CLINICAL STAGING AND NATURAL HISTORY OF UNTREATED HIV Flashcards
What is the first stage of HIV infection called?
Primary HIV infection
What is the rate of CD4 loss per year in untreated HIV?
Between 50 and 100 cells/microlitre per year
What is the definition of AIDS in terms of CD4 count?
Less than 200 or a CD4 lymphocytes percentage of total lymphocytes of less than 14%
What is the median time from infection to developing AIDS in untreated people? What is the range?
10 years (range: 18 months to 25 years)
What percentage of patients will be able to control HIV viraemia without combination antiretrovirals?
Less than 1% - the elite controllers
What group are more likely to elite controllers?
Children with vertically transmitted disease
Prior to the introduction of antiretrovirals, what was the mean survival time after a diagnosis of AIDS?
Less than 2 years
What is the life expectancy of someone who is HIV positive who is being treated with antiretrovirals?
Almost normal
What are the three categories of HIV infection?
Category A
Category B
Category C
What are the conditions of category A in the classification of HIV infection?
Asymptomatic
Persistent generalised lymphadenopathy
Acute (primary) HIV infection with accompanying illness or history of acute HIV infection
What are the conditions of category B in the classification of HIV infection?
Bacillary angiomatosis
Oropharyngeal candidiasis
Vulvovaginal candidiasis that is persistent, frequent or poorly responsive to therapy
Cervical dysplasia (moderate to severe) or cervical carcinoma in situ
Constitutional symptoms - Fever (38˚) or diarrhoea lasting more than a month*
Hairy leucoplakia - oral
Herpes zoster - shingles, involving at least two distinct episodes or more than one dermatome.
Idiopathic thromobocytopenic purpura.
Listeriosis
PID - particularly if complicated by tuco-ovarian abscess
Peripheral neuropathy
*NB if associated with 10% weight loss then it becomes HIV wasting syndrome and therefore AIDS defining and category C
What are the conditions of category C in the classification of HIV infection?
All AIDS defining conditions (see HIV testing cards)
What is other name for the primary or acute HIV infection?
HIV seroconversion illness
What are the clinical features of HIV seroconversion illness?
Fever (96%)
Lymphadenopathy (74%)
Pharyngitis (70%)
Rash (70%)
Myalgia (54%)
Diarrhoea Headache Nausea and vomiting Hepatosplenomegaly Weight loss Oral candida Neurological symptoms - encephalopathy
How long after exposure do symptoms of HIV seroconversion occur?
1 to 3 weeks
(Not sure about these figures as textbook says that early onset of symptoms in primary HIV infection includes anything less than 3 weeks)
What is occurring during the primary HIV infection?
Time between initial infection to the development of antibodies against HIV.
What is the rash associated with primary HIV infection?
Erythematous, maculopapular rash mainly on face and trunk with or without mucocutaneous ulcers of the mouth, oesophagus or genitals.
What happens to CD4 levels during the primary HIV infection?
They will fall and can fall quite dramatically. This can result in manifestations more often seen later in disease such as oral candida. This can lead to occasional diagnostic confusion as to the stage of HIV infection.
When would cART (combined anti-retroviral treatment) be considered in primary HIV infection?
Only with very severe symptoms - especially encephalopathy, an AIDS defining illness or CD4 count of less than 350 cells/microlitre)
What are the theoretical advantages of starting cART (combined anti-retroviral treatment) early in primary HIV infection?
HIV may be more susceptible due to:
Relatively low diversity of replicating virus
Reduced ability of predominantly non-syncytium-inducing (NSI) strains of virus to infect a wide variety of cell types
Enhanced immune response at this stage
Are people with primary HIV infection, more or less infectious than an untreated asymptomatic individual later on in disease?
More due to high viral load
What are the typical levels of CD4 during the asymptomatic second stage of HIV infection?
Normally above 350 cell/microlitre
Is transmission possible during the asymptomatic second stage of HIV infection?
Yes
What is persistent generalised lymphadenopathy?
Lymphadenopathy that persistes for at least 3 months in at least two-extra inguinal sites and is not due to any other cause.
What are the important differentials to rule out before diagnosing persistent generalised lymphadenopathy in someone who is HIV postitive?
TB
Lymphoma
What lymphatic sites are not part of the definition of persistent generalised lymphadenopathy and should therefore prompt further investigation to exclude infection and neoplasia?
Mediastinal lymphadenopathy
Intra-abdominal lymphadenopathy
How does persistent generalised lymphadenopathy reflect disease progression?
It doesn’t and it is therefore not an indication to start HIV treatment
Is someone considered to have AIDS once symptoms start to develop after the asymptomatic stage?
No. Patients may develop symptoms and conditions that are not AIDS defining and before their CD4 count drops below 200 cells/microlitre.
What are the sites commonly affected first when HIV reaches the symptomatic phase after the latent asymptomatic period?
Category B conditions:
Constitutional symptoms
Skin and mouth
Some haematological disorders
What are the non-AIDS defining constitutional symptoms associated with reactivation of HIV after the asymptomatic latent stage?
Malaise
Fever
Night sweats
Weight loss (that does not meet HIV wasting criteria)
Diarrhoea
What are the exact criteria for diagnosing the AIDS defining HIV wasting syndrome?
10% weight loss from baseline
AND one of:
Fever
Diarrhoea lasting at least 1 month
What are the skin and mouth conditions often seen first upon reactivation of HIV after the asymptomatic latent stage?
Candida
Shingles
Herpes
Oral hairy leucoplakia
What are the haematological problems often seen first upon reactivation of HIV after the asymptomatic latent stage?
Lymphopenia
Moderate neutropenia
Normochromic, normocytic anaemia
Thrombocytopenia
Idiopathic thrombocytopenia purpura (ITP)
Other than CD4 T cells, what cells are affected by HIV?
Immune dysregulation of:
Natural killer cells
Plasmacytoid dendritic cells
CD8 T-cells
What are the diseases that still occur at higher levels of CD4 due to the effect that HIV has on other parts of the immune system? How should these patients be treated?
Idiopathic thrombocytopenic purpura (ITP)
Thrombotic thrombocytopenic purpura (TTP)
HIV-associated nephropathy (HIV AN)
Severe refractory psoriasis
Pulmonary arterial hypertension
HIV vasculitis
These patients should start cART
What are the factors that speed up the progression to AIDS in untreated individuals?
Older age
Higher plasma HIV viral load
Early onset (less than 3 weeks) of primary infection symptoms
Prolonged (more than 2 weeks) or severe symptoms in primary HIV infection
Baseline albumin of less than 35 mg/ml
CXCR4 (syncitium inducing) strain of HIV
Rapid rate of fall of absolute CD4 cell count
Route of infection - blood transfusion
What are the two most widely used markers of disease progression?
CD4 counts
Viral load
If a patient is found to have a low CD4 count on a blood test, what should happen before therapy is initiated?
Blood test should be repeated as CD4 count is subject to diurnal and seasonal variation and reduced by intercurrent infection.
At what CD4 count might you expect a patient to develop pneumocystis pneumonia (PCP)?
Less than 200 cells/microlitre
At what CD4 count might you expect a patient to develop toxoplasmosis?
Less than 100 cells/microlitre
At what CD4 count might you expect a patient to develop cryptococcosis?
Less than 100 cells/microlitre
At what CD4 count might you expect a patient to develop oesophageal candidiasis?
Less than 100 cells/microlitre
At what CD4 count might you expect a patient to develop disseminated cytomegalovirus?
Less than 50 cells/microlitre
At what CD4 count might you expect a patient to develop disseminated Mycobacterium avium complex?
Less than 50 cells/microlitre
