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BackgroundRetirement age in most of sub-Saharan Africa is between 55 and 60 years, even in academic and research institutions. There is no mechanism to retain even the few most experienced and outstanding among them. There is evidence that institutions retaining experienced researchers access better large research grants.MethodsWe conducted literature review and shared views and experiences among peer research scientistsResultsMost African scientists obtain their first degrees aged 25–30 years. Economic needs compounded with work experience requirements for PhD studies delay their research career development such that most PhD graduates are 40–50 years of age. However, unlike in the developed world where the majority acquire their PhDs in their late 20’s or early 30’s, there is no mechanism to retain them longer at work to maximise their contributions to scientific developments. Instead, African scientists are forced to retire young at 60 years of age. On the contrary, developed countries scientists graduate earlier, work longer and have retention mechanisms even after retirement. African countries do not consider retaining even the few who have demonstrated outstanding performance. Consequently, outstanding research scientists retire at the time when they are needed most. They seek and get jobs abroad or in externally owned projects (brain drain). Their decade or so of work, generates more resources abroad, depriving Africa of resource generating capacity. Secondly, retiring at the height of their performance is economically counterproductive. Thirdly, this affects negatively the career development of young scientists for lack of experienced supervisors and mentors.ConclusionAfrica must rethink the retirement age of its research scientists and create incentives to retain outstanding research scientists who reach retirement age. This is urgently needed to stop brain drain, contribute to economic development, and accelerate ongoing efforts to build sustainable research capacity and mentorship programmes in Africa.

BackgroundRemarkable progress has been achieved in decreasing AIDS-related deaths and HIV-1 transmission through ART. Nevertheless, an affordable, effective and durable HIV-1 vaccine protection remains the best solution for halting the AIDS epidemic.Our aim is to develop a vaccine inducing cytotoxic T lymphocytes (CTL), which effectively inhibit HIV-1 replication and complement bnAbs for prevention; such T cells are likely critical for a successful cure. Central to our strategy is to focus HIV-1-specific CTL on the most functionally conserved regions (not a string of epitopes and not full-length proteins) common to most HIV-1 variants, which HIV-1 typically cannot change without losing fitness. These conserved regions were defined by bioinformatics, and a bivalent mosaic was computationally designed to increase the vaccine perfect match of potential T-cell epitopes to 80% of global HIV-1 variants; if successful, the vaccine will be suitable for global deployment. Furthermore, we maximised the inclusion of protective epitopes associated with viral control in treatment-naive HIV-1-positive individuals defined on 4 continents. These immunogens are delivered by the non-replicating simian adenovirus ChAdOx1 prime and non-replicating poxvirus MVA boost regimen, clinically proven safe and potent.MethodsThe GREAT consortium has been established to build capacity for a future efficacy trial in Zambia, around Lake Victoria and in Kenya by engaging populations at documented high risk for HIV-1 infection, despite preventive interventions, by diverse clades. We will conduct a phase I/IIa clinical trial HIV-CORE 006 to assess the safety and immunogenicity of the conserved-region vaccines, in preparation for an efficacy trial in these at-risk populations.ConclusionThe aims of the GREAT consortium are to ensure that at the completion of the programme grant, the vaccine regimen will be proven safe and potent, and the sites will be prepared to launch an appropriately designed trial to prove vaccine efficacy.

BackgroundThere remains an urgent need for a prophylactic HIV vaccine to control generalised epidemics. PrEP has demonstrated effectiveness of 86% and is recommended by WHO; uptake is generally high, but retention is disappointing in some settings. The EDCTP2 project PrEPVacc will assess the efficacy of two combination prophylactic vaccine regimens (DNA, MVA and Env protein/adjuvant) each compared to placebo and the proportion of infections averted by F/TAF in comparison to TDF/FTC. A Registration Cohort, recruiting HIV negative volunteers at risk of HIV will precede the trial.MethodsThe PrEPVacc partnership agreed that 70% vaccine efficacy had public health relevance. The trial uses nstage software for multi-arm, multi-stage designs (MAMS) and the averted infections ratio (AIR) methodology with participants randomised (i) 1:1:1 to active product or placebo (ii) 1:1 to TDF/FTC : F/TAF until week 26 (presumed peak immunogenicity). Access to PrEP in the Registration Cohort and after week 26 will be standard of care. HIV seroconversions occurring between weeks 0–26 will inform the PrEP analysis, incorporating HIV incidence amongst those who do not take up PrEP locally in the Registration Cohort. Seroconversions after week 26 will inform vaccine analyses.ResultsUp to 556 participants per group affords 92% power to detect vaccine efficacy of 70% at the final analysis, assuming incidence of 4/100-person years and 10% loss with 81% and 97% power to conclude that F/TAF can avert half or more of the infections prevented by TDF/FTC if effectiveness of TDF/FTC is 70% and 80%, respectively.ConclusionPrEPVacc adopts a pragmatic approach to uncertainties around HIV incidence in settings where PrEP is increasingly available. This innovative adaptive trial design uses validated software to determine vaccine efficacy and a novel methodology to evaluate a new PrEP agent, overcoming the challenge of demonstrating non-inferiority when adherence to TDF/FTC is high and the number of outcome events very low.

BackgroundEACCR2 is an EDCTP-funded, Eastern African-led network established in May 2009, with 23 regional partners from Ehtiopia, Kenya, Sudan, Tanzania, and Uganda, and 8 northern partners from Germany, Netherlands, Norway, Sweden and United Kingdom. The objective is to strengthen capacity to conduct health research to international standards with specific focus on clinical trials on poverty-relevant diseases such as HIV, TB, malaria and neglected infectious diseases. EACCR2 optimises the use of shared research infrastructures and other regional capacity building resources and opportunities.ActivitiesThe activities of the network are implemented in five work packages cutting across ‘nodes’ in different countries. Capacity building programmes and studies funded by EDCTP are implemented by coordinators at the disease nodes. The Uganda Virus Research Institute (UVRI) hosts the secretariat of the consortium of five nodes located in the following institutions: Malaria Node in Kilifi-Kenya Medical Research Institute Wellcome Trust, Tanzania; Training Node in Kilimanjaro Clinical Research Institute, Tanzania; Tuberculosis Node at the National Institute of Medical Research- Muhimbili, Tanzania; the Neglected and Re-Emerging Tropical Diseases Node at the University of Khartoum, Sudan; and the HIV Node at UVRI, Uganda.Coordinators form the project implementation committee which meets via skype or teleconference every quarter to assess progress, share best practice and challenges of the network. Scientific and annual meetings are arranged every year in one of the implementing institutions. During such meetings, students, the nodes and steering committee also meet to minimise travel costs while helping teams to network.EACCR2 learns from the experiences, best practice and challenges of EACCR1 while implementing its current activities. Careful planning and consensus building from all partners has been the driving force to build and implement activities of this virtual network. EACCR2 also works closely with other EDCTP Networks of Excellence, i.e. in Central Africa (CANTAM), West Africa (WANETAM), and Southern Africa (TESA).

BackgroundThe Globally Relevant AIDS Vaccine Europe-Africa Trials (GREAT) partnership is an EDCTP-funded project that aims to foster collaboration between institutions in Europe and sub-Saharan Africa to build capacity among African clinical research centres (CRCs) for the design and conduct of HIV-1 vaccine efficacy trials.MethodsIn January 2017, the University of Oxford (UOXF) and five CRCs in Kenya, Uganda and Zambia were awarded a 5 year grant for capacity building and to support conduct of an HIV-1 vaccine trial in different high-risk populations across Africa using cross-clade (conserved protein regions) T-cell vaccines. UOXF and CRCs embarked on activities to strengthen capacity of the CRCs for future efficacy trials. This included training, community engagement, cohort preparation and infrastructure upgrade.ResultsIn the first year, the African investigators at the CRCs collaborated on the development of a protocol aimed at assessing the safety and immunogenicity of the tHIVconsvX vaccines. In preparation for the planned vaccine trial, infrastructure upgrades were prioritised at all partner sites and this included building laboratory space and procurement of appropriate laboratory equipment. Planned infrastructure upgrades will also ensure that high-risk populations can be safely and confidentially included in HIV prevention clinical trials. Systematic community engagement was implemented at all sites, training in GCP/GCLP was provided and training is planned for nominated CRC staff to lead community engagement efforts.ConclusionImproved infrastructure and the provision of targeted training will enhance future trials and increase the capacities of CRCs and staff to conduct quality trials in previously hard-to-reach populations. Early collaboration between investigators from European and sub-Saharan African institutions, with equal responsibilities in the protocol development process, established a meaningful partnership. EDCTP funding also offers a unique opportunity for capacity building.

Background These two trials under Europe-Africa collaborations aim at addressing two factors relevant for Africa i.e helminth infections and HIV-1 diversity. EV06 used a novel combination of DNA expressing clade C Env, Gag and Pol-nef co-administered with AIDSVAX®B/E Env protein to study the effect of S. mansoni on vaccine responses. GREAT is a recently awarded trial using a 2nd generation improved conserved tHIVConsvX T-cell vaccine candidate combined with bivalent mosaic design to increase breadth and protective epitopes. Methods EV06 enrolled 72 males and females aged 18–45, half infected with S. mansoni (SM+). In each arm 30 received vaccine and 6 placebo at week 0, 4 and 24. Responses were evaluated at week 0, 6, 26 and 36. Humoral responses were measured as binding IgG against a panel of HIV-1 envelope glycoproteins and as neutralizing antibodies (Nabs), using TZM/ bl cells and tier 1 pseudoviruses. Cellular responses were measured as HIV-specific CD4+ and CD8+ T-cell by IFN-γ ELIS-pot and multi-cytokine intracellular staining flow cytometry. GREAT will be a phase IIa trial and preparation for efficacy trials in Kenya, Uganda and Zambia testing ChAdOx1.tHIVconsv5 and ChAdOx1.tHIVconsv6 followed by MVA.tHIVconsv3 and MVA.tHIVconsv4 on week 2 (Arm 1) or week 8 (Arm 2). Progress Differences in binding IgG response rates were observed in vaccinated participants against the vaccine matched clade C V1V2 (gp70–96ZM651.02 V1V2) at week 6: 56% among SM+ versus 86% among SM – (p=0.039). At week 36, response magnitudes were statistically lower in the SM+ against gp120 and gp140 proteins (p=0.04 for both). SM+ also had lower Nabs and ELISpot responses at various time points. Still blinded data on the first 20 volunteers show 80% responders for CD4 T cell at w26 and 70% CD8 responders at w36. These trials will provide more data on challenges facing HIV vaccine development in Africa.

Background The General Population Cohort (GPC) in Southwestern Uganda is a low-risk population with low HIV incidence rates ( Methods A total of 2049 pol sequences of participants diagnosed from 2003–2015 were included in this analysis; pol sequences were from GPC (n=1049), Central Uganda (n=800) and Eastern Uganda (n=200). Phylogenetic analysis was used to identify transmission networks. The demographic and clinical characteristics of the transmission clusters were analysed. Results The overall subtype distribution was: A (45%), C (3%), D (40%) and others (12%). The subtype distribution by region was for GPC: A (41%), C (2%), D (45%) and others (12%). For Central: A (49%), C (4%), D (35%) and others (12%). Eastern: A (60%), C (3%), D (24%) and others (13%). We identified 233 transmission clusters (cluster size variation 2–10) that comprised of 559 (27%) of the 2049 participants. The majority of clusters comprised transmission pairs (n=186) and triplets (n=30). The majority (∼60%) of the 233 clusters was from the GPC and all 13 large clusters (≥5) were also from the GPC. A significant number of clusters (n=25, 11%) was formed between individuals from different geographic locations. Participants in transmission networks were associated with high-risk sexual behaviour: low condom use, high alcohol use, and partner change even with known HIV-positives. Conclusions The transmission networks identified among individuals from the GPC and other populations or geographic regions may imply HIV introductions from outside communities. This suggests that HIV introductions into communities are common and account for a substantial number of new infections in the GPC. HIV prevention efforts should therefore target the broader communities beyond the GPC.

Background The Government of Uganda uses empirical evidence for policy formulation. The Uganda Virus Research Institute (UVRI) and the International Association of National Public Health Institutions (IANPHI) trained journalists and scientists to communicate research processes and findings to the public. This improved the capacity to communicate important information during outbreaks and to disseminate research findings as part of policy formulation. Methods Through training workshops, 30 research scientists including study coordinators, research officers and principal investigators interacted with 12 health reporters from various media houses. Training covered writing policy briefs and press releases. Attendees were taken through the ‘dos and don9ts’ when being interviewed by television/radio journalist while journalists were trained in basic epidemiology terms and research processes. They analysed research papers to find different story angles. They conducted mock media talk shows for television and radio and these sessions were reviewed by all those in attendance, identifying areas for improvement. Results Key findings revealed that journalists do not ably write about research findings because they do not understand the scientific research procedure. Training journalists on health research communication, ethical issues and research procedure enabled them to appreciate the scientific research process. Continued interaction was found to be of help to articulate research findings for health journalist before they are presented in print and audio media for the wider audience/public. This method built capacity of participating scientists to communicate to the lay audiences. It also helped the scientists plan for the media and policy makers during future dissemination of their research findings. Conclusions Meaningful engagement of journalists and the public by scientists results in proper understanding of the ethical and scientific research procedure. This calls for systematic investment by research organisations and, during proposal development, budgeting for communication and knowledge translation of research findings to benefit policy makers and the wider research community.

Background In May 2009, EDCTP supported the establishment of the East African Consortium for Clinical Research (EACCR) involving 35 regional institutions and 6 northern partners to promote capacity development for collaborative multi-site clinical trials and research. EACCR aims to contribute to overcoming a situation of: under-funded, fragmented and uncoordinated regional health research; too few African scientists; inadequate infrastructure; insufficient networking and knowledge-sharing. We present updates on achievements and lessons learnt on increased preparedness to conduct globally-competitive research and clinical trials on poverty-related, neglected and emerging infectious diseases. Methods Retrospectively, we conducted a quasi-purposive summative evaluation through document review, participatory appraisal, direct observation and case studies of the EACCR work packages for governance, research, training and mentoring, infrastructure, and networking between November 2015 and February 2016. Results In the past five years, the Eastern Africa-led consensus-driven consortium has contributed to the following results (at least): 15 new research and capacity-strengthening grants; 150 peer-reviewed publications; 15 trials monitored; 531 scientists and associates mentored; 12 electronic training modules on research and bio-ethics; 2 newly ISO-accredited laboratories; 24 research sites upgraded; 20 partnerships harnessed; 2 knowledge-sharing platforms of the East African Health Research Commission; an interactive website (www. eaccr.org); and an additional 2 million euros leveraged. Conclusions EACCR has increased its capacity and partnerships for on-going and planned multisite clinical trials; we can sustain coordinated collaborative GCP-compliant multisite trials and health research. We can intensify high-level advocacy and resource mobilisation in Eastern Africa in partnership with policy makers, other consortia and development partners. We stand firm on the shoulders of current and promising giants of EACCR, other consortia, EDCTP and other like-minded partners and are thus prepared to conduct and disseminate more African-led health research and capacity-strengthening initiatives on poverty-related, neglected and emerging infectious diseases in Africa during the second programme of EDCTP.