An investigation into the psychosocial factors associated with willingness to test for HIV among a sample of first year psychology students at a South African tertiary institution.

Thesis (M.A.)-University of KwaZulu-Natal, Pietermaritzburg, 2006.HIV/AIDS has exacted a devastating death toll on sub-Saharan Africa. Of the African countries South Africa has been the hardest hit by the epidemic. Young people between the ages 15-24 have been identified as the group most at risk for contracting HIV. The introduction of highly active antiretroviral therapy (HAART) has been shown to decrease opportunistic infections and increase lifespan and quality of life of HIV infected people. VCT is an entry point to accessing life saving treatment as well as psycho-emotional and social support. A concern is that not all people who are at risk for VCT get tested. It is important to examine which psychosocial factors affect the uptake of VCT. A questionnaire that measures willingness to test for HlV and various other psychosocial and socio-demographic factors affecting VCT uptake, was administered to a group of first year psychology students, (N= 181). Chi Square (X2 ) analysis determined that knowledge of HIV transmission, knowledge of VCT, fear of testing, perceived social support and perceived social stigma were significantly associated with willingness to test for HIV (

The association of organizational contextual factors and HIV-Tuberculosis service integration following exposure to quality improvement interventions in primary healthcare clinics in rural KwaZulu-Natal.

Doctoral Degree. University of KwaZulu-Natal, Durban.A key strategy to reduce Tuberculosis (TB)-related mortality among people living with HIV is integrating HIV and TB diagnostic and treatment services. In South Africa, integrated HIV-TB service provision is standard of care, however, there is evidence that patients accessing primary healthcare clinics (PHC) are missed for HIV and TB testing and screening, diagnosis, linkage to treatment, and preventive services. Gaps in the HIV-TB care cascade are indicative of weaknesses in healthcare systems at the frontline. Quality Improvement (QI) collaboratives are a widely adopted approach to facilitating improvement among multiple clinics and scaling up best practices to improve on a given health topic. Little is known of the effectiveness of QI collaboratives and less is known of the role of organizational contextual factors (OCFs) in influencing the success of QI collaboratives to improve integrated HIV-TB services. Scaling up TB/HIV Integration (SUTHI) was a cluster-randomised trial designed to test the effectiveness of a QI intervention to enhance integrated HIV-TB services on mortality in HIV, TB, and HIV-TB patients. The study was from 01 December 2016-31 December 2018. Sixteen nurse supervisors (clusters) overseeing 40 PHC clinics were randomized (1:1) to receive either a structured QI intervention (QI group), which comprised, clinical training, three QI workshops timed at 6-month intervals, and in-person mentorship visits; or standard of care (SOC group) supervision and support for HIV-TB service delivery. This PhD project was a nested sub-study embedded in the SUTHI trial which aimed to describe and assess the influence of OCFs on the QI intervention to improve process indicators of HIV-TB services. A description of the QI intervention, including change ideas generated and lessons learned from practical application of the intervention in 20 QI clinics are presented in Paper I. Baseline performance of indicators was highlighted as important in influencing the size of improvements. OCFs that undermined the QI process were poor data quality, data capturing backlogs, lack of data analytic skills among clinic staff, poor transfer of training knowledge to peers, low clinic staff motivation to consistently track performance and limited involvement of the clinic management team in QI activities due to heavy workloads. A comparison between the QI and SOC group clinics showed that the QI intervention was only effective in improving two of five HIV-TB indicators, HIV testing services (HTS) andIsoniazid Preventive Therapy (IPT) initiation rates in new antiretroviral therapy patients. HTS was 19% higher (94.5% versus (vs) 79.6%; Relative Risk (RR)=1.19; 95% CI:1.02% - 1.38%; p=0.029) and IPT initiation was 66% higher (61.2% vs 36.8%; RR=1.66; 95% CI:1.02% -2.72%; p=0.044), in the QI group compared to the SOC group. Small clusters showed larger improvements in IPT initiation rates compared to big clusters, likely due to better coordination of efforts (Paper II). Several OCFs were quantitatively assessed and inserted into a linear mixed model to determine which factors likely influenced the improvement observed in the IPT initiation rates (Paper III). The practice of monitoring data for improvement was significantly associated with higher IPT initiation rates (Beta coefficient (β)=0.004; p=0.004). The main recommendations made from the PhD project are to encourage the practice of monitoring data for improvement among clinic teams; provision of widespread QI training for all levels of staff, different staff categories and leadership; to ensure good quality of routine data, and provision of regular performance feedback from upper management to the clinics

Integrating human immunodeficiency virus and tuberculosis drug treatment.

Ph. D. University of KwaZulu-Natal, Durban 2014.The human immunodeficiency virus (HIV) and tuberculosis (TB) epidemics are major global public health challenges. Worldwide, approximately 42% of TB patients are also co-infected with HIV, and sub-Saharan Africa (SSA) is home to the majority of the world’s infections of both HIV and TB. Dual infection has been shown to be associated with a higher risk of death. Integrating drug treatment for both diseases is therefore essential to improve survival. However, drug interactions between antiretroviral therapy (ART) and anti-TB medication remain a challenge to effective treatment integration. Although several drug interactions have been identified, only some are clinically relevant. The impact of significant interactions on public health outcomes is expected to be greatest when large numbers of patients are prescribed interacting drugs. Efavirenz (EFV) is the most commonly prescribed nucleoside reverse transcriptase inhibitor (NNRTI) component of first line ART in sub-Saharan Africa, particularly when rifampicin (RIF) based TB treatment is co-administered. RIF is known to up-regulate cytochrome P450 (CYP450) drug metabolizing enzymes resulting in decreased exposure to concomitantly administered drugs that utilize similar metabolic pathways. Therefore, the concomitant use of EFV with RIF would be expected to increase EFV clearance while absorption of TB drugs may also be compromised by advanced HIV disease. The efficacy of both TB and HIV treatment may thus be compromised by pharmacokinetic interactions, while more recent evidence also implicates genetic variation in drug metabolism as a predictor of drug exposure. To understand the significance of the EFV-RIF interaction better in a South African population, the pharmacokinetics of EFV during and after RIF-based TB treatment were investigated as an ancillary study of the ‘Starting Tuberculosis and Antiretroviral Therapy’ (START) trial (CAPRISA 001: NCT00091936). Participants were randomized to receive both ART and TB treatment simultaneously (integrated arm) or to initiate ART only on completion of TB treatment (sequential arm). In both arms, the ART regimen included once daily enteric-coated didanosine (400 mg for participants >60 kg; 250 mg for participants <60 kg), lamivudine 300mg and efavirenz. Based on the expected drug interactions, when EFV was administered in the presence of TB treatment, participants weighing less than 50kg received 600mg and those weighing 50kg or more received 800mg daily. After TB treatment was successfully completed, all patients received EFV 600mg. Blood samples for trough EFV plasma concentrations were obtained at the end of months 1, 2 and 3 during TB treatment and at the same time points after TB treatment was successfully completed. Additionally, approximated peak RIF concentrations were measured 2.5 hours post-dose at the end of months 1, 2 and 3 of TB treatment. The influence of single nucleotide polymorphisms, in CYP2B6, CYP2A6, and UGT2B7 on EFV concentrations, and in drug transporter genes (SLCO1B1) on RIF concentrations, was assessed post-trial from stored peripheral blood mononuclear cell (PBMC) samples. EFV concentration-time data were analyzed using a population pharmacokinetic nonlinear mixed effects model (NONMEM) to quantify the impact of RIF-based TB treatment on EFV clearance. Unexpectedly, there was an overall 29.5% reduction in EFV clearance during TB treatment. A bimodal distribution of EFV apparent clearance (CL/F) was evident and indicated that slow EFV metabolisers accounted for 21.9% of the population. EFV clearance after oral administration in fast metabolisers was 11.5 L/h/70kg off TB treatment and 7.6 L/h/70kg when on TB treatment. In slow metabolisers, however, the clearance estimates were 2.9 and 4.3 L/h/70kg in the presence and absence of TB treatment respectively. Building on the findings of the NONMEM analysis and in response to the US FDA prescribing change in 2012, that approved an EFV dose increase from 600mg to 800mg in patients weighing 50kg and more when on concomitant RIF, the presence and influence of pharmacogenetic polymorphisms of the CYP450 enzyme system on NNRTI plasma exposure during and after TB co-treatment and the effect of increasing the EFV dose was investigated. During TB treatment, median (IQR) EFV Cmin was 3.2 (2.6-6.3) μg/mL and 3.3 (2.4-9.5) μg/mL in the EFV 800mg and 600mg groups respectively, while off TB treatment Cmin was 2.0 (1.4 - 3.5) μg/mL. The frequency of the CYP2B6 *1, *6 and *18 haplotypes was 18.5%, 38.9% and 25.9% respectively. Polymorphisms in all three CYP2B6 genes studied (516T-785G-983C) were present in 11.1% of patients. Median (IQR) EFV concentrations in patients with the three mutations were 19.2 (9.5-20) μg/mL and 4.7 (3.5-5.6) μg/mL when on and off TB treatment. TB treatment, composite genotypes CYP2B6 516 GT/TT, CYP2B6 983 TC/CC or being a CYP2A6*9B carrier predicted median EFV Cmin > 4 μg/mL. Therefore, increasing the EFV dose to 800mg during TB treatment is unnecessary in African patients with these polymorphisms. As a critical component of first line TB treatment concerns about sub-optimal TB drug bioavailability were examined for RIF. The influence of drug transporter gene polymorphisms on RIF concentrations was also assessed. Median RIF (IQR) C2.5hr was found to be 3.6 (2.8-5.0) μg/mL while polymorphism frequency of the SLCO1B1 (rs4149032) drug transporter gene was high (0.76) and was associated with low RIF concentrations as was male gender and having a low haemoglobin. Increased RIF dosage warrants urgent consideration in African TB-HIV co-infected patients. In conclusion, concomitant RIF-containing TB treatment unexpectedly reduced EFV CL/F with a corresponding increase in EFV exposure. Polymorphisms of EFV metabolizing enzymes were frequent in this population and contribute to this outcome. While in South Africa where TB-HIV co-treatment is associated with elevated EFV concentrations, peak RIF concentrations were alarmingly low and well below the recommended target range of 8 to 24 μg/mL. Increased RIF dosage may be warranted in African TB-HIV co-infected patients whilst the need for EFV dose increase is not supported by these data. Recommendations for public health benefit, in this generalized epidemic in South Africa, include the consideration of an EFV dose reduction as a cost saving to improve life-long treatment sustainability, and a RIF dose increase to curb TB treatment failure and future development of multiple-drug resistant (MDR) TB

A qualitative study of patient motivation to adhere to combination antiretroviral therapy in South Africa.

CAPRISA, 2015.Abstract available in pdf

Addressing challenges in scaling up TB and HIV treatment integration in rural primary healthcare clinics in South Africa (SUTHI): a cluster randomized controlled trial protocol

Background A large and compelling clinical evidence base has shown that integrated TB and HIV services leads to reduction in human immunodeficiency virus (HIV)- and tuberculosis (TB)-associated mortality and morbidity. Despite official policies and guidelines recommending TB and HIV care integration, its poor implementation has resulted in TB and HIV remaining the commonest causes of death in several countries in sub-Saharan Africa, including South Africa. This study aims to reduce mortality due to TB-HIV co-infection through a quality improvement strategy for scaling up of TB and HIV treatment integration in rural primary healthcare clinics in South Africa. Methods The study is designed as an open-label cluster randomized controlled trial. Sixteen clinic supervisors who oversee 40 primary health care (PHC) clinics in two rural districts of KwaZulu-Natal, South Africa will be randomized to either the control group (provision of standard government guidance for TB-HIV integration) or the intervention group (provision of standard government guidance with active enhancement of TB-HIV care integration through a quality improvement approach). The primary outcome is all-cause mortality among TB-HIV patients. Secondary outcomes include time to antiretroviral therapy (ART) initiation among TB-HIV co-infected patients, as well as TB and HIV treatment outcomes at 12 months. In addition, factors that may affect the intervention, such as conditions in the clinic and staff availability, will be closely monitored and documented. Discussion This study has the potential to address the gap between the establishment of TB-HIV care integration policies and guidelines and their implementation in the provision of integrated care in PHC clinics. If successful, an evidence-based intervention comprising change ideas, tools, and approaches for quality improvement could inform the future rapid scale up, implementation, and sustainability of improved TB-HIV integration across sub-Sahara Africa and other resource-constrained settings. Trial registration Clinicaltrials.gov, NCT02654613. Registered 01 June 2015

Organizational contextual factors that predict success of a quality improvement collaborative approach to enhance integrated HIV-tuberculosis services: a sub-study of the Scaling up TB/HIV Integration trial

Background: A quality improvement (QI) collaborative approach to enhancing integrated HIV-Tuberculosis (TB) services may be effective in scaling up and improving the quality of service delivery. Little is known of the role of organizational contextual factors (OCFs) in influencing the success of QI collaboratives. This study aims to determine which OCFs were associated with improvement in a QI collaborative intervention to enhance integrated HIV-TB services delivery. Methods: This is a nested sub-study embedded in a cluster-randomized controlled trial. Sixteen nurse supervisors (clusters) overseeing 40 clinics were randomized (1:1) to receive QI training and mentorship, or standard of care support (SOC). In the QI arm, eight nurse supervisors and 20 clinics formed a “collaborative” which aimed to improve HIV-TB process indicators, namely HIV testing, TB screening, isoniazid preventive therapy (IPT) initiations, viral load testing, and antiretroviral therapy for TB patients. OCFs measured at baseline were physical infrastructure, key staff, flexibility of clinic hours, monitoring data for improvement (MDI), and leadership support. Surveys were administered to clinic staff at baseline and month 12 to assess perceptions of supportiveness of contexts for change, and clinic organization for delivering integrated HIV-TB services. Linear mixed modelling was used to test for associations between OCFs and HIV-TB process indicators. Results: A total of 209 clinic staff participated in the study; 97 (46.4%) and 112 (53.6%) from QI and SOC arms, respectively. There were no differences between the QI and SOC arms scores achieved for physical infrastructure (78.9% vs 64.7%; p = 0.058), key staff (95.8 vs 92; p = 0.270), clinic hours (66.9 vs 65.5; p = 0.900), MDI (63.3 vs 65; p = 0.875, leadership support (46.0 vs 57.4; p = 0.265), and perceptions of supportiveness of contexts for change (76.2 vs 79.7; p = 0.128 and clinic organization for delivering integrated HIV-TB services (74.1 vs 80.1; p = 0.916). IPT initiation was the only indicator that was significantly improved in the parent study. MDI was a significantly associated with increasing IPT initiation rates [beta coefficient (β) = 0.004; p = 0.004]. Discussion: MDI is a practice that should be fostered in public health facilities to increase the likelihood of success of future QI collaboratives to improve HIV-TB service delivery. Trial registration: Clinicaltrials.gov, NCT02654613. Registered 01 June 2015

Ritonavir/saquinavir safety concerns curtail antiretroviral therapy options for tuberculosis–HIV-co-infected patients in resource-constrained settings.

CorrespondenceNo abstract available

Open Access A Quality Improvement Intervention to Inform Scale-Up of Integrated HIV-TB Services: Lessons Learned From KwaZulu-Natal, South Africa

In South Africa, mortality rates among HIV-TB coinfected patients are among the highest in the world. The key to reducing mortality is integrating HIV-TB services, however, a generalizable implementation method and package of tested change ideas to guide the scale-up of integrated HIV-TB services are unavailable. We describe the implementation of a quality improvement (QI) intervention, health systems’ weaknesses, change ideas, and lessons learned in improving integrated HIV-TB services. / Methods: Between December 1, 2016, and December 31, 2018, 8 nurse supervisors overseeing 20 primary health care (PHC) clinics formed a learning collaborative to improve a set of HIV-TB process indicators. HIV-TB process indicators comprised: HIV testing services (HTS), TB screening among PHC clinic attendees, isoniazid preventive therapy (IPT) for eligible HIV patients, antiretroviral therapy (ART) for HIV-TB coinfected patients, and viral load (VL) testing at month 12. Routine HIV-TB process data were collected and analyzed. / Results: Key change interventions, generated by health care workers, included: patient-flow redesign, daily data quality checks; prior identification of patients eligible for IPT and VL testing. Between baseline and post-QI intervention, IPT initiation rates increased from 15.9% to 76.4% (P=.019), HTS increased from 84.8% to 94.5% (P=.110), TB screening increased from 76.2% to 85.2% (P=.040), and VL testing increased from 61.4% to 74.0% (P=.045). ART initiation decreased from 95.8% to 94.1% (P=.481). / Discussion: Although integrating HIV-TB services is standard guidance, existing process gaps to achieve integration can be closed using QI methods. QI interventions can rapidly improve the performance of processes, particularly if baseline performance is low. Improving data quality enhances the success of QI initiatives

Mortality in HIV and tuberculosis patients following implementation of integrated HIV-TB treatment: Results from an open-label cluster-randomized trial

Background: HIV-TB treatment integration reduces mortality. Operational implementation of integrated services is challenging. This study assessed the impact of quality improvement (QI) for HIV-TB integration on mortality within primary healthcare (PHC) clinics in South Africa. // Methods: An open-label cluster randomized controlled study was conducted between 2016 and 2018 in 40 rural clinics in South Africa. The study statistician randomized PHC nurse-supervisors 1:1 into 16 clusters (eight nurse-supervisors supporting 20 clinics per arm) to receive QI, supported HIV-TB integration intervention or standard of care (control). Nurse supervisors and clinics under their supervision, based in the study health districts were eligible for inclusion in this study. Nurse supervisors were excluded if their clinics were managed by municipal health (different resource allocation), did not offer co-located antiretroviral therapy (ART) and TB services, services were performed by a single nurse, did not receive non-governmental organisation (NGO) support, patient data was not available for > 50% of attendees. The analysis population consists of all patients newly diagnosed with (i) both TB and HIV (ii) HIV only (among patients previously treated for TB or those who never had TB before) and (iii) TB only (among patients already diagnosed with HIV or those who were never diagnosed with HIV) after QI implementation in the intervention arm, or enrolment in the control arm. Mortality rates was assessed 12 months post enrolment, using unpaired t-tests and cox-proportional hazards model. (Clinicaltrials.gov, NCT02654613, registered 01 June 2015, trial closed). // Findings: Overall, 21 379 participants were enrolled between December 2016 and December 2018 in intervention and control arm clinics: 1329 and 841 HIV-TB co-infected (10·2%); 10 799 and 6 611 people living with Human Immunodeficiency Virus (HIV)/ acquired immunodeficiency syndrome (AIDS) (PLWHA) only (81·4%); 1 131 and 668 patients with TB only (8·4%), respectively. Average cluster sizes were 1657 (range 170–5782) and 1015 (range 33–2027) in intervention and control arms. By 12 months, 6529 (68·7%) and 4074 (70·4%) were alive and in care, 568 (6·0%) and 321 (5·6%) had completed TB treatment, 1078 (11·3%) and 694 (12·0%) were lost to follow-up, with 245 and 156 deaths occurring in intervention and control arms, respectively. Mortality rates overall [95% confidence interval (CI)] was 4·5 (3·4–5·9) in intervention arm, and 3·8 (2·6–5·4) per 100 person-years in control arm clusters [mortality rate ratio (MRR): 1·19 (95% CI 0·79–1·80)]. Mortality rates among HIV-TB co-infected patients was 10·1 (6·7–15·3) and 9·8 (5·0–18·9) per 100 person-years, [MRR: 1·04 (95% CI 0·51–2·10)], in intervention and control arm clusters, respectively. // Interpretation: HIV-TB integration supported by a QI intervention did not reduce mortality in HIV-TB co-infected patients. Demonstrating mortality benefit from health systems process improvements in real-world operational settings remains challenging. Despite the study being potentially underpowered to demonstrate the effect size, integration interventions were implemented using existing facility staff and infrastructure reflecting the real-world context where most patients in similar settings access care, thereby improving generalizability and scalability of study findings

COVID-19 vaccine hesitancy in KwaZulu-Natal, South Africa: A survey of unvaccinated adults

Background: Concerns and misconceptions surrounding coronavirus disease 2019 (COVID-19) vaccines may account for vaccine hesitancy and low uptake. Aim: To determine prevalence of COVID-19 vaccine hesitancy, vaccine-related misconceptions, and predictors of vaccine hesitancy among South Africans. Setting: Community setting in five districts in KwaZulu- Natal province. Methods: Between August 20, 2021, and September 27, 2021, we conducted a cross-sectional survey, interviewing 300 unvaccinated adults amid the national vaccination campaign. Predictors of hesitancy were identified through multivariable logistic regression analysis. Results: Participants had a median age of 29 years (IQR: 23–39), 86.7% were Black African, 63.2% were male, 53.3% resided in rural communities, and 59.3% (95% CI: 53.8% – 64.9%) were classified as vaccine hesitant. The primary reason for not vaccinating was a lack of trust in the vaccine (62.1%). Factors associated with reduced vaccine hesitancy included age (participants aged 35–49 years: OR: 0.28, 95% CI: 0.18–0.64, p = 0.003; participants over 50 years: OR: 0.18, 95% CI: 0.07–0.47, p = 0.0004), previous COVID-19 infection (OR: 0.31, 95% CI: 0.11–0.87, p = 0.03), and receiving vaccine information from healthcare workers (OR: 0.32, 95% CI: 0.10–1.0, p = 0.05). Unemployed (OR: 2.14, 95% CI: 1.1–4.2, p = 0.03) and self-employed individuals (OR: 2.98, 95% CI: 1.27–7.02, p = 0.01) were more likely to be vaccine hesitant. Conclusion: COVID-19 vaccine hesitancy rates are high in KwaZulu-Natal. Uptake could be enhanced by healthcare workers leading information campaigns with messages targeting younger individuals, the unemployed, and the self-employed. Contribution: This survey provides evidence to improve COVID-19 vaccination uptake in South Africa