Virologic response of treatment experienced HIV-infected Ugandan children and adolescents on NNRTI based first-line regimen, previously monitored without viral load.

BACKGROUND: Many HIV-infected African children gained access to antiretroviral treatment (ART) through expansion of PEPFAR programs since 2004 and introduction of "Test and Treat" WHO guidelines in 2015. As ART access increases and children transition from adolescence to adulthood, treatment failure is inevitable. Viral load (VL) monitoring in Uganda was introduced in 2016 replacing clinical monitoring. However, there's limited data on the comparative effectiveness of these two strategies among HIV-infected children in resource-limited settings (RLS). METHODS: HIV-infected Ugandan children aged 1-12 years from HIV-care programs with > 1 year of first-line ART using only immunologic and clinical criteria to monitor response to treatment were screened in 2010. Eligible children were stratified by VL ≤ 400 and > 400 copies/ml randomized to clinical and immunological (control) versus clinical, immunological and VL monitoring to determine treatment failure with follow-up at 12, 24, 36, and 48 weeks. Plasma VL was analyzed retrospectively for controls. Mixed-effects logistic regression models were used to compare the prevalence of viral suppression between study arms and identify factors associated with viral suppression. RESULTS: At baseline all children (n = 142) were on NNRTI based ART (75% Nevirapine, 25% efavirenz). One third of ART-experienced children had detectable VL at baseline despite high CD4%. Median age was 6 years (interquartile range [IQR]: 5-9) and 43% were female. Overall, the odds of viral suppression were not different between study arms: (arm by week interaction, p = 0.63), adjusted odds ratio [aOR]: 1.07; 95%CI: 0.53, 2.17, p = 0.57) and did not change over time (aOR: 0 vs 24 week: 1.15; 95% CI: 0.91, 1.46, p = 0.24 and 0 vs 48 weeks: 1.26; 95%CI: 0.92, 1.74, p = 0.15). Longer duration of a child's ART exposure was associated with lower odds of viral suppression (aOR: 0.61; 95% CI: 0.42, 0.87, p < .01). Only 13% (9/71) of children with virologic failure were switched to second-line ART, in spite of access to real-time VL. CONCLUSION: With increasing ART exposure, viral load monitoring is critical for early detection of treatment failure in RLS. Clinicians need to make timely informed decisions to switch failing children to second-line ART. TRIAL REGISTRATION: ClinicalTrials.gov NCT04489953 , 28 Jul 2020. Retrospectively registered. ( https://register.clinicaltrials.gov ).

Career development for infection and immunity research in Uganda: a decade of experience from the Makerere University - Uganda Virus Research Institute research and training programme.

Background: The Makerere University/Uganda Virus Research Institute (UVRI) Centre of Excellence for Infection & Immunity Research and Training (MUII) is a collaborative programme supporting excellence in Infection and Immunity (I&I) research in Uganda. Set up in 2008, MUII aims to produce internationally competitive Ugandan and East African I&I research leaders, and develop human and infrastructural resources to support research and training excellence. We undertook an internal evaluation of MUII's achievements, challenges and lessons learned between 08-2008 and 12-2019, to inform programmes seeking to build Africa's health research expertise. Methods: Quantitative data were abstracted from programme annual reports. Qualitative data were obtained in 03-04/2019: a cross-sectional evaluation was undertaken among a purposefully selected representative sample of 27 trainees and two programme staff. Qualitative data was analysed according to pre-determined themes of achievements, challenges, lessons learned and recommendations for improvement. Results: By 12-2019, MUII had supported 68 fellowships at master's-level and above (50% female: 23 Masters, 27 PhD, 15 post-doctoral, three group-leaders) and over 1,000 internships. Fellows reported career advancement, mentorship by experts, and improved research skills and outputs. Fellows have published over 300 papers, secured grants worth over £20m, established over 40 international collaborations, and taken on research and academic leadership positions in the country. Key lessons were: i) Efficient administration provides a conducive environment for high quality research; ii) Institutions need supportive policies for procurement, including provisions for purchases of specific biological research reagents from international manufacturers; iii) Strong international and multi-disciplinary collaboration provides a critical mass of expertise to mentor researchers in development; and iv) Mentorship catalyses young scientists to progress from graduate trainees to productive academic researchers, relevant to society's most pressing health challenges. Conclusions: Sustainable academic productivity can be achieved through efficient operational support, global collaboration and mentorship to provide solutions to Africa's health challenges.

Continuous research monitoring improves the quality of research conduct and compliance among research trainees: internal evaluation of a monitoring programme.

Background: Research site monitoring (RSM) is an effective way to ensure compliance with Good Clinical Practice (GCP). However, RSM is not offered to trainees (investigators) at African Institutions routinely. The Makerere University/Uganda Virus Research Institute Centre of Excellence in Infection and Immunity Research and Training (MUII-Plus) introduced internal monitoring to promote the quality of trainees' research projects. Here, we share our monitoring model, experiences and achievements, and challenges encountered. Methods: We analysed investigators' project reports from monitoring visits undertaken from April 2017 to December 2019. Monitors followed a standard checklist to review investigator site files and record forms, and toured site facilities. We planned four monitoring visits for each trainee: one at site initiation, two interim, and a closeout monitoring visit. A team of two monitors conducted the visits. Results: We monitored 25 out of the 26 research projects in progress between April 2017 and December 2019. Compliance with protocols, standard operating procedures, GCP, and GCLP improved with each monitoring visit. Median (IQR) compliance rate was 43% (31%, 44%) at site initiation visit for different monitoring items, 70% (54%, 90%) at the 1st interim monitoring visit, 100% (92%, 100%) at 2nd interim monitoring visit and all projects achieved 100% compliance at site closeout.  All investigators had good work ethics and practice, and appropriate facilities. Initially, some investigators' files lacked essential documents, and informed consent processes needed to be improved. We realized that non-compliant investigators had not received prior training in GCP/GCLP, so we offered them this training. Conclusions: Routine monitoring helps identify non-compliance early and improves the quality of research. We recommend continuous internal monitoring for all research studies. Investigators conducting research involving human subjects should receive GCP/GCLP training before commencing their projects. Institutional higher degrees and research ethics committees should enforce this as a requirement for project approvals.

Post - effects of obstetric fistula in Uganda; a case study of fistula survivors in KITOVU mission hospital (MASAKA), Uganda.

BACKGROUND: Obstetrical fistula (OF) is a public health challenge that is among the previously neglected components of maternal health in the developing world. The condition, which in the recent past has increasingly drawn more attention from the public, has a devastating impact on the health and wellbeing of both women and girls worldwide. The most common cause of obstetric fistula in developing countries is prolonged obstructed labor affecting approximately 2 million women and girls across Africa and Asia. The objective of this study was to examine the post-effects of fistula and reintegration strategies of fistula survivors in Uganda. METHODS: A descriptive case study design was used to collect data from women aged 15-49 years who had experienced OF and been successfully treated/repaired. Data collection was aided by in-depth interview guides designed for collecting qualitative data which was analyzed using thematic and content analysis. RESULTS: The study results showed that 45.6% were aged 18-24 years, 43% had only primary level education and 55.7% of the women were married. Fistula survivors continue to suffer from shame, rejection, isolation and stigma, trauma and disgrace among other effects even after successful repair/surgery. Some of the reintegration strategies for fistula survivors include; seeking for successful repair, remarriage and relocation from their parent communities to new environments. CONCLUSION: In addition to capacity building, changing attitudes and strengthening the health system, a comprehensive and holistic fistula care approach is required to facilitate the reintegration process and restoration of women dignity.

Agony resulting from cultural practices of canine bud extraction among children under five years in selected slums of Makindye: a cross sectional study.

BACKGROUND: Canine Bud Extraction (CBE) is a process of removing or gouging children's healthy canine tooth buds embedded underneath the gum using traditional unsterilized tools. The practice of CBE commonly known as false teeth removal continues to be an adopted cultural intervention of choice, in the prevention of morbidity and mortality from common childhood illnesses. However, it is a practice against the rights of the children with serious consequences. While CBE is associated with the perceived myth of curative gains, the agony emanating from the cultural practice exposes children to ill-health conditions such as dehydration, malnutrition, blood-borne diseases like HIV/AIDs, septicemia, fever and death. This research sought to understand the factors underpinning the practice of CBE among urban slum dwellers. METHOD: A cross-sectional study was conducted from five randomly selected slums in Makindye division; 298 household heads or guardians with children below 5 years, who had ever suffered from false teeth were interviewed. The variables measured included guardians' socio-demographic profiles, determinants of CBE, common childhood illnesses assumed to be treated with CBE and the reported side-effects associated with the practice. RESULTS: Of the 298 respondents with children who had ever suffered from "false teeth" interviewed, 56.7% had two or more children below 5 years and 31.9% were from the central region. The proportion of households practicing CBE was 90.3%; 69.8% of the caretakers mentioned that it was done by traditional healers and for 12.1% by trained health workers (dentists). Number of children (OR = 2.8, 95% CI: 1.1-7.2) and the belief that CBE is bad (OR = 0.1, 95% CI: < 0.001, p < 0.001) had a statistically significant association with CBE. Additionally, number of children (χ2 = 4.9, p = 0.027) and 2 sets of beliefs (CBE treats diarrhea (χ2 = 12.8, p = 0.0017) and CBE treats fever (χ2 = 15.1, p = 0.0005) were independent predictors of CBE practice. A total of 55.7% respondents knew that there were side effects to CBE and 31% mentioned death as one of them. CONCLUSION: The high proportion of households practicing CBE from this study ought to awaken the perception that the practice is ancient. CBE in this community as the study suggests was strongly driven by myths. The strong belief that CBE is bad provides an opportunity for concerted effort by primary health care providers, policy makers and the community to demystify the myths associated with false teeth and the gains of CBE.