Effectiveness Of Drugs Used In Treatment Of Hiv Biology Essay

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HIV is a human immunodeficiency virus. This virus directly attacks human immune system as well as few organs of human like heart, kidneys and brain. Immune system normally produces white blood cells and antibodies to fight against viruses and bacteria. If the immune system is damaged by HIV, the human body prone to develop severe infections such as fungal infections or disease like cancer.

HIV primarily attacks CD4 lymphocyte cells in the blood, which helps in direct immune function in the body. When CD4 cells decrease below the critical level, the immune system stops working and the body eventually becomes more susceptible to infections.

When HIV enters into the body it is engulfed by CD4 cells. HIV attaches to the CD4 receptor then the viral RNA enters into the cell. Viral RNA is converted into viral DNA by reverse transcriptase enzyme. This viral DNA is integrated into the cell nucleus of the host cell by integrase enzyme. Finally the viral DNA is converted to RNA, then protease enzyme develops new viral cell and finally viral cell detaches from the host cell.

There are two types of HIV 1 and HIV 2. HIV 1 is most virulent and infectious. Majority of HIV occurring globally is the HIV 1. Comparatively HIV 2 is less infective and fewer exposure due to its poor capacity to transmit.

According to the American Health Authority CDC that is Centre for Disease Control and Prevention

Based on CD4 cell count there are 3 categories of HIV which includes

Category 1: > 500 cells/mm2

Category 2: 200-499 cells/mm2

Category 3: < 200 cells/mm2

Based on severity of the disease there are 3 stages which includes

Stage A: both acute HIV infection and the latency period come under this stage. Acute HIV infection occurs about 3-6 weeks and followed by latency period which ends up in 10 years. Symptoms of this stage include headache, nausea, fever, lymph node swelling, skin eruptions, muscular pain and throat inflammation.

Stage B: consists of various symptoms of disease which weakens immune system further, that includes Candida infection of throat and mouth, viral infections like belt rose along with stage A symptoms.

Stage C: this is the final stage of HIV infection that is AIDS. In this stage immune system is collapsed and various infections of virus, fungus and diseases like cancer occur. Finally strong weight loss and further death occurs.

Diagnostic tests include standard ELISA which is mostly used due to its cost effectiveness and accurate method for screening infection and followed by western blot confirmatory test. Other tests include Rapid serum HIV antibody tests, saliva and urine based antibody tests, home HIV antibody tests, HIV RNA tests, Polymerase chain reaction test which gives the accurate count of HIV in blood in 2 or 3 weeks and P24 antibody assay which measures viral capsid.

Mode of transmission of HIV is mostly through sexually. Other modes of transmission is through blood, blood products, artificial insemination and tissue transplantation, mother to child transmission and injection of drugs with infected syringe.

According to WHO published in November 2009 by UNAIDS the global summary of the AIDS epidemic 2008

No. of people living with HIV: Total 33.4 mio Adults 31.3 mio

Women 15.7 mio

Children under 15 yrs 2.1 mio

No. of people newly infected with HIV: Total 2.7 mio Adults 2.7 mio

Women -

Children under 15 yrs 4, 30,000

AIDS related deaths: Total 2 mio Adults 1.7 mio

Children under 15 yrs 2, 80, 000

HIV infected without knowledge: 40%

25 million people died since 1981. In developing and transitional countries, 9.5 million people are in immediate need of life saving AIDS drugs, of them only 4 million people are receiving the drugs.

TREATMENTS: PAST AND PRESENT

1987- Nucleoside Reverse Transcriptase (NRTI'S)

1997- Non Nucleoside Reverse Transcriptase (NNRTI'S)

1995- Protease Inhibitors

2003- Fusion or Entry Inhibitors

2007- Integrase Inhibitors

For the past five years, significant progress has been made regarding the treatment of HIV and prevention of some of the infections and cancers that may be caused by it. Antiretroviral can directly attack HIV and stop it from reproducing and causing further damage. Certain antibiotics called prophylactic medication can effectively prevent opportunistic infections. In the early 1980's when HIV infections were starting to appear, HIV was associated primarily with gay men. Then it became a disease that can affect almost anyone who is monogamous with an uninfected person.

In past 15 years, the provisions of simple antiretroviral regimens during pregnancy have been shown to dramatically reduce the risk of transmission of HIV from mother to child. HIV-1 resistance and subsequent virologic failure occur in a substantial proportion of HIV infected patients receiving HAART regimens.

Tenofovir showed a reduced virologic response in the presence of 3 or more NAMS including M4IL or L21OW, as well as in the presence of T69 insertions. Hypersusceptability to Non Nucleoside Reverse Transcriptase Inhibitors (NNRTI'S) has recently been described in association with increased resistance to nucleoside analogues and it seems to enhance the immunologic and virologic response in patients receiving efavirenz containing regimens. Protease inhibitors is an lower class resistance profile cross resistance occurs between amprenavir and lopinavir in the presence of only four APV related mutations.

Introduction of HAART in the management of HIV disease has led to a sustained suppression of viral replication, partial restoration of the immune system in the incidence of complications and mortality. Due to poor adherence and factors like genetic variability relating sub therapeutic drug levels, there are persistent viral replication with HIV-1 resistance and subsequent virologic failure. Genotypic and phenotypic resistance tests are helpful in guiding ART, in patients recently infected and or previously failed in therapy. Zidovudine resistance mutation is included in nucleoside analogue mutations (NAMS) and which are recognized having a role in resistance to other nucleosides except for lamivudine. NAMS are selected by ZDV and accumulated in step wise manner, from a fold reduction with the 1st mutation to over 100 fold later in the course of treatment.

The present drug include raltegravir which is an HIV-1 integrase inhibitor comparing with the placebo the safety and efficacy of the raltegravir was proved in multidrug resistant virus of HIV-1 in different doses and also from various studies of raltegravir ,HIV-1 integrase is confirmed as an valid target for ART. It is also proved that raltegravir is an important component of combination treatment regimens to treat pretreated patients failing current therapies with MDR virus and limited treatment options.

COMPLIMENTARY AND ALTERNATIVE MEDICINE (CAM)

According to Expert Committee on Complementary Medicines in Health System, in 2003 estimated 2.3 billion was spent on CAM. This number was gradually increasing to manage symptoms and drug side effects due to dissatisfaction of convention treatment (Petersen, 2007). Various studies demonstrated high use of this CAM in people living with HIV/AIDS (PLWHA) both before and after the introduction of Antiretroviral (ARV) treatment. One of the qualitative research projects examined the meaning of CAM practices in PLWHA as well as the relation between their use of CAM and western allopathic medicine.

In 2004, a sample of nine PLWHA were recruited including 2 women in Melbourne, Australia so as to study the phenomenon of CAM usage among the PLWHA. This study demonstrated 5 themes which includes Focus on holistic health not illness: all the users of CAM believed that mind and body are important elements of well being which includes mental, emotional, and physical which is a holistic approach. In case of HIV, holistic approach represents resistance to stigma associated with HIV and an acceptance of one's HIV status (Cherry and Smith, 1993). Resistance to Antiretroviral therapy (ART) and adherence: one of the participant saw the need for ART as a bad portent: ''I felt that by going on the medication it was one foot in the grave, the beginning of the end of everything I fought for, that this was now the final chapter". 3of the 4 users of CAM using ART in this study were struggled to accept the adherence of ART due to some drug-drug interactions (Targ, 2000). Allopathic medicine regarded as narrow: most CAM users viewed HIV conventional treatment as narrow due to its focus on symptoms, viral load and CD4 where as CAM focuses on health and well being. Problems disclosing to doctors: users of CAM as well as ART mentioned that their medical practitioners were not interested in CAM when they said about CAM. Most users of CAM said that they would like together working of the medical and CAM practitioners. Continuum of CAM use: five of the CAM users in this study were taking ART but planning to quit in the future due to their concern about long-term efficacy and toxicity.

UPCOMING TREATMENTS

Various upcoming treatments are available in the treatment of HIV-1 which includes Chromosome engineering technology: this technology includes Human Artificial Chromosome (HAC) which is an artificially constructed eukaryotic vector (Harrington et al. 1997, Ikeno et al.1998), is inserted into hematopoietic stem cells which are capable of differentiating into CD4+ lymphocytes. This is done with use of antisense RNA technology. The antisense strand of the reverse transcriptase encodes the gene which is inserted into the therapeutic HAC; this produces an mRNA that is complementary to reverse transcriptase coded by infecting virus. This would inhibit retroviral life cycle at early stage itself. Bone marrow is said to be the ideal site for delivering the engineered stem cells (chromos molecular systems 2005). CCR5-negative stem cells transplantation and transgenic approaches to HIV therapy: due to long-term suppression of HIV-1 replication was below the level of detection in the majority of patients under combination ART. Life expectancy was gradually increased in the past few years due to HAART but as M Bickel emphasized in his talk that drug resistance, side effects, comorbidity and adherence are now emerging as main factors that limit treatment efficacy. This approach to HIV treatment holds good for future curative interventions in HIV patients. This would replace lifelong HAART by once in a lifetime treatment which would have numerous benefits for patients as well as for healthcare system. Nanocarriers' drug delivery system: due to challenging for treatment and prevention of HIV disease, the use of Nanocarriers to achieve more efficient delivery to antiretroviral drugs has been studied. Nanocarriers provide the means of cellular and anatomical barriers to drug delivery. Nanoparticles include polymers, inorganic and solid lipid. This is helpful to decrease this pandemic disease. This Nanoparticles ARV drug delivery system involves the use of single ART agents. Further studies have to be conducted regarding short and long term toxicity of Nanocarriers and also safety and efficacy profiles of ARV Nanocarriers.

CONCLUSION

From this overview of effectiveness of various therapies of HIV-1 treatment, suggest that Raltegravir can be used as current treatment as the HIV-1 integrase has a proven valid target as well as has a proof of one of the important component of combination therapy to treat the patients failed in previous therapy. Whereas the Tripanavir is also an effective drug used in the HIV-1 therapy which inhibits wild type protease with high potency and demonstrate durable efficacy in the treatment of HIV-1 containing multicommon mutations. The upcoming therapies need to have more conducted further studies to have more proofs. If so there would be treatment once in a lifetime which may have various benefits for patients as well as for healthcare system. Along with these therapies the patients should be following the regular therapy of CAM which involves the improvement of health and well being instead of viewing the viral load and CD4 cell count.

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