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1.
N Engl J Med ; 387(9): 799-809, 2022 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-36053505

RESUMEN

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.).


Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , Inhibidores de la Proteasa del VIH , VIH-1 , Compuestos Heterocíclicos con 3 Anillos , Oxazinas , Piperazinas , Nacimiento Prematuro , Piridonas , Adulto , Fármacos Anti-VIH/efectos adversos , Fármacos Anti-VIH/uso terapéutico , Sulfato de Atazanavir/efectos adversos , Sulfato de Atazanavir/uso terapéutico , Cobicistat/efectos adversos , Cobicistat/uso terapéutico , Estudios de Cohortes , Darunavir/efectos adversos , Darunavir/uso terapéutico , Femenino , Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Proteasa del VIH/efectos adversos , Inhibidores de la Proteasa del VIH/uso terapéutico , Compuestos Heterocíclicos con 3 Anillos/efectos adversos , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Humanos , Recién Nacido , Oxazinas/efectos adversos , Oxazinas/uso terapéutico , Piperazinas/efectos adversos , Piperazinas/uso terapéutico , Embarazo , Nacimiento Prematuro/inducido químicamente , Piridonas/efectos adversos , Piridonas/uso terapéutico , Quinolonas/efectos adversos , Quinolonas/uso terapéutico , Raltegravir Potásico/efectos adversos , Raltegravir Potásico/uso terapéutico , Rilpivirina/efectos adversos , Rilpivirina/uso terapéutico , Ritonavir/efectos adversos , Ritonavir/uso terapéutico , Estados Unidos
2.
J Infect Dis ; 230(4): 878-888, 2024 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-38839047

RESUMEN

BACKGROUND: Pregnant people with coronavirus disease 2019 (COVID-19) experience higher risk for severe disease and adverse pregnancy outcomes, but no pharmacokinetic (PK) data exist to support dosing of COVID-19 therapeutics during pregnancy. We report PK and safety data for intravenous remdesivir in pregnancy. METHODS: IMPAACT 2032 was a phase 4 prospective, open-label, nonrandomized opportunistic study of hospitalized pregnant and nonpregnant women receiving intravenous remdesivir as part of clinical care. Intensive PK sampling was performed on infusion days 3, 4, or 5 with collection of plasma and peripheral blood mononuclear cells (PBMCs). Safety data were recorded from first infusion through 4 weeks after last infusion and at delivery. Geometric mean ratios (GMR) (90% confidence intervals [CI]) of PK parameters between pregnant and nonpregnant women were calculated. RESULTS: Fifty-three participants initiated remdesivir (25 pregnant; median gestational age, 27.6 weeks; interquartile range, 24.9-31.0 weeks). Plasma exposures of remdesivir, its 2 major metabolites (GS-704277 and GS-441524), and the free remdesivir fraction were similar between pregnant and nonpregnant participants. Concentrations of the active triphosphate (GS-443902) in PBMCs increased 2.04-fold (90% CI, 1.35-3.03) with each additional infusion in nonpregnant versus pregnant participants. Three adverse events in nonpregnant participants were related to treatment (1 grade 3; 2 grade 2 resulting in treatment discontinuation). There were no treatment-related adverse pregnancy outcomes or congenital anomalies detected. CONCLUSIONS: Plasma remdesivir PK parameters were comparable between pregnant and nonpregnant women, and no safety concerns were identified based on our limited data. These findings suggest no dose adjustments are indicated for intravenous remdesivir during pregnancy. CLINICAL TRIALS REGISTRATION: NCT04582266.


Asunto(s)
Adenosina Monofosfato , Alanina , Antivirales , COVID-19 , Complicaciones Infecciosas del Embarazo , SARS-CoV-2 , Humanos , Femenino , Embarazo , Alanina/análogos & derivados , Alanina/farmacocinética , Alanina/efectos adversos , Alanina/administración & dosificación , Alanina/uso terapéutico , Adenosina Monofosfato/análogos & derivados , Adenosina Monofosfato/farmacocinética , Adenosina Monofosfato/efectos adversos , Adenosina Monofosfato/administración & dosificación , Adenosina Monofosfato/uso terapéutico , Adulto , Antivirales/farmacocinética , Antivirales/efectos adversos , Antivirales/administración & dosificación , Antivirales/uso terapéutico , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Complicaciones Infecciosas del Embarazo/virología , Estudios Prospectivos , SARS-CoV-2/efectos de los fármacos , Tratamiento Farmacológico de COVID-19 , Adulto Joven
3.
Clin Infect Dis ; 79(3): 727-733, 2024 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-38531012

RESUMEN

BACKGROUND: There are little data on changes in insulin sensitivity during the first few years of life following in utero human immunodeficiency virus (HIV) and antiretroviral (ARV) exposure. METHODS: The Tshilo Dikotla study enrolled pregnant persons with HIV (PWH) (receiving tenofovir/emtricitabine or lamivudine plus dolutegravir or efavirenz) and pregnant individuals without HIV, as well as their liveborn children. Newborns were randomized to receive either zidovudine (AZT) or nevirapine (NVP) postnatal prophylaxis. Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) was assessed at birth and 1, 18, 24, and 36 months of life. We fit linear mixed-effects models to evaluate the association between in utero HIV/ARV exposure and average HOMA-IR from birth through 36 months of life, adjusting for confounders. RESULTS: A total of 419 children were included (287 with in utero HIV/ARV exposure and uninfected [CHEU] and 132 without in utero HIV/ARV exposure [CHUU]). CHEU were born to older women (29.6 vs 25.3 years of age) with higher gravidity (3 vs 1). HOMA-IR was persistently higher in CHEU versus CHUU in adjusted analyses (mean difference of 0.07 in log10 HOMA-IR, P = .02) from birth through 36 months of life. Among CHEU, no differences in HOMA-IR were observed from birth through 36 months by in utero ARV exposure status or between AZT and NVP infant prophylaxis arms. CONCLUSIONS: In utero HIV/ARV exposure was associated with lower insulin sensitivity throughout the first 36 months of life, indicating persistent early life metabolic disturbances which may raise concern for poorer metabolic health later in life.


Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , Resistencia a la Insulina , Complicaciones Infecciosas del Embarazo , Humanos , Femenino , Infecciones por VIH/tratamiento farmacológico , Embarazo , Botswana , Lactante , Recién Nacido , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Fármacos Anti-VIH/uso terapéutico , Fármacos Anti-VIH/efectos adversos , Adulto , Masculino , Zidovudina/uso terapéutico , Zidovudina/efectos adversos , Preescolar , Ciclopropanos/uso terapéutico , Efectos Tardíos de la Exposición Prenatal , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Emtricitabina/uso terapéutico , Lamivudine/uso terapéutico , Lamivudine/efectos adversos , Alquinos , Adulto Joven , Oxazinas/uso terapéutico , Benzoxazinas/uso terapéutico , Benzoxazinas/efectos adversos , Nevirapina/uso terapéutico , Piridonas/uso terapéutico , Tenofovir/uso terapéutico
4.
HIV Med ; 25(2): 233-244, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37845017

RESUMEN

BACKGROUND: The role of body fat on metabolic complications remains poorly understood in young people living with perinatally acquired HIV (YPHIV). OBJECTIVE: Our objective was to assess the association of changes in adiposity over 2 years with metabolic outcomes in YPHIV. METHODS: The PHACS Adolescent Master Protocol (AMP) study enrolled YPHIV from 2007 to 2009 across 15 US sites, including Puerto Rico. We included YPHIV aged 7-19 years with body composition data assessed by whole-body dual-energy X-ray absorptiometry (DXA) at baseline and 2 years later. Metabolic outcomes included homeostatic model assessment of insulin resistance (HOMA-IR) and non-high-density lipoprotein cholesterol (non-HDL-C). We fitted linear regression models to assess the association of increase in body fat over 2 years with metabolic outcomes at years 2 and 3. RESULTS: In all, 232 participants had a second DXA and either HOMA-IR or non-HDL-C measured at year 2. Participant characteristics at the first DXA were: age 12 years (9-14) [median (Q1-Q3)], 69% Black, and median CD4 count 714 cells/µL; 70% with HIV RNA <400 copies/mL. In adjusted analyses for every 1% increase in body fat from baseline to year 2, HOMA-IR was higher by 1.03-fold at year 3 (95% CI: 1.00, 1.05). We observed that for every 1% increase in body fat from baseline to year 2, non-HDL-C was 0.72 mg/dL higher at year 2 (95% CI: -0.04-1.49) and 0.81 mg/dL higher at year 3 (95% CI: -0.05-1.66). CONCLUSIONS: Increases in adiposity over time may lead to downstream decreased insulin sensitivity and dyslipidaemia in YPHIV.


Asunto(s)
Infecciones por VIH , Resistencia a la Insulina , Adolescente , Humanos , Infecciones por VIH/complicaciones , Adiposidad , Obesidad/complicaciones , Colesterol , Tejido Adiposo/diagnóstico por imagen , Absorciometría de Fotón
5.
AIDS Care ; : 1-6, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38976581

RESUMEN

Few studies have evaluated postpartum depression (PPD) in women living with HIV (WLHIV) in Botswana, a high prevalence HIV setting. The Edinburgh Postnatal Depression Scale (EPDS) was used to evaluate PPD symptoms in WLHIV (n = 300) and women who are HIV-uninfected (n = 131) in the Tshilo Dikotla study, an observational cohort study with a nested randomized trial. The EPDS was administered at 2, 6, and 12 months postpartum. We assessed the association of (1) HIV infection and (2) antiretroviral therapy (ART) with odds of PPD symptoms (EPDS ≥ 10 or thoughts of self-harm) in the first year postpartum using generalized estimating equations. Of WLHIV, 24 (8.00%) had PPD symptoms at one or more follow-up time points, compared to 9 (6.9%) women who were HIV-seronegative. There was no association between HIV status and PPD symptoms (adjusted odds ratio [aOR]:1.69, 95% confidence interval [CI]: 0.73-3.93, p = 0.225); however, WLHIV on efavirenz-based ART regimens had higher odds of experiencing PPD symptoms compared to dolutegravir-based ART (aOR:3.05, 95% CI:1.16-8.03, p = 0.024).

6.
Clin Obstet Gynecol ; 67(2): 381-398, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38450526

RESUMEN

Over the last 4 decades, significant advances in the care of HIV during pregnancy have successfully reduced, and nearly eliminated, the risk of perinatal HIV transmission. The baseline risk of transmission without intervention (25% to 30%) is now <1% to 2% in the United States with contemporary antepartum, intrapartum, and postnatal interventions. In this review, we discuss 3 landmark clinical trials that substantially altered obstetric practice for pregnant individuals with HIV and contributed to this extraordinary achievement: 1) the Pediatric AIDS Clinical Trials Group 076 Trial determined that antepartum and intrapartum administration of antiretroviral drug zidovudine to the pregnant individual, and postnatally to the newborn, could reduce the risk of perinatal transmission by approximately two-thirds; 2) the European Mode of Delivery Collaboration Trial demonstrated performance of a prelabor cesarean birth before rupture of membranes among pregnant people with viremia reduced the risk of perinatal transmission compared with vaginal birth; and 3) the International Maternal Pediatric Adolescent AIDS Clinical Trials Network 2010 Trial identified that dolutegravir-containing, compared with efavirenz-containing, antiretroviral regimens during pregnancy achieved a significantly higher rate of viral suppression at delivery with shorter time to viral suppression, with fewer adverse pregnancy outcomes. Collectively, these trials not only advanced obstetric practice but also advanced scientific understanding of the timing, mechanisms, and determinants of perinatal HIV transmission. For each trial, we will describe key aspects of the study protocol and outcomes, insights gleaned about the dynamics of perinatal transmission, how each study changed clinical practice, and relevant updates to current practice since the trial's publication.


Asunto(s)
Alquinos , Fármacos Anti-VIH , Infecciones por VIH , Transmisión Vertical de Enfermedad Infecciosa , Complicaciones Infecciosas del Embarazo , Piridonas , Zidovudina , Humanos , Embarazo , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/transmisión , Infecciones por VIH/prevención & control , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Piridonas/uso terapéutico , Zidovudina/uso terapéutico , Fármacos Anti-VIH/uso terapéutico , Oxazinas/uso terapéutico , Piperazinas/uso terapéutico , Ciclopropanos/uso terapéutico , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Ensayos Clínicos como Asunto , Benzoxazinas/uso terapéutico , Benzoxazinas/administración & dosificación , Recién Nacido , Cesárea
7.
J Infect Dis ; 227(5): 720-730, 2023 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-36592383

RESUMEN

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


Asunto(s)
Síndrome de Inmunodeficiencia Adquirida , Infecciones por VIH , Embarazo , Femenino , Humanos , Niño , Estados Unidos , Proteína C-Reactiva , Interleucina-6 , Estudios de Cohortes , Receptores de Lipopolisacáridos , Inflamación , Biomarcadores , Infecciones por VIH/complicaciones , Síndrome de Inmunodeficiencia Adquirida/complicaciones
8.
Clin Infect Dis ; 77(8): 1133-1136, 2023 10 13.
Artículo en Inglés | MEDLINE | ID: mdl-37293702

RESUMEN

Infants who are human immunodeficiency virus (HIV)-exposed uninfected (iHEU) experience higher risk of infectious morbidity than infants HIV-unexposed uninfected (iHUU). We compared tuberculosis (TB) infection prevalence in 418 Bacillus Calmette-Guérin vaccinated sub-Saharan African iHEU and iHUU aged 9-18 months using T-SPOT.TB. Prevalence of TB infection was low and did not differ by HIV exposure status.


Asunto(s)
Infecciones por VIH , Tuberculosis Latente , Tuberculosis , Lactante , Humanos , Niño , VIH , Infecciones por VIH/epidemiología , Tuberculosis/prevención & control , Prevalencia
9.
Clin Infect Dis ; 76(3): e744-e747, 2023 02 08.
Artículo en Inglés | MEDLINE | ID: mdl-36031390

RESUMEN

We followed 54 infants with in utero HIV after initiating very early antiretroviral treatment. At weeks 24 and 48, ≥80% had CD4 ≥1500 cells/mm3 and CD4% ≥25%. Routine Pneumocystis jirovecii pneumonia prophylaxis in the first year of life may not be necessary for all very early treated infants. CLINICAL TRIALS REGISTRATION: NCT02140255.


Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , Pneumocystis carinii , Neumonía por Pneumocystis , Humanos , Lactante , Infecciones por VIH/tratamiento farmacológico , Neumonía por Pneumocystis/tratamiento farmacológico , Terapia Antirretroviral Altamente Activa , Fármacos Anti-VIH/uso terapéutico , Antirretrovirales/uso terapéutico , Recuento de Linfocito CD4
10.
J Infect Dis ; 226(11): 2002-2009, 2022 11 28.
Artículo en Inglés | MEDLINE | ID: mdl-36240387

RESUMEN

BACKGROUND: Few data exist on early-life metabolic perturbations in newborns with perinatal HIV and antiretroviral (ARV) exposure but uninfected (HEU) compared to those perinatally HIV unexposed and uninfected (HUU). METHODS: We enrolled pregnant persons with HIV (PWH) receiving tenofovir (TDF)/emtricitabine or lamivudine (XTC) plus dolutegravir (DTG) or efavirenz (EFV), and pregnant individuals without HIV, as well as their liveborn infants. Newborns were randomized to receive either zidovudine (AZT) or nevirapine (NVP) postnatal prophylaxis. Preprandial homeostasis model assessment for insulin resistance (HOMA-IR) was assessed at birth and 1 month. Linear mixed models were fit to assess the association between in utero HIV/ARV exposure and average HOMA-IR from birth to 1 month, adjusting for confounders. RESULTS: Of 450 newborns, 306 were HEU. HOMA-IR was higher in newborns HEU versus HUU after adjusting for confounders (mean difference of 0.068 in log HOMA-IR, P = .037). Among newborns HEU, HOMA-IR was not significantly different between TDF/XTC/DTG versus TDF/XTC/EFV in utero ARV exposure and between AZT versus NVP newborn postnatal prophylaxis arms. CONCLUSIONS: Newborns HEU versus HUU had lower insulin sensitivity at birth and at 1 month of life, raising potential concern for obesity and other metabolic perturbations later in life for newborns HEU. CLINICAL TRIALS REGISTRATION: NCT03088410.


Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , Resistencia a la Insulina , Lactante , Embarazo , Femenino , Recién Nacido , Humanos , Botswana , Infecciones por VIH/tratamiento farmacológico , Antirretrovirales/uso terapéutico , Nevirapina/uso terapéutico , Zidovudina/uso terapéutico , Fármacos Anti-VIH/uso terapéutico
11.
Clin Infect Dis ; 75(6): 945-952, 2022 09 29.
Artículo en Inglés | MEDLINE | ID: mdl-35090002

RESUMEN

BACKGROUND: The association between gut dysfunction and body fat composition in youth living with perinatal human immunodeficiency virus infection (YPHIV) has not been investigated. METHODS: We included YPHIV aged 7-19 years from the Pediatric HIV/AIDS Cohort Study Adolescent Master Protocol with plasma available within 6 months of baseline whole-body dual energy x-ray absorptiometry (DXA) and HIV RNA ≤1000 copies/mL within 3 months of baseline DXA and a second DXA 2 years later. Plasma markers of bacterial translocation and gut barrier dysfunction (lipopolysaccharide binding protein [LBP], zonulin, and intestinal fatty acid binding protein [I-FABP]) were measured at baseline by enzyme-linked immunosorbent assay and log10 transformed. Adiposity outcomes included percentage total body, truncal, and extremity fat in kilograms from DXA. Linear regression models were fit using generalized estimating equations to assess associations of baseline gut markers (log10) on adiposity outcomes at baseline and 2 years, adjusted for demographic variables, current antiretroviral therapy exposure, and physical activity. RESULTS: Two hundred sixty-one youth were included; 128 had a second DXA. Median age at first DXA was 12 years (interquartile range, 10-14 years), 49% were female, and 69% were Black. After adjustment for potential confounders, log10 LBP was positively associated with percentage total body fat at baseline (ß = 4.08, P < .01) and zonulin with adiposity measures at both time points (ß = .94 to 6.50, P ≤ .01). I-FABP was inversely associated with percentage total body fat at baseline and year 2 (ß = -2.36 and -3.01, respectively, P ≤ .02). CONCLUSIONS: Despite viral suppression, gut damage and the resultant bacterial translocation are associated with body composition measures in YPHIV.


Asunto(s)
Infecciones por VIH , Lipopolisacáridos , Absorciometría de Fotón/métodos , Adiposidad , Adolescente , Biomarcadores , Composición Corporal , Niño , Estudios de Cohortes , Proteínas de Unión a Ácidos Grasos , Femenino , VIH , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Humanos , Masculino , Obesidad , ARN
12.
Clin Infect Dis ; 75(12): 2211-2218, 2022 12 19.
Artículo en Inglés | MEDLINE | ID: mdl-35486952

RESUMEN

BACKGROUND: We describe trends in prevalence and identify factors associated with Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), syphilis, and Trichomonas vaginalis (TV) diagnosed in pregnancy among US people with human immunodeficiency virus (PWH) and evaluate associations of sexually transmitted infections (STIs) with preterm birth (PTB). METHODS: We included pregnant PWH enrolled in the Surveillance Monitoring for ART Toxicities dynamic cohort of the Pediatric HIV/AIDS Cohort Study network who delivered between 2010 and 2019. Multivariable log-binomial or Poisson generalized estimating equation models were used to estimate the association of calendar year with each STI, controlling for confounders; the association of demographic and clinical factors with each STI; and the association of each STI with PTB. RESULTS: The sample included 2241 pregnancies among 1821 PWH. Median age at delivery was 29.2 years; 71% of participants identified as Black or African American. STI prevalence was: CT 7.7%, NG 2.3%, syphilis 2.4%, and TV 14.5%; 30% had unknown TV status. There were no temporal changes in STI prevalence. Younger age and initial HIV viral load ≥400 copies/mL were associated with increased risk of CT, NG, and TV. Recreational substance use was a risk factor for NG, syphilis, and TV. No STI was associated with PTB. CONCLUSIONS: Unlike nationwide trends, no changes in STI prevalence during the study period were observed. The large proportion with unknown TV status underscores the need for increased adherence to screening guidelines. STIs diagnosed during pregnancy in PWH were not associated with risk of PTB.


Asunto(s)
Síndrome de Inmunodeficiencia Adquirida , Infecciones por Chlamydia , Gonorrea , Infecciones por VIH , Complicaciones Infecciosas del Embarazo , Nacimiento Prematuro , Enfermedades de Transmisión Sexual , Sífilis , Tricomoniasis , Trichomonas vaginalis , Recién Nacido , Embarazo , Femenino , Humanos , Niño , Adulto , Sífilis/epidemiología , VIH , Gonorrea/epidemiología , Estudios de Cohortes , Tricomoniasis/epidemiología , Complicaciones Infecciosas del Embarazo/epidemiología , Infecciones por Chlamydia/epidemiología , Enfermedades de Transmisión Sexual/epidemiología , Neisseria gonorrhoeae , Chlamydia trachomatis , Prevalencia , Infecciones por VIH/epidemiología
13.
Pediatr Res ; 92(1): 233-241, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-34446848

RESUMEN

BACKGROUND: Early-life metabolic derangements in HIV-exposed uninfected (HEU) infants have been reported. METHODS: Pregnant women with HIV and HIV-uninfected pregnant women were enrolled with their newborns in a US cohort from 2011 to 2015. We measured cord insulin, C-peptide, and metabolic cytokines of HEU and HIV-unexposed uninfected (HUU) newborns using ELISA and metabolites, lipid subspecies, and eicosanoids via liquid chromatography/mass spectrometry. Linear regression was employed to assess the association of intrauterine HIV/ART with insulin and C-peptide. Graphical lasso regression was used to identify differences between metabolite/lipid subspecies networks associated with C-peptide. RESULTS: Of 118 infants, 56 were HEU, ART exposed. In adjusted analyses, mean cord insulin (ß = 0.295, p = 0.03) and C-peptide (ß = 0.522, p < 0.01) were significantly higher in HEU vs. HUU newborns. HEU neonates exhibited primarily positive associations between complex lipids and C-peptide, indicative of fuel storage, and augmented associations between cord eicosanoids and cytokines. HUU neonates exhibited negative associations with lipids and C-peptide indicative of increased fuel utilization. CONCLUSION: Higher cord insulin and C-peptide in HEU vs. HUU newborns as well as differences in cord metabolites, metabolic-related cytokines, and eicosanoids may reflect a propensity for fuel storage and an inflammatory milieu suggestive of fetal metabolic changes associated with in utero HIV/ART exposure. IMPACT: There is a paucity of studies assessing cord blood and neonatal metabolic health in HIV-exposed uninfected (HEU) newborns, an increasing population worldwide. Compared to HIV-unexposed uninfected (HUU) newborns, HEU newborns exhibit alterations in fuel homeostasis and an inflammatory milieu associated with in utero HIV/antiretroviral therapy (ART) exposure. The long-term implications of these neonatal findings are as yet unknown, but merit continued evaluation as this important and growing population ages into adulthood.


Asunto(s)
Infecciones por VIH , Complicaciones Infecciosas del Embarazo , Adipoquinas , Adulto , Antirretrovirales/uso terapéutico , Péptido C , Citocinas , Femenino , Sangre Fetal , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Humanos , Lactante , Recién Nacido , Lipidómica , Lípidos , Embarazo
14.
AIDS Care ; 34(9): 1151-1158, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-34236921

RESUMEN

Youth living with perinatally acquired HIV (YLPHIV) have been found to have a range of mental disorders. Some adult HIV studies have linked mental health to adverse metabolic outcomes due to dysregulation of the sympathetic nervous system and hypothalamic-pituitary-adrenal axis, but this association has not previously been explored in YLPHIV.We investigated the association of mental health measures with metabolic outcomes in YLPHIV and HIV-uninfected youth (HIV-U) and linear regression was used to assess the adjusted associations.Overall, 203 YLPHIV (median age = 10.7years; 52% female; mean duration on ART 8 years, 12% CD4 count <500 cells/µL, 18% viral load >50 copies/mL) and 44 HIV-U (median age = 10.3 years; 55% female) were enrolled. YLPHIV had higher median total cholesterol (4.2 vs 3.9 mmol/L, p = 0.049) and triglyceride (0.9 vs 0.7 mmol/L, p < 0.001) compared to HIV-U. We found higher percentage of poor functional competence (40% vs 25%, p = 0.02) and self-concept (23% vs 9%, p = 0.03) and higher depression (6% vs 2%, p < 0.01), anger (6% vs 2%, p = 0.04) and disruptive behaviour (4% vs 0%, p < 0.01) in YLPHIV as compared to HIV-U. Among YLPHIV, higher scores of anger were associated with higher total cholesterol and higher low-density lipoprotein (ß = 0.010, p = 0.041 and ß = 0.012, p = 0.048 respectively) and disruptive behaviour with higher low-density lipoprotein (ß = 0.010, p = 0.043) after adjusting for age, sex and BMIZ.This is the one of first study to investigate the association of mental health with metabolic outcomes among YLPHIV. The association of increased anger and disruptive behaviour with increased lipid concentration is a novel finding. Further longitudinal studies are needed to evaluate the causal relationships between mental health and metabolic outcomes.


Asunto(s)
Infecciones por VIH , Adolescente , Adulto , Antirretrovirales/uso terapéutico , Niño , Colesterol , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Humanos , Sistema Hipotálamo-Hipofisario , Lipoproteínas LDL/uso terapéutico , Masculino , Salud Mental , Sistema Hipófiso-Suprarrenal , Sudáfrica/epidemiología
15.
J Neurovirol ; 27(5): 702-715, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34524627

RESUMEN

We investigated the association of metabolic syndrome (MetS) and its components [abdominal obesity, elevated triglycerides (TG), low HDL cholesterol, elevated blood pressure (BP), and impaired fasting glycemia (IFG)] with neurocognitive impairment in youth with perinatally acquired HIV (YPHIV) or who are perinatally HIV-exposed uninfected (YPHEU). This was an observational study with a comparison group of 350 YPHIV and 68 YPHEU ages 10-19 years. Youth with MetS components measured between 1 year before and 3 months after a baseline neurocognitive assessment (Wechsler Intelligence Scale) were selected from the Pediatric HIV/AIDS Cohort Study (PHACS). A sub-group completed another assessment 3 years later. We assessed the association of each baseline MetS component with five standardized neurocognitive indices at baseline and changes in indices over time. At baseline, 15% of YPHIV and 18% of YPHEU met criteria for ≥ 2 MetS components. Among YPHIV, there was no association between MetS components and neurocognitive indices at baseline; however, over time, elevated baseline BP was associated with a greater decrease in mean Perceptual Reasoning scores (-4.3;95%CI: -8.8,0.3) and ≥ 2 MetS components with a greater decrease in mean Processing Speed scores (-5.1;95%CI: -9.4, -0.8). Among YPHEU, elevated TG was associated with lower mean Verbal Comprehension, Perceptual Reasoning, and Full-scale IQ scores at baseline, and IFG with lower mean Verbal Comprehension scores. Components of MetS in YPHIV (elevated BP) and YPHEU (elevated TG and IFG) were associated with lower neurocognitive performance index scores. Studies to elucidate how modifying metabolic risk factors early in life may improve neurocognitive outcomes in this population are warranted.


Asunto(s)
Infecciones por VIH , Síndrome Metabólico , Adolescente , Adulto , Niño , Estudios de Cohortes , Infecciones por VIH/psicología , Humanos , Obesidad/complicaciones , Factores de Riesgo , Adulto Joven
16.
Am J Obstet Gynecol ; 225(5): 494-499, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-33932342

RESUMEN

Since the 1990s, perinatal transmission of HIV has decreased substantially, largely as a result of improved detection secondary to routine HIV screening in pregnancy and the use of antiretroviral therapy. However, despite reductions in HIV transmission, elimination of perinatal transmission, defined as an incidence of perinatal HIV infection of <1 per 100,000 live births and a transmission rate of <1%, remains elusive. An estimated 80% of perinatal transmissions occur after 36 weeks' gestation, which highlights the importance of diagnosis and treatment of maternal HIV infection before the highest-risk period for perinatal transmission. With timely identification of seroconversion, intrapartum and neonatal interventions can lower the risk of perinatal transmission from 25% to 10%, substantially reducing perinatal transmission events. The American College of Obstetricians and Gynecologists and the Centers for Disease Control and Prevention recommend that routine HIV testing be performed in all pregnancies, as early in the prenatal course as possible. Third-trimester repeat testing is only recommended for individuals known to be at high risk of acquiring HIV (ie, those who are incarcerated; who reside in jurisdictions with elevated HIV incidence; who are receiving care in facilities that have an HIV incidence in pregnant women > 1 per 1000 per year; or have signs or symptoms of acute HIV). However, among reproductive-age women, heterosexual intercourse is the most common mode of HIV transmission, and the risk of HIV seroconversion is greater during pregnancy than outside of pregnancy. Furthermore, state statutes for HIV testing in pregnancy are largely lacking. In this clinical opinion, we reviewed the evidence in support of universal third-trimester repeat HIV testing in pregnancy using a successful state-mandated testing program in Illinois. In addition, we provided clinical recommendations to further reduce missed perinatal transmission cases by implementing universal third-trimester repeat testing, obtaining hospital buy-in, monitoring testing adherence, bridging communications across multidisciplinary teams, and engaging clinicians in advocacy work.


Asunto(s)
Infecciones por VIH/transmisión , Prueba de VIH , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Tercer Trimestre del Embarazo , Análisis Costo-Beneficio , Femenino , Infecciones por VIH/diagnóstico , Prueba de VIH/economía , Política de Salud/legislación & jurisprudencia , Humanos , Illinois , Guías de Práctica Clínica como Asunto , Embarazo
17.
Clin Infect Dis ; 71(2): 332-339, 2020 07 11.
Artículo en Inglés | MEDLINE | ID: mdl-31504291

RESUMEN

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


Asunto(s)
Infecciones por VIH , Niño , Estudios de Cohortes , Femenino , VIH , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Hospitalización , Humanos , Incidencia , Lactante , Embarazo , Estados Unidos/epidemiología
18.
Clin Infect Dis ; 71(10): e672-e679, 2020 12 17.
Artículo en Inglés | MEDLINE | ID: mdl-32285090

RESUMEN

BACKGROUND: Human immunodeficiency virus (HIV) and antiretroviral therapy (ART) confer cardiovascular disease (CVD) risk in adults with HIV. Few studies have assessed endothelial dysfunction (ED), an early marker of subclinical CVD risk, in youth living with perinatally acquired HIV (YLPHIV). METHODS: Using peripheral arterial tonometry, we compared ED in YLPHIV and age-matched youth without HIV. A reactive hyperemic index ≤1.35 was defined as ED. Eligible participants included those aged 9-14 years and on ART ≥6 months at enrollment. RESULTS: Overall, 431 YLPHIV and 93 youth without HIV with a median age of 14.1 versus 13.9 years, respectively, were included. YLPHIV had a lower BMI z score (BMIZ; -0.2 vs 0.4; P < .01) but higher rates of hypercholesterolemia (10% vs 1%; P = .01) than youth without HIV. Among YLPHIV, mean log viral load (VL) was 4.83 copies/mL with 21.7% having a CD4 count <500 cell/mm3; median duration on ART was 9.8 years with 38% initiating at <2 years of age. YLPHIV had higher rates of ED than youth without HIV (50% vs 34%; P = .01); this relationship persisted after adjusting for age, sex, BMIZ, elevated BP, and hypercholesterolemia (RR, 1.43; P = .02). Among YLPHIV, CD4 count >500 cell/mm3 (RR, 1.04; P = .76), VL (RR, 1.01; P = .78), and current ART class (protease inhibitor based vs nonnucleoside inhibitor based: relative risk, 0.90; P = .186) were not associated with ED after adjustment. CONCLUSIONS: Even after adjusting for physiologic differences, YLPHIV appear to be at increased risk of ED compared with age-matched youth without HIV. These findings have important implications for the life course of YLPHIV who may be at increased risk of premature CVD and complications.


Asunto(s)
Infecciones por VIH , Adolescente , Adulto , Antirretrovirales/uso terapéutico , Recuento de Linfocito CD4 , Niño , VIH , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Humanos , Carga Viral
19.
Am J Perinatol ; 37(10): 1038-1043, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32498092

RESUMEN

With the coronavirus disease 2019 (COVID-19) pandemic in the United States, a majority of states have instituted "shelter-in-place" policies effectively quarantining individuals-including pregnant persons-in their homes. Given the concern for COVID-19 acquisition in health care settings, pregnant persons with high-risk pregnancies-such as persons living with HIV (PLHIV)-are increasingly investigating the option of a home birth. Although we strongly recommend hospital birth for PLHIV, we discuss our experience and recommendations for counseling and preparation of pregnant PLHIV who may be considering home birth or at risk for unintentional home birth due to the pandemic. We also discuss issues associated with implementing a risk mitigation strategy involving high-risk births occurring at home during a pandemic. KEY POINTS: · Coronavirus disease 2019 pandemic has increased interest in home birth.. · Women living with HIV are pursuing home birth.. · Safe planning is paramount for women living with HIV desiring home birth, despite recommending against the practice..


Asunto(s)
Infecciones por Coronavirus/epidemiología , Infecciones por VIH/epidemiología , Parto Domiciliario/métodos , Pandemias/prevención & control , Neumonía Viral/epidemiología , Resultado del Embarazo , Embarazo de Alto Riesgo , Adulto , COVID-19 , Comorbilidad , Infecciones por Coronavirus/prevención & control , Consejo , Parto Obstétrico/métodos , Femenino , Parto Domiciliario/estadística & datos numéricos , Humanos , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Pandemias/estadística & datos numéricos , Seguridad del Paciente/estadística & datos numéricos , Neumonía Viral/prevención & control , Embarazo , Medición de Riesgo , Estados Unidos
20.
AIDS Care ; 30(9): 1168-1172, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-29776314

RESUMEN

"Depression (as noted in chart by a physician)" was compared between HIV infected pregnant women and controls. Perinatally HIV-infected (PHIV), non-perinatally HIV-infected (NPHIV), and HIV-uninfected (HIV-U) pregnant women were all compared using a logistic regression model. Overall, HIV-infected women had higher rates of depression than HIV-U, with PHIV women demonstrating a clinically and statistically significant increased risk compared to HIV-U women [adjusted OR: 15.9, 95% CI = 1.8-143.8]. Future studies in larger populations are warranted to confirm these findings and further elucidate mental health outcomes of PHIV and NPHIV pregnant women.


Asunto(s)
Depresión/complicaciones , Infecciones por VIH/psicología , Complicaciones Infecciosas del Embarazo/psicología , Adulto , Estudios de Casos y Controles , Estudios de Cohortes , Femenino , Infecciones por VIH/complicaciones , Humanos , Embarazo , Adulto Joven
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