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Highly Active Antiretroviral Therapy (HAART) Cocktail Therapy. Examples of anti-retroviral drugs. Cocktail Drug Mixtures Protease inhibitors Non-nucleoside RT Inhibitors (NNRTIs) Nuleoside/nucleotide RT inhibitors (NRTIs) * Fusion Inhibitors *Fuzeon Integrase Inhibitors.
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Highly Active Antiretroviral Therapy (HAART)Cocktail Therapy
Examples of anti-retroviral drugs • Cocktail Drug Mixtures • Protease inhibitors • Non-nucleoside RT Inhibitors (NNRTIs) • Nuleoside/nucleotide RT inhibitors (NRTIs) • * Fusion Inhibitors *Fuzeon • Integrase Inhibitors
Fusion Inhibitors block • Co-receptors on host cell • Gp120/gp 41 on viral particle or
Symptoms of AIDS • Decrease T cell count • Rapid weight loss • Recurring fever and dry cough • Profound fatigue • Swollen lymph glands
Symptoms of AIDS • Persistent diarrhea • Unusual blemishes on the tongue, mouth, or throat • pneumonia • memory loss, depression
Acquired Immunodeficiency SyndromeOpportunistic Diseases and cancer • pneumonia • Kaposi’s Sarcoma Kaposi’s Sarcoma
Transmission of HIV • Biological fluids • Blood • Sexual transmission (Semen) • Breast milk • Transplant tissues
Non-transmitting sources of HIV • Tears • Saliva • Mosquito or insects • Swimming pool • Food handling
Prevention • Condoms • Clean needles • Treatment of pregnant mother with anti-viral drugs • Blood screening • Abstinence
Normal CD4+ count Normal CD4+ (%) AIDS 500-1600/mm3 20-40% <350/mm3 begin anti-viral treatment <14% serious immune damage Acquired Immunodeficiency Syndrome
Experimental drugs are italicized, and approved drugs are in regular, non-italicized type)
Interesting links on HIV • http://www.niaid.nih.gov/factsheets/aidsstat.htm • Links to global and US HIV/AIDS statistics • http://www.avert.org/pregnanc.htm • Links to HIV and pregnancy as well as numerous other links including statistics on global epidemic; HIV/AIDS quizzes and treatment. • http://www.cdc.gov/hiv/pubs/facts/transmission.htm • Links to CDC and a comprehensive fact sheet on HIV transmission
Experimental drugs are italicized, and approved drugs are in regular, non-italicized type)Brand NameGeneric NameAbbreviationExperimental Code Pharmaceutical Company Fuzeon™enfuvirtideENFT-20Trimeris and Hoffmann-La Roche BMS-488043Bristol-Myers SquibbGSK-873,140GlaxoSmithKlinePRO-542Progenics PharmaceuticalsSCH-DSchering-Plough CorporationTNX-355Tanox and Biogen IdecUK-427,857Pfizer What are Entry Inhibitors (including Fusion Inhibitors)?Entry inhibitors work by preventing HIV from entering healthy T-cells in the body. They work differently than many of the approved anti-HIV drugs – the protease inhibitors (PIs), the nucleoside reverse transcriptase inhibitors (NRTIs), and the non-nucleoside reverse transcriptase inhibitors (NNRTIs) – which are active against HIV after it has infected a T-cell. Entry inhibitors work by attaching themselves to proteins on the surface of T-cells or proteins on the surface of HIV. In order for HIV to bind to T-cells, the proteins on HIV's outer coat must bind to the proteins on the surface of T-cells. Entry inhibitors prevent this from happening. Some entry inhibitors target the gp120 or gp41 proteins on HIV's surface. Some entry inhibitors target the CD4 protein or the CCR5 or CXCR4 receptors on a T-cell's surface. If entry inhibitors are successful in blocking these proteins, HIV is unable to bind to the surface of T-cells and gain entry into the cells. Only one entry inhibitor has been approved by the U.S. Food and Drug Administration (FDA): Fuzeon™ (T-20). This drug targets the gp41 protein on HIV's surface. Some experimental drugs target proteins on T-cells: BMS-488043 targets the gp120 protein, PRO-542 and TNX-355 target the CD4 protein, and SCH-D, GSK-873,140 and UK-427,857 target the CCR5 protein. HIV-positive people who have become resistant to PIs, NRTIs, and NNRTIs will likely benefit from the entry inhibitors because they are a different class of drugs. This is good news for HIV-positive people who have tried and failed many of the currently approved anti-HIV medications.To learn more on how HIV infects a T-cell and begins to create more viruses, and where each class of anti-HIV drugs blocks this process, click on the following lesson link:The HIV Life Cycle (and the targets of each class of anti-HIV drugs)