Treatment of AIDS

“Antiretroviral therapy & vaccines”

HAART(Highly active antiretroviral therapy)

In HAART we use antiretroviral drugs which interfere with the life cycle of HIV and inhibit there growth

In HAART there are 4 different kinds of antiretroviral drugs are used-

NRTI( nucleotide reverse transcriptase inhibitor):-

NRTI are similar to structure of normal DNA bases except 3 prime –OH group and phosphate group.NRTI is activated inside the cell by the additon of three phosphate groups to their deoxyribose moiety, to form NRTI triphosphate.This phosphorylation step is carried out by cellular kinase enzyme

Examples of NRTI:

• Didanosine

• Stavudine

• Abacavir

• Lamivudine

• Zidovudine

NtRTI(Nucleoide reverse transcriptase inhibitor):-

It is similar to structure of normal DNA bases except 3 prime –OH group so the NtRTI is incorporated into the growing chain and terminates the chain elongation during replication.

Examples:-

Tenofovir

Adefovir

NNRTI(Non nucleoside reverse transcriptase inhibitors):-

These drugs act via non-competetive binding to a hydrophobic pocket close to the reverse transcriptase enzyme of HIV

Examples of NNRTIS are-

• Nevirapine

• Efavirenz

• Delavirdine

Protease Inhibiors(PI):-

Processing of large HIV precursor protein encoded by gag ang gag-pol genes of HIV into structural proteins of the viral core is performed via proteolytic cleavage by HIV encoded aspartic protease and is necessary for maturation of immature virus particle. These drugs are synthetic analogues of the HIV protein and block the action of HIV protease. Protease inhibitors also decrease CD4 apoptosis through decreased CD4 interleukin-1beta-converting enzyme(ICE or caspase 1)

Examples of protease inhibitors includes-

Nelfinavir

Saquinavir

Ritonavir

Indinavir

Inhibition of fusion of HIV with target cell:-

This type of drug prevents the fusion of HIV to the target cells. This type of drug corresponds to 36 amino acids within C-terminal hapted repeat region(HR2) of HIV1 gp41 subunit of the viral envelope (env) protein. This prevents the conformational changes to form a stable complex required membrane fusion to target cell.

HAART Regimens:-

• HAART regiments may include combinations of one or more of NRTI/NtRTI,NNRTI and PI

The standard combination of drugs may be as follows according to clinical trails, adverse effect, efficacy-

• NRTI+NRTI+PI• NRTI+NRTI+NNRTI• NRTI+NRTI+PI+PI

Mutidrug rescue therapy(MDRT):-

• This therapy is the combination of 9 antiviral drugs. This is used to treat the patients infected with several drug resistant strain of HIV

Result of HAART therapy:-

• CD4 count typically increases • Increases the life of treated patients by decreasing

the frequency and severity of opportunistic infection

• It reduces HIV1 RNA levels in plasma• Without treatment, the net median survival time

after infection with HIV is estimated to be 9 to 11 years, depending on the HIV subtype . The development of HAART as effective therapy for HIV infection and AIDS reduced the death rate from this disease by 80%, and raised the life expectancy for a newly diagnosed HIV-infected person to about 20 years

Disadvantage of HAART:-

• It causes some unhealthy condition in patients who cannot tolerate the regimen

• The unhealthy condition include lactic acidosis, abdominal pain, nousa, vomiting, headache, bone marrow suppression with anemia, panceatitis, peripheral neuropathy and sometimes myopathy also

• In appropriate treatment with HAART regimen also give rise to drug resistant strains of HIV which is the major clinical problem

Vaccine :-

Several approaches are taken to develop vaccine against HIV, These include-

• Use of pox virus such as vaccinia as recombinant vector for vaccination with HIV envelope protein

• Gene therapy• Vaccine development targeting on HIV gp120

and gp160 envelope protein to induce humoral response.

• Blocking the HIV entry into the cell.

Difficulties of Vaccine development—• HIV epitope variability

• HIV avoidance of immune response through cell to cell transmission

• Lack of effective neutralizing antibody response and induction of adverse immune reactions through HIV homology to endogenous human proteins.

Although several researches are going on there is no particular treatment which can cure HIV. HAART therapy can increase the life span of infected persons but can not cure the disease. So, it is better to avoid all the chances of HIV infection though the maintenance of safety healthcare guidelines regarding to AIDS.