hiv well into the 21st century - creighton university...4/26/2019 1 hiv well into the 21st century...

4/26/2019

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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

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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

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Risk Factors for HIV

When to start ART?

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When to start ART?

Anytime & everyone with HIV.

Retrovirus Life Cycle

Fusion inhibitors

Reverse transcriptase

inhibitorsProtease inhibitors

Co-receptor inhibitors

HIV

CD4

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• 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

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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

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• 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

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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?

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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

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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

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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

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Dolutegravir + Lamivudine as maintenance therapy

J Antimicrob Chemother. 2019 Mar 1;74(3):739

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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

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ATLAS: Switch to Long‐Acting Cabotegravir + Rilpivirine in Virologically Suppressed Adults

DTG+3TC

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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

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What is U=U?

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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

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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?

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›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.

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Thank You!