Although many HIV cure strategies seek to expand HIV-specific CD8 + T cells to control the virus, all are likely to fail if cellular exhaustion is not prevented. A loss in stem-like memory properties (i.e., the ability to proliferate and generate secondary effector cells) is a key feature of exhaustion; little is known, however, about how these properties are regulated in human virus–specific CD8 + T cells. We found that virus-specific CD8 + T cells from humans and nonhuman primates naturally controlling HIV/SIV infection express more of the transcription factor TCF-1 than noncontrollers. HIV-specific CD8 + T cell TCF-1 expression correlated with memory marker expression and expansion capacity and declined with antigenic stimulation. CRISPR-Cas9 editing of TCF-1 in human primary T cells demonstrated a direct role in regulating expansion capacity. Collectively, these data suggest that TCF-1 contributes to the regulation of the stem-like memory property of secondary expansion capacity of HIV-specific CD8 + T cells, and they provide a rationale for exploring the enhancement of this pathway in T cell–based therapeutic strategies for HIV.

Pharmacological dosing of all--retinoic acid (atRA) controls adiposity in rodents by inhibiting adipogenesis and inducing fatty acid oxidation. Retinol dehydrogenases (Rdh) catalyze the first reaction that activates retinol into atRA. This study examined postnatal contributions of Rdh10 to atRA biosynthesis and physiological functions of endogenous atRA. Embryonic fibroblasts from heterozygote hypomorphs or with a total knockout exhibit decreased atRA biosynthesis and escalated adipogenesis. atRA or a retinoic acid receptor (RAR) pan-agonist reversed the phenotype. Eliminating one copy in vivo ( ) yielded a modest decrease (≤25%) in the atRA concentration of liver and adipose but increased adiposity in male and female mice fed a high-fat diet (HFD); increased liver steatosis, glucose intolerance, and insulin resistance in males fed an HFD; and activated bone marrow adipocyte formation in females, regardless of dietary fat. Chronic dosing with low-dose atRA corrected the metabolic defects. These data resolve physiological actions of endogenous atRA, reveal sex-specific effects of atRA in vivo, and establish the importance of Rdh10 to metabolic control by atRA. The consequences of a modest decrease in tissue atRA suggest that impaired retinol activation may contribute to diabesity, and low-dose atRA therapy may ameliorate adiposity and its sequelae of glucose intolerance and insulin resistance.

Congenital syphilis is the result of placental transmission from mother to fetus of Treponema pallidum. Although congenital syphilis is preventable through timely treatment, the rate of new infections in the United States (US) has increased each year since 2013, and is increasing at a noticeably greater pace in California (CA). Most research into congenital syphilis has focused on individual psychosocial and behavioral factors that contribute to maternal vulnerability for syphilis. The aim of this study was to evaluate structural barriers to prenatal care access and utilization and congenital syphilis prevention in Kern County, CA. Transcripts from 8 in-depth interviews with prenatal care providers and 5 focus group discussions with 42 pregnant and postpartum persons were examined using thematic analysis. Structural barriers experienced by pregnant and postpartum persons to prenatal care access and utilization included (1) burdens of poverty; (2) stigma around substance use in pregnancy; (3) citizenship status; (4) lack of healthcare coverage; (5) low sexual health literacy; and (6) gender inequality Structural barriers experienced by prenatal care providers in congenital syphilis prevention included (1) limited guidance on clinical management of syphilis in pregnancy; (2) decay in public health infrastructure; and (3) inadequate support for managing patients’ social comorbidities. The response to congenital syphilis prevention will require an examination of the complex context of social determinants of health in which persons diagnosed with syphilis live in.

ObjectiveMycoplasma genitalium (MG) is a sexually transmitted organism associated with cervicitis and pelvic inflammatory disease in women and has been shown to increase the risk of HIV acquisition and transmission. Little is known about the prevalence and incidence of MG in pregnant women. Our study sought to evaluate the prevalence and incidence of MG infection in HIV-infected and HIV-uninfected pregnant women.MethodsWe conducted a cohort study of 197 women ≥18 years receiving antenatal care in South Africa from November 2017 to February 2019. We over-recruited HIV-infected pregnant women to compare MG by HIV infection status. Self-collected vaginal swabs, performed at the first antenatal visit, third trimester and within 1 week post partum, were tested for MG using the Aptima assay (Hologic, USA). We report on the prevalence and incidence of MG and used multivariable logistic regression to describe correlates of MG and adverse pregnancy and birth outcomes (preterm delivery, miscarriage and vertical HIV transmission), adjusting for maternal age and HIV infection status.ResultsAt first antenatal visit, the median age was 29 years (IQR=24–34) and the gestational age was 19 weeks (IQR=14–23); 47% of women enrolled in the study were HIV-infected. MG prevalence was 24% (95% CI 16% to 34%, n=22) in HIV-infected and 12% (95% CI 6.8% to 20%, n=13) in HIV-uninfected pregnant women. MG incidence during pregnancy and early post partum was 4.7 infections per 100 woman-years (95% CI 1.2 to 12.9) or 3.9 per 1000 woman-months (95% CI 1.0 to 10.7). Adjusting for maternal age, HIV-infected women had over three times the odds of being infected with MG (adjusted OR=3.09, 95% CI 1.36 to 7.06).ConclusionWe found a high prevalence and incidence of MG in pregnant women. Younger maternal age and HIV infection were associated with MG infection in pregnancy. Further research into birth outcomes of women infected with MG, including vertical transmission of HIV infection, is needed.

Objectives Congenital syphilis (CS) is the result of antepartum transmission from mother to fetus of the spirochete Treponema pallidum. Although preventable through timely screening and treatment, the incidence of CS in the United States is increasing. This review describes the epidemiological trends in CS in the United States from 1980 to 2019 and characteristics of mothers of infants with CS. Methods We performed a narrative review of epidemiological studies of CS following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for reporting of observational studies in epidemiology. Quality and bias of included studies were assessed using the Newcastle-Ottawa Scale. Studies that described the demographics and characteristics of pregnant women with syphilis or who delivered an infant with CS in the United States were identified from PubMed and Embase. Results We identified a total of 2771 studies, of which 309 were selected for further review and 27 were included in the final analysis. Substance use during pregnancy was a risk factor for CS in 16 studies. Maternal cocaine use was described in 11 of the 16 studies, 10 of which were published between the years 1980 and 1999. No prenatal care was a risk factor for CS in 17 studies. Evidence of inadequate syphilis testing (i.e., no maternal screen, first screen after the first trimester, or no repeat screen in third trimester) or treatment (i.e., no treatment, treatment <30 days before delivery, or nonpenicillin treatment) was significantly associated with CS in 13 studies. Finally, higher rates of CS were reported among African American women in 11 studies. Conclusions Infection with and antepartum transmission of syphilis disproportionately affect certain subgroups of women. Women who report substance use during pregnancy are more likely to give birth to an infant with CS. No prenatal care and evidence of inadequate syphilis testing and treatment during pregnancy are also significantly associated with giving birth to an infant with CS. Finally, cases of CS disproportionately affect African American women. Addressing the CS epidemic will require identification and targeted allocation of resources to communities at elevated risk for syphilis, removal of barriers to prenatal care, and ensuring timely treatment and adequate partner notification of identified cases.