BACKGROUND:Few studies have evaluated the ototoxic effects of in utero antiretroviral (ARV) exposure on hearing in children HIV-exposed uninfected (CHEU). Concerns have been identified for some ARVs: tenofovir disoproxil fumarate (TDF), emtricitabine (FTC), lamivudine (3TC), zidovudine (ZDV) and atazanavir (ATV). The aims are to describe hearing outcomes in 5-year-old CHEU in the Surveillance Monitoring for Antiretroviral Therapy Toxicities study and evaluate their association with in utero ARV exposures. METHODS:Hearing evaluations including pure-tone thresholds and distortion product otoacoustic emissions (DPOAEs) were completed in CHEU at 5 years. Log-binomial regression models were fit to assess associations of maternal ARV exposures with risk of sensorineural hearing loss (SNHL) and incomplete DPOAE responses. RESULTS:Among 1078 CHEU, 13% had SNHL. Among those exposed to <13 weeks gestation, there was 28% higher risk (95% confidence interval: -37% to 158%) of SNHL with TDF/FTC with ATV and 38% lower risk (95% confidence interval: -68% to 19%) with ZDV/3TC without ATV than for regimens containing TDF/FTC without ATV. There was a higher risk of incomplete DPOAE responses for ZDV/3TC without ATV and a lower risk for TDF/FTC with ATV. For CHEU with first ARV exposure at 13-26 weeks gestation, those exposed to TDF/FTC with ATV or ZDV/3TC without ATV had a lower risk for SNHL compared with TDF/FTC without ATV. Despite nontrivial relative risks, all confidence intervals were wide. CONCLUSIONS:While SNHL was relatively common, there were no consistent associations between in utero ARV exposure and SNHL or incomplete DPOAEs. Further research is needed on ARV exposures and other hearing measures in CHEU.

Background: To collect and compare selected hearing measures in a pilot study of young adults with perinatally acquired HIV (YAPHIV) and those with perinatal HIV exposure who are uninfected young adults with PHEU (YAPHEU). Setting: Cross-sectional hearing measures in YAPHIV and YAPHEU enrolled in the Pediatric HIV/AIDS Cohort Study Adolescent Master Protocol (AMP) for Participants 18 Years of Age and Older (AMP Up). Methods: Pure-tone air conduction audiometry and distortion product otoacoustic emission (DPOAE) data were collected in 1 visit. A low-frequency pure-tone average (PTA) (LFPTA, at 0.25, 0.5, 1, and 2 kHz), a speech-frequency PTA (SFPTA, at 0.5, 1, 2, and 4 kHz), and a high-frequency PTA (HFPTA, at 3, 4, 6, and 8 kHz) were calculated. Hearing loss was defined as worse ear SFPTA of ≥20 dB HL. Separate linear regression models were fit for worse ear LFPTA, SFPTA, and HFPTA to assess associations with PHIV status. DPOAE signal-to-noise ratios (SNRs) were obtained at 3 frequencies in each ear. Results: Forty-seven YAPHIV and 9 YAPHEU completed hearing testing. All adjusted mean PTAs were similar between YAPHIV and YAPHEU. Hearing loss occurred more in YAPHIV (7/47, 15.2%; 95% CI: 6.3%–28.9%), compared with YAPHEU (0/9, 0%). No associations were detected between HIV disease severity measures and worse ear SFPTA. DPOAE SNRs were similar between YAPHIV and YAPHEU. Conclusions: In this pilot study, peripheral hearing (ie, PTAs) and cochlear function (ie, DPOAEs) were similar between YAPHIV and YAPHEU. A larger study is warranted to confirm these findings.

Studies have observed neurodevelopmental (ND) challenges among young children perinatally HIV-exposed yet uninfected (CHEU) with in utero antiretroviral (ARV) exposure, without clear linkage to specific ARVs. Atazanavir (ATV) boosted with ritonavir has been a preferred protease inhibitor recommended for pregnant women, yet associations of ATV with ND problems in CHEU have been reported. Studies among early school-age children are lacking. The pediatric HIV/AIDS cohort study (PHACS) surveillance monitoring for antiretroviral therapy (ART) toxicities (SMARTT) study evaluated 5-year-old monolingual English-speaking CHEU using the behavior assessment system for children, Wechsler preschool and primary scales of intelligence, and test of language development-primary. A score ≥1.5 standard deviations worse than population norms defined a signal within each domain. Analyses of risk for signals were stratified by timing of any ARV initiation. Associations between ARV exposure and risk of ND signals were assessed using proportional odds models, adjusting for confounders. Among 230 children exposed to ARVs at conception, 15% had single and 8% had multiple ND problems; ATV exposure was not associated with higher risk of signals [adjusted cumulative odds ratio (cOR) = 0.66, confidence interval (CI): 0.28-1.56]. However, among 461 children whose mothers initiated ARVs during pregnancy, 21% had single and 12% had multiple ND problems; ATV exposure was associated with higher risk of signals (cOR = 1.70, CI: 0.82-3.54). The specific regimen tenofovir/emtricitabine/ATV was associated with higher risk (cOR = 2.31, CI: 1.08-4.97) relative to regimens using a zidovudine/lamivudine backbone combined with non-ATV ARVs. It remains important to monitor neurodevelopment of CHEU during early childhood and investigate the impact and the role of timing of in utero exposure to specific ARVs.

BackgroundCMV infection of the fetus or neonate can lead to devastating disease, and there are no effective prevention strategies to date. Vitamin D is a potent immunomodulator, supports antiviral immune responses, and plays an important role in placental immunity.MethodsRetrospective cohort study to evaluate the impact of low maternal vitamin D on congenital and early postnatal transmission of CMV among HIV-infected, non-breastfeeding women and their HIV exposed but negative infants from an urban HIV clinic. Vitamin D panel was performed on stored maternal plasma obtained near time of delivery. Infant CMV testing at 0-6 months included urine and oral cultures, and/or serum polymerase chain reaction testing.ResultsCohort included 340 mother-infant pairs (births 1991-2014). Among 38 infants (11%) with a CMV+ test between 0-6 months, 4.7% (14/300) had congenital CMV transmission (CMV+ test 0-3 weeks), and 7.6% (24/315) had peri/postnatal CMV (CMV+ test >3 weeks-6 months). Women with lower calcitriol (1,25-dihydroxyvitamin D), the active form of vitamin D, were more likely to have an infant with congenital (OR 12.2 [95% CI 1.61-92.2] P = 0.02) and peri/postnatal (OR 9.84 [95% CI 2.63-36.8] P = 0.0007) infections in multivariate analyses, independent of maternal HIV viral load and CD4 count.ConclusionThis study demonstrates an association between inadequate maternal calcitriol during pregnancy and increased congenital and early postnatal acquisition of CMV among non-breastfeeding women with HIV and their HIV negative infants.

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.

BACKGROUND:Global immune activation and HLA alleles are each associated with the pathogenesis of human immunodeficiency virus (HIV) and hepatitis C virus .METHODS:We evaluated the relationship between 44 HLA class I and 28 class II alleles and percentages of activated CD8 (CD8+CD38+DR+) and CD4 (CD4+CD38+DR+) T cells in 586 women who were naive to highly active antiretroviral therapy. We used linear generalized estimating equation regression models, adjusting for race/ethnicity, age, HIV load, and hepatitis C virus infection and controlling for multiplicity using a false discovery rate threshold of 0.10.RESULTS:Ten HLA alleles were associated with CD8 and/or CD4 T-cell activation. Lower percentages of activated CD8 and/or CD4 T cells were associated with protective alleles B*57:03 (CD8 T cells, -6.6% [P = .002]; CD4 T cells, -2.7% [P = .007]), C*18:01 (CD8 T cells, -6.6%; P < .0008) and DRB1*13:01 (CD4 T cells, -2.7%; P < .0004), and higher percentages were found with B*18:01 (CD8 T cells, 6.2%; P < .0003), a detrimental allele. Other alleles/allele groups associated with activation included C*12:03, group DQA1*01:00, DQB1*03:01, DQB1*03:02, DQB1*06:02, and DQB1*06:03.CONCLUSION:These findings suggest that a person's HLA type may play a role in modulating T-cell activation independent of viral load and sheds light on the relationship between HLA, T-cell activation, immune control, and HIV pathogenesis.

Abstract Objective To examine the association of vitamin D insufficiency and risk of pregnancy-induced hypertension (PIH) among human immunodeficiency virus (HIV)-infected pregnant women. Study Design This is a retrospective cohort study evaluating the impact of low maternal vitamin D levels on PIH and perinatal outcomes among HIV-infected pregnant women receiving care at an urban HIV center from 1991 to 2014. Results A total of 366 pregnant women were included, of which 11% developed PIH. Lower levels of 25-hydroxyvitamin D (25(OH)D) and bioactive 1,25-dihydroxyvitamin D (1,25(OH)2D) were associated with increased HIV disease activity. 25(OH)D levels were not significantly associated with the incidence of PIH. Higher 1,25(OH)2D levels were associated with reduced incidence of PIH in univariate (odds ratio, OR: 0.87 [95% confidence interval, CI: 0.79–0.95], p = 0.004) and multivariate (OR: 0.88 [95% CI: 0.80–0.97], p = 0.010) analyses. No association was found between 25(OH)D levels and other obstetric outcomes. Lower 1,25(OH)2D levels were associated with group B Streptococcus colonization (OR: 0.92 [95% CI: 0.86–0.99]) and low birth weight (LBW) (OR: 0.90 [95% CI: 0.83–0.98]) on multivariate analysis. Mean 1,25(OH)2D levels were significantly lower in women with preterm delivery and LBW infants. Conclusion Lower bioactive vitamin D levels are related to PIH in HIV-infected women. This association may be related to the coexistence of abnormal placental vitamin D metabolism and abnormal placental implantation.

Background: Metabolic perturbations in HIV-exposed uninfected (HEU) obese youth may differ from those in the general obese pediatric population. Methods: Metabolic parameters of obese (body mass index Z-score >95th percentile) HEU youth in the Pediatric HIV/AIDS Cohort Study (PHACS) Surveillance Monitoring of ART Toxicities (SMARTT) study were compared with a matched sample of obese youth from the US National Health and Nutrition Examination Survey (NHANES). We evaluated systolic and diastolic hypertension (blood pressure ≥90th percentile for age, sex, and height), total cholesterol >200 mg/dL, high-density lipoprotein cholesterol <35 mg/dL, low-density lipoprotein cholesterol >130 mg/dL, triglycerides (TGs) >150 mg/dL, and Homeostatic Model Assessment–Insulin Resistance >4.0. Modified Poisson regression models were fit to quantify the prevalence ratio (PR) of each outcome comparing the 2 cohorts, adjusting for confounders. Results: The blood pressure outcome analytic subgroup included 1096 participants (n = 304 HEU), the total cholesterol and high-density lipoprotein cholesterol subgroup 1301 participants (n = 385 HEU), and the low-density lipoprotein cholesterol, TG, and Homeostatic Model Assessment–Insulin Resistance subgroup 271 (n = 83 HEU). After adjustment, obese HEU youth had a higher prevalence of systolic and diastolic hypertension [PR = 3.34, 95% confidence interval (CI): 2.48 to 4.50; PR = 2.04, 95% CI: 1.18 to 3.52, respectively], but lower prevalence of insulin resistance (PR = 0.67, 95% CI: 0.54 to 0.85) and hypercholesterolemia (PR = 0.67, 95% CI: 0.44 to 1.01) compared with obese NHANES youth. Conclusions: In the United States, obese HEU youth seem to have an increased risk of hypertension, but lower risk of insulin resistance and hypercholesterolemia, compared with a general obese pediatric population. Monitoring for cardiovascular morbidity in adulthood may be warranted in HEU children.

Background Perinatal HIV transmission has substantially decreased with combination antiretroviral regimens, but complications in children who are HIV-exposed but uninfected, such as microcephaly, warrant ongoing surveillance. We aimed to evaluate whether individual in utero antiretroviral exposures were associated with increased risk of microcephaly based on long-term follow-up of infants and children who are HIV-exposed but uninfected. Methods We evaluated children aged younger than 18 years who were HIV-exposed but uninfected with at least one head circumference measurement while enrolled in the Surveillance Monitoring for ART Toxicities (SMARTT) study at 22 clinical sites in the USA, including Puerto Rico. This prospective cohort study was done by the Pediatric HIV/AIDS Cohort Study network. Microcephaly was defined as having a head circumference Z score <-2 according to the 2000 US Centers for Disease Control and Prevention growth charts for children 6-36 months old and according to Nellhaus standards (head circumference <2nd percentile) after 36 months (SMARTT criteria); an alternate definition for microcephaly was based on applying Nellhaus standards across all ages (Nellhaus criteria). Modified Poisson regression models were fit to obtain relative risks (RRs) for associations between in utero antiretroviral exposure and microcephaly status, adjusted for potential confounders. Neurodevelopmental functioning was compared in children who are HIV-exposed but uninfected with or without microcephaly. Findings Between March 21, 2007, and Aug 1, 2017, 3055 participants enrolled in SMARTT had at least one head circumference measurement. The cumulative incidence of microcephaly over a median of 5.1 years of follow-up (IQR 3.0-7.2) was 159 (5.2%, 95% CI 4.4-6.1) by Nellhaus criteria and 70 (2.3%, 1.8-2.9) by SMARTT criteria. In adjusted models, in utero exposure to efavirenz (4.7% exposed) was associated with increased risk of microcephaly by both Nellhaus standards (adjusted RR 2.02, 95% CI 1.16-3.51) and SMARTT criteria (2.56, 1.22-5.37). These associations were more pronounced in children exposed to combination regimens of efavirenz that included zidovudine plus lamivudine than those including tenofovir plus emtricitabine. Protective associations were observed for darunavir exposure (adjusted RR 0.50, 95% CI 0.24-1.00). Children who are HIV-exposed but uninfected with microcephaly had lower mean scores on neurodevelopmental assessments at age 1 and 5 years and a higher prevalence of neurodevelopmental impairment than those without microcephaly. Interpretation These findings support consideration of alternatives to efavirenz as part of first-line antiretroviral therapy for pregnant women. Copyright (C) 2019 Elsevier Ltd. All rights reserved.

Objectives To estimate birth prevalence of congenital cytomegalovirus (cCMV) in HIV-exposed uninfected children born in the current era of combination antiretroviral therapy and describe cCMV-related neurodevelopmental and hearing outcomes. Study design The Surveillance Monitoring for ART Toxicities cohort study follows HIV-exposed uninfected children at 22 sites in the US and Puerto Rico. Birth cCMV prevalence was estimated in a subset of participants who had blood pellets collected within three weeks of birth and underwent >= 1 of 6 assessments evaluating cognitive and language development including an audiologic examination between 1 and 5 years of age. Detection of CMV DNA by polymerase chain reaction testing of peripheral blood mononuclear cells was used to diagnose cCMV. Proportions of suboptimal assessment scores were compared by cCMV status using Fisher exact test. Results Mothers of 895 eligible HIV-exposed uninfected children delivered between 2007 and 2015. Most (90%) were on combination antiretroviral therapy, 88% had an HIV viral load of <= 400 copies/mL, and 93% had CD4 cell counts of >= 200 cells/mu L. Eight infants were diagnosed with cCMV, yielding an estimated prevalence of 0.89% (95% CI, 0.39H-1.75%). After adjusting for a sensitivity of 70%-75% for the testing method, projected prevalence was 1.2%-1.3%. No differences were observed in cognitive, language and hearing assessments by cCMV status. Conclusions Although birth cCMV prevalence in HIV-exposed uninfected children born to women with well-controlled HIV is trending down compared with earlier combination antiretroviral therapy-era estimates, it is above the 0.4% reported for the general US population. HIV-exposed uninfected children remain at increased risk for cCMV.

Abstract Background The prevalence of congenital cytomegalovirus infection (cCMV) at birth is 0.5%–1% in the United States. Most cCMV newborns are asymptomatic at birth with 10%–15% subsequently developing sequelae, such as hearing loss. Higher cCMV prevalence (2.5%–11.4%) is reported in infants born to HIV-infected women, associated with maternal immune suppression and lack of antiretroviral therapy (ART), with few studies addressing neurodevelopmental (ND) outcomes in their offspring. We report birth prevalence of cCMV in a cohort of HIV-exposed, uninfected infants (HEU) born to women on combination ART with well-controlled HIV and describe ND outcomes through age 5 years. Methods The Surveillance Monitoring for ART Toxicities (SMARTT) study is an ongoing NICHD-funded observational multi-centered cohort study (United States and Puerto Rico) of growth and development of HEU children that commenced in 2007. As of August 1, 2017, participants with stored blood pellets collected ≤3 weeks after birth and at least 1 ND assessment ≥1 year of age had pellets tested by DNA PCR to establish cCMV. Comparisons of ND outcomes (defined in figure) at ages 1, 2, and 5 by cCMV status were made using Wilcoxon and Fisher’s Exact tests. Results Of 895 children meeting study criteria (55% black; 32% white; 40% Latino), 8 had cCMV, yielding a birth prevalence of 0.89% (95% CI 0.39–1.75%). All were asymptomatic and similar to CMV-uninfected infants in gestational age and anthropometric measurements at birth. The last HIV viral load prior to delivery was undetectable in 88% of women. The last available CD4% was <20% in 3/8 mothers of cCMV newborns compared with 112/873 in those without (38% vs. 13%, P < 0.07). The mean duration of follow-up (± standard deviation) of children with cCMV was 7.2 years (1.6) and those without 5.9 (2.3) years (P < 0.11). ND assessments for language development (CDI at 1, A&S at 2, TOLD-P:3 at 5), cognition (Bayleys-III at 1), intelligence (WPPSI-III at 5), and hearing (PTA at 5) did not differ by cCMV status (figure). Conclusion Birth prevalence of cCMV in HEU children born within the last decade approaches national US prevalence. Preschool HEU children with asymptomatic cCMV at birth did not show poorer language, hearing, and developmental outcomes compared with CMV-uninfected HEU children. Disclosures All authors: No reported disclosures.

BACKGROUND:Perinatally HIV-exposed but uninfected (HEU) children have elevated risk of late language emergence at 1 year of age, with possible links to in utero antiretroviral (ARV) exposure. We investigated possible risks for speech impairments (SIs) and language impairments (LI) in preschool monolingual HEU children in the United States. METHODS:Speech and language assessments were conducted as part of the Pediatric HIV/AIDS Cohort Study Surveillance Monitoring of ART Toxicities study at ages 3 (N = 208) and 5 (N = 429) years. Domains of speech, overall language, vocabulary and grammar were assessed. SI and LI were defined by standardized scores <15th percentile and categorized as primary (normal nonverbal IQ ≥ 85 without hearing loss) and concomitant (low nonverbal IQ and/or presence of hearing loss). Logistic regression models were used to estimate odds of SI and LI for different ARV exposures, adjusted for confounding variables. RESULTS:The risk for language impairments in HEU children was higher than population norms; risk for SIs was not elevated. Risk factors for impairments included male sex, black race and other socioeconomic measures, although these varied by age, primary (P) versus concomitant (C) impairment and by speech or language measure. Adjusted logistic regression models revealed lower and increased risk for specific ARVs. Tenofovir exposure was associated with increased risk for SI at 3 years of age but was associated with decreased risk for concomitant language impairment at 5 years of age. CONCLUSIONS:Further investigation of combination ARV exposure and speech/language impairment among preschool children is needed to confirm associations.

Objective: We sought to describe the current status of perinatal HIV exposure surveillance (PHES) activities and regulations in the United States and to make recommendations to strengthen PHES.Methods: In 2014, we sent an online survey to health departments in the 50 states, District of Columbia, Puerto Rico, Virgin Islands, and 6 cities and counties (Chicago, Illinois; Houston, Texas; Los Angeles, California; New York, New York; Philadelphia, Pennsylvania; and San Francisco, California). We analyzed responses from 56 of the 59 (95%) jurisdictions.Results: Thirty-three of 56 jurisdictions (59%) reported conducting PHES and following infants to determine their infection status. Of the 33 jurisdictions performing PHES, 28 (85%) linked maternal and infant data, but only 12 (36%) determined the HIV care status of postpartum women. Themes of respondents' recommendations for strengthening PHES centered on updating laws and regulations to support PHES, reporting all HIV test results and linking vital records with PHES data to identify and follow HIV-exposed infants, communicating with health care providers to improve reporting, training staff, and getting help from experienced jurisdictions to implement PHES.Conclusions: Our findings indicate that data on perinatal exposure collected through the current system are inadequate to comprehensively monitor and prevent perinatal HIV exposure and transmission. Comprehensive PHES data collection and reporting are needed to sustain the progress that has been made toward lowering perinatal HIV transmission rates. We propose that minimum standards be established for perinatal HIV exposure reporting to improve the completeness, quality, and efficiency of PHES in the United States.

To evaluate the impact of low maternal vitamin D levels in pregnant HIV-infected women on the incidence of preterm birth (PTB), low birth weight (LBW) and small-for-gestational age (SGA) infants Retrospective cohort study evaluating the impact of low maternal vitamin D levels on perinatal outcomes among HIV-infected women receiving prenatal care at a major urban HIV perinatal center. Comprehensive vitamin D panels (1,25-dihydroxyvitamin D (1,25(OH)2D), 25-hydroxyvitamin D (25(OH)D), free and bioavailable fractions) were performed on maternal plasma samples collected and stored near the time of delivery (births 1991-2014) as part of a natural history study. Multivariate analyses controlled for potential confounders including indices of HIV disease severity and control. The cohort included 366 mother-baby pairs, of which 13.7% (N=50) were delivered preterm (<37 weeks of gestation), 10.4% (N=38) were LBW (<2500 grams), and 2.3% (N=10) were SGA (birthweight <10th percentile). Higher 1,25(OH)2D levels, the active form of vitamin D, were protective against PTB (OR 0.92 [95% CI 0.85-0.98], p=0.01) and LBW (OR 0.91 [95% CI 0.84-0.99], p=0.03). The associations remained significant in multivariate analyses for both PTB (OR 0.92 [95% CI 0.84-1.0], p=0.04) and LBW (OR 0.91 [95% CI 0.84-0.99], p=0.03), controlling for maternal demographics, mode of delivery, HIV treatment regimen, and measures of HIV disease control. Correlates of vitamin D levels included maternal race, season, CD4, HIV viral load, and antiretroviral regimen. CD4 counts <200 were independently associated with preterm birth (p=0.002). Maternal HIV viral load was a significant correlate of both 1,25(OH)D2 and 25(OH)D, but was not itself associated with the obstetric outcomes. Lower vitamin D levels are associated with HIV disease severity in pregnant HIV-infected women. Lower levels of 1,25-dihydroxyvitamin D, the active circulating form of vitamin D, were independently associated with an increased risk of preterm birth and LBW infants in this cohort.

BACKGROUND:Plasma HIV RNA is the most significant determinant of cervical HIV shedding. However, shedding is also associated with sexually transmitted infections (STIs) and cervical inflammation. The mechanism by which this occurs is poorly understood. There is evidence that systemic immune activation promotes viral entry, replication, and HIV disease progression. We hypothesized that systemic immune activation would be associated with an increase in HIV genital shedding.METHODS:Clinical assessments, HIV RNA in plasma and genital secretions, and markers of immune activation (CD38(+)DR(+) and CD38(-)DR(-)) on CD4(+) and CD8(+) T cells in blood were evaluated in 226 HIV+ women enrolled in the Women's Interagency HIV Study. There were 569 genital evaluations of which 159 (28%) exhibited HIV RNA shedding, defined as HIV viral load >80 copies per milliliter. We tested associations between immune activation and shedding using generalized estimating equations with logit link function.RESULTS:In the univariate model, higher levels of CD4(+) and CD8(+) T-cell activation in blood were significantly associated with genital tract shedding. However, in the multivariate model adjusting for plasma HIV RNA, STIs, and genital tract infections, only higher levels of resting CD8(+) T cells (CD38(-)DR(-)) were significantly inversely associated with HIV shedding in the genital tract (odds ratios = 0.44, 95% confidence interval: 0.21 to 0.9, P = 0.02).CONCLUSIONS:The association of systemic immune activation with genital HIV shedding is multifactorial. Systemic T-cell activation is associated with genital tract shedding in univariate analysis but not when adjusting for plasma HIV RNA, STIs, and genital tract infections. In addition, women with high percentage of resting T cells are less likely to have HIV shedding compared with those with lower percentages. These findings suggest that a higher percentage of resting cells, as a result of maximal viral suppression with treatment, may decrease local genital activation, HIV shedding, and transmission.

Background. Language impairment (LI) risk is increased for perinatally acquired human immunodeficiency virus-infected (PHIV) and perinatally exposed to HIV but uninfected (PHEU) youth. This study evaluates the persistence of LI in these groups.Methods. The Clinical Evaluation of Language Fundamentals was repeated on participants of the Pediatric HIV/AIDS Cohort Study Adolescent Master Protocol 18 months postbaseline. Regression models identified factors associated with change in standardized score (SC) and the resolution or development of LI.Results. Of 319 participants, 112 had LI at baseline. Upon re-evaluation, SCs were highly stable and changes were similar in PHIV (n = 212) and PHEU (n = 107) participants. Those with family history of language delays had a 2.39 point lower mean increase in SCs than those without, after controlling for demographic and socioeconomic factors and baseline LI status. Among PHIV participants, CD4 count,350 cells/mm(3) was associated with lower mean SC change (4.32 points), and exposure to combination antiretroviral therapy (cART) or protease inhibitors (PIs) was associated with a higher mean SC change (5.93 and 4.19 points, respectively). Initial LI was persistent in most cases (78%); 20 new cases occurred (10%). Female sex was associated with higher odds of LI resolution. Among PHIV, duration and baseline cART and history of PI use were associated with LI resolution; higher percentage of detectable viral loads before baseline was associated with lower odds of resolution.Conclusions. The PHIV and PHEU youth are at risk for persistent LI, and family history of language delays was a risk factor for persistence of problems. Measures of successful HIV treatment predicted more favorable outcomes among PHIV youth.

HIV-related stigma affects people living with HIV (PLWH), especially in communities of color. In our study, African American and Latina/Hispanic women living with HIV (WLWH) described experiences of stigma through PhotoVoice, a community-based participatory method of documentary photography. Ten WLWH from Los Angeles documented stigma experiences through photographs for up to 5 weeks and discussed their images during a focus group or semi-structured individual interview. Qualitative interpretive phenomenological analysis of participant narratives and photographs revealed lack of education and cultural myths as the main triggers of the stigma our participants faced. Stigma was experienced in health care settings, and participants identified depression, fear of intimate relationships, and nondisclosure of HIV status as its consequences. Social support and faith were noted as key coping mechanisms. WLWH recommended involving PLWH and public health officials in stigma reduction campaigns and youth education. PhotoVoice was perceived as a useful tool for education and self-improvement. Copyright (C) 2016 Association of Nurses in AIDS Care

Objective: To investigate whether prenatal atazanavir (ATV) exposure, assessed by meconium antiretroviral (ARV) quantification, predicts early child language outcomes. Prenatal ATV exposure previously was associated with poorer language development in 1-year olds.Methods: Pregnant women with HIV and their uninfected infants enrolled in the Surveillance Monitoring of Antiretroviral Therapy Toxicities study. Meconium ARV concentrations were quantified by liquid chromatography-tandem mass spectrometry. Language development at 1 year was assessed with MacArthur-Bates Communicative Development Inventory (CDI) and Bayley Scales of Infant and Toddler Development-Third Edition (Bayley-III). Late language emergence was defined as >= 1 of 4 CDI scores <= 10th percentile for age. Associations between fetal ATV exposure timing and duration, meconium ATV concentration, and language outcomes were evaluated, adjusting for potential confounders.Results: Through 2013, meconium samples were available from 175 of 432 infants with prenatal ATV exposure. Valid Bayley-III (n = 93) and CDI (n = 106) assessments also were available. After adjustment for potential confounders, higher ATV meconium concentrations were associated with lower late language emergence risk (P = 0.04) and cumulative ATV exposure duration also was associated with higher Bayley-III Language scores (P = 0.03). Maternal ATV duration and initiation week correlated with ATV meconium concentrations (positively and negatively, respectively).Conclusions: Higher meconium ATV concentrations were protective against developmental language delays at 1 year, suggesting the importance of fetal ATV detoxification into meconium. This information supports ATV exposure safety for infant language development. ATV is a preferred ARV for pregnant women with HIV, suggesting the importance of ATV safety investigations. Additionally, further pursuit of the influences on language development in HIV-exposed uninfected infants is required.

Objectives:Hepatitis C virus (HCV) infection causes an alteration in T-cell maturation and activation in patients coinfected with human immunodeficiency virus (HIV). Because interleukin 7 (IL-7) is a major cytokine controlling T-cell homeostasis, we analyzed the potential influence of HCV coinfection on circulating IL-7 levels in HIV-infected women before and after highly active antiretroviral therapy (HAART). Design and Methods:This prospective study included 56 HIV monoinfected, 55 HIV/HCV coinfected without HCV viremia, 132 HIV/HCV coinfected with HCV viremia, and 61 HIV/HCV-uninfected women for whom plasma levels of IL-7 were determined by enzyme-linked immunosorbent assay at 1 or more follow-up visits before and after HAART. Cross-sectional analyses of the associations between plasma IL-7 levels and HCV infection, demographic, clinical, and immunologic characteristics were evaluated using univariate and multivariate linear regression models before and after HAART. Results:In multivariate models, IL-7 levels were significantly higher in coinfected HCV viremic women than in HIV monoinfected women (multiplicative effect = 1.48; 95% confidence interval: 1.01 to 2.16; P = 0.04) before HAART, but were similar between these two groups among women after HAART. In addition to HCV viremia, higher IL-7 levels were associated with older age (P = 0.02), lower CD4+ T-cell count (P = 0.0007), and higher natural killer T-cell count (P = 0.02) in women before HAART. Among HAART-treated women, only lower CD4+ T-cell count was significantly associated with IL-7 level (P = 0.006). Conclusions:Our data demonstrate that in HIV-infected women, circulating levels of IL-7 are strongly associated with CD4+ T-cell depletion both before and after HAART. Our data also demonstrate that HCV viremia increases circulating IL-7 levels before HAART but not after HAART in coinfected women. This suggests that the effect of HCV on lymphopenia is abrogated by HAART.