AntiRetroviral Therapy Basics E Duke David Spachs National

Anti-Retroviral Therapy Basics E Duke

David Spach’s National HIV Curriculum https: //www. hiv. uw. edu/page/treatment/drugs

HIV Virion

HIV Virion Integrase ss. RNA Reverse Transcriptase

CD 4 T Lymphocyte

HIV Infection HIV CCR 5 co-receptor CD 4 receptor Nucleus Human CD 4+ T cell

HIV Infection CCR 5 co-receptor CD 4 receptor Nucleus Human CD 4+ T cell

HIV Infection Nucleus Human CD 4+ T cell

HIV Infection Nucleus Human CD 4+ T cel

HIV Infection proviral dna Reverse transcriptase (RT) viral rna Nucleus Human CD 4+ T cel

HIV Infection proviral dna viral rna Nucleus Human CD 4+ T cell https: //www. genome. gov/26524120

proviral dna Integrase viral rna Nucleus Human CD 4+ T cell https: //www. genome. gov/26524120

proviral dna Integrase 46 chromosomes viral rna Nucleus Human CD 4+ T cell https: //www. genome. gov/26524120

HIV Infection proviral dna 46 chromosomes viral rna Nucleus Human CD 4+ T cell https: //www. genome. gov/26524120

HIV Infection proviral dna 46 chromosomes viral rna Nucleus Human CD 4+ T cell https: //www. genome. gov/26524120

HIV Replication/Maturation/ Budding

SUMMARY OF HIVMECHANISMS INFECTION MECHANISMS ART Barre-Sinoussi et al. Nat Rev Micro, 2013.

FUSION/ENTRY INHIBITORS MARAVIROC = MVC Barre-Sinoussi et al. Nat Rev Micro, 2013.

HIV Infection TROFILE ASSAY = “MIXED” OR “WILD-TYPE” CXCR 4 co-receptor HIV CCR 5 co-receptor CD 4 receptor Nucleus Human CD 4+ T cell

FUSION/ENTRY INHIBITORS ENFUVIRTIDE = FUZEON = T-20 MARAVIROC = MVC Barre-Sinoussi et al. Nat Rev Micro, 2013.

FUSION/ENTRY INHIBITORS Fusion Inhibitor = ENFUVIRTIDE Entry Inhibitor = MARAVIROC (MUST HAVE CCR 5 -TROPIC VIRUS) TROFILE ASSAY

ART MECHANISMS REVERSE TRANSCRIPTASE INHIBITORS RT proviral dna viral rna Nucleus Human CD 4+ T cell https: //www. genome. gov/26524120

INTEGRASE INHIBITORS INTEGRASE Nucleus Human CD 4+ T cell https: //www. genome. gov/26524120

PROTEASE INHIBITORS PROTEASE

SPECIFIC DRUG NAMES AND THEIR MECHANISMS

REVERSE TRANSCRIPTASE INHIBITORS RT proviral dna viral rna Nucleus Human CD 4+ T cell https: //www. genome. gov/26524120

REVERSE TRANSCRIPTASE INHIBITORS NUCLEOSIDE RTIs (NRTIs) = NUKES NON-NUCLEOSIDE RTIs (NNRTIs) = non-NUKES

BUILDING A 3 -DRUG REGIMEN INSTI NNRTI PI 2 NUKE BACKBONE + 1 DRUG FROM ANOTHER CLASS

REVERSE TRANSCRIPTASE INHIBITORS NUCLEOSIDE RTIs (NRTIs) = NUKES Tenofovir Emtricitabine Abacavir Lamivudine Zidovudine Didanosine Stavudine NON-NUCLEOSIDE RTIs (NNRTIs) = non-NUKES

BUILDING A 3 -DRUG REGIMEN 2 NUKE BACKBONE

REVERSE TRANSCRIPTASE INHIBITORS NUCLEOSIDE RTIs (NRTIs) = NUKES Tenofovir Emtricitabine Abacavir Zidovudine Didanosine Stavudine Lamivudine = NON-NUCLEOSIDE RTIs (NNRTIs) = non-NUKES TRUVADA

REVERSE TRANSCRIPTASE INHIBITORS NUCLEOSIDE RTIs (NRTIs) = NUKES NON-NUCLEOSIDE RTIs (NNRTIs) = non-NUKES Tenofovir Emtricitabine = TRUVADA Abacavir Lamivudine = EPZICOM Zidovudine Didanosine Stavudine

REVERSE TRANSCRIPTASE INHIBITORS NUCLEOSIDE RTIs (NRTIs) = NUKES NON-NUCLEOSIDE RTIs (NNRTIs) = non-NUKES Tenofovir Emtricitabine = TRUVADA Abacavir Lamivudine = EPZICOM Zidovudine Lamivudine = COMBIVIR Didanosine Stavudine

REVERSE TRANSCRIPTASE INHIBITORS NUCLEOSIDE RTIs (NRTIs) = NUKES NON-NUCLEOSIDE RTIs (NNRTIs) = non-NUKES Tenofovir Emtricitabine = TRUVADA Abacavir Lamivudine = EPZICOM Zidovudine Lamivudine = COMBIVIR = CIMDUO Didanosine Stavudine TEMIXYS

REVERSE TRANSCRIPTASE INHIBITORS NUCLEOSIDE RTIs (NRTIs) = NUKES NON-NUCLEOSIDE RTIs (NNRTIs) = non-NUKES Abacavir Lamivudine = EPZICOM Zidovudine Lamivudine = COMBIVIR = TRIZIVIR

QUIZ QUESTION 1

QUIZ QUESTION 2

REVERSE TRANSCRIPTASE INHIBITORS NUCLEOSIDE RTIs (NRTIs) = NUKES NON-NUCLEOSIDE RTIs (NNRTIs) = non-NUKES Efavirenz Rilpivirine Etravirine Nevirapine Doravirine -VIR-A-SOMETHING -VIR in the MIDDLE

REVERSE TRANSCRIPTASE INHIBITORS NUCLEOSIDE RTIs (NRTIs) = NUKES NON-NUCLEOSIDE RTIs (NNRTIs) = non-NUKES Tenofovir Emtricitabine Efavirenz Abacavir Lamivudine Rilpivirine Zidovudine Etravirine Didanosine Nevirapine Stavudine Doravirine No Naming Pattern -VIR-SOMETHING -VIR in the MIDDLE

BUILDING A 3 -DRUG REGIMEN INSTI NNRTI PI 2 NUKE BACKBONE + 1 DRUG FROM ANOTHER CLASS

REVERSE TRANSCRIPTASE INHIBITORS NUCLEOSIDE RTIs (NRTIs) = NUKES Tenofovir Emtricitabine = TRUVADA + NON-NUCLEOSIDE RTIs (NNRTIs) = non-NUKES Efavirenz = Atripla

REVERSE TRANSCRIPTASE INHIBITORS NUCLEOSIDE RTIs (NRTIs) = NUKES NON-NUCLEOSIDE RTIs (NNRTIs) = non-NUKES Tenofovir Emtricitabine = TRUVADA + Efavirenz = Atripla + Rilpivirine = Complera

REVERSE TRANSCRIPTASE INHIBITORS NUCLEOSIDE RTIs (NRTIs) = NUKES NON-NUCLEOSIDE RTIs (NNRTIs) = non-NUKES Tenofovir Emtricitabine = TRUVADA + Efavirenz = Atripla + Rilpivirine = Complera Tenofovir Lamivudine = CIMDUO + Doravirine = Tenofovir Lamivudine = CIMDUO + Efavir Delstrigo = Symfi Lo

QUIZ QUESTION 3

PROTEASE INHIBITORS: Boosters Darunavir Atazanavir Cobicistat Lopinavir Indinavir Fosamprenavir Tipranavir Saquinavir Nelfinavir Ritonavir

PROTEASE INHIBITORS Darunavir Atazanavir Lopinavir Indinavir Fosamprenavir Tipranavir Saquinavir Nelfinavir Ritonavir -NAVIR

PROTEASE INHIBITORS: Boosters Darunavir/r Ritonavir Atazanavir/r Cobicistat Lopinavir/r Indinavir/r Fosamprenavir/r Tipranavir/r Saquinavir/r Nelfinavir/r

PROTEASE INHIBITORS: Boosters Darunavir Ritonavir Atazanavir Cobicistat Lopinavir Indinavir Fosamprenavir Tipranavir Saquinavir Nelfinavir + = Kaletra

PROTEASE INHIBITORS: Boosters Ritonavir Cobicistat Prezista Darunavir + Atazanavir + Cobicistat = Prezcobix

BUILDING A 3 -DRUG REGIMEN INSTI NNRTI PI 2 NUKE BACKBONE + 1 DRUG FROM ANOTHER CLASS

INTEGRASE Strand Transfer INHIBITORS “INSTIs” Raltegravir -GRAVIR Elvitegravir Dolutegravir Bictegravir

QUIZ QUESTION 4

QUIZ QUESTION 5

QUIZ QUESTION 6

INTEGRASE INHIBITORS Raltegravir Elvitegravir + + TRUVADA = STRIBILD Dolutegravir + EPZICOM = TRIUMEQ Bictegravir Cobicistat

COMBO TIME NRTIs NNRTIs IIs PIs Booster TDF Efavirenz ELV/cobi Darunavir Cobicistat TAF Rilpivirine Dolutegravir Abacavir Atazanavir Lopinavir Emtricitabine Ritonavir Lamivudine Zidovudine TRUVADA

COMBO TIME NRTIs NNRTIs IIs PIs Booster Tenofovir Efavirenz ELV/cobi Darunavir Cobicistat Abacavir Rilpivirine Dolutegravir Atazanavir Emtricitabine Lopinavir Lamivudine Ritonavir Zidovudine ATRIPLA

COMBO TIME NRTIs NNRTIs IIs PIs Booster Tenofovir Efavirenz ELV/cobi Darunavir Cobicistat Abacavir Rilpivirine Dolutegravir Atazanavir Emtricitabine Lopinavir Lamivudine Ritonavir Zidovudine COMPLERA

COMBO TIME NRTIs NNRTIs IIs PIs Booster Tenofovir Efavirenz ELV/cobi Darunavir Cobicistat Abacavir Rilpivirine Dolutegravir Emtricitabine Atazanavir Bictegravir Lopinavir Lamivudine Ritonavir Zidovudine STRIBILD

COMBO TIME NRTIs NNRTIs IIs PIs Booster Tenofovir Efavirenz ELV/cobi Darunavir Cobicistat Abacavir Rilpivirine Dolutegravir Emtricitabine Atazanavir Bictegravir Lopinavir Lamivudine Ritonavir Zidovudine TRIUMEQ

3 LETTER ABBREVIATIONS: NRTIs ZIDOVUDINE AZT LAMIVUDINE 3 TC EMTRICITABINE FTC TENOFOVIR TDF ABACAVIR ABC DIDANOSINE dd. I STAVUDINE d 4 T

3 LETTER ABBREVIATIONS: NRTIs and NNRTIs ZIDOVUDINE AZT EFAVIRENZ EFV LAMIVUDINE 3 TC RILPIVIRINE RPV EMTRICITABINE FTC ETRAVIRINE ETV TENOFOVIR TDF NEVIRAPINE NVP ABACAVIR ABC DORAVIRINE DOR DIDANOSINE dd. I STAVUDINE d 4 T

3 -LETTER ABBREVIATIONS: PIs AND IIs PROTEASE INHIBITORS INTEGRASE INHIBITORS DARUNAVIR DRV RALTEGRAVIR RAL ATAZANAVIR ATV ELVITEGRAVIR EVG DOLUTEGRAVIR DTG BICTEGRAVIR BIC BRAND NAME TIVICAY

QUIZ QUESTION 7

Let’s talk about TAF TDF = Tenofovir disoproxil fumarate TAF = Tenofovir alafenamide

TAF COMBOS Tenofovir Emtricitabine = TRUVADA TAF Emtricitabine = DESCOVY TRUF

TAF COMBOS TRUVADA (TRU) + Rilpivirine = COMPLERA DESCOVY (TRUF) + Rilpivirine = ODEFSEY TRUVADA (TRU) = STRIBILD + ELV/cobi DESCOVY (TRUF) + ELV/cobi = GENVOYA DESCOVY (TRUF) + BICTEGRAVIR = BIKTARVY DESCOVY (TRUF) + DARUNAVIR/COBI = SYMTUZA

TAF COMBO TIME NRTIs NNRTIs IIs PIs Booster TDF Efavirenz ELV/cobi Darunavir Cobicistat TAF Rilpivirine Dolutegravir Abacavir Atazanavir Bictegravir Lopinavir Emtricitabine Ritonavir Lamivudine Zidovudine DESCOVY

TAF COMBO TIME NRTIs TDF NNRTIs IIs PIs Booster Efavirenz ELV/cobi Darunavir Cobicistat Rilpivirine Dolutegravir Atazanavir Bictegravir Abacavir Lopinavir Ritonavir Lamivudine Zidovudine TAF Emtricitabine DESCOVY BIKTARVY

TAF COMBO TIME NRTIs TDF NNRTIs IIs PIs Booster Efavirenz ELV/cobi Darunavir Cobicistat Rilpivirine Dolutegravir Atazanavir Bictegravir Abacavir Lopinavir Ritonavir Lamivudine Zidovudine TAF Emtricitabine DESCOVY PREZCOBIX SYMTUZA

QUIZ QUESTION 8

QUIZ QUESTION 9

QUIZ QUESTION 10

3 - DRUG THERAPY: SINGLE TABLET REGIMENS NRTIs TRUVADA TDF/3 TC DESCOVY EPZICOM NNRTIs IIs + Efavirenz = Atripla + Rilpivirine = Complera + Doravirine = Delstrigo + Efavirenz = Symfi (Lo) + Rilpivirine + = Odefsey PIs ELV/cobi = Stribild ELV/cobi = Genvoya BIC = Biktarvy Dolutegravir = Triumeq DRV/cobi = Symtuza

2 - DRUG THERAPY: THE NEW WORLD ORDER NRTIs NNRTIs Rilpivirine = Lamivudine IIs + JULUCA + = Dolutegravir DOVATO Dolutegravir PIs

WHAT TO START ? NEED TO EAT DOESN’T MATTER Genvoya STRIBILD BIKTARVY Odefsey Complera DESCOVY TRIUMEQ DTG TRU DTG

WHAT TO START ? NEED TO EAT DOESN’T MATTER Genvoya STRIBILD BIKTARVY Odefsey Complera DESCOVY Certain inhaled/nasal steroids Certain HCV regimens Lower dosing of statins TRIUMEQ DTG TRU DTG

WHAT TO START ? NEED TO EAT DOESN’T MATTER Genvoya STRIBILD BIKTARVY Odefsey Complera DESCOVY PPIs, Seizure meds, Rifampin TRIUMEQ DTG TRU DTG

WHAT TO START ? NEED TO EAT DOESN’T MATTER Genvoya STRIBILD BIKTARVY Odefsey Complera DESCOVY TRIUMEQ Twice daily dosing of DTG with rifampin; lower dosing of Metformin while on DTG TRU DTG

WHAT TO START ? NEED TO EAT Genvoya STRIBILD DOESN’T MATTER BIKTARVY DESCOVY TRIUMEQ Mg++, Ca++, Fe++ DTG TRU DTG

EXERCISE NNRTI in EFAVIRENZ ATRIPLA ELVITEGRAVI II in STRIBILD R NNRTI in RILPIVIRINE ODEFSEY NNRTI: RILPIVIRINE COMPLERA DTG TIVICAY NEWEST DORAVIRINE NNRTI EMTRICITABIN FTC E WHAT’S IN PREZCOBIX? DRV/COBI NRTIs in DESCOVY TAF/FTC LAMIVUDINE 3 TC II in BIKTARVY BICTEGRAVIR RILPIV/DTG d 4 T

MORE FUN TAF/FTC 3 TC/DTG EVG/C/TAF/FT C DTG/RPV ABC/3 TC/DTG DRV/COBI TAF/FTC/DRV/ COBI TAF/FTC/RPV II IN TRIUMEQ PI IN PREZCOBIX II IN GENVOYA

3 - DRUG THERAPY: SINGLE TABLET REGIMENS NRTIs TRUVADA TDF/3 TC DESCOVY EPZICOM NNRTIs IIs + Efavirenz = Atripla + Rilpivirine = Complera + Doravirine = Delstrigo + Efavirenz = Symfi (Lo) + Rilpivirine + = Odefsey PIs ELV/cobi = Stribild ELV/cobi = Genvoya BIC = Biktarvy Dolutegravir = Triumeq DRV/cobi = Symtuza

MUTATIONS M 184 V K 103 N EMTRICITABINE EFAVIRENZ LAMIVUDINE NEVIRAPINE TENOFOVIR