Natural history of HIV

Natural History of HIV:
The course of HIV if it is not treated or manipulated in any way e.g. from infection to death.

Life Cycle of HIV
• Life cycle of HIV is divided into seven (7) main steps as described below

o Attachment of HIV virus through the interaction between viral glycoprotein and CD4
receptors and co-receptors:
The spikes on HIV virus attach to special areas on the surface of T-cells called
receptors.
o Fusion and release of RNA into the cytoplasm of the cell:
After attachment the envelope and capsid fuse with cell membrane of the human cell thus releasing the RNA into the cytoplasm of the human white blood cell.
o Reverse transcription to produce viral DNA Using other components from the T- cell, the viral enzyme, reverse transcriptase
produces a DNA copy of viral RNA; this DNA copy is called a pro-viral DNA.
o Integration of pro-viral DNA to host DNA using other components from the T- cell.
The viral enzyme (integrase) integrates the proviral DNA into the T-cell DNA.
o Synthesis of viral proteins: using other cellular components from T. cell, the viral
enzyme (protease) synthesises viral protein necessary for a completion of virion.
o Assembly and release of a complete virion.
o Virions are distributed to infect other more T-helper cell: virion are released from T-cells and can infect more T-cell.
ce: MOHSW 2008

HIV Types and Subtypes
• There are two types of HIV which are HIV-1 and HIV-2
• Globally HIV-1 is much more common than HIV-2 and that many types of sub-groups exist within HIV-1 but none for HIV-2
• There are many sub-types within HIV-1 (A-K)
• Predominant subtypes in Tanzania are A and C it of HIV on the Immune System
• HIV infects CD4 cell (CD4 cell have the CD4 receptors necessary for HIV-1 and HIV-2 entry into the cells).
• The CD4 cells infected with HIV are eventually destroyed and consequently decrease in numbers.
• Decrease in number of CD4 cells leading to immune suppression that predisposes the patient to opportunistic infections (OIs).

Factors Affecting HIV Progression
Host Factors
• Age: Progression is more rapid in children and the elderly (>55)
• Strength of the Immune System
o Individuals can control the initial viremia to different extents
o This difference explains why some individuals have different viral loads
• Presence of other infections, such as TB and other OIs
• Nutritional status
o Poor nutrition and micronutrient deficiencies affect progression
• Viral Set Points
o The viral load of a patient infected with HIV stabilises after a period of acute HIV
infection
o It is reached after the immune system has developed antibodies to the HIV virus and begins to fight the virus
o The higher the set point, the faster the progression and vice versa
o There are various reasons why people with HIV have different viral set points such as Host factors such e.g. Genetic, immune system and age (children have higher set points)

Mode of transmission e.g. those who are infected by blood transfusion progresses
faster than those who get from other means

Viral Factors
• Viral fitness – a ‘fit’ virus is able to multiply faster and survive better in the human body
• Patients with symptomatic primary infection progress more rapidly
• HIV subtype and viral ability to cause disease (virulence)
• Dual HIV infection
o Infection with more than one HIV strain may lead to more rapid disease progression

Unknown factors
• Sometimes the reasons for different viral set points cannot be found or explained

Clinical Features Associated with HIV
• The features seen during the course of HIV are either due to the acute viral infection, opportunistic infections, malignancies or other complications of HIV
•  Feature of the acute HIV infection: fever, headache, cough, lymphadenopathy and skin rashes, which resolve spontaneously
• Patients may present with an acute mental illness (dementia) which also resolves
• Other may not develop any symptoms for a long time
o The natural history can be explained in different stages or clinical presentation of HIV

Acute HIV infection (syndrome): can present as any acute viral illness (a mono-like illness)
o Window period
     HIV antibodies take time to be produced and show up on a blood test
     The window period is the period between time of infection and when initial detection of HIV antibodies is possible by laboratory tests
         For this reason, people who test HIV negative must test again in 3 months, when antibodies should have developed
         DNA/RNA testing can be used to diagnose HIV infection before antibodies are formed
o Latent HIV infection
       This is a period of when the patient has no symptoms at all
        The body is still able to fight against most of the diseases just as in HIV negative individuals
      The infections s/he gets are not different from those in the general population e.g. malaria and pneumonia
        Patient may have generalized lymphadenopathy
o Early stages of HIV infection
       In this stage the immunity fall to the extent of exposing the patient to mild
opportunistic infections e.g. PPE, Herpes zoster and Herpes Virus infections

o Late stages of HIV infection.       
         The immunity of the patient falls further and severe life threatening infections start to occur e.g. cryptococcal meningitis, toxoplasmosis and Pneumocystis
pneumonia
         Opportunistic Infections (OI’s) Of HIV Infection
• An opportunistic infection (OI): An infection caused by an organism that does not usually cause disease in a healthy person with a normal immune system.
• When the immune system is compromised such as through HIV infection, the pathogen then gets an opportunity ‘to infect and cause disease’.
• Other examples of people with suppressed immunity include very young children and very old people, patient with advanced cancer and/or on chemotherapy, patients taking steroids for a long time, and those on immunosuppressive therapy following organ transplantation.

• OIs affecting Gastrointestinal System include:
o Oral-oesophageal candidiasis (thrush)
o Herpes Simplex Virus
o Kaposi sarcoma as well as diarrhoeal Illnesses
o CMV

• OIs affecting Respiratory System includes:
o Pneumocystis carinii pneumonia (PCP), currently is also known as pneumocystis
jirovecii pneumonia (PJP)
o Recurrent respiratory tract infection (RTI), bacterial pneumonias
o Pulmonary tuberculosis (PTB) and pleura infusion

• OIs in the cardiovascular system can lead to the following include;
o Pericarditis
o Cardiomyopathy

• OIs affecting Skeletal Muscular System include:
o Herpes zoster and herpes simplex

o Kaposi’s sarcoma
o Pyomyositis and Abscesses

• OIs affecting Central Nervous System include:
o Cryptococcus Meningitis
o Toxoplasmosis
WHO Clinical Staging System in Adults
• The WHO Clinical staging system is based on clinical features believed to have prognostic significance resulting in four stages of disease progression
• WHO staging is done where HIV infection is confirmed by HIV antibody or virological markers
•  Staging determines eligibility for ART
•  WHO staging looks at the clinical presentation of the client or patient
•  WHO clinical staging can be used effectively without access to CD4 or other laboratory testing
• If available, laboratory markers (CD4 counts or percentages and/or Total Lymphocytes
Count (TLC)) are used to:
o Support and reinforce clinical decision-making
o Categorize the immuno-suppression
• Note that WHO clinical staging in children will be dealt in the paediatric module
WHO Clinical Stage I: Asymptomatic
• A person with Stage I infection:
o Feels well and can do all his or her normal activities
o Has no signs or symptoms of any illness
o May experience Persistent Generalized Lymphadenopathy (PGL)
WHO Clinical Stage II: Minor Symptoms
• A person in this stage may feel ill at times, but still can perform all of his or her activities
• Moderate unexplained weight loss (<10% body weight)
• Recurrent respiratory tract infections
• Minor mucocutaneous manifestations
• Herpes zoster
WHO Clinical Stage III: Moderate Symptoms
• People in this stage often cannot do their usual activities, but are in bed less than half the time
• Severe unexplained weight loss (<10% of presumed or measured body weight)
• Unexplained chronic diarrhoea for >1 month
• Unexplained persistent fever above 37.6C intermittent or constant for >1 month
• Persistent oral candidiasis
• Oral hairy leukoplakia
• Pulmonary tuberculosis (current)
• Severe bacterial infections
• Acute necrotising ulcerative stomatitis, gingivitis or periodontitis

WHO Clinical Stage IV: AIDS-Defining Conditions
• A person in this stage is ill often and may stay in bed more than 50% of the time
• Wasting can take place in this stage: weight loss >10% of body weight
• Involved organ systems:
o Cutaneous and oral
o Respiratory
o Gastrointestinal
o Neurological and ocular
o Generalised
• Main infections include:
o Kaposi sarcoma
o Cryptococcal meningitis
o CNS toxoplasmosis
o Pneumocystis pneumonia

Posted by
Welfare Jambo