HIV: HISTORYCURRENT STATUS AND FUTURE

John G. BartlettJohns Hopkins University

School of Medicine

Conflicts -- None

HIV REVIEW

HistoryCurrent standards

Future

HIV NATURAL HISTORY

HIV transmission↓ 2- 4 weeks

Acute HIV (50 – 90 %)↓ 1- 3 weeks

Asymptomatic ↓ 8 years

AIDS ↓ 1.3 yearsDeath

HIV RISK CATEGORIES (2010)CDC data – 48,298 cases

MSM (gay men) – 63%Injection drug use – 8%Heterosexual transmission – 25% Blood transfusions – 0% Perinatal transmission – (162)African American – 44%Poverty – 2.1% (8 x ↑)

HIV: HISTORY 1981-2013

1981: PCP Cluster 1994: ACTG 0761982: “AIDS”named 1996: Vancouver IAS – “HAART”1983: HIV reported 1997: FDA accepts Viral Load as

end point1985: Serologic test 2003: PEPFAR born1986: AZT trial 2008: First cure1987: Act-up 2012: Prevention and cure1990: Ryan White Act 2013: “AIDS-free generation” –

Hilary Clinton1991: Magic Johnson

CDC: MMWR June 5, 1981 9 MSM with PCP

CDC: MMWR July 3, 1981

HIV/AIDS – FIRST DECADE

HIV: Circa 1981-91Patients: Most died• Diarrhea• Dementia• Disgrace• Image: IDU & MSM• Fear: Contagion• Untreatable

WHO WINNING PHOTO AWARD:AIDS – THE HUMAN TRAGEDY

ID/IMMUNOLOGY:Wegener disease & polyarteritis

nodosa; Director of NIAID

Anthony Fauci“Goose pimples” 1981

1984 Ryan WhiteChild with hemophilia –

HIV discovered 12/17/84 – banned from school and given 6 month diagnosis. Died 5 years later, 4 months before passage of the Ryan White Care Act – now $2 billion/year for HIV drugs for 500,000. Bono – “Greatest man I ever met”

C. Everett Koop“The Letter” 1987

Surgeon General under President Reagan

Champion of – Sex educationCondomsHandicapped childrenCigarette harm“The Letter” was an AIDS

wakeup call

AIDS QUILT – 1987

Panel are 3’ by 6’ with tributes to people who were lost to HIV → Washington Mall 1987-1996, weight = 54 tons, 94,000 names (20%)

AIDS COALITION to UNLEASH POWER: 1987

Civil disobedience: Wall Street 1987, NY Post Office 1987, St. Patrick’s Cathedral

1989, NIH 1990 (Now TAG)

Martin DelaneyActivist (without AIDS)

1945-2008

Founded Project Inform “for medically supervised guerrilla trials” – Major force in NIAID, FDA and

ethics

The Trial: AZT vs. placebo (n=282). DSMB stopped study: 19 deaths (placebo) vs. 1 (AZT)

(Fischl MA. NEJM 1987;317:185)

Jeff Murray, MDDeputy Director

Division of Antimicrobial Drug Products for FDA

Major facilitator of HIV drugs (n=28) and, more recently HCV (#24 in trials)

MAGIC JOHNSONThe Announcement: 1991

“I have AIDS”(Trumped efforts of millions to destigmatize HIV

infection)

PROTEASE 1996

The development of protease inhibitors and beginning of HAART

■ IDV / 3TC / AZT

● IDV

∆ AZT / 3TC

THE STUDY THAT CHANGED AIDSGulick RM. Merck 035 NEJM 1997;337:734

HAART: IDV/AZT/3TCResults for NDV at 52 weeks – 80% vs. zero

David Ho

“Hit hard and hit early” …Time Magazine: Man-of-the-year, 1996

Mortality From 1990-2004 in the Johns Hopkins HIV Clinical Cohort

Lau B, et al. Non-AIDS Related Mortality Risk Exceeds AIDS-related Mortality Among Injecting Drug Users with CD4+ Counts Above 200 Cells/mm3. CROI Denver, CO, 2006

NRTI NNRTI PI El CCR5 II1987 AZT ------ ------ ------ ------

------1991-92 ddI, ddC ------ ------ ------ ------ ------1995 d4T ------ ------ ------ ------

------1996 3TC ------ SQV ------ ------ ------1997 ------ NVP RTV, IDV ------ ------

------1997 ------ DLV NFV ------ ------ ------1998 ------ EFV ------ ------ ------

------1999 ABC ------ APV ------ ------

------2000 ------ ------ LPV ------ ------

------2001 TDF ------ ------ ------ ------

------2003 FTC ------ ATV ENF ------

------2005 ------ ------ TPV ------ ------

------2006 ------ ------ DRV ------ ------

------2007 ------ ------ ------ ------ MVC

RAL2008 ------ ETR ------ ------ ------

------2011 ------ RPV ------ ------ ------

------2012 ------ ------ ------ ------ ------

EVG2013 ------ ------ ------ ------ ------

DTG

HIV SCIENCE AND CARE1996-2013

US & Europe (“Resource Rich”)1. Fine tuning 1996-now2. Treatment “done” – 2008 (Fauci)3. New priorities:

• International• Domestic: Cure & Prevention

International (“Low Resource”)4. Resource limits: Drugs5. Infrastructure for chronic care6. WHO – Plan universal ART when

resources allow

President Bill ClintonState of the Union Speech: 2000

“AIDS in Africa is so devastating – it threatens the social, political and economic stability of the world”

↓ Clinton Foundation (2001) • Low cost drugs • Pediatric HIV

Subsaharan Africa:12% global population

69% of HIV cases

CLINTON FOUNDATION 2002-

2002 2012

Art:Cost/yr $12,000 $100-200

No. on ART 20,000 6,000,000

President George W. BushPEPFAR: 2002

Bush: Do those HIV drugs work?

O’Neil: “Let me tell you about my morning in the Moore Clinic”

Bush: “Tony , we need to do something, Think big – really big”

President George W. Bush

Fauci: “Thinking big”Collaborators –

M. Dybul,P. Mugyeni, E. Goosby, J.W. Pape

Plan Proposed: Would be considered

January 2003: “Seldom have we been offered the opportunity to do so much for so many”

Peter Mugyeni and Laura BushState of the Union Address

Bush: “$15 billion for Africa”Mugyeni: Jumped up → cheered →

hugged the First Lady

Bono: “PEPFAR – Greatest act of heroism since we jumped into WWII” NYTimes 12/1/11

Need to put banner Prominent Voices to Address AIDS 2012

Leaders from the worlds of science, diplomacy, politics, philanthropy and entertainment are speaking at AIDS 2012, including: 

•  President Bill Clinton • U.S. Secretary of State Hillary Rodham Clinton • U.S. Secretary of Health and Human Services Kathleen Sebelius • South African Deputy President Kgalema Motlanthe • Former U.S. First Lady Laura Bush • HRH Mette-Marit, Crown Princess of Norway • World Bank President Jim Yong Kim • UNAIDS Executive Director Michel Sidibé • Nobel Laureate Françoise Barré-Sinoussi • NIAID Director Anthony Fauci • Philanthropist Bill Gates • Humanitarian Elton John • Actress Whoopi Goldberg

Hillary Rodham Clinton2012 IAS Conference – Washington DC

“Blueprint for an AIDS-free generation”

HIV REVIEW

HistoryCurrent standards

Future

HIV TREATMENT (DHHS & IAS-USA)

Test: All persons age 13-64 yrs yrs(CDC); annual if risk

Treat: Everybody with HIVWhat: TDF/FTC or ABC/3TC plus

EFV, DRV/r, ATV/r, RALMonitor: VL, CD4, etc.Change: VL >200 or ADR

LIFE EXPECTANCY – DENMARKHelleberg M. CID 2012 [in press]

35 year old man HIVHIV Smokes Survivalo o 78.4 yrs+ o 73.3 yrso + 66.1 yrs+ + 62.6 yrs

HIV CARE AND RESEARCH1983-1996 2005-2013

Care: OIs, PCP, CMV, MAC, KS, Crypto

Care: CVD, Lipids, DM, HBP, Bones

Neuro: Dementia, Neuropathy Neuro: Dementia

Psych: Depression Psych: Variable

Patients: Stigma Patients: Same

Provider: Burn-out Provider: Is it a specialty?

Research: Vaccine and Treatment Research: Immune activa- tion, prevention

HIV REVIEW

HistoryCurrent standards

Future

HIV: THE FUTURE (US)

Research priorities• Treatment – done (2008)• Prevention• CureOperational challenges• Care delivery: 28% have controlled HIV

viremia• Who will be primary provider (Is this a

specialty• Healthcare reform

TransmissionHIV transmission efficiency correlates with Viral Load – No transmissions with VL <1500 c/mL (2000)

Transmission efficiency• 1/900 coital acts• M→F & F→M near equal• Maximum risk in primary HIV

Treatment for prevention• HPTN 052 (2012)• Changed Global policy

Never been a confirmed case with sexual transmission (BMHIVA) (2013)

Quinn T. NEJM 2000;342:921

HIV TREATMENT FOR PREVENTION:HPTN 052 M. Cohen (PI)

(Cohen MS. NEJM 2011;365:493)

Protocol: Discordant couples, CD4 350-550: Randomized to ART vs. no ART until CD4 <250

Results: N=1,763 (M=890, F-873)ART No Artn=886 n=877

HIV transmission* 1*** 27** *Linked cases (28 transmissions unlinked) **Protection with ART = 96% -- Study continues to determine durability***Single exception preceded viral suppression

HPTN 052: The study that changed HIV global strategy

Treatment as Prevention: Effect of ART Coverage on HIV Incidence in Rural South Africa(Tanser F. 2012 CROI;Abstr. 136LV)

• Annual population based HIV surveillance in rural KwaZulu-Natal• 2004 – 2011: 1395 HIV seroconversions among 16,588 HIV negative

adults ≥15 years of ageAdjusted HIV Infection Rate by ARV

Coverage CategorySpatial Estimates of Proportion of HIV

Patients on ART

P=0.590

P=0.002

P<0.001 P=0.015

2007 2008 2009

2010 2011

<10%

10-20%

20-30%

30-40%

>40%

Tanser F, et al. 19th CROI; Seattle, WA; March 5-8, 2012. Abst. 136LB.

Efficacy of Daily OralFTC/TDF PrEP

Trial Pop. Efficacy 95% CI

iPrEx MSM 42% 18 to 60%

Partners PrEP Men 83% 49 to 94%

Women 62% 19 to 82%

TDF2 Men 80% 25 to 97%

FemPrep* Women 49% -22 to 81%

VOICES* women TDF only arm discontinued

Candidates: High risk MSM and discordant couplesFDA approved TDF/FTC for PrEP July 2012 .

“The Berlin Patient”

• HIV + leukemia → chemotherapy and stem cell tx → 5 yrs; No HIV detected (R. Siliciano)

• 2012: 2 more patients – Brigham Hospital, Boston(IAS Conference 2012)

The “Gardner Cascade”(Gardner EM. CID 2011;52:793)

Estimated 14% have viral suppression!!

MAKE IT EASYSensitivity: 93%• Specificity: 99.8%• Distribution:

Walmart, CVS, Walgreens, RiteAid, Kroger, etc.

P4P4P: THE STATUS OF PAYING PATIENTS FOR SELF CARE

Practice: Widespread and internationalIncentives: Cash, groceries, lottery tickets, meal

tickets.Conditions: Chronic – smoking, obesity , BP

control, diabetes, HIVHIV trial: HPTN 65 – Controlled trial, (unblinded)

HIV test – $25, Enroll in care – $70, NDV – $280/yr (1.7% of HIV care cost)

Status: Widely practiced, no one wants to talk about it. Adherence guidelines refused (Ann Intern Med 2012;156:817)

A TEST OF FINANCIAL INCENTIVES TO IMPROVE WARFARIN ADHERENCE

(Volpp KG. BMC Health Sys Res 2008;8:272)

COST OF CAREContemporary costs/yr.(AIDS 2010;24:2705)• HAART – $12,000 (72%)• Meds – other – $2,100• In-patient – $600• Out-patient – $400 (2%)Total (Meds) – $16,600Generic 3TC/EFV +TDF: Reduce cost

$6K/yr=$1B – BUT 3 pills/d(Walensky R. Ann Intern Med 2013;158:84)

HIV WITH 2013 HEALTHCARE REFORM

SUMMARYHistory: GloriousFailure: Vaccine and cureChallenge: Care delivery, prevention

and costFuture: Who will provide HIV care and

who will payExpectation: Diabetes model