Susanna Capone

Multiple-Dose Pharmacokinetics of Efavirenz with and without the Use of Rifampicin in HIV-Positive Patients

Rifampicin (RIF) decreases serum concentrations of several antiretroviral drugs. We carried out a prospective, comparative study to define efavirenz (EFV) pharmacokinetics in 16 cases and 13 controls. Cases were HIV and tuberculosis (TB) co-infected adults assuming RIF 600 mg once daily and EFV 800 mg once daily. Patients on EFV at standard 600 mg dose without RIF were taken as controls. EFV levels in plasma were assayed by high-performance liquid chromatography (HLPC) predose (C(trough)) and at 1, 2, 3, 4, 5, 6, 8, 10, 11, 12, 13, 14, 16, 18, 22 and 24 hours post-dose, and pharmacokinetic parameters were determined by non-compartmental methods. Among cases, 81% were males, mean age was 37 years, 50% were Caucasians, mean weight was 64 kg, mean CD4 cell counts and log HIV RNA copies were 160/microl and 5.2 /microl, respectively. Cases had a significantly higher Cl/F/kg if compared with controls (0.269 +/- 0.12 versus 0.167 + 0.05 L/h/kg, p<0.01). Otherwise, dose-dependent pharmacokinetic parameters of EFV were similar between cases and controls. Interindividual variability was consistently higher among TB cases compared to controls for all considered parameters. All cases completed combined treatment and no increased EFV toxicity was observed. These results suggest that a dose of 800 mg of EFV in association with rifampicin may be appropriate for patients of weight > 60 kg in Europe. Therapeutic drug monitoring may be beneficial for patients on combination therapy with RIF.

Paradoxical Reaction during Tuberculosis Treatment in HIV-Seronegative Patients

1. Cook PP. Rifampin and pyrazinamide for treatment of latent tuberculosis infection. Clin Infect Dis 2006; 42:892 (in this issue). 2. McElroy PD, Ijaz K, Lambert LA, et al. National survey to measure rates of liver injury, hospitalization, and death associated with rifampin and pyrazinamide for latent tuberculosis infection. Clin Infect Dis 2005; 41: 1125–33. 3. National Institutes of Health. Division of AIDS table for grading the severity of adult and pediatric adverse events, version 1. December 2004. Available at: http://rcc.tech-res -intl.com/tox_tables.htm. Accessed 28 November 2005. 4. Centers for Disease Control and Prevention. Update: adverse event data and revised American Thoracic Society/CDC recommendations against the use of rifampin and pyrazinamide for treatment of latent tuberculosis infectionUnited States, 2003. MMWR Morb Mortal Wkly Rep 2003; 52:735–9. 5. McNeill L, Allen M, Estrada C, Cook P. Pyrazinamide and rifampin vs isoniazid for the treatment of latent tuberculosis. Chest 2003; 123:102–6. 6. Priest DH, Vossel LF, Sherfy EA, Hoy DP, Haley CA. Use of intermittent rifampin and pyrazinamide therapy for latent tuberculosis infection in a targeted tuberculin testing program. Clin Infect Dis 2004; 39:1764–71. 7. Gordin F, Chaisson RE, Matts JP, et al. Rifampin and pyrazinamide vs isoniazid for prevention of tuberculosis in HIV-infected persons. JAMA 2000; 283:1445–50. 8. Halsey NA, Coberly JS, Desormeaux J, et al. Randomised trial of isoniazid versus rifampicin and pyrazinamide for prevention of tuberculosis in HIV-1 infection. Lancet 1998; 351:786–92. 9. Mwiga A, Hosp M, Godfrey-Faussett P, et al. Twice weekly tuberculosis preventive therapy in HIV infection in Zambia. AIDS 1998; 12: 2447–57. 10. Nolan CM, Goldberg SV, Buskin SE. Hepatotoxicity associated with isoniazid preventive therapy: a 7-year survey from a public health tuberculosis clinic. JAMA 1999; 281:1014–8.

Outcome and Predictive Factors of Mortality in Hospitalized HIV-Patients in Burkina Faso

Background:The aim of this study was to describe the clinical presentation and predictors of death in a HIV population hospitalized in Ouagadougou, Burkina Faso.Materials and Methods:Baseline demographics, viro-immunological status, clinical presentations, and outcome have been analyzed by univariate analysis and a multivariate model.Results:A total of 1,071 hospitalizations of HIV-positive patients was recorded between 1 January, 2004 and 31 August, 2006, the majority of whom were female (64.1%). The baseline CD4 cell count/μl was higher in the female patients than in the male ones (166.1 vs 110.9). Gastroenteric symptoms were the first cause of hospitalization (61.7%). The crude mortality rate was higher in males than females (38% vs 25.3%). Baseline World Health Organization clinical stage IV (OR 9.22), neurological syndrome (OR 3.04) or wasting syndrome at admission (OR 2.9), positive malaria film (OR 2.17), and an older age independently predicted death. Weight at admission > 40 kg and a higher platelet count at admission were independently associated with a better outcome.Conclusions:Females are admitted to hospital earlier than males, probably as an indirect result of the Prevention of Mother-to-Child Transmission (PMTCT) public health initiative. An active search of HIV status in other members of the family (PMTCT-plus) may result in the detection of asymptomatic HIV-infected patients as well. A Plasmodium falciparum-positive smear during admission significantly impacted on outcome as well as low platelet count.

New antituberculosis drugs: from clinical trial to programmatic use

Treatment of multidrug-resistant tuberculosis (MDR-TB) cases is challenging because it relies on second-line drugs that are less potent and more toxic than those used in the clinical management of drug-susceptible TB. Moreover, treatment outcomes for MDR-TB are generally poor compared to drug sensitive disease, highlighting the need for of new drugs. For the first time in more than 50 years, two new anti-TB drugs were approved and released. Bedaquiline is a first-in-class diarylquinoline compound that showed durable culture conversion at 24 weeks in phase IIb trials. Delamanid is the first drug of the nitroimidazole class to enter clinical practice. Similarly to bedaquiline results of phase IIb studies showed increased sputum-culture conversion at 2 months and better final treatment outcomes in patients with MDR-TB. Among repurposed drugs linezolid and carbapenems may represent a valuable drug to treat cases of MDR and extensively drug-resistant TB. The recommended regimen for MDR-TB is the combination of at least four drugs to which M. tuberculosis is likely to be susceptible for the duration of 20 months. Drugs are chosen with a stepwise selection process through five groups on the basis of efficacy, safety, and cost. Clinical phase III trials on new regimen are ongoing that could prove transformative against MDR-TB, by being shorter (six months), simpler (an all-oral regimen) and safer than current standard therapy. It is fundamental that the adoption of the new drugs is done responsibly to avoid inappropriate use. Concentration of in-patient MDR-TB treatment in specialized centers could be considered in countries with low numbers of cases in order to provide appropriate clinical case management and to prevent emergence of drug resistance.

Vaginal colonization with Candida spp. in human immunodeficiency virus – infected women: a cohort study

We have conducted a longitudinal study on factors associated with candidal vaginal colonization, a precursor of vaginitis, in a cohort of HIV-infected women in Italy. All consecutive women attending a single, tertiary care clinical site were offered free screening for sexually transmitted infections and genital disorders every 6–12 months. Candidal vaginal colonization was defined as a positive culture for Candida spp. in an asymptomatic woman. From January 1998 to July 2002 we analysed 214 women. The baseline prevalence of candidal vaginal colonization was 16.8%. In the logistic regression analysis, the time since HIV infection ≥36 months (odds ratio [OR] = 0.18, 95% confidence interval [CI] 0.016–0.53, P = 0.002) and a plasma viral load ≥10,000 copies/mL (OR = 3.9, 95% CI 1.03–14.9, P = 0.045) were independently associated with candidal colonization. Among 130 women who were followed for a mean period of 24 months, the incidence of vaginal colonization was 10.7/100 women-years. In the Cox regression analysis, a CD4+ T-lymphocytes count <100 cells/μL during the follow-up was associated with an increased risk of candidal vaginal colonization (OR = 4.45, C.I. = 1.20–16.81, P = 0.03). Risk of candidal vaginal colonization episodes in HIV-infected women significantly increase when CD4+ T-lymphocytes are less than 100.

Tuberculosis elimination and the challenge of latent tuberculosis

Latent tuberculosis infection (LTBI) affects one third to one fourth of the human population and is the reservoir for a significant proportion of emerging active tuberculosis (TB) cases, especially in low incidence countries. The World Health Organization launched in 2015 the END-TB strategy that aims at TB elimination and promotes, for the first time ever, the management of LTBI. The preventive package, basically consisting of testing and treatment for LTBI in groups at high risk of reactivation, is a mainstay of the first pillar of the strategy, alongside prompt diagnosis and early treatment of both drug-susceptible and drug-resistant TB disease. Testing and treatment for LTBI should be pursued with a programmatic perspective. This implies strong political commitment, adequate funding and an effective monitoring and evaluation system. People living with HIV and children under five years of age who are household contact of a contagious TB cases are primarily targeted in all epidemiological setting. In high resource and low incidence setting, additional at risk populations should also be the target for systematic LTBI testing and treatment. Research is urgently needed to develop diagnostic tests with higher predictive value to identify individuals that progress from infection to disease. Similarly, shorter and safer treatment regimens are needed to make the trade-off between potential benefits and harms more favourable for an increasing proportion of infected individuals.

The Holy Grail of prevention of sexually transmitted infections in travellers

In this issue of the journal, two articles1 ,2 provide new evidence on sexual behaviours among travellers. Tanton et al report the rate of new sexual relationships of British residents during travel abroad. They used the Britains third National Survey of Sexual Attitudes and Lifestyles, a probability survey undertaken in the UK between 2010 and 2012, and analysed data from 12 530 men and women aged 16–74 years reporting ≥1 sexual partner(s) in the previous 5 years. They found that 9.2% of men and 5.3% of women reported new sexual partner(s) while overseas. Among those who reported new partners while overseas, 72% of men and 58% of women reported partner(s) who were not UK residents. In another article in this issue of the journal, Lewis and de Wildt report high proportions of backpackers, a younger, mobile population of travellers known to exhibit high risk-taking behaviour, engaging in unsafe sex while travelling through Thailand. By using a cross-sectional convenience sampling design and an anonymous self-administered questionnaire, they showed that over one-third of backpackers travelling without a long-term partner or spouse had vaginal and/or anal intercourse with a new partner; one-third of these did not use condoms consistently. The limitation of the study is the …

Antimicrobial prevention and therapy for travelers' infection.

International journeys are increasing and more than 70 million people from industrialized countries cross the borders of tropical countries every year. More than 50% of them will suffer from some form of infectious illness, ranging from mild travelers’ diarrhea to severe dengue fever to fatal malaria, with a wide spectrum of microbiological entities. Travel-related respiratory infections, including TB, and sexually transmitted infections are also increasingly reported. Awareness of travel-related risk is not always adequate among international travelers. Specific training on travel medicine-related issues, as well as better diagnostic facilities for imported diseases, is crucial for physicians and nurses in industrialized countries.

Screening for active and latent tuberculosis among asylum seekers in Italy: A retrospective cohort analysis

BACKGROUND The World Health Organization conditionally recommends systematic screening of tuberculosis (TB) and Latent Tuberculosis Infection (LTBI) among asylum seekers (AS) from high-burden countries, but the effectiveness of different screening approaches is controversial. METHODS We report the results of a retrospective cohort analysis of TB and LTBI screening among consecutive AS in Brescia, Italy during 2015-2016. TB screening was based on symptoms, LTBI screening on the tuberculin skin test (TST). Logistic regression analysis was performed to identify factors associated with screening uptake. RESULTS Of 2904 registered AS 2567 (88.4%) were evaluated for TB, 62 (2.4%) had symptoms and active TB yield was 155/100,000. Prevalence and incidence TB rates were 545/100,000 persons and 220/100,000 person-years. Questionnaire screening identified 28.6% (4/14) prevalent cases. Of 2303 (89.7%) AS with TST result, the positivity rate was 36.6% (843/2303). Of the 843 candidates for LTBI treatment 413 (49.0%) completed the screening. LTBI treatment was prescribed to 190 (47.9%) of 397 eligible individuals, 10.8% (91) completed treatment. CONCLUSIONS TB prevalence and incidence rates were high in this AS population, but symptom-based screening performed poorly. LTBI cascade losses were significant and mainly attributable to the defragmentation of the health care system.