Skip to main content
NCBI home page
Journal of Virus Eradication logoLink to Journal of Virus Eradication
. 2016 May 1;2(Suppl 1):1–7.

Speaker presentations

PMCID: PMC5058489
J Virus Erad. 2016 May 1;2(Suppl 1):1–7.

S1 Hepatitis E: current status and future perspectives

Harry Dalton 1

Until recently, HEV was thought not to occur in developed countries. It is now clear that locally acquired HEV is common in many developed countries. HEV infection acquired in these areas differs from that in developing countries in a number of important aspects: it is caused by genotype 3 (and 4 in China and Japan); it mainly affects middle-aged/elderly males; it is zoonotic with a porcine primary host. Pig herds worldwide are infected with HEV genotype 3 and HEV has been found in the human food chain in a number of developed countries. However, the route of transmission is not fully understood, since most cases are not obviously associated with pigs/pig products. HEV can be transmitted by blood transfusion and surprisingly high numbers of asymptomatic blood donors are viraemic at the time of donation: Netherlands 1: 600, Germany 1:1200, England 1:2848.

Our understanding of the clinical phenotype of HEV infection in humans has undergone a sea-change in recent years. Previously, HEV was thought to cause only acute self-limiting hepatitis. However, HEV may cause persistent disease in the immunocompromised. Patients with chronic HEV infection have no symptoms, but some develop rapidly progressive liver cirrhosis. The full clinical spectrum of HEV is still emerging. HEV has important extra-hepatic manifestations, which deserve further investigation. For example, HEV can cause a wide range of neurological illness. In particular, very recent data suggests that Guillain–Barré syndrome and neuralgic amyotrophy are associated with locally acquired HEV in approximately 5% and 10% of cases, respectively.

J Virus Erad. 2016 May 1;2(Suppl 1):1–7.

S2 HCV: is mission accomplished? The pros

Stanislas Pol 1

An average of 150 million people are chronically infected by Hepatitis C virus (HCV) worldwide resulting in significant morbidity and mortality (500.000 to 1.4 million yearly), related to hepatic and extra-hepatic manifestations. The sustained virologic response (SVR), which corresponds to a complete recovery and is allowed by antiviral treatments, significantly reduces both morbidity (hepatocellular carcinoma, liver transplantation) and hepatic as well as extra-hepatic mortality. The overall mortality in those patients achieving SVR was reduced by 75%, especially in cirrhotic patients but also in HIV/HCV co-infected patients receiving interferon-including regimen and the occurrence of hepatocellular carcinoma at 5 years of follow-up dropped from 15 to 5% and need of liver transplantation from 10 to 1.2%, respectively in a recent meta-analysis. In a prospective French study of more than 1300 HCV-infected patients with biopsy-proven cirrhosis (the Cirvir ANRS CO12 cohort), at 3 or 5 years of post-treatment follow-up a significant decrease in the occurrence of hepatocellular carcinoma, of bacterial spontaneous peritoneal infection or other cirrhosis complications was reported in cirrhotic patients achieving SVR but also a 50% decrease in the occurrence of vascular disease (cardio- or cerebro-vascular disease). All these data, in line with registry studies, underline the need of achieving SVR in most if not all the HCV-infected patients, which means a large screening, an improvement of access to care of infected patients and of therapies.

The combination of pegylated interferon alfa and ribavirin (PR) which led to a sustained virologic response in around 45% of patients with HCV genotype (GT)1, 65% with HCV GT4, 70% with HCV GT3 and around 85% with HCV GT2 which was the standard of care for two decades. It has been replaced from 2011 to 2013 by a combination with PR and first-generation NS3/4A protease inhibitors (Telaprevir or Boceprevir) in GT 1-infected patients, allowing around 70% of SVR with a reduction of the duration of therapy from 48 to 24 weeks in half of treated patients. These first-generation regimens unexpectedly disappeared in 2014 with the rapid availability of interferon-free regimens combining different direct-acting antiviral drugs (DAAs). These DAAs target the main viral proteins involved in the replication cycle of HCV and combine NS3/4A protease inhibitors (Simeprevir or Paritaprevir boosted by ritonavir), NS5B nucleos(t)idic (Sofosbuvir) and non nucleos(t)idic (Dasabuvir) polymerase inhibitors, NS5A replication complex inhibitors (Daclatasvir, Ledipasvir, Elbasvir, Velpatasvir). This therapeutic revolution combines 2 or 3 second wave DAAs, with or without ribavirin (RBV) but without interferon. The combinations are given for 8 to 24 weeks, according to baseline factors including fibrosis stage, GT and subtype, baseline viral load, prior therapeutic history of the patient (naïve or experienced) and pre-existing resistance-associated substitutions (RASs) and reach SVR rates greater than 90% with a good tolerance. The SVR rates (and the safety) are similar in the clinical trials and in the real-life, usually higher than 95% in per-protocol analysis.

The costs (which will be markedly reduced with the generic drugs), the risk of rare severe adverse events (<1% in “priority” patients) and the risk of resistance-associated substitutions (around 4%) are the unique and rare limitations for considering the access to cure in HCV-infected patients.

J Virus Erad. 2016 May 1;2(Suppl 1):1–7.

S3 The contribution of sexology in the overall care of patients consulting for the screening of IST

Sandra Guiadeur 1

The 2015 Social Security financing law organizing, through the fusion of CDAG and CIDDIST, the new CeGIDD has opened the door to sexology and has therefore allowed to reaffirm the importance of a place where all questions about sexuality can be discussed.

Basing her action on counselling and not judging, with empathy and a positive view on things, the Conjugal Counselor/Sexologist can question the affective, relational and sexual dysfunctions.

Sexual Health is seen as an important factor of general health because it has an impact on the patient's whole life.

This place where people can speak confidentially, anonymously, with or without appointment allows patients to get information on the risks they take but also to take some time to express their emotions and try to speak about their problems.

It's a place where people can improve their knowledge on the mode of contamination, prevention, contraception but also to allow themselves to speak about personal problems.

Because the patients are not judged and their convictions are respected, it's by experiencing this free speech that they can mobilize personal and environmental resources to be able to face their troubles in a better way and find their own solutions.

The Conjugal Counselor and Family Sexologist guides patients toward other professions in the same field because her work can only be done through interdisciplinarity.

She neither examines nor prescribes, she's a professional of listening, counselling, supporting on all relational, affective and sexual problems, for single persons, couples, for all types of people, with all types of sexual orientations. She facilitates access to information that everyone can understand.

Conjugal Counselling, because of its long experience (it appeared in France in 1930s), and sexology, supported by the medical world, can both compare their views and suggest specific and complementary care. A few issues on which she can advise patients: lack of desire and pleasure, absence of orgasm, arousal problems, erection and ejaculation problems, misunderstanding, violence, unreal expectations, wrong ideas about sexuality, lack of knowledge on masculine and feminine sexuality, taboos …

These places where people can speak are also necessary to fight against gender stereotypes and against a sexuality which is endured and repressive.

J Virus Erad. 2016 May 1;2(Suppl 1):1–7.

S4 HIV genotypic drug resistance testing: digging deep, reaching wide?

Kristel Van Laethem 1

For many years, population-based Sanger sequencing has enabled personalized strategies for the treatment of Human Immunodeficiency Virus Type 1 infected patients in resource-rich settings. At diagnosis and entry into care, genotypic testing is to uncover transmitted drug resistance while at virological failure, causality assessment of failure is the aim. In both instances, the detected mutation profile guides the clinician in the subsequent selection of a potent antiviral therapy. Often, the data generated within this framework are subsequently used for research and surveillance purposes: to understand therapy responses and to gain insights into epidemiological processes. In the absence of simple and affordable resistance tests, resource-limited settings opted for a public health approach with the implementation of drug resistance surveillance at sentinel sites to guide the decisions on country-wide antiviral therapy programs. Next-generation sequencing may enable the roll-out of powerful genotypic testing in both resource-rich and –limited settings and contribute to a more comprehensive assessment of the emergence and spread of drug resistance and how to maintain long-term suppressive antiviral therapy. The decision whether these new technologies can transit from research purposes to clinical and epidemiological settings will largely depend on the strength of findings from large studies. From such efforts, continuous growth of data and knowledge will speed up the development of standardized testing systems, covering wet-lab automation to bioinformatics pipelines, and guidance documents for its clinical implementation.

J Virus Erad. 2016 May 1;2(Suppl 1):1–7.

S5 HIV healthcare providers' burnout

Tamar Ginossar 1

Stresses related to providing care for People Living with HIV (PLWH) changed with the dramatic decline in HIV- related deaths following the availability of antiretroviral therapy. However, caring for PLWH remains physically and emotionally taxing and HIV healthcare providers are at increased risk of burnout compared to other healthcare providers. Burnout is a psychological syndrome resulting from prolonged interpersonal stressors in occupational setting. Individuals suffering from burnout feel emotional exhaustion, reduced professional accomplishment and demonstrate callousness toward clients and peers. Providers’ burnout is a significant concern as it increases turnover in health care organizations and decreases the quality of care provided to patients.

Burnout research has typically focused on the relationship between burnout and individual-level factors. However, as burnout is caused by chronic occupational stress, it is pertinent to consider organizational-level factors that might influence burnout. An important organizational factor that was not previously examined refers to organizational culture, or the shared expectations for behavior in the organization. Specific organizational cultural factors that might influence providers’ burnout include teamwork, involvement in organizational decision making, and social undermining. Examining organizational-level influences on providers’ burnout has the potential to expand the theoretical and practical knowledge of this syndrome and can inform the design of effective interventions to reduce burnout among HIV healthcare providers.

In this presentation I will discuss the importance of considering the role of organizational culture in provider burnout, and review a short survey instrument measuring organizational culture. I will describe a study that utilized a cross sectional survey design to examine the relationship between HIV healthcare providers’ burnout and organizational culture factors. The results of multiple regression analysis indicated that positive organizational culture was negatively related to burnout. These findings suggest that effective organizational communication might protect HIV healthcare providers from burnout. Drawing on this study and on healthcare organizational research, I will provide directions for exploring the impact of organizational culture on providers’ experiences of burnout, and the potential of interventions to change current burnout rates in HIV healthcare organizations.

* This presentation is based on the following article:

Ginossar, T., Oetzel, J., Hill, R., Avila M., Archiopoli, A., & Wilcox, B. (2014). HIV healthcare providers’ burnout: Can organizational culture make a difference? AIDS Care 2014 26: 1605–1608.

J Virus Erad. 2016 May 1;2(Suppl 1):1–7.

S6 The Zika virus: a new threat?

Nikolaos Vasilakis 1

Zika virus (ZIKV), a previously obscure flavivirus closely related to dengue, Spondweni and yellow fever viruses, re-emerged in 2007 to cause a series of rolling epidemics in the South Pacific and most recently in the Americas reaching pandemic levels. ZiKV, who has been originated and evolved in sub-Saharan Africa, it spread in the distant past to Asia and has probably re-emerged on multiple occasions into human transmission cycles involving Aedes (Stegomyia) spp. mosquitoes and human amplification hosts. Like many other arboviruses, it is often misdiagnosed because its mild flu-like illness resembling mild dengue-like illness. The unprecedented numbers of people infected during recent outbreaks in the South Pacific and the Americas may have resulted in enough ZIKV infections to notice relatively rare congenital microcephaly, Guillain–Barré and other rare ocular or auditory syndromes. Another hypothesis is that phenotypic changes in Asian lineage ZIKV strains led to these disease outcomes. Here, a review potential strategies to accurately diagnose and control the ongoing outbreak through vector-centric approaches as well as the prospects for the development of vaccines and therapeutics will be presented.

J Virus Erad. 2016 May 1;2(Suppl 1):1–7.

S7 The Médecins Sans Frontières experience with Ebola

Armand Sprecher 1

Notwithstanding the experience gained during multiple previous Ebola outbreaks, Médecins Sans Frontières (MSF) was not prepared for the devastating 2014-2016 epidemic and rapidly overstretched while tackling the typical six-pillar approach: patients’ isolation and care, safe burials, community engagement, disease surveillance, contact tracing and re-establishing healthcare systems. The unpredictable epidemic spread forced MSF to make the strategic choice to concentrate on the most technical, setting up and managing 15 Ebola treatment and transit centers in the three countries while supporting and training other actors to contribute to the outreach activities. The international response came late, the importance of engaging affected communities underestimated and the support to the crumbling health system quasi inexistent. Forty years of known Ebola virus existence had not resulted in substantial scientific advances, or generated research and development of medical countermeasures outside preparedness for bioterrorism. As main service provider, MSF decided to engage in clinical trials to rapidly identify agents improving survival or diminishing transmission, facing risks and unforeseen challenges related to choice of intervention, trial design, community acceptance and results’ interpretation. The positive outcome of the rVSV vaccine trial enabled further deployment of the ring vaccination strategy when required. While this outbreak has triggered improvements on infection control, outline and organization of treatment centers, triage and monitoring of patients and use of invasive interventions, major knowledge gasps were not addressed as disease pathophysiology, optimal supportive therapy, infectivity or effectiveness of community strategies. Ebola survivors need medical, psychological and social attention and support but the ethically sound balance needs to be made between care and research. A lot of data and biological samples were collected during this recent outbreak, making it a unique opportunity to gain knowledge provided there is a transparent process with coordination of the research agenda, communities’ trust and involvement are respected and benefit sharing guaranteed.

It is uncertain whether the world is better prepared for outbreaks with unknown or neglected pathogens. The Zika epidemic generates a lot of attention but there is limited support for the current yellow fever outbreak in Angola for which no therapy exists and vaccine stocks are largely inadequate.

J Virus Erad. 2016 May 1;2(Suppl 1):1–7.

S8 Challenges, opportunities and lessons learned from the Ebola virus outbreak in Guinea, West Africa

Abdoul Habib Beavogui 1

Introduction:

On December 29th, 2015, WHO officially declared Guinea free of the Ebola Virus Disease (EVD) outbreak that started in December 2013. The purpose of this work is to draw lessons learned on various aspects during the outbreak.

Materials and methods

We conducted a qualitative analysis of the EVD outbreak and its socio-economic consequences in the country. This situational analysis focused on actors’ field experiences, strategies of response and clinical research. Epidemiological features of the EDV, mains constraints, challenges and lessons learned in terms of impacts, achievements and prospects are presented.

Results

Since the recognition of EVD outbreak of the EDV on March 23th, 2014 in Guinea, the national Ebola response was organized with the support of the international community. The EVD affected 27 out of the 34 country's health districts along with the capital city Conakry. As of December 29, 2015, a total of 3805 cases (confirmed, probable and suspect) were recorded nationally, with 2,536 deaths (67%). Among health care workers, 211 confirmed cases were recorded with 115 deaths (55%).

Key findings

A weak national health system with low public funding, lack of qualified human resources, weak organization and management of health services, low attractiveness of health services, poor infection prevention measures, lack of strong community-based services, inappropriate communication strategies and weaknesses in the disease surveillance system including early warnings were the main factors hindering the Ebola response in Guinea.

Negative impacts

curtailing of visits within health structures, loss of lives, stigmatization of the survivors, disruption of social habits and practices, mobility, community reluctance, slowness of the economy, and decrease of household incomes.

Achievements/opportunities

obvious political support, more national and international solidarity and development of further partnerships with international universities and health research institutions, more community involvement, national capacity building (training of local actors in surveillance, public response), promotion of hygiene, possible reduction of water borne diseases, strengthening of International Health regulation implementation within Guinea, development of clinical research to improve the disease control strategies. Engagement of initiatives aiming at strengthening Health systems

Conclusions

The EVD highlighted weaknesses in Guinea's health care system. In addition to human loss, it negatively impacted all numerous socio-economic indicators of the country. Conversely, the national response supported by the international community led to the control of the outbreak providing better capacities for the future. As the epidemic is unpredictable, there is a need for increased and continued vigilance along with sustaining of good practices.

J Virus Erad. 2016 May 1;2(Suppl 1):1–7.

S9 New immunological tools for HIV research and monitoring

Lucy Dorrell 1

CD8+ T cells play a key role in the initial control of HIV during primary infection but are unable to eliminate the virus. Intensive effort has been devoted to characterising CD8+ T cell function in rare individuals who achieve sustained control of HIV without antiretroviral therapy (ART), in the hope that this will inform the design of more effective vaccines and therapies. However, the knowledge gained has yet to be translated into a cure; the reality for the majority of those living with HIV is a lifetime of pill-taking. Strategies that harness effective HIV-specific CD8+ T cells may be necessary to achieve an ART-free remission. We have shown that the capacity of CD8+ T cells to block HIV replication in culture can be measured reproducibly in patient cohorts with diverse genetic backgrounds and viral subtypes and provides a robust predictor of both CD4+ T cell preservation and virological control. Furthermore, we have shown that this antiviral activity is dependent on CD8+ T cells that target sites of vulnerability in the HIV proteome. Initiation of ART during chronic infection does not appear to lead to recovery of effective CD8+ T cell function. However, early ART and/or therapeutic immunisation with new rationally designed immunogens that focus responses towards vulnerable epitopes may be beneficial, particularly when vaccines are combined with agents to reactivate latent HIV. Finally, encouraging data are emerging from in vitro studies with bispecific T cell-retargeting agents that harness polyclonal CD8+ T cells to kill HIV-infected cells. These agents show potential as a component of viral eradication strategies.

J Virus Erad. 2016 May 1;2(Suppl 1):1–7.

S10 The HIV PreP debate

Laurent Cotte 1

The sustained transmission of HIV urged for the development of new tools for prevention, including regular testing in high-risk groups, early treatment for HIV-infected persons and pre-exposure prophylaxis (PrEP). The efficacy of a pre- and post-exposition antiretroviral treatment for the prevention of HIV transmission has been demonstrated in macaques. Tenofovir (TDF) has been extensively tested, due to a rapid antiviral activity, the scarcity of circulating resistant viruses and high concentrations in the rectal and vaginal tissues following oral administration. Several ways of administration have been tested, as vaginal gel and pills, combined or not with emtricitabine (FTC). Every day and on demand administration have been tested in heterosexual populations and in men having sex with men (MSM). The efficacy of PrEP for the prevention of HIV infection appears highly correlated with treatment adherence, reaching 86% in high-risk MSM in the ANRS IPERGAY and PROUD trials. The clinical and biological tolerability appears good, similar as that observed in HIV-infected patients under combination antiretroviral treatment. Resistance to TDF or FTC has been rarely observed in case of HIV infection in PrEP trials, the majority of infected patients having stopped the treatment for months. Resistance mutations usually do not persist more than a few months following infection. A high incidence of sexually transmitted infections (STIs) is observed in patients under PrEP, in a context of a global rise in STIs in these high-risk populations. Medico-economic analyses suggest that PrEP will be cost-effective in high-risk populations. PrEP became available in the US in 2014 and in France at the beginning of 2016. First results of these programs indicate the interest and good adherence of high-risk populations to this preventive strategy.

J Virus Erad. 2016 May 1;2(Suppl 1):1–7.

S11 HIV PreP opens the door to STDs. The pros

Alain Lafeuillade 1

HIV-1 pre-exposure prophylaxis with Truvada™ has been shown capable to reduce viral transmission in several trials including the French-Canadian IPERGAY trial. However, nothing is currently known on the possible effect on the transmission of other STDs when PreP is used outside a clinical trial.

In France, a significant increase in the transmission of syphilis is observed since the year 2000, in particular in MSM. Gonococcal infections also increase in the same group regularly since 2005.

When we look at the analysis of risk behavior among MSM in the IPERGAY trial, it is striking to note that overall 70 percent of participants reported condomless anal intercourse during their most recent encounter without significant change during follow-up. This means that despite regular counseling in the context of a clinical trial, high risk MSM did not change their practices. In other words, it means that participants are quite only preoccupied by the risk of HIV transmission but not the risk of other STDs which, even HCV, are curable.

This lack of sexual risk behavior decrease let us think that, in real life and over the years, the implementation of PreP will increase the rate of other STDs.

J Virus Erad. 2016 May 1;2(Suppl 1):1–7.

S12 HIV PrEP opens the door to STDs. The cons

Mark Wainberg 1

The use of condoms is clearly able to defend against the transmission of HIV as well as all other sexually transmitted diseases. Concern has therefore been expressed that non-barrier approaches to HIV prevention including the use of PrEP, that is specific for HIV, may result in higher rates of transmission of other sexually transmitted illnesses such as syphilis, gonorrhea, and lymphogranuloma venereum among others. Indeed, there is evidence that this has already happened. The question is therefore whether this trend can be reversed. To this end, it follows that more education and awareness are needed to appraise people at risk of acquisition of HIV and that PrEP will only protect against HIV and not other STDs.

Recommendations must continue to state that condoms be used together with PrEP in order to provide maximal protection against all forms of STDs. In addition, efforts to test and treat all persons infected by HIV must be intensified so as to reach the WHO 90-90-90 goals as soon as possible, since the HIV epidemic can at present be stalled most effectively by ensuring that as many people as possible receive adequate therapy, thereby reducing viral loads and rendering HIV-infected persons non-infectious for their sexual contacts. However, there is widespread consensus that the identification of the 90% of people who are HIV positive will be far more difficult to achieve than the attainment of their successful treatment. We must therefore urgently strive to identify everyone who is HIV-infected and serious consideration should be given to the notion that financial incentives be offered to people at risk so that they agree to be tested for HIV. The successful treatment of HIV-infected populations everywhere will ultimately lead to an end to the HIV epidemic, thus obviating the need for PrEP.

In the meantime, we must continue to insist on the principle that condoms are used together with PrEP in order to ensure that transmission of non-HIV STDs does not increase.

J Virus Erad. 2016 May 1;2(Suppl 1):1–7.

S13 HIV cure is unachievable. The pros

Marie-Lise Gougeon 1

The question is: what do we mean by a cure of HIV infection? Is it sustained virologic remission or sterilizing cure? Based on our current knowledge, I believe that a sustained control of the virus in the absence of ART is reachable by enhancement of the host's HIV specific immune response and/or administration of immune-mediating agents and vaccines. In contrast, I do not believe that completely and permanently eliminating HIV in an infected individual is possible. The mechanisms involved in the maintenance and persistence of HIV reservoirs will be discussed, focusing on new sources of replicating viruses and reservoirs. The recent therapeutic approaches aiming at eradicate HIV reservoirs and their impact on virus persistence, in particular in tissues, will be reviewed, and the consequences on the concept of virus eradication will be debated.

J Virus Erad. 2016 May 1;2(Suppl 1):1–7.

S14 HIV cure is unachievable. The cons

Jean-Pierre Routy 1

Antiretroviral therapy (ART) has reshaped the lives of millions of individuals infected with human immunodeficiency virus (HIV). Patients initiating ART early in the course of infection benefit from a considerable reduction in the risks of developing acquired immune deficiency syndrome (AIDS) and HIV-related inflammatory events. However, the absence of spontaneous cure and lifelong requirements of treatment highlight the imperative need to develop better tools to monitor persistent infection on ART and to validate more sensitive markers of immune activation for lymphoid and myeloid cells while improving antibodies (ADCC) and cytotoxic HIV-specific immunotherapeutic strategy.

Like for cancer, a paradigm shift has occurred with the contribution of immune activation, digestive dysbiosis and their metabolites in a context of leaky gut leads to microbial translocation priming aberrant systemic immunity in restricting the ability of the host to mount an effective immune response. The development of gene therapy with the revolutionary CRISPR Cas9 technology and/or the combined approaches that include 1) enhanced ART distribution in anatomic reservoirs like lymph nodes, digestive tract, brain and testis with 2) inhibition of immune activation and modulation of follicular T cells in germinal centers 3) breakage of viral latency 4) HIV-specific vaccination and 5) immune restoration should lead to a functional or sterilizing cure.

J Virus Erad. 2016 May 1;2(Suppl 1):1–7.

S15 The future of HIV care

Roy Gulick 1

Worldwide, 16 million people currently receive antiretroviral therapy (ART). Current ART controls HIV infection long-term and helps successfully treated HIV-infected individuals achieve a life expectancy near or the same as that of the general population. There are 29 antiretroviral drugs approved for the treatment of HIV infection in 6 mechanistic classes. Current ART guidelines recommend an initial treatment regimen consisting of a combination of 2 nucleoside analogue reverse transcriptase inhibitors (NRTIs) and a third drug, either a non-nucleoside reverse transcriptase inhibitor (NNRTI), a boosted protease inhibitor (PI), or an integrase inhibitor (II). Current ART regimens are highly potent, safe, tolerable, and convenient. One pill, once-daily regimens are widely available and current virologic suppression rates can exceed 90% in clinical trials and cohort studies. Newer strategies, formulations, and investigational antiretroviral agents continue to move HIV treatment forward. Although a 3-drug ART regimen is standard, potent 2-drug regimens are under investigation. New formulations of current drugs include co-formulations of drugs that reduce pill counts. Long-acting injectable compounds are under study including an injectable investigational formulation of the approved NNRTI, rilpivirine, and an investigational integrase inhibitor, cabotegravir, that can be dosed together every 1-2 months. Other investigational formulations include implantable devices that provide sustained release of antiretrovirals, and other newer technologies. The investigational antiretroviral pipeline contains new agents in existing classes (NRTI, NNRTI, PI, II) and some of these are associated with less toxicity than current drugs (e.g. tenofovir pro-drug TAF; NNRTI, doravirine). Two new mechanistic antiretroviral classes under investigation are the CD4 attachment inhibitors (e.g. BMS-663068) and the HIV maturation inhibitors (e.g. BMS-955176), and candidate drugs in each class are in phase 2-3 clinical development. Recognizing the great success of antiretroviral therapy, a newer goal is the cure of HIV infection. While only a single unique patient under extraordinary circumstances is considered cured to date, research is underway to develop strategies to safely identify and target the latently HIV-infected cell reservoir and attempt to eliminate it. While awaiting the further exploration of HIV cure research strategies, we currently can control HIV infection long-term with potent, safe, and convenient antiretroviral therapy.

J Virus Erad. 2016 May 1;2(Suppl 1):1–7.

S16 Anti-HCV DAA are needed whatever liver fibrosis is. The pros

Albert Tran 1

According to different guidelines, it is now recommended to treat HCV positive patients with advanced fibrosis. Cirrhotic patients cured of their hepatitis C have less incidence of liver-related complications and less liver-related mortality. What about patients with less severe liver damage? Treatment of these patients is largely justified in the era of direct anti-virals. In many cohort studies, virologic efficacy is over 90%. The tolerance of these drugs is excellent. When ribavirin is not necessary, it is similar to placebo. The efficacy of current anti-virals is lower when patients have cirrhosis, in particular when they are infected with genotypes 2 or 3. The evaluation of liver damage by liver biopsy or by non-invasive methods is not always easy and devoid of mistakes. Sustained virological response improves the quality of life of patients and their productivity at work. It also improves the extrahepatic manifestations, including cardiovascular complications. Finally, the modeling shows that the reservoir of patients with hepatitis C can only be removed in the early 2025 only if patients with mild lesions are treated today. Finally, the real question is not ‘whether to treat patients with mild liver lesions,’ but ‘am I allowed to treat such patients’ given the constraints of the various health insurance.

J Virus Erad. 2016 May 1;2(Suppl 1):1–7.

S17 Anti-HCV DAA are needed whatever liver fibrosis is. The cons

Pablo Barreiro 1

Direct-acting antiviral (DAA) drug-based combination therapies constitute a milestone in the treatment of chronic infections, as for the first time we can truly speak of virus eradication for such conditions. Efficacy of these therapies is also very significant, while in the small proportion of failures HCV resistance is very frequent. This type of failure may be due to NS5A inhibitors resistant viral populations present before therapy, which most likely affects less susceptible infected populations (HCV-1a infection, advanced liver fibrosis, previous failures to pegylated interferon-based therapy). Right after virological failure, HCV resistant quasispecies predominate. In the case of NS3-4A protease inhibitors resistance, wild type virus returns as main population within weeks to months after treatment interruption. Conversely, NS5A inhibitor resistant viruses may be circulating for years. Although retreatment options in case of failure to DAA drug-based combinations are now at hand, patients with prior failure and selection of HCV mutants may again have lower chances to respond.

The issue of cost of DAA drugs may also be considered as a factor to prioritize HCV treatment according to the extent of liver fibrosis. Ideally all HCV infected patients should have access to therapy, but we have to acknowledge this is not feasible in many parts of the World, particularly in those areas where HCV infection is more prevalent. The possibility of examining liver fibrosis by non-invasive means also facilitates selection of patients with the “fibrosis criterion”.

Clinical prognosis of patients with chronic hepatitis C and not significant liver fibrosis is nearly comparable to that of general population. It is true that chronic hepatitis C is related with greater cardiovascular risk, metabolic and immune mediated complications, but there is still lack of evidence to indicate HCV therapy before liver fibrosis is advanced for those reasons.

J Virus Erad. 2016 May 1;2(Suppl 1):1–7.

S18 Progress toward HIV cure

Daniel Kuritzkes 1

The advent of potent combination antiretroviral therapy (ART) has led to a dramatic decrease in the incidence of AIDS and AIDS-related mortality worldwide. For most patients, full suppression of human immunodeficiency virus type 1 (HIV-1) replication can be achieved by once-daily administration of an ART regimen available as a fixed-dose combination that is safe, convenient and well-tolerated. Nevertheless, a treatment that led to durable drug-free remission or eradication (cure) of HIV-1 could reduce the burden, cost, toxicities and stigma associated with long-term ART, and might lower immune activation and the associated risk of non-AIDS clinical events. The search for a cure therefore remains a high priority for clinicians, investigators and patients. To date, only a single individual (Mr. Timothy Ray Brown, known as the “Berlin” patient) has had apparent cure of HIV infection. In his case, the patient underwent allogeneic hematopoietic stem cell transplantation (HSCT) for treatment of acute myelogenous leukemia using cells from a donor homozygous for a deletion in the CCR5 gene. Although ART was stopped at the time of transplantation, HIV did not rebound and has remained undetectable during more than 7 years of follow-up. Attempts to repeat this approach in other patients have been unsuccessful to date. Current efforts at eradicating HIV infection or inducing long-term ART-free remission include activation of HIV transcription in latently infected CD4+ T-cells; enhancing HIV-specific immunity in order to target and destroy cells harboring latent infectious proviruses; and cell-based therapies using genetically modified CD4+ T-cells or hematopoietic stem cells. Several exploratory pilot studies are underway with each of these approaches. Major challenges include the difficulty of quantifying the HIV reservoir, the uncertain safety of the experimental treatments under study, and the need to balance the risk of these interventions against the generally well-tolerated and proven efficacy of long-term ART.

J Virus Erad. 2016 May 1;2(Suppl 1):1–7.

S19 Prospects for a HIV vaccine

Dan Barouch 1

We have recently reported the protective efficacy of Ad26/MVA and Ad26/Env vaccines against SIVmac251 and SHIV-SF162P3 challenges in rhesus monkeys. In particular, we showed that an Env gp140 protein boosted functional antibody responses and improved protection. I will review and update these preclinical data and discuss the correlates of immune protection in this model. I will also provide an update of our phase 1/2a clinical trial program with these vaccine regimens and outline plans for further clinical development towards phase 2b/3 efficacy trials.

J Virus Erad. 2016 May 1;2(Suppl 1):1–7.

S20 New approaches toward STDs screening and diagnosis with the new CeGIDD model of care

Thierry Troussier 1

Background

These new strategies form part of a national context where sexual health indicators are alarming. Persistence of the HIV epidemic among men who have sex with men (MSM) and resurgence of STIs in this population but also among young people. Indicators in the field of reproductive health are not entirely satisfactory, particularly in the overseas territories. The new measures, voted on January 26, 2016, the Modernization Act of Our Health System introduced in the Code of Public Health, sexual and reproductive health, the waiver of parental consent for minors for the prevention, screening and treatment in the field of sexual and reproductive health, the course health and patient autonomy.

Methods

The High Public Health Council (HCSP) was seized in early 2015 by the Directorate General of Health to evaluate the national plan against HIV and STIs 2010-2014 and to make recommendations on sexual health strategy and reproductive health. Reviews were published in April 2016, HCSP considers that support sexual health is currently fragmented among many institutions and in various plans and public health policies with no real connection between them. It proposes to transform the approach by pathology and risk in a comprehensive, enhanced by a sexual health course with special attention to the individual, its specificities and its choice.

Results

Based on the HCSP recommendations on sexual and reproductive health, General Health Directorate develop in 2016 a national strategy for sexual and reproductive health function that associates axes such as national and territorial coordination for better access to the sexual health; information, education, training; the reproductive health; prevention and screening for STIs; the inclusion of people with specific features research. It is transforming the approach by pathology and risk in a comprehensive, enhanced by a sexual health course with special attention to the individual, its specificities and its choice.

Conclusion and discussion

The development of a sexual health strategy must address several issues:

  • –

    It is part of the implementation of the national health strategy which defines the framework of public action for the coming years: fight injustice and health inequalities such as access to the health system, investing including the field of health promotion and prevention and developing a proactive approach to health education.

  • –

    It implements new measures related to sexual and reproductive health, passed January 26, 2016, the Modernization Act of Our Health System introduced in the Code of Public Health.

  • –

    It must promote a health its integrated offering sexual health, reproductive health, the fight against HIV, STIs and viral hepatitis

  • –

    It must answer to societal determinants who deal directly on individual sexual behavior (poverty, social exclusion, gender inequalities, discrimination) promoting legislation in conformity with human rights.

This new strategy is a national challenge that requires a multisectoral approach between the laws and human rights, education, society and culture, the economy and health systems.

J Virus Erad. 2016 May 1;2(Suppl 1):1–7.

S21 Performance of rapid diagnostic tests for the screening of HIV infection during primary infection and at the chronic stage

Agnès Gautheret-Dejean 1

In 2014, The World Health Organization (WHO) estimated that 36.9 million of adults and children were living with HIV. Among them, 2 million were newly infected, and around 19 million of the infected people didn't know their seropositivity. In order to target to end the AIDS epidemic as a public health threat by 2030, world health authorities have proposed three objectives for 2020: 90% of the people living with HIV know their HIV status, 90% of the people who know their HIV status receive treatment, and 90% of the people who receive treatment have suppressed viral load. Thus, the diagnosis of HIV infection becames a priority of public health. In July 2015, new consolidated guidelines on HIV testing have been published by the WHO, including the use of two or three assays in case of positivity. Countries choose at first from 6 to 10 assays prequalified by the WHO and, secondly, have to find an adequate combination according to the local epidemiologic specificities. Around the world, a majority of HIV infections are diagnosed by the use only of rapid diagnostic tests (RDTs). As a consequence, their performance in terms of sensitivity and specificity are crucial.

The main advantages of RDTs are rapid result obtaining, high accessibility to go as closely as possible to the population to be tested, possibility of self-testing, for some RDTs differentiation between HIV-1 and HIV-2 infection. However, numerous limits exist including subjectivity of reading conducing to misinterpretation, false negative result during primary infection and for some HIV strains (in particular HIV-1 group O), false positive results, cross-reactivities between HIV-1 and HIV-2 antigens suggesting the existence of a false dual infection, only few data available on their stability at high temperature of storage, the absence of traceability, detection of infection by HIV only. Studies to illustrate these main advantages and limits of the RDTs used currently will be presented.

J Virus Erad. 2016 May 1;2(Suppl 1):1–7.

S22 The French surveillance system of syphilis: current epidemiological trends

Nadjet Benhaddou 1

Sexually transmitted infections (STIs) are a public health problem because of their frequency, risk of sequelae (infertility) and increased HIV transmission. Surveillance of syphilis since 2000 based on the RésIST network volunteer clinicians practicing in various diagnostic areas: information centers, screening and diagnosis of STIs (CIDDIST), anonymous and free screening consultations (CDAG), consultations hospital dermatology, infectious diseases and internal medicine, private medical practices. The cases of recent syphilis are defined by clinical and biology. The clinic includes three stages of infectious syphilis: Primary (presence of a chancre), secondary (presence of mucocutaneous lesions localized or diffuse) and early latent (without clinical signs, the initial infection has occurred in the last 12 month). The case must be confirmed biologically (darkfield microscopy, VDRL and TPHA serology, gene amplification: PCR). STI surveillance data in 2014: Patients diagnosed in Ile-de-France represent almost 30% cases. The homo- bisexual men account for over 80 % of patients. An increase in the number of cases is also seen among heterosexuals since 2012.The median age for men was 36 years versus 29 years for women. the existence of clinical signs of STIs motivates 61% of consultations while a routine screening concerns 21% of cases. The existence of an STI in a partner (2%) and medical monitoring of HIV status (11%) are less frequent reasons for consultation. One third of patients was co-infected with HIV: 31% of seropositive HIV were known while 3% were discovered during the diagnosis of syphilis. these co-infections affect 40% of homo-bisexual men, 23% of heterosexual men and 3% women. Among patients whose HIV status was known positive at diagnosis of syphilis, 75% were receiving antiretroviral therapy. Sexual behavior is globally stable in regard to both the number of sexual partners that consistent condom use. The systematic use over the last 12 months of condoms during oral sex is rare (<2% in 2014), regardless of sexual orientation, while syphilis can be transmitted via this route.

J Virus Erad. 2016 May 1;2(Suppl 1):1–7.

S23 Prospects for current hepatitis C treatment failures

Vicente Soriano 1

Introduction

Chronic hepatitis C virus (HCV) infection has become a curable disease. Sustained virologic response rates above 90% have been achieved with recommended direct-acting antiviral (DAA) combinations in most registration trials. However, outcomes in real-world patients are lower. In patients experiencing DAA failure, resistance-associated variants (RAVs) are almost universally selected. At this time, it is unclear when and how to re-treat hepatitis C in patients with prior DAA failure.

Areas covered

The rate of DAA failure and predictors of lack of treatment response using distinct DAA combinations are analyzed. We discuss the management of HCV treatment failure and the impact of RAVs on re-treatment strategies.

Conclusion

Failure to DAA combinations occurs more often in chronic hepatitis C patients with baseline predictors of poor response, including RAVs, genotypes 3 or 1a, advanced liver cirrhosis, elevated serum HCV-RNA and perhaps HIV coinfection. Impaired antiviral efficacy may be recognized when multiple of these factors are present. On-treatment predictors of DAA failure are poor drug adherence and development of side effects. Extending the length of therapy, adding ribavirin and/or using DAA from other drug families may allow successful re-treatment of most prior DAA failures.

J Virus Erad. 2016 May 1;2(Suppl 1):1–7.

S24 Search for chronic HBV infection curative therapies

Markus Cornberg 1

The definition of cure of chronic Hepatitis B Virus (HBV) infection is not well defined. Can we achieve complete cure that means complete elimination of covalently closed circular DNA (cccDNA) or only functional/clinical cure? So far HBsAg seroclearance as surrogate of inactive cccDNA is the anticipated end-point associated with clinical cure of HBV-infection. Current direct antiviral therapies with nucleos(t)ide analogues (NA) only achieve HBsAg clearance in less than 5% and life-long treatment is required in almost all cases. Treatment with interferon alpha (IFN) slightly increases HBsAg loss rates to 10%. Therefore, add-on or switch IFN studies are currently on going. However, there is an unmet need for more effective strategies. One concept is the modulation of innate and adaptive immune responses to combat infected hepatocytes. Different approaches are in preclinical or early clinical development such as Toll-like receptor agonist, therapeutic vaccinations, transferring of engineered HBV-specific T cells or targeting checkpoint regulators (i.e. PD-1). Interestingly, stopping NA and subsequent HBV DNA rebound combined with ALT flares may also indicate induction of immune responses and considerable HBsAg loss rates have been documented in small trials. Another approach is the inhibition of cell entry. The discovery of the HBV receptor NTCP will lead to new discoveries. Myrcludex, a synthetic N-acetylated pre-S1 peptide that can also dock to NTCP is already tested in phase II studies. The inhibition of HBV protein translation via RNA interference (siRNA) is currently evaluated and may not only lead to reduction of HBV proteins (i.e. HBsAg) but also to restoration of immune responses. A very promising target of small molecules is the core protein (Cp) because it is very conserved; Cp binds cccDNA and maintains the mini-chromosome in a transcriptionally active state; Cp is also important for the capsid formation and cccDNA replenishment and Cp inhibits interferon stimulated genes (ISG) expression. Thus, so-called core protein assembly modulators (CpAM) could have different ways to inhibit HBV. First drugs are in early clinical development. However, there is a very high bar for all these new developments in terms of safety because they will be compared to the once daily well-tolerated oral NA therapy.

J Virus Erad. 2016 May 1;2(Suppl 1):1–7.

S25 Multi-resistant tuberculosis

Maryline Bonnet 1

Multidrug resistant tuberculosis (MDR-TB) is caused by M. tuberculosis strains that are resistant to the most potent anti-tuberculosis drugs in standard treatment, isoniazid and rifampin. Globally, an estimated 3.3% of new TB cases and 20% of previously treated cases have MDR-TB, half of them in China, India and the Russian Federation. MDR-TB is especially prevalent in Eastern Europe and Central Asia, where up to a third of new TB cases are MDR-TB, but is also increasing in Africa. Acquired drug resistance resulting from poor treatment adherence or mismanagement is common but spread of MDR-TB particularly in Eastern Europe and Central Asia have been also found to be associated with a specific phylogenetic lineage/genotype of the M. tuberculosis, the Beijing genotype. In Africa, the correlation between HIV infection and MDR-TB remains controversial.

Despite an increase of MDR-TB detection thank to the expansion of the rapid test XpertMTB/RIF® allowing simultaneous detection of M. tuberculosis and rifampicin drug resistance, in 2014 only 123,000 new MDR-TB patients of the 480,000 estimated, worldwide, were actually diagnosed.

In 2014, an estimated 190,000 people died of MDR-TB. The lack of a safe and effective treatment is a major obstacle to delivering appropriate treatment to MDR-TB patients. Fewer, 111,000 (23%), ever received any treatment with second-line TB drugs and only half of them are cured globally. Due, in part, to a 50-year drought in anti-TB drug development, patients are exposed to 18-24 months of toxic, poorly tolerated treatment regimens of that result in frequent default and further amplification of drug resistance to second-line TB drugs. On average 9.0% of MDR-TB cases have extensively drug-resistance TB (XDR-TB) defined by additional resistance to an injectable agent and a fluoroquinolone.

Finally, in 2013 and 2014, two new anti-TB drugs, bedaquiline and delamanid were approved by stringent regulatory authorities for the treatment of MDR-TB. The pivotal trials of these drugs simply added each to a background regimen, improving interim and long-term outcomes, but retaining the toxic, long, standard of care. Integration of these drugs in novel, shorter oral, MDR-TB treatments are under investigations.

J Virus Erad. 2016 May 1;2(Suppl 1):1–7.

S26 Facing the influenza challenge

Bruno Lina 1

Influenza viruses are emerging and re-emerging threats with both economic and medical impact. Beside the yearly epidemics due to seasonal influenza whose burden can be very high as observed during the 2014-2015 winter season in the Northern hemisphere, alerts related to avian viruses that may result into pandemic viruses in case of adaptation. Hence, the challenges are multiples on all these facets of the influenza viruses. These challenges include a better monitoring and anticipation of the epidemics, a better disease management with the antivirals and vaccines available as of today. Amongst the expected improvements, we have recently implemented tools for the rapid identification of the antigenic variants escaping the vaccine-induced protection. In the future we hope to be able to anticipate these mutations, and prepare vaccines that would protect against future variants. Recently, new seasonal vaccines have been developed and proposed to specific target groups. This can be seen as one of the future challenges: personalized influenza vaccination in link with your immune status, age group and chronic conditions.

Beside seasonal influenza, the monitoring, surveillance and management of avian influenza viruses both in human cases and during large scale infections in birds is also crucial. We have now a quite large knowledge on the adaptive mutations required for these avian viruses to infect and subsequently spread in the human population, but the rapid development and implementation of large vaccination campaigns remains difficult and a real challenge. In addition, the number of available antivirals to treat influenza cases remains too limited and there is a need for additional drugs.

When dealing with influenza viruses, it is now well established that we can expect anything form this constantly moving target. Again, this emerging and re-emerging virus is a permanent challenge for which we need to be prepared to face unexpected events during seasonal epidemics or during a pandemic, with a need to be prepared for the worst while hoping the best.

Articles from Journal of Virus Eradication are provided here courtesy of Elsevier

RESOURCES