Background Data on chronic kidney disease development in HIV infection is important towards building a comprehensive knowledge of HIV, ageing and polypharmacy in Africa. Several previous studies on tenofovir-associated kidney disease in Africa have shown conflicting results. This review summarises what is known about the development of kidney disease in HIV-positive African patients on tenofovir disoproxil fumarate (TDF)-containing ART. We set out to document the occurrence of kidney disease in HIV-positive Africans on TDF-containing ART in population-based studies and to evaluate the renal safety of TDF in Africans. Methods We conducted a systemic review using published studies which were identified through a computerized search of original research using the Medline/PubMed database, EMBASE, EBM Reviews, Proquest Google Scholar and Global Health reported from inception until 5 October 2017. Two reviewers independently abstracted the data and performed quality assessment of the included studies. We screened 595 articles and included 31 in the qualitative analysis performed. Results A total of 106 406 patients (of whom 66,681 were on Tenofovir) were involved in these 31 studies with sample sizes ranging from 30 to 62,230. Duration on tenofovir-containing ART ranged from those initiating ART at baseline to those who received TDF for up to 9 years. All but one of the studies involved only patients 16 years and older. The studies had differing definitions of kidney dysfunction and were of variable study design quality. The documented outcomes had substantial discrepancies across the studies, most likely due to methodological differences, study size and disparate outcome definitions. Conclusions Our review identified studies in Africans reporting statistically significant renal function decline associated with TDF use but the clinical significance of this effect was not enough to contraindicate its continued use in ART regimens. Consistent with studies in other populations, patients are at greater risk if they have pre-existing renal disease and are more advanced in age. More research is needed on paediatric populations under 16 years of age. Trial registration This review was registered on Prospero (registration number CRD42018078717). Electronic supplementary material The online version of this article (10.1186/s12981-019-0227-1) contains supplementary material, which is available to authorized users.
BackgroundA growing number of drug development studies that include pharmacokinetic evaluations are conducted in regions lacking a specialised pharmacology laboratory. This necessitated the development of an International Pharmacology Specialty Laboratory (IPSL) in Zimbabwe.ObjectivesThe aim of this article is to describe the development of an IPSL in Zimbabwe.MethodsThe IPSL was developed collaboratively by the University of Zimbabwe and the University at Buffalo Center for Integrated Global Biomedical Sciences. Key stages included infrastructure development, establishment of quality management systems and collaborative mentorship in clinical pharmacology study design and chromatographic assay development and validation.ResultsTwo high performance liquid chromatography instruments were donated by an instrument manufacturer and a contract research organisation. Laboratory space was acquired through association with the Zimbabwe national drug regulatory authority. Operational policies, standard operating procedures and a document control system were established. Scientists and technicians were trained in aspects relevant to IPSL operations. A high-performance liquid chromatography method for nevirapine was developed with the guidance of the Clinical Pharmacology Quality Assurance programme and approved by the assay method review programme. The University of Zimbabwe IPSL is engaged with the United States National Institute of Allergy and Infectious Diseases Division of AIDS research networks and is poised to begin drug assays and pharmacokinetic analyses.ConclusionsAn IPSL has been successfully established in a resource-limited setting through the efforts of an external partnership providing technical guidance and motivated internal faculty and staff. Strategic partnerships were beneficial in navigating challenges leading to laboratory development and training new investigators. The IPSL is now engaged in clinical pharmacology research.
BackgroundRenal abnormalities in HIV infected children may be due to the HIV infection or treatment among other factors. Tenofovir disoproxil fumarate (TDF) is associated with proximal renal tubular dysfunction, proteinuria and decrease in glomerular function. Studies in developed countries have shown variable prevalence of proximal renal tubular dysfunction in children on TDF. There are no known studies in developing countries, including Zimbabwe, documenting the proximal tubular function in HIV infected children on TDF. The aim of this study was to assess renal and proximal renal tubular function in HIV infected children receiving TDF and determine factors associated with proximal tubular dysfunction. MethodsA descriptive cross-sectional study was conducted in HIV infected patients below 18 years of age attending outpatient clinics at two tertiary hospitals in Harare, who received a TDFcontaining antiretroviral regimen for at least six months. Dipstick protein and glucose, serum and urine phosphate and creatinine levels were measured. Fractional excretion of phosphate was calculated. Estimated glomerular filtration rate (eGFR) was calculated using the Schwartz formula. Tubular dysfunction was defined by at least two of the following characteristics: normoglycaemic glycosuria, hypophosphatemia and fractional excretion of phosphate > 18%.
While important advances have been made in the prevention and treatment of Human Immunodeficiency Virus (HIV) infection, limited expertise and resource constraints to effectively manage rollout of HIV programs often contribute to poor treatment outcomes in Sub-Saharan Africa. In 1998, the University of Zimbabwe (UZ) and the University at Buffalo, State University of New York (UB), developed a collaborative clinical pharmacology capacity building program in Zimbabwe to train the next generation of HIV researchers and support rollout of the national HIV program. The collaboration was funded by research and training grants that were competitively acquired through United States of America government funding mechanisms, between 1998 and 2016. Thirty-eight research fellows were trained and a specialty clinical pharmacology laboratory was established during this period. Knowledge and skills transfer were achieved through faculty and student exchange visits. Scientific dissemination output included sixty-two scholarly publications that influenced three national policies and provided development of guidelines for strategic leadership for an HIV infection—patient adherence support group. The clinical pharmacology capacity building program trained fellows that were subsequently incorporated into the national technical working group at the Ministry of Health and Child Care, who are responsible for optimizing HIV treatment guidelines in Zimbabwe. Despite serious economic challenges, consistent collaboration between UZ and UB strengthened UZ faculty scholarly capacity, retention of HIV clinical research workforce was achieved, and the program made additional contributions toward optimization of antiretroviral therapy in Zimbabwe.
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