COHORT PROFILE: The Complications of Long-Term Antiretroviral Therapy study in Uganda (CoLTART), a prospective clinical cohort.

BACKGROUND: Antiretroviral therapy (ART) improves the survival and quality of life of HIV-positive individuals, but the effects of long-term ART use do eventually manifest. The Complications of Long-Term Antiretroviral Therapy cohort study in Uganda (CoLTART) was established to investigate the metabolic and renal complications of long-term ART use among Ugandan adults. We describe the CoLTART study set-up, aims, objectives, study methods, and also report some preliminary cross-sectional study enrolment metabolic and renal complications data analysis results. METHODS: HIV-positive ART naïve and experienced adults (18 years and above) in Uganda were enrolled. Data on demographic, dietary, medical, social economic and behaviour was obtained; and biophysical measurements and a clinical examination were undertaken. We measured: fasting glucose and lipid profiles, renal and liver function tests, full blood counts, immunology, virology and HIV drug resistance testing. Plasma samples were stored for future studies. RESULTS: Between July 2013 and October 2014, we enrolled 1095 individuals, of whom 964 (88.0%) were ART experienced (6 months or more), with a median of 9.4 years (IQR 7.0-9.9) on ART. Overall, 968 (88.4%) were aged 35 years and above, 711 (64.9%) were females, 608 (59.6%) were or had ever been on a Tenofovir ART regimen and 236 (23.1%) on a Protease Inhibitor (PI) regimen. There were no differences in renal dysfunction between patients on Tenofovir and Non-Tenofovir containing ART regimens. Patients on PI regimens had higher total cholesterol, lower high density lipoprotein, higher low density lipoprotein, higher triglycerides, and a high atherogenic index for plasma than the non-PI regimen, p = 0.001 or < 0.001. Patients on Non-PI regimens had higher mean diastolic hypertension than patients on PI regimens, p < 0.001. CONCLUSIONS: Our finding of no differences in renal dysfunction between patients on Tenofovir and those on Non-Tenofovir containing ART regimens means that Tenofovir based first line ART can safely be initiated even in settings without routine renal function monitoring. However, integration of cardiovascular risk assessment, preventive and curative measures against cardiovascular disease are required. The CoLTART cohort is a good platform to investigate the complications of long-term ART use in Uganda.

Decreased renal function and associated factors in cities, towns and rural areas of Tanzania: a community-based population survey.

OBJECTIVES: Data on renal dysfunction in sub-Saharan Africa, comparing urban and rural areas, have not yet been reported. Therefore, we aimed to determine the distribution of low estimated glomerular filtration rates (eGFRs) in urban and rural Tanzania, to describe factors associated with low eGFR and to quantify fractions attributable to common risk factors. METHODS: We conducted a community-based survey of 1095 randomly selected Tanzanian adults (≥18 years). A structured questionnaire and examinations were used to document sociodemographic characteristics, diet, physical activity, anthropomorphic measurements and blood pressure. Blood tests were performed for HIV infection, diabetes mellitus and creatinine. eGFR was calculated using two equations recommended for African adults. RESULTS: Serum creatinine was available for 1043 participants: 170 in Mwanza city, 326 in district towns and 547 in rural areas. Mean age was 35.5 years and 54% were females. The prevalence of eGFR < 60 ml/min/1.73 m(2) in these 3 strata was 2.3% (95% CI = 0.8-6.6%), 7.5% (4.7-11.8%) and 7.4% (5.1-10.6%), respectively. When age standardised to the WHO world population, prevalences were 3.8%, 10.1% and 8.1%. Factors associated with low eGFR included district town residence, older age, greater wealth, less physical activity and hypertension. Only 21% of cases with eGFR < 60 ml/min/1.73 m(2) were attributable to HIV, hypertension or diabetes. CONCLUSIONS: Decreased renal function is common in Tanzania, particularly in district towns, and unique risk factors for kidney disease may exist in this population. Population-specific strategies for prevention, early diagnosis and treatment of kidney disease are needed for Africa.

The effect of Tenofovir on renal function among Ugandan adults on long-term antiretroviral therapy: a cross-sectional enrolment analysis.

BACKGROUND: WHO recommends using Tenofovir containing first line antiretroviral therapy (ART), however, Tenofovir has been reported to be associated with renal impairment and dysfunction. We compared renal function among individuals on Tenofovir and those on non-Tenofovir containing ART. METHODS: In a cross-sectional study of HIV-Positive adults on ART, at enrolment into a prospective cohort to study the long-term complications of ART in Uganda, information on biophysical measurements, medical history, clinical examination and renal function tests (RFTs) was collected. Fractional Tubular phosphate reabsorption and estimated glomerular filtration rate (eGFR) were calculated. Mean values of RFTs and proportions with abnormal RFTs were compared between non-Tenofovir containing (Non-TDF) and Tenofovir containing (TDF-ART) ART regimen groups using a general linear regression model. Durations of TDF exposure were also compared. RESULTS: Between July 2013 and October 2014, we enrolled 953 individuals on ART for 6 or more months, median duration on ART was 9.3 years, 385 (40.4 %) were on non-TDF and 568 (59.6 %) on TDF-ART regimens. The proportion of participants with Proteinuria (>30 mg/dl) was higher among the TDF-ART group than the non-TDF ART group. However, in multivariable analysis, there were no significant differences in the adjusted mean differences of eGFR, serum urea, serum creatinine, fractional tubular reabsorption of phosphate and serum phosphates when patients on TDF-ART were compared with those on non-TDF containing ART. There were no differences in renal function even when different durations on Tenofovir were compared. CONCLUSIONS: We found no differences in renal function among patients on Tenofovir and non-Tenofovir containing ART for almost a decade. Tenofovir based first line ART can therefore safely be initiated even in settings without routine renal function monitoring.

Re-testing as a method of implementing external quality assessment program for COVID-19 real time PCR testing in Uganda.

BACKGROUND: Significant milestones have been made in the development of COVID19 diagnostics Technologies. Government of the republic of Uganda and the line Ministry of Health mandated Uganda Virus Research Institute to ensure quality of COVID19 diagnostics. Re-testing was one of the methods initiated by the UVRI to implement External Quality assessment of COVID19 molecular diagnostics. METHOD: participating laboratories were required by UVRI to submit their already tested and archived nasopharyngeal samples and corresponding meta data. These were then re-tested at UVRI using the WHO Berlin protocol, the UVRI results were compared to those of the primary testing laboratories in order to ascertain performance agreement for the qualitative & quantitative results obtained. Ms Excel window 12 and GraphPad prism ver 15 was used in the analysis. Bar graphs, pie charts and line graphs were used to compare performance agreement between the reference Laboratory and primary testing Laboratories. RESULTS: Eleven (11) Ministry of Health/Uganda Virus Research Institute COVID19 accredited laboratories participated in the re-testing of quality control samples. 5/11 (45%) of the primary testing laboratories had 100% performance agreement with that of the National Reference Laboratory for the final test result. Even where there was concordance in the final test outcome (negative or positive) between UVRI and primary testing laboratories, there were still differences in CT values. The differences in the Cycle Threshold (CT) values were insignificant except for Tenna & Pharma Laboratory and the UVRI(p = 0.0296). The difference in the CT values were not skewed to either the National reference Laboratory(UVRI) or the primary testing laboratory but varied from one laboratory to another. In the remaining 6/11 (55%) laboratories where there were discrepancies in the aggregate test results, only samples initially tested and reported as positive by the primary laboratories were tested and found to be false positives by the UVRI COVID19 National Reference Laboratory. CONCLUSION: False positives were detected from public, private not for profit and private testing laboratories in almost equal proportion. There is need for standardization of molecular testing platforms in Uganda. There is also urgent need to improve on the Laboratory quality management systems of the molecular testing laboratories in order to minimize such discrepancies.

Prevalence of bloodstream pathogens is higher in neonatal encephalopathy cases vs. controls using a novel panel of real-time PCR assays.

BACKGROUND: In neonatal encephalopathy (NE), infectious co-morbidity is difficult to diagnose accurately, but may increase the vulnerability of the developing brain to hypoxia-ischemia. We developed a novel panel of species-specific real-time PCR assays to identify bloodstream pathogens amongst newborns with and without NE in Uganda. METHODOLOGY: Multiplex real-time PCR assays for important neonatal bloodstream pathogens (gram positive and gram negative bacteria, cytomegalovirus (CMV), herpes simplex virus(HSV) and P. falciparum) were performed on whole blood taken from 202 encephalopathic and 101 control infants. Automated blood culture (BACTEC) was performed for all cases and unwell controls. PRINCIPAL FINDINGS: Prevalence of pathogenic bacterial species amongst infants with NE was 3.6%, 6.9% and 8.9%, with culture, PCR and both tests in combination, respectively. More encephalopathic infants than controls had pathogenic bacterial species detected (8.9%vs2.0%, p = 0.028) using culture and PCR in combination. PCR detected bacteremia in 11 culture negative encephalopathic infants (3 Group B Streptococcus, 1 Group A Streptococcus, 1 Staphylococcus aureus and 6 Enterobacteriacae). Coagulase negative staphylococcus, frequently detected by PCR amongst case and control infants, was considered a contaminant. Prevalence of CMV, HSV and malaria amongst cases was low (1.5%, 0.5% and 0.5%, respectively). CONCLUSION/SIGNIFICANCE: This real-time PCR panel detected more bacteremia than culture alone and provides a novel tool for detection of neonatal bloodstream pathogens that may be applied across a range of clinical situations and settings. Significantly more encephalopathic infants than controls had pathogenic bacterial species detected suggesting that infection may be an important risk factor for NE in this setting.