"I feel drug resistance testing allowed us to make an informed decision": qualitative insights on the role of HIV drug resistance mutation testing among children and pregnant women living with HIV in western Kenya.

BACKGROUND: Pregnant women and children living with HIV in Kenya achieve viral suppression (VS) at lower rates than other adults. While many factors contribute to these low rates, the acquisition and development of HIV drug resistance mutations (DRMs) are a contributing factor. Recognizing the significance of DRMs in treatment decisions, resource-limited settings are scaling up national DRM testing programs. From provider and patient perspectives, however, optimal ways to operationalize and scale-up DRM testing in such settings remain unclear. METHODS: Our mixed methods study evaluates the attitudes towards, facilitators to, and barriers to DRM testing approaches among children and pregnant women on antiretroviral therapy (ART) in five HIV treatment facilities in Kenya. We conducted 68 key informant interviews (KIIs) from December 2019 to December 2020 with adolescents, caregivers, pregnant women newly initiating ART or with a high viral load, and providers, laboratory/facility leadership, and policy makers. Our KII guides covered the following domains: (1) DRM testing experiences in routine care and through our intervention and (2) barriers and facilitators to routine and point-of-care DRM testing scale-up. We used inductive coding and thematic analysis to identify dominant themes with convergent and divergent subthemes. RESULTS: The following themes emerged from our analysis: (1) DRM testing and counseling were valuable to clinical decision-making and reassuring to patients, with timely results allowing providers to change patient ART regimens faster; (2) providers and policymakers desired an amended and potentially decentralized DRM testing process that incorporates quicker sample-to-results turn-around-time, less burdensome procedures, and greater patient and provider "empowerment" to increase comfort with testing protocols; (3) facility-level delays, deriving from overworked facilities and sample tracking difficulties, were highlighted as areas for improvement. CONCLUSIONS: DRM testing has the potential to considerably improve patient health outcomes. Key informants recognized several obstacles to implementation and desired a more simplified, time-efficient, and potentially decentralized DRM testing process that builds provider comfort and confidence with DRM testing protocols. Further investigating the implementation, endurance, and effectiveness of DRM testing training is critical to addressing the barriers and areas of improvement highlighted in our study. TRIAL REGISTRATION: NCT03820323.

"After viral load testing, I get my results so I get to know which path my life is taking me": qualitative insights on routine centralized and point-of-care viral load testing in western Kenya from the Opt4Kids and Opt4Mamas studies.

BACKGROUND: Viral suppression (VS) is a marker of effective HIV therapy, and viral load (VL) testing is critical for treatment monitoring, especially in high-risk groups such as children and pregnant/postpartum women. Although routine VL testing, via centralized laboratory networks, was implemented in Kenya starting in 2014, optimization and sustainable scale up of VL testing are still needed. METHODS: We conducted a mixed methods study to evaluate the impact of higher frequency, point-of-care (POC) VL testing in optimizing VS among children and pregnant/postpartum women on antiretroviral treatment (ART) in five HIV treatment facilities in western Kenya in the Opt4Kids and Opt4Mamas studies. We conducted 68 key informant interviews (KIIs) from December 2019 to December 2020 with children and pregnant women living with HIV, child caregivers, providers, laboratory/facility leadership, and county- or national-level policymakers. Our KII guide covered the following domains: (1) barriers and facilitators to ART use and VS, (2) literacy and experiences with VL in routine care and via study, and (3) opinions on how to scale up VL testing for optimal programmatic use. We used inductive coding and thematic analysis to identify dominant themes with convergent and divergent subthemes. RESULTS: Three main themes regarding VL testing emerged from our analysis. (1) Key informants uniformly contrasted POC VL testing's faster results turnaround, higher accessibility, and likely cost-effectiveness against centralized VL testing. (2) Key informants also identified areas of improvement for POC VL testing in Kenya, such as quality control, human resource and infrastructure capacity, supply chain management, and integration of VL testing systems. (3) To enable successful scale-up of VL testing, key informants proposed expanding the POC VL testing scheme, electronic medical records systems, conducting quality checks locally, capacity building and developing strong partnerships between key stakeholders. CONCLUSION: The more accessible, decentralized model of POC VL testing was deemed capable of overcoming critical challenges associated with centralized VL testing and was considered highly desirable for optimizing VS for children and pregnant/postpartum women living with HIV. While POC VL testing has the potential to improve VS rates among these populations, additional research is needed to develop strategies for ensuring the sustainability of POC VL testing programs. TRIAL REGISTRATION: NCT03820323, 29/01/2019.

Point-of-care HIV viral load and targeted drug resistance mutation testing versus standard care for Kenyan children on antiretroviral therapy (Opt4Kids): an open-label, randomised controlled trial.

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.

Costs of Point-of-Care Viral Load Testing for Adults and Children Living with HIV in Kenya.

BACKGROUND: The number of people living with HIV (PLHIV) in need of treatment monitoring in low-and-middle-income countries is rapidly expanding, straining existing laboratory capacity. Point-of-care viral load (POC VL) testing can alleviate the burden on centralized laboratories and enable faster delivery of results, improving clinical outcomes. However, implementation costs are uncertain and will depend on clinic testing volume. We sought to estimate the costs of decentralized POC VL testing compared to centralized laboratory testing for adults and children receiving HIV care in Kenya. METHODS: We conducted microcosting to estimate the per-patient costs of POC VL testing compared to known costs of centralized laboratory testing. We completed time-and-motion observations and stakeholder interviews to assess personnel structures, staff time, equipment costs, and laboratory processes associated with POC VL administration. Capital costs were estimated using a 5 year lifespan and a 3% annual discount rate. RESULTS: We estimated that POC VL testing cost USD $24.25 per test, assuming a clinic is conducting 100 VL tests per month. Test cartridge and laboratory equipment costs accounted for most of the cost (62% and 28%, respectively). Costs varied by number of VL tests conducted at the clinic, ranging from $54.93 to $18.12 per test assuming 20 to 500 VL tests per month, respectively. A VL test processed at a centralized laboratory was estimated to cost USD $25.65. CONCLUSION: POC VL testing for HIV treatment monitoring can be feasibly implemented in clinics within Kenya and costs declined with higher testing volumes. Our cost estimates are useful to policymakers in planning resource allocation and can inform cost-effectiveness analyses evaluating POC VL testing.

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

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.