A Systematic Review of the Inclusion (or Exclusion) of Women in HIV Research: From Clinical Studies of Antiretrovirals and Vaccines to Cure Strategies.

INTRODUCTION: The effect of clinical interventions can differ because of sex/gender. Studies have shown that women are often under-represented in medical research. The aim of this systematic literature review was to characterize women's participation in HIV clinical studies of antiretroviral drugs (ARV), prophylactic vaccines (VAX), and curative strategies (CURE). METHODS: Systematic PubMed searches were conducted to identify ARV, VAX, and CURE studies. Data were extracted on the number of women, date of publication, sources of funding, country of study, and trial phase. Correlates of female participation were assessed. RESULTS: Women represented a median of 19.2% participants in ARV studies (387), 38.1% in VAX studies (53), and 11.1% in CURE studies (104). Funding source was not correlated with the proportion of female participants in VAX and CURE studies but was for ARV studies (P = 0.03). ARV trials funded by private noncommercial sources had the highest proportion of women, whereas publicly funded trials had the lowest female participation (median 16.7%). The median proportion of women in ARV trials that were fully or partially funded by the National Institutes of Health was significantly lower than the median in trials funded by other sources (19.6% vs. 22.3%, P = 0.001). CONCLUSIONS: Although women comprise nearly half of people living with HIV, they continue to be under-represented in clinical studies. Despite federal policies that have been established to address this, our study shows that publicly funded ARV trials recruit even fewer women than other trials. There is an urgent need to ensure that HIV clinical studies consider sex/gender dimensions.

Iron depletion and repletion with ferrous sulfate or electrolytic iron modifies the composition and metabolic activity of the gut microbiota in rats.

Iron (Fe) deficiency anemia is a global health concern and Fe fortification and supplementation are common corrective strategies. Fe is essential not only for the human host but also for nearly all gut bacteria. We studied the impact of Fe deficiency and Fe repletion on the gut microbiota in rats. Weanling rats were fed an Fe-deficient diet for 24 d and then repleted for 13 d with FeSO4 (n = 15) or electrolytic Fe (n = 14) at 10 and 20 mg Fe · kg diet⁻¹. In addition, one group of rats (n = 8) received the Fe-deficient diet and one group (n = 3) received a Fe-sufficient control diet for all 37 d. Fecal samples were collected at baseline and after the depletion and repletion periods, and colonic tissues were examined histologically. Microbial metabolite composition in cecal water was measured and fecal samples were analyzed for microbial composition with temporal temperature gradient gel electrophoresis and qPCR. Compared to Fe-sufficient rats, Fe-deficient rats had significantly lower concentrations of cecal butyrate (-87%) and propionate (-72%) and the abundance of dominant species was strongly modified, including greater numbers of lactobacilli and Enterobacteriaceae and a large significant decrease of the Roseburia spp./E. rectale group, a major butyrate producer. Repletion with 20 mg FeSO4 · kg diet⁻¹ significantly increased cecal butyrate concentrations and partially restored bacterial populations compared to Fe-deficient rats at endpoint. The effects on the gut microbiota were stronger in rats repleted with FeSO4 than in rats repleted with electrolytic Fe, suggesting ferrous Fe may be more available for utilization by the gut microbiota than elemental Fe. Repletion with FeSO4 significantly increased neutrophilic infiltration of the colonic mucosa compared to Fe-deficient rats. In conclusion, Fe depletion and repletion strongly affect the composition and metabolic activity of rat gut microbiota.