Baseline Xpert MTB/RIF ct values predict sputum conversion during the intensive phase of anti-TB treatment in HIV infected patients in Kampala, Uganda: a retrospective study

Abstract Background In resource-limited settings, sputum smear conversion is used to document treatment response. Many People living with HIV (PLHIV) are smear-negative at baseline. The Xpert MTB/RIF test can indirectly measure bacterial load through cycle threshold (ct) values. This study aimed to determine if baseline Xpert MTB/RIF could predict time to culture negativity in PLHIV with newly diagnosed TB. Methods A subset of 138 PLHIV from the ‘SOUTH’ study on outcomes related to TB and antiretroviral drug concentrations were included. Bacterial load was estimated by Mycobacterium Growth Indicator Tubes (MGIT) culture time-to-positivity (TTP) and Lowenstein Jensen (LJ) colony counts. Changes in TTP and colony counts were analyzed with Poisson Generalised Estimating Equations (GEE) and multilevel ordered logistic regression models, respectively, while time to culture negativity analysed with Cox proportional hazard models. ROC curves were used to explore the accuracy of the ct value in predicting culture negativity. Results A total of 81 patients (58.7%) were males, median age 34 (IQR 29 ̶ 40) years, median CD4 cell count of 180 (IQR 68 ̶ 345) cells/μL and 77.5% were ART naive. The median baseline ct value was 25.1 (IQR 21.0 ̶ 30.1). A unit Increase in the ct value was associated with a 5% (IRR = 1.05 95% CI 1.04 ̶ 1.06) and 3% (IRR = 1.03 95% CI 1.03 ̶ 1.04) increase in TTP at week 2 and 4 respectively. With LJ culture, a patient’s colony grade was reduced by 0.86 times (0R = 0.86 95% CI 0.74 ̶ 0.97) at week 2 and 0.84 times (OR = 0.84 95% CI 0.79 ̶ 0.95 P = 0.002) at week 4 for every unit increase in the baseline ct value. There was a 3% higher likelihood of earlier conversion to negativity for every unit increase in the ct value. A ct cut point ≥28 best predicted culture negativity at week 4 with a sensitivity of 91. 7% & specificity 53.7% while a cut point ≥23 best predicted culture negativity at week 8. Conclusion Baseline Xpert MTB/RIF ct values predict sputum conversion in PLHIV on anti-TB treatment. Surrogate biomarkers for sputum conversion in PLHIV are still a research priority.

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Cohort profile of a study on outcomes related to tuberculosis and antiretroviral drug concentrations in Uganda: design, methods and patient characteristics of the SOUTH study

BMJ Open ◽

10.1136/bmjopen-2016-014679 ◽

2017 ◽

Vol 7 (9) ◽

pp. e014679 ◽

Cited By ~ 5

Author(s):

Christine Sekaggya-Wiltshire ◽

Barbara Castelnuovo ◽

Amrei von Braun ◽

Joseph Musaazi ◽

Daniel Muller ◽

...

Keyword(s):

Treatment Outcomes ◽

Patient Characteristics ◽

Sub Saharan Africa ◽

Pharmacokinetic Analysis ◽

People Living With Hiv ◽

Cd4 Cell Count ◽

Pulmonary Tb ◽

Tb Treatment ◽

Drug Concentrations ◽

Sub Saharan

PurposeTuberculosis (TB) is a leading cause of death among people living with HIV in sub-Saharan Africa. Several factors influence the efficacy of TB treatment by leading to suboptimal drug concentrations and subsequently affecting treatment outcome. The aim of this cohort is to determine the association between anti-TB drug concentrations and TB treatment outcomes.ParticipantsPatients diagnosed with new pulmonary TB at the integrated TB-HIV outpatient clinic in Kampala, Uganda, were enrolled into the study and started on first-line anti-TB treatment.Findings to dateBetween April 2013 and April 2015, the cohort enrolled 268 patients coinfected with TB/HIV ; 57.8% are male with a median age of 34 years (IQR 29–40). The median time between the diagnosis of HIV and the diagnosis of TB is 2 months (IQR 0–22.5). The majority of the patients are antiretroviral therapy naive (75.4%). Our population is severely immunosuppressed with a median CD4 cell count at enrolment of 163 cells/µL (IQR 46–298). Ninety-nine per cent of the patients had a diagnosis of pulmonary TB confirmed by sputum microscopy, Xpert/RIF or culture and 203 (75.7%) have completed TB treatment with 5099 aliquots of blood collected for pharmacokinetic analysis.Future plansThis cohort provides a large database of well-characterised patients coinfected with TB/HIV which will facilitate the description of the association between serum drug concentrations and TB treatment outcomes as well as provide a research platform for future substudies including evaluation of virological outcomes.Trial registration numberNCT01782950; Pre-results.

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Risk Factors for Unfavorable Treatment Outcomes among the Human Immunodeficiency Virus-Associated Tuberculosis Population in Tashkent City, Uzbekistan: 2013–2017

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18094623 ◽

2021 ◽

Vol 18 (9) ◽

pp. 4623

Author(s):

Sherali Massavirov ◽

Kristina Akopyan ◽

Fazlkhan Abdugapparov ◽

Ana Ciobanu ◽

Arax Hovhanessyan ◽

...

Keyword(s):

Risk Factors ◽

Human Immunodeficiency Virus ◽

Treatment Outcomes ◽

Sputum Smear ◽

People Living With Hiv ◽

Tb Treatment ◽

Cell Counts ◽

Cd4 Cell Counts ◽

Immunodeficiency Virus ◽

Positive Sputum Smear

Tuberculosis (TB) and human immunodeficiency virus (HIV) co-infection poses a growing clinical challenge. People living with HIV have a higher chance of developing TB, and once the disease has progressed, are at greater risk of having unfavorable TB treatment outcomes. Data on TB treatment outcomes among the HIV-associated TB population in Uzbekistan are limited. Thus, we conducted a cohort study among 808 adult patients with HIV-associated TB registered at the Tashkent TB referral hospital from 2013–2017 to document baseline characteristics and evaluate risk factors for unfavorable TB treatment outcomes. The data were collected from medical records and ambulatory cards. About 79.8% of the study population had favorable treatment outcomes. Antiretroviral therapy (ART) coverage at the admission was 26.9%. Information on CD4-cell counts and viral loads were largely missing. Having extrapulmonary TB (aOR 2.21, 95% CI: 1.38–3.53, p = 0.001), positive sputum smear laboratory results on admission (aOR 1.62, 95% CI: 1.07–2.40), diabetes (aOR 5.16, 95% CI: 1.77–14.98), and hepatitis C (aOR 1.68, 95% CI: 1.14–2.46) were independent risk factors for developing unfavorable TB treatment outcomes. The study findings provide evidence for targeted clinical management in co-infected patients with risk factors. Strengthening the integration of TB/HIV services may improve availability of key data to improve co-infection management.

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The Prevalence of Absolute and Functional Iron Deficiency Anemia in New Cases of Smear-positive Pulmonary Tuberculosis and Their Sputum Conversion Rate at the End of Intensive Tuberculosis Treatment Phase

Prague Medical Report ◽

10.14712/23362936.2020.3 ◽

2020 ◽

Vol 121 (1) ◽

pp. 35-41

Author(s):

Maliheh Metanat ◽

Mohammad Ali Mashhadi ◽

Roya Alavi-Naini ◽

Leli Rezaie-Kahkhaie ◽

Nahid Sepehri-Rad ◽

...

Keyword(s):

Iron Deficiency ◽

Iron Deficiency Anemia ◽

Treatment Phase ◽

Deficiency Anemia ◽

Sputum Smear ◽

Tb Treatment ◽

Significant Difference ◽

Smear Positive Pulmonary Tuberculosis ◽

Sputum Conversion ◽

Positive Sputum Smear

About one third of the population is infected with tuberculosis (TB). On the other hand, iron deficiency is the most common micronutrient deficiency in the world. A number of studies have documented anemia in patients with TB, however, this study aimed to assess the prevalence of iron deficiency anemia (IDA) in patients with acid-fast bacilli (AFB) sputum smear-positive, and sputum conversion in these two groups of patients with absolute and functional IDA at the end of the second month of anti-TB therapy in Zahedan, Iran. The results of this study revealed that 91 out of 198 (45.9%) sputum positive pulmonary TB patients were anemic, and among those 72 (79.1%) had iron deficiency anemia. The overall prevalence of IDA in this study was 36.3%. In 72 patients with IDA, 54 (75%) had functional while the remainder had absolute IDA 18 (25%). Twenty-one out of 72 (29.2%) of patients with IDA remained sputum positive and among 126 non IDA patients 47 (37.3%) had positive sputum smear at the end of intensive TB treatment phase (p=0.278). Approximately, less than half of patients with tuberculosis had anemia among them 79% had iron deficiency anemia. The frequency of functional IDA was three times more than absolute IDA. There was no statistically significant difference in sputum conversion between two groups of IDA and non-IDA patients after intensive phase of anti-TB therapy.

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Longitudinal body weight and sputum conversion in patients with tuberculosis, Southwest Ethiopia: a retrospective follow-up study

BMJ Open ◽

10.1136/bmjopen-2017-019076 ◽

2018 ◽

Vol 8 (9) ◽

pp. e019076 ◽

Cited By ~ 2

Author(s):

Mersha Filate ◽

Zelalem Mehari ◽

Yihun Mulugeta Alemu

Keyword(s):

Body Weight ◽

Control Strategies ◽

Sputum Smear ◽

Inverse Association ◽

Southwest Ethiopia ◽

Positive Type ◽

Follow Up Study ◽

Tb Treatment ◽

Sputum Conversion

ObjectivesTo describe the association between change in body weight and sputum smear conversion and to identify factors linked with body weight and sputum smear conversion in Jimma University Specialized Hospital, Southwest Ethiopia.DesignA retrospective follow-up study.SettingTeaching hospital in Southwest Ethiopia.ParticipantsA total of 450 patients with tuberculosis (TB) were included in the follow-up between 2011 and 2013.Main outcome measuresThe association between body weight and sputum conversion was measured using joint modelling.ResultsThe association between change in body weight and change in sputum conversion was −0.698 (p<0.001). A strong inverse association between change in body weight and change in sputum conversion was observed. The study variables sex, age, type of TB, HIV status, dose of anti-TB drug and length of enrolment to TB treatment were significantly associated with change in body weight of patients with TB. The study variables age, type of TB, dose of anti-TB drug and length of enrolment were significantly associated with change in sputum status of patients with TB.ConclusionsAmong patients with TB who were on anti-TB treatment, increase in body weight and positive sputum status were inversely related over time. TB prevention and control strategies should give emphasis on factors such as female sex, older age, non-pulmonary positive type of TB, HIV-positive, lower dose of anti-TB drug and length of enrolment to TB treatment during monitoring of trends in body weight and sputum status.

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Tuberculosis treatment outcomes among people living with HIV diagnosed using Xpert MTB/RIF versus sputum-smear microscopy in Botswana: a stepped-wedge cluster randomised trial

BMC Infectious Diseases ◽

10.1186/s12879-019-4697-5 ◽

2019 ◽

Vol 19 (1) ◽

Author(s):

Tefera Agizew ◽

Violet Chihota ◽

Sambayawo Nyirenda ◽

Zegabriel Tedla ◽

Andrew F. Auld ◽

...

Keyword(s):

Treatment Outcomes ◽

Sputum Smear ◽

Smear Microscopy ◽

People Living With Hiv ◽

Sputum Smear Microscopy ◽

Stepped Wedge ◽

Empiric Treatment ◽

Tb Treatment ◽

Living With Hiv

Abstract Background Xpert® MTB/RIF (Xpert) has high sensitivity for diagnosing tuberculosis (TB) compared to sputum-smear microscopy (smear) and can reduce time-to-diagnosis, time-to-treatment and potentially unfavorable patient-level treatment outcome. Methods People living with HIV (PLHIV) initiating antiretroviral therapy at 22 HIV clinics were enrolled and underwent systematic screening for TB (August 2012–November 2014). GeneXpert instruments were deployed following a stepped-wedge design at 13 centers from October 2012–June 2013. Treatment outcomes classified as an unfavorable outcome (died, treatment failure or loss-to-follow-up) or favorable outcome (cured and treatment completed). To determine outcome, smear was performed at month 5 or 6. Empiric treatment was defined as initiating treatment without/before receiving TB-positive results. Adjusting for intra-facility correlation, we compared patient-level treatment outcomes between patients screened using smear (smear arm)- and Xpert-based algorithms (Xpert arm). Results Among 6041 patients enrolled (smear arm, 1816; Xpert arm, 4225), 256 (199 per 2985 and 57 per 1582 person-years of follow-up in Xpert and smear arms, respectively; adjusted incidence rate ratio, 9.07; 95% confidence interval [CI]: 4.70–17.48; p < 0.001) received TB diagnosis and were treated. TB treatment outcomes were available for 203 patients (79.3%; Xpert, 157; smear, 46). Unfavorable outcomes were reported for 21.7% (10/46) in the smear and 13.4% (21/157) in Xpert arm (adjusted hazard ratio, 1.40; 95% CI: 0.75–2.26; p = 0.268). Compared to smear, in Xpert arm median days from sputum collection to TB treatment was 6 days (interquartile range [IQR] 2–17 versus 22 days [IQR] 3–51), p = 0.005; patients with available sputum test result had microbiologically confirmed TB in 59.0% (102/173) versus 41.9% (18/43), adjusted Odds Ratio [aOR], 2.00, 95% CI: 1.01–3.96, p = 0.048). In smear arm empiric treatment was 68.4% (39/57) versus 48.7% (97/199), aOR, 2.28, 95% CI: 1.24–4.20, p = 0.011), compared to Xpert arm. Conclusions TB treatment outcomes were similar between the smear and Xpert arms. However, compared to the smear arm, more patients in the Xpert arm received a TB diagnosis, had a microbiologically confirmed TB, and had a shorter time-to-treatment, and had a lower empiric treatment. Further research is recommended to identify potential gaps in the Botswana health system and similar settings. Trial registration ClinicalTrials.gov Identifier: NCT02538952. Retrospectively registered on 2 September 2015.

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Comparing rates of mycobacterial clearance in sputum smear-negative and smear-positive adults living with HIV

BMC Infectious Diseases ◽

10.1186/s12879-021-06133-4 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Edith E. Machowski ◽

Matebogo Letutu ◽

Limakatso Lebina ◽

Ziyaad Waja ◽

Reginah Msandiwa ◽

...

Keyword(s):

Clinical Trials ◽

Treatment Response ◽

Bacterial Load ◽

Sputum Smear ◽

Smear Microscopy ◽

People Living With Hiv ◽

Treatment Regimens ◽

Early Treatment Response ◽

Smear Negative ◽

Living With Hiv

Abstract Background Pulmonary tuberculosis (TB) in people living with HIV (PLH) frequently presents as sputum smear-negative. However, clinical trials of TB in adults often use smear-positive individuals to ensure measurable bacterial responses following initiation of treatment, thereby excluding HIV-infected patients from trials. Methods In this prospective case cohort study, 118 HIV-seropositive TB patients were assessed prior to initiation of standard four-drug TB therapy and at several time points through 35 days. Sputum bacillary load, as a marker of treatment response, was determined serially by: smear microscopy, Xpert MTB/RIF, liquid culture, and colony counts on agar medium. Results By all four measures, patients who were baseline smear-positive had higher bacterial loads than those presenting as smear-negative, until day 35. However, most smear-negative PLH had significant bacillary load at enrolment and their mycobacteria were cleared more rapidly than smear-positive patients. Smear-negative patients’ decline in bacillary load, determined by colony counts, was linear to day 7 suggesting measurable bactericidal activity. Moreover, the decrease in bacterial counts was comparable to smear-positive individuals. Increasing cycle threshold values (Ct) on the Xpert assay in smear-positive patients to day 14 implied decreasing bacterial load. Conclusion Our data suggest that smear-negative PLH can be included in clinical trials of novel treatment regimens as they contain sufficient viable bacteria, but allowances for late exclusions would have to be made in sample size estimations. We also show that increases in Ct in smear-positive patients to day 14 reflect treatment responses and the Xpert MTB/RIF assay could be used as biomarker for early treatment response.

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Tuberculosis and Human Immunodeficiency Virus Co-Infection: Clinico-Demographic Determinants at an Anti-Retroviral Therapy Center in Northern India

SAARC Journal of Tuberculosis Lung Diseases and HIV/AIDS ◽

10.3126/saarctb.v14i2.19333 ◽

2018 ◽

Vol 14 (2) ◽

pp. 12-17

Author(s):

Om Prakash Giri ◽

Vishal Prakash Giri ◽

Kirti Vishwakarma ◽

Debranjan Datta

Keyword(s):

Cell Count ◽

Sputum Smear ◽

People Living With Hiv ◽

Cd4 Cell Count ◽

Northern India ◽

Ciency Virus ◽

Human Immunodefi Ciency Virus ◽

Migrant Labourer ◽

Therapy Center ◽

Cd4 Cell

Background: In India, Tuberculosis (TB) is endemic and Human immunodefi ciency virus (HIV) infection is epidemic in few states. The risk of developing TB in people living with HIV (PLHIV) is about 19 (27-22) times greater than those without it. TB is major cause of death in HIV-TB co-infected patients. Globally 0.4 million deaths occur annually due to HIV-TB disease.Material & Methods:The present observational study was conducted at Darbhanga Medical College and Hospital ART (Antiretroviral therapy) center during period from January to June 2017. Data of HIV-TB co-infected patients was collected from HIV-TB register and entered into Microsoft Excel sheet for analysis using Statistical Package for the Social Sciences.Results:Young persons mostly from the labouring class working in other states were most affected. Pulmonary tuberculosis (sputum smear positive) was most common co-infection. Baseline CD4 cell count at the time of presentation was observed to be low (less than 200 cells/μL) in 46.64℅ HIV-TB co-infected patients.Conclusion: Rural young people working as migrant labourer need focus of health interventions. They should be educated and screened for HIV and TB. Baseline CD4 cell count should be done in all PLHIV cases to assess their immune status.SAARC Journal of Tuberculosis, Lung Diseases and HIV/AIDS, Vol. 14, No. 2, 2017, Page: 12-17

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Prognostic values of serum IP-10 and IL-17 in Patients with Pulmonary Tuberculosis

Disease Markers ◽

10.1155/2011/938794 ◽

2011 ◽

Vol 31 (2) ◽

pp. 101-110 ◽

Cited By ~ 17

Author(s):

Yung-Che Chen ◽

Chien-Hung Chin ◽

Shih-Feng Liu ◽

Chao-Chien Wu ◽

Chia-Cheng Tsen ◽

...

Keyword(s):

Sputum Smear ◽

Interleukin 17 ◽

High Association ◽

Protein Levels ◽

Tb Treatment ◽

Sputum Conversion ◽

Positive Sputum Smear ◽

Inducible Protein ◽

Risk Of Relapse

Objective:To identify patients at high risk of relapse after anti-tuberculosis (TB) therapy or with poor long-term outcomes.Methods:Fifty-one patients with pulmonary TB: 7 were classified as high association with both cavitations on initial chest radiography and positive sputum smear/cultures after two months of anti-TB treatment (HA group); 19 medium association (MA, one risk alone); and 25 low association (LA, neither risk). Serum interferon (IFN)-γ-inducible protein 10 (IP-10), interleukin-17 (IL-17), and C-reactive protein levels were investigated.Results:There was a trend towards higher serum IP-10 levels (p= 0.042) for HA patients throughout the 6-month treatment period. Month-2 IP-10 levels were higher in the HA than in the MA/LA group (656.2 ± 234.4 vs. 307.6 ± 258.5 pg/ml, adjustedp= 0.005). Receiver operating characteristic curves showed that the risk of relapse was well-captured by month-2 IP-10 levels at a cut-off value of 431 pg/ml (AUC=0.857, 95% CI 0.75–0.97,p= 0.003). Month-2 serum IL-17 levels were lower in non-survivors than survivors (15.7 ± 2.9 pg/ml vs. 24.6 ± 8.2 pg/ml,p= 0.001). Multivariate analysis demonstrated that a month-2 serum IL-17 level of ≤ 17 pg/ml (p= 0.026) was independently associated with all-cause mortality.Conclusions:Serum IP-10 and IL-17 levels after 2 months of anti-TB treatment may be biomarkers for estimating risk of both cavitation and delayed sputum conversion, and for predicting long-term mortality, respectively.

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Serological Responses to Toxoplasma gondii and Matrix Antigen 1 Predict the Risk of Subsequent Toxoplasmic Encephalitis in People Living with HIV

Clinical Infectious Diseases ◽

10.1093/cid/ciaa1917 ◽

2021 ◽

Author(s):

Jianchun Xiao ◽

Fiona Bhondoekhan ◽

Eric C Seaberg ◽

Otto Yang ◽

Valentina Stosor ◽

...

Keyword(s):

Predictive Performance ◽

Toxoplasmic Encephalitis ◽

People Living With Hiv ◽

Serum Samples ◽

Peptide Antigens ◽

Unit Increase ◽

At Risk Populations ◽

Living With Hiv ◽

Nested Case Control ◽

Control Study

Abstract Background Clinically useful predictors for fatal toxoplasmosis are lacking. We investigated the value of serological assays for antibodies to whole Toxoplasma antigens and to peptide antigens of the Toxoplasma cyst protein MAG1, for predicting incident toxoplasmic encephalitis (TE) in people living with HIV (PLWH). Methods We performed a nested case control study, conducted within the Multicenter AIDS Cohort Study (MACS), using serum samples obtained 2 years prior to diagnosis of TE from 28 cases, and 37 HIV disease-matched Toxoplasma seropositive controls at matched time-points. Sera were tested for Toxoplasma antibodies using a commercial assay and for antibodies to MAG1_4.2 and MAG1_5.2 peptides in ELISA. Results Two years prior to clinical diagnosis, 68% of TE cases were MAG1_4.2 seropositive compared with 16% of controls (OR 25.0, 95% CI 3.14-199.18). Corresponding results for MAG1_5.2 seropositivity were 36% and 14% (OR 3.6, 95% CI 0.95-13.42). Higher levels of antibody to MAG1_4.2 (OR 18.5 per doubling of the OD value, 95% CI 1.41-242) and to Toxoplasma (OR 2.91 for each OD unit increase, 95% CI 1.48-5.72) were also associated with the risk of TE. When seropositivity was defined as the presence of MAG1 antibody or relatively high levels of Toxoplasma antibody, the sensitivity was 89% and specificity was 68% for subsequent TE. Conclusions Antibodies to MAG1 showed predictive value on the occurrence of TE in PLWH, and the predictive performance was further improved by adding the levels of Toxoplasma antibody. These measures could be clinically useful for predicting subsequent diseases in multiple at-risk populations.

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Factors Influencing Sputum Conversion among Smear-Positive Pulmonary Tuberculosis Patients in Morocco

ISRN Pulmonology ◽

10.1155/2013/486507 ◽

2013 ◽

Vol 2013 ◽

pp. 1-5 ◽

Cited By ~ 6

Author(s):

Khalid Bouti ◽

Mohammed Aharmim ◽

Karima Marc ◽

Mouna Soualhi ◽

Rachida Zahraoui ◽

...

Keyword(s):

Pulmonary Tuberculosis ◽

Stepwise Regression ◽

Control Measures ◽

Sputum Smear ◽

Tuberculosis Patients ◽

Infection Control Measures ◽

Factors Influencing ◽

Smear Positive Pulmonary Tuberculosis ◽

Sputum Conversion ◽

A Prospective Study

Background. Sputum smear-positive pulmonary tuberculosis patients expel infectious viable bacilli for a period following the commencement of treatment. Objective. To determine the time to sputum smear conversion and study the factors influencing it. Design. A prospective study was undertaken at our hospital in Rabat over a six-month period on a cohort of 119 sputum smear positive patients. Patients were followed up fortnightly. At each followup, specimens were collected and processed for microscopy using standard protocol. Results. 96.6% of our patients completed the study (4 deaths). Sputum conversion rate was 42% after two weeks, 73% after one month, and 95% after two months. Univariate and stepwise regression analysis showed that patients who had high smear grading, miliary, and bilateral radiologic lesions were more likely to undergo delayed sputum conversion (P<0.05). Other factors were thought to influence sputum conversion but were not statistically proven in our study. Conclusion. Since viable bacilli continue to be expelled for up to two months, infection control measures should be maintained for such a time. Patients with high smear grading, miliary, and bilateral radiologic lesions need to be monitored more closely.

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