Isoniazid Preventive Therapy Treatment Research Articles

Low completion rate for the 6-months course of isoniazid preventive therapy among people living with HIV, North Eastern Uganda, 2015-2017.

isoniazid preventive therapy (IPT) is highly effective at preventing tuberculosis among Persons Living with HIV (PLHIV). However, IPT completion rates in Uganda have not been studied. We examined completion rates for the 6-month course of IPT and factors associated with non-completion among PLHIV in northeastern Uganda. we conducted a retrospective cohort study using routinely collected program data in nine Antiretroviral Therapy (ART) sites in northeastern Uganda. The study period covered January 20 15-December 20 17. Non-completion was defined as failure to pick up any of the six IPT refills over 6 months. We abstracted data on IPT treatment site, IPT completion, and demographic and clinical characteristics from the IPT register and patient HIV care card. We used generalized linear regression to identify factors associated with non-completion. among 543 patients who started IPT, 175 (32%) completed the full 6-month course. Among those who did not complete, 193 (52%) stopped due to drug stockouts, and 175 (48%) were lost to follow-up. Being at World Health Organization (WHO) HIV clinical stages III and IV at initiation were associated with a higher risk of IPT non-completion compared to those who were at WHO clinical staging I and II (aRR 1.4, 95%CI 1.2-1.5). IPT completion rate among PLHIV in northeastern Uganda was suboptimal, largely due to IPT drug stockouts. The National TB and Leprosy Program should streamline the IPT supply chain to address drug stockouts and improve completion rates.

Prevalence and predictors of tuberculosis among HIV patients who completed isoniazid preventive therapy (IPT) at Reach out Mbuya community health initiative

Tuberculosis (TB) continues to be the leading cause of morbidity and mortality among human immunodeficiency virus (HIV) infected individuals in Sub Saharan Africa, including Uganda. Isoniazid prophylaxis therapy (IPT) is a major public health intervention to limit tuberculosis disease among people living with HIV. However, there is limited information about the influence of IPT on TB disease incidence and its associated risk factors among HIV positive patients in Uganda especially at Reach out-Mbuya community health initiative hence the study. A cross sectional study was conducted among HIV positive adult patients who completed a 6-months long daily treatment of Isoniazid preventive therapy. Sputum samples and urine samples were collected and analysed using Gene Xpert and lateral flow urine Lipoarabinomannan (LF-LAM) tests respectively for presence of Tuberculosis disease. Data analysis was performed using STATA (version 14). Bivariate and multivariate logistic regression were performed to assess the risk factors associated with tuberculosis among the study population and significance estimated at 95% confidence level. A total of 103 HIV positive adults was studied. The mean age of the participants was 42.1 (10.5) and median age was 43 (IQR = 16). The prevalence of tuberculosis disease among HIV positive adult patients who completed Isoniazid preventive therapy was 5.8% (6/103). Counselling, the only significant factor, reduced the likelihood of occurrence of TB disease among HIV patients on IPT treatment (aOR:0.028, P-value < 0.001). A low prevalence of TB disease was observed among HIV patients on IPT treatment. Counselling is a protective factor of TB disease among HIV patients on IPT treatment.

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.

Successful implementation of isoniazid preventive therapy at a pediatric HIV clinic in Tanzania

BackgroundIn accordance with international guidance for tuberculosis (TB) prevention, the Tanzanian Ministry of Health recommends isoniazid preventive therapy (IPT) for children aged 12 months and older who are living with HIV. Concerns about tolerability, adherence, and potential mistreatment of undiagnosed TB with monotherapy have limited uptake of IPT globally, especially among children, in whom diagnostic confirmation is challenging. We assessed IPT implementation and adherence at a pediatric HIV clinic in Tanzania.MethodsIn this prospective cohort study, eligible children living with HIV aged 1–15 years receiving care at the DarDar Pediatric Program in Dar es Salaam who screened negative for TB disease were offered a 6-month regimen of daily isoniazid. Patients could choose to receive IPT via facility- or community-based care. Parents/caregivers and children provided informed consent and verbal assent respectively. Isoniazid was dispensed with the child’s antiretroviral therapy every 1–3 months. IPT adherence and treatment completion was determined by pill counts, appointment attendance, and self-report. Patients underwent TB symptom screening at every visit.ResultsWe enrolled 66 children between July and December 2017. No patients/caregivers declined IPT. Most participants were female (n = 43, 65.1%) and the median age was 11 years (interquartile range [IQR] 8, 13). 63 (95.5%) participants chose the facility-based model; due to the small number of participants who chose the community-based model, valid comparisons between the two groups could not be made. Forty-nine participants (74.2%) completed IPT within 10 months. Among the remaining 17, 11 had IPT discontinued by their provider due to adverse drug reactions, 5 lacked documentation of completion, and 1 had unknown outcomes due to missing paperwork. Of those who completed IPT, the average monthly adherence was 98.0%. None of the participants were diagnosed with TB while taking IPT or during a median of 4 months of follow-up.ConclusionsHigh adherence and treatment completion rates can be achieved when IPT is integrated into routine, self-selected facility-based pediatric HIV care. Improved record-keeping may yield even higher completion rates. IPT was well tolerated and no cases of TB were detected. IPT for children living with HIV is feasible and should be implemented throughout Tanzania.

Effectiveness of isoniazid preventive therapy on incidence of tuberculosis among HIV-infected adults in programme setting.

Background & objectives:As India and other developing countries are scaling up isoniazid preventive therapy (IPT) for people living with HIV (PLHIV) in their national programmes, we studied the feasibility and performance of IPT in terms of treatment adherence, outcome and post-treatment effect when given under programmatic settings.Methods:A multicentre, prospective pilot study was initiated among adults living with HIV on isoniazid 300 mg with pyridoxine 50 mg after ruling out active tuberculosis (TB). Symptom review and counselling were done monthly during IPT and for six-month post-IPT. The TB incidence rate was calculated and risk factors were identified.Results:Among 4528 adults living with HIV who initiated IPT, 4015 (89%) successfully completed IPT. IPT was terminated in 121 adults (3%) due to grade 2 or above adverse events. Twenty five PLHIVs developed TB while on IPT. The incidence of TB while on IPT was 1.17/100 person-years (p-y) [95% confidence interval (CI) 0.8-1.73] as compared to TB incidence of 2.42/100 p-y (95% CI 1.90-3.10) during the pre-IPT period at these centres (P=0.017). The incidence of TB post-IPT was 0.64/100 p-y (95% CI 0.04-1.12). No single factor was significantly associated with the development of TB.Interpretation & conclusions:Under programmatic settings, completion of IPT treatment was high, adverse events minimal with good post-treatment protection. After ruling out TB, IPT should be offered to all PLHIVs, irrespective of their antiretroviral therapy (ART) status. Scaling-up of IPT services including active case finding, periodic counselling on adherence and re-training of ART staff should be prioritized to reduce the TB burden in this community.

Predictors of isoniazid preventive therapy completion among HIV-infected patients receiving differentiated and non-differentiated HIV care in rural Uganda

ABSTRACT Rates of Isoniazid Preventive Therapy (IPT) completion remain low in programmatic settings in sub-Saharan Africa. Differentiated HIV care models may improve IPT completion by addressing joint barriers to IPT and HIV treatment. However, the impact of differentiated care on IPT completion remains unknown. In a cross-sectional study of people with HIV on antiretroviral therapy in 5 communities in rural Uganda, we compared IPT completion between patients receiving HIV care via a differentiated care model versus a standard HIV care model and assessed multi-level predictors of IPT completion. A total of 103/144 (72%) patients received differentiated care and 85/161 (53%) received standard care completed IPT (p < 0.01). Adjusting for age, gender and community, patients receiving differentiated care had higher odds of completing IPT (aOR: 2.6, 95% CI: 1.5–4.5, p < 0.01). Predictors of IPT completion varied by the care model, and differentiated care modified the positive association between treatment completion and the belief in the efficacy of IPT and the negative association with side-effects. Patients receiving a multi-component differentiated care model had a higher odds of IPT completion than standard care, and the model’s impact on health beliefs, social support, and perceived side effects to IPT may underlie this positive association.

Evaluation of the Isoniazid Preventive Therapy Care Cascade Among HIV-Positive Female Sex Workers in Mombasa, Kenya.

Kenyan female sex workers (FSWs) have a high HIV prevalence, increasing their tuberculosis (TB) risk. Despite recommendations that HIV-positive individuals be offered isoniazid preventive therapy (IPT), uptake has been limited. In this longitudinal cohort of HIV-positive FSWs, we retrospectively characterized the IPT care cascade between March 2000 and January 2010, including reasons for cascade loss or appropriate exit. Cascade success required completion of 6 months of IPT. Baseline characteristics were assessed as potential correlates of cascade loss using multivariable logistic regression. Among 642 HIV-positive FSWs eligible for IPT evaluation, median age was 31 years (IQR 26-35) with median CD4 lymphocyte count of 409 (IQR 292-604) cells per cubic millimeter. There were 249 (39%) women who successfully completed 6 months of IPT, 157 (24%) appropriately exited the cascade, and 236 (37%) were cascade losses. Most cascade losses occurred at symptom screen (38%, 90/236), chest radiograph evaluation (28%, 66/236), or during IPT treatment (30%, 71/236). Twenty-nine women were diagnosed with tuberculosis, including one after IPT initiation. Most women initiating IPT completed the course (71%, 249/351); <5% had medication intolerance. Younger women [<25 and 25-35 vs. >35 years; adjusted odds ratio (AOR) 2.65, 95% confidence interval (CI): 1.46 to 4.80 and AOR 1.78, 95% CI: 1.13 to 2.80, respectively], and those evaluated for IPT after antiretroviral availability in 2004 (AOR 1.92, 95% CI: 1.31 to 2.81), were more likely to be cascade losses. Implementation of IPT among HIV-positive FSWs in Kenya is feasible. However, significant losses along the IPT care cascade underscore the need for strategies improving retention in care.

Implementation and evaluation of an isoniazid preventive therapy pilot program among HIV-infected patients in Vietnam, 2008-2010.

WHO recommends screening for TB and evaluation for isoniazid preventive therapy (IPT) based on evidence that they reduce TB-related morbidity and mortality among HIV-infected persons. In Vietnam, an IPT pilot was implemented in two provinces; TB screening, treatment and outcomes were evaluated to inform the adoption and scale-up of IPT. During April 2008 to March 2010, eligible HIV-infected persons aged >15 years, with no previous or current TB treatment, alcohol abuse or liver disease were screened for TB. If TB disease was ruled out based on symptoms, chest x-rays and sputum smears, isoniazid was administered for 9 months. Among 1281 HIV-infected persons who received initial eligibility screening, 520 were referred to and evaluated at district TB clinics for TB disease or IPT eligibility. Active TB was diagnosed in 17 patients and all were started on treatment. Of 520 patients evaluated, 416 (80.0%) initiated IPT: 382 (91.8%) completed IPT, 17 (4.1%) stopped treatment, 8 (1.9%) died, 3 (0.7%) developed TB during IPT and 6 (1.4%) had unknown outcomes. No severe adverse events were reported. IPT treatment completion was high; no serious complications occurred. Improving and expanding intensified case-finding and IPT should be considered in Vietnam.

Interventions to improve delivery of isoniazid preventive therapy: an overview of systematic reviews.

BackgroundUptake of isoniazid preventive therapy (IPT) to prevent tuberculosis has been poor, particularly in the highest risk populations. Interventions to improve IPT delivery could promote implementation. The large number of existing systematic reviews on treatment adherence has made drawing conclusions a challenge. To provide decision makers with the evidence they need, we performed an overview of systematic reviews to compare different organizational interventions to improve IPT delivery as measured by treatment completion among those at highest risk for the development of TB disease, namely child contacts or HIV-infected individuals.MethodsWe searched the Cochrane Database of Systematic Reviews, the Database of s of Reviews of Effects (DARE), and MEDLINE up to August 15, 2012. Two authors used a standardized data extraction form and the AMSTAR instrument to independently assess each review.ResultsSix reviews met inclusion criteria. Interventions included changes in the setting/site of IPT delivery, use of quality monitoring mechanisms (e.g., directly observed therapy), IPT delivery integration into other healthcare services, and use of lay health workers. Most reviews reported a combination of outcomes related to IPT adherence and treatment completion rate but without a baseline or comparison rate. Generally, we found limited evidence to demonstrate that the studied interventions improved treatment completion.ConclusionsWhile most of the interventions were not shown to improve IPT completion, integration of tuberculosis and HIV services yielded high treatment completion rates in some settings. The lack of data from high burden TB settings limits applicability. Further research to assess different IPT delivery interventions, including those that address barriers to care in at-risk populations, is urgently needed to identify the most effective practices for IPT delivery and TB control in high TB burden settings.

Isoniazid preventive treatment: predictors of adverse events and treatment completion

Villa Marelli Institute (VMI), Niguarda Ca'Granda Hospital, Milan, Italy. A recent report on the fatal side effects of isoniazid preventive therapy (IPT) from the United States has re-ignited discussion on the safety of this intervention. To evaluate IPT feasibility, treatment completion and adverse events (AE) and their determinants under field conditions. Data from consecutive subjects undergoing IPT at the VMI were recorded in an electronic database from 1992 to 2009. Logistic regression analysis was performed to detect completion and AE determinants. A total of 11,963 patients were included in the study. AE (odds ratio [OR] 2.70, 95%CI 2.22-3.28) and human immunodeficiency virus positive status (OR 5.20, 95%CI 2.10-12.93) were the main determinants of treatment interruption among Italians, while social weakness (no housing/job; OR 2.88, 95%CI 2.43-3.42), AEs (OR 1.33, 95%CI 1.15-1.53, 2.22-3.28) and screening in undocumented subjects (OR 1.20, 95%CI 1.01-1.44) prevailed among foreigners. Age was the main determinant of transaminase increase (OR 1.03, 95%CI 1.03-1.04), as were AEs of the gastrointestinal (OR 1.02, 95%CI 1.02-1.03), central nervous (OR 1.02, 95%CI 1.02-1.05) and peripheral nervous systems (OR 1.04, 95%CI 1.02-1.05). This analysis demonstrates the feasibility and safety of IPT, with determinants of interruption and AEs being predictable and addressable.