Human immunodeficiency virus: Difference between revisions
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− | = Definition = |
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* A chronic immunodeficiency resulting from infection with the human immunodeficiency virus (HIV) |
* A chronic immunodeficiency resulting from infection with the human immunodeficiency virus (HIV) |
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* Acquired immune deficiency syndrome (AIDS) is a severe form of HIV characterized by low CD4 count resulting in characteristic infections |
* Acquired immune deficiency syndrome (AIDS) is a severe form of HIV characterized by low CD4 count resulting in characteristic infections |
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− | = |
+ | = Microbiology = |
+ | |||
+ | * A member of the Retroviridae family |
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+ | |||
+ | == Clades / Subtypes == |
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+ | |||
+ | * HIV-1 |
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+ | ** M group |
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+ | *** Clade A: common in East Africa |
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+ | *** Clade B: is common in Canada, Americas, Europe |
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+ | * HIV-2 |
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+ | |||
+ | = Life Cycle = |
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+ | |||
+ | * Two phases: initial viral attachment, fusion, reverse transcription, and integration; and the following lifetime of the viral infection |
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+ | * Initial cellular infection |
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+ | *# Binding or attachment of the virion gp120 Env surface protein to the CD4 receptor with CCR5 or CXCR4 coreceptor (on macrophage or T-cell, respectively). |
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+ | *# Binding the receptor triggers a conformational change that exposes the fusion domain on gp41, which facilitates fusion and viral entry. The proceeding viral disassembly requires viral protein p24 to bind to cellular cyclophilin A. |
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+ | *# In the cytoplasm, reverse transcriptase converts viral RNA into viral DNA. The RNA is degraded, then the complementary strand of DNA created. |
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+ | *# The preintegration complex of double-stranded DNA is imported into the nucleus using viral Gag, viral protein R (Vpr), and integrase. Unlike other retroviruses, HIV does not require active replication to enter the nucleus. |
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+ | * Infection of lymphoid cells and lymph nodes, especially gut-associated lymphoid tissue (GALT) |
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+ | ** Infection therefore kills a large proportion of CD4 cells in the gut |
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+ | * HIV enters from the mucosa to infect activated Langerhans macrophages, which then get to the local lymphoid tissue |
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+ | |||
+ | = Epidemiology = |
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+ | * 63,000 Canadians living with HIV in 2016 |
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+ | * 14% don't know they have it |
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+ | * Methods of acquisition in Canada |
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+ | ** MSM (52% of cases) |
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+ | ** People who inject drugs (17% of cases) |
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+ | ** Heterosexual sex (33% of cases) |
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+ | |||
+ | = Risk Factors = |
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+ | |||
+ | * High-risk exposures |
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+ | ** MSM |
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+ | ** Multiple partners |
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+ | ** Injection drug use |
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+ | ** Sex work |
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+ | * Aboriginal Canadians (2.7x higher incidence) |
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+ | * African and Caribbean people (endemic countries) |
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+ | * Prior STIs |
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= Presentation = |
= Presentation = |
Revision as of 13:15, 13 August 2019
- A chronic immunodeficiency resulting from infection with the human immunodeficiency virus (HIV)
- Acquired immune deficiency syndrome (AIDS) is a severe form of HIV characterized by low CD4 count resulting in characteristic infections
Microbiology
- A member of the Retroviridae family
Clades / Subtypes
- HIV-1
- M group
- Clade A: common in East Africa
- Clade B: is common in Canada, Americas, Europe
- M group
- HIV-2
Life Cycle
- Two phases: initial viral attachment, fusion, reverse transcription, and integration; and the following lifetime of the viral infection
- Initial cellular infection
- Binding or attachment of the virion gp120 Env surface protein to the CD4 receptor with CCR5 or CXCR4 coreceptor (on macrophage or T-cell, respectively).
- Binding the receptor triggers a conformational change that exposes the fusion domain on gp41, which facilitates fusion and viral entry. The proceeding viral disassembly requires viral protein p24 to bind to cellular cyclophilin A.
- In the cytoplasm, reverse transcriptase converts viral RNA into viral DNA. The RNA is degraded, then the complementary strand of DNA created.
- The preintegration complex of double-stranded DNA is imported into the nucleus using viral Gag, viral protein R (Vpr), and integrase. Unlike other retroviruses, HIV does not require active replication to enter the nucleus.
- Infection of lymphoid cells and lymph nodes, especially gut-associated lymphoid tissue (GALT)
- Infection therefore kills a large proportion of CD4 cells in the gut
- HIV enters from the mucosa to infect activated Langerhans macrophages, which then get to the local lymphoid tissue
Epidemiology
- 63,000 Canadians living with HIV in 2016
- 14% don't know they have it
- Methods of acquisition in Canada
- MSM (52% of cases)
- People who inject drugs (17% of cases)
- Heterosexual sex (33% of cases)
Risk Factors
- High-risk exposures
- MSM
- Multiple partners
- Injection drug use
- Sex work
- Aboriginal Canadians (2.7x higher incidence)
- African and Caribbean people (endemic countries)
- Prior STIs
Presentation
Acute seroconversion
- Influenza-like illness
- Rash
- ...
Chronic HIV
- Fever
- Weight loss
- Dyspnea, cough, hemoptysis
- Dysphagia, diarrhea
- Anemia, neutropenia, thrombocytopenia
- Metabolic derangements
- [Opportunistic infections](Complications/Opportunistic infections/Opportunistic infections.md)
Investigations
- HIV serology
- If concern for acute seroconversion syndrome, may need to repeat serology
- HIV viral load and CD4 count
Management
Initial management
- See [HIV first clinic visit](Treatment/HIV first clinic visit.md) and [single-tablet regimens](Treatment/Single-tablet regimens.md)
Follow-up
- HIV viral load
- Every 4 to 6 weeks until undetectable
- Then every 3 months until undetectable for 1 year
- Then every 6 months
- CD4 count
- Every 3 to 4 months until viral load undetectable and CD4 count >350 for 1 year
- Then every 6 months until viral load undetectable for at least 2 years and CD4 count > 500
- Then stop monitoring routinely unless evidence of treatment failure
- Assess for failure if RNA level remains detectable at 24 weeks or if it increases to above 50 at any time
- Repeat RNA level within 4 weeks