Liver enzyme elevations in a cohort of HIV/AIDS patients on first-line antiretroviral therapy in Namibia: Findings and implications

Introduction: All antiretroviral therapies (ARTs) are potentially toxic to the liver. In sub-Saharan Africa, the rising incidence of ART induced adverse events has complicated treatment leading to recent revisions of Namibian ART guidelines. Unfortunately there have been limited studies to date evaluating ART induced liver injury in Namibia to guide further revisions if needed. Objective: Determine the current patterns and grades of ALT elevation in Namibia’s HIV/AIDS. Methods: Retrospective cohort analysis. Patterns of alanine amino transferase (ALT) liver enzyme elevation were determined in a cohort of ART naïve HIV patients on firstline ART regimen in a referral hospital in Namibia over a 1 year treatment period. Patterns of ALT changes at baseline, 3 months and 6 months were analyzed using ANOVA and Bonferroni test for pairwise comparisons. Results: Of 79 eligible patients, 72 developed significant ALT elevation within 3 months of ART initiation (F (3, 76) = 6.4, p = 0.002, η2 = 0.193). Four 4 (5.6%) and 1 (1.38%) patient respectively developed grade 2 and grade 3 ALT elevation by month 3. There was no significant difference between mean ALT levels at baseline and month 6. A CD4 count of <350 cells/mm3; female gender and age over 40 years were the main factors associated with moderate or severe ALT elevation. Conclusions: First line ART commonly induces mild self-limiting liver enzyme elevation in Namibian HIV patients especially in the first 3 months. Consequently, there is a need to monitor ALT levels for at least 3 months after initiation mainly in high risk patients to reduce side-effect concerns. This is already happening

Steady-state Pharmacokinetic Comparison of Generic and Branded Formulations of Lamivudine, Stavudine, and Nevirapine in HIV-infected Ugandan Adults

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Assessing adherence to Antihypertensive therapy in primary health care in Namibia: findings and implications

Namibia has the highest burden and incidence of hypertension in sub-Sahara Africa. Though non-adherence to antihypertensive therapy is an important cardiovascular risk factor, little is known about potential ways to improve adherence in Namibia following universal access. The objective of this study is to validate the Hill-Bone compliance scale and determine the level and predictors of adherence to antihypertensive treatment in primary health care settings in sub-urban townships of Windhoek, Namibia

Compliance to guidelines for the prescribing of antibiotics in acute infections at Namibia’s national referral hospital : a pilot study and the implications

Background: Sub-optimal antibiotic prescribing remains a public health concern in Namibia. The objective is to determine the level and predictors of compliance to guidelines in the prescribing of antibiotics in acute infections at a national referral hospital in Namibia to improve future prescribing. Methods: Descriptive observational cross-sectional study. The clinical records of patients receiving care were reviewed. Prescribing practices were assessed using a self- administered questionnaire with reference to Namibia Standard Treatment Guidelines (NSTG). Results: The majority of prescriptions (62%) complied with the NSTGs; however, lower than national targets (95%). Most prescriptions were empiric and prescribers typically made reference to the NSTG (58%). Diagnosed infections were principally respiratory infections (58%) and penicillins were the most used antibiotics. Good concurrence between signs and symptoms with the diagnosis; diagnosis of upper respiratory tract, oral-dental and urogenital infections with prescribing of penicillins. Combination antibiotics and amphenicols were independent predictors of compliance to the NSTGs. The main behaviours associated with antibiotic prescribing were patient influences, clinical state, and access to guidelines. Conclusions: Compliance to NSTGs is suboptimal. Prescribing of combination antibiotics, penicillins and diagnosis of oral dental, genitourinary and ear, nose and throat infections were important predictors for NSTG compliance. There is a need to implement antibiotic indicators and stewardship programmes, and ensure access to NSTGs, to improve future antibiotic prescribing in Namibia

Response to the Novel Corona Virus (COVID-19) Pandemic Across Africa: Successes, Challenges, and Implications for the Future

Background: The COVID-19 pandemic has already claimed considerable lives. There are major concerns in Africa due to existing high prevalence rates for both infectious and non-infectious diseases and limited resources in terms of personnel, beds and equipment. Alongside this, concerns that lockdown and other measures will have on prevention and management of other infectious diseases and non-communicable diseases (NCDs). NCDs are an increasing issue with rising morbidity and mortality rates. The World Health Organization (WHO) warns that a lack of nets and treatment could result in up to 18 million additional cases of malaria and up to 30,000 additional deaths in sub-Saharan Africa. Objective: Document current prevalence and mortality rates from COVID-19 alongside economic and other measures to reduce its spread and impact across Africa. In addition, suggested ways forward among all key stakeholder groups. Our Approach: Contextualise the findings from a wide range of publications including internet-based publications coupled with input from senior-level personnel. Ongoing Activities: Prevalence and mortality rates are currently lower in Africa than among several Western countries and the USA. This could be due to a number of factors including early instigation of lockdown and border closures, the younger age of the population, lack of robust reporting systems and as yet unidentified genetic and other factors. Innovation is accelerating to address concerns with available equipment. There are ongoing steps to address the level of misinformation and its consequences including fines. There are also ongoing initiatives across Africa to start addressing the unintended consequences of COVID-19 activities including lockdown measures and their impact on NCDs including the likely rise in mental health disorders, exacerbated by increasing stigma associated with COVID-19. Strategies include extending prescription lengths, telemedicine and encouraging vaccination. However, these need to be accelerated to prevent increased morbidity and mortality. Conclusion: There are multiple activities across Africa to reduce the spread of COVID-19 and address misinformation, which can have catastrophic consequences, assisted by the WHO and others, which appear to be working in a number of countries. Research is ongoing to clarify the unintended consequences given ongoing concerns to guide future activities. Countries are learning from each other

Ongoing and planned activities to improve the management of patients with Type 1 diabetes across Africa : implications for the future

BACKGROUND: Currently about 19 million people in Africa are known to be living with diabetes, mainly Type 2 diabetes (T2DM) (95%), estimated to grow to 47 million people by 2045. However, there are concerns with early diagnosis of patients with Type 1 diabetes (T1DM) as often patients present late with complications. There are also challenges with access and affordability of insulin, monitoring equipment and test strips with typically high patient co-payments, which can be catastrophic for families. These challenges negatively impact on the quality of care of patients with T1DM increasing morbidity and mortality. There are also issues of patient education and psychosocial support adversely affecting patients' quality of life. These challenges need to be debated and potential future activities discussed to improve the future care of patients with T1DM across Africa. METHODOLOGY: Documentation of the current situation across Africa for patients with T1DM including the epidemiology, economics, and available treatments within public healthcare systems as well as ongoing activities to improve their future care. Subsequently, provide guidance to all key stakeholder groups going forward utilizing input from senior-level government, academic and other professionals from across Africa. RESULTS: Whilst prevalence rates for T1DM are considerably lower than T2DM, there are concerns with late diagnosis as well as the routine provision of insulin and monitoring equipment across Africa. High patient co-payments exacerbate the situation. However, there are ongoing developments to address the multiple challenges including the instigation of universal health care and partnerships with non-governmental organizations, patient organizations, and pharmaceutical companies. Their impact though remains to be seen. In the meantime, a range of activities has been documented for all key stakeholder groups to improve future care. CONCLUSION: There are concerns with the management of patients with T1DM across Africa. A number of activities has been suggested to address this and will be monitored

Evaluation of Namibia's antiretroviral therapy guidelines' recommendations for switching from first-line to second-line, using predictors of first-line treatment failure : an exploratory study

Objectives: The objective of this study was to find out the extent to which the antiretroviral therapy (ART) switching guidelines were complied with and to assess whether immediate switching from first- to second-line ART would have been appropriate than attempting to comply with the guidelines. Methods: A case–control study. Cases and controls were patients on second- and first-line ART, respectively. Regression analysis was used to identify factors that were associated with switching to second-line ART. Confidence level was 95% and significance at a p-value 1000 copies/ml (aHR = 20.2), 1000 copies/ml was a predictor of switching. New local research is underway, with a large number of patients, to assess whether this finding applies to the dolutegravir-based regimens

Effect of TDF-containing regimens on creatinine clearance in HIV patients in Namibia with a baseline CrCl <60ml/min; findings and implications

Background and aims: The advent of antiretroviral therapy (ART) and early diagnosis of the human immunodeficiency virus (HIV) has resulted in an appreciable reduction in morbidity and mortality among people infected with HIV. However, tenofovir disoproxil fumarate (TDF)-containing ART regimens are associated with a reduction in creatinine clearance (CrCl). No evaluation has been conducted in Namibia to date on the relationship between TDF-containing ART and CrCl among patients with moderate to severe reductions in CrCl to guide future practice. We aimed to address this.Methodology: Retrospective longitudinal study between January 2008 to December 2016 evaluating CrCl in patients with a baseline CrCl <60ml/min who were receiving TDF-containing ART in a leading hospital in Namibia. We identified patients who had experienced an improvement in CrCl and compared their characteristics with those whose CrCl did not improve. We assessed factors for an association with improvement in CrCl using binary logistic regression.Results: 389 patients were included, the majority were female (n = 294). Female vs. male assessments showed no difference in age (p = 0.340), weight (p = 0.920), number who experienced an improvement (105 vs 39, p = 0.349), or absence of improvement (189 vs. 56, p = 0.349). The improvement group (male and female) had a lower baseline CrCl (45.9 vs. 55.0, p < 0.001). The follow-up CrCl for the improvement and no improvement groups were 72.6 and 55.9 respectively. Multivariate analysis showed that the odds of improvement were: 0.905 (0.871-0.940, p < 0.001) for each unit rise in the baseline CrCl, and 0.904(0.880-0.923) for each year of follow-up.Conclusion: More improvement than decline in CrCl was observed. Improvement occurred more in patients with lower baseline CrCl, and occurred in the early period of ART with reduced odds of experiencing this with time. Our findings indicate that TDF may be used in patients with a low baseline CrCl

Nevirapine pharmacokinetics when initiated at 200 mg or 400 mg daily in HIV-1 and tuberculosis co-infected Ugandan adults on rifampicin

Background Rifampicin lowers nevirapine plasma concentrations by inducing cytochrome P450. However, few data are available on this interaction during the lead-in period of nevirapine treatment. Methods Eighteen HIV-1/tuberculosis co-infected adults receiving rifampicin daily as part of anti-tuberculosis therapy were evenly randomized to nevirapine initiation by dose escalation (NVP200) or nevirapine initiation at 200 mg twice daily (NVP400). Subjects underwent 12 h intensive pharmacokinetic sampling on Days 7, 14 and 21 of nevirapine treatment. A minimum effective concentration (MEC) of 3000 ng/mL was used to interpret nevirapine concentrations 12 h after dosing (C(12)). Trial registration number: NCT00617643 (www.clinicaltrials.gov). Results Day 7 geometric mean nevirapine C(12) [90% confidence interval (CI)] was 1504 (1127-2115) ng/mL and 3148 (2451-4687) ng/mL in the NVP200 and NVP400 arms, respectively (P < 0.01). Nevirapine C(12) on Days 14 and 21 was similar. On Day 21, nevirapine concentration in 64% of patients was below the MEC. On Day 7, geometric mean area under the curve (AUC(0-12)) was lower in the NVP200 arm, 25 223 (90% CI, 21 978-29 695) ng.h/mL versus 43 195 (35 607-57 035) ng.h/mL in the NVP400 arm (P < 0.01). Similarly, on Day 14, nevirapine AUC(0-12) was lower in the NVP200 arm 23 668 (18 253-32 218) ng.h/mL versus the NVP400 arm 44 918 (36 264-62 769) ng.h/mL (P = 0.03). Conclusions In co-treated patients, nevirapine concentrations were below the MEC during initiation with dose escalation. Nevirapine initiation at the maintenance dose of 200 mg twice daily is preferred. Sub-therapeutic nevirapine concentrations were common at Day 21 with either regimen. Evaluation of higher nevirapine maintenance doses may be considered