Summary
Highlights
The lecture begins by introducing antiretroviral drugs and stresses the importance of understanding the HIV life cycle, which involves the virus attaching to CD4 receptors, reverse transcription, integration into the host DNA, and maturation. Understanding these stages is crucial for comprehending how different drug classifications target the virus.
The video explains that HIV and AIDS treatment involves Highly Active Antiretroviral Therapy (HAART), which combines at least three different antiviral drugs to attack various points in the HIV life cycle. The classifications discussed include Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs), Nucleoside Reverse Transcriptase Inhibitors (NRTIs), Protease Inhibitors, Fusion Inhibitors, CCR5 Coreceptor Antagonists, and Integrase Inhibitors.
NNRTIs, such as those ending in '-virine' or '-virenz,' directly block the HIV reverse transcriptase, preventing the formation of viral DNA and making replication impossible. They are indicated for documented AIDS or AIDS-related complex, often in combination with other antivirals. Contraindications include pregnancy and severe hepatic impairment. Adverse effects can include dizziness, blurred vision, headache, GI issues, and flu-like symptoms.
NRTIs were the first class of drugs developed for HIV. They compete with natural nucleosides, preventing the lengthening of the viral DNA chain. They are used in combination therapy for HIV, chronic hepatitis B, and to prevent maternal transmission of HIV (e.g., zidovudine). Contraindications include pregnancy (except zidovudine), hepatic dysfunction, renal impairment, and bone marrow suppression. Adverse effects range from hypersensitivity reactions (abacavir) to pancreatitis, hepatomegaly, neurological problems, and severe bone marrow suppression (zidovudine).
Protease inhibitors render the virus immature and infective by blocking the protease enzyme essential for viral maturation. These drugs, often ending in '-navir,' are used in combination therapy for HIV. Contraindications include pregnancy (caution advised as some cross breast milk), hepatic dysfunction, and use with anti-diabetic drugs due to potential for hyperglycemia. Adverse effects can include GI upset, liver function changes, elevated cholesterol and triglycerides, and dermatological reactions like Stevens-Johnson syndrome.
Fusion inhibitors, such as enfuvirtide, prevent the fusion of the HIV virus with the human cellular membrane, blocking viral entry. Introduced in 2003, they are administered subcutaneously and indicated for patients with HIV-1 replication despite ongoing antiretroviral therapy. Contraindications include pregnancy and hypersensitivity. Adverse effects include insomnia, depression, peripheral neuropathy, GI upset, pneumonia, and injection site reactions.
CCR5 coreceptor antagonists, like maraviroc, block the CCR5 receptor on the cell membrane that HIV needs to enter the cell. These drugs are used in combination therapy with other antiviral agents. Contraindications include pregnancy, lactation, hypersensitivity, and renal impairment. Safety in children is not established. Adverse effects can include dizziness, changes in consciousness, and hepatotoxicity, often preceded by allergic reactions like rash.
Integrase inhibitors, introduced in 2007, prevent the viral DNA from integrating into the host DNA, decreasing viral load. They are reserved for patients treated with other antivirals where replication persists. Contraindications include hypersensitivity, risk for rhabdomyolysis or myopathy, and pregnancy. Adverse effects primarily include headache, dizziness, rhabdomyolysis, and myopathy. The video also briefly discusses antidiarrheal drugs, like crofelemer, approved for symptomatic diarrhea in adults on antiretroviral therapy, emphasizing the need to rule out infectious causes. It is also not recommended during pregnancy or for breastfeeding mothers.