HIV salvage therapy
HIV: the Disease, Invincible
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 side-effects, 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.
The Fight against the Disease
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.
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 life-cycle. 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-
2 NRTIs (Nucleotide Reverse Transcritase Inhibitors) + 1 PI (Protease Inhibitors); or,
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 inhibitors- zidovudine, 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.
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.
Tackling HIV, the Indian Way!!
India has a sizable population of People living with HIV, with approximately 2.39 Million people living with HIV/AIDS. Thus, the Government has made several steps to tackle with the situation. India rolled out free Anti Retroviral Therapy (ART) in 2008, with 7.5 Lakh people availing of it in 2014. of these, around 7500 HIV+ people were moved to the second line regimen after developing resistance.
National AIDS Control Organization (NACO) has been entrusted with the task of checking the spread of HIV, and creating an awareness regarding HIV/AIDS. In the background of the pressing need to develop the third line of treatment, due to the resistant shown by the people living with HIV/AIDS, the Government has planned to launch the Third Line of Treatment in India, to check the spread of HIV.
NACO, apart from introducing third line treatment, also plans to double the existing second line treatment. However, the challenge before the government is the high cost of the third line treatment, which costs about Rs 15000 per person per month; in contrast to the first line and second line costs which amount lesser.
Indian Government has launched the Third-line Therapy for people living with HIV/AIDS and extended free ART to more people, by revising the eligibility norms. The programme was launched at the launch of National AIDS Control Programme Phase IV (2012-2017), by Union Health Minister Ghulam Nabi Azad, with an aim to enhance the longevity and improve the quality of life of patients.
According to the Indian Standards, in order to receive free ART, the minimum CD4 count had been reduced from 500 to 350.
The Government tabled the Human Immunodeficiency Virus Acquired Immune Deficiency Syndrome (Prevention and Control) Bill, 2014, in the Rajya Sabha. It seek to prevent the spread of HIV/AIDS and protect the Human Rights of people living with HIV/AIDS. The bill seek to prohibit any kind of discrimination against the infected person, like- denial or termination of employment or occupation; unfair treatment; denial of access to any sector and forcible HIV testing.
Norms for HIV Treatment in USA: A Comparison
The treatment guidelines specifically for the US are set by the US Department of Health and Human Services (DHHS). The current guidelines for adults and adolescents were started on December 1, 2009.
ART should be initiated in all patients with a history of an AIDS defining illness or with a CD4 count of Less than 350 cells/mm3.
ART should also be initiated, regardless of CD4 count, in patients with the conditions like- pregnancy, HIV-associated nephropathy, and Hepatitis-B virus.
Patients initiating ART should be willing and able to commit to lifelong treatment and should understand the benefits and risks of therapy and the importance of adherence.
Thus, we notice that the guidelines in US take no chance in treating the HIV. Unlike India, treatment is given even to those with suspected cases.
In Lieu of Conclusion
The Salvage therapy for treating HIV/AIDS has been developed as a means to check the worsening form of HIV, in the human body. Since the nature of HIV is such that it mutates to develop a resistance to the immune system and the medications, it is pertinent that a mechanism be developed that counters the growth and spread of HIV.
However, the salvage therapy also fails to provide a lasting solution. It has not been able to terminate the HIV from the human body. The value of salvage therapy is to be realized in the context of the more imminent task of saving the precious human life.
The true treatment of HIV looks a distant dreams, as of now. It can only be expected that the developments in the field of HIV medication would lead to more concrete and fruitful results in the future.