Gestational Diabetes Mellitus: What Can Medical Nutrition Therapy Do?

Gestational diabetes mellitus (GDM) is one of the common complications during pregnancy. Numerous studies have shown that GDM is associated with a series of adverse effects on both mothers and offspring. Due to the particularity of pregnancy, medical nutrition treatment is considered to be the first choice for the treatment of GDM. This contribution reviews the research progress of medical nutrition treatment in GDM, summarizes the international recommendations on the intake of various nutrients and the influence of nutrients on the prevalence of GDM, and the improvement effect of nutritional intervention on it, in order to provide references for research in related fields of GDM and the targeted development of enteral nutrition.

Experimental Study on the Effect of Pitch Sloshing on the Heat Transfer and Pressure Drop of an LNG Spiral-Wound Heat Exchanger.

With the development and utilization of offshore liquefied natural gas, it is increasingly important to study the influence of the heat transfer performance of a spiral-wound heat exchanger under sloshing conditions. This study focused on the effects of different sloshing amplitudes and sloshing periods on the heat transfer and pressure drop performance of a heat exchanger. Through experimental research, the results showed that the fluctuation of the UA (U is the heat transfer coefficient; A is the heat exchange area) value first increased and then decreased with an increase in the sloshing amplitude. The UA value increased by 12.92% and decreased by 42.03% compared to the static value at 3 and 9°, respectively. The fluctuation in the UA value first decreased and then increased with an increase in the sloshing period. The UA value decreased by 36.66% and increased by 10.82% slowly compared to the static value when the sloshing period was 6 and 20 s, respectively. Based on this, a mathematical model of heat transfer under the condition of pitch sloshing was established.

Association of Perceived Social Support with Viral Suppression Among Young Adults with Perinatally-Acquired HIV in the US-based Pediatric HIV/AIDS Cohort Study (PHACS).

Purpose: To determine the relationship between perceived social support and viral suppression among young adults with perinatally-acquired HIV (YAPHIV). Participants and Methods: We included YAPHIV ≥18 years enrolled in AMP Up, a study of PHACS (Pediatric HIV/AIDS Cohort Study), with social support evaluations and ≥1 HIV viral load (VL) measured over the next year. We evaluated emotional, instrumental, and friendship social support via the NIH Toolbox. We defined social support, measured at study entry and year 3 (if available), as low (T-score ≤40), average (41-59) or high (≥60). We defined viral suppression as all VL <50 copies/mL over the one year after social support measures. We fit multivariable Poisson regression models using generalized estimating equations, and evaluated transition from pediatric to adult care as an effect modifier. Results: Among 444 YAPHIV, low emotional and instrumental support and friendship at entry were reported by 37%, 32% and 36%. Over the next year, 44% were virally suppressed. Of 136 with year 3 data, 45% were suppressed. Average or high levels of all three social support measures were associated with higher likelihood of viral suppression. Instrumental support was associated with viral suppression among those in pediatric (adjusted proportion suppressed among those with average/high vs low support=51.2% vs 28.9%; risk ratio (RR)=1.77, 95% confidence interval (CI)=1.37, 2.29), but not adult care (40.0% vs 40.8%; RR=0.98, 95% CI=0.67, 1.44). Conclusion: Sufficient social support increases likelihood of viral suppression among YAPHIV. Strategies to enhance social support may promote viral suppression as YAPHIV prepare for adult clinical care transition.

Unique Profile of Inflammation and Immune Activation in Pregnant People With HIV in the United States.

BACKGROUND: Little is known about inflammation/immune activation during pregnancy in people with HIV (PWH) and growth in their children who are HIV-exposed and uninfected (CHEU). METHODS: Using data from the Pediatric HIV/AIDS Cohort Study and an HIV-seronegative comparison group, we assessed associations of (1) HIV status, mode of HIV acquisition (perinatally vs nonperinatally acquired), and type of antiretroviral therapy (ART) with inflammation/immune activation in pregnancy; and (2) inflammation/immune activation in pregnancy with growth of CHEU at 12 months. Interleukin 6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), soluble(s) TNF-α receptor 1 and 2 (sTNFR1, sTNFR2), sCD14, and sCD163 were measured between 13 and 27 weeks' gestation. Linear regression models were fit to estimate differences between groups for each log-transformed biomarker, adjusted for confounders. RESULTS: Pregnant PWH (188 total, 39 perinatally acquired, 149 nonperinatally acquired) and 76 HIV-seronegative persons were included. PWH had higher IL-6, sTNFR1, sCD14, and sCD163 and lower sTNFR2 compared to HIV-seronegative persons in adjusted models. Among PWH, sCD163 was higher in those with perinatally versus nonperinatally acquired HIV and on PI-based versus INSTI-based ART. Higher maternal concentrations of IL-6, sTNFR2, and hs-CRP were associated with poorer growth at 12 months. CONCLUSIONS: Maternal HIV status is associated with a distinct profile of inflammation/immune activation during pregnancy, which may influence child growth.

Markers of intestinal immune activation and inflammation are not associated with preterm birth among women with low level HIV viremia.

BACKGROUND: Maternal markers of intestinal immune activation may be used to predict preterm birth (PTB) in pregnant women living with HIV. METHODS: This study used de-identified samples from the International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT) Protocol P1025 study. Singleton pregnancies with ≥3 ml plasma available and HIV viral load ≤400 copies/ml within 4 weeks of specimen collection were included. Frequency matching of PTB cases and term birth controls was performed on basis of maternal race, number of available plasma specimens, and timing of plasma sample collection in a 1:1 ratio. Plasma progesterone, 25-hydroxy vitamin D, soluble CD14, intestinal fatty acid binding protein (I-FABP), Lipopolysaccharide (LPS)-binding protein, and inflammatory cytokines (IL-1B, IFN-gamma, IL-6, TNF-alpha) were measured. Generalized mixed linear regression modeling was used to examine the association between PTB and biomarkers, adjusting for covariates and confounders. Data analyses were performed using SAS 9.4 (Cary, NC). RESULTS: We included 104 PTB compared to 104 controls. Third trimester log2 IL-1B was lower among PTB versus term birth controls by univariate analysis (-1.50 ± 2.26 vs. -.24 ± 2.69, p = .01) though this association was no longer significant by regression modeling. In an uncontrolled, exploratory sub-analysis, subjects with prior PTB had increased odds of PTB with higher I-FABP [aOR 2.72, 95% CI 1.18-6.24] and lower IFN-gamma [aOR .23, 95% CI .12-.41] after adjustment for covariates and confounders. CONCLUSIONS: Intestinal immune activation measured by soluble CD14 or intestinal fatty acid binding protein was not associated with preterm birth among pregnant women with low-level HIV viremia.

Emerging roles of selenium on metabolism and type 2 diabetes.

Selenium is recognized as an essential element for human health and enters human body mainly via diet. Selenium is a key constituent in selenoproteins, which exert essential biological functions, including antioxidant and anti-inflammatory effects. Several selenoproteins including glutathione peroxidases, selenoprotein P and selenoprotein S are known to play roles in the regulation of type 2 diabetes. Although there is a close association between certain selenoproteins with glucose metabolism or insulin resistance, the relationship between selenium and type 2 diabetes is complex and remains uncertain. Here we review recent advances in the field with an emphasis on roles of selenium on metabolism and type 2 diabetes. Understanding the association between selenium and type 2 diabetes is important for developing clinical practice guidelines, establishing and implementing effective public health policies, and ultimately combating relative health issues.

Dolutegravir in Pregnancy as Compared with Current HIV Regimens in the United States.

BACKGROUND: Data on the effectiveness and safety of dolutegravir-based antiretroviral therapy (ART) for human immunodeficiency virus type 1 (HIV-1) infection in pregnancy as compared with other ART regimens commonly used in the United States and Europe, particularly when initiated before conception, are limited. METHODS: We conducted a study involving pregnancies in persons with HIV-1 infection in the Pediatric HIV/AIDS Cohort Study whose initial ART in pregnancy included dolutegravir, atazanavir-ritonavir, darunavir-ritonavir, oral rilpivirine, raltegravir, or elvitegravir-cobicistat. Viral suppression at delivery and the risks of infants being born preterm, having low birth weight, and being small for gestational age were compared between each non-dolutegravir-based ART regimen and dolutegravir-based ART. Supplementary analyses that included participants in the Swiss Mother and Child HIV Cohort Study were conducted to improve the precision of our results. RESULTS: Of the pregnancies in the study, 120 were in participants who received dolutegravir, 464 in those who received atazanavir-ritonavir, 185 in those who received darunavir-ritonavir, 243 in those who received rilpivirine, 86 in those who received raltegravir, and 159 in those who received elvitegravir-cobicistat. The median age at conception was 29 years; 51% of the pregnancies were in participants who started ART before conception. Viral suppression was present at delivery in 96.7% of the pregnancies in participants who received dolutegravir; corresponding percentages were 84.0% for atazanavir-ritonavir, 89.2% for raltegravir, and 89.8% for elvitegravir-cobicistat (adjusted risk differences vs. dolutegravir, -13.0 percentage points [95% confidence interval {CI}, -17.0 to -6.1], -17.0 percentage points [95% CI, -27.0 to -2.4], and -7.0 percentage points [95% CI, -13.3 to -0.0], respectively). The observed risks of preterm birth were 13.6 to 17.6%. Adjusted risks of infants being born preterm, having low birth weight, or being small for gestational age did not differ substantially between non-dolutegravir-based ART and dolutegravir. Results of supplementary analyses were similar. CONCLUSIONS: Atazanavir-ritonavir and raltegravir were associated with less frequent viral suppression at delivery than dolutegravir. No clear differences in adverse birth outcomes were observed with dolutegravir-based ART as compared with non-dolutegravir-based ART, although samples were small. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others.).

Ageing with HIV: a longitudinal study of markers of resilience in young adults with perinatal exposure to HIV, with or without perinatally acquired HIV.

INTRODUCTION: Medical challenges, including perinatally acquired HIV (PHIV), can be considered adversity with the potential to compromise individuals' ability to meet societal expectations across the lifespan. Studies suggest that resilience, defined as positive adaptation in the context of adversity, helps individuals overcome challenges and improve their quality of life. Few longitudinal studies have examined resilience in young adults with perinatally acquired HIV (YAPHIV) or perinatal HIV exposure, uninfected (YAPHEU). We examined three young adult milestones, which can affect the life-long quality of life, as markers of resilience: high school graduation, postsecondary education and current employment. METHODS: Analyses included YAPHIV and YAPHEU, ages 19-27 years, followed in longitudinal cohort studies: Pediatric HIV/AIDS Cohort Study Adolescent Master Protocol (AMP) (7-17 years) and AMP Up (≥18 years). Factors known to influence the attainment of milestones (outcomes) were examined: executive function, cognitive efficiency (working memory and processing speed), behavioural/social-emotional functioning, parent/caregiver mental/physical health and cumulative risk. HIV disease markers for YAPHIV were examined. The most recent AMP assessment was used for each factor; outcomes were measured at AMP Up 1-year follow-up. Separate robust Poisson regression models were used to assess associations of each factor with each outcome; PHIV status was explored as an effect modifier of each association. RESULTS: Participants (N = 315; YAPHIV = 228): 58% female, 67% Black and 27% Hispanic. Compared to YAPHEU, YAPHIV were older and from families with higher median income and fewer symptoms of parent/caregiver mental health/substance use disorders. Proportions of YAPHIV and YAPHEU, respectively, who achieved each milestone were comparable: 82% versus 78% for high school graduation (p = 0.49), 45% versus 51% for postsecondary education (p = 0.35) and 48% versus 54% for current employment (p = 0.32). Higher cognitive efficiency was positively associated with postsecondary education and current employment. Higher executive function, age-appropriate behavioural/social-emotional functioning and lower cumulative risk were associated with academic milestones. Among YAPHIV, positive associations were: higher current CD4 with postsecondary education and lower nadir CD4 with current employment. PHIV status did not modify any association. CONCLUSIONS: YAPHIV and YAPHEU demonstrated resilience, attaining at least one young adult milestone. Cognitive, behavioural and social resources to support resilience in childhood and adolescence may provide the foundation for continued achievement throughout adulthood.

Immunologic and Virologic Factors Associated With Hospitalization in Human Immunodeficiency Virus-Exposed, Uninfected Infants in the United States.

BACKGROUND: Human immunodeficiency virus (HIV)-exposed, uninfected (HEU) infants experience higher rates of morbidity and mortality than HIV-unexposed, uninfected (HUU) infants. Few studies have examined whether particular infections and/or immune responses are associated with hospitalization among HEU infants born in the United States. METHODS: We evaluated a subset of HEU infants enrolled in the International Maternal Pediatric Adolescent AIDS Clinical Trials Group P1025 and/or Pediatric HIV/AIDS Cohort Study Surveillance Monitoring for ART Toxicities studies. We determined seroconversion to 6 respiratory viruses and measured antibody concentrations to 9 vaccine antigens using quantitative ELISA or electrochemiluminescence. Multivariable modified Poisson regression models were fit to evaluate associations of seroconversion to each respiratory virus/family and antibody concentrations to vaccine antigens with risk of hospitalization in the first year of life. Antibody concentrations to vaccine antigens were compared between HEU infants and HUU infants from a single site using multivariable linear regression models. RESULTS: Among 556 HEU infants, seroconversion to respiratory syncytial virus (RSV) and parainfluenza was associated with hospitalization (adjusted risk ratio, 1.95 [95% CI, 1.21-3.15] and 2.30 [1.42-3.73], respectively). Antibody concentrations to tetanus toxoid, pertussis, and pneumococcal vaccine antigens were higher among 525 HEU compared with 100 HUU infants. No associations were observed between antibody concentrations with any vaccine and hospitalization among HEU infants. CONCLUSIONS: RSV and parainfluenza contribute to hospitalization among HEU infants in the first year of life. HEU infants demonstrate robust antibody responses to vaccine antigens; therefore, humoral immune defects likely do not explain the increased susceptibility to infection observed in this population.

Extent of In Utero Transfer of Tenofovir From Mother to Fetus: A Paired Analysis of Hair Specimens Collected at Birth From a Cohort in the United States.

Understanding in utero transfer of antiretrovirals is critical for interpreting safety. Hair levels measure cumulative exposure. We measured tenofovir (TFV) concentrations in hair at delivery among women living with human immunodeficiency virus receiving TFV disoproxil fumarate-based treatment and their infants, using liquid chromatography-tandem mass spectrometry. Among 103 mother-infant pairs, the mean log10 ratio of infant-to-maternal TFV levels was 1.08 (95% confidence interval, .97-1.20). TFV transfer was 60% lower from mothers who had preterm compared with term deliveries and 42% lower from mothers who had cesarean compared with vaginal deliveries. Like prior studies assessing transfer via short-term measures (plasma, cord blood, amniotic fluid), we found high cumulative transfer using hair.

Detectable HIV RNA in late pregnancy associated with low tenofovir hair levels at time of delivery among women living with HIV in the United States.

OBJECTIVE: We evaluated peripartum tenofovir (TFV) exposure via hair measures among women living with HIV in the United States. DESIGN: Observational cohort study. METHODS: Hair samples were collected at or shortly after childbirth among mothers enrolled in the Surveillance Monitoring for Antiretroviral Therapy Toxicities Study of the Pediatric HIV/AIDS Cohort Study between 6/2014 and 7/2016. Among mothers receiving TFV disoproxil fumarate (TDF)-based regimens during pregnancy, TFV hair concentrations were analyzed using liquid chromatography/tandem mass spectrometry. Weight-normalized TFV concentrations were log10 transformed. Multivariable linear regression assessed correlates of TFV concentrations. RESULTS: Overall, 121 mothers on TDF-based antiretroviral therapy during pregnancy had hair specimens tested for TFV concentrations and were included in the analysis. Median age at delivery was 31 years [interquartile range (IQR) 26-36]; 71% self-identified as non-Hispanic black, and 10% had unsuppressed viral loads in late pregnancy (HIV RNA ≥ 400 copies/ml). Median time from birth to hair collection was 3 days (IQR 1-14) and median TFV hair concentration was 0.02 ng/mg (IQR 0.01-0.04). In multivariable models, an unsuppressed viral load in late pregnancy was associated with 80% lower adjusted mean peripartum TFV concentrations than pregnancies with viral suppression (95% confidence interval: -90% to -59%, P < 0.001). Use of TDF only in the first trimester and attaining high school graduation were also associated with lower TFV hair concentrations. CONCLUSION: Unsuppressed viral load during late pregnancy was strongly associated with lower maternal TFV hair concentrations at birth, though viremia was rare. Efforts to improve maternal virological outcomes and eliminate vertical HIV transmission could incorporate drug exposure monitoring using hair or other metrics.

Repeat Pregnancies Among US Women Living With HIV in the SMARTT Study: Temporal Changes in HIV Disease Status and Predictors of Preterm Birth.

BACKGROUND: Birth rates among women living with HIV (WLHIV) have increased recently, with many experiencing multiple pregnancies. Yet, viral suppression is often not sustained between pregnancies. In addition, protease inhibitors (PIs) have been associated with preterm birth, but associations between integrase strand transfer inhibitors (INSTIs) and preterm birth are less well characterized. METHODS: We studied WLHIV with ≥2 live-born infants enrolled into the Pediatric HIV/AIDS Cohort Study Surveillance Monitoring for Antiretroviral Treatment Toxicities (SMARTT) study between 2007 and 2018, comparing CD4 counts and viral loads (VLs) between 2 consecutive SMARTT pregnancies. We evaluated associations of covariates with CD4 and viral suppression and the association of PI/INSTI use during pregnancy with odds of preterm birth. RESULTS: There were 736 women who had ≥2 live-born children enrolled in SMARTT (1695 pregnancies). Median CD4 counts remained stable over repeat pregnancies. Although >80% of women achieved VL suppression during pregnancy, more than half had a detectable VL early in their subsequent pregnancy. In adjusted models including all singleton pregnancies, an increased odds of preterm birth was observed for women with first trimester PI initiation (adjusted odds ratio: 1.97; 95% confidence interval: 1.27 to 3.07) compared with those not receiving PIs during pregnancy and for first trimester INSTI initiation (adjusted odds ratio: 2.39; 95% confidence interval: 1.04 to 5.46) compared with those never using INSTIs during pregnancy. CONCLUSIONS: Most WLHIV achieved VL suppression by late pregnancy but many were viremic early in subsequent pregnancies. First trimester initiation of PIs or INSTIs was associated with a higher risk of preterm birth.

Brain morphometric differences in youth with and without perinatally-acquired HIV: A cross-sectional study.

Youth with perinatally-acquired HIV (PHIV) experience specific and global cognitive deficits at increased rates compared to typically-developing HIV-uninfected youth. In youth with PHIV, HIV infects the brain early in development. Neuroimaging studies have demonstrated altered grey matter morphometry in youth with PHIV compared to typically-developing youth. This study examined cortical thickness, surface area, and gyrification of grey matter in youth (age 11-20 years old) with PHIV (n = 40) from the Pediatric HIV/AIDS Cohort Study (PHACS) compared to typically-developing presumed HIV uninfected and unexposed youth (n = 80) from the Pediatric Imaging, Neurocognition and Genetics Study (PING) using structural magnetic resonance imaging. This study also examined the relationship between grey matter morphometry and age. Youth with PHIV had reduced cortical thickness, surface area, and gyrification compared to typically-developing youth. In addition, an inverse relationship between age and grey matter volume was found in typically-developing youth, but was not observed in youth with PHIV. Longitudinal studies are necessary to understand the neurodevelopmental trajectory of youth with PHIV.

Healthcare Transition Outcomes Among Young Adults With Perinatally Acquired Human Immunodeficiency Virus Infection in the United States.

BACKGROUND: Young adults with perinatally acquired HIV (YPHIVs) living in the United States are transitioning to adult clinical care, yet there is little information on factors that affect transition outcomes. METHODS: YPHIVs aged ≥18 years in the Pediatric HIV/AIDS Cohort Study (PHACS) AMP Up cohort approaching or having completed transition from pediatric to adult healthcare were included. Demographic and clinical characteristics and self-reported ability to self-manage healthcare were compared by transition status, and multivariable logistic regression models examined factors associated with satisfaction with, and retention in, adult clinical care (clinic visit within the previous 6 months). RESULTS: Most of the 455 YPHIVs, regardless of transition status, reported satisfaction with their clinic and care provider, but many reported antiretroviral medication nonadherence. Of the 124 YPHIVs who had transitioned, 56% had periods of unsuppressed HIV-1 RNA in the year before transition. Those who had transitioned were more likely to report high ability to self-manage their healthcare (ability to manage ≥7 of 8 skills) than those not transitioned. High self-management was associated with retention after transition (odds ratio, 3.40; 95% confidence interval, 1.33-9.12). Higher perceived emotional social support was also associated with retention. Older age at transition was associated with greater satisfaction with provider and clinic. CONCLUSIONS: YPHIVs have positive associations with their clinical care around the time of their transition to adult care, but unsuppressed viral load and suboptimal adherence are a concern. Strengthening skills that increase ability to self-manage care and enhance social support may increase retention in care and improve clinical health.

Rates of Hospitalization and Infection-Related Hospitalization Among Human Immunodeficiency Virus (HIV)-Exposed Uninfected Children Compared to HIV-Unexposed Uninfected Children in the United States, 2007-2016.

BACKGROUND: Studies from multiple countries have suggested impaired immunity in perinatally human immunodeficiency virus (HIV)-exposed uninfected children (HEU), with elevated rates of all-cause hospitalization and infections. We estimated and compared the incidence of all-cause hospitalization and infection-related hospitalization in the first 2 years of life among HEU and HIV-unexposed uninfected children (HUU) in the United States. Among HEU, we evaluated associations of maternal HIV disease-related factors during pregnancy with risk of child hospitalization. METHODS: HEU data from subjects enrolled in the Surveillance Monitoring for Antiretroviral Therapy Toxicities Study (SMARTT) cohort who were born during 2006-2017 were analyzed. HUU comparison data were obtained from the Medicaid Analytic Extract database, restricted to states participating in SMARTT. We compared rates of first hospitalization, total hospitalizations, first infection-related hospitalization, total infection-related hospitalizations, and mortality between HEU and HUU using Poisson regression. Among HEU, multivariable Poisson regression models were fitted to evaluate associations of maternal HIV factors with risk of hospitalization. RESULTS: A total of 2404 HEU and 3 605 864 HUU were included in the analysis. HEU children had approximately 2 times greater rates of first hospitalization, total hospitalizations, first infection-related hospitalization, and total infection-related hospitalizations compared with HUUs. There was no significant difference in mortality. Maternal HIV disease factors were not associated with the risk of child infection or hospitalization. CONCLUSIONS: Compared with HUU, HEU children in the United States have higher rates of hospitalization and infection-related hospitalization in the first 2 years of life, consistent with studies in other countries. Closer monitoring of HEU infants for infection and further elucidation of immune mechanisms is needed.

Antiretroviral Prescribing Practices Among Pregnant Women Living With HIV in the United States, 2008-2017.

Importance: Since 1994, the US Department of Health and Human Services has published treatment guidelines for pregnant women living with HIV. Understanding how well prescribing patterns correspond with treatment guidelines could inform health policy and influence future clinical practice. Objectives: To compare antiretroviral prescribing practices over time among pregnant women living with HIV with Department of Health and Human Services treatment guidelines and identify factors associated with receiving recommended regimens. Design, Setting, and Participants: A prospective cohort study of 1582 pregnant women living with HIV were enrolled in the Pediatric HIV/AIDS Cohort Study Surveillance Monitoring of ART (antiretroviral therapy) Toxicities study between January 1, 2008, and June 30, 2017. The study was conducted at 18 academic research hospitals in the United States. Exposures: Antiretroviral medications (ARVs) prescribed during pregnancy. Main Outcomes and Measures: Proportion of regimens prescribed to pregnant women living with HIV qualifying as preferred or alternative according to Department of Health and Human Services guidelines, stratified by timing of initiation. Results: Of 1867 pregnancies (among 1582 pregnant women living with HIV with a mean [SD] age of 28.6 [6.1] years at conception), 1264 (67.7%) occurred among women self-identified as black, 480 (25.7%) self-identified as white, and 123 (6.6%) self-identified as other or unreported race/ethnicity. Antiretroviral medications were initiated prior to conception for 790 women (42.3%), resumed during pregnancy for 625 women (33.5%), and initiated during pregnancy for 452 women (24.2%). Only 925 pregnancies (49.5%) were associated with prescribed ARVs designated as preferred or alternative, while 492 (26.4%) involved ARVs with insufficient evidence for use during pregnancy and 136 (7.3%) involved ARVs that were not recommended during pregnancy. A higher proportion of treatment-naive pregnant women initiating ARVs were prescribed preferred or alternative ARVs compared with those resuming ARVs or those treated with ARVs before conception (316 of 452 [69.9%] vs 325 of 625 [52.0%] vs 284 of 790 [35.9%]; P < .001). A total of 91 of 452 women (20.1%) initiating ARVs during pregnancy were prescribed ARVs with insufficient evidence for use during pregnancy or not recommended during pregnancy. Among women resuming ARVs, those with a viral load greater than 1000 copies/mL early in pregnancy had higher odds of being prescribed guideline-recommended ARVs (adjusted odds ratio, 2.03 [95% CI, 1.33-3.10]) compared with those with a viral load of 400 copies/mL or less. Conclusions and Relevance: This study suggests that US ARV prescribing practices for pregnant women living with HIV do not align well with national guidelines. This finding is particularly concerning when treatment is initiated during pregnancy. Further research is needed to understand disparities between prescribing practices and evidence-based guideline recommendations.

Brief Report: Markers of Spontaneous Preterm Delivery in Women Living With HIV: Relationship With Protease Inhibitors and Vitamin D.

BACKGROUND: Women living with HIV (WLHIV) have increased risk of spontaneous preterm delivery (SPTD). We sought to identify plasma predictors of SPTD and their correlations with factors that increase the risk of SPTD, such as vitamin D deficiency and use of protease inhibitors. DESIGN: Plasma was obtained from 103 WLHIV with SPTD (≤35 weeks gestation) and 205 controls with term deliveries (TDs; ≥37 weeds) matched to cases 2:1 by race and gestational age at blood draw. TNFα, IFNγ, IL6, IL8, IL1ß, IL18, IL17, granulocyte colony stimulating factor (GCSF), MCP1, IP10, sIL2Rα, sCD14, vascular endothelial factor a, monocyte colony stimulation factor, GROα, MMP9, IL10, TGFß, sCTLA4, and eicosanoids were compared between cases adjusting for known SPTD risk factors. RESULTS: Participants had similar demographic characteristics, but cases had higher plasma HIV RNA, lower CD4 cells, and more advanced HIV disease compared with controls. High sIL2Rα was associated with increased risk of SPTD. High sCD14, GCSF, PGF2α, and 5-HEPE were marginally associated with increased risk of SPTD. Women who initiated protease inhibitors-containing antiretroviral treatment before or during the first trimester had higher levels of GCSF and 5-HEPE compared with women without such exposure before plasma collection. Vitamin D insufficiency was associated with higher inflammatory sCD14 and PGF2α, and lower anti-inflammatory 5-HEPE. CONCLUSIONS: The best plasma predictor of SPTD in WLHIV was sIL2Rα, a marker of T-cell activation. Markers of monocyte activation and eicosanoids were marginally increased in WLHIV and SPTD, suggesting that they may also play a role in the pathogenesis of this disorder.

Nonadherence and unsuppressed viral load across adolescence among US youth with perinatally acquired HIV.

OBJECTIVE: To identify factors associated with nonadherence and unsuppressed viral load across adolescence among youth with perinatally acquired HIV. DESIGN: Longitudinal study at 15 US clinical sites. METHODS: Self-reported antiretroviral medication nonadherence (any missed dose, past week) and unsuppressed viral load (HIV RNA > 400 copies/ml) were assessed annually. Individual, caregiver, social, and structural factors associated with nonadherence and unsuppressed viral load were identified by age (years): 8-11 (preadolescence), 12-14 (early adolescence), 15-17 (middle adolescence), and 18-22 (late adolescence/young adulthood), utilizing multivariable generalized linear mixed effects models. RESULTS: During a median 3.3-year follow-up, 381 youth with perinatally acquired HIV contributed viral load measurements and 379 completed 1190 adherence evaluations. From preadolescence to late adolescence/young adulthood, prevalence of nonadherence increased from 31 to 50% (P < 0.001); prevalence of unsuppressed viral load increased from 16 to 40% (P < 0.001). In adjusted analyses, in pre, middle, and late adolescence/young adulthood, perceived antiretroviral side effects were associated with nonadherence. Additional factors associated with nonadherence included: in preadolescence, using a buddy system (as an adherence reminder); in early adolescence, identifying as black, using buddy system; in middle adolescence, CD4% less than 15%, unmarried caregiver, indirect exposure to violence, stigma/fear of inadvertent disclosure, stressful life events. Associations with unsuppressed viral load included: in early adolescence, youth unawareness of HIV status, lower income; in middle adolescence, perceived antiretroviral side effects, lower income; in late adolescence/young adulthood, distressing physical symptoms, and perceived antiretroviral side effects. CONCLUSION: Prevalence of nonadherence and unsuppressed viral load increased with age. Associated factors varied across adolescence. Recognition of age-specific factors is important when considering strategies to support adherence.

Sertraline Pharmacokinetics in HIV-Infected and Uninfected Children, Adolescents, and Young Adults.

Objective: Due to potential disease and drug interactions, the appropriate sertraline starting dose and titration range may require adjustment in pediatric patients living with HIV. This is the first report of sertraline pharmacokinetics in HIV-infected youth. Methods: IMPAACT P1080 was a multicenter pilot study describing psychiatric medication pharmacokinetics in HIV-infected and uninfected youth. Participants were stable on sertraline, >6 to <25 years old, and (1) HIV-uninfected (HIV(-)), (2) HIV-infected taking efavirenz (EFV), or (3) HIV-infected taking boosting ritonavir/protease inhibitor (PI/r). Sampling occurred at pre-dose, 2, 4, 6, 12, and 24-h post-dose. Analyses were performed for sertraline and N-desmethylsertraline, and CYP2D6 phenotyping was completed with dextromethorphan. Results: Thirty-one participants (16 HIV(-), 12 PI/r, and 3 EFV) had median (range) weight, age, and dose of 69.5 (31.5-118.2) kg, 21.8 (9.1-24.7) years, and 75.0 (12.5-150.0) mg once daily. Sertraline exposure was highest for HIV(-) and lowest for EFV cohorts; median dose-normalized AUC 0-24 was 1176 (HIV(-)), 791 (PI/r) and 473 (EFV) ng*hr/mL, and C24 was 32.7 (HIV(-)), 20.1 (PI/r), and 12.8 (EFV) ng/mL. The urinary dextromethorphan/dextrorphan (DXM/DXO) ratio was higher in HIV(-) vs. PI/r cohorts (p = 0.01). Four HIV(-) participants were CYP2D6 poor metabolizers (ln(DXM/DXO) of >-0.5). Conclusions: HIV(-) cohort had the highest sertraline exposure. Sertraline exposure was ~40% lower in the PI/r cohort than in HIV(-); the need to alter sertraline dose ranges for PI/r participants is not clear. The impact of efavirenz on sertraline needs further investigation due to limited numbers of EFV participants.

Mental Health Diagnoses, Symptoms, and Service Utilization in US Youth with Perinatal HIV Infection or HIV Exposure.

Youth perinatally HIV infected (PHIV) or HIV exposed, but uninfected (PHEU), are aging into adolescence and adulthood with multiple complex risk factors for mental health (MH) problems and poor MH treatment utilization. Our aims were to estimate prevalence of MH diagnoses, clinically significant symptoms, and MH treatment utilization among youth with PHIV and among PHEU youth, 10-22 years old. We also aimed to identify correlates of diagnoses and treatment utilization. Analyses of data from standardized interviews, behavioral assessments, and chart review of 551 youth revealed that 36% had a previous or current MH diagnosis, with no significant HIV status group differences. Prevalence of clinically significant symptoms was 15% for both groups, of whom a third had no diagnosis, and half were not receiving treatment. Among youth with a current MH diagnosis, those with PHIV had greater utilization of services than PHEU youth (67% vs. 51%; p = 0.04). Factors associated with MH diagnoses and/or treatment utilization included caregiver characteristics, age and sex of child, HIV status, and stressful life events. Prevalence of MH diagnoses was higher than in the general population, but lower than in similar perinatally HIV-exposed cohorts, with some unmet service needs, particularly in PHEU youth. Family characteristics warrant careful consideration in early diagnosis and treatment of MH problems among youth affected by HIV.