HIV Treatment Flashcards
Who is HIV treatment indicated for? (3)
- All individuals diagnosed with HIV
- To reduce morbidity and mortality
- To prevent transmission to sexual partners and infants - Initiate as soon as possible
- Especially important for those who have AIDS-defining conditions, acute/recent infection, and individuals who are pregnant
What are the benefits of ARV’s? (4)
- Allows restoration and preservation of immunologic function
- Reduces HIV-related morbidity & mortality
- Increases duration and quality of life
- Prevents transmission
What does “readiness to start” encapsulate? (4)
- Ability to take meds consistently
- Mentally ready?
- Do they require any supports? (housing, addictions support)
- Provide education around HIV, how the meds will help, medication adherence, side effects
How do antiretrovirals work? (3)
- Antiretrovirals block viral replication within the CD4 cell
- Prevents destruction of CD4 cells and allows restoration of immune function
- Requires more than 1 active antiretroviral to achieve and maintain suppression
How do Nucleoside Reverse Transcriptase Inhibitors (NRTIs) work? (3)
- HIV reverse transcription process is a multistep process that results in a copy of linear, double-strand HIV DNA being generated from single strand HIV RNA
- During this process of DNA synthesis, the HIV reverse transcriptase incorporates host nucleotides into the elongating primer strand, which is forming opposite to the HIV template strand
- NRTIs act as host nucleotide decoys and cause termination of the elongating HIV DNA chain
How do Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) work?
NNRTIs bind directly to the HIV reverse transcriptase enzyme and inhibit the function of the enzyme
How do Integrase Strand Transfer Inhibitors (INSTIs) work? (3)
- For replication, retroviruses must integrate the linear, double-stranded HIV DNA formed by reverse transcription into the host DNA. The integration of HIV DNA into host DNA is a multistep process and the HIV enzyme integrase performs two key catalytic reactions: 3’ processing of the HIV DNA and strand transfer of the HIV DNA into the host DNA
- Currently, available HIV integrase inhibitors utilize multiple mechanisms to block the integrase strand transfer step
- When the HIV integration process is blocked, the HIV DNA becomes a substrate for host repair enzymes that subsequently convert the HIV DNA complex into byproduct 2-long terminal repeat (2-LTR) circles
How do protease inhibitors (PIs) work? (2)
- The HIV protease inhibitors are structurally complex molecules that bind to the active site of HIV protease and inhibit the protease enzyme activity
- The HIV protease inhibitors disrupt the normal Gag and Gag-Pol polyprotein processing, causing arrest of the normal maturation process, which thereby prevents infection of new cells
What are the 4 classes commonly used to make up a regimen?
- NRTI’s
- NNRTI’s
- INSTI’s
- PI’s (almost always boosted)
How many ARV agents are typically used in a regimen?
- 3 active agents from 2 different classes
- Dual therapy regimens used now
- Monotherapy is never used
List the NRTI medications (5) (TTALE)
- Tenofovir Disoproxil Fumarate (TDF)
- Tenofovir Alafenamide (TAF)
- Abacavir
- Lamivudine
- Emtricitabine
What is Tenofovir often paired with?
Emtricitabine or Lamivudine as the NRTI backbone of a regimen
How often is TDF dosed?
PO once daily
What are the ADEs of Tenofovir (TDF)? (7)
- Decreased BMD
- Potential for renal toxicity (↓ eGFR, Fanconi syndrome) especially combined with a PK booster like ritonavir or cobicistat
- Headache (shared)
- Diarrhea (shared)
- Nausea (shared)
- Decreases lipids
- Severe exacerbation of hepatitis for patients co-infected with HBV/HIV when TDF is discontinued (shared)
How often is TAF dosed?
PO once daily (generally)
What are the ADEs of Tenofovir (TAF)? (6)
- Renal toxicity and decreases in BMD (less likely than with TDF)
- Weight gain (minimal) possible especially when combined with Dolutegravir or Bictegravir
- Diarrhea (shared)
- Nausea (shared)
- Headache (shared)
- Severe exacerbation of hepatitis for patients co-infected with HBV/HIV when TAF is discontinued (shared)
How often is abacavir dosed?
PO once daily
Abacavir is often paired with?
Lamivudine to form NRTI backbone
What are the ADEs of abacavir? (4)
- Risk of hypersensitivity reaction (check HLA-B*5701 prior to initiating)
- Potential risk of MI
- Nausea
- Diarrhea
Why is abacavir not used too often?
CV events (MI)
What is emtricitabine often paired with?
Tenofovir (TDF or TAF)
How often is emtricitabine dosed?
PO once daily
What are the ADEs of emtricitabine? (3)
- Minimal toxicity
- Hyperpigmentation
- Exacerbation of hepatitis in those co-infected with HBV/HIV who discontinue emtricitabine
What is lamivudine often paired with?
Abacavir, Tenofovir in other countries as part of TLD regimen
How often is lamivudine dosed?
PO once daily
What are the ADEs of lamivudine? (2)
- Minimal toxicity
- Exacerbation of hepatitis in those co-infected with HBV/HIV who discontinue Lamivudine
List the NNRTI medications (REND) (4)
- Rilpivirine
- Efavirenz
- Nevirapine
- Doravirine
How often is doravirine dosed?
PO once daily
What are the ADEs of Doravirine? (4)
- Nausea
- Dizziness
- Abnormal dreams
- Very well tolerated by most.
How often is efavirenz dosed?
PO once daily, taken at bedtime on an empty stomach
What are the ADEs of efavirenz? (4)
WE DON’T LIKE THIS ONE
1. Neuropsychiatric symptoms
2. Transaminase elevations
3. Hyperlipidemia
4. QT prolongation
How often is rilpivirine dosed?
PO once daily - also part of an injectable regimen
What are the ADEs of rilpivirine? (5)
- Depression
- Insomnia
- Headache
- QT interval prolongation
- Injection site reaction with Cabenuva
(Not used too often)
How is nevirapine dosed?
Once daily x14 days then BID. Don’t even worry about this one because not used much in adults. Liquid form for babies though (special access)
What are the ADEs of nevirapine? (2)
- Rash (including Stevens-Johnson Syndrome)
- Symptomatic hepatitis (more common in females with CD4’s greater than 250, males greater than 400)
List the INSTI drugs (5) (BCDER)
- Bictegravir
- Dolutegravir
- Cabotegravir
- Elvitegravir
- Raltegravir
How often is bictegravir dosed?
PO once daily ONLY AVAILABLE AS PART OF BIKTARVY
What are the ADEs of bictegravir? (4)
- Diarrhea
- Headache
- Nausea
- Weight gain
How often is dolutegravir dosed?
PO once daily (unless resistance present, may be 50mg po BID)
What are the ADEs of dolutegravir? (5)
- Insomnia
- Headache
- Depression
- Weight gain
- Rare hypersensitivity reactions
How often is cabotegravir dosed?
Either a part of injectable or a PO tablet
Pretty mid medication though
What are the ADEs of cabotegravir? (6)
- Headache
- Nausea
- Abnormal dreams
- Anxiety
- Insomnia
- Depression
Very well tolerated in most patients.
How often is elvitegravir dosed?
PO once daily (only available in STR format)
What are the ADEs of elvitegravir? (5)
- Nausea
- Diarrhea
- Sleep disturbance
- Headache
- Weight gain
How often is raltegravir dosed?
BID
What are the ADEs of raltegravir? (6)
- Nausea
- Diarrhea
- Headache
- CK elevation
- Weight gain
- Rarely rash
What is the only PI drug to know?
Darunavir
How often is darunavir dosed?
PO once daily or BID if resistance present
What are the ADEs of darunavir? (9)
- Tolerability not as good as other arv regimens
- Significant GI side effects
- Diarrhea
- Nausea
- Hyperlipidemia
- Fat maldistribution
- Implications for CVD
- Skin rash
- Hepatoxicity possible but not common
What is the 1st complete injectable ARV option?
Cabenuva (Cabotegravir + Rilpivirine)
(Oral lead in optional now)
Cabenuva has a very long PK tail. What does that imply?
Implications for resistance if patient discontinues injection
Go through the checklist for suitability of Cabenuva injections (10)
- No known or suspected mutations to Cabotegravir or Rilpivirine
- No evidence of chronic Hepatitis B Infection
- CrCl ≥30 mL/min
- No signs of liver failure (Child-Pugh C)
- Not currently pregnant or planning to become pregnant
- Patient is virally suppressed before receiving their first injection (ideally for 6 months or greater as a marker of stability/durability)
- Patient is able to commit to regular injections (monthly or every 2 months)
- Has reliable contact information to coordinate injection appts and followup
- Travel considerations- if patient is away for extended periods of time, may impact ability to use inj arv’s. Would have to bridge with po arv’s if outside of 7 day target treatment date
- No significant drug interactions exist: Anticonvulsants (CBZ, OxCBZ, PHB, PHT), Antimycobacterials (RFB, RIF), Dexamethasone (>1 dose), St. John’s wort
What is rapid start?
Starting ARV therapy within days up to 2 weeks from when the patient is diagnosed
What are the benefits of rapid initiation? (5)
- Earlier linkage to care
- Higher rates of retention in care
- Higher rates of suppression and shorter time to suppression
- Health benefits to the patient
- Reduces onward transmission
What are the rapid start regimens? (3)
- Generally looking at Biktarvy or Truvada + Tivicay. Less often may consider Truvada + boosted PI (Darunavir/Cobicistat or Darunavir/Ritonavir)
- Takes approximately 6 weeks to get genotype results back, these regimens have a low likelihood of resistance if the patient happened to have transmitted resistance
- No INSTI use in someone who has been on CAB-LA for PrEP until genotype results back
What are some laboratory values to get before initiating ART? (5)
- HIV viral load (VL), CD4
- Resistance testing
- Renal & hepatic function
- Viral hepatitis
- Pregnancy
What are some patient characteristics to consider before initiating ART? (4)
- Comorbidities
- CV, renal or liver disease, psychiatric illness, osteoporosis
- Opportunistic infections - Other medications
- Drug interactions - Pregnancy, child-bearing age
- Social factors
- Social lifestyle - chaotic, stable
- Convenience, food requirements
- Adverse effects
What are the baseline tests needed for HIV monitoring? (16)
- Baseline-Resistance testing
- CD4
- HIV VL
- HLA-B 5701
- HAV & HBV serology
- HCV screening,
- Toxo serology
- TB screening
- CBC
- Scr
- PO4
- Liver enzymes
- Lipids
- Random glucose
- U/A
- Pregnancy test if applicable
What is the lab monitoring schedule for patient on ART? (2)
- HIV VL-4-6 weeks after initiating arv’s or after switching,
otherwise q 3-6 months generally - CD4 count-q 3-6 months
- If consistent adherence and suppressed, can lengthen to q 12 months
- If CD4 is >500, CD4 monitoring is optional now (after 2 yrs with suppressed VL)
How can you manage ART-related nausea?
Can try Gravol or Ondansetron
How can you manage ART-related diarrhea?
Can try Metamucil to help bulk the stool or Immodium
How can you manage ART-related headache?
Can prescribe usual remedies like Acetaminophen, Ibuprofen, Naproxen
- Caution when using NSAIDs with TDF especially in boosted regimens
Why is adherence to ART so important?
It’s the major factor in ensuring virologic success and is a significant determinant of survival
How to check for adherence? (4)
- Ask patient, non-judgmental language
- Check PIP fill history
- Talk to community pharmacy
- Touch base with HIV care team
What are some factors associated with poor adherence? (7)
- Active alcohol or drug use
- Competing priorities (housing, food)
- Depression
- Lack of social support
- Low literacy
- Advanced HIV infection
- Young age
What are some reasons for non-adherence? (11)
- Experiencing side effects (or attributing symptoms to ARVs)
- Regimen is too complex, too many pills
- Forgetting to take the medication
- Oversleeping and missing a dose
- Being away from home
- Not understanding importance of adherence
- Concerns around confidentiality→don’t want to be seen taking meds in front of others
- Active substance abuse
- Mental health challenges
- Social issues (homelessness, lack of support)
- Cost
What are some strategies to help adherence? (10)
- Bubble packing by community pharmacies
- Weekly pill organizer/pill box
- Place medication near something patient does everyday
- Set an alarm on a cell phone, utilize apps
- Ask family members or friends to remind patient (if they’re aware of the diagnosis)
- Plan ahead for changes in routine including travel
- Keep a back-up supply in a purse or backpack
- Work with community pharmacy to set up auto refills, delivery
- Pair methadone fills with arv fills
- Keep clinic appointments with care team
How does HIV drug resistance occur? (6)
- HIV begins to multiply (billions of virions daily)
- HIV drugs block replication and reduce viral load
- Person stops taking ARV’s regularly & virus multiplies again. Possibility of virus mutating.
- New mutant virus does not respond to previous drugs to block replication, resulting in resistance
- Person must change ARV’s to effectively block replication
- Adherence is key to prevent mutations of the virus and prevent production of drug-resistant HIV
What are the 2 types of HIV drug resistance?
- Transmitted resistance
- When a person acquires a strain of HIV that is already resistant to certain ARV drugs - Acquired resistance
- When a drug-resistant strain of HIV emerges while a person is taking ART
What are some factors that contribute to suboptimal levels of drug-PK parameters? (3)
- Adherence
- Malabsorption
- Drug-drug interactions
What are resistance mutations?
Mutations cause conformational changes to a viral enzyme’s binding site
Explain how you would interpret M184V mutation notation
M (wildtype amino acid)
184 (codon position 184-located within the gene that codes for reverse transcriptase)
V (mutant amino acid)
Meaning there is a methionine –> valine amino acid substitution, alters susceptibility to the drug
What does a high genetic barrier to resistance allow for?
Allows a medication to bind itself tightly to the virus and keeps working even if the virus has changed
What is virologic suppression?
HIV RNA level below the LLOD of the assay
What is virologic failure?
Inability to achieve or maintain suppression of viral replication to <200 copies/mL
What is incomplete virologic response?
Two consecutive HIV RNA levels 200+ copies/mL after 24 weeks on an ARV regimen in a patient who hasn’t had documented virologic suppression on that regimen
What is virologic blip?
After being suppressed, an isolated detectable HIV RNA level that returns to suppression
What is low-level viremia?
Confirmed detectable HIV RNA level <200 copies/mL
What opportunistic infections can present at CD4 < 200? (2)
- Pneumocystis pneumonia
- Oropharyngeal candidiasis
What opportunistic infections can present at CD4 <100? (3)
- Cryptococcal pneumonia and meningitis
- Toxoplasmosis
- Esophageal candidiasis
What opportunistic infections can present at CD4 < 50? (2)
- Disseminated MAC
- CMV retinitis
How to treat candidiasis OI?
Oral fluconazole
When is PCP prophylaxis suggested?
For those with a CD4 count <200 cells/mm3 or <14%
What is the recommended agent for PCP prophylaxis?
Trimethoprim-Sulfamethoxazole (Septra)
- 1 DS or SS tab daily
When to discontinue PCP primary prophylaxis?
When CD4 over 200 cells x 3 months or in some cases where CD4 is between 100 and 200 and patient is suppressed.
How is PCP treated? (3)
- Sulfa-Trim (Septra) DS 2 tabs q8h x 21 days for mild to moderate
- 15-20mg of TMP component/kg/day IV x21 days for moderate to severe
- Secondary prophylaxis should begin once patient has completed treatment
What to know about MAC prophylaxis? (3)
- Prophylaxis is not recommended in those starting ARV therapy and expected to suppress, regardless of CD4 count
- Prophylaxis is indicated for people with CD4 counts less than 50 cells/mm3 and not on ARVs or who remain viremic despite ARV therapy
- Typically use Azithromycin 1250 mg po once weekly
- MAC blood cultures prior to initiating proph to rule out active infection
How is MAC treated? (6)
- Two or more antimycobacterial drugs - prevents resistance from developing
1) Clarithromycin 500 mg bid (alt. Azithromycin if DI’s or intolerance)
2) Ethambutol 15 mg/kg/day
3) Rifabutin 300 mg q24h (RCT showed improved survival with addition of a 3rd drug) - 3 or 4 drugs considered when CD4 <50, high mycobacterial load, absence of effective ART
- Maintain treatment for 12 months and until CD4 is > 100 x 6 months
What is IRIS (Immune Reconstitution Inflammatory Syndrome)? (2)
- Exaggerated inflammatory reaction to a disease-causing microorganism that can occur when the immune system starts to recover following initiation of ARV’s
- Unmasking IRIS-refers to a flare-up of a previously undiagnosed infection soon after arv’s are started
- Paradoxical IRIS-refers to the worsening of a previously diagnosed infection after arv’s are started - IRIS can be mild or life-threatening
How is mild IRIS treated?
NSAIDs, symptomatic treatment (inhaled steroids for cough), OI treatment
How is severe IRIS treated?
Corticosteroids may be indicated, interruption in arv’s in severe steroid-refractory cases, specialist involvement needed
What are some common drug interactions with ARVs? (8)
- TB meds-rifampin in particular (induction)
- Acid reducers, PPI’s, H2RA’s, antacids
- Anticoagulants, Antiplatelets
- Statins
- Steroids all routes
- Anticonvulsants
- Antidepressants, Anxiolytics, Antipsychotics
- Alpha adrenergic antagonists for BPH
What are some red flags to check for in HIV treatment/OI treatment? (4)
- Enzyme inhibition interactions
- PK boosters ritonavir and cobicistat - Enzyme inducing interactions
- Rifampin, Rifabutin, Carbamazepine, Phenytoin - Increased gastric pH
- ARV malabsorption (Rilpivirine, Atazanavir) - Cation chelation/complex formation resulting in ARV malabsorption with INSTI’s
- Ca, Mg, Zn, Fe, Al
Biktarvy and Rifabutin. Yay or nay?
Nay
