HIV

Focus on classes, main combo products

Background and diagnosis

● Transmission
○ Infected blood, semen, vaginal secretions, unprotected intercourse, sharing needles, vertical
transmission from mother to child during pregnancy, birth, or breastfeeding
● Screening and diagnosis
○ Who
■ Between ages 13-64
■ Pregnancy
■ Anyone being treated for STDs
■ Anyone with high risk behaviors (annual)
○ Screening Tests
■ Preferred: combination HIV Ab (produced 4 weeks-6 months) and HIV p24 antigen (produced at
2 weeks) immunoassay test
■ Alternate: HIV immunoassay (ELISA)
○ Confirmatory test
■ Preferred: HIV1/HIV2 antibody differentiation test
■ Alternate: HIV RNA viral load, western blot
○ Need positive screening + positive confirmatory test for diagnosis
○ Over the counter HIV testing
■ Home access express HIV test system
● Finger stick blood test → mail in → results available next day
■ OraQuick in home HIV test
● Oral swab → results in 20-40 minutes
■ Recommended to be performed > 3 months after exposure (both are antibody tests)
■ Patients still need positive confirmatory test by a provider before official diagnosis
Human CD4 cell

1. Binding/Attachment
-CCR5 antagonist: Maraviroc (Selzentry)
-CD4-Directed Post-Attachment Inhibitor:
Ibalizumab-uiyk (Trogarzo) IV

2. Fusion
-Enfuvirtide (Fuzeon) sq

3. Reverse Transcription
-NNRTIs (work in cytoplasm) abacavir,
lamivudine, emtricitabine, TDF, TAF,
zidovudine, stavudine, didanosine
-NRTIs (work in cytoplasm) efavirenz,
rilpivirine, nevirapine, etravirine

4. Integration
-INSTIs (work in nucleus) elvitegravir,
bictegravir, dolutegravir, raltegravir

5. Replication (no drugs)

6. Assembly (no drugs)

7. Budding
-PIs (work in newly formed HIV) darunavir,
atazanavir, fosamprenavir, indinavir,
lopinavir, nelfinavir, saquinavir, tipranavir

Initial evaluation and monitoring

● CD4 count
○ Goal: normal or high as possible
○ Amount of CD4 cells in the blood
○ Indicator of immune function
○ When CD4 < 200, patient is at risk for opportunistic infections
● HIV RNA viral load
○ Goal: undetectable or low as possible
○ Amount of HIV virus in the blood
○ Indicator of response to ART
● Testing for Hep B and C
● Baseline: LFTs, electrolytes, pregnancy test
HIV Drug Classes
● 1. CCR5 antagonist
○ Maraviroc (Selzentry)
○ Only works for CCR5 tropic disease (not for CXCR4 tropic)
● 1. CD4 directed post attachment HIV1 inhibitor (aka post attachment inhibitor)
○ Ibalizumab-uiyk (Trogarzo)
○ IV
○ For MDR HIV
● 2. Fusion inhibitor
○ Enfuvirtide (Fuzeon)
○ Sq injection
● 3. NNRTIs
○ Key features
■ All are CYP3A4 substrates
● Inducers: nevirapine and etravirine
● Inhibitor: delavirdine
● Both: efavirenz
■ No renal adjustments (avoid Atripla and Complera if CrCl < 50 ml/min)
■ Hepatotoxicity and ​rash ​including SJS (nev > other)
■ Monitor for erythema, facial edema, skin necrosis, blisters, and tongue swelling
○
NNRTI BBW Warnings / Side Notes
effects

Efavirenz (Sustiva) CNS toxicity esp vivid Take on empty stomach at

Capsule, tablet, can be dreams bedtime to minimize CNS
sprinkled

Rilpivirine (Edurant) CNS depression, Requires acidic env, C/I with

Tablet mood, and insomnia, PPIs and separate from
QT prolong aa/H2, take with full meal >
500 kcal
Avoid in patients with >
100,000 copies/ml viral load
and < 200 CD4

Nevirapine (Viramune) Hepatotoxicity and Increased LFTs Do not initiate in women

Tablet and suspension SJS with CD4 > 250 or men CD4 >
400

Etravirine (Intelence) Rash For treatment resistant pts

Tablet

● 3. NRTIs
○ Key features
■ No CYP450 drug interactions
■ Renal dose adjustment required except abacavir
■ Warning: ​lactic acidosis ​and hepatomegaly with steatosis (zidovudine, stavudine, didanosine
more than other NRTIs)
■ Monitoring: LFTs, renal function, HepB status
○
NRTI BBW Warnings / Side effects Notes

Abacavir (Ziagen) Serious delayed Increased risk of MI in Test for HLA-B*5701,

Tablet, solution hypersensitivity, stop CVD, caution with alcohol needs to be negative
and do not rechallenge, (metabolized by ALDH) Triumeq contains
dispense warning card N/V, ha, rash, inc LFTs,
hyperlipidemia

L​amivudine Active against HepB → Well tolerated Do not use with

(Epivir for HIV, Epivir Reactivation of HepB N/V/D, ha, emtricitabine
HBV for HepB) upon d/c fatigue,insomnia, inc
Tablet, solution LFTs,

E​mtricitabine Active against HepB → Well tolerated Do not use with

Capsule, solution Reactivation of HepB N/V/D, ha, dizziness, lamivudine
upon d/c insomnia,
hyperpigmentation

T​enofovir disoproxil Active against HepB → N​ephrotoxicity Mix powder with 2-4
fumarate​ (TDF, Viread) Reactivation of HepB O​steoporosis oz of soft food, not
Tablet, powder upon d/c F​anconi (phosphate liquid
wasting)
N/V/D, ha

T​enofovir alafenamide Active against HepB → Nausea, decreased bone Higher intracellular
(TAF) Reactivation of HepB density concentrations,
Tablet upon d/c lower blood levels,
LET​ me treat your HepB lower side effects

Zidovudine Neutropenia and M​ toxicities (macrocytic Available IV, used

Old anemia, myopathy anemia and myopathy), during childbirth
lactic acidosis and
hepatomegaly

Stavudine Pancreatitis Pancreatitis and

Old, not in guidelines peripheral neuropathy
N/V/D, hyperbili,
lipoatrophy, lactic
acidosis and
hepatomegaly

Didanosine Pancreatitis Pancreatitis, peripheral

Old, not in guidelines neuropathy, and pink skin
rash
N/V/D, amylase, lactic
acidosis and
hepatomegaly
○
● 4. INSTIs (-tegravir)
○ Key features
■ No renal dosing except noted below
■ No major CYP interactions alone but combo products will have interactions bc of their non-INSTI
components
■ Increase CPK (raltegravir > others)
■ Headache, insomnia
■ Seperate from polyvalent cations
○
INSTI BBW Warnings / Side Notes
effects

Elvitegravir (with Proteinuria, ha, Stribild do not start CrCl < 70

Boost with cobic for qd emtricitabine and insomnia and d/c < 50
Stribild (+ emtri/TDF) tenofovir) (with e and t lactic Genvoya do not start CrCl <
Genvoya (+ emtri/TAF) reactivation of acidosis and 30
Tablets HepB hepatomeg) Dont use with 3A4 inducers

Bictegravir (with (with e and t lactic Biktarvy do not start CrCl <
Biktarvy (+emtri/TAF) emtricitabine and acidosis and 30
Tablet tenofovir) hepatomeg) Dont use with dofetilide or
reactivation of Diarrhea, dizziness, rifampin
HepB nausea

Dolutegravir (Tivicay) Insomnia, ha, inc SCr Don't use with dofetilide
Tablet

Raltegravir (Isentress) Inc CPK, rhabdo

Tablet, powder
○
● 7. ​PIs​ (-navir)
○ Key features
■ CYP450 inhibitors ​DI​ drug interactions
■ No renal dose adjustments
■ Hepatotoxicity
■ Metabolic abnormalities​ (hyperlipidemia, hyperglycemia)
■ Increased CVD risk
■ ECG changes
■ Rash
■ GI​ upset, take with food (except fos and lopin)
○
PI BBW Warnings / Side Notes
effects

Darunavir (Prezista) Hepatitis, SJS, N/V/D, Caution in sulfa allergy

Must be boosted inc LFTs
Tablet, suspension

Atazanavir (Reyataz) Indirect hyperbili Requires acidic env, separate

Capsule, powder (bananavir), from acid suppressants, max
hepatotox, omeprazole 20 mg daily
 nephrolithiasis (kidney
stones), cholelithiasis,
skin reactions, PR
prolong

Fosamprenavir (Lexiva) Rash

Tablet, suspension

Indinavir (Crixivan) Nephrolithiasis, Without ritonavir: empty

Capsule N/V/D, ha, highest risk With ritonavir: with food
of hyperglycemia

Lopinavir + ritonavir QT/PR prolong, Tablets with/out food,

(Keletra) N/V/D, highest risk of solution with food, 42%EtOH
Tablets, solution hyperglycemia Avoid qd dosing with
carbamaz, phenytoin,
phenobarb, pregnancy

Nelfinavir (Viracept) Diarrhea No PPIs

Doesn't need boosted
Tablet

Saquinavir (Invirase) QT/PR prolong,

Must be boosted with nausea
ritonavir
Capsule (syrup or jam),
tablet

Tipranavir (Aptivus) Hepatitis, hepatic Intracranial Structurally similar to

Must be boosted with decompensation, hemorrhage, N/V/D warfarin, caution in sulfa,
ritonavir intracranial capsules have 7% alcohol,
Capsule (refrig), hemorrhage solution has vitamin E
solution (room temp)

○ Boosters
■ Strong ​3A4 inhibitors
● Contraindicated with amiodarone, carbamazepine, lovastatin, phenobarb, phenytoin,
rifampin, simvastatin, St. john’s wort, any NTW that depends on 3A4 for clearance
■ Ritonavir
● Can be used alone but not for HIV, used strictly for boosting the levels of another PI,
hard to formulate with other antiretrovirals
■ Cobicistat
● No antiretroviral activity, can be coformulated with other antiretrovirals

● Select complications of ART

○ Immune reconstitution inflammatory syndrome (IRIS) = resistance
○ Lipodystrophy (redistribute fat, buffalo hump, mostly with PIs)
○ Diarrhea (mostly with PIs)
ART
● Recommended for all HIV infected patients
● Requires > 95% adherence for long term efficacy (missing 1 dose/month)
● Patients have to be willing and able and consent to start therapy
● Recommended ​initial ​regimens for most patients (all have 2 NRTI “nuc” backbone)
○ 2 NRTIs +
■ INSTI (-tegravir)
● Bictegravir
● Dolutegravir
● Elvitegravir
● Raltegravir

■
■ Or Boosted PI
● Recommended initial regimens for pregnant women
○ 2 NRTIs +
■ Abacavir/lamivudine
■ Tenofovir disoproxil fumarate/emtricitabine
■ Tenofovir disoproxil fumarate/lamivudine
○ INSTI
■ Raltegravir
○ Or Boosted PI
■ Atazanavir + ritonavir
■ Darunavir + ritonavir (BID only)
● Complete regimens (single tablet regimens)

○
 ○
○ Can switch to Juluca to avoid side effects or drug interactions, preserve susceptibility for future use
● Other combination products that ​must be used with additional ARTs​ to form a complete regimen

○
○ Not as popular as single tablet regimens
○ Truvada used as backbone and in PrEP

With food Without food

All PIs (except fosamprenavir suspension) Anything with efavirenz (Atripla, Symfi)
Atazanavir and Evataz Fosamprenavir suspension
Darunavir and Prezcobix Didanosine
Indinavir boosted Indinavir unboosted
Kaletra oral solution
Nelfinavir
Ritonavir
Saquinavir
Tipranavir
Genvoya
Stribild
Rilpivirine, Complera, Juluca, Odefsey
Etravirine (after meals)
Symtuza
Tenofovir powder
HIV Prevention strategies
● Treatment as prevention
○ Risk of HIV is directly proportional to viral load
○ Treatment of HIV infected patient with any complete and effective ART regimen
○ Goal is to decrease HIV viral load and thus reduce HIV transmission to another individual
● Pre-Exposure Prophylaxis (PrEP)
○ Given to HIV negative indiv to prevent HIV infection
○ Indicated for those at high risk for sexual exposure to HIV and IVDU
○ Emtricitabine/TDF (Truvada) 1 tab po daily
○ HIV Ab testing at baseline and every 3 months to ensure HIV negative status
● Nonoccupational Post-Exposure Prophylaxis (nPEP)
○ Exposure to HIV after sexual, IVDU or other nonoccupational event
○ Test exposed patient for HIV Ab at baseline, 4-6 weeks, 3 months, and 6 months
○ Begin any recommended 3 drug ART regimen within 72 hours of exposure and continue for 28 days
● Occupational Post-Exposure Prophylaxis (PEP)
○ Exposure of HCP to HIV = needlestick
○ Recommended only if source is HIV positive
○ Test exposed HCP for HIV at baseline, 4-6 weeks, 3 months, and 6 months
○ Begin Truvada + raltegravir (Isentress) within 72 hours and continue for 28 days

**Most need to be dispensed in original container, keep dessicant in bottle**

Preferred initial ART regimens are generally considered equally efficacious. Regimen based on side effects, pill burden,
and resistance markers
Side effects are additive when you combine drugs
Drug interactions are not unique to HIV