Optimizing viral load suppression in Kenyan children on antiretroviral therapy (Opt4Kids)

Rena C Patel, Patrick Oyaro, Beryne Odeny, Irene Mukui, Katherine K Thomas, Monisha Sharma, James Wagude, Eunice Kinywa, Frederick Oluoch, Francesca Odhiambo, Boaz Oyaro, Grace C John-Stewart, Lisa L Abuogi, Rena C Patel, Patrick Oyaro, Beryne Odeny, Irene Mukui, Katherine K Thomas, Monisha Sharma, James Wagude, Eunice Kinywa, Frederick Oluoch, Francesca Odhiambo, Boaz Oyaro, Grace C John-Stewart, Lisa L Abuogi

Abstract

Background: As many as 40% of the 1 million children living with HIV (CLHIV) receiving antiretroviral treatment (ART) in resource limited settings have not achieved viral suppression (VS). Kenya has a large burden of pediatric HIV with nearly 140,000 CLHIV. Feasible, scalable, and cost-effective approaches to ensure VS in CLHIV are urgently needed. The goal of this study is to determine the feasibility and impact of point-of-care (POC) viral load (VL) and targeted drug resistance mutation (DRM) testing to improve VS in children on ART in Kenya.

Methods: We are conducting a randomized controlled study to evaluate the use of POC VL and targeted DRM testing among 704 children aged 1-14 years on ART at health facilities in western Kenya. Children are randomized 1:1 to intervention (higher frequency POC VL and targeted DRM testing) vs. control (standard-of-care) arms and followed for 12 months. Our primary outcome is VS (VL < 1000 copies/mL) 12 months after enrollment by study arm. Secondary outcomes include time to VS and the impact of targeted DRM testing on VS. In addition, key informant interviews with patients and providers will generate an understanding of how the POC VL intervention functions. Finally, we will model the cost-effectiveness of POC VL combined with targeted DRM testing.

Discussion: This study will provide critical information on the impact of POC VL and DRM testing on VS among CLHIV on ART in a resource-limited setting and directly address the need to find approaches that maximize VS among children on ART.

Trials registration: NCT03820323.

Keywords: Antiretroviral therapy; Children; Drug resistance mutations (DRM); HIV; Point-of-care (POC) testing; Viral load.

© 2020 The Authors. Published by Elsevier Inc.

Figures

Fig. 1
Fig. 1
CONSORT flow diagram.
Fig. 2
Fig. 2
Viral load and drug resistance mutation testing algorithm for children on ART by study arm (modified from Kenya MOH ART Guidelines 2018).

References

    1. Boerma R.S., Boender T.S., Bussink A.P. Suboptimal viral suppression rates among HIV-infected children in low- and middle-income countries: a meta-analysis. Clin. Infect. Dis. 2016;63(12):1645–1654.
    1. Boender T.S., Sigaloff K.C., McMahon J.H. Long-term virological outcomes of first-line antiretroviral therapy for HIV-1 in low-and middle-income countries: a systematic review and meta-analysis. Clin. Infect. Dis. 2015;61(9):1453–1461.
    1. Cohen S., Smit C., van Rossum A.M. Long-term response to combination antiretroviral therapy in HIV-infected children in The Netherlands registered from 1996 to 2012. AIDS. 2013;27(16):2567–2575.
    1. UNAIDS. Understanding Fast-Track: Accelerating Action to End the AIDS Epidemic by 2030.
    1. National AIDS Control Council . Kenya Ministry of Health; 2016. Kenya AIDS Response Progress Report 2016. Nairobi, Kenya.
    1. National AIDS and STI Control Programme (NASCOP) Kenya Ministry of Health; Nairobi, Kenya: 2020. Preliminary KENPHIA 2018 Report.
    1. World Health Organization . World Health Organization; Geneva, Switzerland: 2013. Consolidated Guidelines on the Use of Antiretroviral Drugs for Treating and Preventing HIV Infection: Recommendations for a Public Health Approach.
    1. NASCOP . Kenya Ministry of Health; Nairobi, Kenya: 2015. National Plan for Accelerating HIV Care and Treatment 2015-2017.
    1. Lecher S., Williams J., Fonjungo P.N. Progress with scale-up of HIV viral load monitoring—seven sub-Saharan African countries. MMWR (Morb. Mortal. Wkly. Rep.) 2016;65(47):1332–1335. January 2015–June 2016.
    1. Lecher S., Ellenberger D., Kim A.A. Scale-up of HIV viral load monitoring—seven sub-Saharan African countries. MMWR (Morb. Mortal. Wkly. Rep.) 2015;64(46):1287–1290.
    1. NASCOP . Kenya Ministry of Health; Nairobi, Kenya: 2016. Guidelines on Use of Antiretroviral Drugs for Treating and Preventing HIV Infection in Kenya. 2016.
    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. 15 Apr 2016;62(8):1043–1048. doi: 10.1093/cid/ciw001. Epub 2016 Jan 6.
    1. Rutstein S.E., Golin C.E., Wheeler S.B. 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. Kadima J., Patterson E., Mburu M. Adoption of routine virologic testing and predictors of virologic failure among HIV-infected children on antiretroviral treatment in western Kenya. PloS One. 2018;13(11)
    1. Glass T.R., Motaboli L., Nsakala B. The viral load monitoring cascade in a resource-limited setting: a prospective multicentre cohort study after introduction of routine viral load monitoring in rural Lesotho. PloS One. 2019;14(8)
    1. Stevens W.S., Marshall T.M. Challenges in implenting HIV load testing in South Africa. JID (J. Infect. Dis.) 2010;201(Supplement_1):S78–S84.
    1. Hermans L.E., Moorhouse M., Carmona S. Effect of HIV-1 low-level viraemia during antiretroviral therapy on treatment outcomes in WHO-guided South African treatment programmes: a multicentre cohort study. Lancet Infect. Dis. 2018;18(2):188–197.
    1. Etoori D., Ciglenecki I., Ndlangamandla M. 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(10)
    1. Simeon K., Sharma M., Dorward J. Comparative cost analysis of point-of-care versus laboratory-based testing to initiate and monitor HIV treatment in South Africa. PloS One. 2019;14(10)
    1. Phillips A., Shroufi A., Vojnov L. Sustainable HIV treatment in Africa through viral-load-informed differentiated care. Nature. 2015;528(7580):S68–S76.
    1. HIV Drug Resistance Report 2019. World Health Organization; Geneva, Switzerland: 2019. (WHO/CDS/HIV/19.21) (accessed April 2 2020)
    1. Chohan B.H., Tapia K., Benki-Nugent S. Nevirapine resistance in previously nevirapine-unexposed HIV-1-Infected Kenyan infants initiating early antiretroviral therapy. AIDS Res. Hum. Retrovir. 2015;31(8):783–791.
    1. Ndembi N., Hamers R.L., Sigaloff K.C. Transmitted antiretroviral drug resistance among newly HIV-1 diagnosed young individuals in Kampala. AIDS. 2011;25(7):905–910.
    1. Wamalwa D., Lehman D.A., Benki-Nugent S. Long-term virologic response and genotypic resistance mutations in HIV-1 infected Kenyan children on combination antiretroviral therapy. J. Acquir. Immune Defic. Syndr. 1999;62(3):267. 2013.
    1. Crowell C.S., Maiga A.I., Sylla M. High rates of baseline drug resistance and virologic failure among ART naïve HIV-infected children in Mali. Pediatr. Infect. Dis. J. 2017;36(11):e258.
    1. Kuhn L., Hunt G., Technau K.-G. Drug resistance among newly-diagnosed HIV-infected children in the era of more efficacious antiretroviral prophylaxis. AIDS (Lond.) 2014;28(11):1673.
    1. NASCOP . Program NASCOP. Kenya Ministry of Health; Nairobi, Kenya: 2016. Report of the 2013 cross-sectional survey of acquired HIV drug resistance among adults and children on antiretroviral therapy at sentinel sites in Kenya.
    1. Katzenstein D.A. Oxford University Press; 2014. Editorial Commentary: HIV RNA and Genotype in Resource-Limited Settings: Can We Do Better?
    1. Sandbulte M.R., Gautney B.J., Maloba M. Infant HIV testing at birth using point-of-care and conventional HIV DNA PCR: an implementation feasibility pilot study in Kenya. Pilot and feasibility studies. 2019;5:18.
    1. Bwana P., Ageng'o J., Mwau M. Performance and usability of Cepheid GeneXpert HIV-1 qualitative and quantitative assay in Kenya. PloS One. 2019;14(3)
    1. National HIV, Refernce Lab.Standardized Protocol for Method Validation/Verification, Kenya Ministry of Health, Nairobi, Kenya.
    1. NASCOP . Kenya Ministry of Health; Nairobi, Kenya: 2016. Kenya HIV County Profiles.
    1. NASCOP . Kenya Ministry of Health; Nairobi, Kenya: August 2018. Guidelines on Use of Antiretroviral Drugs for Treating and Preventing HIV Infection in Kenya 2018 Edition. Print.
    1. NASCOP . Ministry of Health; Nairobi, Kenya: 2019. New Guidance on ART Transition for Children and Adolescents Less than 15 Years of Age Living with HIV (CALHIV) in Kenya.
    1. Abrams E.J., Weedon J., Steketee R.W. Association of human immunodeficiency virus (HIV) load early in life with disease progression among HIV-infected infants. JID (J. Infect. Dis.) 1998;178(1):101–108.
    1. Palumbo P.E., Kwok S., Waters S. Viral measurement by polymerase chain reaction-based assays in human immunodeficiency virus-infected infants. J. Pediatr. 1995;126(4):592–595.
    1. Shearer W.T., Quinn T.C., LaRussa P. Viral load and disease progression in infants infected with human immunodeficiency virus type 1. N. Engl. J. Med. 1997;336(19):1337–1342.
    1. UNITAID . Fourth ed. World Health Organization; Geneva, Switzerland: 2014. HIV/AIDS Diagnostics Technology Landscape 2014.
    1. Goel N., Ritchie A.V., Mtapuri-Zinyowera S. 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. Jani I.V., Meggi B., Mabunda N. Accurate early infant HIV diagnosis in primary health clinics using a point-of-care nucleic acid test. JAIDS Journal of Acquired Immune Deficiency Syndromes. 2014;67(1):e1–e4.
    1. Ritchie A.V., Ushiro-Lumb I., Edemaga D. SAMBA HIV semiquantitative test, a new point-of-care viral-load-monitoring assay for resource-limited settings. J. Clin. Microbiol. 2014;52(9):3377–3383.
    1. Scott L., Gous N., Carmona S., Stevens W. Laboratory evaluation of the Liat HIV Quant (IQuum) whole-blood and plasma HIV-1 viral load assays for point-of-care testing in South Africa. J. Clin. Microbiol. 2015;53(5):1616–1621.
    1. Moyo S., Mohammed T., Wirth K.E. Point-of-care Cepheid Xpert HIV-1 viral load test in rural African communities is feasible and reliable. J. Clin. Microbiol. 2016;54(12):3050–3055.
    1. Cepheid Innovation Inc. Solna; Sweden: 2015. Xpert HIV-1 Viral Load, Package Insert.
    1. Zhou Z., Wagar N., DeVos J.R. Optimization of a low cost and broadly sensitive genotyping assay for HIV-1 drug resistance surveillance and monitoring in resource-limited settings. PloS One. 2011;6(11)
    1. Tang M.W., Liu T.F., Shafer R.W. The HIVdb system for HIV-1 genotypic resistance interpretation. Intervirology. 2012;55(2):98–101.
    1. World Health Organization . World Health Organization; Geneva: 2010. CHOICE: Choosing Interventions that Are Cost Effective.
    1. Eaton J.W., Menzies N.A., Stover J. Health benefits, costs, and cost-effectiveness of earlier eligibility for adult antiretroviral therapy and expanded treatment coverage: a combined analysis of 12 mathematical models. The Lancet Global Health. 2014;2(1):e23–e34.
    1. Calman L., Brunton L., Molassiotis A. Developing longitudinal qualitative designs: lessons learned and recommendations for health services research. BMC Med. Res. Methodol. 2013;13(1):14.
    1. Srivastava A., Thomson S.B. 2009. Framework Analysis: a Qualitative Methodology for Applied Policy Research.
    1. Shaw J.A. Reflexivity and the “Acting Subject” conceptualizing the unit of analysis in qualitative health research. Qual. Health Res. 2016;26(13):1735–1744.
    1. Graneheim U.H., Lundman B. Qualitative content analysis in nursing research: concepts, procedures and measures to achieve trustworthiness. Nurse Educ. Today. 2004;24(2):105–112.
    1. Hammersley M. Routledge; 2013. What's Wrong with Ethnography?
    1. Patton M.Q. Enhancing the quality and credibility of qualitative analysis. Health Serv. Res. 1999;34(5 Pt 2):1189.
    1. UNAIDS Global HIV & AIDS statistics — 2019 fact sheet.
    1. Duong T., Judd A., Collins I.J. Long-term virological outcome in children on antiretroviral therapy in the UK and Ireland. AIDS (Lond.) 2014;28(16):2395.
    1. Ford N., Orrell C., Shubber Z., Apollo T., Vojnov L. HIV viral resuppression following an elevated viral load: a systematic review and meta-analysis. J. Int. AIDS Soc. 2019;22(11)
    1. Davies M.A., Pinto J. Targeting 90-90-90--don't leave children and adolescents behind. J. Int. AIDS Soc. 2015;18(Suppl 6):20745.
    1. Violari A., Cotton M.F., Gibb D.M. Early antiretroviral therapy and mortality among HIV-infected infants. N. Engl. J. Med. 2008;359(21):2233–2244.
    1. Hoare J., Heany S.J., Fouche J.P. Initiation of antiretroviral therapy after the critical neuronal developmental period of the second postnatal year affects white matter microstructure in adolescents living with HIV. J. Neurovirol. 2019;25(2):254–262.
    1. Laughton B., Cornell M., Grove D. Early antiretroviral therapy improves neurodevelopmental outcomes in infants. AIDS. 2012;26(13):1685–1690.
    1. Jenabian M.A., Costiniuk C.T., Mboumba Bouassa R.S., Chapdeleine Mekue Mouafo L., Brogan T.V., Belec L. Tackling virological failure in HIV-infected children living in Africa. Expert Rev. Anti Infect. Ther. 2015;13(10):1213–1223.
    1. Rutherford G.W., Anglemyer A., Easterbrook P.J. Predicting treatment failure in adults and children on antiretroviral therapy: a systematic review of the performance characteristics of the 2010 WHO immunologic and clinical criteria for virologic failure. AIDS. 2014;28(Suppl 2):S161–S169.
    1. Drain P.K., Dorward J., Bender A. Point-of-Care HIV viral load testing: an essential tool for a sustainable global HIV/AIDS response. Clin. Microbiol. Rev. 2019;32
    1. Medicine Sans Frontiers Making viral load routine: successes and challenges in the implementation of routine HIV viral load monitoring. 2017.
    1. Janz N.K., Becker M.H. The health Belief model: a decade later. Health Educ. Q. 1984;11(1):1–47.
    1. Reddy S., Gibbs A., Spooner E. Assessment of the impact of rapid point-of-care CD4 testing in primary healthcare clinic settings: a survey study of client and provider perspectives. Diagnostics. 2020;10(2):81.
    1. Fonjungo P.N., Alemnji G.A., Kebede Y. Combatting global infectious diseases: a network effect of specimen referral systems. Clin. Infect. Dis. 2017;64(6):796–803.
    1. Dorward J., Drain P.K., Garrett N. Point-of-care viral load testing and differentiated HIV care. The lancet HIV. 2018;5(1):e8–e9.
    1. Setty H.G., Kumar M., Hewlett I.K. Point of care technologies for HIV. AIDS Res. Treat. 2014;2014
    1. Boerma R.S., Sigaloff K.C., Akanmu A.S. Alarming increase in pretreatment HIV drug resistance in children living in sub-Saharan Africa: a systematic review and meta-analysis. J. Antimicrob. Chemother. 2017;72(2):365–371.
    1. Nasuuna E., Kigozi J., Babirye L., Muganzi A., Sewankambo N.K., Nakanjako D. Low HIV viral suppression rates following the intensive adherence counseling (IAC) program for children and adolescents with viral failure in public health facilities in Uganda. BMC Publ. Health. 2018;18(1):1048.

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