Week 6: HIV testing and treatment Flashcards


Question: What is differential diagnosis and what tests to be performed?

- HIV
- allergic dermatitis
- secondary syphilis
- coxsackie
- scarlet fever (throat swab rapid antigen test or culture
*
Great start at Prevention & Treatment of HIV

HIV screening guidelines

Case

- so not strep
- has secondary syphilis
- could have HIV depending on generation of test

Clinical course of HIV and CD4 count and viral load
- viral load goes from nothing to very high around 10 million copies and very contagious but too soon to have antibody test
- viral load could be high but Ab test could be negative
- sero-conversion is Ab negative to Ab positive
- CD4 cells are located everywhere in the body (test the blood)
- HIV only infects via CD4 receptor and only activated CD4 cells
- HIV is enveloped so when it replicates it takes a piece of the cell membrane with it
- so CD4 goes down then back up as they are recruited and then slow decline around 100 cells per year
- Immune system is constantly stimulated because HIV viral replication is very prone to mutation which keeps changing

HIV testing

Forms of HIV testing
- HIV Ab Elisa screen
- Western blot
- HIV Ab Elisa followed by automatic WB confirmation
Rapid HIV Testing
HIV Ab Elisa screen
HIV Confirmatory testing
Western blot
3rd generation HIV screening
- HIV Ab Elisa followed by automatic WB confirmation
- Antigens bind HIV antibodies from patient sample
- Allows detection in early seroconversion
- 6-8 week window period
Features of HIV Ab Elisa screen
- High sensitivity
- false-positive possible
- 6-8 week window period
Features of Western blot HIV testing
- High specificity
- Confirmatory testing
Features of 4th generation HIV testing
- Antigens bind HIV Abs from patient sample & monoclonal Abs detect p24 antigen
- Allows detection prior to seroconversion
- Detect between 12-26 days from exposure
What is Acute Retroviral Syndrome?
Symptomatic acute HIV infection that occurs 2-4 weeks after infection which presents like nonspecific flu-like illness for 3-14 days
Diagnosis of Acute Retroviral Syndrome
3rd or 4th generation HIV screening test negative or indeterminate with HIV RNA high
Are you contagious in Acute Retroviral Syndrome?
Highly infectious at this time
Presentation of Acute Retroviral Syndrome
Symptomatic acute HIV infection presenting as non-specific flu-like illness for 3-14 days 2-4 weeks post HIV infection
HIV screening algorithm

Continued case presentation

Potentially infectious agents of HIV
- Blood
- Breast milk
- Tissue
- Semen
- Vaginal secretions
- Anal secretions
- Visibly bloody fluids
- Other bodily fluids
NOT infectious agents of HIV
- Urine
- Saliva
- Sweat
- Tears
- Nasal secretions
- Sputum
- Vomitus
- Stool
Forms of higher risk HIV transmission risk
- Receptive anal sex 0.3% - 3%
- Needle sharing 0.67%
Forms of lower risk HIV transmission risk
- oral sex 0.06%
- Insertive sex 0.03 - 0.14%
CD4 count of HIV clinical Assessment
- Used to stage disease
- Stage 1: asymptomatic CD4>500
- Stage 2: CD4 200-500
- Stage 3: CD4 <200, <14%, or opportunistic disease or malignancy
HIV Viral load of HIV clinical Assessment
- Used to monitor ARV therapy
- Well controlled: viral load undetectable
- Suboptimally or uncontrolled viral load detectable
Stage 1 HIV
- asymptomatic
- CD4>500
Stage 2 HIV
CD4 200-500
Stage 3 HIV
- CD4<200, <14%
- opportunistic disease or malignancy
Well controled HIV
viral load is undetectable
Suboptimally or uncontrolled HIV
- Viral load is detectable
How is HIV viral load determined
HIV RNA Quantitative PCR
Describe the natural history of HIV infection

What stage are most new diagnosis of HIV?
- 38% of new HIV diagnosis in the U.S. already have advanced disease
Why is it important to diagnose HIV early?
People who know they have HIV can begin treatment
HIV treatment
- HAART/ART
- results in viral suppression and markedly reduced transmission
What is the best treatment for HIV?
Prevention but also treating those with HIV reduces risk of transmission with HAART/ART treatment

When to start HIV treatment
ASAP in all HIV-infected adults as long as the patient is ready (A1 recommendation)
HIV Treatment must start conditions
- opportunistic infections
- Tuberculosis
- HIV-AN, Co-infection with HBV or HCV
- Pregnant women
ARV agents mechanism of action

ARV Mechanism of action cont.

NRTI Antiretroviral Medications
NRTI means?
nucleoside reverse transcriptase inhibitors
NNRTI Antiretroviral Medications
NNRTI means?
non-nucleoside reverse transcriptase inhibitors
PI Antiretroviral Medications
PI means?
Protease Inhibitor
Types of antiretroviral medications
6 listed
- NRTIs
- NNRTIs
- PIs
- Integrase Inhibitors
- Entry inhibitors
- Phamokinetic boosters
Current NRTI Antiretroviral Medications
- Abacavir
- didanosine
- Emtricitabine
- Lamivudine
- Stavudine
- Tenofovir AF or DF
- Zidovudine
Current NNRTI Antiretroviral Medications
5 listed
- Doravirine
- Efavirenz
- Etravirine
- Nevirapine
- Rilpivirine
Current PI Antiretroviral Medications
*Include booster*
- Atazanavir
- Darunavir
- Fosamprenavir
- Indinavir
- Lopinavir
- Nelfinavir
- Saquinavir
- Tipranavir
Current Integrase Inhibitors Antiretroviral Medications
4 listed
- Bictegravir
- Dolutegravir
- Elvitegravir (with cobicistat)
- Raltegravir
Current Entry Inhibitiors Antiretroviral Medications
3 listed
- Enfuvirtide
- Ibalizumab
- Maraviroc
Current Pharmacokinetic Boosters Antiretroviral Medications
2 listed
- Ritonavir
- Cobicistat
HAART guidelines: Initial Regiment

Describe prevention of HIV Resistance

Explain steps of HIV infection & replication
10 listed
FBIRITAABM
- Free virus
- Binding and fusion: to a CD4 molecule and one of two coreceptors (either CCR5 or CXCR4) Receptor molecules are common on the cell surface. Then the virus fuses with the cell
- Infection: Virus penetrates cell and contents are emptied into cell
- Reverse Transcription: Single strans of viral RNA are converted into double-stranded DNA by the reverse transcriptase enzyme
- Integration: Viral DNA is combined with the cell’s own DNA by the integrase enzyme
- Transcription: When the infected cell divides the viral DNA is “read” and long chains of proteins are made
- Assembly: Sets of viral protein chains come together
- Budding: Immature virus pushes out of the cell taking some of the cell membrane with it. The protease enzume starts processing the proteins in the newly forming virus
- Immature virus breaks free of the infected cell
- Maturation: The protease enzyme finishes cutting HIV protein chains into infividual proteins that combine to make a new working virus
How drug resistance arises in HIV Treatment

Causes of HIV Resistance to Antiretrovirals (ARVs)

ARVs AKA
Antiretrovirals
CD4 coreceptors for HIV
CCR5 and CXCR4
HIV Fusion Inhibitors
- Enfuvitide
- Maraviroc
Maraviroc MOA
CCR5 inhibitor to prevent binding and fusion of HIV
Enfuvitide MOA
prevent HIV fusion with CD4 cells
Contents of HIV virus capsid
- Single-stranded RNA
- Three enzymes
- Reverse Transcriptase
- Integrase
- Protease
Drugs that target retroviral (HIV) reverse transcriptase
- NRTIs
- NNRTIs
Antiretroviral medications molecular targets
5 listed
- Fusion inhibitors
- CCR5 inhibitor
- Reverse transcriptase
- Integrase inhibitors
- Protease inhibitors
Old guidelines of HAART
2 NRTIs + (II or boosted-PI or NNRTI)
Most recent HAART guidelines
2 NRTIs + Integrase inhibitor
How to prevent HIV Drug Resistance?
3 agents of at least 2 different classes

If a person is taking adequate antiretroviral therapy, can they develop drug resistance?
No, if the virus is not replicating, no new mutations can occur!
How does HIV resistance arise?
- Basically the drugs stop the virus from replicating but if something happens where drug resistance is formed than drug resistant virus will predominate

Causes of HIV Resistance to ARVs
- Inadequate drug therapy
- Poor adherence causing subtherapeutic drug levels
- Poor absorption causing subtherapeutic drug levels
- Drug-drug interactions
- Infected with resistant virus during initial infection
- Superinfection with resistant virus

How to determine if a patient is infected with a drug resistant strain of HIV?
Genotype testing
- Compares the genetic makeup of the patient’s HIV versus the wild-type strain
- Identifies known mutations which are associated with resistance to specific genes
When to order HIV genotype?
- At acute infection/entry into care
- Suboptimal suppression of viral load after starting HAART
- Virologic failure during ART
- USed to assist in selecting active drugs for a new regimen
Case

ARV drug-interactions
- HIV medications are metabolized by the cytochrome P450 mechanism in the liver
- These antiretroviral medications have many potential drug-interactions with other medications that are also metabolized by this system
- Inducers: can decrease levels of other drugs
- Inhibitors: can increase levels of other drugs
- Check for drug-drug interactions prior to starting any new medication or if someone has side-effects
Drug interactions of “Boosters”
- Ritonavir or Cobicistat
- Drug induced Cushing’s
- Intranasal, inhaled, intra-articular, IM steroid in patients on ritonavir or cobicistat
- Beclomethasone appears safe
- Statins, SSRIs, others
Antiretrovirals that require acidic stomach
- Atazanavir
- Rilpivirine
Drug interactions of Integrase Inhibitors
- Avoid cations
- DTG increases metformin
Case

Why screen ALL pregnant women for HIV?

What is the effect of HAART on the risk of vertical HIV transmission

Case

Question

Methods of reducing acquisition of HIV
11 listed

Explain HIV virus distribution after infection

PEP vs PrEP

What is HIV PEP?
Post-exposure prophylaxis
When is HIV PEP indicated?
- Given after high-risk exposure to reduce risk of HIV infection
- Start within 72 hours of exposure
HIV PEP dosing
28 day course of daily 3-drug regimen
What is HIV PrEP?
Pre-exposure prophylaxis
When is HIV PrEP indicated?
- Daily regimen given before exposure to reduce risk of HIV infection
- Start at least 7 days prior to exposure
HIV PrEP dosing
Daily 2-drug regimen
HIV PEP drugs
Start 3 drug regimen <= 72 hours from exposure
2 NRTIs (Tenofovir/emtricitabine) + II (Raltegravir)
HIV PEP
HIV PEP Side effects
- Mild nausea
- Diarrhea
- Headache
HIV PrEP contrainidications
3 listed
- Active HIV
- Renal dysfunction
- Caution with HBV
PrEP drugs
Currently only one FDA-approved formulation
- Tenofovir disoproxil fumarate (TDF)/Emtricitabine (FTC) 1 tab qday
- Approved for adolescents & adults >= 35 kg (77 lbs)
Question

Case


Case CXR


What are the general clinical clues of HIV infection?
11 listed

What are the lab clinical clues of HIV infection?
5 listed
- Leukopenia
- Anemia
- Thrombocytopenia
- Polyclonal hypergammaglobulinemia
- Endocrinopathies
Common Bacterial Pulmonary syndromes associated with HIV
Common mycobacterial pulmonary syndromes associated with HIV
- M. tuberculosis
- M. avium complex
Common viral pulmonary syndromes associated with HIV
- Influenza
- RSV
- CMV
Common parasitic pulmonary syndromes associated with HIV
- Toxoplasmosis
- Strongyloides
Common Fungi pulmonary syndromes associated with HIV
- Pneumoncystis jirovecii
- Cryptococcus
- Histoplasmosis
- Coccidiodomycosis
- Blastomycosis
- Aspergillus
Common non-infectious pulmonary syndromes associated with HIV
6 listed
- Kaposi’s Sarcoma
- Non-Hodgkin’s Lymphoma
- Bronchogenic carcinoma
- Lymphocutic interstitial pneumonitis (LIP)
- Crack lung
- Primary pulmonary hypertension
Case

What is Pneumocystic jirovecii and where is it found?
Ubiquitous yeast in the environment
Pneumocystic jirovecii infections caused by?
Disease from reactivation or new infection
Who is most commonly infected with Pneumocystic jirovecii
Majority of cases of Pneumocystis pneumonia are in patients who are unaware of their HIV status or CD4 <200
A common co-infection of Pneumocystic jirovecii
Oral Candidiasis (thrush) is a common co-infection of Pneumocystic jirovecii
Clinical presentation of Pneumocystic jirovecii
- Subacute, progressive dyspnea, non-productive cough, pleuritic chest pain
- Hypoxemia, especially with activity (LDH>500)
Pneumocystic jirovecii CXR findings
Variable
- Classic: diffuse, bilateral interstitial infiltrates
- May be normal in early disease
Chest CT of Pneumocystic jirovecii
Patchy-ground glass attenuation
Treatment of Pneumocystic jirovecii
- TMP/SMX high dose x 21 days
- Add prednisone if pO2 < 70 mmHg or A-a gradient > 35 mmHg
PCP Prophylaxis When and What

Case


Opportunistic infections with CNS involvment classes of disease
- Meningitis
- Encephalitis
- Neurosyphilis
- CNS Lymphoma
Opportunistic infections with CNS involvment: Meningitis
5 listed
- Cryptococcus
- M. tuberculosis
- Listeria monocytogenes
- Typical bacterial
- Typical viral
Opportunistic infections with CNS involvment: Encephalitis
- Reactivation of latent infections
- CMV, HSV, VZV
- JV virus: PML (Progressive Multifocal Leukoencephalopathy)
- Toxoplasma gondii
Opportunistic infections with CNS involvment: Neurosyphilis
syphilis
Opportunistic infections with CNS involvment: CNS lymphoma
CNS lymphoma
How is Toxoplasma gondii encephalitis caused?
- Reactivation of latent tissue cysts
- Primary infection is from undercooked meat or shed in cat feces
Toxoplasma gondii encephalitis clinical presentation
- Focal encephalitis with headache, confusion, seizure or motor weakness & fever
Toxoplasma gondii encephalitis CT/MRI
Single or multiple contrast-enhancing lesion with edema
Toxoplasma gondii encephalitis Treatment
- Pyrimethamine + Sulfadiazine + Leukovorin for 6 weeks
- Long-term secondary prophylaxis
Toxoplasma gondii encephalitis reactivation prophylaxis When and What

Case


Case cont


Classes of Causes of pancytopenia
- Bacterial
- Mycobacterial
- Viral
- Malignancy
- Fungal
- Malnutrition
- Drug/toxin
Bacterial Causes of pancytopenia
Sepsis
Mycobacterial Causes of pancytopenia
- M. Tuberculosis
- M. avium complex
Viral Causes of pancytopenia
- CMV
- Parvovirus B-19
Malignancy causes of pancytopenia
Lymphoma
Fungal Causes of pancytopenia
- Cryptococcosis
- Blastomycosis
- Coccidiodomycosis
- Histoplasmosis
Drug/toxin Causes of pancytopenia
- Fapsone
- Alcohol
- Additive to cocaine
Case cont cont.


What is Mycobacterium avium Complex and where is it found?
AFB (Acid-Fast Bacteria) that is ubiquitous in the environment
How is infection with Mycobacterium avium Complex transmitted?
- Inhalation
- Ingestion
Risk factors for Mycobacterium avium Complex infection
- CD4 < 100; Most are < 50
- HIV RNA > 100,000 copies/mL
Mycobacterium avium Complex Clinical presentations
Can present as Disseminated multi-organ infection or local infection
Clinical presentation of disseminated multi-organ infection of Mycobacterium avium Complex
- Fever
- Night sweats
- Weight loss
- diarrhea
- Abdominal pain
- Anemia
- Elevated Alk Phos
- Lymadenopathy
- Hepatosplenmegaly
Clinical presentation of local Mycobacterium avium Complex infection
- Pneumonia
- Colitis
Treatment of Mycobacterium avium Complex infection
Clarithromycin + Ethambutol + Rifabutin
The challenges of Treating Mycobacterium avium Complex infections
- Drug-interactions with HAART
- Medication toxicity
MAC AKA
Mycobacterium avium Complex
Mycobacterium avium Complex prophylaxis What and When?

Opportunistic infections at any CD4 level
PPD or IGRA reactive
Opportunistic infections at CD4 < 200 cells/uL
PJP Prophylaxis
Opportunistic infections at CD4 < 100 cells/uL
Toxoplasma prophylaxis
Opportunistic infections at CD4 < 50 cells/uL
MAC Prophylaxis
Case


Assesing need for prophylaxis
