HIV Flashcards
WHO Clinical Staging of HIV/AIDS for adults and adolescents with confirmed HIV Infection - Stage 1
Asymptomatic
Persistent generalized lymphadenopathy
WHO Clinical Staging of HIV/AIDS for adults and adolescents with confirmed HIV Infection - Stage 2
• Unexplained moderate weight loss(<10% of presumed or measured body weight)
• Recurrent respiratory tract infections (sinusitis, tonsillitis, otitis media and pharyngitis)
• Herpes Zoster
• Angular Cheilitis
• Recurrent oral ulceration
• Pruritic popular eruption
• Seborrhoeic dermatitis
• Fungal nail infections
WHO Clinical Staging of HIV/AIDS for adults and adolescents with confirmed HIV Infection - Stage 3
• Unexplained severe weight loss (>10% of presumed or measured body weight)
• Unexplained chronic Diarrhoea for longer than one month
• Unexplained persistent fever (above 37.5C intermittent or constant, for longer than one month)
• Persistent oral candidiasis
• Oral hairy leukoplakia
• Pulmonary TB
• Severe bacterial infections ( eg. Pneumonia, empyrean, pyomyositis, bone or joint infection, meningitis, bacteremia)
• Acute necrotizing ulcerative stomatitis, gingivitis or periodontitis
• Unexplained anemia (<8g/dl), neutropenia (<0.5 x 10^9 per liter) and/or chronic theombocytopenia (<50 x 10 ^9 per liter)
WHO Clinical Staging of HIV/AIDS for adults and adolescents with confirmed HIV Infection - Stage 4a
• HIV wasting syndrome
• Pneumocystis pneumonia
• Recurrent severe bacterial pneumonia
• Chronic herpes simplex infection ( orolabial, genital or anorectal of more than one month’s duration or visceral at any site)
• Oesophageal candidiasis (or candidiasis of trachea, bronchi or lungs)
• Extrapulmonary TB
• Kaposi sarcoma
• CMV infection (retinitis or infection of other organs)
• CNS Toxoplasmosis
WHO Clinical Staging of HIV/AIDS for adults and adolescents with confirmed HIV Infection - Stage 4b
• HIV encephalopathy
• Extrapulmonary cryptococcis including meningitis
• Disseminated non-tuberculous mycobacterial infection
• Chronic cryptosporidiosis
• Chronic isoporidiasis
• Disseminated Nicosia ( Extrapulmonary histoplasmosis or coccidiomycosis)
• Recurrent septicemia (including non-typhoidal Salmonella)
• Lymphoma (cerebral or B-cell non-Hodgkin)
• Invasive cervical carcinoma
• Atypical disseminated leishmaniasis
• HIV associated nephropathy or HIV associated cardiomyopathy
When does Western Blot show indeterminate results?
• Early HIV infection
• HIV-2 infection
• Influenza vaccine
• Autoimmune Disease
• Pregnancy
• recent tetanus toxoid administration.
When is HIV rapid antibody test done?
• Occupational exposure
• Pregnant women presenting in labor with no previous HIV testing
• Patients who are unlikely to return for results of HIV test
Conditions that require urgent ART
• Pregnancy
• AIDS - defining conditions, including HIV-associated dementia and AIDS - associated malignancies
• Acute opportunistic infections (OIs)
• Lower CD4 counts (e.g., <200 cells/mm3)
• HIV - associated Nephropathy (HIVAN)
• HIV/Hepatitis B virus co-infection
• HIV/Hepatitis C virus co-infection
What do you look for when monitoring efficacy of ARV’s?
- Weight gain
- Decrease or disappearance of symptoms
- Decrease in frequency and/or severity of OIs
- Increase in CD4+ count of an average of 100 cells per year
- Sustained suppression of HIV viral loads to undetectable levels
How is HIV trasmitted?
- Sexually
- Parenterally e.g. transfusion of infected blood, shared IV drug paraphernalia, needle stick injury with infected blood
- Vertically i.e. mother-to-child transmission (MTCT), which can occur during pregnancy, delivery or breastfeeding
What are the two main types of HIV and how do they cause disease
HIV - 1
HIV - 2
Either one can infect a host or both can infect a host.
How many groups of HIV 1 exist and what do they represent?
Four groups of HIV-1 exist and represent three separate transmission events from chimpanzees (M, N, and O), and one from gorillas (P)
HIV 1 Subgroups, Clades and Distribution
Group M is the cause of the global HIV pandemic; consists of nine clades: A–D, F–H, J, and K
Group N, O, and P are restricted to west Africa
HIV 1 Clade C and B areas
Clade C predominates in Africa and India
Clade B predominates in western Europe, the Americas, and Australia
Why is there marked diversity in HIV 1?
The marked genetic diversity of HIV-1 is a consequence of the error prone function of reverse transcriptase which results in a high mutation rate
What are the implications for the global distribution of the clades
The global distribution of the various clades has implications for vaccines development
Differences between HIV 2 and HIV 1
*HIV-2 is largely confined to West Africa and causes a similar illness to HIV-1
* Immunodeficiency progresses more slowly in HIV-2 so it has a longer asymptomatic phase than HIV-1
* HIV-2 is less infectious and less transmissible than HIV-1, with a 5-fold lower rate of sexual transmission and 20- to 30-fold lower rate of vertical transmission
* Persons infected with HIV-2 tend to have a lower viral load than those with HIV-1; the high viral load in HIV-1 infection is associated with more rapid progression to AIDS
How is HIV 2 transmitted?
- Perinatal transmission rates of HIV-2 is low with or without intervention (0% to 4%)
- The commonest mode of HIV-2 transmission is sexually
- HIV-2 can also be transmitted through breastfeeding
Does HIV - 2 protect against HIV -1 and dual infection?
HIV-2 infection does not protect against HIV-1 and dual infection, which carries the same prognosis as HIV-1 mono-infection can occur
Why is it that most of the research, vaccine and drug development has been focused on HIV-1
Because HIV-2 is rare in the developed world, most of the research, vaccine and drug development has been focused on HIV-1
Describe the structure of HIV
- An RNA retrovirus- subfamily Lentivirus
Contains:
* 2 copies of RNA
* 3 Enzymes:
Reverse Transcriptase
Integrase
Protease
* Two major envelope proteins:
gp120
gp41
What are the steps in the life cycle of HIV in a host cell?
Attachment
Co-receptor binding
Fusion
Uncoating
Reverse transcription
Integration
Transcription
Translation
Assembly
Budding
Maturation
Which cells are infected by HIV?
CD4+ Helper T lymphocytes - Mainly.
* Other cells expressing CD4+ receptors are also infected i.e. monocytes, macrophages and dendritic cells
Where does CD4+ independent infection occur?
CD4+ independent HIV infection of cells occurs notably in astrocytes (causing HIV-associated neurocognitive disorder) and renal epithelial cells (causing HIV nephropathy)
What protein facilitates binding to the CD4 receptors
HIV viral-envelope protein-gp120
What does Membrane fusion and entry into the host cell require?
Membrane fusion and entry into the host cell requires further interaction betweenchemokine co-receptors CXCR4 & CCR5 present on the host cell membrane andgp41
Describe the life cycle of HIV from the production of pro-viral DNA to the budding of new viral proteins
- Viral reverse transcriptase catalyzes the conversion of viral RNA into DNA
- Pro-viral DNA enters the nucleus and becomes integrated into chromosomal DNA of host cell (catalyzed by integrase)
- Expression of viral genes leads to production of viral RNA and proteins
- Protease enzyme cleaves proteins into functional mature products
- Viral proteins and viral RNA are assembled at the cell surface into new viral particles which leave the host through budding
Factors contributing to the risk of acquisition of HIV infection
The nature of the exposure (the route & size of the inoculum)
The virulence of the virus
The nature of the host susceptibility to infection
Compare the risk of acquiring HIV infection from a blood transfusion and needlestick injury
Transfusion of HIV-infected blood carries a 95% risk of transmission compared to a 1:300 risk of acquiring HIV from a needle-stick with infected blood
Transmucosal infection risks
Transmucosal infection risks vary according to the site of exposure with risks of transmission through rectal exposure > vaginal exposure > oral mucosa
What other factors increase the risk of HIV transmission
The presence of ulcerative STDs, trauma, menstruation and lack of male circumcision increases the risk of transmission
When is Mother to Child Transmission of HIV higher
MTCT of HIV is higher in women with high plasma HIV RNA
Waht foru mechanisms explain the syndromes caused by HIV infection?
Immunodeficiency
Chronic inflammation and immune activation
Autoimmunity
Allergic and hypersensitivity reactions
Cause of Immunodeficiency in HIV
Immunodeficiency is a direct result of the effects of HIV upon immune cells causing a spectrum of OIs and neoplasms
What causes the inflammation and immune activation
The chronic viral infection causes a generalized state of inflammation and immune activation resulting in a spectrum of diseases
What are the most common clinically apparent manifestations of HIV?
Autoimmunity, allergic and hypersensitivity reactions may be the only clinically apparent manifestation or may coexist with obvious manifestations of immunodeficiency
Why does autoimmunity occur in HIV?
Autoimmunity can occur as a result of disordered cellular immune function or B lymphocyte dysfunction e.g. include Lymphocytic interstitial pneumonitis, Immunologic thrombocytopenia
Allergic and hypersensitivity reactions in HIV patients
- HIV infected individuals tend to have higher rates of allergic reactions to unknown allergens e.g. eosinophilic pustular folliculitis.
- HIV infected individuals have increased rates of hypersensitivity reactions to medications
What are the three stages of HIV infection. How does progress through these stages vary from person to person?
Acute HIV infection - High viral load, Low CD4 count. Lasts weeks to months
Chronic HIV infection - Viral load drops and rises slowly. CD4 count rises a bit and progressively declines.
AIDS
- The time it takes for each individual to go through these stages varies
*For the majority of people however, the progression of HIV disease is fairly slow, taking several years from infection to development of AIDS
What is Acute HIV infection?
Is the period of time between the initial HIV infection and seroconversion usually 6 to 12 weeks, rarely up to 6 months
