MOESM2 of Toxicological investigation of acute and chronic treatment with Gnidia stenophylla Gilg root extract on some blood parameters and histopathology of spleen, liver and kidney in mice

Additional file 2. Histomicrograph of kidney

Efficacy and Safety of Antiretroviral Therapy Initiated One Week after Tuberculosis Therapy in Patients with CD4 Counts < 200 Cells/μL: TB-HAART Study, a Randomized Clinical Trial

<div><p>Background</p><p>Given the high death rate the first two months of tuberculosis (TB) therapy in HIV patients, it is critical defining the optimal time to initiate combination antiretroviral therapy (cART).</p><p>Methods</p><p>A randomized, open-label, clinical trial comparing efficacy and safety of efavirenz-based cART initiated one week, four weeks, and eight weeks after TB therapy in patients with baseline CD4 count < 200 cells/μL was conducted. The primary endpoint was all-cause mortality rate at 48 weeks. The secondary endpoints were hepatotoxicity-requiring interruption of TB therapy, TB-associated immune reconstitution inflammatory syndrome, new AIDS defining illnesses, CD4 counts, HIV RNA levels, and AFB smear conversion rates. All analyses were intention-to-treat.</p><p>Results</p><p>We studied 478 patients with median CD4 count of 73 cells/μL and 5.2 logs HIV RNA randomized to week one (n = 163), week four (n = 160), and week eight (n = 155). Sixty-four deaths (13.4%) occurred in 339.2 person-years. All-cause mortality rates at 48 weeks were 25 per 100 person-years in week one, 18 per 100 person-years in week four and 15 per 100 person-years in week eight (P = 0.2 by the log-rank test). All-cause mortality incidence rate ratios in subgroups with CD4 count below 50 cells/μL versus above were 2.8 in week one (95% CI 1.2–6.7), 3.1 in week four (95% CI 1.2–8.6) and 5.1 in week eight (95% CI 1.8–16). Serum albumin < 3gms/dL (adjusted HR, aHR = 2.3) and CD4 < 50 cells/μL (aHR = 2.7) were independent predictors of mortality. Compared with similar subgroups from weeks four and eight, first-line TB treatment interruption was high in week one deaths (P = 0.03) and in the CD4 subgroup <50 cells/μL (P = 0.02).</p><p>Conclusions</p><p>Antiretroviral therapy one week after TB therapy doesn’t improve overall survival. Despite increased mortality with CD4 < 50 cells/μL, we recommend cART later than the first week of TB therapy to avoid serious hepatotoxicity and treatment interruption.</p><p>Trial Registration</p><p>ClinicalTrials.gov <a href="https://clinicaltrials.gov/ct2/show/NCT01315301" target="_blank">NCT 01315301</a></p></div

Frequency distribution of demographic and clinical variables, Addis Ababa, Ethiopia, August 2004-March 2005

<p>Frequency distribution of demographic and clinical variables, Addis Ababa, Ethiopia, August 2004-March 2005</p

Patient characteristics at enrolment.

<p>Patient characteristics at enrolment.</p

Multivariate analyses of an association between sub-clinical hepatotoxicity with different clinical variables, Addis Ababa, August 2004–March 2005

<p>Multivariate analyses of an association between sub-clinical hepatotoxicity with different clinical variables, Addis Ababa, August 2004–March 2005</p

Risk factors for death among the 64 patients.

<p>Risk factors for death among the 64 patients.</p

Risk factors for development of sub-clinical and clinical hepatotoxicity, Addis Ababa, Ethiopia, August 2004-March 2005

<p>Risk factors for development of sub-clinical and clinical hepatotoxicity, Addis Ababa, Ethiopia, August 2004-March 2005</p

Comparison of incidence (Figure 1A) and severity grade of DILI in study participants stratified by treatment groups: HIV patients without TB co-infection (Arm-1) treated with efavirenz based HAART alone, TB-HIV co-infected patients with CD4 count ≤ 200 cells/μL treated with concomitant anti-TB and HAART therapy (Arm-2), TB-HIV co-infected patients with CD4 count >200 cells/μL treated with anti-TB therapy alone (Arm-3) and TB patients without HIV co-infection treated anti-TB therapy alone (Arm-4).

<p>Figure 1B indicates severity grade distribution among the total 159 DILI cases.</p

Univariate and Multivariate Cox proportional regression analysis to show the risk factors for developing DILI. HR = hazard ratio.

<p>Univariate and Multivariate Cox proportional regression analysis to show the risk factors for developing DILI. HR  =  hazard ratio.</p

Distribution of the different types of liver injuries (hepatocellular, cholestatic and mixed type) that were observed in each treatment group (Figure 2A) and stratified by severity grade (Figure 2B): HIV patients without TB co-infection (Arm-1) treated with efavirenz based HAART alone, TB-HIV co-infected patients with CD4 count ≤ 200 cells/μL treated with concomitant anti-TB and HAART therapy (Arm-2), TB-HIV co-infected patients with CD4 count >200 cells/μL treated with anti-TB therapy alone (Arm-3) and TB patients without HIV co-infection treated anti-TB therapy alone (Arm-4).

<p>Distribution of the different types of liver injuries (hepatocellular, cholestatic and mixed type) that were observed in each treatment group (Figure 2A) and stratified by severity grade (Figure 2B): HIV patients without TB co-infection (Arm-1) treated with efavirenz based HAART alone, TB-HIV co-infected patients with CD4 count ≤ 200 cells/μL treated with concomitant anti-TB and HAART therapy (Arm-2), TB-HIV co-infected patients with CD4 count >200 cells/μL treated with anti-TB therapy alone (Arm-3) and TB patients without HIV co-infection treated anti-TB therapy alone (Arm-4).</p