Lehne Chapter 94 Flashcards
Drugs for HIV Infection and Related Opportunistic Infections
Human immunodeficiency virus is a retrovirus (HIV-1 and HIV-2)
HIV has RNA as genetic material
Uses reverse transcriptase to convert RNA into DNA and integrase to insert its DNA into ours
Target cells: CD4 T cells (helper lymphocytes)
Transmission via blood and body fluids
Virus is present in all body fluids
Human Immunodeficiency Virus
Promotes immunodeficiency by killing CD4 T lymphocytes Transmission of HIV Clinical progression Difference between HIV and AIDS Global epidemic Standard antiretroviral therapy (ART) Reduced AIDS deaths by 72% Highly active antiretroviral therapy (HAART)
Classification of
Antiretroviral Drugs
Five types of antiretroviral drugs Inhibit enzymes required for HIV Reverse transcriptase inhibitors Integrase strand transfer inhibitors Protease inhibitors Block viral entry into cells Fusion inhibitors CCR5 antagonists
Nucleoside Reverse Transcriptase Inhibitors (NRTIs): Zidovudine [Retrovir]
Inhibits HIV replication by suppressing synthesis of viral DNA Adverse effects Hematologic toxicity Lactic acidosis with hepatomegaly Myopathy Gastrointestinal effects Central nervous system (CNS) reactions Others Drug interactions
Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
Differ from NRTIs in structure and mechanism of action NNRTIs bind to active center of reverse transcriptase and cause direct inhibition Active as they are administered Efavirenz [Sustiva] Nevirapine [Viramune] Delavirdine [Rescriptor] Etravirine [Intelence] Rilpivirine [Edurant]
Efavirenz [Sustiva]
Preferred agent for treating HIV
Only NNRTI recommended for first-line therapy of HIV infection
Drug interactions
Adverse effects
Transient adverse CNS effects in 50% of patients
Rash
Teratogenicity
Protease Inhibitors
Among the most effective antiretroviral drugs Nine are available Used in combination with NRTIs; can reduce viral load to an undetectable level Resistance Adverse effects Hyperglycemia/diabetes Fat redistribution Hyperlipidemia Reduced bone density Increased bleeding in people with hemophilia Reduced bone mineral density Elevation of serum transaminase Drug interactions Lopinavir/ritonavir Ritonavir Indinavir Saquinavir Nelfinavir Fosamprenavir Atazanavir Tipranavir Darunavir
HIV Integrase Strand
Transfer Inhibitors
Raltegravir [Isentress]
Indicated for combined use with other antiretroviral agents to treat adults infected with HIV-1
Adverse side effects
Insomnia, headache, and rare hypersensitivity reactions
FDA pregnancy risk: Category C
Enfuvirtide [Fuzeon]
HIV fusion inhibitor Widely known as T-20 First and only HIV fusion inhibitor Blocks entry of HIV into CD4 T cells Twice-daily subQ dosing Adverse effects Injection-site reactions, pneumonia, and hypersensitivity reactions
Maraviroc [Selzentry]
CCR5 antagonist
Indicated for combined use with other antiretroviral drugs to treat patients age 16 years or older who are infected with CCR5-tropic HIV-1 strains
Adverse effects
Drug interactions
Principal Laboratory Tests
Used to Guide Therapy
CD4 T-cell counts: Principal indicator of how much immunocompetence remains
Plasma HIV RNA (viral load) assays: Ongoing treatment of HIV infection is guided primarily by monitoring viral load, which is determined by measuring HIV RNA in plasma
HIV Drug Resistance
In most cases, resistance emerges over the course of treatment as a result of nonadherence to the prescribed regimen
Rarely, resistance results from primary infection with a drug-resistant HIV variant
Resistance tests can be used to guide drug selection, especially when changing a regimen that has failed
HIV Treatment in Pregnancy
Same principles that guide antiretroviral therapy in nonpregnant adults
Mother-to-child transmission HIV
Risk for transmission can be greatly reduced by ART, which minimizes maternal viral load
The same general principles apply to children
HIV Treatment
Treatment of young patients Treatment of older patients Preventing HIV infection with drugs Pre- and postexposure prophylaxis Preventing perinatal HIV transmission Prophylaxis and treatment of opportunistic infections
HIV Vaccines
Obstacles to vaccine development
Current status of vaccine development
