Anti-Retrovirals Flashcards
What are retroviruses?
Retroviruses are RNA viruses that synthesize DNA from an RNA template using reverse transcriptase.
What is HIV?
HIV (Human Immunodeficiency Virus) is an RNA retrovirus that targets CD4+ T lymphocytes, reducing CD4 counts and leading to immune suppression.
What are the two forms of HIV?
HIV-1, which can lead to Acquired Immunodeficiency Syndrome (AIDS), and HIV-2, which causes less severe immune suppression.
How does HIV replicate?
HIV binds to CD4+ T cells, enters the host cell, reverse transcribes its RNA into DNA, integrates into the host genome, and uses the host’s machinery to produce new virions.
What are the targets for antiretroviral drugs?
Targets include co-receptor antagonists, fusion inhibitors, reverse transcriptase inhibitors (NRTIs and NNRTIs), integrase strand transfer inhibitors (INSTIs), and protease inhibitors (PIs).
How do Nucleoside Reverse Transcriptase Inhibitors (NRTIs) work?
NRTIs are nucleoside analogues phosphorylated to active forms that competitively inhibit reverse transcriptase, causing DNA chain termination.
What is an example of an NRTI?
Zidovudine (ZDV, formerly AZT), which was the first approved NRTI.
How do Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) work?
NNRTIs bind non-competitively to reverse transcriptase at a different site than NRTIs, directly inhibiting the enzyme without requiring phosphorylation.
What are examples of NNRTIs?
Nevirapine, delavirdine, and efavirenz.
What are the adverse effects of NNRTIs?
Common adverse effects include rash and hepatotoxicity. Many NNRTIs interact with cytochrome P450 enzymes.
How do Protease Inhibitors (PIs) work?
PIs inhibit HIV-1 protease, preventing the cleavage of polypeptide products into functional viral proteins, thereby halting the maturation of infectious virions.
What are examples of PIs?
Saquinavir, ritonavir, indinavir, nelfinavir, and lopinavir.
What is the role of ritonavir in antiretroviral therapy?
Ritonavir inhibits CYP450 3A4, boosting the concentrations of co-administered PIs.
How do fusion inhibitors work?
Fusion inhibitors like enfuvirtide bind to gp41, preventing the fusion of the HIV envelope with the host cell membrane.
What is maraviroc and how does it work?
Maraviroc is a co-receptor antagonist that binds to CCR5 on CD4+ T cells, blocking the interaction with HIV gp120.
How do Integrase Strand Transfer Inhibitors (INSTIs) work?
INSTIs, like raltegravir, inhibit HIV integrase, preventing the integration of viral DNA into the host genome.
What is cART?
Combination Antiretroviral Therapy (cART) typically includes a combination of 3-4 drugs, such as 2 NRTIs with an NNRTI or 1-2 PIs.
What are the goals of cART?
The goals are to suppress viral load, restore and preserve immune function, reduce HIV-related morbidity and mortality, and prevent HIV transmission.
What causes HIV drug resistance?
Drug resistance arises due to the high mutation rate during HIV replication and can be treatment-emergent or transmitted.
What strategies minimize viral resistance?
Strategies include adherence counseling, avoiding monotherapy, optimizing serum drug levels, managing drug interactions, and ensuring co-formulated regimens for compliance.
What is the UNAIDS 90-90-90 target?
By 2020, the goal was for 90% of people with HIV to know their status, 90% of diagnosed individuals to receive sustained ART, and 90% of those on ART to achieve viral suppression.
