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

SETTING: 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. OBJECTIVE: To evaluate predictors of IPT completion in individuals newly diagnosed with HIV. DESIGN: Predictors of IPT completion among adults newly diagnosed with HIV in rural Malawi were evaluated using a multilevel logistic regression model. RESULTS: 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. CONCLUSION: 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

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

SETTING: 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. OBJECTIVE: To evaluate predictors of IPT completion in individuals newly diagnosed with HIV. DESIGN: Predictors of IPT completion among adults newly diagnosed with HIV in rural Malawi were evaluated using a multilevel logistic regression model. RESULTS: 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. CONCLUSION: 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

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

Evaluating the Impact of Strategies for Tuberculosis Prevention and Control in High-Burden, Low-Resource Settings: Data for Evidence-Based Decision-Making in Local Contexts

Background: While incidence rates of tuberculosis (TB) are on the decline globally, the TB burden in sub-Saharan Africa and Southeast Asia remains high. If the goal of reducing the global TB incidence rate to < 10/100,000 population per year is to be achieved by 2035, additional TB control interventions will need to be deployed in high burden settings. Research is needed to identify effective, efficient interventions that prevent additional TB cases, identify and properly diagnose incident cases, as well as to provide timely, appropriate treatment and ensure treatment completion. We sought to evaluate several TB control interventions as implemented in local contexts, including a household contact tracing in rural South Africa, a cost-effectiveness analysis of interferon-γ release assays (IGRAs) in India, and predictors of isoniazid preventive therapy (IPT) completion in rural Malawi. This research aims to provide data for policy-makers and government officials tasked with the deployment of scarce TB control resources in local contexts, with the goal of identifying strategies to integrate TB case finding and prevention activities into programs with limited resources. Methods: We recruited 130 newly diagnosed TB patients (“index cases”) from public clinics in Vhembe District, Limpopo Province, South Africa, and visited their homes to test their household contacts for TB via sputum smear microscopy and culture. Clinical and demographic characteristics, including HIV status, were assessed via self-report. We calculated the yield of previously undiagnosed TB disease among household contacts (defined as the number of new TB cases identified for every 100 index cases traced) and evaluated risk factors for TB disease among household contacts using multilevel logistic regression. Next we evaluated the incremental cost-effectiveness of IGRAs compared to a base-case scenario of empirical diagnosis (without microbiological testing), as well as sputum smear microscopy and Xpert MTB/RIF. We performed our analysis from the perspective of the Indian TB Control Program, and evaluated the cost, disability-adjusted life years, deaths, and secondary cases averted, and false positive diagnoses resulting from the use of these diagnostics in a hypothetical cohort of 1 million adult Indian TB suspects. We performed one-way sensitivity analyses, as well as a probabilistic sensitivity analysis to generate uncertainty ranges around our estimates. Finally we evaluated factors associated with IPT completion in a cohort of 974 newly diagnosed adult HIV patients in Malawi who were started on IPT after active TB disease was excluded. Participants were recruited as part of a larger cluster randomized trial of TB screening being conducted in 12 clinics across rural Malawi. IPT completion was defined as receipt of ≥150 doses of isoniazid during routine clinical visits. We assessed factors associated with IPT completion using a multilevel logistic regression model adjusted for patient clinical and demographic characteristics. Results: A total of 282 household contacts were enrolled in our household contact tracing study between December 1, 2013 and September 30, 2014. A total of 11 individuals tested positive for TB disease, for a household TB disease prevalence of 3.9% (95% CI: 2.0-6.9%) and a yield of 8.5 cases per 100 index cases traced (95% CI: 4.2-15.1). The majority of TB cases identified by the study (10/11, 90.9%) were smear-negative/culture-positive. The presence of TB symptoms was not significantly associated with increased odds of active TB disease in our population (aOR: 0.3, 95% CI: 0.1-1.4). Our cost-effectiveness analysis found that IGRAs were less cost-effective than sputum smear microscopy or Xpert MTB/RIF when diagnosing active TB in India. This was largely due to the poor specificity of IGRAs for active TB in a setting with high background rates of latent TB infection. Relative to sputum smear microscopy, IGRAs resulted in 315,700 (95% uncertainty range [UR]: 118,300 – 388,400) false-positive TB diagnoses, at an incremental cost of US$49.3 million (95$34.9 - $58.0 million) per 1 million population tested. Relative to Xpert MTB/RIF (including the cost of treating drug resistant TB), IGRAs averted 70,400 (95$14.6 million (95% UR: [-$7.2] -$28.7 million) more. In Malawi, 732 of the 974 (75%) individuals who started IPT completed their course of therapy. Individuals completing IPT were significantly older than non-completers (34 vs. 31, p2 months (7.1% vs. 80%, p=0.01). After controlling for potential confounders, participants younger than 25 years (compared to those over 45 years, aOR: 0.33, 95% CI: 0.18-0.60) and males (compared to non-pregnant women, aOR: 0.57, 95% CI: 0.37-0.88) had significantly lower odds of IPT completion. Concomitant receipt of ART drugs, being a current or former smoker, and self-reported alcohol use were not significantly associated with IPT completion in our study. Discussion: Identification of effective and cost-effective interventions operationalizing case finding and prevention of TB will be vital in controlling TB and meeting ambitious global targets by 2035, especially in high-burden settings. We evaluated potential prevention and case-finding interventions in local settings, providing data useful to TB control programs and governments in sub-Saharan Africa and Southeast Asia, where high TB burdens and scarce resources present substantial challenges to meeting global TB control targets

Access and adherence to isoniazid preventive therapy and occurrence of active TB in a cohort of people living with HIV: a retrospective cohort study in Sao Paulo, Brazil

Tuberculosis (TB) is still a leading cause of morbidity and mortality among people living with HIV (PLHIV). The diagnosis of latent TB is required for the implementation of prophylactic therapy with isoniazid (PTI). However, low access to diagnosis of latent TB and non-adherence to PTI may hinder potential benefits of this essential intervention. In this study, we addressed the access and adherence to PTI in a cohort of PLHIV with positive tuberculin skin test (TST) in a reference HIV clinic in Sao Paulo, Brazil. We have also analyzed the occurrence of active TB over a median of 131 months after a positive TST among study participants. Our findings revealed that 88.3% of the 238 TST-positive patients had access to PTI, and 196 (93.3%) of those with access adhered to PTI. Active tuberculosis was diagnosed in three of the 196 TST-positive patients who adhered to PTI (1.5%; 95% confidence interval [CI] 0.3-4.4%), whereas seven cases were detected among 42 patients without access or who did not adhere to PTI (16.6%; 95% CI 7.0-31.3%). The apparent beneficial effect of PTI in our cohort is consistent with previous studies including PLHIV, and highlights the importance of reliably delivering each of the steps between screening for latent TB and provision of PTI

Survival of HIV-1 vertically infected children

PURPOSE OF REVIEW: It is 20 years since the start of the combination antiretroviral therapy (cART) era and more than 10 years since cART scale-up began in resource-limited settings. We examined survival of vertically HIV-infected infants and children in the cART era. RECENT FINDINGS: Good survival has been achieved on cART in all settings with up to 10-fold mortality reductions compared with before cART availability. Although mortality risk remains high in the first few months after cART initiation in young children with severe disease, it drops rapidly thereafter even for those who started with advanced disease, and longer term mortality risk is low. However, suboptimal retention on cART in routine programs threatens good survival outcomes and even on treatment children continue to experience high comorbidity risk; infections remain the major cause of death. Interventions to address infection risk include a cotrimoxazole prophylaxis, isoniazid preventive therapy, routine childhood and influenza immunization, and improving maternal survival. SUMMARY: Pediatric survival has improved substantially with cART and HIV-infected children are aging into adulthood. It is important to ensure access to diagnosis and early cART, good program retention as well as optimal comorbidity prophylaxis and treatment to achieve the best possible long-term survival and health outcomes for vertically infected children

Isoniazid preventive therapy uptake among people living with HIV and enrolled in care in Butebo district, Uganda

Background: Tuberculosis (TB) remains a major public health problem worldwide, especially in developing countries. Despite clear evidence that isoniazid preventive therapy (IPT) can reduce the risk of TB disease among PLHIV, uptake of IPT is low in many resource-limited settings with high TB-burden. Therefore, this study was carried out to determine the level of IPT uptake and its associated factors amongst PLHIV who do not have active TB disease. Methodology: This was a retrospective quantitative study amongst newly diagnosed PLHIV who do not have active TB in the FY 2019/20 and enrolled for ART in HIV/TB Clinics in Butebo district in Uganda. Demographic factors (age, sex, religion, marital status, employment status, education level, area of residence, household density), health facility factors (pre-IPT counselling), community factors (distance from H/C, incurred costs to reach H/C), and IPT drug related factors (IPT adherence, default on IPT, frequency of INH refill, INH stockouts) data were collected from 4 selected health facilities using questionnaire tool. Descriptive statistics was used to generate frequency cross tables. Results: A total of 272 eligible cases were included in the study amongst which 93 (34.2%) achieved IPT uptake. Mean duration (years) between HIV diagnosis and start of IPT was 4.31 (SD ±3.782). IPT Uptake among males 34 (37%) and females 59 (32.8%). Modal age group for IPT Uptakes was 20-35 years. 7 (70%) of the employed took up IPT compared to 86 (32.8%) of the employed. IPT uptake was highest among the married 62 (39.5%). Majority of the uptake cases were Christians of which 75 (35.4%) started IPT. Other factors which affected the rate of IPT Uptake include Education level, residence status, household density, Incurrence of costs to reach H/C, Distance from H/C, and Pre-IPT counselling. IPT completion was 91 (97.8%). All cases with good adherence to IPT adherence completed treatment 84 (100%) compared to 7 (77.8%) among those with poor adherence. Of the cases who defaulted on IPT 4 (66.7%) completed IPT while 87 (100%) of those who did not default completed. All the cases 88 (100%) who had regular INH refill completed IPT compared to 3 (60%) with irregular refill. 91 (97.8%) did not experience INH stock outs and completed IPT. Conclusion: This study showed that IPT Uptake was very low at 34.2%. IPT uptake may be scaled up by addressing the factors affecting IPT Uptake, as well as integrating IPT services in routine HIV care, enhancing supervision and monitoring, simplifying screening procedures, providing free screening, training of health workers, and improving logistical supplies at the health centers. The shortcomings need to be discussed at all levels of management from the Health Center, the District and centrally at the Ministry of Health Tuberculosis Control Program.open석

Burden of disease and risk factors for death among children treated for tuberculosis in Malawi

Tuberculosis is a leading cause of childhood death. There is limited patient-level data on pediatric TB in Malawi that can be used to guide programmatic interventions

Isoniazid preventive therapy-related adverse events among Malawian adults on antiretroviral therapy: A cohort study.

Adverse events may be a cause of observed poor completion of isoniazid preventive therapy (IPT) among people living with HIV in high tuberculosis burden areas. Data on IPT-related adverse events (AE) from sub-Saharan Africa are scarce. We report IPT-related AEs, associated clinical characteristics, and IPT discontinuations in adults who were stable on antiretroviral therapy (ART) when they initiated IPT. Cohort study nested within a randomized, controlled, clinical trial of cotrimoxazole and chloroquine prophylaxis in Malawians aged ≥ 18 years and virologically suppressed on ART. Eight hundred sixty-nine patients were followed for a median of 6 months after IPT initiation. IPT relatedness of AEs was determined retrospectively with the World Health Organization case-causality tool. Frailty survival regression modeling identified factors associated with time to first probably IPT-related AE. The overall IPT-related AE incidence rate was 1.1/person year of observation. IPT relatedness was mostly uncertain and few AEs were severe. Most common were liver and hematological toxicities. Higher age increased risk of a probably IPT-related AE (aHR = 1.02; 95% CI 1.00-1.06; P = .06) and higher weight reduced this risk (aHR = 0.98; 95% CI 0.96-1.00; P = .03). Of 869 patients, 114 (13%) discontinued IPT and 94/114 (82%) discontinuations occurred at the time of a possibly or probably IPT-related AE. We observed a high incidence of mostly mild IPT-related AEs among individuals who were stable on ART. More than 1 in 8 persons discontinued IPT. These findings inform strategies to improve implementation of IPT in adults on ART, including close monitoring of groups at higher risk of IPT-related AEs

Early experiences with Isoniazid Preventive Therapy roll-out in an ART programme : a pharmacist's perspective.

Masters Degree. University of KwaZulu-Natal, Durban.Tuberculosis (TB) remains the leading cause of mortality amongst people infected with Human Immunodeficiency Virus (HIV). Additionally, TB recurrence after successful treatment completion occurs more frequently amongst HIV positive people. Isoniazid provided as part of isoniazid preventive therapy (IPT) has been the gold standard of TB preventive therapy provision for the last few decades. IPT has been recommended by the World Health Organisation (WHO) and implemented by national health programmes in countries across the world. Despite global efforts and campaigns to promote IPT, uptake still remains a challenge and, progress in the operational scale- up of IPT is slow. Both international and in-country guidelines have advanced to recommending the use of IPT in HIV infected patients who have previously been treated for TB because these patients remain at risk for recurrent TB especially in TB endemic settings. However, there still remains a paucity in data on the successful programmatic use of IPT secondary to previous cured TB among HIV infected patients and is the focus of the current analysis from a pharmacists’ perspective. Methods: A retrospective secondary analysis was conducted from October 2009 to October 2013, amongst HIV infected patients, previously treated for TB, accessing HIV care at the urban CAPRISA clinical research clinic in Durban, South Africa. The aim of the study was to evaluate the implementation of Isoniazid Preventive Therapy (IPT) within the parent study titled “TB recurrence upon treatment with HAART” (TRuTH). Data was collected on IPT uptake, course completion, drug toxicity, treatment interruption, and the occurrence of incident TB either during treatment or post IPT completion. The multidisciplinary team approach in providing IPT to at risk HIV infected patients, including the specific role of the pharmacist, was also assessed. Results: There were 402 patients enrolled in the parent study. Of these 344 (85.6%) were eligible to receive IPT and of whom 212 (61.6%) initiated IPT. Among those that commenced IPT, 184 (86.8%) completed the six-month course, 24 (11.3%) permanently discontinued IPT and of these, 3.8% discontinued due to side effects. More women (n=130; 61.3%) were initiated on IPT (p=0.001) than men. Overall median adherence to IPT was 97.6% (IQR: 94.2 - 99.4). There were 22 cases of incident TB in this cohort: 13 occurred prior to IPT and nine after IPT (incidence rate ratio 0.67; 95% CI 0.29- 1.58; p=0.362). CONCLUSIONS: Overall, we demonstrated a successful IPT roll-out in a high TB endemic setting with good uptake of IPT, minimal course interruptions or side effects reported. IPT is a safe and tolerable TB prevention intervention within ART programmes and importantly amongst patients on ART with previous TB treatment experience. The pharmacist played an important role in continuum of care in IPT provision within an ART programme. This role included ensuring stable supply chain management, supporting clinic staff in monitoring safe IPT use and provided data on IPT course completion rate