On the 11th to 13th October 2017, we undertook the Site Initiation Visit (SIV) for the DolPHIN-2 study in Kampala, Uganda. Shortly after, the SIV in Cape Town, South Africa also took place. The SIV is a time when all members of the team – including senior investigators, pharmacists, lab runners, laboratory workers, study nurses and physicians, drivers, regulatory officers and collaborating clinical specialists – come together for training on the protocol, study procedures and any other specific process that are necessary for that study.
The SIV is a very important time for the study team. Up to this point, there have been many months of preparation – discussion, protocol writing, ethical submissions, obtaining regulatory approvals and work on specific aspects of the project. However the SIV brings the whole team together for a focussed discussion regarding the specific details of the study. Whenever I attend an SIV, I feel the protocol really comes to life. Often the most important questions come from members of the study team who will be recruiting and working with the trial participants on a day-to-day basis. Often there are logistical questions which need to be resolved, and as the whole team works together, we start to move from a written protocol to a real-life study.
The DolPHIN-2 study is important and unique. Despite the availability of effective antiretroviral therapy (ART) that can reduce transmission of HIV from mother to infant, there continue to be a proportion of women who do not seek antenatal care until late in their pregnancy. These women often become aware of the fact they are HIV-positive towards the end of their pregnancy. In addition to the psychological distress this brings, there is also a real biomedical challenge: the current standard of care in many parts of the world, including Uganda and South Africa, takes several months to reduce the level of virus in the mother’s blood sufficiently to offer maximum protection to the infant. In a late-presenting pregnant mother, there is simply not enough time for the existing best treatments to work fully, and the risk to the baby remains.
It is possible that dolutegravir will offer a solution; in non-pregnant adults, the time taken to reduce viral load is significantly shorter, and if this is also true in pregnant mothers, there may be reduced rates of infant infection. But as well as the biomedical question of whether or not dolutegravir offers superior treatment to efavirenz-based ART, there are also important social science questions which warrant exploration. Why do women continue to present late when it is widely known that treatments are available? What are the main barriers to seeking care? What are the main challenges to taking treatment as prescribed? Does a mother who presents with untreated HIV in late pregnancy need additional supportive interventions compared to a woman who has been on ART for longer? To address these issues, a qualitative research network led by Dr Yussif Al Hassan and Dr Miriam Taegtmeyer at Liverpool School of Tropical Medicine will run in parallel to the main clinical study.
It is increasingly recognised that it is ethically imperative to study a drug in the population where it is to be used. In other parts of the world, dolutegravir is now considered an ideal first-line treatment for HIV. However, in sub-Saharan African, where women have high fertility rates and low uptake of contraception, countries such as Uganda wish to see data regarding the safety and efficacy of the drug in pregnant women and their newborn children (or neonates) before recommending that dolutegravir is widely used throughout the population.
Through both the clinical trial, and the associated qualitative and health economic work packages, the DolPHIN-2 consortium will provide the much needed information about the health care perceptions and needs of this highly vulnerable population, of the safety and efficacy of dolutegravir compared to existing best treatment, and the cost-effectiveness of rolling out a novel treatment option. The SIV was a time when we could share our excitement about seeing these important research questions being addressed in a population with unmet needs, and moved us a step closer to first patient first visit. I feel privileged to be part of this research team.