Chapter 1 Notes

Chapter 1 - The Natural History of the HIV Epidemic

• HIV has infected over 65 million people, 30 million deaths, spreads via bodily fluids

• Antiviral drugs reduce risk of transmission

• HIV is an intracellular parasite incapable of reproducing on its own, afflicts immune system

• HIV virions enter host cells by binding to proteins on surface, then use host machinery to make new virions

• Dendritic cells patrol vulnerable tissues, take viruses to lymph nodes, present bits of its protein to naive helper T cells, these cells divide to produce helper T cells

• Effector helper T cells stimulate B cells to mature into plasma cells, which make antibodies

• Killer T cells destroy infected host cells

• HIV infection depletes CD4+ T cells in gut, impaired gut defenses allow translocation of bacteria into bloodstream, activates immune response, effector T cell proliferation, gives HIV more target cells, chronic infection and inflammation, damaged lymph nodes

Why Does HIV Therapy Using Just One Drug Ultimately Fail?

• Drugs inhibit enzymes that are special to the virus

• AZT blocks reverse transcription, loses effectiveness, population of virions become resistant to disruption by AZT

• Categories of drugs used: Coreceptor inhibitors, fusion inhibitors, reverse transcriptase inhibitors, integrase inhibitors, protease inhibitors

• Multiple drugs that target different point in HIV life cycle is much more effective, reduces the genetic variation for resistance, HIV can be resistant to multidrug cocktails