This study explored how multinational HIV experts weigh clinical, evidential, and ethical considerations regarding pre-exposure prophylaxis in pregnant/breastfeeding women. Semi-structured interviews were conducted with experts in HIV policy, research, treatment, and implementation from three global regions. A constant comparative approach identified major themes. Experts noted that exclusion of pregnant women from research limits evidence regarding risks/benefits, emphasizing that underinclusion of pregnant women in RCTs shifts the onus of evidence-building to clinical care. Experts discussed approaches for weighing evidence to make decisions, including triangulating evidence from sources other than RCTs. Likelihood and severity of disease strongly influenced decisions. Less effective interventions with limited fetal risk were preferred over interventions of uncertain safety, unless the disease was serious. Experts resisted the dichotomous choice between protecting maternal and fetal interests, arguing that these interests are intertwined and that more holistic approaches to maternal-fetal balance support greater inclusion of pregnant women in research.

miR-122 is a highly expressed liver microRNA that is activated perinatally and aids in regulating cholesterol metabolism and promoting terminal differentiation of hepatocytes. Disrupting expression of miR-122 can re-activate embryo-expressed adult-silenced genes, ultimately leading to the development of hepatocellular carcinoma (HCC). Here we interrogate the liver transcriptome at various time points after genomic excision of miR-122 to determine the cellular consequences leading to oncogenesis. Loss of miR-122 leads to specific and progressive increases in expression of imprinted clusters of microRNAs and mRNA transcripts at the Igf2 and Dlk1-Dio3 loci that could be curbed by re-introduction of exogenous miR-122. mRNA targets of other abundant hepatic microRNAs are functionally repressed leading to widespread hepatic transcriptional de-regulation. Together, this reveals a transcriptomic framework for the hepatic response to loss of miR-122 and the outcome on other microRNAs and their cognate gene targets.

Zinc deficiency causes immune dysfunction. In T lymphocytes, hypozincemia promotes thymus atrophy, polarization imbalance, and altered cytokine production. Zinc supplementation is commonly used to boost immune function to prevent infectious diseases in at-risk populations. However, the molecular players involved in zinc homeostasis in lymphocytes are poorly understood. In this paper, we wanted to determine the identity of the transporter responsible for zinc entry into lymphocytes. First, in human Jurkat cells, we characterized the effect of zinc on proliferation and activation and found that zinc supplementation enhances activation when T lymphocytes are stimulated using anti-CD3/anti-CD28 Abs. We show that zinc entry depends on specific pathways to correctly tune the NFAT, NF-κB, and AP-1 activation cascades. Second, we used various human and murine models to characterize the zinc transporter family, Zip, during T cell activation and found that Zip6 was strongly upregulated early during activation. Therefore, we generated a Jurkat Zip6 knockout (KO) line to study how the absence of this transporter affects lymphocyte physiology. We found that although Zip6KO cells showed no altered zinc transport or proliferation under basal conditions, under activation, these KO cells showed deficient zinc transport and a drastically impaired activation program. Our work shows that zinc entry into activated lymphocytes depends on Zip6 and that this transporter is essential for the correct function of the cellular activation machinery.

Passive administration of HIV neutralizing antibodies (nAbs) can protect macaques from hard-to-neutralize (tier 2) chimeric simian-human immunodeficiency virus (SHIV) challenge. However, conditions for nAb-mediated protection after vaccination have not been established. Here, we selected groups of 6 rhesus macaques with either high or low serum nAb titers from a total of 78 animals immunized with recombinant native-like (SOSIP) Env trimers. Repeat intrarectal challenge with homologous tier 2 SHIVBG505 led to rapid infection in unimmunized and low-titer animals. High-titer animals, however, demonstrated protection that was gradually lost as nAb titers waned over time. An autologous serum ID50 nAb titer of ∼1:500 afforded more than 90% protection from medium-dose SHIV infection. In contrast, antibody-dependent cellular cytotoxicity and T cell activity did not correlate with protection. Therefore, Env protein-based vaccination strategies can protect against hard-to-neutralize SHIV challenge in rhesus macaques by inducing tier 2 nAbs, provided appropriate neutralizing titers can be reached and maintained.

Though mother-to-child HIV transmission has been dramatically reduced in the past decade, there are currently an estimated 1.8 million children living with HIV across the globe, and over 30% of all new HIV infections occur among youth ages 15-25. While all youth experience developmental challenges, children and adolescents who are living with HIV must navigate these challenges within the context of high HIV stigma and must cope with a host of psychosocial and health-related challenges. In addition, because HIV disproportionately impacts individuals from minority statuses (e.g., race, ethnicity, gender, sexuality) and people living in poverty, vulnerabilities are often compounded. Resilience frameworks emphasize the capacity for positive adaptation to adversity, and thus provide a useful lens to identify and build upon individual and community strengths. This article introduces a special issue of AIDS Care that examines factors associated with resilience among children and adolescents affected by or living with HIV, as well as innovative interventions designed to build resilience among HIV youth populations. The articles highlighted within this issue examine the possibility of building resilience across diverse settings (e.g., schools, communities, healthcare clinics) and with varied populations (e.g., youth living with HIV, AIDS orphans, young men who have sex with men). We also highlight innovative approaches to resilience-building, including a new mobile Health (mHealth) smartphone game that aims to improve adherence among youth living with HIV in the United States.

Myeloid sarcoma (MS) is a solid extra-medullary tumor of immature myeloid cells which could occur before, during or after remission of acute leukemia at any site on the body. Owing to variation in differential diagnosis, pathologic evaluation and immunohistochemical staining are essential for definitive diagnosis. Rarely, MS has been shown as an isolated extramedullary relapse (iEMR) after allogeneic stem cell transplantation (allo-SCT), which often does not necessarily result in bone marrow involvement. It seems that despite chemotherapy and graft-versus-leukemia (GVL) effects on bone marrow, leukemic cells could remain alive in the extra-medullary region. However, in order to achieve longer survival, timely diagnosis as well as combined systemic, local, and cellular therapeutic modalities should be considered in any patient with iEMR after allo-SCT. We report a left lateral neck isolated MS presented as acute otitis externa in a patient with prior allo-SCT due to acute myeloid leukemia (AML). Therefore, MS should be considered in patients with any history of acute leukemia even if the patient presents with signs and symptoms of an infectious disease.

In 2015, 36.7 million people globally were estimated to be living with HIV. As well as reduc- ing the morbidity and mortality of HIV-infected persons associated with HIV infection, effec- tive antiretroviral therapy has been demonstrated to reduce the risk of HIV transmission to sexual partners from HIV-infected person dramatically. Current treatment guidelines recom- mend antiretroviral therapy for all HIV-infected individuals, regardless of CD4 cell count.