Background
South Africa has made considerable gains in improving prevention of mother-to-child transmission of HIV (PMTCT) services coverage since being identified as a Global Plan Priority country in 2009 [
1]. In 2012, nearly 4 million women in the country lived with HIV and antenatal HIV prevalence was 30% [
2]. The PMTCT Cascade of Care (CoC) refers to key steps in the clinical pathway from early diagnosis of HIV in pregnancy/postpartum to achieving long-term maternal HIV virologic suppression on antiretroviral therapy (ART), retention-in-care, and early infant diagnosis and treatment [
3]. Leakages in the PMTCT care cascade hinder progress towards eliminating paediatric HIV and protecting maternal and child health.
Among pregnant women who are HIV-positive, HIV viral load (VL) testing is critical to judge the clinical performance of ART and to prevent vertical transmission of HIV from mother to child [
4,
5]. Vertical transmission risk increases with maternal VL [
6,
7]. VL testing can identify virologic failure early, leading to timely interventions such as adherence counselling, resistance testing and treatment switches, and enhanced antiretroviral prophylaxis for HIV-exposed infants [
8]. Moreover, VL testing is important because large proportions of pregnant women on ART are failing virologically (by some estimates 20–40% [
9,
10]). The South African National PMTCT guidelines recommend universal ART for pregnant women who are HIV-positive and regular VL testing to monitor the clinical performance of ART [
11]. However, in many communities in South Africa and other sub-Saharan African countries the majority of pregnant women on ART, and non-pregnant women and men, do not receive regular VL tests [
12‐
15].
Repeat HIV testing of pregnant women who are HIV-negative is important because HIV incidence in pregnancy is high in many countries [
16]. In South Africa, HIV incidence in pregnancy and postpartum is estimated to be above 4% [
10,
16]. Since VL increases markedly shortly after infection, the risk of MTCT is particularly high among recently infected women [
17]. Early diagnosis of HIV and initiation of ART are thus critical to ensure that MTCT is eliminated, but this requires pregnant women who are HIV-negative to be re-tested at regular intervals [
18]. The South African National PMTCT guidelines thus recommend pregnant women who are HIV-negative to be tested in three-monthly intervals after the initial HIV test during the first antenatal visit [
11]. However, in South Africa and other countries in sub-Saharan Africa large proportions of pregnant women who are HIV-negative do not receive repeat HIV tests [
17,
19,
20].
In addition to the need for improvements in early diagnosis of HIV and regular VL monitoring of ART in antenatal care, adherence to clinical guidelines and quality of care continue to be major challenges following delivery in many countries [
21,
22], undermining the delivery of effective postnatal care to mothers and children including ART, safe infant feeding and postnatal contraception.
One important approach to improving quality of care in the health sector is Continuous Quality Improvement (CQI) [
23,
24]. Several features of CQI make it an attractive choice to improve quality of care and adherence to clinical guidelines in pregnancy-related care in sub-Saharan Africa. First, CQI uses time-tested and robust management techniques to diagnose quality problems, develop solutions and monitor progress. These techniques can be adapted to improve many different processes and healthcare functions, depending on clinical contextual needs and opportunities for improvement identified with real-time data [
23,
24]. Second, CQI empowers health workers to develop approaches and take actions to improve quality of care on an ongoing basis. CQI mentors work with local clinic staff to facilitate the development of solutions to quality of care shortcomings that the staff identify as best suited to their local contexts. Third, CQI works within existing resource constraints and does not require large long-term investments to ensure sustained improvements in quality of care [
25].
Several randomized controlled trials have demonstrated that CQI initiatives can be successful in improving quality of hospital care in resource-rich countries [
26‐
28]. However, despite major CQI initiatives in primary care in several sub-Saharan African countries [
29‐
33], rigorous scientific evidence on CQI effectiveness in these settings is largely lacking.
The MONARCH stepped-wedge cluster RCT will for the first time establish the effectiveness of an intervention to improve VL testing in pregnant women who are HIV-positive and repeat HIV testing in pregnant women who are HIV-negative in primary care clinics in rural South Africa.
More broadly, the trial will contribute to our understanding of the effectiveness of CQI in improving the quality of antenatal and postnatal care and add to the scarce but growing evidence on the effectiveness of CQI as an approach to improve quality of care in sub-Saharan Africa [
34,
35]. This evidence is important because several governments in sub-Saharan Africa are using CQI to improve quality of care in public-sector healthcare provision [
29‐
33].
Primary and secondary endpoints
Our primary endpoints are (i) viral load testing among pregnant women who are HIV-positive and (ii) repeat HIV testing among pregnant women who are HIV-negative. Our secondary endpoints are:
(i)
Patient experiences of healthcare quality among all pregnant women
(ii)
Maternal health outcomes including:
a.
Postnatal care attendance within 6 weeks postpartum among all pregnant women
b.
Maternal retention in HIV care among women who are HIV-positive
c.
ART utilization among women who are HIV-positive
d.
Maternal HIV virologic suppression among women who are HIV-positive
e.
HIV seroconversion in pregnancy among women who are HIV-negative
(iii)
Infant health outcomes including:
a.
Mother-to-child transmission of HIV
b.
Nevirapine prophylaxis for HIV-exposed infants
c.
Infants with weight, length, and head circumference measured
(iv)
Maternal knowledge and uptake of key services including:
(v)
Healthcare provider job satisfaction and motivation
Discussion
The MONARCH stepped-wedge RCT is the first trial to determine the effectiveness of an intervention to increase testing for health indicators among pregnant women that are critical for good health outcomes in HIV hyperendemic communities: VL testing among pregnant women who are HIV-positive and repeat HIV testing among pregnant women who are HIV-negative. The MONARCH study is also one of the first to measure the causal effect of CQI on ANC and PNC services in sub-Saharan Africa.
The MONARCH trial was embedded within the public health system and implemented within routinely available resources including the physical infrastructure of primary care clinics, data systems, and human resources. The success of the CQI intervention depends not only on this context, including staff motivation and the other resources available to change clinical processes. One of the advantages of CQI is that it leads to a selection of actions that can lead to successful improvements given the local abilities and constraints. Through local data collection and clinic-specific analysis health workers are empowered to identify the root causes of existing shortcomings; through small-scale tests in PDSA cycles they can develop the locally best solutions to address these shortcomings. The iterative manner in which CQI unfolds ensures that candidate solutions are repeatedly tested and modified until robust and sustainable approaches have been identified [
44,
45]. Given significant resource constraints, it is particularly important to understand the mechanisms of the locally developed approaches and the determinants of their success. The Process Evaluation, which was nested in this trial, will therefore be highly informative in understanding the implementation of this complex intervention.
The MONARCH trial has several limitations. First, it took place in a real-life setting where normal service delivery and targets had to be met during CQI implementation – this may have limited the availability of healthcare providers to participate in the intervention. This test of the effectiveness of CQI was thus a test of CQI “in real life” and we cannot conclude from a null finding that CQI cannot be highly effective in a context with fewer outside pressures and more resource commitments. Second, advertisement of the study to DoH sub-district and facility staff prior to MONARCH study start may have driven changes towards endpoint targets and biased impact evaluation towards the null. Finally, the health workers in the control clusters might have learned about CQI methods and approaches to improve endpoint attainment from the health workers in the intervention clusters, also resulting in bias towards the null. Conversely, our efforts to reduce such contamination – such as blinding health workers to the randomisation status of their clinic and instructing the CQI mentors not to suggest solutions developed by previous clinic teams in their interactions with new clinic teams until post-randomisation – run counter to the philosophy of CQI, which includes sharing of solutions and approaches between CQI teams. These measures, which increase the validity of the trial, may have reduced the effectiveness of the CQI intervention that we have tested.
Overall, we expect that the results of the MONARCH trial and nested process evaluation will be useful for policy makers and practitioners seeking to increase the quality of care for pregnant women in HIV hyperendemic communities. It will also be useful for health systems managers striving to improve quality of primary care in severely resource-constrained clinics. Study results will be shared with local and regional policy makers during policy engagement workshops and presentations. We will also disseminate our results via peer-reviewed journals and presentations at scientific conferences.
Trial status
The study commenced in mid-July 2015 and ended on 30 January 2017. At the time of submission of the manuscript, no other articles pertaining to the protocol are published or under consideration for publication.
Acknowledgements
The authors wish to thank: [1] the Centre for Rural Health, University of KwaZulu-Natal for implementing the CQI intervention at clinics; [2] South African National Department of Health partners at Hlabisa Hospital, uMkhanyakude District and KwaZulu-Natal Provincial Department of Health for their engagement in developing the study concept and supporting the study, including Dr Hervey Williams, Dr Martin Tshipuk, Sr Makhozana Themba, Ms Nontokozo Mathabela, Sr Xolani Ndlovu, and Mr Nkosinathi Mabika; [3] colleagues at AHRI supporting day-to-day project operations including Research Nursing Manager Mr Siphephelo Dlamini; [4] the MONARCH DSMB members; and [5] all study participants including postnatal women and healthcare providers for allowing us to conduct this study.