Classes of antiretroviral drugs
- Reverse transcriptase inhibitors - NRTI, NNRTI
- Protease inhibitors
- Integrase inhibitors
- Entry inhibitors - fusion, CCR5
How do NRTI’s work
Compete with the natural substrate to bind to reverse transcriptase active site.
Prodrugs of tenofovir
Tenofovir alfenamide and tenofovir disoproxil fumarate
Tenofovir AF has greater plasma stability
NRTI drugs
Zidovudine, lamivudine, abacavir, tenofovir DF, emtricitabine, emtricitabine/tenofovir AF
How do NNRTI’s work?
Non competitive inhibitors of reverse transcriptase and bind to an allosteric site.
- Highly specific (only active against HIV-1/)
- Develop resistance rapidly
- Cross resistance exists
NNRTI drugs
Nevirapine, Rilpivirine , efaverinz and etravirine
How do protease inhibitors work?
Bind to active site of protease enzymes
Prevent cleavage of transcribed polyproteins
Stop late phase HIV replication
- Develop resistance slowly
Protease inhibitor drugs
Ritonavir, darunavir, atazunavir, atazunavir with cobistat and darunavir with cobistat
How do integrase inhibitors work?
Block action of viral integrase
- Requires metabolism
Integrase inhibitor drugs
Raltegravir, elvitegravir and dolutegravir
CCR5 drug
Maraviroc
- Tropism test is carried out to determine which co-receptor the virus is using
- Causes postural hypotention
Fusion inhibitor drug
Enfuvirtide
- Subcutaneous twice daily
- Salvage therapy
Starting ARV
Drug 1: NRTI
Drug 2: NRTI
Drug 3: NNRTI/Protease inhibitor/Integrase inhibitor
Two backbones of ARV
- Tenofovir DF/emtricitabine
- Effective against hepatitis B
- Causes renal impairment
- Reduces bone density - Abacavir/lamivudine
Higher cardiovascular risk with abacavir
Lamivudine has low barrier resistance to hepatitis B
