Use Of Isoniazid Preventive Therapy Research Articles

Latent Tuberculosis Infection and Isoniazid Preventive Therapy among Human Immunodeficiency Virus positive adults in Southern Nigeria

Aim/objectives: It was aimed to assess the prevalence of latent TB among HIV+ patients, evaluate the coverage of isoniazid preventive therapy (IPT), the continuous risk of latent tuberculosis infection, and factors associated with the presence of latent Tb in HIV+ patients.
 Methods: This is an analytical cross-sectional study of HIV+ patients attending the HIV clinic or admitted not previously treated for TB and did not have clinical and laboratory evidence of active TB and matched HIV-negative population attending our GOC. Data collected with a pre-tested investigator administered questionnaire included the age, sex, height and weight, medical and drug history, and relevant physical examination findings such as body temperature and respiratory rate. Active TB was excluded by history, sputum AFB Z-N staining, or GeneXpert test and chest radiography. Whole blood samples were collected from participants for QuantiFERON TB Gold Plus for quantification of Interferon Gamma Release assay (IGRA) in order to diagnose or exclude latent TB. Data were analyzed using IBM SPSS version 25.0 software at a level of significance of p < 0.05. Association between means and qualitative variables was analyzed with student-t-test and Chi-square test
 Results: The mean ages of the HIV+ and control groups were 42.69 ± 9.91 and 41.29 ± 9.20 years respectively with no significant statistical difference. 76(95.0%) of HIV+ patients and 74(92.5%) controls had no symptoms of TB and chronic lung disease. 18(22.5%) HIV+ patients and 2(2.5%) controls were exposed to persons with chronic cough (p=<0.001). The prevalence of latent TB among HIV+ patients was 22.50% and 10.0% among controls (p- value=0.001). 8(44.4%) out of 18 with latent TB had prior use of IPT compared with 24 (38.7%) out of 62 without latent TB (p-value =0.67). CD4 count was a significant factor associated with the presence of latent TB among HIV+ persons (p-0.03). Similarly, there was a significant association between viral load and positive IGRA (p<0.001).
 Conclusion: Latent TB infection remains significantly higher among HIV+ than HIV-negative patients which may account for the higher incidence of active disease amongst them. Isoniazid preventive therapy coverage was poor amongst HIV+ patients in this study.

Prevalence and associated factors of tuberculosis among isoniazid users and non-users of HIV patients in Dessie, Ethiopia

Tuberculosis (TB) is major public health concern and Isoniazid Preventive Therapy (IPT) helps to prevent TB development among patients living with human immune deficiency virus (PLWHIV). However, the evidence is limited especially in the study area. Therefore, this study aimed to determine the prevalence and factors associated with TB among IPT users and non-IPT users of PLWHIV in Dessie, Ethiopia. A comparative cross-sectional study was employed for1 month in Dessie. A total of 326 respondents were selected using systematic random sampling. Bivariable and multivariable logistic regression analyses were computed to identify factors associated with Tuberculosis. In multivariable analysis, AOR with 95% CI was used to declare statistically significant variables with TB. The prevalence of TB among non-IPT users was 48.5%, (95% CI 40.8–56.2%), and among IPT users was 8%, (95% CI 5–13%). Cotrimoxazole prophylaxis therapy (CPT) (AOR = 5.835, 95% CI 2.565–13.274), IPT (AOR = 10.359, 95% CI 4.054–26.472), ART adherence (AOR = 30.542, 95% CI 12.871–72.475), and believing that IPT use prevents TB (AOR = 0.093, 95% CI 0.018–0.484) were statistically significant factors. The prevalence of TB was higher among non-IPT users than among IPT users. Therefore, efforts should be strengthened to implement widespread use of IPT among adult PLWHIV.

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<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.
 Keywords: IPT Completion; Isoniazid Preventive Therapy; PLHIV; Tuberculosis; Southwest Nigeria

Effectiveness of a 6-Month Isoniazid on Prevention of Incident Tuberculosis Among People Living with HIV in Eritrea: A Retrospective Cohort Study.

IntroductionA 6-month isoniazid as tuberculosis preventive therapy (TPT) for people living with HIV (PLHIV) was nationally introduced in Eritrea in 2014. However, its effectiveness in preventing tuberculosis (TB) and duration of protection was questioned by physicians. This study was, therefore, conducted to evaluate the impact of the isoniazid preventive therapy (IPT) primarily on the prevention of TB and duration of its protection in PLHIV.MethodsA retrospective cohort study was conducted that selected all eligible PLHIV attending HIV care clinics in all national and regional referral hospitals in Eritrea. Data was collected from patients’ clinical cards using a structured data extraction sheet. The association between use of IPT and outcomes of interest was assessed using a Cox proportional hazard regression model and Kaplan–Meier curve.ResultsA total of 6803 patients were selected, which accounted for 75% of all PLHIV-accessing HIV care clinics in Eritrea. About 76% of patients were exposed to IPT while the remaining 24% were unexposed. The mean follow-up time was 4.9 years (SD 1.4). The incidence rate of TB was 1.7 and 10 cases per 1000 person-years in the exposed and unexposed, respectively. The unexposed had a higher risk of incident TB (adjusted hazard ratio [aHR] 3.75, 95% confidence interval [CI] 2.89, 6.13) and all-cause mortality (HR 2.41, 95% CI 1.85, 3.14) compared to the exposed. A Kaplan–Meier curve showed that the exposed group had a higher TB-free follow-up probability (98.8%) compared to the unexposed (95%) at 65 months of follow-up (p < 0.001). IPT protection decreased rapidly 6 months after isoniazid completion.ConclusionUse of a 6-month isoniazid as TPT was found to be effective in reducing incident TB in PLHIV-accessing HIV care clinics in Eritrea. However, the protection appeared to diminish soon, namely 6 months after completion of isoniazid, which warrants immediate attention from policy makers.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40121-022-00589-w.

Active TB infection and its associated factors among HIV-1 infected patients at Jimma medical center, Southwest Ethiopia

BackgroundHuman immune deficiency virus (HIV) increases the susceptibility to primary infection or reinfection and the risk of tuberculosis (TB) reactivation for patients with latent TB. There was no current report on the rate of active TB infection among HIV-1 infected patients in our teaching and referral hospital. Therefore, this study was aimed to determine the prevalence and factors associated with active TB infection among HIV-1 infected patients.MethodsHospital-based retrospective cross-sectional study was conducted at the Anti-Retroviral Therapy (ART) chronic follow-up clinic. Systematic random sampling was used to include the patients. A structured questionnaire was used to collect data. Data were analyzed using SPSS version 25. Descriptive statistics were used to describe the findings and multivariate logistic regression was performed to identify factors associated with active TB infection.Result150 HIV-1 infected patients (female 54.7%) were included. The median (interquartile range, IQR) age of the patients was 33.5 (25.7, 40.0) years. Twenty-six (17.3%) of the patients had developed active TB infection, which was independently associated with the WHO clinical stage III and IV (AOR: 9.67, 95% confidence interval (CI); 2.21–42.37), p = 0.003). The use of isoniazid preventive therapy (IPT) (AOR: 0.123, 95CI; 0.034–0.44, p = 0.001) and having good adherence to ART medications (AOR: 0.076, 95CI; 0.007–0.80, p = 0.032) was associated with the reduced risk of active TB infection among HIV-1 infected patients.ConclusionsAdvanced WHO clinical stages increased the risk of active TB infection, while the use of IPT and good adherence to ART medications reduced the risk of active TB infection. Therefore, patients with advanced WHO clinical stage should be screened for TB infection, and starting IPT for the candidate patients should be strengthened to reduce the burden of active TB incidence. ART medication adherence should also be supported.

Isoniazid preventive therapy plus antiretroviral therapy for the prevention of tuberculosis: a systematic review and meta-analysis of individual participant data

Isoniazid preventive therapy prevents active tuberculosis in people with HIV, but previous studies have found no evidence of benefit in people with HIV who had a negative tuberculin skin test, and a non-significant effect on mortality. We aimed to estimate the effect of isoniazid preventive therapy given with antiretroviral therapy (ART) for the prevention of tuberculosis and death among people with HIV across population subgroups. We searched PubMed, Embase, the Cochrane database, and conference abstracts from database inception to Jan 15, 2019, to identify potentially eligible randomised trials. Eligible studies were trials that enrolled HIV-positive adults (age ≥15 years) taking ART who were randomly assigned to either daily isoniazid preventive therapy plus ART or ART alone and followed up longitudinally for outcomes of incident tuberculosis and mortality. We approached all authors of included trials and requested individual participant data: coprimary outcomes were relative risk of incident tuberculosis and all-cause mortality. We did a single-stage meta-analysis of individual participant data using stratified Cox-proportional hazards models. We did prespecified subgroup analyses by sex, CD4 cell count, and evidence of immune sensitisation to tuberculosis (indicated by tuberculin skin test or interferon-γ release assays [IGRAs]). We also assessed the relative risk of liver injury in an additional prespecified analysis. This study is registered with PROSPERO, CRD42019121400. Of 838 records, we included three trials with data for 2611 participants and 8584·8 person-years of follow-up for the outcome of incident tuberculosis, and a subset of 2362 participants with 8631·6 person-years of follow-up for the coprimary outcome of all-cause mortality. Risk for tuberculosis was lower in participants given isoniazid preventive therapy and ART than participants given ART alone (hazard ratio [HR] 0·68, 95% CI 0·49-0·95, p=0·02). Risk of all-cause mortality was lower in participants given isoniazid preventive therapy and ART than participants given ART alone, but this difference was non-significant (HR 0·69, 95% CI 0·43-1·10, p=0·12). Participants with baseline CD4 counts of less than 500 cells per μL had increased risk of tuberculosis, but there was no significant difference in the benefit of isoniazid preventive therapy with ART by sex, baseline CD4 count, or results of tuberculin skin test or IGRAs. 65 (2·5%) of 2611 participants had raised alanine aminotransferase, but data were insufficient to calculate an HR. Isoniazid preventive therapy with ART prevents tuberculosis across demographic and HIV-specific and tuberculosis-specific subgroups, which supports efforts to further increase use of isoniazid preventive therapy with ART broadly among people living with HIV. National Institutes of Health and National Institute of Allergy and Infectious Diseases.

Uptake of tuberculosis prevention therapy in people living with HIV/AIDS in northern Nigeria: a programme to increase use of isoniazid preventive therapy

BackgroundTuberculosis is a main cause of death in people living with HIV and results in around 39 000 deaths every year in Nigeria. Isoniazid preventive therapy (IPT), the standard tuberculosis preventive therapy used in Nigeria, has been shown to significantly reduce mortality and prevent tuberculosis in people with HIV. Despite efforts and strategies to scale up this treatment in Nigeria, the process has remained very slow. Here we describe a programme to increase IPT uptake in health facilities in four states in northern Nigeria, while also monitoring trends in IPT use with the aim of increasing access for people with HIV. MethodsData were collected at 90 health facilities in Nasarawa, Kano, and Katsina states and the Federal Capital Territory (FCT), Nigeria, between Oct 1, 2017, and March 31, 2019. A monitoring tool was used to track clinic attendance, IPT eligibility status, and percentage uptake of isoniazid (the proportion of people with HIV starting a 6 month course of isoniazid) in patients with HIV at these health facilities. Baseline data were collected between Oct 1, 2017, and Feb 28, 2018, and identified reasons for low IPT uptake included: stockout of isoniazid, documentation gaps, improper filling of the relevant source documents, and poor clinician awareness of use of IPT. In response to these barriers to uptake, interventions such as folder tagging and electronic prompts of eligible clients prior to clinic visits, clinician sensitisations through training and retraining to raise the awareness of IPT, and active tracking of eligible clients were implemented. We collected post-intervention data from March 1, 2018, to March 31, 2019. Analysis was done using Excel and STATA. FindingsDuring the 6 month pre-intervention period, 3659 (14%) patients were commenced on isoniazid out of 26 136 eligible patients. In the initial 6 months post-intervention, 18 367 (80%) patients were started on isoniazid out of 22 020 eligible patients. Uptake dropped suddenly in October, 2018, due to stockout of isoniazid. Remedial stock redistribution resulted in a steady increase of isoniazid uptake and a total number of 43 075 patients out of 50 050 patients (86%) commenced isoniazid within the 12 month review period. InterpretationCapacity building of health-care workers on isoniazid through training and retraining resulted in marked improvements in IPT uptake through: increased health-care worker knowledge about IPT; proper documentation on the relevant source documents and the electronic medical records; and availability, and use of, isoniazid electronic prompts to highlight clients who were eligible for IPT. However, there is a need to strengthen drug logistics, especially in guaranteeing a consistent and adequate supply of isoniazid in all facilities to avoid stockouts, thus ensuring optimum IPT uptake or access for people living with HIV in Nigeria. FundingInstitute of Human Virology, Nigeria

Improving coverage and completion rate of isoniazid preventive therapy among eligible HIV patients using quality improvement approaches: a case study of State Hospital, Ijebu Ode, Ogun State, Nigeria.

IntroductionTuberculosis (TB) is a major killer of people living with HIV. One key strategy to reduce the incidence of tuberculosis in HIV patients is the use of Isoniazid Preventive Therapy (IPT). However, coverage of IPT among eligible HIV clients is poor. This study aims to improve IPT coverage using quality improvement approaches that help identify the root cause and improve coverage of isoniazid preventive therapy.MethodsThe quality improvement (QI) project spanned over six months corresponding to three PDSA cycles. Root causes for low IPT initiation and completion in State Hospital Ijebu Ode were identified using fishbone analysis. The root causes were subjected to prioritization matrix and implementation plan was developed for the first two root causes with the highest composite matrix scores. Longitudinal data were collected over the six months period with learning session at the end of every two-month PDSA cycle. Data was analyzed using Microsoft Excel 2010 and presented in charts and tables.ResultsThe two most contributory factors to low IPT initiation and completion in the facility with prioritization matrix scores of 30 and 25 respectively were poor tracking system for IPT eligible clients and poor documentation of IPT commencement in the patients care cards and IPT registers. Findings showed improvement in both IPT initiation and completion with increase in initiation rate from 11% to above 50%, and increase in completion rate from 53% to 95.4%.ConclusionThe use of quality improvement approaches can improve coverage and completion rate of IPT among eligible HIV patients. Government and health programmers should support facilities to apply QI approaches to solving health service delivery.

Evaluation of the intensified tuberculosis case finding guidelines for children living with HIV.

Out-patient paediatric human immunodeficiency virus (HIV) clinic in Soweto, South Africa. To evaluate the yield of symptom screening for intensified tuberculosis (TB) case finding (ICF) and potential eligibility for isoniazid preventive therapy (IPT) in children living with HIV on antiretroviral treatment (ART). A cohort of 247 children (age 0-8 years) was systematically screened for TB symptoms during the first 2 years of ART. Children with symptoms were assessed using chest X-ray, smear microscopy and culture. Over 2 years, 1346 TB symptom screens were performed in 220 children not on anti-tuberculosis treatment. Only 48 (3.6%) screens in 39 children were positive for current cough, current fever, weight loss (>5%) or contact with a TB patient. The positive predictive value of symptom screening was 8.9% (95%CI 2.5-21.2); the sensitivity was 57.1% (95%CI 18.4-90.1). Most children (85.8%) were IPT-eligible according to World Health Organization guidelines; however, few (1.2%) were eligible according to South African guidelines. The yield of TB symptom screening was relatively poor in children on ART, highlighting the need for future research on paediatric TB symptom screening approaches in this population. The vastly different criteria for IPT eligibility between guidelines suggest that research is also needed to define the optimal use of IPT in children on ART.

Assessing the impact of antiretroviral therapy on tuberculosis notification rates among people with HIV: a descriptive analysis of 23 countries in sub-Saharan Africa, 2010\u20132015

BackgroundHIV is a major driver of the tuberculosis epidemic in sub-Saharan Africa. The population-level impact of antiretroviral therapy (ART) scale-up on tuberculosis rates in this region has not been well studied. We conducted a descriptive analysis to examine evidence of population-level effect of ART on tuberculosis by comparing trends in estimated tuberculosis notification rates, by HIV status, for countries in sub-Saharan Africa.MethodsWe estimated annual tuberculosis notification rates, stratified by HIV status during 2010–2015 using data from WHO, the Joint United Nations Programme on HIV/AIDS, and the United Nations Population Division. Countries were included in this analysis if they had ≥4 years of HIV prevalence estimates and ≥ 75% of tuberculosis patients with known HIV status. We compared tuberculosis notification rates among people living with HIV (PLHIV) and people without HIV via Wilcoxon rank sum test.ResultsAmong 23 included countries, the median annual average change in tuberculosis notification rates among PLHIV during 2010–2015 was -5.7% (IQR -6.9 to -1.7%), compared to a median change of -2.3% (IQR -4.2 to -0.1%) among people without HIV (p-value = 0.0099). Among 11 countries with higher ART coverage, the median annual average change in TB notification rates among PLHIV was -6.8% (IQR -7.6 to -5.7%) compared to a median change of -2.1% (IQR -6.0 to 0.7%) for PLHIV in 12 countries with lower ART coverage (p = 0.0106).ConclusionTuberculosis notification rates declined more among PLHIV than people without HIV, and have declined more in countries with higher ART coverage. These results are consistent with a population-level effect of ART on decreasing TB incidence among PLHIV. To further reduce TB incidence among PLHIV, additional scale-up of ART as well as greater use of isoniazid preventive therapy and active case-finding will be necessary.

Serious hepatotoxicity following use of isoniazid preventive therapy in HIV patients in Eritrea.

WHO information note indicates that isoniazid preventive therapy (IPT) is generally safe with little risk of hepatotoxicity. However, when the policy of IPT for HIV patients was introduced in Eritrea, frequent IPT‐associated hepatotoxicity and fatality have been reported to the Pharmacovigilance Centre. The aim of the study is to assess the causal association of IPT and hepatotoxicity and identify possible risk factors in patients on Highly Active Anti‐retroviral Therapy (HAART). This is a case series assessment of spontaneously reported cases to the Eritrean Pharmacovigilance Centre. Data extracted from VigiFlow (reported between 2014 and 2016) were exported to excel spread sheet for descriptive and qualitative analysis. Naranjo probability scale and Austin Bradford‐Hill criteria were used to assess causality. The P‐Method was used to assess preventability. A total of 31 of cases of hepatotoxicity related to IPT were retrieved. Majority (80.6%) of the cases were marked as “serious” due to life‐threatening situation (n = 15), hospitalization (n = 6), and death (n = 4). Baseline liver function test was normal in 61.3% and hepatitis B and C infections were ruled out in 77.4%. IPT was discontinued in 26 cases and reaction abated in 22 of them. Causality assessment using Austin Bradford‐Hill criteria found that the association was strong, consistent and specific with a plausible temporal relationship and biological mechanism. IPT‐associated hepatotoxicity that led to treatment interruption and death was observed in patients on HAART in Eritrea. Hence, close laboratory monitoring of patients is recommended to minimize the risk.

Delivery of isoniazid preventive therapy to reduce occupational TB among healthcare workers in Swaziland

Healthcare workers (HCWs) in Swaziland are at increased risk of acquiring tuberculosis (TB), but existing infection control and occupational health policies often fall short of mitigating the risk of acquiring TB in the workplace. Health service failure to systematically offer isoniazid preventive therapy (IPT) to HCWs, which is endorsed by the World Health Organisation (WHO), contributes significantly to the TB incidence among HCWs in high HIV prevalence settings. This paper describes a pilot introduction of IPT to HCWs, and expounds possible determinants for adherence and non-acceptance to IPT. Acceptance to the widespread use of IPT among HCWs can be improved through education on risk and counselling.

Assessment of isoniazid preventive therapy in the reduction of tuberculosis among ART patients in Arba Minch Hospital, Ethiopia.

BackgroundTuberculosis (TB) is the most frequent life-threatening opportunistic disease among people living with HIV and remains a leading cause of mortality, even among persons receiving antiretroviral therapy (ART). Isoniazid preventive therapy (IPT) and cotrimoxazole prophylaxis have been recommended for the benefit of HIV/AIDS-infected individuals to prevent opportunistic infections. The aim of this study was to assess IPT prophylaxis in the reduction of TB among ART patients.MethodsThe study was a hospital-based retrospective study. A total of 271 study participants’ available information such as demographic data, the type of prophylaxis used, and TB/HIV coinfection status as well as other variables were collected from clinical laboratory and HIV care/ART follow-up clinic. Data analysis was performed using Statistical Package for the Social Sciences (SPSS) version 20.0.ResultsTB-infected ART patients were higher among non-IPT group (37 [27.8%]) compared to IPT group (12 [8.7%]). The finding showed that IPT prophylaxis significantly reduces acquiring TB with the relative risk =0.31 (95% confidence interval =0.122, 0.49) in ART patients of this study site where the tuberculosis prevalence is prominent. ART had significant contribution for CD4+ T-cell lymphocyte count improvement in both IPT and non-IPT groups (P<0.05) in this study.ConclusionIPT had significant contributions to reduce the burden of TB in ART patients than non-IPT group. This result highlights the use of IPT for the prevention of TB, especially for all ART patients. Other longitudinal studies are needed to observe the benefits and side effects of IPT prophylaxis in tuberculin skin test-positive individuals.

High prevalence and low cure rate of tuberculosis among patients with HIV in Xinjiang, China

BackgroundTuberculosis and HIV co-epidemics are problems in many parts of the world. Xinjiang is a high tuberculosis and HIV prevalence area in China. We aimed to investigate the prevalence and cure rate of tuberculosis among HIV positive patients in Xinjiang.MethodsIn a retrospective study between 2006 and 2011, clinical and laboratory data on 333 patients with HIV and tuberculosis were compared to 2668 patients with HIV only. There were 31 HIV positive patients with no data on tuberculosis.ResultsThe prevalence of tuberculosis co-infection among the HIV positive patients was 11% (95% CI 10–12%), significantly higher than the national figure in China of 2%. In most cases HIV was diagnosed late, with advanced immunodeficiency. The use of isoniazid preventive therapy was only 57.9% in patients without tuberculosis who fulfilled the criteria for receiving this prevention. The cure rate one year after diagnosis was 69.2%, which was lower than the officially reported 91.4% in all tuberculosis cases in Xinjiang in 2011. The hazard of not surviving over the five years was significantly higher in patients with HIV + tuberculosis compared to HIV only after adjusting for sex and Intravenous drug use with HR = 1.84 (95% CI 1.43-2.35; p < 0.0001).ConclusionsThe prevalence of tuberculosis among HIV positive patients in Xinjiang was higher than in China taken as a whole, and HIV was diagnosed late, with underuse of isoniazid preventive therapy. The low cure rate and reduced survival can be due to late diagnosis of HIV and no testing for antibiotic resistance, together with insufficient control of adherence to the treatment regimens for tuberculosis and HIV.

Tuberculosis along the continuum of HIV care in a cohort of adolescents living with HIV in Ethiopia.

Eight health facilities in Ethiopia. To determine tuberculosis (TB) incidence rates and associated factors among adolescents living with the human immunodeficiency virus (ALHIV). This was a retrospective cohort study. Adolescents enrolled in HIV care between January 2005 and 31 December 2013 constituted the study population. The main outcome variable was TB diagnosis during follow-up. Baseline World Health Organization (WHO) clinical stage, CD4 count, previous history of TB and use of isoniazid preventive therapy (IPT) were the main independent variables. We estimated TB incidence rates as incident cases per 100 person-years of observation (PYO). Cox regression analysis was used to control for confounders. Of the 1221 adolescents screened, 1072 were studied; 60.1% were girls. TB incidence rate was 16.32 per 100 PYO during pre-antiretroviral therapy (pre-ART) follow-up but declined to 2.25 per 100 PYO after initiation of ART. Advanced WHO clinical stage (adjusted hazard ratio [aHR] 2.71, 95%CI 1.69-4.33) and CD4 count <350 cells/μl (aHR 2.28, 95%CI 1.10-4.81) predicted TB incidence in the pre-ART cohort. IPT use was associated with a significant reduction in TB incidence in the ART cohort, but not in the pre-ART group. Although TB was a significant problem in ALHIV, timely administration of ART and IPT had a significant protective effect.

Benefits of continuous isoniazid preventive therapy may outweigh resistance risks in a declining tuberculosis/HIV coepidemic.

Extending the duration of isoniazid preventive therapy (IPT) among people living with HIV (PLHIV) may improve its effectiveness at both individual and population levels, but could also increase selective pressure in favor of isoniazid-resistant tuberculosis (TB) strains. The objective of this study was to determine the relative importance of these two effects. Transmission dynamic model. We created a mathematical model of TB transmission incorporating HIV incidence and treatment, mixed strain latent TB infections, and four different phenotypes of TB drug resistance (pan-susceptible, isoniazid monoresistant, rifampicin monoresistant, and multidrug resistant). We used this model to project the effects of IPT duration on the incidence of isoniazid-sensitive and isoniazid-resistant TB as well as mortality among PLHIV. We evaluated the sensitivity of our baseline model, which was calibrated to data from Botswana, to different assumptions about the future trajectory of the TB epidemic. Our model suggests that, in the context of a declining TB epidemic such as that currently observed in Botswana, the incidence and mortality benefits of continuous IPT for PLHIV are likely to outweigh the potential resistance risks associated with long-duration IPT. However, should TB epidemics fail to remain in control, as was observed during the initial emergence of HIV, the selective pressure imposed by widespread use of continuous IPT on isoniazid-resistant TB incidence may erode its initial benefits. Resistance concerns are likely insufficient to rule out use of continuous IPT when coupled with effective TB treatment, case finding, and HIV control.

Implications of the 2015 World Health Organization isoniazid preventive therapy recommendations on tuberculosis prevention efforts in Namibia.

The World Health Organization recently released guidelines recommending 36-month use of isoniazid preventive therapy in adults and adolescents living with HIV in resource-limited settings. Namibia continues to grapple with one of the highest incidences of tuberculosis (TB) worldwide. Implementation of these guidelines requires considerations of TB epidemiology, health infrastructure, programmatic priorities and patient adherence. This article explores the challenges Namibia currently faces in its fight against TB and the implications of the new guidelines on Namibian TB prevention efforts.

Delivery of isoniazid preventive therapy to reduce occupational TB among healthcare workers in Swaziland

Healthcare workers (HCWs) in Swaziland are at increased risk of acquiring tuberculosis (TB), but existing infection control and occupational health policies often fall short of mitigating the risk of acquiring TB in the workplace. Health service failure to systematically offer isoniazid preventive therapy (IPT) to HCWs, which is endorsed by the World Health Organisation (WHO), contributes significantly to the TB incidence among HCWs in high HIV prevalence settings. This paper describes a pilot introduction of IPT to HCWs, and expounds possible determinants for adherence and non-acceptance to IPT. Acceptance to the widespread use of IPT among HCWs can be improved through education on risk and counselling.

Abandonment of Treatment for Latent Tuberculosis Infection and Socioeconomic Factors in Children and Adolescents: Rio De Janeiro, Brazil.

BackgroundRoutine data on the use of isoniazid preventive therapy (IPT) in children and adolescents are scarce in high tuberculosis (TB) burden countries.ObjectiveTo describe the factors related to abandonment of IPT in children and adolescents with latent tuberculosis infection (LTBI) receiving routine care.MethodsRetrospective (2005–2009) descriptive study of 286 LTBI cases with indication of IPT and serviced at a pediatric hospital in the State of Rio de Janeiro, Brazil. Survival analysis of the risk of abandonment of IPT over six months was performed, including multivariate analysis using the Cox proportional hazards model.ResultsOut of the 245 cases of LTBI included, 62 abandoned IPT (25.3%; 95% CI: 20%-31%). On multivariate analysis, the variables related to the IPT abandonment hazard ratio were the Human Development Index (HDI) (hazard ratio—HR: 0.004; 0.000–0.569) of the place of residence and the contact with adults that were not undergoing anti-TB treatment (HR: 7.30; 1.00–53.3).ConclusionThis study reveals the relevance of the relation of abandonment of IPT to the socioeconomic conditions at the place of residence and poor adherence to the active TB treatment. Educational measures to stimulate preventive treatment of child contacts and curative treatment of index cases should target the full familial setting.

Tuberculosis incidence is high in HIV-infected African children but is reduced by co-trimoxazole and time on antiretroviral therapy.

BackgroundThere are few data on tuberculosis (TB) incidence in HIV-infected children on antiretroviral therapy (ART). Observational studies suggest co-trimoxazole prophylaxis may prevent TB, but there are no randomized data supporting this. The ARROW trial, which enrolled HIV-infected children initiating ART in Uganda and Zimbabwe and included randomized cessation of co-trimoxazole prophylaxis, provided an opportunity to estimate the incidence of TB over time, to explore potential risk factors for TB, and to evaluate the effect of stopping co-trimoxazole prophylaxis.MethodsOf 1,206 children enrolled in ARROW, there were 969 children with no previous TB history. After 96 weeks on ART, children older than 3 years were randomized to stop or continue co-trimoxazole prophylaxis; 622 were eligible and included in the co-trimoxazole analysis. Endpoints, including TB, were adjudicated blind to randomization by an independent endpoint review committee (ERC). Crude incidence rates of TB were estimated and potential risk factors, including age, sex, center, CD4, weight, height, and initial ART strategy, were explored in multivariable Cox proportional hazards models.ResultsAfter a median of 4 years follow-up (3,632 child-years), 69 children had an ERC-confirmed TB diagnosis. The overall TB incidence was 1.9/100 child-years (95 % CI, 1.5–2.4), and was highest in the first 12 weeks following ART initiation (8.8/100 child-years (5.2–13.4) versus 1.2/100 child-years (0.8–1.6) after 52 weeks). A higher TB risk was independently associated with younger age (<3 years), female sex, lower pre-ART weight-for-age Z-score, and current CD4 percent; fewer TB diagnoses were observed in children on maintenance triple nucleoside reverse transcriptase inhibitor (NRTI) ART compared to standard non-NRTI + 2NRTI.Over the median 2 years of follow-up, there were 20 ERC-adjudicated TB cases among 622 children in the co-trimoxazole analysis: 5 in the continue arm and 15 in the stop arm (hazard ratio (stop: continue) = 3.0 (95 % CI, 1.1–8.3), P = 0.028). TB risk was also independently associated with lower current CD4 percent (P <0.001).ConclusionsTB incidence varies over time following ART initiation, and is particularly high during the first 3 months post-ART, reinforcing the importance of TB screening prior to starting ART and use of isoniazid preventive therapy once active TB is excluded. HIV-infected children continuing co-trimoxazole prophylaxis after 96 weeks of ART were diagnosed with TB less frequently, highlighting a potentially important role of co-trimoxazole in preventing TB.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-016-0593-7) contains supplementary material, which is available to authorized users.