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33 Cards in this Set

  • Front
  • Back
In whom should you consider the diagnosis of HIV infection?
Anyone presenting with symptoms compatible with an HIV-related disorder or in an asymptomatic person with any risk factor for acquisition.
What is the basis for establishing non-acute HIV infection?
HIV antibody detection
Describe the HIV antibody detection test
The initial test is typically an ELISA test that can be HIV-1 specific or may screen for both HIV-1 and HIV-2

A positive ELISA antibody must be confirmed by a second test, typically a Western blot test

Rapid HIV antibody tests are now widely available (results in 30min-1hr)
Describe the western blot for HIV
It detects serum antibodies to specific HIV proteins that are separated on a gel
Describe diagnosis of acute infection
-Seroconversion may not have occurs
-HIV antibody tests should be done, but may be negative
-Plasma HIV-1 RNA test should be done as the viral load is typically very high during the acute phase of HIV infection
-Follow up antibody test should be done to confirm that full seroconversion has occured
HIV is part of what virus family?
Describe the structure of HIV
-ssRNA virus
-Icosahedral nucleocapsid
-Lipid envelope
-Virion has two identical copies of RNA
-Carries a unique viral enzyme, reverse transcriptase
Describe the viral replication scheme
1. Binding an infection
2. Reverse transcription and integration of viral DNA
3. Transcription and translation
4. Modification and assembly
5. Budding and final assembly
Describe the HIV genome
-Consists of 3 major segments (Gag, Pol, Env) and 6 accessory genes
What does the Gag segment of the genome do?
Encodes for internal structural proteins
What does the Pol segment of the genome do?
Codes for major enzymes of the virus- reverse transcriptase, protease, and integrase
What does the Env part of the genome encode?
The gp120 envelope glycoprotein and the gp41 transmembrane protein. These proteins mediate attachment and entry of the virus into the cell
What are the accessory proteins of HIV and what do they do?
-Tat, Rev, Nef, Vif, Vpr, Vpu
-Involved in amplification of virus replication, infectivity, and pathogenesis
What cell first encounters HIV after its deposition on mucosal surfaces?
The dendritic cell
What strain of HIV is generally involved in primary infection?
What is the receptor for HIV on the dendritic cell?
What are the steps during the primary HIV infection?
1) Virus-dendritic cell interaction
2) Delivery of virus to the lymph nodes
3) Hight levels of viremia and viral dissemination
4) Downregulation of virus replication by immune response
5) Viral set point is reached
What occurs when HIV virus reaches the lymph nodes during primary HIV infection?
Very active replication takes place. In general, dendritic cells act as transporters of HIV and do not primarily support HIV replication.
What occurs with the high levels of viremia and viral dissemination during acute HIV infection?
There is massive loss of CD4+ T lymphocytes from the GALT which is not fully reflected in the peripheral blood CD4 count. The GALT may contain up to 40% of the body's total lymphoid tissue.
Describe the downregulation of virus replication by the immune system during primary HIV infection
-Primarily mediated by CD8+ cytotoxic T cells

-Neutralizing antibodies are formed but virus titers fall before these antibodies are fully developed
How long after primary HIV infection does it take to reach the viral "set point"?
6 months
What is the viral set point predictive of?
The rate of subsequent disease progression
Describe viral replication once HIV infection is established
-Active viral replication present throughout the course of disease despite an often long clinical latency period between the time of infection and the development of what is clinical AIDS
What is clinical AIDS defined as?
-CD4 count <200/mm^3
-Development of an HIV-related opportunistic infection or malignancy
Describe reservoirs of HIV
Although one measures the virus in the peripheral blood, major reservoirs exist outside of the blood compartment.

These include:
-lymphoreticular tissues (the major "factory" of HIV in lymph nodes, spleen and GI tract)
-Genital tract
Describe the distribution of HIV strains in an infected individual
-Virus exists as multiple quasispecies or swarms of viruses
-Mixtures of bviruses with differential phenotypic and genotypic characteristics may coexist in the same body compartment or across body compartments
-Viruses with different cell tropisms or drug resistance patterns may and do coexist in an infected person
How many virions are produced daily in an infected individual?
What is the halflife of HIV in plasma?
What are the person specific codeterminnats of outcome in HIV infection?
-Strength of innate and adaptive immune responses (esp CD8 cytotoxic T cells)
-Chemokine receptor status
-HLA type
What is risk of clinical illness associated with?
The clinical illness develops as the CD4 cell count falls, particularly as it falls bellow 200/mm3. The risk is progressive as the CD4 cell count falls below this level.
What is the average time from infection to clinical AIDS? What is the distribution of times?
Typically 8-10 years

There are rapid progressors who develop AIDS within 2 years or so of infection and long-term non-progressors who maintain normal CD4 cell counts and very low viral loads in the absence of treatment for >10-15 years

A subgroup of LTNPs has been termed "elite controllers". These indivudals maintain plasma HIV-1 RNA (viral load) levels <50 copies/ml in the absence of antiretroviral therapy. These elite controllers form a very small percentage of the overall HIV infected population but are being studied intensively for the insights they may provide into the effective immune controls they exhibit which might be mimicked in an HIV vaccine.
What are Non-AIDS conditions?
Cardiovascular, hepatic, and renal disease events as well as a number of non-AIDS-defining malignancies that have been reported to be associated with ongoing HIV viremia even in persons with relatively well maintained CD4 counts
What are some of the proposed mechanisms responsible for non-AIDs conditions?
-Direct effects of HIV
-The immune activation associated with uncontrolled HIV replication
-Subtle immune deficiency (in persons with higher CD4 counts)