CROI 2017 Abstract e-Book

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Oral Abstracts

have focused on healthcare settings, with little attention to communities, where over 50% of transmission may be occurring. Known and novel interventions to halt transmission include universal access to DST, rapid initiation of effective treatment, monitoring for emergence of resistance, screening of close contacts and environmental controls (e.g., germicidal UV, improving ventilation, reducing crowding). This talk will review the global epidemiology of TB, the growing data on the role of transmission in drug-resistant TB epidemics, and potential interventions aimed at reducing transmission. 51 EMERGING TREATMENT ISSUES IN MDR-TB Francesca Conradie, Univ of the WItswatersrand, Johannesburg, South Africa The treatment of Drug Resistant TB involved the use of long regimens with poor efficacy and a high drug related adverse event rate. Internationally, a successful outcome of treatment of who are diagnosed DR TB was 50%. Many patients started on treatment are loss to the program in part due to the side effects. In addition, there is increasing evidence of that transmission of DR TB is occurring in the community. While standardised regimens are used when DR TB is diagnosed, the evidence base for is of poor quality and based largely on cohort data. However in the last few years there have been major advances. The World Health Organisation issued guideline in May 2016 that included the use of a shortened course for the treatment of MDR. This session will discuss the rationale and some of the challenges in implementing this new recommendation. In addition, there have been a number of new and repurposed drugs have been introduced into the treatment of DR TB. Some of the research into the use of these drugs will be presented as well as the outcomes of their use in National TB programs. 52 NEW DIAGNOSTIC TECHNOLOGIES FOR MDR-TB Catharina C. Boehme, Fndn for Innovative New Diagnostics (FIND), Geneva, Switzerland The diagnostic gap remains greater for TB than for any other infectious disease; more than 80% of patients with multi-drug resistance remain undiagnosed or unreported. Many years of lab strengthening efforts have shown that scaling up BSL3 capacity for culture drug susceptibility testing will not be a feasible, or sustainable solution. Remarkable progress has been made in the development and introduction of rapid molecular TB drug susceptibility tests, but limitations notably with regard to ease of use and available drug spectrum hamper the impact on case management. To address drug resistant TB, complimentary diagnostic strategies are necessary: Expanded decentralized drug susceptibility testing to inform regimen choice is required at the point of first patient contact, i.e. at low levels of the health care system, especially given the anticipated introduction of short-course regimens and decentralization of MDR treatment. Comprehensive, rapid DST for individualized therapy must be available at more centralized levels. Where are we on the R&D path to much needed new tools? The understanding of the genetics and clinical mutation relevance of TB drug resistance particularly for second-line drugs and newly developed drugs is rapidly improving. WHO and FIND hosted a meeting earlier this year that essentially concluded that genotypic testing should replace culture DST, but at this stage there is no diagnostic solution available or in development that would allow to actually do this. FIND is working with Rutgers University and Cepheid on an expanded DST cartridge for the Omni platform. Initial performance of the assay is excellent, with >95% sensitivity and >99% specificity for detection of mutations in katG, inhA, gyrA, and rrs, and >81% sensitivity for eis mutations. Other companies also join in and strive to develop expanded molecular DST. Experts agree that next generation sequencing represents the future of TB drug resistance testing, initially for surveillance, but within 5 years for individual patient management, and offers huge potential in terms of speed, comprehensiveness and ease of use. A standardized, all-in one solution would ease deployment. The successful uptake of all novel TB diagnostics will critically depend on a strengthening of the patient care cascade and innovative delivery and testing strategies. 53 THE CHALLENGES OF TREATING MDR-TB IN CHILDREN H. Simon Schaaf, Stellenbosch Univ, Cape Town, South Africa The paucibacillary nature of tuberculosis (TB) and the difficulty in obtaining samples for bacteriology in children are important barriers to diagnosis of paediatric MDR-TB. Although 25,000 children were estimated to have developed MDR-TB in 2014, only a small number are reported in the literature as appropriately treated from 1990-2014. Early and appropriate diagnosis is a major challenge in treating MDR-TB in children. The principles of MDR-TB treatment are the same for adults and children; however there are child-specific considerations. The optimal doses of second-line TB drugs, including old, repurposed and new drugs, are only now being determined through paediatric pharmacokinetic and safety studies. The lack of child-friendly formulations of these drugs makes manipulation of adult formulations necesssary, reducing medication palatability and making accurate dosing in children challenging. Extrapulmonary sites of TB, such as TB meningitis, are common in children, making drug penetration, particularly into the cerebrospinal fluid, an important consideration. Although adverse effects are common with second-line anti-TB drugs, most are mild and appear less frequent in children than adults. Some are serious and irreversible, the most important being injectable-associated permanent hearing loss, making the development of injectable-sparing regimens in children essential. Treatment success (cure/treatment completion) in children with MDR-TB is 78-91% in several studies – much better than the 54% reported in one large individual patient data analysis in adults. The generally lower bacillary load in children compared to adolescents and adults could favour MDR-TB treatment regimens with fewer drugs and shorter durations. Observational studies have shown shorter regimens, including shorter durations of injectable agents, to have good outcomes in non-severe disease. After some delay, the novel TB drugs bedaquiline and delamanid are now being evaluated in children, and are likely to be key drugs going forward. Finally, prevention is better than cure; the burden of children exposed to MDR-TB is much larger than those developing MDR-TB disease. The challenge is to determine effective regimens to prevent MDR-TB (and beyond) in high-risk child contacts of MDR-TB source cases. Several trials evaluating regimens containing fluoroquinolones or novel anti-TB drugs are underway or soon to begin, and have the opportunity to change global policy and practice. 54 VAGINAL MICROBIOME AND SUSCEPTIBILITY TO HIV R. Scott McClelland, Univ of Washington, Seattle, WA, USA Several prospective studies published over nearly two decades have explored the relationship between vaginal dysbiosis and women’s risk of HIV acquisition. These studies have typically used Gram stain scoring based on bacterial morphotypes to characterize vaginal microbiota in categories including normal (scores 0-3), intermediate vaginal microbiota (scores 4-6), and bacterial vaginosis (BV; scores 7-10). Together, these data suggest that both intermediate vaginal microbiota and BV are associated with about a 1.5-fold increase in women’s risk of HIV infection. Because disruption of the vaginal microbiota is highly prevalent, particularly in populations at substantial risk for HIV infection, these conditions could have a sizable impact on HIV transmission at a population level. Newer approaches that characterize the vaginal microbiota using nucleic acid amplification based techniques have illuminated much greater heterogeneity among women with vaginal dysbiosis than previously appreciated. Studies presented during the past year suggest that vaginal bacterial community characteristics and the presence of specific bacterial taxa may play a key role in mediating women’s risk of HIV infection. Vaginal microbiota could impact susceptibility to HIV through multiple pathways including inflammation, the presence and concentrations of soluble innate and adaptive immune mediators, production of HIV inducing factors, and disruption of structural barriers to HIV infection including vaginal and cervical mucus and epithelium. Interventions aimed at elimination of high-risk bacterial taxa could reduce women’s risk of acquiring HIV. 55 ANTIBIOTIC PROPHYLAXIS FOR STIs: PROMISES OR PERILS Jean-Michel Molina, Univ of Paris Diderot, Paris, France Background: Every day more than 1 million of STIs are acquired worldwide, and each year there are an estimated 146 million of new infections with chlamydia, 78 million of gonorrhea and 6 million of syphilis. In the US, 2015 was the second year in a row with an increase in STIs, with syphilis increasing at an alarming rate among MSM. The implementation of PrEP for HIV prevention has also highlighted the increasing prevalence and incidence of STIs in PrEP users. Current efforts to contain the spread of STIs are obviously not sufficient. In addition to counseling and behavioral interventions including condom promotion and scaling-up of more effective STIs services, new preventive

Oral Abstracts

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CROI 2017