W3P1 Flashcards
Where did HIV come from?
What are the two types?
Zoonotic disease
Made the leap to humans from African chimpanzees somewhere between 1911 and 1941
First documented case in humans: Kinshasa 1959
2 types of HIV:
HIV-1 and HIV-2
Which region has the greated HIV prevalence
Eastern and Souther Africa (20 /37 million)
Which provinces in Canada have the highest HIV rates?
Prairies (SK, MB) : because of high needle use
QC: because of immigrants from endemic areas
Demographic make-up of HIV infected population in Canada
Half - gay, bisexual and MSM
15%: drug users
of which 23% are female
ART stands for
Anti Retroviral Therapy
HIV stands for
Human Immunodeficiency Virus
HIV Life Cycle
The single stranded RNA virus is the INFECTIOUS form
In order for it to work it becomes double stranded DNA using reverse transcriptase
You need two receptors: the CD4 and the KEY: CXCR4 and chemokine receptors that live on our surfaces. If people are mutant and don’t have this receptor, they cannot get HIV/ they don’t have the key hole for the virus to enter the cell
Integrase: to combine viral DNA into host DNA
how does HIV enter cells
HIV (gp120)
Human T cell receptor
Human co-receptor (CCR5 or CXCR4 or both)
HIV
- What cells does it infect
CD4+ T lymphocytes*** Dendritic cells skin, lymph nodes, brain Macrophages CD8+ T lymphocytes Natural killer cells Natural killer T cells Viral reservoir
Where does HIV live?
LYMPHOID ORGANS
Peripheral lymph nodes
Gastrointestinal lymph nodes
- Neonatal transmission
Bone marrow
CENTRAL NERVOUS SYSTEM
HIV Tat protein disrupts the blood-brain barrier
- Microglial and dendritic cells
Reservoir for HIV replication
GENITOURINARY SYSTEM HIV crosses blood-testis barrier; infects semen Renal epithelium Macrophages and lymphocytes in cervix Reservoir for HIV replication
HIV mutation
Reverse transcriptase is extremely error-prone
High rate of genomic mutation
- Spontaneous mutations over time
- Many are silent/no-effect
- By chance alone some confer resistance to medications
Drug-driven mutations
- use of drugs increases mutant/resistance strains
Mutated vs Wild Type HIV when medications are given
By allowing viral replication to occur, mutants develop
A highly mutated HIV is a “less fit” virus, not as infectious
- Overtake wild type virus if medications are failing
- Less fit to replicate
- Mutants accumulate
Wild type HIV
- More Easily transmissible
- Replicates more efficiently
- Returns once medications are stopped*
- Overtake mutant virus
Mutants are held in reserve
- Return to overtake wild type virus once medications are restarted
Initial Viremia
vs Secondary Viremia
vs Window Period
Initial viremia leads to infection of lymph nodes
Secondary viremia
- Mononucleosis-like illness
“Window period” - happens AFTER the secondary viremia
Silent viral replication in lymph nodes
Little or no HIV antibodies
From ½ - 3 months (depending on test used)
- PCR: about 1-2 weeks AVERAGE
- Advanced serology tests: 2-4 weeks AVERAGE
- Old serology tests: 3 months AVERAGE
Infectious mononucleosis (mono)
mono is often called the kissing disease. The virus that causes mono (Epstein-Barr virus) is spread through saliva. You can get it through kissing, but you can also be exposed by sharing a glass or food utensils with someone who has mono. However, mononucleosis isn’t as contagious as some infections, such as the common cold.
Symptoms of Mono
what other illness do these symptoms resemble?
Symptoms extreme fatigue. fever. sore throat. head and body aches. swollen lymph nodes in the neck and armpits. swollen liver or spleen or both. rash.
Secondary viremia for HIV presents as mono-like illness
Acute HIV Syndrome
mononucleosis-like illness
- fever, malaise, non-exudative pharyngitis, maculopapular rash (50%), - myalgias, headache, GI distress
- generalized lymphadenopathy, hepatosplenomegaly, oral or vaginal thrush
- lymphopenia then acute lymphocytosis
HIV antibody negative but PCR and antigen positive
1-6 weeks after infection
Lasts up to 3 weeks
Spontaneous resolution
HIV disease progression
Destruction of CD4+ T cells - By CD8+ T cells - By HIV - Bone marrow suppression Reaching of a “set point” of viral copies and CD4+ cells Steady progression of immune destruction
What is the CD4 count for a person that signals SEVERE HIV = AIDs
Anyone over 6 years old with a CD4 count less than 200 is SERIOUS this is considered AIDS
What is the natural history/timeline of HIV disease
you measure progression based on CD4 levels
This is how the progression happens:
- Acute infection = large drop in CD4
- Body recovers
- Asymptomatic infection due to decreasing CD4- based on “set point”
- Once it gets under 200 then its AIDS
Diagnosing HIV
HIV serology
- Screening and confirmatory test in humans > 18 months age
- can’t rely on serology for younger because they still have mothers antibodies
HIV PCR
- Screening and confirmatory test in humans < 18 months age
Viral load Determination of viral copy number Viral RNA numbers Expressed as number of copies/ml blood, or log log 2 = 100 copies/ml log 3 = 1000 copies/ml < log 1.3 = < 20 copies/ml ~ “undetectable” “Undetectable”
What kind of symptoms does HIV lead to?
INFECTIONS Sinopulmonary infections Salmonellosis Meningitis Candidiasis
CARDIOMYOPATHY
HIV-related
GROWTH AND SEXUAL DEVELOPMENT
Delayed
Decrease in testosterone/libido
Osteoporosis
NEUROLOGICAL
Cognitive delay
Encephalopathy
Dementia
RENAL
HIV nephropathy
PSYCHIATRIC
Depression
ADHD
HIV disease GI manifestations
DISORDERS OF THE ESOPHAGUS
⅓ of all AIDS patients have esophageal disease Typical symptoms Dysphagia and odynophagia Esophageal inflammation Ulceration Infectious and noninfectious causes
HIV-associated idiopathic esophageal ulcers
40% of ulcers seen in AIDS
Associated with severe immunosuppression
Likely caused by HIV
Seen in lymphocytes and lamina propria
Esophagoscopic lesions are similar to CMV
Which three pathogens leads to esophagitis in HIV patients?
- Candida esophagitis
- Herpes virus esophagitis
- CMV esophagitis
Types of Infectious Oral lesions from HIV
- Their cause
- painful vs not painful
Cold sores around the outter and inner lips
- Herpes Simplex
Oral Hairy Leukoplakia
- EBV related (not painful)
White patches on the soft palette of the mouth
- Candidiases (painful)
Neoplastic Lesions in HIV patients
Dark oval spots in MANY places: could be on their back, mouth, shins
Caused by Kaposi’s Sacroma
- KSHV or HHV8
- severe immunosuppression
Disorders of the liver in HIV caused by HBV
Hepatitis B and/or Hepatitis C
- Shared routes of transmission
HBV
Chronic HBV infection
- 20% of HIV co-infected people
- 5% of HIV negative people
Spontaneous reactivation seen in AIDS
- 19 times more likely to die if HIV/HBV co-infected*
- Cirrhosis, liver failure, carcinoma
HBV does not influence HIV progression
Disorders of the liver in HIV caused by HCV
HCV liver-related mortality in HIV+ people
- 94 fold risk higher than general population
*HCV may affect progression of HIV
All HIV+ patients should be screened for HCV
- HCV antibody
- HCV RNA PCR
OTHER causes of disorders of the liver in HIV patients
Pharmacological Hepatitis - Protease inhibitors (ritonavir) - NNRTI (nevirapine) - Antimycobacterial drugs (rifampin, rifabutin, INH)
Jaundice
- Protease inhibitors (atazanavir)
- Septra, macrolides
Steatosis
- With mitochondrial toxicity and lactic acidosis
- NRTI (ZDV, d4T, ddI) - Protease inhibitors (ritonavir)
Ritonavir
- Side effects
This is a protease inhibitor
When used for HIV patients can lead to
- Hepatitis
- Steatosis
Diarrhea in HIV patients
Diarrhea
Worldwide major cause of morbidity and mortality in AIDS patients
- 95% of AIDS patients in 3d World
- 72% 10-month mortality (chronic diarrhea)
Causes are MANY
Colitis
Malabsorption
Disorders of the Intestines in HIV caused by bacterial and viral agents
Bacterial SSCYE, Listeria monocytogenes Mycobacterium avium complex Obstructive as well Mycobacterium tuberculosis Obstructive as well Toxin-mediated Clostridium difficile Bacterial overgrowth
Viral
CMV, Adenovirus, Rotavirus, HIV
Other causes of viral gastroenteritis
Infections of the intestines in HIV patients caused by parasitic or fungal pathogens
Parasitic
MANY
Giardia lamblia
Cryptosporidium parvum, Microsporida, Isospora belli, Cyclospora cayetanensis, Entamoeba histolytica
Fungal
Histoplasma capsulatum
Risk factors for disorders of the Intestine in HIV patients
Risk factors Severe immunosuppression Environmental conditions Travel-related exposures MSM
Pharmacological
Most all antiretrovirals
Antibiotics
Immune-mediated
Inflammatory bowel disease
Immune Reconstitution Syndrome
Celiac disease
Neoplastic
Idiopathic
- 50% of chronic diarrhea
HPV stands for
Human Papilloma Virus
HPV disease
Important to have HIV positive patients be vaccinated against HPV*
Cervical papillomas
Proctitis [inflammation of the lining of the rectum]
Sexually transmitted:
Chlamydia trachomatis
Neisseria gonorrhea
Treponema pallidum
HPV disease
Anal condillomatosis
Cervical/Anal cancer
AIDS is….
Opportunistic infections: Pneumocystis jiroveci Toxoplasma gondii Candida esophagitis/moniliasis Cytomegalovirus Disseminated varicella zoster Mycobacterium avium intercellulare JC virus/Progressive multifocal leukoencephalopathy
Other infections Salmonellosis Crypto/microsporidiosis Isospora belli Giardia lamblia Neoplastic transformations HHV-8:Kaposi sarcoma, Castleman disease CNS lymphoma Other manifestations of HIV Cardiomyopathy, nephropathy (proteinuria, nephrotic syndrome), hepatitis, wasting syndrome
What is the outcome of having HIV disease
Death
HIV: initially considered to be 100% lethal
Chronic disease
- HAART
The course of the disease has been altered
prior to HAART: median duration was 7.8 years
after HAART: median duration > 15 years
List some bacterial opportunistic pathogens for HIV
Pneumocystis jiroveci
Mycobacterium avium complex
Mycobacterium tuberculosis
Cryptococcus neoformans
List some viral opportunitic pathogens for HIV
CMV
Retinitis, uveitis, retinal detachment, visual loss, pneumonitis, disseminated
HSV, VZV
Reactivation
Erosive or extensive disease
HHV-8
Kaposi’s sarcoma
HBV, HCV
Progressive cirrhosis
JCV
Progressive multifocal leukoencephalopathy
List some parasitic pathogens for HIV
Toxoplasma gondii
- only ONE we’ve learnt
Pneumocystis jiroveci ** and HIV
- Treatment
Most frequent opportunistic pathogen in AIDS patients
25 – 60% of all
Fever, cough, SOB
HYPOXIA
10 –20% mortality
Can involve extra-pulmonary areas as well (liver)
TREATMENT: Primary Prophylaxis: Septra po - For all HIV+ children < 1 year old regardless of CD4 count - For older children and adults: When CD4 < 200 (or < 15% of total lymphocyte count)
Treatment:
Septra (IV or po)
Systemic corticosteroids
Supplemental oxygen
Secondary prophylaxis
Septra
Until CD4 > 200 for 3 months
Mycobacterium avium complex and HIV
- treatment
example of bacterial opportunistic pathogen
Mycobacterium avium intracellulare - Among others Disseminated disease based in the gastrointestinal tract and reticuloendothelial system Pulmonary disease Fever and weight loss
TREATMENT
Primary Prophylaxis Azithromycin or clarithromycin For children < 6 years old Severe immunosuppression For people > 6 years of age CD4 < 50 cells
Treatment
Macrolide + rifabutin
Other second-line drugs
Secondary prophylaxis
Macrolide + rifabutin
Until CD4 > 75 for 3 months
Mycobacterium tuberculosis in HIV patients
- IMPORTANT distinguishing outcome from this type of infection*
Acts like an opportunistic bacterial pathogen
Mycobacterium tuberculosis Lymphadenopathy Pulmonary disease Intra-abdominal disease THE GREAT IMITATOR
HIV patients can transmit this to others much easier than non-HIV patients
LEADING CAUSE OF DEATH WORLDWIDE FOR HIV INFECTED PATIENTS
Infection can occur at ANY time in the immune history of a patient with HIV
ALL patients with TB should be screened for HIV
ALL HIV patients should be screened for TB
What is the leading cause of death worldwide for HIV patients?
mycobacterium tuberculosis infection
What should all patients with HIV be screened for?
TB!
and all patients with TB should be screened for HIV because this is the leading cuase of death worldwise for HIV patients
ALL HIV POSITIVE patients need HEP B, HEP C and TB SCREENING, because it will affect the way you move forward with this patient
will be on exam
Cryptococcus neoformans in HIV patients
- symptoms and conditions it leads to
- Treatment
Acts as opportunistic fungal pathogen
Cryptococcus neoformans: MENINGITIS* Raised intracranial pressure Necrotizing lymphadenitis (mediastinal, cervical) Necrotizing pneumonitis Skin abscesses
Treatment: Amphotericin B + Fluconazole IV Followed by fluconazole po for ?weeks to months Secondary prophylaxis Usually lifelong
Which opportunistic pathogen is known to lead to meningitis in HIV patients?
Cryptococcus Neoformans
this is a yeast (fungus)
Examples of Opportunistic Viral Pathogens in HIV
CMV
Retinitis, uveitis, retinal detachment, visual loss, pneumonitis, disseminated
HSV, VZV
Reactivation
Erosive or extensive disease
HHV-8
Kaposi’s sarcoma
HBV, HCV
Progressive cirrhosis
JCV
Progressive multifocal leukoencephalopathy
Opportunistic Parasite in HIV
- how is it transmitted
- symptoms
- Is there a treatment?
Toxoplasma gondii Parasite Consumption of raw beef Consumtion of organism from cat feces Encephalitis, seizures, disseminated CNS lesions (ring enhancing)
Treatment:
JUST KNOW THERE IS ONE. [Sulfadiazine + pyrimethamine + folinic acid (leucovorin)]
Secondary prophylaxis. just know there is one
HIV Therapy
JUST KNOW: HAART: Highly Active AntiRetroviral Therapy
- combination therapy with NRTI, NNRTI, PI, FI, Integrase Inhibitors, and/or CCR5 receptor antagonists
aim:
reduction of HIV viral load to undetectable levels
elevation of CD4 T-helper lymphocyte counts
standard of care
“Undetectable = Untransmissible”.
[NRTI = inhibits RT that’s a nucleoside NNRTI = inhibits RT that’s a NON-nucleoside ]
Which HIV treatment is the backbone of HIV therapy
Integrase Inhibitors & CCR5 coreceptor antagonists
Integrase inhibitors
Prevent integration of pro-viral DNA into human chromosomal DNA
[i.e. Cabotegravir – once monthly injection (depot delivery)]
Coreceptor antagonists
Prevent binding of HIV on to human cells
“Boosting” the antiretrovirals
Inhibition of liver cytochrome p450 enzymes that metabolize some antiretrovirals (protease inhibitors, elvitegravir)
Aim: increase levels of antiretrovirals in the blood and tissues for maximum efficacy
When to treat HIV
on exam*
All HIV+ children < 1 year of age
All HIV+ pregnant women
All symptomatic HIV+ patients regardless of CD4 count
All patients with moderate immune suppression regardless of symptoms
CD4 count <350 cells/ml
Pendulum has swung:
Start as soon as possible after diagnosis and regardless of CD4 count to preserve immune function and prevent chronic inflammatory damage (to heart, blood vessels etc).
Viral load log > 5.0
Goals of HIV management
- What treatments do we use for these goals
Decrease Viral Load to undetectable levels Improve immunity Preserve immunity Prevent toxicity Treat/prevent OI Maintain well-being of the patient PREVENT TRANSMISSION
treatments: HAART Monitor CD4 and VL every 3 months if patient is stable OI prophylaxis Vaccinations Multidisciplinary approach
