Use of Tenofovir Diphosphate Levels to Predict Viremia During the Postpartum Period in Women Living With Human Immunodeficiency Virus (HIV): A Nested Case-Control Study.

BACKGROUND: There are few data on the utility of tenofovir diphosphate (TFV-DP) in dried blood spots (DBSs) to predict future viral load (VL) in postpartum women with HIV on antiretroviral therapy (ART). METHODS: We conducted a nested case-control study within a trial of postpartum ART delivery strategies. Participants started ART containing tenofovir disoproxil fumarate (TDF) in pregnancy, were <10 weeks postpartum, and had a VL <400 copies/mL. VL and TFV-DP samples were taken every 3-6 months over 24 months. Cases had ≥1 VL ≥20 copies/mL; controls were randomly sampled from women with persistent viral suppression (VS; VL <20 copies/mL). Generalized estimating equations were used to calculate likelihood odds ratios (LORs) for future VL ≥20 copies/mL by TFV-DP concentration at the preceding visit. RESULTS: 61 cases and 20 controls contributed 365 DBS-VL pairs (median ART duration, 16 months). Sensitivity and specificity of TFV-DP <700 fmol/punch to detect future viremia were 62.9% (95% CI, 54.7-70.6%) and 89.7% (84.9-93.4%), respectively. Adjusting for age, ART duration, previous VL, and duration between the TFV-DP and VL measures, LORs of viremia for TFV-DP concentrations 350-699 and <350 fmol/punch versus TFV-DP ≥1850 fmol/punch were 3.5 (95% CI, 1.1-10.8; P = .033) and 12.9 (3.6-46.6; P < .0001), respectively. Including only samples taken during VS, the LOR of future viremia for TFV-DP concentration <350 fmol/punch versus TFV-DP ≥1850 fmol/punch was 9.5 (1.9-47.0). CONCLUSIONS: TFV-DP concentrations in DBSs were strongly associated with future viremia and appear useful to identify nonadherence and predict future elevated VL.

COVID-19 underscores the important role of Clinical Ethics Committees in Africa.

BACKGROUND: The COVID-19 pandemic has magnified pre-existing challenges in healthcare in Africa. Long-standing health inequities, embedded in the continent over centuries, have been laid bare and have raised complex ethical dilemmas. While there are very few clinical ethics committees (CECs) in Africa, the demand for such services exists and has increased during the COVID-19 pandemic. The views of African healthcare professionals or bioethicists on the role of CECs in Africa have not been explored or documented previously. In this study, we aim to explore such perspectives, as well as the challenges preventing the establishment of CECs in Africa. METHODS: Twenty healthcare professionals and bioethicists from Africa participated in this qualitative study that utilized in-depth semi-structured interviews with open-ended questions. Themes were identified through thematic analysis of interviews and open-ended responses. RESULTS: Kenya and South Africa are the only countries on the continent with formal established CECs. The following themes emerged from this qualitative study: (1) Lack of formal CECs and resolution of ethical dilemmas; (2) Role of CECs during COVID-19; (3) Ethical dilemmas presented to CECs pre-COVID-19; (4) Lack of awareness of CECs; (5) Lack of qualified bioethicists or clinical ethicists; (6) Limited resources to establish CECs; (7) Creating interest in CECs and networking. CONCLUSIONS: This study illustrates the importance of clinical ethics education among African HCPs and bioethicists, more so now when COVID-19 has posed a host of clinical and ethical challenges to public and private healthcare systems. The challenges and barriers identified will inform the establishment of CECs or clinical ethics consultation services (CESs) in the region. The study results have triggered an idea for the creation of a network of African CECs.

Clinical Ethics Committees in Africa: lost in the shadow of RECs/IRBs?

BACKGROUND: Clinical Ethics Committees (CECs) are well established at healthcare institutions in resource-rich countries. However, there is limited information on established CECs in resource poor countries, especially in Africa. This study aimed to establish baseline data regarding existing formal CECs in Africa to raise awareness of and to encourage the establishment of CECs or Clinical Ethics Consultation Services (CESs) on the continent. METHODS: A descriptive study was undertaken using an online questionnaire via SunSurveys to survey healthcare professionals and bioethicists in Africa. Data were subjected to descriptive analysis and Fischer's exact test was applied to determine associations. Texts from the open-ended questions were thematically analysed. RESULTS: In total 109 participants from 37 African countries completed the survey in December 2019. A significant association was found between participants' bioethics qualification or training and involvement in clinical ethics (p = 0.005). All participants were familiar with Research Ethics Committees (RECs), and initially conflated RECs with CECs. When CECs were explained in detail, approximately 85.3% reported that they had no formal CECs in their institutions. The constraints to developing CECs included lack of training, limited resources, and lack of awareness of CECs. However, the majority of participants (81.7%) were interested in establishing CECs. Participants listed assistance required in establishing CECs including funding, resources, capacity building and collaboration with other known CECs. The results do not reflect CECs established since the onset of COVID-19 in Africa. CONCLUSIONS: This study provides a first look into CECs in Africa and found very few formal CECs on the continent indicating an urgent need for the establishment of CECs or CESs in Africa. While the majority of healthcare professionals and bioethicists are aware of ethical dilemmas in healthcare, the concept of formal CECs is foreign. This study served to raise awareness of CECs. Research ethics and RECs overshadow CECs in Africa because international funders from the global north support capacity development in research ethics and establish RECs to approve the research they fund in Africa. Raising awareness via educational opportunities, research and conferences about CECs and their role in improving the quality of health care in Africa is sorely needed.

Evaluating a South African mobile application for healthcare professionals to improve diagnosis and notification of pesticide poisonings.

BACKGROUND: Mobile health is a fast-developing field. The use of mobile health applications by healthcare professionals (HCPs) globally has increased considerably. While several studies in high income countries have investigated the use of mobile applications by HCPs in clinical practice, few have been conducted in low- and middle-income countries. The University of Cape Town developed a pesticide notification guideline which has been adapted and embedded into a South African Essential Medical Guidance mobile application. This study evaluated the usefulness of the guideline within a mobile application for improving the ability of HCPs to diagnose and notify on acute pesticide poisonings (APPs). METHODS: A descriptive online questionnaire, with 15 open- and 20 closed-ended questions, was completed by 50 South African emergency medicine physicians and registrars (i.e. medical doctors training as specialists) between December 2015 to February 2016. Descriptive statistics were used to calculate response frequencies and percentages using SPSS version 23. Texts from the open-ended questions were thematically analysed. Fisher's exact test was applied to determine associations. RESULTS: A significant association was found between participants' knowledge that APP is a notifiable condition, and ever reporting the poisoning to the National Department of Health (p = 0.005). Thirty four percent of the participants were aware of the guideline within the Essential Medical Guidance application despite only seven participants having used it. Those who used the guideline found it provided useful information for the identification of unlabelled pesticides products and promoted reporting these cases to the National Department of Health for surveillance purposes. In addition, it appeared to facilitate the prompt diagnosis and treatment of APP cases, and most intended to continue using it for training and educational purposes. CONCLUSIONS: Mobile health applications appear to support overburdened medical education programmes and promote better patient care. However, since most participants were not aware of the existence of the pesticide guideline within the studied essential medicine application, there is potential for the use of healthcare applications to play a more central role in healthcare systems and medical training. Furthermore, the field of medical informatics could support HCPs through mobile applications in improving reporting of APP.

Cross-border data sharing through the lens of research ethics committee members in sub-Saharan Africa.

BACKGROUND: Several factors thwart successful data sharing-ambiguous or fragmented regulatory landscapes, conflicting institutional/researcher interests and varying levels of data science-related expertise are among these. Traditional ethics oversight mechanisms and practices may not be well placed to guarantee adequate research oversight given the unique challenges presented by digital technologies and artificial intelligence (AI). Data-intensive research has raised new, contextual ethics and legal challenges that are particularly relevant in an African research setting. Yet, no empirical research has been conducted to explore these challenges. MATERIALS AND METHODS: We explored REC members' views and experiences on data sharing by conducting 20 semi-structured interviews online between June 2022 and February 2023. Using purposive sampling and snowballing, we recruited representatives across sub-Saharan Africa (SSA). We transcribed verbatim and thematically analysed the data with Atlas.ti V22. RESULTS: Three dominant themes were identified: (i) experiences in reviewing data sharing protocols, (ii) perceptions of data transfer tools and (iii) ethical, legal and social challenges of data sharing. Several sub-themes emerged as: (i.a) frequency of and approaches used in reviewing data sharing protocols, (i.b) practical/technical challenges, (i.c) training, (ii.a) ideal structure of data transfer tools, (ii.b) key elements of data transfer tools, (ii.c) implementation level, (ii.d) key stakeholders in developing and reviewing a data transfer agreement (DTA), (iii.a) confidentiality and anonymity, (iii.b) consent, (iii.c) regulatory frameworks, and (iii.d) stigmatisation and discrimination. CONCLUSIONS: Our results indicated variability in REC members' perceptions, suboptimal awareness of the existence of data protection laws and a unanimously expressed need for REC member training. To promote efficient data sharing within and across SSA, guidelines that incorporate ethical, legal and social elements need to be developed in consultation with relevant stakeholders and field experts, along with the training accreditation of REC members in the review of data-intensive protocols.

Experiences of transfer of care among postpartum women living with HIV attending primary healthcare services in South Africa.

Transfers between health facilities for postpartum women living with HIV are associated with disengagement from care. In South Africa, women must transfer from integrated antenatal/HIV care to general HIV services post-delivery. Thereafter, women transfer frequently e.g. due to geographic mobility. To explore barriers to transfer, we conducted in-depth interviews >2 years post-delivery in 28 participants in a trial comparing postpartum HIV care at primary health care (PHC) antiretroviral therapy (ART) facilities versus a differentiated service delivery model, the adherence clubs, which are the predominant model implemented in South Africa. Data were thematically analysed using inductive and deductive approaches. Women lacked information including where they could transfer to and transfer processes. Continuity mechanisms were affected when women transferred silently i.e. without informing facilities or obtaining referral letters. Silent transfers often occurred due to poor relationships with healthcare workers and were managed inconsistently. Fear of disclosure to family and community stigma led to transfers from local PHC ART facilities to facilities further away affecting accessibility. Mobility and the postpartum period presented unique challenges requiring specific attention. Information regarding long-term care options and transfer processes, ongoing counselling regarding disclosure and social support, and increased health system flexibility are required.

The role of inflammation in HPV infection of the Oesophagus.

BACKGROUND: Several human cancers are known to be associated with inflammation and/or viral infections. However, the influence of tumour-related inflammation on viral uptake is largely unknown. In this study we used oesophageal squamous cell carcinoma (OSCC) as a model system since this type of cancer is associated with chronic irritation, inflammation and viral infections. Although still debated, the most important viral infection seems to be with Human Papillomavirus (HPV). The present study focused on a possible correlation between inflammation, OSCC development and the influence of HPV infection. METHODS: A total of 114 OSCC biopsies and corresponding normal tissue were collected at Groote Schuur Hospital and Tygerberg Hospital, Cape Town (South Africa), that were subjected to RNA and DNA isolation. RNA samples were analysed by quantitative Light Cycler RT-PCR for the expression of selected genes involved in inflammation and infection, while conventional PCR was performed on the DNA samples to assess the presence of integrated viral DNA. Further, an in vitro infection assay using HPV pseudovirions was established to study the influence of inflammation on viral infectivity using selected cell lines. RESULTS: HPV DNA was found in about 9% of OSCC patients, comprising predominantly the oncogenic type HPV18. The inflammatory markers IL6 and IL8 as well as the potential HPV receptor ITGA6 were significantly elevated while IL12A was downregulated in the tumour tissues. However, none of these genes were expressed in a virus-dependent manner. When inflammation was mimicked with various inflammatory stimulants such as benzo-α-pyrene, lipopolysaccharide and peptidoglycan in oesophageal epithelial cell lines in vitro, HPV18 pseudovirion uptake was enhanced only in the benzo-α-pyrene treated cells. Interestingly, HPV pseudovirion infectivity was independent of the presence of the ITGA6 receptor on the surface of the tested cells. CONCLUSION: This study showed that although the carcinogen benzo-α-pyrene facilitated HPV pseudovirion uptake into cells in culture, HPV infectivity was independent of inflammation and seems to play only a minor role in oesophageal cancer.

Mobility during the post-partum period and viraemia in women living with HIV in South Africa.

BACKGROUND: We investigated the association between travel and viraemia in post-partum women with human immunodeficiency virus on antiretroviral therapy (ART). METHODS: Data are from a trial of post-partum ART delivery strategies. Women who initiated ART during pregnancy, were clinically stable with a viral load (VL) <400 copies/ml and were <10 weeks post-partum were enrolled at a primary care antenatal clinic in Cape Town, South Africa. Study visits at 3, 6, 12, 18 and 24 months post-partum included questions about travel, defined as ≥1 night spent outside of the city, and VL testing. Generalised mixed effects models assessed the association between travel and subsequent VL ≥400 copies/ml. RESULTS: Among 402 women (mean age 29 y, 35% born in the Western Cape), 69% reported one or more travel events over 24 months. Being born beyond the Western Cape (adjusted odds ratio [aOR] 2.03 [95% confidence interval {CI} 1.49 to 2.77]), duration post-partum in months (aOR 1.03 [95% CI 1.02 to 1.05]) and living with the child (aOR 0.60 [95% CI 0.38 to 0.93]) were associated with travel. In multivariable analyses, a travel event was associated with a 92% increase in the odds of a VL ≥400 copies/ml (aOR 1.92 [95% CI 1.19 to 3.10]). CONCLUSIONS: Interventions to support women on ART who travel are urgently required.

Virologic outcomes after early referral of stable HIV-positive adults initiating ART to community-based adherence clubs in Cape Town, South Africa: A randomised controlled trial.

BACKGROUND: Differentiated service delivery (DSD) models are recommended for stable people living with HIV on antiretroviral therapy (ART) but there are few rigorous evaluations of patient outcomes. METHODS: Adherence clubs (ACs) are a form of DSD run by community health workers at community venues with 2-4 monthly ART refills and annual nurse assessments). Clinic-based care involves 2-monthly ART refills and 4-monthly nurse/doctor assessments. We compared virologic outcomes in stable adults randomised to ACs at four months post-ART initiation to those randomised to primary health care (PHC) ART clinics through 12 months on ART in Cape Town, South Africa (NCT03199027). We hypothesised that adults randomised to ACs would be more likely to be virally suppressed at 12 months post-ART initiation, versus adults randomised to continued PHC care. We enrolled consecutive adults on ART for 3-5 months who met local DSD ['adherence clubs' (AC)] eligibility (clinically stable, VL<400 copies/mL). The primary outcome was VL<400 copies/mL at 12 months on ART. RESULTS: Between January 2017 and April 2018, 220 adults were randomised (mean age 35 years; 67% female; median ART duration 18 weeks); 85% and 94% of participants randomised to ACs and PHCs attended their first service visit on schedule respectively. By 12 months on ART, 91% and 93% randomised to ACs and PHCs had a VL<400 copies/mL, respectively. In a binomial model adjusted for age, gender, previous ART use and nadir CD4 cell count, there was no evidence of superiority of ACs compared to clinic-based care (RD, -2.42%; 95% CI, -11.23 to 6.38). Findings were consistent when examining the outcome at a threshold of VL <1000 copies/mL. CONCLUSION: Stable adults referred to DSDs at 4 months post-ART initiation had comparable virologic outcomes at 12 months on ART versus PHC clinics, with no evidence of superiority. Further research on long-term outcomes is required.

Improved virologic outcomes in postpartum women living with HIV referred to differentiated models of care.

OBJECTIVES: Differentiated service delivery (DSD) models are used to deliver antiretroviral therapy (ART) but data are limited in postpartum women, who are at high risk of non-adherence and elevated viral load (VL) over the extended postpartum period. DESIGN: Randomized controlled trial. METHODS: We enrolled consecutive postpartum women who initiated ART during pregnancy and met local DSD eligibility (clinically stable, VL less than 400 copies/ml) at a large primary healthcare (PHC) clinic. Women were randomized to a community-based 'adherence club' (AC, the local DSD model: community health worker-led groups of 20-30 patients with ART dispensing at a community venue) or routine PHC clinics (local standard of care with nurse/doctor-led services). Follow-up visits with VL separate from routine care took place at 3, 6, 12, 18 and 24 months postpartum. Endpoints were time to VL of at least 1000 copies/ml (primary) and VL of at least 50 copies/ml (secondary) by intention-to-treat. RESULTS: At enrolment ( n  = 409), the median duration postpartum was 10 days, all women had a VL less than 1000 copies/ml and 88% had a VL less than 50 copies/ml; baseline characteristics did not differ by arm. Twenty-four-month retention was 89%. Sixteen and 29% of women in AC experienced a VL of at least 1000 copies/ml by 12 and 24 months, compared to 23 and 37% in PHC, respectively (hazard ratio [HR] = 0.71; 95% confidence interval [CI] = 0.50-1.01). Thirty-two and 44% of women in ACs had a VL of at least 50 copies/ml by 12 and 24 months, compared to 42 and 56% in PHC, respectively (HR = 0.68; 95% CI = 0.51-0.91). CONCLUSIONS: Early DSD referral was associated with reduced viraemia through 24 months postpartum and may be an important strategy to improve maternal virologic outcomes.

Brief Report: Viral Load Monitoring in Pregnancy to Predict Peripartum Viremia in South Africa.

INTRODUCTION: Enhanced postnatal prophylaxis is recommended in infants of women with viremia during labor, as identified by viral load (VL) testing late in pregnancy. However, data on the use of antenatal VL to predict peripartum viremia are few, particularly in women starting antiretroviral therapy (ART) in pregnancy who experience initial VL declines. METHODS: Between January 2016 and August 2017, we identified HIV-infected women who initiated ART (tenofovir, emtricitabine, and efavirenz) antenatally and had a VL <400 copies/mL before delivery in Cape Town, South Africa. VLs were repeated postdelivery, and sensitivity, specificity, and positive and negative likelihood ratios (LR+ and LR-) for antenatal VL <100 copies/mL in predicting peripartum VLs <100 and <400 copies/mL were calculated. RESULTS: Among 322 women (median age 29 years, 44% with a history of ART use, median gestation of antenatal VL 33 weeks), antenatal VL was <100 copies/mL in 89% and 100-400 copies/mL in 11%. At a median 9 days postpartum, 91%, 7%, and 2% of women had a VL <100, 100-400, and >400 copies/mL, respectively. Sensitivity of antenatal VL <100 copies/mL in predicting peripartum VL <100 copies/mL was 0.95 (95% confidence interval: 0.92 to 0.97), and specificity was 0.71 (95% confidence interval: 0.51 to 0.87; LR+ 3.28, LR- 0.07). Performance was slightly weaker to detect peripartum VL <400 copies/mL but was similar across strata of gestation at antenatal VL and history of ART use. DISCUSSION: Antenatal VL is a useful predictor of peripartum viremia in women who started ART in pregnancy and attained a VL <400 copies/mL antenatally and may be used to target enhanced postnatal prophylaxis interventions.