RESUMEN
BACKGROUND: A significant proportion of individuals reports persistent clinical manifestations following SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) acute infection. Nevertheless, knowledge of the burden of this condition-often referred to as 'Long COVID'-on the health care system remains limited. This study aimed to evaluate healthcare utilization potentially related to Long COVID. METHODS: Population-based, retrospective, multi-center cohort study that analyzed hospital admissions and utilization of outpatient visits and diagnostic tests between adults aged 40 years and older recovered from SARS-CoV-2 infection occurred between February 2020 and December 2021 and matched unexposed individuals during a 6-month observation period. Healthcare utilization was analyzed by considering the setting of care for acute SARS-CoV-2 infection [non-hospitalized, hospitalized and intensive care unit (ICU)-admitted] as a proxy for the severity of acute infection and epidemic phases characterized by different SARS-CoV-2 variants. Data were retrieved from regional health administrative databases of three Italian Regions. RESULTS: The final cohort consisted of 307 994 previously SARS-CoV-2 infected matched with 307 994 uninfected individuals. Among exposed individuals, 92.2% were not hospitalized during the acute infection, 7.3% were hospitalized in a non-ICU ward and 0.5% were admitted to ICU. Individuals previously infected with SARS-CoV-2 (vs. unexposed), especially those hospitalized or admitted to ICU, reported higher utilization of outpatient visits (range of pooled Incidence Rate Ratios across phases; non-hospitalized: 1.11-1.33, hospitalized: 1.93-2.19, ICU-admitted: 3.01-3.40), diagnostic tests (non-hospitalized: 1.35-1.84, hospitalized: 2.86-3.43, ICU-admitted: 4.72-7.03) and hospitalizations (non-hospitalized: 1.00-1.52, hospitalized: 1.87-2.36, ICU-admitted: 4.69-5.38). CONCLUSIONS: This study found that SARS-CoV-2 infection was associated with increased use of health care in the 6 months following infection, and association was mainly driven by acute infection severity.
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COVID-19 , Hospitalización , Aceptación de la Atención de Salud , SARS-CoV-2 , Humanos , COVID-19/epidemiología , Masculino , Estudios Retrospectivos , Femenino , Persona de Mediana Edad , Anciano , Adulto , Hospitalización/estadística & datos numéricos , Italia/epidemiología , Aceptación de la Atención de Salud/estadística & datos numéricos , Síndrome Post Agudo de COVID-19 , Estudios de Cohortes , Recursos en Salud/estadística & datos numéricos , Unidades de Cuidados Intensivos/estadística & datos numéricosRESUMEN
Measles vaccination is currently recommended at 9 months, since maternal antibodies are supposed to protect infants until that age. In this study of 6-month-old Malawian infants 98.3% (58/59) had non-protective IgG levels against measles, irrespective of HIV exposure. Anticipating the first dose at 6 months could be considered.
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Sarampión , Humanos , Lactante , Sarampión/prevención & control , Vacunación , Anticuerpos Antivirales , Esquemas de Inmunización , Vacuna AntisarampiónRESUMEN
Among 733 pregnant women with HIV followed between 2013 and 2021, only 8 (1.1%) had prior HPV vaccination. One had low-grade squamous intraepithelial lesions [LSIL], and none had HPV type information. Among the 725 non-vaccinated women, 578 (79.7%) had information on cervical cytology. Rate of cytologic abnormalities in this group was 20.6% (0.2% atypical glandular cells of undetermined significance [AGC], 1.7% atypical squamous cells of undetermined significance [ASC-US], 11.1% LSIL, and 7.6% high-grade squamous intraepithelial lesions [HSIL]). Among 56 women with HPV type information, 75.0% carried high risk types, with similar occurrence in women with and without cytologic abnormalities, 30.4% had multiple high-risk types, and 75.9% carried at least one of the types included in the currently recommended 9-valent vaccine.
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Infecciones por VIH , Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , Femenino , Infecciones por VIH/epidemiología , Humanos , Papillomaviridae/genética , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/prevención & control , Embarazo , Mujeres Embarazadas , Prevalencia , VacunaciónRESUMEN
BACKGROUND: The impaired transplacental passage of IgG from mothers living with HIV to their infants could be one of the causes of the high vulnerability to infections of HIV-exposed uninfected (HEU) infants, but controversial results have been obtained in different settings. The aim of this study was to assess in 6-week old HEU and HIV-unexposed, uninfected (HUU) Malawian infants the total IgG levels, the subclasses profile and the concentrations of global anti-pneumococcal capsular polysaccharide (anti-PCP) IgG and IgG2. METHODS: Dried blood spots were collected from 80 infants (40 HEU, 40 HUU) and antibodies concentrations determined by nephelometric method (total IgG and subclasses), or using ELISA (anti-PCP total IgG and IgG2). Results are expressed as median levels with IQR, while the proportions of each subclass out of the total IgG are used to describe the subclasses profile. RESULTS: At 6 weeks HEU infants had higher median levels of total IgG and IgG1 and a significantly lower level of IgG2 [0.376 (0.344-0.523) g/l vs 0.485 (0.374-0.781) g/l, p = 0.037] compared to the HUU counterparts. The IgG subclasses distribution confirmed the underrepresentation of IgG2 (IgG2 represented 5.82% of total IgG in HEU and 8.87% in HUU). The anti-PCP IgG and IgG2 levels were significantly lower in HEU infants [8.9 (5.4-15.1) mg/l vs 16.2 (9.61-25.8) mg/l in HUU, p < 0.001, and 2.69 (1.90-4.29) mg/l vs 4.47 (2.96-5.71) mg/l in HUU, p = 0.001, respectively]. CONCLUSION: Compared to HUU infants, HEU infants have IgG abnormalities mainly represented by low IgG2 levels, suggesting that despite maternal antiretroviral therapy, the mechanisms of IgG transplacental passage continue to be impaired in women living with HIV. HEU infants also showed a significantly lower level of specific anti-PCP IgG, possibly favouring a high vulnerability to S. pneumoniae infection at an age when protection is mostly depending on maternal IgG.
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Infecciones por VIH , Inmunoglobulina G , Ensayo de Inmunoadsorción Enzimática , Femenino , Infecciones por VIH/prevención & control , Humanos , Lactante , MadresRESUMEN
PURPOSE: To evaluate associations between CD4/CD8 ratio and pregnancy outcomes in women with HIV. METHODS: We evaluated, in a national study of pregnant women with HIV receiving antiretroviral treatment (ART), values of CD4/CD8 ratio at entry in pregnancy, changes between first and third trimester, and possible associations with preterm delivery, low birthweight, and HIV-RNA < 50 copies/ml at third trimester in univariate and multivariate analyses. RESULTS: Among 934 women, 536 (57.4%) were already on ART at conception. CD4/CD8 ratio (baseline value 0.570) increased significantly between the first and third trimesters, particularly in women who started ART in pregnancy (+ 0.163, vs. + 0.036 in women already on treatment). The rate of CD4/CD8 ratio normalization, defined by achieving a ratio ≥ 1 at the third trimester, was 13.2%. In multivariable analyses, women who entered pregnancy with a CD4/CD8 ratio < 0.3, compared to women with ratio ≥ 1, were almost four-times less likely to have third-trimester HIV-RNA < 50 copies/ml (AOR 0.258, 95%CI 0.111-0.601), and more than twice as likely to have preterm delivery (AOR 2.379, 95%CI 1.082-5.232). For preterm delivery, also a baseline CD4/CD8 ratio between 0.3 and 0.45 was significantly associated with an increased risk (AOR: 3.415, 95%CI 1.690-6.900). CONCLUSION: We described for the first time independent associations of low CD4/CD8 ratio with preterm delivery and HIV-RNA suppression.
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Infecciones por VIH , Complicaciones Infecciosas del Embarazo , Linfocitos T CD8-positivos , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Humanos , Recién Nacido , Embarazo , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Complicaciones Infecciosas del Embarazo/epidemiología , Resultado del Embarazo/epidemiología , Mujeres Embarazadas , Carga ViralRESUMEN
BACKGROUND: Epidemiological data obtained during the initial wave of the COVID-19 epidemic showed that persons dying with COVID-19 were typically older men with multiple chronic conditions. No studies have assessed if the characteristics of patients dying with COVID-19 have changed in the second phase of the epidemic, when the initial wave subsided. The aim of the present study was to compare characteristics of patients dying with COVID-19 in Italy in the first 'peak' phase of the epidemic and in its second phase. METHODS: Medical charts of patients with COVID-19 who died while in hospital in Italy were reviewed to extract information on pre-existing comorbidities, in-hospital complications, and disease trajectories. The course of the epidemic was classified in two 3-month periods: March-May 2020 and June-August 2020. FINDINGS: Overall, in the Italian population, 34,191 COVID-19 deaths occurred in March-May 2020 and 1,404 in June-August 2020. Patients dying in March-May were significantly younger (80.1 ± 10.6 vs. 82.8 ± 11.1 years, p < 0.001) and less frequently female (41.9% vs. 61.8%, p < 0.001) than those dying in June-August. The medical charts of 3533 patients who died with PCR-confirmed SARS-CoV-2 infection in March-May 2020 (10.3% of all deaths occurring in this period) and 203 patients who died in June-August 2020 (14.5% of all deaths occurring in this period) were analysed. Patients who died in March-May 2020, compared to those who died in June-August 2020, had significantly lower rates of multiple comorbidities (3 or more comorbidities: 61.8% vs 74.5%, p = 0.001) and superinfections (15.2% vs. 52.5%, p < 0.001). Treatment patterns also substantially differed in the two study periods, with patients dying in March-May 2020 being less likely to be treated with steroids (41.7% vs. 69.3%, p < 0.001) and more likely to receive antivirals (59.3% vs. 41.4%, p < 0.001). Survival time also largely differed, with patients dying in March-May 2020 showing a shorter time from symptoms onset to death (mean interval: 15.0 vs. 46.6 days, p < 0.001). The differences observed between the two periods remained significant in a multivariate analysis. INTERPRETATION: The clinical characteristics of patients dying with COVID-19 in Italy, their treatment and symptom-to-death survival time have significantly changed overtime. This is probably due to an improved organization and delivery of care and to a better knowledge of disease treatment.
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COVID-19 , Pandemias , Anciano , Femenino , Hospitales , Humanos , Italia/epidemiología , Masculino , SARS-CoV-2RESUMEN
BACKGROUND: Persons with Down syndrome (DS) are presumed to be at high risk of severe CoVID-19, due to immune dysregulation and often compromised cardiopulmonary function. Aim of the present study is to assess epidemiological and clinical characteristics of individuals with DS deceased in Italian hospitals with CoVID-19. METHODS: We used a nationwide database of 3,438 patients deceased with RT-PCR-confirmed SARS-CoV-2 infection in Italy (10.4% of all deaths with CoVID-19 in the country at the time of analysis). Data on demographics, pre-existing comorbidities and in-hospital complications leading to death were extracted from medical charts obtained from hospitals. Data on individuals with DS deceased with CoVID-19 were obtained from this sample. RESULTS: Sixteen cases of death in individuals with DS (0.5% of all charts analyzed) were identified. Acute respiratory distress syndrome occurred in all 16 cases. Compared with individuals without DS, those with DS deceased with CoVID-19 were younger (52.3 ± 7.3 vs. 78.1 ± 10.6 years, p < .001) and presented a higher incidence of superinfections (31.2 vs. 13.0%, p = .029). Autoimmune diseases (43.8 vs. 4%, p < .001), obesity (37.5 vs. 11%, p = .009), and dementia (37.5 vs. 16.3%, p = .012) were more prevalent in individuals with DS. ICU admissions was similar in both groups (25 vs. 18.8%, p = .129). CONCLUSIONS: Individuals with DS deceased with CoVID-19 are younger than individuals without DS. Comorbidity burden and increased risk of complications (i.e., bacterial superinfections) can influence CoVID-19 prognosis in individuals with DS. Specific strategies to prevent and mitigate the effects of CoVID-19 in the population with DS are needed.
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COVID-19/epidemiología , Síndrome de Down/epidemiología , Pandemias , Anciano , COVID-19/virología , Comorbilidad , Femenino , Hospitalización , Humanos , Unidades de Cuidados Intensivos , Italia/epidemiología , Masculino , Persona de Mediana EdadRESUMEN
PURPOSE: Recommended regimens for pregnant women with HIV-1 are composed of two nucleoside reverse transcriptase inhibitors (NRTI) plus either a ritonavir-boosted protease inhibitor (PI) or an integrase strand transfer inhibitor (ISTI), with non-nucleoside reverse transcriptase inhibitors (NNRTI) representing an alternative drug class. The study's purpose was to compare these three options in terms of pregnancy outcomes. METHODS: Data from a national observational study of pregnant women with HIV-1 were used. The analysis included all pregnancies reported between 2008 and 2018, ending in live births and exposed within 32 weeks of gestation to three-drug regimens composed of a NRTI backbone plus a PI, a NNRTI or a ISTI, without class switching during pregnancy. Clinical and laboratory outcomes were evaluated in univariate and multivariable analyses. RESULTS: Overall, 794 exposed pregnancies were analyzed (PI 78.4%, NNRTI 15.4%, ISTI 6.2%). Almost all outcomes had similar rates in the three groups. Women who received PI in pregnancy were less likely to be virologically suppressed at third trimester. PI use was associated with higher bilirubin and triglyceride levels, and ISTI use with a lower rate of low birthweight. The differences in viral suppression at third trimester and in low birthweight were not maintained in multivariable analyses that were adjusted for confounders. DISCUSSION: We found no major differences in a wide range of outcomes relevant for pregnant women with HIV. Such results are reassuring, and this information may be helpful in a context of preconception counseling when therapeutic choices for pregnancy are discussed between women and care providers.
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Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Inhibidores de Integrasa/uso terapéutico , Inhibidores de Proteasas/uso terapéutico , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Adulto , Fármacos Anti-VIH/efectos adversos , Peso al Nacer , Femenino , VIH-1 , Humanos , Inhibidores de Integrasa/efectos adversos , Análisis Multivariante , Embarazo , Resultado del Embarazo , Inhibidores de Proteasas/efectos adversos , ARN Viral/sangre , Inhibidores de la Transcriptasa Inversa/efectos adversosRESUMEN
Background: Few studies have evaluated in pregnant women with HIV the prevalence of smoking and its associations with maternal and neonatal outcomes. Objectives: to assess the prevalence of smoking among women with HIV in early pregnancy and the association between smoking and pregnancy outcomes in this particular population. Methods: We used data from a multicenter observational study to define the prevalence of smoking in women with HIV in early pregnancy, and the role of smoking status and intensity as risk factors for adverse maternal and neonatal outcomes. Main outcome measures were fetal growth restriction [FGR], preterm delivery [PD] and low birthweight [LB], evaluated in univariate and multivariate analyses. Results: The overall (2001-2018) prevalence of reported smoking (at least one cigarette/day) was 25.6% (792/3097), with a significant decrease in recent years (19.0% in 2013-2018). Women who smoked were less commonly African, had lower body mass index, older age, a longer history of HIV infection and higher CD4 counts. In univariate analyses, smokers were significantly more likely to have PD, LB, FGR and detectable HIV viral load at third trimester. Multivariable analyses confirmed for smokers a significantly higher risk of LB (adjusted odds ratio [AOR]: 1.69, 95%CI 1.22-2.34) and FGR (AOR 1.88, 95%CI 1.27-2.80), while the associations with detectable HIV and PD were not maintained. Conclusions: The common prevalence of smoking among pregnant women with HIV and its association with adverse outcomes indicates that smoking cessation programs in this population may have a significant impact on neonatal and maternal health.
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Infecciones por VIH/epidemiología , Mujeres Embarazadas , Fumar/epidemiología , Adulto , Peso al Nacer , Femenino , Edad Gestacional , Humanos , Recién Nacido , Italia/epidemiología , Masculino , Embarazo , Resultado del Embarazo , Prevalencia , Prevención del Hábito de FumarRESUMEN
PURPOSE: To evaluate the maternal and neonatal safety of vaginal delivery in women with HIV following the implementation of a national protocol in Italy. METHODS: Vaginal delivery was offered to all eligible women who presented antenatally at twelve participating clinical sites. Data collection and definition of outcomes followed the procedures of the National Program on Surveillance on Antiretroviral Treatment in Pregnancy. Pregnancy outcomes were compared according to the mode of delivery, classified as vaginal, elective cesarean (ECS) and non-elective cesarean section (NECS). RESULTS: Among 580 women who delivered between January 2012 and September 2017, 142 (24.5%) had a vaginal delivery, 323 (55.7%) had an ECS and 115 (19.8%) had an NECS. The proportion of vaginal deliveries increased significantly over time, from 18.9% in 2012 to 35.3% in 2017 (p < 0.001). Women who delivered vaginally were younger, more commonly nulliparous, diagnosed with HIV during current pregnancy, and antiretroviral-naïve, but had a slightly longer duration of pregnancy, with significantly higher birthweight of newborns. NECS was associated with adverse pregnancy outcomes. The rate of HIV transmission was minimal (0.4%). There were no differences between vaginal and ECS about delivery complications, while NECS was more commonly associated with complications compared to ECS. CONCLUSIONS: Vaginal delivery in HIV-infected women with suppressed viral load appears to be safe for mother and children. No cases of HIV transmission were observed. Despite an ongoing significant increase, the rate of vaginal delivery remains relatively low compared to other countries, and further progress is needed to promote this mode of delivery in clinical practice.
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Cesárea/estadística & datos numéricos , Parto Obstétrico/estadística & datos numéricos , Infecciones por VIH/virología , Carga Viral , Adulto , Femenino , Humanos , Italia , Adulto JovenRESUMEN
BACKGROUND: Tuberculosis is a major health concern in several countries, and effective diagnostic algorithms for use in human immunodeficiency virus (HIV)-positive patients are urgently needed. METHODS: At prescription of antiretroviral therapy, all patients in 3 Mozambican health centers were screened for tuberculosis, with a combined approach: World Health Organization (WHO) 4-symptom screening (fever, cough, night sweats, and weight loss), a rapid test detecting mycobacterial lipoarabinomannan in urine (Determine TB LAM), and a molecular assay performed on a sputum sample (Xpert MTB/RIF; repeated if first result was negative). Patients with positive LAM or Xpert MTB/RIF results were referred for tuberculosis treatment. RESULTS: Among 972 patients with a complete diagnostic algorithm (58.5% female; median CD4 cell count, 278/µL; WHO HIV stage I, 66.8%), 98 (10.1%) tested positive with Xpert (90, 9.3%) or LAM (34, 3.5%) assays. Compared with a single-test Xpert strategy, dual Xpert tests improved case finding by 21.6%, LAM testing alone improved it by 13.5%, and dual Xpert tests plus LAM testing improved it by 32.4%. Rifampicin resistance in Xpert-positive patients was infrequent (2.5%). Among patients with positive results, 22 of 98 (22.4%) had no symptoms at WHO 4-symptom screening. Patients with tuberculosis diagnosed had significantly lower CD4 cell counts and hemoglobin levels, more advanced WHO stage, and higher HIV RNA levels. Fifteen (15.3%) did not start tuberculosis treatment, mostly owing to rapidly deteriorating clinical conditions or logistical constraints. The median interval between start of the diagnostic algorithm and start of tuberculosis treatment was 7 days. CONCLUSIONS: The prevalence of tuberculosis among Mozambican HIV-positive patients starting antiretroviral therapy was 10%, with limited rifampicin resistance. Use of combined point-of-care tests increased case finding, with a short time to treatment. Interventions are needed to remove logistical barriers and prevent presentation in very advanced HIV/tuberculosis disease.
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Infecciones por VIH/tratamiento farmacológico , Técnicas de Diagnóstico Molecular , Sistemas de Atención de Punto , Pruebas en el Punto de Atención , Tuberculosis Pulmonar/diagnóstico , Adulto , Algoritmos , Terapia Antirretroviral Altamente Activa/estadística & datos numéricos , Antituberculosos/uso terapéutico , Femenino , Infecciones por VIH/epidemiología , Infecciones por VIH/microbiología , Seropositividad para VIH , Humanos , Lipopolisacáridos/orina , Masculino , Mozambique/epidemiología , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/genética , Prevalencia , Sensibilidad y Especificidad , Esputo/microbiología , Tuberculosis Pulmonar/tratamiento farmacológico , Tuberculosis Pulmonar/epidemiología , Tuberculosis Pulmonar/microbiologíaRESUMEN
OBJECTIVES: No data are available on bone metabolism in infants exposed to tenofovir during breastfeeding. We investigated bone metabolism markers in the first year of life in infants from mothers who received tenofovir, lamivudine and efavirenz during pregnancy and 12 months of breastfeeding in a national Option B+ programme in Malawi. METHODS: Serum samples collected at 6 and 12 months in tenofovir-exposed infants and in a small sample of tenofovir-unexposed infants from the same clinical centre were analysed in batches for levels of bone-specific alkaline phosphatase (BAP; marker of bone formation) and of C-terminal telopeptide of type I collagen (CTX; marker of bone resorption). RESULTS: Overall, 136 tenofovir-exposed infants were evaluated. No infant had at either timepoint CTX values above the upper normal limit, while most of them had at 6 and 12 months levels of BAP above the upper normal limit for the age range. Levels of bone markers showed no differences by gender and no association with growth parameters. Tenofovir-unexposed and -exposed children had similar mean levels of bone markers at 6 months (CTX: 0.62 versus 0.55 ng/mL, Pâ=â0.122; BAP: 384 versus 362 U/L, Pâ=â0.631). CONCLUSIONS: No significant association between treatment with tenofovir and CTX or BAP levels was found. The high levels of BAP, coupled to the normal levels observed for CTX, might reflect primarily skeletal growth. Potential negative effects of prolonged exposure to tenofovir through breastfeeding cannot however be excluded and longitudinal studies that evaluate bone mineralization status in children enrolled in Option B+ programmes are warranted.
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Fármacos Anti-VIH/efectos adversos , Resorción Ósea/inducido químicamente , Lactancia Materna , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/prevención & control , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Tenofovir/efectos adversos , Adulto , Fosfatasa Alcalina/sangre , Alquinos , Fármacos Anti-VIH/administración & dosificación , Benzoxazinas/administración & dosificación , Biomarcadores/sangre , Colágeno Tipo I/sangre , Ciclopropanos , Femenino , Humanos , Lactante , Recién Nacido , Lamivudine/administración & dosificación , Malaui , Masculino , Péptidos/sangre , Embarazo , Tenofovir/administración & dosificación , Adulto JovenRESUMEN
OBJECTIVES: To evaluate antiretroviral drug concentrations in mothers and infants enrolled under the Option B-Plus approach for the prevention of HIV mother-to-child transmission in Malawi and to assess the maternal virological response after 1 year of treatment. PATIENTS AND METHODS: Forty-seven women and 25 children were studied. Mothers were administered during pregnancy a combination of tenofovir, lamivudine and efavirenz and continued it during breastfeeding (up to 2 years) and thereafter. Drug concentrations were evaluated in mothers (plasma and breast milk) at 1 and 12 months post-partum and in infants (plasma) at 6 and 12 months of age. Drug concentrations were determined using an LC-MS/MS validated methodology. RESULTS: In breast milk, tenofovir concentrations were very low (breast milk/maternal plasma ratioâ=â0.08), while lamivudine was concentrated (breast milk/plasma ratioâ=â3) and efavirenz levels were 80% of those found in plasma. In infants, median levels at 6 months were 24 ng/mL tenofovir, 2.5 ng/mL lamivudine and 86.4 ng/mL efavirenz. At month 12, median levels were below the limit of quantification for the three drugs. No correlation was found between drug concentrations and laboratory parameters or indices of growth. HIV-RNA >1000 copies/mL was seen at month 1 in 15% of the women and at month 12 in 8.5%. Resistance was found in half of the women with detectable viral load. CONCLUSIONS: Breastfeeding infants under Option B-Plus are exposed to low concentrations of antiretroviral drugs. With this strategy, mothers had a good virological response 1 year after delivery.
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Terapia Antirretroviral Altamente Activa , Benzoxazinas/farmacocinética , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/transmisión , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Lamivudine/farmacocinética , Tenofovir/farmacocinética , Adulto , Alquinos , Recuento de Linfocito CD4 , Cromatografía Liquida , Ciclopropanos , Femenino , Infecciones por VIH/diagnóstico , Humanos , Lactante , Malaui , Embarazo , Complicaciones Infecciosas del Embarazo , Espectrometría de Masas en Tándem , Carga Viral , Adulto JovenRESUMEN
There is limited information on the variations of HIV-1 DNA mutation profile in reverse transcriptase (RT) and protease (PR) genes during suppressive antiretroviral treatment (plasma HIV-1 RNA continuously <50 copies/ml) with raltegravir (RAL)-based regimens in patients with baseline RT/PR resistant HIV. Twelve multidrug resistant (RT: 12/12, PR: 8/12) HIV-infected patients were followed during effectively suppressive RAL-based therapy. Total and integrated HIV-1 DNA were assessed by real time PCR at baseline and every 6 months. Ultrasensitive (threshold: 2.5 copies/ml) plasma HIV-1 RNA and genotypic analysis of RT and PR in proviral DNA were performed at baseline and at 24 months. Half of the patients had full viral suppression (plasma HIV-RNA < 2.5 copies/ml) at month 12. Total HIV-1 DNA declined significantly after 12 months of therapy (from 249.2 to 145.7 copies/106 cells, P = 0.023), and remained stable until 24 months, when total HIV-1 DNA levels raised, concomitantly with a less stringent suppression of HIV-1 RNA (81.8% of patients with >2.5 copies/ml). Integrated HIV-1 DNA did not show fluctuations during the study period. Sequencing of the PR and RT regions from HIV-1 DNA revealed changes in the resistance mutation profile in five patients. Total HIV-1 DNA declined after the introduction of RAL-based therapy, with a rebound after 2 years. No changes were observed in levels of integrated DNA, suggesting limited effect on archived HIV. The RT and PR sequence changes in archived HIV-1 DNA suggest that variation of the mutation profile can occur even in the absence of detectable HIV-1 RNA. J. Med. Virol. 88:2115-2124, 2016. © 2016 Wiley Periodicals, Inc.
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Fármacos Anti-VIH/uso terapéutico , ADN Viral/genética , Farmacorresistencia Viral Múltiple , Proteasa del VIH/genética , Transcriptasa Inversa del VIH/genética , VIH-1/enzimología , VIH-1/genética , Raltegravir Potásico/uso terapéutico , Adulto , Fármacos Anti-VIH/efectos adversos , Terapia Antirretroviral Altamente Activa , Femenino , Variación Genética , Genotipo , VIH-1/fisiología , Humanos , Masculino , Persona de Mediana Edad , Mutación , ARN Viral/sangre , ARN Viral/genética , Raltegravir Potásico/efectos adversos , Carga ViralRESUMEN
PURPOSE: To provide information about main pregnancy outcomes in HIV-HCV coinfected women and about the possible interactions between HIV and HCV in this particular population. METHODS: Data from a multicenter observational study of pregnant women with HIV, conducted in Italian University and Hospital Clinics between 2001 and 2015, were used. Eligibility criteria for analysis were HCV coinfection and at least one detectable plasma HCV-RNA viral load measured during pregnancy. Qualitative variables were compared using the Chi-square or the Fisher test and quantitative variables using the Mann-Whitney U test. The Spearman's coefficient was used to evaluate correlations between quantitative variables. RESULTS: Among 105 women with positive HCV-RNA, median HCV viral load was substantially identical at the three trimesters (5.68, 5.45, and 5.86 log IU/ml, respectively), and 85.7 % of the women had at least one HCV-RNA value >5 log IU/ml. Rate of preterm delivery was 28.6 % with HCV-RNA <5 log IU/ml and 43.2 % with HCV-RNA >5log (p = 0.309). Compared to women with term delivery, women with preterm delivery had higher median HCV-RNA levels (third trimester: 6.00 vs. 5.62 log IU/ml, p = 0.037). Third trimester HIV-RNA levels were below 50 copies/ml in 47.7 % of the cases. No cases of vertical HIV transmission occurred. Rate of HCV transmission was 9.0 % and occurred only with HCV-RNA levels >5 log IU/ml. CONCLUSIONS: Coinfection with HIV and HCV has relevant consequences in pregnancy: HIV coinfection is associated with high HCV-RNA levels that might favour HCV transmission, and HCV infection might further increase the risk of preterm delivery in women with HIV. HCV/HIV coinfected women should be considered a population at high risk of adverse outcomes.
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Coinfección/epidemiología , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Hepatitis C/complicaciones , Hepatitis C/epidemiología , Complicaciones Infecciosas del Embarazo/epidemiología , Adulto , Femenino , Hepacivirus/aislamiento & purificación , Hospitales Universitarios , Humanos , Recién Nacido , Italia/epidemiología , Masculino , Embarazo , Resultado del Embarazo , Nacimiento Prematuro , ARN Viral/sangre , Carga ViralRESUMEN
Current guidelines recommend treatment optimization in virologically suppressed patients through switching/ simplification strategies to minimize long-term toxicities and improve adherence. The assessment of inflammation/ coagulation profiles may support therapeutic decisions. We undertook a prospective, non-randomized study to evaluate the efficacy and safety of switching to ABC/3TC from ZDV/3TC or TDF/FTC backbones, in 40 HIV-1 infected patients with HIV-RNA levels <37 copies/mL (>24 months). Main endpoints were viral load levels, CD4+ T cells and toxicities after 48 weeks. Serum inflammation/coagulation markers (ESR, CRP, D-dimer and fibrinogen) and pro-inflammatory cytokines (IL-6, TNF-α, adiponectin, resistin) were evaluated. Baseline characteristics were similar in the two arms, with significantly lower values of e-GFR in patients on TDF/FTC. Markers of inflammation/ coagulation and cytokine profile were also similar, except for higher values of resistin in patients on TDF/ FTC. During follow up, CD4+ T cells increased and viral load remained undetectable in both groups. Patient from ZDV/3TC had significantly greater changes in total cholesterol and serum creatinine. Markers of inflammation/ coagulation remained unchanged. Adiponectin significantly increased in patients from ZDV/3TC. Switching to ABC/3TC was effective and safe. Inflammatory markers remained low in both groups. Some changes in metabolic, kidney and cytokine profiles were apparently specific for baseline cART treatment.
Asunto(s)
Fármacos Anti-VIH/administración & dosificación , Didesoxinucleósidos/administración & dosificación , Infecciones por VIH/tratamiento farmacológico , Lamivudine/administración & dosificación , Adulto , Recuento de Linfocito CD4 , Citocinas/inmunología , Combinación de Medicamentos , Sustitución de Medicamentos , Femenino , Infecciones por VIH/inmunología , VIH-1/efectos de los fármacos , VIH-1/fisiología , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Resultado del Tratamiento , Carga Viral/efectos de los fármacosRESUMEN
BACKGROUND: Atazanavir and lopinavir represent the main HIV protease inhibitors recommended in pregnancy, but comparative data in pregnant women are limited. METHODS: Women from a national observational study, exposed in pregnancy to either atazanavir or lopinavir, were compared for glucose and lipid profiles, liver function tests, CD4 count, HIV RNA and main pregnancy outcomes. Statistical methods included univariate and multivariable analyses. RESULTS: The study population included 428 pregnancies (lopinavir, 322; atazanavir, 106). The lopinavir group was characterized by higher rates of HIV diagnosis in pregnancy and treatment indication for maternal health, lower CD4 counts, higher HIV RNA levels, less frequent antiretroviral treatment at conception and shorter duration of drug exposure during pregnancy. No differences in pregnancy outcomes, glucose metabolism and weight gain were observed. The two groups also showed in a multivariable analysis similar odds for detectable HIV RNA in the third trimester (adjusted OR 0.85, 95% CI 0.35-2.10, P = 0.730). Total lipid levels were significantly higher in the lopinavir group (median values in the third trimester 239 versus 221 mg/dL for total cholesterol and 226 versus 181 mg/dL for triglycerides; P < 0.001 for both comparisons) and bilirubin levels were significantly higher in the atazanavir group (1.53 versus 0.46 mg/dL, P < 0.001). CONCLUSIONS: In this observational study atazanavir and lopinavir showed similar safety and activity in pregnancy, with no differences in the main pregnancy outcomes. Atazanavir use was associated with a better lipid profile and with higher bilirubin levels. Overall, the study findings confirm that these two HIV protease inhibitors represent equally valid alternative options.
Asunto(s)
Fármacos Anti-VIH/administración & dosificación , Infecciones por VIH/tratamiento farmacológico , Lopinavir/administración & dosificación , Oligopéptidos/administración & dosificación , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Piridinas/administración & dosificación , Adulto , Fármacos Anti-VIH/efectos adversos , Sulfato de Atazanavir , Recuento de Linfocito CD4 , Femenino , Humanos , Lípidos/sangre , Pruebas de Función Hepática , Lopinavir/efectos adversos , Oligopéptidos/efectos adversos , Embarazo , Resultado del Embarazo , Piridinas/efectos adversos , ARN Viral/sangre , Carga ViralRESUMEN
BACKGROUND: Health-related quality of life (HRQoL) has been recognized as a central measure of the overall health status in HIV patients. With the availability of different highly effective drug combinations, maximizing quality-adjusted survival has become a major target of HIV treatment. Although the association of HIV RNA and CD4 cell count with clinical HIV progression has been well established, the relation between these markers and HRQoL measures is still unclear. METHOD: This cross-sectional study investigated the relationship linking HIV RNA and CD4 to HRQoL measures in 181 triple-class-experienced patients with advanced HIV disease. The instrument used was the ISSQoL, a self-administered and HIV-specific HRQoL questionnaire. RESULTS: Data showed no correlation between HRQoL measures and CD4 counts. Higher HIV RNA levels were, however, associated with poor HRQoL scores in 3 out of 9 scales of social functioning, depression and anxiety, and satisfaction with quality of life. In multivariable analyses, only the satisfaction with quality of life mean score remained significantly lower for the HIV RNA â¯100,000 copies/mL group compared to the HIV RNA 50 to 10,000 copies/mL group. CONCLUSIONS: Although other determinants of HRQoL in people with HIV should also be considered, this finding suggests a negative impact of high viral load on perceived HRQoL that adds to other described determinants of lower quality of life in people with HIV, such as lower social support and self-reported symptoms.
Asunto(s)
Fármacos Anti-VIH/clasificación , Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Calidad de Vida , Carga Viral/efectos de los fármacos , Adulto , Anciano , Recuento de Linfocito CD4 , Estudios Transversales , Femenino , Infecciones por VIH/psicología , Humanos , Masculino , Persona de Mediana Edad , ARN Viral/sangre , Encuestas y Cuestionarios , Adulto JovenRESUMEN
HIV testing is recommended as part of routine preconception and prenatal care but some cases of vertical transmission still occur because of missed HIV testing in pregnancy. We estimated the percentage of women missing HIV testing before delivery, and we evaluated factors related with it. An anonymous survey was distributed to women giving birth during a two-week period in the maternity units of hospitals in the Lazio region of Italy in 2011. Among the 1568 women who filled out the questionnaire, only 33.6% had an HIV test prior to conception, while 88.2% were tested during pregnancy; main reasons reported for missed testing were: not requested by the gynaecologist (57.0%), performed previously (20.7%), requested by the gynaecologist but not done (13.3%) and structural/organisational barriers (4.4%). The percentage of women who missed the HIV test as part of preconception care or during pregnancy was 9.1% (95% confidence interval, CI: 7.7-10.6). Multivariate analysis showed that those with missed test were younger (p = 0.05), of lower education level (p < 0.01), with a lower HIV-knowledge score (p < 0.01) and with fewer visits during pregnancy (p < 0.01). Around 10% of delivering women were not tested for HIV during pregnancy or as part of preconception care. Absence of a specific request by the gynaecologist was the most frequent reason given. The association of missed HIV testing with poor sociocultural level and limited maternal HIV knowledge emphasise the importance of promoting HIV information among women and prenatal care providers. Strategies to increase routine testing may include the adoption of an opt-out approach. Finally, availability of rapid HIV testing in the delivery room should be encouraged.
Asunto(s)
Serodiagnóstico del SIDA/estadística & datos numéricos , Infecciones por VIH/diagnóstico , Conocimientos, Actitudes y Práctica en Salud , Aceptación de la Atención de Salud/estadística & datos numéricos , Cooperación del Paciente/estadística & datos numéricos , Complicaciones Infecciosas del Embarazo/diagnóstico , Atención Prenatal/estadística & datos numéricos , Adulto , Distribución por Edad , Escolaridad , Femenino , Infecciones por VIH/prevención & control , Infecciones por VIH/transmisión , Humanos , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Italia , Embarazo , Complicaciones Infecciosas del Embarazo/prevención & control , Atención Prenatal/métodos , Encuestas y CuestionariosRESUMEN
Persistent immune activation and chronic inflammation significantly contribute to non-AIDS morbidity in HIV-infected patients. The HIV inhibitor maraviroc (MVC) targets the cellular chemokine CCR5 HIV co-receptor, which is involved in important inflammatory pathways. MVC could have significant anti-inflammatory and anti-atherosclerotic effects, also reducing immune activation. We designed a pilot study to determine which plasma biomarkers of inflammation, endothelial dysfunction, and hypercoagulability were modified by MVC in 2 groups of 10 patients starting MVC-free or MVC-containing regimens. Ten age- and gender-matched healthy controls were also included. We found higher levels of all inflammatory biomarkers in HIV-infected patients compared to healthy controls. Both groups showed decreasing levels of interleukin (IL)-17, IL-10, and macrophage inflammatory protein (MIP)-1a following the achievement of viral suppression. Vascular cell adhesion molecule (VCAM)-1 levels were decreased in the MVC group and increased in the MVC-free group. In conclusion, some inflammatory biomarkers tend to decrease with the salvage regimen; MVC was not associated with a better impact on these measured markers.