Isoniazid Preventive Therapy Completion 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.

Completion of isoniazid preventive therapy for latent tuberculosis infection among children and adolescents compared to adults living with HIV in Kinshasa, Democratic Republic of the Congo.

Little is known about isoniazid preventive therapy (IPT) completion rates among children or adolescents compared to adults living with HIV in Kinshasa, Democratic Republic of the Congo (DRC). We conducted a retrospective cohort analysis including children, adolescents, and adults living with HIV who were treated at FHI360 and partners-implemented HIV care programs at six health zones in Kinshasa, DRC, from 2004 to 2020. The primary outcome was the proportion of children, adolescents versus adults who did complete 6 months of daily self-administered IPT. Log-binomial regression assessed independent predictors of IPT non-completion and Kaplan-Meier technique for survival analysis. Of 11,691 eligible patients on ART who initiated IPT, 429 were children (<11 years), 804 adolescents (11-19 years), and 10,458 adults (≥20 years). The median age was 7 (IQR: 3-9) years for children, 15 (IQR: 13-17) years for adolescents, and 43 (35-51) years for adults. Among those who were initiated on IPT, 5625 out of 11,691 people living with HIV (PLHIV) had IPT completion outcome results, and an overall 3457/5625 (61.5%) completion rate was documented. Compared to adults, children and adolescents were less likely to complete IPT [104/199 (52.3%) and 268/525 (51.0%), respectively, vs. 3085/4901 (62.9%)]. After adjustment, the only independent predictors for IPT non-completion were health zone of residence and type of ART regimen. Kaplan-Meier analysis showed comparable poor survival among patients who completed IPT versus those who did not (p-value for log-rank test, 0.15). The overall sub-optimal IPT completion rate in adults as well as children/adolescents in this setting is of great concern. Prospective studies are needed to elucidate the specific barriers to IPT completion among children, adolescents, and adults in DRC as well as the scale-up of evidence-informed interventions to improve IPT completion, such as adoption of shorter TB preventive regimens.

Isoniazid preventive therapy completion and factors associated with non-completion among patients on antiretroviral therapy at Kisenyi Health Centre IV, Kampala, Uganda.

Isoniazid preventive therapy (IPT) is given to HIV patients to reduce the risk of active tuberculosis (TB). However, treatment completion remains suboptimal among those that are initiated. This study aimed to determine the completion level of IPT and the factors associated with non-completion among patients on antiretroviral therapy (ART) at Kisenyi Health Center IV in Kampala, Uganda. A mixed-methods facility-based retrospective cohort study utilizing routinely collected data from 341 randomly selected HIV patients initiated on IPT was conducted. Data extracted from the registers was used to determine IPT completion. Robust Poisson regression was conducted to determine the associated factors of IPT non-completion, while in-depth interviews were conducted to explore barriers to IPT completion from the patient's perspective. A total of 341 patients who started on isoniazid (INH) were retrospectively followed up, with 69% (236/341) being female. Overall IPT completion was 83%. Multivariate analysis revealed the prevalence of IPT non-completion among males was 2.24 times the prevalence among females (aPR 2.24, 95% CI: 1.40-3.58, p = 0.001). The prevalence of IPT non-completion among patients with a non-suppressed HIV viral load was 3.00 times the prevalence among those with a suppressed HIV viral load (aPR 3.00, 95% CI: 1.44-6.65, p = 0.007). The prevalence of IPT non-completion among patients who were married, or cohabiting was 0.31 times the prevalence among those who were single (aPR 0.31, 95% CI: 0.17-0.55, p<0.000). Lack of IPT-related health education, pill burden, distance to the health facility, and patient relocation were reported as barriers to IPT completion. IPT completion was found to be 83% among the cohort studied. However, lower completion levels persist among males and HIV-virally non-suppressed patients. Lack of IPT-related health education, pill burden, distance to the health facility, and patient relocation were reported as barriers to IPT completion. Interventions that target these groups of people need to be intensified.

Isoniazid preventive therapy completion in children under 5 years old who are contacts of tuberculosis cases in Lima, Peru: study protocol for an open-label, cluster-randomized superiority trial

BackgroundChildren < 5 years old in contact with TB cases are at high risk for developing severe and fatal forms of TB. Contact investigation, BCG vaccination, and isoniazid preventive therapy (IPT) are the most effective strategies to prevent TB among children. However, the implementation of IPT faces challenges at several stages of the cascade of care of TB infection among children, particularly those less than 5 years old. In Peru, a large proportion of children do not complete IPT, which highlights the need to design effective interventions that enhance preventive therapy adherence and completion. Although the body of evidence for such interventions has grown, interventions in medium TB incidence settings are lacking. This study aims to test the effectiveness, acceptability, and feasibility of an intervention package to increase information and motivation to complete IPT among children < 5 who have been prescribed IPT.MethodsAn open-label, cluster-randomized superiority trial will be conducted in two districts in South Lima, Peru. Thirty health facilities will be randomized as clusters, 10 to the intervention and 20 to control (standard of care). We aim to recruit 10 children from different households in each cluster. Participants will be caretakers of children aged < 5 years old who initiated IPT. The intervention consists of educational material, and short message services (SMS) reminders and motivators. The primary outcomes will be the proportion of children who picked up > 90% of the 24 weeks of IPT (22 pick-ups) and the proportion of children who picked up the 24 weeks of IPT. The standard of care is a weekly pick-up with monthly check-ups in a health facility. Feasibility and acceptability of the intervention will be assessed through an interview with the caretaker.DiscussionUnfavorable outcomes of TB in young children, high effectiveness of IPT, and low rates of IPT completion highlight the need to enhance adherence and completion of IPT among children < 5 years old. Testing of a context-adapted intervention is needed to improve IPT completion rates and therefore TB prevention in young children.Trial registrationClinicalTrials.gov NCT03881228. Registered on March 19, 2019.

High Isoniazid Preventive Therapy Completion Rate among Household Contacts of Tuberculosis Patients in Duhok Province

High Isoniazid Preventive Therapy Completion Rate among Household Contacts of Tuberculosis Patients in Duhok Province

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.

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.

Determinants of Isoniazid Preventive Therapy Completion among People Living with HIV in Oyo and Ogun States, Southwest Nigeria

Background: The World Health Organization (WHO) recommends the use of Isoniazid Preventive Therapy (IPT) among People Living with HIV (PLHIV) to reduce morbidity and mortality from Tuberculosis (TB). This study assessed the rate of IPT completion and its associated factors among PLHIV in South West Nigeria.Methods: A review of records of 1526 PLHIV who commenced IPT between October 2017 and December 2018 was done. Data were extracted from facility level IPT service documentation tools using study-developed data abstraction template. The chi-square test was used to assess the association between the independent variables and the patient’s IPT completion status at 0.05 significance level. Logistic regression was used to determine the predictors of IPT completion.Results: The mean age of the study population was 42.3±11.3 years and 1154 (75.6%) of them were females. About 1342 (87.9%) completed IPT within six months of initiation. Major reasons for non-completion of IPT were lost to follow up 86 (46.7%) and nonadherence to IPT 60 (32.6%). Higher proportion of respondents who were Igbo (92.9%), ART-naïve (97.6%) or active on ART regimen (94.8%) completed their IPT regimen within 6 months of initiation when compared to those of other tribes (p=0.023), ART experienced (87.7%), (p=0.023) or inactive on treatment (0.9%), (p&lt;0.001) respectively. Traders/farmers were 6 times more likely to complete IPT compared to public/civil servants (AOR=6.110, 95%CI=2.180-17.112, p=0.001).Conclusion: IPT completion rate was high among study participants. Intensified counselling on IPT benefits among ART patients with focus on civil/public servants might further improve IPT completion.&#x0D; Keywords: IPT Completion; Isoniazid Preventive Therapy; PLHIV; Tuberculosis; Southwest Nigeria

Isoniazid Preventive Therapy for Tuberculosis in People Living with HIV: A Cross Sectional Study in Butebo, Uganda.

BackgroundDespite evidence that isoniazid preventive therapy (IPT) can reduce the risk of tuberculosis (TB) disease among People Living with Human Immunodeficiency Virus (PLHIV), uptake of IPT is low in many resource-limited settings. This study determined the level of IPT uptake and its associated factors amongst PLHIV.Materials and MethodsThis was a retrospective quantitative study amongst PLHIV who do not have active TB and enrolled in 2019 - 2020 for anti-retroviral therapy (ART) in Butebo district, Uganda. Data related to demographic factors (age, sex, religion, marital status, employment status, education level, area of residence, household density), health facility factors (pre-IPT counseling), community factors [distance from Health Center (H/C), incurred costs to reach H/C], and IPT drug-related factors [frequency of Isoniazid (INH) refill, INH stock-outs] were collected from four health facilities using a checklist. The data was analyzed into descriptive statistics and relationships determined using Chi-square tests.ResultsAmong eligible PLHIV (272), 34.2% achieved IPT uptake. The mean duration between HIV diagnosis and the start of IPT was 4.31 years, with IPT Uptake among males (37.0%), females (32.8%), married (39.5%), and Christians (35.4%). Factors that affect the rate of IPT uptake include employment, education, residence, costs to reach H/C, and pre-IPT counseling. The IPT completion rate was 97.8%. All the cases who had regular INH refill completed IPT compared to 60.0% with the irregular refill, while 97.8% did not experience INH stock-outs and completed IPT.ConclusionPre-IPT counseling was the most significant contributing factor for IPT uptake. IPT uptake may be scaled up by integrating IPT services in routine HIV care, enhancing counseling for IPT and supervision and monitoring, training of health workers, and improving logistical supplies at the health centers.

Caregivers' knowledge and perceptions are associated with children's TB preventive treatment completion.

Forty-six health centers in south Lima, Peru. To assess the association between caregivers' knowledge and perceptions around isoniazid preventive therapy (IPT) and whether their children complete IPT. We conducted a retrospective medical record review of children who initiated IPT during 2017-2018. We administered structured surveys to caregivers of the children about their knowledge about and perceptions of IPT. We used a modified Poisson regression to determine factors associated with IPT completion. We included 550 children, of whom 31% did not complete IPT. Independent factors associated with not completing IPT were low caregiver knowledge about TB and IPT (adjusted risk ratio [aRR] 1.41, 95% CI 1.06-1.78), low caregiver perception of the importance of IPT (aRR 1.76, 95% CI 1.30-2.39), low caregiver satisfaction with the health services (aRR 1.57, 95% CI 1.14-2.16), experience of adverse events (aRR 2.08, 95% CI 1.51-2.87), and living in a household with moderate or severe family dysfunction (aRR 1.53, 95% CI 1.07-2.19). IPT completion among children was associated with the knowledge and perceptions of their caregivers, as well as the experience of adverse events. To improve IPT completion among children, health care providers should prioritize education and counseling for caregivers, promote positive interpersonal relationships with them, and monitor adverse events.

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

Can isoniazid preventive therapy be scaled up rapidly? Lessons learned in Kenya, 2014-2018.

BACKGROUND: TB is the leading cause of mortality among people living with HIV (PLHIV), for whom isoniazid preventive therapy (IPT) has a proven mortality benefit. Despite WHO recommendations, countries have been slow in scaling up IPT. This study describes processes, challenges, solutions, outcomes and lessons learned during IPT scale-up in Kenya.METHODS: We conducted a desk review and analyzed aggregated Ministry of Health (MOH) IPT enrollment data from 2014 to 2018 to determine trends and impact of program activities. We further analyzed IPT completion reports for patients initiated from 2015 to 2017 in 745 MOH sites in Nairobi, Central, Eastern and Western Kenya.RESULTS: IPT was scaled up 75-fold from 2014 to 2018: the number of PLHIV covered increased from 9,981 to 749,890. The highest percentage increases in the cumulative number of PLHIV on IPT were seen in the quarters following IPT pilot projects in 2014 (49%), national launch in 2015 (54%), and HIV treatment acceleration in 2016 (158%). Among 250,069 patients initiating IPT from 2015 to 2017, 97.5% completed treatment, 0.2% died, 0.8% were lost to follow-up, 1.0% were not evaluated, and 0.6% discontinued treatment.CONCLUSIONS: IPT can be scaled up rapidly and effectively among PLHIV. Deliberate MOH efforts, strong leadership, service delivery integration, continuous mentorship, stakeholder involvement, and accountability are critical to program success.

Pulmonary tuberculosis screening in anti-retroviral treated adults living with HIV in Kenya

BackgroundPeople living with HIV (PLHIV) who reside in high tuberculosis burden settings remain at risk for tuberculosis disease despite treatment with anti-retroviral therapy and isoniazid preventive therapy (IPT). The performance of the World Health Organization (WHO) symptom screen for tuberculosis in PLHIV receiving anti-retroviral therapy is sub-optimal and alternative screening strategies are needed.MethodsWe enrolled HIV-positive adults into a prospective study in western Kenya. Individuals who were IPT-naïve or had completed IPT > 6 months prior to enrollment were eligible. We evaluated tuberculosis prevalence overall and by IPT status. We assessed the accuracy of the WHO symptom screen, GeneXpert MTB/RIF (Xpert), and candidate biomarkers including C-reactive protein (CRP), hemoglobin, erythrocyte sedimentation rate (ESR), and monocyte-to-lymphocyte ratio for identifying pulmonary tuberculosis. Some participants were evaluated at 6 months post-enrollment for tuberculosis.ResultsThe study included 383 PLHIV, of whom > 99% were on antiretrovirals and 88% had received IPT, completed a median of 1.1 years (IQR 0.8–1.55) prior to enrollment. The prevalence of pulmonary tuberculosis at enrollment was 1.3% (n = 5, 95% CI 0.4–3.0%): 4.3% (0.5–14.5%) among IPT-naïve and 0.9% (0.2–2.6%) among IPT-treated participants. The sensitivity of the WHO symptom screen was 0% (0–52%) and specificity 87% (83–90%). Xpert and candidate biomarkers had poor to moderate sensitivity; the most accurate biomarker was CRP ≥ 3.3 mg/L (sensitivity 80% (28–100) and specificity 72% (67–77)). Six months after enrollment, the incidence rate of pulmonary tuberculosis following IPT completion was 0.84 per 100 person-years (95% CI, 0.31–2.23).ConclusionsIn Kenyan PLHIV treated with IPT, tuberculosis prevalence was low at a median of 1.4 years after IPT completion. WHO symptoms screening, Xpert, and candidate biomarkers were insensitive for identifying pulmonary tuberculosis in antiretroviral-treated PLHIV.

Closing the loop in child TB contact management: completion of TB preventive therapy outcomes in western Kenya

SettingChildren especially those <5 years of age exposed to pulmonary tuberculosis (TB) are at a high risk of severe TB disease and death. Isoniazid preventive therapy (IPT) has been shown...

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.

Assessment of Isoniazid Preventive Therapy Outcome Among People Living with HIV in a Referral Hospital, Northeast Ethiopia.

BackgroundTuberculosis is said to be one of the prevalent opportunistic infections and the leading cause of death among people living with human immunodeficiency virus. Although isoniazid preventive therapy (IPT) is thought to reduce the incidence of TB in HIV patients, its implementation has faced many obstacles. This study was concerned with the assessment of the outcome of IPT among people living with HIV who were on follow-up at Dessie referral Hospital (DRH), Northeast, Ethiopia.MethodsA retrospective study of medical records of 220 patients, who were enrolled at Dessie Referral Hospital from January 10/2016 to December 11/2018, were conducted from March 23/2019 to April 6/2019. A systematic random sampling method was used to select the samples for the study, and a data abstraction format was used to capture the data. All data were entered, cleared and analyzed using SPSS version 21. Chi-square test was used to identify the association of outcome between the two IPT groups, and P-value <0.05 was considered as statistical significance.ResultsThe total TB prevalence in this study was 25 (11.36%). The occurrence of TB in the IPT group was 9(4.09%) and 16 (7.27%) for the non-IPT group but not statistically significant (p=0.137). From the study, about 40.9% of patients developed opportunistic infections. Of these, 62.81% and 37.18% of opportunistic infections were developed among patients in the non-IPT and the IPT groups, respectively (p=0.002), which were statistically significant, and the IPT completion rate was 61.81%.ConclusionAlthough the current study showed that the IPT had not significantly reduced the prevalence of TB between IPT and the non-IPT group, the IPT has shown to significantly reduce the prevalence of opportunistic infections.

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.

Factors affecting uptake and completion of isoniazid preventive therapy among HIV-infected children at a national referral hospital, Kenya: a mixed quantitative and qualitative study

BackgroundTuberculosis (TB) is the most common opportunistic infection and the leading cause of death in people living with HIV (PLHIV). HIV-infected children are at a higher risk of TB infection and disease compared to those without HIV. Isoniazid preventive therapy (IPT) is an effective intervention in preventing progression of latent TB infection to active TB. The World Health Organization (WHO) currently recommends that all children aged > 12 months and adults living with HIV in whom active TB has been excluded should receive a 6-months course of IPT as part of a comprehensive package of HIV care. Despite this recommendation, the uptake of IPT among PLHIV has been suboptimal globally. This study sought to determine the factors affecting IPT uptake and completion among HIV-infected children in a large HIV care centre in Nairobi, Kenya.MethodThis was a cross-sectional mixed methods study comprising of quantitative and qualitative study designs. Medical records of 225 HIV-infected children aged 1 to < 10 years, in care in the Kenyatta National Hospital Comprehensive Care Centre (KNH CCC) were retrospectively reviewed, and 8 purposively selected healthcare providers and 18 consecutively selected caregivers of children were interviewed.ResultsIPT uptake among CLHIV in care in the KNH CCC was 68% (152/225) while the treatment completion rate was 82% (94/115). IPT-related health education and counselling were the main facilitators of IPT uptake and completion, while fear of adverse drug reaction, pill burden and lack of an integrated monitoring and evaluation system for IPT were the major barriers.ConclusionThe IPT uptake in this study was low and fell short of the set global target of > 90%. The completion rate was however acceptable. There is an urgent need to address the identified barriers.

Determinants of isoniazid preventive therapy completion among people living with HIV attending care and treatment clinics from 2013 to 2017 in Dar es Salaam Region, Tanzania. A cross-sectional analytical study

BackgroundTuberculosis (TB) disease is a common opportunistic infection among people living with HIV (PLHIV). WHO recommends at least 6 months of isoniazid Preventive Therapy (IPT) to reduce the risk of active TB. It is important to monitor the six-month IPT completion since a suboptimal dose may not protect PLHIV from TB infection. This study determined the six-month IPT completion and factors associated with six-month IPT completion among PLHIV aged 15 years or more in Dar es Salaam region, Tanzania.MethodsSecondary analysis of routine data from PLHIV attending 58 care and treatment clinics in Dar es Salaam region was used. PLHIV, aged 15 years and above, who screened negative for TB symptoms and initiated IPT from January, 2013 to June, 2017 were recruited. Modified Poisson regression with robust standard errors was used to estimate prevalence ratios (PR) and 95% confidence interval (CI) for factors associated with IPT completion. Multilevel analysis was used to account for health facility random effects in order to estimate adjusted PR (APR) for factors associated with IPT six-month completion.ResultsA total of 29,382 PLHIV were initiated IPT, with 21,808 (74%) female. Overall 17,092 (58%) six-month IPT completion, increasing from 42% (773/1857) in year 2013 to 76% (2929/3856) in 2017. Multilevel multivariable model accounting for health facilities as clusters, showed PLHIV who were not on ART had 46% lower IPT completion compared to those were on ART (APR: 0.54: 95%CI: 0.45–0.64). There was 37% lower IPT completion among PLHIV who transferred from another clinic (APR: 0.63: 95% CI (0.54–0.74) compared to those who did not transfer. PLHIV aged 25–34 years had a 6% lower prevalence of IPT completion as compared to those aged 15 to 24 years (APR:0.94 95%CI:0.89–0.98).ConclusionThe IPT completion rate in PLHIV increased over time, but there was lower IPT completion in PLHIV who transferred from other clinics, who were aged 25 to 34 years and those not on ART. Interventions to support IPT in these groups are urgently needed.

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.