Half of people living with HIV worldwide are women, yet the drugs used to treat women are tested mostly in men, with women comprising only about 10% of the patients included in clinical trials. This discrepancy was the inspiration for the Women AntiretroViral Efficacy and Safety (WAVES) study, the first-ever clinical trial of antiretrovirals enrolling only women.
Results of WAVES were presented at ICAAC/ICC 2015 in San Diego, and they offered important insights on the best treatment regimen for women with HIV. The study compared two antiretroviral treatments (ART). Women taking elvitegravir/cobicistat/emtricitabine/tenofovir (Stribild) had better viral suppression and fewer side effects than women taking ritonavir (Norvir)-boosted atazanavir (Reyataz) plus tenofovir/emtricitabine (Truvada).
The results of the study were illuminating because they indicated that an all-female group of patients might respond slightly differently to ART regimens than a mostly male population. In fact, Gilead Pharmaceuticals, the company that sells Stribild, used a mostly male trial to support the drug's approval with the FDA. The approval trial also tested EVG/COBI/FTC/TDF against ATV+RTV+TDF/FTC, and found that the regimens were roughly equivalent. In contrast, WAVES found EVG/COBI/FTC/TDF to be safer and more effective.
The study author of WAVES, Sally Hodder, M.D., director of the West Virginia Clinical and Translational Science Institute, cautioned against directly comparing the two trials. The respective patient populations in WAVES and Stribild's approval trial had many different characteristics aside from gender ratio, she pointed out.
Yet WAVES did definitively show that, in an all-female population, EVG/COBI/FTC/TDF was the clear winner. (In contrast, the Stribild approval trial didn't include enough women to draw any meaningful conclusions about the relative performance of either drug regimen in women.)
"This trial will inform the world of antiretroviral treatment," said Hodder, speaking at a press event at the ICAAC/ICC meeting. Incorporating women into clinical trials is becoming increasingly important, she said, noting that the U.S. Food and Drug Administration has started to ask drug companies for more data on women.
Overall, 575 women participated in WAVES. None of these women had ever been treated with another antiretroviral before they enrolled in the trial. The women were randomly split into different treatment groups and treated for 48 weeks. Clinicians kept track of rates of viral suppression, a key indicator of a drug's effectiveness, and found that EVG/COBI/FTC/TDF was superior to ATV+RTV+TDF/FTC. In addition, none of the patients taking EVG/COBI/FTC/TDF developed resistant mutations, compared to three women treated with ATV+RTV+TDF/FTC.
Another important feature of WAVES was that it was a truly global study. Gilead, the trial sponsor, recruited women from 80 different trial sites across the globe. Of the 575 women enrolled, 192 were in Russia, 161 were in Uganda and 116 were in the United States. The remainder was located in Europe, Dominican Republic, Mexico and Thailand.
Based on regional data, Hodder and her colleagues were able to compare how women in different countries responded to treatment. Interestingly, they found that U.S. women had lower rate of virological suppression compared to women in Russia and Uganda.
During the press event, Hodder noted that this variance indicates that the medical community needs to be thinking carefully about women's health in the U.S. The WAVES study clearly identified a problem, and the next step is to address the root cause of why women in the U.S. don't do as well on treatment compared to their counterparts in other countries.
There could be many reasons for this, Hodder said. For example, compared to other trial participants, the U.S. women were slightly older; had higher body mass indexes; were less likely to be married and were more likely to suffer from anxiety, depression or mood disorders.
"These [U.S.] women are very resilient, but they have a lot of responsibilities," said Hodder, speaking at the press event. She noted that U.S. women have high poverty levels, often have children and need to care for elderly parents.
"My personal opinion is that women put themselves last," she said. "I think some of those factors may be important ... and the WAVES trial put emphasis on women's health[.]"