Impact of Umoyo mother-infant pair clinics on HIV-positive mothers’ social support, perceived stigma and 12-month retention of their HIV-exposed infants in PMTCT Care: Evidence from a cluster randomised control trial in Zambia

Background Public health systems in resource constrained settings have a critical role to play in the elimination of vertical HIV transmission but are unable to carry out some of the promising interventions such as mother-to-mother peer support programs due to financial constraints. This study is an evaluation of a mother-infant-pair clinic called Umoyo, which was designed to be scalable in a public health system due to the relatively low costs required. Umoyo clinics 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. Methods A cluster randomized trial including 28 facilities was conducted across two provinces of Zambia to investigate 12-month retention of HEIs in care. These were facilities that were offering prevention of mother to child transmission (PMTCT) services and supported by the same implementing partner. Random allocation was achieved by use of the covariate constrained optimization technique. The primary outcome of interest was to establish whether Umoyo clinic days would improve 12-month retention of HEIs. 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 unweighted t-test. Results From 13 control and 11 intervention facilities, 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 and reducing perceived stigma from health care workers. 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,


Introduction
The goal of eliminating vertical HIV transmission is embedded within the UNAIDS 90-90-90 targets which are to be achieved by 2020. It is important for pregnant women living with HIV to know their status early and put on antiretroviral therapy (ART). Taking ART during pregnancy and delivery can significantly suppress the HIV viral load of a pregnant woman, reducing the risks of mother-to-child transmission to negligible levels (1). Women should then continue ART for life to maintain viral suppression; however, more than half of mother-to-child transmissions occur during breastfeeding, signalling the need for more attention on postpartum follow-up and retention in care during breastfeeding (2). After immunization of the child at 6 weeks of age, attendance at post-natal care visits tends to decrease substantially, thereby limiting the opportunities for prevention of mother-to-child transmission (PMTCT) follow-up services (2). With limited opportunities for early identification of children who seroconvert along the PMTCT cascade, the health outcomes of such children are worsened. Therefore, postpartum continuum of care for HIV-positive mothers is critical for continued support for mother-infant pairs (MIPs) in order to achieve virtual elimination of mother-to-child transmission, keep the mother in care, and increase the identification and initiation of HIV-positive infants on ART.
The World Health Organization (WHO) and the Joint United Nations Programme on HIV/AIDS (UNAIDS) recognise HIV stigma and discrimination to be important detractors to the achievement of the 90-90-90 targets, especially in efforts to eliminate mother-to-child transmission of HIV (3). There is evidence that HIV stigma and discrimination are strong barriers against accessing HIV prevention, testing, and treatment services (4; 5; 6). Furthermore, in contexts where evidence exists, it has been found that a majority of the population do exhibit discriminatory attitudes towards people living with HIV/AIDS (PLWHA) (3). The ability of PLWHA to cope with negative health stressors such as discrimination and stigma depends to a large degree on the extent of the social support received from informal networks of family and friends (7). Social support has been associated with positive health outcomes for PLWHA such as self-efficacy, adherence to ART, quality of life, physical health and mental health (8; 9; 10; 11; 12). Indeed, the WHO has recognised that PLWHA have important psychosocial needs that need to be integrated into HIV care such as prevention and treatment of mental health disorders, assistance on coping with discrimination and stigma and financial forms of assistance (13).
While the vast majority of research linking ART adherence to social support has been conducted on adults, limited information is known about the relationship between social support for mothers and health outcomes of their HIV-exposed infants (HEIs). The role of social support in improving PMTCT outcomes has been partially addressed through evaluations of interventions focused on structured peer support models such as the Mother2mother (m2m) mentor program. In this approach, local mothers living with HIV are empowered as peer supporters in health centres and communities to provide education and support to HIV-positive pregnant and breastfeeding women. Such models have been evaluated in Kenya, Lesotho, Malawi, Nigeria, South Africa, Swaziland, Uganda and Zimbabwe with mixed results on the impact of social support on retention of HEIs along the PMTCT cascade (14; 15; 16). An early evaluation of the m2m approach showed that clients who met two or more times with a mentor mother were over two times more likely to test their baby for HIV at six weeks; almost two times more likely to exclusively breastfeed during the first six months and over two times more likely to take ARVs after giving birth (14). The benefits of having a peer mentor support a newly diagnosed pregnant woman living with HIV immediately after receiving their HIV test results during the perinatal period was also evaluated in KwaZulu Natal, South Africa, and showed a reduction in depressive symptoms among mothers and fewer underweight children in the clinics where the peer mentoring program was implemented (16; 17).
In resource-constrained settings like Zambia, efforts to eliminate mother-to-child transmission of HIV are challenged by limited health care worker capacity; stock outs of testing commodities; limited human resources for health; prolonged turnaround times for early infant diagnosis (EID) test results; poor 24-month retention with an increasing number of children infected in the breastfeeding period; weak cohort monitoring systems for tracking mother infant pairs (MIP) along the PMTCT cascade; and limited community support systems (18). Though Zambia has made significant strides in increasing PMTCT service utilisation and coverage with the national roll out of WHO Option B+ in 2013, more needs to be done to achieve elimination of mother-to-child transmission. For example, in 2016 nearly 8,900 infants were newly infected with HIV within the year, and data from the Zambian health information management system (HMIS) from 2016 suggests that the HIV positivity rates for EID tests done at 6 weeks, 6 months, 12 months and 18 months of age increase with age (19).
The m2m and other peer support models in the literature have been facilitated by implementing partners and require availability of financial resources to remunerate the mentor-mothers. In the context of constrained budgets and competing health needs, such interventions are unlikely to be prioritised for support by the Zambian Ministry of Health (MOH) and this has implications on equity in health as not all needy communities would be served. Alternative approaches that can be feasibly implemented by public health systems are needed. In Zambia, an MIP clinic model was being implemented in selected facilities in two districts (Kitwe in Copperbelt Province and Chipata in Eastern Province). This MIP clinic approach, called Umoyo which is translated as "Clinic of Life" from a local Zambian dialect, was started at Mtendere Mission Hospital with support from Churches Health Association of Zambia (CHAZ) in Chirundu District of Lusaka Province in 2007. In Kitwe and Chipata Districts, the model was being sustained by a lean staff of health workers supported by few volunteers without external financing or material support. By creating a separate clinic day for HIV-positive mothers and their HEIs to receive integrated HIV and routine PNC services, the Umoyo MIP clinic ensures that mother-infant pairs receive the services they need and fosters the development of informal mother-to-mother peer support systems. The Zambian MOH was interested in evidence on whether this model could successfully improve retention of HIV-exposed infants in care. In resourceconstrained health systems like Zambia, the Umoyo MIP clinic approach would be a significant contribution to the elimination of mother to child transmission of HIV efforts.
However, only anecdotal evidence existed in support of this model and therefore a rigorous evaluation of this clinic model would generate evidence to inform policy makers.
Umoyo MIP clinics are expected to increase the knowledge of mothers on HIV and retention, improve social support, and decrease perceived stigma. By achieving these proximal outcomes, it is expected that a mother's clinic attendance would increase (11; 10), and as a result, her HIV-exposed child would also be retained in care, more so than if they had not participated in Umoyo. A theory of change for the Umoyo MIP clinic intervention is shown in Figure 1 below. While this study focuses on proximal or intermediate outcomes, the potential long-term outcomes are also listed. This study seeks to answer the question: "What is the impact of Umoyo MIP clinics on retention of HIV exposed infants in PMTCT care at 12 months after birth?"

Study design
This impact evaluation was a two-arm difference-in-difference cluster randomized controlled trial conducted in Lusaka and Eastern provinces of Zambia. It assessed the change in proportion of HIV-exposed infants retained in care 12 months before and after the Umoyo MIP clinic was launched in 14 intervention sites compared to the change in retention in 14 control sites with the standard of care.

Study population
There were three main target populations from which the sample was drawn: health facilities, HEIs and HIV-positive mothers. Whereas the primary cohort for the study was a narrow cohort of infants in 2016 and 2017, the population eligible for the intervention was any infant born to an HIV positive mother all the way up to 24 months of age. In addition, MIPs can remain in the Umoyo MIP clinic until cessation of breastfeeding and/or the child is 24 months. Those infants who test HIV negative at 24 months are discharged from PMTCT care while those who seroconvert are transitioned to continue treatment at the normal ART clinic together with their mothers.
Before the intervention began, an orientation of staff in charge of facilities and the mother and child health (MCH) departments in the intervention facilities was conducted. The District PMTCT coordinators for all districts in the sample were also invited to this training to ensure district buy-in and ownership throughout the process. This constituted a two-day training, which included introducing them to the Umoyo model and also mentoring them on data quality. The orientation of the Umoyo MIP clinics was done by the Kitwe District PMTCT Coordinator and staff from health facilities in Kitwe that were implementing Umoyo using the human and financial resources provided by the public health system. After this general orientation, a follow-up, on-site orientation of all facility staff, including lay counselors, on how to implement Umoyo MIP clinics was conducted with the help of the CIDRZ team. Additionally, a nurse within MCH was identified to be the custodian of the list of defaulters and was responsible for communicating with the lay counsellors regarding any MIPs that needed follow up within the community. This on-site orientation marked the beginning of the first month of the Umoyo MIP clinic implementation. Therefore, the support of CIDRZ in the roll out of the intervention was to facilitate the on-site orientation of Umoyo MIP clinics in the intervention sites, monitor the implementation fidelity of intervention (at least once within a quarter), ensure that each facility has adequate supplies of requisite medical supplies needed for PMTCT service provision and mentorship on data quality.
Intervention sites were also provided with a job aid (Annex 1) to help the health facility staff with scheduling their monthly Umoyo MIP clinics. Intervention sites were also instructed to keep an attendance book (Annex 2) for the Umoyo program. At the control sites, the facilities continued to function on a business as usual basis providing services as per public facility standard of care.

Study Outcomes
The primary outcome of interest was the change in the proportion of HEIs who were retained in care at 12 months; this outcome combined HEIs with negative or unknown HIV status receiving a test at 12 months with HIV-positive infants attending the scheduled 12month visit for ARV drug refills. Secondary outcomes included:

1.
Change in the proportion of HEIs retained at 6 months;

2.
Change in the proportion of HEIs with regular attendance as defined by retention in care at 6, 9 and 12 months of age;

3.
Change in perceived social support of mothers with HEIs and;

4.
Change in perceived stigma of mothers with HEIs.
To evaluate these outcomes, a cluster-randomized trial was conducted in 28 facilities.
Each of the facilities were selected based on availability of PMTCT services and approximately 10 or more HIV-exposed infants born each month. The sample of HEIs was selected from the HEI registers based on the inclusion criteria in Table 1.
For the primary outcome, we report the a priori estimated effect size we could detect assuming 14 facilities in each of two arms and 30 MIPs per facility (pre-and post-). The following equation (20) with the specific parameters in Table 2 was used to estimate that we would be able to determine a 12% difference in the average change in the proportion of HEI who returned for their 12-month visit (alpha 0.05 and power of 80%).
(Due to technical limitations, the equation has been placed in the Supplementary Files section.) For the mother interviews, mothers were approached during clinic days when PMTCT services were offered: women were eligible if they were the mother of an HEI born within 24 months of the survey date, and if the mothers were over the age of 18. Women and children who did not meet these criteria or those that did not attend the under-five clinic on the day the research team visited the facility were excluded.

Randomisation
Given the relatively small number of facilities per arm (N=14), a covariate constrained optimization technique was used to randomize intervention assignment and achieve balance in the two arms (21). Using estimates for annual expected HEI live births, the 2016 catchment population and districts, facilities were randomized using covariateconstrained randomization. The 28 sites were randomized 1,000 times and those iterations in which there was imbalance with an alpha of 0.1 on the aforementioned characteristics were removed. Among those remaining iterations where there was no imbalance detected at a threshold (F test beta = 0, alpha 0.1), an iteration of assignment was then selected at random.

Data collection
Three key sources were collected: patient registers, mother exit interviews, and facilitylevel questionnaires. In the original protocol, we had intended to gather data on monthly visits using the Septrin/Cotrimoxazole booklets (often called Septrin booklets in Zambia) and information on TB treatment using the Zambia National TB & Leprosy Control Program, IPT Register. However, we found that these booklets were not utilized in a standard way across all facilities. Thus, to minimize bias, the outcomes within this report rely on the HIV Exposed Infant (and mothers) Follow-Up Register only. We list our specific method of defining "retained" for each outcome by HIV status within the analysis section below.
For the mothers' stigma and social support, we performed mother exit surveys. The tools were translated into local dialect and back translated by an independent contractor. The surveys were created as follows: Social support: Nine questions were adapted from the Social Provisions Scale (22) to assess the degree of social support that women received from other women that attend the standard of care under-five clinic (pre-implementation) or the Umoyo MIP clinic (postimplementation). Adaptations reduced the scale to three items ("Disagree", "Not sure", and "Agree") and included an option for "Don't know, refused or don't want to say".
Stigma: 28 questions on stigma have been adapted from the HIV/AIDS stigma instrument (HASI-P) to include questions on internalized stigma and enacted stigma (e.g., verbal, fear of contagion, social isolation, and work place stigma) (23). We adapted the scale to limit to three (rather than four options), "Never", "Once or twice", and "Several times"; we also included an option for "Don't know/refused/ not applicable". Questions regarding HCW stigma were added and had a similar coding.
Facility level data was collected from surveys with key facility-level personnel to assess the general working environment in the facilities during the period of the study. The aspects relating to general working environment included frequency of stock-outs for key commodities relevant to the study outcomes, and whether sites received any additional support for PMTCT and/or paediatric HIV from implementing partners other than CIDRZ.
Data was collected at three points in time, with training of data collectors immediately prior to the start of each data collection (table 3).
Data collectors were hired specifically for this study and received three-day training.
Direct supervision within facilities was conducted for all enumeration teams on a rolling basis and troubleshooting support was provided to all enumerators. All data was electronically entered using SurveyCTO at the point of collection except the mother interviews which were administered using paper tools. At the end of the data collection period, all the mothers' questionnaires were entered twice by two different enumerators.
Once the double data entry was complete, the discrepancies in entry were reconciled by checking with the entry in the hardcopy.

Analysis
Facility, child, and mother characteristics were compared to examine balance between the two arms before the intervention was implemented. For the facility characteristics, the self-reported values from the HCW were assumed to be facility-specific and the distribution (percentage and 99% confidence interval [CI]) was calculated. For the child and mother characteristics, an average estimate was calculated for each facility which was then pooled together per arm; to this end, the values, unless otherwise specified, are aggregate facility-level values. This analysis method for cRCTs produces a conservative estimate of difference when the facility sample size is less than 10 facilities per arm [6].
The difference between the two arms during the pre-implementation phase, as well as in the change from pre-to post-implementation was tested using unweighted t-tests.
Given that the evaluation was being implemented in a natural setting, monitoring of Umoyo exposure was not standardized or rigorously maintained, thus per protocol analysis was not carried out. All analysis reported are intent-to-treat.
For the outcomes, we categorized the eligible children from both the pre-implementation period and post-implementation period as retained according to the outcomes as listed in Table 4. For mothers regarding social support and stigma outcomes all mothers received a score similar to the Holzmer 2007 work but accounting for the fact we included an 'N/A' response and had a lower maximum possible range (23). To this end, we gave all "Don't Know, refused, or don't want to say, or NA" responses a missing value. We then gave those who had the lowest answer on the item (e.g., disagree, or never occurred, or no) a zero and those with the next two levels of responses a one or two, accordingly. We then created a weighted score: all items for the specific topic were summed and the mother received a score by dividing this sum by the total number of non-missing items. Thus, the score always represented the highest level of either social support or stigma. Similar to the child outcomes, the analysis was run in two methods: a facility-aggregate analysis using unweighted t-tests and an individual-level linear GEE. For the multivariable linear GEE model, though differences were not statistically significant, we included covariates for the average number of interviews per facility, if the mother was over 40, if she were married, or had been on HIV treatment for a year.
All analyses were conducted assuming intent-to-treat for a conservative estimate as written in the original protocol. Given the lack of a robust and rigorous method to identify true exposure of the children, a per protocol analysis was not reported. Figure 2 illustrates the final sample of facilities obtained for the study. In Table 6, we report the child-level outcomes for the outcomes of interest. We found that the Umoyo program did not improve the proportion of children who were retained in care at 12 months (-11%; 99% CI: -40.1%, 17.2%) or continually from 6 to 12 months (-6.5; 99%

Results
CI: -24.7%, 11.7%). In logistic GEE models, evidence even suggested that the Umoyo program may have had a significantly negative impact on retention as the treatment effect overtime (i.e. interaction term) showed a reduction of 0.2 lower odds of retention at retention at 12 months (with 6-and 9-month retention) from baseline to endline for children enrolled in an Umoyo facility as compared to the change for children in control facilities (Table 7). Table 8 shows distribution of the mothers' outcomes on stigma and social support for mother exit interviews. Over time, according to an alpha of <0.01, we did not see evidence that the Umoyo program improved the social support scores (mean 0.2, 99% CI: With the linear GEE models, however, we did that the treatment effect overtime (i.e. the interaction term) showed that mothers in the intervention arm from baseline to endline increased their social support score 0.31 units more as compared to the change in social support score for mothers in control facilities (99% CI: 0.08, 0.54). We also found that the HCW stigma decreased overtime to a larger degree from baseline to endline for mothers in the intervention facilities as compared to the change in reported HCW stigma for mothers in control facilities (mean diff: -0.27; 99%CI: -0.46, -0.08) (table 9).

Discussion
The findings of this study show that the Umoyo MIP clinic did not have a significant impact on the 12-month postpartum retention of HEIs in PMTCT care. Rather, GEE results suggest that the 12-month retention outcomes overtime for HEIs in control facilities were better than that observed in the intervention sites. At the same time, the Umoyo MIP clinic may have had a statistically significant impact on improving social support overtime and reducing HCW stigma but did not have any effect on reducing internalized stigma nor enacted stigma.
The finding that the Umoyo MIP clinics did not have a significant effect on retention of HEIs has been found in cluster randomized controlled trials testing the impact of Umoyo MIP clinic-like interventions in similar settings such as Malawi and Zimbabwe. In Malawi, an MIP clinic offering integrated services to HIV-positive mothers and their HEIs on the same day including sending SMS reminders to mothers on follow-up appointments found no statistically significant impact on retention of infants in PMTCT care. The lack of impact was largely attributed to partial implementation fidelity where about 42% of the mothers were exposed to the intervention (24). In Zimbabwe, a cluster randomized controlled trial found that mother support groups at health facilities had no statistically significant impact on retention of HEIs at 12 months (25). However, compared to our work these studies found a higher proportion of retention in the intervention than in the control, though insignificant, while our study suggested a lower rate of retention due to the program.
There are two possible reasons for the potentially null or negative impact observed in this study. First, the evidence on exposure to the intervention was limited but shown to be relatively low at roughly 50%. Based on conversations with the facility staff and field visits, it was obvious that the intervention was implemented in non-standard ways, pointing to weak monitoring of the intervention. Even in places where strong Umoyo MIP clinic champions were present at facility level at the outset, staff turn-over led to variable content and quality of Umoyo MIP clinics. The second possible reason for the negative impact of Umoyo MIP clinics on retention of HEIs is that facility staff reported that the intervention may have had an adverse effect on data completeness of facility registers.
Anecdotally, facility staff in intervention sites mentioned that they were the busiest on Umoyo clinic days due to the huge volume of services to be provided, a fact that was compounded by constrained human resources. Therefore, it is possible that staff may have de-prioritized the need to update the facility registers even though PMTCT-related services had been provided.
The indicative positive results of the intervention on social support and HCW stigma are similar to other peer-to-peer mentor support studies because the Umoyo MIP clinics are founded on the idea that mothers interact with the mothers much more than would be the case without them (16; 17). Additionally, since the running of Umoyo MIP clinics is HCWdriven, it is possible that a reduction in HCW stigma was observed. However, there is no literature on studies that have evaluated the evolution of stigma using the HASI-P instrument in order to compare with our study findings for non-improvement in internalized and enacted stigma.

Limitations
Our study has several limitations. One limitation is that three facilities in the intervention arm and one in the control arm were excluded from the difference-in-difference analysis due to lack of implementation. Thus, power was lower than anticipated and our minimal effect size and precision were relatively large. Another limitation is that though there was no statistical difference between the two arms and examined covariates (save for the patient load per facility), there may have been residual imbalance at the time the intervention began and we were not able to collect individual-level data about other potential confounders.
This study aimed to build on existing health system protocols and documentation without creating additional requirements or resources, however it should be noted that completeness of the data registers was an issue. We sometimes found registers other than the primary register as alternative sources of the required information. As these secondary registers were not present in all facilities, the extent to which they had complete data compared to the primary register is unknown. Therefore, in facilities where other registers were preferred by facility staff as the primary register for recording information, then the outcomes may have been underestimated. The study also did not account for the variability in the use of the primary register across all the facilities nor did the study compare the data completeness in these secondary registers to the primary register. Thus, the findings from this work could potentially be biased.
The other limitation of the study relates to the overall fidelity of the intervention. Some facilities, usually the small facilities, had near perfect fidelity to the intervention while the large volume sites had poor fidelity. Finally, regarding the mothers' stigma and peer support outcomes, the limitation with these results is that they were not performed on the same mothers before and after the intervention. Therefore, their applicability is subject to the limitations of the methodology employed i.e. confounding factors may be able to explain the presence or absence of the impact seen.

Conclusions
Results of this cluster randomised control trial found that a low-cost intervention such as the Umoyo program had no impact on increasing retention of HEIs within PMTCT and did not reduce internalized and enacted stigma using both the GEE estimates and the unweighted T-test comparison estimates. Regarding peer support and HIV stigma, the two estimation procedures provided different conclusions. The GEE gave support that Umoyo increases social support and reduced HCW stigma but the un-weighted t-test showed no impact. Factors such as low exposure to the intervention due to poor implementation fidelity, de-prioritization of filling in the primary source of data collection for this study in the intervention sites due to the burden of the intervention on Umoyo MIP clinic days, and non-use of a potential key register for the 12-month testing information could explain the absence of impact and an association with worse outcomes for HEIs in the intervention.
Alternative models that can improve retention of HIV exposed infants in PMTCT care within a public health system in resource constrained settings need to be evaluated. If Umoyo is to be scaled, specific systems improvements should be made including increasing the number of HCW per facility.

Consent for publication
Not applicable

Availability of data and material
The datasets used during the current study are available from the corresponding author on reasonable request.

Competing interests
The authors declare that they have no competing interests.        0.01 (-0.29, 0.32) *Removed the facilities that do not have data in pre-or post-intervention period.