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Abstract Background While initiation of highly active antiretroviral therapy (HAART) during primary HIV-1 infection occasionally results in transient control of viral replication after treatment interruption, the vast majority of patients eventually experience a rebound in plasma viremia. Results Here we report a case of a patient who was started on HAART during symptomatic primary infection and who has subsequently maintained viral loads of < 50 copies/mL for more than nine years after the cessation of treatment. This patient had a high baseline viral load and has maintained a relatively high frequency of latently infected CD4+ T cells. In addition, he does not have any known protective HLA alleles. Thus it is unlikely that he was destined to become a natural elite controller or suppressor. The mechanism of control of viral replication is unclear; he is infected with a CCR5/CXCR4 dual-tropic virus that is fully replication-competent in vitro. In addition, his spouse, who transmitted the virus to him, developed AIDS. The patient's CD4+ T cells are fully susceptible to HIV-1 infection, and he has low titers of neutralizing antibodies to heterologous and autologous HIV-1 isolates. Furthermore, his CD8+ T cells do not have potent HIV suppressive activity. Conclusion This report suggests that some patients may be capable of controlling pathogenic HIV-1 isolates for extended periods of time after the cessation of HAART through a mechanism that is distinct from the potent cytotoxic T lymphocyte (CTL) mediated suppression that has been reported in many elite suppressors.

Little is known about the central nervous system (CNS) risk in high-grade B-cell lymphoma, not otherwise specified (HGBL, NOS). Hence, we sought to describe the rates of baseline CNS involvement, risk of CNS recurrence after primary therapy, and management strategies in HGBL, NOS. In this multicenter retrospective study, we included 160 adults with newly diagnosed HGBL, NOS treated between 2016 and 2021 at 20 US institutions. Eleven patients (7%) had baseline CNS involvement at diagnosis (leptomeningeal=6, parenchymal=4, and both=1). Baseline CNS involvement was significantly associated only with MYC rearrangement (OR=3.5) and testicular (in men) or female pelvic (in women) involvement (OR=8.1). There was no significant difference in survival outcomes between HGBL, NOS patients with (median PFS=4 years) or without (median PFS=2.4 years) baseline CNS involvement (p=0.45). The cumulative incidence of CNS recurrence at 3 years was 11%. Patients with baseline CNS involvement were at the highest risk (48.5% versus 8% for those without baseline CNS involvement) and were excluded from the risk factors analysis for CNS recurrence. The risk for CNS recurrence was significantly associated with blood or bone marrow involvement, CD5 expression, non-GCB subtype, and DEL phenotype, however, high CNS-IPI was not. The prognosis of relapsed HGBL, NOS was poor, regardless of whether recurrence was systemic or limited to the CNS, and with currently available salvage strategies, including autologous transplantation and CAR T-cell modalities, almost all patients with CNS recurrence ultimately succumbed to their disease. These patients represent an unmet need and should be prioritized for experimental approaches., (Copyright © 2024 American Society of Hematology.)

Regulatory elements are important constituents of plant genomes that have shaped ancient and modern crops. Their identification, function, and diversity in crop genomes however are poorly characterized, thus limiting our ability to harness their power for further agricultural advances using induced or natural variation. Here, we use DNA affinity purification-sequencing (DAP-seq) to map transcription factor (TF) binding events for 200 maize TFs belonging to 30 distinct families and heterodimer pairs in two distinct inbred lines historically used for maize hybrid plant production, providing empirical binding site annotation for 5.3% of the maize genome. TF binding site comparison in B73 and Mo17 inbreds reveals widespread differences, driven largely by structural variation, that correlate with gene expression changes. TF binding site presence-absence variation helps clarify complex QTL such as vgt1 , an important determinant of maize flowering time, and DICE, a distal enhancer involved in herbivore resistance. Modification of TF binding regions via CRISPR-Cas9 mediated editing alters target gene expression and phenotype. Our functional catalog of maize TF binding events enables collective and comparative TF binding analysis, and highlights its value for agricultural improvement.

Objective: This study was part of a national, multisite demonstration project evaluating the impact of integrated buprenorphine/naloxone treatment and HIV care. The goals of this study were to describe the baseline demographic, clinical, and substance use characteristics of the participants and to explore HIV transmission risk behaviors in this group., Methods: Nine sites across the United States participated. Data obtained by interview and chart review included demographic information, medical history, substance use, and risk behaviors.We performed a descriptive analysis of patient characteristics at entry and used logistic regression to evaluate factors associated with 1) unprotected anal or vaginal sex; and 2) needle-sharing within the previous 90 days., Results: Three hundred eighty-six individuals were included in the study: 303 (78.5%) received buprenorphine/naloxone; 41 (10.6%) received methadone; and 42 (10.9%) received another form of treatment. The analysis of risk behaviors was limited to those in the buprenorphine group (n = 303). Among those reporting vaginal or anal sex in the previous 90 days, 24% had sex without a condom. Factors significantly associated with unprotected sex were: having a partner; female gender; and alcohol use in previous 30 days. A total of 8.9% of participants shared needles in the previous 90 days. Factors significantly associated with needle-sharing were: amphetamine use; marijuana use; homelessness; and anxiety., Conclusions: Addressing transmission risk behaviors is an important secondary HIV prevention strategy. In addition to treatment for opioid dependence, addressing other substance use, social issues, particularly housing, and mental health may have important implications for reducing HIV transmission in HIV-infected opioid-dependent patients.

Background: Buprenorphine/naloxone allows the integration of opioid dependence and HIV treatment., Methods: We conducted a prospective study in HIV-infected opioid-dependent patients to investigate the impact of buprenorphine/naloxone treatment on drug use. Self-report and chart review assessments were conducted every 3 months (quarters 1-4) for 1 year. Outcomes were buprenorphine/naloxone treatment retention, drug use, and addiction treatment processes., Results: Among 303 patients enrolled between July 2005 and December 2007, retention in buprenorphine/naloxone treatment was 74%, 67%, 59%, and 49% during Quarters 1, 2, 3, and 4, respectively. Past 30-day illicit opioid use decreased from 84% of patients at baseline to 42% in retained patients over the year. Patients were 52% less likely to use illicit opioids for each quarter in treatment (Odds ratio = 0.66; 95% CI: 0.61 to 0.72). Buprenorphine/naloxone doses and office visits approximated guidelines published by the United States Department of Health and Human Services. Urine toxicology monitoring was less frequent than recommended., Conclusions: Buprenorphine/naloxone provided in HIV treatment settings can decrease opioid use. Strategies are needed to improve retention and address ongoing drug use in this treatment population.