Analysis of efficiency of Isoniazid Preventive Therapy Programme among Human Immunodeficiency Virus-infected clients

Measures have been taken to reduce the mortality rate of Human Immunodeficiency Virusinfected clients. The use of isoniazid preventive therapy was one of those measures. Irrespective of using isoniazid preventive therapy mortality rate increased. The aim of this article is to analyse the causes and the factors that led to mortality among Human Immunodeficiency Virus-infected people who received isoniazid preventive therapy. A retrospective quantitative, explorative, descriptive isoniazid preventive therapy design was used. The records of 80 deceased patients who received isoniazid preventive therapy were reviewed through the use of a checklist. Of the records (N = 80), 75% were for female. The most highly indicated causes of death were gastroenteritis (18.75%), cryptococcal meningitis (17.5%) and pneumonia (16.25%).The causes of death of the patients who died before completing the six months of isoniazid preventive therapy; (28.75%) were gastroenteritis (21.7%), symptoms and signs of bacterial pneumonia (17.4%), cryptococcal meningitis (13%), pulmonary tuberculosis (13%), septicaemia (13%), and murder (13%). A breakdown in isoniazid preventive therapy, cotrimoxazole prophylaxis therapy and antiretroviral therapy interventions and the lack of holistic care for people living with Human Immunodeficiency Virus led to opportunistic infections leading to mortality among patients receiving isoniazid preventive therapy. A reorganisation of services of care for Human Immunodeficiency Virus-infected persons, such as provision of cotrimazole prophylaxis therapy and isoniazid preventive therapy to ensure a holistic approach to care, is recommended.Health Studie

Isoniazid Preventive Therapy Added to ART to Prevent TB: An Individual Participant Data Meta-Analysis

Background: 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. Methods: 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. Findings: 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. Interpretation: 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. Funding: National Institutes of Health and National Institute of Allergy and Infectious Diseases

Initiation and completion rates of isoniazid preventive therapy among people living with HIV in Far-Western Region of Nepal : a retrospective cohort study

Objectives: Isoniazid preventive therapy (IPT), for people living with HIV (PLHIV) is the proven and recommended intervention to avert tuberculosis (TB). In 2015, Nepal implemented 6 months of IPT for all PLHIV registered for HIV care in antiretroviral therapy (ART) centres. After programmatic implementation, there has been no systematic assessment of IPT initiation and completion rates among PLHIV. We aimed to assess IPT initiation and completion rates in the Far-Western Region (FWR) of Nepal. Design: We conducted a retrospective cohort study using secondary data extracted from registers maintained at ART centres. Setting: All 11 ART centres in the FWR of Nepal. Participants: All PLHIV registered for care between January 2016 and December 2017 in 11 ART centres. Primary outcome measures: IPT initiation and completion rates were summarised as percentages with 95% CI. Independent association between patient characteristics and non-initiation of IPT was assessed using cluster-adjusted generalised linear model (log binomial regression) and adjusted relative risk (RR) with 95% CI was calculated. Result: Of the 492 PLHIV included, 477 (97.0%) did not have active TB at registration. Among 477 without active TB, 141 (29.8%, 95% CI 25.7% to 34.1%) had been initiated on IPT and 85 (17.8%) were initiated within 3 months of registration. Of 141 initiated on IPT, 133 (94.3%, 95% CI 89.1% to 97.5%) had completed 6 months of IPT. Being more than 60 years of age (RR-1.3, 95% CI 1.1 to 1.7), migrant worker (RR-1.3, 95% CI 1.1 to 1.4) and not being initiated on ART (RR-1.4, 95% CI 1.1 to 1.8) were significantly associated with IPT initiation. Conclusions: In FWR of Nepal, three out of 10 eligible PLHIV had received IPT. Among those who have received IPT, the completion rate was good. The HIV care programme needs to explore the potential reasons for this low coverage and take context specific corrective action to fix this gap

A Trial of Early Antiretrovirals and Isoniazid Preventive Therapy in Africa

BACKGROUND: In sub-Saharan Africa, the burden of human immunodeficiency virus (HIV)-associated tuberculosis is high. We conducted a trial with a 2-by-2 factorial design to assess the benefits of early antiretroviral therapy (ART), 6-month isoniazid preventive therapy (IPT), or both among HIV-infected adults with high CD4+ cell counts in Ivory Coast. METHODS: We included participants who had HIV type 1 infection and a CD4+ count of less than 800 cells per cubic millimeter and who met no criteria for starting ART according to World Health Organization (WHO) guidelines. Participants were randomly assigned to one of four treatment groups: deferred ART (ART initiation according to WHO criteria), deferred ART plus IPT, early ART (immediate ART initiation), or early ART plus IPT. The primary end point was a composite of diseases included in the case definition of the acquired immunodeficiency syndrome (AIDS), non-AIDS-defining cancer, non-AIDS-defining invasive bacterial disease, or death from any cause at 30 months. We used Cox proportional models to compare outcomes between the deferred-ART and early-ART strategies and between the IPT and no-IPT strategies. RESULTS: A total of 2056 patients (41% with a baseline CD4+ count of ≥500 cells per cubic millimeter) were followed for 4757 patient-years. A total of 204 primary end-point events were observed (3.8 events per 100 person-years; 95% confidence interval [CI], 3.3 to 4.4), including 68 in patients with a baseline CD4+ count of at least 500 cells per cubic millimeter (3.2 events per 100 person-years; 95% CI, 2.4 to 4.0). Tuberculosis and invasive bacterial diseases accounted for 42% and 27% of primary end-point events, respectively. The risk of death or severe HIV-related illness was lower with early ART than with deferred ART (adjusted hazard ratio, 0.56; 95% CI, 0.41 to 0.76; adjusted hazard ratio among patients with a baseline CD4+ count of ≥500 cells per cubic millimeter, 0.56; 95% CI, 0.33 to 0.94) and lower with IPT than with no IPT (adjusted hazard ratio, 0.65; 95% CI, 0.48 to 0.88; adjusted hazard ratio among patients with a baseline CD4+ count of ≥500 cells per cubic millimeter, 0.61; 95% CI, 0.36 to 1.01). The 30-month probability of grade 3 or 4 adverse events did not differ significantly among the strategies. CONCLUSIONS: In this African country, immediate ART and 6 months of IPT independently led to lower rates of severe illness than did deferred ART and no IPT, both overall and among patients with CD4+ counts of at least 500 cells per cubic millimeter. (Funded by the French National Agency for Research on AIDS and Viral Hepatitis; TEMPRANO ANRS 12136 ClinicalTrials.gov number, NCT00495651.)

Integrating Community-Based Interventions to Reverse the Convergent TB/HIV Epidemics in Rural South Africa.

The WHO recommends integrating interventions to address the devastating TB/HIV co-epidemics in South Africa, yet integration has been poorly implemented and TB/HIV control efforts need strengthening. Identifying infected individuals is particularly difficult in rural settings. We used mathematical modeling to predict the impact of community-based, integrated TB/HIV case finding and additional control strategies on South Africa's TB/HIV epidemics. We developed a model incorporating TB and HIV transmission to evaluate the effectiveness of integrating TB and HIV interventions in rural South Africa over 10 years. We modeled the impact of a novel screening program that integrates case finding for TB and HIV in the community, comparing it to status quo and recommended TB/HIV control strategies, including GeneXpert, MDR-TB treatment decentralization, improved first-line TB treatment cure rate, isoniazid preventive therapy, and expanded ART. Combining recommended interventions averted 27% of expected TB cases (95% CI 18-40%) 18% HIV (95% CI 13-24%), 60% MDR-TB (95% CI 34-83%), 69% XDR-TB (95% CI 34-90%), and 16% TB/HIV deaths (95% CI 12-29). Supplementing these interventions with annual community-based TB/HIV case finding averted a further 17% of TB cases (44% total; 95% CI 31-56%), 5% HIV (23% total; 95% CI 17-29%), 8% MDR-TB (68% total; 95% CI 40-88%), 4% XDR-TB (73% total; 95% CI 38-91%), and 8% TB/HIV deaths (24% total; 95% CI 16-39%). In addition to increasing screening frequency, we found that improving TB symptom questionnaire sensitivity, second-line TB treatment delays, default before initiating TB treatment or ART, and second-line TB drug efficacy were significantly associated with even greater reductions in TB and HIV cases. TB/HIV epidemics in South Africa were most effectively curtailed by simultaneously implementing interventions that integrated community-based TB/HIV control strategies and targeted drug-resistant TB. Strengthening existing TB and HIV treatment programs is needed to further reduce disease incidence

Efficacy of secondary isoniazid preventive therapy among HIVinfected Southern Africans: time to change policy?

Objective. To determine the efficacy of secondary preventive therapy against tuberculosis (TB) among goldminers working in South Africa. Design. An observational study. Methods. The incidence of recurrent TB was compared between two cohorts of HIV-infected miners: one cohort had received secondary preventive therapy with isoniazid and the other had not. Setting. Health service providing comprehensive care for goldminers. Participants. 338 men received secondary preventive therapy and 221 did not. Main outcome measure. Incidence of recurrent TB. Results. The overall incidence of recurrent TB was reduced by 55% among men who received isoniazid preventive therapy (IPT) compared to those who did not (incidence rates 8.6 and 19.1 per 100 person-years respectively, incidence rate ratio 0.45; 95% CI 0.26 – 0.78). The efficacy of isoniazid preventive therapy was unchanged after controlling for CD4 count and age. The number of person-years of isoniazid preventive therapy required to prevent one case of recurrent TB among individuals with a CD4 count < 200/µl and &#8805;&#61472;200/µl was 5 and 19, respectively. Conclusion. Secondary preventive therapy reduces TB recurrence: the absolute impact appears to be greatest among individuals with low CD4 counts. International TB preventive therapy guidelines for HIV-infected individuals need to be expanded to include recommendations for secondary preventive therapy in settings where TB prevalence is high. Southern African Journal of HIV Medicine Vol. 5(3) 2004: 8-1

Isoniazid Preventive Therapy and Risk for Resistant Tuberculosis

Preventive therapy may increase risk for drug resistance

A trial of mass isoniazid preventive therapy for tuberculosis control.

BACKGROUND: Tuberculosis is epidemic among workers in South African gold mines. We evaluated an intervention to interrupt tuberculosis transmission by means of mass screening that was linked to treatment for active disease or latent infection. METHODS: In a cluster-randomized study, we designated 15 clusters with 78,744 miners as either intervention clusters (40,981 miners in 8 clusters) or control clusters (37,763 miners in 7 clusters). In the intervention clusters, all miners were offered tuberculosis screening. If active tuberculosis was diagnosed, they were referred for treatment; if not, they were offered 9 months of isoniazid preventive therapy. The primary outcome was the cluster-level incidence of tuberculosis during the 12 months after the intervention ended. Secondary outcomes included tuberculosis prevalence at study completion. RESULTS: In the intervention clusters, 27,126 miners (66.2%) underwent screening. Of these miners, 23,659 (87.2%) started taking isoniazid, and isoniazid was dispensed for 6 months or more to 35 to 79% of miners, depending on the cluster. The intervention did not reduce the incidence of tuberculosis, with rates of 3.02 per 100 person-years in the intervention clusters and 2.95 per 100 person-years in the control clusters (rate ratio in the intervention clusters, 1.00; 95% confidence interval [CI], 0.75 to 1.34; P=0.98; adjusted rate ratio, 0.96; 95% CI, 0.76 to 1.21; P=0.71), or the prevalence of tuberculosis (2.35% vs. 2.14%; adjusted prevalence ratio, 0.98; 95% CI, 0.65 to 1.48; P=0.90). Analysis of the direct effect of isoniazid in 10,909 miners showed a reduced incidence of tuberculosis during treatment (1.10 cases per 100 person-years among miners receiving isoniazid vs. 2.91 cases per 100 person-years among controls; adjusted rate ratio, 0.42; 95% CI, 0.20 to 0.88; P=0.03), but there was a subsequent rapid loss of protection. CONCLUSIONS: Mass screening and treatment for latent tuberculosis had no significant effect on tuberculosis control in South African gold mines, despite the successful use of isoniazid in preventing tuberculosis during treatment. (Funded by the Consortium to Respond Effectively to the AIDS TB Epidemic and others; Thibela TB Current Controlled Trials number, ISRCTN63327174.)