BackgroundIPT with or without concomitant administration of ART is a proven intervention to prevent tuberculosis among PLHIV. However, there are few data on the routine implementation of this intervention and its effectiveness in settings with limited resources.ObjectivesTo measure the level of uptake and effectiveness of IPT in reducing tuberculosis incidence in a cohort of PLHIV enrolled into HIV care between 2007 and 2010 in five hospitals in southern Ethiopia.MethodsA retrospective cohort analysis of electronic patient database was done. The independent effects of no intervention, “IPT-only,” “IPT-before-ART,” “IPT-and-ART started simultaneously,” “ART-only,” and “IPT-after-ART” on TB incidence were measured. Cox-proportional hazards regression was used to assess association of treatment categories with TB incidence.ResultsOf 7,097 patients, 867 were excluded because they were transferred-in; a further 823 (12%) were excluded from the study because they were either identified to have TB through screening (292 patients) or were on TB treatment (531). Among the remaining 5,407 patients observed, IPT had been initiated for 39% of eligible patients. Children, male sex, advanced disease, and those in Pre-ART were less likely to be initiated on IPT. The overall TB incidence was 2.6 per 100 person-years. As compared to those with no intervention, use of “IPT-only” (aHR = 0.36, 95% CI = 0.19–0.66) and “ART-only” (aHR = 0.32, 95% CI = 0.24–0.43) were associated with significant reduction in TB incidence rate. Combining ART and IPT had a more profound effect. Starting IPT-before-ART (aHR = 0.18, 95% CI = 0.08–0.42) or simultaneously with ART (aHR = 0.20, 95% CI = 0.10–0.42) provided further reduction of TB at ∼80%.ConclusionsIPT was found to be effective in reducing TB incidence, independently and with concomitant ART, under programme conditions in resource-limited settings. The level of IPT provision and effectiveness in reducing TB was encouraging in the study setting. Scaling up and strengthening IPT service in addition to ART can have beneficial effect in reducing TB burden among PLHIV in settings with high TB/HIV burden.

Immunological monitoring is part of the standard of care for patients on antiretroviral treatment. Yet, little is known about the routine implementation of immunological laboratory monitoring and utilization in clinical care in Ethiopia. This study assessed the pattern of immunological monitoring, immunological response, level of immunological treatment failure and factors related to it among patients on antiretroviral therapy in selected hospitals in southern Ethiopia. A retrospective longitudinal analytic study was conducted using documents of patients started on antiretroviral therapy. Adequacy of timely immunological monitoring was assessed every six months the first year and every one year thereafter. Immunological response was assessed every six months at cohort level. Immunological failure was based on the criteria: fall of follow-up CD4 cell count to baseline (or below), or CD4 levels persisting below 100 cells/mm3, or 50% fall from on-treatment peak value. A total of 1,321 documents of patients reviewed revealed timely immunological monitoring were inadequate. There was adequate immunological response, with pediatric patients, females, those with less advanced illness (baseline WHO Stage I or II) and those with higher baseline CD4 cell count found to have better immunological recovery. Thirty-nine patients (3%) were not evaluated for immunological failure because they had frequent treatment interruption. Despite overall adequate immunological response at group level, the prevalence of those who ever experienced immunological failure was 17.6% (n=226), while after subsequent re-evaluation it dropped to 11.5% (n=147). Having WHO Stage III/IV of the disease or a higher CD4 cell count at baseline was identified as a risk for immunological failure. Few patients with confirmed failure were switched to second line therapy. These findings highlight the magnitude of the problem of immunological failure and the gap in management. Prioritizing care for high risk patients may help in effective utilization of meager resources.

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BackgroundAchieving optimal adherence to highly active antiretroviral therapy (HAART) is necessary to attain viral suppression and hence optimal clinical outcome. Interruptions in antiretroviral therapy medication often occur, but a substantial proportion restart treatment. Long-term care engagement practices and clinical outcomes have not been described among cohorts of individuals on HAART in Ethiopia.MethodsIn this study we describe treatment interruption patterns over time among clients who interrupt and subsequently resume HAART, and those who are continuously engaged in treatment, and determine clinical factors associated with loss to engagement.An observational, longitudinal, retrospective cohort design was engaged, using secondary treatment program data. We analyzed differences in treatment interruption among clients who were continuously active and those that interrupted and restarted treatment at months 6, 12, 18, and 24. Cox proportional hazards regression analysis was used to identify predictors of loss from treatment. We estimated time to first treatment interruption, time to restarting after interruption, and time to second interruption. Data from all clients registered to receive HAART in ten study health facilities, from 2005 to 2014, were used to study clinical and treatment outcomes up to 60 months or study end.ResultsIn this study, 39% (8,759/22,647) of clients interrupted treatment for more than 1 month at least at one point during follow-up. Of these, only 35% ever restarted treatment. At the end of follow-up, the hazard of unfavorable treatment outcome (dead, lost, stopped HAART) for clients who restarted treatment at months 6, 12, 18 and 24 was higher by a factor of 1.9, 2.4, 2.6 and 2.4, as compared to those who never discontinued treatment at those times.ConclusionHAART treatment interruption was common in the study population. In those with a history of treatment interruption, long term clinical outcomes were found to be suboptimal. Targeted interventions are required to address follow-up challenges and prevent treatment interruption.Electronic supplementary materialThe online version of this article (doi:10.1186/s12913-017-2172-9) contains supplementary material, which is available to authorized users.

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.

Background Household Contacts (HHCs) of patients with pulmonary tuberculosis (PTB) have a higher risk of developing TB. Contact investigation is recommended to reach this group and identify undiagnosed cases. In this study, we have determined the yield of contact investigation among HHCs of patients with smear-positive PTB, and estimated TB burden. Methods We conducted retrospective record review for the occurrence of TB among HHCs of Index PTB+ cases treated between November 2010 and April 2013 in 12 public health facilities in Boricha district. HHCs were followed up monthly and revisited between March and June 2015. Information on additional TB cases diagnosed and treated among HHCs were documented. HHCs who were diagnosed as having TB after the index cases were diagnosed and treated were considered as ‘incident cases’. Presumptive TB case was defined as those having cough for ≥2 weeks or enlarged lymph node. Diagnosis of TB among HHCs were made using smear-microscopy and/or X-rays, and clinically for Extra-pulmonary TB (EPTB). Results One thousand five hundred and seventeenth HHCs of 344 index cases were visited and screened for TB and followed up for a median of 37 months. 77 (5.1% - 72 with PTB and 5 with EPTB) HHCs developed TB during 4713 person-years of follow-up with an estimated incidence of 1634 (95% CI: 1370-2043) per 100,000 person-years follow-up which is much higher than the estimated TB incidence for the general population in Ethiopia of 210/100,000. Half (41/77) of incident TB cases were diagnosed within the first year of diagnosis of the index cases and 88% (68/77) were adults (Hazard Ratio: 4.03; 95% CI: 2.00–8.12). Conclusion HHCs of index PTB+ cases have high risk of developing active TB. Long term follow-up of HHCs could help improve TB case finding depending on country contexts. Further studies on effectiveness and feasibility of the approach and integration in routine settings are needed.

Background There are a number of risk factors being used to identify undiagnosed HIV infected adults. As the number of undiagnosed people gets lesser and lesser, it is important to know if existing risk factors and risk assessment tools are valid for use. In this study, we validate existing HIV risk assessment tools and see if they are worth using for HIV case finding among adults who remain undiagnosed. Methods The Tanzania and Zambia Population-Based HIV Impact Assessment (PHIA) household surveys were conducted during 2016. We used adult interview and HIV datasets to assess validity of different HIV risk assessment tools. We first included 12 risk factors (being divorced, separated or widowed (DSW); having an HIV+ spouse; having one of the following within 12 months of the survey: paid work, slept away from home for at least a month, had multiple sexual partners, paid for sex, had sexually transmitted infection (STI), being a tuberculosis (TB) suspect, being very sick for at least 3 months; had ever sold sex; diagnosed with cervical cancer; and had TB disease into a risk assessment tool and assessed its validity by comparing it against HIV test result. Sensitivity, specificity and predictive value of the tool were assessed against the HIV test result. A receiver operator characteristic (ROC) analysis was conducted to determine a suitable cut-off score in order to have a tool with better sensitivity, specificity, and PPV. ROC comparison statistics was used to statistically test equality between AUC (area under the curve) of the different scores. ROC comparison statistics was also used to determine which risk assessment tool was better compared to the tool that contained all risk factors. Results Of 14,820 study participants, 57.8% were men, and had a median age of 30 (IQR: 21-24). HIV prevalence was 2.3% (95% confidence interval (CI): 2.0-2.6). For the tool containing all risk factors, HIV prevalence was 1.0% when none of the risk factors were positive (Score 0) compared to 3.2% when at least one factor (Score ≥1) was present and 8.0% when ≥4 risk factors were present. Sensitivity, specificity, PPV, and NPV were 82.3% (78.6%-85.9%), 41.9% (41.1%-42.7%), 3.2% (2.8%-3.6%), and 99.0% (98.8%-99.3%), respectively. The use of a tool containing conventional risk factors (all except those related with working and sleeping away) was found to have higher AUC compared to the use of all risk factors (p value <0.001), with corresponding sensitivity, specificity, PPV, and NPV of 63.5% (58.9%-68.1%), 66.2% (65.5%-67.0%), 4.2% (3.6%-4.8%), and 98.7% (98.5%-98.9%), respectively. Conclusion Use of a screening tool containing conventional risk factors improved HIV testing yield compared to doing universal testing. Prioritizing people who fulfil multiple risk factors should be explored further to improve HIV testing yield.

BackgroundThere are a number of risk factors being used to identify undiagnosed HIV infected adults. As the number of undiagnosed people gets lesser and lesser, it is important to know if existing risk factors and risk assessment tools are valid for use. In this study, we validate existing HIV risk assessment tools and see if they are worth using for HIV case finding among adults who remain undiagnosed. Methods The Tanzania and Zambia Population-Based HIV Impact Assessment (PHIA) household surveys were conducted during 2016. We used adult interview and HIV datasets to assess validity of different HIV risk assessment tools. We first included 12 risk factors (being divorced, separated or widowed (DSW); having an HIV+ spouse; having one of the following within 12 months of the survey: paid work, slept away from home for at least a month, had multiple sexual partners, paid for sex, had sexually transmitted infection (STI), being a tuberculosis (TB) suspect, being very sick for at least 3 months; had ever sold sex; diagnosed with cervical cancer; and had TB disease into a risk assessment tool and assessed its validity by comparing it against HIV test result. Sensitivity, specificity and predictive value of the tool were assessed against the HIV test result. A receiver operator characteristic (ROC) analysis was conducted to determine a suitable cut-off score in order to have a tool with better sensitivity, specificity, and PPV. ROC comparison statistics was used to statistically test equality between AUC (area under the curve) of the different scores. ROC comparison statistics was also used to determine which risk assessment tool was better compared to the tool that contained all risk factors. Results Of 14,820 study participants, 57.8% were men, and had a median age of 30 (IQR: 21-24). HIV prevalence was 2.3% (95% confidence interval (CI): 2.0-2.6). For the tool containing all risk factors, HIV prevalence was 1.0% when none of the risk factors were positive (Score 0) compared to 3.2% when at least one factor (Score ≥1) was present and 8.0% when ≥4 risk factors were present. Sensitivity, specificity, PPV, and NPV were 82.3% (78.6%-85.9%), 41.9% (41.1%-42.7%), 3.2% (2.8%-3.6%), and 99.0% (98.8%-99.3%), respectively. The use of a tool containing conventional risk factors (all except those related with working and sleeping away) was found to have higher AUC compared to the use of all risk factors (p value <0.001), with corresponding sensitivity, specificity, PPV, and NPV of 63.5% (58.9%-68.1%), 66.2% (65.5%-67.0%), 4.2% (3.6%-4.8%), and 98.7% (98.5%-98.9%), respectively. Conclusion Use of a screening tool containing conventional risk factors improved HIV testing yield compared to doing universal testing. Prioritizing people who fulfil multiple risk factors should be explored further to improve HIV testing yield.