HIV: Chapter 26

what kind of virus is HIV and how does it replicate

• single-stranded RNA retrovirus that replicates in CD4 t helper cells

what is an indicator of HIV replication

increased viral load and decreased CD4 count

how is infection trasmitted

• blood, semen, vaginal or rectal secretions, breast milk

• unprotected vaginal or rectal sex and sharing drug needles

• mother-to-child or vertical transmission

screening for patients

• once for all patients 13-64

• annually for high risk patients: durg needles, high risk sexual behaviors, hx of hepatitis or TB

stages of infection

• acute infection presents as flu-like symptoms and then become asymptomatic after

• ~2 weeks post infection, HIV RNA and p24 antigens can be detected with an HIV-1/HIV-2 antigen/antibody test

  • positive results are differentiated/confirmed between HIV-1 and HIV-2 which can be detected about 4-12 weeks after contracting

diagnostic testing algorithm

• initial screening for p24 antigens and HIV-1/HIV-2 antibodies

• if negative = non reactive/ no infection

• if positive = reactive/infection

  • confirmatory testing is done to differentiate HIV-1 and HIV-2

    • if indeterminate or negative, HIV-1 nucleic acid test quantifies viral load →if undetectable then likely no HIV

    • if positive = HIV

OTC HIV testing

• OraQuick which detects HIV antibodies

• should be used >3 months from exposure due to lag in antibody production

• if positive, follow up with confirmatory lab test

• 2 lines = positive

HIV replication stages

1. binding/attachment to CD4 receptor and coreceptors CXCR4 or CCR5

2. fusion to CD4 cell membrane and release of contents (RNA, viral proteins, and enzymes)

3. reverse transcription of RNA to DNA and enter nucleus

4. integration of HIV DNA into host cell DNA

5. replication of HIV DNA into HIV RNA and long chain proteins

6. assembly of HIV RNA, proteins, and enzymes into an immature HIV

7. budding and maturation of immature HIV, protease breaks up long chain proteins creating mature virus

routine lab test and evaluation

• CD4 count

• HIV viral load (want undetectable with ART therapy)

• drug resistance testing

• CMP

• Hep B and C screening

• preg test

• HLA-B*5701 allele is considering ABC or tropism assay if considering maraviroc

initial tx for most tx-naive adults (brands and generics)

1 INSTI and 2 NRTIs:

• Biktarvy: Bictegravir, Emtricitabine, Tenofovir ala

• Triumeq: Dolutegravir, ABC, Lamivudine

• Dovato: Dolutegravir, lamivudine

• Tivicay: Dolutegravir + Truvada: Emtricitabine, TDF

• Tivicay: Dolutegravir + Descovy: Emtricitabine, TAF

what is included in the preferred intial treatment

1 INSTI + 2 NRTIs

a complete ART regimen contains

one base(PI, NNRTI, or INSTI) + 2 NRTIs to serve as a backbone

Nucleoside/Nucleotide Reverse Transcriptase inhibitors (NRTIs) brand and generics

• Zidovudine (Retrovir)

• Lamivudine (Epivir)

• Abacavir

• Tenofovir alafenamide

• Tenofovir disoproxil fumarate (Viread)

• Emtricitabine

• Zayn ❤ LATTEs

MOA of NRTIs

inhibit reverse transcriptase: HIV RNA to HIV DNA (stage 3)

what is given during labor and delivery to protect the baby

iv zidovudine (Retrovir)

all NRTIs have a warning for

lactic acidosis and hepatomegaly with steatosis (BOXED for zidovudine)

severe acute HBV exacerbation can occur if which medications are abruptly discontinued

emtricitabine, lamivudine (epivir), Tenofovir-containing products

warnings with Abacavir

• BOXED: hypersensitivity reaction

• screen for HLA-B*5701 allele and never rechallenge

• consider avoiding with CVD due to potential increase in MI

SE of emtricitabine

hyperpigmentation of palms of hands and soles of feet

tenofovir-containing products warnings

• nephrotoxicity (including Fanconi syndrome)

• decreased bone mineral density: consider calcium/vit D and DEXA scan

• monitor lipids if switching from TDF to TAF

warnings for zidovudine

neutropenia and anemia, myopathy, increased MCV is a sign of adherence

Integrase Strand Transfer Inhibitors (INSTIs) brand and generic names

• Bictegravir (in Biktarvy)

• Raltegravir (Isentress, Isentress HD)

• Elvitegravir (in Stribild and Genvoya)

• Dolutegravir (Tivicay)

• BRED

MOA of INSTIs

block integrase preventing insertion into host DNA (stage 4)

which drugs cannot be used if CrCl <70ml/min

do not start Stribild (Elvitegravir/cobicistat/emtricitabine/TDF)

which drugs cannot be started if CrCl<50ml/min

TDF containing

which drugs cannot be started if CrCl<30 ml/min

TAF containing

which INSTIs increase SCr with no effect on renal function

bictegravir, dolutegravir

which INSTIs increase CPK, myopathy, rhabdo, and cause HSR

raltegravir, dolutegravir

warning for dolutegravir

hepatotoxicity

preferred INSTI during pregnancy

dolutegravir

all INSTIs cause

insomnia, wt gain, rare risk of depression and suicidal ideation in pts with pre-existing psychiatric conditions

separating INSTIs and polyvalent cations

• take INSTIs 2 hours before or 6 hours after

• dolutegravir and bictegravir can be taken with oral calcium or iron if also taken with food

• avoid raltegravir with polyvalent cations if possible

Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) brand and generic names

• Efavirenz

• Rilpivirine

MOA of NNRTIs

inhibit reverse transcriptase (stage 3)

all NNRTIs have a risk of

hepatotoxicity and SJS/TEN (highest risk with nevirapine)

warnings with Efavirenz

depression, CNS (take ES with food), increase cholesterol and TGs

warnings with rilpivirine

depression, increase SCr, do not use if viral load >100,000 or CD4<200, take with meal and water (needs acid)

Drug interactions NNRTIs

• major 3A4 substrates

  • efavirenz 3a4 inducer

rilpivirine and acid supressants

• do not use PPIs

• take H2RAs 12 hours before or 4 hours after

• take antacids 2 hours before or 4 hours after

protease inhibitors brand and generic

Atazanavir (reyataz), Darunavir (Prezista)

protease inhibitors MOA

inhibit HIV protease enzyme in stage 7

all protease inhibitors need

to be taken with a booster (ritonavir, cobicistat), and food

warnings with all protease inhibitors

• metabolic syndrome: increased LDL/TG, BG, body fat, CVD risk (lower with atazanavir and darunavir)

• hepatic dysfunction

• HSR

atazanavir warnings

• hyperbilirubinemia (bananavir)

• take atazanavir 2 hours before or 1 hour after antacids

• take atazanavir 2 hours before or 10 hours after H2RAs

• take atazanavir 12 hours after PPIs

which protease inhibitors require caution with sulfa allergy

• darunavir, fosamprenavir, tipranavir

Lopinavir/Ritonavir (Kaletra) warning

contains 42% alcohol, avoid with flagyl

tipranavir warning

intercranial hemorrhage

drug interactions with Protease inhibitors

major 3A4 substrates

what are the boosters names

ritonavir (norvir), cobicistat (Tybost)

how does ritonavir boost ART

3A4 inhibitor

drug interactions with boosters

3A4 inhibitors, and CD6 and pgp

CCR5 antagonist drug, MOA, and special considerations

• Maraviroc

• blocks binding at CCR5 co-receptor in stage 1

• tropism assay - can only bind to CCR5

• BOXED hepatotoxicity

attachment inhibitor

Fostemsavir, stage 1

post attachment inhibitor

Ibalizumab-uiyk in stage 1

fusion inhibitor

Enfuviritide in stage 2, SC self injection

what drugs are in Biktarvy

Bictegravir, emtricitabine, TAF

what drugs are in Triumeq

Dolutegravir, ABC, lamivudine ( HLA 5701 test)

what drugs are in dovato

Dolutegravir, lamivudine

what drugs are in Stribild

Elvitegravir, cobicistat, Emtricitabine, TDF (take with food)

what drugs are in Genvoya

Elvitegravir, cobicistat, emtricitabine, TAF (take with food)

what drugs are in complera

Rilpivirine, emtricitabine, TDF (take with food)

what drugs are in Odefsey

Rilpivirine, emtricitabine, TAF

what drugs are in Epzicom

ABC, lamivudine

what drugs are in Truvada

Emtricitabine, TDF

what drugs are in Descovy

emtricitabine, TAF

when is AIDS disgnosed

CD4 <200 or AIDs-defining condition

what are the AIDs-defining conditions

• OIs

• Kaposi’s sarcoma, several cancers

• HIV wasting syndrome (give dronabinol or megestrol)

what is immune reconstitution inflammatory syndrome (IRIS)

when ART is started, an underlying conditions activates - continue ART and treat underlying condition

can you breastfeed on ART therapy

no - possible HIV transmission

PrEP options

• Truvada (CrCl >60) or Descovy (Crcl >30, males)

• or

• ER IM injection of Cabotegravir (Apretude) monthly for 2 doses then every 2 months

before starting PrEP

• confirm HIV negative

• screen for Hep B and STIs

PrEP follow up visits

• test for HIV

• Truvada, Descovy: every 90 days

• Apretude: 1 month after first injection, then every 2 months

PEP tx

• WITHIN 72 HOURS for 28 day tx

• Truvada (CrCl >60) or

• Dolutegravir (Tivicay)

• Raltegravir (Isentress)