Pregnant or potentially pregnant women have historically been excluded from clinical trials of new medications. However, it is increasingly recognised that it is imperative to generate evidence from the population in whom the drugs are likely to be used to inform safe, evidence‐based shared clinical decision making. Reluctance by researchers and regulators to perform such studies often relates to concerns about risk, particularly to the foetus. However, this must be offset against the risk of untreated disease or using a drug in pregnancy where safety, efficacy and dosing information are not known. This review summarises the historical perspective, and the ethical and legal frameworks that inform the conduct of such research, then highlights examples of innovative practice that have enabled high quality, ethical research to proceed to inform the evidence‐based use of medication in pregnancy.

The success of fecal microbiota transplant (FMT) in treating recurrent Clostridioides difficile infection has led to growing excitement about the potential of using transplanted human material as a therapy for a wide range of diseases and conditions related to microbial dysbiosis. We anticipate that the next frontier of microbiota transplantation will be vaginal microbiota transplant (VMT). The composition of the vaginal microbiota has broad impact on sexual and reproductive health. The vaginal microbiota in the “optimal” state are one of the simplest communities, dominated by one of only a few species of Lactobacillus. Diversity in the microbiota and the concomitant depletion of lactobacilli, a condition referred to as bacterial vaginosis (BV), is associated with a wide range of deleterious effects, including increased risk of acquiring sexually transmitted infections and increased likelihood of having a preterm birth. However, we have very few treatment options available, and none of them curative or restorative, for “resetting” the vaginal microbiota to a more protective state. In order to test the hypothesis that VMT may be a more effective treatment option, we must first determine how to screen donors to find those with minimal risk of pathogen transmission and “optimal” vaginal microbiota for transplant. Here, we describe a universal donor screening approach that was implemented in a small pilot study of 20 women. We further characterized key physicochemical properties of donor cervicovaginal secretions (CVS) and the corresponding composition of the vaginal microbiota to delineate criteria for inclusion/exclusion. We anticipate that the framework described here will help accelerate clinical studies of VMT.

It is unfortunately true that clinicians lack the necessary evidence to know how to use medications properly in large sections of the population and do not have optimal treatments to use for many neglected tropical diseases (NTDs). NTDs often disproportionately affect neglected populations that are left out of research efforts, such as children and pregnant women. As reliable access to safe, effective preventives and treatments can break the cycle of poverty, illness, and ensuing debility that further perpetuates poverty, it is of paramount importance to investigate and develop new medicines for neglected populations suffering from NTDs. Furthermore, there is not only a need to develop and evaluate novel therapies, but also to ensure that these are affordable, available, and adapted to the communities who need them. The NIH has proposed a “4 C's” framework which is relevant for neglected diseases and populations and should be leveraged for the study of the Twice Neglected: Consider inclusion; Collect data from neglected populations with neglected conditions; Characterize differences through meaningful analysis; Communicate findings pertaining to neglected diseases and populations. With this editorial, the British Journal of Clinical Pharmacology hereby launches a call for high‐quality articles focusing on NTDs in special populations, to facilitate and encourage the reversal of this dual neglect.

“Undetectable equals untransmittable” (U = U) is the concept that a person living with HIV who has an undetectable plasma HIV RNA viral load cannot pass HIV to another person through sexual contact. In the 4 years that have passed since the health equity advocacy group Prevention Access Campaign launched its groundbreaking 2016 U = U initiative, scientific support for the movement has only grown, and 1000 organizations worldwide have now endorsed the original consensus statement ( 1). The message is clear and unequivocal and has gone a long way toward lifting internal and external stigma faced by people living with HIV and strengthening advocacy for universal access to antiretroviral therapy (ART) for all people living with HIV—a key tactic in ending the HIV pandemic, which has claimed 32 million lives.

Despite highly effective HIV pre-exposure prophylaxis (PrEP) options, no options provide on-demand, non-systemic, and behaviorally-congruent PrEP that many desire. A tenofovir-medicated rectal douche before receptive anal intercourse (RAI) may provide this option. Three tenofovir rectal douches - 220-mg iso-osmolar Product A, 660-mg iso-osmolar Product B, and 660-mg hypo-osmolar Product C – were studied in 21 HIV-negative men who have sex with men. We sampled blood and colorectal tissue to assess safety, acceptability, pharmacokinetics, and pharmacodynamics. The douches had high acceptability without toxicity. Median plasma tenofovir peak concentrations for all products were several-fold below trough concentrations associated with oral tenofovir disoproxil fumarate (TDF). Median colon tissue mucosal mononuclear cell (MMC) tenofovir-diphosphate concentrations exceeded target concentrations from 1-hour through 3-to-7-days after dosing. For 6-7-days after a single Product C dose, MMC tenofovir-diphosphate exceeded concentrations expected with steady-state oral TDF 300-mg on-demand “2-1-1” dosing. Compared to pre-drug baseline, HIV replication after ex vivo colon tissue HIV challenge demonstrated a concentration-response relationship with 1.9 log₁₀ maximal effect. All three tenofovir douches achieved tissue tenofovir-diphosphate concentrations and colorectal antiviral effect exceeding oral TDF with lower systemic tenofovir. tenofovir douches may provide a single dose, on-demand, behaviorally-congruent PrEP option and warrant continued development.