Search

The impact of anti-tuberculosis co-treatment on efavirenz (EFV) exposure is still uncertain as contradictory reports exist, and the relevance of CYP2B6*6 genetic polymorphism on efavirenz clearance while on-and-off anti-tuberculosis co-treatment is not well investigated. We investigated the determinants of long-term efavirenz pharmacokinetics by enrolling HIV (n = 20) and HIV/Tuberculosis (n = 36) subjects undergoing efavirenz and efavirenz/rifampicin co-treatment respectively. Pharmacokinetic samplings were done 16 weeks after initiation of efavirenz-based anti-retroviral therapy and eight weeks after completion of rifampicin-based anti-tuberculosis treatment. Population pharmacokinetic modeling was used to characterize variabilities and covariates of efavirenz pharmacokinetic parameters. CYP2B6*6 genetic polymorphism but not rifampicin co-treatment was the statistically significant covariate. The estimated typical efavirenz clearance in the HIV only subjects with the CYP2B6*1/*1 genotype was 23.6 L/h/70 kg, while it was 38% and 69% lower in subjects with the CYP2B6*1/*6 and *6/*6 genotypes, respectively. Among subjects with the same CYP2B6 genotypes, efavirenz clearances were comparable between HIV and HIV/Tuberculosis subjects. Typical efavirenz clearances before and after completion of anti-tuberculosis therapy were comparable. In conclusion, after 16 weeks of treatment, efavirenz clearance is comparable between HIV and HIV/Tuberculosis patients with the same CYP2B6 genotype. CYP2B6 genotyping but not anti-tuberculosis co-treatment should guide efavirenz dosing to optimize treatment outcomes.

Purpose: Efavirenz-based combination antiretroviral therapy (cART) is associated with neuropsychiatric adverse events. We investigated the time to onset, duration, clinical implications, impact of pharmacogenetic variations, and anti-tuberculosis co-treatment on efavirenz-associated neuropsychiatric manifestations., Methods: Prospective cohort study of cART naïve HIV patients with or without tuberculosis (HIV-TB) co-infection treated with efavirenz-based cART. Rifampicin-based anti-tuberculosis therapy was initiated 4 weeks prior to efavirenz-based cART in HIV-TB patients. Data on demographic, clinical, laboratory, and a 29-item questionnaire on neuropsychiatric manifestations were collected for 16 weeks after cART initiation. Genotyping for CYP2B6, CYP3A5, SLCO1B1, and ABCB1 and quantification of efavirenz plasma concentration were done on the 4th and 16th week., Results: Data from 458 patients (243 HIV-only and 215 HIV-TB) were analyzed. Overall incidence of neuropsychiatric manifestations was 57.6% being higher in HIV-only (66.7%) compared to HIV-TB patients (47.4%) (p < 0.01). HIV-only patients were more symptomatic, with proportionately higher grades of manifestations compared to HIV-TB patients. Median time to manifestations was 1 week after cART initiation in HIV-only and 6 weeks after anti-TB (i.e., 2 weeks after cART initiation) in HIV-TB patients. HIV-only patients had significantly higher efavirenz plasma concentrations at 4 weeks after cART compared to HIV-TB patients. No association of sex or genotype was seen in relation to neuropsychiatric manifestations. Risk for neuropsychiatric manifestations was three times more in HIV-only patients compared to HIV-TB (p < 0.01)., Conclusions: Incidence of neuropsychiatric manifestations during early initiation of efavirenz-based cART is high in Tanzanian HIV patients. Risk of neuropsychiatric manifestations is lower in HIV patients co-treated with rifampicin containing anti-TB compared to those treated with efavirenz-based cART only.

There is scarcity of information on the burden of alcohol use among people living with HIV in Tanzania despite the high burden of HIV. We examined the prevalence and factors associated with alcohol use among HIV and tuberculosis (TB) co-infected patients in fourteen clinics with highest notification of TB in Dar es Salaam, Tanzania, between October 2010 and December 2011. Proportions were used to describe the prevalence and pattern of alcohol use. Logistic regression was used to assess the association of various participant characteristics with alcohol use. Out of the 515 participants, 38 (7.4%) were current alcohol drinkers, 183 (35.5%) were ex-drinkers and the rest, 294 (57.1%) denied ever drinking alcohol. Approximately, 15% of past and current drinkers were classified as heavy drinkers. Patients with normal BMI, cigarette smokers, and those with higher income were more likely to be drinkers. Similarly, compared to civil servants, those in petty trade and other occupations were more likely to be drinkers. We concluded that, the level of current alcohol use among HIV positive people receiving pulmonary TB treatment in this population was low. Nevertheless, alcohol use screening and assessment should be added as an integral part of service provision in HIV clinics given the effect of alcohol on health outcomes among HIV positive patients.

Background: Reports on tuberculosis (TB) presentation among the elderly in sub-Sahara Africa are scarce at a time when the elderly population is increasing. This dearth of information is likely to lead to an increase in the number of undetected TB cases in the region., Objective: To describe TB presentation and response to anti-tuberculosis treatment at 2 months among elderly patients., Methods: Consecutive patients referred to TB centres in Dar es Salaam, Tanzania, underwent clinical, microbiological and chest X-ray (CXR) evaluations at baseline and after 2 months of anti-tuberculosis treatment. Patients aged 60 years were considered elderly and those aged 18-59 years formed the comparison group., Results: Elderly patients with TB were more likely to have smear-negative TB (76.7% vs. 49.3%, P < 0.0001) and lower-zone lesions on CXR (41% vs. 17%, P < 0.001), but less likely to have cavities on CXR (77.6% vs. 50.4%, P < 0.0001) than the comparison group. Hypertension and diabetes mellitus were more common among the elderly than among controls. Mortality at 2 months was respectively 18.6% and 8.1% among the elderly and among controls. Human immunodeficiency virus infection and smoking increased mortality, while hypertension was associated with reduced mortality., Conclusion: TB in the elderly was associated with atypical clinical and radiological presentations. A high index of suspicion could minimise delays in diagnosis and treatment.

Background: One of the reasons why Isoniazid preventive therapy (IPT) for Tuberculosis (TB) is not widely used in low income countries is concerns on cost of excluding active TB. We analyzed the cost-effectiveness of IPT provision in Tanzania having ruled out active TB by a symptom-based screening tool., Methods: Data on IPT cost-effectiveness was prospectively collected from an observational cohort study of 1283 HIV-infected patients on IPT and 1281 controls; followed up for 24 months. The time horizon for the analysis was 2 years. Number of TB cases prevented and deaths averted were used for effectiveness. A micro costing approach was used from a provider perspective. Cost was estimated on the basis of clinical records, market price or interviews with medical staff. We annualized the cost at a discount of 3%. A univariate sensitivity analysis was done. Results are presented in US$ at an average annual exchange rate for the year 2012 which was Tanzania shillings 1562.4 for 1 US $., Results: The number of TB cases prevented was 420/100,000 persons receiving IPT. The number of deaths averted was 979/100,000 persons receiving IPT. Incremental cost due to IPT provision was US$ 170,490. The incremental cost effective ratio was US $ 405.93 per TB case prevented and US $ 174.15 per death averted. These costs were less than 3 times the 768 US $ Gross Domestic Product (GDP) per capita for Tanzania in the year 2014, making IPT provision after ruling out active TB by the symptom-based screening tool cost-effective. The results were robust to changes in laboratory and radiological tests but not to changes in recurrent, personnel, medication and utility costs., Conclusion: IPT should be given to HIV-infected patients who screen negative to symptom-based TB screening questionnaire. Its cost-effectiveness supports government policy to integrate IPT to HIV/AIDS care and treatment in the country, given the availability of budget and the capacity of health facilities.

Objectives: The scale and impact of background isoniazid resistance in TB- and HIV-endemic countries requires definition to improve treatment success and guide the scale-up of isoniazid preventive therapy (IPT). We describe the effects of isoniazid resistance on TB treatment outcomes among patients with or without HIV infection in Dar es Salaam, Tanzania., Methods: A multicentre, prospective observational study was conducted among TB patients commencing WHO-recommended first-line TB treatment. In multivariate analysis we ascertained the relationship between isoniazid resistance at presentation with a composite of poor treatment outcomes (death, failure or default from TB therapy)., Results: Of 861 patients, 250 (29.0%) were HIV infected and 23 (2.7%) had isoniazid resistance. Seven hundred and ninety-seven (92.6%) of the patients were successfully treated and 25 (2.9%) died. Isoniazid resistance [relative risk (RR) = 6.0; 95% CI = 1.9-18.7; P  <   0.01] and HIV infection with (RR = 2.3; 95% CI = 1.0-5.2; P  =   0.05) or without (RR = 3.1; 95% CI = 1.5-6.2; P  <   0.01) ART were independent predictors of poor treatment outcomes., Conclusions: Background isoniazid resistance and HIV infection adversely affected TB treatment outcomes. Early laboratory detection of isoniazid resistance is important for successful TB therapy. Studies on the impact of background isoniazid resistance on the efficacy of isoniazid prophylaxis are recommended., (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Introduction: Cigarette smoking is one of the major risk factors for non-AIDS related morbidities and is highly prevalent among HIV infected people. However, no reports exist from Tanzania, one of the countries highly affected by the HIV pandemic and one of Africa's biggest tobacco producer., Methods: We examined the patterns and prevalence of cigarette smoking among HIV and TB co-infected adult patients in Dar es Salaam using a cross sectional study design. Proportions were used to describe the pattern of cigarette smoking. Logistic regression was used to assess the association of various participant characteristics with smoking., Results: Out of the 518 participants, 17 (3.3%) were current smokers, 96 (18.5%) were ex-smokers and the rest (78.2%) denied ever smoking. Male sex (p<0.001), alcohol (p<0.001), and illicit substance use (p<0.001) were significantly associated with cigarette smoking., Conclusions: The study indicates that, the level of current cigarette smoking among HIV/TB co-infected patients in Dar es Salaam is low. Nevertheless, the preponderance of cigarette smoking among men, alcohol drinkers, and those who use illicit substances provides a unique opportunity for targeting such population with smoking cessation interventions; HIV care and treatment clinics are uniquely positioned to provide such interventions., (Published by Elsevier Ireland Ltd.)

AIDS, caused by the retrovirus HIV, remains the largest cause of morbidity in sub-Saharan Africa yet almost all genetic studies have focused on cohorts from Western countries. HIV shows high co-morbidity with tuberculosis (TB), as HIV stimulates the reactivation of latent tuberculosis (TB). Recent clinical trials suggest that an effective anti-HIV response correlates with non-neutralising antibodies. Given that Fcγ receptors are critical in mediating the non-neutralising effects of antibodies, analysis of the extensive variation at Fcγ receptor genes is important. Single nucleotide variation and copy number variation (CNV) of Fcγ receptor genes affects the expression profile, activatory/inhibitory balance, and IgG affinity of the Fcγ receptor repertoire of each individual. In this study we investigated whether CNV of FCGR2C, FCGR3A and FCGR3B as well as the HNA1 allotype of FCGR3B is associated with HIV load, response to highly-active antiretroviral therapy (HAART) and co-infection with TB. We confirmed an effect of TB-co-infection status on HIV load and response to HAART, but no conclusive effect of the genetic variants we tested. We observed a small effect, in Ethiopians, of FCGR3B copy number, where deletion was more frequent in HIV-TB co-infected patients than those infected with HIV alone.

Many studies have documented a high prevalence of anemia among tuberculosis (TB) patients and anemia at TB diagnosis has been associated with an increased risk of death. However, little is known about the factors contributing to the development of TB-associated anemia and their importance in TB disease progression. Data from a randomized clinical trial of micronutrient supplementation in patients with pulmonary TB in Tanzania were analyzed. Repeated measures of anemia with iron deficiency, anemia without iron deficiency, and iron deficiency without anemia were assessed as risk factors for treatment failure, TB recurrence, and mortality. The prevalence of anemia (hemoglobin < 110 g/L) at baseline was 64%, more than one-half of which was related to iron deficiency (mean corpuscular volume , 80 fL). We found no evidence of an association between anemia (with or without iron deficiency) or iron deficiency without anemia at baseline and the risk of treatment failure at 1 mo after initiation. Anemia without iron deficiency was associated with an independent, 4-fold increased risk of TB recurrence [adjusted RR = 4.10 (95% CI = 1.88, 8.91); P < 0.001]. Iron deficiency and anemia (with and without iron deficiency) were associated with a 2- to nearly 3-fold independent increase in the risk of death [adjusted RR for iron deficiency without anemia = 2.89 (95% CI = 1.53, 5.47); P = 0.001; anemia without iron deficiency = 2.72 (95% CI = 1.50, 4.93); P = 0.001; iron deficiency anemia = 2.13 (95% CI = 1.10, 4.11); P = 0.02]. Efforts to identify and address the conditions contributing to TB-associated anemia, including iron deficiency, could play an important role in reducing morbidity and mortality in areas heavily affected by TB.

Objectives: To investigate the timing, incidence, clinical presentation, pharmacokinetics and pharmacogenetic predictors for antiretroviral and anti-tuberculosis drug induced liver injury (DILI) in HIV patients with or without TB co-infection., Methods and Findings: A total of 473 treatment naïve HIV patients (253 HIV only and 220 with HIV-TB co-infection) were enrolled prospectively. Plasma efavirenz concentration and CYP2B6*6, CYP3A5*3, *6 and *7, ABCB1 3435C/T and SLCO1B1 genotypes were determined. Demographic, clinical and laboratory data were collected at baseline and up to 48 weeks of antiretroviral therapy. DILI case definition was according to Council for International Organizations of Medical Sciences (CIOMS). Incidence of DILI and identification of predictors was evaluated using Cox Proportional Hazards Model. The overall incidence of DILI was 7.8% (8.3 per 1000 person-week), being non-significantly higher among patients receiving concomitant anti-TB and HAART (10.0%, 10.7 per 1000 person-week) than those receiving HAART alone (5.9%, 6.3 per 1000 person-week). Frequency of CYP2B6*6 allele (p = 0.03) and CYP2B6*6/*6 genotype (p = 0.06) was significantly higher in patients with DILI than those without. Multivariate cox regression model indicated that CYP2B6*6/*6 genotype and anti-HCV IgG antibody positive as significant predictors of DILI. Median time to DILI was 2 weeks after HAART initiation and no DILI onset was observed after 12 weeks. No severe DILI was seen and the gain in CD4 was similar in patients with or without DILI., Conclusions: Antiretroviral and anti-tuberculosis DILI does occur in our setting, presenting early following HAART initiation. DILI seen is mild, transient and may not require treatment interruption. There is good tolerance to HAART and anti-TB with similar immunological outcomes. Genetic make-up mainly CYP2B6 genotype influences the development of efavirenz based HAART liver injury in Tanzanians.

Setting: Tuberculosis (TB) infected adults attending out-patient TB clinics in Dar es Salaam, Tanzania., Objective: To examine the association of anemia with human immunodeficiency virus (HIV) co-infection, indicators of socio-economic status (SES) and anthropometric status in TB-infected adults., Design: Cross-sectional data collection during screening for a clinical trial., Results: Overall, 750 females and 1693 males participated in this study, of whom respectively 49% and 24% were co-infected with HIV-1. Hemoglobin levels were significantly lower in females than in males and in HIV-positive than in HIV-negative participants. HIV co-infection in this antiretroviral-naïve population was also associated with severe anemia (hemoglobin < 85 g/l) in both women (prevalence ratio [PR] = 2.07, 95%CI 1.65-2.59) and men (PR 3.45, 95%CI 2.66-4.47). Although severe anemia was negatively associated with indicators of SES, especially in males, adjustment for SES indicators only marginally changed its association with HIV co-infection. In both sexes, anemia was inversely associated with anthropometric status, independently of HIV infection and SES., Conclusion: Among TB-infected adults, anemia is strongly associated with HIV co-infection and anthropometric status, independently of SES indicators. As anemia is a risk factor for morbidity and mortality in both infections, the management of anemia in TB-HIV co-infected patients warrants special attention.

Setting: The development of tuberculosis (TB) in HIV-1-infected individuals is associated with accelerated HIV-1 disease progression., Objective: To examine the predictors of incident TB in HIV-1-infected Tanzanian women., Design: A prospective cohort of 1078 HIV-1-infected pregnant women was enrolled in a randomized clinical trial to examine the role of vitamin supplements in HIV-1 disease progression and fetal outcomes., Results: Of 1008 women evaluated for TB, 88 (8.7%) developed TB. After controlling for age, education and hemoglobin concentration, in multivariate analysis, low CD4 cell count, elevated erythrocyte sedimentation rate (ESR), decreased mid-upper arm circumference, and high viremia were associated with an increased risk of TB. CD4 <200 vs. > or = 500 cells/mm3 was associated with a 4.44-fold increase in risk of TB (95%CI 2.10-9.40). Individuals with high viremia (> or = 50,000 copies/ml) had a 2.43-fold increase in risk of TB (95%CI 1.24-4.76). Elevated malarial parasite density was slightly associated with a 65% (95%CI 19-85) decreased risk of TB., Conclusions: The risk of developing TB was elevated among women with low CD4 cell counts, elevated ESR, coinfections with other pathogens, poor nutrition and high viremia. There is a slight inverse association between malarial infection and TB, possibly because treating malaria may reduce the risk of TB.

Objective: To determine the acceptability, compliance and side effects of isoniazid (INH) prophylaxis against tuberculosis among HIV infected police officers (PO) in Dar es Salaam., Design: A nested study from a prospective follow up of a cohort of police officers., Setting: Dar es Salaam, Tanzania., Subjects: One hundred and forty three HIV-1 infected police officers., Main Outcome Measures: Acceptance and compliance to INH prophylaxis., Results: Of the 400 HIV-1 infected officers, 143 (35.7%) came forward for post-test counselling and HIV test results. Sixty per cent (87/143) of them accepted to be on INH prophylaxis. However only 42.5% (37/87) came forward for evaluation regarding their suitability for INH prophylaxis. During the evaluation, eight (21.6%) of 37 otherwise asymptomatic PO were found to have active pulmonary tuberculosis (TB). Eventually only 29 PO were actually started on INH, and only 16 (55.2%) of them completed the six months course. No serious side effects were observed. One PO developed TB two months after loss to follow up before completing the six months., Conclusions: There was low acceptability of and poor compliance with INH prophylaxis among the HIV-1 infected PO despite being educated on the benefits of prophylaxis. The prevalence of PTB among asymptomatic HIV-1 infected PO was high, and therefore persons with HIV infection should be examined for TB even in the absence of symptoms.