July 30, 2012
Hooray for two posters at AIDS 2012 that looked at how men and women respond to antiretroviral treatment. Why hooray? Helena Kwakwa, the primary investigator of one of the studies, said it best right in her abstract: "Despite the changing epidemiology of HIV among women, they are often underrepresented in clinical trials evaluating antiretroviral therapy (ART)." Women comprise more than half of HIV infections worldwide but remain systematically under-represented and under-analyzed in research trials.
These two posters, at least, bucked the trend. Kwakwa et al's study assessed gender differences in response to antiretroviral therapy, while a study presented by Guilherme Calvet compared pre-menopausal to post-menopausal women in Brazil.
Of all the randomized, controlled antiretroviral clinical trials and meta-analyses published from 1996 to January 2012, Kwakwa and her colleagues were able to identify only 13 that included viral suppression and failure rates for both men and women on antiretroviral treatment. The total number of people in all published trials was 11,856 (2,981 women, 8,875 men). The investigators also included unpublished gender data from two additional studies in their final analysis, which brought the total to 14,030 (10,605 men, 3,425 women).
Kwakwa and colleagues conducted a meta-analysis of seven trials in which people started antiretroviral treatment for the first time and for which 96 weeks of data were reported on virologic suppression stratified by sex. They found that women were 28% less likely to get to a suppressed viral load than men. The analysis did not explore the reasons for this significant difference.
Calvet and colleagues from the Instituto de Pesquisa Clinica Evandro Chagas in Rio de Janeiro, Brazil, looked at 383 HIV-infected women who were starting their first antiretroviral regimen between January 2000 and December 2009 to see if their menopausal status made a difference in how they responded to treatment. Most of the women (85%) were pre-menopausal, but there were enough post-menopausal women (15%) to make the comparison scientifically meaningful. Of the 383 women, 164 were white and 219 were non-white.
Before starting treatment, the two groups had statistically similar viral loads and CD4+ cell counts, though the CD4+ cell counts of the pre-menopausal women were slightly higher (231 cells/mm3 vs. 208 cells/mm3, respectively). After starting treatment, the viral loads and CD4+ cell counts of the two groups were compared at three points: 6, 12 and 24 months. At the end of two years, 63.7% of all participants were virologically suppressed, with no difference seen between the two groups along the way.
By the same note, at six and 12 months, the CD4 counts and viral loads in the two groups were very similar. However, at 24 months, the change in CD4 counts among women in the post-menopausal group was significantly lower than those in the pre-menopausal group (+184 cells/mm3 versus +273 cells/mm3, respectively).
Pieces of data like these beg the larger questions. Why didn't more women get to a virologically suppressed state? Did the specific antiretroviral drugs -- or classes of drugs -- they took make a difference? Did they get side effects that caused them to stop treatment? Why is the CD4 change so much lower in a group of post-menopausal women on treatment in Brazil -- is it related to hormone levels, or aging in general, or something else entirely?
If the history of a lack of female representation in HIV clinical trial research holds, the answers to these questions -- and many others -- will be slow in coming.