Effect Of Isoniazid Preventive Therapy Research Articles

Effectiveness of isoniazid preventive therapy (IPT) and risk factors for IPT failure in children below 5 years of age who are household contacts of smear positive adult patients with tuberculosis

The Journal is the primary organ of Continuing Paediatric Medical Education in Sri Lanka. The journal also has a website. Free full text access is available for all readers.The Sri Lanka Journal of Child Health is now indexed in SciVerse Scopus (Source Record ID 19900193609), Index Medicus for South-East Asia Region (IMSEAR), CABI (Centre for Agriculture and Bioscience International Global Health Database), DOAJ and is available in Google, as well as Google Scholar.The policies of the journal are modelled on the Committee on Publication Ethics (COPE) Guidelines on Principles of Transparency and Best Practice in Scholarly Publishing. Sri Lanka Journal of Child Health is recognised by the International Committee of Medical Journal Editors (ICMJE) as a publication following the ICMJE Recommendations.

Sustained effect of isoniazid preventive therapy among household contacts in Brazil.

BACKGROUND: Isoniazid preventive therapy (IPT) is highly effective in preventing TB disease; however, its long-term benefit in household contacts (HHCs) of infectious TB cases is unclear.METHODS: We conducted a retrospective analysis of two household contact studies in Vitoria, ES, Brazil, between 2008 and 2015. Households with smear-positive, culture-proven TB disease were enrolled. Eligible HHCs with tuberculin skin test (TST) indurations of ≥10 mm were referred to local TB clinics and IPT was started according to national guidelines. We reviewed the national dataset information system in January 2020 to identify HHCs with a diagnosis of TB disease. Time to event and Cox proportional regression analysis were conducted to identify factors associated with TB disease.RESULTS: Of the 1097 HHCs enrolled, 654 (60%) had TST ≥10 mm; 160 (24%) initiated IPT, of whom 115 (71.9%) completed IPT, which accounts for an overall completion rate of 18% among the population at risk; 42 (6%) TB cases were identified. IPT was associated with a 71% decrease in TB disease rates (HR 0.29, 95% CI 0.10-0.82; P = 0.02) among HHCs with TST ≥10 mm. IPT effect was sustained, as TB cases in HHCs without IPT occurred along the 7.9-year follow-up, whereas all four TB cases in HHCs with IPT were diagnosed within the first 3 years after exposureCONCLUSION: Isoniazid provides long-term protection for TB disease in household contacts of culture-proven TB cases.

Effect of Isoniazid Preventive Therapy on the Incidence of Tuberculosis among Seropositive Children Attending HIV/AIDS Care in Two General Hospitals, Northwest Ethiopia, 2021.

The human immune deficiency virus (HIV) is the strongest risk factor for the incidence of tuberculosis (TB) by way of reactivation of latent or new infection. The provision of isoniazid preventive therapy (IPT) is one of the public health interventions for the prevention of TB. To date, there have been limited clinical data regarding the effectiveness of isoniazid preventive therapy (IPT) on TB incidence. This study aimed to assess the effect of isoniazid preventive therapy on the incidence of tuberculosis for seropositive children in Northwest Ethiopia. Methods. A facility-based retrospective follow-up was employed for reviewing 421 files from 1 January 2015 up to 30 December 2019. EpiData version 3.2 and Stata/14 software were used for data entry and analysis, respectively. Categorical variables at bivariable Cox regression were assessed for candidates transferred at P value <0.25 for multivariable Cox regression to claiming predictors associated with TB incidence rate at 95% CI at P < 0.005. Result. The overall incidence of TB was found to be 4.99 cases per 100 person-years at 95% CI (3.89–6.53). Missed IPT (AHR = 7.45, 95% CI: 2.96, 18.74, P < 0.001), missed cotrimoxazole preventive therapy (CPT) (AHR = 2.4, 95% CI: 1.84–4.74, P < 0.022), age ≥ 11 years (AHR = 4.2, 95% CI: 1.04–7.03, P < 0.048), MUAC ≤ 11.5 cm (AHR = 4.36, 95% CI: 1.97–9.97, P < 0.001), WHO stages III and IV (AHR = 2.04, 95% CI: 1.12–3.74, P < 0.022), and CD4 count ≤100 cells/μl (AHR = 3.96, 95% CI: 1.52–10.34, P < 0.005) were significantly associated with TB incidence. Conclusion. Concomitant administration of ART with IPT had demoted more than ninety-six percent of new TB incidences for this report. Undertaking in-depth TB screening and frequent follow-up among all these children is critical in order to prevent and control tuberculosis.

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.

Effect of Isoniazid Preventive Therapy on Tuberculosis Prevalence among HIV Patients Attending Bahati Comprehensive Care Centre, Nairobi, Kenya

Effect of Isoniazid Preventive Therapy on Tuberculosis Prevalence among HIV Patients Attending Bahati Comprehensive Care Centre, Nairobi, Kenya

Effect of isoniazid preventive therapy on pulmonary tuberculosis activity in people living with HIV/AIDS at Wangaya hospital in Denpasar, Bali, Indonesia: a prospective cohort study

Background: Isoniazid Preventive Therapy (IPT) can reduce the Active Pulmonary Tuberculosis (APT) in People living with HIV/AIDS (PLWHA). Â IPT is recommended by the World Health Organization (WHO). It has not been implemented routinely in all countries.Aim: To evaluate whether IPT in PLWHA reduces the APT at Wangaya Hospital, in Denpasar, Bali, Indonesia.Methods: A prospective cohort study was conducted during October 2014 until November 2016. A total of 244 PLWHA were included in this study. The first group were 122 participants received antiretroviral therapy (ART) and IPT and 122 participants received only ART (second group). Cox regression analysis was employed to calculate effects in both groups and to identify predictor factors for active tuberculosis. The statistical analysis performed with cox proportional hazard model.Results: There were 137 (56.1%) males and 107 (43.9%) females. Incidence of APT in the IPT group was 1.09 per 100 person years and non IPT groups was 12.57 per 100 person years. Incidence of APT in the non IPT groups was significantly higher than in the IPT groups with crude hazard ratio (cHR) of 12.59 (95% CI: 2.70-53.43). After variables adjustment for age, sex and CD4 count, the incidence of APT in the non IPT group were found with adjustment hazard ratio (aHR) of 10.26 (95% CI: 2.15-48.99).Conclusion: Â The incidence of APT was significantly higher in the non IPT group than in the IPT group.

Safety and Effectiveness of Isoniazid Preventive Therapy in Pregnant Women Living with Human Immunodeficiency Virus on Antiretroviral Therapy: An Observational Study Using Linked Population Data.

BackgroundIsoniazid preventive therapy (IPT) is widely used to protect against tuberculosis (TB) in people living with human immunodeficiency virus (HIV). Data on the safety and efficacy of IPT in pregnant women living with HIV (PWLHIV) are mixed. We used an individual-level, population-wide health database to examine associations between antenatal IPT exposure and adverse pregnancy outcomes, maternal TB, all-cause mortality, and liver injury during pregnancy through 12 months postpartum.MethodsWe used linked routine electronic health data generated in the public sector of the Western Cape, South Africa, to define a cohort of PWLHIV on antiretroviral therapy. Pregnancy outcomes were assessed using logistic regression; for maternal outcomes we applied a proportional hazards model with time-updated IPT exposure.ResultsOf 43 971 PWLHIV, 16.6% received IPT. Women who received IPT were less likely to experience poor pregnancy outcomes (adjusted odds ratio [aOR], 0.83 [95% confidence interval {CI}, .78–.87]); this association strengthened with IPT started after the first trimester compared with none (aOR, 0.71 [95% CI, .65–.79]) or with first-trimester exposure (aOR, 0.64 [95% CI, .55–.75]). IPT reduced the risk of TB by approximately 30% (aHR, 0.71 [95% CI, .63–.81]; absolute risk difference, 1518/100 000 women). The effect was modified by CD4 cell count with protection conferred if CD4 count was ≤350 cells/μL (aHR, 0.51 [95% CI, .41–.63]) vs 0.93 [95% CI, .76–1.13] for CD4 count >350 cells/µL).ConclusionsThis analysis of programmatic data is reassuring regarding the safety of antenatal IPT, with the greatest benefits against TB disease observed in women with CD4 count ≤350 cells/μL.

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.

The protective effect of isoniazid preventive therapy on tuberculosis incidence among HIV positive patients receiving ART in Ethiopian settings: a meta-analysis

BackgroundTuberculosis (TB) and HIV makeup a deadly synergy of infectious disease, and the combined effect is apparent in resource limited countries like Ethiopia. Previous studies have demonstrated inconsistent results about the protective effect of isoniazid preventive therapy (IPT) on active TB incidence among HIV positive patients receiving ART. Therefore, the aim of this meta-analysis was, first, to determine the protective effect of IPT on active tuberculosis incidence, and second, to assess the pooled incidence of active TB among HIV positive patients taking ART with and without IPT intervention in Ethiopia.MethodsPubMed, Google scholar and Cochran library databases were searched from April 1 to 30, 2018. Two independent authors explored and assessed studies for eligibility, and extracted data based on predefined criteria. Studies that reported TB incidence among HIV positive patients taking ART in Ethiopia with and without IPT concomitant intervention, and with a clear stratified data on the incidence of TB based on the duration of IPT intervention were selected. A random effects model was used to estimate risk ratios and the pooled incident TB with the respective 95% confidence intervals.ResultsWe identified 7 suitable studies in this analysis. Accordingly, IPT reduced the risk of TB incidence by 74%, risk ratio (RR) 0.26 (95% CI; 0.16–0.43%), compared to no IPT group. Moreover, IPT for 12 months reduced incident TB by 91% (RR: 0.09, 95% CI: 0.04 to 0.21), whereas 6 months IPT averted TB incidence by 63% (RR: 0.37, 95% CI: 0.26 to 0.52). The overall pooled incident TB among HIV infected patients receiving ART was 10.30% (95% CI; 7.57–13.02%). Specifically, incident TB among study cohorts with and without IPT was 3.79% (95% CI; 2.03–5.55%) and 16.32% (95% CI; 11.57–21.06%) respectively.ConclusionIPT reduced the risk of incident TB among HIV positive patients receiving ART in Ethiopian settings. Moreover, the duration of IPT intervention has effect on its protective role. Thus, scaling up the isoniazid preventive therapy program and its strict compliance is necessary to avert HIV fueled tuberculosis.Study protocol registrationCRD42018090804.

Effect of isoniazid preventive therapy on tuberculosis incidence and associated risk factors among HIV infected adults in Tanzania: a retrospective cohort study

BackgroundTuberculosis (TB) continues to be the leading cause of morbidity and mortality among human immunodeficiency virus (HIV) infected individuals in Sub Saharan Africa including Tanzania. Provision of isoniazid preventive therapy (IPT) is one of the public health interventions to reduce the burden of TB among HIV infected persons. However there is limited information about the influence of IPT on TB incidence in Tanzania. This study aimed at ascertaining the effect of IPT on TB incidence and to determine risk factors for TB among HIV positive adults in Dar es Salaam region.MethodsA retrospective cohort study was conducted using secondary data of HIV positive adults receiving care and treatment services in Dar es Salaam region from 2011 to 2014. TB incidence rate among HIV positive adults on IPT was compared to those who were not on IPT during the follow up period. Risk factors for incident TB were estimated using multivariate Cox proportional hazards regression model.ResultsA total of 68,378 HIV positive adults were studied. The median follow up time was 3.4 (IQR = 1.9–3.8) years for patients who ever received IPT and 1.3 (IQR = 0.3–1.3) years among those who never received IPT. A total of 3124 TB cases occurred during 114,926 total person-years of follow up. The overall TB incidence rate was 2.7/100 person-years (95%CI; 2.6–2.8). Patients on IPT had 48% lower TB incidence rate compared to patients who were not on IPT (IRR = 0.52, 95%CI; 0.46–0.59). Factors associated with higher risk for incident TB included; being male (aHR = 1.8, 95% CI; 1.6–2.0), WHO stage III (aHR = 2.7, 95% CI; 2.3–3.3) and IV (aHR = 2.4, 95% CI; 1.9–3.1),being underweight (aHR = 1.7, 95% CI; 1.5–1.9) while overweight (aHR = 0.7, 95% CI; 0.6–0.8), obese (aHR = 0.5, 95% CI; 0.4–0.7), having baseline CD4 cell count between 200 and 350 cells/μl (aHR = 0.7, 95% CI; 0.6–0.8) and CD4 count above 350 cells/μl (aHR = 0.5, 95% CI; 0.4–0.6) were associated with lower risk of developing TB.ConclusionIsoniazid preventive therapy (IPT) has shown to be effective in reducing TB incidence among HIV infected adults in Dar es Salaam. More efforts are needed to increase the provision and coverage of IPT.

Programmatic review of safety and effectiveness of isoniazid preventive therapy in HIV-infected pregnant women on ART in routine care

The aim of Network Design Problem with Vulnerability Constraints (NDPVC), is to design survivable telecommunications networks that impose length bounds on the communication paths of each commodity pair, before and after the failure of any k links. This problem was proposed as an alternative to the Hop-Constrained Survivable Network Design Problem (kHSNDP), which addresses similar issues, but imposes very conservative constraints, possibly leading to unnecessarily expensive solution or even rendering instances infeasible. In fact, it is known that the cost of the optimal solutions of the NDPVC never exceeds that of the related kHSNDP. However, previous results using the standard methods of a general-purpose integer linear (ILP) solver, combined with several ILP formulations, show that such methods fail to solve most instances in the benchmarking test set, within a time limit of two hours.In this paper, we propose three branch-and-cut algorithms, which are significantly more efficient in solving the NDPVC. The first algorithm is a cutting-plane method devised in the context of a new layered graph ILP formulation, whereas the other two are based on Benders decomposition methods of previously known formulations. With the proposed new methods, we are able to solve substantially more instances of the NDPVC and therefore able to provide a more complete comparison of its solutions to those of the kHSNDP.

Effect of isoniazid preventive therapy on tuberculosis incidence in people living with HIV-AIDS at Hasan Sadikin hospital

Indonesia is the second largest number of tuberculosis (TB) in the world. Isoniazid Preventive Therapy (IPT) as one of the three I’s TB-HIV collaboration to manage TB in people living with HIV / AIDS (PLHIV) has not been fully performed. It is related to doubt to get rid of TB in PLHIV. This study aims to see the effect of IPT on the incidence of TB in PLHIV. This issue is a retrospective cohort study based on medical record data in HIV clinic. Inclusion criteria are PLHIV ≥ 15 years of age who were registered to visit the CST service and obtain IPT with good adherence if they were receiving ART. Of 462 patients, HIV- infected patients receiving IPT were 154 (33.3%). IPT administration has a protective effect on PLHIV where the rate of TB incidence in PLHIV who received IPT were 0.21 times lower than those who did not receive IPT (IRR = 0.21, 95% CI 0.023-0.881, p 0.008). In this population, IPT administration reduces 79% risk of PLHIV to suffer TB.IPT administration reduces the incidence of TB.

Effect of isoniazid preventive therapy on risk of death in west African, HIV-infected adults with high CD4 cell counts: long-term follow-up of the Temprano ANRS 12136 trial.

Temprano ANRS 12136 was a factorial 2 × 2 trial that assessed the benefits of early antiretroviral therapy (ART; ie, in patients who had not reached the CD4 cell count threshold used to recommend starting ART, as per the WHO guidelines that were the standard during the study period) and 6-month isoniazid preventive therapy (IPT) in HIV-infected adults in Côte d'Ivoire. Early ART and IPT were shown to independently reduce the risk of severe morbidity at 30 months. Here, we present the efficacy of IPT in reducing mortality from the long-term follow-up of Temprano. For Temprano, participants were randomly assigned to four groups (deferred ART, deferred ART plus IPT, early ART, or early ART plus IPT). Participants who completed the trial follow-up were invited to participate in a post-trial phase. The primary post-trial phase endpoint was death, as analysed by the intention-to-treat principle. We used Cox proportional models to compare all-cause mortality between the IPT and no IPT strategies from inclusion in Temprano to the end of the follow-up period. Between March 18, 2008, and Jan 5, 2015, 2056 patients (mean baseline CD4 count 477 cells per μL) were followed up for 9404 patient-years (Temprano 4757; post-trial phase 4647). The median follow-up time was 4·9 years (IQR 3·3-5·8). 86 deaths were recorded (Temprano 47 deaths; post-trial phase 39 deaths), of which 34 were in patients randomly assigned IPT (6-year probability 4·1%, 95% CI 2·9-5·7) and 52 were in those randomly assigned no IPT (6·9%, 5·1-9·2). The hazard ratio of death in patients who had IPT compared with those who did not have IPT was 0·63 (95% CI, 0·41 to 0·97) after adjusting for the ART strategy (early vs deferred), and 0·61 (0·39-0·94) after adjustment for the ART strategy, baseline CD4 cell count, and other key characteristics. There was no evidence for statistical interaction between IPT and ART (pinteraction=0·77) or between IPT and time (pinteraction=0·94) on mortality. In Côte d'Ivoire, where the incidence of tuberculosis was last reported as 159 per 100 000 people, 6 months of IPT has a durable protective effect in reducing mortality in HIV-infected people, even in people with high CD4 cell counts and who have started ART. National Research Agency on AIDS and Viral Hepatitis (ANRS).

Post-treatment effect of isoniazid preventive therapy on tuberculosis incidence in HIV-infected individuals on antiretroviral therapy.

In HIV-uninfected individuals, isoniazid preventive therapy (IPT) has been associated with long-term protection against tuberculosis (TB). For HIV-infected/antiretroviral therapy (ART)-naive individuals, high TB rates have been observed following completion of IPT, consistent with a lack of 'cure' of infection. Recent trial data of IPT among HIV-infected individuals on ART in Khayelitsha, South Africa, have suggested that the effect of IPT persisted following completion of IPT. Using mathematical modelling, we explored if this increased duration of protection may be due to an increased curative ability of IPT when given in combination with ART. The model was used to estimate the annual risk of infection and proportion of individuals whose latent infection was 'cured' by IPT, defined such that they must be reinfected to be at risk of disease. The estimated annual risk of infection was 4.0% (2.6-5.8) and the estimated proportion of individuals whose latent Mycobacterium tuberculosis infection was cured following IPT was 35.4% (2.4-76.4), higher than that previously estimated for HIV-infected/ART-naive individuals. Our results suggest that IPT can cure latent M. tuberculosis infection in approximately one-third of HIV-infected individuals on ART and therefore provide protection beyond the period of treatment. Among HIV-infected individuals on ART in low incidence settings, 12 months of IPT may provide additional long-term benefit. Among HIV-infected individuals on ART in high incidence settings, the durability of this protection will be limited because of continued risk of reinfection, and continuous preventive therapy together with improved infection control efforts will be required to provide long-term protection against TB.

Abstract: Effectiveness of Isoniazid Preventive Therapy on Incidence of Tuberculosis in Adult People Living with HIV in Selected Districts of Rwanda

Abstract Background Tuberculosis is a major cause of death in people living with HIV. Despite available evidence suggesting that Isoniazid Preventive Therapy (IPT) reduces the incidence of tuberculosis among people living with HIV, its implementation is low. The present study intended to establish whether Isoniazid reduced the incidence of active tuberculosis in people living with HIV. Methods This was a retrospective cohort design using medical records of 2,172 people living with HIV (PLHIV) from six health facilities in three districts of Rwanda. An SPSS version 20 statistical analysis program was used to analyze the data. Survival analysis and Poisson regression were used to compare rates and factors contributing to TB in PLHIV on IPT and those not on IPT. Results The overall TB incidence rate (IR) was 1.131 cases per 100 person-years. The IR of TB in patients on IPT was significantly lower than those who were not on IPT (0.56/100PY vs 2.04/100PY) and Incidence Rate Ratio was 0.275. Cox proportional hazard model revealed 81% reduction in TB risk among patients who received IPT. Being on anti retroviral therapy, having CD4 cell count >350, HIV clinical stage 1 and 2 and high income were factors contributing to lower IR of TB among people living with HIV on IPT. Patients on IPT lost their protection gradually but it was rapidly lost in patients not on IPT. Conclusion The use of IPT in people living with HIV was associated with a low IR of TB. The results would indicate a need to scale up the IPT to other health facilities. Key words: isoniazid preventive therapy, tuberculosis, people living with HIV, Rwanda

Effect of isoniazid preventive therapy on tuberculosis or death in persons with HIV: a retrospective cohort study.

BackgroundIsoniazid preventive therapy (IPT) is a recommended strategy for prevention of tuberculosis (TB) in persons with Human Immunodeficiency Virus (HIV) although the benefits have not been unequivocally demonstrated in routine clinical practice with widespread ART adoption. Therefore, we assessed the effectiveness of IPT in prevention of TB or death in patients treated with antiretroviral therapy (ART) in a chronic care setting.MethodsRetrospective cohort study of HIV patients enrolled in chronic care from 2007 to 2013. Eligible participants were HIV infected subjects (age > 15 years) with no (history of) TB. The combined effect of IPT and ART on the composite outcome (TB or death) was estimated using time-dependent Cox regression with adjustment for baseline covariates.Results1,922 patients were included, 374 (19.4 %) received IPT and 258 (13.4 %) developed TB or deceased. The median follow-up duration of the cohort was 839 days, with a total of 5491 person years. In unadjusted analysis, the combination of IPT and ART lowered the hazard of TB or death by 65 % [HR = 0.35; 95 % CI (0.16, 0.77)] compared to ART alone. Even after adjustment for confounders, the combined effect of ART and IPT resulted in a 60 % hazard reduction of TB or death in comparison to participants who received ART without IPT [HR = 0.40; 95 % CI (0.18, 0.87)]. The IPT-specific benefit in patients not receiving ART could not be reliably estimated due to high rates of ART adoption.ConclusionThe combined effect of IPT and ART to prevent TB or death in HIV patients in a non-experimental setting in comparison to ART alone was estimated to be 60 %.

The effect of isoniazid preventive therapy on incidence of tuberculosis among HIV-infected clients under pre-ART care, Jimma, Ethiopia: a retrospective cohort study.

BackgroundTuberculosis (TB) is a major public health problem that accounts for almost half a million human immunodeficiency virus (HIV) associated deaths. Provision of isoniazid preventive therapy (IPT) is one of the public health interventions for the prevention of TB in HIV infected individuals. However, in Ethiopia, the coverage and implementation of IPT is limited. The objective of this study is to compare the incidence rate of TB, TB-free survival time and identify factors associated with development TB among HIV-infected individuals on pre-ART follow up.MethodsA retrospective cohort study was conducted from January, 2008 to February 31, 2012 in Jimma hospital. Kaplan-Meier survival plots were used to calculate the crude effect in both groups on TB-free survival probabilities and compared using the log rank test. A Cox proportional hazard model was used to identify predictors of TB.ResultA total of 588 patients on pre-ART care (294 IPT and 294 non-IPT group) were followed retrospectively for a median duration of 24.1 months. The median CD4+ cell count was 422 cells/μl (IQR 344 – 589). During the follow up period, 49 individuals were diagnosed with tuberculosis, giving an overall incidence of 3.78 cases per 100 person year (PY). The incidence rate of TB was 5.06 per 100 PY in non-IPT group and 2.22 per 100 PY in IPT user group. Predictors of higher TB risk were: being on clinical WHO stage III/IV (adjusted hazard ratio (AHR = 3.05, 95% confidence interval (CI): 1.61, 5.81); non-IPT user (AHR = 2.02, 95% CI: 1.04, 3.92); having CD4+ cell count less than 350 cells/μl (AHR = 3.16, 95% CI: 1.04, 3.92) and between 350–499 cells/μl, (AHR = 2.87; 95% CI: 1.37 - 6.03) and having episode of opportunistic infection (OI) in the past (AHR = 2.41, 95% CI: 1.33-4.34).ConclusionIPT use was associated with fifty percent reduction in new cases of tuberculosis and probability of developing TB was higher in non-IPT group. Implementing the widespread use of IPT has the potential to reduce TB rates substantially among HIV-infected individuals in addition to other tuberculosis prevention and control effort in resource limited settings.

643The effectiveness of Isoniazid Preventive Therapy in reducing incidence of Tuberculosis among HAART receiving HIV-infected patients: A retrospective study

643The effectiveness of Isoniazid Preventive Therapy in reducing incidence of Tuberculosis among HAART receiving HIV-infected patients: A retrospective study

Beneficial effect of isoniazid preventive therapy and antiretroviral therapy on the incidence of tuberculosis in people living with HIV in Ethiopia.

BackgroundIPT with or without concomitant administration of ART is a proven intervention to prevent tuberculosis among PLHIV. However, there are few data on the routine implementation of this intervention and its effectiveness in settings with limited resources.ObjectivesTo measure the level of uptake and effectiveness of IPT in reducing tuberculosis incidence in a cohort of PLHIV enrolled into HIV care between 2007 and 2010 in five hospitals in southern Ethiopia.MethodsA retrospective cohort analysis of electronic patient database was done. The independent effects of no intervention, “IPT-only,” “IPT-before-ART,” “IPT-and-ART started simultaneously,” “ART-only,” and “IPT-after-ART” on TB incidence were measured. Cox-proportional hazards regression was used to assess association of treatment categories with TB incidence.ResultsOf 7,097 patients, 867 were excluded because they were transferred-in; a further 823 (12%) were excluded from the study because they were either identified to have TB through screening (292 patients) or were on TB treatment (531). Among the remaining 5,407 patients observed, IPT had been initiated for 39% of eligible patients. Children, male sex, advanced disease, and those in Pre-ART were less likely to be initiated on IPT. The overall TB incidence was 2.6 per 100 person-years. As compared to those with no intervention, use of “IPT-only” (aHR = 0.36, 95% CI = 0.19–0.66) and “ART-only” (aHR = 0.32, 95% CI = 0.24–0.43) were associated with significant reduction in TB incidence rate. Combining ART and IPT had a more profound effect. Starting IPT-before-ART (aHR = 0.18, 95% CI = 0.08–0.42) or simultaneously with ART (aHR = 0.20, 95% CI = 0.10–0.42) provided further reduction of TB at ∼80%.ConclusionsIPT was found to be effective in reducing TB incidence, independently and with concomitant ART, under programme conditions in resource-limited settings. The level of IPT provision and effectiveness in reducing TB was encouraging in the study setting. Scaling up and strengthening IPT service in addition to ART can have beneficial effect in reducing TB burden among PLHIV in settings with high TB/HIV burden.

Isoniazid plus antiretroviral therapy to prevent tuberculosis: a randomised double-blind, placebo-controlled trial

Antiretroviral therapy reduces the risk of tuberculosis, but tuberculosis is more common in people with HIV than in people without HIV. We aimed to assess the effect of isoniazid preventive therapy on the risk of tuberculosis in people infected with HIV-1 concurrently receiving antiretroviral therapy. For this pragmatic randomised double-blind, placebo-controlled trial in Khayelitsha, South Africa, we randomly assigned (1:1) patients to receive either isoniazid preventive therapy or a placebo for 12 months (could be completed during 15 months). Randomisation was done with random number generator software. Participants, physicians, and pharmacy staff were masked to group assignment. The primary endpoint was time to development of incident tuberculosis (definite, probable, or possible). We excluded tuberculosis at screening by sputum culture. We did a modified intention-to-treat analysis and excluded all patients randomly assigned to groups who withdrew before receiving study drug or whose baseline sputum culture results suggested prevalent tuberculosis. This study is registered with ClinicalTrials.gov, number NCT00463086. 1329 participants were randomly assigned to receive isoniazid preventive therapy (n=662) or placebo (n=667) between Jan 31, 2008, and Sept 31, 2011, and contributed 3227 person-years of follow-up to the analysis. We recorded 95 incident cases of tuberculosis; 37 were in the isoniazid preventive therapy group (2·3 per 100 person-years, 95% CI 1·6-3·1), and 58 in the placebo group (3·6 per 100 person-years, 2·8-4·7; hazard ratio [HR] 0·63, 95% CI 0·41-0·94). Study drug was discontinued because of grade 3 or 4 raised alanine transaminase concentrations in 19 of 662 individuals in the isoniazid preventive therapy group and ten of the 667 individuals in the placebo group (risk ratio 1·9, 95% CI 0·90-4·09). We noted no evidence that the effect of isoniazid preventive therapy was restricted to patients who were positive on tuberculin skin test or interferon gamma release assay (adjusted HR for patients with negative tests 0·43 [0·21-0·86] and 0·43 [0·20-0·96]; for positive tests 0·86 [0·37-2·00] and 0·55 [0·26-1·24], respectively). Without a more predictive test or a multivariate algorithm that predicts benefit, isoniazid preventive therapy should be recommended to all patients receiving antiretroviral therapy in moderate or high incidence areas irrespective of tuberculin skin test or interferon gamma release assay status. Department of Health of South Africa, the Wellcome Trust, Médecins Sans Frontières, European and Developing Countries Clinical Trials Partnership, Foundation for Innovation and New Diagnostics, the European Union, and Hasso Plattner (Institute of Infectious Diseases and Molecular Medicine, University of Cape Town).