Isoniazid Preventive Therapy Initiation Research Articles

Initiation of Isoniazid Prophylactic Therapy among Newly Diagnosed HIV-Positive Persons in Three High HIV-Burden Districts of South Africa

Background: South Africa is experiencing the worst HIV-driven tuberculosis (TB) epidemic in the world. More than 300,000 new cases of active TB are reported in the country each year with 60% co-infected with HIV. Isoniazid preventive therapy (IPT) is a key public health intervention for the prevention of TB among people living with HIV (PLHIV) and is recommended as part of a comprehensive HIV and AIDS care strategy. However, program data suggests that coverage of IPT service to be very low. This study aims to assess IPT initiation rate among newly diagnosed HIV-positive persons in three high HIV-burden districts of South Africa. Methods: A cross-sectional study was conducted using routine data generated from pre-ART and ART programs in 35 purposively selected primary health care (PHC) clinics in South Africa. The facilities were selected from three high HIV-burden districts with a mix of urban and rural settings. TB screening and IPT initiation status was assessed within a window period of one-year post HIV diagnosis. Initiation rate of IPT services among newly diagnosed HIV-positive persons was assessed. The chi-squared test was used to determine whether there was a significant difference in the proportion of newly diagnosed HIV-positive persons who were initiated on IPT by sex, age group, pregnancy status, health facility, district and location of facility. Results: We identified 12,413 newly diagnosed HIV patients aged 12-years-old and above between June 1, 2014 and March 31, 2015. TB screening was not conducted among 33% of newly diagnosed HIV-positive persons to rule out or confirm the presence of active TB. IPT was initiated in 42.2% of known IPT-eligible HIV-positive persons. Initiation of IPT services was lower in younger patients aged 12 to 20-years-old compared to older patients. The proportion of pregnant women who were initiated on IPT was higher compared to the proportion in non-pregnant women (51.0% and 40.1% respectively; P Conclusion: This analysis shows that initiation rate of IPT services among newly diagnosed HIV positive persons was low in the 35 participating facilities during the period under investigation. There was variability in IPT initiation rates across the facilities included in this study and among different sub-groups of the study sample. This study has identified specific population groups and geographic settings that should be targeted by programs to improve IPT services. There is a need to identify factors that contributed to the low initiation rate of IPT services among young HIV positive persons, women with unrecorded pregnancy status and in facilities located in inner city of Johannesburg. Customized interventions tailored to the specific needs of facilities and population groups should be instituted to strengthen uptake of IPT services.

Contact evaluation and isoniazid preventive therapy among close and household contacts of tuberculosis patients in Lima, Peru: an analysis of routine data

Contacts of pulmonary tuberculosis (TB) cases are at high risk of TB infection and progression to disease. Close and household contacts and those <5years old have the highest risk. Isoniazid preventive therapy (IPT) can largely prevent TB disease among infected individuals. International and Peruvian recommendations include TB contact investigation and IPT prescription to eligible contacts. We conducted a study in Lima, Peru, to determine the number of close and household contacts who were evaluated, started on IPT, and who completed it, and the factors associated to compliance with national guidelines. We conducted a longitudinal retrospective study including all TB cases diagnosed between January 2015 and July 2016 in 13 health facilities in south Lima. Treatment cards, TB registers and clinical files were reviewed and data on index cases (sex, age, smear status, TB treatment outcome), contact investigation (sex, age, kinship to the index case, evaluations at month 0, 2 and 6) and health facility (number of TB cases notified per year, proportion of TB cases with treatment success) were extracted. We tabulated frequencies of contact evaluation by contact and index case characteristics. To investigate determinants of IPT initiation and completion, we used generalised linear mixed models. A total of 2323 contacts were reported by 662 index cases; the median number of contacts per case was four (IQR, 2-5). Evaluation at month 0 was completed by 99.2% (255/257) of contacts <5 and 98.1% (558/569) of contacts aged 5-19years. Of 191 eligible contacts <5years old, 70.2% (134) started IPT and 31.4% (42) completed it. Of 395 contacts 5-19years old, 36.7% (145) started IPT and 32.4% (47) completed it. Factors associated to not starting IPT among contacts <5years old were being a second-degree relative to the index case (OR 6.6 95CI% 2.6-16.5), not having received a tuberculin skin test (TST) (OR 3.9 95%CI 1.4-10.8), being contact of a smear-negative index case (OR 5.5 95%CI 2.0-15.1) and attending a low-caseload health facility (OR 2.8 95%CI 1.3-6.2). Factors associated to not starting IPT among 5-19year-olds were age (OR 13.7 95%CI 5.9-32.0 for 16-19 vs. 5-7years old), being a second-degree relative (OR 3.0 95%CI 1.6-5.6), not having received a TST (OR 5.4, 95%CI 2.5-11.8), being contact of a male index case (OR 2.1 95CI% 1.2-3.5), with smear-negative TB (OR 1.9 95%CI 1.0-3.6), and attending a high-caseload health facility (OR 2.1 95%CI 1.2-3.6). Factors associated to not completing IPT, among contacts who started, were not having received a TST (OR 3.4 95%CI 1.5-7.9 for <5year-olds, and OR 4.3 95%CI 1.7-10.8 for those 5-19years old), being contact of an index case with TB treatment outcome other than success (OR 9.3 95%CI 2.6-33.8 for <5year-olds and OR 15.3 95%CI 1.9-125.8 for those 5-19years old), and, only for those 5-19years old, attending a health facility with high caseload (OR 3.2 95%CI 1.4-7.7) and a health facility with low proportion of TB cases with treatment success (OR 4.4 95%CI 1.9-10.2). We found partial compliance to TB contact investigation, and identified contact, index case and health facility-related factors associated to IPT start and completion that can guide the TB programme in increasing coverage and quality of this fundamental activity.

Improving coverage and completion rate of isoniazid preventive therapy among eligible HIV patients using quality improvement approaches: a case study of State Hospital, Ijebu Ode, Ogun State, Nigeria.

IntroductionTuberculosis (TB) is a major killer of people living with HIV. One key strategy to reduce the incidence of tuberculosis in HIV patients is the use of Isoniazid Preventive Therapy (IPT). However, coverage of IPT among eligible HIV clients is poor. This study aims to improve IPT coverage using quality improvement approaches that help identify the root cause and improve coverage of isoniazid preventive therapy.MethodsThe quality improvement (QI) project spanned over six months corresponding to three PDSA cycles. Root causes for low IPT initiation and completion in State Hospital Ijebu Ode were identified using fishbone analysis. The root causes were subjected to prioritization matrix and implementation plan was developed for the first two root causes with the highest composite matrix scores. Longitudinal data were collected over the six months period with learning session at the end of every two-month PDSA cycle. Data was analyzed using Microsoft Excel 2010 and presented in charts and tables.ResultsThe two most contributory factors to low IPT initiation and completion in the facility with prioritization matrix scores of 30 and 25 respectively were poor tracking system for IPT eligible clients and poor documentation of IPT commencement in the patients care cards and IPT registers. Findings showed improvement in both IPT initiation and completion with increase in initiation rate from 11% to above 50%, and increase in completion rate from 53% to 95.4%.ConclusionThe use of quality improvement approaches can improve coverage and completion rate of IPT among eligible HIV patients. Government and health programmers should support facilities to apply QI approaches to solving health service delivery.

Tracking the rate of initiation and retention on isoniazid preventive therapy in a high human immunodeficiency virus and tuberculosis burden setting of Lesotho.

BackgroundTuberculosis (TB) remains a public health problem, particularly in people living with human immunodeficiency virus (PLHIV). Yet, efforts to reduce TB incidence using isoniazid preventive therapy (IPT) have been curtailed by poor uptake of this intervention. This study reviewed the rate of IPT initiation in the sub-Saharan country of Lesotho, which has one of the highest TB incidences in the world.MethodsTime to IPT initiation in randomly sampled medical records of PLHIV was analysed using Cox’s proportional hazards regression. Differences in the periods of enrolment into Human immunodeficiency virus (HIV) care were controlled for by considering the year IPT was launched (2011) as the base year and stratifying the medical records into the 2004–2010 cohort (before the launch of IPT) and the 2011–2016 cohort (after the launch).ResultsOut of 2955 patients included in the final analysis, 68.8% had received IPT by the study exit time. However, the overall rate of IPT initiation was 20.6 per 100 person-years, with 135 (6.6%) treatment interruptions. Compared to the 2004–2010 cohort, the 2011–2016 had a significantly (p < 0.05) higher rate of initiation (15.8 vs. 27.0 per 100 person-years, respectively). Age group, district category and duration of antiretroviral therapy emerged as the most significant predictors of IPT initiation, while district category and gender significantly predicted IPT therapy interruption.ConclusionThese findings indicate a high uptake of IPT with a slow rate of implementation. Significant factors associated with disparities in the initiation and interruption of IPT therapy in this study are important for policy review.

Isoniazid Preventive Therapy and Pregnancy Outcomes in Women Living With Human Immunodeficiency Virus in the Tshepiso Cohort.

BackgroundBoth pregnancy and human immunodeficiency virus (HIV) increase the risk of tuberculosis disease, which results in poor maternal, pregnancy, and infant outcomes. Isoniazid preventive therapy (IPT) reduces mortality among individuals living with HIV in high-burden settings but has recently been associated with adverse pregnancy outcomes when initiated during pregnancy.MethodsIn this secondary analysis, we used multivariable logistic regression to evaluate the association between IPT exposure and adverse pregnancy outcomes (fetal demise, prematurity, low birth weight, congenital anomaly) in pregnant women living with HIV enrolled as controls in the Tshepiso study, a prospective observational cohort of pregnant women living with HIV with and without tuberculosis disease in Soweto, South Africa, from 2011–2014.ResultsThere were 151 women enrolled with known pregnancy outcomes; 69 (46%) reported IPT initiation during pregnancy. Of the 69 IPT-exposed women, 11 (16%) had an adverse pregnancy outcome compared with 23 (28%) IPT-unexposed women. The adjusted odds of having an adverse pregnancy outcome was 2.5 (95% confidence interval, 1.0–6.5; P = .048) times higher in IPT-unexposed women compared with IPT-exposed women after controlling for maternal age, CD4 count, viral load, antiretroviral regimen, body mass index, and anemia.ConclusionsIPT exposure during pregnancy was not negatively associated with pregnancy outcomes after controlling for demographic, clinical, and HIV-related factors. These results provide some reassurance that IPT can be safely used in the second or third trimester of pregnancy. Additional research is needed to evaluate the safety of IPT and new short-course tuberculosis preventive therapies during pregnancy.

Isoniazid preventive therapy: Uptake, incidence of tuberculosis and survival among people living with HIV in Bulawayo, Zimbabwe.

SettingFour primary health care clinics providing tuberculosis (TB) and Human Immunodeficiency Virus care services in Bulawayo, Zimbabwe.ObjectivesTo assess isoniazid preventive therapy (IPT) initiation and completion, factors associated with IPT uptake and incidence of TB, and TB and antiretroviral treatment (ART) outcomes among people living with HIV (PLHIV).DesignThis was a cohort study using routine data in the records for PLHIV initiated on ART from October 2013 to March 2014 with 31 December 2017 as the end of the follow-up period.ResultsA total of 408 PLHIV were eligible for IPT, 214 (52%) were initiated on IPT and 201 (94%) completed IPT. No person in the IPT-initiated group developed Tuberculosis (TB). Six persons with TB were reported among the non-IPT-initiated group leading to an incidence of 9 cases/1,000 person-years of follow-up. About 70% of those who developed and were treated for TB had a successful TB treatment outcome. The survival on ART at four years of follow-up was 88% among the IPT-initiated PLHIV that was significantly higher than the 75% survival in the group not- initiated on IPT.ConclusionThe study revealed low IPT initiation among eligible PLHIV who, if started on IPT, completed the six month regimen. TB was reported only among the PLHIV not-initiated on IPT and the four year ART survival was higher in the IPT-initiated group than in the non-initiated group. These findings reinforce the need to strengthen IPT uptake among PLHIV in Bulawayo.

Isoniazid Preventive Therapy in HIV-Infected Pregnant and Postpartum Women

BackgroundThe 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.MethodsIn 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.ResultsA 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).ConclusionsThe 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.)

Brief Report: High Programmatic Isoniazid Preventive Therapy (IPT) Use in Pregnancy Among HIV-Infected Women.

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. 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. 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)]. 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.

Prevalence And Factors Associated With Initiation Of Isoniazid Preventive Therapy Among Children Aged Below Five Years in Kisumu County

Prevalence And Factors Associated With Initiation Of Isoniazid Preventive Therapy Among Children Aged Below Five Years in Kisumu County

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.

Health system barriers to implementation of TB preventive strategies in South African primary care facilities.

BackgroundIsoniazid preventive therapy (IPT) is a key component of TB/HIV control, but few countries achieve high IPT coverage.MethodsUsing a behavioural COM-B design approach, the intervention consisted of a training on IPT guidelines and tuberculin skin testing (TST), identification of the optimal IPT implementation strategy by the health care workers (HCWs) of 3 primary care clinics, and a 2-month mentoring period. Using routine register data, TST and IPT uptake was determined 3 months before and 5 months after the intervention. Records were reviewed to identify factors associated with IPT initiation and HCW fidelity to the guidelines. A survey among HCWs was conducted to determine barriers to IPT.ResultsTwo clinics implemented TST-guided IPT for all clients receiving HIV care, one clinic decided against use of TST. According to routine register data, the proportion of clients initiating IPT increased substantially at the clinic not opting for TST (6% vs 36%), but minimally (34% vs 37% and 0.7% vs 3%) in the two other clinics. TST uptake did not increase (0 vs 0% and 0.5%). In addition to poor IPT uptake, HCW fidelity to investigation for TB and timing of IPT initiation was poor, with only 68% of symptomatic patients investigated and IPT initiation delayed to a median of 374 days post-ART initiation. In multivariate analysis, pregnancy (aOR 18.62, 95% CI 6.99–53.46), recent HIV diagnosis (aOR 3.65, 95% CI 1.73–7.41), being on ART (aOR 9.44, 95% CI 3.05–36.17), and CD4 <500 cells/mm3 (aOR 2.19, 95% CI 1.22–4.18) were associated with IPT initiation. Time needed to perform a TST, motivating patients to return for TST reading, and low IPT patient awareness were the main barriers to IPT implementation.ConclusionDespite using a behavioural intervention framework including training and participatory development of the clinic IPT strategy, HCW fidelity to the guidelines was poor, resulting in low TST coverage and low IPT uptake under primary care conditions. To achieve the benefits of IPT, health system level approaches including TST-free guidelines and sensitization are needed.

Breakthrough tuberculosis disease among people with HIV – Should we be worried? A retrospective longitudinal study

IntroductionIsoniazid preventive therapy (IPT) is a proven means to prevent tuberculosis (TB) disease among people living with HIV (PLHIV). However, there is a concern that patients often develop tuberculosis disease while receiving IPT, defined here as breakthrough tuberculosis, which may affect treatment outcome. In this study, we assessed the magnitude and determinants of breakthrough tuberculosis.MethodsA multisite retrospective longitudinal study from the year 2005 to 2014 involving 11 randomly selected hospitals from the Addis Ababa, SNNPR (Southern Nations Nationalities and Peoples Region), and Gambela regions of Ethiopia was carried out to assess the occurrence of breakthrough tuberculosis. Cox regression analysis was used to study factors associated with breakthrough TB.Results4,484 patients in chronic HIV care received IPT. Eighty percent of the same number received antiretroviral therapy (ART). Tuberculosis developed in 88 of 4,484 (2%) patients of which 24 (0.5%) were diagnosed while receiving IPT. Breakthrough TB incidence was 1106 per 100,000 person-years (PY) (95% CI: 742–1651) while TB incidence after completing IPT was 624 per 100,000 PY (95% CI: 488–797). Seven of the 24 (29%) breakthrough TB cases were diagnosed within the first month of IPT initiation. Of 15 patients who developed breakthrough TB while on ART, nine (60%) were diagnosed within the first six months of ART initiation. Having high CD4 cell count and being on ART were associated with having lower risk of developing TB and breakthrough TB.ConclusionBreakthrough TB was uncommon in the study setting. Even then, taking ART reduced the risk of its occurrence. Slightly more than a quarter of the cases of breakthrough TB occurred in the first month of treatment and may be existing undiagnosed TB cases which were missed during diagnostic work-up.

Scaling up isoniazid preventive therapy in Zimbabwe: has operational research influenced policy and practice?

Setting: Following the operational research study conducted during the isoniazid preventive therapy (IPT) pilot phase in Zimbabwe, recommendations for improvement were adopted by the national antiretroviral therapy (ART) programme. Objectives: To compare before (January 2013-June 2014) and after the recommendations (July 2014-December 2015), the extent of IPT scale-up and IPT completion rates, and after the recommendations the risk factors for IPT non-completion, in 530 ART clinics. Design: Retrospective cohort study. Results: People living with the human immunodeficiency virus newly initiating IPT increased every quarter (Q), from 585 in Q 1, 2013 to 4246 in Q 4, 2015, with 5648 new IPT initiations in the 18 months before the recommendations compared to 20 513 in the 18 months after the recommendations were made. The number of ART clinics initiating IPT increased from 10 (2%) in Q 1, 2013 to 198 (37%) in Q 4, 2015. Overall IPT completion rates were 89% in the post-recommendation period compared with 81% in the pilot phase (P < 0.001). After adjusting for confounders, being lost to follow-up from clinic review visits 1 year prior to IPT initiation was associated with a higher risk of not completing IPT, while having synchronised IPT and ART resupplies was associated with a lower risk. Conclusions: Implementation of recommendations from the initial operational research study have improved IPT scale-up in Zimbabwe.

Maternal priorities for preventive therapy among HIV-positive pregnant women before and after delivery in South Africa: abest-worst scaling survey.

IntroductionPregnant women newly diagnosed with HIV during pregnancy are often lost to follow up and their adherence rates drop after delivery. We quantified changes in priorities related to isoniazid preventive therapy (IPT) and antiretroviral therapy (ART) among pregnant women living with HIV.MethodsWe enrolled pregnant women recently diagnosed with HIV from 14 primary health clinics during pregnancy and followed them after delivery in Matlosana, South Africa. Best–worst scaling (BWS) was used to determine the women's priorities out of 11 attributes related to preventive therapy in the ante‐ versus postpartum periods. Aggregate BWS scores were calculated based on the frequency with which participants selected each attribute as the best or worst among five options (across multiple choice sets). Individual BWS scores were also calculated and rescaled from 0 (always selected as worst) to 10 (always selected as best), and changes in BWS scores in the ante‐ versus postpartum periods were compared, using a paired t‐test. Factors associated with the changes in BWS scores were examined in multiple linear regressions. Spearman's rho was used to compare the ranking of attributes.ResultsOut of a total of 204 participants, 154 (75.5%) completed the survey in the postpartum at the median 15 (IQR: 11 to 27) weeks after delivery. Trust in healthcare providers was most highly prioritized both in the ante‐ (individual BWS Score = 7.34, SE = 0.13) and postpartum periods (BWS = 7.21 ± 0.11), followed by living a long life (BWS = 6.77 ± 0.09 in the ante‐ vs. BWS = 6.86 ± 0.10 in the postpartum). Prevention for infants’ health was more prioritized in the post‐ (BWS = 6.54 ± 0.09) versus antepartum periods (BWS = 6.11 ± 0.10) (p = 0.05). This change was associated with IPT initiation at enrolment (regression coefficient = 0.78 ± 0.33, p = 0.001). Difficulty in daily pill‐uptake was significantly more prioritized in the postpartum (BWS = 5.03 ± 0.11) than in the antepartum (BWS = 4.43 ± 0.10) (p < 0.01). Transportation cost and worry about side effects of pills were least prioritized. Overall ranking of attributes was similar in both time periods (spearman's rho = 0.90).ConclusionsComprehensive interventions to build trust in healthcare providers and support adherence may increase uptake of preventive therapy. Counselling needs to emphasize medication benefits for both maternal and infant health among HIV‐positive pregnant women.

Tuberculosis Contact Screening and Isoniazid Preventive Therapy Among Children Under 5 in the Mbeya and Songwe Regions, Tanzania

The World Health Organization (WHO) recommends contact screening and initiation of isoniazid preventive therapy (IPT) for children under 5 years of age exposed to a sputum smear-positive (SS+) tuberculosis (TB) source case. We conducted this study in order to assess implementation of these recommendations in southwestern Tanzania.We conducted this cross-sectional study from June to August 2015 in 12 selected health facilities in the Mbeya and Songwe regions of Tanzania. Adult SS+ pulmonary TB patients living in the same household as children under 5 were enrolled. Structured questionnaires were used to obtain sociodemographic information and details about screening and intervention activity related to contact children under 5. Data were analysed using Stata version 11.0.We enrolled 257 index cases, who collectively had 433 contact children under 5. The median age of the index cases was 34 years (interquartile range 28 to 41) and 52.9% were male. Out of 433 contacts, 31 (7.2%) were screened for TB, of whom 7 (22.6%) were treated for presumptive TB. Among those screened, 24 were not diagnosed with TB, of whom only 8 (33.3%) received IPT.Low uptake of TB contact screening and IPT administration among eligible children under 5 was observed in this study. Health-care workers should be sensitized to screening of household contacts of adults with SS+ TB and initiate IPT in those who are eligible.

The effect of partner HIV status on motivation to take antiretroviral and isoniazid preventive therapies: a conjoint analysis

ABSTRACTAntiretroviral therapy (ART) and isoniazid preventive therapy (IPT) are important to reduce morbidity and mortality among people newly diagnosed of HIV. The successful uptake of ART and IPT requires a comprehensive understanding of patients’ motivation to take such therapies. Partners also play an important role in the decision to be initiated and retained in care. We quantified patients’ motivation to take preventive therapies (ART and IPT) and compared by partner HIV status among people newly diagnosed of HIV. We enrolled and surveyed adults (≥18 years) with a recent HIV diagnosis (<6 months) from 14 public primary care clinics in Matlosana, South Africa. Participants received eight forced-choice tasks comparing two mutually exclusive sub-sets of seven possible benefits related to preventive therapies. A linear probability model was fitted to estimate the probability of prioritizing each benefit. Tests of concordance were conducted across partner HIV status (no partner, HIV- or unknown, or HIV+). A total of 424 people completed surveys. At the time of interview, 272 (64%) were on ART and 334 (79%) had a partner or spouse. Keeping themselves healthy for their family was the most important motivator to take preventive therapies (p < 0.001). Preventing HIV transmission to partners was also highly prioritized among participants with current partners independent of partner’s HIV status (p < 0.001), but it was least prioritized among those without current partners (p = 0.72). Keeping themselves healthy was less prioritized. We demonstrate that social responsibility such as supporting family and preventing HIV transmission to partners may pose greater motivation for ART and IPT initiation and adherence compared to individual health benefits. These messages should be emphasized to provide effective patient-centered care and counseling.

Household point of care CD4 testing and isoniazid preventive therapy initiation in a household TB contact tracing programme in two districts of South Africa.

BackgroundIn South Africa, TB household contact tracing provides an opportunity for increased TB and HIV case finding. We aimed to determine the effect of two new potential interventions for TB contact tracing programmes: Point of Care CD4 (PoC CD4) on HIV linkage to care and household Isoniazid Preventive Therapy (IPT) provision on uptake and retention of IPT.MethodsA pragmatic, three-arm, cluster-randomized trial was undertaken. TB Household contacts were randomised to 3 arms: 1) Standard of Care TB and HIV testing (SOC); 2) SOC with POC CD4 for those testing HIV positive; 3) SOC with POC CD4 and IPT for eligible household members. Linkage to care within 90 days was assessed either through patient visits (at 10 weeks and 6 months) or via telephonic contact.Results2,243 index TB patients and 3,012 contacts (64,3% female, median age 30 years) were enrolled. On self-report, 26(1.2%) were currently receiving TB treatment and 1816 (60.3%) reported a prior HIV test. HIV testing uptake was 34.7% in the SoC arm, 40.2% in the PoC CD4 arm (RR1.16, CI 0.99–1.36, p-value = 0.060) and 39.9% in the PoC CD4 + HH-IPT arm (RR = 1.15, CI 0.99–1.35, p-value = 0.075). Linkage to care within 3 months was 30.8% in the SoC arm and 42.1% in the POC CD4 arms (RR 1.37; CI: 0.68–2.76, p-value = 0.382). 20/21 contacts (95.2%) initiated IPT in the PoC CD4 + HH-IPT arm, compared to 3/20 (15.0%) in the PoC CD4 arm (p = 0.004; p-value from Fisher’s exact test < 0.001). Among 3,008 contacts screened for tuberculosis, 15 (3.4%) had bacteriologically confirmed TB with an overall yield of TB of 0.5% (95% CI: 0.3%, 0.8%).ConclusionsHousehold PoC CD4 testing and IPT initiation is feasible. There was only weak evidence that PoCCD4 led to a small increase in HCT uptake and no evidence for an increase in linkage-to-care. IPT initiation and completion was increased by the household intervention. Although feasible, these interventions had low impact due to the low uptake of HIV testing in households.

Tuberculosis Contact Screening and Isoniazid Preventive Therapy Among Children Under 5 in the Mbeya and Songwe Regions, Tanzania

Introduction:The World Health Organization (WHO) recommends contact screening and initiation of isoniazid preventive therapy (IPT) for children under 5 years of age exposed to a sputum smear-positive (SS+) tuberculosis (TB) source case. We conducted this study in order to assess implementation of these recommendations in southwestern Tanzania.Methods:We conducted this cross-sectional study from June to August 2015 in 12 selected health facilities in the Mbeya and Songwe regions of Tanzania. Adult SS+ pulmonary TB patients living in the same household as children under 5 were enrolled. Structured questionnaires were used to obtain sociodemographic information and details about screening and intervention activity related to contact children under 5. Data were analysed using Stata version 11.0.Results:We enrolled 257 index cases, who collectively had 433 contact children under 5. The median age of the index cases was 34 years (interquartile range 28 to 41) and 52.9% were male. Out of 433 contacts, 31 (7.2%) were screened for TB, of whom 7 (22.6%) were treated for presumptive TB. Among those screened, 24 were not diagnosed with TB, of whom only 8 (33.3%) received IPT.Conclusion:Low uptake of TB contact screening and IPT administration among eligible children under 5 was observed in this study. Health-care workers should be sensitized to screening of household contacts of adults with SS+ TB and initiate IPT in those who are eligible.

Completion of the tuberculosis care cascade in a community-based HIV linkage-to-care study in South Africa and Uganda.

IntroductionTuberculosis (TB) is the leading cause of HIV‐associated mortality in Africa. As HIV testing, linkage to care and antiretroviral treatment initiation intensify to meet UNAIDS targets, it is not known what effect these efforts will have on TB detection and prevention. We aimed to characterize the TB care cascade of screening, diagnostic testing, treatment and provision of isoniazid preventive therapy (IPT) in a study of community‐based HIV screening and linkage to care and determine whether symptom screening results affected progress along the cascade.MethodsBetween June 2013 and March 2015, HIV‐infected adults enrolled in the Linkages study, a multi‐site, community‐based, randomized HIV screening and linkage‐to‐care study in South Africa and Uganda. All participants were screened for TB symptoms at entry after testing positive for HIV and referred to local clinics for care. During the 9 month follow‐up, participants were periodically surveyed about clinic linkage and initiation of HIV care as well as subsequent TB testing, treatment, or IPT. We compared outcomes between persons with and without a positive symptom screen at baseline using descriptive statistics and Poisson regression to calculate relative risks of outcomes along the care cascade.Results and discussionOf the 1,325 HIV‐infected adults enrolled, 26% reported at least one TB symptom at the time of HIV diagnosis. Loss of appetite and fever were the most commonly reported symptoms on a TB symptom screen. Despite 92% HIV linkage success, corresponding TB linkage was incomplete. Baseline TB symptoms were associated with an increased risk of a TB diagnosis (relative risk 3.23, 95% CI 1.51 to 6.91), but only 34% of symptomatic persons had sputum TB testing. Fifty‐five percent of participants diagnosed with TB started TB treatment. In South Africa, only 18% of asymptomatic participants initiated IPT after linkage to HIV care, and presence of symptoms was not associated with IPT initiation (relative risk 0.86 95% CI 0.6 to 1.23).Conclusions HIV linkage to care interventions provide an opportunity to improve completion of the TB care cascade, but will require additional support to realize full benefits.

Increasing isoniazid preventive therapy uptake in an HIV program in rural Papua New Guinea.

Setting: Tuberculosis (TB) is the leading cause of death among people living with the human immunodeficiency virus (PLHIV) in Papua New Guinea. Despite a policy for isoniazid preventive therapy (IPT) among PLHIV, implementation has been slow. Objective: We prospectively evaluated a standardized guided screening process, including TB diagnostic support, to increase IPT initiation in adult PLHIV on antiretro-viral treatment. Design: The guided process included a paper-based IPT screening tool that prompted review of patient history and TB symptoms and sputum analysis by smear microscopy and Xpert® MTB/RIF. Chest X-ray was performed at the provider's discretion. We quantified the yield of this guided process on IPT initiation and detection of TB and rifampicin resistance, and examined the contributions of each diagnostic modality. Results: Among 532 patients, TB was ruled out and IPT initiated in 450 (84%). TB was diagnosed and treatment was started in 82 (15%) patients. Xpert detected rifampicin resistance in one of 21 patients (5%, 95%CI 0.24-21.3) with a positive Xpert result. All TB cases were diagnosed by chest X-ray and/or Xpert. No cases were diagnosed by sputum smear alone. Conclusion: A standardized guided process, including TB diagnostic support, successfully enabled IPT initiation and identified a large burden of undetected TB.