Co-infected Patients Research Articles

604. Effect of rifabutin in dolutegravir dosing: a case series

Abstract Background Tuberculosis (TB) is the leading cause of death in human immunodeficiency virus (HIV) infected people worldwide. Patients with HIV who have latent TB are 20-30 times more likely to develop active TB. Integrated antiretroviral therapy (ART) early in the treatment for tuberculosis is recommended due to improved morbidity and mortality, however, there can be serious drug interactions. Rifamycins are potent inducers of the CYP3A4 isoform, which can cause sub-therapeutic concentrations of anti-retroviral drugs, among these, rifabutin (RBN) is a less potent inducer of CYP3A4. Pharmacokinetic (PK) studies done on healthy adults showed that rifampin decreased dolutegravir (DTG) concentrations by more than 50 % whereas RBN decreased it by 30%. RBN has been preferred given that its favorable pharmacokinetic and toxicity profile. Currently there are no studies examining the use of RBN and DTG in co-infected persons. This is a case series of 4 co-infected patients receiving both agents who underwent PK analysis. Methods Retrospective analysis of patients in the respiratory care unit (RCU) at Jackson Memorial Hospital in Miami. We included adult patients, admitted to the RCU, with a concomitant diagnosis of HIV and active TB disease who received DTG and RBN, and for which DTG and RBN plasma concentrations were measured for therapeutic drug monitoring (TDM). A non-compartmental analysis was performed and the area under the concentration-time curve (AUC) was calculated for DTG and RBN. Results We report 4 patients (Figure 1) that met criteria and underwent PK analysis. All patients with TB who were treated with RBN had low concentrations of DTG, requiring higher doses of DTG (Table 1 & 2). After adjustments based on PK analysis, there was evidence of a favorable response to treatment in 2 patients, with a less than robust in the 2 others. Adequate suppression of viral load could not be determined for 3 of the patients because of the short observation time. Figure 1:Timelines of patients describing admission and HIV and tuberculosis treatment providedDTG, dolutegravir. RFB, rifabutin. VL, viral load. AFB, Acid fast bacilli. LAD, lymphadenopathy. TAF, Tenofovir alafenamide. FTC, Emtricitabine. TDF, Tenofovir Disoproxil Fumarate. INH, Isoniazid. PYZ, Pyrazinamide. BID, twice a day. QD, daily. IRIS, Immune reconstitution inflammatory syndrome. GU, genitourinary. TB, tuberculosis.Table 1:Patients’ pharmacokinetics of DTGAUCX-Y, area under the concentration-time curve from time X to Y hours; AUC0-tau, area under the concentration-time curve from time zero to the end of the dosing interval; DTG, dolutegravir; TDM, therapeutic drug monitoring. a) AUC0-6 was calculated.Table 2:Patients’ pharmacokinetics of RBNAUCX-Y, area under the concentration-time curve from time X to Y hours; AUC0-tau, area under the concentration-time curve from time zero to the end of the dosing interval; RBN, Rifabutin; TDM, therapeutic drug monitoring. a) All RBN doses given every 24 hours, b) RBN value was trace and AUC was not calculated. Conclusion All patients with HIV and TB who were treated with RBN had low concentrations of DTG. This case series demonstrates that for optimal concomitant use of rifabutin and dolutegravir it is highly recommended to use TDM. Prospective clinical studies are needed to further determine the PK interactions between RBN and DTG and virologic response to treatment. Disclosures All Authors: No reported disclosures.

Evaluation of Amino Acids Profile as Non-Invasive Biomarkers of Hepatocellular Carcinoma in Egyptians.

Hepatocellular carcinoma (HCC) is the most dangerous complication of chronic liver disease. It is a multifactorial complicated disease. Hepatitis C and hepatitis B viruses (HCV and HBV, respectively) represent the main causes of HCC in Egypt. Early diagnosis is very important to aid in early intervention. The goal of this research is to evaluate the metabolic role of different amino acids as non-invasive biomarkers over the course of HCC. This study included 302 participants with 97 diagnosed, untreated HCC patients, 81 chronic HCV patients, 56 chronic HBV patients, 18 co-infected patients, and a control group of 50 normal age and gender-matched individuals. All participants provided complete medical histories and underwent complete clinical examinations, abdominal ultrasonography and/or computed tomography, routine laboratory investigations, estimation of serum α-fetoprotein, and determination of amino acid levels using ultra-performance liquid chromatography (UPLC MS/MS). This work revealed a decline in branched chain amino acids (BCAA) and increase in aromatic amino acids (AAA) among infected groups (HCC, HBV, HCV, and co-infected patients) compared to control subjects and a marked change in Fisher's and the BCAAs/tyrosine molar concentration ratios (BTR) between controls and infected groups. Different amino acids could be used as non-invasive markers to discriminate and follow chronic hepatitis patients to predict the course of HCC.

Quality of Life in Co-Infection of Tuberculosis (Tb) and Human Immune Deficiency Virus/ Acquired Immune Deficie ncy Syndrome HIV/AIDS Positive Patients

OBJECTIVES The objective of our study was to compare the quality of life of HIV/AIDS and TB co-infected patients visiting Family Care Center HMC, Peshawar. METHODOLOGY It was a descriptive cross-sectional study, carried out from 1st october to december 2021 at the Family Care Center department of Hayatabad Medical Complex (HMC), Peshawar.The study sample comprised of 46 participants who were selected by Non probability convenient sampling technique.Out of the total 46 participants 23 were HIV positive with TB co-infected and 23 were HIV positive patients only. Data were collected using World Health Organization Quality of Life WHOQOL-BREF validated structured questionnaires were filled from both male & female participants. RESULT 31 study participants were males participants (67.4%) and 15were females (32.6%). Which included on HIV/AIDS group 13 males (56.5%) and 10 females participants (43.5%) and HIV/AIDS with TB co-infected patients 18 males (78.3%) and 5 females (21.7%).The quality of life was poor in TB Co-infection HIV/AIDS positive patients than in only HIV/AIDS positive patients. The overall quality of life was < 60 % in which 8.6 % find out in HIV/AIDS +ve and 13.1 % in co-infection of Tb with HIV/AID. CONCLUSIONS The difference in the quality of life among the two groups was not significant. Although there was some difference in psychological, social and physical domains in HIV/AIDS with TB co-infection patients as compared to HIV /AIDS. We identified that stigmatization, lack of awareness, and early screening plus treatment were prominent issues.

A survival analysis of prognostic determinant factors of time-to-death of HIV/TB co-infected patients under HAART followed-up in a public hospital in Ethiopia

ENWEndNote BIBJabRef, Mendeley RISPapers, Reference Manager, RefWorks, Zotero AMA Gebreyes DE. A survival analysis of prognostic determinant factors of time-to-death of HIV/ TB co-infected patients under HAART followed-up in a public hospital in Ethiopia. HIV & AIDS Review. International Journal of HIV-Related Problems. 2022. doi:10.5114/hivar.2022.121399. APA Gebreyes, D. E. (2022). A survival analysis of prognostic determinant factors of time-to-death of HIV/ TB co-infected patients under HAART followed-up in a public hospital in Ethiopia. HIV & AIDS Review. International Journal of HIV-Related Problems. https://doi.org/10.5114/hivar.2022.121399 Chicago Gebreyes, Delelegn E. 2022. "A survival analysis of prognostic determinant factors of time-to-death of HIV/ TB co-infected patients under HAART followed-up in a public hospital in Ethiopia". HIV & AIDS Review. International Journal of HIV-Related Problems. doi:10.5114/hivar.2022.121399. Harvard Gebreyes, D. (2022). A survival analysis of prognostic determinant factors of time-to-death of HIV/ TB co-infected patients under HAART followed-up in a public hospital in Ethiopia. HIV & AIDS Review. International Journal of HIV-Related Problems. https://doi.org/10.5114/hivar.2022.121399 MLA Gebreyes, Delelegn. "A survival analysis of prognostic determinant factors of time-to-death of HIV/ TB co-infected patients under HAART followed-up in a public hospital in Ethiopia." HIV & AIDS Review. International Journal of HIV-Related Problems, 2022. doi:10.5114/hivar.2022.121399. Vancouver Gebreyes D. A survival analysis of prognostic determinant factors of time-to-death of HIV/ TB co-infected patients under HAART followed-up in a public hospital in Ethiopia. HIV & AIDS Review. International Journal of HIV-Related Problems. 2022. doi:10.5114/hivar.2022.121399.

Treatment outcome and its associated factors among HIV-MTB co-infected patients in Sichuan, China: A retrospective study.

Human immunodeficiency virus (HIV)-Mycobacterium tuberculosis (MTB) co-infection has become a pressing global public health problem. Although tuberculosis (TB) is both treatable and curable, it has been exacerbated by the HIV/acquired immune deficiency syndrome (AIDS) epidemic. HIV-MTB co-infected patients have a variety of disease-specific, and treatment-related factors that can adversely affect their treatment outcomes. This study was conducted to assess the outcomes of TB treatment and its associated factors among HIV-MTB co-infected patients in Sichuan, Southwest China. A retrospective study was performed on HIV-MTB co-infected patients who were diagnosed and registered in TB designated hospitals in Sichuan from January 1, 2016, to December 31, 2020. Data were collected from patients' electronic medical records regarding their demographic, clinical, and social support information, and categorical data, such as sex, were reported using numbers and percentages. χ2 and t-tests were conducted to compare groups in relation to different levels of medical institutions. A binary logistic regression model was used to identify the factors associated with unsuccessful TB treatment outcomes. For logistic regression analysis performed using an α of 0.05, odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated for various risk factors. A total of 3677 registered HIV-MTB co-infected patients were enrolled. After adjusting for other variables, male, advanced age, receiving TB treatment at the municipal medical institution, being diagnosed with external pulmonary TB, referral or tracing, being sputum smear positive, not initiating antiretroviral therapy (ART) and not using fixed-dose combinations were the main risk factors for treatment failure of HIV-MTB co-infected patients in Sichuan province. Sex, age, hospital level, patient source, other diagnostic factors (e.g., sputum smear results, anatomical site of TB), and factors of therapeutic schemes (e.g., antiretroviral therapy, fixed-dose combinations) may serve as risk factors to estimate the likely treatment outcome of HIV-TB co-infection.

Clinical characteristics and molecular epidemiology of human metapneumovirus in children with acute lower respiratory tract infections in China, 2017 to 2019: A multicentre prospective observational study.

Human metapneumovirus (HMPV) infection is one of the leading causes of hospitalization in young children with acute respiratory illness. In this study, we prospectively collected respiratory tract samples from children who were hospitalized with acute lower respiratory tract infection in six hospitals in China from 2017 to 2019. HMPV was detected in 145 out of 2733 samples (5.3%) from the hospitalized children. The majority of HMPV-positive children were under the age of two (67.6%), with a median age of one year. HMPV can independently cause acute lower respiratory tract infection in young children, while all patients showed mild clinical symptoms. Of all the co-infected patients, HMPV was most commonly detected with enterovirus (EV) or rhinovirus (RhV) (38.0%, followed by respiratory syncytial virus (RSV) (32.0%). The highest detection rate occurred from March to May in both northern and southern China. Out of 145 HMPV positive samples, 48 were successfully typed, of which 36 strains were subgrouped into subtypes A2c (75%), eight strains were included in subtype B1 (16.7%), and four strains were included in subtype B2 (8.3%). Moreover, 16 A2c strains contained 111-nucleotide duplications in the G gene. Twenty-seven complete HMPV genomes were successfully obtained, and 25 (92.6%) strains belonged to subtype A2c, whereas one strain was included in subgroup B1 and another was included in subgroup B2. A total of 277 mutations were observed in the complete genomes of 25 A2c strains. All results presented here improve our understanding of clinical characteristics and molecular epidemiology of HMPV infection in children.

The burden of TB/HIV co-infection among clients attending DOTs clinic in a tertiary centre in Southwestern, Nigeria: A 5-year retrospective study.

Tuberculosis (TB) and human immunodeficiency virus (HIV) are closely correlated and continue to cause deleterious effects in co-infected patients. This study aimed to determine the prevalence and associated factors of TB/HIV co-infection among directly observed treatment short-course (DOTs) clinic clients in Ogun State, Nigeria. The TB register and treatment cards of patients that visited the DOTs centre in Federal Medical Centre Abeokuta between January 2015 and December 2019 were reviewed. A total of 726 TB patients' records were reviewed, among which 186 (22.5%) were co-infected with HIV. TB/HIV co-infection was significantly associated with the ⩽19 years age group 54 (37.2%), females 85 (26.7%), divorced and separated 8 (34.8%), rural residents 18 (34.0%), those who had no formal education 53 (39.8%) and the unemployed 63 (31.7%). Gender and educational status remained significant predictors of TB/HIV co-infection after adjustment for confounding factors. Gender-sensitive programming and interventions geared towards improving knowledge of TB and HIV using a wide array of approaches should be considered.

Direct-Acting Antivirals and the Risk of Hepatitis B Reactivation in Hepatitis B and C Co-Infected Patients: A Systematic Review and Meta-Analysis.

Hepatitis B (HBV) reactivation was observed to be more than 10% in patients receiving interferon-based therapy for hepatitis C (HCV) co-infection. At present, when direct-acting antiviral (DAA) has become the main treatment for HCV, there are few large-scale studies on the reactivation of HBV in these population. We studied HBV reactivation risk and prophylactic HBV treatment efficacy in HBV/HCV co-infected patients receiving DAA therapy. Relevant studies were selected from the Ovid-Medline, Ovid-EMBASE, Cochrane Central Register of Controlled Trials, KoreaMed, KMbase, and RISS databases through 4 September 2020. Data pooling was carried out using the random-effects method. We identified 39 articles with 119,484 patients with chronic (n = 1673) or resolved (n = 13,497) HBV infection under DAA therapy. When the studies were pooled, the HBV reactivation rate was 12% (95% confidence interval (CI) 6-19, I2 = 87%), indicating that this population needs careful attention. When stratified by baseline HBV DNA, the undetectable HBV DNA group showed a significantly lower risk of reactivation than the detectable HBV DNA group (odds ratio (OR) 0.30, 95% CI 0.11-0.86, I2 = 0%). Prophylactic HBV therapy reduced HBV reactivation risk (OR 0.25, 95% CI 0.07-0.92, I2 = 0%). Patients with a resolved HBV infection showed a negligible rate (0.4%) of HBV reactivation. In conclusion, patients with detectable HBV DNA levels warrant careful monitoring for HBV reactivation and may benefit from preventive anti-HBV treatment.

Accuracy of FIB-4 and APRI scores compared to transient elastography for liver fibrosis in patients with HIV and HBV co-infection.

Due to economic shortages and concern about occupational exposure to HIV, liver biopsy and transient elastography (TE) are rarely available in patients with HIV/HBV co-infection in China, where HIV/HBV co-infection is prevalent. The accuracy of FIB-4 and APRI for predicting liver fibrosis was compared with TE results in a series of 460 HIV/HBV co-infected patients. FIB-4 and APRI scores were strongly correlated to liver stiffness measurement scores by TE, and the correlation index was 81.4-96.3. An FIB-4 index >1.5 had a positive predictive value of 95.2% to consider fibrosis with a sensitivity of 85.7%. An APRI index >0.5 had a positive predictive value of 98.2% to consider fibrosis with a sensitivity of 76.0%. A FIB-4 value <1.5 or APRI <0.5 were concordant with TE results to exclude fibrosis in 94.4% and 96.8%, respectively. A FIB-4 value >1.5 or APRI >0.5 were concordant with fibrosis diagnosed by TE in 77.6-89.4% and 70.7-80.9%, respectively. In areas with limited resources, FIB-4 and APRI indexes were accurate, simple and inexpensive methods for assessing liver fibrosis in patients with HIV/HBV co-infection.

Seroprevalence and effect of HBV and HCV co-infections on the immuno-virologic responses of adult HIV-infected persons on anti-retroviral therapy.

Chronic hepatitis negatively affects persons living with HIV. While varying in their transmission efficiency, HIV, HBV, and HCV have shared routes of transmission. Available data suggest widely variable rates of HBV and HCV infections in HIV-infected populations across sub-Saharan Africa. With prolonged survival rates due to increased accessibility to antiretroviral drugs, HBV and HCV have the potential to complicate the prognosis of HIV co-infected patients by contributing significantly to continued morbidity and mortality. The study sought to determine the seroprevalence of HIV/HBV and HIV/HCV co-infections among HIV patients on antiretroviral therapy and to evaluate the effect of HIV/HBV and HIV/HCV co-infections on the immunologic and virologic responses of patients. A cross-sectional study in which samples were taken from 500 people living with HIV and attending ART clinic at the Fevers unit of the Korle Bu Teaching Hospital and tested for Hepatitis B Surface Antigen (HBsAg) and Hepatitis C virus antibody (HCV). CD4 cell counts and HIV-1 RNA levels were estimated as well. Data generated were analysed using IBM SPSS version 22. The seroprevalence of HIV/HBV and HIV/HCV co-infections among people living with HIV was 8.4% and 0.2% respectively. HIV/HBV coinfection included 15/42 (35.7%) males and 27/42 (64.3%) females out of which the majority (97.6%) were in the 21-60 years old bracket. HIV/HBV and HIV/HCV co-infections have varied effects on the immunological and virological response of HIV patients on ART. The mean CD cell count was 361.0 ± 284.0 in HIV/HBV co-infected patients and 473.8 ± 326.7 in HIV mono-infected patients. The mean HIV-1 RNA level was not significantly different (X2 [df] = .057 [1]; P = .811) among HIV/HBV co-infected patients (Log102.9±2.0 copies/mL), compared to that of HIV mono-infected patients (Log102.8±2.1 copies/mL) although HIV mono-infected patients had lower viral load levels. One-third (14/42) of HIV/HBV co-infected patients had virologic failure and the only HIV/HCV co-infected patient showed viral suppression. 336/500 (67.2%) patients had HIV-1 viral suppression (females [66.1%]; males [33.9%]) while 164/500 (32.8%) had virologic failure (females [67.7%]; males [32.3%]). The mean CD4 count of patients with viral suppression and patients with virologic failure was 541.2 cells/μL (95% CI 508.5-573.8) and 309.9 cell/μL (95% CI 261.9-357.9) respectively.The study concludes that, HIV/HBV and HIV/HCV coinfections do not significantly affect the immunologic and virologic responses of patients who have initiated highly active antiretroviral therapy, and treatment outcomes were better in females than in males. There was no HBV/HCV co-infection among patients.

Treatment outcomes and costs of a simplified antiretroviral treatment strategy for hepatitis C among Hepatitis C Virus and Human Immuno deficiency Virus co-infected patients in Ukraine.

To demonstrate the use of a standard dose of ledipasvir (LDV) and sofosbuvir (SOF), with or without ribavirin, to treat hepatitis C and hepatitis C/HIV co-infection in Ukraine. Eligible HCV viraemic adults from two clinics in Kyiv were treated with LDV/SOF with or without weight-based ribavirin for 12 weeks. Clinical assessments were performed at screening and at week 24, and as needed; treatment was dispensed every 4 weeks. The primary outcome was sustained virologic response (SVR) 12 weeks after treatment, with analysis by intention to treat. Cost per patient was estimated in USD (2018) over the 24-week period. Of 868 patients included in the study and initiated on therapy, 482 (55.5%) were co-infected with HIV. The common genotypes were 1 (74.1%) and 3 (22%). Overall, SVR was achieved in 831 of the 868 patients (95.7%). SVR in patients with hepatitis C alone and hepatitis C/HIV co-infection was 98.4% and 93.6%, respectively. Adverse events were infrequent and usually mild. Using generic medication, cost per patient was estimated at US$680. A standard dose of LDV and SOF, with ribavirin as per protocol, resulted in good outcomes for patients with both hepatitis C alone and co-infected with hepatitis C/HIV. Program costs in Ukraine were modest using generic medication.

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.

Tuberculosis and COVID-19 co-infection in Serbia: Pandemic challenge in a low-burden country.

COVID-19 and tuberculosis (TB) represent global threats to the public health system. The impact of COVID-19 on TB results in a reduction in the number of notified TB cases, delayed diagnosis and treatment, and increased case fatality and mortality rates. The aim of the study was to analyze the TB/COVID-19 co-infected cohort in Serbia as a low-burden country and compare it to the global TB/COVID-19 cohort. A retrospective analysis was done on 53 TB and COVID-19 co-infected patients treated in COVID hospital "Batajnica" in Belgrade and Special Hospital for Pulmonary Diseases "Ozren" Sokobanja in the period from 6 March 2020 to 1 April 2022. A comparative analysis with the global cohort published recently was also performed. TB/COVID-19 cohort in Serbia included significantly fewer migrants and diabetes cases, but more cases with chronic respiratory diseases compared to the global. Descriptive analysis of TB cases in the Serbian TB/COVID-19 cohort showed fewer cases diagnosed with sputum smear and Gene Xpert/HAIN, fewer EPTB and mono-resistant cases, and more cases diagnosed with solid culture, unilateral pulmonary infiltrate (with bilateral cavity lesions), and bilateral pulmonary infiltrate (no cavities) compared to TB/COVID-19 cases worldwide. Nasal congestion and fever were more common COVID-19 symptoms in the global cohort. Radiology was more commonly used for the diagnosis of COVID-19 in Serbia. Typical bilateral ground opacities were less common among Serbian patients. Serbian patients spent fewer days in the hospital and achieved a higher PCR conversion rate and TB treatment success rate. The Serbian TB/COVID-19 cohort achieved a higher treatment success rate compared to the global cohort. Encouraging vaccination against SARS-CoV-2 for people with a current or past TB disease, as well as rapid diagnosis and targeted treatment of TB in highly specialized pulmonology institutions, presents key points to avoid excessive morbidity and mortality.

Clinical Characteristics and Treatment Outcomes of HIV+ and HIV- Tuberculosis Patients Followed and Treated at the Regional Hospital of Oyem, Northern Gabon: A Two-Year Retrospective Study

Background: The objective of this study was to analyse the clinical characteristics of HIV+ and HIV- tuberculosis patients followed and treated at the Oyem Regional Hospital Centre (ORHC).&#x0D; Materials and Methods: During this study conducted between January 2019 and December 2021, data collection was based on the exploitation of medical records and registers of results from the medical analysis laboratory of the regional hospital of Oyem, in which there were personal data (gender and age) of the patients, the status of HIV infection, clinical characteristics (pulmonary or extra pulmonary TB), and finally, the therapeutic outcomes of the patients after anti-tuberculosis and antiretroviral treatment. Binomial test following the Normal distribution was used to find an association between the percentages of extrapulmonary TB and TB+/HIV+ co-infection.&#x0D; Results: In this study, 128 confirmed TB cases were selected. While 54 (42.19%) were co-infected with TB+/HIV+, 74 patients (57.81%) were monoinfected with TB+/HIV+. Among all these patients, 93 (72.66%) were reported to have extra pulmonary TB and 35 (27.34%) had pulmonary TB. A normal binomial test showed that TB+/HIV+ co-infection was significantly associated with extrapulmonary TB (p=0.04). Patients were put on anti-tuberculosis treatment according to the manufacturers' indications. Despite a total of 15 deaths (8.93%) in both mono- and co-infected patients, there was a favourable outcome, with 35 patients (27.34%) declared cured. With 8 deaths, mortality was higher in the co-infected than in the non-HIV infected TB patients who recorded 7 deaths.&#x0D; Conclusion: By indicating a relatively high prevalence of HIV infection in TB patients, this study showed that TB+/HIV+ co-infection was associated with extra pulmonary TB, the severe form of the disease, and increased mortality in patients, hence the need to strengthen joint activities to control this co-infection.

Survival rate and predictors of mortality among TB/HIV co-infected adult patients: retrospective cohort study

Nowadays, Tuberculosis remains the major cause of HIV-associated mortality, which accounts for 1 out of every 5 HIV-related mortality worldwide. This study aimed to determine the survival rate and predictors of mortality among TB/HIV co-infected patients. An institution-based retrospective cohort study was undertaken on adult TB/HIV co-infected individuals between 1st February 2014 and 30th January 2022 at Mettu Karl Referral Hospital. A Cox regression model was used to identify predictors of survival time to death among TB/HIV co-infected patients. This study comprised 402 TB and HIV co-infected adult patients. Among these, 84 (20.9%) died, and 318 (79.1%) were censored. The study subjects have been followed up for 6920 person-months with an overall median survival time of 17.6 months. The overall incidence rate was 12.1 per 1000 person months [95% CI: 9.77–14.98]. The results of a multivariable Cox regression analysis showed that being at an older age, urban residence, WHO clinical stage II & IV, CD4 count of ≥ 200 cells/mm3, bedridden functional status, using INH, and using CPT were associated with the survival time of TB and HIV co-infected patients at a significance level of alpha = 0.05. This retrospective study found that high mortality of TB/HIV co-infected patients occurred in the earlier months of treatment initiation. Close monitoring of patients with low CD4, who do not utilize CPT, who are in advanced WHO stages, and who have poor functional levels can help them improve their health and live longer.

Effect of active tuberculosis on the survival of HIV-infected adult patients who initiated antiretroviral therapy at public hospitals of Eastern Ethiopia: A retrospective cohort study.

In resource-limited countries such as Ethiopia, tuberculosis is the major cause of morbidity and mortality among people living with the human immunodeficiency virus. In the era of antiretroviral therapy, the effect of tuberculosis on the survival of patients who are living with human immunodeficiency virus has been poorly understood in Ethiopia. Therefore, this study aimed to determine the effect of active tuberculosis on the survival of HIV-infected adult patients who initiated antiretroviral therapy in public hospitals in Eastern Ethiopia. An institution-based retrospective cohort study was conducted among 566 participants from January 1, 2014, to June 30, 2018. The collected data were entered into EpiData version 3.1 before being exported to Stata version 14 for analysis. A Cox proportional hazard model was used to determine the effect of active tuberculosis on the survival of HIV-infected adult patients who initiated antiretroviral therapy, and a p-value less than 0.05 and a 95% confidence level were used to declare statistical significance. Of the 566 patients included in the study, 76 died. The mortality rate was 11.04 per 100 person-years in tuberculosis co-infected patients, while it was 2.52 per 100 person-years in non-tuberculosis co-infected patients. The patients with tuberculosis co-infection had a 2.19 times higher hazard of death (AHR: 2.19; 95% CI: 1.17, 4.12) compared to those without tuberculosis. Advanced clinical stage, low CD4+ cell count, and previous episodes of an opportunistic infection other than tuberculosis were found to be independent predictors of mortality. Co-infection with tuberculosis at antiretroviral therapy initiation increases the hazard of death approximately two-fold. Hence, we recommend key organizations to enhance the region's collaborative interventional and preventative strategies for TB and HIV.

Co-infection of SARS-CoV-2 with other respiratory pathogens in patients with liver disease.

Respiratory illness caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) was first documented in Wuhan, China, in December 2019, followed by its rapid spread across the globe. Accumulating evidence has demonstrated viral/bacterial co-infection in the respiratory tract could modulate disease severity and its outcome in COVID-19 infection. In this retrospective study, 300 chronic liver disease patients with radiologically confirmed lower respiratory tract infection were enrolled from September 2020 to December 2021. In all of them, along with SARS-CoV-2, other respiratory viral/bacterial pathogens were studied. In total, 23.7 % (n=71) patients were positive for SARS-CoV-2. Among the positive patients, 23.9 % (n=17) had co-infection with other respiratory pathogens, bacterial co-infections being dominant. The SARS-CoV-2 negative cohort had 39.7 % positivity (n=91) for other respiratory pathogens, the most common being those of the rhinovirus/enterovirus family. Ground glass opacity (GGO) with consolidation was found to be the most common radiological finding among SARS-CoV-2 positive co-infected patients, as compared to only GGO among SARS-CoV-2 mono-infected patients. Accurate diagnosis of co-infections, especially during pandemics including COVID-19, can ameliorate the treatment and management of suspected cases.

Detection and prevalence of SARS-CoV-2 co-infections during the Omicron variant circulation in France

From December 2021-February 2022, an intense and unprecedented co-circulation of SARS-CoV-2 variants with high genetic diversity raised the question of possible co-infections between variants and how to detect them. Using 11 mixes of Delta:Omicron isolates at different ratios, we evaluated the performance of 4 different sets of primers used for whole-genome sequencing and developed an unbiased bioinformatics method for the detection of co-infections involving genetically distinct SARS-CoV-2 lineages. Applied on 21,387 samples collected between December 6, 2021 to February 27, 2022 from random genomic surveillance in France, we detected 53 co-infections between different lineages. The prevalence of Delta and Omicron (BA.1) co-infections and Omicron lineages BA.1 and BA.2 co-infections were estimated at 0.18% and 0.26%, respectively. Among 6,242 hospitalized patients, the intensive care unit (ICU) admission rates were 1.64%, 4.81% and 15.38% in Omicron, Delta and Delta/Omicron patients, respectively. No BA.1/BA.2 co-infections were reported among ICU admitted patients. Among the 53 co-infected patients, a total of 21 patients (39.6%) were not vaccinated. Although SARS-CoV-2 co-infections were rare in this study, their proper detection is crucial to evaluate their clinical impact and the risk of the emergence of potential recombinants.

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.

Dose optimization with population pharmacokinetics of ritonavir-boosted lopinavir for Thai people living with HIV with and without active tuberculosis

BackgroundPrior to dolutegravir availability, ritonavir-boosted lopinavir (LPV/r) was an alternative recommendation when first-line drugs could not be used. A high concentration of protease inhibitors was observed in the Thai people living with HIV (PLWH). Thus, dose reduction of LPV/r may be possible. However, the pharmacokinetics and dose optimization of LPV/r have never been investigated. This study aimed to develop a population pharmacokinetic model of LPV/r and provide dosage optimization in Thai PLWH. MethodsLPV and RTV trough concentrations from Thai PLWH were combined with intensive data. The data were analyzed by the nonlinear mixed-effects modeling approach. The influence of RTV concentration on LPV oral clearance (CL/F) was investigated. ResultsRifampicin (RIF) use increased LPV and RTV CL/F by 2.16-fold and 1.99-fold, respectively. The reduced dose of 300/75 and 200/150 mg twice daily provided a comparable percentage of patients achieving LPV target trough concentration to the standard dose for PI-naïve patients. For HIV/TB co-infected patients receiving RIF who could not tolerate the recommended dose, the reduced dose of 600/150 mg twice daily was recommended. ConclusionThe population pharmacokinetic model was developed by integrating the interaction between LPV and RTV. The reduced LPV/r dosage offers sufficient LPV exposure for Thai PLWH.