TB-HIV Co-infected Patients Research Articles

Differential Epigenetic Regulation in Uninfected and Tuberculosis-Human Immunodeficiency Virus Co-Infected Patients.

This study aimed to compare the degree of epigenetic modifications between a TB-HIV co-infected cohort and uninfected subjects. Formalin-fixed paraffin-embedded (FFPE) tissues were retrieved from 45 TB-HIV co-infected and 45 control individuals. Real-time PCR was applied to compare the level of expression of genes involved in epigenetic regulation. The protein multiplex assay was used to assess the degree of protein modification. DNA sequencing was used to determine the evolutionary relationships between the infecting HIV and Mtb strains. Our results indicated a significant increase in the expression of the five candidate genes in the patients with TB-HIV relative to the control cohort. A sharp increase in the degree of histone methylation, acetylation and phosphorylation was observed in TB-HIV co-infected patients. The phylogenetic analysis classified the strains into three distinct HIV clusters and five Mtb clusters. The disparities in the expression profiles of our candidate genes between the TB-HIV cohort and non-TB-HIV group highlights the important role played by various TB and HIV strains in regulating the host gene expression landscape.

Survival Rate and Predictors of Mortality Among TB-HIV Co-Infected Patients During Tuberculosis Treatment at Public Health Facilities in Bahir Dar City, Northwest Ethiopia.

Tuberculosis and human immunodeficiency virus co-infection pose a major public health concern, particularly in developing countries. The survival and predictors of mortality were not sufficiently studied among TB-HIV co-infected patients in Ethiopia. This study aimed to investigate the survival rate and predictors of mortality among TB-HIV co-infected patients during TB treatment at public health facilities in Bahir Dar, Northwest Ethiopia. A retrospective follow-up study was conducted among 401 TB-HIV co-infected patients who were treated for tuberculosis between July 2018 and June 2022 at public health facilities in Bahir Dar city, Ethiopia. Data were collected using a structured checklist from patient charts. Data entry and analysis were done using EpiData 3.1 and Stata version 15, respectively. A Cox proportional Hazard regression model was used to identify predictors of mortality. Predictors with P < 0.05 in the multivariable regression were considered statistically significant. Among the 401 TB-HIV co-infected patients, 59 (14.7%) died during the follow-up period. Predictors like lower BMI (AHR = 3.00, 95% CI = 1.44, 6.28), extrapulmonary TB infection (AHR = 3.30, 95% CI = 1.50, 7.29), presence of opportunistic infection (AHR = 5.07, 95% CI = 2.55, 10.08), functional status (bedridden: AHR = 4.49, 95% CI = 1.63, 12.33), and adherence to TB treatment (fair = AHR = 2.74, 95% CI = 1.41, 7.20, and poor = AHR = 3.75, 95% CI = 1.52, 9.23) were associated with mortality. Mortality among TB and HIV coinfected people was high at public health facilities in Bahir Dar city. This result suggested that in order to increase patient survival, it would be necessary to enhance nutritional status, increase adherence to TB treatment, and prevent opportunistic infections.

Assessment of treatment outcome among HIV positive tuberculosis patients in Visakhapatnam

In March 2016, RNTCP revised its technical and operational guidelines. One of the major additions was introduction of Daily Regimen in the treatment of Drug sensitive TB, started initially among TB-HIV co-infected patients in 2017. The present study was taken up to assess the treatment outcomes of Tuberculosis among TB-HIV co-infected patients and certain factors related to the poorer outcome of the treatment.An Observational Longitudinal study conducted at an ART centre, attached to King George Hospital in Visakhapatnam District, Andhra Pradesh, among all TB-HIV co-infected patients newly diagnosed with Drug Susceptible Tuberculosis, aged above 18years, at the selected ART centre, from the month of June 2018 to December 2018. The sample size calculated was 88 with an absolute precision of 10. Ethical clearance from Institutional Ethics Committee, Andhra Medical College; Written informed consent from all the study participants were taken prior to start of study. Confidentiality of the study participants was maintained Qualitative variables were presented as proportions. Analytical statistics include chi-square test and regression analysis. 74% of the patients had a favourable treatment outcome, 15% of the patients died and 11% of the patients were lost to follow up. Occupational status of the study participant, Socio- economic class, tobacco using habit and their CD4 counts had a statistically significant impact on their TB treatment outcome.CD4 count below 200cells/mm, Tobacco use, Diabetes Mellitus- factors responsible for unfavourable treatment outcome of Tuberculosis treatment Case-specific approaches among LFUs may be carried out to bring improvements in the strategies which are already existing or framing new strategies.

Improving the diagnosis of active tuberculosis: a novel approach using magnetic particle-based chemiluminescence LAM assay

ObjectivesTuberculosis (TB) is a significant global health concern, given its high rates of morbidity and mortality. The diagnosis using urine lipoarabinomannan (LAM) primarily benefits HIV co-infected TB patients with low CD4 counts. The focus of this study was to develop an ultra-sensitive LAM assay intended for diagnosing tuberculosis across a wider spectrum of TB patients.Design & MethodsTo heighten the sensitivity of the LAM assay, we employed high-affinity rabbit monoclonal antibodies and selected a highly sensitive chemiluminescence LAM assay (CLIA-LAM) for development. The clinical diagnostic criteria for active TB (ATB) were used as a control. A two-step sample collection process was implemented, with the cutoff determined initially through a ROC curve. Subsequently, additional clinical samples were utilized for the validation of the assay.ResultsIn the assay validation phase, a total of 87 confirmed active TB patients, 19 latent TB infection (LTBI) patients, and 104 healthy control samples were included. Applying a cutoff of 1.043 (pg/mL), the CLIA-LAM assay demonstrated a sensitivity of 55.2% [95%CI (44.13%~65.85%)], and a specificity of 100% [95%CI (96.52%~100.00%)], validated against clinical diagnostic results using the Mann-Whitney U test. Among 11 hematogenous disseminated TB patients, the positive rate was 81.8%. Importantly, the CLIA-LAM assay consistently yielded negative results in the 19 LTBI patients.ConclusionOverall, the combination of high-affinity antibodies and the CLIA method significantly improved the sensitivity and specificity of the LAM assay. It can be used for the diagnosis of active TB, particularly hematogenous disseminated TB.

Burden of mortality and its predictors among TB-HIV co-infected patients in Ethiopia: Systematic review and meta-analysis.

Human immunodeficiency virus (HIV) and tuberculosis (TB) are still the two major deadly pandemics globally, causes 167,000 deaths in 2022. The two lethal combinations pose a substantial challenge to public health, especially in areas with high burden of both diseases such as Sub-Saharan Africa including Ethiopia. However, there is no study that showed national figure on mortality of TB/HIV co-infected patients. Hence, this review intended to provide pooled mortality rate and its predictors among patients co- infected with twin pandemics. Using reputable electronic data bases, primary studies were searched from January 25 to February 5, 2024. The review included papers published in English language conducted between 2004 and 2024. Heterogeneity between included studies was evaluated using Cochrane Q-test and the I2 statistics. Sub-group analysis was done to mitigate significant heterogeneity. Sensitivity analysis was also done to evaluate the effect of single studies on pooled estimated result. In this systematic review and meta-analysis a total of 5,210 study participants were included from 15 primary studies. The review disclosed that the pooled proportion and incidence of mortality were 18.73% (95% CI: 15.92-20.83) and 4.94 (95% CI: 2.98-6.89) respectively. Being bedridden and ambulatory functional status, poor ART adherence, CD4 count below the threshold (<200 cells/mm3), advanced WHO clinical staging, not provision of cotrimoxazole and isoniazid preventing therapy, anemia and extra pulmonary TB were significant predictors of mortality. The analyzed data of this systematic review and meta-analysis depicted that the national pooled proportion and incidence of mortality among TB-HIV co-infected patients were considered to be still high. The authors strongly recommended scale up and continuous provision of cotrimoxazole and isoniazid preventive therapy. In addition, early identification and treatment of anemia will greatly halt the high burden of mortality. Generally, to reduce mortality and improve survival, a collaborative effort is mandatory to emphasize close follow up of patients with identified predictors.

Nutritional Management of Severe Malnutrition in HIV-TB Co-Infected Patients: A Case Report

Background: Malnutrition is a global health issue associated with high rates of mortality and morbidity. Patients suffering from malnutrition are more susceptible to diseases due to compromised immune systems and often face prolonged hospital stays. Chronic infections like Human Immunodeficiency Virus (HIV) and Tuberculosis (TB) significantly contribute to malnutrition. Here, we report on the nutritional management of a patient with severe malnutrition due to an HIV-TB co-infection. Case Description: A 21-year-old male patient with HIV-TB infection, currently in the intensive phase of TB treatment, presented in a severely weakened state. Over the past six months, he had experienced a weight loss of approximately 10 kg. Confined to bed, he was unable to perform any activities. His total energy requirements were calculated to be 2300 kcal, including 115 grams of protein, 280 grams of carbohydrates, and 80 grams of fat. After six days of nutritional therapy, the patient showed clinical improvement, with an increase in appetite and a weight gain of 0.8 kg. At a follow-up 41 days later, the patient had gained a total of 2.5 kg and exhibited significant clinical improvement, along with better laboratory results. Conclusion: Tailored nutritional therapy, combined with effective patient education, can significantly improve the clinical condition of patients with HIV-TB co-infection. Proper nutritional management helps to minimize drug side effects, maintain overall health, and prevent complications that could exacerbate the patient’s condition.

Factors associated with mortality in HIV-TB co-infected patients during and after the course of TB treatment in high-burden settings, Mumbai, India: A cohort analysis.

Knowledge of factors associated with TB mortality during treatment and post treatment will help us develop better monitoring and implementation strategies for TB control. We designed the present study to examine the factors associated with mortality in HIV-TB co-infected patients during and after the course of TB treatment. This study is a cohort analysis of secondary data collected from 1804 HIV-TB co-infected individuals from 16 anti-retroviral therapy (ART) centres affiliated with the Mumbai Districts AIDS Control Society, Mumbai, India. We used Kaplan Meier survival curves and hazard ratios to estimate the mortality in patients. The overall mortality rate in this cohort was 1.14 per 100 per month. The mortality proportion was 18% (95% CI: 16.1%, 20.1%) during treatment and 10.6% (95% CI: 8.9%, 12.5%) in the post-treatment period. Mortality was significantly higher in those with a CD4 count 0-200 cells/mm3 (HR: 3.04, 95% CI: 2.13, 4.15; p < 0.001), and in patients who were ART naïve and referred to the ART centre with a diagnosis of TB (HR: 1.39, 95% CI: 1.06, 1.82; p = 0.016). Mortality was also significantly higher in the first 6 months after initiation of ART (HR: 1.36, 95% CI: 1.06, 1.75; p = 0.016). A decrease in the CD4 counts from initial levels at start of TB treatment to end of TB treatment was associated with higher mortality in the post-treatment period. The overall mortality remains high; early identification of TB and HIV disease, and use of rapid point of care tests for diagnosis of TB are needed across all health care facilities. Post-treatment follow-up and monitoring is important in HIV-TB co-infected patients, and post-treatment mortality should also be considered as one of the indicators for successful TB control programmes.

Impact of human immunodeficiency virus on category I pulmonary tuberculosis cases in a tertiary care hospital: a case control study

Background: Tuberculosis (TB) is an opportunistic infection (OI). OIs are infections that occur more often or are more severe in people with weakened immune systems than in people with healthy immune systems. Human immunodeficiency virus (HIV) weakens the immune system, increasing the risk of TB in people with HIV. This case control study was done to assess the impact of HIV on clinical aspects and treatment outcome of newly diagnosed bacteriologically positive pulmonary tuberculosis. Methods: This study was done among unmatched 75 cases and 75 controls who were pulmonary TB and TBHIV co-infected patients. Data were collected using a pretested, structured, interviewer-administered questionnaire and was analyzed using descriptive and analytical statistics. Results: Total 150 patients were enrolled in the study out of which 75 patients had HIV-TB co-infection while remaining 75 patients were diagnosed as pulmonary TB. Treatment success rates are 74.7 % (56/75) for TB-HIV co-infected patients and 82.7% (62/75) for pulmonary TB patients. TB-HIV co-infected patients had a higher risk of an unsuccessful treatment outcome [(p = 0.232) with OR and 95% CI of 0.68 (0.28-1.36)]. The risk of unsuccessful treatment outcome was associated with family history of TB, Tobacco use, low BMI. Conclusions: TB treatment success rate is good as compared to the WHO minimum requirement. Successful treatment outcome is lower among patients with HIV infection, tobacco use, low BMI, &lt;200 /mm3 CD4 count patients. Therefore, due emphasis should be given to these high-risk groups.

The socio-demographic, clinical characteristics and outcomes of tuberculosis among HIV infected adults in Lithuania: A thirteen-year analysis.

Tuberculosis (TB) is a public health problem in Lithuania, among the 18 high-priority TB countries in the European region, and the most common AIDS-indicative disease with the highest proportion in the EU/EEA since 2015. The study aimed to identify socio-demographic, clinical characteristics and their relationship with TB outcomes in TB-HIV co-infected patients in Lithuania. A retrospective chart review analysed the characteristics of TB-HIV co-infected adults registered in State Information System of Tuberculosis over 2008-2020. The factors associated with drug-resistant TB and unsuccessful treatment outcome were identified by multivariable logistic regression. The study included 345 cases in 311 patients (239 new, 106 previously treated cases), median age 40 years (IQR 35-45), 80.7% male. 67.8% patients knew their HIV-positive status before TB diagnosis, median time to TB diagnosis was 8 years (IQR 4-12). 83.6% were unemployed, 50.5%-anytime intravenous drug users (IDU), 34.9% abused alcohol. Drug-resistant TB rates in new and previously treated TB cases were 38.1% and 61.3%, respectively. In multivariable analysis, higher risk of drug-resistant TB was associated with imprisonment in new (aOR 3.35; 95%CI 1.17-9.57) and previously treated (aOR 6.63; 95%CI 1.09-40.35) cases. In 52.3% of new TB cases and in 42.5% previously treated TB cases the treatment outcomes were unsuccessful. In multivariable analysis of new TB cases, current imprisonment (aOR 2.77; 95%CI 1.29-5.91) and drug-resistant TB (aOR 2.18; 95%CI 1.11-4.28) were associated with unsuccessful treatment outcome. In multivariable analysis of previously treated TB cases, female gender (aOR 11.93; 95%CI 1.86-76.69), alcohol abuse (aOR 3.17; 95%CI 1.05-9.58), drug-resistant TB (aOR 4.83; 95%CI 1.53-15.28) were associated with unsuccessful treatment outcome. In the TB-HIV-infected adult cohort in Lithuania, unemployment, imprisonment, IDU, alcohol abuse, known to be risk factors for TB, were very frequent. Drug resistance was an undeniable risk factor for unsuccessful treatment outcome and imprisonment was associated with drug resistant TB.

Prevalence, Profile and Treatment Outcome of Tuberculosis-Human Immunodeficiency Virus Co-Infection in South Eastern Nigeria: A 3-Year Retrospective Study.

Tuberculosis (TB) and the Human Immune Deficiency Virus (HIV) represent major public health challenges and are intricately linked to each other. This is more prevalent in the sub-Saharan African region, where about 80% of this co-infection is recorded. This study aimed to review the prevalence, profile, and treatment outcome of TB-HIV co-infected patients. A hospital-based retrospective study was conducted in a tertiary center in southeast Nigeria for the period 2015-2017. Information elicited from participant's medical records included socio-demographic profile (age, sex, residential area, and occupation), Cluster of Differentiation 4 (CD4) count level at the time of diagnosis of co-infection, weight, treatment outcome, as well as the record of the number of TB patients who presented within this same period. The total number of TB/HIV co-infected patients who participated in the study during this period was 207, with a prevalence of TB/HIV co-infection of 33.9%. The highest proportion of cases was recorded among participants within the age group of 31-40, and the cases of co-infection were more common in males (58.9%) and students (27.5%). The results also showed a significant relationship between gender, occupation, residential area, and TB/HIV co-infection. Most of the co-infected participants had a CD4 count of <300 cells/mm3 and an associated poor treatment outcome of 41.1%. TB/HIV co-infection needs to be properly addressed, and screening for HIV among TB patients should be a priority. This will help in early diagnosis and subsequently improve the treatment outcome of both diseases.

Application of Invariant Analysesto Study Survival Trends of Patients onAntiretroviral Therapy (ART) and TB Treatment in Kenya

Kenya is one of the countries, globally, with a high burden of human immunodeficiency virus and tuberculosis. The co-infection between tuberculosis and human immunodeficiency virus/acquired immunodeficiency syndrome makes the management of the infection more complicated and reduces the chances of survival. The current study evaluates the trends in the survival of individuals with ART and TB management, especially in relation to various Counties in the country. The specific objective wasto establish the survival trends of patients on Antiretroviral Therapy (ART) and TB treatment in Kenya using Kaplan Meier function. The study used a retrospective cohort study design. The target population included patients on co-therapy TB and ART management who attended the health facilities between 1st January 2015 and 31st December 2019. The sample of the study was obtained from all the available HIV-TB co-infected patients’ records in National AIDS &amp; STIs Control Program (NASCOP) database (secondary data) from the selected counties in Kenya. Kaplan Meier estimator was used in the estimation of the survival function. Analysis was done using STATA v14.2 and Bayes’ v3.0.2. The study also found that HIV-TB patients’ death rates for the period between 2015 and 2019 varied from one County to another. The study also established that the distribution of TB and HIV deaths in the 47 Counties varied across the five years. In the year 2015, the total number of TB and HIV deaths in the 47 Countries was 1077, which decreased to 921 TB and HIV deaths in 2016 before decreasing to 391 in 2017, 106 in 2018 and 60 in 2019. The study found that the main factors significantly influencing HIV-TB confections include gender, marital status, WHO clinical stage, age, weight and facility levels.

HIV-TB Cross-referral and Collaborative Strategy: 8 Years of Our Experience from An Urban Health Centre in North India

Human immunodeficiency virus (HIV) and tuberculosis (TB) epidemics continue to fuel each other and with dual infections with these two deadly diseases on the rise, it becomes imperative to devise effective HIV-TB collaborative strategies. The present study was designed to evaluate the existing HIV-TB cross-referral mechanism at an urban health centre; to determine HIV sero-prevalence among pulmonary TB patients referred from chest clinic to the integrated counselling and testing centre (ICTC); and to evaluate the TB suspects referred from ICTC to the chest clinic for a possible TB aetiology. The present study was a retrospective analysis of HIV-TB cross-referrals whereby a line list of all the patients referred under this strategy from January 2006 to December 2013 was retrieved and analysed. A total of 3726 TB cases were referred to the ICTC and 641 TB suspects were identified by ICTC counsellors and referred to the chest clinic during this period. HIV sero-prevalence among TB patients was 2.8% (106 of 3726) and TB prevalence among HIV sero-positive and sero-negative TB suspects was 9.3% (10/108) and 4.3% (9/211), respectively (p=0.07). HIV prevalence was found to be significantly higher among male (n=2024) than among female (n=1702) TB patients (4.4% versus 0.9%; p<0.0001). Only 319 of 641 (49.8%) ICTC patients referred to the chest clinic reached there. Our study highlights the strong need to scale up the integration and partnership between HIV and TB programmes for better and integrated diagnosis and care of HIV-TB co-infected patients.

Costs incurred by patients with tuberculosis co-infected with human immunodeficiency virus in Bhavnagar, western India: a sequential explanatory mixed-methods research

BackgroundIndia reports the highest number of tuberculosis (TB) and second-highest number of the human immunodeficiency virus (HIV) globally. We hypothesize that HIV might increase the existing financial burden of care among patients with TB. We conducted this study to estimate the costs incurred by patients with TB co-infected with HIV and to explore the perspectives of patients as well as program functionaries for reducing the costs.MethodsWe conducted a descriptive cross-sectional study among 234 co-infected TB-HIV patients notified in the Bhavnagar region of western India from 2017 to 2020 to estimate the costs incurred, followed by in-depth interviews among program functionaries and patients to explore the solutions for reducing the costs. Costs were estimated in Indian rupees (INR) and expressed as median (interquartile range IQR). The World Health Organization defines catastrophic costs as when the total costs incurred by patients exceed 20% of annual household income. The in-depth interviews were audio-recorded, transcribed, and analyzed as codes grouped into categories.ResultsAmong the 234 TB-HIV co-infected patients, 78% were male, 18% were sole earners in the family, and their median (IQR) monthly family income was INR 9000 (7500–11,000) [~US$ 132 (110–162)]. The total median (IQR) costs incurred for TB were INR 4613 (2541–7429) [~US$ 69 (37–109)], which increased to INR 7355 (4337–11,657) [~US$ 108 (64–171)] on adding the costs due to HIV. The catastrophic costs at a 20% cut-off of annual household income for TB were 4% (95% CI 2–8%), which increased to 12% (95% CI 8–16%) on adding the costs due to HIV. Strengthening health systems, cash benefits, reducing costs through timely referral, awareness generation, and improvements in caregiving were some of the solutions provided by program functionaries and the patients.ConclusionWe conclude that catastrophic costs due to TB-HIV co-infection were higher than that due to TB alone in our study setting. Bringing care closer to the patients would reduce their costs. Strengthening town-level healthcare facilities for diagnostics as well as treatment might shift the healthcare-seeking of patients from the private sector towards the government and thereby reduce the costs incurred.

Joint clinical and socio-demographic determinants of CD4 cell count and body weight in HIV/TB co-infected adult patients on HAART

BackgroundTuberculosis is one of the most lethal communicable diseases in the world. In tuberculosis patients, HIV speeds up the course of the infection from latent to active illness. This study aimed to identify joint clinical and socio demographic determinant factors of CD4+ cell count and body weight in HIV/TB co-infected adult patients. MethodsFrom January 2013 to December 2019, 374 HIV/TB co-infected individuals were treated and had follow-ups. This study used descriptive data analysis, a linear mixed effects model for longitudinal data, and joint modeling of the two longitudinal outcome variables. ResultsIn this study, 51.1% of the 374 HIV-TB co-infected patients were women, 47.1% were rural dwellers, and 71.9% developed extra pulmonary TB. Females made up 54.3% of all patients who died. To detect the presence of correlation among repeated measured data, the AR (1) structure was chosen. The joint model was more appropriate for analysing and interpreting current data. ConclusionsBaseline age, follow-up time, baseline weight, place of residence, adherence level, educational background, functional status, WHO clinical stage, smoking status and type of TB developed were identified as significant joint factors in CD4 cell count and weight of HIV/TB co-infected patients from potential joint predictor variables. Therefore, the concerned bodies, specifically the FMOH and regional health staffs, should enhance public awareness about the factors that lead to a drop in CD4 count and weight gain, as well as an increased risk of death from HIV/TB co-infection. Furthermore, special attention should be paid to women and patients with poor adherence. Medication and treatment must be affordable and accessible to all co-infected patients in order to maximize their CD4 count and proportional body weight to their height, and to lengthen the lives of individuals who are co-infected.

Clinicodemographic profile and outcome of tuberculosis treatment in TB-HIV co-infected patients receiving daily ATT under a single window TB/HIV services delivery initiative.

The risk of death in HIV-TB coinfected individuals is far greater than in HIV-only patients. It is critical to provide timely and appropriate therapy in HIV-TB coinfected patients in order to reduce morbidity and mortality. The purpose of this study was to evaluate the clinical presentation and outcome of TB treatment in HIV-TB co-infected patients receiving daily anti-tubercular therapy (ATT) and concurrent antiretroviral therapy (ART) at a tertiary respiratory care centre in New Delhi, India. The research was cross-sectional, observational, and hospital-based A. From September 2018 to August 2019, a total of 53 patients with HIV-TB coinfection were enrolled at the Institute's ART centre. Patients were evaluated with a structured proforma. Data were evaluated using SPSS version 23.0 and p-value of less than 0.05 was considered statistically significant. Among the patients enrolled, the mean age was 35.98 years. Among the patients enrolled, 56.6% patients had EPTB, 32% had PTB and 11.3% had both PTB and EPTB. The majority of the enrolled patients (n=46, 86.7%) had favourable TB treatment outcomes, while 13.3% (n=7) had unfavourable outcome [including death (n=5) and loss to follow up (n=2)]. During the study and follow-up period, no patients transferred out or relapsed. In univariate analysis, low SES, bedridden functional status, low BMI, anaemia, hypoalbuminemia, and a low CD-4 cell count (<100 cells/mm3 were significantly associated with an unfavourable outcome. Bedridden functional status (p=0.002), anaemia (p=0.040), and low BMI (p<0.001) were independently associated with a poor outcome. Adequate disease knowledge and health education can be very beneficial in reducing morbidity and mortality. Early ART in combination with ATT can reduce mortality in TB-HIV co-infected patients.

Impact of on-site Xpert on TB diagnosis and mortality trends in Uganda.

Since 2012, Uganda expanded the Xpert® MTB/RIF network for diagnosis of TB. We compared TB care cascades at health facilities with on-site Xpert vs. facilities that accessed the assay through specimen referral. We analysed secondary aggregate data of the National TB and Leprosy Program (NTLP) from 2016 to 2019. We computed the proportions of notified TB cases and mortality ratios in relation to the estimated TB burden. TB case notifications per annum increased from 24,287 in 2016 to 30,739 in 2019, and the proportion of cases diagnosed at facilities with on-site Xpert testing increased from 62% (15,070/24,287) to 81% (24,829/30,739) (P < 0.001). TB mortality at facilities with on-site Xpert decreased from 8.6% (1,302/15,070) to 7.8% (1,938/24,829) (P = 0.41), while it increased at facilities without on-site Xpert from 6.9% (638/9,217) to 8.8% (521/5,910) (P = 0.23). Furthermore, mortality among TB-HIV co-infected patients at facilities with on-site Xpert dropped from 5.0% (760/15,070) in 2016 to 4.8% (1,187/24,826) in 2019 (P = 0.84) compared to 4.4% (407/9,217) in 2016 to 5.3% (315/5,910) in 2019 (P = 0.57). Wider installation and decentralisation of Xpert leads to increased case-finding. However, the impact on reduction in mortality remains limited. Interventions to address TB-related mortality in addition to Xpert roll-out are required.

Constitutive androstane receptor and pregnane X receptor genotype influence efavirenz plasma concentration and CYP2B6 enzyme activity

Efavirenz is metabolized by CYP2B6, an inducible enzyme whose expression is regulated by the constitutive androstane receptor and pregnane X receptor nuclear receptors. CAR and PXR are encoded by genetically polymorphic NR1I2 and NR1I3, respectively. We examined the impact of NR1I2 and NR1I3 genotype on plasma EFV concentration and CYP2B6 enzyme activity among TB-HIV co-infected patients in Ethiopia. Treatment-naïve HIV patients with TB co-infection (n = 80) were enrolled and received first-line EFV-based antiretroviral and rifampicin-based anti-TB therapy. Plasma EFV and 8-hydroxy-EFV concentrations at the 4th and 16th week of EFV treatment were determined using LC/MS/MS. EFV/8-hydroxy-EFVmetabolic ratio was used as CYP2B6 metabolic activity index. In multivariate regression analysis, NR1I3 rs3003596C or NR1I2 rs2472677T variant allele carriers had significantly lower plasma EFV concentrations than non-carriers. Patients with NR1I2 rs3814057C/C genotype or NR1I3 rs3003596C allele carriers had significantly lower mean log EFV MR. Among CYP2B6*6 allele carriers, patients with NR1I3 rs2502815T/T or NR1I2 rs3814057C/C genotype had significantly lower mean log EFV MR. In conclusion, genetic variants in NR1I2 and NR1I3 genes influence plasma EFV exposure and CYP2B6 enzyme activity in TB-HIV co-infected patients on drug treatment.

Treatment of Tuberculosis and the Drug Interactions Associated With HIV-TB Co-Infection Treatment

Tuberculosis (TB) is a communicable disease that is a major source of illness, one of the ten causes of mortality worldwide, and the largest cause of death from a single infectious agent Mycobacterium tuberculosis. HIV infection and TB are a fatal combination, with each speeding up the progression of the other. Barriers to integrated treatment as well as safety concerns on the co-management of HIV- TB co-infection do exist. Many HIV TB co-infected people require concomitant anti-retroviral therapy (ART) and anti-TB medication, which increases survival but also introduces certain management issues, such as drug interactions, combined drug toxicities, and TB immune reconstitution inflammatory syndrome which has been reviewed here. In spite of considerable pharmacokinetic interactions between antiretrovirals and antitubercular drugs, when the pharmacological characteristics of drugs are known and appropriate combination regimens, dosing, and timing of initiation are used, adequate clinical response of both infections can be achieved with an acceptable safety profile. To avoid undesirable drug interactions and side effects in patients, anti TB treatment and ART must be closely monitored. To reduce TB-related mortality among HIV-TB co-infected patients, ART and ATT (Anti Tuberculosis Treatment) outcomes must improve. Clinical practise should prioritise strategies to promote adherence, such as reducing treatment duration, monitoring and treating adverse events, and improving treatment success rates, to reduce the mortality risk of HIV-TB co-infection.

OUTCOME OF TUBERCULOSIS IN HIV INFECTED PATIENTS WITH SPECIAL REFERENCE TO CD4 COUNT IN AN ART CENTRE, WEST BENGAL

Background: Opportunistic Infections in HIV are major determinants of mortality in HIV patients. Tuberculosis is a leading cause of mortality. Tuberculosis is a public health challenge specially in developing countries like India. The incidence of TB HIVco-infection is gradually increasing. Methods: This was institution based, retrospective study. Study was conducted at ART Centre, North Bengal Medical College &amp; Hospital, Sushruta Nagar, Darjeeling, West Bengal from January 2015 to January 2020 including 105 HIV-TB co-infected patients. Data was collected and template was generated in MS excel sheet and analysis was done on SPSS software. Results: 105, HIV-TB co-infected patients were registered with majority being male (n=79), mean age for male and female patients were 36.78 years and 35.73 years respectively.. The number of patients diagnosed with Extra-pulmonary tuberculosis (EPTB) and Pulmonary tuberculosis (PTB) were almost equal. Majority of patients (34.3%) had CD4 counts &lt;200 whereas (33.3%) had CD4 counts between 200-349. Favourable outcome in terms of cured patients were 82.85% with a statistically signicant pre-treatment and post-treatment improvement in body weight (p value&lt;0.0001) and CD4 count (p value&lt;0.002. Conclusions: There is a strong association between incidence of TB and HIV infection. Early diagnosis and treatment are essential to reduce mortality and morbidity in people living with HIV. Strict adherence to treatment and dedicated counseling for drug compliance is the need of the hour.

Mortality in HIV and tuberculosis patients following implementation of integrated HIV-TB treatment: Results from an open-label cluster-randomized trial.

SummaryBackgroundHIV-TB treatment integration reduces mortality. Operational implementation of integrated services is challenging. This study assessed the impact of quality improvement (QI) for HIV-TB integration on mortality within primary healthcare (PHC) clinics in South Africa.MethodsAn open-label cluster randomized controlled study was conducted between 2016 and 2018 in 40 rural clinics in South Africa. The study statistician randomized PHC nurse-supervisors 1:1 into 16 clusters (eight nurse-supervisors supporting 20 clinics per arm) to receive QI, supported HIV-TB integration intervention or standard of care (control). Nurse supervisors and clinics under their supervision, based in the study health districts were eligible for inclusion in this study. Nurse supervisors were excluded if their clinics were managed by municipal health (different resource allocation), did not offer co-located antiretroviral therapy (ART) and TB services, services were performed by a single nurse, did not receive non-governmental organisation (NGO) support, patient data was not available for > 50% of attendees. The analysis population consists of all patients newly diagnosed with (i) both TB and HIV (ii) HIV only (among patients previously treated for TB or those who never had TB before) and (iii) TB only (among patients already diagnosed with HIV or those who were never diagnosed with HIV) after QI implementation in the intervention arm, or enrolment in the control arm. Mortality rates was assessed 12 months post enrolment, using unpaired t-tests and cox-proportional hazards model. (Clinicaltrials.gov, NCT02654613, registered 01 June 2015, trial closed).FindingsOverall, 21 379 participants were enrolled between December 2016 and December 2018 in intervention and control arm clinics: 1329 and 841 HIV-TB co-infected (10·2%); 10 799 and 6 611 people living with Human Immunodeficiency Virus (HIV)/ acquired immunodeficiency syndrome (AIDS) (PLWHA) only (81·4%); 1 131 and 668 patients with TB only (8·4%), respectively. Average cluster sizes were 1657 (range 170–5782) and 1015 (range 33–2027) in intervention and control arms. By 12 months, 6529 (68·7%) and 4074 (70·4%) were alive and in care, 568 (6·0%) and 321 (5·6%) had completed TB treatment, 1078 (11·3%) and 694 (12·0%) were lost to follow-up, with 245 and 156 deaths occurring in intervention and control arms, respectively. Mortality rates overall [95% confidence interval (CI)] was 4·5 (3·4–5·9) in intervention arm, and 3·8 (2·6–5·4) per 100 person-years in control arm clusters [mortality rate ratio (MRR): 1·19 (95% CI 0·79–1·80)]. Mortality rates among HIV-TB co-infected patients was 10·1 (6·7–15·3) and 9·8 (5·0–18·9) per 100 person-years, [MRR: 1·04 (95% CI 0·51–2·10)], in intervention and control arm clusters, respectively.InterpretationHIV-TB integration supported by a QI intervention did not reduce mortality in HIV-TB co-infected patients. Demonstrating mortality benefit from health systems process improvements in real-world operational settings remains challenging. Despite the study being potentially underpowered to demonstrate the effect size, integration interventions were implemented using existing facility staff and infrastructure reflecting the real-world context where most patients in similar settings access care, thereby improving generalizability and scalability of study findings.FundingResearch reported in this publication was supported by South African Medical Research Council (SAMRC), and UK Government's Newton Fund through United Kingdom Medical Research Council (UKMRC).