Pharmacological Treatment Options for HIV/AIDS

Latasha Weeks, PharmD Candidate 2007

Therapeutic Class/Agents
Nucleoside Reverse Transcriptase Inhibitors (NRTIs) / Therapeutic Class/Agents
Nucleotide Reverse Transcriptase Inhibitors (NtRTIs) / Therapeutic Class/Agents
Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs) / Therapeutic Class/Agents
Protease Inhibitors
(PIs)
Product Availability
Generic
(Brand) / Single Agent:
§  Abacavir, ABC
(Ziagen®)
§  Didanosine, ddI
(Videx®)
§  Enteric coated didanosine, ddI EC
(Videx EC ®)
§  Emtricitabine, FTC (EmtrivaTM)
§  Lamivudine, 3TC (Epivir ®)
§  Stavudine, d4T (Zerit®)
§  Zalcitabine, ddC (Hivid®)
§  Zidovudine, AZT, ZDV (Retrovir®)
Combination Agents:
§  Abacavir/Lamivudine (EpzicomTM)
§  Abacavir/Lamivudine/Zidovudine (Trizivir®)
§  Emtricitabine/Tenofovir (Truvada®)
§  Lamivudine/Zidovudine (Combivir®) / §  Tenofovir disoproxil fumarate, TDF (Viread ®) / §  Delavirdine, DLV
(Rescriptor ®)
§  Efavirenz, EFV
(Sustiva ®)
§  Nevirapine, NVP
(Viramune ®) / §  Amprenavir, APV
(Agenerase ®)
§  Atazanavir, ATV
(Reyataz TM)
§  Darunavir, TMC-114
(PrezistaTM)
§  Fosamprenavir, FOS-APV (LexivaTM)
§  Indinavir, IDV (Crixivan®)
§  Lopinavir/Ritonavir, LPV/RTV (Kaletra®)
§  Nelfinavir, NFV (Viracept®)
§  Ritonavir, RTV (Norvir®)
§  Saquinavir, SQV (Invirase®)
§  Tipranavir, TPV (Aptivus®)
Mechanism
of Action / §  Dideoxynucleoside analogs; must be triphosphorylated into a dideoxynucleotide that can now compete with naturally occurring nucleotides for DNA incorporation
§  When incorporated into HIV DNA during reverse transcription, the DNA chain cannot be completed due to the absence of the 3’-hydroxyl group on the ribose moiety of the nucleotide analog
§  The 3’-hydroxyl group is required for DNA chain elongation
§  This process blocks HIV from replicating in a cell / §  Dideoxynucleotide analog; pre-activated with the presence of phosphate groups so phosphorylation step is not necessary
§  Sine the phosphorylation step is not necessary, nucleotide analogs can incorporate into DNA chain more rapidly than nucleoside analogs
§  When incorporated into HIV DNA during reverse transcription, the DNA chain cannot be completed due to the absence of the 3’-hydroxyl group on the ribose moiety of the nucleotide analog
§  The 3’-hydroxyl group is required for DNA chain elongation
§  This process blocks HIV from replicating in a cell
§  The chemical structure of these analogs allows it to avoid a viral mechanism of nucleoside resistance / §  Works synergistically with most NRTIs
§  Binds to reverse transcriptase enzyme at an allosteric site (site other than the active site utilized by the NRTI)
§  This binding causes a conformational change in the reverse transcriptase enzyme that will result in alteration of an active site pocket and reduced binding of naturally-occurring nucleosides
§  This interferes with the enzyme’s ability to convert HIV RNA into HIV DNA, and hence, DNA elongation / §  Peptide-like molecules that mimic the gag-pol protein (type of HIV polyproteins)
§  Reversible competitive inhibitor of HIV protease enzymes causing displacement of HIV polyproteins and prevention of accumulation of structural proteins required for new virion formation
§  Protease inhibition results in the virus being noninfectious
EFFICACY
(Indication/Use, Clinical Data Support)
SAFETY
(Major Drug Interactions,
Pre-cautions, Contra-indications,
Adverse Effects,
Pregnancy Risk Category)
Therapeutic Class/Agents / Therapeutic Class/Agents / Therapeutic Class/Agents / Therapeutic Class/Agents
Dosage & Administration
(Include renal and/or hepatic adjustments)
Monitoring
(Efficacy and Toxicity Parameters)
Patient Education
Cost
(1-month)
References
(Guidelines, Drug Info Sources)

Latasha Weeks, PharmD Candidate 2007 Pharmacotherapy Presentation – Pharmaceutical Care Rotation

University of Maryland School of Pharmacy Happy Harry’s Pharmacy Patient Care Center, Perryville, MD