Rena C Patel1, Patrick Oyaro2, Katherine K Thomas3, James Wagude4, Irene Mukui5, Evelyn Brown6, Shukri A Hassan7, Eunice Kinywa8, Frederick Oluoch8, Francesca Odhiambo9, Boaz Oyaro10, Leonard Kingwara11, Enericah Karauki6, Nashon Yongo6, Lindah Otieno9, Grace C John-Stewart12, Lisa L Abuogi13. 1. Department of Medicine, University of Washington, Seattle, WA, USA; Department of Global Health, University of Washington, Seattle, WA, USA. Electronic address: rcpatel@uw.edu. 2. Health Innovations Kenya (HIK), Kisuma, Kenya. 3. Department of Global Health, University of Washington, Seattle, WA, USA. 4. Department of Health, Siaya County, Kenya. 5. Drugs for Neglected Diseases Initiative (DNDI), Nairobi, Kenya. 6. UWKenya, Nairobi, Kenya. 7. Department of Medicine, University of Washington, Seattle, WA, USA. 8. Department of Health, Kisumu County, Kenya. 9. Family AIDS Care and Education Services, Kenya Medical Research Institute, Kisumu, Kenya. 10. Kenya Medical Research Institute-CDC, Kisian, Kenya. 11. National HIV Reference Laboratory, Kenya Ministry of Health, Nairobi, Kenya. 12. Department of Medicine, University of Washington, Seattle, WA, USA; Department of Global Health, University of Washington, Seattle, WA, USA; Departments of Pediatrics and Epidemiology, University of Washington, Seattle, WA, USA. 13. Department of Pediatrics, University of Colorado, Denver, CO, USA.
Abstract
BACKGROUND: Feasible, scalable, and cost-effective approaches to ensure virological suppression among children living with HIV are urgently needed. The aim of the Opt4Kids study was to determine the effect of point of care viral load and targeted drug resistance mutation testing in improving virological suppression among children on antiretroviral therapy (ART) in Kenya. METHODS: In this open-label, individually randomised controlled trial, we enrolled children living with HIV aged 1-14 years and who were either newly initiating or already receiving ART at five study facilities in Kenya. Participants were randomly allocated 1:1 to receive the intervention of point-of-care viral load testing every 3 months, targeted drug resistance mutation testing, and clinical decision support (point-of-care testing) or to receive the standard care (control group), stratified by facility site and age groups (1-9 years vs 10-14 years). Investigators were masked to the randomised group. The primary efficacy outcome was virological suppression (defined as a viral load of <1000 copies per mL) by point-of-care viral load testing at 12 months after enrolment in all participants with an assessment. This study is registered with ClinicalTrials.gov, NCT03820323. FINDINGS: Between March 7, 2019, and December 31, 2020, we enrolled 704 participants. Median age at enrolment was 9 years (IQR 7-12), 344 (49%) participants were female and 360 (51%) were male, and median time on ART was 5·8 years (IQR 3·1-8·6). 536 (76%) of 704 had documented virological suppression at enrolment. At 12 months after enrolment, the proportion of participants achieving virological suppression in the intervention group (283 [90%] of 313 participants with a 12 month point-of-care viral load test) did not differ from that in the control group (289 [92%] of 315; risk ratio [RR] 0·99, 95% CI 0·94-1·03; p=0·55). We identified 138 episodes of viraemia in intervention participants, of which 107 (89%) samples successfully underwent drug resistance mutation testing and 91 (85%) had major drug resistance mutations. The median turnaround time for viral load results was 1 day (IQR 0-1) in the intervention group and 15 days (10-21) in the control group. INTERPRETATION: Point-of-care viral load testing decreased turnaround time and targeted drug resistance mutation testing identified a high prevalence of HIV drug resistance mutations in children living with HIV, but the combined approach did not increase rates of virological suppression. Further research in combination interventions, including point-of-care viral load and drug resistance mutation testing coupled with psychosocial support, is needed to optimise virological suppression for children living with HIV. FUNDING: National Institutes of Mental Health of the US National Institutes of Health, Thrasher Research Fund.
BACKGROUND: Feasible, scalable, and cost-effective approaches to ensure virological suppression among children living with HIV are urgently needed. The aim of the Opt4Kids study was to determine the effect of point of care viral load and targeted drug resistance mutation testing in improving virological suppression among children on antiretroviral therapy (ART) in Kenya. METHODS: In this open-label, individually randomised controlled trial, we enrolled children living with HIV aged 1-14 years and who were either newly initiating or already receiving ART at five study facilities in Kenya. Participants were randomly allocated 1:1 to receive the intervention of point-of-care viral load testing every 3 months, targeted drug resistance mutation testing, and clinical decision support (point-of-care testing) or to receive the standard care (control group), stratified by facility site and age groups (1-9 years vs 10-14 years). Investigators were masked to the randomised group. The primary efficacy outcome was virological suppression (defined as a viral load of <1000 copies per mL) by point-of-care viral load testing at 12 months after enrolment in all participants with an assessment. This study is registered with ClinicalTrials.gov, NCT03820323. FINDINGS: Between March 7, 2019, and December 31, 2020, we enrolled 704 participants. Median age at enrolment was 9 years (IQR 7-12), 344 (49%) participants were female and 360 (51%) were male, and median time on ART was 5·8 years (IQR 3·1-8·6). 536 (76%) of 704 had documented virological suppression at enrolment. At 12 months after enrolment, the proportion of participants achieving virological suppression in the intervention group (283 [90%] of 313 participants with a 12 month point-of-care viral load test) did not differ from that in the control group (289 [92%] of 315; risk ratio [RR] 0·99, 95% CI 0·94-1·03; p=0·55). We identified 138 episodes of viraemia in intervention participants, of which 107 (89%) samples successfully underwent drug resistance mutation testing and 91 (85%) had major drug resistance mutations. The median turnaround time for viral load results was 1 day (IQR 0-1) in the intervention group and 15 days (10-21) in the control group. INTERPRETATION: Point-of-care viral load testing decreased turnaround time and targeted drug resistance mutation testing identified a high prevalence of HIV drug resistance mutations in children living with HIV, but the combined approach did not increase rates of virological suppression. Further research in combination interventions, including point-of-care viral load and drug resistance mutation testing coupled with psychosocial support, is needed to optimise virological suppression for children living with HIV. FUNDING: National Institutes of Mental Health of the US National Institutes of Health, Thrasher Research Fund.
Authors: Shirley Lecher; Dennis Ellenberger; Andrea A Kim; Peter N Fonjungo; Simon Agolory; Marie Yolande Borget; Laura Broyles; Sergio Carmona; Geoffrey Chipungu; Kevin M De Cock; Varough Deyde; Marie Downer; Sundeep Gupta; Jonathan E Kaplan; Charles Kiyaga; Nancy Knight; William MacLeod; Boniface Makumbi; Hellen Muttai; Christina Mwangi; Jane W Mwangi; Michael Mwasekaga; Lucy W Ng'Ang'A; Yogan Pillay; Abdoulaye Sarr; Souleymane Sawadogo; Daniel Singer; Wendy Stevens; Christiane Adje Toure; John Nkengasong Journal: MMWR Morb Mortal Wkly Rep Date: 2015-11-27 Impact factor: 17.586
Authors: Esther Nasuuna; Joanita Kigozi; Patience A Muwanguzi; Joyce Babirye; Laura Kiwala; Alex Muganzi; Nelson Sewankambo; Damalie Nakanjako Journal: BMC Health Serv Res Date: 2019-03-07 Impact factor: 2.655
Authors: Matthew R Sandbulte; Brad J Gautney; May Maloba; Catherine Wexler; Melinda Brown; Natabhona Mabachi; Kathy Goggin; Raphael Lwembe; Niaman Nazir; Thomas A Odeny; Sarah Finocchario-Kessler Journal: Pilot Feasibility Stud Date: 2019-01-25
Authors: 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 Journal: Contemp Clin Trials Commun Date: 2020-10-27
Authors: Michelle Ann Bulterys; Patrick Oyaro; Evelyn Brown; Nashon Yongo; Enericah Karauki; James Wagude; Leonard Kingwara; Nancy Bowen; Susan Njogo; Anjuli D Wagner; Irene Mukui; Frederick Oluoch; Lisa Abuogi; Rena Patel; Monisha Sharma Journal: Diagnostics (Basel) Date: 2021-01-19