Evaluation of a training intervention to improve cancer care in Zimbabwe: Strategies to Improve Kaposi Sarcoma Outcomes (SIKO), a prospective community-based stepped-wedge cluster randomized trial

Katherine R Sabourin, Margaret Borok, Samantha Mawhinney, Maxwell Matimba, Francis Jaji, Suzanne Fiorillo, Dickson D Chifamba, Claudios Muserere, Busisiwe Mashiri, Chenjerai Bhodheni, Patricia Gambiza, Rachael Mandidewa, Mercia Mutimuri, Ivy Gudza, Matthew Mulvahill, Camille M Moore, Jean S Kutner, Eric A F Simões, Thomas B Campbell, Katherine R Sabourin, Margaret Borok, Samantha Mawhinney, Maxwell Matimba, Francis Jaji, Suzanne Fiorillo, Dickson D Chifamba, Claudios Muserere, Busisiwe Mashiri, Chenjerai Bhodheni, Patricia Gambiza, Rachael Mandidewa, Mercia Mutimuri, Ivy Gudza, Matthew Mulvahill, Camille M Moore, Jean S Kutner, Eric A F Simões, Thomas B Campbell

Abstract

Introduction: Most Zimbabweans access medical care through tiered health systems. In 2013, HIV care was decentralized to primary care clinics; while oncology care remained centralized. Most persons in Zimbabwe with Kaposi sarcoma (KS) are diagnosed late in their disease, and the prognosis is poor. Little is known about whether educational interventions could improve KS outcomes in these settings.

Methods: Interventions to improve KS detection and management were evaluated at eight Zimbabwe primary care sites (four rural/four urban) that provided HIV care. Interventions included a standardized KS clinical evaluation tool, palliative care integration, standardized treatment and improved consultative services. Interventions were implemented between February 2013 and January 2016 using a randomized stepped-wedge cluster design. Sites were monitored for KS diagnosis rates and KS outcomes, including early diagnosis (T0 vs. T1 tumour stage), participant retention and mortality. Analyses controlled for within-clinic correlations.

Results: A total of 1102 persons with suspected KS (96% HIV positive) were enrolled: 47% incident (new diagnosis), 20% prevalent (previous diagnosis) and 33% determined as not KS. Early (T0) diagnosis increased post-intervention, though not significant statistically (adjusted odds ratio [aOR] = 1.48 [95% confidence interval (95% CI): 0.66-3.79], p = 0.37). New KS diagnosis rates increased 103% (95% CI: 11-273%), p = 0.02) post-intervention; although paired with an increased odds of incorrectly diagnosing KS (aOR = 2.08 [95% CI: 0.33-3.24], p = 0.001). Post-intervention, non-significant decreases in 90-day return rates (adjusted hazard ratio [aHR] = 0.69 [95% CI: 0.38-1.45], p = 0.21) and survival (aHR = 1.36 [95% CI: 0.85-2.20], p = 0.20) were estimated.

Conclusions: KS training interventions at urban and rural Zimbabwe decentralized primary care clinics significantly increased overall and incorrect KS diagnosis rates, but not early KS diagnosis rates, 90-day return rates or survival.

Trial registration: ClinicalTrials.gov NCT01764360.

Keywords: HIV; KS; Kaposi sarcoma; palliative care; primary community care; training intervention tools.

Conflict of interest statement

No competing interests were reported by any authors.

© 2022 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.

Figures

Figure 1
Figure 1
Timeline for study implementation and completion for randomized stepped‐wedge cluster trial. Each site was monitored for Kaposi sarcoma diagnoses and outcomes throughout the entire study period (evaluation period, weeks 0–150). The light‐shaded area shows the time when each of the eight sites was monitored prior to implementation of the Intervention Package (pre‐intervention period). The dark‐shaded area shows the time when sites were monitored after the implementation of the Intervention Package (intervention period). The time of intervention implementation was randomly assigned for each site; because the Urban‐1, Urban‐2 and Urban‐4 sites are in close geographic proximity, and share staff and patients, these three sites were randomized as a cluster. The Urban‐3 site was the first site to begin the intervention at week 15. The last site to begin the intervention was the Rural‐1 site at week 64.
Figure 2
Figure 2
Effect of the training intervention on Kaposi sarcoma (KS) diagnosis rate. The proportion of all weekly HIV clinic visits that were patients with a suspected KS diagnosis is shown for the duration of the study period for each site. Vertical dashed lines indicate the time that the training intervention was introduced. Sites are grouped by urban (left panel) and rural locations (right panel). The tick mark rug indicates study enrolment times for confirmed KS cases (black tick marks) and participants initially identified as having KS but later determined to not have KS by expert opinion (grey tick marks).
Figure 3
Figure 3
Diagram for identification of Kaposi sarcoma (KS) cases. A total of 1102 suspected cases of KS were evaluated during the combined pre‐intervention and intervention periods: 358 were determined to not be KS by expert opinion. Of the 744 confirmed KS cases, in 224 cases, the diagnosis of KS was made prior to study week 0. Of the 520 confirmed KS cases diagnosed after week 0, 74 were diagnosed during the pre‐intervention period and 446 during the intervention period.
Figure 4
Figure 4
Kaposi sarcoma (KS) diagnoses relative to the time of implementation of the intervention for each clinic. Time of diagnosis is shown for the 520 new confirmed KS cases relative to the time of the intervention at each site (vertical shaded line). Filled circles are ACTG stage T0 KS; empty circles are ACTG stage T1. The proportion of T0 diagnosis in each period is shown.
Figure 5
Figure 5
Adjusted Cox proportional hazards model of survival. Adjusted Cox proportional hazards model of survival of new (incident) Kaposi sarcoma (KS) cases by pre‐ and post‐intervention status (denoted by line width) with stratification by enrolment at a rural (vs. urban) clinic and tuberculosis status (denoted by colour). Adjustment covariates age, sex and time since HIV diagnosis were set to median values (age = 37 years, sex = male, time from HIV to KS = 0.92 years) with separate graphs for T0 and T1 status. Only the 520 confirmed incident (newly diagnosed) KS cases were included in the analysis. Censoring occurred at the maximum clinic visit.

References

    1. Chokunonga E, Borok MZ, Chingonzoh T, Chirenje ZM, Makunike‐Mutsa R, Manangazira P, et al. Pattern of cancer in Zimbabwe in 2016. Zimbabwe National Cancer Registry (ZNCR); 2018.
    1. Nelson BC, Borok MZ, Mhlanga TO, Makadzange AT, Campbell TB. AIDS‐associated Kaposi sarcoma: outcomes after initiation of antiretroviral therapy at a university‐affiliated hospital in urban Zimbabwe. Int J Infect Dis. 2013;17:e902–6.
    1. Kingham TP, Alatise OI, Vanderpuye V, Casper C, Abantanga FA, Kamara TB, et al. Treatment of cancer in sub‐Saharan Africa. Lancet Oncol. 2013;14:e158‐67.
    1. Singogo E, Keegan TJ, Diggle PJ, van Lettow M, Matengeni A, van Oosterhout JJ, et al. Differences in survival among adults with HIV‐associated Kaposi's sarcoma during routine HIV treatment initiation in Zomba district, Malawi: a retrospective cohort analysis. Int Health. 2017;9:281‐7.
    1. Borok M, Fiorillo S, Gudza I, Putnam B, Ndemera B, White IE, et al. Evaluation of plasma human herpesvirus 8 DNA as a marker of clinical outcomes during antiretroviral therapy for AIDS‐related Kaposi sarcoma in Zimbabwe. Clin Infect Dis. 2010;51:342‐9.
    1. Bekolo CE, Soumah MM, Tiemtore OW, Diallo A, Yuma JD, Di Stefano L, et al. Assessing the outcomes of HIV‐infected persons receiving treatment for Kaposi sarcoma in Conakry‐Guinea. BMC Cancer. 2017;17:806.
    1. Sengayi MM, Kielkowski D, Egger M, Dreosti L, Bohlius J. Survival of patients with Kaposi's sarcoma in the South African antiretroviral treatment era: a retrospective cohort study. S Afr Med J. 2017;107:871‐6.
    1. Chu K, Misinde D, Massaquoi M, Pasulani O, Mwagomba B, Ford N, et al. Risk factors for mortality in AIDS‐associated Kaposi sarcoma in a primary care antiretroviral treatment program in Malawi. Int Health. 2010;2:99‐102.
    1. Chu KM, Mahlangeni G, Swannet S, Ford NP, Boulle A, Van Cutsem G. AIDS‐associated Kaposi's sarcoma is linked to advanced disease and high mortality in a primary care HIV programme in South Africa. J Int AIDS Soc. 2010;13:23.
    1. World Health Organization . Summary country profile for HIV/AIDS treatment scale‐up ‐ Zimbabwe. World Health Organization. 2005.
    1. Challinor JM, Galassi AL, Al‐Ruzzieh MA, Bigirimana JB, Buswell L, So WKW, et al. Nursing's potential to address the growing cancer burden in low‐ and middle‐income countries. J Glob Oncol. 2016;2:154‐63.
    1. Borok M, Hakim J, Kutner J, Mawhinney S, Simoes E, Campbell T. Strategies to Improve Kaposi Sarcoma Outcomes (SIKO): an educational intervention in Zimbabwe. Cancer Control; 2014.
    1. Hemming K, Lilford R, Girling AJ. Stepped‐wedge cluster randomised controlled trials: a generic framework including parallel and multiple‐level designs. Stat Med. 2015;34:181‐96.
    1. Hussey MA, Hughes JP. Design and analysis of stepped wedge cluster randomized trials. Contemp Clin Trials. 2007;28:182‐91.
    1. Sessions M . Overview of the President's Emergency Plan for AIDS Relief (PEPFAR). 2021. [cited 2021 Jan 25] .
    1. Ely S, Gapara M, Lammersen K, Darden J, Borok M, Hosseinipour MC, et al. Pathology External Quality Assurance Program for Kaposi's Sarcoma International Clinical Trials AMC‐067/A5264 and AMC‐066/A5263. 15th International Conference on Malignancies in AIDS and Other Acquired Immunodeficiencies (ICMAOI). Bethesda, MD; 2015.
    1. Krown SE, Metroka C, Wernz JC. Kaposi's sarcoma in the acquired immune deficiency syndrome: a proposal for uniform evaluation, response, and staging criteria. AIDS Clinical Trials Group Oncology Committee. J Clin Oncol. 1989;7:1201‐7.
    1. Zurcher K, Mooser A, Anderegg N, Tymejczyk O, Couvillon MJ, Nash D, et al. Outcomes of HIV‐positive patients lost to follow‐up in African treatment programmes. Trop Med Int Health. 2017;22:375‐87.
    1. Fardhdiani V, Molfino L, Zamudio AG, Manuel R, Luciano G, Ciglenecki I, et al. HIV‐associated Kaposi's sarcoma in Maputo, Mozambique: outcomes in a specialized treatment center, 2010–2015. Infect Agent Cancer. 2018;13:5.
    1. Burger H, Ismail Z, Taljaard JJ. Establishing a multidisciplinary AIDS‐associated Kaposi's sarcoma clinic: patient characteristics, management and outcomes. S Afr Med J. 2018;108:1059‐65.
    1. Herce ME, Kalanga N, Wroe EB, Keck JW, Chingoli F, Tengatenga L, et al. Excellent clinical outcomes and retention in care for adults with HIV‐associated Kaposi sarcoma treated with systemic chemotherapy and integrated antiretroviral therapy in rural Malawi. J Int AIDS Soc. 2015;18:19929.
    1. Harris B, Goudge J, Ataguba JE, McIntyre D, Nxumalo N, Jikwana S, et al. Inequities in access to health care in South Africa. J Public Health Policy. 2011;32(Suppl 1):S102‐23.
    1. Goudge J, Gilson L, Russell S, Gumede T, Mills A. Affordability, availability and acceptability barriers to health care for the chronically ill: longitudinal case studies from South Africa. BMC Health Serv Res. 2009;9:75.
    1. Amerson E, Buziba N, Wabinga H, Wenger M, Bwana M, Muyindike W, et al. Diagnosing Kaposi's sarcoma (KS) in East Africa: how accurate are clinicians and pathologists? Infect Agent Cancer. 2012;7(Suppl 1):P6.
    1. Yaqub S, Stepenaskie SA, Farshami FJ, Sibbitt WL Jr, Fangtham M, Emil NS, et al. Kaposi sarcoma as a cutaneous vasculitis mimic: diagnosis and treatment. J Clin Aesthet Dermatol. 2019;12:23‐6.
    1. van Bogaert L‐J. Clinicopathological proficiency in the diagnosis of Kaposi's sarcoma. ISRN AIDS. 2012;2012:565463.
    1. Maskew M, Fox MP, van Cutsem G, Chu K, MacPhail P, Boulle A, et al. Treatment response and mortality among patients starting antiretroviral therapy with and without Kaposi sarcoma: a cohort study. PLoS One. 2013;8:e64392.
    1. Amerson E, Woodruff CM, Forrestel A, Wenger M, McCalmont T, LeBoit P, et al. Accuracy of clinical suspicion and pathologic diagnosis of Kaposi sarcoma in East Africa. J Acquir Immune Defic Syndr. 2016;71:295‐301.
    1. Slaught C, Williams V, Grover S, Bigger E, Kayembe M, Chiyapo S, et al. A retrospective review of patients with Kaposi's sarcoma in Botswana. Int J Dermatol. 2019;58:707‐12.
    1. Tsang MW, Kovarik CL. The role of dermatopathology in conjunction with teledermatology in resource‐limited settings: lessons from the African Teledermatology Project. Int J Dermatol. 2011;50:150‐6.
    1. Okuku F, Krantz EM, Kafeero J, Kamya MR, Orem J, Casper C, et al. Evaluation of a predictive staging model for HIV‐associated Kaposi sarcoma in Uganda. J Acquir Immune Defic Syndr. 2017;74:548‐54.
    1. Letang E, Lewis JJ, Bower M, Mosam A, Borok M, Campbell TB, et al. Immune reconstitution inflammatory syndrome associated with Kaposi sarcoma: higher incidence and mortality in Africa than in the UK. AIDS. 2013;27:1603‐13.
    1. Mosam A, Shaik F, Uldrick TS, Esterhuizen T, Friedland GH, Scadden DT, et al. A randomized controlled trial of highly active antiretroviral therapy versus highly active antiretroviral therapy and chemotherapy in therapy‐naive patients with HIV‐associated Kaposi sarcoma in South Africa. J Acquir Immune Defic Syndr. 2012;60:150‐7.

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