HIV/AIDS – At A Glance

HIV (Human immunodeficiency virus is a retrovirus that can lead to AIDS (Acquired immunodeficiency syndrome), a condition in humans in which the immune system begins to fail leading to life threatening opportunistic infections. 


Why it is called as RETRO ?

  • Because of the presence of the enzyme reverse transcriptase which has the ability to transcribe the RNA genome into double stranded proviral DNA and it is essential for their replication

Types Of HIV
  • HIV – type 1
  • HIV – type 2
 
 
Structure Of HIV
  • It is about 120nm in diameter
  • It is composed of two identical single stranded RNA of positive polarity, that codes for the 9 genes of the virus, which is enclosed by a conical capsid made up of 2000 copies of the viral protein P24
  • The single stranded RNA is tightly bound to nucleocapsid proteins P7
  • Enzymes that are responsible for the development of the virion is found within the nucleocapsid. Enzymes are…. 
    • Reverse transcriptase 
    • Proteases 
    • Integrase 
    • Ribonuclease 
  • The matrix which is formed by the viral protein P17, surrounds the nucleocapsid ensuring the integrity of the virion particle
  • This is in turn surrounded by a viral envelope which is composed of a lipid bilayer derived from the cell membrane of the host, taken at the time of the budding process
  • At the exterior of the cell, there are glycoprotein complexes that enables the virus to integrate with the CD4 receptors and mediate the fusion of the viral envelope with the cell membrane at the time of infection and thereby initiate the infectious cycle
  • The glycoprotein complex is made of a “cap” & a “stem”
  • “Cap” is made up of three glycoprotein molecules of gp120 which is responsible for the integration with the CD4 receptors on the cell surface
  • “Stem” is made up of three glycoprotein molecules of gp41 which mediate the fusion of the viral envelope with the cell membrane at the time of infection
 
Human Immunodeficiency Virus Structure - Mapping Ignorance
 
 
Genes Of HIV & Structural Components 
 
Out of the nine genes, three of them are responsible for the synthesis of the structural components of the virus. 
  • gag
    • p24, p7 (nucleocapsid) 
    • p17 (matrix) 
  • pol
    • Reverse transcriptase 
    • Proteases 
    • Integrase 
  • env
    • g120 (responsible for the integration with the CD4 receptors) 
    • g41 (mediate the fusion of the viral envelope with the cell membrane) 
 
Other six genes are…. 
  • tat, nef, vpr, rev, vif, vpu
  • These genes are regulatory genes that control the ability of virus, to…. 
    • Infect cells
    • Replicate 
    • Cause the disease
 
 
Pathogenesis Of HIV 
 
After entering into the blood 
                  ↓
Enter into lymphoid organs
                  ↓
Binds with the CD4 receptors of helper T – cells with gp120 
                  ↓
gp41 mediates the fusion of the viral envelope & the receptor 
                  ↓
Interact with the chemokine receptors (CXCR4, CCR5) 
                  ↓
Virion enters into the cell 
                  ↓
Viral mRNA produce DNA by reverse transcription 
                  ↓
Proviral DNA migrate into the nucleus of the host cell and become integrate to host cell DNA 
                  ↓
Proviral DNA produce mRNA by transcription & by translation it produces several polyproteins 
                  ↓
Polyproteins are cleaved to form structural proteins (Core proteins, envelope proteins, reverse transcriptase enzyme) 
                  ↓
Virion is assembled within the cytoplasm & release from the cell by budding 
                  ↓
The active process of budding ruptures the cell and cause death of the CD4+ T – lymphocytes 
                  ↓
Dysfunction or depletion of CD4+ T – lymphocytes 
                  ↓
Leads to immunodeficiency
 
 
Transmission Of HIV
  • Sexual transmission
    • More common among male homosexuals than heterosexuals 
    • Vaginal sex 
    • Anal sex 
    • Oral sex (Rare, it can occur only when there is any breach in the oral mucosa)
  • Parenteral transmission
    • Blood & blood products 
    • Contaminated needles, syringes, surgical instruments 
    • Drug abusers 
  • Vertical transmission
    • Across the placenta 
    • At birth 
    • Through breast milk

* AIDS cannot be transmitted from person to person, but HIV can be transmitted from the methods mentioned above
 
HIV is not transmitted through….
  • Hugging, kissing 
  • Spitting 
  • Dancing
  • Contact with unbroken skin – Hand shaking, massages  
  • Sharing toilets, swimming pools
  • Mouth-to-mouth resuscitation 
  • Insect bites
  • Not transmitted through air or water
 
 
Clinical Features Of HIV
 
There are 3 phases 
  • Acute or Early HIV / Primary infection / HIV seroconversion illness
  • Chronic HIV / Latent infection
  • AIDS / Late infection
 
Acute or Early HIV / Primary Infection / HIV Seroconversion Illness
  • Majority of the patients (80%) will experience flu like illness 
  • These are 
  • This usually takes place 2 – 6 weeks after the entry of the virus into the body
  • These symptoms will last for 1 – 2 weeks and then the patient will remain asymptomatic for years
  • Flu like illness includes symptoms, such as….
    • Fever
    • Lethergy
    • Sore throat 
    • Arthralgia, myalgia
    • Rash – Maculopapular rash
    • Generalized lymphadenopathy
    • Splenomegaly
    • Hepatomegaly
  • Patients recover spontaneously from this flu like illness in about 3 weeks
  • In some cases, these symptoms are mild and can easily be missed 
  • Flu like illness occur because our immune system is trying to put up a fight in order to destroy the virus
  • Leukopenia can be present at this stage, but the CD4 T – lymphocytes are normal
 
Chronic HIV / Latent infection
  • Patient remains asymptomatic during this period 
  • Usually lasts up to 10 years
  • When the disease progress and the immune system is severely damaged, patient will begin to develop symptoms of ARC (AIDS related complex)
  • ARC (AIDS Related Complex)
    • It is a condition in HIV infected patients where they become ill with a variety of problems that can be relatively trivial but the constitutional symptoms occur due to the immunodeficiency caused by the HIV infection. 
    • Most common manifestations are…. 
      • Chronic fever for more than 2 months
      • Chronic diarrhoea for more than 1 month
      • Unexplained night sweats for more than 1 month
      • Weight loss which occurs in 10% of cases which is not related to dieting
      • Recurrent infections
      • Leukopenia with progressive diminution of CD4 T – lymphocytes
 
AIDS / Late Infection
  • It is the late stage of HIV infection which is caused by the human immunodeficiency virus, where the CD4 cell count of the body has fallen below 200/mm3 or 400/μL with an increase in the severity and frequency of opportunistic infections where the common curable infectious diseases turn into life threatening incurable diseases due to the immunodeficiency caused by the HIV infection.
  • Develops persistent generalized lymphadenopathy, splenomegaly along with opportunistic infections (Mentioned below)


Investigations For HIV
 
Even if there is no cure for HIV yet, but early diagnosis carries better prognosis and can prevent the development of AIDS with effective treatment.
Therefore diagnosing the disease as early as possible is very important.
 
Diagnosis is made by doing HIV tests. 
These tests are negative at the very early stage of the disease and usually starts to become positive after 1 month of the disease process. 
 
There are tests which are performed at clinical setup as well as at home by yourself.
Self tests which are performed at home is done by using saliva and it also gives accurate results.
In clinical setup, tests are performed using blood.
 
To diagnose the disease
  1. Rapid ELISA test
    • Screening for HIV
    • Detection of IgG antibiodies against HIV envelop particles
  2. Western blot 
    • Confirmatory test for HIV
    • Combined with ELISA test can give accurate results up to 99.9%
  3. Nucleic acid tests (NATs)
    • Detection of viral RNA in blood
    • This is the first test to become positive after an exposure
    • Best done, if exposure is suspected to be few weeks ago
 
To stage and to assess further management 
  1. CD4 T cell count
  2. CD4 : CD8 ratio
  3. Viral load – Reverse transcription polymerase chain reaction (RT-PCR)
  4. Drug resistance 
  5. FBC and blood picture
    • Lymphopenia
    • Thrombocytopenia
    • Atypical lymphocytes
 
 
Opportunistic Infections In AIDS
  • Muconutaneous diseases
    1. Seborrhoeic dermatitis
    2. Multidermatomal herpes zoster
    3. Norwegian scabies
    4. Oral / oesophageal candidiasis
    5. Oral hairy leukoplekia 
    6. Chicken pox 
  • Eye diseases
    1. CMV retinitis
  • Neurological diseases
    1. Meningitis caused by CMV, HIV, Cryptococcus neoformans
    2. Tuberculoma
    3. HIV dementia
    4. Peripheral neuropathy
  • Renal diseases
    1. HIV associated nephropathy
    2. Nephrotic syndrome
  • Respiratory diseases
    1. Pneumocystis carinii pneumonia
    2. CMV pneumonia
    3. Tuberculosis
  • GIT diseases
    1. Chronic diarrhoea caused by Cryptosporidium parvumIsospoa belliSalmonella typhi
  • Malignancies
    1. Kaposi sarcoma
    2. Non Hodgkins lymphoma
 
 
Treatment Of HIV
 
There is no cure for HIV, but the current treatments are very effective in controlling the disease.
This treatment is called as Antiretroviral therapy (ART) / Highly active antiretroviral therapy (HAART) 
Every patient diagnosed with HIV should be started on ART, irrespective of the phase of the disease.
  • Antiretrovial therapy (ART)
    • Combination of drugs are given to prevent the development of resistance
    • Viral load is assessed to see the effectiveness of the disease
    • Viral load become undetectable usually after 6 months of ART
    • There are several classes of anti-HIV drugs 
    • Usually a patient is prescribed with two drugs of the same class and one drug from another class
    • The best combination is determined by the physicians  
    • Classes of Anti-HIV drugs
      • Non-nucleoside reverse transcriptase inhibitors (NNRTIs) 
        • Rilpivirine 
        • Doravirine
      • Nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs) 
        • Lamivudine 
        • Zidovudine
      • Protease inhibitors (PIs) 
        • Abacavir
      • Integrase inhibitors
 
 
Prevention Of HIV
  1. Treatment as prevention
    • Keeping the viral load at undetectable levels will not transmit the disease
    • This is called as treatment as prevention
  2. Use of condoms and lubricants 
    • Both male and female condoms are effective
    • Water based lubricants are preferred over oil based lubricants, because oil based lubricants can weaken the integrity of a condom leading to a break or tear in the condom
  3. Avoid sharing needles among drug users
  4. Pre exposure prophylaxis 
    • Can reduce the risk of getting HIV through sexual transmission up to 90% 
  5. Post exposure prophylaxis 
    • Should be initiated within 72 hours of contact 
    • Should be taken daily for 1 month 
  6. Screening for HIV in pregnancy 
    • Done during the antenatal period
    • This prevent vertical transmission of the disease to the newborn 
    • If mother is found to be positive should start ART immediately 
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