A prospective cohort study of outcomes for isoniazid prevention therapy: a nested study from a national QI collaborative in Uganda.

BACKGROUND: Tuberculosis (TB) and human immunodeficiency virus (HIV) co-infection constitute a deadly infectious disease synergy disease and major public health problem throughout the world. The risk of developing active TB in people living with HIV (PLHIV) is 21 times higher than the rest of the world population. The overlap of latent TB infection and HIV infection has resulted in marked increases in TB incidence in countries with dual epidemics. Although antiretroviral therapy (ART) is the single most significant way to reduce incident TB in PLHIV, besides early ART initiation, isoniazid preventive therapy (IPT) is the key intervention to prevent TB among PLHIV. This prospective cohort and longitudinal study aimed to document; retention, adherence, development of active TB disease, possible adverse drug reactions and completion among patients initiated on IPT in Jan 2019. METHODS: This was both a prospective cohort and longitudinal study nested within a national quality improvement collaborative in which multiple quality improvement teams tested changes in care delivery to improve the delivery of IPT. The prospective cohort were HIV patients without TB disease initiated on a dosage of Isoniazid 300 mg/day for adults and 150 mg/day for children for a period of 6 months. Association statistics were used to describe patient characteristics and outcomes. Variables with p-value < 0.05 were used to determine linear by linear associations between patient characteristics assumed to influence both primary and secondary outcomes. Variables with a p-value < 0.05 were included in the logistical regression model. The final model included those factors that retained statistical significance. The odds ratios (OR) and adjusted OR (AOR) along with its 95% confidence interval were used to determine the power of relationship in determining the outcomes of interest. The model was tested for fitness using goodness-of-fit Hosmer-Lemeshow tests. RESULTS: The completion of IPT was at 89%. A significant proportion of patients adhered to treatment (89%) and kept their appointment schedules-retention (89%). All patients (100%) received IPT at each appointment visit. Only 4% of patients experienced side effects of isoniazid (INH) but none of them developed active TB at the end of the 6 month INH dose. Multivariate logistic regression analysis of covariates of IPT completion revealed a strong and statistical association between IPT completion and age, gender, retention and side effects of INH. Our multivariate model found that children below 15 years were less likely to complete INH than patients ≥ 15 years (AOR = 0.416, p = 0.230, df = 1). Female patients were 2 times more likely to complete INH dose than male patients (AOR = 1.598, p = 0.018). Patients who kept all their appointment schedules were 10 times more likely to complete IPT than those who missed one or more schedules (AOR = 10.726, p = 0.000, df = 1). We also found that patients who did not report any side effects associated with INH were 2 times more likely to complete INH (AOR = 1.958, p = 0.016, df = 1) than patients who reported one or more side effects. CONCLUSION: Treatment completion is the end-point of the IPT initiation strategy in Uganda. With a completion rate of 89%, our results seem re-assuring and suggest that improvement collaborative is an effective approach to achieving results through combined efforts. The high rates of completion are encouraging indicators of progress in the implementation of collaborative activities in the study setting. However, such collaboratives would require periodic evaluation to prevent possible relapses in progress attained.

Multivariate analysis of covariates of adherence among HIV-positive mothers with low viral suppression.

BACKGROUND: As part of efforts to improve the prevention of mother-to-child transmission in Northern Uganda, we explored reasons for poor viral suppression among 122 pregnant and lactating women who were in care, received viral load tests, but had not achieved viral suppression and had more than 1000 copies/mL. Understanding the patient factors associated with low viral suppression was of interest to the Ministry of Health to guide the development of tools and interventions to achieve viral suppression for pregnant and lactating women newly initiating on ART as well as those on ART with unsuppressed viral load. METHODS: A facility-based cross-sectional and mixed methods study design was used, with retrospective medical record review. We assessed 122 HIV-positive mothers with known low viral suppression across 31 health facilities in Northern Uganda. Adjusted odds ratios were used to determine the covariates of adherence among HIV positive mothers using logistic regression. A study among health care providers shed further light on predictors of low viral suppression and a history of low early retention. This study was part of a larger national evaluation of the performance of integrated care services for mothers. RESULTS: Adherence defined as taking antiretroviral medications correctly everyday was low at 67.2%. The covariates of low adherence are: taking other medications in addition to ART, missed appointments in the past 6 months, experienced violence in the past 6 months, and faces obstacles to treatment. Mothers who were experiencing each of these covariates were less likely to adhere to treatment. These covariates were triangulated with perspectives of health providers as covariates of low adherence and included: long distances to health facility, missed appointments, running out of pills, sharing antiretroviral drugs, violence, and social lifestyles such as multiple sexual partners coupled with non-disclosure to partners. Inadequate counseling, stigma, and lack of client identity are the frontline factors accounting for the early loss of mothers from care. CONCLUSIONS: Adherence of 67% was low for reliable viral suppression and accounts for the low viral suppression among HIV-positive mothers studied, in absence of any other factors. This study provided insights into the covariates for low adherence to ART and low viral load suppression; these covariates included taking other medications in addition to ART, missed appointments in the past 6 months, feels like giving up, doesn't have someone with whom to share private concerns, experienced violence in the past 6 months, and faces obstacles to treatment and confirmed by health providers. To improve adherence, we recommend use of a screening tool to identify mothers with any of these covariates so that more intensive adherence support can be provided to these mothers.

Quality improvement as a framework for behavior change interventions in HIV-predisposed communities: a case of adolescent girls and young women in northern Uganda.

BACKGROUND: Despite the conventional approaches to HIV prevention being the bedrock for early reductions in HIV infections in Uganda, innovations that demonstrate reduction in risk to infection in vulnerable populations need to be embraced urgently. In the past 2 years, a USAID-funded project tested a quality improvement for behavior change model (QBC) to address barriers to behavioral change among adolescent girls and young women (AGYW) at high risk of HIV infection. The model comprised skills building to improve ability of AGYW to stop risky behavior; setting up and empowering community quality improvement (QI) teams to mobilize community resources to support AGYW to stop risky behavior; and service delivery camps to provide HIV prevention services and commodities to AGYW and other community members. METHODS: We recruited and followed a cohort of 409 AGYW at high risk of HIV infection over a 2-year period to examine the effect of the QBC model on risky behaviors. High-risk behavior was defined to include transactional sex, having multiple sexual partners, and non-use of condoms in high-risk sex. We documented unique experiences over the period to assess the effect of QBC model in reducing risky behavior. We analyzed for variances in risk factors over time using repeated measures ANOVA. RESULTS: There were statistically significant declines in high-risk behavior among AGYW over the QBC roll-out period (p < 0.05). Univariate analysis indicated reduction in AGYW reporting multiple sexual partners from 16.6% at baseline to 3.2% at follow up and transactional sex from 13.2 to 3.6%. The proportion of AGYW experiencing sexual and other forms of gender based violence reduced from 49% a baseline to 19.5% at follow up due to the complementary targeting of parents and partners by QI teams. CONCLUSION: The QBC model is appropriate for the context of northern Uganda because it provides a framework for the community to successfully drive HIV prevention efforts and therefore is recommended as a model for HIV prevention in high-risk groups.

Improving TB case notification in northern Uganda: evidence of a quality improvement-guided active case finding intervention.

BACKGROUND: Strategies to identify and treat undiagnosed prevalent cases that have not sought diagnostic services on their own, are necessary to treat TB in patients earlier and interrupt transmission. Late presentation for medical services of symptomatic patients require special efforts to detect early and notify TB in high risk populations. An intervention that combined quality improvement with facility-led active case finding (QI-ACF) was implemented in 10 districts of Northern Uganda with the highest TB burden to improve case notification among populations at highest risk of TB. METHODS: Using QI-ACF intervention approach in 48 facilities, we; 1) targeted key vulnerable populations, 2) engaged district and facility teams in TB systems strengthening, 3) conducted systematic screening and diagnosis in vulnerable groups (people living with HIV, fishing communities, and prisoners), and 4) trained health workers on national x-ray diagnosis guidelines for smear-negative patients. Facility-led QI-ACF meant that health care providers identified the target population, mobilized and massively screened suspects, and addressed gaps in documentation. Chest X-ray diagnosis was promoted for smear-negative TB among those suspects whose sputum examination was negative. The effect of the intervention on case notification was then assessed separately over the post intervention period. RESULTS: Over all TB case notification in the intervention districts increased from 171 to 223 per 100,000 population between the baseline months of October-December 2016 and end line month of April-June 2017. TB patient contacts had the majority of TB positive cases identified during active case finding (40, 6.1%). Fishing communities had the highest TB positivity rate at 6.8%. Prisoners accounted for the lowest number of TB positive cases at 34 (2.3%). CONCLUSION: Targeting should be applied at all levels of TB intervention to improve yield: targeting districts and facilities with the lowest rates of case notification and targeting index patient contacts, HIV clients, and fishing communities. Screening tools are useful to guide health workers to identify presumptive cases. Efforts to improve availability of x-ray for TB diagnosis contributed to almost half of the new cases identified. Having all HIV patients who were eligible for viral load provide sputum for TB screening proved easy to implement.

Applying a Three-Tier Approach to Address Gaps in Oral Pre-Exposure Prophylaxis Uptake and Continuity in Uganda: A Mixed Methods Approach.

BACKGROUND: We describe a 3-tier approach involving a gap analysis, root cause analysis, and pre-exposure prophylaxis (PrEP) collaborative to understand the gap and identify and address the main barriers to oral PrEP uptake and continuity in Uganda. METHODS: We used a mixed methods design with retrospective, cross-sectional, and prospective components. The gap analysis involved descriptive analysis of PrEP uptake and continuity. The RCA identified the main barriers to initiation and continuity on PrEP among 1,334 clients who declined to start PrEP and 1,266 who missed their appointment but were at risk. The PrEP collaborative tested changes mapped onto specific barriers to optimize the PrEP clinical service delivery. A trend analysis of routinely collected data of the PrEP cascade determined significant shifts and trends in PrEP uptake and continuity. RESULTS: Only 60% of the high-risk population eligible for PrEP were enrolled, while fewer than 30% of the cumulative number of PrEP users were refilled each quarter. Uncertainty and fear of side effects, perceptions about the harmfulness of the medication, perceived inability to adhere to PrEP, and stigma were the main reasons why clients rejected PrEP. Lack of access to the facility, side effects, pill burden, stigma, perceived low-risk exposure to HIV, and preference of staying at work as opposed to picking up refills affected continuity on PrEP. The collaborative registered statistically significant shifts in PrEP enrollment from 64% to 89% and continuity from 51% to 78% between July 21 and November 22 following the collaborative intervention. CONCLUSIONS: We recommend using a 3-tier approach for other similar implementation contexts to strengthen PrEP programming, given the marked statistical shift in PrEP uptake and continuity. This begins with understanding the gap and barriers to use among clients, followed by mapping interventions to specific barriers through a quality improvement collaborative.

Clients in Uganda accessing preferred differentiated antiretroviral therapy models achieve higher viral suppression and are less likely to miss appointments: a cross-sectional analysis.

INTRODUCTION: The Uganda Ministry of Health recommends facility- and community-based differentiated antiretroviral therapy (DART) models to support person-centred care for eligible clients receiving antiretroviral therapy (ART). Healthcare workers assess client eligibility for one of six DART models upon initial enrolment; however, client circumstances evolve, and their preferences are not routinely adjusted. We developed a tool to understand the proportion of clients accessing preferred DART models and compared the outcomes of clients accessing preferred DART models to the outcomes of clients not receiving preferred DART models. METHODS: We conducted a cross-sectional study. A sample of 6376 clients was selected from 113 referrals, general hospitals and health centres purposely selected from 74 districts. Clients receiving ART accessing care from the sampled sites were eligible for inclusion. Healthcare workers interviewed clients (caretakers of clients under 18), over a 2-week period between January and February 2022 using a client preference tool to elicit whether clients were receiving DART services through their preferred model. Treatment outcomes of viral load test, viral load suppression and missed appointment date were extracted from clients' medical files before or immediately after the interview and de-identified. The descriptive analysis determined the interaction between client preferences and predefined treatment outcomes by comparing outcomes of clients whose care aligned with their preferences to outcomes of clients whose care misaligned with their preferences. RESULTS: Of 25% (1573/6376) of clients not accessing their preferred DART model, 56% were on facility-based individual management and 35% preferred fast-track drug refills model. Viral load coverage was 87% for clients accessing preferred DART models compared to 68% among clients not accessing their preferred model. Viral load suppression was higher among clients who accessed the preferred DART model (85%) compared to (68%) clients who did not access their preferred DART model. Missed appointments were lower at 29% for clients who accessed preferred DART models compared to 40% among clients not enrolled in the DART model of their choice. CONCLUSIONS: Clients who accessed their preferred DART model have better clinical outcomes. Preferences should be integrated throughout health systems, improvement interventions, policies and research efforts to ensure client-centred care and client autonomy.

Saving Mothers, Giving Life Approach for Strengthening Health Systems to Reduce Maternal and Newborn Deaths in 7 Scale-up Districts in Northern Uganda.

BACKGROUND: Uganda's maternal and newborn mortality remains high at 336 maternal deaths per 100,000 live births and 27 newborn deaths per 1,000 live births. The Saving Mothers, Giving Life (SMGL) initiative launched in 2012 by the U.S. government and partners, with funding from the U.S. President's Emergency Plan for AIDS Relief, focused on reducing maternal and newborn deaths in Uganda and Zambia by addressing the 3 major delays associated with maternal and newborn deaths. In Uganda, SMGL was implemented in 2 phases. Phase 1 was a proof-of-concept demonstration in 4 districts of Western Uganda (2012 to 2014). Phase 2 involved scaling up best practices from Phase 1 to new sites in Northern Uganda (2014 to 2017). PROGRAM DESCRIPTION: The SMGL project used a systems-strengthening approach with quality improvement (QI) methods applied in targeted facilities with high client volume and high maternal and perinatal deaths. A QI team was formed in each facility to address the building blocks of the World Health Organization's health systems framework. A community component was integrated within the facility-level QI work to create demand for services. Above-site health systems functions were strengthened through engagement with district management teams. RESULTS: The institutional maternal mortality ratio in the intervention facilities decreased by 20%, from 138 to 109 maternal deaths per 100,000 live births between December 2014 and December 2016. The institutional neonatal mortality rate was reduced by 30%, while the fresh stillbirth rate declined by 47% and the perinatal mortality rate by 26%. During this period, over 90% of pregnant women were screened for hypertension and 70% for syphilis during antenatal care services. All women received a uterotonic drug to prevent postpartum hemorrhage during delivery, and about 90% of the women were monitored using a partograph during labor. CONCLUSIONS: Identifying barriers at each step of delivering care and strengthening health systems functions using QI teams increase partcipation, resulting in improved care for mothers and newborns.