Acquired Immunedeficiency Disease (AIDS)

Study guide:

Definitions:  

  • Human immundeficiency virus (HIV) belongs to the lentivirus group of  the retroverdae family of viruses. They are enveloped single stranded RNA viruses.

  • AIDS is a spectrun of infections caused by HIV virus starting fom a flu-like syndrome to compromising the immune system.  

 

Pathophysiology:

◦ Virology: Important HIV virus genes and their functions

• Structural genes:

1. Env genes:

a. Gp120 → helps virus attach to CD4 T cell membrane and its coreceptors

b. Gp41 → Transmembrane fusion after attachement allowing virus to enter cell

2. Gag genes:

a. P23 → Capsid protein, first protein body develops antibody against, and first antibody to be detected

3. Pol genes:

a. Reverse transciptase → synthesizes double stranded DNA from viral RNA which is later integrated into host genome.

  • Regulatory genes:

1. Nef → Virulence factor. Decreses expression of MHC I and CD4 manipulating T-cell activation pathway. A rquirement for the development of AIDS.

a. Long term survival may results in the absence of functional nef protein

  • CD4 coreceptors are CCR5 and CXCR4:

1. Some people are born with mutations in CCR5. If the mutation is heterozygous, they will have a slower course.

2. If the mutations is homozygous, they will have immunity against HIV virus.

Disease Process:

  • HIV enters the body via sexual contact, IV drug use or vertical transmission from mother to child.

  • The virus attaches via its structural proteins to CD4 T-cell receptors.

  • Viral genome is transcribed from ssRNA to dsDNA via reverse transciptase and then incorprated into the host’s genome via viral integrases creating a provirus.

  • The provirus form stays latent untill activation with low levels of virion production enough to be detected in patient’s sera and to cause mild flue like illness. 

Clinical presentation: 4 Fs of HIV stages: Flu like (acute), feeling fine (latency), falling count, final crisis.  

  1. Flu like (acute): patients have mononuclosis like symptoms 2-4 weeks after exposure to HIV.

    • Mononucleosis like → Fever, lymphadenopathy, pharyngitis, rash, myalgias and arthralgia

  2. Feeling fine (latency): asymptomatic disease for several years (4-7 years), however patients are seropositive. Early detection and treatment may prolong latent phase.

  3. Falling count: Evidence of immune system dysfuction starts to appear. This manifests by generalized lymphadenopathy, fungal infections, resistant vaginal yeast or trichomonal infections in women, skin disorders such as seborrheic dermatitis and costitutional symptoms.

  4. Final crisis (AIDS): CD4 count decreses to <200 cell/mm2 leading to opprtinstic infections. 

Diagnosis:

  • Initial diagnosis is with ELISA (screening).

  • Defenitive test is by westren blot to confirm diagnosis.

  • CD4 count: AIDS is diagnosed when CD4 is lower than 200/mm3. It is used to meaure severity of immunedeficiency.

  • HIV PCR/viral load: test of choice for acute HIV infection

    • Allows monitoring of drug effect on viral load

    • New born screening.

Treatment:

  • Antiretroviral therapy (ART): The recommendation is to start ART once CD4 count declines below 500 or the disease is symptomatic.

    • If patient is pregnant, has HIV associated nephropathy or on antiheptaitis B management, start ART regardless of CD4 count.

  • The goal of treatemnt is to prevent viral replication and and resistance. To achieve this combination of 3 medications of at least 2 different classes is preferred. There are many best initial choices one examle is:

✔︎Efavirenz, tenofovir, emtricitabine.

  • ART classes:

References:

  1. USMLE Step 1 Immunology and Microbiology KAPLAN lectures notes.

  2. USMLE Step 1 Pharmacology KAPLAN Lectures Notes.

  3. Step Up to Medicine.

  4. The Johns Hopkins Internal Medicine Board Reviews. 

 

Written by: Dr. Amal Almoamary                                                           

Format editor: Roaa Amer

Web Publisher:   Shaden Almushawwah

Reviewed by:

Roaa Amer

Abdulaziz Beit AlMal

 

 

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