IAVI Report - July / September 2001

This issue of the IAVI Report is devoted to women and gender-related issues in AIDS vaccine research. It's a focus that could raise eyebrows: What is there to talk about? After all, vaccine science has rarely paused to consider gender differences, and has rarely had to. Successful vaccines for polio, tetanus and many other infectious diseases were made without considering the ebb and flow of sex hormones or the male and female genital mucosae. 

But unlike any of these diseases, HIV is a sexually transmitted virus. And while HIV disease progresses in similar ways in men and women, there are also some differences in how it interacts with men's and women's bodies. 

In the pages that follow, we report on some of the issues that arise when looking beyond a gender-neutral view of HIV. We begin with two articles focused on HIV in women (one on mother-to-child transmission [MTCT], the other on HIV immunity) and then move to an overview of data on gender differences that may be relevant to AIDS vaccine development. Interspersed among these feature articles are interviews with researchers at the front lines of AIDS vaccine trials, who give testimony to both the extreme vulnerability of young women-the fastest growing risk group in many parts of the world-and to the implications of their high risk and lower societal status for vaccine trials.

On the scientific front, what emerges first are questions, not answers. As with other diseases, data on HIV are usually not analyzed by gender unless that is a primary focus of the study. The result: a dearth of direct, comparative information. Most of what is known about gender-specific disease effects comes from natural history cohorts or retrospective analysis of studies undertaken with a different purpose. In "Gender, HIV Transmission and Vaccines," Anne-christine d'Adesky combs through studies that bear on the issue of HIV infectiousness in men versus women. What she finds are compelling arguments for looking at possible gender-specific effects as a matter of course, not a matter of special interest.

What do these arguments look like? There is the well-documented phenomenon that women have lower viral loads than men from the time of acute infection onwards. Researchers are also finding that both men and women have distinct viral populations and immune responses in their genital tracts (and possibly breast milk in women) compared with blood.

These data may seem like a tangle of disparate findings. But there are key lines of inquiry that emerge, many of which span research on vaccines, microbicides, antiretrovirals and MTCT. On the short-list: How do viral load and immune responses vary in the male and female genital tracts, plasma, breast milk, and semen? What defines infectiousness in these different compartments and fluids, each with its own set of immune players? 

HIV vaccinologists cannot address all of these basic science questions. But forward-thinking collaborations with other fields can help fill in the picture. One area where this is starting to happen is in research on vaccines to reduce HIV transmission via breast milk. As Emily Bass reports in "AIDS Vaccines and HIV Transmission via Breastfeeding," some seasoned clinicians are preparing to test whether HIV vaccines given to newborns can help safeguard breastfeeding by HIV-positive mothers, a widespread practice in the developing world both for cultural reasons and because of the health risks associated with formula feeding. Along the way, the researchers are conducting and supporting studies of breast milk immunology and viral load dynamics in trials of other MTCT preventions—knowledge that could help guide evaluation of vaccines in this context.

Turning to AIDS vaccines in adults, the question is whether, and how, gender might impact vaccine efficacy. The working model behind most current strategies (although it is not formally validated) is that without sterilizing immunity, vaccines which control viral load will provide significant benefits in terms of prolonging life, and presumably in reducing transmission. To assess vaccines by these criteria means understanding how much lowered viral load levels will slow disease progression and decrease infectivity. Yet, as d'Adesky describes, a new study of serodiscordant couples in Zambia suggests there are gender differences in how viral load relates to transmissibility. It's a confounding finding—and one which demands closer attention. Will viral load levels for health and for transmission turn out to be gender-specific? Given the existing data, we cannot afford to assume otherwise. 

Moving from transmission to acquisition—the step vaccines target—there is now good evidence that immune protection to HIV can be achieved. As Richard Jefferys reports in "Closing in on Immune Protection in the Women of Pumwani," some of it comes from studies of women in the Kenyan sex worker cohort, who have been providing samples and sharing information about their lives for years. A small minority of them do not seroconvert despite repeated exposure to HIV from many different partners. Since the mid-1990's, researchers have been working to identify both the immune players behind their apparent resistance and the precise regions of HIV that stimulate the protective responses. With their successes will come valuable information for designing and evaluating vaccines. 

But when all is said and done, could a vaccine really show significant differences in men versus women? As far-fetched as that may sound, there could now be a first example: an experimental vaccine against HSV-2, the virus that causes genital herpes. As Patricia Kahn reports in "Possibly, a Vaccine Against Herpes—But for Women Only?" two Phase III trials of GlaxoSmithKline's Simplirix^® vaccine suggest that it provides some protection in women, but none in men. While further testing is planned to confirm this finding-and begin looking for explanations-there's a message to heed: vaccines may not always be gender-blind. 

Practically speaking, the way to find out is by enrolling enough men and women to power trials for detecting gender differences. But including high-risk women can be difficult in practice. VaxGen's two Phase III trials, the only efficacy studies of an HIV vaccine so far, focus on gay men and IV drug users, resulting in cohorts that are over 90% male. Uganda's Phase I ALVAC trial drew from the military and surrounding communities, resulting in a majority of male participants. 

In articles from three disparate settings—two in sub-Saharan Africa and one in New York City—several clinical researchers discuss women's HIV risks and their involvement in vaccine trials. All three share some common themes, starting with the huge impact of women's lower status, poverty and economic disenfranchisement on their vulnerability to HIV. Another is the need for vaccine trial staff to engage in the social context—a practice which has been the exception rather than the rule in research—if they are to successfully recruit and retain high-risk women. It's an approach that stems from the understanding that "high risk" is a catch-all phrase encompassing many factors, including poverty, drug-use, physical and sexual abuse and lack of autonomy.

To get the gender-specific data that are needed, then, vaccine trials will need to address gender both from a scientific and social perspective. This will not move the field away from its scientific goals, but should take us closer to the heart of the matter.

010710
IAVI2001-0701

©2001. The IAVI Report.

AEGiS is made possible through unrestricted grants from Boehringer Ingelheim, iMetrikus, Inc., John M. Lloyd Foundation, the National Library of Medicine, and donations from users like you. Always watch for outdated information. This article first appeared in 2001. This material is designed to support, not replace, the relationship that exists between you and your doctor.

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1990, 2001. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content.