Point-of-care viral load monitoring: outcomes from a decentralized HIV programme in Malawi

Sarala Nicholas, Elisabeth Poulet, Liselotte Wolters, Johanna Wapling, Ankur Rakesh, Isabel Amoros, Elisabeth Szumilin, Monique Gueguen, Birgit Schramm, Sarala Nicholas, Elisabeth Poulet, Liselotte Wolters, Johanna Wapling, Ankur Rakesh, Isabel Amoros, Elisabeth Szumilin, Monique Gueguen, Birgit Schramm

Abstract

Introduction: Routinely monitoring the HIV viral load (VL) of people living with HIV (PLHIV) on anti-retroviral therapy (ART) facilitates intensive adherence counselling and faster ART regimen switch when treatment failure is indicated. Yet standard VL-testing in centralized laboratories can be time-intensive and logistically difficult in low-resource settings. This paper evaluates the outcomes of the first four years of routine VL-monitoring using Point-of-Care technology, implemented by Médecins Sans Frontières (MSF) in rural clinics in Malawi.

Methods: We conducted a retrospective cohort analysis of patients eligible for routine VL- testing between 2013 and 2017 in four decentralized ART-clinics and the district hospital in Chiradzulu, Malawi. We assessed VL-testing coverage and the treatment failure cascade (from suspected failure (first VL>1000 copies/mL) to VL suppression post regimen switch). We used descriptive statistics and multivariate logistic regression to assess factors associated with suspected failure.

Results and discussion: Among 21,400 eligible patients, VL-testing coverage was 85% and VL suppression was found in 89% of those tested. In the decentralized clinics, 88% of test results were reviewed on the same day as blood collection, whereas in the district hospital the median turnaround-time for results was 85 days. Among first-line ART patients with suspected failure (N = 1544), 30% suppressed (VL<1000 copies/mL), 35% were treatment failures (confirmed by subsequent VL-testing) and 35% had incomplete VL follow-up. Among treatment failures, 80% (N = 540) were switched to a second-line regimen, with a higher switching rate in the decentralized clinics than in the district hospital (86% vs. 67%, p < 0.01) and a shorter median time-to-switch (6.8 months vs. 9.7 months, p < 0.01). Similarly, the post-switch VL-testing rate was markedly higher in the decentralized clinics (61% vs. 26%, p < 0.01). Overall, 79% of patients with a post-switch VL-test were suppressed.

Conclusions: Viral load testing at the point-of-care in Chiradzulu, Malawi achieved high coverage and good drug regimen switch rates among those identified as treatment failures. In decentralized clinics, same-day test results and shorter time-to-switch illustrated the game-changing potential of POC-based VL-testing. Nevertheless, gaps were identified along all steps of the failure cascade. Regular staff training, continuous monitoring and creating demand are essential to the success of routine VL-testing.

Keywords: HIV; 90-90-90; Decentralization; HIV Care Continuum; Health System Strengthening; Treatment failure; Treatment monitoring.

© 2019 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
Flowchart of patients eligible for VL test and selected for analysis.
Figure 2
Figure 2
Turnaround time (in days) from sample collection to clinical review of VL test result by site.
Figure 3
Figure 3
Treatment failure cascade among suspect‐failure patients on first‐line ART within 18 months of the first VL test, and the percent (%) who received a follow‐up VL test or a regimen switch according to the adapted MOH treatment failure algorithm.

References

    1. WHO . Consolidated ARV guidelines 2013. Vol. 14, Geneva: World Health Organization; 2013.
    1. WHO . HIV drug resistance. Global report on early warning indicators of HIV drug resistance. 2016.
    1. Sigaloff KC, Hamers RL, Wallis CL, Kityo C, Siwale M, Ive P, et al. Unnecessary antiretroviral treatment switches and accumulation of HIV resistance mutations: two arguments for viral load monitoring in Africa. J Acquir Immune Defic Syndr. 2011;58(1):23–31.
    1. Rewari BB, Bachani D, Rajasekaran S, Deshpande A, Chan PL, Srikantiah P. Evaluating patients for second‐line antiretroviral therapy in India: the role of targeted viral load testing. J Acquir Immune Defic Syndr. 2010;55:610–4.
    1. Rawizza HE, Chaplin B, Meloni ST, Eisen G, Rao T, Sankalé JL, et al. Immunologic criteria are poor predictors of virologic outcome: implications for HIV treatment monitoring in resource‐limited settings. Clin Infect Dis. 2011;53(12):1283–90.
    1. Bonner K, Mezochow A, Roberts T, Ford N, Cohn J. Viral load monitoring as a tool to reinforce adherence: a systematic review. J Acquir Immune Defic Syndr. 2013;64(1):74–8.
    1. Kanapathipillai R, McGuire M, Mogha R, Szumilin E, Heinzelmann A, Pujades‐Rodríguez M. Benefit of viral load testing for confirmation of immunological failure in HIV patients treated in rural Malawi. Trop Med Int Health. 2011;16(12):1495–500.
    1. Haas AD, Keiser O, Balestre E, Brown S, Bissagnene E, Chimbetete C, et al. Monitoring and switching of first‐line antiretroviral therapy in adult treatment cohorts in sub‐Saharan Africa: collaborative analysis. Lancet HIV. 2015;2(7):e271–8.
    1. Wilson D, Keiluhu AK, Kogrum S, Reid T, Seriratana N, Ford N, et al. HIV‐1 viral load monitoring: an opportunity to reinforce treatment adherence in a resource‐limited setting in Thailand. Trans R Soc Trop Med Hyg. 2009;103(6):601–6.
    1. Horter S, Simelane‐Mahlinza L, Dlamini V, Kourline T, Kerschberger B, Stringer B, et al. Viral load monitoring: how do HIV‐positive patients interpret and understand their results? In: MSF UK Scientific Day. 2015.
    1. UNAIDS (Joint United Nations Programme on HIV/AIDS) . Fast‐Track Ending the AIDS epidemic by 2030. UNAIDS. 2014.
    1. Phillips A, Shroufi A, Vojnov L, Cohn J, Roberts T, Ellman T, et al. Sustainable HIV treatment in Africa through viral‐load‐informed differentiated care. Nature. 2015;528(7580):S68–76.
    1. Keiser O, Chi BH, Gsponer T, Boulle A, Orrell C, Phiri S, et al. Outcomes of antiretroviral treatment in programmes with and without routine viral load monitoring in Southern Africa. AIDS. 2011;25(14):1761–9.
    1. Calmy A, Ford N, Hirschel B, Reynolds SJ, Lynen L, Goemaere E, et al. HIV viral load monitoring in resource‐limited regions: optional or necessary? Clin Infec Dis. 2007;44(1):128–34.
    1. Stevens WS, Marshall TM. Challenges in implementing HIV load testing in South Africa. J Infect Dis. 2010;201 Suppl 1:S78–84.
    1. Usdin M, Guillerm M, Calmy A. Patient needs and point‐of‐care requirements for HIV load testing in resource‐limited settings. J Infect Dis. 2010;201 Suppl 1:S73–7.
    1. Lecher S, Ellenberger D, Kim AAAA, Fonjungo PNPN, Agolory S, Borget MYMY, et al. Scale‐up of HIV viral load monitoring – seven Sub‐Saharan African countries. MMWR Morb Mortal Wkly Rep. 2015;64(46):1287–90.
    1. Roberts T, Cohn J, Bonner K, Hargreaves S. Scale‐up of routine viral load testing in resource‐poor settings: current and future implementation challenges. Clin Infect Dis. 2016;62(8):1043–8.
    1. Peter T, Ellenberger D, Kim AA, Boeras D, Messele T, Roberts T, et al. Early antiretroviral therapy initiation: access and equity of viral load testing for HIV treatment monitoring. Lancet Infect Dis. 2017;428(4):709–19.
    1. Pham MD, Romero L, Parnell B, Anderson DA, Crowe SM, Luchters S. Feasibility of antiretroviral treatment monitoring in the era of decentralized HIV care: a systematic review. AIDS Res Ther. 2017;14(1):3.
    1. Ehrenkranz PD, Baptiste SL, Bygrave H, Ellman T, Doi N, Grimsrud A, et al. The missed potential of CD4 and viral load testing to improve clinical outcomes for people living with HIV in lower‐resource settings. PLoS Med. 2019;16:e1002820.
    1. WHO . 2018 Progress Report Hiv Drug Resistance: Global Action Plan on HIV Drug Resistance 2017–2021. 2018.
    1. Pannus P, Fajardo E, Metcalf C, Coulborn RM, Duran LT, Bygrave H, et al. Pooled HIV‐1 viral load testing using dried blood spots to reduce the cost of monitoring antiretroviral treatment in a resource‐limited setting. J Acquir Immune Defic Syndr. 2013;64(2):134–7.
    1. Roberts T, Bygrave H, Fajardo E, Ford N. Challenges and opportunities for the implementation of virological testing in resource‐limited settings. J Int AIDS Soc. 2012;15(2):17324.
    1. Rutstein SE, Hosseinipour MC, Kamwendo D, Soko A, Mkandawire M, Biddle AK, et al. Dried blood spots for viral load monitoring in malawi: feasible and effective. PLoS One. 2015;10(4):1–17.
    1. Monleau M, Aghokeng AF, Eymard‐Duvernay S, Dagnra A, Kania D, Ngo‐Giang‐Huong N, et al. Field evaluation of dried blood spots for routine HIV‐1 viral load and drug resistance monitoring in patients receiving antiretroviral therapy in Africa and Asia. J Clin Microb. 2014;52(2):578–86.
    1. Van Zyl GU, Preiser W, Potschka S, Lundershausen AT, Haubrich R, Smith D. Pooling strategies to reduce the cost of HIV‐1 RNA load monitoring in a resource‐limited setting. Clin Infect Dis. 2011;52(2):264–70.
    1. Laursen L. Point‐of‐care tests poised to alter course of HIV treatment. Nat Med. 2012;18(8):1156.
    1. Aleku GA, Adoga MP, Agwale SM. HIV point‐of‐care diagnostics: meeting the special needs of sub‐Saharan Africa. J Infect Dev Ctries. 2014;8(10):1231–43.
    1. Stevens W, Gous N, Ford N, Scott LE. Feasibility of HIV point‐of‐care tests for resource‐limited settings: challenges and solutions. BMC Med. 2014;12(1):173.
    1. Haleyur Giri Setty MK, Hewlett IK. Point of care technologies for HIV. AIDS Res Treat. 2014;2014:497046.
    1. WHO . Global Action Plan on HIV Drug Resistance 2017‐2021 [Internet]. 2016. [cited 2017 May 2]. Available from:
    1. United National Children's Fund (UNICEF) . Key considerations for introducing HIV Point‐of‐Care Diagnostic Technologies in National Health Systems. 2018.
    1. Dorward J, Drain PK, Garrett N. Point‐of‐care viral load testing and differentiated HIV care. Lancet HIV. 2018;5(1):e8–9.
    1. Medecins Sans Frontieres . Making viral load routine. Successes and challenges in the implementation of routine HIV viral load monitoring. Part 1: Programmatic Strategies [Internet]. 2016. [cited 2018 May 2]. Available from: Report_Web_2016_ENG.pdf
    1. Medecins Sans Frontieres . Making Viral Load Routine: Successes and challenges in the implementation of routine HIV viral load monitoring. Part 2: The Viral Load Laboratory. 2016.
    1. Lee HH, Dineva MA, Chua YL, Ritchie AV, Ushiro‐Lumb I, Wisniewski CA. Simple amplification‐based assay: a nucleic acid‐based point‐of‐care platform for HIV‐1 testing. J Infect Dis. 2010;201 Suppl 1:S65–72.
    1. Ritchie AV, Ushiro‐Lumb I, Edemaga D, Joshi HA, De Ruiter A, Szumilin E, et al. SAMBA HIV semiquantitative test, a new point‐of‐care viral‐load‐monitoring assay for resource‐limited settings. J Clin Microbiol. 2014;52(9):3377–83.
    1. Goel N, Ritchie AV, Mtapuri‐Zinyowera S, Zeh C, Stepchenkova T, Lehga J, et al. Performance of the SAMBA I and II HIV‐1 Semi‐Q Tests for viral load monitoring at the point‐of‐care. J Virol Methods. 2017;244:39–45.
    1. Maman D, Chilima B, Masiku C, Ayouba A, Masson S, Szumilin E, et al. Closer to 90‐90‐90. The cascade of care after 10 years of ART scale‐up in rural Malawi: a population study. J Int AIDS Soc. 2016;19:20673.
    1. Schito M, Peter TF, Cavanaugh S, Piatek AS, Young GJ, Alexander H, et al. Opportunities and challenges for cost‐efficient implementation of new point‐of‐care diagnostics for HIV and tuberculosis. J Infect Dis. 2012;205 Suppl 2:169–80.
    1. CDC . Viral Load And Early Infant Diagnosis Performance Testing [Internet]. [cited 2019 Jun 16]. Available from:
    1. Nguyen S, Ramos A, Chang J, Li B, Shanmugam V, Boeras D, et al. Monitoring the quality of HIV‐1 viral load testing through a proficiency testing program using dried tube specimens in resource‐limited settings. J Clin Microbiol. 2015;53(4):1129–36.
    1. Malawi Ministry of Health . Clinical management of HIV in children and adults. 2011.
    1. Malawi Ministry of Health . Malawi Guidelines for Clinical Management of HIV in Children and Adults (3rd Edition). [Internet]. 2016. [cited 2019 May 15]. Available from:
    1. Malawi Ministry of Health . Malawi Integrated Guidelines and Standard Operating Procedures for Providing HIV Services. [Internet]. 2018. [cited 2019 May 20]. Available from:
    1. Tassie J, Balandine S, Szumilin E, Andrieux‐Meyer I, Biot MCP. FUCHIA: a free computer program for the monitoring of HIV/AIDS medical care at the population level. International AIDS Conference; Barcelona, Spain. 2002. C11029 p.
    1. Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)‐A metadata‐driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009;42(2):377–81.
    1. StataCorp LP . Stata Statistical Software: Release 13. 2013.
    1. Swannet S, Decroo T, de Castro SMTL, Rose C, Giuliani R, Molfino L, et al. Journey towards universal viral load monitoring in Maputo, Mozambique: many gaps, but encouraging signs. Int Health. 2017;9(4):206–14.
    1. Jobanputra K, Parker LA, Azih C, Okello V, Maphalala G, Jouquet G, et al. Impact and programmatic implications of routine viral load monitoring in Swaziland. J Acquir Immune Defic Syndr. 2014;67(1):45–51.
    1. PEPFAR . Malawi Country Operational Plan COP 2018 Strategic Direction Summary [Internet]. 2018. [cited 2019 Jun 10]. Available from:
    1. Gibb J, Chitsulo J, Chipungu C, Chivwara M, Schooley A, Hoffman RM. Supporting quality data systems: lessons learned from early implementation of routine viral load monitoring at a large clinic in Lilongwe, Malawi. J Clin Res HIV AIDS Prev. 2017;3(1):1–9.
    1. Labhardt ND, Ringera I, Lejone TI, Cheleboi M, Wagner S, Muhairwe J, et al. When patients fail UNAIDS' last 90 – The “failure cascade” beyond 90‐90‐90 in rural Lesotho, Southern Africa: a prospective cohort study. J Int AIDS Soc. 2017;20(1):1–10.
    1. ICAP. ICAP Approach to Implementation of Routine Viral Load Monitoring [Internet]. 2017[cited 2019 Jun 10]. Available from:
    1. Mwau M, Syeunda CA, Adhiambo M, Bwana P, Kithinji L, Mwende J, et al. Scale‐up of Kenya's national HIV viral load program: findings and lessons learned. PLoS One. 2018;13(1):1–13.
    1. WHO . HIV Drug Resistance Report [Internet]. 2017. [cited 2018 May 2]. p. 82 pages. Available from:
    1. Secretary for Health and Population . Malawi HIV Policy updates: the government of Malawi's commitment and plan to reach HIV Epidemic control trough 90‐90‐90 in Malawi by 2020. The secretary for health and Population, Lilongwe, Malawi. 21st March 2019. 2019.
    1. Hoare A, Kerr SJ, Ruxrungtham K, Ananworanich J, Law MG, Cooper DA, et al. Hidden drug resistant HIV to emerge in the era of universal treatment access in Southeast Asia. PLoS One. 2010;5(6):1–8.
    1. Johnston V, Fielding KL, Charalambous S, Churchyard G, Phillips A, Grant AD. Outcomes following virological failure and predictors of switching to second‐line antiretroviral therapy in a South African treatment program. J Acquir Immune Defic Syndr. 2012;61(3):370–80.
    1. Madec Y, Leroy S, Rey‐Cuille MA, Huber F, Calmy A. Persistent difficulties in switching to second‐line ART in sub‐Saharan Africa – a systematic review and meta‐analysis. PLoS One. 2013;8:e82724.
    1. Rohr JK, Ive P, Robert Horsburgh C, Berhanu R, Shearer K, Maskew M, et al. Marginal structural models to assess delays in second‐line HIV treatment initiation in South Africa. PLoS One. 2016;11(8):1–11.
    1. Laborde‐Balen G, Taverne B, Ndour CT, Kouanfack C, Peeters M, Ndoye I, et al. The fourth HIV epidemic. Lancet Infect Dis. 2018;18(4):379–80.
    1. Etoori D, Ciglenecki I, Ndlangamandla M, Edwards CG, Jobanputra K, Pasipamire M, et al. Successes and challenges in optimizing the viral load cascade to improve antiretroviral therapy adherence and rationalize second‐line switches in Swaziland. J Int AIDS Soc. 2018;21:e25194.
    1. Minchella PA, Chipungu G, Kim AA, Sarr A, Ali H, Mwenda R, et al. Specimen origin, type and testing laboratory are linked to longer turnaround times for HIV viral load testing in Malawi. PLoS One. 2017;12(2):1–13.
    1. Drain PK, Dorward J, Violette L, Quame‐Amaglo J, Thomas K, Samsunder N, et al. Point‐of‐care Viral Load testing improves HIV viral suppression and retention in care (Abstract Number 53). Seattle, Washington: CROI ; 2019.
    1. WHO . Considerations for Developing a Monitoring and Evaluation Framework for Viral Load Testing [Internet]. 2019. [cited 2019 Jun 12]. p. 1–56. Available from:
    1. Murphy RA, Court R, Maartens G, Sunpath H. Second‐line antiretroviral therapy in sub‐Saharan Africa: it's time to mind the gaps. AIDS Res Hum Retroviruses. 2017;33(12):1181–4.
    1. Rutstein SE, Golin CE., Wheeler SB., Kamwendo D, Hosseinipour MC, Weinberger M, et al. On the front line of HIV virological monitoring: barriers and facilitators from a provider perspective in resource‐limited settings. AIDS Care. 2016;28(1):1–10.
    1. Killingo BM, Taro TB, Mosime WN. Community‐driven demand creation for the use of routine viral load testing: a model to scale up routine viral load testing. J Int AIDS Soc. 2017;20:4–8.
    1. Peter T, Zeh C, Katz Z, Elbireer A, Alemayehu B, Vojnov L, et al. Scaling up HIV viral load – lessons from the large‐scale implementation of HIV early infant diagnosis and CD4 testing. J Int AIDS Soc. 2017;20:9–15.
    1. Shroufi A, Van Cutsem G, Cambiano V, Bansi‐Matharu L, Duncan K, Murphy R, et al. Simplifying switch to second‐line ART: predicted effect of defining failure of first‐line efavirenz‐based regimens in sub‐Saharan Africa by a single viral load more than 1000 copies/ml. AIDS. 2019;33(10):1635–44.

Source: PubMed

3
Abonnieren