To our readers: A farewell

By Patricia Kahn, Ph.D.*

I’m writing to say adieu from my perch at the IAVI Report. In August 2003, after three years as editor of the newsletter, I left IAVI to resume freelance writing, editing and teaching. My successor at the Report is Simon Noble, a virologist by training and most recently an associate editor at Nature Medicine, where he was responsible for selection of the journal’s AIDS-related research papers (among many other topics). Simon will write to you separately in the next issue. Suffice it to say that he and the Report team will continue to bring you news and analysis of the global AIDS vaccine effort, through the vehicles of the newsletter (and Vax, its new sister publication for non-technical audiences), Clinical Trials Database and revamped Web site.

As I thought about what to write in taking leave, I’ve been leafing through past issues of the Report. What struck me was how they reflect a clear dichotomy in the field, one that has become more pronounced as the afterglow of the landmark Durban conference in July 2000 gave way to both an expanded global vaccine effort and some familiar frustrations in moving forward.

Leaving Durban, it was hard not to feel a heady sense of optimism that maybe, finally, the world would commit to a comprehensive response commensurate with the scale of the epidemic and its devastating consequences. Some of that optimism extended to vaccines, where things were looking up after many long, slow years. The development pipeline was beginning to expand and diversify; a ramped-up, more internationalized effort was taking shape; and vaccines were increasingly being seen as a key weapon in the fight against AIDS, rather than as a backwater populated mostly by scientists from developed countries. And the tendency to pit prevention and treatment against each other, branding the former more “cost-effective,” was starting to abate as recognition grew that the two are inextricably linked.

It’s heartening that most of these trends have continued since Durban—although more would certainly be better. But in other crucial areas, progress is excruciatingly slow. One huge uncertainty concerns the basic premise behind nearly all candidates now in the clinical pipeline: that vaccines which fail to block infection but can suppress viral load will delay HIV disease and reduce transmission significantly. Until efficacy data on one or more good candidate tells us whether this concept holds water—data we won’t have for at least another four years—the entire crop of current candidates is essentially stuck in limbo.

At the same time, there’s been little headway made on most of the longstanding scientific challenges to AIDS vaccine development—with the result that there’s no new generation of candidates (based on different concepts) poised to enter the pipeline any time soon.

The list of these obstacles is well-known, but I’ll mention two that are crucial for designing this next generation of products, however long it may take.

One is to figure out how to induce broadly neutralizing antibodies, which will hopefully yield candidates able to block HIV infection. It’s a goal that continues to elude vaccine developers, although efforts and progress are now clearly accelerating.

Another is to determine whether immune responses at key mucosal sites are among the long-sought correlates of protection. Mucosal tissues are not only ports of entry for HIV (via the genital tract in sexual transmission and the gut in breastfeeding), but also key targets: the gut is home to the vast majority of the body’s lymphocytes (as compared with about 2% in blood) and is a primary site of both HIV replication and early pathogenesis, regardless of initial infection route. So a vaccine that prevents HIV from establishing a beachhead at crucial mucosal sites might profoundly impact the course of HIV infection. Yet, while the issue of mucosal immunity is often raised on vaccine agendas, it tends to be quickly dismissed for a well-worn (albeit valid) list of reasons, from the difficulties of evaluating mucosal responses in humans, especially in a clinical trials context, to a lack of information on which (if any) mucosal sites and responses really matter and which vaccine designs and delivery routes best induce them.

It goes without saying that big issues loom beyond the science, such as creating the right context for vaccine efficacy trials in developing countries. These trials represent an important opportunity to help shore up local capacity to provide AIDS testing and counseling and other prevention services, along with treatment and improved health care. Seen another way, unless they do, it will prove difficult to raise the local support without which these trials cannot succeed.

That brings us back to the issue of commitment and where we are today. Clearly one of the greatest post-Durban disappointments is that the global response has not matched the high hopes this conference generated. While potentially groundbreaking programs and proposals are in the air and prices for ARVs (antiretrovirals) have plummeted, severe underfunding and other obstacles mean that little has changed at the bottom line: for example, no more than 2% of people who need immediate ARV treatment in Africa are now receiving it. So it also goes with vaccines (and microbicides, and other elements of the response to AIDS), where the level of resources remains far below the needs.

Helping to close this gap is one place where news and information have a critical role to play. On that note, I leave with a profound sense of gratitude for the support we at the IAVI Report have received—from our readers, whose interest in the publication has sustained it; from the many people in the field who shared their insights, experience and (often unpublished) data with us; and to IAVI, for supporting a unique operation dedicated to collecting first-hand information on AIDS vaccine development. It has been immensely humbling and inspiring to bear witness to this global battle which, difficult and discouraging as it is, we can’t afford to lose.

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*Patricia Kahn, Ph.D., is former editor of the IAVI Report