1 44% new infections in Blacks vs 12% of U.S. population AR1: - - PDF document

1

Diane Havlir, MD Professor of Medicine University of California, San Francisco

Top 10 stories in HIV Medicine Disclosures

n Receive funding for research from NIH n Gilead sciences provides antiretroviral therapy

for NIH funded SEARCH research study

Story 1: United States Epidemic: Spotlight on the Real News

n What is the big

picture?

n Are new HIV

infections going up

• r down?

n Who and where are

the newly infected?

n Who is living with

HIV?

n What is happening

in San Francisco?

The “Big Picture” in the U.S.

n Number of new HIV diagnosis: 37,600 n Number of persons living with HIV: 1.2 million n Percent of persons infected with HIV who do not

know it: 13%

n Percent of people diagnosed with HIV who are

virally suppressed: 55%

2

44% new infections in Blacks vs 12% of U.S. population AR1: >50% of new infections are in what region of the U.S.?

n Northeast n Southeast n South n Central n West n Islands/District

Answer: the South

3

States with the most cases and the highest rates of infection HIV: Spanning life stages

n New Infections: 17% of new HIV infections in the

U.S. among persons 50 years and older

• Among these 43% black 36% white and 17% latino

n Presentation: 40% are persons 55 and older and

had AIDS at time of diagnosis

n Living with HIV: 45% living with HIV are aged 50

and older

• San Francisco 63% over 50 years of age

New HIV diagnoses, deaths, prevalence in San Francisco 2006-2016

SFDPH HIV Epidemiology Annual Report 2016

2013:Getting To Zero: Expand PREP,RAPID,LINCS 2010:Universal ART 2012: PREP/ RAPID 16% decline new infections in one year

Disparities in achieving viral suppression in San Francisco

• Females
• African

Americans

• Youth
• PWID
• Homeless

Lower rates of viral suppression among:

4

Conclusions: Real News calls for Real Action

n Nationally, there was a very modest decline in

rates of HIV over the last 6 years (18%)

n Overall viral suppression rates are suboptimal

(55%)

n Disparities must be addressed for prevention and

treatment approaches

Youth, women, PWID, homeless, foreign born, others

n We need to find persons early in disease--Late

presentations can be lethal

n We need resources and investment for our aging

population

Story 2: ART – a new framework for initial therapy in DHSS Guidelines

n Recommended for

“most people with HIV”

n Recommended for

“certain clinical situations”

AR2: First line therapy– which is Not recommended for “most people with HIV”?

n DTG + ABC/3TC n DTG+ TDF*/FTC n EVG+ TDF*/FTC n RAL+ TDF*/FTC n DRV/C + TDF/FTC

* Or TAF

Answer: DRV/c + TDF/FTC is Not recommended for most people

DHSS guidelines, October 2017

5

n Patient virus or genetics– drug resistance,

HLAB5701+

n Patient preference

• Fewer pills
• Taking pills with food
• Smaller pills

n Co-morbidities

• Renal disease
• Cardiovascular disease
• Hepatitis B
• TB

Recommended “in certain situations”– what kind of situations? Recommended “in certain clinical situations” (e.g. DRV/c+ TDF/FTC ), we will discuss these during the conference Story 3: INSTIs: The “First Line” … but never alone 2 studies with DTG monotherapy: High virologic failure and resistance

Blanco JL, et al. CROI 2017. Abstract

Dolumono Study N=104

n Adults, suppressed

• n ART x 6 months

n DTG 50 mg qd vs

continue ART

n All switch to DTG at

24 weeks

n RESULTS: 8 Virologic

failures by week 72 Retrospective review DTG monotherapy N=122

n RESULTS: 11 Virologic

failures

n 9/11 INSTI resistance

6

Summary

n Old thinking– Dolutegravir has a very high genetic

barrier and resistance unlikely to happen in patients with no prior INSTI

n New thinking- Dolutegravir resistance can happen:

• Never use DTG monotherapy
• Make sure combination therapy has potency to protect DTG

n Under study/new data

• DTG+ 3TC for treatment naïve and for switch
• DTC+ rilpivirine for switch

Story 4: Switch Mania Switching ART in patients with viral load suppression

n Why? – toxicity, potency, simplicity, drug

interactions, pregnancy

n Why not? Patients like current regimen, unknown

drug resistant mutations, lack of data on such a switch for patient with a complicated history

n Why is this such an issue now? New data, new

co-formulated drugs, new drug combinations suited for specific situations

SWITCH: Boosted PI/TDF/FTC to Single tablet Darunavir/cobi/FTC/TAF

Orkin, Lancet HIV, 2017 EMERALD STUDY

• N=1141
• Endpoint: Virologic

Failure

• 48 weeks
• Findings: Single tablet

PI combination effective and safe

7

Virologic outcomes

Percentage-point difference DTG + RPV is non-inferior to CAR with respect to snapshot in the ITT- E population (<50 c/mL) at Week 48

95 95 <1 1 5 4

aAdjusted for age and baseline 3rd agent.

SWORD (1 and 2) POOLED

• N=1024
• Endpoint: Virologic

suppression

• 48 weeks
• Findings: DTG/RPV

effective and safe Libre, CROI, 2017

SWITCH: ART to 2 Drug Dolutegravir+Rilpivirine SWITCH: ART to 2 Drug Dolutegravir + 3TC

LAMIDOL Joly, CROI, 2017

• N=104 entered phase II
• Endpoint: Virologic

suppression at 48 weeks

• Findings: 97% viral

suppression at week 48, no INSTI resistance; 1 NRTI resistance

SWITCH: ART to 2 drug injection Cabotegravir + Rilpivirine

LATTE-2 Margolis, Lancet, 2017

• N=309
• Oral cabotegravir +

ABC/3TC

• Randomize to

injection (Q4 or 8 weeks) cabotegravir+ rilpivirine vs continue

• ral
• Endpoint: Virologic

suppression

• Findings: Injection( q4
• r 8 weeks) effective

and safe q8 q4 Oral

Summary: Switch for patients with viral load suppression

n “Switch” ART is major and complicated element of

HIV medicine – but it can help our patients!

n New options with robust data (examples)

• Single pill protease inhibitor combination: Darunavir, cobicistat,

FTC, TAF (Prezcobix)

• 2 drug: Dolutegravir + Rilpivirine

n

2 drug options under study in Phase III trials (examples)

• INSTI: Dolutegravir + 3TC
• Injection: Cabotegravir+ Rilpivirine

8

Story 5: 2 New antiretroviral Agents*

Pipeline and innovation

*among many

Doravirine

n NNRTI, once-daily dosing (100 mg), active in vitro

against common NNRTI resistance mutations (including K103N, Y181C, E138K)

n No food or PPI restrictions n Phase 2: Doravirine + TDF/FTC: HIV RNA

suppression matches efavirenz, fewer adverse events

LAI M-T. CROI 2016. Abs 506

Doravirine vs Darunavir/r

Molina JM, et al. CROI 2017. Abstract 45LB.

Virologic Nonresponse

Wk 48

HIV-1 RNA < 50 c/mL No Data 100 80 60 40 20

Pts (%)

84 80 11 13 5 7

Treatment difference: 3.9% (95% CI: -1.6% to 9.4%)

DOR + 2 NRTIs (n = 383) DRV + RTV + 2 NRTIs (n = 383)) DRIVE FORWARD study

• N=766, ART naïve
• Endpoint: Virologic

suppression

• 48 weeks
• Findings: Viral

suppression Doravirine similar to darunavir regimen

• NNRTI resistance

seen in failure Molina, CROI, 2017

Bictegravir

n INSTI, once daily 50 mg, unboosted n Active against many INSTI resistance mutations (in

vitro)

n Phase 2: performed comparably to dolutegravir n CYP3A4 metabolized

Tsiang M, Antimicro Agents Chemother, 2016

9

Bictegravir/TAF/FTC (single pill) combination vs Dolutegravir + TAF/FTC

GS- 1490 study Sax, Lancet, HIV 2017

• N=657, ART naïve
• Endpoint: Virologic

suppression

• 48 weeks
• Findings: Viral

suppression Bictegarvir similar to dolutegravir regimen

• No INSTI resistance

Story 6: Intermittent PrEP – is it time ? AR3: New data suggest intermittent (vs daily) PrEP is promising option for

n MSM n Women n Both n Neither

Answer: MSM

n IPERGAY extension study

• 361 participants
• On demand PrEP
• Median 18 pills/month
• Compare HIV incidence to prior

control arm of IPERGAY

n Results:

• 97% reduction in new HIV

infections with intermittent PrEP

• Condomless sex increased

77% to 86% -- high, but no increase in STI’s

Molina, Lancet HIV, 2017

10

Where are we in PrEP?

n CDC recommends daily PrEP for MSM

• Recommendation based on IPrEX and Partners PrEP
• IPERGAY study not considered sufficient to change

recommendation

n CDC recommends daily PrEP for women

• Pharmacokinetic data support this recommendation

n What is happening in communities?

• Persons are already using intermittent PrEP
• Communities are in discussion on policy
• Providers are faced with a variety of new situations

regarding PrEP, PEP and seroconversion

Story 7: Steroids—any role in TB IRIS for prevention? AR4: In what situation does addition of steroids have positive effect on outcomes?

n Cryptococcal meningitis (reduce mortality) n TB (reduce IRIS) n Both Cryptococcal meningitis and TB

AR4: In what situation does addition of steroids have positive effect on outcomes?

n Cryptococcal meningitis (reduce mortality) n TB (reduce IRIS) n Both Cryptococcal meningitis and TB

11

Answer: TB IRIS prevention: “PredART” Study

• Double blind,

placebo controlled RCT

• TB/HIV N=240
• CD4<100
• Start ART,

prednisone vs no prednisone

• 30% more IRIS in placebo group
• Faster time to IRIS

Meintjes, CROI, 2017

Add prednisone (40 mg for 2 weeks, 20 mg for 2 weeks) in HIV/TB cases with CD4<100 to prevent IRIS because this intervention :

• Reduced TB-IRIS by 30%
• Reduced treatment TB-IRIS by 53%
• No excess infection/malignancy

Summary: Change of practice: Use prednisone to prevent TB IRIS in high risk patients

Reminder from last year: Steroids had no benefit on IRIS/outcomes for HIV+ persons treated for cryptococcal meningitis Beardsley, NEJM, 2016

Story 8: Heart Health: Time for Pitavastatin?

INTREPID Study

n What is optimal

lipid lowering agent?

n Double blind RCT,

N=252

n HIV+, ART>6

months, HIV RNA< 200, dyslipidemia

n Pitavastatin better: 31%

vs 20% LDL reduction

n No difference AE,

glucose metabolism

Aberg, Aberg, Lancet, HIV 2017 THE DRUG

n Pitavastatin

4 mg vs pravastatin 40 mg

STUDY INTERVENTION RESULTS

12

INTREPID Conclusions- change of practice?

n Aging HIV population n Persons with HIV are at greater risk for

cardiovascular disease

n Consider pitavastatin 4 mg daily as front line

agent for persons with cardiovascular risk factors REPRIEVE N= 6500: Pitavastatin vs therapeutic lifestyle changes, 6 year study Ongoing primary prevention clinical outcome study:

Story 9: Global aspirations

n Move to INSTI first line n Same day ART start n Self testing

19.5 million persons on ART: Moving to INSTI first line

New WHO Recommendation: Rapid ART Initiation

n “Rapid ART initiation should be offered to all people

living with HIV following a confirmed HIV diagnosis and clinical assessment.”

• “Rapid” defined as within 7 days

n “ART initiation should be offered on the same day

to people who are ready to start.”

WHO Guidelines, July 2017

WHO 2017 ART Guildelines update DHSS 2017 ART Guildelines update: “Same day ART initiation is investigational”

13

South Africa: Rapid patients started sooner

Rosen, PLOS Medicine, 2016

n

N=463

n 97% of patients in

rapid start on ART by 90 days

n 75% started on the

same day

n Rapid patients spent

2.5 hours on average in their ART start visit

n Viral suppression

higher with rapid: 64% vs 55%

HIV Self Testing

Distribution pathways: Community lay workers, mail, storefronts, home, health fairs, events ( AMC), share among young adults, men, sex worker HIV Self Testing: 2 fold higher than standard care:

WHO Guidelines on HIV self testing 2015

Addresses Barriers:

• Awareness
• Stigma

UNITAIDS Self Testing Africa (STAR)

n Goal: 4.8 million HIV self test kits distributed across Malawi,

Zambia, Zimbabwe, South Africa, Lesotho and Swaziland by 2020.

n Approach: Door to door, lay-workers, sex workers, peers,

workplace, VAMC

n Outcomes:

• Distributed 380,000 HIV self test kits in first year
• 12-26% first time testers
• Increased uptake in youth and men

“A hora e agora” Brazil

n “The time is now” n Secure web based

platform

n Free HIV oral ST n Online tutorials,

24 hour hotline

n Confirmatory testing

at clinic

14

Story 10: Global 90-90-90 report card

73% “population level” suppression

Figure 4.2. Recommended antiretroviral therapy initiation threshold among people living with HIV per Ministry of Health guidelines, by country, global, MID-2017

COUNTRIES ADOPTING THE TREAT ALL GLOBAL STANDARD

Treat all regardless of CD4 count CD4 count of 500 cells/mm3 or less CD4 count of 350 cells/mm3 or less No data

UNAIDS, Global AIDS Update, 2017

Which countries have adapted “Treat all”? AR5: What percent of persons with HIV globally are aware of their status?

n 30% n 50% n 70% n 90%

15

THE HIV TESTING AND TREATMENT CASCADE

Source: UNAIDS special analysis, 2017; see annex on methods for more details.

Figure 3.4. Knowledge of HIV status, treatment coverage and viral load suppression, global, 2016

37 18.5 Number of people living with HIV (million) Per cent 100 75 50 25 People living with HIV who know their status 70% [51–84%] Gap to reaching the first 90: 7.5 million People living with HIV

• n treatment

Gap to reaching the second 90: 10.2 million 53% [39–65%] People living with HIV who are virally suppressed Gap to reaching the third 90: 10.8 million 44% [32–53%]

UNAIDS, Global AIDS Update, 2017

• Significant progress, but significant disparities persist
• E.g. In Moscow, HIV+ gay men who know their HIV status: 13%

Answer: 70% aware HIV status

UNAIDS Report 2017

HIV annual new infections: 1.8 million -- 16% decline 2010-2016

44% population level suppression

Achieving “90-90-90” is possible: SEARCH: 84% population suppression

65% 80% 86% 94% 91% 88% 96% 93% 90% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% % HIV+ w/ Prior Dx % Prior Dx ever on ART % Ever on ART w/ Supp

Cascade Coverage Among Prevalent Adult HIV+

Baseline Follow Up Year 1 Follow Up Year 2

• Test and treat study

in rural Uganda and Kenya

• 340,000 persons
• Multi-disease health

fair and home testing

• “Streamlined” patient

centered care with same day ART start

• Achieved 90-90-90 in

2 years Petersen, JAMA, 2017

Summary

n We need to re-double our efforts in the U.S --

including PrEP and care for aging

n INSTI inhibitors are invaluable– our first line

agents around the world, and we need to use them wisely

n HIV patients have new and upcoming choices for

simplifying therapy– clinicians need to guide

n ART response in global epidemic encouraging–

but we need to put millions more on ART and reduce disparities

n Treatment, vaccine and cure will all be needed to

end the epidemic

Acknowledgments

Begin, be bold and venture to be wise Horace Persons living with HIV Monica Gandhi Annie Luetkemeyer Susan Scheer + team Susan Buchbinder Gabe Chamie Vivek Jain Moses Kamya Maya Petersen Meg Newman Colleagues at WHO UNAIDS and the Global Fund SF Getting to zero consortium

Special thanks to:

16

UNAIDS Global AIDS Update 2017

Substantial progress has been made towards the 90–90–90 targets and a major milestone has been reached: for the first time, more than half

• f all people living with

HIV are on treatment.

LIFE EXPECTANCY REBOUND FOLLOWING TREATMENT SCALE-UP

Life expectancy at birth (years) 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005 2010 2015 70 60 50 40 30 20 10 Botswana Lesotho Malawi Namibia South Africa Swaziland United Republic of Tanzania Uganda Zimbabwe Average 1996–97: Peak in new HIV infections 2003: PEPFAR and 3 by 5 Initiative 2001: First discounted generic antiretroviral medicine 2007: Provider-initiated HIV testing 2002: The Global Fund to Fight AIDS, Tuberculosis and Malaria 2010: Antiretroviral therapy coverage in eastern and southern Africa was 23% [19–27%] 2015: ART coverage in eastern and southern Africa was 53% [43–60%] Zambia

“Ending AIDS: Progress Towards the 90-90-90 Targets” – Released July 2017

UNAIDS, Global AIDS Update, 2017