Focus on Projects: Strategic Primer Grants: completed projects

The Strategic Primer Grants call for proposals was published on 12 December 2011. The purpose of the call was to provide funding to research groups in sub-Saharan Africa and Europe to conduct innovative studies that will generate results to inform future clinical trials. It also aimed to sustain and strengthen the capacity built under the first EDCTP programme as well as further the networking of research programmes in African and European countries. Fourteen projects received funding and three of these have recently been completed.

1 - Improving the reproductive health of adolescent girls in sub-Saharan Africa

Prevalence and incidence of HIV infection and other sexually transmitted infections (STI) are particularly high among adolescent girls in Southern and Eastern Africa. The mechanisms underlying this high vulnerability are poorly understood. However, there is some evidence suggesting that male-to-female transmission of HIV is more efficient in sub-Saharan Africa than in high-income countries. The project, led by Anne Buvé (Institute of Tropical Medicine, Belgium) aimed to assess the acceptability of studies on reproductive health in adolescent girls and to characterise their vaginal microbiome in Mwanza, Tanzania.

A total of 401 girls of 17-18 years old and attending school were recruited for a cross-sectional study; they were interviewed and tested for reproductive tract infections (RTIs). Self-administered vaginal swabs were used to test for RTIs and to assess the vaginal microbiome with qRT PCR. Of the enrolled girls, 43% reported that they had sex. HPV infection was the most common sexually transmitted infection (33%). The prevalence of bacterial vaginosis was 32% among sexually experienced girls and 19% among sexually naïve girls. Preliminary analyses showed large differences in the composition of the vaginal microbiome between sexually experienced and sexually naïve girls.

2 - Factors affecting HIV susceptibility in the adolescent genital mucosa

A project led by Dr Jo-Ann Passmore (University of Cape Town, South Africa) studied whether sexually transmitted infections (STIs) and microbiome fluctuations during puberty drive activation, inflammation and recruitment of HIV susceptible target cells to the genital tract. The project enrolled 297 adolescent females and 150 adolescent males (aged 16-22 year) from 3 clinical trial sites in South Africa to conduct mucosal sampling to investigate the influence of age on state of T cell activation and the type of inflammatory markers in the adolescent genital tracts.

The project showed that asymptomatic STIs and bacterial vaginosis are highly prevalent in young South African women and that there is an urgent need to complement the current national syndromic management guidelines. Levels of inflammation were higher in women from Cape Town than in women from Johannesburg, which was associated with significant shifts in the vaginal microbiome and HIV target cell activation.

In young males at the time of medical male circumcision (MMC), 16% had an asymptomatic STI at the time of surgery. The study found increased numbers of CD4+ T cells and Langerhans’ Cells in foreskin tissue, both potential HIV target cells. It was concluded that MMC protects through removal of target cells that infiltrate this epithelial tissue. Asymptomatic STIs may increase HIV risk in uncircumcised men by increasing influx of HIV target cells.

3 - Acceptability of vaginal rings for protection from HIV and unintended pregnancy

Vaginal rings are polymeric drug delivery devices designed to provide controlled release of drugs for intravaginal administration over extended periods of time. Compared to systemic dosing, the sustained local release of drug maximizes efficacy at lower doses, which reduces side effects. In recent years, vaginal rings have become popular for contraception and estrogen replacement therapy. However, contraceptive vaginal rings are not yet on the market in any African country, and acceptability of such rings has not yet been studied.

The project led by Tania Crucitti (Institute of Tropical Medicine, Belgium) aimed to study the acceptability of vaginal rings for women in Africa and to assess the effect of the ring on the vaginal microbiome. This open-label, single-centre, randomised, controlled clinical trial was conducted at Rinda Ubuzima (Kigali, Rwanda) among two groups of study participants. One group used a contraceptive vaginal ring (CVR) for three weeks followed by one week off. The other group used a CVR for three weeks and inserted a new CVR without break. Of the 174 women who were invited for enrolment, 126 attended the visit and 120 were enrolled on 27 December 2013. The last follow-up visit took place on 19 March 2014.

 

The study showed that women liked the ring because it had limited side effects and that it was used independently of the regimen. It increased appetite for food, lubrication, sexual desire and increased discussion about sex because men wanted to discuss the ring. There were no serious adverse events; a low incidence of self-reported or clinician-observed adverse events were reported. Characterisation of the vaginal flora and biofilm assessment is still ongoing.