The AT LAST Trial
Finally a Study Designed By and For Women
Data on the natural history of HIV disease in women are still limited, (almost 20 years into the epidemic). In addition to getting many of the opportunistic infections seen in men, women have sex-specific symptoms that are often either hormone related or gynecological in nature. Recently, information in several different studies suggest that women have lower viral loads than men, although HIV disease appears to progress at the same rate in both sexes. Women probably differ from men in absorbing, metabolizing and experiencing the clinical effects of certain medications. Drug dosing, absorption, efficacy and toxicity are likely to be affected by differences in hormones, weight and body-composition between men and women. The need to explore these differences and determine the best course of medical treatment for women, is supported by findings from ACTG 175. This study showed that women were more likely than men to develop severe HIV symptoms. It also showed that women required their first dose modification sooner than men, and that the length of time to the need for the first dose modification occurred earlier for women. (Again last year in LA County, AIDS death rates were down for men, and up for women, leaving a survival gap of 18%. It's hard to believe that this discrepancy can be attributed entirely to "lack of access to care." This is Los Angeles, where most (not all) have access. Perhaps the new medications aren't working as well for women as they are for men.)
Furthermore, the lack of sufficient data supporting the use of certain antiretrovirals in female patients serves as a barrier to their use for both the patient and the health-care provider.
Considering the complexity of the various possible combinations of antiretrovirals and the relative lack of data available, there is a definite need to further assess the use of these drugs in women. Prior to 1993, women were, for the most part, excluded from participating in clinical trials. Treatment interventions, toxicity and safety data were studied in men only, and then applied to women. In '93, as a result of pressure from activists, the Food and Drug Administration (FDA) finally mandated the inclusion of women in clinical trials. Despite this gain, women still only comprise about 12% of the total participants in clinical trials.
By 1996, many questions still remained unanswered about HIV-infected women and treatment interventions, gender specific toxicities and safety. Women Alive, a grass-roots organization based in Los Angeles, and created by and for women with HIV/AIDS, began organizing with other activist women living with HIV throughout the country. They highlighted the issue that researchers still had not equalized the gender-bias in clinical trials. Moreover, they decided it was time to demand answers from the researchers as to why there is still life-threateningly limited information concerning women. Why women were still poorly represented in AIDS clinical trials; and why there was hardly any information available about the effects of hormones on HIV infected women (with and without medications). Out of this pressure and constant and persistent activism by women with HIV, members of Women Alive and other activists, came the development of research projects to look at these issues. AIDS activist women took their seat at the same table with scientists, researchers, and pharmaceutical companies to develop sound research tailored to the needs of women with HIV.
Since the availability of protease inhibitors in 1996, AIDS deaths declined considerably. However recently, reports of new onsets of diabetes, abnormal distribution of body fat, and hyperlipidemia (large amounts of fat in the blood) occurring during treatment with protease inhibitor-containing regimens have received widespread attention. Whether the metabolic disorders are a direct result of PIs or because of the effects of HIV on the body over time, is unclear. Considering the complex combinations of antiretrovirals and the serious lack of data, there is a dire need to assess the use of these drugs in women. Not only is it imperative to include women in clinical trials, we must conduct studies on the effects of HIV antiretrovirals in women. Thus, this year, women with HIV/AIDS have seen their efforts moved one step closer, from a vision to reality. The AT LAST (Antiretroviral Therapy Looking At Sex and Treatment) study is now underway in several parts of the country.
The AT LAST study is designed for those patients whose first experience with antiretroviral therapy (ART) has been with a non-protease combination of either a NNRTI (such as Viramune, Sustiva) or a NRTI (AZT + 3TC + ABC) and have either developed viral rebound (RNA >500 copies/mL) or one of the above combinations was intolerable or unable to suppress HIV RNA replication.
AT LAST will look at a new formulation of ddI, (the enteric coated tablet, which means it's absorbed in the intestine, instead of the stomach) and will offer Crixivan and Norvir along with Zerit and Videx together twice daily. But more importantly, the AT LAST study will evaluate the differences between women and men. Little is known about the impact of PI therapy on hormonal levels in women with HIV/AIDS. The AT LAST trial will examine the impact of a treatment regimen containing a combination of Protease Inhibitors on hormones, menstrual cycles, and the impact of hormone levels on the risk of developing metabolic changes.
Women Alive will provide a national peer support advocate component throughout the duration of the study. The Women Alive PSA's will conduct peer education, support, and advocacy sessions for participants at each site. The peer support advocate will discuss each study participant's needs in regards to travel, childcare, practical daily needs and/or any other issue that may affect the person's ability to fully participate in the trial and to adapt to study procedures and/or adhere to an HIV antiretroviral drug regimen.
The history of clinical research in HIV disease has been unusual in many respects. Even more than with other illnesses, the scientist/clinician and the patient/advocate have crossed paths. Their meeting has produced fascinating, frustrating, and fruitful exchange. People living with HIV and their advocates have demanded changes in the way research is conducted. AT LAST, a study for women.
This study is going on in the following U.S. Cities:
If you are interested in participating, and/or if you would like more information about the AT LAST study, please contact Ana Rodriguez at Women Alive (800)554-4876.
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This article was provided by Women Alive. It is a part of the publication Women Alive Newsletter.