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1.
Int J Antimicrob Agents ; 55(3): 105893, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31926287

RESUMO

This was a retrospective study on the efficacy and drug resistance mutations selected at virological failure (VF) in prospectively-followed HIV-infected patients switched to dolutegravir plus rilpivirine (DTG+RPV) or lamivudine (DTG+3TC) while virologically suppressed (HIV-RNA <50 copies/mL). VF was defined as HIV-RNA >50 copies/mL in two consecutive determinations or in a single determination if followed by treatment modification, or >1000 copies/mL in a single determination. Totally, 374 patients were analysed (307 switched to DTG+3TC and 67 to DTG+RPV); 220 had documented historical resistance. The median (IQR) time with HIV-RNA <50 copies/mL before switch was 4.52 (1.93-8.14) years. VF occurred in 17 patients after a median of 1.74 (0.90-2.46) years of follow-up in the 3TC group [incidence rate (95% CI) 3.34 (2.08-5.37) per 100-PYFU] and in 2 patients after a median of 1.78 (1.10-2.99) years of follow-up in the RPV group [incidence rate (95% CI) 1.57 (0.4-6.28) per 100-PYFU]. The 48-week estimated probabilities to maintain virological suppression during treatment with a two-drug regimen were 97.8% (95% CI 95.1-99.0%) vs. 98.3% (95% CI 88.6-99.8%) in the 3TC versus RPV group (P = 0.311). At switch, patients with VF had undetectable HIV-RNA since 0.71 (0.23-1.07) years versus 1.49 (0.64-2.2) years in those without VF (P = 0.001). In the 3TC group, VF was not associated with the presence of historical resistance to nucleoside analogues, and DTG-resistant variants were not selected at VF. One VF to DTG+RPV occurred because of historical resistance to RPV, accompanied by newly selected G140A and Q148R mutations. VF was infrequent with these regimens and was negatively associated with duration of viral undetectability. Drug resistance mutations selected at failure of these regimens were those expected in case of failure of any regimen including DTG, 3TC or RPV, but the impact of resistance to NRTIs on efficacy of DTG+3TC seems lower than expected.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Lamivudina/uso terapêutico , Inibidores da Transcriptase Reversa/uso terapêutico , Rilpivirina/uso terapêutico , Fármacos Anti-HIV/administração & dosagem , Farmacorresistência Viral , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Humanos , Lamivudina/administração & dosagem , Estudos Retrospectivos , Rilpivirina/administração & dosagem , Resultado do Tratamento
2.
S Afr Med J ; 109(12): 919-926, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31865953

RESUMO

BACKGROUND: World Health Organization guidelines recommend that HIV patients who do not achieve viral suppression on efavirenz-based first-line antiretroviral therapy (ART) should be changed to a protease inhibitor (PI)-based regimen. In South Africa (SA), ~200 000 people are on second-line treatment, but little is known about these patients. OBJECTIVES: To describe second-line black African patients in a large urban area. METHODS: A quantitative retrospective study of 825 second-line patients in central Johannesburg, SA (subdistrict F), was performed with data extracted from government databases. Demographic characteristics, treatment status and laboratory information were gathered, then analysed with CD4+ cell count, viral load (VL) and retention-in-care data as outcome variables. RESULTS: The average recorded time to VL measurement after the switch to a PI-based ART regimen was 20 months, and 83.1% (570/686) of patients with a recent VL achieved viral suppression while on second-line treatment. The most recent median CD4+ cell count for the cohort was 286 cells/µL (interquartile range 160 - 478), which represented a 177 cells/µL increase from the baseline count at the start of first-line ART. Slightly less than three-quarters (72.4%) of the population remained active in care in the study clinics from initiation on first-line ART. Demographic characteristics such as being <25 years of age, male sex and geographical transfer (started initial treatment in a different region) independently predicted low CD4+ cell counts and virological failure on second-line treatment. Patients with virological failure were most likely (odds ratio (OR) 3.13, 95% confidence interval (CI) 1.50 - 6.56) to be lost to follow-up after the switch, while patients from Hillbrow Community Health Centre (OR 0.27, 95% CI 0.16 - 0.44), South Rand Hospital (OR 0.24, 95% CI 0.12 - 0.47) and Jeppe Clinic (OR 0.38, 95% CI 0.16 - 0.88), three larger sites, were most likely to remain active in care. CONCLUSIONS: VL suppression was high in patients on second-line treatment, but one-fifth of patients were lost to follow-up. Younger age, male sex and transfer from other treatment sites predicted poor treatment outcomes, highlighting opportunities for prioritisation of adherence interventions.


Assuntos
Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/uso terapêutico , Adesão à Medicação/estatística & dados numéricos , Carga Viral , Adulto , Fatores Etários , Contagem de Linfócito CD4 , Bases de Dados Factuais , Quimioterapia Combinada , Feminino , Infecções por HIV/imunologia , Humanos , Lamivudina/uso terapêutico , Lopinavir/uso terapêutico , Perda de Seguimento , Masculino , Pessoa de Meia-Idade , Retratamento , Estudos Retrospectivos , Inibidores da Transcriptase Reversa/uso terapêutico , Ritonavir/uso terapêutico , Fatores Sexuais , Tenofovir/uso terapêutico , Falha de Tratamento , Organização Mundial da Saúde , Zidovudina/uso terapêutico
3.
Top Antivir Med ; 27(3): 123-127, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31634859

RESUMO

Antiretroviral therapy (ART) should be started as soon as possible after HIV diagnosis. Recommended starting ART regimens in patients with any baseline viral load include ictegravir plus tenofovir alafenamide (TAF)/emtricitabine (FTC), dolutegravir (DTG) plus abacavir/lamivudine, DTG plus TAF (or TDF)/FTC, or DTG plus 3TC. Initial laboratory evaluation includes CD4+ cell count, plasma HIV-1 RNA, and testing for HIV reverse transcriptase and protease resistance mutations. ART regimens do not need to be altered for virologic blips due to release of virus from chronically latently infected cells in patients otherwise exhibiting viral suppression. Patients with continuously undetectable viral load on ART pose virtually no risk of transmitting infection through sexual contact. This article is based on a case-based presentation by Michael S. Saag, MD, at the 2018 Clinical Conference at the National Ryan White Conference on HIV Care & Treatment in December 2018 and intended for clinicians who are new to HIV disease management.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Adenina/análogos & derivados , Adenina/uso terapêutico , Adulto , Terapia Antirretroviral de Alta Atividade/métodos , Contagem de Linfócito CD4 , Didesoxinucleosídeos/uso terapêutico , Combinação de Medicamentos , Quimioterapia Combinada , Emtricitabina/uso terapêutico , Feminino , Infecções por HIV/transmissão , Transcriptase Reversa do HIV/efeitos dos fármacos , HIV-1/genética , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Humanos , Inibidores de Integrase/uso terapêutico , Lamivudina/uso terapêutico , Estágios do Ciclo de Vida/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Mutação , RNA Viral/sangue , Tenofovir/uso terapêutico , Carga Viral
4.
Zhonghua Gan Zang Bing Za Zhi ; 27(8): 604-609, 2019 Aug 20.
Artigo em Chinês | MEDLINE | ID: mdl-31594077

RESUMO

Objective: To investigate the curative effect of antiviral therapy and related factors influencing the curative affect in children with immune-tolerant phase chronic hepatitis B. Methods: From May 2014 to April 2015, 46 children with chronic hepatitis B, aged 1 to 16 years with immune-tolerant phase were enrolled as the treatment group. All cases in the treated group either received interferon alpha (3-5 MIU/m(2), once daily) in lamivudine combination (if HBV DNA decreased < 2 log(10)) or repeatedly received interferon-alpha alone (if HBV DNA decreased >2 log(10)) for 12 weeks. Interferon was discontinued at 72 weeks and followed-up period was continued with lamivudine for 24 weeks. At the same time, data of 23 cases of untreated children with immune-tolerant phase chronic hepatitis B were collected as the control group. The treatment group and the control group were divided into two age groups: 1-7 years old and 7-15 years old. Data measurements were compared using t-test, analysis of variance and single factor analysis methods, and the count data were analyzed by χ (2) test. Multiple logistic regression analysis was used to analyze the effects of different factors on response. Results: (1) There were 22 cases aged 1-7 years in the treatment group (47.8%) and 12 cases aged 1-7 years in the control group (52.2%). The cases of mother-to-child transmission (MTCT) in treatment and control group were 34 (73.9%) and 17 (73.9%), while children with normal baseline ALT in the treatment and control group were 18 (39.1%) and 10 (43.5%). (2) At the end of follow-up, 15 cases in the treatment group (32.6%) had HBeAg serological conversion. Among them, nine (19.6%) cases had HBsAg clearance or HB-Ag seroconversion with anti-HBs, and one (2.2%) case had HBsAg clearance, but both HBeAg and anti-HBe were positive. In the control group, one case had HBV DNA lower than the lower limit of detection level, and one case had HBeAg seroconversion without HBsAg clearance. (3) At the end of follow-up, the seroconversion rates of HBeAg in patients aged 1 to 7 years and patients aged 7 to 15 years were 45.5% and 20.8%, respectively (P = 0.078) and the clearance rates of HBsAg were 36.4% and 8.3% (P = 0.023). The serum conversion rates of normal and abnormal baseline alanine aminotransferase levels were 5.6% and 50.0% (P = 0.005), and the clearance rates of HBsAg were 5.6% and 32.1% (P = 0.077), respectively. There was no statistically significant difference in gender, mother-to-child transmission, HBV DNA genotyping and baseline HBsAg level in antiviral efficacy among children (P > 0.05). (4) HBsAg and HBeAg clearance occurred in 100% of patients at the end of follow-up who had HBsAg < 3 000 IU/ml at 24 weeks of treatment. (5) Multivariate logistic regression analysis showed that serum HBeAg conversion rate had relation with non-MTCT transmission and abnormal baseline alanine aminotransferase. Furthermore, HBsAg clearance rate was associated with the age of children. Conclusion: Sequential combination of interferon and lamivudine with a prolonged course can improve the HBV DNA negative conversion rate, HBeAg seroconversion rate, HBsAg loss rate and mild ALT abnormalities at baseline in children under the age of 7 years with immune-tolerant phase chronic hepatitis B.


Assuntos
Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Interferons/uso terapêutico , Lamivudina/uso terapêutico , Adolescente , Criança , Pré-Escolar , DNA Viral/sangue , Quimioterapia Combinada , Antígenos de Superfície da Hepatite B/sangue , Antígenos E da Hepatite B/sangue , Humanos , Lactente , Transmissão Vertical de Doença Infecciosa , Resultado do Tratamento
5.
BMC Infect Dis ; 19(1): 741, 2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-31443633

RESUMO

BACKGROUND: The use of fixed combination antiretroviral therapy with a low genetic barrier for the treatment of patients infected with human immunodeficiency virus (HIV) may affect the local HIV transmitted drug resistance (TDR) pattern. The present study aimed to investigate changes in the prevalence of HIV TDR following the implementation of a fixed regimen of HIV treatment in Taiwan in 2012. METHODS: TDR was measured in antiretroviral treatment-naïve HIV-1-infected individuals who participated in voluntary counseling and testing between 2007 and 2015 in southern Taiwan. Antiretroviral resistance mutations were interpreted using the HIVdb program from the Stanford University HIV Drug Resistance Database. RESULTS: Sequences were obtained from 377 consecutive individuals between 2007 and 2015. The overall prevalence rates of TDR HIV among the study population from 2007 to 2011 and 2012-2015 were 10.6 and 7.9%, respectively. Among the detected mutations, K103 N and V179D + K103R were more frequently observed after 2012. Four HIV-infected patients with K103 N variants were detected after 2012, and 4 of the 5 patients with V179D + K103R variants were found after 2012. No significant differences were observed in the TDRs among nucleoside reverse transcriptase inhibitors (NRTIs), non-NRTIs (NNRTIs), protease inhibitors, multiple drug resistance, and any drug resistance between period 1 (2007-2011) and period 2 (2012-2015). CONCLUSIONS: A fixed treatment regimen with zidovudine/lamivudine + efavirenz or nevirapine as first-line therapy for treatment-naïve patients infected with HIV did not significantly increase the TDR during the 4-year follow-up period. Due to the increase in NNRTI resistance associated with mutations after 2012, a longer follow-up period and larger sample size are needed in future studies.


Assuntos
Farmacorresistência Viral/genética , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , HIV-1/genética , Mutação , Adulto , Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Benzoxazinas/uso terapêutico , Combinação de Medicamentos , Farmacorresistência Viral/efeitos dos fármacos , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Humanos , Lamivudina/uso terapêutico , Masculino , Nevirapina/uso terapêutico , Prevalência , Inibidores da Transcriptase Reversa/uso terapêutico , Taiwan/epidemiologia , Zidovudina/uso terapêutico
6.
Medicine (Baltimore) ; 98(32): e16813, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31393412

RESUMO

Dolutegravir (DTG) has shown effectiveness in combination with rilpivirine in with experience of antiretroviral therapy (ART) and with 3TC in naïve patients (GEMINI trial). The main objectives of this real-life study were to analyze the effectiveness and safety of 3TC plus DTG in virologically suppressed HIV-1 patients and to conduct a pharmacoeconomic analysis.We conducted an observational, retrospective and multicenter study of HIV+ patients pretreated for at least 6 months with ART that was then simplified to 3TC + DTG for any reason. We gathered data on viral loads (VLs) during exposure to the DT, calculating the rate with VL < 50 copies/mL at week 48, and on associated adverse effects.The 177 HIV+ patients were collected, 77.4% male, with average age of 48.5 years and mean count of 252.2cell/µL CD4+ nadir lymphocytes; 96.6% had VL < 50 copies/mL and 674 cells/µL CD4+ lymphocytes. Median time since HIV diagnosis was 15 years, and median ART duration was 13 years, and 34.5% of patients were on mono- or dual-therapy before the switch. At week 48, 82.4% of patients had VL < 50 cop/µL using an intention-to-treat (ITT) analysis, 89.6% according to mITT, and 96.7% according to Per-Protocol analysis. 3.3% patients had virological failure (VF). These effectiveness data and costs were compared with those for 2 reference triple therapies (DTG/ABC/3TC and EVG/cobi/FTC/TAF) in a cost minimization analysis, showing cost savings with administration of DTG+3TC (2741 &OV0556;/year vs DTG/ABC/3TC and 4164 &OV0556;/year vs EVG/cobi/FTC/TAF) and in a cost-effectiveness analysis, finding the DT to be the most cost-effective approach (ICER = -548 vs DTG/ABC/3TC and ICER = -4,627&OV0556; vs EVG/cobi/FTC/TAF)The combination of 3TC with DTG appears to be a safe and effective option for the simplification of ART in pretreated and virologically stable HIV-positive patients, being cost-effective and offering the same effectiveness as the triple therapy it replaces.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Lamivudina/uso terapêutico , Adulto , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/economia , Contagem de Linfócito CD4 , Análise Custo-Benefício , Quimioterapia Combinada , Farmacoeconomia , Honorários Farmacêuticos/estatística & dados numéricos , Feminino , HIV-1 , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Compostos Heterocíclicos com 3 Anéis/economia , Humanos , Lamivudina/administração & dosagem , Lamivudina/efeitos adversos , Lamivudina/economia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Carga Viral
7.
Virol J ; 16(1): 88, 2019 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-31272463

RESUMO

BACKGROUND: Currently, there is no consensus on the effects and safety of lamivudine therapy for chronic hepatitis B (CHB) in children. METHOD: Both English and Chinese databases were searched comprehensively. An odds ratio (OR) and a standard mean difference (SMD) were used to assess the effects and safety of lamivudine therapy for CHB in children. RESULTS: Thirteen eligible studies were included in our analysis. The rates of Hepatitis B virus (HBV) response, biochemical response, hepatitis B e antigen (HBeAg) loss, HBeAg seroconversion, and hepatitis B surface antigen (HBsAg) loss were significantly higher in the lamivudine (LAM) therapy group than in the control group. The changes in children's weight and height were similar between the two groups. CONCLUSIONS: LAM therapy was efficacious for CHB in children. Additionally, it had no side effect on children's height and weight.


Assuntos
Antivirais/uso terapêutico , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/tratamento farmacológico , Lamivudina/uso terapêutico , Criança , Farmacorresistência Viral , Humanos , Lamivudina/administração & dosagem , Razão de Chances
8.
Clin Drug Investig ; 39(9): 835-846, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31228017

RESUMO

BACKGROUND AND OBJECTIVE: Oral nucleoside/nucleotide analogues (NAs) have been advocated for chronic hepatitis B (CHB) treatment with good efficacy. However, less attention has been put on their adverse events. Therefore, a Bayesian network meta-analysis (NMA) was performed to evaluate the relative safety of five NAs (lamivudine, adefovir dipivoxil, entecavir, telbivudine, and tenofovir disoproxil fumarate) in CHB treatment among adults. METHODS: Eligible randomized clinical trials (RCTs) and prospective cohort studies were systematically and thoroughly searched until May 1, 2019. Poisson-prior-based Bayesian NMA was performed to synthesize both direct and indirect evidence with reporting hazard ratios (HRs) and 95% credible intervals (CrIs) for serious adverse events (SAEs) and hepatic/renal impairments. RESULTS: Thirty-three RCTs and 11 prospective cohort studies were identified. As to SAEs, no statistically significant difference was found of any comparison among five NAs. In terms of hepatotoxicity, lamivudine was safer than telbivudine (HR 0.45; 95% CrI 0.21, 0.85), and entecavir increased the risk by 102% (entecavir vs lamivudine: HR 2.02; 95% CrI 1.19, 3.27). CONCLUSIONS: The findings from this large NMA could influence clinical practice, and the methodological framework of this study could provide evidence-based support to analyze sparse safety data in the field.


Assuntos
Antivirais/efeitos adversos , Teorema de Bayes , Hepatite B Crônica/tratamento farmacológico , Meta-Análise em Rede , Adenina/efeitos adversos , Adenina/análogos & derivados , Adenina/uso terapêutico , Antivirais/uso terapêutico , Guanina/efeitos adversos , Guanina/análogos & derivados , Guanina/uso terapêutico , Humanos , Lamivudina/efeitos adversos , Lamivudina/uso terapêutico , Organofosfonatos/efeitos adversos , Organofosfonatos/uso terapêutico , Estudos Prospectivos , Telbivudina/efeitos adversos , Telbivudina/uso terapêutico , Tenofovir/efeitos adversos , Tenofovir/uso terapêutico
9.
Drugs Today (Barc) ; 55(5): 297-304, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31131840

RESUMO

The current standard of care for treating HIV infection is the use of three antiretroviral drugs: a combination of two nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) and a third agent from either the integrase strand transfer inhibitor (INSTI), boosted protease inhibitor (PI) or non-nucleoside reverse transcriptase inhibitor (NNRTI) classes. In an effort to minimize the long-term adverse effects and cost of antiretroviral therapy, the use of regimens with fewer drugs in the combination has been under active investigation. To this end, the combination of dolutegravir (DTG) plus lamivudine (3TC), two antiretroviral drugs with a long track record of efficacy and safety in the treatment of HIV infection, is undergoing clinical evaluation in treatment-naive HIV-infected participants. The promising results of the PADDLE study, with 90% of study participants achieving the primary endpoint of HIV-1 RNA lower than 50 copies/mL, were confirmed by the results of ACTG A5353, a phase II, single-arm, open-label study. Subsequently, GEMINI-1 and -2, two phase III, double-blind, noninferiority studies, compared DTG + 3TC to a three-drug regimen of DTG, tenofovir disoproxil fumarate and emtricitabine in 1,433 antiretroviral treatment-naive adults, and demonstrated noninferior efficacy at 48 weeks with no emergence of NRTI or INSTI mutations and a more favorable safety profile. This dual regimen should be avoided in those patients with existing mutations and chronic hepatitis B virus infection. In addition, data in patients with CD4 counts less than 200/mm3 is limited.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Lamivudina/uso terapêutico , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Estudos de Equivalência como Asunto , HIV-1 , Humanos
10.
Rev Chilena Infectol ; 36(1): 32-40, 2019 Feb.
Artigo em Espanhol | MEDLINE | ID: mdl-31095202

RESUMO

BACKGROUND: Clinical studies aimed to evaluating the quality of generic drugs may be useful to strengthen policies of access to combined antiretroviral therapy (cART). AIM: To describe the effectiveness and safety of the generic schema lamivudine/tenofovir/efavirenz (3TC/TDF/EFV) in patients with HIV/AIDS naive, belonging to a comprehensive care program. METHODS: A nonrandomized, open-label, phase IV study, during 2012 to 2014 naive HIV-infected patients 18 years or older with indication to receive cART were recruited. Patients were treated with generic scheme 3TC/TDF/EFV and were followed-up during 12 months. Clinical, immunological and laboratory parameters were assessed at baseline, 3, 6 and 12 months of treatment. RESULTS: Of the 40 patients, 30 (75%) met the 12 months of treatment; of them, 80% achieved undetectable viral load (< 40 copies/mL) and 83.3% viral load < 50 copies/mL. Additionally, there was a significant increase (173 cells/mm3) in the median for CD4 T lymphocyte count. Moreover, the results of the whole blood count, creatinine and transaminases were preserved in normal ranges and did not generate changes in the cART. Potential side effects of antiretroviral drugs occurred in less than 10% of patients and had no serious implications. CONCLUSIONS: In this small group of patients, the generic scheme 3TC/TDF/EFV is effective and safe in the treatment of patients with HIV/AIDS naïve, and its effectiveness and safety profile is similar to show by innovator scheme 3TC/TDF/EFV in patients with similar clinical conditions. Registro Estudio: Registro Público Cubano de Ensayos Clínicos (RPCEC) ID: RPCEC00000134. Registered 20 July 2012.


Assuntos
Síndrome de Imunodeficiência Adquirida/tratamento farmacológico , Fármacos Anti-HIV/uso terapêutico , Benzoxazinas/uso terapêutico , Medicamentos Genéricos/uso terapêutico , Lamivudina/uso terapêutico , Tenofovir/uso terapêutico , Adulto , Análise de Variância , Colômbia , Feminino , Humanos , Masculino , Estudos Prospectivos , Reprodutibilidade dos Testes , Estatísticas não Paramétricas , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
11.
Mikrobiyol Bul ; 53(2): 144-155, 2019 Apr.
Artigo em Turco | MEDLINE | ID: mdl-31130119

RESUMO

Chronic hepatitis B (CHB) is an important public health problem affecting over 240 million people all around the world. The aim of the treatment in chronic hepatitis B is to prevent progression to cirrhosis and liver cancer. Interferons (standard and peginterferon) (Peg-IFN) and nucleoside/nucleotide analogues (NAs) are widely used in the treatment of CHB. The use of long-term therapy can however result in drug resistant mutations, which can lead to treatment failure. In patients with chronic hepatitis B, in addition to primary drug resistance mutations in the pol gene, compensatory mutations were reported. The genom of HBV polymerase (pol) gene overlaps with the envelope (S) gene. Nucleoside/nucleotide analogue (NA) resistance mutations in the pol gene of HBV, either from selection of primary or secondary resistance mutations, typically result in changes in HBsAg. Recent studies have conferred a new acronym for these HBV pol/S gene overlap mutants; ADAPVEMs, for antiviral drug-associated potential vaccine-escape mutants. The aim of this study was to investigate clinically and epidemiologically significant HBV pol/S gene mutations in NA treated CHB patients. In the study, a total of 100 patients who received nucleoside/nucleotide analogue therapy for one year or more were included. The levels of HBV DNA from serum samples were detected by the commercial real-time PCR assay and the mutations of pol/S genes by direct sequencing. Sixteen samples with low HBV DNA levels (> 200 IU/ml) could not be interpreted by sequencing due to insufficient amplification. Of the remaining 84 patients that could be sequenced HBV pol gene of HBV, 53 (63.09%) were males and 31 (36.91%) were women and the mean age was 47 ± 14.99 years (range: 20-67). Primary/secondary drug mutations (rtM204I/V, rtI169S, rtL180M, rtT184L, rtA194V, rtM204I/rtL91I, rtQ149K, rtQ215H/S, rtN238D) were detected in 38 (45.2%) of the patients. Because of the HBV pol/S gene overlapping, in 27 patients immun-selected amino acid substitutions (sI110L, sT127P, sS114A, sT123A), in nine patients HBIg selected escape mutants (sP120R, sT123N, sE164D, sY134F, sQ129H, sT118A, sP127K), in seven patients vaccine escape mutants (sT126I, sP120S, sG145A, s S193L) and in one patient misdiagnosis of HBsAg (sT131I) were detected. In addition, antiviral drug-associated potential vaccine-escape mutants were detected in 13 (15.4%) patients. In patients with chronic HBV, NAs including commonly used lamivudine were observed to have the potential for ADAPVEM to emerge during treatment. It was concluded that after determination of antiviral drug resistance and ADAPVEMs replanning of treatment should be done in the NA treatment of patients with CHB.


Assuntos
Antivirais , Farmacorresistência Viral , Produtos do Gene pol , Vírus da Hepatite B , Hepatite B Crônica , Mutação , Proteínas do Envelope Viral , Adulto , Idoso , Antivirais/uso terapêutico , Farmacorresistência Viral/genética , Feminino , Produtos do Gene pol/genética , Antígenos de Superfície da Hepatite B/metabolismo , Vírus da Hepatite B/genética , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/virologia , Humanos , Lamivudina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Mutação/genética , Nucleotídeos/uso terapêutico , Proteínas do Envelope Viral/genética , Adulto Jovem
12.
Medicine (Baltimore) ; 98(17): e15149, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31027057

RESUMO

RATIONALE: With the existence of the human immunodeficiency virus (HIV) infection as a chronic disease, more often adverse effects of its treatment with the various antiretroviral therapies (ARTs) available have been recognized. Going further, Triumeq has been associated with a myriad of adverse effects, of which rhabdomyolysis is rarely reported in the literature. PATIENT CONCERNS: The patient presented with muscle tenderness over the lower limbs and dark brown-to-red colored urine. DIAGNOSIS: Given the presenting symptoms, as well as the laboratory testing, including elevated serum creatine kinase and liver enzymes, the diagnosis of rhabdomyolysis was made. INTERVENTIONS: Improvement was achieved rapidly after starting intravenous fluid therapy and with discontinuation of Triumeq. OUTCOMES: After discharge, repeated creatine kinase levels in the clinic have been normal and decision was made to initiate another ART and until now, no further episodes of rhabdomyolysis have developed. Regular outpatient follow-up has been ongoing for over 1 year and no complications have been identified. LESSONS: This case aims to recognize rhabdomyolysis as a rare, but possible adverse effect associated with the use of Triumeq for HIV-infected patients and therefore clinicians prescribing this combination should be aware of this potential side effect and counsel their patients accordingly.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Didesoxinucleosídeos/efeitos adversos , Infecções por HIV/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Lamivudina/efeitos adversos , Rabdomiólise/etiologia , Fármacos Anti-HIV/uso terapêutico , Didesoxinucleosídeos/uso terapêutico , Combinação de Medicamentos , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Humanos , Lamivudina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Rabdomiólise/diagnóstico , Rabdomiólise/terapia
13.
Int J STD AIDS ; 30(5): 467-471, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30999834

RESUMO

Raltegravir (RAL) is an HIV-1 integrase strand transfer inhibitor that is well established as a component of highly active antiretroviral therapy regimens for the treatment of adults living with human immunodeficiency virus (HIV), due to its high virological efficacy and good tolerability profile. To date, limited data are available on the use of RAL with abacavir/lamivudine (ABC/3TC). We investigated retrospectively 62 HIV-1 infected patients managed by three Italian Infectious Diseases Outpatient Departments, including 57 treatment-experienced patients and 5 treatment-naïve patients, treated with ABC/3TC plus RAL. In all five naïve patients (100%), virological suppression was achieved and maintained , while 55 experienced patients (96.5%) maintained viral suppression at the most recent review. In the treatment-experienced patients, we observed a significant decrease in triglyceride levels (p < 0.01), while liver transaminases, renal function and cholesterol levels remained substantially stable. In the 34 treatment-experienced patients who switched from a protease inhibitor (PI)-based regimen, we observed a significant improvement of total cholesterol (p=0.03) and triglyceride (p < 0.01) levels. No significant alterations were found on renal and liver function and serum lipid profile of treatment-naïve patients. Despite the small number of participants, results support the efficacy and safety of ABC/3TC plus RAL, either in treatment-naïve or treatment-experienced patients.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Didesoxinucleosídeos/uso terapêutico , Infecções por HIV/tratamento farmacológico , Inibidores de Integrase de HIV/uso terapêutico , HIV-1/efeitos dos fármacos , Lamivudina/uso terapêutico , Raltegravir Potássico/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Fármacos Anti-HIV/efeitos adversos , Terapia Antirretroviral de Alta Atividade/métodos , Colesterol/sangue , Didesoxinucleosídeos/efeitos adversos , Combinação de Medicamentos , Quimioterapia Combinada , Feminino , Infecções por HIV/virologia , Inibidores de Integrase de HIV/efeitos adversos , Humanos , Testes de Função Renal , Lamivudina/efeitos adversos , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Raltegravir Potássico/efeitos adversos , Resultado do Tratamento , Triglicerídeos/sangue
14.
Int J Infect Dis ; 84: 39-43, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30951880

RESUMO

OBJECTIVE: The clinical syndrome in symptomatic HIV associated CNS viral escape is poorly defined. We attempted to describe the clinical syndrome, laboratory profile, radiological features and outcomes of HIV infected patients with symptomatic central nervous system (CNS) viral escape in our study. METHODS: This is a retrospective study were adult patients with HIV infection on cART admitted with a diagnosis of CD8 encephalitis or CNS viral escape in a large teaching hospital in South India was identified. RESULTS: The mean age of the eleven patients included in the study was 37.5 years. Most patients had received almost a decade of antiretroviral treatment at diagnosis (mean: 11.18 years). All patients presented with global cerebral syndrome. Cognitive decline, tremors, and headaches were common manifestations. All patients had lymphocytic pleocytosis (mean cell count: 44.63 cells/ml; lymphocyte percentage: 94.81%) with elevated protein (mean: 125.36 mg/dl). All patients were on boosted protease inhibitors (81.8% on Atazanavir and 18.18% Lopinavir). All except one patient was on Tenofovir and lamivudine combination therapy. White matter changes and deep brain nuclei involvement were common. Most patients required a change of cART to regimens with better CNS penetration and suppression of the resistant virus in the plasma and improved. CONCLUSION: CNS viral escape should be considered as a differential among patients on Atazanavir presenting with non-focal cerebral syndrome and CSF lymphocytic pleocytosis.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Viroses do Sistema Nervoso Central/virologia , Infecções por HIV/complicações , Adulto , Terapia Antirretroviral de Alta Atividade , Viroses do Sistema Nervoso Central/tratamento farmacológico , Viroses do Sistema Nervoso Central/etiologia , Encefalite/tratamento farmacológico , Encefalite/etiologia , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Humanos , Índia , Lamivudina/uso terapêutico , Lopinavir/uso terapêutico , Masculino , Plasma , Estudos Retrospectivos , Carga Viral
15.
J Acquir Immune Defic Syndr ; 81(4): 463-472, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-30985556

RESUMO

BACKGROUND: Doravirine is a novel, nonnucleoside reverse transcriptase inhibitor with demonstrated efficacy in treatment-naive adults with HIV-1. METHODS: In this open-label, active-controlled, noninferiority trial, adults with HIV-1 virologically suppressed for ≥6 months on 2 nucleoside reverse transcriptase inhibitors plus a boosted protease inhibitor, boosted elvitegravir, or a non-nucleoside reverse transcriptase inhibitor were randomized (2:1) to switch to once-daily, single-tablet doravirine 100 mg with lamivudine 300 mg and tenofovir disoproxil fumarate 300 mg (DOR/3TC/TDF) or to continue their current therapy (Baseline Regimen) for 24 weeks. The primary endpoint was the proportion of participants with HIV-1 RNA <50 copies/mL (defined by the FDA Snapshot approach), with the primary comparison between DOR/3TC/TDF at week 48 and Baseline Regimen at week 24 and a secondary comparison between the groups at week 24 (noninferiority margin, -8%). RESULTS: Six hundred seventy participants (447 DOR/3TC/TDF, 223 Baseline Regimen) were treated and included in the analyses. At week 24, 93.7% on DOR/3TC/TDF vs 94.6% on Baseline Regimen had HIV-1 RNA <50 copies/mL [difference -0.9 (-4.7 to 3.0)]. At week 48, 90.8% on DOR/3TC/TDF had HIV-1 RNA <50 copies/mL, demonstrating noninferiority vs Baseline Regimen at week 24 [difference -3.8 (-7.9 to 0.3)]. In participants on ritonavir-boosted protease inhibitor at entry, mean reductions in fasting LDL-C and non-HDL-C at week 24 were significantly greater for DOR/3TC/TDF vs Baseline Regimen (P < 0.0001). Adverse events occurred in 68.9% on DOR/3TC/TDF and 52.5% on Baseline Regimen by week 24, leading to treatment discontinuation in 2.5% and 0.4%, respectively. CONCLUSIONS: Switching to once-daily DOR/3TC/TDF is a generally well-tolerated option for maintaining viral suppression in patients considering a change in therapy. REGISTRATION: ClinicalTrials.gov NCT02397096.


Assuntos
Antirretrovirais/uso terapêutico , HIV-1/efeitos dos fármacos , Lamivudina/uso terapêutico , Piridonas/uso terapêutico , Tenofovir/uso terapêutico , Triazóis/uso terapêutico , Adulto , Idoso , Antirretrovirais/administração & dosagem , Estudos de Equivalência como Asunto , Feminino , Humanos , Lamivudina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Inibidores de Proteases/uso terapêutico , Piridonas/administração & dosagem , Quinolonas/uso terapêutico , Ritonavir/uso terapêutico , Tenofovir/administração & dosagem , Resultado do Tratamento , Triazóis/administração & dosagem , Adulto Jovem
16.
Biosci Rep ; 39(3)2019 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-30867251

RESUMO

Purpose. ERF3, having been found expressing differently in liver tissues in our previous work, including eRF3a and eRF3b, which are structural homologs named GSPT1 and GSPT2 Recent studies have indicated that eRF3b involved in the development and proliferation of HepG2 cell, and eRF3a may be associated with tumor susceptibility. Based on this, we tested the effects of GSPT1 and GSPT2 single-nucleotide polymorphisms for all major Hepatitis B virus (HBV) outcomes and lamivudine (LAM) treatment in Han Chinese. Method. A total of 1649 samples were enrolled, and peripheral blood samples were collected in the present study. The single-nucleotide polymorphisms in the GSPT1 and GSPT2 region were genotyped using MALDI-TOF MS. Results. Our study demonstrated there was no obvious relevance of either GSPT1-rs33635 or GSPT2-rs974285 polymorphisms with HBV susceptibility, spontaneous recovery, and development of HBV-related diseases. However, we showed for the first time to our knowledge that GSPT1-rs33635C was a predictor for LAM therapy (viral response: odds ratio (OR) = 2.436, P=0.022; biochemical response: OR = 3.328, P=1.73 × 10-4). Conclusions. These findings might provide potential implications for therapeutic guidance.


Assuntos
Predisposição Genética para Doença/genética , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B/tratamento farmacológico , Lamivudina/uso terapêutico , Fatores de Terminação de Peptídeos/genética , Polimorfismo de Nucleotídeo Único , Adulto , Grupo com Ancestrais do Continente Asiático/genética , China , Feminino , Predisposição Genética para Doença/etnologia , Genótipo , Hepatite B/genética , Hepatite B/virologia , Vírus da Hepatite B/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Transcriptase Reversa/uso terapêutico
17.
Acta Gastroenterol Belg ; 82(1): 31-34, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30888751

RESUMO

AIMS: To compare the efficacy of treatment with lamivudine (LAM) plus adefovir (ADV) or entecavir (ETV) monotherapy in LAM treatment failure patients with HBeAg negative chronic hepatitis B (CHB) patients during 48 weeks of therapy. PATIENTS AND METHODS: Thirty patients with HBeAg negative CHB were enrolled in the study. The serum levels of HBV DNA, HBsAg/HBsAb, and ALT were assessed by enzyme-linked immunosorbent assay at 0, 12, 24, 36, and 48 weeks. RESULTS: The rate of undetectable HBV DNA in the LAM+ADV group was 100%, which was higher than the ETV group at 48 weeks (73.33%, χ2 = 4.615, P = 0.032). Multivariate analysis using the Cox proportional hazards model showed that therapy with LAM+ADV or baseline levels of HBV DNA <107 copies/ml were independent predictive factors for undetectable HBV DNA rates in all patients (RR: 2.488, P = 0.042; RR: 0.201, P = 0.035). CONCLUSIONS: During the 48 weeks of treatment in patients with HBeAg negative CHB, LAM plus ADV suppressed HBV replication more effectively than ETV monotherapy. In addition, no virologic breakthrough was detected in the LAM add-on ADV group. Additionally, therapy with LAM+ADV or baseline levels of HBV DNA <107copies/ml were independent predictive factors for undetectable HBV DNA rates in patients.


Assuntos
Adenina/análogos & derivados , Antivirais/uso terapêutico , DNA Viral/efeitos dos fármacos , Farmacorresistência Viral/efeitos dos fármacos , Guanina/análogos & derivados , Vírus da Hepatite B/isolamento & purificação , Hepatite B Crônica/tratamento farmacológico , Lamivudina/uso terapêutico , Organofosfonatos/uso terapêutico , Adenina/efeitos adversos , Adenina/uso terapêutico , DNA Viral/sangue , Quimioterapia Combinada , Ensaio de Imunoadsorção Enzimática , Guanina/efeitos adversos , Guanina/uso terapêutico , Antígenos E da Hepatite B/sangue , Vírus da Hepatite B/genética , Humanos , Lamivudina/efeitos adversos , Organofosfonatos/efeitos adversos , Modelos de Riscos Proporcionais , Falha de Tratamento , Resultado do Tratamento
18.
J Coll Physicians Surg Pak ; 29(4): 317-323, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30925952

RESUMO

OBJECTIVE: To compare the reduction of hepatocellular carcinoma (HCC) risk between long-term treatment of entecavir and low genetic barrier antiviral agents in hepatitis B virus (HBV)-related cirrhotic patients. STUDY DESIGN: An observational study. PLACE AND DURATION OF STUDY: Department of Infectious Diseases and Hepatology, the Second Hospital of Shandong University, Jinan, China, from October 2008 to October 2016. METHODOLOGY: HBV-related cirrhotic patients with antiviral treatment for at least 12 months were consecutively included. Propensity score matching analysis was performed to improve comparability of the data from both entecavir group and the control group. Log-rank test was used to compare influence of various nucleos(t)ide analogs (NAs) for incidence of HCC. Independent risk factors were estimated by multivariable Cox proportional hazards models. RESULTS: The total cohort included 207 HBV-related cirrhotic patients, of which 83 patients were treated with entecavir initially. The present study found no statistical difference for the incidence of HCC between entecavir group and the control group in the total cohort (p=0.525). However, the difference became statistically significant (p=0.014) after propensity score matching. Number needed to treat (NNT) were 8 patients, 6 patients and 3 patients at years 2, 3 and 4, respectively. Multivariable Cox regression in propensity score matching cohort revealed older age (HR: 1.066, p=0.041), NAs of low generic barrier (HR: 6.944, p=0.016), NAs resistance (HR: 3.648, p=0.041), and lower platelet counts (<80x10 9/L) (HR: 6.718, p=0.009) as independent risk factors for HCC incidence. CONCLUSION: Entecavir is more efficient in reducing the incident HCC risk for HBV-related cirrhotic patients in comparison to low genetic barrier NAs.


Assuntos
Antivirais/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Guanina/análogos & derivados , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Adenina/análogos & derivados , Adenina/uso terapêutico , Adulto , Idoso , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/virologia , China/epidemiologia , Feminino , Guanina/uso terapêutico , Vírus da Hepatite B/genética , Vírus da Hepatite B/isolamento & purificação , Humanos , Incidência , Lamivudina/uso terapêutico , Cirrose Hepática/epidemiologia , Cirrose Hepática/virologia , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Organofosfonatos/uso terapêutico , Estudos Retrospectivos , Fatores de Risco , Telbivudina/uso terapêutico
19.
BMC Pregnancy Childbirth ; 19(1): 82, 2019 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-30819147

RESUMO

BACKGROUND: Adherence to Option B plus Antiretroviral Therapy plays a vital role in preventing mother to child transmission of Human Immunodeficiency Virus and development of drug resistance. This study was aimed to assess adherence to option B plus ART and associated factors among HIV positive pregnant women at public Hospitals in Southern Ethiopia. METHODS: Facility based cross sectional study was conducted on HIV positive pregnant mothers attending public health facilities' antenatal care unit. Systematic random sampling technique was employed to select 290 HIV positive pregnant women enrolled in the Option B plus program. Data were collected by using structured questionnaire. Bivariate and multivariable logistic regression analysis were used to identify factors associated with option B plus ART adherence. P-value less than 0.05 was considered as cut of point to declare statistical significance. RESULTS: The overall adherence to option B plus ART among HIV positive pregnant women was 236 (81.4%). Three in twenty, (14.8%) participants were none adherent to Option B plus ART due to difficulty in adopting time schedule and forgetting to take medication. During first trimester of pregnancy, 16 (5.5%) were stopped taking ART medication due to side effects. Pregnant women who started ART at the time of HIV diagnosis [AOR = 1.99, 95% CI: (1.02, 3.95)], and who had five or more antenatal care visits [AOR = 4.10, 95% CI (1.65, 10.02)] were more likely to adhere to option B plus ART. Women who should travel 30-60 min on foot to access ART from service delivering facilities were less likely to adhere to option B plus [AOR = 0.39, 95% C I: (0.17, 0.88)]. CONCLUSIONS: The overall adherence to option B plus ART was suboptimal. Measures that improve recalling ability of individuals to take ART on time, and minimize ART side effects during first trimester of pregnancy need to be given emphasis. The study finding indicates the need for reconsidering the ad-hoc focused antenatal care visit at policy and program level by increasing the number of follow up visit with proper counseling on ART adherence benefits, and improving service accessibility.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Países em Desenvolvimento/estatística & dados numéricos , Soropositividade para HIV/tratamento farmacológico , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Adesão à Medicação/estatística & dados numéricos , Adolescente , Adulto , Fármacos Anti-HIV/efeitos adversos , Benzoxazinas/uso terapêutico , Estudos Transversais , Aconselhamento Diretivo , Quimioterapia Combinada , Etiópia , Feminino , Acesso aos Serviços de Saúde/estatística & dados numéricos , Hospitais Públicos , Humanos , Lamivudina/uso terapêutico , Gravidez , Cuidado Pré-Natal/estatística & dados numéricos , Inquéritos e Questionários , Tenofovir/uso terapêutico , Fatores de Tempo , Viagem , Adulto Jovem
20.
Arab J Gastroenterol ; 20(1): 8-13, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30857834

RESUMO

BACKGROUND AND STUDY AIMS: Mother-infant hepatitis B virus (HBV) transmission is the current leading cause of chronic infection. We aimed to assess the efficacy of lamivudine use in hepatitis B surface antigen (HBsAg)-positive pregnant women to decrease viral load and thus aid in the prevention of transmission. PATIENTS AND METHODS: A study of 73 mother-infant pairs. All mono-infected HBsAg-positive pregnant females of any age, who were a candidate for lamivudine during pregnancy were recruited, and a comparison group of HBsAg-positive pregnant females who did not receive any antiviral treatment. All infants received HBV immunoglobulin and vaccine at birth and completed the vaccination schedule and tested after 6 months of age. HBV viral markers and viral load quantitation were performed to all enrolled participants. RESULTS: 34 (46.6%) females were enrolled in the lamivudine group; 9 (26.5%) received the drug in the last trimester, 25 (73.5%) all through. The comparison group was 39 (53.4%) females; 32 (82.1%) were not candidate for antiviral during pregnancy, and 7 (17.9%) were diagnosed late near delivery. Seventy-one infants tested after full immunization, with their ages ranged between 6.5 and 18 months. Only one infant (1.4%) was positive for HBsAg and HBV DNA in the non-treated group. Maternal viremia near delivery showed a significant reduction in cases that used lamivudine during pregnancy. CONCLUSION: The use of lamivudine during pregnancy can effectively lower maternal viral load. Timely conducted post-vaccination serological testing is crucial to detect positive cases and immunize susceptible infants.


Assuntos
Hepatite B/tratamento farmacológico , Hepatite B/transmissão , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Lamivudina/uso terapêutico , Complicações Infecciosas na Gravidez/tratamento farmacológico , Inibidores da Transcriptase Reversa/uso terapêutico , Adulto , DNA Viral/sangue , Feminino , Hepatite B/sangue , Antígenos de Superfície da Hepatite B/sangue , Vacinas contra Hepatite B , Vírus da Hepatite B/genética , Humanos , Imunoglobulinas , Lactente , Recém-Nascido , Gravidez , Complicações Infecciosas na Gravidez/sangue , Estudos Prospectivos , Vacinação , Carga Viral/efeitos dos fármacos , Viremia/tratamento farmacológico , Viremia/virologia , Adulto Jovem
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