HIV is a retrovirus that infects and destroys CD4 cells of the immune system. It originated from chimpanzees in Central Africa and has led to a global pandemic. Over 34 million people were living with HIV in 2010. The virus progresses through acute infection, asymptomatic infection, symptomatic infection, and AIDS if untreated. It is transmitted through body fluids and destroys CD4 cells over time if not treated with antiretroviral drugs.

1. Pathophysiology: HIV and AIDS
HIV = Human Immunodeficiency Virus (Initial Infection)
AIDS = Acquired Immunodeficiency Syndrome (Sequale of HIV)
 The first AIDs cases = in USA (1981)
 34,000,000 people were living with HIV in 2010
 1,800,000 people died of AIDS in 2010
 Sub-Saharan Africa = Greatest Incidence of HIV
HIV is thought to have originated from cross-species
transfers from Chimpanzees in Central Africa –
potentially through the Bush Meat Trade 
Spread of HIV follows trucking routes around Africa.
Transmission
Transmission is Via Infected Body
Fluids:
 Blood
 Serous effusions
 Cerebrospinal fluid
 Semen
 Vaginal fluid
 Breast milk
Or other body fluids containing
infected blood such as: Saliva, Vomit and
Urine
 Common routes of transmission
The Virus
 HIV is a Retrovirus (Genus = Lentivirus)
 Its Features include:
o Enveloped
o Diploid
o An RNA Virus (with a DNA intermediate)
 There are two different types:
1. HIV-1 = Global Pandemic
2. HIV-2 = Mostly Western Africa
 HIV-1 is more transmissible and associated with
a faster rate of CD4 decline than HIV-2.
 Both types of HIV contain the 3 Retroviral Genes:
o Gag encodes for Inner Structural
Proteins
o Pol encodes for enzymes:
 Polymerase
 Integrase
 Protease
o Env encodes for the Viral Envelope:
 On which is Glycoprotein 120 (Attaches to CD4 of host)

2. Immunology:
1. HIV infects human  Attaches to cells
bearing the CD4 protein:
o T- Helper Lymphocytes
o Macrophages
o Monocytes
o Neural Cells
2. Uncoating: The Viral envelope fuses to
host cell membrane and the Viral
Nucleus is released from its’ Capsid into
the Host’s Cytoplasm
3. Reverse Transcription:
o An enzyme is created by HIV = Reverse Transcriptase
o This enzyme is used by the Virus, to Reverse Transcribe its own RNA genomes
into DNA that can be integrated into the host’s DNA.
o So: HIV’s own RNA Genome  Reverse Transcriptase  Proviral DNA
o NB: The above is ESSENTIAL to understand the main HIV drug mechanisms
4. Circularisation: This pro-viral DNA becomes circular (increases efficiency apparently)
and migrates to the Host Cell nucleus.
5. Integration: The enzyme Integrase integrates the Proviral DNA into the cellular DNA
6. Transcription: Proviral DNA  Transcription by the Cell’s Polymerase  Proviral mRNA
7. Translation: Proviral mRNA  Translation by the Cell’s Ribosomes  Viral Proteins
8. Core Particle Assembly:
o Viral Proteins  Transported to the Cell membrane Immature Virions
o Polypeptide Precursors  Processed by Viral Protease  Mature Virus
Particles
9. Budding:
o Release of Mature Virus Particles and Immature Virions from Host Cell
Following release: these new replications of HIV infect further CD4 cells. This whole process
essentially has TWO effects:
1. Increases the Viral Load of HIV
2. Decreases the number of functional CD4 cells

3. Natural History:
Clinically there are FOUR phases of HIV infection:
1. Acute HIV Infection
2. Asymptomatic HIV Infection
3. Symptomatic HIV Infections
4. AIDS defining Illness
Acute HIV Infection
 Also known as “Seroconversion”
 2-4 weeks after initial exposure in 60% of sufferers
 Similar symptoms to Glandular Fever 
 Serology = Negative or Indeterminate
Asymptomatic HIV Infection
 The virus is in balance with the immune
system
 The only sign may:
o Generalised Lymphadenopathy
 Varies in Length – average around 8 years
Symptomatic HIV Infection
 CD4 Count has started to fall – treatment
level is <350cells/mm³
 Viral Load is increasing steadily
 Constitutional Symptoms
o Fever and Diarrhoea
 Opportunistic Infections 
 Always consider HIV in presentations that are:
o Atypical
o Recurrent
o Severe
AIDS defining Illness
A diagnosis of AIDS depends on the TWO things:
1. CD4 Count:
o 1 = CD4 of 500cells/mm³
o 2 = CD4 of 200-499cells/mm³
o 3 = CD4 of <200cells/mm³
2. Clinical Stage:
o A = Asymptomatic HIV
o B = Symptomatic HIV
o C = AIDS defining Diagnoses 
AIDS is classified as any patient with:
 A Combined Classification of:
o C1 / C2 / C3 / A3 / B3 / C3
 So basically anyone who has:
o Ever had a CD4 count of
<200cells/mm³ - whatever their
current clinical state
o Ever had an AIDS defining
diagnosis – whatever their current
CD4 count

4. Clinically it is important to check for co-infections with similar routes of Transmission:
o Hepatitis C / B and Herpes Virus
Key Points:
 The greatest incidence of HIV infection is in Sub-Saharan Africa
 The main HIV risk groups include:
o Gay men, IV Drug Abusers, Sex Workers and Sub-Saharan Africans
 HIV is an RNA Retrovirus, with a DNA intermediate to allow integration into Host Cells
 The Virology of HIV is important to learn to understand HAART (Highly Active Anti-Retroviral
Therapy – see David’s PBL)
 HIV infection results in a reduced CD4 count predisposing to Opportunistic Infections
 To diagnose AIDS a patient must have at one point had:
o A CD4 count of <200cells/mm³
o An AIDS defining diagnosis
References:
1. Sierra et al. Basics of the Virology and HIV-1and its Replication. Journal of Clinical
Virology. Volume 34. Issue 4; 2005.
2. Dr N David. Clinical HIV Management. UEA Seminar; January 2012
3. Centres for Disease Control and Prevention (CDC). Revised Classification System for
HIV Infection and Expanded Surveillance Case Definition for AIDS Among Adolescents
and Adults; 1993
4. Medscape. HIV Disease. Available at:
http://emedicine.medscape.com/article/211316-overview#a0101
5. Patient UK. HIV. Available at: http://www.patient.co.uk/showdoc/40000389/