Briefing on the American AIDS Briefing on the American AIDS EpidemicEpidemic

Innovations in HIV TreatmentInnovations in HIV TreatmentMay 28, 2009May 28, 2009

Mark Feinberg, MD, PhDMark Feinberg, MD, PhDMerck Vaccines and Infectious Merck Vaccines and Infectious

DiseasesDiseases

22

Key MessagesKey MessagesMore potent, better tolerated and simpler More potent, better tolerated and simpler treatments have transformed HIV infection from treatments have transformed HIV infection from a commonly fatal to a chronic conditiona commonly fatal to a chronic condition

New treatments will need to be continually New treatments will need to be continually developeddeveloped

Earlier treatment of infected individuals saves Earlier treatment of infected individuals saves lives and treatment may decrease the risk of HIV lives and treatment may decrease the risk of HIV spreadspread

However- However- not all HIV-infected people receive the not all HIV-infected people receive the benefits of early diagnosis and improved carebenefits of early diagnosis and improved care

We need to plan for increased numbers of We need to plan for increased numbers of people being treated for and living with HIV people being treated for and living with HIV infectioninfection

33

Factors affecting HIV treatment Factors affecting HIV treatment successsuccess

Drug potencyDrug potency

Genetic barrier to resistanceGenetic barrier to resistance

Targeting multiple stages in the virus Targeting multiple stages in the virus life cyclelife cycle

Drug tolerabilityDrug tolerability

Drug regimen simplicityDrug regimen simplicity

44

Development of HIV therapies targeting several steps in the HIV life cycle

•Over 30 drugs total in 6 different classes• Combinations therapies suppress but do not eradicate HIV infection

Integration

Protease

55

Trends in Annual HIV Death Rates and Benefit of Combination Antiretroviral Therapy

Introduction of combination therapy

66

Improvements in HIV TherapiesImprovements in HIV Therapies

2010200019901980

Current TherapyCurrent Therapy–More choices (drug More choices (drug

classes)classes)–More potentMore potent– Improved tolerabilityImproved tolerability–Fewer toxicitiesFewer toxicities–Smaller pill burdensSmaller pill burdens

Earlier TherapyEarlier Therapy–Limited treatment Limited treatment

options of variable options of variable potencypotency

–Considerable side Considerable side effectseffects

–ToxicitiesToxicities–Large pill burdensLarge pill burdens

AZT

77

Regimen Simplification:Regimen Simplification:From Individual Agents to CombinationsFrom Individual Agents to Combinations

+

+==

=

ABC

TDF

ZDV3TC

FTCFTC

++EFV

+ =LPVLPV RTVRTV

TDF FTC

Fixed-dose combinations

ZDV/3TC

ABC/3TC

TDF/FTC

EFV/EFV/TDF/TDF/FTCFTC

LPV/RTV

Individual Agents

88

Simpler, better tolerated & very effective therapies Simpler, better tolerated & very effective therapies have transformed HIV to a manageable chronic have transformed HIV to a manageable chronic

condition (for those with access to care)condition (for those with access to care)

2010200019901980

99

Individuals with multi-Individuals with multi-drug resistant viruses drug resistant viruses will need new drugs will need new drugs with with novel mechanismsnovel mechanisms of actionof action

There is also a need There is also a need for:for:–more therapies with more therapies with

fewer side effects & fewer side effects & fewer drug-drug fewer drug-drug interactionsinteractions

– longer-acting longer-acting formulations with even formulations with even simpler dosingsimpler dosing

New treatments will need to be New treatments will need to be continually developedcontinually developed

1010

Earlier treatment appears to be Earlier treatment appears to be associated with a lower risk of deathassociated with a lower risk of death

0

10

20

30

40

50

60

70

80

90

100

>500 <500

% IncreasedRisk of Death

Recent data:Recent data:Deferral of treatment to Deferral of treatment to CD4<500 is associated with a CD4<500 is associated with a 94% increased risk of death94% increased risk of deathKitahata et al, New Engl J Med. 2009.Kitahata et al, New Engl J Med. 2009.

CD4 count at therapy initiation

Current GuidelinesCurrent Guidelines reflect a balance between reflect a balance between the demonstrated benefits the demonstrated benefits and potential adverse and potential adverse effects of therapy. effects of therapy.

DHHSDHHS (11/08) (11/08)Initiate therapy in patients Initiate therapy in patients with with CD4<350CD4<350 or with history or with history of AIDS.of AIDS.

IASIAS (9/08) (9/08)Therapy recommended for Therapy recommended for symptomatic HIV disease or symptomatic HIV disease or for asymptomatic disease for asymptomatic disease with with CD4<350CD4<350..

1111

HIV

RN

A L

eve

lH

IV R

NA

Le

vel Risk of sexual transmission

1/30-1/200

Acute Infection

Asymptomatic

Infection

AIDS

1/1000-1/10,000

1/100-1/1000

Treatment is hypothesized to be associated Treatment is hypothesized to be associated with a decreased risk of HIV transmissionwith a decreased risk of HIV transmission

HIV transmission is associated with the level of viremia in an infected personHIV transmission is associated with the level of viremia in an infected person

By reducing viremia, HIV treatment may lead to a decreased risk of By reducing viremia, HIV treatment may lead to a decreased risk of transmission*transmission*

*CDC Expert Consult on Effect of Antiretroviral Therapy *CDC Expert Consult on Effect of Antiretroviral Therapy on Risk of Sexual Transmission of HIV Infection, Oct. on Risk of Sexual Transmission of HIV Infection, Oct.

20082008

1212

The need to identifyThe need to identifymore HIV-infected people more HIV-infected people earlierearlier

1.2 million infected1.2 million infected– over 25% of new infections over 25% of new infections

are in womenare in women

Half receive late diagnosisHalf receive late diagnosis– miss life-extending benefits miss life-extending benefits

of therapyof therapy

20-50% of infected 20-50% of infected individuals are unaware individuals are unaware of their infectionof their infection– these individuals are these individuals are

estimated to lead to 75% of estimated to lead to 75% of new infectionsnew infections

56,300 new infections/yr

1313

The Challenge of Universal HIV The Challenge of Universal HIV Diagnosis and TreatmentDiagnosis and Treatment

Routine opt-out HIV screening is now Routine opt-out HIV screening is now recommended for all individuals 13-64 yrs recommended for all individuals 13-64 yrs (CDC, ACP)(CDC, ACP)– routine screening removes the stigma routine screening removes the stigma

associated with risk-based testing associated with risk-based testing – cost-effectivecost-effective

However-However-– Slow uptake of the new testing Slow uptake of the new testing

recommendationsrecommendations– Recommendations will only be effective with Recommendations will only be effective with

routine access to health care for allroutine access to health care for all

1414

Enabling Access and Benefits of Enabling Access and Benefits of HIV Therapy Moving ForwardHIV Therapy Moving Forward

Early diagnosisEarly diagnosis

Ready access to informed health care Ready access to informed health care providersproviders

Access to most effective antiretroviral therapiesAccess to most effective antiretroviral therapies

Drug regimen simplicity and tolerabilityDrug regimen simplicity and tolerability

Availability of essential supportive services Availability of essential supportive services (e.g. mental health, substance abuse (e.g. mental health, substance abuse treatment)treatment)

Continuing innovation in HIV care and Continuing innovation in HIV care and treatmenttreatment

1515

0

17,000

34,000

51,000

68,000

85,000

1985 1987 1989 1991 1993 1995 1997 1999 2001 2003

0

140,000

280,000

420,000

New AIDS Cases

People Living with AIDS

New AIDS Cases, Deaths, and New AIDS Cases, Deaths, and People Living with AIDSPeople Living with AIDS in the U.S. in the U.S.

Deaths among People with AIDS

Note: Data are estimates.Source: CDC, Data Request, 2006.

Dea

ths

and

New

AID

S D

iag

no

ses

Peo

ple L

iving

with

AID

S

2004

1616

With effective treatment, more With effective treatment, more people will be living with HIVpeople will be living with HIV

• HIV diagnosis, care and HIV diagnosis, care and treatment programs treatment programs need to be adequately need to be adequately funded to ensure the funded to ensure the greatest individual and greatest individual and public health benefit.public health benefit.

• Progress in preventing Progress in preventing HIV infection will be HIV infection will be essential for long-term essential for long-term success.success.

1717

Thank you for your interest, Thank you for your interest, commitment and efforts!commitment and efforts!