LIVE FROM IAS: MONDAY, JULY 24, 2017
Christina Psomas, MD, PhD is our « grand reporter »
Early this morning took place the first non-commercial satellite symposium around systemic PrEP (MOSA02) organised by HPTN/FHI 360.
Myron Cohen from UNC School of Medicine, United States, did an overview of the field of systemic PrEP (MOSA0202). She reminded combination of four prevention opportunities, namely a behavioural one to avoid exposition, the precoital/coital and postcoital ones to decrease the effect of a possible transmission, and Treatment AS Prevention (TASP) in order to reduce infectivity of People Living with HIV (PLWHIV). The challenge of sustained adherence to the daily regimen of oral TRUVADA for PrEP imposes the constant need of new agents, such as Long Acting injectable formulations, BnABs and antiviral implants.
Monoclonal antibodies for HIV prevention were interestingly developed by Nyradzo Mavis Mgodi of the University of Zimbabwe, Zimbabwe (MOSA0203). The AMP study is a phase 2b study that is underway, including two harmonized test-of-concept trials. It evaluates the efficacy of VRC01 broadly neutralizing monoclonal antibody in high risk populations of 47 sites (11 countries). Combination of VRC01 with new generation of neutralising antibodies (VRC07-523) will likely improve potency and breadth of protection.
Thomas John Hope from Northwestern University, United States, presented next generation drugs and delivery for PrEP, namely Sustained Long Acting Protection from HIV (SLAP-HIV). SLAP-HIV concerns injectable formulations, as well as biodegradable and removable implants. Remains yet to prove the comparative efficacy of oral PrEP (systemic) vs topical PrEP (microbicides), as well as if prevention of systemic infection also means prevention of infection at the cellular level. In a small study conducted on 9 pigtail macaques vaginally challenged with SIVmac239, immunostaining and fluorescent microscopy revealed that smaller foci of infected cells were observed in animals treated with oral PrEP compared to those treated with topical PrEP (IntraVaginal Ring or IVR). Indeed, in the way of herd immunity, systemic PrEP prevents systemic infection even if drug coverage is incomplete.
Connie Celum from University of Washington, United States, analyzed how to optimize oral PrEP delivery. Even if PrEP is a safe and effective prevention option, stigma, lack of knowledge of PrEP and lack of access to PrEP are key barriers to PrEP use. Young African women is a group particularly at risk, affected by more than 1/3 of new HIV infections. Multiple studies to understand PrEP uptake and adherence are underway in this population, in order to develop captivating and effective messaging, easier delivery options, and interventions to maximize adherence (developing for instance peer support and open discussions). She concluded proposing a personalised approach for PrEP for every person, ensuring a positive and engaging messaging, as well as a simple delivery procedure.
In the first plenary lecture Yves Lévy from INSERM, France, gave an overview on the current knowledge on therapeutic vaccines, HIV reservoirs, and immunological mechanisms in HIV control (MOPL0101). Results from trials with dendritic cell-based therapeutic vaccines, TLR7 agonists and broadly neutralising antibodies have shown adaptive immune signatures and partial viral control. New strategies combining antigen delivery and control of immune-modulatory signals may have synergistic effects and achieve sustained viral control.
Wafaa El-Sadr from Columbia University, United States, presented cascades of care and recent world epidemiology regarding new HIV infections, as well as cART coverage (MOPL0102). Despite scaling up of treatment, reaching the WHO 90-90-90 goals involve expanding ART coverage, achieving high quality care and improving efficiency. A client-centered approach, known as Differentiated Service Delivery will be needed in order to address these challenges.
Sheena McCormack from University College London, United Kingdom, did an overview of the various prevention technologies from the mid 90s to this day (MOPL0103). Even if PrEP is effectively scaled up in Australia, Kenya and France, newer multipurpose technologies are needed to impact not only HIV transmission, but also pregnancy and STDs. Her new ABCD of Prevention involves Awareness of PrEP, changing of Behaviour, trusting the Community and just Do it.
Despite a quiet march in front of the Grand Amphitheater Nanina Anderegg from University of Bern, Switzerland, opened the Oral Abstract Session about ART describing temporal trends in the median CD4 cell count at cART initiation in low-, middle-, and high-income countries (MOAB0101). Using data from the International epidemiology Databases to Evaluate AIDS (IeDEA) and from the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE) she analyzed temporal trends in median CD4 cell count using additive mixed models. She concluded that even if median CD4 cell count at cART start increased in all income groups, it generally remained below 350 cells/uL. Thus, additional efforts are required in order to increase testing coverage, achieving earlier diagnosis and initiation of cART.
Jean-Daniel Lelièvre from Vaccine Research Institute, France, presented results of the ANRS 146 OPTIMAL trial (MOAB0102). It was a European, randomized, phase III trial studying the effect of maraviroc (MVC) vs placebo and in addition to cART, on disease progression and death in naive patients with low CD4 cell count. The W72 results of this large trial showed that adding MVC to standard cART did not impact the occurence of serious events, death, virological control or CD4 T cell restoration in advanced HIV-infected patients. However, post-hoc analysis showed that Kaplan-Meier curves for the primary endpoints had different kinetics between MVC and placebo, suggesting a trend to a beneficial effect of MVC on the occurence of clinical events during the first six months of use, that subsequently disappeared.
Raoul Moh from the department of Dermatology and Infectious Diseases, Côte d’Ivoire, presented results of the 48-weeks efficacy of a third-line regimen in HIV-infected adults who failed second-line treatment in sub-Saharan Africa (ANRS 12269 THILAO study)(MOAB0104). This pilot study proved that even if third-line ART was effective and well tolerated, conferring rare resistance accumulation, an adherence reinforcement phase should help to distinguish between patients who need or do not need to switch their current regimen.
Joel Gallant from Southwest CARE Center, United States presented results of a phase 3 randomized controlled clinical trial of bictegravir in a fixed dose combination B/F/TAF vs ABC/DTG/3TC in treatment-naive adults (MOAB0105LB). At W48, B/F/TAF achieved virology suppression in 92.4% of treatment-naïve adults and was non inferior to ABC/DTG/3TC. No emergent resistance has been found. Safety profiles were similar among the two groups, except significantly less nausea in the bictegravir arm.
Pedro Cahn from the Fundacion Huesped, Argentina, presented W24 results of the randomized ANDES study that compared DRV/RTV + 3TC to TDF/DRV/RTV/3TC (MOAB0106LB). The generic combination of DRV/RTV in fixed-dose plus 3TC showed non-inferiority to the generic triple drug regimen of DRV/RTV/TDF/3TC, with a similar safety profile in both arms.
Babafemi Taiwo from the Northwestern, United States, presented W24 results of the ACTG A5353 study which is a phase II, pilot study of DTG+3TC for initial treatment of HIV participants with HIV-1 RNA < 500,000 copies/mL. DTG+3TC demonstrated potent virology efficacy except in 3 patients with suboptimal adherence. Randomised trials of the regimen vs standard of care are underway.
Nikoloz Chkhartishvili opened the HIV and Liver Oral Abstract Session (MOAB0301) describing the hepatitis C care cascade for PLWHIV in the country of Georgia. Because of gap in diagnosis stage only 15% of estimated 3300 persons living with HIV/HCV coinfection were cured.
Nadine Kronfli from McGill University Health Centre, Canada, discussed trends in cause-specific mortality in HIV-HCV co-infected patients in Canada (MOAB0302). All cause mortality decreased over time and increased HCV treatment uptake has coincided with decreased liver-specific mortality, but modifiable risk factors (tobacco and drug use) need to be addressed.
Karine Lacombe from Université de Pierre et Marie Curie, France, presented results of the EXPEDITION-2 study in HIV/HCV co-infected patients (MOAB0303). This phase 3 study evaluated once-daily glecaprevir/pibrentasvir (G/P) 300 mg/120 mg treatment in co-infected adults without or with compensated cirrhosis, for 8 or 12 weeks, respectively. Rates of response at the end of treatment and post-treatment week 4 reached 98.7% and 98.6% respectively, regardless of baseline HCV ARN or treatment experience.
Maud Lemoine from Imperial College London, United Kingdom, presented results of the METAFIB study. In 468 HIV-monoinfected individuals obesity and insulin resistance were independent factors of significant fibrosis (≥F2) and remained associated after adjustment on MetS. Serum levels of leptin and sCD163 were significantly associated with the degree of liver fibrosis even after adjustment on MetS.
Hugo Perazzo Pedroso Barbosa from Fundação Oswaldo Cruz, Brazil, presented the PROSPEC-HIV study evaluating risk factors associated with liver fibrosis and steatosis by transient elastography in HIV mono-infected patients under cART (MOAB0305). In age and gender adjusted multivariate analysis, factors associated [OR (95%CI)] with liver fibrosis were: age > 45 years [2.91 (1.19-7.15); p=0.020]; CD4 count < 200 cells [5.00 (1.38-18.21); p=0.014] and type-2 diabetes [3.04 (0.97-9.55); p=0.056]. Male gender [5.69 (2.68-12.04); p< 0.001]; dyslipidemia [2.86 (1.46-5.60); p=0.002]; type 2 diabetes [6.00 (2.08-17.28); p=0.001] and central obesity [10.24 (4.11-25.50); p< 0.001] were independently associated with liver steatosis.