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

Acquired Immunodeficiency Disease

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 Syndrome Opportunistic Diseases and cancer pneumonia Kaposi’s Sarcoma Kaposi’s Sarcoma

Transmission of HIV

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

For Your Information and Files

Acquired Immunodeficiency Syndrome Normal CD4+ count Normal CD4+ (%) AIDS 500-1600/mm3 20-40% <350/mm3 begin anti-viral treatment <14% serious immune damage

Antiretroviral Agents Table 1. For Your personal Information: not for lecture. Antiretroviral Agents    Agent Type Dose Major Toxicities AZT NRTI 300 mg bid nausea, headache,  low blood counts ddI 125-200 mg bid or 250-400 mg qd (tablet form) diarrhea, pancreatitis,  peripheral neuropathy ddC 0.750 mg tid diarrhea,  peripheral neuropathy d4T 30-40 mg bid abnormal liver function tests, peripheral neuropathy 3TC 150 mg bid minor abacavir hypersensitivity reaction tenofovir NRTI (nucleotide) 300 mg qd nausea, diarrhea, vomiting, flatulence

AZT/3TC (Combivir) NRTI one pill bid (300 mg AZT/150 mg 3TC) see above AZT/3TC/abacavir (Trizivir) one pill bid (300 mg AZT/150 mg 3TC/ 300 mg abacavir) nevirapine NNRTI 200 mg bid rash delavirdine 400 mg tid efavirenz 600 mg qhs rash, dizziness, impaired concentration, insomnia, abnormal dreams saquinavir (Fortovase) PI 1200 mg tid diarrhea ritonavir 600 mg bid nausea/vomiting, drug interactions indinavir 800 mg tid kidney stones nelfinavir 750 mg tid or 1250 mg bid amprenavir 1200 mg bid nausea/vomiting,  diarrhea, rash lopinavir/ritonavir three capsules bid (133.3 mg lopinavir/33.3 mg ritonavir) diarrhea, nausea, weakness, headache

Experimental drugs are italicized, and approved drugs are in regular, non-italicized type) Brand Name Generic Name Abbreviation Experimental Code Pharmaceutical Company Fuzeon™ enfuvirtide ENF T-20 Trimeris and Hoffmann-La Roche   BMS-488043 Bristol-Myers Squibb GSK-873,140 GlaxoSmithKline PRO-542 Progenics Pharmaceuticals SCH-D Schering-Plough Corporation TNX-355 Tanox and Biogen Idec UK-427,857 Pfizer

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 Squibb   GSK-873,140GlaxoSmithKline   PRO-542Progenics Pharmaceuticals   SCH-DSchering-Plough Corporation   TNX-355Tanox and Biogen Idec   UK-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)