Isoniazid Preventive Therapy Initiation Research Articles

Isoniazid preventive therapy completion between July-September 2019: A comparison across HIV differentiated service delivery models in Uganda.

Tuberculosis (TB) remains the leading cause of death among people living with HIV (PLHIV). To prevent TB among PLHIV, the Ugandan national guidelines recommend Isoniazid Preventive Therapy (IPT) across differentiated service delivery (DSD) models, an effective way of delivering ART. DSD models include Community Drug Distribution Point (CDDP), Community Client-led ART Delivery (CCLAD), Facility-Based Individual Management (FBIM), Facility-Based Group (FBG), and Fast Track Drug Refill (FTDR). Little is known about the impact of delivering IPT through DSD. We reviewed medical records of PLHIV who initiated IPT between June-September 2019 at TASO Soroti (TS), Katakwi Hospital (KH) and Soroti Regional Referral Hospital (SRRH). We defined IPT completion as completing a course of isoniazid within 6-9 months. We utilized a modified Poisson regression to compare IPT completion across DSD models and determine factors associated with IPT completion in each DSD model. Data from 2968 PLHIV were reviewed (SRRH: 50.2%, TS: 25.8%, KH: 24.0%); females: 60.7%; first-line ART: 91.7%; and Integrase Strand Transfer Inhibitor (INSTI)-based regimen: 61.9%. At IPT initiation, the median age and duration on ART were 41.5 (interquartile range [IQR]; 32.3-50.2) and 6.0 (IQR: 3.7-8.6) years, respectively. IPT completion overall was 92.8% (95%CI: 91.8-93.7%); highest in CDDP (98.1%, 95%CI: 95.0-99.3%) and lowest in FBG (85.8%, 95%CI: 79.0-90.7%). Compared to FBIM, IPT completion was significantly higher in CDDP (adjusted rate ratio [aRR] = 1.15, 95%CI: 1.09-1.22) and CCLAD (aRR = 1.09, 95% CI 1.02-1.16). In facility-based models, IPT completion differed between sites (p<0.001). IPT completion increased with age for FBIM and CCLAD and was lower among female participants in the CCLAD (aRR = 0.82, 95%CI 0.67-0.97). IPT completion was high overall but highest in community-based models. Our findings provide evidence that supports integration of IPT within DSD models for ART delivery in Uganda and similar settings.

Assessment of Isoniazid Preventive Therapy and Incidence of Tuberculosis among People Living with Human Immunodeficiency Virus Seeking Care in an Anti-retroviral Therapy Center, Puducherry.

One in three deaths among people living with human immunodeficiency virus (PLHIV) is due to Tuberculosis. Isoniazid preventive therapy (IPT) was implemented in antiretroviral therapy (ART) center Puducherry in July 2017. We have determined the proportion of PLHIV who were eligible, initiated, completed IPT and also the incidence of tuberculosis before and after implementation of IPT. It was a facility based longitudinal descriptive study. All PLHIV, aged 10 years and above, seeking care in ART Centers was included. The number of PLHIV eligible, initiated and completed IPT was summarized as proportion with 95% CI. Among the registered PLHIV (999), the proportion of PLHIV those were found eligible for IPT was 93% [95% CI (91.24%-94.67%)] and initiated on IPT was 92% [95% CI (90.20%-93.95%)]. Completion rate of IPT was 96.3% [95% CI (94.59%-97.63%)]. Initiation of IPT was relatively less among newly registered PLHIV as compared to older cohort of PLHIV.

Prevalence of neurotoxicity symptoms among postpartum women on isoniazid preventive therapy and efavirenz-based treatment for HIV: an exploratory objective of the IMPAACT P1078 randomized trial

BackgroundThis exploratory analysis investigates the prevalence and risk factors of neurocognitive toxicity in postpartum women on HIV treatment in response to a concern of an Isoniazid Preventive Therapy (IPT)/Efavirenz interaction.Trial DesignPregnant women on HIV treatment from countries with high TB prevalence were randomized in IMPAACT P1078 to 28 weeks of IPT started either during pregnancy or at 12 weeks postpartum. Partway through study implementation, the Patient Health Questionnaire 9, the cognitive complaint questionnaire, and the Pittsburg Sleep Quality Index were added to evaluate depression, cognitive function, and sleep quality at postpartum weeks. Screening for peripheral neuropathy was conducted throughout the study.MethodsWe summarized percentages of women with depression symptoms, cognitive dysfunction, poor sleep quality and peripheral neuropathy and assessed the association of 11 baseline risk factors of neurotoxicity using logistic regression, adjusted for gestational age stratum.ResultsOf 956 women enrolled, 749 (78%) had at least one neurocognitive evaluation. During the postpartum period, the percentage of women reporting at least mild depression symptoms, cognitive complaint and poor sleep quality peaked at 13%, 8% and 10%, respectively, at 12 weeks, and the percentage of women reporting peripheral neuropathy peaked at 13% at 24 weeks. There was no evidence of study arm differences in odds of all four neurotoxic symptoms.ConclusionsTiming of IPT initiation and EFV use were not associated with symptoms of neurotoxicity. Further study is advised to formally assess risk factors of neurotoxicity.

Initiation and adherence to isoniazid preventive therapy in children under 5 years of age in Manhiça, Southern Mozambique.

The WHO recommends preventive treatment for all pediatric contacts of a confirmed TB case, but coverage remains low in many high TB burden countries. We aimed to assess the coverage and adherence of the isoniazid preventive therapy (IPT) program among children under 5 years of age with household exposure to an adult pulmonary TB case in a rural district of Southern Mozambique. The estimated IPT coverage was 11.7%. A longer distance to the health center and lower age of the children hindered IPT initiation. Among patients who started IPT, 12/18 (69.9%) were adherent to the 6-month treatment.

EFFECTIVENESS OF ISONIAZID PREVENTIVE THERAPY ON INCIDENCE OF TUBERCULOSIS AMONG PEOPLE LIVING WITH HIV IN SOUTHERN MAHARASHTRA

Tuberculosis being the foremost opportunistic infection associated with Human Immunodeciency Virus infection contributes to high morbidity and mortality among HIV seropositive persons. As per World Health Organisation TB statistics for 2020, and the India TB Report 2021- The incidence of TB cases including HIV in India was 193 per 100000 population, of which mortality was 32 per 100000 cases. Isoniazid Preventive Therapy reduces the reactivation of latent Tuberculosis infection and reduces the risk of acquiring TB by 70-90% among HIV co-infected individuals. WHO recommends use of ART and Isoniazid Preventive Therapy (IPT) combination to reduce the burden of TB among HIV infected patients. Considering the benets of IPT in PLHIV patients, this study was conducted over a period of 2 years from January 2020 to December 2021 in patients attending ART OPD of a tertiary care hospital in southern Maharashtra. Methods A prospective observational study was conducted on patients attending ART OPD along with General Medicine OPD at a tertiary care hospital from January 2020 to December 2021. A total of 1497 PLHIV patients were started on IPT during this period and followed up. Results 92.18% i.e. 1380 of 1497 patients completed 6 months of IPT with remaining 7.82% i.e. 117 patients not able to complete the entire 6 months due to treatment related side effects, follow up difculties or mortality. Of 1497 patients, only 2 patients (0.13%) developed Pulmonary Tuberculosis after initiation of IPT and the remaining didn't show any signs or symptoms of tuberculosis on follow up. Conclusion Results of IPT in PLHIV were highly effective with only 0.13% i.e. 2 patients developing Tuberculosis during the course of treatment with the remaining not having tuberculosis even on follow up or being reported till date. The results of the study along with other studies conducted worldwide clearly indicate the effectiveness of IPT in PLHIV and thereby its implementation should be further strengthened.

Isoniazid preventive therapy-related adverse events among Malawian adults on antiretroviral therapy: A cohort study.

Adverse events may be a cause of observed poor completion of isoniazid preventive therapy (IPT) among people living with HIV in high tuberculosis burden areas. Data on IPT-related adverse events (AE) from sub-Saharan Africa are scarce. We report IPT-related AEs, associated clinical characteristics, and IPT discontinuations in adults who were stable on antiretroviral therapy (ART) when they initiated IPT. Cohort study nested within a randomized, controlled, clinical trial of cotrimoxazole and chloroquine prophylaxis in Malawians aged ≥ 18 years and virologically suppressed on ART. Eight hundred sixty-nine patients were followed for a median of 6 months after IPT initiation. IPT relatedness of AEs was determined retrospectively with the World Health Organization case-causality tool. Frailty survival regression modeling identified factors associated with time to first probably IPT-related AE. The overall IPT-related AE incidence rate was 1.1/person year of observation. IPT relatedness was mostly uncertain and few AEs were severe. Most common were liver and hematological toxicities. Higher age increased risk of a probably IPT-related AE (aHR = 1.02; 95% CI 1.00–1.06; P = .06) and higher weight reduced this risk (aHR = 0.98; 95% CI 0.96–1.00; P = .03). Of 869 patients, 114 (13%) discontinued IPT and 94/114 (82%) discontinuations occurred at the time of a possibly or probably IPT-related AE. We observed a high incidence of mostly mild IPT-related AEs among individuals who were stable on ART. More than 1 in 8 persons discontinued IPT. These findings inform strategies to improve implementation of IPT in adults on ART, including close monitoring of groups at higher risk of IPT-related AEs.

A mid-level health manager intervention to promote uptake of isoniazid preventive therapy among people with HIV in Uganda: a cluster randomised trial

SummaryBackgroundDespite longstanding guidelines endorsing isoniazid preventive therapy (IPT) for people with HIV, uptake is low across sub-Saharan Africa. Mid-level health managers oversee IPT programmes nationally; interventions aimed at this group have not been tested. We aimed to establish whether providing structured leadership and management training and facilitating subregional collaboration and routine data feedback to mid-level managers could increase IPT initiation among people with HIV compared with standard practice.MethodsWe conducted a cluster randomised trial in Uganda among district-level health managers. We randomly assigned clusters of between four and seven managers in a 1:1 ratio to intervention or control groups. Our intervention convened managers into mini-collaboratives facilitated by Ugandan experts in tuberculosis and HIV, and provided business leadership and management training, SMS platform access, and data feedback. The control was standard practice. Participants were not masked to trial group, but study statisticians were masked until trial completion. The primary outcome was IPT initiation rates among adults with HIV in facilities overseen by participants over a period of 2 years (2019–21). We conducted prespecified analyses that excluded the third quarter of 2019 (Q3–2019) to understand intervention effects independent of a national 100-day IPT push tied to a financial contingency during Q3–2019. This trial is registered with ClinicalTrials.gov (NCT03315962), and is ongoing.FindingsBetween Nov 15, 2017, and March 14, 2018, managers from 82 of 82 eligible districts (61% of Uganda’s 135 districts) were enrolled and randomised: 43 districts to intervention, 39 to control. Intervention delivery took place between Dec 6, 2017, and Feb 2, 2022. Over 2 years, IPT initiation rates were 0·74 versus 0·65 starts per person-year in intervention versus control groups (incidence rate ratio [IRR] 1·14, 95% CI 0·88–1·46; p=0·16). Excluding Q3–2019, IPT initiation was higher in the intervention group versus the control group: 0·32 versus 0·25 starts per person-year (IRR 1·27, 95% CI 1·00–1·61; p=0·026).InterpretationFollowing an intervention targeting managers in more than 60% of Uganda’s districts, IPT initiation rates were not significantly higher in intervention than control groups. After accounting for large increases in IPT from a 100-day push in both groups, the intervention led to significantly increased IPT rates, sustained after the push and during the COVID-19 pandemic. Our findings suggest that interventions centred on mid-level health managers can improve IPT implementation on a large, subnational scale, and merit further exploration to address key public health challenges for which strong evidence exists but implementation remains suboptimal.FundingNational Institute of Allergy and Infectious Diseases.

Isoniazid Adherence Reduces Mortality and Incident Tuberculosis at 96 Weeks Among Adults Initiating Antiretroviral Therapy With Advanced Human Immunodeficiency Virus in Multiple High-Burden Settings.

BackgroundPeople with human immunodeficiency virus (HIV) and advanced immunosuppression initiating antiretroviral therapy (ART) remain vulnerable to tuberculosis (TB) and early mortality. To improve early survival, isoniazid preventive therapy (IPT) or empiric TB treatment have been evaluated; however, their benefit on longer-term outcomes warrants investigation.MethodsWe present a 96-week preplanned secondary analysis among 850 ART-naive outpatients (≥13 years) enrolled in a multicountry, randomized trial of efavirenz-containing ART plus either 6-month IPT (n = 426) or empiric 4-drug TB treatment (n = 424). Inclusion criteria were CD4 count <50 cells/mm3 and no confirmed or probable TB. Death and incident TB were compared by strategy arm using the Kaplan-Meier method. The impact of self-reported adherence (calculated as the proportion of 100% adherence) was assessed using Cox-proportional hazards models.ResultsBy 96 weeks, 85 deaths and 63 TB events occurred. Kaplan-Meier estimated mortality (10.1% vs 10.5%; P = .86) and time-to-death (P = .77) did not differ by arm. Empiric had higher TB risk (6.1% vs 2.7%; risk difference, −3.4% [95% confidence interval, −6.2% to −0.6%]; P = .02) and shorter time to TB (P = .02) than IPT. Tuberculosis medication adherence lowered the hazards of death by ≥23% (P < .0001) in empiric and ≥20% (P < .035) in IPT and incident TB by ≥17% (P ≤ .0324) only in IPT.ConclusionsEmpiric TB treatment offered no longer-term advantage over IPT in our population with advanced immunosuppression initiating ART. High IPT adherence significantly lowered death and TB incidence through 96 weeks, emphasizing the benefit of ART plus IPT initiation and completion, in persons with advanced HIV living in high TB-burden, resource-limited settings.

Adherence of HIV clinics to guidelines for the delivery of TB screening among people living with HIV/AIDS in Ghana

BackgroundTuberculosis screening of people living with HIV (PLHIV) – an intervention to reduce the burden of TB among PLHIV – is being implemented at HIV clinics in Ghana since 2007, but TB screening coverage remains low. Facility adherence to intervention guidelines may be a factor but is missing in implementation science literature. This study assesses the level of HIV clinic adherence to the guidelines and related facility characteristics in selected district hospitals in Ghana.MethodsThis cross-sectional study was conducted in all 27 district hospitals with HIV clinics, X-ray and geneXpert machines in Ghana. These hospitals are in 27 districts representing about 27% of the 100 district hospitals with HIV clinics in Ghana. A data collection tool with 18-items (maximum score of 29) was developed from the TB/HIV collaborative guidelines to assess facility adherence to four interrelated components of the TB screening programme as stated in the guidelines: intensive TB case-finding among PLHIV (ITCF), Isoniazid preventive therapy initiation (IPT), TB infection control (TIC), and programme review meetings (PRM). Data were collected through record review and interviews with 27 key informants from each hospital. Adherence scores per component were summed to determine an overall adherence score per facility and summarized using medians and converted to proportions. Facility characteristics were assessed and compared across facilities with high (above median) versus low (below median) overall adherence scores, using nonparametric test statistics.ResultsFrom the 27 key interviews and facility records reviewed, the median adherence scores for ITCF, IPT, TIC, and PRM components were 85.7% (IQR: 85.5–100.0), 0% (IQR: 0–66.7), 33.3% (IQR: 33.3–50.0), and 90.0% (IQR: 70.0–90.0), respectively. The overall median adherence score was 62.1% (IQR: 58.6–65.1), and 17 clinics (63%) with overall adherence score above the median were categorized as high adherence. Compared to low adherence facilities, high adherence facilities had statistically significant lower PLHIV clinic attendees per month (256 (IQR: 60–904) vs. 900 (IQR: 609–2622); p = 0.042), and lower HIV provider workloads (28.6 (IQR: 8.6–113) vs. 90 (IQR: 66.7–263.5); p = 0.046), and most had screening guidelines (76%, p < 0.01) and questionnaire (80%, p < 0.01) available on-site.ConclusionPRM had highest score while the IPT component had the lowest score. Almost a third of the facilities implemented the TB screening programme activities with a high level of adherence to the guidelines. We suggest to ensure adherence to all four components, reducing staff workloads and making TB screening questionnaires and guidelines available on-site would increase facility adherence to the intervention and ultimately achieve intervention targets.

A Quality Improvement Intervention to Inform Scale-Up of Integrated HIV-TB Services: Lessons Learned From KwaZulu-Natal, South Africa.

In South Africa, mortality rates among HIV-TB coinfected patients are among the highest in the world. The key to reducing mortality is integrating HIV-TB services, however, a generalizable implementation method and package of tested change ideas to guide the scale-up of integrated HIV-TB services are unavailable. We describe the implementation of a quality improvement (QI) intervention, health systems' weaknesses, change ideas, and lessons learned in improving integrated HIV-TB services. Between December 1, 2016, and December 31, 2018, 8 nurse supervisors overseeing 20 primary health care (PHC) clinics formed a learning collaborative to improve a set of HIV-TB process indicators. HIV-TB process indicators comprised: HIV testing services (HTS), TB screening among PHC clinic attendees, isoniazid preventive therapy (IPT) for eligible HIV patients, antiretroviral therapy (ART) for HIV-TB coinfected patients, and viral load (VL) testing at month 12. Routine HIV-TB process data were collected and analyzed. Key change interventions, generated by health care workers, included: patient-flow redesign, daily data quality checks; prior identification of patients eligible for IPT and VL testing. Between baseline and post-QI intervention, IPT initiation rates increased from 15.9% to 76.4% (P=.019), HTS increased from 84.8% to 94.5% (P=.110), TB screening increased from 76.2% to 85.2% (P=.040), and VL testing increased from 61.4% to 74.0% (P=.045). ART initiation decreased from 95.8% to 94.1% (P=.481). Although integrating HIV-TB services is standard guidance, existing process gaps to achieve integration can be closed using QI methods. QI interventions can rapidly improve the performance of processes, particularly if baseline performance is low. Improving data quality enhances the success of QI initiatives.

Organizational contextual factors that predict success of a quality improvement collaborative approach to enhance integrated HIV-tuberculosis services: a sub-study of the Scaling up TB/HIV Integration trial

BackgroundA quality improvement (QI) collaborative approach to enhancing integrated HIV-Tuberculosis (TB) services may be effective in scaling up and improving the quality of service delivery. Little is known of the role of organizational contextual factors (OCFs) in influencing the success of QI collaboratives. This study aims to determine which OCFs were associated with improvement in a QI collaborative intervention to enhance integrated HIV-TB services delivery.MethodsThis is a nested sub-study embedded in a cluster-randomized controlled trial. Sixteen nurse supervisors (clusters) overseeing 40 clinics were randomized (1:1) to receive QI training and mentorship, or standard of care support (SOC). In the QI arm, eight nurse supervisors and 20 clinics formed a “collaborative” which aimed to improve HIV-TB process indicators, namely HIV testing, TB screening, isoniazid preventive therapy (IPT) initiations, viral load testing, and antiretroviral therapy for TB patients. OCFs measured at baseline were physical infrastructure, key staff, flexibility of clinic hours, monitoring data for improvement (MDI), and leadership support. Surveys were administered to clinic staff at baseline and month 12 to assess perceptions of supportiveness of contexts for change, and clinic organization for delivering integrated HIV-TB services. Linear mixed modelling was used to test for associations between OCFs and HIV-TB process indicators.ResultsA total of 209 clinic staff participated in the study; 97 (46.4%) and 112 (53.6%) from QI and SOC arms, respectively. There were no differences between the QI and SOC arms scores achieved for physical infrastructure (78.9% vs 64.7%; p = 0.058), key staff (95.8 vs 92; p = 0.270), clinic hours (66.9 vs 65.5; p = 0.900), MDI (63.3 vs 65; p = 0.875, leadership support (46.0 vs 57.4; p = 0.265), and perceptions of supportiveness of contexts for change (76.2 vs 79.7; p = 0.128 and clinic organization for delivering integrated HIV-TB services (74.1 vs 80.1; p = 0.916). IPT initiation was the only indicator that was significantly improved in the parent study. MDI was a significantly associated with increasing IPT initiation rates [beta coefficient (β) = 0.004; p = 0.004].DiscussionMDI is a practice that should be fostered in public health facilities to increase the likelihood of success of future QI collaboratives to improve HIV-TB service delivery.Trial registrationClinicaltrials.gov, NCT02654613. Registered 01 June 2015.

A cluster-randomized controlled trial to improve the quality of integrated HIV-tuberculosis services in primary healthcareclinics in South Africa.

Introduction: Tuberculosis (TB) remains the most common cause of death among people living with HIV. Integrating HIV and TB services reduces mortality but is sub‐optimally implemented. Quality improvement (QI) methods offer a low‐cost and easily implementable approach to strengthening healthcare delivery systems. This trial assessed a QI intervention on key process indicators for delivering integrated HIV‐TB care in rural South African primary healthcare (PHC) clinics.MethodsSixteen nurse supervisors, (each with a cluster of clinics) overseeing 40 PHC clinics, were randomized 1:1 to the intervention or the standard of care (SOC) groups. The QI intervention comprised three key components: clinical and QI skills training, on‐site mentorship of nurse supervisors and clinic staff, and data quality improvement activities to enhance accuracy and completeness of routine clinic data. The SOC comprised monthly supervision and data feedback meetings. From 01 December 2016 to 31 December 2018, data were collected monthly by a team of study‐appointed data capturers from all study clinics. This study's outcomes were HIV testing services (HTS), TB screening, antiretroviral therapy (ART) initiation, isoniazid preventive therapy (IPT) initiation and viral load (VL) testing.ResultsThe QI group (eight clusters) comprised 244 clinic staff who attended to 13,347 patients during the trial compared to the SOC group (eight clusters) with 217 clinic staff who attended to 8141 patients. QI mentors completed 85% (510/600) of expected QI mentorship visits to QI clinics. HTS was 19% higher [94.5% vs. 79.6%; relative risk (RR)=1.19; 95% CI: 1.02–1.38; p=0.029] and IPT initiation was 66% higher (61.2 vs. 36.8; RR=1.66; 95% CI: 1.02–2.72; p=0·044), in the QI group compared to SOC group. The percentage of patients screened for TB (83.4% vs. 79.3%; RR=1.05; p=0.448), initiated on ART (91.7 vs. 95.5; RR=0.96; p=0.172) and VL testing (72.2% vs. 72.8%; RR=0.99; p=0.879) was similar in both groups.ConclusionsQI improved HIV testing and IPT initiation compared to SOC. TB screening, ART initiation and VL testing remained similar. Incorporating QI methods into routine supervision and support activities may strengthen integrated HIV‐TB service delivery and increase the success of future QI scale‐up activities.

Implementation of isoniazid preventive therapy in southern Lima, Peru: an analysis of health center characteristics

BackgroundTuberculosis (TB) prevention through the use of preventive treatment is a critical activity in the elimination of TB. In multiple settings, limited staffing has been identified as a barrier to managing preventive treatment for TB contacts. This study aims to determine how health center staffing, service type, and TB caseload affects implementation of isoniazid preventive therapy (IPT) for TB contacts in southern Lima.MethodsWe conducted an ecological study in 2019 in southern Lima, Peru. Through the review of medical records, we identified contacts of TB patients who initiated IPT during 2016–2018, and who were 0–19 years old, the age group eligible for IPT according to Peruvian guidelines. We assessed bivariate associations between health center characteristics (numbers of physicians and nurses, types of services available, annual TB caseload) and IPT initiation and completion using binomial logistic regression.ResultsAmong 977 contacts, 69% took more than a week to start IPT and 41% did not complete IPT. For those who successfully completed IPT, 58% did not complete full medical follow-up. There was no significant difference in IPT completion or adherence based on whether health centers had more physicians and nurses, more comprehensive services, or higher TB caseloads. Among contacts, female sex was associated with delay in initiating IPT (P = 0.005), age 5–19 years old was associated with completion of IPT (P = 0.025) and age < 5 years old was associated with completion of clinical evaluations (P = 0.041).ConclusionsThere are significant gaps in IPT implementation in health centers of southern Lima, Peru, but insufficient staffing of health centers may not be responsible. Further research is needed to identify how IPT implementation can be improved, potentially through improving staff training or monitoring and supervision.Graphic abstract

Active household contact screening for tuberculosis and provision of isoniazid preventive therapy to under-five children in Afghanistan.

This observational study analyzed the performance of the National TB Control Program (NTP) in Afghanistan in household contact screening from 2011 to 2018 and its use as an entry point for isoniazid preventive therapy (IPT), as well as the IPT completion rates for children under age five. From 2011 to 2018, the Afghanistan NTP released guidelines for passive and active contact screening of bacteriologically confirmed TB cases. Health workers were trained in contact screening. Presumptive TB cases gave sputum for AFB smear microscopy; other diagnostics were used if patients could not produce sputum. Children under five (excluding those with active TB) were treated for latent TB infection. We calculated the yield and the number needed to screen and number needed to test to find a case of TB, as well as the rates of IPT initiation and completion. From 2011 to 2018, 142,797 bacteriologically confirmed TB cases were diagnosed in Afghanistan. The number of household members eligible for screening was estimated to be 856,782, of whom 586,292 (81%) were screened for TB and 117,643 (20.1%) were found to be presumptive TB cases. Among the cases screened, 10,896 TB cases (all forms) were diagnosed (1.85%, 95% CI 1.82-1.89), 54.4% in females. The number needed to screen to diagnose a single case of TB (all forms) was 53.8; the number needed to test was 10.7. Out of all children under five, 101,084 (85.9%) were initiated on IPT, and 69,273 (68.5%) completed treatment. Program performance in contact screening in Afghanistan is high, at 81%, and the yield of TB is also high-close to 10 times higher than the national TB incidence rate. IPT initiation and completion rates are also high as compared to those of many other countries but need further improvement, especially for completion.

Individual and Composite Adverse Pregnancy Outcomes in a Randomized Trial on Isoniazid Preventative Therapy Among Women Living With Human Immunodeficiency Virus.

BackgroundInternational Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) P1078, a randomized noninferiority study designed to compare the safety of starting isoniazid preventive therapy (IPT) in women living with human immunodeficiency virus (HIV) either during pregnancy or after delivery, showed that IPT during pregnancy increased the risk of composite adverse pregnancy outcomes, but not individual outcomes. Many known factors are associated with adverse pregnancy outcomes: these factors’ associations and effect modifications with IPT and pregnancy outcomes were examined.MethodsPregnant women living with HIV from 8 countries with tuberculosis incidences >60/100 000 were randomly assigned to initiate 28 weeks of IPT either during pregnancy or at 12 weeks after delivery. Using univariable and multivariable logistic regression and adjusting for factors associated with pregnancy outcomes, composite and individual adverse pregnancy outcome measures were analyzed.ResultsThis secondary analysis included 925 mother-infant pairs. All mothers were receiving antiretrovirals. The adjusted odds of fetal demise, preterm delivery (PTD), low birth weight (LBW), or a congenital anomaly (composite outcome 1) were 1.63 times higher among women on immediate compared to deferred IPT (95% confidence interval [CI], 1.15–2.31). The odds of fetal demise, PTD, LBW, or neonatal death within 28 days (composite outcome 2) were 1.62 times higher among women on immediate IPT (95% CI, 1.14–2.30). The odds of early neonatal death within 7 days, fetal demise, PTD, or LBW (composite outcome 3) were 1.74 times higher among women on immediate IPT (95% CI, 1.22–2.49).ConclusionsWe confirmed higher risks of adverse pregnancy outcomes associated with the initiation of IPT during pregnancy, after adjusting for known risk factors for adverse pregnancy outcomes.

Choice architecture-based prescribing tool for TB preventive therapy: a pilot study in South Africa.

All people with HIV who screen negative for active tuberculosis (TB) should receive isoniazid preventive therapy (IPT). IPT implementation remains substantially below the 90% WHO target. This study sought to further understanding of IPT prescription by piloting a simplified prescribing approach. Primary care clinics in Matlosana, South Africa. This was a mixed-methods implementation study. Nine providers were recruited and underwent training on 2018 WHO guidelines. A simplified prescribing tool containing antiretroviral therapy (ART) and IPT prescriptions was introduced into the workflow for 2 weeks. Prescription data were collected from file review. Interviews were conducted with prescribers. During the study period, 41 patients were evaluated for ART initiation; 34 (83%) files used the simplified prescribing tool. Thirty-seven (90%) patients were eligible for same-day ART and IPT initiation, of whom 36 (97%) received IPT prescription. Qualitative interviews identified the following barriers to IPT prescription: cognitive burden, extensive documentation, limited management support, paucity of training, stock-outs, and patient-related factors. Provider acceptability of the tool was favorable, with unanimous recommendation to colleagues on the basis of streamlining documentation and reminding to prescribe. This simplified prescribing device for IPT was feasible to implement. Streamlining documentation and reminding providers to prescribe can reduce work-flow barriers to IPT provision.

Contact Screening and Isoniazid Preventive Therapy Initiation for Under-Five Children among Pulmonary Tuberculosis-Positive Patients in Bahir Dar Special Zone, Northwest Ethiopia: A Cross-Sectional Study.

Background Children are highly susceptible to Mycobacterium tuberculosis infection, and about 70% of children living in the same households with pulmonary tuberculosis-positive patients will become infected. However, pulmonary positive tuberculosis is a common phenomenon and the implementation of the recommended contact screening and initiation of isoniazid preventive therapy is very low. Therefore, this study is aimed at assessing contact screening practice and initiation of isoniazid preventive therapy of under-five children among pulmonary tuberculosis-positive patients in Bahir Dar, northwest Ethiopia. Methods A facility-based cross-sectional study was conducted from March 1 to 30, 2016. A total of 267 pulmonary tuberculosis-positive patients were included in this study. To identify independent predictors of contact screening and isoniazid preventive therapy initiation, we performed multivariable logistic regression analyses using SPSS version 20 with CI of 95% at p value < 0.05. Results A total of 230 (90.2%) pulmonary tuberculosis-positive patients had single contacts with their under-five children. One hundred nine (64.8%) children were screened. From those screened, 11 (7.4%) developed tuberculosis disease and started antituberculosis treatment. Forty-four (31.9%) children started isoniazid preventive therapy. Sex of the participants, place of service delivery, relationship with contacts, HIV status, and attitude of PTB+ cases were significant predictors of contact screening (p < .05). Participant's knowledge, attitude of participants, and relationship of the child with participant were significant predictors of isoniazid preventive therapy initiation (p < 0.05). Conclusion Contact screening practice and isoniazid preventive therapy initiation of children under the age of 5 in Bahir Dar zone were very low. Intimate family contact with pulmonary tuberculosis-positive patients, place of service delivery, and attitude towards screening are the key factors of contact screening. Participant's knowledge, attitude of participants, and relationship of the child with participant are the key factors of isoniazid preventive therapy initiation. Therefore, household contact screening and isoniazid preventive therapy initiation should be paid attention to reduce transmission.

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

BackgroundTuberculosis (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.MethodsThis 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.ResultsThe 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.ConclusionTreatment 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.

TB prevention strategies and unanswered questions for pregnant and postpartum women living with HIV: the need for improved evidence.

TB prevention strategies and unanswered questions for pregnant and postpartum women living with HIV: the need for improved evidence.

To start or to complete? – Challenges in implementing tuberculosis preventive therapy among people living with HIV: a mixed-methods study from Karnataka, India

ABSTRACT Background: Isoniazid preventive therapy (IPT) has been shown to reduce the risk of tuberculosis (TB) among people living with HIV (PLHIV). In 2017, India began a nationwide roll-out of IPT, but there is a lack of evidence on the implementation and the challenges. Objectives: Among PLHIV newly initiated on antiretroviral therapy (ART) from January 2017 to June 2018, to: (i) assess the proportion who started and completed IPT and (ii) explore reasons for non-initiation and non-completion from health-care providers’ and patients’ perspectives. Methods: An explanatory mixed-methods study was conducted in two selected districts of Karnataka, South India. A quantitative phase (cohort analysis of routinely collected program data) was followed by a qualitative phase involving thematic analysis of in-depth interviews with providers (n = 22) and patients (n = 8). Results: Of the 4020 included PLHIV, 3780 (94%) were eligible for IPT, of whom, 1496 (40%, 95% CI: 38%-41%) were initiated on IPT. Among those initiated, 423 (28.3%) were still on IPT at the time of analysis. Among 1073 patients with declared IPT outcomes 870 (81%, 95% CI: 79%-83%) had completed the six-month course of IPT. The main reason for IPT non-initiation and non-completion was frequent drug stock-outs. This required health-care providers to restrict IPT initiation in selected patient subgroups and earmark six-monthly courses for each patient to ensure that, once started, treatment was not interrupted. The other reasons for non-completion were adverse drug effects and loss to follow-up. Conclusion: The combined picture of ‘low IPT initiation and high completion’ seen in our study mirrors findings from other countries. Drug stock-out was the key challenge, which obliged health-care providers to prioritize ‘IPT completion’ over ‘IPT initiation’. There is an urgent need to improve the procurement and supply chain management of isoniazid.