LIVE FROM CROI: THURSDAY, FEBRUARY 16, 2017
Christina Psomas, MD, PhD is our « grand reporter »
« If you can make it there, you can make it anywhere » told Dr Demetre C. Daskalakis from New York (108) as he entered the scene of the thursday plenary session PL-3 to talk to us about Ending the HIV epidemic in New York. He described how to transform activism that begins on the street, in political will; how to consider HIV as an emergency and treat it that way. The city of New York managed to minimize new HIV diagnoses, apart in poverty areas (80% of new diagnoses in 2015). They declare « ZERO » perinatally infected children in 2015. Their « Ending the Epidemic » programs are heading in the right direction, even if they still have to accelerate. For instance, the New York City EtE plan combines multiple strategies; transform STD clinics into « Destination Clinics » for sexual health services, make sexual health clinics efficient gateways for HIV treatment and prevention, support NYC community providers of HIV prevention (PrEP and PEP delivery system), support priority populations using novel strategies, take NYC viral suppression from good to excellent, and make NYC status neutral. Their NYC Sexual Health Centers have become real HIV Hubs, in order to enter the system and impose their PlaySure PrEP Network: « Kiss it with PrEP ». The first lesson learned in order to End AIDS with Love is to « Dream big and Take Risks ». You should have been there. Timothy Brown alias the « Berlin patient » was.
Dr Charles R. Bangham from London (109) made a very interesting overview of the human leukaemia virus HTLV-1 causing disabling chronic inflammatory diseases or agressive malignancies (10% of the infected people). The risk of these diseases is strongly correlated with the proviral HTLV-1 viral load in peripheral blood mononuclear cells and constitutes the result of different phenomena: 1) set-point proviral load, 2) protective immune response, depending on the dynamics and the determinants of cytotoxic T lymphocyte (CTL) quality, and 3) the number of clones participating in HTLV-1 latency. HTLV-1 alters host chromatin structure in the infected cell, in order to deregulate host gene expression and act as an oncogenic driver.
Dr Priscilla Hsue from San Francisco (126) made the first presentation of the Oral Abstract session O-12 about Inflammation and Age-Related complications. She described an open label study of Il-1beta inhibition using canakinumab (human monoclonal antibody) in 10 HIV-infected and virologically suppressed individuals that had an established cardiovascular risk. In this pilot study a single dose of canakinumab was well tolerated, did not modify HIV parameters (CD4+ T cells, CD4/CD8 ratio or HIV RNA level) and significantly reduced inflammatory markers (IL-6, hsCRP and sCD163) without impacting T cell activation or monocyte phenotypes. The imaging explorations by FDG-PET/CT seemed to show a reduction of both arterial inflammation and bone marrow activity. This small study will be followed by a randomized placebo controlled trial in 100 individuals that will receive 2 doses of canakinumab.
Dr Vincent C. Marconi from Atlanta (127) analyzed associations between bilirubin levels (categorized into quartiles) and cardiovascular events in the Veterans Aging Cohort Study (around 98 000 HIV+ and HIV- participants). After adjusting for CVD risk factors, higher bilirubin seemed to be associated with a lower hazard ratio (HR) for Heart Failure (HF) and Acute Myocardial Infarction (AMI). When the model included only HIV+ participants, significant associations persisted only for HF and not for AMI (similar findings but not significant). Death rates were highest in the lowest and highest bilirubin quartiles.
Dr Lene Ryom from Denmark (128LB) presented analysis of risk of cardiovascular disease (CVD) under contemporary PIs (DRV/r and ATV/R) among participants of the D:A:D study. In this large heterogeneous study the Incidence Risk of CVD seemed to gradually increase especially with exposure to DRV/r (association less pronounced for ATV/r). After adjustment for confounding factors, cumulative use of DRV/r but not ATV/r was associated with a small but gradually increasing CVD risk of 59% per 5 years exposure. Causal interference is limited by the observational nature of their data.
Dr Rosan van Zoest from Amsterdam (129) presented results of a study that evaluated the impact of HIV-related and traditional cardiovascular prevention interventions in Dutch HIV-positive patients on risk of CVD. An individual-based model of CVD was constructed from the national ATHENA cohort, in order to predict CVD and evaluate interventions. The model followed patients in care, was validated on 2010-2015 data and CVD was simulated by incorporating the D:A:D CVD risk equation into the model (5-year CVD risk). Four intervention were evaluated between 2017 and 2030: reducing the number of late presenters, use of cART with no known increased CVD risk, a smoking cessation program, intensified monitoring and drug treatment of hypertension and dyslipidemia. The model predicts that annual CVD incidence will increase between 2015 and 2030. Intensified monitoring and drug treatment of hypertension and dyslipidemia will have the greatest impact on averting CVD events (compared to earlier HIV diagnosis and treatment), preventing 17.0-20.0% of CVD cases annually, and followed by smoking cessation. Future studies will address the cost-effectiveness of these interventions.
Dr Keri N. Althoff from Baltimore (130) presented a study estimating the proportion of myocardial infarctions (MI) that could potentially be avoided if HIV-infected adults were unexposed to HIV-related or traditional MI risk factors (population attributable fractions or PAFs). In 7 contributing cohorts of the NA-ACCORD, a total of 29515 adults presented 347 MIs. After adjustment for demographics, eliminating smoking, treated hypertension and hypercholesterolemia would avert 38%, 41% and 43% of MIs, respectively; eliminating all three would avert 86% of MIs. HIV could not be evaluated as a risk factor, but HIV-related risk factors and HCV infection had smaller PAFs. In order to reduce excess MI burden, we should essentially prevent traditional CVD risk factors as early as possible in aging HIV-infected adults.
Dr Leah Shepherd from London (131) estimated cancer rates after smoking cessation in 39701 HIV+ persons from the D:A:D study. Smoking duration was associated with the occurrence of all cancers combined, lung, but not that of other smoking related cancers. Incidence of smoking related cancers excluding lung, rapidly declined following one-year cessation. Lung cancer incidence appears to remain elevated in HIV+ persons even > 5 years after cessation.
Dr Jingyan Yang from New York (132) estimated if the predictive accuracy of fracture probability assessment of traditional FRAX (only based on clinical risk factors) improves by adding femoral neck bone mineral density (BMD) T-score and lumbar spine trabecular bone score (TBS). The study included 1148 women of the Women’s Interagency HIV study. Traditional FRAX was less accurate in HIV-infected than uninfected women for predicting major osteoporotic and hip fractures. Among HIV-infected women accuracy of FRAX is improved with addition of DXA parameters (FNT and TBS), especially for prediction of hip fracture. Concerning prediction of major osteoporotic fractures in the same population FRAX calculated with HIV (as a cause of secondary osteoporosis) is similar to that of FRAX with DXA parameters.
Dr Damani A. Piggott from Baltimore (133) closed the session presenting his study on frailty progression and recovery among persons aging with HIV and substance use. He assessed frailty semiannually (Fried frailty phenotype) among HIV-infected and uninfected persons with a history of injection drug use within the ALIVE cohort between 2005 and 2013. Using Markov transition models he assessed the relationship of sociodemographics, chronic comorbid disease, HIV clinical factors and inflammation to transition between frailty states. The major finding is that HIV-status conferred 66% more risk to be frail, and frailty predicted increased hospitalization risk and increased risk of death in HIV+ adults. HIV independent (younger age, improved socioeconomic status and reduced chronic disease comorbidity) and HIV dependent parameters (virologic suppression, early HIV control, reduced inflammation) were significantly associated with reduced frailty progression and better frailty recovery.
Dr Charles W. Flexner from Baltimore (147) made an interesting overview of Long-Acting and Extended-Release (LA/ER) formulations of antiretroviral therapy during the last symposium S-9 on modern ART. These new approaches to drug delivery (oral products, intramuscular treatment or subcutaneous implants) are ideal for patients having difficulties with adherence, infants or patients suffering from stigma. Two IM injectable LA formulations of rilpivirine and cabotegravir are in Phase 3 clinical testing, and several others have already entered or are good candidates for clinical development (broadly neutralizing monoclonal antibodies). Prodrug approaches could make them amenable to nanoformulations and thus, reduce cost for low and middle-income countries. Main drawbacks of LA/ER approaches concern drug resistance, missed doses, drug interactions, pregnancy and side effects.
Dr Jose R. Arribas from Madrid (148) exposed the controversy of ART simplification in virologically suppressed patients during a very clear and exhaustive presentation. Using regimens with less than three antiretroviral drugs (monotherapy with boosted PIs, dual therapies sparing NNRTIs or NNRTIs/PIs) demand taking into account critical virological, pharmacological and behavioral factors such as potency and genetic barrier of the new regimen, the presence of archived mutations, duration of virological suppression and patient’s pattern of adherence.
Dr Beatriz Grinsztejn from Brazil (149) closed the 2017 CROI meeting defining the notion of the ideal antiretroviral regimen. Even if currently immediate initiation of ART is recommended for all individuals with HIV infection, economic burden, drug availability, and considerations of special populations, such as infants, children, adolescents, pregnant women, and those with hepatitis or tuberculosis co-infections affect ART regimen choices. Simultaneously with advances in drug formulations and novel compounds, we always have to considerate the probability of transmitted drug resistance patterns.
See you next year in beautiful Boston.