Tuberculosis Isoniazid Preventive Therapy Research Articles

Safety and tolerability of isoniazid preventive therapy for tuberculosis for persons with HIV with and without alcohol use: a single arm trial.

Isoniazid (INH) preventive therapy is recommended to prevent tuberculosis (TB) disease for persons with HIV (PWH), except for those with regular and heavy alcohol consumption, due to hepatotoxicity concerns. We aimed to quantify the incidence of severe INH-related toxicity among PWH with and without recent alcohol consumption. Prospective study of PWH receiving INH. We included PWH in southwest Uganda with recent (prior three months) (n = 200) or no (prior year) self-reported alcohol consumption (n = 101), on antiretroviral therapy, TB infected (≥5 mm on tuberculin skin test), and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2x the upper limit of normal (ULN). Grade 3+ INH-related toxicity was ALT or AST ≥5x the ULN or severe symptoms; we stopped IPT upon detection. Grade 2 INH-related toxicity was ALT or AST 2-5x the ULN or moderate symptoms. The cumulative incidence of Grade 3+ INH-related toxicity was 8.3% (95% CI: 5.7-12.0); all resolved after INH cessation. Incidence was 6.0% (95% CI: 3.1-10.2) among those reporting recent alcohol use and 12.9% (95% CI: 7.0-21.0) of those reporting no prior year alcohol use. We found no differences by baseline phosphatidylethanol-confirmed alcohol severity. The cumulative incidence of Grade 2 toxicities (without Grade 3+) was 21.7% (95% CI: 17.2-27.0); 25.0% (95% CI: 19.0-31.8) among those with recent alcohol use and 14.8% (95% CI: 8.1-23.9) among those with no prior year alcohol use. Alcohol use does not appear to increase risk for serious INH-related toxicity among PWH without significant liver enzyme elevations at baseline (≤2x ULN).

Medication adherence and adverse drug reactions of isoniazid preventive therapy for tuberculosis in people living with HIV (PLHIV) in a tertiary care teaching hospital, Kakinada

Medication adherence and adverse drug reactions of isoniazid preventive therapy for tuberculosis in people living with HIV (PLHIV) in a tertiary care teaching hospital, Kakinada

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.

Uptake of isoniazid preventive therapy for tuberculosis among HIV patients in Kano, Nigeria

Context: Despite convincing data on its efficacy and recommendation by the World Health Organisation that isoniazid preventive therapy (IPT) be included as part of the minimum package of care for people living with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome, IPT has not been widely implemented. Aims: The study assessed uptake and predictors of IPT among HIV patients in Kano, Nigeria. Methods and Material: Using a cross-sectional study design, an interviewer-administered questionnaire was used to collect information from 320 HIV patients from 2 primary health-care centres using systematic sampling technique. Statistical analysis used: Data were analysed using SPSS version 20.0. Results: Majority of the respondents (309; 96.9%) believed that tuberculosis (TB) poses a threat to health and well-being of HIV patients and up to 307 (95.9%) knew that TB is preventable, but slightly over a half (172; 53.8%) of the respondents were using IPT for prevention of TB. Age, education, awareness and disclosure were found to be independent predictors of IPT uptake. Respondents who were 30 years or older (adjusted odds ratio [AOR] = 2.46, 95% confidence interval [CI] = 1.16–5.24) and those who disclosed their HIV status to partner/family (AOR = 1.52, 95% CI = 1.15–3.68) had higher odds of IPT uptake, whereas respondents with informal education (AOR = 0.46, 95% CI = 0.14–0.93) and those who lack awareness of IPT were less likely to uptake IPT (AOR = 0.23, 95% CI = 0.08–0.68). Conclusions: IPT is being underutilised for the prevention of TB among HIV patients in Kano. This implies the need for health-care workers to introduce strategies to improve counseling and disclosure.

Barriers to the implementation of isoniazid preventive therapy for tuberculosis in children in endemic settings: A review.

Isoniazid preventive therapy is one of the key interventions in reducing the risk of active disease among children exposed to tuberculosis. However, initiation and maintenance of this treatment is poor in many areas. This review summarises the existing literature on barriers to implementation of isoniazid preventive therapy for tuberculosis in children in endemic settings. MEDLINE, EMBASE and CINAHL databases were used to search for primary research studies published between 1998 and 2018, specifically mentioning isoniazid preventive therapy, tuberculosis and children. Barriers identified in most study settings included absence of parental risk perception, health-care worker knowledge gaps and treatment access. Focusing on patient-centred care, enhancing community and health-care worker education and securing stable medication supply to effectively deliver this therapy is crucial in order to reduce childhood morbidity and mortality from tuberculosis.

Adherence to isoniazid preventive therapy for tuberculosis among HIV patients in Kano, Nigeria

Background: Tuberculosis (TB) is the most common opportunistic infection among human immunodeficiency virus (HIV)-infected individuals. It is a major cause of mortality among patients with HIV and poses a risk throughout the course of HIV disease. Adherence to isoniazid preventive therapy (IPT) is a critical factor that needs to be considered in scaling up services in developing countries. Objectives: The study aimed to assess adherence and associated factors to IPT among HIV patients in Kano. Methods: Using a cross-sectional study design, interviewer-administered questionnaire was used to collect information from 320 HIV patients from two comprehensive health centers (CHCs). Results: Up to two-third, 211 (65.9%) of the participants were aware of the use of isoniazid for the prevention of TB among HIV/AIDS patients, but only about half 172 (53.8%) of the respondents interviewed were currently using IPT for TB prevention. Up to 158 (89.5%) of the 172 respondents interviewed had good level of adherence to IPT and the main reasons to enhance adherence were disclosure of HIV status to partner/relatives (77.9%), adequate counseling about IPT (62.8%), and awareness of IPT for TB prevention (65.9%). Conclusion: Good level of adherence to IPT from this study implies that the need for improve strategies to ensure IPT scale up as adherence to IPT among HIV clients in Kano is optimal, but uptake remains low.

Long-term protection from isoniazid preventive therapy for tuberculosis in HIV-infected patients in a medium-burden tuberculosis setting: the TB/HIV in Rio (THRio) study.

The duration of protection against tuberculosis provided by isoniazid preventive therapy is not known for human immunodeficiency virus (HIV)-infected individuals living in settings of medium tuberculosis incidence. We conducted an individual-level analysis of participants in a cluster-randomized, phased-implementation trial of isoniazid preventive therapy. HIV-infected patients who had positive tuberculin skin tests (TSTs) were followed until tuberculosis diagnosis, death, or administrative censoring. Nelson-Aalen cumulative hazard plots were generated and hazards were compared using the log-rank test. Cox proportional hazards models were fitted to investigate factors associated with tuberculosis diagnosis. Between 2003 and 2009, 1954 patients with a positive TST were studied. Among these, 1601 (82%) initiated isoniazid. Overall tuberculosis incidence was 1.39 per 100 person-years (PY); 0.53 per 100 PY in those who initiated isoniazid and 6.52 per 100 PY for those who did not (adjusted hazard ratio [aHR], 0.17; 95% confidence interval [CI], .11-.25). Receiving antiretroviral therapy at time of a positive TST was associated with a reduced risk of tuberculosis (aHR, 0.69; 95% CI, .48-1.00). Nelson-Aalen plots of tuberculosis incidence showed a constant risk, with no acceleration in 7 years of follow-up for those initiating isoniazid preventive therapy. Isoniazid preventive therapy significantly reduced tuberculosis risk among HIV-infected patients with a positive TST. In a medium-prevalence setting, 6 months of isoniazid in HIV-infected patients with positive TST reduces tuberculosis risk over 7 years of follow-up, in contrast to results of studies in higher-burden settings in Africa.

Isoniazid preventive therapy for tuberculosis in South Africa: an assessment of the local evidence base.

Worldwide, South Africa (SA) has the worst tuberculosis (TB) epidemic. In SA, there are > 6.1 million people living with HIV (PLWH) and the country now has the largest antiretroviral treatment programme with > 2 million people receiving combination therapy. While there has been a marked recent decline in HIV-associated deaths, > 50% of TB cases still continue to be diagnosed in PWLH. The current TB control strategy based on passive case finding, chemotherapy of childhood TB contacts and directly observed therapy has clearly failed to control endemic TB in SA. Two recent meta-analyses have shown a > 60% reduction in TB in HIV-infected adults after isoniazid preventive therapy (IPT). SA has implemented the World Health Organization policy and IPT is now recommended for HIV-positive people for up to 36 months. Originally, there was only one SA study included in the evidence base supporting this policy, but subsequently four randomised controlled trials have been conducted in SA populations. These studies, together with local observational studies, are the subject of this local, evidence-based review.

High Prevalence of Pulmonary Tuberculosis but Low Sensitivity of Symptom Screening among HIV-Infected Pregnant Women in South Africa

Symptom screening is a recommended component of intensified case-finding (ICF) for pulmonary tuberculosis (TB) among HIV-infected individuals. Symptomatic individuals are further investigated to either exclude or diagnose pulmonary TB, thus reducing the number of individuals requiring costly laboratory investigation. Those with laboratory evaluations negative for pulmonary TB or who lack symptoms may be eligible for antiretroviral therapy (ART) and/or TB isoniazid preventive therapy (IPT). A four-part symptom screen has been recommended by the World Health Organization (WHO) for identifying TB suspects and those unlikely to have TB. A meta-analysis of studies among HIV-infected individuals calculated a sensitivity of 90.1% for the four-part symptoms screen - of any of cough, fever, night sweats, or weight loss - among patients in clinical care, making it an effective tool for identifying most patients with TB. An important population for intensified case-finding not included in that meta-analysis was HIV-infected pregnant women. We undertook a cross-sectional survey among HIV-infected pregnant women receiving prenatal care at community clinics in South Africa. We obtained a four-symptom review and sputum smear microscopy and mycobacterial culture on all participants. Among 1415 women, 226 (16%) had a positive symptom screen, and 35 (2.5%) were newly diagnosed with culture-positive TB. Twelve were on TB treatment at the time of screening, yielding 47 (3.3%) women with prevalent TB. Symptom screening among women without known TB had a sensitivity of 28% and specificity of 84%. The poor performance of symptom screening to identify women with TB suggests that other approaches may be needed for intensified case-finding to be effective for this population.

Modelling the economic benefits of tuberculosis preventive therapy for people with HIV

To assess the economic benefits and costs of providing isoniazid preventive therapy for tuberculosis (TB) in HIV-infected persons in Zambia. A spreadsheet model incorporating variables drawn from published studies and unpublished data. Data drawn from a number of different studies and published literature involving a range of subjects. Zambia. Using data primarily from Zambia we have modelled the costs and benefits of a TB preventive therapy programme using daily isoniazid for 6 months. The basecase scenario assumes recruitment at a voluntary testing and counselling site where HIV seroprevalence is 30%; persons with HIV have a 25% probability of developing active TB during their lifetime; two additional cases of TB would be prevented per person completing a course of preventive therapy; compliance would be 63%, and the efficacy of the isoniazid in preventing active TB of 60%. The costs under this scenario would exceed the benefits by a factor of 1.16 [benefit: cost ratio (BCR) of 0.86]. However, if preventing one case of TB prevented an additional five cases, the benefits would exceed the costs by a significant margin (BCR of 1.71). Other scenarios indicate that the targeted preventive therapy of persons with HIV whose occupation or living situation places them in contact with a large number of others (teachers and students, health personnel, military and police, miners, prisoners, etc.) would yield significant net benefit. The operational challenge for TB preventive therapy is thus to identify and target large numbers of such persons.

Isoniazid Preventive Therapy for Tuberculosis: Decision Analysis Considering Ethnicity and Gender

The decision to prescribe or withhold isoniazid (INH) preventive therapy for low-risk tuberculin reactors has been highly controversial, primarily due to isoniazid's possible hepatotoxic effects. Previous analyses have explored the INH decision only from the perspective of patient age, recognizing that the risks of INH-induced hepatotoxicity are age related. Decision analyses presented in this paper assess the impact of gender and ethnic group, as well as age, on the INH decision. Results for low-risk patients favor prescribing INH preventive therapy for all 20-yr-olds, all 35-yr-olds except black women, and no 50-yr-olds, projecting life expectancy benefits that range from 3 to 19 days. A comparison set of analyses performed for high-risk patients favors prescribing INH for all groups except 50-yr-old black women. These findings suggest that ethnicity, gender, and age should be considered when making the decision to prescribe or withhold INH preventive therapy.

Isoniazid Preventive Therapy for Tuberculosis: Are We Losing Our Enthusiasm?

Contact investigation activities of the Tennessee Department of Health and Environment (TDHE) Tuberculosis (TB) Control Program from 1979 to 1985 were reviewed. Out of 32,722 identified contacts, 6,030 (20.1 percent) were infected (positive purified protein derivative [PPD]). Only 2,731 (45 percent) of the infected contacts were started on preventive therapy. Both the absolute number and the relative percentage of infected contacts starting on INH prevention therapy have gradually declined over the years. While 569 (67 percent) of the infected contacts were started on preventive treatment in 1979, only 296 (37.5 percent) received isoniazid (INH) preventive therapy in 1985. Although an increasing percentage of those starting preventive therapy completed the prescribed course, the enthusiasm for recommending preventive therapy has declined for the infected individuals above the age of 15. More enthusiasm and efforts are needed from physicians in initiating and maintaining INH preventive therapy to accomplish tuberculosis eradication.