MALE SPEAKER: Good morning. Okay. Good morning, everyone. We would like to start on time, so people who want to attend the other sessions at 10:00 can leave after the last speaker for the plenary has finished.

So please, I would encourage the chairs of the sessions to keep strong with the time of each speaker. I know that’s not an easy task, but I think we need to do that, otherwise the last speaker is finding that everyone is leaving through the sessions.

The session of today was aimed to prevention. As you know, this conference has tried to highlight as much as possible, prevention. We have talked about the prevention science.

And today, we put together prevention speakers from different point of view, from some biological approaches to some public health approaches. The two chairs of the sessions will be Zena Stang (MS?), epidemiologist, professors of psychiatry and public health, working at the University of Columbia in New York.

And Jeree Chaktugan (MS?), who is the health minister of India, and who is not yet here, but we hope will arrive in a few minutes. So please, Zena, the table’s yours.

ZENA STANG: Good morning. And on adding to the welcome of our principal, we’ve got a very interesting session. And we’ve got - we’re trying to start absolutely punctually. And speakers, we have four wonderful speakers, and a very balanced program of prevention.

We’re trying to keep to yesterday’s theme of clinical and - clinical and the thinking in our minds of the incidence and prevalence around the world, which we were told yesterday and was so chilling.

And so, we’re going to have four sections on how we see prevention. And we’re starting with Dr. Helene Gayle, who’s known to many people. Helene’s known because she works in W.H.O., UNICEF, UNAID and other international organizations. And she’s been a major player in the CDC in the U.S. for many years, ending up as director of the program on preventive program on HIV, TB and STDs, very close to everybody’s interest.

And then she moved recently, to work with the Gates Foundation. So as I was teasing her, she’s very familiar with governmental and the foundation world. She’s just recently, I think two days ago, accepted the honor of being president-elect of the International AIDS Society.

Just like to say one thing about Helene - while she’s particularly appropriate to start our session, I think it must be ten years ago when she wrote “Kill the Cockroach,” (MS?) an important paper, saying prevention in developing countries, developing world, must include thinking about treatment.

I think that was the first paper that really challenged our understanding of prevention as a single, rather autonomous discipline.

So Helene is talking first, and I don’t want to waste our rather precious time. Please, Helene, over to you.

(Applause)

HELENE Gayle: Thank you, Zena, and good morning. I’m very honored to be part of this plenary session on HIV prevention. We’ve all been given our orders to try to keep this concise. So what I’d like to address in the time that I have is first, what we know about prevention currently. Second, what are some of the new developments and new challenges for prevention. And last, try to paint a vision for prevention in the future.

Before I begin, I’d like to thank many people for their contribution to this talk. First, the members of the Global HIV Prevention Working Group, who released a report last week that I will discuss shortly. And then I’d like to thank the people too numerous to mention, who provided critical input into the development of this talk, and whose work I will recite throughout. So thank you to all of you.

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 these data also demonstrated 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.

The importance of HIV prevention could not be clearer. Expectations that HIV infection rates would plateau in the hardest-hit countries in Africa have proven wrong. And the Caribbean continues to be the second most effective region in the world.

HIV infection rates are rising rapidly in some of the world’s most populous countries, such as China, India and Russia. In industrialized countries, there’s 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 and ever-unfolding epidemic. These challenges demand a stronger and sustained global commitment to prevention.

The Bill and Melinda Gates Foundation and the Henry J. Kaiser Family Foundation recently convened a global working group on HIV prevention, composed of people in public health, clinical care, biomedical, behavioral and social sciences, and people living with HIV and AIDS.

The working group was assembled to review the scientific evidence on HIV prevention, and to assess the global status of prevention efforts. The working group’s first report, “A Blueprint for Action,” to prevent 29 million new infections by the end of the decade, issued last week in advance of the International AIDS conference. And the report surveyed available data, identified some of the obstacles to prevention, and made recommendations for scaling up effective prevention strategies.

These effective prevention tools shown here on this slide are the tools that have been proven to be effective, and that, if scaled up and used to their full potential, could prevent nearly two out of three new infections by the end of the next decade.

In addition, considerable data now exists on the cost-effectiveness of HIV prevention interventions, seen in this slide. All of these fall well below recognized standards for cost-effectiveness. For instance, in the first row, condom distribution and STD treatment for female sex workers cost only between $11 and $17 to prevent one case of HIV and cost $1 per D.A.L.Y. or Disability Adjusted Life Gains.

And as you can see, the other interventions have similar cost- effectiveness. But I think we all ask ourselves the question, “Why hasn’t HIV prevention been more effective?” These slides show some of the reasons why.

The global epidemic continues to worsen. And it’s understandably led to many asking the question, why HIV prevention hasn’t succeeded in reducing new numbers of infection.

Has HIV prevention failed? In fact, HIV prevention hasn’t failed, we have failed prevention. The most obvious failing 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 that is needed to mount effective prevention efforts.

As a result, we have a major gap in access to prevention information and prevention services. Current best estimates are that only between 10% and 20% of people at risk for HIV in low-income countries are reached by interventions to prevent sexual transmission, and even smaller proportion have access to voluntary counseling and testing, or interventions to reduce mother-to-child transmissions.

Prevention efforts have also suffered in many countries, due to a lack of a comprehensive plan of action and strategic focus, 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 one’s ability to take preventive action.

In the report released last week, we were at – we issued several recommendations - first, that a major increase in funding for HIV prevention is necessary at the level of $4.8 billion by the year 2005.

Second, a critical need is –

(AUDIO GAP)

- behavioral strategies. Because of the time limitation, I will restrict my comments to research to prevention of sexual transmission, which is the predominant mode of HIV transmission worldwide.

Clearly, there’s still urgent research and need for expanded options for preventing mother-to-child and blood-borne transmission. And because other speakers will address vaccines and microbicides, I won’t go into great detail here about those interventions.

First, let me talk about improving STD control. Much has been said about treatment of sexually transmitted diseases for reducing the spread of HIV. 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 actually assess the impact of treating STDs on HIV transmission.

Now we know that there have been some conflicting findings between the studies done in Wanza, Tanzania, and the studies done in the Kai district of Uganda. And many studies continue to look at what some of the reasons for those differences are.

But although many factors still need to be evaluated to understand these differences, the presence of herpes simplex virus II, a treatable, but as yet incurable viral disease that is associated with increased risk of HIV, may play a role.

Therefore, planning is near completion of an NIH-sponsored HIV prevention trial network, Study 039, a Phase III trial that will examine whether Aciclovir, the treatment for HSVT II, could help reduce HIV transmission. HSVT II.

This trial is planned to take place in Peru, Zambia, Zimbabwe and the United States. Similar to the STDs, the lack of male circumcision has been a consistent risk factor associated with HIV. Shown here in a meta analysis of studies of male circumcision and HIV, 15 studies that were adjusted for potential confounding factors, demonstrated a strong protective effect, reducing the risk of HIV infection by greater than 40%.

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, and intervention studies are under way or planned in Kenya and Uganda, to look at a variety of issues that will help guide policies in this area.

There are many current questions that remain, and I’ve listed there questions about the actual biological mechanism, questions about whether behavioral practices in groups that also routinely circumcise explain the differences that are observed, whether the effect of circumcision is age-dependent, how acceptable and feasible male circumcision is across the range of cultural and social economic conditions. And finally, whether male circumcision also decreases transmission from men to their sexual partners.

Finding additional barrier methods that are female-controlled is a high 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, barriers such as diaphragms or cervical caps that cover the cervix could help protection against HIV.

There are now ongoing studies of diaphragm acceptability and use in Zimbabwe, Cote D’Ivoire and Kenya. And based on the results of these studies, plans are being made for clinical trials of diaphragm use, to prevent STD and HIV transmission.

The advent of highly active – highly effective and highly active antiretroviral therapy, new and improved pharmaceutical agents and continued expanding treatment access will have an ever-increasing impact on prevention.

Post-exposure of prophylaxis, or PEP, is already the standard of care in wealthy nations for health care workers, who have an occupational exposure to HIV, and is responsible for some of the vaccine and antiretroviral use for preventing mother-to-child transmissions.

In both developed and developing countries, there are 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 condom breakage or forced sexual acts, et cetera.

Although there are limited data about the use of PEP, recent data from Brazil and San Francisco suggest that PEP may be effective in reducing HIV acquisition.

And as you can see in the data from Brazil, the risk for infection was seven times higher for those who did not receive PEP, or the no-PEP group. In addition, the San Francisco study showed other interesting findings.

First, that medication was initiated later than one might have hoped, that adherence was good, however, approaching 80%, that there was no increase in STDs reported in the year following administration of PEP, that although participants reported subjective side effects, there were no laboratory toxicities found.

And additionally, participants as a whole significantly reduced risk behaviors.

Clearly, future research will be necessary in order to understand the usefulness of PEP on a more widespread basis.

Another potential use of antiretroviral therapy for prevention is for pre-exposure prophylaxis use. Tenofovir, a recently licensed treatment for HIV, is being considered for a study of its preventive effect.

Some of the reasons that Tenofovir is being considered is that it has a highly potent antiviral activity, has a very long half life, allowing for once-a-day dosing, has shown promising results in preventing HIV infection in animals exposed to HIV, has minimal interaction with other drugs that could complicate future long-term use.

It has not been associated with serious toxicities, and has pharmokinetics that are similar in infected and uninfected people.

I think given all of the important research that’s going on in prevention, it’s likely that prevention options will continue to expand in the future.

However, since none of these new technologies are likely to be 100% percent effective in preventing transmissions, it’s always going to be important to maintain a balance between biomedical options and behavioral prevention.

In many of the nations in the north, there has been a failure to strengthen prevention in parallel, as treatment becomes more effective and more widely used.

This slide summarizes some of the studies that demonstrates the prevention challenges by improved therapy in high-income countries. These studies look at the impact of treatment optimism on risk behaviors and perceptions. It shows that in countries like the U.K., the U.S., Australia and other wealthy nations, among gay men, discordant couples and other groups, there is a substantial increase in risk behaviors, decrease in concern about risk, and a sense that HIV is a less serious threat.

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

Treatment also has an enormously potential positive impact for prevention. Greater treatment access will offer people greater incentives to learn their HIV sero status.

Enhanced access to treatment will also help reduce AIDS stigma by valuing the lives 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.

And this hypothesis is going to be tested by another HIV prevention trial network study, HPTN 052, a planned study of antiretroviral therapy among discordant couples in Brazil, India, Malawi, Thailand and Zimbabwe.

If results of these and other important trials demonstrate an effectiveness of antiretroviral use in reducing transmission, more aggressive expansion of testing services and early initiation of therapy than is currently recommended, maybe warranted.

Voluntary counseling and testing is the linchpin for the integration of HIV prevention and care. As in the earlier slide, VCT has an independent prevention impact, especially when coupled with counseling. Broader knowledge to Sero status permits development and prevention programs that are tailored to individual needs, including people living with HIV.

Unfortunately, most people at risk for HIV in developing countries, over 90%, are still unaware of their Sero status. Achieving the potential prevention, as well as care benefits of voluntary counseling and testing, demand an urgent scale-up of VCT programs.

And finally, let me talk for a couple of minutes about refinements of behavioral interventions. 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 interventions that have oftentimes been done under very different circumstances, and develop how best to prevent relapses, as we’re seeing in some of the industrialized countries, relapses in risk behavior, address synergistic risk, and finally, better understand the impact of societal factors and develop more and concrete ways to address those.

Let me just talk for a couple of minutes about some of these – some of the second points. And this slide here on co-morbidities and vulnerabilities of HIV infection in men who have sex with men looks at the – has an increasing risk of HIV, as well as sexual risk-taking associated with greater numbers of the risk factors as described here - drug and alcohol abuse, depression, partner violence, child sexual abuse.

And so, as the number of those risk factors increase, so does the rate of HIV and risk-taking behavior. In this regard, American men who have sex with men are illustrative, not unique. In countries both rich and poor, every population that is vulnerable to HIV confronts multiple social, economic and political factors that increase vulnerability to HIV.

Long-term efforts to reduce HIV must also effectively address the social conditions and economic circumstances of the most vulnerable individuals in our societies and in our communities. Whether we’re discussing young people, women who are victimized by sexual coercion or poverty, people addicted to drugs, or men who have sex with men, who confront ostracism and potential violence, people must be given a reason to believe in their future.

Although considerable discussion has taken place here, and continues to take place about some of these societal issues, it’s important that we remember that these issues must also be addressed, and need more concrete work to develop and implement interventions that operate at this environmental or structural level.

So effective prevention is more than any one intervention. It is more than just education. Effective 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 of therapy, attacks risk behaviors by multiple routes, alters behavioral factors, empowers individuals to make decisions through enabling environments, and provides the necessary services and commodities in multiple and reinforcing ways. And this framework here tries to put together all the different aspects, all the different ways in which we must come together to truly affect prevention.

So in closing, although prevention options will continue to expand in both the biomedical and behavioral realms, the world has the capacity now to dramatically alter the course of this epidemic.

Without major new resources matched by sustainable global, political commitment, however, these successes will not be possible. In my country, there has been enormous sadness over the more than 3,000 lives lost in September 11th attacks. Recently, many have asked whether we knew enough before that date to have prevented those lives from being lost. As these newspaper clippings indicate, there is considerable doubt whether there was enough information to have prevented the attack from occurring.

The same cannot be said about 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 the bottom line reflects not only a continuing unacceptable gap in access to prevention, but also represents an equally unacceptable gap in our conscience, in our sense of social and moral responsibility, and in our sense of justice.

In a recent editorial on the future of AIDS in “The British Medical Journal,” Gavin Yammy and William Renkin wrote, “when the philosopher Lucidities 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.

When will we all become as indignant to this injustice as the millions of people living with HIV and who face the ever-present risk of contracting HIV in the next several years? If only. It has been said that the two most anguished words in the English language are “if only.” If only, in 1993 the then World Health Organization 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 in associated costs.

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

The positive is that we do still have the opportunity to make a difference. And the sooner we start, the greater the difference will be.

So in closing, while the best time to plant a tree is 20 years ago, the next best time is now. Thank you.

(Applause)

FEMALE SPEAKER: The fantastically comprehensive account of the range of treatments offered to us. And now again, to pick up one aspect, she mentioned work that is done in laboratory, with clinical trials and with applications in the population. And Lee mentioned vaccines. And she also mentioned microbicides. Not everybody knows that a microbicide is to debilitate, a substance like a little gel that one puts between partners.

(AUDIO GAP)

Lawrence Corey: Thank you, Dr. Stein, Minister Simhan (MS?). My talk today will review some of the key scientific and policy issues that are facing the field of HIV vaccine development, hopefully to provide background as to why there is cautious optimism from investigators in this field.

I will first discuss the scientific issues revolving around vaccine development, and then review the current state of clinical trials of vaccines.

I’m going to start at the beginning of what does an HIV vaccine need to do. In general secretions as well as in blood, HIV is found as both frevirions (MS?) and viral-infected cells. As such, HIV vaccines need to induce both antibody and T-cell responses to the infecting virus.

This slide illustrates the process of vaccine-elucidated neutralizing and binding antibodies, binding up HIV virions (MS?) upon subsequent exposure to the virus.

The next slide depicts the process of eliciting T-cell memory, especially cytotoxic T-cell responses to HIV-infected cells. Because destruction, or what we term apoptotic (MS?) death of viral-infected cells upon entry into the body.

Now, what’s the timeframe for which these immune responses must appear? We have learned from the primate model of SIV that viral infection across mucosal tissue establishes itself from one to three days post- exposure.

That virus then is spread to the regional lymphoid tissue within three to five days, and that rapid replication of systemic dissemination occurs within six to nine days post-infection.

Vaccines that induce sterilizing immunity, or those that would abrogate establishment of latency or early infection, must work early in this process, as shown by the black arrows.

There are examples of this with other vaccines - the influenza vaccine, polio vaccine, and likely measles vaccine work within these timeframes. As such, while the immunological requirements for an HIV vaccine regimen that accomplishes these tests are substantial, they do appear achievable.

Why then has it been difficult to construct an HIV vaccine? Perhaps the easiest answer is that unlike hepatitis B or polio, there has not emerged any definitive marker of protection, perhaps because the virus employs several immune evasion strategies.

These include masking of its neutralizing epitotes, as well as antigenic diversity that causes escape from neutralizing, as well as helper and cytotoxic T-cell responses.

There are also economic issues that have influenced HIV vaccine development. Developing an HIV vaccine has been and still is a high-risk scientific venture. And as such, has been viewed in the context of other competing interests within pharmaceutical and biotechnology companies.

Moreover, vaccines need to be highly effective, have negligible toxicity and be inexpensive. As such, vaccines have competed poorly for company resources. This reality remains unchanged.

Fortunately, some of these economic perceptions are changing. Public funding of HIV vaccine research and development has increased substantially in the last five years, with increasing recognition of the importance of economic push mechanisms to increase the resources in vaccine research.

Concomitant with this, and perhaps behind these increased resources, is increasing political support for HIV vaccines. I think this stems from the recognition of the importance of a vaccine for controlling the epidemic, and the advocacy of economists, such as Jeff Saks, that have shown the importance of poor health on economic development.

The ideal pipeline for HIV vaccine development, in my opinion, would be one in which one sees a steady flow of ideas to vaccine constructs, to clinical trials, with adequate resources both in scientific personnel and money, to make flow through the pipeline unobstructed and free.

In reality, the pipeline is much different. This slide, which depicts the reality of HIV vaccine trials in the last decade, shows that at present, the pipeline is more of a trickle than a steady of stream of clinical trials.

Constriction in the pipeline occurs substantially in pre-clinical development, with many vaccines having difficulties in meeting the development timelines and manufacturing requirements for entering clinical trials, some not producing adequate immunogenicity in humans in early clinical trials, and hence, only a few entering widespread testing.

Let’s now briefly review the roads so far traveled. To date, HIV vaccine development is, I think, best characterized in waves. The first wave of activity took place between 1987 and 2000, and involved over 20 different types of vaccines, almost all envelope subunit vaccines. Over 5,000 volunteers were entered into trials that were conducted in a number of regions of the world.

The most notable importance of the trials was the establishment of the safety of these products, albeit the immune responses they induced were narrow in their breadth and magnitude, and none of these vaccines induced the consistently detectable CDA/CTL response.

In the mid-1990s, there was a shift in emphasis to the development of vaccines that would induce cytotoxic T-cell responses to HIV. Vaccines that used viral vectors to introduce HIV 1 genes into the class 1 pathway to antigen processing cells were constructed. The most common early approach utilized poxvirus vectors, such as the canary pox or MBA.

The second wave of clinical trials were initiated in 1999 and 2000, which demonstrated that CD-8 T-cell responses to HIV-infected cells could be detected after vaccination with these poxvirus vectors.

This year has brought several new important developments in HIV vaccine research. The near-completion of the GP-120 trials in the United States and Thailand have shown us that global HIV vaccine development can be done successfully. This meeting also brings the recent announcement from the Thai HIV vaccine program, of their initiation of a Phase III clinical trial of an all-vac vector in combination with GP-120.

2002 also marks what I will call the third wave of vaccine clinical trials, the use of combination vaccines involving DNA priming and viral vector boosting, to increase T-cell responses after vaccination.

This combination vaccine regimen has been shown to be quite effective in controlling viral replication after experimental challenge in primates.

The next cartoon illustrates the effects of such vaccines in reducing the initial burst and subsequent set point of viral replication after acquisition of HIV. The yellow line depicts the vaccinated individuals, and the blue line that of a natural infected individual. The slide shows the potential reduction from a set point of 50,000 to 1,000 RNA copies per ML.

If one looks at the slide I showed you previously of the early events of HIV infection, these vaccines seem to produce their greatest effect in reducing systemic dissemination, and perhaps early regional spread of the virus.

T-cell-directed vaccines bring with them several new scientific and policy challenges. Now, conceptually, it is easy to understand how a vaccine that modifies our replication would help the individual, delay progression to AIDS and even enhance antiretroviral therapy.

However, vaccines designed to modify viral replication offer several new challenges in clinical trial design. What level of viremia (MS?) control and how long this level should be sustained or must be sustained for the use of such product.

The durability of viremia control is the major determinant in clinical, as well as population-based effects of such vaccines. This is an especially pertinent question, in that low-grade replication may eventually lead to the development of a (MS?), and subsequent higher levels of replication in disease transmission and progression, an observation recently demonstrated in primates.

Perhaps the most important issue raised by T-cell-mediated vaccine regimens is, would these vaccines reduce transmission? Now the best data we have on the relationship between viral load and transmission is from the study conducted in Rakai (MS?), that shows a nearly linear relationship between viral load and transmission.

Similar data exists from maternal fetal transmission, where transmission rates for the infant are markedly reduced among mothers with HIV viral loads of less than 1,000 copies per amelia (MS?) plasma.

Thus, there are theoretical reasons and experimental data to believe that vaccines that control viremia (MS?) can impact transmission. This slide from Ira Longini from the Emory Vaccine Center depicts a mathematical model utilizing prevalence data from Kenya in modeling the effect of the vaccine that reduces viremia to 1,000 copies per ML on an ongoing HIV-run epidemic.

One can see that after initiating a population-based vaccination contain, which starts at year five into the epidemic on this slide, one would see a leveling off of the epidemic and a reduction in prevalence in the general population. But it will take time and sustained energy.

Such mathematical models are reassuring, but to really plan vaccination policy for a country or region, I think real data on transmission are needed. The typical Phase III clinical trial takes three to four years to conduct. Traditionally, population-based trials to evaluate the impact of a vaccine upon transmission in communities are done after efficacy is established.

To perform such studies sequentially seems unacceptably long to me, with an epidemic that is consuming 5.3 million new cases yearly and growing. We must think of novel ways of deriving these data quickly. HVTN scientists led by Drs. Judy Wasserheit (MS?), Steve Self and Susan Buckbinder are involved in designing in trials to measure these effects within the context of our initial Phase III trials of these vaccines.

T-cell-directed vaccines also raise the issue of whether clade-specific (MS?) vaccines are needed. Clade typing is largely based on envelope sequence and antibody diversity. As I will discuss with you, cross plate T-cell responses are well documented in both natural infection and after alvac (MS?) vaccination or DNA ando virus vaccination.

These next two slides illustrate this point. Cross plate CTL responses have been demonstrated after receipt of a clade B alvac vaccine. This slide depicts cytotoxic T-cell responses to HIV-infected cells, using a panel of strains derived from different clades of HIV.

Note that CTL responses are directed to prototype clade A, C, V and E, as well as clade B isolates in this vaccinee. Cross clade T-cell responses have also been observed by investigators at Merck Research Labs, who measured T-cell responses by the elispondacity (MS?) to clade A, B, and C consensus peptides after administration of an adno virus clade B gag vaccine.

T-cell responses to clade A and C peptides were detected quite frequently, as you can see. At this meeting, these investigators report that the magnitude of these responses are somewhat lower than clade B responses, but still at substantive levels, more than 150 to 200 gamma interferon-producing cells per million PBMCS, a level that I will come back to shortly.

I want to conclude my talk with several messages. The first message is that there is increasing momentum in the HIV vaccine field. More constructs with greater scientific novelty and with greater pre-clinical immunogenicity are entering the pipeline.

The T-cell responses we are seeing in early clinical trials are approaching the level seen with other successful vaccines. For example, this slide illustrates recent data on the levels of gamma interferon-producing T-cells after receipt of a smallpox vaccination from – with vaccinia (MS?) virus.

The number of interferon gamma-producing T-cells averages 200 to 400 cells per million PBMCs. That’s in the left column with the yellow dots.

The next slide shows early data from the Merck clade D vaccine trial, which shows somewhat higher levels of such cells, after DNA adno virus vaccination. The data are early and the subjects few, but the trend is encouraging.

My second message is, while we do not have a vaccine construct that produces the breadth and the magnitude of neutralizing antibodies that we would like, there are data to make us optimistic that we can achieve clinical and population benefits with T-cell-based vaccines.

Cross-clade T-cell responses are being achieved with T-cell-based vaccines. And there is increasing scientific rationale to study clademisic-matched T-cell vaccines.

I am often asked, “why should a country participate in clinical trials of vaccines that are not clade-matched?” The best reason, in my opinion, is reduction in time to determining if a vaccine will be useful to its people.

Recombinant viral vector vaccines are difficult to manufacture. Scientific and technical resources to develop and manufacture country- specific vaccines are not currently available. Scale up and regulatory processes involved in making vaccines for clinical trials is still a formidable task.

It seems to me that cross clade responses to a potent vaccine that has received concentrated support through its clinical development may produce a greater benefit than a country-specific vaccine that it’s either less potent, or what I see increasingly, its non-existence.

Message four, HIV vaccine development requires more international cooperation from both scientists and the global community than previous experimental vaccines. Phase I clinical trials are in essence, a part of the pre-clinical development of HIV vaccines. Combination vaccines are required.

This necessitates collaboration and cooperation among investigators, inventors and the communities involved in vaccine research.

The HVTN was established in 1999 to do just this task. While initially it consisted of ten centers, nine in the U.S. and one in South Africa, it was expanded to 27 clinical trial sites in 12 countries. All the site expansion that has occurred or is planned is outside of the United States. And clinical trial sites now exist in the Caribbean, South America, Africa and Asia.

Collaborations with other organizations, such as the CDC, IAVI (MS?), the Walter Reed Army Institute of Research, Eurovac and UNAID to conduct vaccine research throughout the globe are being initiated. We must maximize resources and achieve global coordination and collaboration at HIV vaccine development.

Message five, we are asking communities involved in the HIV epidemic to participate in vaccine clinical trials sooner, and on a greater scale, than any other vaccine program. We have found that debating the ethical and policy implications of HIV vaccines are a necessary prelude for initiating clinical trials for HIV vaccines in a country.

Message six is perhaps my most important message. HIV vaccine development is not a sprint. HIV vaccines need to be developed within the context of a larger prevention effort. Vaccine development has always been an iterative process, with gradual improvements in vaccines over time.

Community education is critical, not only for participation in clinical trials, but also to continue safe sex and safe injection behaviors. Moreover, I feel and we feel that the infrastructure training and education required to bring expanded ART therapy to communities globally is complementary, and not competitive, with HIV vaccine development.

The international investigators in the HVTM believe that antiretroviral should be available to its trial participants when they need it. Communities who participate in vaccine research should be providing antiretrovirals. But if this is not possible, then individuals who participate in vaccine trials and develop HIV while on the trials, should be eligible for antiretrovirals when they and their physicians feel it is needed.

The HVTM is committed to utilize its expanding global network to bring these messages to HIV vaccine developments.

In summary, the most common problem that we have in HIV development continue to be delays in the scientific, regulatory and political process of vaccine development.

The need for an even partially effective HIV vaccine is great. HIV vaccine research should be, in my opinion, a model for the linkage between science and medicine, a world that values the rich and the poor, the north and the south, women and men, young and old alike, a world that speeds vaccine development to all in need.

After all, the virus recognizes the similarity among people on this planet. Scientists, policymakers and communities must act similarly. Thank you.

(applause)

Now there are many people – many people who contributed to the talk. Judy Wasserheit, especially, who co-directs the HVTM with me. Peggy Johnson, Ed Trumot (MS?) and Gloria Flores from the NNID. Julie Mcerwath (MS?) and Ken Reinhold provided the CTL data. Steve Self, who’s designed the trials. And Steve Wakefield, who has led our community programs.

Scientists obviously at Merck Labs, Aventist Pasteur and the Walter Reed have provided data. And of course, Jose Hespartsa (MS?), whose advocacy and support at UNAID has been invaluable.

And lastly, I want to thank Tony Fauci (MS?), who while recognized for his work on HIV pathogenesis, is perhaps less appreciated for the increasing support he has provided to global vaccine research programs. Thank you.

(applause)

FEMALE SPEAKER: Well, thank you very much, Dr. Corey (MS?). I think we’ve had an extensive and thorough and wonderful exposition on that hope we have for prevention.

For the next speaker, I’m going to ask Dr. Juan Corin (MS?). He’s the director, director general of drug abuse and AIDS here in the Ministry of Health in Catalinia (MS?). And we’re going to ask him to introduce briefly our next speaker.

DR. JUAN CORIN: Thank you. Good morning to everybody. It’s a pleasure for me to introduce Kasia Malinowska-Sempruch (MS?). She’s director of the International Harm Reduction Development Program at the (MS?) Society Institute, which has (MS?) technical and financial support for harm reduction projects across Eastern Europe and countries of the former Soviet Union.

Under her direction, the program based in New York has expanded its support to communities – its support to underprivileged communities, such as prisoners, street children and sex workers.

Among other things, she co-chaired the first national AIDS program for Poland and designed training programs. She’s a doctoral candidate in public health at Columbia University and has made presentations on harm reduction users at countless conference and published widely on the topic.

She was recently appointed to serve on the first international technical review panel of the Global Forum to Fight AIDS, Tuberculosis and Malaria.

Kasia, when you wish.

(applause)

Kasia Malinowska-Sempruch: Distinguished guests and esteemed colleagues, I am honored to be given the opportunity to speak at the first ever plenary presentation on Eastern Europe and the former Soviet Union.

Those of us who have worked in the area of HIV in this region have spent well over ten years talking about the social, economic and human factors that make our country susceptible to HIV, advocating action.

Now in 2002, we no longer speak of what may be. HIV and AIDS have arrived. And as everywhere else, the virus is causing devastation.

For three years in a row, UNAID has reported that HIV is growing faster in Eastern Europe and the former Soviet Union than anywhere in the world. Today, there are over 200,000 officially registered HIV infections in Russia.

The total number of people living with HIV is estimated to be much higher, at least 1 million, 90% of them injecting drug users. The situation is equally dire in neighboring Ukraine, where close to 1% of the population is estimated to have HIV. Again, the majority of them are injecting drug users.

As a native of Poland, not only I’m terrified at the prospect of the rapidly growing HIV epidemic, but I’m frustrated and angry as well. The world celebrated with us when the Berlin wall fell, and then left us alone to deal with the consequences.

Although many countries of our region embraced democracy over the past decade, the promised economic benefits have yet to arrive. We are richer in terms of human rights and some essential personal freedoms, but we are poorer in many other ways.

From Czech Republic to Uzbekistan, public health systems are crumbling, as the regions’ economies continue to struggle. Absolute poverty levels are up, while living standards (MS?) are falling.

Per capita gross domestic product in Russia is less than $5,000 a year, lower than in countries such as Brazil and Thailand, that have long been considered less developed.

As bad as the economic systems are in Russia, they’re even worse in Ukraine and Central Asia, where a growing number of people are forced to get by on less than $2 a day. In Central Asia, some women are trafficking drugs to buy school books and shoes for their children.

The sex industry is rapidly expanding throughout the region. I would like to hope that things will get better before they get worse, but now our countries are facing two linked health crises that threaten to dwarf all other issues - soaring injecting drug use, and HIV infections.

If the world is unable or unwilling to turn its attention to this region and offer help in dealing with this looming disaster, the consequences will be horrific.

You’ve heard all of this before, of course. Think back to over a decade ago, when activists first raised the alarm about the crushing AIDS epidemic sweeping much of Africa and large parts of Asia. For a variety of reasons, governments, international organizations and pharmaceutical companies preferred to ignore the imminent African AIDS epidemic, even after the first signs of catastrophe appeared.

Before long, it was impossible to ignore. The continent had already buried millions of people and tens of thousands more had been infected.

Not only this an economic and social disaster, but a moral one as well. No matter how much attention other nations give to Africa now, it will never be forgotten that the world fell brutally short of meeting its humane obligations.

(applause)

As we respond to the African epidemic and consider strategies for Eastern Europe and the former Soviet Union, we have an opportunity to apply lessons learned so tragically in other parts of the world.

Unlike in most other regions, HIV in Eastern Europe and Central Asia is spreading primarily through injecting drug use. Economic despair, social dislocation and easy access to heroin and other opiates have all contributed to an explosion of drug use.

Already on the margins of society, injecting drug users receive little or no sympathy from the general population. There remains an illusion that drug users are somehow separate and isolated, and that illness and death among them has no impact on the fabric of society.

We’ve heard reports of parents in Central Asia watching their children die of overdoses, so afraid of police harassment of the entire family, that they will not bring them to a hospital. This type of fear and silence, which authorities have so far failed to adequately counter, breeds on HIV and offers further proof that drug policies are intimately connected to AIDS policies.

Often in countries that are experiencing rapid increase of drug use, the (MS?) reaction is to become tougher on drug users. Locking people up in prisons for their drug use is not a solution. It’s an intervention that only makes things worse by driving users underground, and making them less likely to access what few services do exist for them.

The United States, with its failed war on drugs, offers an example of futility of focusing on incarceration as a strategy to address drug use.

(Cheers and applause)

Addiction rates there have not gone down, despite aggressive enforcement of sero tolerance laws that have filled the nation’s prisons with people caught using drugs, even the small amount of drugs. Instead of allocating resources toward harm reduction and drug treatment, American policymakers spent billions of dollars on new prisons, making U.S. the world’s leading incarcerator.

(applause)

By favoring confinement over treatment in Eastern Europe and the former Soviet Union, authorities are condemning drug users to overcrowded prisons, where needles are shared and HIV rates are surging at even faster rates than among the population at large.

In Russia alone, there are more than 33,000 prisoners who have tested positive for HIV. A large percentage of these prisoners will be infected with TB, which itself has reached epidemic levels in the former Soviet Union. TB is now the most common killer of HIV-infected people in the region. And in prisons alone, more than 30% of those who have TB have a multidrug-resistant strain of the disease.

Prison sentence, often for a minor offense, now becomes a death sentence. Halting the spread of HIV among drug users requires entirely new ways of thinking. National and local governments must implement flexible and caring health policies that focus on helping drug users, not punishing them.

And along with the governmental response, or even more importantly, we need to look at our own national prejudices, our own professional stereotypes, our own professional judgments that stand in the way of providing those in need with immediate assistance.

We know what works. At the Open Society Institute, we strongly believe in the concept of harm reduction as the most humane and realistic way to stem the spread of HIV among drug users. By this, we mean meeting drug users on their own ground, providing non-judgmental access to ways they can reduce the risk that they will contract HIV or other serious conditions, such as hepatitis.

One key element of most harm reduction programs is needle exchange. Hundreds of studies around the world have shown that providing injecting drug users with access to clean needles greatly reduces needle sharing, and thus, HIV infection.

W.H.O., the American Medical Association, UNAID and many others consider provision of clean syringes to be an effective and necessary method of preventing HIV transmission among injecting drug users.

Treatment programs that offer methadone and substitution therapies are another vital part of harm reduction efforts. Unfortunately, rigid and repressive drug policies in many countries mean that such programs are few and far between.

Even so, harm reduction is not an unknown concept in the region. Small NGOs have set up shop to provide needle exchange in nearly every country, with or without the acceptance or support of the local government.

There are committed people in the region, who have long dared to defy conventional wisdom and treat drug users as human beings, deserving as much care, education and assistance as all other members of society.

In Poland, there is a doctor who, early on, spoke about the need for methadone maintenance, to be implemented as a frontline approach to the drug use epidemic. And most public health officials in my country now accept such programs as vital.

In Bulgaria, there is a small group of volunteers who drive a battered bus into isolated communities that offer clean needles to injecting drug users who have faced more discrimination and stigma than most of us can possibly imagine.

In Ukrainian cities, the former drug users who risk entrapment and arrest by going directly to shooting galleries and handing out information and offers of support to homeless youth, who are desperate and malnourished.

In St. Petersburg, elderly women can get their blood pressure checked in the mobile clinics, as drug users exchange needles. The mayors and public health officials across the regions who do their best to provide free space for drop-in centers, and their physicians and nurses who take off their white coats and transform into outreach workers.

Such local efforts are the cornerstone on which harm reduction should be built. But these and other harm reduction services that do exist have limited resources and risk being swamped, as the number of clients and those living with HIV continue to climb.

Needle exchange is easy from an intervention standpoint. Certainly it’s easier to offer effective prevention in the area of injecting drug use than sexual health, for example.

As we know from years of experience on behavior change in the area of sexual health, there is a long list of reasons why people do not want to use condoms. “I don't need to with my wife.” “He will think I’m a slut.” “They reduce sensation.” “It’s against my religion.” “Stopping to put them on breaks the mood.” The reasons go on.

Drug users would make a very different list of reasons for not using clean needles. These would have little to do with individual choice, and might include “syringes are not available.” “I am afraid of being stopped by the police outside of the pharmacy.” “Walking into a needle exchange might cause my children to be taken away.”

When I visit programs that we support throughout the region, I’m always amazed that people are in fact willing and motivated to travel, often a few times a week in minus 20-degree weather, across town for clean needles, for a warm cup of tea, for a visit with a nurse, who can look at an abscess without delivering a sermon.

If a harm reduction program is well designed, if it’s user-friendly, well located and committed, it can reach large amounts of people. And there is no reason for people not to use clean needles.

If every drug user today were provided with clean syringes and needles, the overwhelming majority of them will use them. Harm reduction makes a huge difference and saves countless lives, but we need to go even further.

Along with HIV prevention, we must offer hope to those who are already infected, including drug users, so they feel enlisted in preventive efforts and are in fact active partners in keeping others free of infections.

This is much harder than it should be, because of lingering stigma and shame. The former Soviet Union is a place where narcologists are required by law to report their patients to the police. This is no longer necessary under current law, but since, in many countries - this is no longer necessary under current law in many countries, but since we’re creatures of habit, this type of dialogue between police and physicians do continue.

In order for effective HIV prevention to happen, significant changes in the way we think of those living with HIV must take place. First, people need to know that they’re infected. In order for them to know, they need to feel to safe and respected. And so, the entire system of HIV testing in the region, still based on the Soviet model, needs to be revamped.

The key is hope. For those living with HIV, hope is imperative. It’s our only ally in holding the HIV epidemic. Social and medical services need to be offered to everyone infected with HIV. I have no illusions that people living in the former Soviet Union will have easy access to sophisticated antiretroviral combinations in the near term, but there is a lot that can be done now, such as providing TB treatment and prophylaxis of opportunistic infections.

The fact that in many places this is not being done fuels the rapidly increasing number of infected. A question often asked is, “why should I get tested? I have everything to lose, and nothing to gain.” This is especially true for a person who uses drugs in parts of the former Soviet Union. We therefore need to help provide the coherent answer to this question, before expecting users to seek out information on their own.

It goes without saying that there are few, if any, HIV treatment options available. HIV-infected drugs users who turn to doctors for help often have doors slammed in their face.

A survey by the Central and Eastern European Harm Reduction Network, publicized last night, found that the region’s drug users are often placed last on the list of those in line for antiretrovirals, are required to stop methadone in order to gain access to HIV, or are denied antiretrovirals altogether.

We all have heard offensive assumptions and stereotypes, used to justify denial of treatment to other groups before. We’ve heard that gay men are self-destructive and not interested in taking care of their health. We’ve heard that Africans cannot tell time and are therefore unable to comply with complicated regimens.

Now we hear that drug users, by virtue of being drug users, are noncompliant and not worth treating.

AIDS service providers and policymakers all over the world must change the condescending way they treat drug users, as though they’re incapable of making informed decisions about their health.

Using noncompliance as a reason for denial of treatment is unfair and unproductive, and it ignores the problem. A friend recently reminded me that one thing that drug users know how to do well is to take drugs.

(applause)

The noncompliance argument must be considered in a light of the interventions being offered. If providers don’t offer treatment in a way that recognizes the realities of drug users’ lives, then it’s hardly surprising that the treatment can’t be followed.

My organization’s experience in the region shows that many users want help to stop injecting. And it’s unethical that there are few services, such as methadone maintenance to help them in this difficult effort.

If drug users are denied access to methadone, or have to wait for months to get accepted into methadone programs, it is the failure of the system that promotes noncompliance.

Most of the clinics I visited throughout the region are open from 8:00 to 3:00, and are quiet places. I tried to pick up a prescription for myself from one of them a few months ago, and missed a doctor who left at 3:00 and a social worker, who was gone 10 minutes later.

I was thrilled to hear of an HIV clinic in Paris open until midnight. I am sure that the number of missed appointments in Warsaw or Kiev and Paris are significantly different.

Our work in the region has shown us that drug users, with appropriate support, are as likely to be compliant as any other person with HIV. Many of them come to needle exchange sites, or for their methadone day after day, regardless of how weak they feel or what transportation obstacles they face.

It’s not a question of not – sorry. It’s not a question of having enough resources or know-how. Russians have orbited the moon and built tens of thousands of nuclear warheads. If they could accomplish these two expensive and complex tasks, they have the infrastructure to produce generic antiretrovirals that are needed right now.

(applause)

If 200,000 infections within three years doesn’t constitute a public health emergency and prompt the development of an aggressive domestic treatment plan, I don’t know what would.

There are, of course, no easy solutions to the AIDS epidemic in Eastern Europe and the former Soviet Union, or in any other region of the world. But that doesn’t mean that people in the region or elsewhere can allow themselves to shy away from making difficult decisions, financially, culturally, or morally about how to address it.

Violence at the hands of police, denial of public services, imprisonment that destroys health and breaks the spirit, so-called “drug treatment” that humiliates clients and their families - all of these human rights abuses experienced by drug users not only make for a repressive society, but also fuel the HIV epidemic.

My father was sentenced to a life in prison at the age 18 for political activity. He spent 12 years in prison and died before Poland became a truly independent country again in late ‘80s. There are hundreds of thousands of men and women who, like my father, sacrificed their lives opposing Communism.

None of them did that to now watch their children or their children’s children or their neighbors’ children be locked up in prison for drug use, or die of overdose or AIDS.

Repressive drug policies fuel the HIV epidemic. Needle exchange and substitution therapies save lives. Drug users care about their health and must be offered HIV treatment.

(applause)

Finally, let me thank those of you are my greatest inspiration, people who are willing to put their professional lives on the line early on, and start delivering much-needed services to drug users. Those of you who have openly advocated for changing the drug policies, allowing for harm reduction to become a reality. Your work in Poland and Russia, in Ukraine, in Kyrghistan, in Moldova, in Bulgaria, in Lithuania and Tajikistan, in Kazakhstan, and in every other country of the region has nothing short of a miracle.

It’s been a privilege working with you all. And I thank you. Your concern and care are what will ultimately turn the tide.

(applause)

FEMALE SPEAKER: Okay, let – a few words are - our thanks to Cassia for a moving and wonderful talk. Now I’m introducing my co-chairman, who’s (MS?) Sina (MS?). And Mr. Sina is not only a famous actor in his own country, and well-known abroad, he’s not only a long-term sponsor and supporter of numerous NGOs concerned with the problems we’re dealing with today, but a few days ago, he was appointed Minister of Health in his own country.

He’s going to chair the last session and introduce our speaker. (MS?)

MR. SINA: Chairperson, distinguished delegates, ladies and gentlemen, my presence at the 14th International AIDS Conference in the beautiful city of Barcelona is an expression of our (MS?) of the gravity of the HIV/AIDS epidemic in India and the consensus and commitment at the highest political level.

(applause)

As part of this commitment, and on behalf of the government of India, I place on record our offer of hosting in India the 16th International AIDS conference.

(Applause)

AIDS is a global issue, and a comprehensive global strategy to combat it is imperative. It is important that this global collaboration takes due account of the sensitivities of the developing societies, which face the brunt of the AIDS epidemic.

The theme of this conference - knowledge and commitment for action - draws attention to the fact that knowledge and research experience gained from basic and clinical sciences has most unfortunately outpaced the political will to implement commitments made by 189 members (MS?) of the U.N. General Assembly Special Session on HIV/AIDS in June 2001.

The response from donor countries and concerned organizations has been far short of expectations. Developing countries like India could benefit greatly from a fulfillment of the promised contributions to the global fund.

The fastest spread of AIDS is taking place among the poorest that remain among the most vulnerable. National, international development strategies must therefore devote the highest attention and resources to the relegation of extreme poverty, being able to satisfy basic human needs of all segments of the population would be the most powerful vaccine against AIDS.

Indian pharmaceutical companies have made major contributions toward supplying antiretroviral AIDS drugs to the world at prices dramatically lower than of those offered by drug multinationals.

(applause)

India is in favor of making such drugs freely available to all those who need it, but dependence on drug therapy for combating HIV/AIDS would be unaffordable without further reductions in prices or availability of international financing.

It would involve an escalating and long-term commitment for poorer countries with other competing varieties in public health, education, nutrition, and development. This is just not a viable option.

For us and for many other countries like India, prevention linked to care and support is the key. And therefore, particularly happy at being asked to co-chair this conversation on prevention strategies in the 21st century.

An effective strategy for preventing and slowing the transmission of HIV/AIDS must include development of appropriate HIV vaccine. Until the vaccine arrives, the focus has to be on other available preventive measures for reducing the spread of AIDS.

The key to this is spreading the message of AIDS awareness. Elevated

views of the mass media, film and TV, even their phenomenal reach are particularly important in this context.

With my own active involvement with the Indian film industry as an actor for over three decades, I’ll attempt to bring in an (MS?) initiative in this area.

Members of parliament have an important responsibility in spreading the AIDS campaign. I’ll pursue the convening of a special session of Indian parliament on this issue, to seek the personal involvement and commitment of members of parliament.

(applause)

I also propose to convene a meeting of Health Ministers of South and Southeast Asian countries, to deliberate a strategy for HIV/AIDS appropriate for these regions.

(applause)

Now, ladies and gentlemen, I’ll be honored to introduce the fourth speaker of the day, Dr. Suniti (MS?) Solomon from India. In 1986, Dr. Suniti Solomon and her colleagues documented the first evidence of HIV infection in India.

She has set up the first voluntary testing and counseling center and an AIDS research group in Madras. In 1993, she founded YRG care, a nonprofit center that offers HIV and sexuality education for adolescents and young adults, counseling and testing services and integral care of people living with HIV.

She offers services for pregnant women living with HIV. She’s a member of the core team supporting the prevention of vertical transmission of AIDS of the National AIDS Control Organization of India. She is also working as a principal investigator with several international institutes.

Ladies and gentlemen, Dr. Suniti Solomon. Thank you.

(Applause)

DR. SUNITI SOLOMON: Honorable Ministers of Health and friends, I acknowledge with gratitude the inspiration from women in the community that I live, work with, and have the honor to serve. My colleagues who provided invaluable editorial support, and my friends, Dr. Kita (MS?) Rao, Sunita Her (MS?), and Kuratia Abdul Kareen (MS?), for having provided relevant literature and guidance.

“I was just 17. My dreams fell apart when I was diagnosed with HIV at the anti-natal clinic. My husband, his parents and even my doctor wanted me to abort. I cried, but could do nothing else. Soon my husband died. And one week before his death, he was diagnosed to be HIV-positive.

My in-laws blamed me and drove me out with no financial support, not even what my husband had saved and legally mine. I could not go back to my parents, as I would have been an obstacle for the wedding of my younger sister.”

It saddens me to say so, but I must say it -- this story is just one of 100 similar stories common in developing countries. Heterosexual transmission continues to be the major mode of HIV transmission in majority of developing countries.

Though the epidemic began in communities with high-risk behavior, today it is evident it has populated into the general population. It is well known that women experience a great deal of gender-based discrimination, which facilitates the spread of HIV.

Girls and young women show a higher rate of acquisition, compared to men of similar ages. On an average, young women are becoming infected ten years earlier than men due to early marriages, rape, being compelled into prostitution arising from economic necessity, or peer pressure.

Gender norms that create an unequal balance so far between male and female are deeply rooted in the social, cultural context of each society and enforced by that society’s institutions.

Most societies cast women in a subordinate, dependent and passive position, with virginity, chastity and obedience as key virtues of an ideal woman.

In sharp contrast, men are characterized as independent, dominant, invulnerable aggressors and providers whose key virtues are virility, strength and courage.

But we should also recognize that multiple forms of masculinity and femininity are dynamic, subject to change, constructed through social interaction.

The subtle understanding of gender is very useful in terms of HIV prevention, because again, it implies that modifications of gender identities is possible over time.

These can serve as models for promoting more gender-equitable relationships and safer sex.

Male boyfriends, and other gender norms often make girls the most vulnerable, and therefore must be given special consideration. When China introduced its family planning policy of one child only, the Chinese worked the system to ensure that the child would be mated, as in many parts of India as well.

Thanks to the ultrasound and the abortions, today there will be 117 boys for every girls. In the – if this process continues, soon there will be millions of men without women.

Rudyard Kipling said that the female of the species is more deadly than the male, but what we see in most societies today is the exact opposite.

The increasing incidence of violence against women is a matter of great concern. Violence reduces women’s desire and ability to negotiate for safe sex. Self-preservation is a human’s primary instinct. How can the target of violence be expected to negotiate with her aggressor, especially for something that the aggressor does not want?

Even as the epidemic expands among women, we also see a movement of the epidemic from urban to rural areas. This makes it an imperative to mobilize resources that would help us to reach in time useable prevention information services to this population.

In developing countries, the challenges of illiteracy, poverty, migration, lack of social and medical services, economic dependence, and a greater proclivity for social mores make this process more complex.

Addressing economic and social gender inequities that lie at the root of pandemic requires a multisectoral response that must increase women’s and girls’ access to productive resources, such as education, employment, legal assistance and a culture of silence and shame that surrounds sexuality, and protect girls and boys from corrosive effects of gender stereotyping.

Our focus needs to be maintained on educating the custodians of power and social control on the key role of stigma in perpetuating HIV. Yet, some countries that have been the most successful in reducing the number of new infections, such as Thailand, Senegal, are those that have used multisectoral approaches in HIV/AIDS.

A one-track mind elicits a one-track response. We must broaden our minds to encompass a variety of approaches, and then implement them. Empowerment is a transforming power relationship and equalizes the balance of power between females and males in order to reduce their vulnerability in the epidemic.

Interventions that empowerment has an end goal also tends to treat HIV/AIDS within the larger context of social and economic development.

The concept of empowerment believes that women are both subjects and agents of change. To design intervention to empower women requires us to first deconstruct the social or (MS?) that are amenable in policy intervention.

The first step towards empowerment is the need to foster and develop a political bill and leadership towards enabling environments.

Another important social power is access to economic resources and assets. 35% of Indians live below the poverty line. According to the Jaypud (MS?) Paradigm, two factors modulate the level of susceptibility and vulnerability in a society -- the level of the distribution of wealth and income and the degree of social cohesion.

Wealth and distribution of wealth is easily quantifiable. Social cohesion is an analytical concept without moral value. Poverty forces women into selling sex, and thus increases their risk of exposure to HIV infection.

Economic and social changes affect the well-being of women, after centuries of male domination. In much of Asia, women’s lives are improving with economic development, social modernization and improved access to health and care services.

More women are (MS?) paid employment, ensuring access to finance. Yet many Asian women still face problems of low status and discrimination, both at home and workplace.

Only one study in rural Bangladesh found that most married women have little or no say in deciding whether to see a doctor when they become ill or whether to buy medicines for a sick child, in spite of her being a breadwinner.

These and other studies have found that high levels of education and household income do not necessarily assure a woman’s status in societies that are strongly male-dominated.

Men largely take control of decision-making about sex and reproduction. Hence, working with men benefits both men and women. It is a paradox that a middle class-educated woman often appears to be restricted within the household than poor, uneducated women who learn to play a strong, more independent role.

We need to ensure the implementation and protection of women’s property and inheritance rights. In Zambia, it is said that when a man dies, his widow can cry with only one eye. The other eye must keep watch over the in-laws, who may strip the widow of her home, her household goods, even her children in a practice known as property grabbing.

This is also common in India. This is an epidemic whose impact becomes absorbed into daily life and with change is shaped, depending on the differing settings and the social economic determinants of people’s daily lives.

There is a considerable variation in the female literacy among developing regions. At the outset of the 21st century, there are still an estimated 880 million adults who cannot read or write in this world, and two-thirds of whom are women.

A changing world compels us to rethink what we mean by literacy. Definition of literacy commonly referred to are still used in everyday life are those that allow one to function competently in their own society.

Even in Sweden, a country that achieved the highest overall score, almost one in ten adults, encountered a severe literacy deficit in everyday life and work.

In India, two-thirds of women over the age of 25 have never been to school. Yet 50% of teachers in primary schools are women. Girls outrank boys in school final exams, but they only remain paper tigresses.

The fundamental source of (MS?) for the men in societies is access to information, education, and skills. We must give women and men basic information about their bodies, sexuality, STI, HIV, reproduction and clarify their myths and misconceptions about sexuality.

Access to information is more importantly a basic human right. Providing women with basic skills, such as to communicate with their partners about sex, and increasing their condom literacy, helps to reduce their risk and vulnerability to infection.

It many countries, the culture (MS?) stigma, attach to the word “sex.” Policymakers and officials would rather call sex education as “family health education.”

Research have shown that being a peer educator gave girls social legitimacy to talk about sex without the risk of being stigmatized as someone who’s sexually promiscuous.

In an effort to bridge this national institute of mental health supported research study in five countries, including our site in (MS?), is attempting a new communication model involving women as community popular opinion leaders.

While it is important to stress the don’ts in the prevention message about HIV/AIDS, it is equally important to highlight the do’s, and not attribute blame and stigma, thereby further alienating the persons for whom the message has been directed to.

Skills should be also developed in a participatory method to replace didactic approaches that are standard practice in formal educational systems in most countries.

Religious health and teachers and parents preach abstinence, instead of giving options to the adolescents. (MS?) studies highlighted the value of mixed group-based intervention for fostering group action on HIV prevention in a wider community.

Economic factors severely affect women’s health, access to the use of services, such as voluntary counseling and testing, STI clinics and the anti-natal clinics.

Economic constraints to pay for services, transportation or loss of wages create significant barriers for women’s use of health services. The larger workload of women who live in poverty, and rural women, who need to travel long distances, make it difficult to take time off to access services.

Thus making reproductive health user-friendly, reducing the waiting time in clinic, and ensuring that the timing for the service provided a convenience for women become achieved to increase their access.

In families where income and resources are pulled from many members of the family, women are still at disadvantage in accessing funds for health services, especially STI treatment, because families allocate resources for men and boys first, and then for the women and girls.

Also, women do not perceive themselves at risk for STI, and therefore, may not access STI services. And hence, it is important to integrate the STI services into the family welfare will facilitate the gynecologist to examine and treat every woman for an STI, even if she has no complaints, since it is well-known that STI increases the transmission of HIV.

Excluding men from sexual and reproductive health services compounds the view that this is not their concern. Efforts to bring the partner for couple counseling will help the woman and man to deal with the results and to reduce the negative impact on the woman.

It is unrealistic to expect a neatly rounded result if one half has no clue as to what’s happening to the other half.

The focus of prevention should not let us ignore the issue of care and the caregivers. The physical and emotional burden of caring for sick or dying HIV/AIDS family members most often falls on women and girls. The women and girls need to gain the knowledge on infection control, with hands-on practical training, so as to prevent infections to themselves.

Due to the economic devastating experience of the families, it can drive girls to barter sex for cash, and to make ends meet. Women are given blood transfusion more frequently than men. Transfusions are most commonly given during childbirth and abortions, as prevalence of anemia amongst pregnant women in developing countries is high.

In India, a study conducted by the Indian Council of Medical Research reported the prevalence of anemia as 87.6% among anti-natal women. Also, we see many health care workers employing the redundant practice of one unit transfusion, which leads to HIV infections.

Blood safety programs and proper training of gynecologists is essential and doable in most countries.

After all, as every medical student knows, the primary dictum is “first do no harm.” Women in prostitution face health problems, such as STDs and HIV. A shining example of avoiding such problems is that of a project carried out at Sonoguchi (MS?) in the red light district of Calcutta, India.

Initially designed as an intervention to reduce the levels of STD and increase condom use among the sex workers, the program has expanded to empower sex workers, to enable them to control their own lives and solve their own problems, to prevent the spread of HIV.

In 1992, 1.1% of sex workers surveyed reported always using condoms, which rose to 50% in 1995. Similarly, while HIV prevalence rose dramatically among sex workers in the other parts of India, Mumbai (MS?) has 58% and Funai (MS?) 55%. It’s only 5.5% among randomly sampled women in Sonoguchi area.

Programs that foster the development of female-controlled prevention are designed to reduce risk and vulnerability of the woman to HIV. Providing women with female condoms, how much is it possible?

Is it feasible in India? Since sterilization accounts for more than 75% of total contraception, and tubectomy account for about 95% of sterilization, how would the woman initiate condom use, even if she is aware that her husband has multiple partners?

In Thailand and India, majority of married women in monogamous relationships are found to be at risk of sexual trespasses of their spouses. A recent study by my center at Chinay (MS?) in collaboration with the Fogerty Program of the Brown University on the acceptability of microbicides, revealed that 69% of women did not perceive risk of HIV, even though 83% of men had multiple partners.

This clearly indicates the overall failure of our communication campaigns. Hence, we need not only to advocate for development of microbicides for women, but also sensitize community leaders, health care workers, policymakers to such programs.

These efforts recognize that the male condom is male-controlled technology, and takes account of imbalance and power in sexual interactions that makes it difficult for women to negotiate condom use, by providing them with an alternative of female-controlled prevention technology.

A new study, HIV prevention trial network 052, starting this year, where (MS?) is also an issue. Interview of the discordant couples for the positive partner will reduce or prevent infection in women will be conducted in many sites in the developing country, including our sites.

We are delighted to participate, as the research question germinated in our minds over five years ago when a discordant couple devoted to safe sex were desperate to abandon all caution, being unable to bear the stigma of being childless.

When we knew that counseling was failing, we had but one thought – could we do something that would reduce her vulnerability? Could it be ART to reduce the viral load? That such a need has now taken form of a study is heartening, but it is after five years, at the same time, saddening.

From our experience, we see that this study also meets the aspiration of such couples to have a child of their own, given their reluctance of choosing adoption or artificial insemination.

The demographics of vaccine trials conducted in developing countries must certainly include equal percentage of men and women.

In conclusion, true empowerment lies in interdependence. As long as gender inequality exists, women’s rights and opportunities to resist infection, to assert their reproductive choices to demand safe sex and to support their families, will be threatened. And the pandemic will grow in scope and in fact.

Unless policymakers, healthcare providers, mass media, development assistant agencies and others concerned with stemming this pandemic, take account of specific gender interests and power dynamics, it will be impossible to devise effective solutions.

But we cannot afford to throw our hands up. The situation is much too serious for that. The stakes are much too high. We absolutely have to make the impossible, possible. And with proper planning and execution, I firmly believe that it can be done.

I learned with humility from this old rural woman, Monger Pasi (MS?), just as the (MS?) will move when both wheels are in balance, the family too will develop only when both man and woman have equality. Thank you very much.

(applause)

FEMALE SPEAKER: Thank you very much, Dr. Suniti. I wonder – I mean, could have had a daughter. Thank you very much. Her symposium has been great. And we thank the audience, too, for their fine response to the various options we’ve been offered. Run!