Cost-effectiveness of intervention combinations towards the elimination of vertical transmission of HIV in limited-resource settings: a mathematical modelling study.

BACKGROUND: Since 2000, there has been a substantial global reduction in the vertical transmission of HIV. Despite effective interventions, gaps still remain in progress towards elimination in many low-income and middle-income countries. We developed a mathematical model to determine the most cost-effective combinations of interventions to prevent vertical transmission. METHODS: We developed a 12-month Markov model to follow a cohort of women of childbearing age (aged 15-49 years) in Zambia (n=1 107 255) who were either pregnant, in delivery, or breastfeeding; the population included in the model reflects the estimated number of pregnant women in Zambia from the 2018 Zambia Demographic and Health Survey. The model incorporated nine interventions: infant prophylaxis; three different HIV retesting schedule options; oral pre-exposure prophylaxis; maternal peer-support groups; regimen shift; tracing of loss to follow-up; and point-of-care viral load testing. We analysed incident HIV infections among mothers and infants, intervention costs, and evaluated 190 scenarios of different combinations of inventions to calculate the incremental cost-effectiveness ratios (ICERs) over 1 year. FINDINGS: Three interventions with the greatest reduction in vertical transmission, individually, were support groups for 80% of those in need (35% reduction in infant infections), HIV retesting schedules (6·5% reduction), and infant prophylaxis (4·5% reduction). Of all 190 scenarios evaluated, eight were on the cost-effectiveness frontier (ie, were considered to be cost-effective); all eight included increasing infant prophylaxis, regimen shift, and use of support groups. Excluding the highest-cost scenarios, for a 1-22% increase in total budget, 23-43% of infant infections could be prevented, producing ICERs between US$244 and $16 242. INTERPRETATION: Using the interventions modelled, it is possible to reduce vertical transmission and to cost-effectively prevent up to 1734 infant HIV infections (43% reduction) in Zambia over a period of 1 year. To optimise their effect, these interventions must be scaled with fidelity. Future work is needed to incorporate evidence on additional innovative interventions and HIV risk factors, and to apply the model to other country contexts to support targeted implementation and resource use. FUNDING: The ELMA Foundation.

Operational demonstration and process evaluation of non-pneumatic anti-shock garment (NASG) introduction to the public health system of Northern Province, Zambia.

BACKGROUND: A disproportionate burden of maternal deaths occurs in low- and middle-income countries (LMICs), and obstetric hemorrhage (OH) is a leading cause of excess mortality. In Zambia, most of maternal deaths are directly caused by OH. The Non-Pneumatic Anti-Shock Garment (NASG) is a first aid tool that uses compression to the abdomen and lower body to stop and reverse hypovolemic shock secondary to OH. We describe the process and experiences introducing the NASG into the Zambia public health system to encourage the development of national policies, clinical guidelines, and implementation plans that feature the NASG. METHODS: We conducted an observational study of NASG introduction to 143 public health facilities in Northern Province, Zambia, organizing observations into the five dimensions of the RE-AIM evaluation framework: reach, effectiveness, adoption, implementation, and maintenance. The NASG was introduced in August 2019, and the introduction was evaluated for 18 months. Data on healthcare worker training and mentorship, cases where NASG was used, and NASG availability and use during the study period were collected and analyzed. RESULTS: The NASG was successfully introduced and integrated into the Zambia public health system, and appropriately used by healthcare workers when responding to cases of OH. Sixteen months after NASG introduction, NASGs were available and functional at 99% of study sites and 88% reported ever using a NASG. Of the 68 cases of recorded OH where a NASG was applied, 66 were confirmed as clinically appropriate, and among cases where shock index (SI) could be calculated, 59% had SI ≥ 0.9. Feedback from healthcare providers revealed that 97% thought introducing the NASG was a good decision, and 92% felt confident in their ability to apply the NASG after initial training. The RE-AIM average for this study was 0.65, suggesting a public health impact that is not equivocal, and that NASG introduction had a positive population-based effect. CONCLUSIONS: A successful NASG demonstration took place over the course of 18 months in the existing health system of Northern Province, Zambia, suggesting that incorporation of NASG into the standard of care for obstetric emergency in the Zambia public sector is feasible and can be maintained without external support.

Uptake of same-day initiation of HIV treatment in Malawi, South Africa, and Zambia as reported in routinely collected data: the SPRINT retrospective cohort study.

Background: Since 2017 global guidelines have recommended "same-day initiation" (SDI) of antiretroviral treatment (ART) for patients considered ready for treatment on the day of HIV diagnosis. Many countries have incorporated a SDI option into national guidelines, but SDI uptake is not well documented. We estimated average time to ART initiation at 12 public healthcare facilities in Malawi, five in South Africa, and 12 in Zambia. Methods: We sequentially enrolled patients eligible to start ART between January 2018 and June 2019 and reviewed their medical records from the point of HIV diagnosis or first HIV-related interaction with the clinic to the earlier date of treatment initiation or 6 months. We estimated the proportion of patients initiating ART on the same day or within 7, 14, 30, or 180 days of baseline. Results: We enrolled 826 patients in Malawi, 534 in South Africa, and 1,984 in Zambia. Overall, 88% of patients in Malawi, 57% in South Africa, and 91% in Zambia were offered and accepted SDI. In Malawi, most who did not receive SDI had not initiated ART ≤6 months. In South Africa, an additional 13% initiated ≤1 week, but 21% had no record of initiation ≤6 months. Among those who did initiate within 6 months in Zambia, most started ≤1 week. There were no major differences by sex. WHO Stage III/IV and tuberculosis symptoms were associated with delays in ART initiation. Conclusions: As of 2020, SDI of ART was widespread, if not nearly universal, in Malawi and Zambia but considerably less common in South Africa. Limitations of the study include pre-COVID-19 data that do not reflect pandemic adaptations and potentially missing data for Zambia. South Africa may be able to increase overall ART coverage by reducing numbers of patients who do not initiate ≤6 months. Registration: Clinicaltrials.gov ( NCT04468399; NCT04170374; NCT04470011).

Optimizing and validating a pediatric screening tool to more efficiently test and identify children living with HIV.

OBJECTIVE: To develop and validate a screening tool to improve testing efficiency and increase case finding of children living with HIV. DESIGN: Cross-sectional study. METHODS: Between November 2020 and September 2021, children 18 months to 14 years presenting at outpatient departments in 30 health facilities in Zambia were administered a 14-question pediatric HIV screening tool and then tested for HIV. Data were analyzed using a randomly extracted 'validation' dataset and multivariable logistic regression to determine the highest performing and optimal number of screening questions. The final tool was then evaluated in the 'test' dataset. Sensitivity and specificity were calculated for both datasets. The final tool was then also implemented in 12 additional facilities to determine operational feasibility and uptake. RESULTS: A total of 9902 children were included in the final analysis. HIV prevalence was 1.3%. Six questions were significantly associated with HIV-positivity. The optimal screening cutoff score was to answer 'yes' to one or more of the six questions; using this cutoff sensitivity was 92.5% [95% confidence interval (CI) 85.7-96.7%] and specificity was 62.9% (95% CI 61.9-64%). In the test dataset, the same tool had a sensitivity of 84.6% (95% CI 65.1-95.6%) and specificity of 64.6% (95% CI 62.4-66.7%). Uptake was 89%. CONCLUSION: The results of this study show sensitivity and acceptable specificity in a six-question validated HIV screening tool. Implementing this screening tool in settings where universal testing is not feasible should more efficiently accelerate identification of children living with HIV (CLHIV) and their timely initiation onto life-saving drugs.

Attrition from HIV treatment after enrollment in a differentiated service delivery model: A cohort analysis of routine care in Zambia.

BACKGROUND: Many sub-Saharan Africa countries are scaling up differentiated service delivery (DSD) models for HIV treatment to increase access and remove barriers to care. We assessed factors associated with attrition after DSD model enrollment in Zambia, focusing on patient-level characteristics. METHODS: We conducted a retrospective record review using electronic medical records (EMR) of adults (≥15 years) initiated on antiretroviral (ART) between 01 January 2018 and 30 November 2021. Attrition was defined as lost to follow-up (LTFU) or died by November 30, 2021. We categorized DSD models into eight groups: fast-track, adherence groups, community pick-up points, home ART delivery, extended facility hours, facility multi-month dispensing (MMD, 4-6-month ART dispensing), frequent refill care (facility 1-2 month dispensing), and conventional care (facility 3 month dispensing, reference group). We used Fine and Gray competing risk regression to assess patient-level factors associated with attrition, stratified by sex and rural/urban setting. RESULTS: Of 547,281 eligible patients, 68% (n = 372,409) enrolled in DSD models, most commonly facility MMD (n = 306,430, 82%), frequent refill care (n = 47,142, 13%), and fast track (n = 14,433, 4%), with <2% enrolled in the other DSD groups. Retention was higher in nearly all DSD models for all dispensing intervals, compared to the reference group, except fast track for the ≤2 month dispensing group. Retention benefits were greatest for patients in the extended clinic hours group and least for fast track dispensing. CONCLUSION: Although retention in HIV treatment differed by DSD type, dispensing interval, and patient characteristics, nearly all DSD models out-performed conventional care. Understanding the factors that influence the retention of patients in DSD models could provide an important step towards improving DSD implementation.

How soon should patients be eligible for differentiated service delivery models for antiretroviral treatment? Evidence from a retrospective cohort study in Zambia.

OBJECTIVES: Patient attrition is high the first 6 months after antiretroviral therapy (ART) initiation. Patients with <6 months of ART are systematically excluded from most differentiated service delivery (DSD) models, which are intended to support retention. Despite DSD eligibility criteria requiring ≥6 months on ART, some patients enrol earlier. We compared loss to follow-up (LTFU) between patients enrolling in DSD models early with those enrolled according to guidelines, assessing whether the ART experience eligibility criterion is necessary. DESIGN: Retrospective cohort study using routinely collected electronic medical record data. SETTING: PARTICIPANTS: Adults (≥15 years) who initiated ART between 1 January 2019 and 31 December 2020. OUTCOMES: LTFU (>30 days late for scheduled visit) at 18 months for 'early enrollers' (DSD enrolment after <6 months on ART) and 'established enrollers' (DSD enrolment after ≥6 months on ART). We used a log-binomial model to compare LTFU risk, adjusting for age, sex, location, ART refill interval and DSD model. RESULTS: For 6340 early enrollers and 25 857 established enrollers, there were no differences in sex (61% female), age (median 37 years) or location (65% urban). ART refill intervals were longer for established versus early enrollers (72% vs 55% were given 4-6 months refills). LTFU at 18 months was 3% (192 of 6340) for early enrollers and 5% (24 646 of 25 857) for established enrollers. Early enrollers were 41% less likely to be LTFU than established patients (adjusted risk ratio 0.59, 95% CI 0.50 to 0.68). CONCLUSIONS: Patients enrolled in DSD after <6 months of ART were more likely to be retained than patients established on ART prior to DSD enrolment. A limitation is that early enrollers may have been selected for DSD due to providers' and patients' expectations about future retention. Offering DSD models to ART patients soon after ART initiation may help address high attrition during the early treatment period. TRIAL REGISTERATION NUMBER: NCT04158882.

Reducing maternal and neonatal mortality through integrated and sustainability-focused programming in Zambia.

Reducing maternal and neonatal mortality is a critical health priority within Zambia and globally. Although evidence-based clinical interventions can prevent a majority of these deaths, scalable and sustainable delivery of interventions across low-resource settings remains uneven, particularly across rural and marginalized communities. The Zambian Ministry of Health and the Clinton Health Access Initiative implemented an integrated sexual, reproductive, maternal, and newborn health (SRMNH) program in Northern Province aimed at dramatically reducing mortality over four years. Interventions were implemented between 2018 and 2021 across 141 government-owned health facilities covering all 12 districts of Northern Province, the poorest performing province nationwide and home to over 1.4 million people, around six pillars of an integrated health system. Data on institutional delivery and antenatal and postnatal care were collected through the national Health Management Information System (HMIS). A community-based system for capturing birth outcomes was established using existing government tools and community volunteers since HMIS did not include community-based mortality. Baseline and endline population-based mortality rates were compared for program-supported areas. From the earliest period of population-based mortality reporting in 2019 to program end in 2021, there were statistically significant decreases of 41%, 45%, and 43% in maternal, neonatal, and perinatal mortality rates respectively. Between 2017 to 2021, institutional maternal, neonatal, and perinatal mortality rates across entirety of Northern Province reduced by 12%, 40%, and 41%, respectively. Service readiness and coverage for SRMNH services improved dramatically, supporting increased numbers of patients. Significant mortality reductions were achieved over a relatively short period, reinforced through an emphasis on sustainability and strengthening existing government systems. These results were attained through a consciously cost-efficient approach backed by substantially lower levels of external investment relative to prior programs, allowing many of the interventions to be successfully adopted by government within public sector budgets.

Changes in HIV treatment differentiated care uptake during the COVID-19 pandemic in Zambia: interrupted time series analysis.

INTRODUCTION: Differentiated service delivery (DSD) models aim to improve the access of human immunodeficiency virus treatment on clients and reduce requirements for facility visits by extending dispensing intervals. With the advent of the COVID-19 pandemic, minimising client contact with healthcare facilities and other clients, while maintaining treatment continuity and avoiding loss to care, has become more urgent, resulting in efforts to increase DSD uptake. We assessed the extent to which DSD coverage and antiretroviral treatment (ART) dispensing intervals have changed during the COVID-19 pandemic in Zambia. METHODS: We used client data from Zambia's electronic medical record system (SmartCare) for 737 health facilities, representing about three-fourths of all ART clients nationally. We compared the numbers and proportional distributions of clients enrolled in DSD models in the 6 months before and 6 months after the first case of COVID-19 was diagnosed in Zambia in March 2020. Segmented linear regression was used to determine whether the outbreak of COVID-19 in Zambia further accelerated the increase in DSD scale-up. RESULTS AND DISCUSSION: Between September 2019 and August 2020, 181,317 clients aged 15 or older (81,520 and 99,797 from 1 September 2019 to 1 March 2020 and from 1 March to 31 August 2020, respectively) enrolled in DSD models in Zambia. Overall participation in all DSD models increased over the study period, but uptake varied by model. The rate of acceleration increased in the second period for home ART delivery (152%), ≤ 2-month fast-track (143%) and 3-month MMD (139%). There was a significant reduction in the enrolment rates for 4- to 6-month fast-track (-28%) and "other" models (-19%). CONCLUSIONS: Participation in DSD models for stable ART clients in Zambia increased after the advent of COVID-19, but dispensing intervals diminished. Eliminating obstacles to longer dispensing intervals, including those related to supply chain management, should be prioritized to achieve the expected benefits of DSD models and minimize COVID-19 risk.

Improving the quality of childbirth services in Zambia through introduction of the Safe Childbirth Checklist and systems-focused mentorship.

Although strong evidence exists about the effectiveness of basic childbirth services in reducing maternal and newborn mortality, these services are not provided in every childbirth, even those at health facilities. The WHO Safe Childbirth Checklist (SCC) was developed as a job aide to remind health workers of evidenced-based practices to be provided at specific points in the childbirth process. The Zambian government requested context-specific evidence on the feasibility and outcomes associated with introducing the checklist and related mentorship. A study was conducted on use of the SCC in four facilities in Nchelenge District of Zambia. Observations of childbirth services were conducted just before and six months after the introduction of the intervention. Observers used a structured tool to record adherence to essential services indicated on the checklist. The primary outcome of interest was the change in the average proportion of essential childbirth practices completed. Feedback questionnaires were administered to health workers before and six months after the intervention. At baseline and endline, 108 and 148 pause points were observed, respectively. There was an increase from 57% to 76% of tasks performed (p = 0.04). Considering only these cases where necessary supplies were available, health workers completed 60% of associated tasks at baseline compared to 84% at endline (p<0.01). Some tasks, such as taking an infant's temperature and hand washing, were never or rarely performed at baseline. Feedback from the health workers indicated that nearly all health workers agreed or strongly agreed with positive statements about the intervention. The performance of health workers in Zambia in completing essential practices in childbirth was low at baseline but improvements were observed with the introduction of the SCC and mentorship. Our results suggest that such interventions could improve quality of care for facility-based childbirth. However, national-level commitment to ensuring availability of trained staff and supplies is essential for success. Trial registration Clinical Trials.gov (NCT03263182) Registered August 28, 2017 This study adheres to CONSORT guidelines.

Impact of the Umoyo mother-infant pair model on HIV-positive mothers' social support, perceived stigma and 12-month retention of their HIV-exposed infants in PMTCT care: evidence from a cluster randomized controlled trial in Zambia.

BACKGROUND: Public health systems in resource-constrained settings have a critical role to play in the elimination of HIV transmission but are often financially constrained. This study is an evaluation of a mother-infant-pair model called "Umoyo," which was designed to be low cost and scalable in a public health system. Facilities with the Umoyo model dedicate a clinic day to provide services to only HIV-exposed infants (HEIs) and their mothers. Such models are in operation with reported success in Zambia but have not been rigorously tested. This work establishes whether the Umoyo model would improve 12-month retention of HEIs. METHODS: A cluster randomized trial including 28 facilities was conducted across two provinces of Zambia to investigate the impact on 12-month retention of HEIs in care. These facilities were offering Prevention of Mother-to-Child-Transmission (PMTCT) services and supported by the same implementing partner. Randomization was achieved by use of the covariate-constrained optimization technique. Secondary outcomes included the impact of Umoyo clinics on social support and perceived HIV stigma among mothers. For each of the outcomes, a difference-in-difference analysis was conducted at the facility level using the unweighted t test. RESULTS: From 13 control (12-month retention at endline: 45%) and 11 intervention facilities (12-month retention at endline: 33%), it was found that Umoyo clinics had no impact on 12-month retention of HEIs in the t test (- 11%; 99% CI - 40.1%, 17.2%). Regarding social support and stigma, the un-weighted t test showed no impact though sensitivity tests showed that Umoyo had an impact on increasing social support (0.31; 99% CI 0.08, 0.54) and reducing perceived stigma from health care workers (- 0.27; 99% CI - 0.46, - 0.08). CONCLUSION: The Umoyo approach of having a dedicated clinic day for HEIs and their mothers did not improve retention of HEIs though there are indications that it can increase social support among mothers and reduce stigma. Without further support to the underlying health system, based on the evidence generated through this evaluation, the Umoyo clinic day approach on its own is not considered an effective intervention to increase retention of HIV-exposed infants. TRIAL REGISTRATION: Pan African Clinical Trial Registry, ID: PACTR201702001970148 . Prospectively registered on 13 January 2017.

Impact of the Safe Childbirth Checklist on health worker childbirth practices in Luapula province of Zambia: a pre-post study.

BACKGROUND: A strong evidence base exists regarding routine and emergency services that can effectively prevent or reduce maternal and new-born mortality. However, even when skilled providers care for women in labour, many of the recommended services are not provided, despite being available. Barriers to the provision of appropriate childbirth services may include lack of availability of supplies, limited health worker knowledge and confidence, or inadequate time. The WHO Safe Childbirth Checklist (SCC) includes reminders for evidenced-based practices at specific points in the childbirth process. Zambia is currently considering nation-wide adoption of the SCC, but there is a need for context-specific evidence. Beginning in September 2017, a program is being implemented in Nchelenge District to pilot use of the SCC, along with coaching that focuses on strengthening the systems that allow the essential practices in childbirth to be performed. METHODS: This study will use a pre-post study design to measure health worker adherence to the essential practices for delivery care outlined in the SCC. Data will be collected through observations of health workers as they care for mothers during childbirth at four facilities. Data collection will take place before the start of the intervention, at 3 months, and at 6 months post-intervention. The primary outcome interest is the change in the average proportion of essential childbirth practices completed. A health worker questionnaire will be administered at the time that the SCC is introduced and 6 months later to gather their perspectives on incorporating the SCC into clinical practice in Zambia. DISCUSSION: Findings are expected to inform plans for introducing the SCC in Zambia. This evaluation will aim to understand uptake and impact of the SCC and associated coaching in the context of a basic level of mentorship that the government could feasibly provide at a national scale. TRIAL REGISTRATION: Clinical Trials.gov ( NCT03263182 ) Registered August 28, 2017.

Impact of passenger engagement through road safety bus stickers in public service vehicles on road traffic crashes in Zambia: a randomized controlled trial.

BACKGROUND: Road Traffic Crashes (RTCs) are the third highest cause of death in Zambia, claiming about 2000 lives annually, with pedestrians and cyclists being the most vulnerable. Human error accounts for 87.3% of RTCs. Minibus and big bus public service vehicles (PSVs) are among the common vehicle types involved in these crashes. Given the alarmingly high rate of road traffic crashes involving PSV minibuses and big buses within Zambia, there is a need to mitigate this through innovative solutions. In other settings, it has been shown that stickers in PSVs encouraging passengers to speak out against reckless driving can reduce RTCs, but it is unclear whether such an intervention could work in Zambia. Based on this evidence, the Zambia Road Transport and Safety Agency (RTSA) has developed a road safety bus sticker campaign for PSVs and before national scale-up, RTSA is interested in evidence of the impact of these stickers. METHODS: This evaluation will be a stratified two-arm randomized controlled trial with a one-to-one ratio. The sample will be stratified by vehicle type, thus creating a two-arm trial for minibuses and a separate two-arm trial for big buses. The sample will include 2110 minibuses and 300 big buses from four towns in Zambia. The primary outcome of interest will be the difference in the rate of RTCs over a 14-month period (7-months before the intervention and 7 months after) between buses with and without the new RTSA road safety bus stickers. DISCUSSION: This study will provide evidence on the impact of the Zambian sticker program on road traffic crashes as implemented through minibuses and big buses, that can help inform the scale up of a national 'Zambia road safety bus sticker campaign'. TRIAL REGISTRATION: PACT-R, PACTR201711002758216 . Registered 13 November 2017-Retrospectively registered.