Routine implementation of isoniazid preventive therapy in HIV-infected patients in seven pilot sites in Zimbabwe.
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ABSTRACT:
SUBMITTER: Takarinda KC
PROVIDER: S-EPMC5526481 | biostudies-other | 2017 Mar
REPOSITORIES: biostudies-other
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Project description:BACKGROUND:The safety, efficacy, and appropriate timing of isoniazid therapy to prevent tuberculosis in pregnant women with human immunodeficiency virus (HIV) infection who are receiving antiretroviral therapy are unknown. METHODS:In this multicenter, double-blind, placebo-controlled, noninferiority trial, we randomly assigned pregnant women with HIV infection to receive isoniazid preventive therapy for 28 weeks, initiated either during pregnancy (immediate group) or at week 12 after delivery (deferred group). Mothers and infants were followed through week 48 after delivery. The primary outcome was a composite of treatment-related maternal adverse events of grade 3 or higher or permanent discontinuation of the trial regimen because of toxic effects. The noninferiority margin was an upper boundary of the 95% confidence interval for the between-group difference in the rate of the primary outcome of less than 5 events per 100 person-years. RESULTS:A total of 956 women were enrolled. A primary outcome event occurred in 72 of 477 women (15.1%) in the immediate group and in 73 of 479 (15.2%) in the deferred group (incidence rate, 15.03 and 14.93 events per 100 person-years, respectively; rate difference, 0.10; 95% confidence interval [CI], -4.77 to 4.98, which met the criterion for noninferiority). Two women in the immediate group and 4 women in the deferred group died (incidence rate, 0.40 and 0.78 per 100 person-years, respectively; rate difference, -0.39; 95% CI, -1.33 to 0.56); all deaths occurred during the postpartum period, and 4 were from liver failure (2 of the women who died from liver failure had received isoniazid [1 in each group]). Tuberculosis developed in 6 women (3 in each group); the incidence rate was 0.60 per 100 person-years in the immediate group and 0.59 per 100 person-years in the deferred group (rate difference, 0.01; 95% CI, -0.94 to 0.96). There was a higher incidence in the immediate group than in the deferred group of an event included in the composite adverse pregnancy outcome (stillbirth or spontaneous abortion, low birth weight in an infant, preterm delivery, or congenital anomalies in an infant) (23.6% vs. 17.0%; difference, 6.7 percentage points; 95% CI, 0.8 to 11.9). CONCLUSIONS:The risks associated with initiation of isoniazid preventive therapy during pregnancy appeared to be greater than those associated with initiation of therapy during the postpartum period. (Funded by the National Institutes of Health; IMPAACT P1078 TB APPRISE ClinicalTrials.gov number, NCT01494038.).
| S-EPMC7051859 | biostudies-literature
Project description:BACKGROUND:The World Health Organization recommends isoniazid preventive therapy (IPT) for people living with HIV (PLHIV) to prevent tuberculosis (TB), including pregnant women. Recent trial results suggest increased adverse pregnancy outcomes associated with IPT during pregnancy. Data are limited regarding programmatic IPT use in pregnant PLHIV. METHODS:We assessed previous programmatic IPT during pregnancy among HIV-infected mothers on enrollment to an infant TB prevention trial in Kenya. Pregnancy IPT use was assessed by the estimated conception date assuming 38 weeks of gestation. Correlates of initiation and completion were analyzed by relative risk regression, using generalized linear models with log link and Poisson family adjusted for IPT initiation year. RESULTS:Between August 15, 2016, to June 6, 2018, 300 HIV-infected women enrolled at 6 weeks postpartum. Two hundred twenty-four (74.7%) women reported previous IPT, of whom 155/224 (69.2%) had any pregnancy IPT use. Forty-five (29.0%) initiated preconception extending into early pregnancy, 41 (26.5%) initiated and completed during pregnancy, and 69 (44.5%) initiated in pregnancy and extended into early postpartum. The median gestational age at IPT pregnancy initiation was 15.1 weeks (interquartile range 8.3-28.4). Pregnancy/early postpartum IPT initiation was associated with new pregnancy HIV diagnosis [adjusted relative risk 1.9 95% confidence interval (CI): 1.6 to 2.2, P < 0.001]. Six-month IPT completion rates were high [147/160 (91.9%)] among women with sufficient time to complete before trial enrollment and similar among preconception or during pregnancy initiators [adjusted relative risk 0.93 (95% confidence interval: 0.83 to 1.04, P = 0.19)]. CONCLUSIONS:Programmatic IPT use was high in pregnant PLHIV, with frequent periconception and early pregnancy initiation. Programmatic surveillance could provide further insights on pregnancy IPT implementation and maternal and infant safety outcomes.
| S-EPMC6697133 | biostudies-literature
Project description:Active tuberculosis (TB) must be excluded before initiating isoniazid preventive therapy (IPT) in persons infected with human immunodeficiency virus (HIV), but currently used screening strategies have poor sensitivity and specificity and high patient attrition rates. Liquid TB culture is now recommended for the detection of Mycobacterium tuberculosis in individuals suspected of having TB. This study compared the efficacy, effectiveness, and speed of the microscopic observation drug susceptibility (MODS) assay with currently used strategies for TB screening before IPT in HIV-infected persons.A total of 471 HIV-infected IPT candidates at 3 hospitals in Lima, Peru, were enrolled in a prospective comparison of TB screening strategies, including laboratory, clinical, and radiographic assessments.Of 435 patients who provided 2 sputum samples, M. tuberculosis was detected in 27 (6.2%) by MODS culture, 22 (5.1%) by Lowenstein-Jensen culture, and 7 (1.6%) by smear. Of patients with any positive microbiological test result, a MODS culture was positive in 96% by 14 days and 100% by 21 days. The MODS culture simultaneously detected multidrug-resistant TB in 2 patients. Screening strategies involving combinations of clinical assessment, chest radiograph, and sputum smear were less effective than 2 liquid TB cultures in accurately diagnosing and excluding TB (P<.01). Screening strategies that included nonculture tests had poor sensitivity and specificity.MODS culture identified and reliably excluded cases of pulmonary TB more accurately than other screening strategies, while providing results significantly faster than Lowenstein-Jensen culture. Streamlining of the ruling out of TB through the use of liquid culture-based strategies could help facilitate the massive up-scaling of IPT required to reduce HIV and TB morbidity and mortality.
| S-EPMC2947458 | biostudies-literature
Project description:BACKGROUND:The potential epidemiological impact of isoniazid preventive therapy (IPT), delivered at levels that could be feasibly scaled up among people living with HIV (PLHIV) in modern, moderate-burden settings, remains uncertain. METHODS:We used routine surveillance and implementation data from a cluster-randomized trial of IPT among HIV-infected clinic patients with good access to antiretroviral therapy in Rio de Janeiro, Brazil, to populate a parsimonious transmission model of tuberculosis (TB)/HIV. We modeled IPT delivery as a constant process capturing a proportion of the eligible population every year. We projected feasible reductions in TB incidence and mortality in the general population and among PLHIV specifically at the end of 5 years after implementing an IPT program. RESULTS:Data on time to IPT fit an exponential curve well, suggesting that IPT was delivered at a rate covering 20% (95% confidence interval: 16% to 24%) of the 2500 eligible individuals each year. By the end of year 5 after modeled program rollout, IPT had reduced TB incidence by 3.0% [95% uncertainty range (UR): 1.6% to 7.2%] in the general population and by 15.6% (95% UR: 15.5% to 36.5%) among PLHIV. Corresponding reductions in TB mortality were 4.0% (95% UR: 2.2% to 10.3%) and 14.3% (14.6% to 33.7%). Results were robust to wide variations in parameter values on sensitivity analysis. CONCLUSIONS:TB screening and IPT delivery can substantially reduce TB incidence and mortality among PLHIV in urban, moderate-burden settings. In such settings, IPT can be an important component of a multi-faceted strategy to feasibly reduce the burden of TB in PLHIV.
| S-EPMC4257469 | biostudies-literature
Project description:BackgroundWe model the epidemiological impact of providing isoniazid preventive therapy (IPT) to South African adolescents, among whom HIV prevalence is low, latent tuberculosis (TB) prevalence is high, and school-based programs may enable population-level coverage.MethodsWe simulate a dynamic compartmental model of age-structured HIV and TB coepidemics in South Africa. HIV dynamics are modeled by infection status, CD4 cell count, and antiretroviral therapy; TB dynamics are modeled by disease stage, diagnosis, treatment, and IPT status. We analyze the effects of continuous IPT coverage among adolescents from 5 (baseline) to 90%.ResultsOur model is calibrated to WHO and the Joint United Nations Programme on HIV/AIDS epidemiological estimates. In simulations, increasing IPT coverage to 50% among adolescents reduced active TB incidence by 5-34%. Increasing coverage to 90% led to a 9-40% reduction in active TB incidence. Expanded IPT access causes TB incidence to decline in the general population of HIV-positive individuals, as well as in adult HIV-positive individuals.ConclusionTargeting IPT to a secondary school population with high latent TB prevalence and low-HIV prevalence, in which risk of false-negative diagnosis of active TB is low and IPT benefits are more established, could have substantial benefits to adolescents and spillover benefits to the adult population.
| S-EPMC6150186 | biostudies-literature
Project description:IntroductionIsoniazid preventive therapy (IPT) taken by People Living with HIV (PLHIV) protects against active tuberculosis (TB). Despite its recommendation, data is scarce on the uptake of IPT among PLHIV and factors associated with treatment outcomes. We aimed at determining the proportion of PLHIV initiated on IPT, assessed TB screening practices during and after IPT and IPT treatment outcomes.MethodsA retrospective cohort study of a representative sample of PLHIV initiated on IPT between July 2015 and June 2018 in Kenya. For PLHIV initiated on IPT during the study period, we abstracted patient IPT uptake data from the National data warehouse. In contrast, we obtained information on socio-demographic, TB screening practices, IPT initiation, follow up, and outcomes from health facilities' patient record cards, IPT cards, and IPT registers. Further, we assessed baseline characteristics as potential correlates of developing active TB during and after treatment and IPT completion using multivariable logistic regression.ResultsFrom the data warehouse, 138,442 PLHIV were enrolled into ART during the study period and initiated 95,431 (68.9%) into IPT. We abstracted 4708 patients' files initiated on IPT, out of which 3891(82.6%) had IPT treatment outcomes documented, 4356(92.5%) had ever screened for TB at every clinic visit, and 4,243(90.1%) had documentation of TB screening on the IPT tool before IPT initiation. 3712(95.4%) of patients with documented IPT treatment outcomes completed their treatment. 42(0.89%) of the abstracted patients developed active TB,16(38.1%) during, and 26(61.9%) after completing IPT. Follow up for active TB at 6-month post-IPT completion was done for 2729(73.5%) of patients with IPT treatment outcomes. Sex, Viral load suppression, and clinic type were associated with TB development (p<0.05). Levels 4, 5, FBO, and private facilities and IPT prescription practices were associated with IPT completion (p<0.05).ConclusionIPT initiation stands at two-thirds of the PLHIV, with a high completion rate. TB screening practices were better during IPT than after completion. Development of active TB during and after IPT emphasizes the need for a keen follow up.
| S-EPMC7710039 | biostudies-literature
Project description:We assessed isoniazid preventive therapy (IPT) completion and predictors among HIV-infected children and adults in two HIV clinics in Kinshasa, Democratic Republic of Congo. Between 1 September 2012 and 15 June 2013, 546 children (1-15 years) and 1532 adults (>15 years) were initiated on IPT; 86.6% (408/470) of the children and 88.2% (1129/1280) of the adults with an IPT outcome completed their therapy. Patients on antiretroviral therapy at IPT initiation were more likely to complete IPT.
| S-EPMC4566165 | biostudies-literature
Project description:BACKGROUND:Symptom-based tuberculosis screening identifies less than one-third of eligible HIV-infected patients as candidates for isoniazid preventive therapy (IPT). We evaluated whether testing for C-reactive protein (CRP) improves patient selection for IPT. METHODS:We measured CRP levels (normal <10 mg/L) using a point-of-care (POC) assay on stored serum samples from HIV-infected Ugandan adults initiating antiretroviral therapy. We assessed diagnostic accuracy in reference to baseline tuberculosis status adjudicated by an expert committee and calculated net reclassification improvement to quantify the incremental discriminatory benefit of POC-CRP in determining IPT eligibility compared to the World Health Organization (WHO) symptom screen. RESULTS:Of 201 patients (median CD4 cell count, 137 cells/?L; interquartile range, 83-206), 5 (2.5%) had tuberculosis. Compared to the WHO symptom screen, POC-CRP had similar sensitivity (100% vs. 80%, P = 0.30) but greater specificity (21% vs. 87%, P < 0.0001) for tuberculosis. If based on the WHO symptom screen, no patients with tuberculosis but only 42 of 196 patients without tuberculosis would have been considered IPT eligible. If POC-CRP were used instead, 1 patient with tuberculosis (reclassification of cases, -20%; P = 0.32) and 129 patients without tuberculosis (reclassification of noncases, +66%; P < 0.001) would have been reclassified as IPT eligible, a net reclassification improvement of 46% (P = 0.03). In addition, POC-CRP testing would have reduced the proportion of patients without active tuberculosis requiring confirmatory tuberculosis testing (87% vs. 21%, P < 0.0001). CONCLUSIONS:POC-CRP testing increased more than 4-fold the proportion of HIV-infected adults immediately identified as IPT eligible and decreased the proportion of patients requiring referral for further tuberculosis diagnostic testing. POC-CRP testing could substantially improve implementation of tuberculosis screening guidelines.
| S-EPMC3999220 | biostudies-literature
Project description:Objectives:Early antiretroviral therapy (ART), isoniazid preventive therapy (IPT), and isoniazid-rifapentine (3HP) are effective strategies for preventing tuberculosis (TB) among people living with HIV (PLHIV). The study aimed to determine the effect of IPT on the TB incidence, follow-up CD4+ T cells, and all-cause mortality rate. Participants. Eligible patients on ART (n?=?1, 863) were categorized into one-to-two ratios of exposed groups to IPT (n?=?621) and nonexposed groups to IPT (n?=?1, 242). Exposed groups entered the cohort at their first prescription of IPT, and unexposed groups entered into the study at the first prescription of ART and then followed until the occurrence of the outcome or date of administrative censoring (June 30, 2017). The outcome endpoints were TB incidence, follow-up CD4+ T cells, and all-cause mortality rate. Results:The follow-up CD4+ T cells for the exposed and nonexposed groups were 405.74 and 366.95?cells/mm (World Health Organization (WHO), 2017), respectively, a statistically significant finding (t 1861?=?-3.770, p < 0.0001; Cohen's d?=?0.186). Nine percent of the exposed patients (620 incidence of TB per 100,000 person-years (PYs)) and 21.9% of the nonexposed patients (3160 incidence of TB per 100,000 PYs) developed TB. Mortality rate (per 100,000 PYs) was 440 for the exposed and 1490 for the unexposed patients. Statistically significant determinants of the all-cause mortality were unscheduled follow-up (AHR?=?1.601; 95% CI: 1.154-2.222) and unable to work properly (AHR?=?2.324; 95% CI: 1.643-3.288). Conclusion:This study demonstrates the effect of IPT in reducing incidence of TB and all-cause mortality rate and improving follow-up CD4+ T cells. Promoting IPT use can help to achieve the TB eradicating national agenda in Ethiopia.
| S-EPMC7204289 | biostudies-literature
Project description:SettingWorld Health Organization advocates for integration of HIV-tuberculosis (TB) services and recommends intensive case finding (ICF), isoniazid preventive therapy (IPT), and infection control ("Three I's") for TB prevention and control among persons living with HIV.ObjectiveTo assess the implementation of the "Three I's" of TB-control at HIV treatment sites in lower income countries.DesignSurvey conducted between March-July, 2012 at 47 sites in 26 countries: 6 (13%) Asia Pacific, 7 (15%), Caribbean, Central and South America, 5 (10%) Central Africa, 8 (17%) East Africa, 14 (30%) Southern Africa, and 7 (15%) West Africa.ResultsICF using symptom-based screening was performed at 38% of sites; 45% of sites used symptom-screening plus additional diagnostics. IPT at enrollment or ART initiation was implemented in only 17% of sites, with 9% of sites providing IPT to tuberculin-skin-test positive patients. Infection control measures varied: 62% of sites separated smear-positive patients, and healthcare workers used masks at 57% of sites. Only 12 (26%) sites integrated HIV-TB services. Integration was not associated with implementation of TB prevention measures except for IPT provision at enrollment (42% integrated vs. 9% non-integrated; p = 0.03).ConclusionsImplementation of TB screening, IPT provision, and infection control measures was low and variable across regional HIV treatment sites, regardless of integration status.
| S-EPMC4830552 | biostudies-literature