Healthcare ethics for Healthcare Practitioners

Healthcare ethics cannot be limited in scope to apply only to the patient but needs to apply to the healthcare practitioner as well. The relationship between the patient and the healthcare practitioner has shifted from a power relationship to a complementary relationship. Leadership, mentorship and coaching play important roles in facilitating this shift. Several themes informed this book on healthcare ethics: Vulnerability in healthcare ethics, Decisions between right and wrong, Quality of healthcare, Life-ending decisions, Community-based research, Ethical decision-making, Spritiuality in healthcar

Pooled testing: A tool to increase efficiency of infant HIV diagnosis and virological monitoring

Background: Pooled testing, or pooling, has been used for decades to efficiently diagnose relatively rare conditions, such as infection in blood donors. Programmes for the prevention of mother-to-child transmission of HIV and for antiretroviral therapy (ART) are being rolled out in much of Africa and are largely successful. This increases the need for early infant diagnosis (EID) of HIV using qualitative nucleic acid testing and for virological monitoring of patients on ART using viral load testing. While numbers of patients needing testing are increasing, infant HIV infections and ART failures are becoming rarer, opening an opportunity for pooled testing approaches

Universitas Academic Health Complex: National Asset or Provincial Liability

Letter to the edito

Low lopinavir plasma or hair concentrations explain second-line protease inhibitor failures in a resource-limited setting.

In resource-limited settings, many patients, with no prior protease inhibitor (PI) treatment on a second-line, high genetic barrier, ritonavir-boosted PI-containing regimen have virologic failure

Fifty Years of Thoracic Surgical Research in South Africa.

We aimed to investigate the scope and trends in clinical research in South African thoracic surgery between 1955 and 2006 and to measure its impact on clinical practice. The vulnerability of a small speciality in a developing country is illustrated by the clear trends that emerged. It provides important indicators for future research, highlights the need for a national database of clinical experience and emphasises the importance of rekindling interest and a culture of research in thoracic surgery

It is time to consider third-line options in antiretroviral-experienced paediatric patients?

<p>Abstract</p> <p>Background</p> <p>The historic use of full-dose ritonavir as part of an unboosted protease inhibitor (PI)-based antiretroviral therapy regimen in some South African children contributes to the frequent accumulation of major PI resistance mutations.</p> <p>Methods</p> <p>In order to describe the prevalence of major PI resistance in children failing antiretroviral therapy and to investigate the clinical, immunological and virological outcomes in children with PI resistance, we conducted a cross-sectional study, with a nested case series, following up those children with major PI resistance. The setting was public health sector antiretroviral clinics in the Western Cape province of South Africa, and the subjects were children failing antiretroviral therapy. The following outcome measures were investigated: CD4 count, viral load and resistance mutations.</p> <p>Results</p> <p>Fourteen (17%) of 82 patients, referred from tertiary hospitals, had major PI resistance. All these patients were exposed to regimens that included ritonavir as a single PI. Immune reconstitution and clinical benefit were achieved when using a lopinavir/ritonavir-based treatment regimen in these children with prior PI resistance. At first HIV-1 viral load follow up after initial resistance testing (n = 11), only one patient had a viral load of less than 400 copies/ml; at a subsequent follow up (n = 9), the viral loads of five patients were less than 400 copies/ml. Patients retained on LPV/r had lower viral loads than those switched to a non-nucleoside reverse transcriptase inhibitor (NNRTI). However, two of three patients with follow-up resistance tests accumulated additional PI resistance.</p> <p>Conclusions</p> <p>In children with pre-existing PI resistance, although initially effective, the long-term durability of a lopinavir/ritonavir-based treatment regimen can be compromised by the accumulation of resistance mutations. Furthermore, a second-line NNRTI regimen is often not durable in these patients. As genotypic resistance testing and third-line treatment regimens are costly and limited in availability, we propose eligibility criteria to identify patients with high risk for resistance and guidance on drug selection for children who would benefit from third-line therapy.</p

Emerging antiretroviral drug resistance in sub-Saharan Africa: novel affordable technologies are needed to provide resistance testing for individual and public health benefits

In industrialized countries, viral load monitoring and genotypic antiretroviral drug resistance testing (GART) play an important role in the selection of initial and subsequent combination antiretroviral therapy (cART) regimens. In contrast, resource constraints in Africa limit access to assays that could detect virologic failure, transmitted drug resistance (TDR) and acquired drug resistance to cART. This has adverse consequences for both individual and public health. Although the further roll-out of antiretrovirals for prevention, including preexposure prophylaxis (PrEP) and universal test and treat (UTT) strategies, could reduce HIV-1 incidence, these strategies may increase TDR [1,2]. Here, we present arguments that the scale up of antiretrovirals use should be accompanied by cost-effective assays for early detection of virologic failure, surveillance of TDR and GART for individual patient management

A qualitative PCR minipool strategy to screen for virologic failure and antiretroviral drug resistance in South African patients on first-line antiretroviral therapy

Please cite as follows: Newman, N. et al. 2014. A qualitative PCR minipool strategy to screen for virologic failure and antiretroviral drug resistance in South African patients on first-line antiretroviral therapy. Journal of Clinical Virology, 60(4):387-391, doi:/10.1016/j.jcv.2014.05.011.The original publication is available at http://www.journalofclinicalvirology.com/article/S1386-6532%2814%2900188-7/pdfThesis (MMed)--Stellenbosch University, 2014.Creative Commons Attribution Non-Commercial No Derivatives License 4.0 CC BY-NC-NDENGLISH ABSTRACT: Background: The high cost of commercial HIV-1 viral load tests for monitoring of patients on antiretroviral treatment limits their use in resource-constrained settings. Commercial genotypic antiretroviral resistance testing is even more costly, yet it provides important benefits. Objectives: We sought to determine the sensitivity and negative predictive value of a qualitative PCR targeting partial reverse transcriptase for detection of virologic failure when 5 patient specimens are pooled. Study Design: A total of 300 South African routine patient samples were included and tested in 60 pools of 5 samples each. A qualitative nested PCR was optimised for testing pools and individual samples from positive pools. All positive samples were sequenced to detect drug resistance-associated mutations. Results were compared to those of conventional viral load monitoring. Results: Twenty-two of 60 pools tested positive. Individual testing yielded 29 positive individual samples. Twenty-six patients had viral loads of above 1000 copies per millilitre. The pooling algorithm detected 24 of those 26 patients, resulting in a negative predictive value of 99.3%, and a positive predictive value of 89.7%. The sensitivity for detecting patients failing therapy was 92%, with a specificity of 98.9%. Of the patients failing first-line ART, 83.3% had NRTI and 91.7% NNRTI resistance mutations. Conclusions: The pooled testing algorithm presented here required 43% fewer assays than conventional viral load testing. In addition to offering a potential cost saving over individual viral load testing, it also provided drug resistance information which is not available routinely in resourced-limited settings.Post-prin

Initial supplementary dose of Dolutegravir in second-line antiretroviral therapy: a noncomparative, double-blind, randomized placebo-controlled trial

BACKGROUND: Dolutegravir concentrations are reduced by efavirenz induction effect necessitating twice-daily dolutegravir dosing when coadministered. Efavirenz induction persists for several weeks after stopping, which could potentially select for dolutegravir resistance if switching occurred with unsuppressed human immunodeficiency virus type 1 (HIV-1) RNA levels and standard dolutegravir dosing. We evaluated the need for a lead-in supplementary dolutegravir dose in adults failing first-line tenofovir-emtricitabine-efavirenz (TEE). METHODS: We conducted a randomized, double-blind, placebo-controlled, phase 2 trial in Khayelitsha, South Africa. Eligible patients had virologic failure (2 consecutive HIV-1 RNA ≥1000 copies/mL) on first-line TEE. Participants were randomly assigned (1:1) to switch to tenofovir-lamivudine-dolutegravir (TLD) with a supplementary 50 mg dolutegravir dose or placebo taken 12 hours later for 14 days. Primary outcome was proportion with HIV-1 RNA <50 copies/mL at week 24. This study was not powered to compare arms. RESULTS: One hundred thirty participants were randomized (65 to each arm). Median baseline HIV-1 RNA was 4.0 log10 copies/mL and 76% had baseline resistance to both tenofovir and lamivudine. One participant died and 2 were lost to follow-up. At week 24, 55 of 64 (86% [95% confidence interval {CI}: 75%-93%]) in the supplementary dolutegravir arm and 53 of 65 (82% [95% CI: 70%-90%]) in the placebo arm had HIV-1 RNA <50 copies/mL. Grade 3 or 4 adverse events were similar in frequency between arms. None of 6 participants (3 in each arm) eligible for resistance testing by 24 weeks developed dolutegravir resistance. CONCLUSIONS: Our findings do not support the need for initial dolutegravir dose adjustment in patients switching to TLD who failed first-line TEE. CLINICAL TRIALS REGISTRATION: NCT03991013

Delays in HIV-1 infant polymerase chain reaction testing may leave children without confirmed diagnoses in the Western Cape province, South Africa

CITATION: Mahlakwane, K. L. et al. 2022. African Journal of Laboratory Medicine, 11(1):1485, doi:10.4102/ajlm.v11i1.1485.The original publication is available at https://ajlmonline.orgBackground: Early diagnosis and confirmation of HIV infection in newborns is crucial for expedited initiation of antiretroviral therapy. Confirmatory testing must be done for all children with a reactive HIV PCR result. There is no comprehensive data on confirmatory testing and HIV PCR test request rejections at National Health Laboratory Service laboratories in South Africa. Objective: This study assessed the metrics of routine infant HIV PCR testing at the Tygerberg Hospital Virology Laboratory, Cape Town, Western Cape, South Africa, including the proportion of rejected test requests, turn-around time (TAT), and rate of confirmatory testing. Methods: We retrospectively reviewed laboratory-based data on all HIV PCR tests performed on children ≤ 24 months old (n = 43 346) and data on rejected HIV PCR requests (n = 1479) at the Tygerberg virology laboratory over two years (2017–2019). Data from sample collection to release of results were analysed to assess the TAT and follow-up patterns. Results: The proportion of rejected HIV PCR requests was 3.3%; 83.9% of these were rejected for various pre-analytical reasons. Most of the test results (89.2%) met the required 96-h TAT. Of the reactive initial test results, 53.5% had a follow-up sample tested, of which 93.1% were positive. Of the initial indeterminate results, 74.7% were negative on follow-up testing. Conclusion: A high proportion of HIV PCR requests were rejected for pre-analytical reasons. The high number of initial reactive tests without evidence of follow-up suggests that a shorter TAT is required to allow confirmatory testing before children are discharged.https://ajlmonline.org/index.php/ajlm/article/view/1485Publisher's versio