CROI 2015 Program and Abstracts

Abstract Listing

Oral Abstracts

Gaps in the current portfolio of diagnostic tests include highly sensitive tests for the diagnosis of extra-pulmonary TB, TB in children and HIV-associated TB. There is a need for a true point-of-care diagnostic (or triage) test for use in remote, low-resource settings and for more simple and rapid tests for accurate detection of resistance to second-line anti-TB drugs. 131 NewMedications, Innovative Approaches: Accelerate the TB Regimen Development Pipeline Michael Hoelscher University of Munich, Munich, Germany This is an exciting time for tuberculosis drug development with a number of clinical trials reporting (REFAQUIN, OFLOTUB, REMoxTB). The challenge facing drug development is illustrated by the flouroquinolones trials to prove the promising results in Phase 2 regimens. It is time that we review drug development methodologies critically. The dizzying number of potential dosages and combinations of novel, established and repurposed agents requires rapid pre-selection of the most promising regimens from pre-clinical and early phase clinical trials. These regimens must be optimized at low cost to select the right regimen for a pivotal registration trial. A combination of innovative animal models, early clinical trial designs that gathers safety and DDI data as early as possible and efficacy outcome measurements in phase II studies that do not only look for bacillary clearance from sputum but also for relapse is needed. This presentation will review the different approaches that are currently under consideration. 132 Tuberculosis in Pregnancy Amita Gupta Johns Hopkins University School of Medicine, Baltimore, MD, US Tuberculosis (TB) is a major cause of morbidity and mortality in women of childbearing age (15 to 44 years), accounting for almost 400,000 deaths in this age group every year. Pregnancy and HIV co-infection increase the likelihood that women with latent TB infection (LTBI) will progress to active TB disease, which raises the risk of poor maternal and infant outcomes. International guidelines differ on the optimal regimen and dosing for TB treatment during pregnancy and postpartum in part because safety, tolerability, and pharmacokinetic (PK) data for many TB drugs are lacking in pregnant and postpartumwomen. This knowledge gap is of particular concern for women being treated for both TB and HIV infection and disease, who face overlapping drug toxicities and drug interactions between TB and antiretroviral drugs. Promising new TB drugs have recently entered clinical development or have already been approved for use in non-pregnant adults, but currently there are no planned trials for any of these new agents in pregnant women. In this talk, I will highlight the management of TB during pregnancy including 1) the current knowledge and gaps regarding use of current and new antimycobacterial drugs during pregnancy as well as how pregnancy impacts the pharmacokinetics of anti-TB drugs and antiretroviral drugs; 2) how to manage antiretroviral therapy together with TB treatment during pregnancy; and 3) highlight new information about prevention of TB and unique aspects of treatment for latent TB infection that must be considered during pregnancy. 133 Tuberculosis in Children Anneke C. Hesseling Stellenbosch University, Cape Town, South Africa This presentation will include an overview of the global epidemiology of tuberculosis in children, including the impact of HIV, and with specific emphasis on emerging data on drug-resistant TB. Data will be presented on the historical challenges of evaluating existing and novel treatment strategies for TB in children. Emerging research opportunities and key early findings from pharmacokinetic studies and trials will be highlighted, addressing key pediatric populations including HIV-infected children, the treatment and prevention of MDR-TB, the use of novel drugs, and special treatment needs in infants and adolescents. An overview of research priories and planned and ongoing trials will be presented, and a framework to the evaluation of new TB drugs and regimens discussed. Diagnostic challenges and new approaches to the diagnosis of TB, including novel biomarkers, molecular approaches and novel sampling strategies will be reviewed and global collaborative research efforts highlighted.

Oral Abstracts

THURSDAY, FEBRUARY 26, 2015 Session PL-1 Plenary

4AB Auditorium

8:30 am– 9:00 am Cardiovascular Disease in HIV Patients: An Emerging Paradigm and Call to Action 134 Cardiovascular Disease in HIV Patients: An Emerging Paradigm and Call to Action Steven Grinspoon Massachusetts General Hospital, Harvard Medical School, Boston, MA, US

Cardiovascular disease (CVD) has emerged as an important co-morbidity in HIV-infected patients. The relative risk of CVD, including myocardial infarction and stroke, is increased in HIV patients compared to age and gender-matched non HIV patients. Although some traditional risks, including smoking, are increased in HIV-infected patients and should be targeted for treatment, very often this disease occurs in relatively young, asymptomatic patients with only modest increases in traditional risk scores. Epidemiological studies suggest unique patterns of CVD in HIV patients, for example younger HIV-infected women may be less protected from CVD than younger women in the general population. Recent studies suggest an emerging mechanistic paradigm in which persistent immune activation and inflammation may contribute to atherosclerotic disease in HIV patients. In the HIV population, this disease manifests itself as subclinical, primarily non-calcified, vulnerable plaque, at increased risk for rupture. Indeed studies show increased rates of sudden cardiac death in the HIV population, consistent with acute rupture of vulnerable plaque. Monocyte activation and trafficking into the arterial surface may contribute to an inflammatory pro-thrombotic local milieu, more amenable to buildup of plaques with lipid laden foam cells and a thin necrotic surface. Indeed, molecular imaging techniques, assessing metabolic indices, suggest increased activity at the arterial surface among HIV patients, in association with immune activation and high risk, low attenuation, positively remodeled plaque. Treatment options to prevent CVD in HIV patients are critically needed. Emerging data suggests that targeting inflammation and immune activation may be useful to reduce CVD risk in the HIV population and specific strategies targeting these pathways are now under investigation. Significant evidence suggests that statins may offer

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CROI 2015