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OBJECTIVE: To evaluate effects of maternal HIV and antiretroviral treatment (ART) on intrauterine fetal growth. DESIGN: Prospective cohort studies of HIV and ZIKA infection among women living with HIV (WLHIV) and women not living with HIV (WNLHIV) conducted in Brazil and the US from 2016 to 2020. METHODS: We evaluated fetal growth via repeated ultrasounds and calculated z scores for fetal growth measures using Intergrowth-21st standards among women with singleton pregnancies. Adjusted linear mixed models were fit for each fetal growth z score by HIV status. Among WLHIV, we compared fetal growth z scores by the most common maternal ART regimens, stratified by timing of ART initiation. RESULTS: We included 166 WLHIV and 705 WNLHIV; none had Zika infection. The z scores were similar for WLHIV and WNLHIV for femur length (latest third trimester medianâ=â1.08) and estimated fetal weight (median ≈0.60); adjusted mean differences in fetal weight z scores by HIV status were less than 0.1 throughout gestation. Other fetal growth measurements were lower for WLHIV than WNLHIV early in gestation but increased more rapidly over gestation. Among WLHIV not on ART at conception, adjusted mean z scores were generally similar across regimens initiated during pregnancy but somewhat lower for atazanavir-based regimens for biparietal diameter compared with efavirenz-based or raltegravir-based regimens. Among WLHIV on ART at conception, mean z scores were similar across ART regimens. CONCLUSION: Within our cohorts, fetal growth was lower in WLHIV than WNLHIV early in gestation but similar by the end of gestation, which is reassuring. Among WLHIV, fetal growth measures were generally similar across ART regimens evaluated.
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Infecções por HIV , Infecção por Zika virus , Zika virus , Gravidez , Humanos , Feminino , Peso Fetal , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Estudos Prospectivos , Ultrassonografia Pré-Natal , Desenvolvimento FetalRESUMO
BACKGROUND: Although sustained access to health care is essential, little is known about the relationship between insurance coverage and health among people born to women living with HIV (WLHIV). SETTING: Prospective cohort studies of youth and young adults born to WLHIV from 2007 to 2019. METHODS: We used adjusted generalized estimating equation models to estimate mean differences in, and relative risks (RRs) of, health-related quality of life (HR-QoL) and HIV disease measures over time by insurance status. HR-QoL scales with limited variability were dichotomized. Modified Poisson models were used to estimate RRs. RESULTS: Six hundred sixty-nine Adolescent Master Protocol (AMP) youth [66% living with perinatally-acquired HIV (PHIV), 72% Black] and 939 AMP Up/AMP Up Lite young adults (89% PHIV, 68% Black) reported insurance. Most were publicly insured (87% youth, 67% young adults). Privately insured young adults living with PHIV had lower risk of antiretroviral therapy nonadherence [adjusted RR (aRR): 0.82, 95% CI: 0.70 to 0.97] than those with public insurance. There was a lower risk of suboptimal role functioning for young adults with private insurance (aRR: 0.58, 95% CI: 0.35 to 0.97) and those unaware of their coverage (aRR: 0.41, 95% CI: 0.21 to 0.78). Young adults with private insurance had higher health perception scores than those with public insurance (adjusted mean difference: 3.87, 95% CI: 0.37 to 7.38). For youth, we observed no differences in HR-QOL and HIV disease measures by insurance. CONCLUSION: These findings suggest meaningful differences in antiretroviral therapy adherence and some HR-QoL outcomes by health insurance coverage among young adults born to WLHIV.
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Infecções por HIV , Qualidade de Vida , Adolescente , Feminino , Humanos , Infecções por HIV/tratamento farmacológico , Cobertura do Seguro , Estudos ProspectivosRESUMO
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.).
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Fármacos Anti-HIV , Infecções por HIV , Inibidores da Protease de HIV , HIV-1 , Compostos Heterocíclicos com 3 Anéis , Oxazinas , Piperazinas , Nascimento Prematuro , Piridonas , Adulto , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/uso terapêutico , Sulfato de Atazanavir/efeitos adversos , Sulfato de Atazanavir/uso terapêutico , Cobicistat/efeitos adversos , Cobicistat/uso terapêutico , Estudos de Coortes , Darunavir/efeitos adversos , Darunavir/uso terapêutico , Feminino , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/efeitos adversos , Inibidores da Protease de HIV/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Humanos , Recém-Nascido , Oxazinas/efeitos adversos , Oxazinas/uso terapêutico , Piperazinas/efeitos adversos , Piperazinas/uso terapêutico , Gravidez , Nascimento Prematuro/induzido quimicamente , Piridonas/efeitos adversos , Piridonas/uso terapêutico , Quinolonas/efeitos adversos , Quinolonas/uso terapêutico , Raltegravir Potássico/efeitos adversos , Raltegravir Potássico/uso terapêutico , Rilpivirina/efeitos adversos , Rilpivirina/uso terapêutico , Ritonavir/efeitos adversos , Ritonavir/uso terapêutico , Estados UnidosRESUMO
Human immunodeficiency virus (HIV) viral load (VL) is an important quantitative marker of disease progression and treatment response in people living with HIV infection, including children with perinatally acquired HIV. Measures of VL are often used to predict different outcomes of interest in this population, such as HIV-associated neurocognitive disorder. One popular approach to summarizing historical viral burden is the area under a time-VL curve (AUC). However, alternative historical VL summaries (HVS) may better answer the research question of interest. In this article, we discuss and contrast the AUC with alternative HVS, including the time-averaged AUC, duration of viremia, percentage of time with suppressed VL, peak VL, and age at peak VL. Using data on youth with perinatally acquired HIV infection from the Pediatric HIV/AIDS Cohort Study Adolescent Master Protocol, we show that HVS and their associations with full-scale intelligence quotient depend on when the VLs were measured. When VL measurements are incomplete, as can be the case in observational studies, analysis results may be subject to selection bias. To alleviate bias, we detail an imputation strategy, and we present a simulation study demonstrating that unbiased estimation of a historical VL summary is possible with a correctly specified imputation model.
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Infecções por HIV , Adolescente , Criança , Estudos de Coortes , Humanos , Testes Sorológicos , Carga Viral , ViremiaRESUMO
INTRODUCTION: Adolescents living with HIV are subject to multiple co-morbidities, including growth retardation and immunodeficiency. We describe growth and CD4 evolution during adolescence using data from the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) global project. METHODS: Data were collected between 1994 and 2015 from 11 CIPHER networks worldwide. Adolescents with perinatally acquired HIV infection (APH) who initiated antiretroviral therapy (ART) before age 10 years, with at least one height or CD4 count measurement while aged 10-17 years, were included. Growth was measured using height-for-age Z-scores (HAZ, stunting if <-2 SD, WHO growth charts). Linear mixed-effects models were used to study the evolution of each outcome between ages 10 and 17. For growth, sex-specific models with fractional polynomials were used to model non-linear relationships for age at ART initiation, HAZ at age 10 and time, defined as current age from 10 to 17 years of age. RESULTS: A total of 20,939 and 19,557 APH were included for the growth and CD4 analyses, respectively. Half were females, two-thirds lived in East and Southern Africa, and median age at ART initiation ranged from <3 years in North America and Europe to >7 years in sub-Saharan African regions. At age 10, stunting ranged from 6% in North America and Europe to 39% in the Asia-Pacific; 19% overall had CD4 counts <500 cells/mm3 . Across adolescence, higher HAZ was observed in females and among those in high-income countries. APH with stunting at age 10 and those with late ART initiation (after age 5) had the largest HAZ gains during adolescence, but these gains were insufficient to catch-up with non-stunted, early ART-treated adolescents. From age 10 to 16 years, mean CD4 counts declined from 768 to 607 cells/mm3 . This decline was observed across all regions, in males and females. CONCLUSIONS: Growth patterns during adolescence differed substantially by sex and region, while CD4 patterns were similar, with an observed CD4 decline that needs further investigation. Early diagnosis and timely initiation of treatment in early childhood to prevent growth retardation and immunodeficiency are critical to improving APH growth and CD4 outcomes by the time they reach adulthood.
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Infecções por HIV , Adolescente , Adulto , Contagem de Linfócito CD4 , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Transtornos do Crescimento/epidemiologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Renda , MasculinoRESUMO
BACKGROUND: Anaemia is common among HIV-infected children and iron supplementation is prescribed routinely for the prevention and management of anaemia among children. Limited evidence suggests iron supplementation may have adverse effects among HIV-infected populations. We aimed to estimate the effect of iron supplement use on mortality, disease progression and haematological outcomes among HIV-infected children in Dar es Salaam, Tanzania. METHODS: A prospective cohort study was conducted among HIV-infected children (aged 0-14 years) receiving antiretroviral treatment or supportive care between October 2004 and September 2014. Clinical data were recorded on morbidity and vital status, haematological status and prescriptions at each clinical visit. Cox proportional hazards models adjusted for time-varying covariates were used to estimate the association of time-varying iron supplementation on the hazard rate of mortality, HIV disease stage progression, tuberculosis incidence and anaemia and microcytosis persistence. RESULTS: In all, 4229 children were observed during 149 260 clinic visits for a mean follow-up of 2.9 years. After adjustment for time-varying clinical covariates, time-varying iron supplementation was associated with a 2.87 times higher hazard rate of mortality (95% CI: 1.70, 4.87) and a 1.48 times higher hazard rate of HIV disease stage progression (95% CI: 1.10, 1.98). Iron supplementation was also associated with a lower rate of anaemia persistence (HR = 0.47; 95% CI: 0.37, 0.61). No differences in the association between iron supplementation and clinical outcomes were observed by antiretroviral therapy or anaemia status. CONCLUSIONS: Iron supplementation may increase the risk of HIV disease stage progression and mortality among HIV-infected children, while reducing the risk of anaemia.
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Anemia , Infecções por HIV , Anemia/epidemiologia , Criança , Estudos de Coortes , Suplementos Nutricionais , Progressão da Doença , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Ferro/uso terapêutico , Estudos Prospectivos , Tanzânia/epidemiologiaRESUMO
BACKGROUND: Developing a causal graph is an important step in etiologic research planning and can be used to highlight data flaws and irreparable bias and confounding. As a case study, we consider recent findings that suggest human papillomavirus (HPV) vaccine is less effective against HPV-associated disease among girls living with HIV compared to girls without HIV. OBJECTIVES: To understand the relationship between HIV status and HPV vaccine effectiveness, it is important to outline the key assumptions of the causal mechanisms before designing a study to investigate the effect of the HPV vaccine in girls living with HIV infection. METHODS: We present a causal graph to describe our assumptions and proposed approach to explore this relationship. We hope to obtain feedback on our assumptions before data analysis and exemplify the process for designing causal graphs to inform an etiologic study. CONCLUSION: The approach we lay out in this paper may be useful for other researchers who have an interest in using causal graphs to describe and assess assumptions in their own research before undergoing data collection and/or analysis.
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Infecções por HIV , Infecções por Papillomavirus , Vacinas contra Papillomavirus , Feminino , Infecções por HIV/complicações , Humanos , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/uso terapêutico , EditoraçãoRESUMO
Importance: Amid the opioid epidemic and evolving legal and social changes with marijuana, little is known about substance use among pregnant and postpartum people living with HIV. Objectives: To evaluate trends in marijuana, alcohol, and opioid use during pregnancy and the first year postpartum among US people living with HIV and the differences in substance use based on marijuana legalization status. Design, Setting, and Participants: Data from the Surveillance Monitoring for Antiretroviral Toxicities (SMARTT) study of the Pediatric HIV/AIDS Cohort Study were analyzed. SMARTT-enrolled, pregnant people living with HIV at 22 US sites from January 1, 2007, to July 1, 2019, with self-reported substance use data available in pregnancy, 1 year postpartum, or both were assessed. Exposures: Calendar year and state marijuana legalization status. Main Outcomes and Measures: The prevalence of any use of each of the following substances was calculated by calendar year, separately for pregnancy and postpartum: marijuana, alcohol, opioid, and concomitant alcohol and marijuana. Log binomial models were fit using general estimating equations to evaluate the mean annual change, accounting for repeat pregnancies. The study also evaluated differences in substance use by state recreational or medical marijuana legalization status. Results: Substance use data were available for 2926 pregnancies from 2310 people living with HIV (mean [SD] age, 28.8 [6.1] years; 822 [28.1%] Hispanic, 1859 [63.5%] non-Hispanic Black, 185 [6.3%] White, 24 [0.8%] of more than 1 race, 24 [0.8%] of other race or ethnicity [individuals who identified as American Indian, Asian, or Native Hawaiian or other Pacific Islander], and 12 [0.4%] with unknown or unreported race or ethnicity). Between 2007 and 2019, marijuana use during pregnancy increased from 7.1% to 11.7%, whereas alcohol and opioid use in pregnancy were unchanged. Postpartum alcohol (44.4%), marijuana (13.6%), and concomitant alcohol and marijuana (10.0%) use were common; marijuana use increased from 10.2% to 23.7% from 2007 to 2019, whereas postpartum alcohol use was unchanged. The adjusted mean risk of marijuana use increased by 7% (95% CI, 3%-10%) per year during pregnancy and 11% (95% CI, 7%-16%) per year postpartum. Postpartum concomitant alcohol and marijuana use increased by 10% (95% CI, 5%-15%) per year. Differences in substance use were not associated with recreational legalization, but increased marijuana use was associated with medical marijuana legalization. Conclusions and Relevance: In this cohort study, opioid use among pregnant people living with HIV remained stable, whereas marijuana use during pregnancy and postpartum increased over time and in states with legalized medical marijuana. These patterns of increasing marijuana use among pregnant and postpartum people living with HIV suggest that enhanced clinical attention is warranted, given the potential maternal and child health implications of substance use.
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Consumo de Bebidas Alcoólicas/epidemiologia , Analgésicos Opioides/efeitos adversos , Infecções por HIV/epidemiologia , Fumar Maconha/epidemiologia , Período Pós-Parto , Complicações na Gravidez/epidemiologia , Adulto , Cannabis , Estudos de Coortes , Feminino , Humanos , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Gravidez , Adulto JovemRESUMO
Zika virus (ZIKV) infection may adversely affect pregnancies of women living with HIV (WLHIV). Because no study to date has focused on maternal and child effects of HIV and ZIKV co-infection in pregnant women, we undertook the International Prospective Cohort Study of HIV and Zika in Infants and Pregnancy (HIV ZIP). The aims of this two-phase study of pregnant women and their infants are to compare the incidence of ZIKV infection among pregnant women with and without HIV infection and to determine the risk of adverse maternal and child outcomes associated with ZIKV/HIV co-infection at clinical sites in Brazil, Puerto Rico, and the continental United States. Phase I was designed to enroll pregnant women/infant pairs who were: (1) infected with HIV only, (2) infected with ZIKV only, (3) infected with HIV and ZIKV, and (4) not infected with either HIV or ZIKV. A key goal of this phase was to assess the feasibility of enrolling 200 women/infant pairs within a year, with a target of 150 WLHIV, 50 HIV-uninfected women, and a minimum of 20 who were co-infected with HIV and ZIKV. If the feasibility of Phase I proved successful, Phase II would enroll up to 1,800 additional pregnant women/infant pairs to the same four groups. Enrolled women in both phases were to be followed throughout their pregnancy and up to 6 weeks post-partum. Infants were also to be followed for 1 year after birth. To date, Phase 1 data collection and follow-up have been completed. Delineation of possible harmful effects of HIV/ZIKV co-infection will allow the formulation of standard-of-care recommendations to minimize adverse effects but enable the continuation of preventive HIV therapy. Furthermore, while the prospective HIV ZIP study was developed before the COVID pandemic, it is especially relevant today since it can be easily adapted to provide critically important information on the impact of COVID-19 infection or other still unrecognized new agents among pregnant women and their offspring worldwide.
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OBJECTIVES: To quantify the rate of change in epigenetic age compared with chronological age over time in youth with perinatally acquired HIV (YPHIV) and youth who are perinatally HIV-exposed uninfected (YPHEU). DESIGN: Longitudinal study of 32 YPHIV and 8 YPHEU with blood samples collected at two time points at least 3 years apart. METHODS: DNA methylation was measured using the Illumina MethylationEPIC array and epigenetic age was calculated using the Horvath method. Linear mixed effects models were fit to estimate the average change in epigenetic age for a 1-year change in chronological age separately for YPHIV and YPHEU. RESULTS: Median age was 10.9 and 16.8 years at time 1 and 2, respectively. Groups were balanced by sex (51% male) and race (67% black). Epigenetic age increased by 1.23 years (95% CI 1.03--1.43) for YPHIV and 0.95 years (95% CI 0.74--1.17) for YPHEU per year increase in chronological age. Among YPHIV, in a model with chronological age, a higher area under the curve (AUC) viral load was associated with an increase in epigenetic age over time [2.19 years per log10âcopies/ml, (95% CI 0.65--3.74)], whereas a higher time-averaged AUC CD4+ T-cell count was associated with a decrease in epigenetic age over time [-0.34 years per 100âcells/µl, (95% CI -0.63 to -0.06)] in YPHIV. CONCLUSION: We observed an increase in the rate of epigenetic aging over time in YPHIV, but not in YPHEU. In YPHIV, higher viral load and lower CD4+ T-cell count were associated with accelerated epigenetic aging, emphasizing the importance of early and sustained suppressive treatment for YPHIV, who will receive lifelong ART.
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Infecções por HIV , Adolescente , Envelhecimento , Contagem de Linfócito CD4 , Criança , Pré-Escolar , Epigênese Genética , Feminino , Humanos , Lactente , Estudos Longitudinais , Masculino , Carga ViralRESUMO
HIV screening in the emergency department (ED), including universal screening irrespective of risk assessments, has shown strong promise in past studies, identifying many new cases of HIV infection among those who lack access to traditional HIV testing services. Yet, over the years a consistent set of challenges and limitations have presented themselves in settings throughout the United States. We review considerations for evaluating and improving the success of ED-based HIV screening programs in the United States.
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BACKGROUND: Women with vertically acquired HIV (VHIV) may have a greater risk of adverse birth outcomes than women with horizontally acquired HIV (HHIV). METHODS: The Tsepamo study performed birth outcomes surveillance at 8 government delivery sites in Botswana from July 2014 through March 2019. Pregnant women diagnosed with HIV before their 11th birthday received VHIV status, and other women had HHIV. Small for gestational age (SGA), preterm delivery (PTD), stillbirth, and neonatal death were compared using χ2 and Fisher's exact tests. Log-binomial regression models determined risk ratios (RRs). RESULTS: VHIV women (n = 402) aged 15-27 years were identified over 4 years of surveillance and compared with HHIV women (n = 8465) of the same age. VHIV women were more likely to use nevirapine (NVP)-based antiretroviral treatment (ART) in pregnancy and to have SGA and very SGA infants, but less likely to have very PTD infants. In unadjusted analyses, VHIV women had a higher risk of any adverse birth outcome combined (RR = 1.21, 95% confidence interval [CI], 1.08-1.36). After adjusting for potential confounders, particularly use of NVP-based regimens, the risk of adverse birth outcomes among VHIV and HHIV women was similar. CONCLUSIONS: NVP-based ART is a primary and modifiable risk factor for adverse birth outcomes. Updating ART regimens could improve birth outcomes for women with HIV.
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Infecções por HIV , Complicações Infecciosas na Gravidez , Antirretrovirais/uso terapêutico , Botsuana/epidemiologia , Feminino , HIV , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Recém-Nascido , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológicoRESUMO
BACKGROUND: We identified host single-nucleotide variants (SNVs) associated with neurocognitive impairment (NCI) in perinatally HIV-infected (PHIV) children. METHODS: Whole-exome sequencing (WES) was performed on 217 PHIV with cognitive score for age (CSA)â <â 70 and 247 CSAâ ≥â 70 (discovery cohort [DC]). SNVs identified in DC were evaluated in 2 validation cohorts (VC). Logistic regression was used to estimate adjusted odds ratios (ORs) for NCI. A human microglia NLRP3 inflammasome assay characterized the role of identified genes. RESULTS: Twenty-nine SNVs in 24 genes reaching Pâ ≤â .002 and OR ≥ 1.5 comparing CSAâ <â 70 to CSA ≥ 70 were identified in the DC, of which 3 SNVs were identified in VCs for further study. Combining the 3 cohorts, SNV in CCRL2 (rs3204849) was associated with decreased odds of NCI (Pâ <â .0001); RETREG1/FAM134B (rs61733811) and YWHAH (rs73884247) were associated with increased risk of NCI (Pâ <â .0001 and Pâ <â .001, respectively). Knockdown of CCRL2 led to decreased microglial release of IL-1ß following exposure to ssRNA40 while knockdown of RETREG1 and YWHAH resulted in increased IL-1ß release. CONCLUSIONS: Using WES and 2 VCs, and gene silencing of microglia we identified 3 genetic variants associated with NCI and inflammation in HIV-infected children.
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Infecções por HIV/complicações , HIV-1 , Transmissão Vertical de Doenças Infecciosas , Inflamação/genética , Transtornos Neurocognitivos/genética , Proteínas 14-3-3 , Criança , Pré-Escolar , Feminino , Estudo de Associação Genômica Ampla , Genômica , Infecções por HIV/psicologia , Infecções por HIV/transmissão , Humanos , Lactente , Inflamassomos , Peptídeos e Proteínas de Sinalização Intracelular , Masculino , Proteínas de Membrana , Microglia , Transtornos Neurocognitivos/diagnóstico , Transtornos Neurocognitivos/virologia , Receptores CCRRESUMO
INTRODUCTION: Salivary metabolite profiles are altered in adults with HIV compared to their uninfected counterparts. Less is known about youth with HIV and how oral disorders that commonly accompany HIV infection impact salivary metabolite levels. OBJECTIVE: As part of the Adolescent Master Protocol multi-site cohort study of the Pediatric HIV/AIDS Cohort Study (PHACS) network we compared the salivary metabolome of youth with perinatally-acquired HIV (PHIV) and youth HIV-exposed, but uninfected (PHEU) and determined whether metabolites differ in PHIV versus PHEU. METHODS: We used three complementary targeted and discovery-based liquid chromatography-tandem mass spectrometry (LC-MS/MS) workflows to characterize salivary metabolite levels in 20 PHIV and 20 PHEU youth with and without moderate periodontitis. We examined main effects associated with PHIV and periodontal disease, and the interaction between them. RESULTS: We did not identify differences in salivary metabolite profiles that remained significant under stringent control for both multiple between-group comparisons and multiple metabolites. Levels of cadaverine, a known periodontitis-associated metabolite, were more abundant in individuals with periodontal disease with the difference being more pronounced in PHEU than PHIV. In the discovery-based dataset, we identified a total of 564 endogenous peptides in the metabolite extracts, showing that proteolytic processing and amino acid metabolism are important to consider in the context of HIV infection. CONCLUSION: The salivary metabolite profiles of PHIV and PHEU youth were overall very similar. Individuals with periodontitis particularly among the PHEU youth had higher levels of cadaverine, suggesting that HIV infection, or its treatment, may influence the metabolism of oral bacteria.
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Infecções por HIV/complicações , Doenças Periodontais/metabolismo , Saliva/metabolismo , Adolescente , Bactérias , Criança , Cromatografia Líquida , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Masculino , Metabolômica , Saúde Bucal , Espectrometria de Massas em Tandem , Adulto JovemRESUMO
OBJECTIVE: To evaluate whether there is an increased risk of neurologic diagnoses in children who are HIV-exposed but uninfected (CHEU) exposed in utero to specific antiretroviral medications. DESIGN: Prospective cohort study of CHEU enrolled from 2007 to 2017. METHODS: We evaluated children for neurologic case status, including microcephaly, febrile seizures, seizure disorders, ophthalmologic disorders, and other neurologic disorders. Adjusted relative risks (aRRs) were estimated for the association between in-utero antiretroviral exposure and neurologic case using log-binomial regression, accounting for potential confounders. Sensitivity analyses were conducted to evaluate robustness of findings. RESULTS: Among 3747 eligible CHEU, 231 (6.2%) met neurologic case criteria (95% CI 5.4--7%). Most eligible children (86%) were exposed in utero to combination antiretroviral regimens. In adjusted models, children exposed to efavirenz at any time during pregnancy had higher risk of neurologic case status (aRRâ=â1.53, 95% CI 0.94--2.51). This association was stronger when comparing efavirenz exposure at conception to no exposure during pregnancy (aRRâ=â1.92, 95% CI 1.09--3.36) and considering follow-up and case diagnosis only through age 2 (aRRâ=â2.14, 95% CI 1.11--4.12). Children exposed to didanosine at conception and during the first trimester had increased risk of neurologic case status (aRRâ=â2.28, 95% CI 1.07--4.87 and aRRâ=â2.02, 95% CI 1.01--4.04, respectively), compared with didanosine-unexposed children. Children with dolutegravir exposure had some suggestion of increased risk of neurologic case (aRRâ=â2.43, 95% CI 0.75--7.84), which was observed consistently across several sensitivity analyses. CONCLUSION: Efavirenz and didanosine exposure during pregnancy were associated with higher risk of neurologic abnormalities in CHEU, and dolutegravir exposure showed some suggestive associations, which warrant further monitoring.
Assuntos
Fármacos Anti-HIV/efeitos adversos , Didanosina/uso terapêutico , Infecções por HIV/tratamento farmacológico , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Microcefalia/etiologia , Complicações Infecciosas na Gravidez/tratamento farmacológico , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Anormalidades Induzidas por Medicamentos/epidemiologia , Adulto , Fármacos Anti-HIV/uso terapêutico , Criança , Pré-Escolar , Feminino , Infecções por HIV/complicações , Infecções por HIV/transmissão , Humanos , Masculino , Microcefalia/epidemiologia , Gravidez , Complicações Infecciosas na Gravidez/virologia , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Estudos Prospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Small studies reported poor post-partum outcomes among young women living with perinatal HIV infection who are now ageing into adulthood and becoming pregnant. For targeted clinical intervention, we sought to identify women in this population at risk of poor post-partum virological control. METHODS: We abstracted data on pregnancy history for women living with perinatal HIV infection in the Pediatric HIV/AIDS Cohort Study-AMP Up protocol, a prospective study of young adults living with perinatal HIV from 14 sites in the USA. Linear models with generalised estimating equations described trends in HIV viral load through 1 year post-pregnancy by pregnancy outcome. We used group-based trajectory modelling to identify viral load trajectory groups in the first post-partum year after livebirths. We then compared sociodemographic and clinical factors across identified groups. We defined viraemia as 400 copies per mL or more. FINDINGS: Between April 15, 2014, and Oct 1, 2017, we enrolled 323 women, of whom 234 had perinatal HIV infection, and reported age at sexual debut and history of heterosexual vaginal intercourse. Of the 172 pregnancies recorded in these women, 147 (85%, 104 livebirths and 43 spontaneous or elective abortions) were eligible for post-pregnancy viral load trajectory analyses (ie, had at least two viral loads in the year after end of pregnancy). Viral load increased by 0·7 log10 copies per mL (95% CI 0·5 to 1·0) in the first 12 weeks post partum after 104 livebirths, and subsequently stabilised from 13 weeks to 1 year post partum (slope -0·01 log10 copies per mL, 95% CI -0·3 to 0·3). By comparison, the average viral load trajectory after 43 spontaneous or elective abortions remained at less than 400 copies per mL. We identified three distinct groups of viral load trajectories after 104 livebirths, classified as reflecting sustained suppression (31 [30%]), rebound viraemia (55 [53%]), and persistent viraemia (18 [17%]). Women with sustained post-partum suppression were older at conception (22·9 years, IQR 19·4-25·9) than those with rebound viraemia (20·4 years, 18·8-22·2), or persistent post-partum viraemia (19·0 years, 17·7-20·5). Pre-conception viraemia and immune suppression were also strong risk factors for post-partum viraemia. INTERPRETATION: Despite success achieving viral load suppression during pregnancy, women living with perinatal HIV infection have a high risk of post-partum viraemia. Younger age at conception, pre-conception viraemia, and pre-conception immune suppression could identify women in this population most likely to benefit from post-partum adherence interventions. FUNDING: National Institutes of Health.
Assuntos
Infecções por HIV/epidemiologia , Complicações Infecciosas na Gravidez/epidemiologia , Adolescente , Adulto , Feminino , Infecções por HIV/virologia , HIV-1/genética , HIV-1/isolamento & purificação , HIV-1/fisiologia , Humanos , Período Pós-Parto , Gravidez , Complicações Infecciosas na Gravidez/virologia , Estudos Prospectivos , Estados Unidos/epidemiologia , Carga Viral , Adulto JovemRESUMO
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. FUNDING: Eunice Kennedy Shriver National Institute of Child Health and Human Development.
Assuntos
Fármacos Anti-HIV/efeitos adversos , Infecções por HIV/tratamento farmacológico , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Microcefalia/etiologia , Complicações Infecciosas na Gravidez/tratamento farmacológico , Adolescente , Adulto , Alcinos , Fármacos Anti-HIV/uso terapêutico , Benzoxazinas/efeitos adversos , Benzoxazinas/uso terapêutico , Criança , Pré-Escolar , Ciclopropanos , Combinação de Medicamentos , Feminino , Seguimentos , Infecções por HIV/transmissão , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , HIV-1/fisiologia , Humanos , Lactente , Lamivudina/efeitos adversos , Lamivudina/uso terapêutico , Masculino , Microcefalia/epidemiologia , Gravidez , Complicações Infecciosas na Gravidez/virologia , Estudos Prospectivos , Porto Rico , Tenofovir/efeitos adversos , Tenofovir/uso terapêutico , Adulto Jovem , Zidovudina/efeitos adversos , Zidovudina/uso terapêuticoRESUMO
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.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Fidelidade a Diretrizes/estatística & dados numéricos , Infecções por HIV/tratamento farmacológico , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Padrões de Prática Médica/estatística & dados numéricos , Complicações Infecciosas na Gravidez/tratamento farmacológico , Adulto , Feminino , Infecções por HIV/transmissão , Humanos , Guias de Prática Clínica como Assunto , Gravidez , Estudos Prospectivos , Estados UnidosRESUMO
OBJECTIVE: To evaluate whether antenatal Zika virus infection is associated with risk of having a small-for-gestational-age (SGA) neonate, risk of preterm birth, and lower mean birth weight of term neonates. METHODS: For this retrospective observational study, we linked birth record data for women who delivered liveborn singleton neonates in New York City in 2016 to data for pregnant women with Zika virus infection reported to the New York City Health Department. We restricted the analysis to nonsmoking, nonwhite women and adjusted for maternal characteristics. Among women with antenatal Zika virus infection, we used modified Poisson regression to assess risks of having an SGA neonate and of delivering preterm, and linear regression to assess the association of infection with mean birth weight of term neonates. RESULTS: Of 116,034 deliveries of singleton neonates in New York City in 2016, 251 (0.2%) were to women with antenatal Zika virus infection. A higher percentage of women with Zika virus infection delivered an SGA neonate compared with those without (11.2% vs 5.8%; adjusted relative risk [RR] 1.8; 95% CI 1.3-2.6). There was no difference in preterm birth prevalence for women with and without Zika virus infection (adjusted RR 1.0; 95% CI 0.69-1.6). Mean birth weight of term neonates born to women with Zika virus infection was 47 g less (95% CI -105 to 11 g); this difference was not statistically significant in crude or adjusted analyses. CONCLUSION: For a cohort of New York City women, antenatal Zika virus infection was associated with an increased risk of having an SGA neonate, but not preterm birth or lower mean birth weight of term neonates. This supports a putative association between Zika virus infection during pregnancy and SGA.