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Haemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening hyperinflammatory syndrome characterised by persistent fevers, cytopenia, hepatosplenomegaly and systemic inflammation. Secondary HLH can be triggered by various aetiologies including infections, malignancies and autoimmune conditions. We highlight the complexity of HLH diagnosis and management by describing a case of an adolescent Salvadoran immigrant with HLH, newly diagnosed HIV, Streptococcal bacteraemia and disseminated histoplasmosis. The patient presented with neurological and ocular findings along with persistent fevers and cytopenia. He was diagnosed with HLH and treated with anakinra in addition to receiving treatment for HIV, Streptococcal bacteraemia and histoplasmosis. The patient's HLH resolved without corticosteroids or chemotherapy, which are considered the mainstays for HLH treatment. This case underscores the need for the evaluation and management of multiple infections and individualised management in patients presenting with HLH to achieve favourable outcomes.
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Histoplasmosis , Linfohistiocitosis Hemofagocítica , Humanos , Linfohistiocitosis Hemofagocítica/diagnóstico , Linfohistiocitosis Hemofagocítica/tratamiento farmacológico , Histoplasmosis/diagnóstico , Histoplasmosis/tratamiento farmacológico , Histoplasmosis/complicaciones , Masculino , Adolescente , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Proteína Antagonista del Receptor de Interleucina 1/uso terapéutico , Proteína Antagonista del Receptor de Interleucina 1/administración & dosificación , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Resultado del TratamientoRESUMEN
Epidemiologic studies have established that mpox (formerly known as monkeypox) outbreaks worldwide in 2022-2023, due to Clade IIb mpox virus (MPXV), disproportionately affected gay, bisexual, and other men who have sex with men. More than 35% and 40% of the mpox cases suffer from co-infection with HIV and sexually transmitted infections (STIs) (e.g., Chlamydia trachomatis, Neisseria gonorrhoeae, Treponema pallidum, and herpes simplex virus), respectively. Bacterial superinfection can also occur. Co-infection of MPXV and other infectious agents may enhance disease severity, deteriorate outcomes, elongate the recovery process, and potentially contribute to the morbidity and mortality of the ensuing diseases. However, the interplays between MPXV and HIV, bacteria, other STI pathogens and host cells are poorly studied. There are many open questions regarding the impact of co-infections with HIV, STIs, or bacterial superinfections on the diagnosis and treatment of MPXV infections, including clinical and laboratory-confirmed mpox diagnosis, suboptimal treatment effectiveness, and induction of antiviral drug resistance. In this review article, we will discuss the progress and knowledge gaps in MPXV biology, antiviral therapy, pathogenesis of human MPXV and its co-infection with HIV, STIs, or bacterial superinfections, and the impact of the co-infections on the diagnosis and treatment of mpox disease. This review not only sheds light on the MPXV infection and co-infection of other etiologies but also calls for more research on MPXV life cycles and the molecular mechanisms of pathogenesis of co-infection of MPXV and other infectious agents, as well as research and development of a novel multiplex molecular testing panel for the detection of MPXV and other STI co-infections.
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Coinfección , Infecciones por VIH , Enfermedades de Transmisión Sexual , Humanos , Masculino , Coinfección/microbiología , Coinfección/virología , Infecciones por VIH/complicaciones , Infecciones por VIH/virología , Monkeypox virus , Mpox/virología , Enfermedades de Transmisión Sexual/microbiología , Enfermedades de Transmisión Sexual/virología , Enfermedades de Transmisión Sexual/complicaciones , Sobreinfección/microbiología , Sobreinfección/virología , FemeninoRESUMEN
Despite the scale-up of telehealth for children and youth living with HIV during the COVID-19 pandemic, their experience and interest in continued telehealth use in the future is unknown. We conducted a quality improvement project to identify areas for improvement of telehealth delivery to children and youth living with HIV and evaluate youth's experiences when using telehealth for mental health services. Children and youth living with HIV (up to 24 years) seen at a specialty HIV program during 2020-2021 were surveyed regarding technology access, telehealth knowledge, barriers to telehealth use and interest in future telehealth use for HIV care. Youth (12-<24 years) who used telehealth for mental health services were surveyed regarding their experiences. Data were analyzed using descriptive statistics. Of the 170 patients in care, we surveyed 103 children and youth living with HIV (median age 17.6 years, 88.3% Black, 52.4% female, 77.7% perinatally infected), of whom 69.9% had prior telehealth use for their clinical visit. Most patients had access to a device with internet (99%) and were interested in future telehealth use for HIV care (87.4%). Reasons for not wanting to use telehealth included privacy concerns, distrust, discomfort with telehealth, preferring in-person visits, technology access issues and needing translation services. Most youth (81%) surveyed regarding telehealth for mental health services were satisfied and very likely to recommend it to others. Despite some reported barriers to telehealth, there is a high desirability for continued telehealth use among children and youth receiving HIV care.
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Infecciones por VIH , Telemedicina , Humanos , Adolescente , Femenino , Niño , Masculino , Pandemias , District of Columbia/epidemiología , Salud Mental , Infecciones por VIH/epidemiología , Infecciones por VIH/terapia , Infecciones por VIH/psicologíaRESUMEN
Prior to January 2023, women living with HIV (WLWH) in the United States (US) were discouraged from breastfeeding due to the potential risk of mother-to-child HIV transmission through breastfeeding. Lack of breastfeeding decision-making and experience among WLWH may negatively affect maternal mental health. We implemented a quality improvement initiative to screen WLWH for postpartum depression (PPD), evaluate their attitudes toward breastfeeding, and assess their experience with breastfeeding decision-making. We collected quantitative data from WLWH using a voluntary, self-administered 6-item breastfeeding decision-making and experience survey (administered 1 month postpartum) and a 10-item Edinburgh Postnatal Depression Scale (EPDS, negative = 0-9; administered 1 and 4 months postpartum) tool. We conducted descriptive statistics and cross tabulation analysis. We analyzed 106 WLWH (93.4% non-Hispanic Black/African American; mean age 33.1 years; 82.1% HIV RNA < 200 copies/mL). One in five (19.1%) WLWH had a positive baseline EPDS screen, with the mean EPDS scores decreasing from 5.3 ± 5.4 (baseline) to 4.6 ± 4.8 (follow-up). Among 55 WLWH who provided baseline and follow-up EPDS scores, only 3/13 with a positive baseline EPDS screen had resolved depressive symptoms at follow-up. Over one-third (37.7%) of WLWH indicated feeling "sadness" when asked whether lack of breastfeeding negatively affected their feelings or emotions. Over half of WLWH (51.9%) were aware of the US breastfeeding recommendations, but the majority (60.4%) had never discussed breastfeeding options with a medical provider. Improved provider-patient discussions on infant feeding options among WLWH is needed to increase awareness of breastfeeding choices and promote informed, autonomous breastfeeding decision-making among WLWH.
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Depresión Posparto , Infecciones por VIH , Lactante , Femenino , Humanos , Adulto , Lactancia Materna , Salud Mental , Infecciones por VIH/psicología , Transmisión Vertical de Enfermedad Infecciosa , Periodo Posparto , Depresión Posparto/diagnóstico , Depresión Posparto/epidemiología , Depresión Posparto/psicologíaRESUMEN
This study explored virological outcomes of two-drug (2DRs) and three-drug (3DRs) antiretroviral regimens in adults with HIV in the DC Cohort. We analyzed 310 treatment-experienced adults with sustained HIV RNA ≤50 copies/mL at baseline, 53 of whom switched to 2DRs and 257 continued 3DRs. Adults on 2DRs and 3DRs had similar demographics (median age 53.3 years, 76.8% cisgender male, 76.1% Black). Adults on 2DRs had more participants with ≥2 comorbidities (62.3% vs. 42.8%, p = .019), had a longer time since HIV diagnosis (median years 20.4 vs. 13.2, p = .017), and received the regimen of interest for a shorter duration (median years 1.3 vs. 3.3, p < .001) compared with adults on 3DRs. Adults receiving 2DRs had a higher, although nonsignificant, risk for virological failure (two consecutive HIV RNA ≥50 copies/mL) at 24 months follow-up than adults on 3DRs (6.7% vs. 1.7%, respectively; p = .10). Future analysis of the effectiveness of 2DRs is needed.
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Fármacos Anti-VIH , Infecciones por VIH , Adulto , Fármacos Anti-VIH/uso terapéutico , Antirretrovirales/uso terapéutico , Estudios de Cohortes , Infecciones por VIH/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , ARN/uso terapéutico , Carga ViralRESUMEN
Transitioning from pediatric to adult services is known to be associated with worsening of health outcomes and decreased retention in care among adolescents and youth living with HIV (AYLHIV). We aimed to identify factors associated with HIV care transition readiness among AYLHIV in care at a pediatric HIV clinic in Washington, DC. This retrospective cohort study from June 2019 through January 2021 collected demographic and clinical characteristics from the clinic database. We adapted the Transition Readiness Assessment Questionnaire (TRAQ; scored 1-4; 1 being the lowest level of preparedness) to evaluate transition readiness over time. We analyzed data using two-sided unadjusted two-sample and paired t-tests and adjusted analysis of variance (ANOVA). We included 103 AYLHIV (50.49% female; 100% non-Hispanic Black/African American; mean age = 19.54 ± 2.78 years; 81.55% virally suppressed). Mean baseline TRAQ score (2.32 ± 0.78) was associated with age (p < 0.0001), gender (p = 0.033), mode of HIV transmission (p = 0.0005), viral suppression (p = 0.0033), and duration of HIV diagnosis (p = 0.012). AYLHIV diagnosed with HIV within the prior year experienced significantly greater mean improvement in transition readiness compared with those living with HIV for >10 years (p = 0.013). Adjusted for covariates, older age (p < 0.0001), undetectable viral load (p = 0.0008), and presence of mental health condition(s) (p = 0.020) were associated with higher TRAQ scores. Lower improvement in transition readiness among youth with a longer history of HIV suggests that AYLHIV with perinatally acquired HIV might require additional support than those with horizontally acquired HIV.
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Infecciones por VIH , Transición a la Atención de Adultos , Adolescente , Adulto , Anciano , Niño , Femenino , Infecciones por VIH/tratamiento farmacológico , Humanos , Masculino , Estudios Retrospectivos , Encuestas y Cuestionarios , Estados Unidos , Carga Viral , Adulto JovenRESUMEN
Background: While physiologically based pharmacokinetic (PBPK) models generally predict pharmacokinetics in pregnant women successfully, the confidence in predicting fetal pharmacokinetics is limited because many parameters affecting placental drug transfer have not been mechanistically accounted for. Objectives: The objectives of this study were to implement different maternal and fetal unbound drug fractions in a PBPK framework; to predict fetal pharmacokinetics of eight drugs in the third trimester; and to quantitatively investigate how alterations in various model parameters affect predicted fetal pharmacokinetics. Methods: The ordinary differential equations of previously developed pregnancy PBPK models for eight drugs (acyclovir, cefuroxime, diazepam, dolutegravir, emtricitabine, metronidazole, ondansetron, and raltegravir) were amended to account for different unbound drug fractions in mother and fetus. Local sensitivity analyses were conducted for various parameters relevant to placental drug transfer, including influx/efflux transfer clearances across the apical and basolateral membrane of the trophoblasts. Results: For the highly-protein bound drugs diazepam, dolutegravir and ondansetron, the lower fraction unbound in the fetus vs. mother affected predicted pharmacokinetics in the umbilical vein by ≥10%. Metronidazole displayed blood flow-limited distribution across the placenta. For all drugs, umbilical vein concentrations were highly sensitive to changes in the apical influx/efflux transfer clearance ratio. Additionally, transfer clearance across the basolateral membrane was a critical parameter for cefuroxime and ondansetron. Conclusion: In healthy pregnancies, differential protein binding characteristics in mother and fetus give rise to minor differences in maternal-fetal drug exposure. Further studies are needed to differentiate passive and active transfer processes across the apical and basolateral trophoblast membrane.
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We report a case of sustained viral suppression with dolutegravir monotherapy in a treatment-experienced adult with perinatally acquired HIV. The patient had recurrent pancreatitis with multiple antiretroviral drugs, leading to discontinuation of antiretroviral therapy for several years. She was ultimately initiated on dolutegravir monotherapy two times per day via a gastrostomy tube. She did not develop any integrase strand transfer inhibitor mutations during the first 2 years on dolutegravir monotherapy. The patient has successfully maintained prolonged viral suppression for over 3 years with intermittent blips secondary only to intermittent medical issues. This case is unique in describing a highly treatment-experienced young adult with perinatal HIV infection who has been virally suppressed on dolutegravir monotherapy for a prolonged follow-up of 156 weeks.
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Infecciones por VIH , Inhibidores de Integrasa VIH , Femenino , Infecciones por VIH/tratamiento farmacológico , Inhibidores de Integrasa VIH/uso terapéutico , Compuestos Heterocíclicos con 3 Anillos , Humanos , Oxazinas/uso terapéutico , Piperazinas/uso terapéutico , Piridonas/uso terapéutico , Respuesta Virológica Sostenida , Carga ViralRESUMEN
We conducted a retrospective analysis of 38 children and youth with human immunodeficiency virus (aged 0-19 years) in the United States and report an increased rate of change of BMI-for-age z score after initiating integrase strand transfer inhibitors (+0.19 z score units/year [95% confidence interval, .01-.37]; Pâ =â .036) for a median follow-up of 527.5 days.
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BACKGROUND AND OBJECTIVE: Little is understood about neonatal pharmacokinetics immediately after delivery and during the first days of life following intrauterine exposure to maternal medications. Our objective was to develop and evaluate a novel, physiologically based pharmacokinetic modeling workflow for predicting perinatal and postnatal disposition of commonly used antiretroviral drugs administered prenatally to pregnant women living with human immunodeficiency virus. METHODS: Using previously published, maternal-fetal, physiologically based pharmacokinetic models for emtricitabine, dolutegravir, and raltegravir built with PK-Sim/MoBi®, placental drug transfer was predicted in late pregnancy. The total drug amount in fetal compartments at term delivery was estimated and subsequently integrated as initial conditions in different tissues of a whole-body, neonatal, physiologically based pharmacokinetic model to predict drug concentrations in the neonatal elimination phase after birth. Neonatal elimination processes were parameterized according to published data. Model performance was assessed by clinical data. RESULTS: Neonatal physiologically based pharmacokinetic models generally captured the initial plasma concentrations after delivery but underestimated concentrations in the terminal phase. The mean percentage error for predicted plasma concentrations was - 71.5%, - 33.8%, and 76.7% for emtricitabine, dolutegravir, and raltegravir, respectively. A sensitivity analysis suggested that the activity of organic cation transporter 2 and uridine diphosphate glucuronosyltransferase 1A1 during the first postnatal days in term newborns is ~11% and ~30% of that in adults, respectively. CONCLUSIONS: These findings demonstrate the general feasibility of applying physiologically based pharmacokinetic models to predict washout concentrations of transplacentally acquired drugs in newborns. These models can increase the understanding of pharmacokinetics during the first postnatal days and allow the prediction of drug exposure in this vulnerable population.
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Compuestos Heterocíclicos con 3 Anillos , Placenta , Adulto , Emtricitabina , Femenino , Humanos , Recién Nacido , Modelos Biológicos , Oxazinas , Piperazinas , Embarazo , Piridonas , Raltegravir PotásicoRESUMEN
OBJECTIVE: To evaluate the uptake of perinatal HIV preventive interventions by the risk of perinatal HIV transmission in mother-infant pairs in a high-HIV prevalence area in the US. STUDY DESIGN: This was a retrospective cohort study of mother-infant pairs with perinatal HIV exposure during 2013-2017 managed at a subspecialty pediatric HIV program in Washington, DC. We collected demographic data, maternal HIV history, delivery mode, maternal and infant antiretroviral drug (ARV) use, and infant HIV test results. We compared the uptake of recommended preventive interventions in low-risk (ie, mothers on antiretroviral therapy [ART] with viral suppression) and high-risk (mothers without ART or viral suppression) mother-infant pairs using the Pearson chi-square, Fisher exact, and Wilcoxon rank-sum tests and logistic regression. RESULTS: We analyzed 551 HIV-exposed infants (HEIs) and 542 mothers living with HIV. The majority of mothers received ARVs (95.5%), had HIV RNA ≤1000 copies/mL before delivery (81.9%), and received intrapartum zidovudine (ZDV; 65.5%). The majority of all HEIs were low risk (82.6%) and received postpartum ARVs (98.9%). Among the low-risk infants, 53.2% were delivered via cesarean delivery (CD), and 62.9% and 96.5% were administered intrapartum and postpartum ZDV, respectively. Among high-risk infants, 84.4% were delivered via CD, 78.1% received intrapartum ZDV, and 62.5% received combination ART. Nine high-risk infants acquired HIV perinatally. CONCLUSION: In an area of high HIV prevalence in the US, a large proportion of low-risk HEIs received intrapartum ZDV and were delivered via CD. We also observed missed opportunities for the prevention of perinatal HIV transmission.
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ADN Viral/análisis , Infecciones por VIH/prevención & control , VIH/genética , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Periodo Posparto , Complicaciones Infecciosas del Embarazo/epidemiología , Adulto , Femenino , Infecciones por VIH/epidemiología , Humanos , Recién Nacido , Masculino , Embarazo , Prevalencia , Pronóstico , Estudios Retrospectivos , Estados Unidos/epidemiología , Adulto JovenRESUMEN
BACKGROUND: Predicting drug pharmacokinetics in pregnant women including placental drug transfer remains challenging. This study aimed to develop and evaluate maternal-fetal physiologically based pharmacokinetic models for two antiretroviral drugs, dolutegravir and raltegravir.
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Infecciones por VIH , Inhibidores de Integrasa VIH , Compuestos Heterocíclicos con 3 Anillos/farmacocinética , Oxazinas/farmacocinética , Piperazinas/farmacocinética , Piridonas/farmacocinética , Raltegravir Potásico/farmacocinética , Femenino , Feto/efectos de los fármacos , Infecciones por VIH/tratamiento farmacológico , Inhibidores de Integrasa VIH/farmacocinética , Inhibidores de Integrasa VIH/uso terapéutico , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Humanos , Exposición Materna , Oxazinas/uso terapéutico , Piperazinas/uso terapéutico , Placenta , Embarazo , Piridonas/uso terapéutico , Raltegravir Potásico/uso terapéuticoRESUMEN
AIM AND OBJECTIVES: To describe the lived experience of young adults with perinatally acquired HIV (PaHIV). BACKGROUND: With the advancement of the highly active antiretroviral treatment, PaHIV infection has transformed into a chronic lifelong illness that is faced by young adults who grew up with HIV. The known challenges that are associated with HIV are poverty, stigma and social and emotional isolation. DESIGN: This was a qualitative single-interview study of a convenience sample of PaHIV-infected young adults receiving care at a large metropolitan pediatric hospital. METHODS: The participants had individual face-to-face interviews which were audio-taped and transcribed verbatim. Themes were developed to describe their living space, and Max Van Manen's lifeworld guide was used to describe their lived experience. FINDINGS: Seventeen participants (eight males/nine females) were enrolled. Four major themes emerged: (i) limited social capital, especially when orphaned participants reflected on a life void of parental guidance; (ii) incomplete education and unemployment, participants described an idle existence; (iii) a harsh life, described as participants facing difficulties meeting their life's milestones; (iv) unanticipated adult issues, where participants described their limited ability to care for themselves and their children. Van Manen lifeworld themes also described the space they occupied, their memories growing up with PaHIV, their health care and relationships. CONCLUSION: Our study provides a valuable insight into the social and emotional difficulties faced by youth with PaHIV. The findings underscore the importance of extensive support and coordination of services between adult and pediatric providers to optimize long-term outcomes among young adults with PaHIV. RELEVANCE TO CLINICAL PRACTICE: The young adults with PaHIV require close attention and support from the healthcare providers, who can offer them a safe space to discuss lived experiences and support their ability to achieve full lives.
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Infecciones por VIH/congénito , Infecciones por VIH/psicología , Calidad de Vida/psicología , Adolescente , Adulto , Enfermedad Crónica , Femenino , Humanos , Masculino , Pobreza , Investigación Cualitativa , Estigma Social , Factores Socioeconómicos , Adulto JovenRESUMEN
The goal of antiretroviral therapy for the prevention of mother-to-child transmission (PMTCT) of HIV is to achieve maximal suppression of maternal viral load with minimal maternal, fetal and infant toxicity during pregnancy, delivery and postpartum. In addition to the efficacy and toxicity of antiretroviral therapy, the consideration of HIV resistance in mothers and infected newborns further complicates therapeutic choices for PMTCT. This manuscript summarizes current approaches to PMTC in diverse international settings.
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Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/prevención & control , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Profilaxis Antibiótica , Femenino , Infecciones por VIH/congénito , Infecciones por VIH/tratamiento farmacológico , Humanos , Recién Nacido , Embarazo , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Complicaciones Infecciosas del Embarazo/prevención & controlRESUMEN
We describe an unintentional significant overdose of darunavir in a treatment-experienced adolescent with decreased darunavir susceptibility and prior treatment failure on darunavir therapy. Minimal toxicity and improved virologic suppression observed with an overdose have prompted consideration of the continued use of a higher than recommended dose. Pharmacokinetic and pharmacodynamic evaluations justified the individualized use of high-dose darunavir, which resulted in virologic suppression, improved CD4 cell count, and resolution of toxicity.
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Infecciones por VIH/tratamiento farmacológico , VIH-1 , Mal Uso de Medicamentos de Venta con Receta , Sulfonamidas/administración & dosificación , Carga Viral/efectos de los fármacos , Recuento de Linfocito CD4/tendencias , Niño , Darunavir , Infecciones por VIH/patología , Infecciones por VIH/virología , Inhibidores de la Proteasa del VIH/administración & dosificación , Humanos , Masculino , Resultado del TratamientoRESUMEN
Antiretroviral therapy (ART) in pregnant women represents a unique combination of therapy and prophylaxis of HIV infection. Until the global epidemic of HIV and the discovery of efficient prevention of perinatal transmission through ART, the world has not witnessed a pharmacologic intervention of such a scale during pregnancy and delivery. The use of ART in pregnancy creates unique challenges in delivering therapeutic agents, targeting the HIV virus in both the pregnant woman and her unborn child, throughout dramatic changes in their physiologic state. With an increased complexity of perinatal ART and the introduction of novel agents into clinical practice, a better understanding of the pharmacokinetics (PK) and pharmacodynamics of ARV drugs is crucial for the safe and most effective use of ARV drugs in women during pregnancy and infants in the first months of life. While PK studies are already difficult to perform during pregnancy, they are particularly challenging in women with HIV infection due to multiple social, economic and cultural constrains. In this paper we provide an overview of published studies of ART disposition during pregnancy, labor, breastfeeding and in the newborn infant after delivery.
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Antirretrovirales/farmacocinética , Embarazo/metabolismo , Antirretrovirales/uso terapéutico , Femenino , Infecciones por VIH/metabolismo , Infecciones por VIH/prevención & control , Humanos , Recién Nacido , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Complicaciones Infecciosas del Embarazo/metabolismo , Complicaciones Infecciosas del Embarazo/prevención & controlRESUMEN
BACKGROUND: Three cases of pediatric HIV transmission attributed to the feeding practice of premasticating food for children have been reported. The degree of risk that premastication poses for pediatric HIV transmission and the prevalence of this behavior among HIV-infected caregivers is unknown. METHODS: During December 2009 to February 2010, we conducted a case-control investigation of late-diagnosed HIV infection in children at 6 HIV clinics using in-person and telephone interviews. A cross-sectional investigation of premastication was conducted in concert with this case-control investigation. RESULTS: We compared 11 case-patients to 35 HIV-exposed controls of similar age. Sixteen (35%) of 46 children were fed premasticated food, 10 (22%) by an HIV-infected caregiver. Twenty-seven percent of case-patients received premasticated food from an HIV-infected caregiver compared with 20% of controls (odds ratio = 1.5; 95% confidence interval = 0.3 to 7.1). In the cross-sectional investigation, 48 (31%) of 154 primary caregivers of children aged ≥6 months reported the children received premasticated food from themselves or someone else. The prevalence of premastication decreased with increasing caregiver age and had been used to feed children aged 1-36 months. CONCLUSIONS: Premastication, a potential route of HIV transmission to children, was a common practice of caregivers. Public health officials and health care providers should educate the public about the potential risk of disease transmission via premastication.
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Infecciones por VIH/transmisión , Alimentos Infantiles , Masticación , Adulto , Estudios de Casos y Controles , Preescolar , Estudios Transversales , Conducta Alimentaria , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Puerto Rico , Estados Unidos , Adulto JovenRESUMEN
OBJECTIVE: CYP3A5, MDR1 (ABCB1), and OATP1 (SLCO1B1) polymorphisms have been associated with variability in the pharmacokinetics (PK) of protease inhibitors. The aim of this study was to investigate the influence of CYP3A5 A6986G, ABCB1 (C3435T and G2677T), and SLCO1B1 (T521C and A388AG) polymorphisms on the PK and virologic outcome of lopinavir/ritonavir (LPV/RTV) in HIV-infected children. DESIGN AND METHODS: We conducted a prospective cohort study in children (4-18 years old) on stable antiretroviral therapy with LPV/RTV. CYP3A5, ABCB1, and SLCO1B1 genotypes were determined using polymerase chain reaction amplification with allelic discrimination assays. The 12-hour plasma area under the concentration-time curves (AUC) and clearances (CL) of LPV and RTV were estimated using noncompartmental models. HIV RNA viral load was evaluated every 12 weeks for a total study period of 52 weeks. Analysis of covariance models with adjustment for age and adherence and allometric adjustment of CL were used to assess associations between studied polymorphisms and AUC, CL, and HIV RNA. RESULTS: Fifty children (median age 11.2 years) were enrolled. Allele frequencies of the genotypes studied were in Hardy-Weinberg equilibrium. There was no statistically significant association between LPV or RTV AUC or CL, and CYP3A5, ABCB1, or SLCO1B1 A388G polymorphisms. There was a significant association between SLCO1B1 T521C genotype and increased LPV AUC (P = 0.042) and a nearly significant association with decreased LPV CL (P = 0.063). None of the studied polymorphisms, including SLCO1B1 T521C, were associated with virologic outcome during 52 weeks of study follow-up. CONCLUSIONS: There was no statistically significant influence of the CYP3A5, ABCB1, or SLCO1B1 A388AG polymorphisms on the PK and virologic outcome of LPV/RTV in HIV-infected children. SLCO1B1 T521C polymorphism was significantly associated with an increase in LPV AUC but was not associated with undetectable HIV RNA during the study period.