hiv well into the 21st century - creighton university...4/26/2019 1 hiv well into the 21st century...
TRANSCRIPT
4/26/2019
1
HIV Well Into the 21st Century
Manasa Velagapudi, MBBS
Assistant Professor
Division of Infectious Diseases
CHI Health CUMC-Bergan
Disclosures
No conflicts of interest
No discussion of “off label” use of medications
4/26/2019
2
Objectives
• Discuss current burden of HIV
• Discuss traditional antiretroviral therapy (ART)
• Newer developments in ART
• 2 drug regimens
• injectable ART
• U=U campaign
• PrEP
• Cause of death in people living with HIV (PLWH)
New HIV Diagnosis in United States by Age
4/26/2019
3
Risk Factors for HIV
When to start ART?
4/26/2019
4
When to start ART?
Anytime & everyone with HIV.
Retrovirus Life Cycle
Fusion inhibitors
Reverse transcriptase
inhibitorsProtease inhibitors
Co-receptor inhibitors
HIV
CD4
4/26/2019
5
• NNRTI– Efavirenz– Nevirapine– Etravirine– Rilpivirine– Doravirine
• PIs– Atazanavir– Darunavir– Lopinavir– Ritonavir– Indinavir
–NRTI– Tenofovir– Abacavir– Emtricitibine– Lamivudine– Zidovudine– Stavudine– Didanosine
Fusion InhibitorEnfuvirtide (T‐20)
CCR5 AntagonistMaraviroc
Medications
3 Drugs in ART
2 NRTIs:
• 1. emtricitabine + tenofovir
• 2. abacavir + lamivudine
Third drug
• Protease inhibitor
• darunavir/ritonavir
• NNRTI
• efavirenz
4/26/2019
6
Adverse Effects
• Abacavir Hypersensitivity syndrome‐fatal
• Tenofovir Fanconi syndrome, decreased bonedensity
• Zidovudine Hematotoxicity, Mitochondrial toxicity
Only approved drug for intrapartum
• Efavirenz Neuropsychiatric symptoms ,rash
• PIs Hyperglycemia, hyperlipidemia,Cardiovascular risk
Retrovirus Life Cycle
Fusion inhibitors
Reverse transcriptase
inhibitors
Integrase inhibitors
Protease inhibitors
Co-receptor inhibitors
HIV
CD4
4/26/2019
7
• NNRTI– Efavirenz– Nevirapine– Etravirine– Rilpivirine– Doravirine
• PIs– Atazanavir– Darunavir– Lopinavir– Ritonavir– Indinavir
• Integrase Inhibitor– Raltegravir– Dolutegravir– Elvitegravir/cobicistat
–NRTI– Tenofovir– Abacavir– Emtricitibine– Lamivudine– Zidovudine– Stavudine– Didanosine
Fusion InhibitorEnfuvirtide (T‐20)
CCR5 AntagonistMaraviroc
Medications
3 Drugs in ART
2 NRTIs:
• 1. emtricitabine + tenofovir
• 2. abacavir + lamivudine
Third drug
• Protease inhibitor
• darunavir/ritonavir
• Integrase inhibitor
• dolutegravir
• raltegravir
• elvitegravir
• NNRTI
• efavirenz
4/26/2019
8
What to start
1. Bictegravir/tenofovir alafenamide/emtricitabine
2. Dolutegravir/abacavir/lamivudine
• only for HLA‐B*5701 negative
3. Dolutegravir+tenofovir/emtricitabine
4. Raltegravir + tenofovir/emtricitabine
DHHS guidelines 2018
Can Everyone Start with 1 Pill Daily?
4/26/2019
9
Single Tablet Regimens
1. Bictegravir/tenofovir alafenamide/emtricitabine
2. Dolutegravir/abacavir/lamivudine HLA‐B*5701 negative
3. Elvitegravir/cobicistat/tenofovir alefenamide/emtricitabine
4. Darunavir/cobicistat/tenofovir alafenamide/emtricitabine
5. Doravirine/Tenofovir disoproxil fumarate/lamivudine
6. Efavirenz/emtricitabine/tenofovir/Rilpivirine/emtricitabine/tenofovir
Milestones in HIV therapy
19963 drug therapy
1987First drug-Zidovudine
2007Single tablet
regimen
20172 drug
regimen
4/26/2019
10
When is 2 > 3?
Switching to dolutegravir + rilpivirine for patients on stable ART
Libre et al. The Lancet 2019;381:839
Well controlled hiv<50 copies/ml
4/26/2019
11
Switching to dolutegravir + rilpivirine for patients on stable ART
Libre et al. The Lancet 2019;381:839
Dolutegravir + Lamivudine as maintenance therapy
Joly et al. J Antimicrob Chemother. 2019 ;74:739
• Open label
• 2 phases‐56 weeks
• treatment experienced
• viral load <50 copies/ml
• CD4 >200
• no major resistance mutations
• no HBV
4/26/2019
12
Dolutegravir + Lamivudine as maintenance therapy
J Antimicrob Chemother. 2019 Mar 1;74(3):739
4/26/2019
13
ATLAS: Switch to Long-Acting Cabotegravir + Rilpivirine in Virologically Suppressed Adults
Multicenter, randomized, open‐label phase III noninferiority trial
Adults on stable ART* (either firstor second
regimen) with HIV< 50 copies/mL for ≥ 6 mos with no previous VF(N = 616)
CAB 30 mg +RPV 25 mg PO QD
(n = 308)
LA CAB 400 mg IM +LA RPV 600 mg IM Q4W†
(n = 303)
Continue Baseline ART‡
(n = 308)
ATLAS: Switch to Long-Acting Cabotegravir + Rilpivirine in Virologically Suppressed Adults
Primary endpoint:
‒HIV‐1 RNA ≥ 50 copies/mL at Wk 48 by FDA Snapshot
‒(6% noninferiority margin)
Secondary endpoints:
‒HIV‐1 RNA < 50 copies/mL at Wk 48 by FDA Snapshot
‒ resistance at confirmed virologic failure
‒ safety and tolerability
‒patient‐reported outcomes
4/26/2019
14
ATLAS: Switch to Long‐Acting Cabotegravir + Rilpivirine in Virologically Suppressed Adults
DTG+3TC
4/26/2019
15
What kills people living with HIV?
NA-ACCORD: Smoking, HTN & Cholesterol Contribute to MI risk in HIV Infection
Smoking
• shortens life span of people with HIV by 6 yr
• far more harmful than well managed HIV itself
HTN
• Major risk factor ‐ CAD
Hypercholesterolemia
• ASCVD score
• Statin use
4/26/2019
16
What is U=U?
4/26/2019
17
Why Is U=U Important
• Knowing U=U can be transformative for people living with HIV (PLWH) & their interpersonal relationships
• Affirms they are not disease vectors & can be touched and loved
• Many PLWH still face both institutional & personal stigma , discrimination
• As a result, many avoid relationships, sexual or otherwise, because of their perceived potential to transmit HIV
Talk to Your Patients about U=U
• Counsel on the necessity of staying undetectable for U=U to work
• Educate on the importance of taking HIV medications every day to stay healthy and also prevent transmission to their sexual partners
• Explain and reinforce that when the virus is suppressed, they will not transmit HIV to partners
• Encourage patients to know their viral load by keeping their medical appointments so they and their partners are sure of their undetectable status
4/26/2019
18
Despite Extraordinary Efficacy, HIV Therapy Can Be Improved
ART approaches under current investigation include:
Virologic suppression rates can barely be improved in adherent patients
But there is room to improve ART:
• Short‐term and long‐term safety
• Tolerability
• Convenience
• Cost
• Activity against panresistantvirus
• Still no available cure
What is PrEP?
4/26/2019
19
4/26/2019
20
›Can we treat our way out of the
HIV epidemic? Treatment as Prevention
GETTING TO
ZEROZERO
NEW INFECTION
ZERODISCRIMINATI
ON
ZEROAIDS
RELATED DEATHS
Have you had more than enough?
The End.
4/26/2019
21
Thank You!