2002 Prevention Now

July 9, 2002
Prepared remarks by Dr. Helene Gayle, former director, HIV/AIDS & TB Initiatives

View slideshow presentation (1.9 MB - PPT)

Good morning. I am honored to be part of this plenary session on HIV prevention now and in the future. In the time I have, I'd like to address:

What we know about prevention currently
Some of the new developments and new challenges for prevention
A vision for prevention in the future

Before I begin I would like to thank many people for their contributions to this talk.
First the members of the Global HIV Prevention Working Group, whose report – – which I will discuss shortly – was released last week.

I would also like to thank people too numerous to mention by name who provided critical input into the development of this talk and whose work I will cite throughout this talk.

Yesterday, Bernhard Schwartlander showed data indicating that if we do not embark on an aggressive new prevention effort, we can expect 45 million new HIV infections this decade. But his data also demonstrate that such a scenario is not inevitable. By bringing a package of 12 proven prevention interventions to scale by 2005, we could prevent nearly two-thirds – that's 29 million – of those infections.

To do this, we will need to rapidly expand all of the HIV prevention strategies that have so far proven effective. HIV infection rates will drop when we implement programs based on sound scientific research, when prevention interventions are integrated and when prevention has the full backing of national leaders and is funded with adequate resources.

The importance of HIV prevention could not be clearer. Defying expectations that infection rates would plateau in the hardest-hit countries in Africa, HIV prevalence continues to increase in Botswana, Zimbabwe, Swaziland and other countries. In Nigeria, the continent's most populous country, HIV prevalence now exceeds the 5% threshold at which incidence often accelerates. The Caribbean continues to be the second-most affected region in the world.

HIV infection rates are rising rapidly in some of the world's most populous countries – in China, India, and Russia, for example. And in industrialized countries, where HIV prevention earlier succeeded in containing the epidemic, there is strong evidence that risk behaviors are on the rise and early evidence that infection rates are increasing, too.

Clearly we are facing an ever evolving, ever unfolding epidemic. These challenges demand a much stronger, and sustained global commitment to HIV prevention.

To help chart the way toward scaling up effective interventions, the Bill & Melinda Gates Foundation and the Henry J. Kaiser Family Foundation this year convened the Global HIV Prevention Working Group. Composed of 37 leading experts in public health, clinical care, and biomedical, behavioral, and social research, and people affected by HIV/AIDS, the Working Group was assembled to review the scientific evidence on HIV prevention and to assess the status of global prevention efforts.

The Working Group's first report – a "blueprint for action" to prevent 29 million new infections by the end of this decade – was issued last week in advance of the International AIDS Conference. The report surveys available data on effective HIV prevention strategies, identifies obstacles to a comprehensive global HIV prevention effort, and makes recommendations for scaling up effective prevention strategies.

The working group report provides evidence that by scaling up the HIV prevention strategies proven to be effective, we could prevent nearly two out of three new infections by the end of the decade. There are several analyses completed over the past couple of years such as the US Centers for Disease Control and Prevention's HIV/AIDS Prevention Research Synthesis Project, or meta-analysis by Mike Merson and colleagues on effectiveness of prevention interventions in developing countries that confirm their effectiveness in reducing behavioral risk for HIV infection.

In addition, considerable data now exists on the cost-effectiveness of the HIV prevention interventions seen in this slide – all of which fall well below recognized standards for cost-effectiveness. Moreover, the raw costs of these HIV prevention interventions are extraordinarily low. Condom distribution and STD treatment for female sex workers, for example, cost only between $11-17 to prevent one case of HIV infection.

The global epidemic, however, continues to worsen. This has understandably led some to ask why HIV prevention hasn't succeeded in reducing the number of new infections.

The most obvious answer is inadequate funding for HIV prevention activities. Our efforts have simply not been funded at the level necessary to achieve the depth and breadth required for maximum results. UNAIDS estimates that spending from all sources this year on HIV prevention activities will total $1.2 billion. This is roughly one-quarter of the amount estimated by UNAIDS needed to mount an effective global HIV prevention effort.

And as a result we have a major gap in access to prevention information and services. Current best estimates are that only between 10-20% of people at risk for infection in low-income countries are reached by interventions to prevent sexual transmission. So more than 4 out of 5 people who need prevention services lack access. Only between 1 and 10% have access to voluntary counseling and testing, or to interventions to prevent mother-to-child transmission.

Prevention efforts have also suffered in many countries due to a lack of a comprehensive plan of action and limited political support. Finally, although individual behavior change is essential, we have for too long ignored developing specific interventions that address community and societal level factors that greatly influence the ability to act at the individual level.

In its report released last week, the Global HIV Prevention Working Group identified a series of specific steps that must be taken now to ensure that proven HIV prevention efforts achieve their maximum effect of reducing new infections. Key recommendations include a major increase in funding for HIV prevention programs, reaching a level of at least $4.8 billion annually by 2005. In recognition of the shortage of human and financial capacity to scale up prevention interventions in many low-income countries, the Prevention Group also urges that the international community invest in training, technology transfer, and other activities to help developing countries build sustainable capacity for HIV prevention programs. In addition, prevention efforts must be more strategically focused; access to key prevention commodities, such as condoms and HIV test kits, must be assured; and high-level political support for prevention must be built and sustained.

It is often said that the only thing constant about life is change. Clearly this is the case for the HIV epidemic and must be the case for our prevention efforts. In the next several years, we are likely to see the emergence of new prevention technologies and new behavioral strategies. Ongoing research will help us refine and improve the interventions we already have. And we must take into account the irony that expanding treatment access often creates additional challenges to HIV prevention efforts – we will see this unintended effect in poor countries in the south just as we have seen in richer nations in the north.

So let me turn to review of some of the ongoing or planned research that will continue to help evolve our ability to prevent new HIV infections. Because of time limitations, I will restrict my comments to research related to prevention of sexual transmission, the predominant mode of HIV transmission worldwide. Clearly there is still urgently needed research for preventing mother to child and blood borne transmission.

Because other speakers are addressing vaccines and microbicides, I won't discuss them here. I would note, though, that models developed by researchers at the London School of Hygiene and Tropical Medicine have demonstrated that even modest coverage for a first-generation microbicide would avert 2.5 million infections over three years. This illustrates how even a marginally effective vaccine or microbicide could significantly strengthen our ability to prevent new infections.

Much has been said about treatment of sexually transmitted infections for reducing HIV transmission. While the literature continued to show an association between STDs and HIV transmission, it wasn't until the mid 1990s that intervention trials were done to assess the actual impact of treating STD on HIV transmission.

Although, treatment of symptomatic STD's in the study done in the Mwanza region of Tanzania resulted in an almost 40% reduction in HIV incidence, the study of mass screening and treatment in the Rakai district of Uganda reduced the number of STD but failed to cut the rate of HIV infections. Although many factors need to be evaluated to understand the difference in findings, the presence of HSV-2, a treatable, but as yet incurable viral infection that is associated with increased risk of HIV transmission, may play a role.

Planning is nearing completion for HPTN—the NIH HIV prevention trials network study 039, a Phase III trial that will examine whether acyclovir treatment for HSV-2 helps protect HSV-positive individuals from HIV transmission. The randomized, double-blind, placebo-control trial will enroll 2,000 individuals from Peru, Zambia, Zimbabwe and the United States.

Similar to STDs, lack of male circumcision has been a consistent risk factor associated with HIV infection. Of 27 observational studies examined in this meta-analysis, 21 found a reduced risk of infection among circumcised men – whose risk was about half that in uncircumcised men. Shown here, in 15 studies that adjusted for potential confounding factors, the association was even stronger. The apparent protective effect of circumcision is strongest among men at especially high risk, such as STD clinic patients and truck drivers.

In order to assess the effectiveness of male circumcision as an intervention, studies are underway or being planned to look at a variety of issues that will help guide policies in this area. Currently questions remain about the actual biologic mechanism for the observed relationship between male circumcision and HIV transmission, questions such as: whether behaviors associated with groups that routinely practice circumcision explain the difference, whether the affect of circumcision is age dependent, and how acceptable and feasible male circumcision is across the range of cultural and socio-economic conditions. Also, since most of the studies have looked at the association of circumcision with acquisition of HIV in men, it would be important to assess the impact of circumcision on transmission of HIV from HIV infected men to their sexual partners.

Finding additional barrier methods that are female controlled is a public health priority. Observational studies indicate that diaphragms appear to decrease susceptibility to STDs. Additionally, since the cervix is likely to be more biologically susceptible to HIV than vaginal tissue, vaginal barriers such as diaphragms or cervical caps that cover the cervix could help protect against HIV infection.

There are ongoing studies of diaphragm acceptability and use in Zimbabwe and Kenya, and based on the results of those studies, plans are being made for clinical trials of diaphragm use to prevent HIV and STD transmission.

The advent of highly effective antiretroviral therapy, new and improved pharmaceutical agents and continued expanding treatment access will continue to have a major impact on prevention.

Post-exposure prophylaxis (PEP) is already the standard of care for health care workers who experience potential occupational exposure to HIV, and is responsible for some of the effect of ARVs for the prevention of mother-to-child transmission . In both developed and developing countries, there is considerable interest in prescribing PEP for a variety of circumstances in which an episode of unprotected sexual exposure to HIV may have occurred, such as sexual assaults, condom breakage during intercourse for discordant couples, or other unplanned, unprotected sexual contact.

Limited data exist about the use of PEP, however; recent data from Brazil and San Francisco suggest that PEP may be effective in reducing HIV acquisition.
The San Francisco study reveals several additional findings:

Medications were initiated later than one might hope – on average, 33 hours after the exposure incident.
Adherence approached 80%. No increase in STDs was reported in the year following use of PEP.
And although participants occasionally reported subjective side effects, no laboratory toxicity was found.
An additional finding from the San Francisco study is that study participants, as a whole, significantly reduced risk behaviors. This was especially true for men who have sex with men, but also, as the slide indicates, for women and heterosexual males.

Future research efforts should seek to obtain additional information regarding efficacy and safety. In addition, studies are needed to help answer basic questions about PEP, such as when PEP must be initiated in order to be effective, how many drugs to prescribe, and how long to treat.

Another potential use of ARVs for prevention is for pre-exposure prophylactic use. The Bill & Melinda Gates Foundation recently awarded a grant to Family Health International to study the use of Tenofovir for pre-exposure prophylaxis. Tenofovir, a recently licensed treatment of HIV infection was chosen because it:

Has a long half-life, allowing for once a day dosing, which should improve adherence and consistency in drug levels
Has shown promising results in preventing HIV infection in animals exposed to HIV
Has minimal interactions with other drugs that complicate future long term use
Has not been associated with serious toxicities
Has pharmocokinetics that are similar in infected and uninfected people

For all of these and many other ongoing studies, we can't count on results until they are in. But it is highly likely that the existing prevention tools we already know to be effective, will over the next several years, be supported by additional prevention technologies.

However, none of these new technologies will likely be 100% effective in preventing transmission or universally available to all populations at risk. Therefore we must maintain a balance between biomedical options and behavioral prevention.

With each new prevention technology that emerges, we will need to be conscious of the possibility of unintended consequences. Planning in advance for unforeseen outcomes will be essential to maximize the long-term success of our prevention efforts. The experience with improved treatment in high-income countries is illustrative of this point.

In the U.S. and some other industrialized countries, we initially failed to strengthen prevention efforts as treatment became more effective and more widely used. This slide summarizes some of the studies that demonstrate the challenges posed by improved therapy in high-income countries. In communities and social networks with already high HIV prevalence, increases in risk behavior of even a relatively small minority of individuals can generate significant numbers of new infections.

The increased access to HIV treatments in low and middle-income countries will inevitably have an important impact on HIV prevention strategies. Continued efforts to expand access to treatment for low and middle-income countries are imperative on moral and public health grounds.

Treatment also has enormous potential prevention benefits. Greater treatment access will offer people greater incentive to learn their serostatus. Enhanced access to treatment will also help reduce AIDS stigma by implicitly valuing the lives and well being of people living with HIV.

In addition, appropriate use of antiretrovirals on a broader scale could help reduce HIV infection by reducing viral load within a population. This hypothesis will be tested by HPTN 052, a planned randomized, placebo-controlled trial of ARV therapy among serodiscordant couples in Brazil, India, Malawi, Thailand and Zimbabwe. If results of this and other trials demonstrate effectiveness in reducing transmission, more aggressive expansion of testing services and earlier initiation of therapy than is currently recommended might be warranted.

Voluntary counseling and testing is the linchpin for the integration of HIV prevention and care. As an earlier slide noted, VCT has an independent prevention benefit, especially when coupled with counseling and other more intensive interventions. This effect has been most consistent for people who test positive.

In countries where the vast majority of people are unaware of their HIV status, prevention efforts must be generalized. Broader knowledge of serostatus permits development of prevention programs that are tailored to individual needs and can specifically be adapted for people living with HIV who might otherwise unintentionally continue transmission.

Unfortunately, most people at risk for HIV infection in developing countries are unaware of their serostatus. Achieving the potential prevention and care benefits of VCT will demand an urgent scale-up of VCT programs.

To respond effectively to the inevitable evolution of the epidemic, behavioral interventions will also have to continue to be refined and improved.

In particular, research is needed to:

Develop interventions for people living with HIV or prevention for positives.
Develop messages that are effective in the context of improved biomedical interventions.
Determine the optimal dose or intensity and duration of prevention intervention that is necessary under different circumstances including resources poor settings. This is particularly important since many of the interventions that have been demonstrated to be effective in changing behavior have been done under rigorous experimental circumstances and may not be as transferable to real world settings.
Determine how best to prevent relapses in risk behavior.
Address synergistic risks.
Better understand the impact of societal factors and more important develop concrete ways to address them.

I will expand on the last two points for a moment, since I think they are important areas for further focus. This study of men who have sex with men in the United States demonstrates that multiple factors impact vulnerability to HIV infection. The rates of sexual risk behavior and HIV infection increase with one or more co-morbidities, defined as drug and alcohol abuse, depression, partner violence and childhood sexual abuse.

In this regard, American MSMs are illustrative, not unique. In countries both rich and poor, every population that is vulnerable to HIV infection confronts multiple social, economic and political factors that increase susceptibility to the virus.

Long-term efforts to reduce HIV risk must effectively address the social conditions and economic circumstances of the most vulnerable individuals and communities. Whether we are discussing young people, women who are victimized by sexual coercion or poverty, people addicted to injection drugs, or men who have sex with men who confront ostracism and potential violence, people must be given a reason to believe in the future. They must experience feelings of belonging and trust. These feelings are sometimes grouped together under the rubric of "social capital." David Holtgrave and colleagues are presenting findings in a poster session later this week on the importance of social capital to good health. Looking at 14 different disease-specific outcomes, they found that a lack of social capital is a significant predictor of poor results on each.

Clearly looking at ways to address these broader societal and environment or structural issues is key to enhancing individual level behavior change.

Although considerable discussion has taken place there has been little concrete work to develop and implement interventions that operate at the level of environmental or structural level and alter the context for individual action.

I have listed several examples here to illustrate structural interventions that most people are probably familiar with, but might not have recognized as such.

This is a useful framework that looks at factors that affect HIV prevention at different levels. To date, most of our prevention efforts have addressed intervention at individual micro-level factors. Prevention effectiveness will be greatly enhanced when we stop simply discussing the other levels and develop concrete interventions that address the many underlying structural and macro societal issues that influence individual behavior and often serve as impermeable barriers to behavior change.

So effective prevention is much more than a condom or a clean needle. It is more than education. Effective HIV prevention involves a combination of interventions tailored to local needs and revised in response to changing circumstances. It requires a combination approach or combination prevention that – just like combination therapy – attacks risk behaviors, alters biologic factors, empowers individuals to make change through enabling environments and provides the necessary services and commodities in multiple, reinforcing ways.

Every country that has succeeded in reducing the number of new infections has used a combination of prevention approaches. Thailand, for example, supported targeted prevention interventions, structural interventions, anti-stigma efforts, public awareness campaigns, and the active involvement of every major sector of society in the fight against AIDS.

So, in closing, although prevention options will continue to expand in both the biomedical and behavioral realms, the world has the capacity to dramatically alter the course of this epidemic with what we know works now. Without major new resources matched by sustainable global political commitment, however, success will not be possible.

In my own country, there has been enormous sadness over the more than 3,000 lives lost in the September 11th attack. Recently, many have asked whether we knew enough before that date to have prevented those lives from being lost. As this newspaper clipping indicates, there is considerable doubt whether there was enough information to have prevented the attack from occurring. The same can't be said in the case of HIV. We know where the future is headed – 45 million new infections. And we know how to prevent this from occurring.

We have not a moment to lose. The cost of waiting is demonstrated by this slide presented yesterday in the opening plenary. The difference between the top and bottom lines reflects not only a continuing unacceptable gap in prevention access, but represents an equally unacceptable gap in our conscience, in our sense of social and moral responsibility, and our sense of justice.

In a recent issue of the British Medical Journal, Gavin Yamey and William Rankin authored an editorial on the future of AIDS. They wrote, "When the philosopher Thucydides was asked when justice would come to Rome, he famously replied that it would come when those who are not injured are as indignant as those who are." It is up to all of us to develop a level of indignation that accurately reflects our understanding of our common humanity and what is at stake for all of us.

HIV attacks our world's most vulnerable people. Will those of us who are more fortunate prove as indignant to this injustice as the millions of people in poor nations who face the ever-present risk of contracting HIV infection in the next several years?

In 1993, the then World Health Organization's Global Program on AIDS projected that as little as $1.5 billion invested in prevention could reduce by half the number of new infections that would occur by the year 2000 and save $90 billion dollars in associated costs.

Today that cost is $4.8 billion. Will we continue to wait until the cost has doubled, tripled, quadrupled and tens of million more lives are lost? Ultimately, we will pay now or pay later, but the longer we wait the cost in monetary and human costs will escalate.

The positive is that we do still have the opportunity to make a difference and the sooner we start the greater that difference will be. So, in closing, while the best time to plant a tree is twenty years ago, the next best time is now.

Thank you.

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