Mid Hiv Diagnosis And Pathogenesis

Front 1

In whom should you consider the diagnosis of HIV infection?

Back 1

Anyone presenting with symptoms compatible with an HIV-related disorder or in an asymptomatic person with any risk factor for acquisition.

Front 2

What is the basis for establishing non-acute HIV infection?

Back 2

HIV antibody detection

Front 3

Describe the HIV antibody detection test

Back 3

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)

Front 4

Describe the western blot for HIV

Back 4

It detects serum antibodies to specific HIV proteins that are separated on a gel

Front 5

Describe diagnosis of acute infection

Back 5

-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

Front 6

HIV is part of what virus family?

Back 6

Retrovirus

Front 7

Describe the structure of HIV

Back 7

-ssRNA virus
-Icosahedral nucleocapsid
-Lipid envelope
-Virion has two identical copies of RNA
-Carries a unique viral enzyme, reverse transcriptase

Front 8

Describe the viral replication scheme

Back 8

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

Front 9

Describe the HIV genome

Back 9

-10kB
-Consists of 3 major segments (Gag, Pol, Env) and 6 accessory genes

Front 10

What does the Gag segment of the genome do?

Back 10

Encodes for internal structural proteins

Front 11

What does the Pol segment of the genome do?

Back 11

Codes for major enzymes of the virus- reverse transcriptase, protease, and integrase

Front 12

What does the Env part of the genome encode?

Back 12

The gp120 envelope glycoprotein and the gp41 transmembrane protein. These proteins mediate attachment and entry of the virus into the cell

Front 13

What are the accessory proteins of HIV and what do they do?

Back 13

-Tat, Rev, Nef, Vif, Vpr, Vpu
-Involved in amplification of virus replication, infectivity, and pathogenesis

Front 14

What cell first encounters HIV after its deposition on mucosal surfaces?

Back 14

The dendritic cell

Front 15

What strain of HIV is generally involved in primary infection?

Back 15

R5

Front 16

What is the receptor for HIV on the dendritic cell?

Back 16

DC-SIGN

Front 17

What are the steps during the primary HIV infection?

Back 17

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

Front 18

What occurs when HIV virus reaches the lymph nodes during primary HIV infection?

Back 18

Very active replication takes place. In general, dendritic cells act as transporters of HIV and do not primarily support HIV replication.

Front 19

What occurs with the high levels of viremia and viral dissemination during acute HIV infection?

Back 19

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.

Front 20

Describe the downregulation of virus replication by the immune system during primary HIV infection

Back 20

-Primarily mediated by CD8+ cytotoxic T cells

-Neutralizing antibodies are formed but virus titers fall before these antibodies are fully developed

Front 21

How long after primary HIV infection does it take to reach the viral "set point"?

Back 21

6 months

Front 22

What is the viral set point predictive of?

Back 22

The rate of subsequent disease progression

Front 23

Describe viral replication once HIV infection is established

Back 23

-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

Front 24

What is clinical AIDS defined as?

Back 24

-CD4 count <200/mm^3
-or-
-Development of an HIV-related opportunistic infection or malignancy

Front 25

Describe reservoirs of HIV

Back 25

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)
-CNS
-Genital tract

Front 26

Describe the distribution of HIV strains in an infected individual

Back 26

-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

Front 27

How many virions are produced daily in an infected individual?

Back 27

10*10^9

Front 28

What is the halflife of HIV in plasma?

Back 28

30min-6hr

Front 29

What are the person specific codeterminnats of outcome in HIV infection?

Back 29

-Strength of innate and adaptive immune responses (esp CD8 cytotoxic T cells)
-Chemokine receptor status
-HLA type

Front 30

What is risk of clinical illness associated with?

Back 30

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.

Front 31

What is the average time from infection to clinical AIDS? What is the distribution of times?

Back 31

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.

Front 32

What are Non-AIDS conditions?

Back 32

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

Front 33

What are some of the proposed mechanisms responsible for non-AIDs conditions?

Back 33

-Direct effects of HIV
-The immune activation associated with uncontrolled HIV replication
-Subtle immune deficiency (in persons with higher CD4 counts)