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An in-depth analysis of hiv infection, including epidemiological facts, modes of transmission, diagnosis methods, and immune response. Hiv heterogeneity, diagnosis techniques, major modes of transmission, and the role of antibodies and cellular immune response in controlling hiv infection.
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Instructor: Phalguni GuptaInstructor: Phalguni Gupta
Global: 40-60 million with HIV infection 33.4 million developed AIDS
Africa: Population 680 million 25 million HIV infected25 million HIV infected 10 million AIDS
US: Population 200 million 1 million HIV infected
India: Population 1.0 Billion China: Population: >1.2 billion 4.0 million HIV infected 1.2 million HIV-infected 0.16-0.36 million AIDS 0.05 million AIDS WHO report, 2004
Indirect Methods:
Direct Methods:
How HIV is Not Transmitted
HIV-
Source: NIAID
CCR5 or CXCR
Endoscopic and histological analysis of GI tract of a person with acute HIV-1 infection
CD4 T cells are stained in histologic sections
Douek, et al., 2004
% CD4 T cells in uninfected and HIV- infected persons
Douek, et al., 2004
gp gp V3 loop CD
Cell Membrane CCR5/CXCR (R5/X4) Adapted from Moore JP et al****. PNAS 2003;100:10598-10602.
Antibodies are not able to control HIV infection
HIV escape from CTL control
McMichael and Klenerman, Science 2002
Rapid Progressors
V-1 Viral Load
Divergent Disease Progressions in HIV-1 infection
8 – 12 weeks 8-10 years
Long Term Non-Progressors
years
Makedonas, et al., 2005
Scatter plot of HIV-specific responses in seronegative subjects exposed to HIV mucosally (Group I) and parenterally (Group II).
HIV early infection and T cell events: High risk seronegatives (HRSNs) or exposed uninfecteds [EUs])
Mechanisms of CD4+ T Cell Dysfunction and Depletion
Direct mechanisms
Problem: Frequency of HIV‐infected cells is mostly 0.1%. Therefore, direct mechanism cannot explain vast depletion of CD4 over time.
A ti HIV 1 CTL
OFF HAART HAART + Immunotherapy Off treatment
Effects of HAART on anti-HIV-1 T cell responses in chronic infection: Can immunotherapy help control residual HIV-1?
Anti-HIV-1 CTL
Anti-HIV- CD4 +^ TH1 cells
Piazza, Fan and Rinaldo, 2002