Months Of Isoniazid Preventive Therapy Research Articles

Financial incentives for reduced alcohol use and increased isoniazid adherence during tuberculosis preventive therapy among people with HIV in Uganda: an open-label, factorial randomised controlled trial

Alcohol use is common among people with HIV and is a risk factor for tuberculosis disease and non-adherence to isoniazid preventive therapy (IPT). Few interventions exist to reduce alcohol use and increase IPT adherence in sub-Saharan Africa. The aim of this study was to test the hypothesis that financial incentives conditional on point-of-care negative urine alcohol biomarker testing and positive urine isoniazid testing would reduce alcohol use and increase isoniazid adherence, respectively, in people with HIV who have latent tuberculosis infection and hazardous alcohol use. We conducted an open-label, 2×2 factorial randomised controlled trial in Uganda. Eligible for the study were non-pregnant HIV-positive adults (aged ≥18 years) prescribed antiretroviral therapy for at least 6 months, with current heavy alcohol use confirmed by urine ethyl glucuronide (biomarker of recent alcohol use) and a positive Alcohol Use Disorders Identification Test-Consumption (AUDIT-C; ≥3 for women, ≥4 for men) for the past 3 months' drinking, no history of active tuberculosis, tuberculosis treatment, or tuberculosis preventive therapy, and a positive tuberculin skin test. We randomly assigned participants (1:1:1:1) initiating 6 months of IPT to: no incentives (group 1); or incentives for recent alcohol abstinence (group 2), isoniazid adherence (group 3), or both (group 4). Escalating incentives were contingent on monthly point-of-care urine tests negative for ethyl glucuronide (groups 2 and 4), or positive on IsoScreen (biomarker of recent isoniazid use; groups 3 and 4). The primary alcohol outcome was non-hazardous use by self-report (AUDIT-C <3 for women, <4 for men) and phosphatidylethanol (PEth; past-month alcohol biomarker) <35 ng/mL at 3 months and 6 months. The primary isoniazid adherence outcome was more than 90% bottle opening of days prescribed. We performed intention-to-treat analyses. This trial is registered with ClinicalTrials.gov (NCT03492216), and is complete. From April 16, 2018, to Aug 2, 2021, 5508 people were screened, of whom 680 were randomly assigned: 169 to group 1, 169 to group 2, 170 to group 3, and 172 to group 4. The median age of participants was 39 years (IQR 32-47), 470 (69%) were male, 598 (90%) of 663 had HIV RNA viral loads of less than 40 copies per mL, median AUDIT-C score was 6 (IQR 4-8), and median PEth was 252 ng/mL (IQR 87-579). Among 636 participants who completed the trial with alcohol use endpoint measures (group 1: 152, group 2: 159, group 3: 161, group 4: 164), non-hazardous alcohol use was more likely in the groups with incentives for alcohol abstinence (groups 2 and 4) versus no alcohol incentives (groups 1 and 3): 57 (17·6%) of 323 versus 31 (9·9%) of 313, respectively; adjusted risk difference (aRD) 7·6% (95% CI 2·7 to 12·5, p=0·0025). Among 656 participants who completed the trial with isoniazid adherence endpoint measures (group 1: 158, group 2: 163, group 3: 168, group 4: 167), incentives for isoniazid adherence did not increase adherence: 244 (72·8%) of 335 in the isoniazid incentive groups (groups 3 and 4) versus 234 (72·9%) of 321 in the no isoniazid incentive groups (groups 1 and 2); aRD -0·2% (95% CI -7·0 to 6·5, p=0·94). Overall, 53 (8%) of 680 participants discontinued isoniazid due to grade 3 or higher adverse events. There was no significant association between randomisation group and hepatotoxicity resulting in isoniazid discontinuation, after adjusting for sex and site. Escalating financial incentives contingent on recent alcohol abstinence led to significantly lower biomarker-confirmed alcohol use versus control, but incentives for recent isoniazid adherence did not lead to changes in adherence. The alcohol intervention was efficacious despite less intensive frequency of incentives and clinic visits than traditional programmes for substance use, suggesting that pragmatic modifications of contingency management for resource-limited settings can have efficacy and that further evaluation of implementation is merited. National Institute on Alcohol Abuse and Alcoholism. For the Runyankole translation of the abstract see Supplementary Materials section.

EFFECTIVENESS OF ISONIAZID PREVENTIVE THERAPY ON INCIDENCE OF TUBERCULOSIS AMONG PEOPLE LIVING WITH HIV IN SOUTHERN MAHARASHTRA

Tuberculosis being the foremost opportunistic infection associated with Human Immunodeciency Virus infection contributes to high morbidity and mortality among HIV seropositive persons. As per World Health Organisation TB statistics for 2020, and the India TB Report 2021- The incidence of TB cases including HIV in India was 193 per 100000 population, of which mortality was 32 per 100000 cases. Isoniazid Preventive Therapy reduces the reactivation of latent Tuberculosis infection and reduces the risk of acquiring TB by 70-90% among HIV co-infected individuals. WHO recommends use of ART and Isoniazid Preventive Therapy (IPT) combination to reduce the burden of TB among HIV infected patients. Considering the benets of IPT in PLHIV patients, this study was conducted over a period of 2 years from January 2020 to December 2021 in patients attending ART OPD of a tertiary care hospital in southern Maharashtra. Methods A prospective observational study was conducted on patients attending ART OPD along with General Medicine OPD at a tertiary care hospital from January 2020 to December 2021. A total of 1497 PLHIV patients were started on IPT during this period and followed up. Results 92.18% i.e. 1380 of 1497 patients completed 6 months of IPT with remaining 7.82% i.e. 117 patients not able to complete the entire 6 months due to treatment related side effects, follow up difculties or mortality. Of 1497 patients, only 2 patients (0.13%) developed Pulmonary Tuberculosis after initiation of IPT and the remaining didn't show any signs or symptoms of tuberculosis on follow up. Conclusion Results of IPT in PLHIV were highly effective with only 0.13% i.e. 2 patients developing Tuberculosis during the course of treatment with the remaining not having tuberculosis even on follow up or being reported till date. The results of the study along with other studies conducted worldwide clearly indicate the effectiveness of IPT in PLHIV and thereby its implementation should be further strengthened.

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.

Perspectives of Healthcare Professionals on Factors Limiting Implementation of Isoniazid Preventive Therapy in People Living with HIV in Eritrea: A Qualitative Study.

PurposeIn Eritrea, a 6-month isoniazid preventive therapy (IPT) was introduced in Eritrea in 2014 to prevent/reduce risk of incident tuberculosis in people living with HIV (PLHIV). The global and local uptake of IPT in newly enrolled PLHIV was reported to be low. Anecdotal reports showed that there was resistance from clinicians against its implementation. This study was therefore conducted to explore the factors that affect implementation of IPT in Eritrea from the perspectives of healthcare professionals.Materials and MethodsAn exploratory qualitative study that used a framework content analysis using inductive approach was employed. Data were collected from a sample of HIV care clinic prescribers from regional and national referral hospitals through in-depth interviews. Senior program officers were also interviewed as key informants. A conceptual framework model was developed using a root cause analysis.ResultsOverall, five themes and 13 sub-themes emerged from the in-depth interviews with healthcare professionals and key informants. Several multi-level causes/factors related to the healthcare system, HIV control program, healthcare professionals, patients and the product were identified as barriers to the implementation of IPT. Information gap on IPT and fear of isoniazid-induced liver injury were identified as the main reasons for the reluctance in administering IPT. It was observed that healthcare professionals had significant information gap that resulted in rumors and doubts on the benefits and risks of IPT, which ultimately caused reluctance on its implementation. Inadequate planning and operationalization during the introduction of IPT and inadequate laboratory setups were found to be the possible root causes for the aforementioned central problems.ConclusionThe root causes/factors for the limited implementation of IPT in Eritrea were mainly related to the HIV control program and the healthcare system. Adequate planning, operationalization and capacitation of the existing laboratory setups are recommended for a successful implementation of IPT.

Predictors of suboptimal adherence to isoniazid preventive therapy among adolescents and children living with HIV.

This study identified factors associated with adherence to a 6-month isoniazid preventive therapy (IPT) course among adolescents and children living with HIV. Forty adolescents living with HIV and 48 primary caregivers of children living with HIV completed a Likert-based survey to measure respondent opinions regarding access to care, quality of care, preferred regimens, perceived stigma, and confidence in self-efficacy. Sociodemographic data were collected and adherence measured as the average of pill counts obtained while on IPT. The rates of suboptimal adherence (< 95% adherent) were 22.5% among adolescents and 37.5% among the children of primary caregivers. Univariate logistic regression was used to model the change in the odds of suboptimal adherence. Independent factors associated with suboptimal adherence among adolescents included age, education level, the cost of coming to clinic, stigma from community members, and two variables relating to self-efficacy. Among primary caregivers, child age, concerns about stigma, and location preference for meeting a community-health worker were associated with suboptimal adherence. To determine whether these combined factors contributed different information to the prediction of suboptimal adherence, a risk score containing these predictors was constructed for each group. The risk score had an AUC of 0.87 (95% CI: 0.76, 0.99) among adolescents and an AUC of 0.76 (95% CI: 0.62, 0.90), among primary caregivers suggesting that these variables may have complementary predictive utility. The heterogeneous scope and associations of these variables in different populations suggests that interventions aiming to increase optimal adherence will need to be tailored to specific populations and multifaceted in nature. Ideally interventions should address both long-established barriers to adherence such as cost of transportation to attend clinic and more nuanced psychosocial barriers such as perceived community stigma and confidence in self-efficacy.

Pharmacokinetics and Drug-Drug Interactions of Isoniazid and Efavirenz in Pregnant Women Living With HIV in High TB Incidence Settings: Importance of Genotyping.

The World Health Organization guidelines recommend that individuals living with HIV receive ≥ 6 months of isoniazid preventive therapy, including pregnant women. Yet, plasma isoniazid exposure during pregnancy, in the antiretroviral therapy era, has not been well‐described. We investigated pregnancy‐induced and pharmacogenetic‐associated pharmacokinetic changes and drug‐drug interactions between isoniazid and efavirenz in pregnant women. Eight hundred forty‐seven women received isoniazid for 28 weeks, either during pregnancy or at 12 weeks postpartum, and 786 women received efavirenz. After adjusting for NAT2 and CYP2B6 genotype and weight, pregnancy increased isoniazid and efavirenz clearance by 26% and 15%, respectively. Isoniazid decreased efavirenz clearance by 7% in CYP2B6 normal metabolizers and 13% in slow and intermediate metabolizers. Overall, both isoniazid and efavirenz exposures were reduced during pregnancy, but the main determinants of drug concentration were NAT2 and CYP2B6 genotypes, which resulted in a five‐fold difference for both drugs between rapid and slow metabolizers.

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

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

Tuberculosis infection risk, preventive therapy care cascade and incidence of tuberculosis disease in healthcare workers at Maputo Central Hospital

BackgroundMozambican healthcare workers have high rates of latent and active tuberculosis, but occupational screening for tuberculosis is not routine in this setting. Furthermore, the specificity of tuberculin skin testing in this population compared with interferon gamma release assay testing has not been established.MethodsThis study was conducted among healthcare workers at Maputo Central Hospital, a public teaching quaternary care hospital in Mozambique. With a cross sectional study design, risk factors for tuberculosis were assessed using multivariable logistic regression. The care cascade is reported for participants who were prescribed six months of isoniazid preventive therapy for HIV or highly reactive testing for latent tuberculosis infection. The agreement of interferon-gamma release assay results with positive tuberculin skin testing was calculated.ResultsOf 690 screened healthcare workers, three (0.4%) had active tuberculosis and 426 (61.7%) had latent tuberculosis infection. Less education, age 35–49, longer hospital service, and work in the surgery department were associated with increased likelihood of being tuberculosis infected at baseline (p < 0.05). Sex, Bacillus Calmette-Guerin vaccination, HIV, outside tuberculosis contacts, and professional category were not. Three new cases of active tuberculosis developed during the follow-up period, two while on preventive therapy. Among 333 participants offered isoniazid preventive therapy, five stopped due to gastrointestinal side effects and 181 completed treatment. For HIV seropositive individuals, the agreement of interferon gamma release assay positivity with positive tuberculin skin testing was 50% among those with a quantitative skin test result of 5-10 mm, and among those with a skin test result ≥10 mm it was 87.5%. For HIV seronegative individuals, the agreement of interferon gamma release assay positivity with a tuberculin skin test result of 10-14 mm was 63.6%, and for those with a quantitative skin test result ≥15 mm it was 82.2%.ConclusionsThere is a high prevalence of tuberculosis infected healthcare workers at Maputo Central Hospital. The surgery department was most heavily affected, suggesting occupational risk. Isoniazid preventive therapy initiation was high and just over half completed therapy. An interferon gamma release assay was useful to discern LTBI from false positives among those with lower quantitative tuberculin skin test results.

Diagnosis and Management of Childhood tuberculosis in Public health Clinics in a rural Area in the Philippines: results from a Community surveillance

Background. Childhood tuberculosis (TB) remains a significant health problem worldwide despite the increase on its emphasis in national health programs.&#x0D; Objective. This study aimed to describe how TB in children is identified and managed in a routine TB program in a rural setting in a high-burden country.&#x0D; Methods. This is a prospective, community-based surveillance study in public rural clinics in the Philippines. Observations on case finding and management of TB in children as well as contact tracing in an existing TB program are described.&#x0D; Results. Out of 266 children with presumptive TB, 41 (15.4%) were cases of TB, 15 (5.6%) had latent TB infection (LTBI), 81 (30.5%) had TB exposure, and 129 (48.5%) had no TB. There were 37 (90%) TB cases who were clinically diagnosed. Ninety-three per cent (93%) of children with TB disease were cured or completed treatment. Among 25 children targeted for isoniazid preventive therapy (IPT) for LTBI and TB exposure, only 12 (52%) completed the recommended 6 months of IPT. Only 40 (43%) children aged 0 to 4 years exposed to smear-positive TB cases were screened.&#x0D; Conclusion. Barriers in the diagnosis, low IPT completion and problems in contact tracing may hinder successful implementation of TB programs for children.

Predictors of isoniazid preventive therapy completion among adults newly diagnosed with HIV in rural Malawi.

To reduce the risk of tuberculosis (TB) among individuals with human immunodeficiency virus (HIV) infection, the World Health Organization recommends at least 6 months of isoniazid preventive therapy (IPT). Completion of IPT remains a major challenge in resource-limited settings. To evaluate predictors of IPT completion in individuals newly diagnosed with HIV. Predictors of IPT completion among adults newly diagnosed with HIV in rural Malawi were evaluated using a multilevel logistic regression model. Of 974 participants who screened negative for active TB and were started on IPT, 732 (75%) completed treatment. Only one IPT-eligible individual refused treatment. Participants who were aged <25 years (compared with those aged 45 years, adjusted OR [aOR] 0.33, 95%CI 0.18-0.60) and male (compared to non-pregnant females, aOR 0.57, 95%CI 0.37-0.88) had lower odds of IPT completion. IPT provision at the time of initial HIV diagnosis was highly acceptable in rural Malawi; three quarters of those who initiated IPT successfully completed therapy. We observed lower odds of completion among males and among female participants aged <25 years. Additional efforts may be needed to ensure IPT completion among males and young females who have recently been diagnosed with HIV.

Isoniazid Preventive Therapy for People With HIV Who Are Heavy Alcohol Drinkers in High TB-/HIV-Burden Countries: A Risk-Benefit Analysis.

Isoniazid preventive therapy (IPT) reduces mortality among people living with HIV (PLHIV) and is recommended for those without active tuberculosis (TB) symptoms. Heavy alcohol use, however, is contraindicated for liver toxicity concerns. We evaluated the risks and benefits of IPT at antiretroviral therapy (ART) initiation to ART alone for PLHIV who are heavy drinkers in 3 high TB-/HIV-burden countries. We developed a Markov simulation model to compare ART alone to ART with either 6 or 36 months of IPT for heavy drinking PLHIV enrolling in care in Brazil, India, and Uganda. Outcomes included nonfatal toxicity, fatal toxicity, life expectancy, TB cases, and TB death. In this simulation, 6 months of IPT + ART (IPT6) extended life expectancy over both ART alone and 36 months of IPT + ART (IPT36) in India and Uganda, but ART alone dominated in Brazil in 51.5% of simulations. Toxicity occurred in 160/1000 persons on IPT6 and 415/1000 persons on IPT36, with fatal toxicity in 8/1000 on IPT6 and 21/1000 on IPT36. Sensitivity analyses favored IPT6 in India and Uganda with high toxicity thresholds. The benefits of IPT for heavy drinkers outweighed its risks in India and Uganda when given for a 6-month course. The toxicity/efficacy trade-off was less in Brazil where TB incidence is lower. IPT6 resulted in fatal toxicity in 8/1000 people, whereas even higher toxicities of IPT36 negated its benefits in all countries. Data to better characterize IPT toxicity among HIV-infected drinkers are needed to improve guidance.

Screening for active tuberculosis before isoniazid preventive therapy among HIV-infected West African adults.

TEMPRANO was a multicentre, open-label trial in which human immunodeficiency virus (HIV) infected adults with high CD4 counts were randomised into early or deferred antiretroviral therapy (ART) arms with or without 6-month isoniazid preventive therapy (IPT) in a setting where the World Health Organization (WHO) recommends IPT in HIV-infected patients. Despite the WHO recommendation, IPT coverage remains low due to fear of the presence of undiagnosed active TB before prescribing IPT, and the related risk of drug resistance. To report the frequency of undiagnosed TB in patients enrolled for IPT and describe the results of a 1-month buffer period to avoid prescribing IPT for active TB cases. Patients were screened using a clinical algorithm and chest X-ray at Day 0 and started on isoniazid at Month 1 if no sign/symptom suggestive of TB appeared between Day 0 and Month 1. Of 1030 patients randomised into IPT arms. 10% never started IPT at Month 1. Of these, 23 had active TB, including 16 with prevalent TB. Among the 927 patients who started IPT, 6 had active TB, including 1 with prevalent TB. Only 1 patient with active TB received IPT due to the 1-month buffer period between Day 0 and IPT initiation. In this study, 1.6% of adults considered free of active TB based on clinical screening at pre-inclusion actually had active 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).

Implementing an isoniazid preventive therapy program for people living with HIV in Thailand.

Treatment of people living with HIV (PLHIV) with latent tuberculosis (TB) infection using isoniazid preventive therapy (IPT) can reduce the risk of TB disease, however, the scale-up of IPT among PLHIV in Thailand and worldwide has been slow. To hasten the implementation of IPT in Thailand, we developed IPT implementation training curricula and tools for health care providers and implemented IPT services in seven large government hospitals. Of the 659 PLHIV enrolled, 272 (41.3%) reported symptoms of TB and 39 (14.3% of those with TB symptoms) were diagnosed with TB. A total of 346 (52.4%) participants were eligible for IPT; 318 (91.9%) of these participants opted to have a tuberculin skin test (TST) and 52 (16.3% of those who had a TST) had a positive TST result. Among the 52 participants with a positive TST, 46 (88.5%) initiated and 39 (75.0%) completed 9 months of IPT: physicians instructed three participants to stop IPT, two participants were lost to follow-up, one chose to stop therapy, and one developed TB. IPT can be implemented among PLHIV in Thailand and could reduce the burden of TB in the country.

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.

Costs of providing tuberculosis diagnosis and treatment services in Viet Nam.

To estimate the cost of providing tuberculosis (TB) diagnosis and treatment packages at different levels of health facilities in Viet Nam. This was a retrospective costing study from the providers' perspective using a standard costing approach. We included typical services for TB diagnosis and treatment based on standard protocols. The least expensive TB service was the 6-month isoniazid preventive therapy regimen for latent tuberculous infection provided by district health centres (US$7.20-14.30, accounting for 0.3-0.7% of Viet Nam's per capita gross domestic product [GDP] of US$2052.30 in 2014). The cost of diagnosing and treating a patient with drug-susceptible TB (the most common type of TB) ranged between US$51.20 and US$180.70, and represented 2.5-8.8% of Viet Nam's per capita GDP in 2014. The most expensive TB service was the diagnosis and treatment of a multidrug-resistant TB case (US$1568.20-2391.20), accounting for 76.4-116.5% of Viet Nam's per capita GDP in 2014). The cost of TB diagnosis and treatment services in Viet Nam varied according to level of health facility, type of TB, different costing options, and different staff cost scenarios.

Routine implementation of isoniazid preventive therapy in HIV-infected patients in seven pilot sites in Zimbabwe.

Setting: Seven pilot sites in Zimbabwe implementing 6 months of isoniazid preventive therapy (IPT) for people living with the human immunodeficiency virus (PLHIV). Objectives: To determine, among PLHIV started on IPT, the completion rates for a 6-month course of IPT and factors associated with non-adherence. Design: A retrospective cohort study. Results: Of 578 patients, 466 (81%) completed IPT. Of the 112 patients who failed to complete IPT, 69 (60%) were lost to follow-up, 30 (27%) stopped treatment with no documented reasons, 8 (7%) developed toxicity/adverse reactions, 5 (5%) were documented as having drug stock-outs and the remainder transferred out or refused to continue treatment. Currently being on antiretroviral therapy (ART) (aOR 0.09, 95%CI 0.03-0.28) and receiving a ⩾2 month supply of isoniazid at the start of treatment were associated with a lower risk of not completing IPT, while missing clinic visits prior to starting IPT (aOR 5.25, 95%CI 2.10-13.14) was associated with a higher risk of non-completion. Conclusion: IPT completion rates in seven pilot sites of Zimbabwe were comparatively high, showing that IPT roll-out in public health facilities is feasible. Enhanced adherence counselling or active tracing among pre-ART patients and those with a history of loss to follow-up may improve IPT completion rates, along with synchronising IPT and ART resupplies.

A mixed-methods evaluation of adherence to preventive treatment among child tuberculosis contacts in Indonesia.

Tuberculosis (TB) can be prevented using isoniazid preventive therapy (IPT) among child contacts. However, the benefits of IPT depend on adherence to at least 6 months of daily treatment. A greater understanding of the barriers to and facilitators of adherence to IPT in resource-poor settings is required to optimise the benefits. We prospectively evaluated adherence to IPT and its associated factors among child contacts (age 0-5 years) eligible for IPT. We undertook in-depth interviews with care givers and a focus group discussion with health care workers, which were thematically analysed to explore barriers to and facilitators of adherence from the perspective of both care givers and health workers. Of 99 eligible children, 49 (49.5%) did not complete 6 months of IPT. Children whose care giver collected their IPT medications from primary health centres were more likely to have incomplete adherence than those who collected them from hospitals (aOR 2.9, 95%CI 1.1-7.8). Thematic analyses revealed major barriers to and facilitators of adherence: regimen-related, care giver-related and health care-related factors, social support and access. Many of these factors are readily modifiable. Providing information about IPT and improving accessibility for care givers to receive IPT at the primary health care facility should be priorities to facilitate implementation.

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.

Outcome of Isoniazid Preventive Therapy in Adults Living with HIV in Penang, Malaysia

Isoniazid preventive therapy (IPT) is a recommended strategy by World Health Organization (WHO) for prevention of active TB infection in people living with HIV. However, data on feasibility and outcome of IPT in Asia are limited. We conducted a retrospective study of 242 HIV patients in Penang who were commenced on IPT between 2011 and 2014, at two HIV specialist clinics in Penang General Hospital and Seberang Jaya Hospital. We evaluated the outcome of IPT in terms of completion rate, adverse events and incidence of active TB. A total of 193 (81.1%) patients completed 6 months of IPT. Patients receiving concurrent highly active antiretroviral therapy (HAART) had significantly higher IPT completion rate (86.1%) compared to those who were not on HAART (67.7%). Major reasons for non-completion were adverse events (21/45) and defaulting from follow-up (17/45). Forty patients (18%) developed adverse events, including hepatotoxicity (8.56%) and rash (5.41%). The risk factors for hepatotoxicity were Hepatitis B/C co-infection and alanine transaminase above the upper limit of normal at baseline. None of our patients who received IPT developed active TB up to 1 year of follow-up. IPT is feasible and relatively safe. Coadministration of IPT with HAART does not compromise safety or compliance.