ANTIRETROVIRAL AGENT INTRODUCTION

The first antiretroviral drug to be licensed, zidovudine, became available in 1987. Until December 1995, the antiretroviral drugs available and approved for clinical use in the United States consisted of only 5 individual drugs belonging to a single class of antiretroviral agents, nucleoside analog reverse transcriptase inhibitors. Since then, numerous other antiretroviral drugs and classes of antiretroviral drugs have been introduced. Additional drugs and newer classes of antiretroviral are in various stages of development. Currently, there are 22 Food and Drug Administration (FDA)-approved antiretroviral agents categorized in 4 classes of drugs: nucleoside/nucleotide analog reverse transcriptase inhibitors, nonnucleoside analog reverse transcriptase inhibitors, protease inhibitors, and fusion inhibitors. The authors review the general characteristics of each class of antiretroviral drugs, including mechanism of action, pharmacologic properties, adverse effects, and drug interactions. A synopsis of current antiretroviral treatment guidelines is also provided. DEFINITION Antiretroviral drugs inhibit the reproduction of retrovirusesiruses composed of RNA rather than DNA. The best known of this group is HIV, human immunodeficiency virus, the causative agent of AIDS. Viruses are obligate intracellular parasite, or infectious agent minimally constructed of two components. (1) Genome of either RNA or DNA (2) Capsid of proteins (3) Many have an envelope as well (All three of these are a virion)

Fig.1 Rotavirus

1 Geetanjali Institute of Pharmacy, Udaipur-313001

ANTIRETROVIRAL AGENT
The smallest viruses possess a diameter of not more than 20 mm while in the large viruses, diameter may go up to 300 mm. According to Lwoff, an infectious agent (1) Possesses simple chemical composition (2) Lacks the metabolic enzyme machinery (3) Lacks the protein-synthesizing system (4) Possesses a host cell dependant machinery of multiplication can be named virus. Viruses consist of one or more strands of linear or helical strands of either DNA or RNA enclosed in a shell of protein known as the CAPSID. ADSORPTION as

The virion invades the host cell membrane. The reactive sites on the Capsid firmly
bind with their complimentary sites on the host cell.

The viral particle is encapsulated by host cell cytoplasm, forming a vacuole.

UNCOATING Process of removing a part or all of the viral protein Capsid. The genetic material or viral genome passes into the host cell leaving the Capsid covering outside the host cell. This step is known as penetration. SYNTHESIS OF VIRAL COMPONENTS Viral genome enters the cytoplasm or nucleoplasm and utilizes the host nucleic acid machinery for the synthesis of new viral protein and production of more viral genome. RELEASE OF THE VIRUSES Viral nucleic acid and Capsid protein materials are synthesized in different parts of host cell by ribosome. The large numbers of newly synthesized viral particles then have to be brought together for assembling into new virions. They are release by budding process. The release virions then invade fresh host cell and repeat the whole process. Antiretroviral drugs are broadly classified by the phase of the retrovirus life-cycle that the drug inhibits.

the

Nucleoside and nucleotide reverse transcriptase inhibitors (NRTI) inhibit reverse transcription by being incorporated into the newly synthesized viral DNA and preventing its further elongation.
2

Geetanjali Institute of Pharmacy, Udaipur-313001

ANTIRETROVIRAL AGENT

Non-nucleoside reverse transcriptase inhibitors (NNRTI) inhibit reverse transcriptase directly by binding to the enzyme and interfering with its function.

Protease inhibitors (PIs) target viral assembly by inhibiting the activity of protease, an enzyme used by HIV to cleave nascent proteins for final assembly of new virons.

Integrase

inhibitors inhibit

the

enzyme integrase,

which

is

responsible

for integration of viral DNA into the DNA of the infected cell. There are several integrase inhibitors currently under clinical trial, and raltegravir became the first to receive FDA approval in October 2007.

Entry inhibitors (or fusion inhibitors) interfere with binding, fusion and entry of HIV-1 to the host cell by blocking one of several

targets. Maraviroc and enfuvirtide are the two currently available agents in this class.

Maturation inhibitors inhibit the last step in gag processing in which the viral capsid polyprotein is cleaved, thereby blocking the conversion of the polyprotein into the mature capsid protein (p24). Because these viral particles have a defective core, the virions released consist mainly of non-infectious particles. There are no drugs in this class currently available, though two are under

investigation, bevirimat and Vivecon.

Broad spectrum inhibitors. Some natural antiviral, such as extracts from certain species of mushrooms, may contain multiple pharmacologically active compounds, which attack the virus at various different stages in its lifecycle.

ANTIRETROVIRAL DRUGS: Raltegravir Vivecon Enfuvirtide Indinavir Ritonavir Efavirenz Nevirapine Abacavir

3 Geetanjali Institute of Pharmacy, Udaipur-313001

ANTIRETROVIRAL AGENT
Lamivudine Stavudine Didanosine Zidovudine:

4 Geetanjali Institute of Pharmacy, Udaipur-313001

ANTIRETROVIRAL AGENT

OBJECTIVE OF STUDY
This study will determine if blood levels of anti-HIV drugs in pregnant women change at different stages of pregnancy and if these changes require dosage adjustments in order to maintain adequate drug levels during pregnancy. Anti-HIV medications are recommended for HIV-infected women during pregnancy not only to treat their infection, but also to reduce the chance of passing the virus to the baby during pregnancy. Changes in the body that occur during pregnancy may affect how the body uses and eliminates these drugs, reducing their levels during pregnancy. Pregnant women 18 years of age or older who are infected with HIV may be eligible for this study. Candidates will have a medical history and physical examination, pregnancy test and blood tests.

5 Geetanjali Institute of Pharmacy, Udaipur-313001

ANTIRETROVIRAL AGENT

SUMMARY & CONCLUSION

Antiretroviral drugs inhibit the reproduction of retrovirusesiruses composed of RNA rather than DNA. The best known of this group is HIV, human immunodeficiency virus, the causative agent of AIDS. Antiretroviral agents are virustatic agents which block steps in the replication of the virus. The drugs are not curative; however continued use of drugs, particularly in multi-drug regimens, significantly slows disease progression.

6 Geetanjali Institute of Pharmacy, Udaipur-313001

ANTIRETROVIRAL AGENT

REFERENCES
1) "Antiviral prodrugs the development of successful prodrug strategies for antiviral chemotherapy", (Wiley-Blackwell), January 2006, 147 (1) 2) Williams David A, Lemk Thomas L, Foyes principles of medical chemistry, 5th edition, 392-398 3) Warrell David A, Cox Timothy M, Firth John D, Oxford Textbook of Medicine, 4th edition, 1.306 , 1.434 4) St. Louis A, Drug facts and Comparisons,56th edition, Walters Kluwer Company,1766 5) Seth S D, Textbook of pharmacology, Textbook of pharmacology, 2nd edition,892-895 6) Haslett Christopher, Chilvers Edwin R, Boon Nicholas A, Colledge Nickie R, Davidsons principles and practice of medicine,19th edition,144-145

7 Geetanjali Institute of Pharmacy, Udaipur-313001