RESUMO
BACKGROUND: Pregnant women with an elevated viral load of hepatitis B virus (HBV) have a risk of transmitting infection to their infants, despite the infants' receiving hepatitis B immune globulin. METHODS: In this multicenter, double-blind clinical trial performed in Thailand, we randomly assigned hepatitis B e antigen (HBeAg)-positive pregnant women with an alanine aminotransferase level of 60 IU or less per liter to receive tenofovir disoproxil fumarate (TDF) or placebo from 28 weeks of gestation to 2 months post partum. Infants received hepatitis B immune globulin at birth and hepatitis B vaccine at birth and at 1, 2, 4, and 6 months. The primary end point was a hepatitis B surface antigen (HBsAg)-positive status in the infant, confirmed by the HBV DNA level at 6 months of age. We calculated that a sample of 328 women would provide the trial with 90% power to detect a difference of at least 9 percentage points in the transmission rate (expected rate, 3% in the TDF group vs. 12% in the placebo group). RESULTS: From January 2013 to August 2015, we enrolled 331 women; 168 women were randomly assigned to the TDF group and 163 to the placebo group. At enrollment, the median gestational age was 28.3 weeks, and the median HBV DNA level was 8.0 log10 IU per milliliter. Among 322 deliveries (97% of the participants), there were 319 singleton births, two twin pairs, and one stillborn infant. The median time from birth to administration of hepatitis B immune globulin was 1.3 hours, and the median time from birth to administration of hepatitis B vaccine was 1.2 hours. In the primary analysis, none of the 147 infants (0%; 95% confidence interval [CI], 0 to 2) in the TDF group were infected, as compared with 3 of 147 (2%; 95% CI, 0 to 6) in the placebo group (P=0.12). The rate of adverse events did not differ significantly between groups. The incidence of a maternal alanine aminotransferase level of more than 300 IU per liter after discontinuation of the trial regimen was 6% in the TDF group and 3% in the placebo group (P=0.29). CONCLUSIONS: In a setting in which the rate of mother-to-child HBV transmission was low with the administration of hepatitis B immune globulin and hepatitis B vaccine in infants born to HBeAg-positive mothers, the additional maternal use of TDF did not result in a significantly lower rate of transmission. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development; ClinicalTrials.gov number, NCT01745822 .).
Assuntos
Antivirais/uso terapêutico , Vírus da Hepatite B/isolamento & purificação , Hepatite B/transmissão , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Complicações Infecciosas na Gravidez/tratamento farmacológico , Tenofovir/uso terapêutico , Adolescente , Adulto , Alanina Transaminase/sangue , Antivirais/efeitos adversos , DNA Viral/isolamento & purificação , Método Duplo-Cego , Feminino , Hepatite B/diagnóstico , Hepatite B/tratamento farmacológico , Vacinas contra Hepatite B , Antígenos E da Hepatite B/sangue , Vírus da Hepatite B/genética , Humanos , Lactente , Recém-Nascido , Masculino , Gravidez , Tenofovir/efeitos adversos , Carga Viral , Adulto JovemRESUMO
In a randomized, double-blind, placebo-controlled trial of tenofovir disoproxil fumarate (TDF) use from 28 weeks gestational age to 2 months postpartum to prevent mother-to-child transmission of hepatitis B virus, there was no significant effect of maternal TDF use on maternal or infant bone mineral density 1 year after delivery/birth. Clinical Trials Registration. NCT01745822.
Assuntos
Antivirais/uso terapêutico , Densidade Óssea/efeitos dos fármacos , Hepatite B/tratamento farmacológico , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Tenofovir/uso terapêutico , Adulto , Método Duplo-Cego , Feminino , Idade Gestacional , Vírus da Hepatite B , Humanos , Lactente , Masculino , Período Pós-Parto , Gravidez , Complicações Infecciosas na Gravidez/prevenção & controle , Complicações Infecciosas na Gravidez/virologia , Carga Viral/efeitos dos fármacos , Adulto JovemRESUMO
We assessed tenofovir exposure during pregnancy and postpartum in hepatitis B virus (HBV)-infected HIV-uninfected women receiving tenofovir disoproxil fumarate (TDF) to prevent mother-to-child transmission of HBV. Data from 154 women who received TDF within a randomized controlled trial were included. Individual plasma tenofovir exposures (area under the concentration-time curve from 0 to 24 h [AUC0-24]) were estimated using a population pharmacokinetic approach. The estimated geometric mean tenofovir AUC0-24 was 20% (95% confidence interval [95% CI], 19 to 21%) lower during pregnancy than during postpartum; this modest reduction in the absence of HBV transmission suggests that no dose adjustment is needed.
Assuntos
Antivirais/farmacocinética , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/transmissão , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Tenofovir/farmacocinética , Administração Oral , Adulto , Antivirais/sangue , Antivirais/farmacologia , Área Sob a Curva , Feminino , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/crescimento & desenvolvimento , Hepatite B Crônica/virologia , Humanos , Período Pós-Parto , Gravidez , Tenofovir/sangue , Tenofovir/farmacologia , Carga Viral/efeitos dos fármacosRESUMO
Zika virus (ZIKV) epidemiological data in Thailand are limited. We assessed ZIKV IgG seroprevalence among young adults during 1997-2017 and determined factors associated with ZIKV IgG seropositivity. This retrospective laboratory study included randomly selected subjects aged 18-25 years participating in large clinical studies conducted in Thailand during 1997-2017. Stored plasma samples were analyzed for ZIKV IgG using an ELISA test (Anti-Zika Virus IgG, EUROIMMUN, Lübeck, Germany). Sociodemographic, clinical and laboratory data were used in univariable and multivariable analyses to identify factors associated with ZIKV IgG positivity. Of the 1648 subjects included, 1259 were pregnant women, 844 were living with HIV and 111 were living with HBV. ZIKV IgG seroprevalence was similar among the HIV-infected and -uninfected pregnant women (22.8% vs. 25.8%, p-value = 0.335) and was overall stable among the pregnant women, with a 25.2% prevalence. Factors independently associated with ZIKV IgG positivity included an age of 23-25 years as compared to 18-20 years, an HIV RNA load below 3.88 log10 copies/mL and birth in regions outside northern Thailand. Our study shows that a large proportion of the population in Thailand probably remains susceptible to ZIKV infection, which could be the ground for future outbreaks. Continued surveillance of ZIKV spread in Thailand is needed to inform public health policies.
Assuntos
Anticorpos Antivirais/sangue , Infecções por HIV/complicações , Imunoglobulina G/sangue , Infecção por Zika virus/epidemiologia , Zika virus/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Infecções por HIV/epidemiologia , HIV-1/genética , Humanos , Modelos Logísticos , Masculino , Gravidez , Gestantes , Estudos Retrospectivos , Estudos Soroepidemiológicos , Tailândia/epidemiologia , Adulto Jovem , Infecção por Zika virus/diagnósticoRESUMO
Even when receiving combination antiretroviral therapy, women living with HIV are at high risk of human papillomavirus (HPV) infection and/or cervical lesions, including cancer. Using data from the PapilloV prospective cohort, we evaluated the prevalence of high-risk HPV (HR-HPV) infections after cervical lesion treatment and investigated factors associated with their carriage. Women were followed up for three years with annual Pap smear and HPV genotyping. We offered treatment to women presenting either a Pap smear with high-grade squamous intraepithelial lesion or higher, and/or a biopsy showing cervical intraepithelial neoplasia II or III. We compared the prevalence of HR-HPV infection at the time of first treatment indication and at the end of follow-up among women who received treatment and those who did not. Overall, 46 women had treatment indication. HR-HPV prevalence significantly decreased from 67% to 27% (p value = 0.001) in the 30 women who received treatment, while it did not significantly decrease (from 56% to 38%) in the 16 women who did not (p value = 0.257). Due to lack of statistical power, the 40% relative difference in HR-HPV carriage between treated and untreated women was not significant. In women living with HIV, the treatment of a cervical lesion may be beneficial for clearing HR-HPV infections.
RESUMO
OBJECTIVES: To estimate the prevalence and factors associated with Human Papillomavirus (HPV) infection, HPV genotypes and cytological/histological high-grade (HSIL+/CIN2+) lesions. METHODS: We conducted a cross-sectional study within a prospective cohort of HIV-infected women on combination antiretroviral therapy (cART). Cervical specimens were collected for cytology and HPV genotyping (Papillocheck®). Any women with High-Risk-HPV (HR-HPV), and/or potentially HR-HPV (pHR-HPV) and/or ASC-US or higher (ASC-US+) lesions were referred for colposcopy. Factors associated with HR-HPV infection and with HSIL+/CIN2+ lesions were investigated using mixed-effects logistic regression models. RESULTS: 829 women were enrolled: median age 40.4 years, on cART for a median of 6.9 years, median CD4 cell-count 536 cells/mm3, and 788 (96%) with HIV-viral load<50copies/mL. Of 214 (26%) infected with HPV: 159 (19%) had ≥1 HR-HPV, of whom 38 (5%) HPV52, 22 (3%) HPV16, 9 (1%) HPV18; 21 (3%) had pHR-HPV, 34 (4%) low risk-HPV infection, and 56 (26%) had multiple genotypes. Younger age, low CD4 cell-counts and low education were independently associated with HR-HPV infection. 72 women (9%) had ASC-US+ and 28 (3%) HSIL+/CIN2+ lesions. HR-HPV infection was independently associated with HSIL+/CIN2+ lesions. CONCLUSION: The prevalence of HPV infection and of cervical lesions was low. The HPV genotype distribution supports the use of 9-valent vaccine in Thailand.
Assuntos
Infecções por HIV , Infecções por Papillomavirus , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Adulto , Antirretrovirais/uso terapêutico , Estudos Transversais , Feminino , Genótipo , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Humanos , Pessoa de Meia-Idade , Papillomaviridae/genética , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/virologia , Tailândia/epidemiologia , Neoplasias do Colo do Útero/complicações , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/virologia , Displasia do Colo do Útero/complicações , Displasia do Colo do Útero/epidemiologia , Displasia do Colo do Útero/virologiaRESUMO
OBJECTIVE: Each year, intrauterine growth retardation (IUGR) affects 20-30 million neonates worldwide, mostly in resource-limited settings. Increased perinatal and infant mortality has been associated with IUGR. Some studies have suggested that HIV infection could increase the risk of IUGR. To confirm this hypothesis, we examined the association between HIV-related factors and the risk of IUGR in Thailand. PATIENTS AND METHODS: Data from a cohort of 1436 HIV-infected pregnant women enrolled in the "Perinatal HIV Prevention Trial-1", a clinical trial conducted from 1997 to 1999 in Thailand, were analyzed using a logistic regression, adjusting for risk factors usually associated with IUGR. RESULTS: The rate of IUGR was 7.6%. Adjusting for a short maternal height, low body mass index, small weight gain during pregnancy, and infant female sex, a low maternal CD4 percentage was independently associated with IUGR (odds ratio 0.96, per 1% increment, 95% confidence interval 0.93 to 0.99, P = 0.03). CONCLUSIONS: The current World Health Organization recommendation to initiate combination antiretroviral therapy for immunocompromised women as early as possible during pregnancy for their own health and for the prevention of HIV mother-to-child transmission is likely to also decrease the incidence of IUGR. Encouraging immunocompromised HIV-infected women who plan to become pregnant to wait until immune restoration has been achieved may help to reduce the risk of IUGR.