Stepped-Wedge Cluster Randomized Controlled Trial to Promote Option B+ Retention in Central Mozambique.

BACKGROUND: This randomized trial studied performance of Option B+ in Mozambique and evaluated an enhanced retention package in public clinics. SETTING: The study was conducted at 6 clinics in Manica and Sofala Provinces in central Mozambique. METHODS: Seven hundred sixty-one pregnant women tested HIV+, immediately initiated antiretroviral (ARV) therapy, and were followed to track retention at 6 clinics from May 2014 to May 2015. Clinics were randomly allocated within a stepped-wedge fashion to intervention and control periods. The intervention included (1) workflow modifications and (2) active patient tracking. Retention was defined as percentage of patients returning for 30-, 60-, and 90-day medication refills within 25-35 days of previous refills. RESULTS: During control periods, 52.3% of women returned for 30-day refills vs. 70.8% in intervention periods [odds ratio (OR): 1.80; 95% confidence interval (CI): 1.05 to 3.08]. At 60 days, 46.1% control vs. 57.9% intervention were retained (OR: 1.82; CI: 1.06 to 3.11), and at 90 days, 38.3% control vs. 41.0% intervention (OR: 1.04; CI: 0.60 to 1.82). In prespecified subanalyses, birth before pickups was strongly associated with failure-women giving birth before ARV pickup were 33.3 times (CI: 4.4 to 250.3), 7.5 times (CI: 3.6 to 15.9), and 3.7 times (CI: 2.2 to 6.0) as likely to not return for ARV pickups at 30, 60, and 90 days, respectively. CONCLUSIONS: The intervention was effective at 30 and 60 days, but not at 90 days. Combined 90-day retention (40%) and adherence (22.5%) were low. Efforts to improve retention are particularly important for women giving birth before ARV refills.

Clinical Impact and Cost-effectiveness of Xpert MTB/RIF Testing in Hospitalized Patients With Presumptive Pulmonary Tuberculosis in the United States.

Background: Microscopic examination of acid-fast-stained sputum smears is the current standard of care in the United States to determine airborne infection isolation (AII) of inpatients with presumptive pulmonary tuberculosis (PTB). However, nucleic acid amplification testing (NAAT) with the Xpert MTB/RIF assay (Xpert) may be more efficient and less costly. Methods: This prospective observational cohort study enrolled a consecutive sample of 318 AII-eligible inpatients from a public hospital in Seattle, Washington, from March 2012 to October 2013. Sputum samples were collected from each inpatient and analyzed using smear microscopy, culture, drug susceptibility testing, and NAAT. The performance, clinical utility (AII duration and survival), and cost-effectiveness from an institutional perspective were compared for 5 testing strategies. Results: Among the 318 admissions with presumptive PTB, 20 (6.3%) were culture-positive for Mycobacterium tuberculosis. The sensitivity of 1 Xpert, 2 Xperts, 2 smears, or 3 smears compared to culture was 0.85 (95% confidence interval [CI], .61­.96), 0.95 (95% CI, .73­1.0), 0.70 (95% CI, .46­.88), and 0.80 (95% CI, .56­.93), respectively. A cost-effectiveness analysis of the study results demonstrated that an Xpert test on 1 unconcentrated sputum sample (assuming equivalent results for unconcentrated and concentrated sputum samples) is the most cost-effective strategy (99.9% preferred at willingness-to-pay of US$50000) and on average would save 51.5 patient-hours in AII and up to $11466 relative to microscopy without a compromise in sensitivity. Conclusions: In hospitalized patients with presumptive PTB in a low-burden setting, NAAT can reduce AII and is comparably sensitive, more specific, and more cost-effective than smear microscopy.

Option B+ in Mozambique: Formative Research Findings for the Design of a Facility-Level Clustered Randomized Controlled Trial to Improve ART Retention in Antenatal Care.

INTRODUCTION: With the rollout of "Option B+" in Mozambique in 2013, initial data indicated major challenges to early retention in antiretroviral therapy (ART) among HIV-positive pregnant women. We sought to develop and test a pilot intervention in 6 large public clinics in central Mozambique to improve retention of mothers starting ART in antenatal care. The results from the formative research from this study described here were used to design the intervention. METHODS: The research was initiated in early 2013 and completed in early 2014 in each of the 6 study clinics and consisted of (1) patient flow mapping and measurement of retention through collection of health systems data from antenatal care registries, pharmacy registries, ART clinic databases, (2) workforce assessment and measurement of patient waiting times, and (3) patient and worker individual interviews and focus groups. RESULTS: Coverage of HIV testing and ART initiation were over 90% at all sites, but retention at 30-, 60-, and 90-day pharmacy refill visits was very low ranging from only 5% at 1 site to 30% returning at 90 days. These data revealed major systemic bottlenecks that contributed to poor adherence and retention in the first month after ART initiation. Long wait times, short consultations, and poor counseling were identified as barriers. CONCLUSIONS: Based on these findings, we designed an intervention with these components: (1) workflow modification to redefine nurse tasks, shift tasks to community health workers, and enhance patient tracking and (2) an adherence and retention package to systematize active patient follow-up, ensure home visits by community health workers, use text messaging, and intensify counseling by health staff. This intervention is currently under evaluation using a stepped wedge design.

Early ART initiation among HIV-positive pregnant women in central Mozambique: a stepped wedge randomized controlled trial of an optimized Option B+ approach.

BACKGROUND: Despite effective prevention strategies and increasing investments in global health, maternal to child transmission (MTCT) of HIV remains a significant problem globally, especially in sub-Saharan Africa. In 2012, there were 94,000 HIV-positive pregnant women in Mozambique. Approximately 15% of these women transmitted HIV to their newborn infants, resulting in nearly 14,000 new pediatric HIV infections that year. To address this issue, in 2013, the Mozambican Ministry of Health implemented the World Health Organization-recommended "Option B+" strategy in which all newly diagnosed HIV-positive pregnant women are counseled to initiate combination anti-retroviral therapy (ART) immediately upon diagnosis regardless of CD4 count and to continue treatment for life. Given the limited experience with Option B+ in sub-Saharan Africa, few rigorous pragmatic trials have studied this new treatment strategy. METHODS: This study utilizes an initial formative research process involving patient and health care provider interviews and focus groups, workforce assessments, value stream mapping, and commodity utilization assessments to understand the strengths and weaknesses in the current Option B+ care cascade. The formative research is intended to guide identification and prioritization of key workflow modifications and the development of an enhanced adherence and retention package. These two components are bundled into a defined intervention implemented and evaluated across six health facilities utilizing a stepped wedge randomized controlled trial study design. The overall objective of this trial is to develop and test a pilot intervention in central Mozambique to implement the new Option B+ guidelines with high fidelity and increase the proportion of HIV-positive pregnant women in target antenatal clinics (ANC) who start ART prior to delivery and are retained in care. DISCUSSION: This pragmatic study utilizes research strategies that have the potential to meaningfully improve the Option B+ care cascade in central Mozambique and to decrease the MTCT of HIV. This trial is designed to identify critical low-cost improvement strategies that can be bundled into a defined intervention. If this intervention has a measurable impact, it can be rapidly scaled up to other ANC in Mozambique and sub-Saharan Africa. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02371265.