Urine colorimetry to detect Low rifampin exposure during tuberculosis therapy: a proof-of-concept study.

BACKGROUND: The cost and complexity of current approaches to therapeutic drug monitoring during tuberculosis (TB) therapy limits widespread use in areas of greatest need. We sought to determine whether urine colorimetry could have a novel application as a form of therapeutic drug monitoring during anti-TB therapy. METHODS: Among healthy volunteers, we evaluated 3 dose sizes of rifampin (150 mg, 300 mg, and 600 mg), performed intensive pharmacokinetic sampling, and collected a timed urine void at 4 h post-dosing. The absorbance peak at 475 nm was measured after rifamycin extraction. The optimal cutoff was evaluated in a study of 39 HIV/TB patients undergoing TB treatment in Botswana. RESULTS: In the derivation study, a urine colorimetric assay value of 4.0 × 10(-2) Abs, using a timed void 4 h after dosing, demonstrated a sensitivity of 92 % and specificity of 60 % to detect a peak rifampin concentration (Cmax) under 8 mg/L, with an area under the ROC curve of 0.92. In the validation study, this cutoff was specific (100 %) but insensitive (28 %). We observed similar test characteristics for a target Cmax target of 6.6 mg/L, and a target area under the drug concentration-versus-time curve (AUC0-8) target of 24.1 mg•hour/L. CONCLUSIONS: The urine colorimetric assay was specific but insensitive to detect low rifampin serum concentrations among HIV/TB patients. In future work we will attempt to optimize sampling times and assay performance, with the goal of delivering a method that can translate into a point-of-care assessment of rifampin exposure during anti-TB therapy.

Understanding Patients' Perspectives on Opt-Out, Incentivized, and Mandatory HIV Testing.

BACKGROUND: Currently, widespread HIV testing is the best preventive action against further spread of the HIV epidemic. However, over 40% of the U.S. population has never been tested for HIV and 25% of those with HIV have never been tested. To increase testing rates, in 2006 the CDC advised healthcare settings to conduct testing on an opt-out basis. METHODS: Qualitative, semi-structured interviews with ten seropositive patients and ten seronegative were conducted to address the lack of studies investigating patients' acceptance of and attitude towards this and more novel testing models, e.g. incentivized or anonymous mandatory testing. Participants were asked about their HIV testing history and attitudes towards opt-out, incentivized, and mandatory anonymous HIV testing. RESULTS: Major themes were identified using grounded theory data analysis. All participants were receptive to opt-out testing, and saw the removal of separate written consent as beneficial as long as patients were given the opportunity to consent in some form. CONCLUSION: Ultimately, both mandatory and opt-out testing were equally indicated by participants as being the most effective testing model at increasing testing rates. A firm understanding of patients' perspectives allows for development of effective HIV testing initiatives that are patient-sensitive and can substantially reduce HIV infection rates.

Weight-based loading of vancomycin in patients on hemodialysis.

We evaluated weight-based loading doses of vancomycin and resulting initial prehemodialysis concentrations. Modeling demonstrated modest correlation between dose administered, age, and initial concentration achieved. Actual body weight-based loading of vancomycin predictably achieves therapeutic initial concentrations in patients who receive hemodialysis.

Frequency of occult high-grade squamous intraepithelial neoplasia and invasive cancer within anal condylomata in men who have sex with men.

Human papillomavirus causes anal condylomata, high-grade anal intraepithelial neoplasia, and anal squamous cell cancer. We found high-grade intraepithelial neoplasia or squamous cell cancer in 75 (47%) of 159 HIV-seropositive men who have sex with men (MSM) and in 42 (26%) of 160 HIV-seronegative MSM with anal condylomata meriting surgery (P<.001, determined by use of the chi(2) test). Anal condylomata in MSM often harbor high-grade intraepithelial neoplasia and squamous cell cancer.

New approaches in the treatment of HIV/AIDS - focus on maraviroc and other CCR5 antagonists.

Treatment of HIV-1 infection has produced dramatic success for many patients. Nevertheless, viral resistance continues to limit the efficacy of currently available agents in many patients. The CCR5 antagonists are a new class of antiretroviral agents that target a necessary coreceptor for viral entry of many strains of HIV-1. Recently, the first agent within this class, maraviroc, was approved by a number of regulatory agencies, including the Food and Drug Administration. Herein we review the role of the CCR5 receptor in HIV-1 infection and potential methods to target it in anti-HIV-1 therapy. We review the various categories of agents and discuss specific agents that have progressed to clinical study. We discuss in detail the recently approved, first in class CCR5 antagonist, maraviroc, and discuss aspects of resistance to CCR5 antagonism and the potential role of CCR5 antagonism in the management of HIV-1 infection.

The growing problem of non-AIDS-defining malignancies in HIV.

PURPOSE OF REVIEW: The incidence and spectrum of non-AIDS-defining cancers has continued to grow. As HIV-infected individuals live longer due to highly active antiretroviral therapy, their risk of dying from one of these cancers is increased. The recent literature pertaining to non-AIDS-defining cancers is reviewed. RECENT FINDINGS: Recent epidemiological studies have identified higher rates of carcinoma of the anus, lung, breast, skin, conjunctiva, liver and prostate; hematopoietic malignancies such as Hodgkin's lymphoma, plasma-cell neoplasia and leukemia; and other neoplasms like melanoma and leiomyosarcoma in HIV-positive patients. The role of HIV-induced immunosuppression in the development of these non-AIDS-defining cancers appears less important than lifestyle habits like smoking and sun exposure, as well as coinfection with human papilloma, hepatitis B, hepatitis C and Epstein-Barr viruses. SUMMARY: It is unclear whether the growing number of reports on non-AIDS-defining cancers reflects a true increased incidence or merely the product of increased surveillance, detection and reporting. Highly active antiretroviral therapy not only promotes longevity in the HIV-positive population, but may increase their risk of developing cancer like Hodgkin's lymphoma. Assertive prevention strategies are needed to adequately deal with non-AIDS-defining cancers in an aging and growing HIV-positive population.

Spectrum of human papillomavirus-related dysplasia and carcinoma of the anus in HIV-infected patients.

The incidence of human papillomavirus (HPV)-related anal squamous cell carcinoma is increasing. It is likely that long-standing HIV-related immunosuppression plays a significant role in the pathogenesis of anal carcinoma; however, a direct HIV-HPV interaction has also been implicated. Using cervical cancer prevention as a paradigm, anal Pap smear screening as part of routine HIV preventive care has been proposed to detect and treat precancerous anal lesions in the hope of decreasing anal cancer rates. All HIV-positive patients with invasive cancer of the anal canal, particularly those with CD4+ cell counts greater than 200/microL and those receiving HAART, should be managed in the same manner as their HIV-negative counterparts.