1. HAART Therapy Christine Ashton Christy Naylor Katherine Tompkins

2. What is HAART? Highly active antiretroviral therapy used for HIV treatment Highly active antiretroviral therapy used for HIV treatment Usually consists of a combination of two nucleoside analogues and a protease inhibitor Usually consists of a combination of two nucleoside analogues and a protease inhibitor

3. Why use HAART? Can still potentially work even if one or two of the drugs fail (b/c it is a triple therapy) Can still potentially work even if one or two of the drugs fail (b/c it is a triple therapy) Can help fight against strains that have become resistant to other antiretrovirals that don’t completely stop the virus from growing Can help fight against strains that have become resistant to other antiretrovirals that don’t completely stop the virus from growing

4. HAART and CD4 On HAART, the CD4 count can increase, the function of the white blood cells (especially lymphocytes) improves, the lymph nodes become more active and many infections will get better. The important white blood cells in HIV (the lymphocytes) exist in many different forms. There is a shift in some of these forms which may be beneficial. One paradox of HAART therapy is that sometimes, perhaps because the immune system is working better, some infections which are present in a quiet form may become active again; however, this does not seem to be a major problem when compared with all of the clinical benefits which do occur with HAART therapy.

5. Benefits of HAART Suppression of viremia and virus shedding in semen and vaginal secretions Suppression of viremia and virus shedding in semen and vaginal secretions Increased CD4+ T cell count Increased CD4+ T cell count Reduced immune activation Reduced immune activation Restoration of lymph node architecture Restoration of lymph node architecture Clinical improvement Clinical improvement –Prolonged survival –Fewer O.I.s and HIV-associated malignancies –Ability to discontinue O.I. prophylaxis and maintenance therapy

6. Disadvantages Doesn’t work in all cases Doesn’t work in all cases Doesn’t clear the latently infected cell pool Doesn’t clear the latently infected cell pool Doesn’t restore HIV-specific immunity Doesn’t restore HIV-specific immunity Doesn’t prevent relapse Doesn’t prevent relapse Offer an affordable therapy for 95% of HIV- infected people in the world (can cost $10,000- $12,000 per year) Offer an affordable therapy for 95% of HIV- infected people in the world (can cost $10,000- $12,000 per year) Prevent spread of infection, even if HIV is not present in blood tests anymore Prevent spread of infection, even if HIV is not present in blood tests anymore

7. Toxicities associated with HAART Lipoatrophy Lipoatrophy Abnormal fat accumulation Abnormal fat accumulation Hyperlipidemia Hyperlipidemia Insulin resistance Insulin resistance Bone loss Bone loss Marrow suppression Marrow suppression Pancreatitis Pancreatitis Hepatitis Hepatitis Nephropathy Nephropathy Neuropathy Neuropathy

8. Effects of protease inhibitors in the form of body deformations and mutilations From:http://www.virusmyth.net/aids/news/ bodydeform.htm

9. References http://www.fda.gov/ohrms/dockets/ac/00/sli des/3652s1_01/tsld002.htm http://www.fda.gov/ohrms/dockets/ac/00/sli des/3652s1_01/tsld002.htm http://www.fda.gov/ohrms/dockets/ac/00/sli des/3652s1_01/tsld002.htm http://www.fda.gov/ohrms/dockets/ac/00/sli des/3652s1_01/tsld002.htm Improving HIV Therapy, John Bartlett and Richard Moore, Scientific American Improving HIV Therapy, John Bartlett and Richard Moore, Scientific American