Antiretroviral drugs are medications for the treatment of infection by retroviruses, primarily HIV. Different classes of antiretroviral drugs act at different stages of the HIV life cycle. Combination of several (typically three or four) antiretroviral drugs is known as Highly Active Anti-Retroviral Therapy (HAART).

2. ANTI RETROVIRAL THERAPY
• Treatment with antiretroviral medicines, against the retrovirus
(HIV), which resides and multiplies within the human body

8. HIV Life Cycle
• Step 1: Attachment of virus at the
CD4 receptor and chemokine co-
receptors CXCR4 or CCR5
• Step 2: viral fusion and uncoating
• Steps 3-5: Reverse transcriptase
makes a single DNA copy of the viral
RNA and then makes another to
form a double stranded viral DNA
• Step 6: migration to nucleus
• Steps 7-8: Integration of the viral
DNA into cellular DNA by the enzyme
integrase
• Steps 9-11: Transcription and RNA
processing
• Steps 12-13: Protein synthesis
• Step 14: protease cleaves
polypeptides into functional HIV
proteins and the virion assembles
• Step 15: virion budding
• Step 16: Virion maturation

27. Some Alternative Therapies
• Virus adsorption inhibitors – interfere with
virus binding to cell surface by shielding the
positively charged sites on the gp-120
glycoprotein
– Polyanionic compounds
• Viral coreceptor antagonists – compete for
binding at the CXCR4 (X4) and CCR5 (R5)
coreceptors
– bicyclams and ligands

28. Combination Therapy
• Combination therapy often called HAART is
standard care for people with HIV.
• Monotherapy created virus resistance to the
individual drug. Some combination therapies
increase the time it takes for the virus to become
resistant.
• Combinations of a PI or NNRTI with one or two
NRTI’s is often recommended.
• Combination therapy may reduce individual drug
toxicity by lowering the dosage of each drug

29. • The combination of drugs chosen is based on
the history of each individual patient and
synergistic drug interactions.
• Some drugs compete with each other for
binding sites or enzymes.
– Example: zidovudine and stavudine
• both nucleoside analogs compete for the same kinase.
Stavudine is not phosphorylated because zidovudine is
preferred

32. References
• NIAID HIV Life Cycle.
http://www.niaid.nih.gov/daids/dtpdp/virpag
e1.htm
• De Clerq, E. New anti-HIV agents and targets.
Med. Res. Rev. 2002, 22(6), 531-565