Anna Cristina Calçada Carvalho

Treatment Optimization in Patients Co-Infected with HIV and Mycobacterium tuberculosis Infections: Focus on Drug–Drug Interactions with Rifamycins

Tuberculosis (TB) and HIV continue to be two of the major causes of morbidity and mortality in the world, and together are responsible for the death of millions of people every year. There is overwhelming evidence to recommend that patients with TB and HIV co-infection should receive concomitant therapy of both conditions regardless of the CD4 cell count level. The principles for treatment of active TB disease in HIV-infected patients are the same as in HIV-uninfected patients. However, concomitant treatment of both conditions is complex, mainly due to significant drug–drug interactions between TB and HIV drugs. Rifamycins are potent inducers of the cytochrome P450 (CYP) pathway, leading to reduced (frequently sub-therapeutic) plasma concentrations of some classes of antiretrovirals. Rifampicin is also an inducer of the uridine diphosphate glucuronosyltransferase (UGT) 1A1 enzymes and interferes with drugs, such as integrase inhibitors, that are metabolized by this metabolic pathway. Rifampicin is also an inducer of the adenosine triphosphate (ATP) binding cassette transporter P-glycoprotein, which may also lead to decreased bioavailability of concomitantly administered antiretrovirals. On the other side, rifabutin concentrations are affected by the antiretrovirals that induce or inhibit CYP enzymes. In this review, the pharmacokinetic interactions, and the relevant clinical consequences, of the rifamycins—rifampicin, rifabutin, and rifapentine—with antiretroviral drugs are reviewed and discussed. A rifampicin-based antitubercular regimen and an efavirenz-based antiretroviral regimen is the first choice for treatment of TB/HIV co-infected patients. Rifabutin is the preferred rifamycin to use in HIV-infected patients on a protease inhibitor-based regimen; however, the dose of rifabutin needs to be reduced to 150xa0mg daily. More information is required to select optimal treatment regimens for TB/HIV co-infected patients whenever efavirenz cannot be used and rifabutin is not available. Despite significant pharmacokinetic interactions between antiretrovirals and antitubercular drugs, adequate clinical response of both infections can be achieved with an acceptable safety profile when the pharmacological characteristics of drugs are known, and appropriate combination regimens, dosing, and timing of initiation are used. However, more clinical research is needed for newer drugs, such as rifapentine and the recently introduced integrase inhibitor antiretrovirals, and for specific population groups, such as children, pregnant women, and patients affected by multidrug-resistant TB.

The cursed duet today: Tuberculosis and HIV-coinfection

The tuberculosis (TB) and HIV syndemic continues to rage and are a major public health concern worldwide. This deadly association raises complexity and represent a significant barrier towards TB elimination. TB continues to be the leading cause of death amongst HIV-infected people. This paper reports the challenges that lay ahead and outlines some of the current and future strategies that may be able to address this co-epidemic efficiently. Improved diagnostics, cheaper and more effective drugs, shorter treatment regimens for both drug-sensitive and drug-resistant TB are discussed. Also, special topics on drug interactions, TB-IRIS and TB relapse are also described. Notwithstanding the defeats and meagre investments, diagnosis and management of the two diseases have seen significant and unexpected improvements of late. On the HIV side, expansion of ART coverage, development of new updated guidelines aimed at the universal treatment of those infected, and the increasing availability of newer, more efficacious and less toxic drugs are an essential element to controlling the two epidemics. On the TB side, diagnosis of MDR-TB is becoming easier and faster thanks to the new PCR-based technologies, new anti-TB drugs active against both sensitive and resistant strains (i.e. bedaquiline and delamanid) have been developed and a few more are in the pipeline, new regimens (cheaper, shorter and/or more effective) have been introduced (such as the Bangladesh regimen) or are being tested for MDR-TB and drug-sensitive-TB. However, still more resources will be required to implement an integrated approach, install new diagnostic tests, and develop simpler and shorter treatment regimens.

Prevalence of Chlamydia trachomatis and Neisseria gonorrhoeae infection in adolescents in Northern Italy: an observational school-based study

BackgroundWe carried out a study to evaluate the prevalence of Chlamydia trachomatis and Neisseria gonorrhoeae genital infections in school-based adolescents in Northern Italy.MethodsSystematic screening for C. trachomatis and N. gonorrhoeae genital infection was performed in 13th grade students in the province of Brescia, an industrialized area in Northern Italy. Student filled in a questionnaire on sexual behaviour and provided a urine sample for microbiological testing.ResultsA total of 2,718 students (mean age: 18.4xa0years; 59.1xa0% females) provided complete data (62.2xa0% of those eligible). Overall 2,059 students (75.8xa0%) were sexually active (i.e. had had at least one partner), and the mean age at sexual debut was 16.1xa0years (SD: 1.4). Only 27.5xa0% of the sexually active students reported regular condom use during the previous 6xa0months, with higher frequency in males than in females (33.8xa0% vs 24.2xa0%). No case of N. gonorrhoeae infection was detected, while C. trachomatis was found in 36 adolescents, with a prevalence of 1.7xa0% (95xa0% CI: 1.2–2.4) among sexually active students, and no statistical difference between females and males (1.9 and 1.4xa0%, respectively). Inconsistent condom use (odds ratio, ORu2009=u20095.5) and having had more than one sexual partner during the previous 6xa0months (ORu2009=u20096.8) were associated with an increased risk of Chlamydia infection at multivariate analysis.ConclusionThe prevalence of C. trachomatis infection among sexually active adolescents in Northern Italy was low, despite a high proportion of students who engage in risky sexual behaviour. No cases of N. gonorrhoeae infection were identified.

A protocol update for the Selenium Treatment and Chagasic Cardiomyopathy (STCC) trial

Several studies evaluating clinical forms of chronic Chagas disease show that about one-third of patients present cardiac involvement. Heart failure, sudden death and cardioembolic stroke are the main mechanisms of death in Chagas heart disease. The impact of specific etiologic treatment on the prognosis of patients with chronic Chagas heart disease is very limited regardless of the presence or absence of heart failure. Patients with symptomatic Chagas heart disease present serum selenium (Se) levels lower than patients without Chagas heart disease. Moreover, Se supplementation in animal models showed promising results. The aim of this trial is to estimate the effect of Se treatment on prevention of heart disease progression in patients with Chagas cardiomyopathy. However, we had to introduce some protocol modifications in order to keep trial feasibility, as follows: the primary outcome was restricted to left ventricular ejection fraction as a continuous variable, excluding disease progression; the follow-up period was decreased from 5 years to 1 year, an adjustment that might increase the participation rate of our study; the superior age limit was increased from 65 to 75xa0years; and diabetes mellitus was no longer considered an exclusion criterion. All of these protocol modifications were extensively debated by the research team enrolled in the design, recruitment and conduction of the clinical trial to guarantee a high scientific quality.Trial registrationClinical Trials.gov, NCT00875173. Registered on 20 October 2008.

Policies and practices on the programmatic management of LTBI: a survey in the African Region

BACKGROUNDnAlthough the management of latent tuberculous infection (LTBI) is a core component of the End TB Strategy, there is limited information about the status of implementation of such interventions in most African countries.nnnMETHODSnA web-based survey involving the 47 countries of the African Region was conducted between November 2016 and April 2017.nnnRESULTSnThe questionnaire was completed by 32/47 (68.1%) National TB Programme managers or their delegates. LTBI guidelines were available in four countries (12.5%), while 13 (40.6%) had an LTBI section in their national TB guidelines; there was no significant association with socio-economic conditions and funding allocation. LTBI diagnosis was mostly based on clinical evaluation to rule out active disease, rather than on systematic use of the tuberculin skin test. Respectively 23 (71.8%) and 17 countries (53.1%) reported providing treatment to child contacts aged <5 years and people living with the human immunodeficiency virus (PLHIV). Over two thirds of respondent countries had ongoing activities targeting at least one of the aforementioned high-risk groups. A recording and reporting system for LTBI-related data on child contacts and PLHIV was available in respectively 14 and 12 countries; 7 countries had an LTBI monitoring and evaluation plan.nnnCONCLUSIONSnThese data suggest that greater effort is needed to appropriately scale up LTBI policies in the African Region.

Tuberculosis elimination: where are we now?

Tuberculosis (TB) still represents a major public health issue in spite of the significant impact of the efforts made by the World Health Organization (WHO) and partners to improve its control. In 2014 WHO launched a new global strategy (End TB) with a vision of a world free of TB, and a 2035 goal of TB elimination (defined as less than one incident case per million). The aim of this article is to summarise the theoretical bases of the End TB Strategy and to analyse progresses and persistent obstacles on the way to TB elimination. The evolution of the WHO recommended strategies of TB control (Directly Observed Therapy, Short Course (DOTS), Stop TB and End TB) are described and the concept of TB elimination is discussed. Furthermore, the eight core activities recently proposed by WHO as the milestones to achieve TB elimination are discussed in detail. Finally, the recently published experiences of Cyprus and Oman on their way towards TB elimination are described, together with the regional experience of Latin America. New prevention, diagnostic and treatment tools are also necessary to increase the speed of the present TB incidence decline. The theoretical principles and the available examples of countries moving towards TB elimination are described in this article http://ow.ly/q8wN30k9UOW

Prevalence of depression among patients with presumptive pulmonary tuberculosis in Rio de Janeiro, Brazil

Objective: To estimate the prevalence of major depressive episode (MDE) in patients with presumptive pulmonary tuberculosis (pre-PTB, defined by cough lasting ≥ 3 weeks) and compare it between patients with pulmonary tuberculosis (PTB) and without PTB. Methods: Patients with pre-PTB (n=260) were screened for depression using the Patient Health Questionnaire (PHQ-9). Those individuals with scores ≥ 10 were subsequently assessed with the depression module of the Mini International Neuropsychiatric Interview (MINI-Plus) to confirm diagnosis. Associations of categorical variables with PTB and MDE were calculated using the chi-square test and OR. Results: PTB was confirmed in 98 patients (37.7%). A high proportion of both groups (active PTB and no PTB) screened positive for depression (60.2 vs. 62.1%, respectively). Among 159 patients who screened positive for depression, a subset of 97 (61.0%) were further evaluated with the MINI-Plus; current MDE was confirmed in 54.6% (53/97). On univariate and multivariate analysis, female sex was the only factor associated with the diagnosis of current MDE (p = 0.04). Conclusion: The prevalence of MDE was high among individuals with prolonged respiratory symptoms, independent of PTB diagnosis. This is consistent with other studies of depression in primary care in Brazil.