CROI 2019 Abstract eBook

Abstract eBook

Oral Abstracts

than cures. Therefore, control is unlikely to occur without improved focus on and success in reducing the number of new HCV infections. Risk factors for HCV infection vary globally, but together result in ~1.75 million new HCV infections annually worldwide. An effective preventative HCV vaccine could prevent transmission regardless of risk factors. While a highly effective vaccine could prevent infection altogether, a vaccine that increases the rate of HCV clearance and prevents chronic infection may be sufficient to reduce transmission and disease burden. Despite vaccine need, barriers to vaccine development remain, including limitations to HCV culture systems, viral diversity, limited models and at-risk populations for testing vaccines, and incomplete understanding of protective immune responses. On the positive side, there is evidence that protective immunity exists in populations at ongoing risk of infection. For those who have cleared initial infection and become reinfected, more rapid and effective control of viral replication with subsequent exposures compared to initial exposure supports that adaptive immunity develops and, while not sterilizing, that it protects against chronic disease. Decades of research have revealed that HCV-specific CD4+ helper T cells, CD8+ cytotoxic T cells, and antibodies are all important in mediating protection against persistent HCV infection. Vaccine strategies to induce all three adaptive immune responses are in development. Adjuvanted envelope or core protein and virally vectored non-structural antigen vaccines have advanced into healthy volunteers not at risk for HCV, with viral vectors encoding non-structural proteins the only vaccine strategy tested in at-risk individuals to date. Despite development challenges, a prophylactic vaccine is necessary for global HCV control. This talk will discuss the need for a vaccine, evidence that a vaccine to prevent chronic infection is possible, challenges to immunologic control of HCV, and the vaccine strategies tested to date. 114 CHOICES AND DILEMMAS: PREVENTING TUBERCULOSIS IN PEOPLE WITH HIV INFECTION Amita Gupta , Johns Hopkins University, Baltimore, MD, USA An estimated 23% of the world's population is infected with tuberculosis infection. Notably, an estimated 300,000 people with HIV died from tuberculosis in 2017 with the vast majority of deaths occurring in low and middle income countries. Preventing tuberculosis in people living with HIV is therefore a global priority. The most common regimen used for tuberculosis preventive therapy has been Isoniazid Preventive therapy. However this regimen requires 6-9 months of daily therapy with longer therapy needed for areas with high community exposure and incidence. Recently several trials have identified newer and shorter regimens for tuberculosis prevention: a one month daily isoniazid with rifapentine regimen; a 3 month weekly isoniazid and rifapentine regimen; and a 4 month daily isoniazid and rifampin regimen. In addition special populations such as children and pregnant women have also been more formally studied in clinical trials. Phase II vaccines trials for the prevention of tuberculosis have also had some interesting results. Lastly, expert guidance statements and new clinical trials have been launched for preventing tuberculosis in those with known exposure to multi-drug tuberculosis. This talk will summarize the data from these different studies and highlight the choices and dilemmas of preventing tuberculosis in people living with HIV infection. 115 TREATING MULTIDRUG-RESISTANT TUBERCULOSIS IN THE REAL WORLD: NEW DRUGS AND REGIMENS Jennifer Furin , Harvard Medical School, Boston, MA, USA The treatment landscape for rifampin-resistant forms of tuberculosis (RR-TB) is rapidly changing with the introduction of new drugs and shorter treatment regimens. For the first time ever, phase III trials and rigorous operational research studies are being done to support policy on the optimal management of RR-TB. This information is being used by programs and normative public health bodies to offer radically different therapeutic options for people living with the disease, including all-oral therapy. There are, however, inherent tensions between the existing RR-TB science, the WHO treatment recommendations, and what is actually being done in countries. This is driven in part by the noxious “standard of care” regimen and the long periods of time it takes to design, execute and complete RR-TB trials. This session will present the 2018 WHO recommendations for the treatment of RR-TB and the science behind those recommendations, including the STREAM-1 and delamanid phase III trials. The status of ongoing RR-TB studies will also be reviewed, with an eye toward improving the way RR-TB clinical trials are done. Finally, the state of the field will be discussed in terms of ethics, human, rights, and an alarming lack of

access to novel therapies in most regions of the world, since advances in RR-TB science mean little if they cannot reach the people who need themmost.


Pietro L. Vernazza , St Gallen Cantonal Hospital, St Gallen, Switzerland The story of U=U began in the 1990s when it became apparent that the risk of sexual transmission of HIV varied by sexual practice. In the beginning of this century, many physicians started to question if there was in fact any risk of HIV transmission at all during fully suppressive antiretroviral therapy. The Rakai data indicted risk of transmission to HIV negative serodifferent partners was strongly correlated with the viral load of the positive partner; and while only two small observational studies prospectively evaluated this question in the setting of fully suppressive cART, the absence of any documented case of transmission with suppressive ART gained attention. In 2008 the Swiss Federal Commission on AIDS related issues published what became rapidly known as the “Swiss statement”. Based on the absence of any reported case and on additional biological data supporting the observation, the commission decided that the evidence was strong enough to claim absence of any risk of sexual transmission in the setting of optimal cART use. The statement also made reference to other similar public health messages, such as non-transmission to household contacts, where the absence of evidence was the only basis for such statements. Furthermore, the publication of the Swiss statement raised the profile of this issue and likely supported the reporting of any observed cases of transmission. The continued absence of evidence of any such cases was a further argument supporting the statement of “no-risk”. The obvious weakness of the “Swiss statement” was the assumed detection and reporting of cases of transmission. Therefore, the development of prospective, well-designed studies actively looking for cases of transmission in the setting of suppressive ART provided important scientific evidence to support the statement of “no-risk”. None of three large studies observed a single case of sexual transmission in the setting of fully suppressive cART. The increasing number of documented exposures without any signal of risk of transmission increases the certainty of the “no risk” statement. Nneka Nwokolo , Chelsea and Westminster Hospital, London, UK U=U, the concept that a person with an undetectable viral load is incapable of transmitting HIV sexually, has transformed the lives of people living with HIV worldwide and is doing much to reduce the stigma associated with this condition (although there is still a long way to go). Evidence for U=U comes from clinical trials involving thousands of couples (both homosexual and heterosexual) in serodifferent relationships in which no linked transmissions occurred from HIV-positive people with fully suppressed viral loads. Clinically, however, the practical implementation of U=U in some circumstances may pose a significant challenge; for example, - Can a clinician discussing the risk of transmission with a patient in a resource-limited setting with poor or no access to viral load monitoring, or where structural factors and competing priorities adversely impact adherence, reassure that patient with the same certainty as they could an individual who doesn’t have these concerns? - Strictly speaking, U=U applies to the risk of sexual transmission; can we reliably apply this message in the context of breastfeeding, to a healthcare worker following a sharps injury or to an HIV negative individual who shares a syringe during intravenous drug use? - Should we offer postexposure prophylaxis to a patient with a sexually transmitted infection whose sexual partner informs him or her that they have an undetectable viral load? So, while at an individual level, U=U provides powerful motivation for adherence to treatment and retention in care, it is crucial that we continue to strive for answers to the many as yet unanswered questions that still remain. Carrie Foote , Indiana University, Bloomington, IN, USA In early 2016, the Undetectable=Untransmissable (U=U) campaign began in an effort to ensure the message of U=U was shared with community; at the time there was much resistance to the science and hesitance to share the message with providers and people living with HIV. Led by people living with HIV, the campaign took off and now has become global; the U=U slogan is now universally known in the HIV arena around the world. This session provides an overview of the global campaign today, some of the main community impacts, and remaining community challenges. Key issues covered include: the impact

Oral Abstracts




CROI 2019

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