people who have developed a resistance for the ARV treatment.

Deep Salvage or True Salvage therapy is when a person has literally no viable treatment options. It is undertaken when a regimen is deemed to be not working.

Since the Salvage therapy has been developed in recent years, there is no defined meaning for it in the HIV medicine. It is currently used to refer to a condition where the individual’s body is resisting the ARV treatment. Such condition of the patient is referred to as Multi-Drug Resistant (MDR).

Salvage therapy has come up as a hope for the HIV+ patients, who are not getting any relief from the mainstream ARV combination medicine.

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