OpenUCT :: Browsing by Author "Orrell, Catherine"

Browsing by Author "Orrell, Catherine"

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Open Access
A cluster randomized controlled trial of extending ART refill intervals to six-monthly for anti-retroviral adherence clubs
(2019-07-30) Wilkinson, Lynne; Grimsrud, Anna; Cassidy, Tali; Orrell, Catherine; Voget, Jacqueline; Hayes, Helen; Keene, Claire; Steele, Sarah J; Gerstenhaber, Rodd
Abstract Background The antiretroviral therapy (ART) adherence club (AC) differentiated service delivery model, where clinically stable ART patients receive their ART refills and psychosocial support in groups has supported clinically stable patients’ retention and viral suppression. Patients and health systems could benefit further by reducing visit frequency and increasing ART refills. We designed a cluster-randomized control trial comparing standard of care (SoC) ACs and six-month ART refill (Intervention) ACs in a large primary care facility in Khayelitsha, South Africa. Methods Existing ACs were randomized to either the control (SOC ACs) or intervention (Intervention ACs) arm. SoC ACs meet five times annually, receiving two-month ART refills with a four-month ART refill over year-end. Blood is drawn at the AC visit ahead of the clinical assessment visit. Intervention ACs meet twice annually receiving six-month ART refills, with a third individual visit for routine blood collection anytime two-four weeks before the annual clinical assessment AC visit. Primary outcomes will be retention in care, annual viral load assessment completion and viral load suppression. (<400copies/mL) after 2 years. Ethics approval has been granted by the University of Cape Town (HREC 652/2016) and the Medecins Sans Frontieres (MSF) Ethics Review Board (#1639). Results will be published in peer-reviewed journals and made widely available through presentations and briefing documents. Discussion Evaluation of an extended ART refill interval in adherence clubs will provide evidence towards novel model adaptions that can be made to further improve convenience for patients and leverage health system efficiencies. Trial registration Registered with the Pan African Clinical Trial Registry: PACTR201810631281009. Registered 11 September 2018.
Open Access
AGILE: a seamless phase I/IIa platform for the rapid evaluation of candidates for COVID-19 treatment: an update to the structured summary of a study protocol for a randomised platform trial letter
(2021-07-26) Griffiths, Gareth O; FitzGerald, Richard; Jaki, Thomas; Corkhill, Andrea; Reynolds, Helen; Ewings, Sean; Condie, Susannah; Tilt, Emma; Johnson, Lucy; Radford, Mike; Simpson, Catherine; Saunders, Geoffrey; Yeats, Sara; Mozgunov, Pavel; Tansley-Hancock, Olana; Martin, Karen; Downs, Nichola; Eberhart, Izabela; Martin, Jonathan W B; Goncalves, Cristiana; Song, Anna; Fletcher, Tom; Byrne, Kelly; Lalloo, David G; Owen, Andrew; Jacobs, Michael; Walker, Lauren; Lyon, Rebecca; Woods, Christie; Gibney, Jennifer; Chiong, Justin; Chandiwana, Nomathemba; Jacob, Shevin; Lamorde, Mohammed; Orrell, Catherine; Pirmohamed, Munir; Khoo, Saye
Background There is an urgent unmet clinical need for the identification of novel therapeutics for the treatment of COVID-19. A number of COVID-19 late phase trial platforms have been developed to investigate (often repurposed) drugs both in the UK and globally (e.g. RECOVERY led by the University of Oxford and SOLIDARITY led by WHO). There is a pressing need to investigate novel candidates within early phase trial platforms, from which promising candidates can feed into established later phase platforms. AGILE grew from a UK-wide collaboration to undertake early stage clinical evaluation of candidates for SARS-CoV-2 infection to accelerate national and global healthcare interventions. Methods/design AGILE is a seamless phase I/IIa platform study to establish the optimum dose, determine the activity and safety of each candidate and recommend whether it should be evaluated further. Each candidate is evaluated in its own trial, either as an open label single arm healthy volunteer study or in patients, randomising between candidate and control usually in a 2:1 allocation in favour of the candidate. Each dose is assessed sequentially for safety usually in cohorts of 6 patients. Once a phase II dose has been identified, efficacy is assessed by seamlessly expanding into a larger cohort. AGILE is completely flexible in that the core design in the master protocol can be adapted for each candidate based on prior knowledge of the candidate (i.e. population, primary endpoint and sample size can be amended). This information is detailed in each candidate specific trial protocol of the master protocol. Discussion Few approved treatments for COVID-19 are available such as dexamethasone, remdesivir and tocilizumab in hospitalised patients. The AGILE platform aims to rapidly identify new efficacious and safe treatments to help end the current global COVID-19 pandemic. We currently have three candidate specific trials within this platform study that are open to recruitment. Trial registration EudraCT Number: 2020-001860-27 14 March 2020 ClinicalTrials.gov Identifier: NCT04746183 19 February 2021 ISRCTN reference: 27106947
Open Access
Antiretroviral therapy in a community clinic - early lessons from a pilot project
(Health and Medical Publishing Group, 2003) Bekker, Linda-Gail; Orrell, Catherine; Reader, Larissa; Matoti, Larissa; Cohen, Karen; Martell, Rob; Abdullah, Fareed; Wood, Robin
Objectives. To report on operational and clinical problems encountered during the first 6 months of a community-based antiretroviral therapy (ART) programme. Methods. ART was implemented in a primary care setting utilising an easily replicable service-delivery model based on a medical officer and nurse. Therapeutic counsellors, themselves HIV-infected, provided counselling and adherence support. Drug and monitoring costs were charitably funded and provincial health authorities supplied the medical infrastructure. The HIV Research Unit, University of Cape Town, supplied training and additional clinical support. Local HIV primary care clinics provided patient referrals. Standardised ART regimens were used with strict entry criteria (AIDS or CD4 count < 200 cells/µl). Results. Demand for the service was high. Referred patients had advanced disease (AIDS 57%, median CD4 count 96/µl) and high pre-treatment mortality (83/100 person-years). Mycobacterial disease was a major contributor to this mortality (40%). Scheduled clinic visit hours were six times higher during recruitment than maintenance. Attributable costs were: drugs 61%, staff 27%, viral load and CD4 cell counts 10% and safety monitoring 2%. Viral load after 16 weeks of therapy was < 400 copies/ml in the first 16 patients. Conclusions. ART can be successfully implemented within a primary care setting. Drug purchases and staff salaries drive programme costing. The service model is capable of managing 250 - 300 patients on chronic ART, but staffing needs to be increased during recruitment. Attention must be given to the diagnosis of tuberculosis during screening and early ART. Incorporating therapeutic counsellors into the programme increased community involvement and utilised a valuable and previously untapped resource.
Open Access
Artesunate and amodiaquine : tolerability and drug interaction study in healthy normal volunteers
(2005) Orrell, Catherine; Smith, Peter
Includes bibliographical references.
Open Access
Brief psychotherapy administered by non-specialised health workers to address risky substance use in patients with multidrug-resistant tuberculosis: a feasibility and acceptability study
(2021-01-19) Calligaro, Gregory L; de Wit, Zani; Cirota, Jacqui; Orrell, Catherine; Myers, Bronwyn; Decker, Sebastian; Stein, Dan J; Sorsdahl, Katherine; Dawson, Rodney
Background Only 55% of multidrug-resistant tuberculosis (MDR-TB) cases worldwide complete treatment, with problem substance use a risk for default and treatment failure. Nevertheless, there is little research on psychotherapeutic interventions for reducing substance use amongst MDR-TB patients, in general, and on their delivery by non-specialist health workers in particular. Objectives To explore the feasibility and acceptability of a non-specialist health worker-delivered 4-session brief motivational interviewing and relapse prevention (MI-RP) intervention for problem substance use and to obtain preliminary data on the effects of this intervention on substance use severity, depressive symptoms, psychological distress and functional impairment at 3 months after hospital discharge. Methods Between December 2015 and October 2016, consenting MDR-TB patients admitted to Brewelskloof Hospital who screened at moderate to severe risk for substance-related problems on the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) were enrolled, and a baseline questionnaire administered. In the 4 weeks prior to planned discharge, trained counsellors delivered the MI-RP intervention. The baseline questionnaire was re-administered 3 months post-discharge and qualitative interviews were conducted with a randomly selected sample of participants (n = 10). Results Sixty patients were screened: 40 (66%) met inclusion criteria of which 39 (98%) were enrolled. Of the enrolled patients, 26 (67%) completed the counselling sessions and the final assessment. Qualitative interviews revealed participants’ perceptions of the value of the intervention. From baseline to follow-up, patients reported reductions in substance use severity, symptoms of depression, distress and functional impairment. Conclusion In this feasibility study, participant retention in the study was moderate. We found preliminary evidence supporting the benefits of the intervention for reducing substance use and symptoms of psychological distress, supported by qualitative reports of patient experiences. Randomised studies are needed to demonstrate efficacy of this intervention before considering potential for wider implementation. Trial registration South African National Clinical Trials Register ( DOH-27-0315-5007 ) on 01/04/2015 ( http://www.sanctr.gov.za )
Open Access
Comparison of six methods to estimate adherence in an ART-naïve cohort in a resource-poor setting: which best predicts virological and resistance outcomes?
(2017) Orrell, Catherine; Cohen, Karen; Leisegang, Rory; Bangsberg, David R; Wood, Robin; Maartens, Gary
BACKGROUND: Incomplete adherence to antiretroviral therapy (ART) results in virologic failure and resistance. It remains unclear which adherence measure best predicts these outcomes. We compared six patient-reported and objective adherence measures in one ART-naïve cohort in South Africa. METHODS: We recruited 230 participants from a community ART clinic and prospectively collected demographic data, CD4 count and HIV-RNA at weeks 0, 16 and 48. We quantified adherence using 3-day self-report (SR), clinic-based pill count (CPC), average adherence by pharmacy refill (PR-average), calculation of medication-free days (PR-gaps), efavirenz therapeutic drug monitoring (TDM) and an electronic adherence monitoring device (EAMD). Associations between adherence measures and virologic and genotypic outcomes were modelled using logistic regression, with the area under the curve (AUC) from the receiver operator characteristic (ROC) analyses derived to assess performance of adherence measures in predicting outcomes. RESULTS: At week 48 median (IQR) adherence was: SR 100% (100-100), CPC 100% (95-107), PR-average 103% (95-105), PR-gaps 100% (95-100) and EAMD 86% (59-94), and efavirenz concentrations were therapeutic (>1 mg/L) in 92%. EAMD, PR-average, PR-gaps and CPC best predicted virological outcome at week 48 with AUC ROC of 0.73 (95% CI 0.61-0.83), 0.73 (95% CI 0.61-0.85), 0.72 (95% CI 0.59-0.84) and 0.64 (95% CI 0.52-0.76) respectively. EAMD, PR-gaps and PR-average were highly predictive of detection of resistance mutations at week 48, with AUC ROC of 0.92 (95% CI 0.87-0.97), 0.86 (0.67-1.0) and 0.83 (95% CI 0.65-1.0) respectively. SR and TDM were poorly predictive of outcomes at week 48. CONCLUSION: EAMD and both PR measures predicted resistance and virological failure similarly. Pharmacy refill data is a pragmatic adherence measure in resource-limited settings where electronic monitoring is unavailable. Trial registration The trial was retrospectively registered in the Pan African Clinical Trials Registry, number PACTR201311000641402, on the 13 Sep 2013 ( www.pactr.org ). The first participant was enrolled on the 12th July 2012. The last patient last visit (week 48) was 15 April 2014.
Open Access
Comparison of six methods to estimate adherence in an ART-naïve cohort in a resource-poor setting: which best predicts virological and resistance outcomes?
(BioMed Central, 2017-04-04) Orrell, Catherine; Cohen, Karen; Leisegang, Rory; Bangsberg, David R; Wood, Robin; Maartens, Gary
Background: Incomplete adherence to antiretroviral therapy (ART) results in virologic failure and resistance. It remains unclear which adherence measure best predicts these outcomes. We compared six patient-reported and objective adherence measures in one ART-naïve cohort in South Africa. Methods: We recruited 230 participants from a community ART clinic and prospectively collected demographic data, CD4 count and HIV-RNA at weeks 0, 16 and 48. We quantified adherence using 3-day self-report (SR), clinicbased pill count (CPC), average adherence by pharmacy refill (PR-average), calculation of medication-free days (PR-gaps), efavirenz therapeutic drug monitoring (TDM) and an electronic adherence monitoring device (EAMD). Associations between adherence measures and virologic and genotypic outcomes were modelled using logistic regression, with the area under the curve (AUC) from the receiver operator characteristic (ROC) analyses derived to assess performance of adherence measures in predicting outcomes. Results: At week 48 median (IQR) adherence was: SR 100% (100–100), CPC 100% (95–107), PR-average 103% (95– 105), PR-gaps 100% (95–100) and EAMD 86% (59–94), and efavirenz concentrations were therapeutic (>1 mg/L) in 92%. EAMD, PR-average, PR-gaps and CPC best predicted virological outcome at week 48 with AUC ROC of 0.73 (95% CI 0.61–0.83), 0.73 (95% CI 0.61–0.85), 0.72 (95% CI 0.59–0.84) and 0.64 (95% CI 0.52–0.76) respectively. EAMD, PR-gaps and PR-average were highly predictive of detection of resistance mutations at week 48, with AUC ROC of 0.92 (95% CI 0.87–0.97), 0.86 (0.67–1.0) and 0.83 (95% CI 0.65–1.0) respectively. SR and TDM were poorly predictive of outcomes at week 48. Conclusion: EAMD and both PR measures predicted resistance and virological failure similarly. Pharmacy refill data is a pragmatic adherence measure in resource-limited settings where electronic monitoring is unavailable. Trial registration The trial was retrospectively registered in the Pan African Clinical Trials Registry, number PACTR201311000641402, on the 13 Sep 2013 (www.pactr.org). The first participant was enrolled on the 12th July 2012. The last patient last visit (week 48) was 15 April 2014
Open Access
Determinants and reasons for switching anti-retroviral regimen among HIV-infected youth in a large township of South Africa (2002–2019)
(2022-06-28) Kabarambi, Anita; Balinda, Sheila; Abaasa, Andrew; Cogill, Dolphina; Orrell, Catherine
Background There are limited data exploring antiretroviral therapy (ART) changes and time to change among South Africa young people living with HIV/AIDS. Objective We describe the time to first drug switch, which includes ART regimen change (three drug switch) and substitutions (single drug switch). We describe common reasons for ART switch among young people aged 10 to 24 years in South Africa. Methods We conducted a retrospective cohort study at a primary health care clinic in Cape Town, South Africa, providing ART to HIV-infected adolescents and adults since 2002. Those aged 10 to 24 years at ART initiation, who accessed care clinic between September 2002 and April 2019. Data was retrieved from electronic information systems: ART regimens, ART changes, dates for initiation or stop of each drug/regimen, laboratory results (viral loads, haemoglobin, liver enzyme results, and creatinine to support the reason for ART switch. From written records, we abstracted reason for single drug switch or regimen change, as well as socio demographic and clinical data. We fitted cox regression models to determine factors associated with ART switch (Having a change in one or more drugs in ART combination) and the rate of occurrence. Results Of 2601 adolescents included, 605 (24.9%) adolescents switched ART over 5090.5 person years at risk (PYAR), a rate of 11.9 /100PYAR. Median follow-up time was 4.4 (± 3.2) years. At multivariable analysis, the older age group was protective of the risk of ART switch: adjusted Hazard Ratio [aHR] 0.78, 95% CI 0.62–0.98, transfer status [transferred out 1.42 [1.11–1.82]. The hazard of ART switch increased with more severe HIV-disease at ART start, as observed by increasing WHO clinical stage or reduced CD4 count at baseline. The primary reasons for ART switch were side effects (20.0%), virological failure (17.9%) and formulation switch (27.8%). Others reasons included pregnancy, Hepatitis B, tuberculosis and psychosis. Conclusion ART switches are frequent and occur at a consistent rate across 7.5 years from initiation. The main reasons for ART switch were virological failure and drug side effects.
Open Access
Healthcare utilization of patients accessing an African national treatment program
(Biomed Central Ltd, 2007) Harling, Guy; Orrell, Catherine; Wood, Robin
BACKGROUND:The roll-out of antiretroviral therapy (ART) in Africa will have significant resource implications arising from its impact on demand for healthcare services. Existing studies of healthcare utilization on HAART have been conducted in the developed world, where HAART is commenced when HIV illness is less advanced. METHODS: This paper describes healthcare utilization from program entry by treatment-naive patients in a peri-urban settlement in South Africa. Treatment criteria included a CD4 cell count <200 cells/mul or an AIDS-defining illness. Data on health service utilization were collected retrospectively from the primary-care clinic and secondary and tertiary referral hospitals. Hospital visits were reviewed to determine the clinical reason for each visit. RESULTS: 212 patients were followed for a median of 490 days. Outpatient visits per 100 patient years of observation (PYO), excluding scheduled primary-care follow-up, fell from 596 immediately prior to ART to 334 in the first 48 weeks on therapy and 245 thereafter. Total inpatient time fell from 2,549 days per 100 PYO pre-ART to 476 in the first 48 weeks on therapy and 73 thereafter. This fall in healthcare utilization occurred at every level of care. The greatest causes of utilization were tuberculosis, cryptococcal meningitis, HIV-related neoplasms and adverse reactions to stavudine. After 48 weeks on ART demand reverted to primarily non-HIV-related causes. CONCLUSION: Utilization of both inpatient and outpatient hospital services fell significantly after commencement of ART for South African patients in the public sector, with inpatient demand falling fastest. Earlier initiation might reduce early on-ART utilization rates.
Open Access
Increasing transfers-out from an antiretroviral treatment service in South Africa: patient characteristics and rates of virological non-suppression
(Public Library of Science, 2013) Nglazi, Mweete D; Kaplan, Richard; Orrell, Catherine; Myer, Landon; Wood, Robin; Bekker, Linda-Gail; Lawn, Stephen D
Objectives: To determine the proportion, characteristics and outcomes of patients who transfer-out from an antiretroviral therapy (ART) service in a South African township. METHODS: This retrospective cohort study included all patients aged ≥15 years who enrolled between September 2002 and December 2009. Follow-up data were censored in December 2010. Kaplan-Meier survival analysis was used to describe time to transfer-out and cox proportional hazard analysis was used to determine associated risk factors. RESULTS: 4511 patients (4003 ART-naïve and 508 non-naïve at baseline) received ART during the study period. Overall, 597 (13.2%) transferred out. The probability of transferring out by one year of ART steadily increased from 1.4% in 2002/2004 cohort to 8.9% for the 2009 cohort. Independent risk factors for transfer-out were more recent calendar year of enrolment, younger age (≤25 years) and being ART non-naïve at baseline (i.e., having previously transferred into this clinic from another facility). The proportions of patients transferred out who had a CD4 cell count <200 cells/µL and/or a viral load ≥1000 copies/mL were 19% and 20%, respectively. CONCLUSIONS: With scale-up of ART over time, an increasing proportion of patients are transferring between ART services and information systems are needed to track patients. Approximately one-fifth of these have viral loads >1000 copies/mL around the time of transfer, suggesting the need for careful adherence counseling and assessment of medication supplies among those planning transfer.
Restricted
Initiating patients on antiretroviral therapy at CD4 cell counts above 200 cells/Âµl is associated with improved treatment outcomes in South Africa
(Wolters Kluwer Health, 2010) Zeinecker, Jennifer; Orrell, Catherine; Wood, Robin
Observational cohort study. Methods Patients presenting to primary care clinics with CD4 cell counts <350 cells/mm3 were randomized to either doctor- or nurse-managed HIV care and followed for at least two years after ART initiation. Clinical and laboratory outcomes were compared by baseline CD4 count. Results 812 patients were followed for a median of 27.5 months and 36% initiated with a CD4 count >200. While 10% of patients failed virologically (VF), the risk was nearly double among those with a CD4 ≤200 vs. >200 (12.2% vs. 6.8%). 21 deaths occurred, with a five-fold increased risk for the low CD4 group (3.7% vs. 0.7%). After adjustment, those with a CD4 count ≤200 had twice the risk of death/VF (HR 1.9; 95% CI: 1.1–3.3) and twice the risk of incident tuberculosis (HR: 1.90; 95% CI: 0.89–4.04) as those >200. Those with either a CD4 ≤200 (HR 2.1; 1.2–3.8) or a WHO IV condition (HR 2.9; 0.93–8.8) alone had a two to three-fold increased risk of death/VF vs. those with neither, but those with both conditions had a 4-fold increased risk (HR 3.9; 95% CI: 1.9–8.1). We observed some increased loss to follow-up among those initiating <200 (HR 0.79; 95% CI: 0.50–1.25). Conclusions Patients initiating ART with higher CD4 counts had reduced mortality, tuberculosis and less virologic failure than those initiated at lower CD4 counts. Our data support increasing CD4 count eligibility criteria for ART initiation.
Open Access
Linkage to HIV care and antiretroviral therapy in Cape Town, South Africa
(Public Library of Science, 2010) Kranzer, Katharina; Zeinecker, Jennifer; Ginsberg, Philip; Orrell, Catherine; Kalawe, Nosindiso N; Lawn, Stephen D; Bekker, Linda-Gail; Wood, Robin
BACKGROUND: Antiretroviral therapy (ART) has been scaled-up rapidly in Africa. Programme reports typically focus on loss to follow-up and mortality among patients receiving ART. However, little is known about linkage and retention in care of individuals prior to starting ART. METHODOLOGY: Data on adult residents from a periurban community in Cape Town were collected at a primary care clinic and hospital. HIV testing registers, CD4 count results provided by the National Health Laboratory System and ART registers were linked. A random sample (n = 885) was drawn from adults testing HIV positive through antenatal care, sexual transmitted disease and voluntary testing and counseling services between January 2004 and March 2009. All adults (n = 103) testing HIV positive through TB services during the same time period were also included in the study. Linkage to HIV care was defined as attending for a CD4 count measurement within 6 months of HIV diagnosis. Linkage to ART care was defined as initiating ART within 6 months of HIV diagnosis in individuals with a CD4 count ≤200 cells/µl taken within 6 months of HIV diagnosis. FINDINGS: Only 62.6% of individuals attended for a CD4 count measurement within 6 months of testing HIV positive. Individuals testing through sexually transmitted infection services had the best (84.1%) and individuals testing on their own initiative (53.5%) the worst linkage to HIV care. One third of individuals with timely CD4 counts were eligible for ART and 66.7% of those were successfully linked to ART care. Linkage to ART care was highest among antenatal care clients. Among individuals not yet eligible for ART only 46.3% had a repeat CD4 count. Linkage to HIV care improved in patients tested in more recent calendar period. CONCLUSION: Linkage to HIV and ART care was low in this poor peri-urban community despite free services available within close proximity. More efforts are needed to link VCT scale-up to subsequent care.
Open Access
Low prevalence of liver disease but regional differences in HBV treatment characteristics mark HIV/HBV co-infection in a South African HIV clinical trial
(Public Library of Science, 2013) Ive, Prudence; MacLeod, William; Mkumla, Nompumelelo; Orrell, Catherine; Jentsch, Ute; Wallis, Carole L; Stevens, Wendy; Wood, Robin; Sanne, Ian; Bhattacharya, Debika
BACKGROUND: Hepatitis B virus (HBV) infection is endemic in South Africa however, there is limited data on the degree of liver disease and geographic variation in HIV/HBV coinfected individuals. In this study, we analysed data from the CIPRA-SA 'Safeguard the household study' in order to assess baseline HBV characteristics in HIV/HBV co-infection participants prior to antiretroviral therapy (ART) initiation. METHODS: 812 participants from two South African townships Soweto and Masiphumelele were enrolled in a randomized trial of ART (CIPRA-SA). Participants were tested for hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), and HBV DNA. FIB-4 scores were calculated at baseline. RESULTS: Forty-eight (5.9%) were HBsAg positive, of whom 28 (58.3%) were HBeAg positive. Of those with HBV, 29.8% had an HBV DNA<2000 IU/ml and ALT<40 IU/ml ; 83.0% had a FIB-4 score <1.45, consistent with absent or minimal liver disease. HBV prevalence was 8.5% in Masiphumelele compared to 3.8% in Soweto (relative risk 2.3; 95% CI: 1.3-4.0). More participants in Masiphumelele had HBeAg-negative disease (58% vs. 12%, p = 0.002) and HBV DNA levels ≤2000 IU/ml, (43% vs. 6% p<0.007). CONCLUSION: One third of HIV/HBV co-infected subjects had low HBV DNA levels and ALT while the majority had indicators of only mild liver disease. There were substantial regional differences in HBsAg and HbeAg prevalence in HIV/HBV co-infection between two regions in South Africa. This study highlights the absence of severe liver disease and the marked regional differences in HIV/HBV co-infection in South Africa and will inform treatment decisions in these populations.
Open Access
Mortality of HIV-infected patients starting antiretroviral therapy in sub-Saharan Africa: comparison with HIV-unrelated mortality
(Public Library of Science, 2009) Brinkhof, Martin W G; Boulle, Andrew; Weigel, Ralf; Messou, Eugène; Mathers, Colin; Orrell, Catherine; Dabis, François; Pascoe, Margaret; Egger, Matthias; (IeDEA), for the International epidemiological Databases to Evaluate AIDS
Comparing mortality rates between patients starting HIV treatment and the general population in four African countries, Matthias Egger and colleagues find the gap decreases over time, especially with early treatment.
Open Access
Prevalence of asymptomatic sexually transmitted infections: a retrospective review of screening data from Desmond Tutu HIV Centre clinical trial cohorts from 2012 to 2017, Cape Town
(2019) Garnett, Nomcebo Precious; Orrell, Catherine
Background: The burden of Sexually transmitted infections (STIs) is high globally. The World Health Organisation (WHO) recommends syndromic management of these STIs, based on presentation with signs and symptoms, in resource-limited countries. Due to this syndromic approach, there is little current data on STI prevalence, including asymptomatic STIs, in high risk populations. Methods: We reviewed secondary data collected as part of the screening procedures of 6 clinical trials between 2012 and 2017 in Cape Town, South Africa. These trials recruited populations of different sexual orientation and gender, mostly key populations at risk of HIV and STI acquisition. Routine screening for STI symptoms and testing for Chlamydia, Gonorrhoea, Trichomonas, Syphilis and HIV was performed for all of the studies at screening/enrollment. Results: A total of 639 participants were screened; 411 (64.3%) self-identifying as female, 198 (31%) males, 29 (4.5%) transgender women and 01 (0.2%) transvestite. Median age was 20 years (IQR: 18-24), with the 15-24-year age category contributing 77% to the cohort. Laboratory testing diagnosed 239 (37.4%) people with STI infections in this cohort; only 28 (11.7%) people were symptomatic. 119 (88.8%) of Chlamydial, 64 (82.1%) of Gonorrhoeal, 23 (92%) of Trichomonal and 31(79.5%) of Syphilis infections elicited no signs and/or symptoms. Conclusion: A vast majority of STIs in this high-risk population were asymptomatic. Laboratory testing of causal organism was more reliable in diagnosing STIs than the use of signs and/or symptoms as recommended by WHO.
Open Access
Public-health and individual approaches to antiretroviral therapy: township South Africa and Switzerland compared
(Public Library of Science, 2008) Keiser, Olivia; Orrell, Catherine; Egger, Matthias; Wood, Robin; Brinkhof, Martin W G; Furrer, Hansjakob; vCutsem, Gilles; Ledergerber, Bruno; Boulle, Andrew; (IeDEA-SA), for the Swiss HIV Cohort Study (SHCS) and the International Epidemiologic Databases
Comparing HIV treatment in Switzerland, where drug selection is individualized, and South Africa, where a programmatic approach is used, Matthias Egger and colleagues find similar virologic outcomes over two years.
Open Access
Rapid scale-up of A community-based HIV treatment service: Programme performance over 3 consecutive years in Guguletu, South Africa
(2006) Bekker, Linda-Gail; Myer, Landon; Orrell, Catherine; Lawn, Steve; Wood, Robin
Background. Despite rapid expansion of antiretroviral therapy (ART) in sub-Saharan Africa there are few longitudinal data describing programme performance during rapid scale-up. Methods. We compared mortality, viral suppression and programme retention in 3 consecutive years of a public sector community-based ART clinic in a South African township. Data were collected prospectively from establishment of services in October 2002 to the censoring date in September 2005. Viral load and CD4 counts were monitored at 4-monthly intervals. Community-based counsellors provided adherence and programme support. Results. During the study period 1 139 ART-naïve patients received ART (161, 280 and 698 in the 1st, 2nd and 3rd years respectively). The median CD4 cell counts were 84 cells/μl (interquartile range (IQR) 42 - 139), 89 cells/μl (IQR 490 - 149), and 110 cells/μl (IQR 55 - 172), and the proportions of patients with World Health Organization (WHO) clinical stages 3 and 4 were 90%, 79% and 76% in each sequential year respectively. The number of counsellors increased from 6 to 28 and the median number of clients allocated to each counsellor increased from 13 to 33. The overall loss to follow-up was 2.9%. At the date of censoring, the Kaplan-Meier estimates of the proportion of patients still on the programme were 82%, 86% and 91%, and the proportion who were virally suppressed (< 400 copies/ml) were 100%, 92% and 98% for the 2002, 2003 and 2004 cohorts respectively. Conclusions. While further operational research is required into optimal models of care in different populations across sub-Saharan Africa, these results demonstrate that a single community-based public sector ART clinic can extend care to over 1 000 patients in an urban setting without compromising programme performance.
Open Access
Rates of switching antiretroviral drugs in a primary care service in South Africa before and after introduction of tenofovir
(Public Library of Science, 2013) Njuguna, Christine; Orrell, Catherine; Kaplan, Richard; Bekker, Linda-Gail; Wood, Robin; Lawn, Stephen D
Introduction Antiretroviral changes (single drug substitutions and regimen switches) limit treatment options and introduce challenges such as increased cost, monitoring and adherence difficulties. Patterns of drug substitutions and regimen switches from stavudine (d4T) and zidovudine (AZT) regimens have been well described but data on tenofovir (TDF) are more limited. This study describes the patterns and risk factors for drug changes of these antiretroviral drugs in adults. Method This retrospective cohort study included HIV positive, antiretroviral treatment (ART) naïve adults aged ≥18 years who started ART with two nucleoside reverse transcriptase inhibitors (NRTIs) and a non-nucleoside reverse transcriptase inhibitor. Follow-up was censored at first drug change and analysis focused on NRTI changes only. RESULTS: Between September 2002 and April 2011, 5095 adults initiated ART in Gugulethu. This comprised 948 subjects on TDF, 3438 on d4T and 709 subjects on AZT. Virological suppression rates at 1 year, regimen switching due to virological failure and overall losses to the programme were similar across the three groups. TDF had the lowest incidence rate of drug substitutions (2.6 per 100 P/Ys) compared to 17.9 for d4T and 8.5 per 100 P/Ys for AZT. Adverse drug reactions (ADRs) accounted for the majority of drug substitutions of d4T. Multivariate analysis showed that increasing age, female sex and d4T exposure were associated with increased hazard of drug substitution due to ADRs. Conversely, TDF exposure was associated with a substantially lower risk of substitution (adjusted hazards ratio 0.38; 95% CI 0.20-0.72). CONCLUSION: Regimen switches and virological suppression were similar for patients exposed to TDF, d4T and AZT, suggesting all regimens were equally effective. However, TDF was better tolerated with a substantially lower rate of drug substitutions due to ADRs.
Open Access
Rates of Switching First-Line Antiretroviral Regimen Tenofovir-Emtricitabine-Efavirenz combination in a Primary Care Service in South Africa
(2020) Huang, David; Namane, Mosedi; Orrell, Catherine
Introduction: Tenofovir-Emtricitabine-Efavirenz (TEE) fixed-dose-combination (FDC) has been recommended since 2013 as the first-line antiretroviral therapy (ART) for treating HIV for people living with the virus (PLWH) in South Africa. More evidence has emerged to show long term adverse effects of Efavirenz(EFV). This study assesses the adverse effect profile of TEE by determining the event rate of switching from co-formulation and the reason for such switch. Method: This retrospective cohort study involved the review of the records of HIV infected adults receiving the TEE fixed dose combination ART over a 5-year period. All adult patients 18 years age or above, non-pregnant, previous ART treatment naïve that started TEE during 1 September 2014 and 31 August 2019 were included. Follow-up was censored at first drug change, transfer-out, loss-of-follow-upon deaths. Results: Two-thousand-and-ninety subjects were newly initiated on ART and 1961 met the inclusion criteria. Ninety-four patients (4.8%) had drug-changes prior censor date whereas 1867 remained on TEE. Forty-seven (50%) were single drug changes due to adverse effects and the other 50% were regimen changes as result of virological failure. The median time to change for TDF and EFV were 0,24 and 1,26 person years respectively. The median time to change for virological failure was 1,02 years. Patients with baseline CD4 count less than 200 cells/uL has higher risk of switch event. The proportion of poor outcome (death or loss to follow up) in patients with no drug switches (8,78%) was similar to those of patients with drug changes(8,5%). Conclusion: Tenofovir-Emtricitabine-Efavirenz combination treatment remains an excellent first-line ART option for people living with HIV, with a low rate of substitutions due to toxicity and high virological suppression. With the advent of Tenofovir-Lamivudine-Dolutegravir combination regimen as the preferred first-line, clinicians should remain cognisant of Tenofovir adverse drug effects.
Open Access
SARS-CoV-2 Infection Is Associated with Uncontrolled HIV Viral Load in Non-Hospitalized HIV-Infected Patients from Gugulethu, South Africa
(2022-06-03) Lambarey, Humaira; Blumenthal, Melissa J; Chetram, Abeen; Joyimbana, Wendy; Jennings, Lauren; Tincho, Marius B; Burgers, Wendy A; Orrell, Catherine; Schäfer, Georgia
In South Africa, high exposure to SARS-CoV-2 occurs primarily in densely populated, low-income communities, which are additionally burdened by highly prevalent Human Immunodeficiency Virus (HIV). With the aim to assess SARS-CoV-2 seroprevalence and its association with HIV-related clinical parameters in non-hospitalized patients likely to be highly exposed to SARS-CoV-2, this observational cross-sectional study was conducted at the Gugulethu Community Health Centre Antiretroviral clinic between October 2020 and June 2021, after the first COVID-19 wave in South Africa and during the second and beginning of the third wave. A total of 150 adult (median age 39 years [range 20–65 years]) HIV-infected patients (69% female; 31% male) were recruited. 95.3% of the cohort was on antiretroviral therapy (ART), had a median CD4 count of 220 cells/µL (range 17–604 cells/µL) and a median HIV viral load (VL) of 49 copies/mL (range 1–1,050,867 copies/mL). Furthermore, 106 patients (70.7%) were SARS-CoV-2 seropositive, and 0% were vaccinated. When stratified for HIV VL, patients with uncontrolled HIV viremia (HIV VL > 1000 copies/mL) had significantly higher odds of SARS-CoV-2 seropositivity than patients with HIV VL < 1000 copies/mL, after adjusting for age, sex and ART status (p = 0.035, adjusted OR 2.961 [95% CI: 1.078–8.133]). Although the cause–effect relationship could not be determined due to the cross-sectional study design, these results point towards a higher risk of SARS-CoV-2 susceptibility among viremic HIV patients, or impaired HIV viral control due to previous co-infection with SARS-CoV-2.