Browsing by Author "Leisegang, Rory"
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- ItemOpen AccessComparison 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, GaryBackground: 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
- ItemOpen AccessEarly and late direct costs in a Southern African antiretroviral treatment programme: a retrospective cohort analysis(Public Library of Science, 2009) Leisegang, Rory; Cleary, Susan; Hislop, Michael; Davidse, Alistair; Regensberg, Leon; Little, Francesca; Maartens, GaryGary Maartens and colleagues describe the direct heath care costs and identify the drivers of cost over time in an HIV managed care program in Southern Africa.
- ItemOpen AccessFactors influencing retention in care after starting antiretroviral therapy in a rural South African programme(Public Library of Science, 2011) Boyles, Tom H; Wilkinson, Lynne S; Leisegang, Rory; Maartens, GaryThe prognosis of patients with HIV in Africa has improved with the widespread use of antiretroviral therapy (ART) but these successes are threatened by low rates of long-term retention in care. There are limited data on predictors of retention in care, particularly from rural sites. METHODS: Prospective cohort analysis of outcome measures in adults from a rural HIV care programme in Madwaleni, Eastern Cape, South Africa. The ART programme operates from Madwaleni hospital and seven primary care feeder clinics with full integration between inpatient and outpatient services. Outreach workers conducted home visits for defaulters. RESULTS: 1803 adults initiated ART from June 2005 to May 2009. At the end of the study period 82.4% were in active care or had transferred elsewhere, 11.1% had died and 6.5% were lost to follow-up (LTFU). Independent predictors associated with an increased risk of LTFU were CD4 nadir >200, initiating ART as an inpatient or while pregnant, and younger age, while being in care for >6 months before initiating ART was associated with a reduced risk. Independent factors associated with an increased risk of mortality were baseline CD4 count <50 and initiating ART as an inpatient, while being in care for >6 months before initiating ART and initiating ART while pregnant were associated with a reduced risk. CONCLUSIONS: Serving a socioeconomically deprived rural population is not a barrier to successful ART delivery. Patients initiating ART while pregnant and inpatients may require additional counselling and support to reduce LTFU. Providing HIV care for patients not yet eligible for ART may be protective against being LTFU and dying after ART initiation.
- ItemOpen AccessImproving the evidence base of Markov models used to estimate the costs of scaling up antiretroviral programmes in resource-limited settings(BioMed Central Ltd, 2010) Leisegang, Rory; Maartens, Gary; Hislop, Michael; Regensberg, Leon; Cleary, SusanBACKGROUND: Despite concerns about affordability and sustainability, many models of the lifetime costs of antiretroviral therapy (ART) used in resource limited settings are based on data from small research cohorts, together with pragmatic assumptions about life-expectancy. This paper revisits these modelling assumptions in order to provide input to future attempts to model the lifetime costs and the costs of scaling up ART. METHODS: We analysed the determinants of costs and outcomes in patients receiving ART in line with standard World Health Organization (WHO) guidelines for resource poor settings in a private sector managed ART programme in South Africa. The cohort included over 5,000 patients with up to 4 years (median 19 months) on ART. Generalized linear and Cox proportional hazards regression models were used to establish cost and outcome determinants respectively. RESULTS: The key variables associated with changes in mean monthly costs were: being on the second line regimen; receiving ART from 4 months prior to 4 months post treatment initiation; having a recent or current CD4 count <50 cells/uL or 50-199 cells/ul; having mean ART adherence <75% as determined by monthly pharmacy refill data; and having a current or recent viral load >100,000 copies/mL. In terms of the likelihood of dying, the key variables were: baseline CD4 count<50 cells/ul (particularly during the first 4 months on treatment); current CD4 count <50 cells/ul and 50-199 cells/ul (particularly during later periods on treatment); and being on the second line regimen. Being poorly adherent and having an unsuppressed viral load was also associated with a higher likelihood of dying. CONCLUSIONS: While there are many unknowns associated with modelling the resources needed to scale-up ART, our analysis has suggested a number of key variables which can be used to improve the state of the art of modelling ART. While the magnitude of the effects associated with these variables would be likely to differ in other settings, the variables influencing costs and survival are likely to be generalizable. This is of direct relevance to those concerned about assessing the long-term costs and sustainability of expanded access to ART.
- ItemOpen AccessA novel Markov model projecting costs and outcomes of providing antiretroviral therapy to public patients in private practices versus public clinics in south Africa(Public Library of Science, 2013) Leisegang, Rory; Maartens, Gary; Hislop, Michael; Sargent, John; Darkoh, Ernest; Cleary, SusanIntroduction Providing private antiretroviral therapy (ART) care for public sector patients could increase access to ART in low- and middle-income countries. We compared the costs and outcomes of a private-care and a public-care ART program in South Africa. METHODS: A novel Markov model was developed from the public-care program. Patients were first tunneled for 6 months in their baseline CD4 category before being distributed into a dynamic CD4 and viral load model. Patients were allowed to return to ART care from loss to follow up (LTFU). We then populated this modeling framework with estimates derived from the private-care program to externally validate the model. RESULTS: Baseline characteristics were similar in the two programs. Clinic visit utilization was higher and death rates were lower in the first few years on ART in the public-care program. After 10 years on ART we estimated the following outcomes in the public-care and private-care programs respectively: viral load <1000 copies/ml 89% and 84%, CD4 >500 cells/μl 33% and 37%, LTFU 14% and 14%, and death 27% and 32%. Lifetime undiscounted survival estimates were 14.1 (95%CI 13.2-14.9) and (95%CI 12.7-14.5) years with costs of 18,734 (95%CI 12,588-14,022) and 13,062 (95%CI 12,077-14,047) USD in the private-care and public-care programs respectively. When clinic visit utilization in the public-care program was reduced by two thirds after the initial 6 months on ART, which is similar to their current practice, the costs were comparable between the programs. CONCLUSIONS: Using a novel Markov model, we determined that the private-care program had similar outcomes but lower costs than the public-care program, largely due to lower visit frequencies. These findings have important implications for increasing and sustaining coverage of patients in need of ART care in resource-limited settings.
- ItemOpen AccessOutcomes and cost-effectiveness of different models of delivery of antiretroviral therapy(2018) Leisegang, Rory; Maartens, Gary; Cleary, SusanBackground: HIV remains a major contributor to the burden of disease in the Eastern and Southern African region, where around half of those with HIV/AIDS reside, according to the 2016 UNAIDS estimates. Data on the direct costs and outcomes of providing health care are important due to competing health needs and limited budgets in resource-limited settings, especially if we are to reach the UNAIDS 90-90-90 goals. This thesis presents a series of studies, which together represent the typical journey followed within an economic evaluation, starting with the establishment of a cohort, then onto cost and outcome analyses and, finally, the development of a Markov model for the purpose of establishing the cost-effectiveness of a particular intervention. Methods: Data for this thesis come from several cohorts within South Africa, with patients commencing ART between 1998 and 2014, and with care provided within a number of different models: private (Aid for AIDS), public-private partnerships or PPP (BroadReach), and public sector (Khayelitsha). The study design for all were retrospective cohort analyses. These cohorts had important strengths in their data: adherence measures (private, PPP); initiating ART at CD4 counts > 200 cells/µL (private); detailed cost data (private); long duration of follow-up with a larger proportion on second-line ART (private); ability to assess health care utilization pre-ART and in patient loss to ART follow-up (private); and availability of national identity numbers, allowing us to confirm mortality from national death register data (private, PPP). Results: The results sections of this thesis are presented in the form of published papers and chapters. In the first analysis (Chapter 4), we present a cohort profile for Aid for AIDS, where we describe the history of the programme and contrast it with the public sector programme in South Africa. In the second analysis (Chapter 5), we present a paper highlighting the profile and determinants of costs on ART over time in the private cohort. We draw attention to the impact of baseline stage and adherence to ART on early and late costs respectively. In the third analysis (Chapter 6), we explore different models of HIV care: GP versus clinic for public sector patients and courier versus collect pharmacy for private sector patients. In the third analysis (Chapter 7), we present a paper which reviews cost-effectiveness studies in LMICs and explores the relative impact of various factors on costs and mortality in preparation for the final analysis (Chapter 8), which required the development of a novel HIV Markov model. Conclusion: Interventions, such as public-private partnerships with GPs or home-refill by courier, which we have found to be associated with lower costs and improved outcomes respectively, should be considered for implementation in South Africa, especially in light of the proposed National Health Insurance. The focus of this thesis on models of ART delivery and the inclusion of under-represented or novel models are significant strengths.
- ItemOpen AccessShort term adherence tool predicts failure on second line protease inhibitor-based antiretroviral therapy: an observational cohort study(BioMed Central, 2014-12-04) Court, Richard; Leisegang, Rory; Stewart, Annemie; Sunpath, Henry; Murphy, Richard; Winternheimer, Philip; Ally, Mashuda; Maartens, GaryBackground: Most patients who experience virologic failure (VF) on second line antiretroviral therapy (ART) in low-middle income countries fail due to poor adherence rather than antiretroviral resistance. A simple adherence tool designed to detect VF would conserve resources by rationally limiting need for viral load (VL) testing and, in those countries with access to third line ART, the need for resistance testing. Methods: We conducted an observational cohort study of patients who initiated second line ART at a clinic in Kwazulu-Natal, South Africa. Using clinical and pharmacy refill data extracted from the clinic’s electronic database, we determined risk factors for VF. Three different methods of calculating short term pharmacy refill adherence were evaluated and compared with long term adherence since second line initiation. We also explored the ability of differing durations of short term pharmacy refill to predict VF on second line ART. Results: We included 274 patients with a median follow up of 27 months on second line ART. VF ranged between 3% and 16% within each six month interval after initiating second line ART. 243 patients with at least one VL after 4 months on second line were analysed in the statistical analysis. Pharmacy refill adherence assessed over shorter periods (4 to 6 months) predicted virologic suppression as well as pharmacy refill assessed over longer periods. The risk of VF fell 73% with each 10% increase in adherence measured from pharmacy refills over a 4 month period. Low CD4 count at second line ART initiation was a significant independent risk factor for VF. Conclusion: Patients identified as poorly adherent by short term pharmacy refill are at risk for VF on second line ART. This pragmatic adherence tool could assist in identifying patients who require adherence interventions, and help rationalize use of VL monitoring and resistance testing among patients on second line ART.