Real-world performance of point-of-care vs. standard-of-care HIV viral load testing in western Kenya: Secondary analysis of Opt4Kids and Opt4Mamas studies.

Routine HIV viral load testing is important for evaluating HIV treatment outcomes, but conventional viral load testing has many barriers including expensive laboratory equipment and lengthy results return times to patients. A point-of-care viral load testing technology, such as GeneXpert HIV-1 quantification assay, could reduce these barriers by decreasing cost and turnaround time, however real-world performance is limited. We conducted a secondary analysis using 900 samples collected from participants in two studies to examine the performance of GeneXpert as point-of-care viral load compared to standard-of-care testing (which was conducted with two centralized laboratories using traditional HIV-1 RNA PCR quantification assays). The two studies, Opt4Kids (n = 704 participants) and Opt4Mamas (n = 820 participants), were conducted in western Kenya from 2019-2021 to evaluate the effectiveness of a combined intervention strategy, which included point-of-care viral load testing. Paired viral load results were compared using four different thresholds for virological non-suppression, namely ≥50, ≥200, ≥400, ≥1000 copies/ml. At a threshold of ≥1000 copies/mL, paired samples collected on the same day: demonstrated sensitivities of 90.0% (95% confidence interval [CI] 68.3, 98.8) and 66.7% (9.4, 99.2), specificities of 98.4% (95.5, 99.7) and 100% (96.5, 100), and percent agreements of 97.7% (94.6, 99.2) and 99.1% (95.0, 100) in Opt4Kids and Opt4Mamas studies, respectively. When lower viral load thresholds were used and the paired samples were collected an increasing number of days apart, sensitivity, specificity, and percent agreement generally decreased. While specificity and percent agreement were uniformly high, sensitivity was lower than expected. Non-specificity of the standard of care testing may have been responsible for the sensitivity values. Nonetheless, our results demonstrate that GeneXpert may be used reliably to monitor HIV treatment in low- and middle- income countries to attain UNAID's 95-95-95 HIV goals.

Optimising HIV drug resistance testing laboratory networks in Kenya: insights from systems engineering modelling.

BACKGROUND: HIV drug resistance (DR) is a growing threat to the durability of current and future HIV treatment success. DR testing (DRT) technologies are very expensive and specialised, relying on centralised laboratories in most low and middle-income countries. Modelling for laboratory network with point-of-care (POC) DRT assays to minimise turnaround time (TAT), is urgently needed to meet the growing demand. METHODS: We developed a model with user-friendly interface using integer programming and queueing theory to improve the DRT system in Kisumu County, Kenya. We estimated DRT demand based on both current and idealised scenarios and evaluated a centralised laboratory-only network and an optimised POC DRT network. A one-way sensitivity analysis of key user inputs was conducted. RESULTS: In a centralised laboratory-only network, the mean TAT ranged from 8.52 to 8.55 working days, and the system could not handle a demand proportion exceeding 1.6%. In contrast, the mean TAT for POC DRT network ranged from 1.13 to 2.11 working days, with demand proportion up to 4.8%. Sensitivity analyses showed that expanding DRT hubs reduces mean TAT substantially while increasing the processing rate at national labs had minimal effect. For instance, doubling the current service rate at national labs reduced the mean TAT by only 0.0%-1.9% in various tested scenarios, whereas doubling the current service rate at DRT hubs reduced the mean TAT by 37.5%-49.8%. In addition, faster batching modes and transportation were important factors influencing the mean TAT. CONCLUSIONS: Our model offers decision-makers an informed framework for improving the DRT system using POC in Kenya. POC DRT networks substantially reduce mean TAT and can handle a higher demand proportion than a centralised laboratory-only network, especially for children and pregnant women living with HIV, where there is an immediate push to use DRT results for patient case management.

Using queueing models as a decision support tool in allocating point-of-care HIV viral load testing machines in Kisumu County, Kenya.

Point-of-care (POC) technologies-including HIV viral load (VL) monitoring-are expanding globally, including in resource-limited settings. Modelling could allow decision-makers to consider the optimal strategy(ies) to maximize coverage and access, minimize turnaround time (TAT) and minimize cost with limited machines. Informed by formative qualitative focus group discussions with stakeholders focused on model inputs, outputs and format, we created an optimization model incorporating queueing theory and solved it using integer programming methods to reflect HIV VL monitoring in Kisumu County, Kenya. We modelled three scenarios for sample processing: (1) centralized laboratories only, (2) centralized labs with 7 existing POC 'hub' facilities and (3) centralized labs with 7 existing and 1-7 new 'hub' facilities. We calculated total TAT using the existing referral network for scenario 1 and solved for the optimal referral network by minimizing TAT for scenarios 2 and 3. We conducted one-way sensitivity analyses, including distributional fairness in each sub-county. Through two focus groups, stakeholders endorsed the provisionally selected model inputs, outputs and format with modifications incorporated during model-building. In all three scenarios, the largest component of TAT was time spent at a facility awaiting sample batching and transport (scenarios 1-3: 78.7%, 89.9%, 91.8%) and waiting time at the testing site (18.7%, 8.7%, 7.5%); transportation time contributed minimally to overall time (2.6%, 1.3%, 0.7%). In scenario 1, the average TAT was 39.8 h (SD: 2.9), with 1077 h that samples spent cumulatively in the VL processing system. In scenario 2, the average TAT decreased to 33.8 h (SD: 4.8), totalling 430 h. In scenario 3, the average TAT decreased nearly monotonically with each new machine to 31.1 h (SD: 8.4) and 346 total hours. Frequency of sample batching and processing rate most impacted TAT, and inclusion of distributional fairness minimally impacted TAT. In conclusion, a stakeholder-informed resource allocation model identified optimal POC VL hub allocations and referral networks. Using existing-and adding new-POC machines could markedly decrease TAT, as could operational changes.

Impact of point-of-care HIV viral load and targeted drug resistance mutation testing on viral suppression among Kenyan pregnant and postpartum women: results from a prospective cohort study (Opt4Mamas).

INTRODUCTION: Lack of viral suppression (VS) among pregnant and breastfeeding women living with HIV poses challenges for maternal and infant health, and viral load (VL) monitoring via centralized laboratory systems faces many barriers. We aimed to determine the impact of point-of-care (POC) VL and targeted drug resistance mutation (DRM) testing in improving VS among pregnant and postpartum women on antiretroviral therapy. METHODS: We conducted a pre/post-intervention prospective cohort study among 820 pregnant women accessing HIV care at five public-sector facilities in western Kenya from 2019 to 2022. The pre-intervention or "control" group consisted of standard-of-care (SOC) centralized VL testing every 6 months and the post-intervention or "intervention" group consisted of a combined strategy of POC VL every 3 months, targeted DRM testing, and clinical management support. The primary outcome was VS (VL ≤1000 copies/ml) at 6 months postpartum; secondary outcomes included uptake and turnaround times for VL testing and sustained VS. RESULTS: At 6 months postpartum, 321/328 (98%) of participants in the intervention group and 339/347 (98%) in the control group achieved VS (aRR 1.00, 95% confidence interval [CI] 0.98, 1.02). When assessing VS using a threshold of <40 copies/ml, VS proportions were lower overall (90-91%) but remained similar between groups. Among women with viraemia (VL>1000 copies/ml) who underwent successful DRM testing in the intervention group, all (46/46, 100%) had some DRMs and 20 (43%) had major DRMs (of which 80% were nucleos(t)ide reverse transcriptase inhibitor mutations). POC VL testing uptake was high (>89%) throughout pregnancy, delivery, and postpartum periods, with a median turnaround time of 1 day (IQR 1, 4) for POC VL in the intervention group and 7 days (IQR 5, 9) for SOC VL in the control group. Sustained VS throughout follow-up was similar between groups with either POC or SOC VL testing (90-91% for <1000 copies/ml, 62-70% for <40 copies/ml). CONCLUSIONS: Our combined strategy markedly decreased turnaround time but did not increase VS rates, which were already very high, or sustained VS among pregnant and postpartum women living with HIV. Further research on how best to utilize POC VL and DRM testing is needed to optimize sustained VS among this population.

HIV Drug Resistance Patterns and Characteristics Associated with Clinically Significant Drug Resistance among Children with Virologic Failure on Antiretroviral Treatment in Kenya: Findings from the Opt4Kids Randomized Controlled Trial.

Increasing HIV drug resistance (DR) among children with HIV (CHIV) on antiretroviral treatment (ART) is concerning. CHIV ages 1-14 years enrolled from March 2019 to December 2020 from five facilities in Kisumu County, Kenya, were included. Children were randomized 1:1 to control (standard-of-care) or intervention (point-of-care viral load (POC VL) testing every three months with targeted genotypic drug resistance testing (DRT) for virologic failure (VF) (≥1000 copies/mL)). A multidisciplinary committee reviewed CHIV with DRT results and offered treatment recommendations. We describe DR mutations and present logistic regression models to identify factors associated with clinically significant DR. We enrolled 704 children in the study; the median age was 9 years (interquartile range (IQR) 7, 12), 344 (49%) were female, and the median time on ART was 5 years (IQR 3, 8). During the study period, 106 (15%) children had DRT results (84 intervention and 22 control). DRT detected mutations associated with DR in all participants tested, with 93 (88%) having major mutations, including 51 (54%) with dual-class resistance. A history of VF in the prior 2 years (adjusted odds ratio (aOR) 11.1; 95% confidence interval (CI) 6.3, 20.0) and less than 2 years on ART at enrollment (aOR 2.2; 95% CI 1.1, 4.4) were associated with increased odds of major DR. DR is highly prevalent among CHIV on ART with VF in Kenya. Factors associated with drug resistance may be used to determine which children should be prioritized for DRT.

"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.

Impacts of the COVID-19 pandemic on access to HIV and reproductive health care among women living with HIV (WLHIV) in Western Kenya: A mixed methods analysis.

Introduction: The COVID-19 pandemic has impacted access to health services. Our objective was to understand the pandemic's impact on access to HIV, pregnancy, and family planning (FP) care among women living with HIV (WLHIV). Methods: Data were collected after June 2020, when questions about the pandemic were added to two ongoing mixed methods studies using telephone surveys and in-depth interviews among WLHIV in western Kenya. The Chaguo Langu (CL) study includes primarily non-pregnant WLHIV receiving HIV care at 55 facilities supported by AMPATH and the Opt4Mamas study includes pregnant WLHIV receiving antenatal care at five facilities supported by FACES. Our outcomes were self-reported increased difficulty refilling medication, accessing care, and managing FP during the pandemic. We summarized descriptive data and utilized multivariable logistic regression to evaluate predictors of difficulty refilling medication and accessing care. We qualitatively analyzed the interviews using inductive coding with thematic analysis. Results: We analyzed 1,402 surveys and 15 in-depth interviews. Many (32%) CL participants reported greater difficulty refilling medications and a minority (14%) reported greater difficulty accessing HIV care during the pandemic. Most (99%) Opt4Mamas participants reported no difficulty refilling medications or accessing HIV/pregnancy care. Among the CL participants, older women were less likely (aOR = 0.95, 95% CI: 0.92-0.98) and women with more children were more likely (aOR = 1.13, 95% CI: 1.00-1.28) to report difficulty refilling medications. Only 2% of CL participants reported greater difficulty managing FP and most (95%) reported no change in likelihood of using FP or desire to get pregnant. Qualitative analysis revealed three major themes: (1) adverse organizational/economic implications of the pandemic, (2) increased importance of pregnancy prevention during the pandemic, and (3) fear of contracting COVID-19. Discussion: The two unique participant groups included in our study encountered overlapping problems during the COVID-19 epidemic. Access to HIV services and antiretrovirals was interrupted for a large proportion of non-pregnant WLHIV in western Kenya, but access to pregnancy/family planning care was less affected in our cohort. Innovative solutions are needed to ensure HIV and reproductive health outcomes do not worsen during the ongoing pandemic.

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.