HIVCARDSrvngszn Flashcards

Kaposi
sarcoma:
caused by
human
herpesvirus 8
(HHV8)

• Medical history and physical exam
• Laboratory evaluation

– CD4 T-cell count
– Plasma HIV RNA (viral load)
– CBC+ differential, chemistry, transaminase, BUN, Scr, urinalysis, serology for
hepatitis: A, B, and C
– Fasting glucose, lipids
– Genotype resistance testing (HIV RNA <500-1,000 copies/mL, may not be
successful)
– HLA B*5701 testing if initiating abacavir
– Viral tropism assay before initiating CCR5 antagonists

given to only those who are immunocompetent

give PNEU-C-13 first followed by Pneu-P atleast 8 wks later.

High dose monovalent hep B vaccine e.g Recombivax

• Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs)
• Integrase strand transfer inhibitors (INSTIs)
• Protease inhibitors (PIs)
• Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
• Pharmacokinetic enhancers
• CCR5 antagonists

-once daily

-no food effect

-TAF/ FTC, TDF/FTC, and ABC/3TC: available as combination products

better virologic response vs ABC/3TC for viral load ≥100,000 (exception,
ABC/3TC + DTG)

ABC/3TC= Abacavir (ABC)/Lamivudine (3TC)

Increased lipids, nausea,
vomiting, hepatic effects, BMD
loss, lactic acidosis, lipoatrophy

Hypersensitivity (multi-
organ involvement), ?MI

Hyperpigmentation

TAF

Renal impairment (Fanconi
syndrome), decreased BMD

Bictegravir(BIC)

Dolutegravir(DTG)

Elvitegravir(EVG)

Raltegravir(RAL)

Cabotegravir

Nausea (may be less than DTG), diarrhea,
headache, insomnia, abnormal dreams

once daily (DTG BID if DI
or resistance)

BID or daily
(HD formulation)

no food
requirements.

take with food

available as BIC, DTG, and EVG

Cabotegravir

Nausea, vomiting, diarrhea, headache,
insomnia, dizziness
Rare: muscle toxicity, depression and
suicidal ideation (usually in patients with
pre-existing psychiatric conditions)

Nausea, diarrhea, headache, insomnia, ↑
lipids, depression and suicidal ideation

Muscle toxicity, nausea, headache, severe
skin reactions, insomnia, depression and
suicidal ideation

Cabotegravir

BIC

DTG

EFV or ATV/r regimens

RAL-*Superiority thought to be due to
fewer discontinuations

Cabotegravir

All can be
administered once
daily (DRV may be
admin BID too)
Administer with
food

DRV/C, ATV/C:

Metabolic abnormalities
including:

-dyslipidemia
-insulin resistance, and
-?MI/stroke

-hepatitis

-skin reactions
-Gastrointestinal ADRs

DRV/r

Generally not as well
tolerated as INSTI
regimens

Lipoatrophy, increased
lipids, rash

Nausea, dizziness,
abnormal dreams

As effective as EFV
and DRV based
regimens, regardless
of baseline viral load

EFV: Psychiatric effects
(depression, insomnia, vivid
dreams), QTc prolongation

Potency persists
regardless of baseline
RNA

RPV: QTc prolongation, fewer CNS ADRs vs EFV.

Higher rates of failure
in patients with HIV
RNA > 100,000
copies/mL

Doravirine (DOR)

Efavirenz (EFV) once daily dosing, taken without
food, ideally at night

DOR, EFV, RPV are available as components
of a one tablet once daily regimen

Doravirine (DOR)

Efavirenz (EFV)

Rilpivirine (RPV)

Used as a PK booster for PIs.
As a PK booster, low-dose
used. Avoid use as a sole PI
because of adverse effects.

Dosing frequency
depends on PI it is
used with.

No antiviral activity. CYP3A
inhibitor used to boost ARVs
(ex: EVG, DRV).

once daily dosing

take with food

Part of combination
products (ex:
Prezcobix®, Stribild®
and Genvoya®)

GI upset, diarrhea, liver enzyme
elevations, hyperlipidemia.
All PIs may be associated with
PR interval prolongation.

Inhibits creatinine secretion by
proximal tubule. Not due to
actual change in gfr.

Less long term experience in naïve patients (not first line)
Requires viral tropism before initiation of therapy.

Twice daily dosing, taken without regard to food

Hepatotoxicity, cough, fever, rash, abdominal pain
Fewer AEs than efavirenz

CYP3A4 substrate (dosing depends on other ARVs),150 mg bid if also taking CYP3A inhibitors (ex: PIs)

1.Patient Characteristics

• Pre-treatment viral load and CD4
• HLA-B*5701 status
• Resistance (genotype) results
• Poor adherence to ARV or inconsistent engagement

2. Comorbidities

• Renal disease
• Osteoporosis
• Psychiatric illness, neurologic
disease
• Methadone maintenance
• CVD, hyperlipidemia
• Co-infection (ex: Hepatitis B, TB)

3. Regimen

• Regimen’s genetic barrier to resistance
• ADRs
• Drug interactions with other medications
• Convenience (pill-burden, dosing frequency, food requirements)
• Cost

Avoid ABC regimens

If HIV RNA > 100,000 copies/mL

Avoid agents listed for HIV RNA > 100,000 copies/mL AND
• DTG/3TC

(DRV/r or DRV/C) or BIC or DTG-based regimens

-High genetic barrier to resistance

Avoid NNRTI-based regimens and and DTG/3TC. Avoid ABC.
Recommended regimens:
• BIC/TAF/FTC
• (DTG) plus (TAF or TDF) plus (3TC or FTC)
• (DRV/r or DRV/C) plus (TAF or TDF) plus (3TC or FTC)

True

More likely to have NNRTI
resistance than PI or INSTI
resistance

Avoid:
• RPV
• DRV/r plus RAL

-higher rate failure

- EVG/c/TDF/FTC
- ATV/c with TDF
- DRV/c with TDF

TDF associated with renal tubulopathy. Cobistat (c) inhibits tubular creatinine secretion.

- TDF, ATV
- Use ABC/3TC
- Use TAF (if CrCl >30 mL/min) or if patient is on
chronic hemodialysis (only studied with
EVG/c/TAF/FTC)

TDF- Use ABC or TAF
Greater decrease in BMD

TAF has less impact on BMD toxicity and renal function than TDF

Consider avoiding EFV and RPV based regimens

and closely monitor INSTI-based regimens

Avoid EFV- may confound monitoring
Favor DTG- or DRV-based regimens-better CNS penetration

Avoid EFV (or increase in methadone may be
needed) + always check for DI with ARVs

-Decreased methadone concentrations,
increased risk of withdrawal

Consider avoiding ABC and PI (esp. lopinavir) regimens
Favor BIC, DOR, DTG, RAL or RPV

- If PI is needed ATV may have an advantage
over DRV

Favor BIC, DOR, DTG, RAL, and RPV (fewer lipid effects)

-Risk of increased lipids with:
- PI/r or C, EFV, EVG/c

Use (TDF or TAF) with (FTC or 3TC) where possible

- EFV-based regimens have fewest DIs (use without dose adjustment)
- If RAL is used, increase RAL dose to 800 mg BID(do not use once-daily RAL)
- DTG 50 mg BID dose only in patients without selected INSTI mutations
- PI/c or PI/r, BIC, EVG, DOR, RPV, or TAF are NOT recommended

PI-based regimen, use rifabutin in place of rifampin
TAF and BIC are not recommended with any rifamycin-containing regimen

- DRV/ r or C
- EVG/c/TDF/FTC
- EVG/c/TAF/FTC
- RPV/TDF/FTC (meal)
- RPV/TAF/FTC (meal)
- RPV/DTG (meal)
- RPV (meal)

EFV- increased CNS ADRs with EFV)

– Decreased AIDS related morbidity
– Improved survival
– Decreased transmission

– Should be started on at least 2 or 3 ARV agents from 2 or more classes

usually 2-3 or 4 different medications

use combo tabs to increase adherence

example of triple therapy

Dual therapy:
• 1 INSTI plus 1 NRTI
• 1 INSTI plus 1 NNRTI

-reduced cost

-less toxicity

-fewer DIs

-incrzd adherence

-increased preserve drug options

incr virological failure

drug resistance

viral escape at compartments

1. DTG/3TC (Dovato)– Option for treatment naive
2. DTG/RPV (Juluca):– Option for treatment experienced, VL suppressed
3. Cabotegravir/RPV (Cabenuva)– Option for treatment experienced, VL suppressed

DTG/3TC (Dovato®

DTG/RPV (Juluca®)

Cabotegravir/RPV (Cabenuva)

one Integrase Strand Transfer Inhibitor (INSTI) plus 2 Nucleoside Reverse Transcriptase Inhibitors (NRTIs)

1. Bictegravir (BIC), tenofovir alafenamide hemifumarate (TAF), emtricitabine (FTC) (AI)

2. Dolutegravir (DTG), abacavir (ABC), lamivudine (3TC) for HLA-B*5701 negative pts and without chronic hepatitis B virus (HBV) coinfection (AI

DTG, [tenofovir disoproxil fumarate (TDF) or TAF], [FTC or 3TC] (AI)

Dolutegravir DTG, 3TC (AI) (Lamivudine)
– Except for individuals with HIV RNA >500,000 copies/mL, HBV coinfection, or before HIV genotypic resistance reverse transcriptase results or HBV testing are available

2 Nucleoside Reverse Transcriptase Inhibitors (NRTIs) plus a third agent
from a different class;

– Integrase Strand Transfer Inhibitor (INSTI)
– Protease Inhibitor (PI) boosted with ritonavir (r) or cobistat (C)
– Non-nucleoside reverse transcriptase inhibitor (NNRTI)

when ABC, TAF, and TDF cannot be used

When ABC, TAF, and TDF are not optimal
• DTG, 3TC (AI) Except for individuals with HIV RNA >500,000 copies/mL, HBV coinfection, or before HIV genotypic resistance
reverse transcriptase results or HBV testing are available
• DRV/r, RAL (administered BID, RNA <100,000 copies/mL and CD4 >200, CI)
• DRV/r once daily, 3TC (CI)

INSTI- based regimen

PI-based (DRV preferred over ATV)
• Darunavir (DRV)/r or C, TDF or TAF, FTC or 3TC (AI )
• DRV/r or C, ABC, 3TC (HLA-B*5701 negative, BII)

NNRTI-based regimen

• Efficacy: Evaluate any presenting signs/symptoms
– Assess adherence
• Toxicity: Tailor to regimen. Monitor for all common and
serious ADRs.
– Follow up shortly after initiating therapy
– At each follow up visit

• Every 3-6 months
– First 2 years of ART
– Viremia on ART
– CD4 <300 cells/mm3
• If ART > 2 years + consistently suppressed VL
– Q 12 months for CD4 300-500 cells/mm3
– Optional for CD4 >500 cells/mm3

• ART intensification by adding ARVs to a suppressive regimen
does not consistently improve CD4 cell recovery or reduce
immune activation and is not recommended (AI)
• In individuals with viral suppression, switching ARV drug
classes does not consistently improve CD4 cell recovery or
reduce immune activation and is not recommended (BIII)

• Complete drug-resistance testing while on failing regimen or within 4
weeks
• Choose a new regimen with at least 2, ideally 3 fully active agents
• Do not add a single ARV to a failing regimen
• Do not discontinue or interrupt ARVs in setting of virologic failure due to
risk of rapid increase in viral load and decrease in CD4 counts

• Resistance mutations confer reduced susceptibility of ART to the virus
– Single mutation may confer complete/near complete resistance to a drug, or partial susceptibility may remain
• Cross-resistance occurs within each drug class, but not between drug classes
– Degree of cross-resistance within a class is variable

• Genotype provides list of mutations and interpretation
– To identify agents that will have reduced susceptibility
• Must do testing while patient is taking the “failing” regimen to catch
mutations

– LB is at risk of complications of HIV and ARV failure due to a drug
interaction between calcium and dolutegravir
– LB is at risk of cumulative renal toxicity secondary to a drug
interaction between TDF and ibuprofen

-INSTIs-Minerals(MG, Fe, Ca) decrz drug levels space DTG 2hr before minls

-DTG-incrz metformin levels 1g max for co-admin-monitor GI UPSET, adjust

-PIs-incrz level steroids-avoid esp systemic 1s (flutic & budesonide) use beclo

-TDF-dcrz TDF elimn (renal toxic)-alternatives to NSAIDS Shud be used

-ARVs requiring gastric acid- dec levels of RPV and ATV/r-PPI CI wit RPV RPV: Antacids: 2h before or 4h after RPV.

H2RAs: separated at least 12h before or 4h after RPV. PPIs: CI.

ATV: Antacids: 1h before or 2h after ATV. H2RAs: ATV 300/100 mg daily with H2RA simultaneously or 10h after H2RA. PPI: not recommended, increase ATV to 400/100mg and do not exceed omeprazole 20 mg.

– Reduce transmission from mother to baby (vertical transmission) during pregnancy/birth

– Reduce the risk of HIV infection from a single exposure to HIV

– Reduce the risk of HIV infection from multiple, ongoing exposures to
HIV

Initiate ART in all pregnant women regardless of viral load/CD4 count
• Combination of antepartum, intrapartum, and infant ARV prophylaxis
are recommended

– Initiate 2 NRTIs (ABC/3TC, TDF/FTC, or TDF/3TC) and
• Integrase inhibitor (RAL, used BID or DTG)
– DTG: if trying to conceive- consider avoiding if initiating ART before 6
weeks gestation
• Ritonavir-boosted PI (ATV/r or DRV/r used BID in pregnancy)

– Chest feeding not recommended
• Suppressive maternal ART significantly reduces, but does not eliminate, risk of transmitting HIV through lactation

– Consult HIV specialist re: infant prophylaxis
• 4 weeks of ZDV administered within 6-12 hours after birth if mother was on
ARV and VL<50 copies/mL
• Presumptive HIV therapy using either ZDV, 3TC, and NVP (treatment dose) or
ZDV, 3TC, and RAL administered from birth up to 6 weeks if VL >50 copies/mL
or presumed newborn HIV exposure

1. Occupational exposure
2. Non-occupational exposure
• When indicated, PEP is taken daily for 28 days for both
occupational and non-occupational exposures

– E.g. sexual assault, “condom malfunction”
– Evidence based on animal studies, vertical transmission, occupational PEP and
some observational data in non-occupational PEP
– Timing of exposure is important (< 72 hr)
– Same regimens recommended as for PEP
– Consider HIV status of source patient
• Known HIV+: Consider PEP if < 72 hr
• Unknown HIV status: Determine if source is available for testing but do not
delay PEP while awaiting results; consider demographics of population

– Type of exposure (fluid type, severity, amount)à Exposure code
• Percutaneous exposure to HIV infected blood – average risk of transmission 0.3%
– Status of exposed source - Status code
• Assess primary prevention strategies to prevent future exposures

Tenofovir disoproxil fumarate (TDF)/ emtricitabine (FTC) 300/200 mg daily
PLUS EITHER
Raltegravir (RAL) 400 mg twice daily
OR
Dolutegravir (DTG) 50 mg daily
OR
Darunavir (DRV) 800 mg daily + Ritonavir (r) 100 mg daily
Initiate PEP as soon as possible, within 72 hours of exposure,
and continue x 4 weeks (28 days)

• Truvada (TDF 300 mg + FTC 200 mg) 1 PO once daily(am)PLUS
• Raltegravir 400 mg PO q12h

Insomnia, nausea(Antiemetics, take with food), fatigue, headache, increase in CK, myopathy and
severe skin and hypersensitivity reactions have been reported.
Drug interactions (rare, space minerals)

Asthenia, headache, diarrhea(loperamide or diphenoxylate), nausea(take with food), vomiting
Nephrotoxicity; should not be administered to individuals with
acute or chronic kidney injury or those with eGFR <60
If the PEP recipient has chronic hepatitis B, withdrawal of this drug
may cause an acute hepatitis exacerbation
Drug interactions (rare, avoid NSAIDs)

Baseline (prior to starting PEP):
• Baseline HIV testing
• Beta HCG if pregnancy is suspected
• CBC, creatinine, ALT

In 72 hours:
• Re-evaluate exposed person if waiting for HIV status of source
• If a source person HIV negative, PEP should be discontinued

Efficacy:

Seroconversion illness (i.e., febrile illness)
– HIV tests 1 month, 3 months, and 6 months* to determine whether infection has
occurred. Also test at 12 months if HCV conversion occurs.
• * HIV testing may be concluded 4 months after exposure if using 4th
generation combination HIVp24 antigen - HIV antibody test
• Toxicity:
– Laboratory monitoring for toxicity: CBC, creatinine, and ALT at baseline and 2 weeks after starting PEP
– Monitor for side effects at 72 hours and weekly to ensure completion of PEP

HIV-negative individual taking antiretroviral therapy (ART) to reduce their risk of becoming infected
• Indicated in those with ongoing high risk HIV exposure
• Taken on a regular basis, starting before being exposed to HIV and continuing afterwards
• Adherence is crucial for PrEP to work
• Can reduce the risk of HIV infection by over 90% if taken every day

Truvada (TDF, FTC)
– PrEP indication approved Feb 2016
– Administration: 1 tab po daily
– High cost: ~$750/ 3 months (generic TDF/FTC)
– Public coverage varies across the country
• Covered by NS pharmacare as of July 2018
– Some private health insurance plans cover
• Co-pays
• Yearly limits

Truvada (TDF, FTC) “on demand”
– 2 tablets of Truvada (TDF/FTC) 2–24 hours before first sexual intercourse,
followed by 1 pill daily until 48 hours after the last sexual activity

– On-demand PrEP is an off-label use of Truvada in Canada and should be viewed as an alternative recommendation due to the lower volume of studies to support its use

– A pill once a month
– Annual implant
– Injections once every 2-6 months
• Cabotegravir
– 1 oral cabotegravir tablet 1 time a day for 1 month (at least 28 days) to assess
cabotegravir tolerance (optional)
– IM gluteal injection once a month for the first 2 months, then once every 2 months

– Assessment of HIV status (including acute HIV infection signs/symptoms)
– Assessment of side effects and advice on how to manage them
• Test creatinine at 3 months and then every 6 months if normal
– Assessment of medication adherence and counseling to support adherence
– Assessment of STI symptoms, HIV risk behavior and counseling support for
risk-reduction practices

• Test for STIs every 6 months or more frequent if symptomatic
• Test for HCV every 6-12 months in (unless already known to be positive),
particularly in those who inject substances and in MSM

– Infection caused by normally non-pathogenic organisms in an
immunocompromised patient.

Patients do not die of AIDS; they die of AIDS complications
– (E.g.: OI, malignancy, ARV toxicity)
• Decreasing incidence of AIDS and OI’s since availability and widespread use of ART
• Risk of OI increases as CD4 count decreases
• Antibiotic prophylaxis reduces the incidence and improves survival associated with
many OIs

-Pneumococcus (Streptococcus pneumoniae)

-Mycobacterium avium complex (MAC),
-Mycobacterium tuberculosis (TB)

-Candida

-Pneumocystis jirovecii pneumonia PJP (previously known as PCP),
-Cryptosporidiosis

Toxoplasma gondii

-Herpes simplex virus (HSV)

-Varicella zoster virus (VZV)

-Cytomegalovirus (CMV)
-Hepatitis A, B

if <200 or < 14% Start prophylaxis for Pneumocystis jirovecii (PJP) pneumonia
<100 If positive serology IgG, start toxoplasmosis prophylaxis if not on
sulfamethoxazole/trimethoprim for PJP prophylaxis
<50 Consider Mycobacterium avium complex (MAC) prophylaxis after ruling out active MAC infection

CD4 < 200 cells/mm3
• CD4 cell percentage < 14%
• History of PCP
• Oral thrush
• Recurrent bacterial pneumonia
• Unintentional weight loss
• Higher HIV RNA levels

First Line:
– Sulfamethoxazole/trimethoprim (TMP-SMX) 1 DS tablet daily or 3 X/week
• Alternatives:
– TMP-SMX-SS 1 tab po q24h
– Pentamidine 300 mg in 6 ml sterile water by aerosol q 4 weeks, OR
– (Dapsone 200 mg po + Pyrimethamine 75 mg po + Folinic acid 25 mg po) once a week (also protection against Toxo) OR
– Atovaquone 1500 mg po q24h with food
• Continue until: CD4 > 200 for > 3 months (or CD4 100-200 cells/mm3 for > 3 months and HIV RNA <400 copies/mL)

Humans are infected by:
– Ingestion of ovocysts in cat feces(under cooked meat)

Most common presentation is focal encephalitis with headache, confusion, motor weakness, and fever

Occurs primarily in those who are sero-positive (11% population in the US)

First line:
– TMP-SMX (DS) po once daily
• Alternatives:
– TMP-SMX (SS) po once daily
– Dapsone 50 mg po q24h + Pyrimethamine 50 mg po q/week + Folinic acid 25 mg po q/week; OR
– Once weekly: Dapsone 200 mg po + Pyrimethamine 75 mg po + Folinic acid 25 mg po; OR
– Atovaquone 1500 mg po q24h
• Continue until: CD4 >200 for 3 months

First line:
– Azithromycin 1250 mg po once weekly
– Clarithromycin 500 mg po BID
• Continue until: CD4 > 100 for > 3 months

• Therapy selection
• Medication acquisition/payment
• Adherence to therapy
• Drug/herbal/natural health product/supplement interactions
• Adverse drug reaction management
• Drug information