HIV Flashcards
What is the life expectancy for HIV patients on modern ARV therapies?
With the advent of HAART, people living with HIV have an expected lifespan similar to those who are HIV-negative as long as patients receive timely diagnosis, CD4 count at the time of treatment initiation, and access to treatment
What are some populations that may experience lower life expectancies following an HIV diagnosis?
Non-white people
Individuals with history of injection drug use
Individuals who start ARV at low CD$ counts
What are some characteristics of standard screen test for HIV?
Uses 4th generation antibody and antigen
Nearly 100% sensitive and specific for chronic HIV (infection event was more than 15-20 days)
Need to wait a few days to 2 weeks to see results
What are some characteristics of point of care screen test for HIV?
Rapid antibody screen for HIV 1 & 2
Need for confirmatory testing, if result is positive
What are some characteristics of the dried blood spot (DBS) screen test for HIV?
Currently utilized in select projects and communities in Sask.
Blood was collected using a finger prick and placed on the sheet. The sheet is sent away for testing
Better confidentiality
Can test for multiple bloodborne diseases on the same card
What cells does HIV infect?
Human Deficiency Virus targets CD4 lymphocytes (T cells)
T cells infected by HIV are no longer able to coordinate immune responses from macrophages, B cells, and CD8 T lymphocytes
What is AIDS?
Acquired Immunodeficiency Syndrome
End stage of HIV infection
CD4 count of less than 200
Presence of 1 or more AIDS-defining illnesses
Opportunistic Infections (Pneumocystis pneumonia, mycobacterium avium complex, cytomegalovirus)
What is HIV?
HIV is a retrovirus that occurs as two types (HIV-1 and HIV-2)
HIV-1 is the most common (95% of all infections)
HIV-2 is mostly found in West Africa (may affect drug choice)
Review slide 40
What HIV-infected body fluids can spread HIV infections?
The following fluids need to come in contact with mucous membranes(rectum, vagina, penis, mouth) or directly injected into the bloodstream for transmission to occur
- Blood
- Semen
- Vaginal fluid
- Rectal fluid
- Breast milk
What are the modes of HIV transmission?
Sexual
- Unprotected sex with someone with HIV
- Insertive and receptive sex (anal, vaginal)
Blood contact
- Sharing needles (PWID, tattoos, piercing, razors)
- Blood transfusions (prior to 1985 in Canada)
- Occupational exposure (needle-stick injuries)
Vertical transmission
- To fetus/infant in utero, at delivery, or via breastmilk
When is the highest risk for vertical transmission?
Highest risk if:
- Seroconversion occurs during pregnancy due to higher viral load
- Pregnant person is HIV+ but not diagnosed or not on ARV
What are some precautions associated with reducing vertical transmission?
Women taking ARV and maintain a suppressed viral load from conception have less than 1% risk of vertical transmission
Recommendation in resource-rich settings is not to breastfeed as HIV can pass through the milk despite the mother being suppressed
What is the risk of transmission among HIV+ patients on antiretrovirals?
Undetectable=Untransmittable
As long as adherent and viral load is below 200 copies/mL
What are some symptoms associated with a new HIV infection?
Flu-like symptoms within 2-4 weeks after infection
- Fever
- Sore throat
- Enlarged lymph nodes
- Night sweats
- Chills
- Fatigue
What is the relevance of CD4 count in HIV?
It is a marker of immune system health
800-1200 is considered to be normal, and declines rapidly without antiretroviral treatment
Lower values may indicate need to initiate prophylaxis for opportunistic infections
What opportunistic infection is a HIV+ patient at risk for at any CD4 count?
TB
More likely for a latent infection to reactivate
What opportunistic infections is a HIV+ patient at risk for when CD4 count is below 250?
<250: Coccidiomycosis
<200: Pneumocystis
<150: Histoplasmosis and Cryptococcus (rare in SK, more common in southern USA)
<100: Toxoplasmosis (start proph if CD4 count falls below 100)
<50: MAC, CMV, PML (pts become very vulnerable)
What is HIV viral load?
Amount of virus present in the blood
Measured as copies/mL
Less than 50 copies/mL is considered to be suppressed
A patient has an undetected viral load when testing devices are unable to pick up any viral copies
Review slide 54 for typical course of untreated HIV infection
For which patient groups is HIV treatment recommended for?
All individuals with HIV
- To reduce morbidity and mortality
- To prevent transmission to sexual partners and infants
Initiate treatment as soon as possible (well tolerated, and better outcomes with treatment)
Especially important to start treatment for those who have AIDS-defining conditions, acute/recent infection, and pregnant
What are some of the benefits of ARVs?
Allows restoration and preservation of immunologic function
Reduces HIV-related morbidity & mortality
Increases duration and quality of life
Prevents transmission
What is the general MOA of antiretrovirals in HIV?
Antiretrovirals block viral replication within the CD4 cell
Prevents destruction of CD4 cells and allows restoration of immune function
Requires more than one active antiretroviral to achieve and maintain suppression
What is the MOA of nucleoside reverse transcriptase inhibitors (NRTIs) in HIV treatment?
As a part of the HIV life cycle, it highjacks host nucelotides in forming double-strand HIV DNA
NRTIs act as host nucleotide decoys and cause termination of the elongating HIV DNA chain
What is the MOA of non-nuclease reverse transcriptase inhibitors (nNRTIs) in HIV treatment?
nNRTIs bind directly to the HIV reverse transcriptase enzyme and inhibit the function of the enzyme to generate double-strand HIV DNA
What is the MOA of integrase strand transfer inhibitors (INSTIs) in HIV treatment?
Use multiple mechanisms to block the integrase strand transfer of HIV DNA into host DNA (inhibition of HIV virus lifecycle)
When the integration process is blocked, the HIV DNA becomes a substrate for host repair enzymes
What is the MOA of protease inhibitors in HIV treatment?
Bind to the active site of HIV protease and inhibit protease activity, which causes arrest of the normal maturation process and prevents infection of new cells
What are the four classes of anti-retrovirals used in HIV treatment?
- Nucleotide reverse transcriptase inhibitors (NRTIs)
- non-Nucleoside reverse transcriptase inhibitors (nNRTIs)
- Integrase inhibitors (INSTIs)
- Protease inhibitors (PI)
Is monotherapy antiretroviral therapy reccomended in HIV therapy?
No, monotherapy is never used
The following regimens are followed in practice:
- 3 active agents from 2 different classes
- Dual therapy regimens
Which drug class is Tenofivir Disoproxil Fumarate (TDF)?
NRTI (Nucleotide Reverse Transcriptase Inhibitors)
What drugs is tenofovir fumarate (TDF) used with?
Often paired with emtricitabine or lamivudine as the NRTI backbone of a regimen
What are some adverse effects associated with tenofovir fumarate (TDF)?
- Decreased BMD
- Renal toxicity (reduced eGFR, Franconi syndrome)
What are some combo products that contain tenofovir fumarate (TDF)?
Atripla
Stribild
Complera
Delstrigo
Which drug class is tenofivir alafenamide (TAF) a member of?
NRTI
What drugs is tenofovir alafenamide (TAF) used with?
Like TDF, TAF is often paired with emtricitabine to form NRTI backbone
What makes TAF different from TDF?
TAF is a prodrug and concentrates intracellularly
What are some combo products that contain tenofovir alafenamide?
Biktarvy (most commonly used, 60-70% of pts on this due to lower resistance)
Genvoya
Odefsey
What are some ADRs associated with tenofovir alafenamide therapy?
Renal tox and reduced BMD (less severe compared to TDF, bc TAF is prodrug and concentrates intracellularly)
Weight gain (esp. when combined with other antiretrovirals)
What drug class is abacavir a part of?
NRTI
What antiretrovirals is abacavir often paired with?
Like TDF, abacavir is paired with Lamivudine to form NRTI backbone
What are some ADRs associated with abacavir?
ADRs are high, which is why abacavir is falling out of favour (still used in infants due to safety data)
Risk of hypersensitivity reaction (check HLA-B*5701 prior to initiation)
Risk of MI (50% higher risk of MACE)
Nausea & Diarrhea
What drug class is emitricitabine a part of?
NRTI
What other antiretrovirals is emitricitabine combined with?
Often paired with tenofovir (TDF or TAF)
What are some combo products that contain emitricitabine?
Biktarvy, Genvoya, Stribild, Complera, Odefsey, Atripla
What are some ADRs associated with emitricitabine use?
Minimal toxicity, hyperpigmentation, exacerbation of hepatitis in those coinfected with HBV/HIV and d/c emtricitabine
What drug class is lamuvidine a part of?
NRTI
What antiretrovirals are combined with lamuvidine?
Often paired with abacavir, tenofovir (in other countries as a part of TLD regimen)
What are some combo products that contain lamivudine?
Triumeq, Delstrigo, Dovato
What are some ADRs associated with lamuvidine?
Minimal toxicity
Exacerbation of hepatitis in pts who have HBV/HIV and d/c lamuvidine
What drug class does doravirine belong to?
nNRTI (non-nucleotide reverse transcriptase inhibitors)
What combo products contain doravirine?
Delstrigo
What are some ADRs associated with doravirine use?
Nausea
Dizziness
Abnormal dreams
Very well tolerated by most (weight neutral)
What drug class is efavirenz a part of?
nNRTIs
What combo products contain efavirenz?
Poorly tolerated (avoid use)
Neuropsych sx, transaminase elevations, hyperlipidemia, QT prolongation
What drug class is rilpivirine a part of?
nNRTI
What are some combo products that contain rilpivirine?
Complera
Odefsey
Juluca (rarely used due to psych sx)
Cabenuva injectable regimen
What are some ADRs associated with rilpivirine?
Depression, insomnia, headache
QT prolongation
Injection site reaction with Cabenuva inj
What drug class is nevirapine a part of?
nNRTIs
What are some ADRs associated with nevirapine use?
- Rash (including SJS)
- Symptomatic hepatitis (more common in females with CD4 greater than 250 and males over 400)
What drug class is bictegravir a part of?
Higher potency INSTI (integrase inhibitors)
What combo products contain bictegravir?
Biktarvy
What are some ADRs associated with bictegravir?
Diarrhea (self-limiting), headaches, nausea, weight gain (affects black & indigenous women)
What drug class is dolutegravir a part of?
INSTI (higher potency)
What combo products include dolutegravir?
Triumeq, Dovato, Juluca
What are some ADRs associated with dolutegravir use?
Insomnia, headache, depression, weight gain, rare hypersensitivity reactions
What is an important drug interaction with dolutegravir?
TB medications
What drug class is cabotegravir a part of?
INSTI
What combo products include cabotegravir?
Cabenuva (cabotegravir+rilpivirine)
What ADRs exist for cabotegravir?
Very well tolerated in most patients
Injection site reactions are most common
Headaches, nausea
Abnormal dreams
Anxiety, insomnia, depression
What drug class is elvitegravir a part of?
INSTI (low potency)
What combo products contain elvitegravir?
Genvoya and Stribild
What are some ADRs associated with elvitegravir?
Avoid in higher CV risk
What drug class is raltegravir a part of?
INSTI (low efficacy)
What combo product contains raltegravir?
Biktarvy
What are some ADRs associated with raltegravir?
Nausea, diarrhea
Headache
CK elevation
Weight gain
What drug class is darunavir a part of?
PI (protease inhibitor)
What drugs must always be used with darunavir?
PK boosters such as ritonavir or cobicstat inhibit CYP metabolism of darunavir
What are some ADRs associated with darunavir use?
Tolerability not as good as other ARV regimens
Significant GI SEs (nausea, diarrhea)
Hyperlipidemia
Fat maldistribution
Hepatotoxicity is possible, but not common
What antiretrovirals are in Descovy?
Tenofovir alafenamide(TAF)+Emitricitabine
What antiretrovirals are in Truvada?
Emitricitabine+Tenofovir fumarate (TDF)
What antiretrovirals are used in Kivexa?
Abacavir+Lamuvidine
Review slide 84 for complete ARV regimens
What are the dual ARV regimens for HIV?
Dovato (dolutegravir+lamuvidine)
Juluca (dolutegravir+rilpivirine)
Cabenuva (cabotegravir+rilpivirine)
Is Cabenuva (cabotegravir+rilpivirine) a complete ARV regimen?
Yes
It is the first complete injectable ARV option
How is Cabenuva administered?
1 gluteal injection every 1-2 months
Review slide 87 for Cabenuva injection patient suitability
What are the recommended HIV ARV regimens?
Review slide 88
- Biktarvy (BIC/TAF/FTC)
- BIC: bictegravir
- TAF: tenofovir alafenamide
- FTC: emtricitabine - Dovato (DTG/3TC)
- DTG: dolutegravir
- 3TC: lamuvidine
3: DTG+(TAF or TDF)+(FTC or 3TC)
What are rapid starts in the context of ARV therapies in HIV?
Start ARV therapy within days and up to 2 weeks of being diagnosed with HIV
Useful when treating high risk patients
What are the benefits of rapid starts for ARV therapy?
- Earlier linkage to care (lower patient drop-off)
- Higher rates of retention in care
- Higher rates of suppression and shorter time to acheive suppression
- Health benefits to the patient
- Reduces onward transmission
What is the one limitation to starting rapid starts with respect to potential treatment resistance?
Patients who have been on long-acting cabotegravir for PrEP should not be started on a INSTI until genotype results are back
What are laboratory values that are importat to consider when initiating ARV therapies for HIV?
- HIV viral load & CD4 counts
- Resistance testing
- Renal and hepatic fxn
- Viral hepatitis
- Pregnancy
What are some patient characteristics that may influence ARV selection?
Comorbidities: CV, renal & liver disease, psychiatric illness, osteoporosis
Other medications
Pregnancy/child-bearing age
Social factors: Chaotic, stable, nutritional deficiencies, adverse effects
How often is viral load and CD4 counts taken?
q3-6 months
Review slide 97-101 for ARV adverse effects review
What is the major factor for ensuring virologic success with ARV therapies?
Adherance
It is a significant determinant of survival
What are some factors that may contribute to poor adherance to ARV therapies?
- Active alcohol use
- Competing priorities (housing, food)
- Depression
- Lack of social supports
- Low literacy
- Advanced HIV infection
- Young age
What are the two types of treatment resistance seen with ARVs in HIV?
Transmitted and Acquired Resistance
What is transmitted resistance to ARVs in HIV?
When a person acquires a strain of HIV that is already resistant to certain antiretroviral drugs
What is acquired resistance to ARVs in HIV?
When a drug-resistant strain of HIV emerges while a person is taking antiretroviral therapy
Usually occurs when pt has poor adherance (here and there dosing is highest risk)
What are some factors that contribute to suboptimal levels of ARVs in the serum?
- Adherance
- Malabsorption (ex. CMV)
- DIs
What is a common HIV mutation that results in ARV resistance?
M184V mutation in the reverse transcriptase gene alters susceptibility to NSTIs and nNSTIs
What does it mean when a patient has acheived virologic supression?
HIV RNA is below the lower limit of detection of the assay
What does it mean if a patient has virologic failure?
Inability to acheive or maintain supression of viral replication to under 200 copies/mL
What does it mean if a patient has an incomplete virologic response?
Two consecutive HIV RNA levels over 200 copies/mL after 24 weeks on an ARV regimen in a patient that has not shown virologic suppression on that regimen
What does it mean if a patient has a virologic blip?
After being suppressed, an isolated detectable HIV RNA level that returns to suppression
What does it mean if a patient has low-level viremia?
Confirmed detectable HIV RNA level under 200 copies/mL
What happens when the HIV virus colonizes parts of the body that have reduced immune activity?
Grows unopposed to the immune system, can release a lot of viral copies into blood stream if compromised
ex. CNS
By how much should viral load decrease with ARV therapies for HIV?
10-100x viral load reduction per month
What ARV therapy drug class causes the most rapid decline in viral load?
Integrase inhibitors
When do we have to worry about ARV resistance when initiating a regimen?
If viral load has decreased by less than 10x after 3 months of therapy
Notify HIV care team
What opportunistic infections are more common when CD4 counts fall below 200?
Pneumocystis pneumonia
Oropharyngeal candidiasis
What opportunistic infections are more common when CD4 counts fall below 100?
Cryptococcal pneumonia and meningitis
Toxoplasmosis
Esophageal candidiasis
What opportunistic infections are more common when CD4 counts fall below 50?
Disseminated MAC
CMV retinitis
What opportunistic infections are all HIV patients at risk for regardless of CD4 counts?
Tuberculosis
What is the most common opportunistic infection seen with HIV patients?
Oropharyngeal candidiasis
Typically seen when CD4 counts falls below 200
How is oropharyngeal candidiasis treated in patients with HIV?
Oral fluconazole preferred 100mg/day x 7-14 days
How is esophageal candidiasis treated in patients with HIV?
Oral fluconazole 100-400mg/day x 14-21 days
Longer treatment duration vs. oropharyngeal candidiasis
HIgher doses and longer duration in pts with lower CD4 counts
What is the presentation of pneumocystis pneumonia (PCP)?
Typically presents in immunocompromised hosts (CD4 under 200) as a subacute onset syndrome of dry cough, fever, exertional dyspnea, chest discomfort, and even respiratory failure
How is pneumocystis pneumonia detected?
Bronchoscopy with bronchoalveolar lavage fluid is the most sensitive (90-98%)
When should prophylaxis for pneucmocystis pneumonia be started?
Suggested in patients with CD4 count under 200
What is used for pneumocystis pneumonia prophylaxis?
TMP/SMX 1 DS tab daily offers cross coverage for toxoplasmosis (imp when test positive and CD4 is under 100) and other bacterial infections
How long should pneumocystis pneumonia prophylaxis be continued for?
Until CD4 is above 200cells/mL for at least 3 months
OR
When CD4 count is between 100-200 cells/mL in cases where the patient is unable to acheive CD4 count of above 200 cells/mL
How is an active pneumocystis pneumonia infection treated?
TMP/SMX 2 DS tabs q8h for 21 days for mild to moderate disease
In addition to antibiotic treatment, what other drug class is also added when treating a moderate-severe pneumocystis pneumonia infection?
Adjunctive steroid
At what CD4 count does Mycobacterium Avium Complex (MAC) considered to be a potential opportunistic infection?
When CD4 counts are below 50
What is the presentation of mycobacterium avium complex (MAC) infections?
Disseminated disease with malaise, fevers, weight loss, diarrhea, lymphadenopathy
Hepatosplenomegaly common (huge abdominal protrusion)
When is prophylaxis started for MAC in HIV patients?
Prophylaxis is not recommended in those starting or already on ARV therapy
Prophylaxis is recommended in patients with CD4 counts below 50 and not on ARV or remain viremic despite ARV therapy
What is used for MAC prophylaxis among HIV patients?
Azithromycin 1250mg PO once weekly
What is included in treatment of MAC infections in HIV patients?
Two or more mycobacterial drugs (to prevent resistance)
- Clarithro (may try azithro if DI or intolerance for clarithro)
- Ethambutol
- Rifabutin
3 or 4 drugs considered in pt with CD4 below 50 and high MAC bacterial load
What is IRIS in the context of HIV treatment?
Immune Reconstitution Inflammatory Syndrome
It is an exaggerated inflammatory reaction to a pathogen after the immune system starts to recover following initiation of ARV therapy
What are the two types of IRIS in HIV treatment?
Unmasking IRIS (flare-up of previously undiagnosed infection)
Paradoxical IRIS (worsening of a previously diagnosed infections)
What is the severity of IRIS after starting ARV therapy in HIV?
Mild to life-threatening
When is IRIS experienced by patients receiving ARV therapy?
Seen most often in the first 8 weeks of ARV therapy in pts with advanced HIV
Most IRIS cases occur in those with low CD4 counts and high viral loads
What is used to treat mild IRIS in patients intiating ARVs?
NSAIDs and symptomatic treatment (inhaled steroids for cough) a
Opportunistic infection treatment
What is used to treat severe IRIS in patients intiating ARVs?
Corticosteroids
Interruption in ARVs in cases that do not respond to steroid therapy
What drug classes commonly have drug interactions with ARV therapies?
- TB meds (esp rifampin)
- PPIs, H2RAs, antacids (with rilpivirine)
- Anticoags, Antiplatelets (with ritonavir and cobicistat)
- Statins
- Steroids all routes (w Genvoya)
- Anticonvulsants (Phenytoin and Biktarvy)
- Antidepressants, Anxiolytics, Antipsychotics
- a-adrenergic antagonists for BPH
- Mineral supplements chelate to INSTIs
What are the four main pillars of HIV prevention?
- Undetectable=untransmittable
- Harm Reduction Programs
- Pre-exposure prophylaxis (PrEP)
- Post-exposure prophylaxis (PEP)
What is PrEP (pre-exposure prophylaxis)?
PrEP is a HIV prevention strategy to reduce the risk of acquiring HIV
ARV taken by HIV-negative patients considered at risk of infection
What drugs are used in PrEP?
Truvada (TDF+emitricitabine)
OR
Descovy (TA+emitricitabine)
Ensure patient is not on ARV monotherapy for PrEP
What is the benefit of PrEP?
Reduces the risk of acquiring sexually transmitted HIV by more than 90% if taken as prescribed
74% reduction among PWIDs
What groups are at highest risk of contracting HIV?
MSM and transgender women engaging in condomless sex in the last six months with the following factors:
- Syphillis or rectal STI
- Recurrent use of post-exposure prophylaxis
- Ongoing relationship with HIV pos partner with risk of transmissible HIV
- High incidence risk score (HIRI-MSM above 11)
What is the schedule for the most common form of PrEP?
Truvada 1 tablet once daily
What are some baseline investigations before PrEP for HIV can be initiated?
Review slides 160 and 161
HIV status (CI if client is HIV positive, may develop resistance)
- Baseline HIV testing, and may repeat 14-21 days after first test)
Hep A, B, and C status
Baseline STIs (treat accordingly)
Pregnancy
CBC, renal panel, eGFR
Comorbidities
Vaccination status
What are the indications for Truvada as PrEP?
Approved for MSM, trans women, heterosexual for once daily regimen
Off-label indications:
- PWIDs for once daily regimen
- MSM for on-demand regimen
Can Truvada PrEP be used safely in pregnancy and lactation?
Yes
When is Truvada PrEP contraindicated?
eGFR is below 60mL/min
What are some common side effects associated with Truvada PrEP?
Headache, fatigue (more common with on-demand regimen vs. once daily)
Renal tox (regularly get bloodwork)
What are some drug interactions associated with Truvada PrEP?
Avoid nephrotoxic agents (ex. NSAIDs and AMG)
Why is long-acting cabotegravir a promising option for PrEP?
Once monthly injection for 2 months, then every 2 months
Good option for patients who struggle with adherance
What is the risk of vertical transmission for women diagnosed with HIV during pregnancy?
9-15x higher
Truvada once daily is the only regimen approved for use in pregnancy and lactation
Does PrEP prevent other STIs besides HIV?
No
When should PrEP be discontinued to minimize risk of infection from past exposures?
In MSM or trans women: d/c PrEP 2-28 days after last exposure
In heterosexuals or PWID: d/c PrEP 28 days after last exposure
On demand regimen: take last tablet 48 hours after last exposure
What is PEP (post-exposure prophylaxis) in the context of HIV?
Involves the use of HIV medications in an HIV negative patient who may have been exposed to HIV to prevent transmission
When should post-exposure prophylaxis for HIV be initiated?
As soon as possible, must be started within 72h of exposure
Where can post-exposure prophylaxis for HIV be accessed?
ER physican will assess risk of exposure and need for post-exposure prophylaxis
How long is the post-exposure prophylaxis treatment course for HIV?
28 day cycle
When is a patient expected to follow up following administration of post-exposure prophylaxis for HIV?
- 4-6 weeks post-exposure
- 3 months post-exposure
- 6 months post-exposure
Assess client for switch to PrEP after completion of PEP if they have ongong risk factors
