The Mental Health Effects and Experiences of Breastfeeding Decision-Making Among Postpartum Women Living with HIV.

Prior to January 2023, women living with HIV (WLWH) in the United States (US) were discouraged from breastfeeding due to the potential risk of mother-to-child HIV transmission through breastfeeding. Lack of breastfeeding decision-making and experience among WLWH may negatively affect maternal mental health. We implemented a quality improvement initiative to screen WLWH for postpartum depression (PPD), evaluate their attitudes toward breastfeeding, and assess their experience with breastfeeding decision-making. We collected quantitative data from WLWH using a voluntary, self-administered 6-item breastfeeding decision-making and experience survey (administered 1 month postpartum) and a 10-item Edinburgh Postnatal Depression Scale (EPDS, negative = 0-9; administered 1 and 4 months postpartum) tool. We conducted descriptive statistics and cross tabulation analysis. We analyzed 106 WLWH (93.4% non-Hispanic Black/African American; mean age 33.1 years; 82.1% HIV RNA < 200 copies/mL). One in five (19.1%) WLWH had a positive baseline EPDS screen, with the mean EPDS scores decreasing from 5.3 ± 5.4 (baseline) to 4.6 ± 4.8 (follow-up). Among 55 WLWH who provided baseline and follow-up EPDS scores, only 3/13 with a positive baseline EPDS screen had resolved depressive symptoms at follow-up. Over one-third (37.7%) of WLWH indicated feeling "sadness" when asked whether lack of breastfeeding negatively affected their feelings or emotions. Over half of WLWH (51.9%) were aware of the US breastfeeding recommendations, but the majority (60.4%) had never discussed breastfeeding options with a medical provider. Improved provider-patient discussions on infant feeding options among WLWH is needed to increase awareness of breastfeeding choices and promote informed, autonomous breastfeeding decision-making among WLWH.

Batch effects removal for microbiome data via conditional quantile regression.

Batch effects in microbiome data arise from differential processing of specimens and can lead to spurious findings and obscure true signals. Strategies designed for genomic data to mitigate batch effects usually fail to address the zero-inflated and over-dispersed microbiome data. Most strategies tailored for microbiome data are restricted to association testing or specialized study designs, failing to allow other analytic goals or general designs. Here, we develop the Conditional Quantile Regression (ConQuR) approach to remove microbiome batch effects using a two-part quantile regression model. ConQuR is a comprehensive method that accommodates the complex distributions of microbial read counts by non-parametric modeling, and it generates batch-removed zero-inflated read counts that can be used in and benefit usual subsequent analyses. We apply ConQuR to simulated and real microbiome datasets and demonstrate its advantages in removing batch effects while preserving the signals of interest.

Factors Associated with Transition of HIV Care Readiness Among Adolescents and Youth from a Specialty Pediatric HIV Clinic in the United States.

Transitioning from pediatric to adult services is known to be associated with worsening of health outcomes and decreased retention in care among adolescents and youth living with HIV (AYLHIV). We aimed to identify factors associated with HIV care transition readiness among AYLHIV in care at a pediatric HIV clinic in Washington, DC. This retrospective cohort study from June 2019 through January 2021 collected demographic and clinical characteristics from the clinic database. We adapted the Transition Readiness Assessment Questionnaire (TRAQ; scored 1-4; 1 being the lowest level of preparedness) to evaluate transition readiness over time. We analyzed data using two-sided unadjusted two-sample and paired t-tests and adjusted analysis of variance (ANOVA). We included 103 AYLHIV (50.49% female; 100% non-Hispanic Black/African American; mean age = 19.54 ± 2.78 years; 81.55% virally suppressed). Mean baseline TRAQ score (2.32 ± 0.78) was associated with age (p < 0.0001), gender (p = 0.033), mode of HIV transmission (p = 0.0005), viral suppression (p = 0.0033), and duration of HIV diagnosis (p = 0.012). AYLHIV diagnosed with HIV within the prior year experienced significantly greater mean improvement in transition readiness compared with those living with HIV for >10 years (p = 0.013). Adjusted for covariates, older age (p < 0.0001), undetectable viral load (p = 0.0008), and presence of mental health condition(s) (p = 0.020) were associated with higher TRAQ scores. Lower improvement in transition readiness among youth with a longer history of HIV suggests that AYLHIV with perinatally acquired HIV might require additional support than those with horizontally acquired HIV.

Brief Report: Supporting Access to HIV Care for Children and Youth During the COVID-19 Pandemic With Telemedicine and Rideshare.

BACKGROUND: In response to the COVID-19 pandemic, we scaled up telemedicine and rideshare services for clinic and laboratory visits for pediatric and adolescent patients with HIV. SETTING: HIV subspecialty program for patients aged 0-24 years at Children's National Hospital, Washington, DC. METHODS: Using the χ2 and Wilcoxon rank sum tests, we compared demographics, visit and laboratory data, and rideshare usage among patients who scheduled telemedicine at least once (telemedicine) versus those who never scheduled telemedicine (no-telemedicine) during the pandemic (April-September 2020). We compared the number and proportion of scheduled and completed clinic visits before the pandemic (April-September 2019) with those during the pandemic. RESULTS: We analyzed 178 pediatric and adolescent patients with HIV (median age 17.9 years, 89.3% Black, 48.9% male patients, 78.7% perinatally infected), of whom 70.2% and 28.6% used telemedicine and rideshare, respectively. Telemedicine patients scheduled more visits (236 vs 179, P < 0.0001) and completed a similar proportion of visits (81.8% vs 86.0%, P = 0.3805) compared with no-telemedicine patients. Laboratory testing rates (81.3% versus 98.5%, P = 0.0005) were lower in telemedicine patients compared with no-telemedicine patients. Rideshare usage (12.4% versus 26.5%, P = 0.0068) was lower in telemedicine versus no-telemedicine patients. During the pandemic, most of the patients (81.0%) had HIV RNA <200 copies/mL. The total number of completed visits and the proportion of visits completed were similar before and during the pandemic. CONCLUSION: Most of the pediatric and adolescent patients with HIV used telemedicine and maintained HIV RNA <200 copies/mL during the pandemic. Despite rideshare usage, laboratory testing rates were lower with telemedicine compared with in-person visits.

Integrase Strand Transfer Inhibitors and Weight Gain in Children and Youth With Perinatal Human Immunodeficiency Virus in the DC Cohort.

We conducted a retrospective analysis of 38 children and youth with human immunodeficiency virus (aged 0-19 years) in the United States and report an increased rate of change of BMI-for-age z score after initiating integrase strand transfer inhibitors (+0.19 z score units/year [95% confidence interval, .01-.37]; P = .036) for a median follow-up of 527.5 days.

HIV Drug Resistance in Children and Adolescents: Always a Challenge?

Purpose of Review: With the expanded roll-out of antiretrovirals for treatment and prevention of HIV during the last decade, the emergence of HIV drug resistance (HIVDR) has become a growing challenge. This review provides an overview of the epidemiology and trajectory of HIVDR globally with an emphasis on pediatric and adolescent populations. Recent Findings: HIVDR is associated with suboptimal virologic suppression and treatment failure, leading to an increased risk of HIV transmission to uninfected people and increased morbidity and mortality among people living with HIV. High rates of HIVDR to non-nucleoside reverse transcriptase inhibitors globally are expected to decline with the introduction of the integrase strand transfer inhibitors and long-acting combination regimens, while challenge remains for HIVDR to other classes of antiretroviral drugs. Summary: We highlight several solutions including increased HIV viral load monitoring, expanded HIVDR surveillance, and adopting antiretroviral regimens with a high-resistance barrier to decrease HIVDR. Implementation studies and programmatic changes are needed to determine the best approach to prevent and combat the development of HIVDR.

Prevention of Perinatal HIV Transmission in an Area of High HIV Prevalence in the United States.

OBJECTIVE: To evaluate the uptake of perinatal HIV preventive interventions by the risk of perinatal HIV transmission in mother-infant pairs in a high-HIV prevalence area in the US. STUDY DESIGN: This was a retrospective cohort study of mother-infant pairs with perinatal HIV exposure during 2013-2017 managed at a subspecialty pediatric HIV program in Washington, DC. We collected demographic data, maternal HIV history, delivery mode, maternal and infant antiretroviral drug (ARV) use, and infant HIV test results. We compared the uptake of recommended preventive interventions in low-risk (ie, mothers on antiretroviral therapy [ART] with viral suppression) and high-risk (mothers without ART or viral suppression) mother-infant pairs using the Pearson chi-square, Fisher exact, and Wilcoxon rank-sum tests and logistic regression. RESULTS: We analyzed 551 HIV-exposed infants (HEIs) and 542 mothers living with HIV. The majority of mothers received ARVs (95.5%), had HIV RNA ≤1000 copies/mL before delivery (81.9%), and received intrapartum zidovudine (ZDV; 65.5%). The majority of all HEIs were low risk (82.6%) and received postpartum ARVs (98.9%). Among the low-risk infants, 53.2% were delivered via cesarean delivery (CD), and 62.9% and 96.5% were administered intrapartum and postpartum ZDV, respectively. Among high-risk infants, 84.4% were delivered via CD, 78.1% received intrapartum ZDV, and 62.5% received combination ART. Nine high-risk infants acquired HIV perinatally. CONCLUSION: In an area of high HIV prevalence in the US, a large proportion of low-risk HEIs received intrapartum ZDV and were delivered via CD. We also observed missed opportunities for the prevention of perinatal HIV transmission.

Pediatric Antiretroviral Therapy.

Human immunodeficiency virus (HIV) is one of the most serious pediatric infectious diseases, affecting around 3 million children and adolescents worldwide. Lifelong antiretroviral treatment (ART) provides multiple benefits including sustained virologic suppression, restoration and preservation of immune function, decreased morbidity and mortality, and improved quality of life. However, access to ART, particularly among neonates and young infants, continues to be challenging due to limited number of suitable formulations and limited access to pediatric ARV drug. Moreover, children and adolescents living with HIV may experience long-term HIV- and ART-associated comorbidities including cardiovascular, renal, neurological, and metabolic complications. We provide an overview of currently available formulations, dosing, and safety considerations for pediatric antiretroviral drugs by drug classes and according to the three age groups including neonates, children, and adolescents.

The Impact of Human Immunodeficiency Virus Infection on Gut Microbiota α-Diversity: An Individual-level Meta-analysis.

BACKGROUND: Whether human immunodeficiency virus (HIV) infection impacts gut microbial α-diversity is controversial. We reanalyzed raw 16S ribosomal RNA (rRNA) gene sequences and metadata from published studies to examine α-diversity measures between HIV-uninfected (HIV-) and HIV-infected (HIV+) individuals. METHODS: We conducted a systematic review and individual level meta-analysis by searching Embase, Medline, and Scopus for original research studies (inception to 31 December 2017). Included studies reported 16S rRNA gene sequences of fecal samples from HIV+ patients. Raw sequence reads and metadata were obtained from public databases or from study authors. Raw reads were processed through standardized pipelines with use of a high-resolution taxonomic classifier. The χ2 test, paired t tests, and generalized linear mixed models were used to relate α-diversity measures and clinical metadata. RESULTS: Twenty-two studies were identified with 17 datasets available for analysis, yielding 1032 samples (311 HIV-, 721 HIV+). HIV status was associated with a decrease in measures of α-diversity (P < .001). However, in stratified analysis, HIV status was associated with decreased α-diversity only in women and in men who have sex with women (MSW) but not in men who have sex with men (MSM). In analyses limited to women and MSW, controlling for HIV status, women displayed increased α-diversity compared with MSW. CONCLUSIONS: Our study suggests that HIV status, sexual risk category, and gender impact gut microbial community α-diversity. Future studies should consider MSM status in gut microbiome analyses.

Intestinal Integrity Biomarkers in Early Antiretroviral-Treated Perinatally HIV-1-Infected Infants.

Intestinal fatty acid binding protein (iFABP) levels did not differ between human immunodeficiency virus type 1 (HIV-1)- infected infants and uninfected infants exposed to HIV-1, but those who breastfed had substantially lower levels. Zonulin levels increased from 3 to 5.3 months of age with perinatal acquisition of HIV-1 despite early antiretroviral treatment. Biomarkers of intestinal integrity (ie, iFABP and zonulin) were compared in 56 HIV-1-positive African infants who received early antiretroviral treatment and 53 HIV-1-exposed but uninfected (HEU) controls. Despite heightened inflammation and immune activation in HIV-positive infants, iFABP and zonulin levels at 3 months of age were not different from those in HEU infants and largely were not correlated with inflammatory and immune activation biomarkers. However, zonulin levels increased and became significantly higher in HIV-positive infants as compared to HEU infants by 5 months of age, despite viral suppression due to antiretroviral treatment. These findings have implications for intestinal integrity biomarker profiling in perinatal HIV-1 infection.

The microbiome and HIV persistence: implications for viral remission and cure.

PURPOSE OF REVIEW: This article discusses the interaction between HIV infection, the gut microbiome, inflammation and immune activation, and HIV reservoirs, along with interventions to target the microbiome and their implications for HIV remission and cure. RECENT FINDINGS: Most studies show that HIV-infected adults have a gut microbiome associated with decreased bacterial richness and diversity, and associated systemic inflammation and immune activation. A unique set of individuals, elite controllers, who spontaneously control HIV replication, have a similar microbiome to HIV-uninfected individuals. Conversely, exposure to maternal HIV in infants was shown to alter the gut microbiome, even in infants who escaped perinatal infection. Emerging research highlights the importance of the metabolomics and metaproteomics of the gut microbiome, which may have relevance for HIV remission and cure. Together, these studies illustrate the complexity of the relationship between HIV infection, the gut microbiome, and its systemic effects. SUMMARY: Understanding the association of HIV with the microbiome, metabolome, and metaproteome may lead to novel therapies to decrease inflammation and immune activation, and impact HIV reservoir size and vaccine responses. Further research in this area is important to inform HIV remission and cure treatments.