Treatment as Prevention: HAART Expansion - A Powerful Strategy to Reduce AIDS Morbidity and Mortality and HIV Incidence - World Health ...

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Treatment as Prevention: HAART Expansion - A Powerful Strategy to Reduce AIDS Morbidity and Mortality and HIV Incidence - World Health ...
Treatment as Prevention:
HAART Expansion - A Powerful Strategy to Reduce
 AIDS Morbidity and Mortality and HIV Incidence

          Julio Montaner MD, FRCPC, FCCP, FRSC
     Director, BC-Centre for Excellence on HIV/AIDS, Providence Health Care
  Professor of Medicine and Head, Division of AIDS, University of British Columbia
                       President, International AIDS Society

                          UNAIDS, Geneva, March 24th 2010

  British Columbia
  Centre for Excellence
  in HIV/AIDS
Treatment as Prevention: HAART Expansion - A Powerful Strategy to Reduce AIDS Morbidity and Mortality and HIV Incidence - World Health ...
USA - Trends in Annual Rates of Death
                                                     Ages 25 to 44

                                40                                             Unintentional
Deaths per 100,000 Population

                                                                               injury
                                35                                             Cancer
                                30
                                                                               Heart
                                25                                             disease
                                                                               Suicide
                                20
                                15                                             HIV infection

                                10                                             Homicide

                                5                                              Chronic liver
                                                                               disease
                                0                                              Stroke
                                     82   84   86    88     90       92   94
                                                                               Diabetes
                                                    Year
Treatment as Prevention: HAART Expansion - A Powerful Strategy to Reduce AIDS Morbidity and Mortality and HIV Incidence - World Health ...
Harald zur Hausen   Françoise Barré-Sinoussi     Luc Montagnier

                                               Announced Oct 6th 2008
Treatment as Prevention: HAART Expansion - A Powerful Strategy to Reduce AIDS Morbidity and Mortality and HIV Incidence - World Health ...
Vancouver 1996
“One World One Hope”
Treatment as Prevention: HAART Expansion - A Powerful Strategy to Reduce AIDS Morbidity and Mortality and HIV Incidence - World Health ...
Vancouver 1996
      “One World One Hope”

         % Progression to AIDS in 3 yrs
                                                          Plasma Viral Load, a strong
                                                            Predictor of outcome in
                                              CD4+
100                                           cells/µL
                                                > 750

                                                            HIV Infected Individuals
 80                                             501-750
                                                351-500
 60                                             201-350
                                                < 200
 40
                                                           High Plasma Viral Load: Poor Prognosis
 20
                                                           Low Plasma Viral Load: Good Prognosis
  0
        > 30   10-30   3-10   0.5-3   < 0.5

      Plasma HIV RNA (thousand copies/mL)
                         J Mellors et al. Annals 1997
Treatment as Prevention: HAART Expansion - A Powerful Strategy to Reduce AIDS Morbidity and Mortality and HIV Incidence - World Health ...
Montaner et al JAMA, March 25th 1998

         Vancouver 1996
      “One World One Hope”                                                                                                   AZT + NVP

                                                                                                                             AZT + ddI

         % Progression to AIDS in 3 yrs

100
                                              CD4+
                                              cells/µL                                                Triple Therapy: AZT + ddI + NVP
                                                > 750
 80                                             501-750
                                                351-500
 60                                             201-350
                                                < 200                                     Gulick et al; JAMA, July 1, 1998
 40
                                                                                 0
 20
                                                          Change in Viral Load

  0
        > 30   10-30   3-10   0.5-3   < 0.5
                                                                                 -1
      Plasma HIV RNA (thousand copies/mL)                                                               Dual Therapy Regimens
                         J Mellors et al. Annals 1997
                                                                             -2

                                                                                                         Triple Therapy: AZT+3TC+IDV
                                                                                 -3
                                                                                      0                                                  52
                                                                                                             Study Weeks
Treatment as Prevention: HAART Expansion - A Powerful Strategy to Reduce AIDS Morbidity and Mortality and HIV Incidence - World Health ...
Impact of HAART in BC-CfE

140                 Death Rate per 1000

120                                                     Greater than 85% reduction
100
                                                         in death rate among those
80
                                                              engaged in care
60

40

20

 0
      1993-94 1995-96 1997-98 1999-00 2001-02 2003-04

                                                             Modified from Hogg et al, Lancet. 2009
Treatment as Prevention: HAART Expansion - A Powerful Strategy to Reduce AIDS Morbidity and Mortality and HIV Incidence - World Health ...
Impact of HAART in BC-CfE

140                 Death Rate per 1000                 35             Life Expectancy at age 20

120                                                     30
100                                                     25
80                                                      20
60                                                      15
40                                                      10
20                                                      5
 0                                                      0
      1993-94 1995-96 1997-98 1999-00 2001-02 2003-04        1993-94   1995-96   1997-98   1999-00   2001-02   2003-04

                                                                   Modified from Hogg et al, Lancet. 2009
Treatment as Prevention: HAART Expansion - A Powerful Strategy to Reduce AIDS Morbidity and Mortality and HIV Incidence - World Health ...
Treatment as Prevention: HAART Expansion - A Powerful Strategy to Reduce AIDS Morbidity and Mortality and HIV Incidence - World Health ...
HAART Can Reduce HIV Transmission

       HAART stops HIV replication
                      ↓
   HIV levels fall to undetectable in blood
        as well as in sexual fluids
                      ↓
 Sharp reduction in HIV transmission
Prevention Strategies
  - Education
  - Change in behavoir
  - Harm reduction
  - New strategies/technology
  - Vaccines

      Existing strategies have failed
   to contain the global HIV pandemic
Vertical
 Transmission
   Canada, 1990 to 2008

Modified from Alimenti et al CAHR, 2009
Discordant Couples

         S Attia, M Egger, M Muller, M Zwahlen and N Lowa. AIDS. 2009 Jul 17;23(11):1397-404
Discordant Couples

    Studies of heterosexual discordant couples observed no
 transmission in patients treated with ART and with viral load
      below 400 c/ml, but data were compatible with one
               transmission per 79 person-years.
                 S Attia, M Egger, M Muller, M Zwahlen and N Lowa. AIDS. 2009 Jul 17;23(11):1397-404
B&M Gates Fdn: HIV Transmission Risk in
 Heterosexual Serodiscordant Couples
   3,400 couples In 7 African countries
   All counseled and given free condoms
   HAART initiated based on CD4 count eligibility
   Over the next 1 to 3 years, 103 new HIV infections
   All but 1 infection occurred in the untreated couples
       Estimated 92% reduction of HIV transmission by HAART
       Unadjusted relative risk: 0.17 (95% CI: 0.004-0.94; P = .037)
       Adjusted relative risk: 0.08 (95% CI: 0.002-0.57; P = .004)
       Adjusted for visit and CD4+ cell count at initiation

                                               Donnell D, et al. CROI 2010. Abstract 136.
B&M Gates Fdn: HIV Transmission Risk in
 Heterosexual Serodiscordant Couples
    3,400
       Morecouples
               recentlyInan7email
                             Africanhascountries
                                        been circulated saying that:
    All “counseled
           The singleand case  of transmission
                             given   free condoms involved a man
         who initiated ARVs 18 days before his 12-month
    HAART
    study       initiated
            visit. At this based
                           visit hisonpartner
                                        CD4 count
                                              testedeligibility
                                                      positive for HIV,
    Over the next having
                        1 tobeen    negative
                             3 years,         at month
                                        103 new          9.”
                                                   HIV infections
    All but 1 infection occurred in the untreated couples
        Estimated 92% reduction of HIV transmission by HAART
        Unadjusted relative risk: 0.17 (95% CI: 0.004-0.94; P = .037)
        Adjusted relative risk: 0.08 (95% CI: 0.002-0.57; P = .004)
        Adjusted for visit and CD4+ cell count at initiation

                                                Donnell D, et al. CROI 2010. Abstract 136.
Wood et al, BMJ, 2009
Wood et al, BMJ, 2009

Whiskers represent 95% confidence intervals.
Wood et al, BMJ, 2009

Whiskers represent 95% confidence intervals.
Wood et al, BMJ,
 May 16, 2009
Impact of HAART in BC-CfE
Frequency of people

                                               6 months                       Baseline

                           Plasma Viral Load (log10 copies/mL) Distribution

                                                          Modified from Anema et al. EIDJ 2009
Impact of HAART in BC-CfE
Frequency of people

                                                                                 Baseline
                        24 months

                              Plasma Viral Load (log10 copies/mL) Distribution

                                                             Modified from Anema et al. EIDJ 2009
New HIV and Syphilis in BC
Rate per 100,000 population

                              M REKART, BC-CDC, 2006
New HIV and Syphilis in BC
Rate per 100,000 population

                              M REKART, BC-CDC, 2006
Cost-Effectiveness of HAART
                             BC-DTP
                 “HIV deficit” in BC in 2005: 400
   Cost of Medical Management of 1 HIV infection over a
                    lifetime = $250,000
800 cases per year

Averted lifetime Rx cost up to 2001 US $96.4M
             A total of 3,963 pts were on HAART in BC in 2005 400 cases per year
          Total actual drug cost (using patented drugs) in 2005
                               $49 million US
Cost-Effectiveness of HAART
                     BC-DTP
          “HIV deficit” in BC in 2005: 400
 Cost of Medical Management of 1 HIV infection over a
                  lifetime = $250,000

Averted lifetime Rx cost up to U$A 100M
     A total of 3,963 pts were on HAART in BC in 2005
   Total actual drug cost (using patented drugs) in 2005

                      U$A 50M
The Bc-CfE Mathematical Model
     Viviane D. Lima et al
           JID 2008
Adhe re nc e : 0 % -
Incremental net benefit (Millions
                                   of CDN $) over 30 years
                                                                                                 Overall population and
                                                                                                 patient-centered
Net Benefit (million $ Can 2005)

                                    800

                                              Overall Population
                                              Patient-Centered                                   incremental net benefit of
                                    600

                                                                                                 increasing uptake of
                                                                                                 HAART from 50% to 75%
                                    400

                                                                                                 over 30 years, based on a
                                    200

                                                                                                 willingness-to-pay
                                                                                                 thresholds of $50,000 per
                                     0

                                          0    5            10        15          20   25   30
                                                                                                 quality-adjusted life year.
                                                                   Time (years)

                                                                                                       K Johnston et al, submitted, 2010
Summary
HAART is widely regarded as a cost effective, life-
 saving strategy

  ↓ Mortality of treated HIV/AIDS patients
  ↓ Morbidity of treated HIV/AIDS patients
  ↓ Health Resource utilization
  ↓ Vertical Transmission of HIV infection

Furthermore, when the impact of HAART on HIV
  transmission is considered, HAART expansion
  becomes a cost-averting strategy
The third approach, though, is the most intriguing. This is to do nothing
more than press ahead faster with the treatment program. Since treatment
reduces viral load, it should, in theory, make those being treated less
infectious. Of course, theory is one thing and practice another. But studies
in Taiwan and British Columbia (the latter by Julio Montaner, the incoming
president of the International AIDS Society, which organizes the conference)
have shown big falls in transmission rates as ARVs have been rolled out.
The Power of HAART: Demographic Model
       Treat 30%

                   HIV prevalence   Cost of treatment
       Treat all                            Treat 30%

                                            Treat all

   Number of
   infections
   prevented

                                        Montaner et al, Lancet 2006
R Granich, C Gilks, C Dye, K De Cock, B Williams. The Lancet Nov 26th 2008
AIDS           Nov 27th 2008, The Economist
Deploying the drugs used to treat AIDS may be the way to limit its spread

                                          Illustration by Peter Schrank

                          Thank you
AIDS           Nov 27th 2008, The Economist
Deploying the drugs used to treat AIDS may be the way to limit its spread

                                          Illustration by Peter Schrank

                          Thank you
An Alternative Approach

  Preliminary Results
Methods
   Prospective ecological study in BC, Canada

   Used administrative records to evaluate the association
    between expansion of HAART coverage, population level
    plasma HIV-1-viral load and new HIV diagnoses

   HIV testing, CD4 & viral load testing and HAART
    distribution are centralized and free in BC

   Data for second half of 2009 is preliminary due to delayed
    reporting, therefore only the first half of 2009 was used for
    statistical analyses

                                              Montaner et al, CROI 2010
January 2004

Summer of 1996
                                                The second expansion of HAART
                                                 occurred prior to the new 2008
                                                IAS-USA Guidelines, which were
                                                adopted in BC at the end of 2008

             The first expansion of HAART
         occurred as a result of the new 1996
           IAS-USA Guidelines, which were
            adopted in BC in the summer of
                          1996

                                   Year
                                                Montaner et al, CROI 2010
1.00
  Incidence/yr

                 0.20

                 0.10

                 0.04                      Acquired resistance
                 1.00
                                               falling
                 0.02

                 0.01
                 0.201995    2000   2005   2010
< 50/mL (%)

                   90
 Viral load

                 0.10
                  80
                                           Plasma viral load
                 0.04                      suppression rising
                  70
                 0.02

                 0.01
                   60
                      1995   2000   2005   2010
Number of Active HAART
                                      Participants and Number of New
Number of Active HAART Participants

                                          HIV+ Diagnoses per Year

                                                                                              Number of New HIV+ Diagnoses
                                      p=0.015

                                         New HIV+ Diagnoses (All)

                                                Active on HAART

                                                  New HIV+ Diagnoses (IDU)

                                                         Year           Montaner et al, CROI 2010
Number of Active HAART
                                      Participants and Number of New
Number of Active HAART Participants

                                          HIV+ Diagnoses per Year

                                                                                              Number of New HIV+ Diagnoses
                                      p=0.015

                                         New HIV+ Diagnoses (All)

                                                Active on HAART
                                                                             p=0.085

                                                  New HIV+ Diagnoses (IDU)

                                                                             p=0.026

                                                         Year           Montaner et al, CROI 2010
“True” New Yearly HIV Diagnoses in BC

                       BC-CDC Updated March 2010
HIV testing in BC, 1985 to 2008
           Year   # of HIV Tests

Jan 2004

                                   BC-CDC Report, 2009
Hepatitis C, 1999-2008          Infectious Syphilis, 1999-2008

           • BC          2004
                                                             • BC
                                                     2004

                                                        x Canada
            x Canada

Genital Chlamydia, 1999-2008    Gonorrhea, 1999-2008

          • BC                            x Canada

          x Canada
                         2004             • BC        2004
Highest
                                  Non IDU           HIV-1- Plasma
                                                    Viral load per
                                                         Year

                                                                    IDU
  Ever on Treatment
          &
Censoring at the time of
   Death or Move

The proportion of HIV infected IDUs engaged in care in BC with plasma viral
  load >1500 c/mL, as a surrogate for “high” community HIV-1-viral load,
       decreased from ~50% in 2000-04 to ~20% in 2009 (p
“Provincial Viral Load”
All Patients Ever Tested for Plasma HIV-1-Viral Load in BC

    Censoring at the time of Death or Move
New Data: Pre HAART CD4 Count

                Montaner et al, 2010, Preliminary Data
Community pVL and New HIV Diagnoses
           San Francisco
                                               30,000       P = .005 for                      Mean CVL
Mean Community Viral Load (copies/mL)

                                                            association*

                                                                                                                                        Number of Newly Diagnosed HIV Cases
                                                                                                                            1200
                                                                                              Newly diagnosed and
                                               25,000                                         reported HIV cases
                                                                                                                            1000

                                               20,000
                                                                                                                            800
                                                               798
                                               15,000
                                                                                                                            600
                                                                             642
                                               10,000                                     523          518
                                                                                                                     434    400

                                                 5000                                                                       200

                                                     0                                                                      0
                                                            2004          2005         2006          2007          2008
                                        *Data insufficient to prove significant association with reduced HIV incidence.

                                                                                              Das-Douglas M, et al. CROI 2010. Abstract 33.
A Formidable Challenge

 A Unique Opportunity
When to Start HAART?
  A matter of Perspective

                         Viral Load

                         CD4 Count

                 years
When to Start HAART?
  A matter of Perspective

                         Viral Load

                         CD4 Count

                 years

      years
When to Start HAART?
  A matter of Perspective

                         Viral Load

                         CD4 Count

                 years

      years

                                      years
When to Start HAART?
  A matter of Perspective

                         Viral Load

                         CD4 Count

                 years

      years

                                      years
Person years on ART (M)                Cost: 2010 to 2050
                          70                                           7

                          60                                           6

                          50                                           5

                                                                           Deaths (M)
     Cost (Bn$)

                          40                                           4

                          30                                           3

                          20                                           2

                          10                                           1

                          0                                            0
                               0
                                   Current
                                      1
                                           200
                                            2
                                                 350
                                                  3
                                                       500
                                                        4
                                                           Immediate
                                                             5     6

             Economics of ART up to 2050 in South Africa
       Current policy vs. Universal Access at different CD4 counts
                                                             Granich. CROI 2010
STOP HIV & AIDS:
           AIDS           Seek and Treat to
        Optimally Prevent HIV & AIDS*

* Supported through a $2.5M five year Avant Garde Award by the
National Institute for Drug Abuse (NIDA) at the NIH in 2008 and
$48M (+ drugs) four year outreach grant by BC Govt in 2010
STOP HIV & AIDS:
           AIDS           Seek and Treat to
        Optimally Prevent HIV & AIDS*
 Prospectively Evaluate the Impact of HAART Expansion
on AIDS Morbidity and Mortality and HIV Incidence in BC

Intervention                            Primary Endpoint
 HAART Expansion                         HIV Incidence
 within medical guidelines               at years 3 to 5
                      Secondary Endpoints:
    MORBIDITY AND MORTALITY, CD4 COUNTS, HIV-1-RNA LEVELS,
        RESISTANCE, ADVERSE EVENTS, SAFETY, ADHERENCE,
            HOSPITALIZATIONS, RESOURCE UTILIZATION

* Supported through a $2.5M five year Avant Garde Award by the
National Institute for Drug Abuse (NIDA) at the NIH in 2008 and
$48M (+ drugs) four year outreach grant by BC Govt in 2010
HAART Expansion to Reduce AIDS
Morbidity & Mortality, and HIV Incidence

   HAART has a substantial added preventive value
       The magnitude of this effect is not yet fully characterized, and
        may well vary in different settings
   Seek and Treat among those who have a medical indication for
    HAART cannot wait for the above to be resolved
       Many lives will be saved and much insight will be gained from
        closely monitoring a more “aggressive”roll out of HAART within Rx
        Guidelines
   Seek and Treat outside the range where treatment is medically
    indicated remains a research question
       However, Rx Guidelines leave few outside the “treatment
        envelope”
   TAP should serve to re-energize Universal Access
Combination prevention
                          Biomedical
                         Interventions

                                             HIV testing,
       Structural                          linkage to care
     Interventions                         and expanded
                                               HAART
                        HIV                   coverage

                     Prevention

                                       Individual
               Community               and small
               Interventions             group
                                       behavioral
                                     interventions

                                                     Modified from T. Coates
A Statistician’s Opinion
   All scientific work is incomplete - whether it be
observational or experimental. All scientific work is
liable to be upset or modified by advancing
knowledge. That does not confer upon us a freedom
to ignore the knowledge we already have, or to
postpone the action that it appears to demand at a
given time.

        Bradford-Hill, A. 1965 The environment and disease: Association or
   Causation? President address at January 14 meeting. Proceedings of the
                            Royal Society of Medicine 163 (seriesB): 295-300
Seek and Treat to Optimally
   Prevent HIV & AIDS
        STOP HIV & AIDS

        R Hogg, E Wood, T Kerr, M Tyndall, A Levy, PR Harrigan,
      Viviane Lima, Aranka Anema, Stephen Smith, Warren O’Brien
         Pedro Cahn, Jose Esparza, Craig Mc Clure, Robin Gorna
                    Jacques Normand, Nora Volkow
        IAS - USA ART Guidelines Panel, IAS, WHO and UNAIDS

                       BC-MoH and MHL&S
                         SPH Foundation
                        Merck, Gilead, ViiV
                    MSHRF, CIHR, NIDA and NIH
                          H&W, Ottawa

                Research Staff and Study Participants

   British Columbia
   Centre for Excellence
   in HIV/AIDS
British Columbia
  Centre for Excellence
  in HIV/AIDS

Thank You
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