Disclosures Updates in HIV Care I have no disclosures Susa Coffey, - - PowerPoint PPT Presentation

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6/22/2016 1

Updates in HIV Care

Susa Coffey, MD

UCSF Division of HIV, Infectious Diseases and Global Medicine San Francisco General Hospital

Disclosures

I have no disclosures

Objectives

To learn about recent developments in:

HIV epidemiology in the U.S. Prevention

PrEP Nonoccupational PEP

Treatment

When to start What to start ARV update (TAF; single-pill regimens) Immediate ART initiation

Intro

Why are we still talking about HIV?

Nearly 50,000 new infections/year in the U.S. Approx 1.1 million living with HIV

• About 13% are unaware of their infection

If untreated, inevitably causes illness and death Disproportionately affects vulnerable populations

But, it’s a preventable disease, and a

treatable disease

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Question

The goal of HIV treatment is suppression of HIV viremia. What percentage of the U.S. HIV population is

• n antiretroviral therapy (ART) with complete

suppression of HIV viremia?

• A. 82%
• B. 66%
• C. 45%
• D. 30%
• E. 25%

8 2 % 6 6 % 4 5 % 3 % 2 5 %

9% 34% 3% 28% 25%

United States HIV Care Continuum, 2011

National HIV Surveillance System,: Estimated number of persons aged ≥13 years living with diagnosed or undiagnosed HIV infection (prevalence) in the United States at the end of the specified year . The estimated number of persons with diagnosed HIV infection was calculated as part of the overall prevalence estimate. Medical Monitoring Project: Estimated number of persons aged ≥18 years who received HIV medical care during January to April of the specified year, were prescribed ART, or whose most recent VL in the previous year was undetectable or <200 copies/mL—United States and Puerto Rico.

Rates of Diagnoses of HIV Infection among Adults and Adolescents, by Sex and Race/Ethnicity, 2014—U.S.

• Note. Data include persons with a diagnosis of HIV infection regardless of stage of disease at diagnosis. All

displayed data have been statistically adjusted to account for reporting delays, but not for incomplete reporting.

a Hispanics/Latinos can be of any race.

HIV by Race/Ethnicity in the U.S.

CDC, 2015

Incidence of HIV in MSM

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Lifetime Risk of HIV

CDC, 2/16

Prevention

PrEP (Pre-Exposure Prophylaxis) PrEP: Pre-Exposure Prophylaxis

A pill taken daily (or peri-coitally?) to

prevent HIV infection

Tenofovir + emtricitabine (TDF/FTC,

Truvada), 1 pill once daily

Approved by FDA, recommended by the

CDC and WHO

• No other medications approved for PrEP*

*Do not use TAF/FTC (Descovy) for PrEP (no clinical data)

Cases

1) 22 yo white MSM, 3 regular partners, 1 HIV+ and on ART, others on PrEP. Usually uses condoms (always with HIV+ partner).

Should he be offered PrEP?

2) 16 yo AA young man, reports sex with girls. Gonorrhea 4 months ago.

Should he be offered PrEP?

3) 34 yo Latina, former IDU, now clean. Delivers 3rd child in hospital; rapid HIV Ab and HIV RNA are neg at delivery.

Should she be offered PrEP?

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USPHS and CDC PrEP Recs

Consider PrEP for individuals who are at substantial risk of HIV acquisition, including:

Substantial risk includes:

• Sexually active MSM
• Heterosexually active

women and men

• IDUs (PWIDs)
• (Transgender women and

men)*

• Using condoms inconsistently
• High number of sex partners
• HIV+ sex partner
• Recent STD
• HIV+ injecting partner
• Sharing injection or drug

preparation equipment

• Commercial sex work

USPHS, CDC et al. PrEP GL 2014.

*Not a specific GL recommendation

PrEP: Pre-Exposure Prophylaxis

What do we know about efficacy and safety?

Highly effective if taken as directed

(preferably daily) - >90%

• iPrEx study in MSM (and TG women), 2

studies in heterosexual men and women

Does NOT work if not taken regularly*

• eg, VOICE and Fem-PrEP studies in women

Efficacy strongly tied to adherence AEs: mild “start-up syndrome” (GI); rare

serious AEs. Small decreases in Cr and bone density.

* # of doses/week required for efficacy is not well defined; may be higher for women than for men.

Clinical trials: Efficacy of TDF/FTC-based PrEP

Trial Population, Location Reduction in HIV infections (95% CI)

Men, transwomen Cisgender women

iPrEx1

MSM, transgender women

Americas, RSA, Thailand

44% (15-63)

92% if

detectable drug

• Partners

PrEP2

Mutually disclosed serodifferent heterosexual couples

Kenya, Uganda

84%

(54-94)

66%

(28-84)

TDF23

Heterosexual men, women Botswana

80%

(25-97)

49%

(-21-81)

Fem- PrEP4

Women

Kenya, RSA, Tanzania

• 6%

(-52-41)

VOICE5

Women

Uganda, RSA, Zimbabwe

• 4%

(-49-27)

PROUD6

MSM (open-label)

UK

86%

(58-96)

• IPERGAY7

MSM (intermittent PrEP) France, Canada

86%

(40-98)

• 1. Grant et al. NEJM 2010. 2. Baeten et al. NEJM 2012. 3. Thigpen et al. NEJM 2012. 4. Van Damme et al. NEJM 2012. 5. Marazzo et al.

NEJM 2015. 6. McCormack et al. Lancet 2015. 7. Molina et al. NEJM 2015.

PrEP – “Real World”

PROUD study

554 high-risk HIV-neg MSM STD clinics in England Randomized immediate vs deferred PrEP

(TDF/FTC [Truvada])

New HIV infections: 3 vs 19; incidence 1.3 vs

8.9 per 100 py

86% reduction in HIV infection (p=0.0002) NN to prevent: 13 Study stopped early

McCormack, Lancet. 2016

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PrEP – “Event-Based”

IPERGAY study

Event-based PrEP 400 high-risk MSM (≥2 partners in previous

6 mos), randomized TDF/FTC vs placebo

2 tabs before sex, 1 tab 24 hrs after, 1 tab

48 hrs after

New HIV infections: 2 (PrEP) vs 14

(placebo); incidence 0.94 vs 6.6 per 100 py

86% reduction in incidence, p=0.002 NN to prevent: 18 Median 16 pills/month

Molina, NEJM, 2015

NEJM

PrEP – Kaiser SF

Kaiser SF

N=657 initiators + 20 restarters, 99% MSM 30% with HIV+ partner NO new HIV infections (July 2012-Feb 2015) Update: >1000 on PrEP by July 2015, NO

HIV infections

Volk, CID, 2015 Volk JE. Clin Infect Dis. 2015. Marcus JL. Curr HIV/AIDS Rep. 2016. A.

More MSM than women

B.

The number of women and MSM is about the same

C.

More IDUs than MSM

Which of the following is true about the number of people in the U.S. with an indication for PrEP?

Question

M

• r

e M S M t h a n w

• m

e n T h e n u m b e r

• f

w

• m

e n . . . M

• r

e I D U s t h a n M S M

78% 17% 4%

CDC indications for PrEP

Number of U.S. adults with indication for PrEP % of U.S. adults with indication for PrEP

MMWR 2015

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PrEP Uptake by Sex

Bush, S. et al; IAPAC Prevention 2015; #74

468,000 ? ? ? ~1,000

PrEP Cascade for U.S. Women

(2015)

Bush, S. et al; IAPAC Prevention 2015; #74

Slide courtesy of D. Seidman ?

Return to Cases

1) 22 yo white MSM, 3 regular partners, 1 HIV+

and on ART, others on PrEP. Usually uses condoms (always with HIV+ partner).

Should he be offered PrEP?

2) 16 yo AA young man, reports sex with girls.

Gonorrhea 4 months ago.

Should he be offered PrEP?

3) 34 yo Latina, former IDU, now clean.

Delivers 3rd child in the hospital. Rapid HIV Ab and HIV RNA are neg there.

Should she be offered PrEP?

PrEP – it’s not rocket science!

1 medication (Truvada) 1 pill 1 time per day

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PrEP Core

Have a referral source for HIV+ patients

At baseline and at least every 3 months:

• Assess HIV risk (sex, drugs)
• Assess for ssx acute HIV
• Test HIV, HBV (baseline only), Cr,

pregnancy, STIs

• Assess and reinforce adherence, and risk

reduction

• Assess pregnancy intentions
• Prescription for ≤90 days at a time

PrEP

Summary

PrEP works if people take it

Need more data in U.S. women

Close adherence required, ideally 7 days

per week

Some data in MSM suggest 4 doses/week

may be adequate (fewer is not protective)

In women, daily dosing may be very

important

No data support less frequent dosing Tissue drug levels may be very low May take 2+ weeks to achieve adequate drug

levels

TFV concentrations up to 100-fold higher in rectal than in cervicovaginal tissues

Tenovovir tissue concentrations Days after TDF/FTC dose

Patterson et al. Sci Transl Med 2011, Garrett KL, CROI 2016, Abs 102LB.

PrEP

Summary (2)

Only Truvada (TDF/FTC) should be used

TAF/FTC (Descovy): no clinical data as PrEP; should not be

used

PrEP failure can result in HIV infection with ARV

resistance

Women (cis- and transgender), AA, Latino, IDU,

• ther risk groups are underserved re PrEP and may

need focused PrEP outreach and education efforts

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Prevention nPEP Nonoccupational Post- Exposure Prophylaxis nPEP

2016 nPEP Guidelines Update

CDC MMWR 2016

nPEP

Recommendations:

• 3 drugs for all

Preferred PEP regimen:

• TDF/FTC (Truvada) + raltegravir (twice daily) or dolutegravir

(once daily)

Alternative regimen: TDF/FTC + darunavir + ritonavir

• Start PEP ASAP after exposure, w/in 72 hrs
• Treat 28 days
• HIV testing at baseline, 4-6 weeks, and 3 months

HIV Ag/Ab test preferred; consider HIV RNA in high-risk

patients

• nPEP and oPEP recommendations now largely the

same

CDC MMWR 2016

nPEP PrEP

For high risk individuals (ongoing risks;

use of PEP ≥ once in past year)

Offer PrEP at the end of 28-day nPEP,

after documenting HIV-negative status

No interruption between nPEP and PrEP nPEP can be an entry point into PrEP

CDC MMWR 2016

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Treatment When to Treat: DHHS Recommendations

Antiretroviral therapy (ART) is recommended

for all HIV-infected individuals, regardless of CD4 T lymphocyte cell count, to reduce the morbidity and mortality …(AI).

ART is also recommended for HIV-infected

individuals to prevent HIV transmission (AI).

New: A1 recommendation for ALL

DHHS Adult/Adolescent ART GL, January 2016

START Study

CD4 cell count >500, randomized to

immediate ART vs deferred until CD4 <350 or AIDS, n= 4685

Primary EP: serious AIDS event, serious non-

AIDS related event, or death

INSIGHT START Study Gp, NEJM, 2015

HR 0.43 (95% CI, 0.30 -0.62; P<0.001) HR .61 (95% CI, 0.38 -0.97; P=0.04

“More than two thirds of the primary end points (68%) occurred in patients with a CD4+ count of >500 cells/mm³” Benefits similar in low, medium, and high income countries

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Question

Which classes of ARVs are recommended by DHHS Guidelines as anchor drugs for initial treatment?

A.

Protease inhibitors

B.

Nonnucleoside reverse transcriptase inhibitors (NNRTIs)

C.

Integrase inhibitors

D.

A and B

E.

A and C

Protease inhibitors Nonnucleoside reverse t... Integrase inhibitors A and B A and C

9% 5% 27% 55% 5%

What to Start: DHHS Recommended Regimens for 1st ART

Integrase Inhibitor based (5 regimens)

• Dolutegravir/ABC/3TC; only if HLA-B*5701

negative

• Dolutegravir (QD) + TDF/FTC
• Elvitegravir/COBI/TAF/FTC; only if pre-ART

CrCl ≥30

• Elvitegravir/COBI/TDF/FTC; only if pre-ART

CrCl >70 mL/min

• Raltegravir + TDF/FTC

PI based (1 regimen)

• Darunavir (QD) + ritonavir (QD) +

TDF/FTC Note: alternatives may be optimal for individual patients

DHHS Adult/Adolescent ART GL, January 2016 www.aidsetc.org

New: Integrase inhibitor regimens dominate; no NNRTI regimens

Supporting Adherence: Simplifying ART

Single-pill regimens

• Atripla: efavirenz/TDF/FTC
• Complera: rilpivirine/TDF/FTC
• Genvoya: elvitegravir/COBI/TAF/FTC*
• Stribild: elvitegravir/COBI/TDF/FTC*
• Triumeq: dolutegravir/ABC/3TC*
• Odefsey: rilpivirine/TAF/FTC (just approved)
• 2 pill regimen
• Dolutegravir + TDF/FTC* or TAF/FTC

*DHHS recommended regimens

New NRTI: Tenofovir alafenamide (TAF)

New tenofovir prodrug

90% lower plasma tenofovir levels, higher intracellular

levels than with TDF

Appears safer for kidneys (less proteinuria, slightly less

decrease in eGFR), bones (less adverse BMD change)

Approved for eGFR ≥30

Available in 3 coformulations:

Elvitegravir/cobi/TAF/FTC (Genvoya) Rilpivirine/TAF/FTC (Odefsey): approved 2016 TAF/FTC (Descovy): approved 2016 Sax, Lancet, 2015. Gallant, CROI, 2016.

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New NRTI: Tenofovir alafenamide (TAF) (2)

Cautions:

PrEP: DO NOT USE AS PrEP

No clinical data PK data in HIV neg women show low TFV-DP

concentrations in cervical, vaginal, and rectal mucosa

• 2-fold lower in cervicovag tissue, 11-fold lower in

cervicovag fluid, 10-fold lower in rectal tissue

Hepatitis B: active against hepatitis B; limited data

in HIV/HBV coinfection (effective in switch study)

CKD: limited data in moderate-severe CKD Dosing: TAF/FTC pill contains 25 mg of TAF

Appears safe, effective with NNRTIs and INIs; not studied

with protease inhibitors (toxicity unknown)

New: TAF = as effective against HIV, perhaps safer than TDF (follow the data)

Garrett, CROI 2016, Abstract 102LB

Case

36 yo man referred today from STD Clinic

with + HIV Ab test

Last HIV test >2 yrs ago: negative Always used condoms … except once, 2

months ago

Question

When would you start ART?

A.

Today

B.

After getting to know the patient over several visits

C.

After results of baseline labs and HIV genotype are available

D.

If CD4 is <500 cells/mm³

Today After getting to know th... After results of baseline ... If CD4 is <500 cells/mm³

60% 0% 36% 4%

Immediate (Same- Day) ART

SFGH Ward 86 RAPID Program (Rapid ART Initiation upon HIV Diagnosis)

Pt referred from HIV testing site SW intake, counseling, insurance/benefits activation

(eg, emergency Medi-Cal)

Intake labs Clinician intake visit including patient education

about ART

Start ART immediately, unless there is a clear

contraindication

F/u next day with SW + prn, clinic visit (SW and

clinician) ≤1 week; close f/u for weeks-months

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Immediate (Same-Day) ART

Rationale for immediate start:

Achieve health benefits earlier (morbidity and

mortality)

Reduce size of HIV reservoir (especially

important in acute/early HIV)

Prevent HIV transmission Early linkage to care Patient expectation

Rationale for delayed start:

No baseline test results Patient may not be ready Adherence may be threatened “Too difficult”

RAPID ART

RAPID Program at SFGH

Time to VL suppression by ART initiation strategy, 2006-2014

RAPID vs. universal ART P<0.001

Universal ART CD4-guided ART

Proportion <200 copies

Pilcher, IAS, 2015

Horizon

Long-acting injectable ARVs for treatment

and for PrEP

Rilpivirine (NNRTI) Cabotegravir (integrase inhibitor)

“Cure” agenda continues

Summary

(Test), Prevent, Treat, Retain! PrEP – consider for all patients at risk; get

it to at-risk populations

nPEP – transition to PrEP Treat all HIV+ persons, as early as possible

Consider immediate treatment upon

diagnosis

Integrase inhibitors preferred for first-line

ART

Choose simple, tolerable combinations Goal is viral suppression TAF – may be safer than TDF (look for

further data)

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Resources

By Phone HIV/AIDS Care Consultation (800) 933-3413 Post-Exposure/PEP Consultation (888) 448-4911 Perinatal HIV Consultation (888) 448-8765 Pre-Exposure/PrEP Consultation (855) 448-7737 http://nccc.ucsf.edu/

“Getting to Zero” in San Francisco

Zero new HIV infections Zero HIV deaths Zero stigma and discrimination

Slide courtesy of D. Havlir Slide courtesy of D. Havlir