twenty years of antiretroviral therapy: lessons learned and unmet needs benjamin young, md phd rose...

Twenty Years of Antiretroviral Therapy:Lessons Learned and Unmet Needs

Benjamin Young, MD PhD

Rose Medical Center

Division of General Internal Medicine

University of Colorado Denver and Health Sciences Center

Denver, Colorado

Overview

Evolution in antiretroviral therapies Changing complexion of HIV epidemic New antiretrovirals Unmet needs

Denver, Colorado

~2.5 million pop. ~8700 HIV/AIDS

Majority MSM Majority white 3000 deaths

Monarch pass, Colorado

Russia

26 years of the 26 years of the EpidemicEpidemic26 years of the 26 years of the EpidemicEpidemic

HIV/AIDS is one of the most formidable public health and HIV/AIDS is one of the most formidable public health and scientific challenges ever confrontedscientific challenges ever confronted

In just two decades, remarkable advances have been made in In just two decades, remarkable advances have been made in the fight against AIDS, but the toll has been staggeringthe fight against AIDS, but the toll has been staggering

1985:1985:– 0 drugs0 drugs– Little known about HIV Little known about HIV

mechanism of actionmechanism of action– Little support for HIV patientsLittle support for HIV patients

who need access to treatmentwho need access to treatment– 16,000 U.S. AIDS cases 16,000 U.S. AIDS cases

reported; 20,000 globallyreported; 20,000 globally

2007:2007:– 27 therapies; 4 drug classes, 2 classes in early 27 therapies; 4 drug classes, 2 classes in early

accessaccess– Major advance in knowledge about Major advance in knowledge about

viral lifecycleviral lifecycle– Network of federal and local Network of federal and local

programsprograms– Over one million people with HIV in U.S.; Over one million people with HIV in U.S.;

38 million worldwide38 million worldwide

Note: U.S. HIV/AIDS statistics from CDC;global statistics from WHO (1985), UNAIDS (2005)

Let’s Go Back to Let’s Go Back to 19951995

1995-1997: 1995-1997: Hope for the First TimeHope for the First Time 1995 1st PI (saquinavir) approved1995 1st PI (saquinavir) approved 1996 1996

First reports of ritonavir extending lifeFirst reports of ritonavir extending life Greeted with skepticism at CROIGreeted with skepticism at CROI

RTV, IDV approved RTV, IDV approved NNRTI (nevirapine) approved by FDA NNRTI (nevirapine) approved by FDA Mortality declinesMortality declines

““Highly Active Antiretroviral Therapy”Highly Active Antiretroviral Therapy” Transformed lives of PWAsTransformed lives of PWAs

- Health improvesHealth improves

- Many return to workMany return to work

QuickTime™ and aTIFF (Uncompressed) decompressor

are needed to see this picture.

HOPS: Mortality and HAART Use Over Time Updated 2Q2004

0

2

4

6

8

10

12

14

1994Q2 1995Q2 1996Q2 1997Q2 1998Q2 1999Q2 2000Q2 2001Q2 2002Q2 2003Q2

Quarter

Deaths per 100 person-years

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

% of Patients on HAART

Deaths per 100 Person Years% Patients on HAART

HOPS: Opportunistic Infections (patients with CD4 < 100)

0

5

10

15

20

25

1994Q21995Q21996Q21997Q21998Q21999Q22000Q22001Q22002Q22003Q2

Quarter

Infections/100 person-years

CMV RetinitisMACPCP

AIDS in Colorado: Survival by year of diagnosis

0102030405060708090

100

1987 1990 1993 1996 1999 2002 2005

PercentLiving

*CDPHE 2006

Initial Problems with ART

Tolerability High pill burden Diet restrictions

Adherence Short term toxicity

Neuropathy, Pancreatitis Long-term toxicity

Lipodystrophy Cardiovascular disease

New Ideas 1997-2001New Ideas 1997-2001

New strategies come and goNew strategies come and go MegaHAARTMegaHAART

Hydroxyurea/ddIHydroxyurea/ddI

IntensificationIntensification

New laboratory tests bring new insights, but more New laboratory tests bring new insights, but more complicated decisionscomplicated decisions Viral loadViral load

Resistance testingResistance testing

New and investigational therapies offer hopeNew and investigational therapies offer hope

- Sustained efficacySustained efficacy

- Improved tolerabilityImproved tolerability

- Convenience, simplificationConvenience, simplification

Dosing Daily pill burden IssuesRegimen

1998ZDV/3TC/efavirenz

5 pills, BID

• Gastrointestinal (GI) effects, anemia, neutropenia

• Central nervous system (CNS) toxicities

• Mitochondrial-related toxicities

1996

d4T/3TC/indinavir

10 pills, TID

• Food restrictions, liquids frequently

• Poor tolerability • Short- and long-term toxicities

2002

3 pills, BIDZDV/3TC/EFV

• Gastrointestinal (GI) effects, anemia, neutropenia

• Central nervous system (CNS) toxicities

• Mitochondrial-related toxicities

Toward “Simpler” ART Regimens

Toward “Simpler” ART Regimens

Dosing Daily pill burden Issues

2006

1 pill QDMinimal to no side effects, good

PK, and no food restrictions without compromising efficacy

2003

3 pills, QDGenerally well tolerated; GI effects, CNS effects (EFV)

TDF/ [FTC or 3TC] / EFV

2005

2 pills QDMinimal to no side effects, good

PK, and no food restrictions without compromising efficacy

Regimen

FDC NRTI +EFV

TDF/FTC/EFV

Antiretrovirals: 2007

Individualized treatment Host factors

Genetics (pharmacogenomics) Side effect aversion Adherence

Viral factors Genetics (resistance)


Treatment permutations: 27 medications, 3 drug regimens 27 x 26 x 25= 17550 potential combinations

How do we construct HAART regimens?


Rise of evidence-based medicine Prospective clinical trials of defined regimens “Expert” opinion Treatment guidelines

DHHS IAS-USA WHO

2006 IAS-USA Guidelines

Recommended Components of Initial Antiretroviral Therapy*

NRTIs NNRTIs PIs

TDF/FTC† EFV LPV/RTV

ZDV/3TC‡ (NVP) ATV/RTV

ABC/3TC‡ FPV/RTV

SQV/RTV

*Therapy should consist of 2 NRTIs + either an NNRTI or PI.†Or 3TC. ‡Or FTC.

Hammer S, et al. JAMA. 2006;296:827-843.


Many permutations of treatment combinations: IAS-USA: 6 NNRTI+12 PI

Cautionary tales… Studies sometimes challenge conventional

view:Early virologic failure of TDF/3TC/NVP qd

(Daufin Study)1

Increased risk of lipoatrophy of efavirenz (ACTG 5142)2

1Rey D et al., 14th CROI, 2007, 2Haubrich R et al., 14th CROI, 2007

Trends in HIV Epidemiology

Thinking Globally…

06/06 e 5

Estimated number of adults and childrennewly infected with HIV, 2005

Total: 4.1 (3.4 – 6.2) million

Western &Central Europe

22 00022 000[18 000 [18 000 –– 33 000] 33 000]

North Africa & Middle East64 00064 000

[38 000 [38 000 –– 210 000] 210 000]

Sub-Saharan Africa2.7 million2.7 million

[2.3 [2.3 –– 3.1 million] 3.1 million]

Eastern Europe& Central Asia

220 000220 000[150 000[150 000–– 650 000] 650 000]

South & South-East Asia830 000830 000[530 000 [530 000 –– 2.3 million] 2.3 million]

Oceania72007200

[3500 [3500 –– 55 000] 55 000]

North America43 00043 000

[34 000 [34 000 –– 65 000] 65 000]

Caribbean37 00037 000

[26 000 [26 000 –– 54 000] 54 000]

Latin America140 000140 000

[100 000 [100 000 –– 420 000] 420 000]

East Asia97 00097 000

[55 000 [55 000 –– 290 000] 290 000]

06/06 e 6

Estimated adult and child deaths from AIDS, 2005

Total: 2.8 (2.4 – 3.3) million


12 00012 000[<15 000][<15 000]


[20 000 [20 000 –– 62 000] 62 000]


[1.7 [1.7 –– 2.3 million] 2.3 million]


53 00053 000[36 000 [36 000 –– 75 000] 75 000]

South & South-East Asia560 000560 000[370 000 [370 000 –– 810 000] 810 000]

Oceania34003400

[1900 [1900 –– 5500] 5500]

North America18 00018 000

[11 000 [11 000 –– 26 000] 26 000]

Caribbean27 00027 000

[19 000 [19 000 –– 36 000] 36 000]

Latin America59 00059 000

[47 000 [47 000 –– 76 000] 76 000]

East Asia33 00033 000

[20 000 [20 000 –– 49 000] 49 000]

06/06 e 11

• Children living with HIV 2.3 million [1.7 – 3.5 million]

• New HIV infections in 2005 540 000 [420 000 – 670 000]

• Deaths due to AIDS in 2005 380 000 [290 000 – 500 000]

2005 global HIV and AIDS estimatesChildren (<15 years)

The Global PandemicThe Global Pandemic

38 million dead38 million dead By 2010 75 million infectedBy 2010 75 million infected By 2025, 83 million dead, 89 By 2025, 83 million dead, 89

million infectionsmillion infections Life expectancy in 9 African Life expectancy in 9 African

countries is already <40 yearscountries is already <40 years

06/06 e

2006 Report on the global AIDS epidemicFig

Impact of AIDS on life expectancy in five African countries, 1970Impact of AIDS on life expectancy in five African countries, 1970 ––20102010

Life expectancy at birth (years)

Source: United Nations Population Division (2004). World Population Prospects: The 2004 Revision, database.

Botswana

South Africa

Swaziland

Zambia

Zimbabwe

1970–1975 1975–1980

1980–19851985–1990

1990–19951995–2000

2000–20052005–2010

70

65

60

55

50

45

40

35

30

25

20

4.1

06/06 e 4

Adults and children estimated to be living with HIV, 2005

Total: 38.6 (33.4 – 46.0) million


720 000720 000[550 000 [550 000 –– 950 000] 950 000]


[250 000 [250 000 –– 720 000] 720 000]


[21.6 [21.6 –– 27.4 million] 27.4 million]


1.5 million1.5 million[1.0 [1.0 –– 2.3 million] 2.3 million]

South & South-East Asia7.6 million7.6 million[5.1 [5.1 –– 11.7 million] 11.7 million]

Oceania78 00078 000

[48 000 [48 000 –– 170 000] 170 000]

North America1.3 million1.3 million

[770 000 [770 000 –– 2.1 million] 2.1 million]

Caribbean330 000330 000

[240 000 [240 000 –– 420 000] 420 000]

Latin America1.6 million1.6 million

[1.2 [1.2 –– 2.4 million] 2.4 million]

East Asia680 000680 000

[420 000 [420 000 –– 1.1 million] 1.1 million]

AIDS in Russia

HIV/AIDS in Russia

30,000 cases in Saint Petersburg 800 on ART ~350 HIV+ pregnancies/year

35,000 cases in Moscow 2500 on ART ~400 HIV+pregnancies/year

High frequency of HIV/TB coinfection Issues of IRIS, drug-drug interactions

HIV/AIDS in Russia

1.5 million cases (148 million population) ~3 times US case rate

Fastest growing epidemic in world ~20-25% per year

Injection drug use : heterosexual 30,000 cases in Saint Petersburg

800 on ART 35,000 cases in Moscow

2500 on ART

HIV in Russian Street Children

Survey of street children of Saint Petersburg (age 15-19)

117/313 (34.9%) HIV infected Subgroups with >60% seroprevalence:

Double orphans Homeless Previous STI Current injection or inhaled drug use Current needle sharing

D Kissin, et.al., 14th CROI 2007 #688

US policy issues

Changing racial and geographic characteristics Delayed diagnosis Clinical outcomes

Ineffective prevention strategies Many HIV+ don’t know status

Role of routine HIV testing Access to care not guaranteed

ADAP waitlists in 6 states ART pricing subject of state and federal investigation

HIV Trends in Colorado

*CDPHE 2004

0

5

10

15

20

25

30

Rate per 100,000

White Black Hispanic

Race

HIV Case Rates 2001-2002

Female

Male

HIV rates among Black men and women are greater than among Whites and Hispanics

Delay in HIV/AIDS diagnosis

Many recently diagnosed HIV+ persons rapidly progress to AIDS Results in higher risk of complications Higher healthcare costs Higher disease burden

41.7% of Colorado HIV+ develop AIDS within 12 months of diagnosis*

*CDPHE 1999-2003

Future trends in HIV therapies?

Future trends in HIV treatment

Pharmacogenetics How will genetic screening affect HIV disease

management? Viral factors Host factors

New drug classes: How will new drugs change combination ART

therapy? CCR5 Inhibitors HIV integrase inhibitors

Pharmacogenetics and HIV

Viral factors Drug resistance Co-receptor tropism

Host factors CCR532 and susceptibility to infection HLA B*5701 and abacavir HSR MDR1 and immunological response to HAART Cytochrome P450 and plasma drug levels UGT1A1*28 and hyperbilirubinemia

Viral genetics in treatments: Viral genetics in treatments: resistance testingresistance testing

HIV drug resistance HIV drug resistance testing recommended testing recommended for management HIV-for management HIV-infected personsinfected persons11

Drug resistance testing Drug resistance testing associated with associated with improved survivalimproved survival22

11DHHS Treatment Guidelines, October 2006DHHS Treatment Guidelines, October 200622Palella et al., 14th CROI, 2007Palella et al., 14th CROI, 2007

Naive to HAART, baseline CD4 < 200: Cox PH multivariate analysis of factors associated with

mortality (N = 257)2

2.09

0.73

0.70

0.56

0.45

0.29

0.22

0.01 0.10 1.00 10.00

HIV Susceptibility Test

IDU

Baseline log viral load ≥ 4

Private health insurance

white race

age > 40

Baseline CD4 0-49

Mortality Hazard Ratio

0.0

0.05

0.10

0.15

0.20

1998/1999 2000/2001 2002/2003 2004 to 7/2005

Possible Abacavir-related symptoms, number ofpatients(including definitive ABC-HSR)

Abacavir HSR, number of patients # 2 pts results not reviewed prior

therapy $ 1 pt with informed choice/

incomplete haplotype

Pro

port

ion

of A

BC

-naï

ve p

atie

nts

disc

ontin

uing

AB

C w

ithin

6 w

eeks

n=68 n=131 n=107 n=60

#

Before genetic screening After genetic screening

#$

*P<0.05

Host Genetics in HIV Treatment:Host Genetics in HIV Treatment:Effect of Effect of HLAB*5701 ScreeningHLAB*5701 Screening

Rauch, et al. Clin Infect Dis 2006;43:99-102.

Pharmacogenomics: Pharmacogenomics: HLA pre-screening and abacavir HSRHLA pre-screening and abacavir HSR

Association between Association between HLA B*5701HLA B*5701 allele and risk of allele and risk of abacavir hypersensitivity reactionabacavir hypersensitivity reaction

Western Australia cohortWestern Australia cohort11::– Decreased suspected abacavir HSRDecreased suspected abacavir HSR

– Decreased abacavir all-cause discontinuationsDecreased abacavir all-cause discontinuations

Paris cohortParis cohort22::– 131 consecutive 131 consecutive B*5701B*5701 negative patients started ABC negative patients started ABC

– No cases of HSRNo cases of HSR

– 1 discontinuation 1 discontinuation

1Rauch, et al., Clin Inf Disease 20062Zucman, et al., JAIDS 2007

Unmet Needs of Current Antiretrovirals

1. Bennett D, et al. CROI 2002. Abstract 372-M. 2. Bennett D, et al. CROI 2005. Abstract 674. 3. Richman D, et al. AIDS. 2004,18:1393-1401.

Access to care

– Cost

– Distribution

– Intellectual property

Drug Resistance

– Transmitted drug resistance occurs in 5% to 15% of patients[1,2]

– Multiclass resistance in large proportion of highly treatment–experienced patients[3]

Unmet Needs of Current Antiretrovirals Toxicity/tolerability issues with current classes

– Cardiovascular: dyslipidemia, insulin resistance

– Lipodystrophy, lipoatrophy

– Other: bone, hematologic, renal, CNS, reproductive

Drug-drug interactions

– Rifamycins

– Methadone

clinicaloptions.com/hiv

Novel Antiretrovirals in Clinical Development

TNX-355CCR5 inhibitorsCXCR4 inhibitors

Maturation InhibitorsBevirimat

Raltegravir Elvitegravir

Entry inhibitors

Reverse transcriptase

inhibitors

Maturevirus

PIsIntegrase inhibitors


MOTIVATE: Maraviroc in Treatment-Experienced Patients With R5 Virus

Nelson M, et al. CROI 2007. Abstract 104aLB. Lalezari J, et al. CROI 2007. Abstract 104bLB.

*Patients receiving PI (other than TPV) or DLV received 150 mg; all others received 300 mg. †OBR: 3-6 ARVs.

Patients with R5 HIV-1; ≥ 5000 copies/mL; stable ART or

no ART for ≥ 4 weeks;resistance to and/or ≥ 6 months

of ≥ 1 antiretroviral from 3 classes or ≥ 2 PIs

MOTIVATE 1 (N = 601) (Canada, US)MOTIVATE 2 (N = 475)(Europe, Australia, US)

Placebo + OBR†

Maraviroc 150 mg or 300 mg* once daily + OBR†

Maraviroc 150 mg or 300 mg* twice daily + OBR†

2:2:1 randomization;stratified by ENF use and VL

Planned interim analysis:Week 24: Week 48

Randomized, double-blind, placebo-controlled, parallel phase IIb/III studies 44% failed screening with X4 or dual/mixed virus detected Primary endpoint: mean change in VL at Week 24 Baseline characteristics similar across treatment arms in the 2 studies

clinicaloptions.com/hivNelson M, et al. CROI 2007. Abstract 104aLB. Lalezari J, et al. CROI 2007. Abstract 104bLB.

MOTIVATE 1 and 2: VL < 400 copies/mL (ITT, NC = F)

61.3%55.5%

23.1%

P < .0001*

P < .0001*

60.4%54.7%

31.4%

P < .0001*

P < .0001*

Placebo + OBR (n = 209) MVC QD + OBR (n = 414)

MOTIVATE 1 MOTIVATE 2

MVC BID + OBR (n = 426)

*P values vs placebo at Week 24.

Pat

ien

ts (

%)

20

10

0

30

40

50

60

70

80

90

100

16 20 240 4 8 12Time (Weeks)

2 6 10 14 18 22 16 20 240 4 8 12Time (Weeks)

2 6 10 14 18 22

Pat

ien

ts (

%)

20

10

0

30

40

50

60

70

80

90

100


MOTIVATE 1 and 2: Adverse Events and Resistance

Nelson M, et al. CROI 2007. Abstract 104aLB. Lalezari J, et al. CROI 2007. Abstract 104bLB.

Similar incidence of adverse events in maraviroc and placebo arms

– Similar low incidence of hepatotoxicity in maraviroc and placebo arms

– Lymphoma diagnosed in 3 patients in maraviroc arms and 2 patients in placebo arms

Resistance

– Mutations seen in V3 loop among patients who failed on the maraviroc arms with R5 virus

– No signature R5 mutations have been defined yet


BENCHMRK-1 and -2: Raltegravir (MK-0518) in Treatment-Experienced Pts

Cooper D, et al. CROI 2007. Abstract 105aLB. Steigbigel R, et al. CROI 2007. Abstract 105bLB.

Raltegravir 400 mg twice daily + OBR*BENCHMRK-1 (n = 232)BENCHMRK-2 (n = 230)

Placebo + OBR*BENCHMRK-1 (n = 118)BENCHMRK-2 (n = 119)

HIV infected;triple-class resistant; VL > 1000 copies/mL

BENCHMRK-1 (N = 350)(Europe, Asia/Pacific, Peru)

BENCHMRK-2 (N = 349)(North, South America)

*Selected investigational antiretrovirals permitted in OBR.

Primary endpoints:

Week 16

Planned duration: Week 48

Randomized, double-blind, placebo-controlled, parallel phase III studies

Primary endpoints: VL, CD4+ cell counts, and adverse events at Week 16


BENCHMRK-1 and -2: VL < 400 copies/mL (ITT, NC = F)

Weeks

Pat

ien

ts W

ith

VL

<

400

co

pie

s/m

L (

%)

P < .001 at Week 16 P < .001 at Week 16

Weeks0 2 4 8 12 16 24

0

20

40

60

80

100

0 2 4 8 12 16 240

20

40

60

80

100 BENCHMRK-2BENCHMRK-1

Raltegravir + OBR Placebo + OBR

77%

41%

77%

43%

230

81

158

118

232

118

n =

n =

229

69

128

119

230

119

n =

n =Cooper D, et al. CROI 2007. Abstract 105aLB. Steigbigel R, et al. CROI 2007. Abstract 105bLB.

clinicaloptions.com/hivMarkowitz M, et al. IAC 2006. Abstract THLB0214.

Raltegravir: Potent Activity of Integrase Inhibitor in Treatment-Naive Patients

Raltegravir 600 mg BID (n = 40)*

Raltegravir 400 mg BID(n = 41)*

Efavirenz 600 mg QD(n = 41)

Treatment-naive patients with no prior antiretroviral therapy

> 6 days in total; VL ≥ 5000 copies/mL;

CD4+ cell count ≥ 100 cells/mm3

(N = 203)*



*8 patients in each raltegravir arm previously treated with same dose of raltegravir monotherapy for 10 days.

Week 48Current analyses:Week 24

Each combined with TDF + 3TC


Raltegravir vs EFV: Therapy Naïve ptsVL < 50 copies/mL at Week 24 (NC = F)

*P < .001 for raltegravir at each dose vs EFV.

Week

RLG 100 mg 39 39 39 39 39 39RLG 200 mg 40 40 40 40 40 40RLG 400 mg 41 41 41 41 41 41RLG 600 mg 40 40 40 40 40 40

EFV 38 38 38 38 38 37

0 2 4 8 12 16 240

20

40

60

80

100

Pat

ien

ts W

ith

VL

<

50

cop

ies/

mL

(%

)

*

*


*Additional AEs seen at ≥ 5% in EFV group: nightmares (11%), vomiting (8%), malaise (8%), fatigue (5%), attention disturbances (5%), lethargy (5%), anxiety (5%).

Raltegravir vs EFV: Adverse Events

AEs Occurring in ≥ 5% of Pts, % RLG (All Doses)(n = 160)

EFV (n = 38)

Nausea 11 13

Headache 9 24

Dizziness 8 26

Diarrhea 7 11

Insomnia 7 11

Abnormal dreams 6 18

Flatulence 6 --

clinicaloptions.com/hivTeppler H, et al. ICAAC 2006. Abstract 256a.

Raltegravir: Serum Lipids at Week 24 in Naive PatientsTreatment Arm Mean B/L TC,

mg/dL (mmol/L)Change From

B/L at Wk 24, % (95% CI)

Mean B/L TG, mg/dL (mmol/L)

Change From B/L at Wk 24,

% (95% CI)

RLG 100 mg BID* (n = 39) 168 (4.35) -7 (-14 to 0)† 129 (1.46) +2 (-22 to 26)

RLG 200 mg BID* (n = 34) 161 (4.17) -2 (-11 to 8)† 110 (1.24) -5 (-20 to 9)†

RLG 400 mg BID* (n = 40) 168 (4.35) -7 (-15 to 2)† 127 (1.44) -2 (-23 to 18)†

RLG 600 mg BID* (n = 35) 162 (4.19) -4 (-12 to 5)† 155 (1.75) -43 (-87 to 1)†

EFV 600 mg QD (n = 36) 170 (4.40) +19 (8 to 30) 128 (1.45) +47 (-1 to 96)

*With NRTI backbone of TDF + 3TC.†Significant difference vs EFV (P < .05).

Challenges Still Challenges Still RemainRemain

The FutureThe Future

The provider crisisThe provider crisis The need for vaccinesThe need for vaccines New affected populationsNew affected populations The rise of denialistsThe rise of denialists

– HIV denialistsHIV denialists– Abstinence-only/ anti-condomAbstinence-only/ anti-condom

The challenge for fundingThe challenge for funding The epidemic of complacencyThe epidemic of complacency

Unmet needs in HIV Care

Prevention Epidemic growing ~10% per year (US) Many HIV+ do not know their status EDUCATION

Address stigma Abstinence Faithfulness Safer drugs/needle exchange Safer sex/condom distribution

Unmet needs in HIV care

Diagnosis Many HIV+ do not know their status CDC now recommends HIV testing as part of

routine health care screening Must address stigma and confidentiality Delayed diagnosis facilitates:

Increased disease burden Increased disease cost Increased risk of transmission


Treatment Access to HIV treatment saves lives

ADAP waitlists Expertise of care provider correlates to survival

~9% of HIV+ do not have access to primary care What prevents HIV+ from access?

Lack of education Fear of stigma Fear of disclosure Fear of side effects


Treatment Long-term tolerability/toxicity

Cardiovascular disease Pregnancy Hepatitis

Costs Drug-drug interactions

TB Methadone

20 Years of Antiretroviral Therapy

Antiretroviral therapies revolutionized care Newer treatments offer well tolerated options Pharmacogenetics impact management New drugs will continue to shape ART Prevention and access to care continue to

challenge

Acknowledgements

Colorado HIV community Rose Medical Center:

Ken Greenberg John Hammer Amy Thomas Peggy Zellner

HOPS/CDC collaborators Howard Grossman Clinical Care Options

Elaine Seekins

Twenty Years of Antiretroviral Therapy:Lessons Learned and Unmet Needs

Benjamin Young, MD PhD

Rose Medical Center

Division of General Internal Medicine

University of Colorado Denver and Health Sciences Center

Denver, Colorado

twenty years of antiretroviral therapy: lessons learned and unmet needs benjamin young, md phd rose...

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