LIVE FROM CROI: WEDNESDAY, FEBRUARY 15, 2017
Christina Psomas, MD, PhD is our « grand reporter »
Dr Shannon L. Hader (58), a Public Health leader from CDC, Atlanta, inaugurated the Wednesday Plenary Session (PL-2) talking about HIV in youth: shifting demographic patterns, complexity to interrupting HIV transmission, complexity to preventing an epidemic development among youth. Growth projection between 2017 and 2050 testify an absolute increase especially in Africa’s young adult population aged 15-24. Yet even with more tools in fighting or preventing HIV than ever before (risk avoidance, voluntary medical male circumcision, condom distribution and use, PrEP, early diagnosis and ARV treatment, TASP) many structural factors may explain persistent HIV risk behaviors: urbanization (highest in the developing world), education, economic growth and employment, contexts of vulnerability including persistent violence. « PEPFAR DREAMS » initiative mobilizes communities to reduce infection among women. Preventing epidemic among youth implicates to act fast, work together, engage young people and foster bold leadership.
Dr Barney S. Graham from NIAID/VRC/NIH, Bethesda (59), described antiviral vaccine development from A (AIDS) to Z (Zika). The problem of emerging viral diseases teaches us that traditional health approaches (licensed vaccines or antibiotics, passive surveillance, contact tracing and quarantine) are inadequate to anticipate or to manage new microbial threats. Most emerging infectious diseases are caused by viruses and are either zoonotic (75%) or vector borne. They are more frequently discovered in developed countries, but their event risk is higher in developing countries. AIDS began as a zoonotic transmission that circulated in humans for decades before evolving to the current pandemic. Research and Development infrastructure currently offers partners for advanced vaccine development. Applying new technology options (structural biology, protein design, high throughput sequencing, advanced imaging, systems biology, new understanding of immunology) should generate the tools to engineer better vaccines and be prepared for their rapid deployment in order to face future pandemics.
Dr Benjamin B. Gelman from Galveston (68) presented his study regarding the latent pool of HIV DNA in deep body compartments such as the central nervous system (CNS). In 29 decedent HIV-infected patients he mapped total and integrated gag-pol HIV DNA and RNA in brain using PCR and the Alu-gag assay. Patterns of brain compartmentalization were analyzed according to systemic viral suppression.
The total size of the latent pools in the brain was nearly always highest in white matter, because the white matter compartment contains the most mass. The intensity of systemic viral replication does not influence HIV reservoir size in brain, PBMCs, gastrointestinal tissue, spleen and kidney. On the contrary, strong systemic viral replication does influence HIV reservoir size in muscle, heart, fat, bone marrow and lungs. But CNS compartmentalization patterns deviated widely with regards to the intensity of systemic viral suppression: the more intensely suppressed brain specimens were, the higher HIV DNA was in white matter (p< 0,02) without a difference in total brain pool size.
Dr Jaclyn Mallard from Chestnut Hill (69), studied 16 SIVmac251-infected and 2 uninfected rhesus macaques in order to assess presence of T cells or monocyte/macrophage (Mo/Mf) in the cerebrospinal fluid (CSF), choroid plexus (CP), and central nervous system (CNS) parenchyma. Phylogeographic analysis of SIV sequences was used to assess compartmentalization of virus in order to determine sources of viral reservoirs.
She detected Mo/Mf but not T cells in CP from SIVE animals. In SIVE animals, CP and CNS parenchymal sequences were highly compartmentalized, which means that these tissues are sources of CNS viral reservoirs. CSF is not a viral reservoir because of the dispersed phylogeny of CSF viral sequences among peripheral and CNS sequences.
Dr Sandhya Vasan from Thailand (70), studied biomarkers of immune activation (Luminex) and CNS cellular infiltrate (Immunohistochemistry or IHC) in SHIV-infected macaques. SHIV RNA was detected in CSF of animals with the highest plasma viral load. Early SHIV infection was characterized by a T-cell mediated process with mild CD3+ infiltrate in the brain parenchyma, increased CD4+ T cells in the meninges, but no increase in parenchyma or meningeal CD68+ macrophages.
Dr Scott Letendre from San Diego (74), evaluated molecular mechanisms associated with neurocognitive (NC) performance of HIV+ adults, namely single nucleotide polymorphisms (SNPs) in the EIF2AK3 gene. 1047 participants from CHARTER’s Genome Wide Association Study (GWAS) had a gene assessment for the presence or absence of 3 SNPs in the EIF2AK3, as well as evaluation of their neurocognitive performance using the Global deficit Score (GDS) and the Global NCI. He concluded that variations in the EIF2AK3 gene were associated with neurocognitive performance.
Dr Dominique Costagliola from Paris (75), presented Microbreak 1 study, that was a sectional study to estimate the prevalence of cerebral small vessel disease (CSVD) detected by MRI in persons living with controlled HIV infection. 456 PLWHIV and 154 uninfected controls were analyzed by means of MRI. The prevalence of CSVD was 52% in a well controlled group of PLWHIV over 50 years of age, with an ORa of 2.3 (1.5-3.6) compared with HIV-uninfected controls. The difference regarding severe CSVD, was not significant between the two groups. Classical risk factors associated with CSVD were age and hypertension. The only HIV related risk factor associated with CSVD was a CD4 nadir cell count < 200/mm3.