Recognizing the Value of Innovation in HIV/AIDS Therapy - White Paper | December 2012

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Recognizing the Value of Innovation in HIV/AIDS Therapy - White Paper | December 2012
White Paper | December 2012

Recognizing the
Value of Innovation
in HIV/AIDS Therapy

Catherine Augustyn, Brigham Walker, and Thomas F. Goss, PharmD

Boston Healthcare Associates, Inc., Boston, MA and Washington, DC
Recognizing the Value of Innovation in HIV/AIDS Therapy - White Paper | December 2012
INTRODUCTION                                          research that must be conducted to secure FDA
                                                      regulatory approval, these studies are designed
In the last two decades, we have seen                 for controlled evaluation of safety and efficacy.
remarkable progress against HIV/AIDS                  Therefore, pre-approval trials are limited in their
(human immunodeficiency virus/acquired                ability to capture the broader and longer-term
immunodeficiency syndrome), transforming the          clinical and quality-of-life benefits that may be
disease from an acute, fatal illness to a chronic     associated with a specific therapy as physicians
condition. In the United States, death rates have     accumulate evidence using the new agents in
fallen 79 percent since 1995 as a result of highly    real-world settings.
active antiretroviral therapy (HAART, or ART
as is more commonly used today) and other             We selected HIV/AIDS as a case study for this
new medications.1 Advances in treatment have          analysis because significant gains in clinical
increased survival, slowed progression, prevented     outcomes have been achieved over the past 15
hospitalizations, and allowed patients to lead full   years, which are clearly documented in scientific
lives. In retrospect, the clinical improvements       literature. This paper evaluates how step-wise
produced by novel treatment options for HIV/AIDS      progress was achieved over time and the
have been far above what could have been              ways in which biopharmaceutical innovations
anticipated or achieved at the time of the initial    have enabled better disease management and
introduction of these individual medicines.           improved quality of life for patients.
Understanding how this progress was achieved —
as well as how the evidence supporting it evolved     This white paper is the second installment in a
— is important to sustaining an environment for       series of papers focused on recognizing value in
future advances.                                      biopharmaceutical innovation. The previous white
                                                      paper, Recognizing Value in Oncology Innovation
This progress has been realized through a             (June 2012), demonstrated how the full clinical
complex process of incremental gains that have        value of a cancer therapy typically evolves
unfolded over many years. Although not well-          significantly after FDA approval. These reports
characterized or understood, this innovation          illustrate how this evolution frequently reveals
process has involved the step-wise accumulation       that for many therapies, greater clinical value is
of treatment improvements over time, which            realized based on real-world experience than
has taken place as research has continued to          was able to be demonstrated prior to launch.
accumulate evidence that has driven changes           These reports also acknowledge that, at times,
in HIV treatment. Our understanding of how            real-world experience can prove a medicine
certain novel therapies may be optimally              to be less valuable than initially expected.
applied to patient care changes and improves
as HIV therapies are introduced and evaluated
in real-world clinical practice, resulting in new     Background on HIV/AIDS
approaches to treatment, which incrementally
increased efficacy and tolerability. The key          HIV infection is one of the most prevalent
element to ensuring continued, and at times,          infectious diseases in the world, affecting more
unexpected innovation that drives improved            than 34 million people globally in 20112 and 1.2
patient outcomes is to ensure flexible access to
                                                      million people in the United States as of 20083.
therapeutic options. This access supports the
step-wise process that has been central to clinical   In people infected with HIV, the virus gradually
gains made in HIV and many other disease areas,       compromises the immune system by entering
and has enabled patients around the world to live     and taking over T-cell lymphocytes. The adoption
longer and better than ever before.
                                                      of antiretroviral therapies to treat HIV/AIDS
Since medical progress with individual                starting in the 1990s has led to sharp mortality
compounds may be realized gradually over              declines and greatly improved quality of life.
time, the optimal role and full value of a therapy    These medicines have fundamentally changed
typically cannot be known at the time of Food
                                                      HIV from an acute fatal illness to a manageable
and Drug Administration (FDA) approval or U.S.
market launch. Although one of the distinctive        chronic disease.
features of new medicines is the rigorous clinical

                                                         Recognizing the Value of Innovation in HIV/AIDS Therapy   |   1
Evolution of the Treatment of HIV Infection: 1980s to Present

            FIGURE 1. Evolution of the Treatment of HIV Infection: 1980s to Present

                                                                                               New Indications               Today
                                                                                                                          HIV/AIDS
                                                                                                                          Chronic,
                                                                      Earlier Use                                        manageable
                                                                                                                          condition

                                          Use in
              1980s–1990s              Combinations
              HIV/AIDS
              Acute, fatal
                illness                                      NEW DRUG APPROVALS

        In this white paper, we will explore the treatment                   Combination Therapy
        of HIV/AIDS and highlight the various ways
        in which additional clinical value – including                       The treatment paradigm for HIV/AIDS has evolved
        improved survival and quality of life – has been                     dramatically over the last several decades to the
        realized over time. The pathways identified here                     point where combination therapy has become
        show some of the ways our understanding of a                         the mainstay in HIV/AIDS treatment. Combination
        medicine’s value changes over time, including                        therapy has been shown to provide the best
        a few that are shared in common with cancer                          opportunity for clinical response and disease
        treatments, as discussed in the previous white                       remission in HIV/AIDS patients, even beyond
        paper:                                                               initial expectations.

        •     Use in combination with other agents                           The value of combination therapies in the
        •     Use earlier in treatment line and earlier in                   treatment of HIV/AIDS cannot be overstated.
              disease state                                                  These combinations are critical to preventing the
        •     Use in different disease indications*                          development of viral resistance and successfully
                                                                             treating the primary infection. Highly active
        FDA approval often marks the “starting point”                        antiretroviral therapy describes a type of
        for a number of additional evaluations of a novel                    combination regimen used in HIV/AIDS treatment
        therapy. Following launch, a larger body of                          that typically includes two nucleoside analogue
        evidence is developed through real-world practice                    reverse transcriptase inhibitors (NRTI) and either
        and ongoing research. In the case of HIV/AIDS,                       a non-nucleoside analogue reverse transcriptase
        antiretroviral therapies have proven to be                           inhibitor (NNRTI), a protease inhibitor (PI), or an
        effective in a broader cohort of patients than were                  integrase inhibitor (II).
        represented in the clinical trial data submitted for
        initial FDA approval. Individual and combination                     In the current era, all four classes are indicated
        therapies have created new opportunities for                         for use in combination with other antiretroviral
        improved disease control and remission, particularly                 agents for the treatment of HIV infection.
        when used in patients with earlier disease stages                    However, this understanding has evolved
        who were not included as part of pre-approval                        significantly over time based on rigorous
        trials, reinforcing that it is important to recognize                evaluation of new combinations, as new classes
        that the full clinical value and potential of a                      of agents have been discovered and approved. In
        therapy may only be identified and realized                          the early stages of HIV/AIDS therapy, combination
        through a “step-wise transformation” over time.

        * This may include both new indications approved by the FDA and off-label uses supported by research and deemed clinically appropriate
        by physicians. The evidence in this paper focuses on new FDA-approved indications.

2   |       Recognizing the Value of Innovation in HIV/AIDS Therapy
regimens were not available and viral resistance       An examination of the death rates among HIV-
quickly became a challenge. It has taken time and      infected individuals over the stages described
real-world clinical practice to identify and test      above (pre-HAART, early-HAART, and late-HAART)
a variety of HAART combinations, which today           reveals a similar change in the United States as
yield improved efficacy and better tolerability and    these innovative therapies and combinations
safety profiles than ever before.                      were introduced. While the death rate does not
                                                       represent a comprehensive measure of mortality,
Since 1996, HAART combination regimens have            it can be indicative of a trend, and in this case
significantly reduced the mortality rate of HIV-       shows the rapid decline in deaths among
infected patients.4 According to 2010 Centers          individuals infected with HIV when the use of
for Disease Control and Prevention (CDC) data,         HAART therapies increased through the 1990s
the age-adjusted number of deaths per 100,000          (See Figure 2).
due to HIV in the United States has decreased
by 79 percent over the last two decades.1 The          Since the 1990s, certain HAART regimens have
Kaiser Family Foundation attributed this dramatic      yielded better outcomes in HIV patients over
improvement as “largely due to [the adoption of]       time as their use has been refined in a real-world
highly active antiretroviral therapy.”5 More than      population. An analysis presented in 2008 at
30 treatment options for HIV have been developed       the 9th International Congress on Drug Therapy
since 1987, arming physicians with increasingly        in HIV Infection compared the efficacy of first-
more therapeutic options that support these kinds      line HAART regimens in 2006 to those used in
of improvements in patient survival.6                  1998.8 The analysis included 146 patients starting
                                                       first-line HAART during these years (67 in 1998;
Over time, moving from the pre-HAART era in            79 in 2006). HIV suppression at 48 weeks was
which no HAART regimens were available, to             observed in 59.1 percent of patients in 1998 and
the early- and then late-HAART eras in which           88.6 percent in 2006 (P < 0.001). In a multivariate
not only have more antiretroviral therapies been       analysis, virologic suppression was independently
developed but also new combinations have               associated only with two factors: at least 48-week
been tested, clinical outcomes have improved           adherence and being treated in 2006 versus 1998.
dramatically. The multitude of antiretroviral agents   These results support an independent association
approved in the past two decades has allowed           between better outcomes and the specific year of
clinicians to tailor therapy to a patient’s specific   treatment, suggesting that the availability of new
needs and viral profile.                               antiretroviral agents allows for more refined and
                                                       effective combination therapy.
One large study by Danish researchers assessed
the mortality rates of 3,990 HIV-infected              These observations may be explained by a
individuals and 379,872 general-population             number of potential factors, including earlier
controls from the pre-HAART (1995-96), early-          diagnosis and treatment, better tolerance of
HAART (1997-99), and late-HAART (2000-05) eras.        available regimens leading to improved efficacy
In these distinct phases, new medicines became         of, and adherence to, treatments, and adoption of
available and researchers discovered more              better understood treatment combinations.
effective combinations. Researchers reported that
the highest mortality rate among HIV-infected          In addition, in recent years we also have seen
patients – 124 per 1,000 person years – was            significant advances in antiretroviral therapy
observed in the pre-HAART period, falling to 38        dosing that have led to simpler regimens
per 1,000 in the early-HAART period, and further       with reduced pill burden on patients. These
to 25 in 1,000 in the late-HAART period.7 These        co-formulations combine two or more
data support the hypothesis that developing and        antiretroviral medications into one dosage
making available more therapeutic options can          form with the same clinical impact, meaning
provide opportunity for clinical breakthroughs as      HIV treatment is more effective today in part
new combination regimens are tested over time.         due to improved patient adherence.

                                                          Recognizing the Value of Innovation in HIV/AIDS Therapy   |   3
FIGURE 2. HIV DeathHIV Death
                              Rates andRates
                                        HAARTand HAART Treatment
                                               Treatment AdvancesAdvances   (U.S., 1990–2010)
                                                                  (U.S., 1990-2010)

                                                                       Pre-HAART        Early-HAART                        Late-HAART
                                                                      59% Increase      67% Decrease             Progress Continues: 49% Decrease
                                                          18

                                                          16
                 Deaths per 100,000 resident population
                   with HIV (age-adjusted) in the U.S.

                                                          14

                                                          12

                                                          10

                                                          8

                                                          6

                                                          4

                                                          2

                                                          0
                                                               1990                  1995                2000                              2005                        2010

          Sources:
          U.S. Department of Health and Human Services (HHS), Centers for Disease Control and Prevention (CDC), National Center for Health Statistics (NCHS), “Health, United
          States, 2011 with Special Feature on Socioeconomic Status and Health,” Table 22, http://www.cdc.gov/nchs/data/hus/hus11.pdf, (2012);
          S.L. Murphy, J. Xu, and K.D. Kochanek, “Deaths: Preliminary Data for 2010,” U.S. HHS, CDC, NCHS, National Vital Statistics Reports 60, no. 4: (2012);
          U.S. HHS, CDC, NCHS, “Health, United States, 2010 with Special Feature on Death and Dying, http://www.cdc.gov/nchs/data/hus/hus10.pdf, (2011);
          K.D. Kochanek, J. Xu, S. L. Murphy, et al., “Deaths: Preliminary Data for 2009,” U.S. HHS, CDC, NCHS, National Vital Statistics Reports 59, no. 4: (2011);
          U.S. HHS, CDC, NCHS, “Health, United States, 2009 with Special Feature on Medical Technology,” Table 38, http://www.cdc.gov/nchs/data/hus/hus09.pdf, (2010);
          U.S. HHS, CDC, NCHS, “Health, United States, 2008 with Special Feature on the Health of Young Adults,” Table 41, http://www.cdc.gov/nchs/data/hus/hus08.pdf, (2009);
          U.S. HHS, CDC, NCHS, “Health, United States, 2003 with Chartbook on Trends in the Health of Americans,” Table 42, http://www.cdc.gov/nchs/data/hus/hus03.pdf, (2003);
          U.S. HHS, CDC, NCHS, “Health, United States, 1996-97 and Injury Chartbook,” Table 44, http://www.cdc.gov/nchs/data/hus/hus97cht.pdf (1997).

        Earlier Use of Advanced                                                                        The 2011 Department of Health and Human
                                                                                                       Services (HHS) Guidelines for the Use of
        Therapies in Disease                                                                           Antiretroviral Agents in HIV-1-Infected Adults
        Management                                                                                     and Adolescents affirm that there is evidence
                                                                                                       to support the benefits of viral suppression and
        In addition to an increased use of combination                                                 immunologic response in patients with higher
        therapy, the treatment paradigm for HIV/AIDS has                                               pre-treatment CD4 counts (immune response
        evolved to reflect the benefits of initiating therapy                                          cells) – in other words, with earlier-phase disease.9
        earlier to better control disease progression.                                                 In HIV-infected individuals who are not treated
        Real-world clinical practice and recent data                                                   adequately, CD4 counts generally decrease as
        support the notion that earlier initiation of                                                  HIV progresses. A low CD4 count indicates a
        treatment in the disease cycle leads to improved                                               weakened immune system and a higher chance
        long-term outcomes and immunologic response.                                                   of acquiring opportunistic infections. However,
                                                                                                       today patients previously considered to be in
        The effectiveness of ART therapy to treat HIV                                                  “pre-treatment” phase (with higher CD4 counts)
        patients has driven not only widespread use                                                    often receive early ART treatment and are able to
        of combination therapy, but also progressively                                                 derive short- and long-term benefits.
        earlier use in the timeline of disease progression.

4   |     Recognizing the Value of Innovation in HIV/AIDS Therapy
The median CD4 count for newly diagnosed                   patients waited to begin treatment until their
patients is around 200 cells/mm3.Yet the HHS               CD4 count fell below 250 cells/mm3 or they had
Guideline Panel gave its highest recommendation            an AIDS-related illness. The findings were robust
that antiretroviral therapy be initiated in all patients   enough that the study was unblinded four
with a CD4 count as high as 500 cells/mm3.The              years early.
Guideline Panel based its recommendation on
several recent developments:9

•   A report from the recent NA-ACCORD cohort
                                                           Use in Additional
    study10 demonstrating survival benefit with            Disease Indications
    initiation of antiretroviral therapy at “pre-
    treatment” CD4 count levels greater than 500           Improved understanding of disease pathology –
    cells/mm3;                                             in many cases at the molecular level – has had
                                                           a direct impact on the development of ART and
    •   The study observed patients who started
                                                           other HIV treatments over the past two decades.
        treatment at CD4 counts greater than 500
                                                           With a better understanding of how the disease
        cells/mm3 or after CD4 counts dropped
                                                           evolves and progresses, therapies have become
        below this threshold.
                                                           more targeted and have proven to be beneficial
    •   The risk of death was 94 percent higher            not only for the treatment of the disease but
        among the 6,935 patients who deferred              also for the prevention of transmission, leading
        therapy until CD4 counts fell to less than         to new uses and indications for many
        500 cells/mm3 compared with rates in the           treatment regimens.
        2,200 patients who started therapy while
        CD4 count was greater than 500                     In the case of HIV infection, access to multiple
        cells/mm3.                                         treatment options has enabled clinicians and
•   Growing awareness that untreated HIV                   researchers to uncover additional and inherent –
    infection may be associated with development           but previously unrecognized – secondary values
    of many non-AIDS-defining diseases, including          of individual regimens. Although by their nature
    cardiovascular disease, kidney disease, liver          antiretrovirals do not lend themselves to new
    disease, and malignancy; and                           indications as much as some other disease areas
                                                           (e.g., oncology), even in this area, potential for
•   Availability of antiretroviral regimens that are
                                                           use in new populations has been uncovered.
    more effective, more convenient, and better
    tolerated than antiretroviral combinations no
                                                           Preventing Maternal-Fetal Transmission
    longer in use.
                                                           Antiretrovirals were developed and first approved
                                                           for patients with primary HIV infection. Yet certain
Citing its own evolution over time, the Guideline
                                                           antiretrovirals have provided additional specific
Panel summarized its findings by stating that
                                                           benefit to infected pregnant women and their
prior concerns about long-term toxicity, reduced
                                                           unborn children, helping to drive down the rate of
quality of life, and the potential for drug
                                                           maternal fetal HIV transmission.
resistance previously acted as barriers to its
recommendation of earlier treatment initiation.9
                                                           The most salient example is zidovudine (ZDV,
But this year, the Guideline Panel concluded that
                                                           Retrovir®), which was initially approved by
increasing evidence supports earlier initiation of
                                                           the FDA in 1989 to treat HIV infection, but
antiretroviral therapy.
                                                           subsequently was approved for the prevention of
                                                           maternal-fetal HIV-1 transmission.12 In February
Extending the research showing the benefits
                                                           1994, results from the Pediatric AIDS Clinical
of early treatment, researchers have found that
                                                           Trials Group indicated a 67 percent reduction
early use of antiretroviral treatments reduced the
                                                           in perinatal HIV transmission using ZDV.13
chances of transmission to an uninfected partner
                                                           Two months later, the CDC issued provisional
by 96 percent.11 This large international study
                                                           guidelines supporting the use of the therapy
compared an early treatment group, in which
                                                           for this purpose, followed by formal FDA
the HIV-infected partner initiated ART treatment
                                                           approval, and finally published consensus
immediately, with a deferred group, in which
                                                           recommendations jointly issued by the

                                                              Recognizing the Value of Innovation in HIV/AIDS Therapy   |   5
Reductions in Mother-to-Child HIV Transmission

        U.S. Public Health Service Task Force (USPHSTF)
        and CDC.14                                                    FIGURE 3. Reductions in Mother-to-Child
                                                                      HIV Transmission
        Antiretroviral use for the purpose of preventing
        perinatal HIV transmission has increased                         35%
        dramatically in the United States, and                           30%
                                                                                           25–30%
        transmission rates have diminished. One multi-
        state study determined that from 1993 – before                   25%
        approval of ZDV for the specific indication
                                                                         20%
        – to post-approval in 1996, infected pregnant
        women were increasingly offered ZDV over                         15%
        other therapies. The authors asserted that “the
                                                                         10%
        proportion of HIV-infected pregnant women
        offered prenatal ZDV increased from 27 percent                    5%
        to 85 percent, the proportion offered intra-partum                                                             2%
        ZDV increased from 5 percent to 75 percent, and                   0%
                                                                                            1994                     2002
        the proportion offered neonatal ZDV increased
        from 5 percent to 76 percent.”15 The expanded
        use of ZDV for this subsequent indication has                 Source: Centers for Disease Control and Prevention, “Achievements
        contributed dramatically to driving maternal HIV              in Public Health: Reduction in Perinatal Transmission of HIV Infection
        transmission rates down from 30 percent to less               – United States, 1985-2005,” MMWR, 55 (2 June 2006) 21, 592-597
                                                                      http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5521a3.htm.
        than two percent.14 (See Figure 3.)

        The updated HHS guidelines specifically                     Prevention of HIV Infection in
        encourage the treatment of infected pregnant                High-Risk Populations
        women to prevent maternal-fetal HIV-1                       Building on the successful use of ART in the
        transmission. The guidelines now recommend                  prevention of maternal-fetal HIV-1 transmission,
        that a combination regimen be initiated in all              researchers have worked to establish the use
        infected pregnant women – even those who                    of these therapies to help prevent HIV infection
        would not be candidates based on their own                  in high-risk populations. Recent evidence has
        clinical presentation – with the goal of preventing         led to the approval of emtricitabine/tenofovir
        perinatal transmission of HIV to the fetus.9 This           disoproxil fumarate (Truvada®) in July 2012 for
        updated recommendation reflects a focus on                  the prevention of HIV/AIDS in uninfected people,
        decreasing maternal-fetal HIV transmission, and             or pre-exposure prophylaxis (PrEP). This is the
        therefore an emerging consideration of risk to              first approval of its kind.
        both a mother and her fetus.
                                                                    Emtricitabine/tenofovir disoproxil fumarate is
        Based on these kinds of clinical observations,              already approved, in combination with other
        physicians and patients can make more informed              antiretroviral agents, for treatment of HIV-1
        decisions today about the differential risks and            infection in adults and pediatric patients ages 12
        rewards of regimens with similar approved                   and older.16 It will now be used, in combination
        indication profiles. Furthermore, because                   with safe sex practices and other prevention
        guidelines now support the use of antiretroviral            strategies, by uninfected individuals who are at
        therapies for the prevention of maternal-fetal              high risk of HIV infection and who may engage in
        HIV-1 transmission, physicians and patients                 sexual activity with HIV-infected partners.17
        together can consider and select the optimal
        therapy regimen based on family planning and                The new indication was approved based on two
        risk to a woman’s fetus. This is another example of         large clinical trials. The iPrEx trial conducted by
        incremental research leading to increased utility           the National Institute of Allergy and Infectious
        and optimized treatment selection that was not              Diseases (NIAID) found that a once-daily oral dose
        proven at the time of approval of certain therapies         of emtricitabine/tenofovir disoproxil fumarate
        like ZDV.                                                   provided protective efficacy of 44 percent among
                                                                    men and transgender women who have sex

6   |     Recognizing the Value of Innovation in HIV/AIDS Therapy
Preventative Drug Treatment Reduces Risk of Infection
with men compared with placebo. Efficacy was
strongly connected with adherence; participants        FIGURE 4. Preventative Drug Treatment
who took PrEP medication on 90 percent or              Reduces Risk of Infection
more days during the treatment period had an
estimated 73 percent HIV risk reduction, while                                                   FTC/TDF resulted in
those who took PrEP medication on more than 50                                                   73% few infections
                                                                     47                          than placebo
percent of days had an estimated 50 percent HIV
risk reduction.18 (See Figure 4.)                                                                    Placebo

A study conducted by the CDC among                                                                   FTC/TDF*

heterosexual men and women in Botswana
showed that emtricitabine/tenofovir disoproxil
fumarate reduced the risk of acquiring HIV                                         13
infection by 62 percent.19 The Partners PrEP study
indicated a reduced risk of transmission from one               Number of patients infected

partner to the other of 75 percent when compared      *FTC/TDF is emtricitabine combined with tenofovir. Data reflect study
to placebo.16 This study, with clinical sites in      results through May 2011 as reviewed by the Partners PrEP Study
Kenya and Uganda, was conducted among                 Data and Monitoring Board.
heterosexual couples where one partner is
                                                      Source: University of Washington International Clinical Research
HIV positive.
                                                      Center press release, “Pivotal Vital Study Finds that HIV Medications
                                                      are Highly Effective as Prophylaxis Against HIV Infection in Men
                                                      and Women in Africa,” (Date through May 2011) http://depts.
Conclusion                                            washington.edu/uwicrc/research/studies/files/PrEP_PressRelease-
                                                      UW_13Jul2011.pdf.
This paper illustrates the substantial clinical
gains that have been made in the treatment
of HIV/AIDS, and some of the important factors       Over the past two decades, a greater understanding
in these gains, over the past two decades.           has evolved of the optimal clinical role and value
HIV/AIDS has evolved from a lethal disease to        of new HIV treatments, both alone and in different
one that is chronic, manageable, and preventable     combination therapies, as well as the value of
for patients who have access to medicines.           their utilization at earlier stages of the disease
Mortality rates related to HIV infection are at      cycle. Early combination regimens are recognized
an all-time low, and the availability of multiple    to offer the best opportunity for disease control
antiretroviral options allows physicians to select   and remission. What is more, many of these
the optimal combination regimen to achieve           treatments have been shown to provide
undetectable viral load and to prevent or delay      previously unrecognized benefit in a variety of
the development of drug resistance. Even patients    new preventative and prophylactic indications.
who have failed prior treatment regimens or          For example, certain antiretrovirals now provide
suffer from drug-resistant virus can generally       tremendous opportunity for the management of
achieve positive outcomes with today’s extensive     pregnant women who are infected with HIV and
therapy options.                                     some have been shown to prevent infection in
                                                     adults.
These gains have been made slowly but steadily
through a complex process of “step-wise              It is important to recognize that these broader
transformation” that involves introduction of a      benefits are frequently not proven at the time of
series of incremental improvements in treatment      initial FDA approval. An assessment based on
over time. The introduction of new medicines         available evidence at the time of launch would
is clearly fundamental to advancing treatment.       have substantially underestimated the full clinical
However, this paper focuses on another               value of these treatments to patients with
important, but less recognized aspect of medical     HIV/AIDS. Over time, real-world practical
progress: the evolution of our understanding         experience and a growing body of published
of value of new medicines over time through          clinical data documenting this experience have
continued research and use in real-world             revealed unforeseen elements of value for
clinical practice.                                   individual therapies. Because the optimal role

                                                        Recognizing the Value of Innovation in HIV/AIDS Therapy               |   7
and full value of an individual therapy cannot be                                        research, innovation, and patient care. On the
        known at the time of FDA approval – for HIV and                                          other hand, flexible policies that are sensitive to
        other disease areas – it is important that patients,                                     the way the evidence of value emerges over time
        and the clinicians who care for them, have access                                        will help ensure that new treatments are properly
        to a full range of treatment options.                                                    valued and available to patients. Such policies,
                                                                                                 which are in line with the incremental scientific
        Policymakers can foster this continued progress,                                         process, will also promote future advances by
        and the evolution of knowledge that supports                                             properly incentivizing innovation. Continued
        it. Policy approaches that seek to assess the                                            innovation and evolution with both existing and
        definitive value of a therapy at the time of                                             as-yet undiscovered therapies provide hope for
        introduction will fail to capture its full value over                                    future clinical advances that will benefit individual
        time and will act as a disincentive to long-term                                         patients and society as a whole.

        Endnot e s
        1 U.S. Department of Health and Human Services (HHS), Centers for Disease                11 M.S. Cohen, Y.Q. Chen, M. McCauley, et al., “Prevention of HIV-1 infection with
        Control and Prevention (CDC), National Center for Health Statistics (NCHS),              early antiretroviral therapy,” New England Journal of Medicine; 365(6):493-505
        “Health, United States, 2011 with Special Feature on Socioeconomic Status and            (2011).
        Health,” Table 22, http://www.cdc.gov/nchs/data/hus/hus11.pdf, (2012).
                                                                                                 12 U.S. FDA, “HIV/AIDS Historical Time Line 1981-1990,” http://www.fda.gov/
        2 UNAIDS, “Together We Will End AIDS,” http://www.unaids.org/en/resources/               ForConsumers/ByAudience/ForPatientAdvocates/HIVandAIDSActivities/
        campaigns/togetherwewillendaids/unaidsreport/, (2012).                                   ucm151074.htm, (2012).

        3 U.S. HHS, CDC, Mortality and Morbidity Weekly Report, “HIV Surveillance –              13 U.S. HHS, CDC, Mortality and Morbidity Weekly Report, “Zidovudine for the
        United States, 1981-2008,” 60(21); 689-693, http://www.cdc.gov/mmwr/preview/             Prevention of HIV Transmission from Mother to Infant,” http://www.cdc.gov/
        mmwrhtml/mm6021a2.htm, (2011).                                                           mmwr/preview/mmwrhtml/00030635.htm, (1994).

        4 M. Zwahlen and M. Egger, “Progression and Mortality of Untreated HIV-Positive          14 U.S. HHS, CDC, Mortality and Morbidity Weekly Report, “Achievements in
        Individuals Living in Resource-Limited Settings: Update of Literature Review and         Public Health: Reduction in Perinatal Transmission of HIV Infection - United
        Evidence Synthesis,” UNAIDS Obligation HQ/05/422204, http://data.unaids.org/pub/         States, 1985—2005,” http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5521a3.
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8   |      Recognizing the Value of Innovation in HIV/AIDS Therapy
Boston Healthcare Associates, Inc.
Boston Healthcare helps biopharmaceutical, medical device, and diagnostics companies unlock the value of
innovation in the global healthcare marketplace. Clients rely on Boston Healthcare to create opportunities,
navigate complexity, grow their businesses, and achieve their objectives through reimbursement and market
access strategy, health economics and outcomes analysis, market and pricing strategies, and business
development support—all delivered to help clients capture value.

Boston Healthcare’s unique approach, combining strategic consulting with a deep understanding of the
evidence-driven value environment, gives clients a real-world edge in assessing, creating, and capturing growth
opportunities. For more information, visit www.bostonhealthcare.com.

Funded by a grant from the Pharmaceutical Research and Manufacturers of America.

Recognizing the
Value of Innovation
in HIV/AIDS Therapy

White Paper | December 2012
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