RESUMO
BACKGROUND: Tuberculosis (TB) and AIDS are the leading causes of infectious disease death worldwide. In some TB-HIV co-infected individuals treated for both diseases simultaneously, a pathological inflammatory reaction termed immune reconstitution inflammatory syndrome (IRIS) may occur. The risk factors for IRIS are not fully defined. We investigated the association of HLA-B, HLA-C, and KIR genotypes with TB, HIV-1 infection, and IRIS onset. METHODS: Patients were divided into four groups: Group 1- TB+/HIV+ (n = 88; 11 of them with IRIS), Group 2- HIV+ (n = 24), Group 3- TB+ (n = 24) and Group 4- healthy volunteers (n = 26). Patients were followed up at INI/FIOCRUZ and HGNI (Rio de Janeiro/Brazil) from 2006 to 2016. The HLA-B and HLA-C loci were typed using SBT, NGS, and KIR genes by PCR-SSP. Unconditional logistic regression models were performed for Protection/risk estimation. RESULTS: Among the individuals with TB as the outcome, KIR2DS2 was associated with increased risk for TB onset (aOR = 2.39, P = 0.04), whereas HLA-B*08 and female gender were associated with protection against TB onset (aOR = 0.23, P = 0.03, and aOR = 0.33, P = 0.01, respectively). Not carrying KIR2DL3 (aOR = 0.18, P = 0.03) and carrying HLA-C*07 (aOR = 0.32, P = 0.04) were associated with protection against TB onset among HIV-infected patients. An increased risk for IRIS onset was associated with having a CD8 count ≤500 cells/mm3 (aOR = 18.23, P = 0.016); carrying the KIR2DS2 gene (aOR = 27.22, P = 0.032), the HLA-B*41 allele (aOR = 68.84, P = 0.033), the KIR2DS1 + HLA-C2 pair (aOR = 28.58, P = 0.024); and not carrying the KIR2DL3 + HLA-C1/C2 pair (aOR = 43.04, P = 0.034), and the KIR2DL1 + HLA-C1/C2 pair (aOR = 43.04, P = 0.034), CONCLUSIONS: These results suggest the participation of these genes in the immunopathogenic mechanisms related to the conditions studied. This is the first study demonstrating an association of HLA-B*41, KIR2DS2, and KIR + HLA-C pairs with IRIS onset among TB-HIV co-infected individuals.
Assuntos
Infecções por HIV/complicações , Infecções por HIV/genética , HIV-1 , Síndrome Inflamatória da Reconstituição Imune/etiologia , Síndrome Inflamatória da Reconstituição Imune/genética , Tuberculose/complicações , Tuberculose/genética , Brasil , Coinfecção/tratamento farmacológico , Coinfecção/genética , Coinfecção/patologia , Feminino , Seguimentos , Frequência do Gene/genética , Marcadores Genéticos , Genótipo , Infecções por HIV/tratamento farmacológico , Infecções por HIV/patologia , Antígenos HLA-B/genética , Antígenos HLA-C/genética , Humanos , Síndrome Inflamatória da Reconstituição Imune/patologia , Masculino , Receptores KIR/genética , Fatores Sexuais , Tuberculose/tratamento farmacológico , Tuberculose/patologiaRESUMO
Background: The presence of antiretroviral drug-associated resistance mutations (DRMs) may be particularly problematic in human immunodeficiency virus (HIV)-infected pregnant women as it can lead to mother-to-child transmission (MTCT) of resistant HIV strains. This study evaluated the prevalence and the effect of antiretroviral DRMs in previously untreated mother-infant pairs. Methods: A case-control design of 1:4 (1 transmitter to 4 nontransmitters) was utilized to evaluate DRMs as a predictor of HIV MTCT in specimens obtained from mother-infant pairs. ViroSeq HIV-1 genotyping was performed on mother-infant specimens to assess for clinically relevant DRMs. Results: One hundred forty infants acquired HIV infection; of these, 123 mother-infant pairs (88%) had specimens successfully amplified using ViroSeq and assessed for drug resistance genotyping. Additionally, 483 of 560 (86%) women who did not transmit HIV to infants also had samples evaluated for DRMs. Sixty-three of 606 (10%) women had clinically relevant DRMs; 12 (2%) had DRMs against >1 drug class. Among 123 HIV-infected infants, 13 (11%) had clinically relevant DRMs, with 3 (2%) harboring DRMs against >1 drug class. In univariate and multivariate analyses, DRMs in mothers were not associated with increased HIV MTCT (adjusted odds ratio, 0.8 [95% confidence interval, .4-1.5]). Presence of DRMs in transmitting mothers was strongly associated with DRM presence in their infants (P < .001). Conclusions: Preexisting DRMs were common in untreated HIV-infected pregnant women, but did not increase the risk of HIV MTCT. However, if women with DRMs are not virologically suppressed, they may transmit resistant mutations, thus complicating infant management.
Assuntos
Fármacos Anti-HIV/farmacologia , Farmacorresistência Viral Múltipla , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , Transmissão Vertical de Doenças Infecciosas , Adolescente , Adulto , Fármacos Anti-HIV/classificação , Feminino , Infecções por HIV/transmissão , HIV-1/genética , Humanos , Lactente , Mutação , Gravidez , Adulto JovemRESUMO
This study aims to evaluate the utility of an optimized enzyme immunoassay (EIA) to detect and quantify antibodies against hepatitis B surface antibody (anti-HBs) in dried blood spots (DBSs) within the context of human immunodeï¬ciency virus (HIV) status. Serum and DBS samples were obtained from 56 HIV+ and 99 HIV- patients and subjected to EIA for the detection of anti-HBs, where sample volume and cut off value were modified for DBS testing. Sensitivities of anti-HBs detection in DBS were 79.8% and 76.8% in HIV- and HIV+ subjects, respectively. Concordant results for anti-HBs in serum and DBS presented high mean CD8 cell counts, HIV viral load and optical density (OD) values of anti-HBs. Anti-HBs titers were significantly higher in serum, whether or not anti-HBs titers were detected in DBS. It was possible to detect anti-HBs in DBS as low as 17.4 and 27.3 IU/mL among HIV+ and HIV- subjects, respectively. In conclusion, DBS can be used to detect and quantify anti-HBs in HIV-infected individuals, which could increase access to diagnosis and vaccination.
Assuntos
Dessecação , Infecções por HIV , Anticorpos Anti-Hepatite B/sangue , Vírus da Hepatite B/imunologia , Hepatite B/imunologia , Programas de Rastreamento/métodos , Manejo de Espécimes/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Antígenos de Superfície da Hepatite B/imunologia , Humanos , Técnicas Imunoenzimáticas/métodos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Adulto JovemRESUMO
Pregnant women who are infected with the Human Immunodeficiency Virus (HIV) are particularly vulnerable to severe and recurrent infections with Human Herpesvirus 2 (HHV-2). Neonatal transmission of HHV-2 has been associated with malformations and neurological sequelae in infants, which makes it very important to perform antenatal monitoring for genital herpes. In the study, 134 pregnant women infected with HIV were tested for HHV-2 IgM and IgG using an enzyme-linked immunosorbent assay (ELISA) and had HHV-2 DNA analyzed by Real Time Polymerase Chain Reaction (qPCR). Fisher's exact test was applied to analyze the epidemiological dates (p < 0.05). A total of 59.7% of the pregnant women infected with HIV had HHV-2 IgG and 3.75% of them showed HHV-2 viremia. HHV-2 IgM was found in 6% of the pregnant women and 25% of them had HHV-2 viremia. The risk factors associated with HHV-2 seropositive were age under 20 and a CD4/CD8 ratio > 1. Our study found high HHV-2/HIV coinfection prevalence and HHV-2 viremia among patients with recurrent and primary genital infection, reinforcing the need of prevention and control of HHV-2 infection in order to avoid this virus transmission.
Assuntos
Coinfecção/epidemiologia , Infecções por HIV/diagnóstico , HIV , Herpes Genital/diagnóstico , Herpesvirus Humano 2/isolamento & purificação , Complicações Infecciosas na Gravidez/virologia , Adulto , Anticorpos Antivirais/sangue , Brasil/epidemiologia , Ensaio de Imunoadsorção Enzimática , Feminino , Infecções por HIV/epidemiologia , Herpes Genital/epidemiologia , Humanos , Masculino , Reação em Cadeia da Polimerase , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Gestantes , Prevalência , Adulto JovemRESUMO
BACKGROUND Human herpesvirus 2 (HHV-2) have DNA genome with a limited genetic variability and have been classified into two clades. OBJECTIVES To identify and characterise six HHV-2 isolates derived from Brazilian women. METHODS HHV-2 isolates were performed polymerase chain reaction (PCR) and sequencing of 2250 pb of the glycoprotein B (gB) coding regions. FINDINGS Four HHV-2 isolates were classified into clade B, while the remaining two, derived from HIV-1 co-infected women, showed a notable genetic divergence (> 1%). MAIN CONCLUSION The results reveal novel HHV-2 variants. The impact of these novel variants on HHV-2 pathogenesis and HIV/HHV-2 coinfection need to be investigated.
Assuntos
Genes Virais/genética , Infecções por HIV/virologia , HIV-1 , Herpes Genital/virologia , Herpesvirus Humano 2/genética , Brasil , Coinfecção/virologia , Feminino , Infecções por HIV/complicações , Herpes Genital/complicações , Humanos , Filogenia , Reação em Cadeia da PolimeraseRESUMO
In occult hepatitis B infection (OBI), hepatitis B virus DNA (HBV DNA) can be detected in serum samples; however, oral fluid collection for detection of HBV DNA has not yet been explored, despite the availability of collection devices. Serum and oral fluid samples from 45 hepatitis B core antibody (anti-HBc)-positive patients were collected for the amplification of the HBV polymerase gene. HBV DNA was detected in five serum and four oral fluid samples (the detection limit for oral fluid was 1.656 log IU/mL in paired serum). In conclusion, simple methodologies of sample collection and in-house polymerase chain reaction (PCR) allowed detection of HBV DNA, and these could be used to improve the diagnosis of OBI, especially in locations with limited resources.
Assuntos
DNA Viral/análise , Anticorpos Anti-Hepatite B/análise , Antígenos de Superfície da Hepatite B/análise , Vírus da Hepatite B/genética , Hepatite B/diagnóstico , Saliva/virologia , Adulto , Idoso , DNA Viral/sangue , Feminino , Vírus da Hepatite B/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Carga ViralRESUMO
BACKGROUND: Congenital Zika virus (ZIKV) syndrome is a newly identified condition resulting from infection during pregnancy. We analyzed outcome data from a mother-infant cohort in Rio de Janeiro in order to assess whether clinical severity of maternal ZIKV infection was associated with maternal virus load, prior dengue antibodies, or abnormal pregnancy/infant outcomes. METHODS: A clinical severity assessment tool was developed based on duration of fever, severity of rash, multisystem involvement, and duration of symptoms during ZIKV infection. ZIKV-RNA load was quantified by polymerase chain reaction (PCR) cycles in blood/ urine. Dengue immunoglobulin G (IgG) antibodies were measured at baseline. Adverse outcomes were defined as fetal loss or a live infant with grossly abnormal clinical or brain imaging findings. Regression models were used to study potential associations. RESULTS: 131 ZIKV-PCR positive pregnant women were scored for clinical disease severity, 6 (4.6%) had mild disease, 98 (74.8%) had moderate disease, and 27 (20.6%) severe manifestations of ZIKV infection. There were 58 (46.4%) abnormal outcomes with 9 fetal losses (7.2%) in 125 pregnancies. No associations were found between: disease severity and abnormal outcomes (P = .961; odds ratio [OR]: 1.00; 95% confidence interval [CI]: 0.796-1.270); disease severity and viral load (P = .994); viral load and adverse outcomes (P = .667; OR: 1.02; 95% CI: 0.922-1.135); or existence of prior dengue antibodies (88% subjects) with severity score, ZIKV-RNA load or adverse outcomes (P = .667; OR: 0.78; 95% CI: 0.255-2.397). CONCLUSIONS: Congenital ZIKV syndrome does not appear to be associated with maternal disease severity, ZIKV-RNA load at time of infection or existence of prior dengue antibodies.
Assuntos
Morte Fetal , Doenças do Sistema Nervoso/epidemiologia , Malformações do Sistema Nervoso/epidemiologia , Complicações Infecciosas na Gravidez/sangue , Infecção por Zika virus/sangue , Infecção por Zika virus/complicações , Adolescente , Adulto , Anticorpos Antivirais/sangue , Encéfalo/anormalidades , Encéfalo/diagnóstico por imagem , Brasil/epidemiologia , Vírus da Dengue/imunologia , Feminino , Humanos , Nascido Vivo/epidemiologia , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/congênito , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/fisiopatologia , Malformações do Sistema Nervoso/diagnóstico , Neuroimagem , Exame Neurológico , Gravidez , Complicações Infecciosas na Gravidez/virologia , Estudos Prospectivos , RNA Viral/sangue , Índice de Gravidade de Doença , Carga Viral , Adulto Jovem , Zika virus/genéticaRESUMO
BACKGROUND: Cytomegalovirus (CMV) urinary shedding in pregnant women infected with human immunodeficiency virus (HIV) was evaluated to determine whether it poses an increased risk for congenital CMV infection (cCMV). METHODS: A subset of mother-infant pairs enrolled in the perinatal NICHD HPTN 040 study (distinguished by no antiretroviral use before labor) was evaluated. Maternal and infant urines were tested by qualitative real-time polymerase chain reaction (RT-PCR) for CMV DNA with quantitative RT-PCR performed on positive specimens. RESULTS: Urine specimens were available for 260 women with 85.4% from the Americas and 14.6% from South Africa. Twenty-four women (9.2%) had detectable CMV viruria by qualitative PCR. Maternal CMV viruria was not associated with mean CD4 cell counts or HIV viral load but was associated with younger maternal age (P = .02). Overall, 10 of 260 infants (3.8%) had cCMV. Women with detectable peripartum CMV viruria were more likely to have infants with cCMV than those without: 20.8% (5/24) versus 2.1% (5/236), (P = .0001). Women with CMV viruria had significantly higher rates of HIV perinatal transmission (29.2% vs. 8.1%, P = .002). They were 5 times (adjusted odds ratio [aOR] = 5.6, 95% confidence interval [CI] 1.9-16.8) and nearly 30 times (aOR, 29.7; 95% CI, 5.4-164.2) more likely to transmit HIV and CMV to their infants, respectively. Maternal gonorrhea (aOR, 19.5; 95% CI, 2.5-151.3) and higher maternal HIV log10 viral load (OR, 2.8; 95% CI, 1.3-6.3) were also significant risk factors for cCMV. CONCLUSION: In this cohort of HIV-infected pregnant women not on antiretrovirals, urinary CMV shedding was a significant risk factor for CMV and HIV transmission to infants. CLINICAL TRIALS REGISTRATION NUMBER: NCT00099359.
Assuntos
Infecções por Citomegalovirus , Citomegalovirus , DNA Viral/urina , Infecções por HIV/complicações , Complicações Infecciosas na Gravidez , Adolescente , Adulto , Citomegalovirus/genética , Citomegalovirus/isolamento & purificação , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/congênito , Infecções por Citomegalovirus/urina , Infecções por Citomegalovirus/virologia , DNA Viral/genética , Feminino , Humanos , Recém-Nascido , Valor Preditivo dos Testes , Gravidez , Complicações Infecciosas na Gravidez/urina , Complicações Infecciosas na Gravidez/virologia , Prevalência , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Fatores de Risco , Carga Viral , Eliminação de Partículas Virais , Adulto JovemRESUMO
The use of saliva and dried blood spots (DBS) could increase access to HCV diagnosis for high-risk populations, such as HIV-infected individuals, but the performance of these assays has not been well established in this group. This study aims to evaluate HIV status, particularly TCD4+ cell count and viral load, in the performance of anti-HCV testing using DBS and saliva. A total of 961 individuals classified as HCV+, HIV+, or HIV/HCV+, as well as negative controls, donated serum, DBS, and saliva samples for anti-HCV testing using a commercial enzyme immunoassay. Sample volume was modified for DBS and saliva, and an ROC curve was used for cut-off determination in saliva. Anti-HCV sensitivities were greater than 93% using DBS and saliva in the HCV+ group, while they were 83.3% and 95.6% for HCV/HIV+ individuals for DBS and saliva assays, respectively. Specificity varied from 91.7% to 100% using saliva and DBS in HIV monoinfected and control subjects. When only anti-HCV/HCV RNA+ serum samples, that is, true positives, were considered, the sensitivities were 98.3% and 100% for DBS and saliva, respectively, in the HCV+ group and 91.6% and 94.8% for DBS and saliva, respectively, in the HIV/HCV+ group. High absorbance values were observed among those presenting with HCV RNA in serum and low HIV viral load (less than 50 copies/mL). In conclusion, DBS and saliva samples could be used for anti-HCV detection, particularly to identify active HCV cases, but low sensitivity was observed for anti-HCV testing using DBS in the HIV/HCV+ group.
Assuntos
Sangue/imunologia , Ensaio de Imunoadsorção Enzimática/métodos , Infecções por HIV/complicações , Anticorpos Anti-Hepatite C/análise , Anticorpos Anti-Hepatite C/sangue , Hepatite C/diagnóstico , Saliva/imunologia , Adulto , Idoso , Contagem de Linfócito CD4 , Dessecação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Manejo de Espécimes/métodos , Inquéritos e Questionários , Carga ViralRESUMO
BACKGROUND: Rifampicin (RIF) induces UGT1A1, an enzyme involved in raltegravir (RAL) elimination, thereby potentially lowering RAL exposure. We examined the pharmacokinetics of RAL in human immunodeficiency virus (HIV)-infected patients on RIF-based antitubercular therapy in the French National Agency for HIV/AIDS and Viral Hepatitis Research 12 180 Reflate Tuberculosis trial. METHODS: Patients started RAL in combination with tenofovir disoproxil fumarate and lamivudine after initiation of RIF (10 mg/kg/day). In arm 1 (n = 21), they received 400 mg RAL twice daily; in arm 2 (n = 16), they received RAL 800 mg twice daily initially then 400 mg twice daily 4 weeks after RIF discontinuation. Pharmacokinetic sampling was performed over 12-hour periods, 4 weeks after initiation of RAL together with RIF (period 1), 4 weeks after RIF discontinuation (period 2), and after the RAL dose reduction in arm 2 (period 3). RESULTS: In arm 1, the geometric mean ratio (GMR) between period 1 and period 2 was 0.94 (90% confidence interval [CI], .64-1.37) for the 12-hour area under the time-concentration curve (AUC0-12), and 0.69 (90% CI, .42-1.13) for the concentration at 12 hours (C12). In arm 2, the corresponding GMRs were 0.75 (90% CI, .48-1.17) and 1.10 (90% CI, .61-2.00) for period 1 vs period 2, and 1.10 (90% CI, .78-1.55) and 1.68 (90% CI, .88-3.23) for period 1 vs period 3. CONCLUSIONS: The double dose of RAL overcompensated for RIF induction, but the standard dose was associated with only small decreases in AUC0-12 and C12 during RIF coadministration, warranting further evaluation in patients with HIV/tuberculosis coinfection. CLINICAL TRIALS REGISTRATION: NCT0082231.
Assuntos
Fármacos Anti-HIV/farmacocinética , Antibióticos Antituberculose/uso terapêutico , Infecções por HIV/tratamento farmacológico , Raltegravir Potássico/farmacocinética , Rifampina/uso terapêutico , Tuberculose/tratamento farmacológico , Adulto , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/uso terapêutico , Coinfecção , Esquema de Medicação , Quimioterapia Combinada , Feminino , Infecções por HIV/complicações , HIV-1/efeitos dos fármacos , Humanos , Lamivudina/administração & dosagem , Lamivudina/uso terapêutico , Masculino , Raltegravir Potássico/administração & dosagem , Tenofovir/administração & dosagem , Tenofovir/uso terapêuticoRESUMO
BACKGROUND: The safety and efficacy of adding antiretroviral drugs to standard zidovudine prophylaxis in infants of mothers with human immunodeficiency virus (HIV) infection who did not receive antenatal antiretroviral therapy (ART) because of late identification are unclear. We evaluated three ART regimens in such infants. METHODS: Within 48 hours after their birth, we randomly assigned formula-fed infants born to women with a peripartum diagnosis of HIV type 1 (HIV-1) infection to one of three regimens: zidovudine for 6 weeks (zidovudine-alone group), zidovudine for 6 weeks plus three doses of nevirapine during the first 8 days of life (two-drug group), or zidovudine for 6 weeks plus nelfinavir and lamivudine for 2 weeks (three-drug group). The primary outcome was HIV-1 infection at 3 months in infants uninfected at birth. RESULTS: A total of 1684 infants were enrolled in the Americas and South Africa (566 in the zidovudine-alone group, 562 in the two-drug group, and 556 in the three-drug group). The overall rate of in utero transmission of HIV-1 on the basis of Kaplan-Meier estimates was 5.7% (93 infants), with no significant differences among the groups. Intrapartum transmission occurred in 24 infants in the zidovudine-alone group (4.8%; 95% confidence interval [CI], 3.2 to 7.1), as compared with 11 infants in the two-drug group (2.2%; 95% CI, 1.2 to 3.9; P=0.046) and 12 in the three-drug group (2.4%; 95% CI, 1.4 to 4.3; P=0.046). The overall transmission rate was 8.5% (140 infants), with an increased rate in the zidovudine-alone group (P=0.03 for the comparisons with the two- and three-drug groups). On multivariate analysis, zidovudine monotherapy, a higher maternal viral load, and maternal use of illegal substances were significantly associated with transmission. The rate of neutropenia was significantly increased in the three-drug group (P<0.001 for both comparisons with the other groups). CONCLUSIONS: In neonates whose mothers did not receive ART during pregnancy, prophylaxis with a two- or three-drug ART regimen is superior to zidovudine alone for the prevention of intrapartum HIV transmission; the two-drug regimen has less toxicity than the three-drug regimen. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development [NICHD] and others; ClinicalTrials.gov number, NCT00099359.).
Assuntos
Antirretrovirais/uso terapêutico , Infecções por HIV/prevenção & controle , HIV-1 , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Lamivudina/uso terapêutico , Nelfinavir/uso terapêutico , Nevirapina/uso terapêutico , Zidovudina/uso terapêutico , Antirretrovirais/efeitos adversos , Farmacorresistência Viral , Quimioterapia Combinada/efeitos adversos , Feminino , Infecções por HIV/mortalidade , Infecções por HIV/transmissão , Humanos , Fórmulas Infantis , Recém-Nascido , Estimativa de Kaplan-Meier , Lamivudina/efeitos adversos , Masculino , Nelfinavir/efeitos adversos , Nevirapina/efeitos adversos , Período Pós-Parto , Gravidez , Complicações Infecciosas na Gravidez , Zidovudina/efeitos adversosRESUMO
BACKGROUND: Sexually transmitted infections (STIs) such as Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) can lead to adverse pregnancy and neonatal outcomes. The prevalence of STIs and its association with HIV mother-to-child transmission (MTCT) were evaluated in a substudy analysis from a randomized, multicenter clinical trial. METHODOLOGY: Urine samples from HIV-infected pregnant women collected at the time of labor and delivery were tested using polymerase chain reaction testing for the detection of CT and NG (Xpert CT/NG; Cepheid, Sunnyvale, CA). Infant HIV infection was determined by HIV DNA polymerase chain reaction at 3 months. RESULTS: Of the 1373 urine specimens, 249 (18.1%) were positive for CT and 63 (4.6%) for NG; 35 (2.5%) had both CT and NG detected. Among 117 cases of HIV MTCT (8.5% transmission), the lowest transmission rate occurred among infants born to CT- and NG-uninfected mothers (8.1%) as compared with those infected with only CT (10.7%) and both CT and NG (14.3%; P = 0.04). Infants born to CT-infected mothers had almost a 1.5-fold increased risk for HIV acquisition (odds ratio, 1.47; 95% confidence interval, 0.9-2.3; P = 0.09). CONCLUSIONS: This cohort of HIV-infected pregnant women is at high risk for infection with CT and NG. Analysis suggests that STIs may predispose to an increased HIV MTCT risk in this high-risk cohort of HIV-infected women.
Assuntos
Infecções por Chlamydia/transmissão , Gonorreia/transmissão , Soropositividade para HIV/complicações , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Mães , Profilaxia Pós-Exposição , Complicações Infecciosas na Gravidez/prevenção & controle , Gestantes , Adulto , Argentina/epidemiologia , Brasil/epidemiologia , Infecções por Chlamydia/imunologia , Infecções por Chlamydia/prevenção & controle , Feminino , Gonorreia/imunologia , Gonorreia/prevenção & controle , Soropositividade para HIV/imunologia , Soropositividade para HIV/transmissão , Humanos , Lactente , Gravidez , Prevalência , Fatores de Risco , África do Sul/epidemiologia , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Rapid tests (RTs) might have several advantages over standard laboratory procedures, increasing access to diagnosis, especially among vulnerable populations and/or those living in remote areas. The aim of this study was to evaluate the performance of RTs for the detection of hepatitis B virus surface antigen (HBsAg) in samples from different populations/settings. METHODS: Three RTs for HBsAg detection (Vikia® HBsAg, HBsAg Teste Rápido®, and Imuno-Rápido HBsAg®) and different biological specimens (serum, whole blood, and saliva) were evaluated. Analyses comprised a reference panel and samples from field studies targeting suspected cases of hepatitis B virus (HBV) (G I), individuals living in deprived areas (G II), and highly vulnerable individuals (G III). Enzyme immunoassay (EIA) was defined as the gold standard in this study. Reproducibility, repeatability, and cross-reactivity with other infectious agents such as dengue, immunodeficiency (HIV), and hepatitis C (HCV) viruses and T. pallidum were determined. RESULTS: For the reference panel, the sensitivity and specificity of all HBsAg RTs were higher than 93.00 %. G I presented the highest kappa values for all rapid assays using sera samples. When using serum, the sensitivity values were higher than 93.40 for G I, 60.00 % for G II and 66.77 % for G III, and the specificity values were higher than 99.50 for GI, 97.20 for G II and 99.10 % for G III for all tests. For whole blood samples & the Vikia® HBsAg assay, the best performance was achieved for GIII (k = 79.75 %). For saliva samples, the Imuno-Rápido HBsAg® assay showed the highest concordance values with EIA for G I (40.68 %) and G II (32.20 %). The reproducibility and repeatability of all RTs for serum and saliva were excellent, and the concordance between HBsAg EIAs and RTs using samples reactive with other infectious agents varied from 70.10 % to 100.00 %. CONCLUSIONS: The overall performance of RTs for HBsAg in serum was high/moderately high for all groups, thereby promoting increased access to HBV diagnosis among vulnerable populations as well as samples from individuals in emergency settings or remote areas. Rapid tests for HBsAg using whole blood could be used in prevalence studies, though these assays should not be used for saliva samples.
Assuntos
Antígenos de Superfície da Hepatite B/sangue , Hepatite B/diagnóstico , Técnicas Imunoenzimáticas/métodos , Adulto , Reações Cruzadas/imunologia , Feminino , Hepacivirus/imunologia , Hepatite B/sangue , Antígenos de Superfície da Hepatite B/análise , Vírus da Hepatite B/imunologia , Hepatite C/diagnóstico , Hepatite C/virologia , Anticorpos Anti-Hepatite C/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
A lopinavir-ritonavir (LPV/r)-based regimen is recommended during pregnancy to reduce the risk of HIV mother-to-child transmission, but the appropriate dose is controversial. We compared the pharmacokinetics of standard and increased LPV/r doses during pregnancy. This randomized, open-label prospective study enrolled 60 pregnant women between gestational weeks 14 and 30. The participants received either the standard dose (400/100 mg twice a day [BID]) or increased dose (600/150 mg BID) of LPV/r tablets during pregnancy and the standard dose for 6 weeks after childbirth. Pharmacokinetics analysis was performed using a high-performance liquid chromatography-tandem mass spectrometry method. Adherent participants who received the standard dose presented minimum LPV concentrations of 4.4, 4.3, and 6.1 µg/ml in the second and third trimesters and postpartum, respectively. The increased-dose group exhibited values of 7.9, 6.9, and 9.2 µg/ml at the same three time points. Although LPV exposure was significantly higher in the increased-dose group, the standard dose produced therapeutic levels of LPV against wild-type virus in all adherent participants, except one patient in the third trimester; 50%, 37.5%, and 25%, and 0%, 15%, and 0% of the participants in the standard- and increased-dose groups failed to achieve therapeutic levels against resistant viruses during the second and third trimesters and after childbirth, respectively. After 12 weeks of treatment and after childbirth, all adherent participants achieved undetectable HIV viral loads, and their babies (49/54) were uninfected. No serious drug-related adverse events were observed. We conclude that the standard dose is appropriate for use during pregnancy and that an increased dose may be necessary for women harboring resistant HIV. (This study has been registered at ClinicalTrials.gov under registration no. NCT00605098.).
Assuntos
Infecções por HIV/sangue , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/farmacocinética , Lopinavir/farmacocinética , Ritonavir/farmacocinética , Adulto , Feminino , Inibidores da Protease de HIV/administração & dosagem , Inibidores da Protease de HIV/uso terapêutico , Humanos , Lopinavir/administração & dosagem , Lopinavir/uso terapêutico , Gravidez , Ritonavir/administração & dosagem , Ritonavir/uso terapêutico , Adulto JovemRESUMO
OBJECTIVE: This study aimed to assess the prevalence of, and associated factors with, anal intraepithelial neoplasia (AIN) among HIV-positive men evaluated at public health services in Brazil. MATERIALS AND METHODS: This is a multicenter cross-sectional study of HIV-positive male patients attending 6 public AIDS referral clinics in urban Brazil. Participants were interviewed for sociodemographic and behavioral characteristics. Anal swab specimens were collected for anal cytology and HPV DNA testing using L1 polymerase chain reaction. Univariate and multivariate analyses were performed to evaluate risk factors associated with the presence of low-grade squamous intraepithelial lesion (LSIL) and/or high-grade squamous intraepithelial lesion (HSIL). RESULTS: Anal swabs were collected from 343 participants. Prevalence of LSIL/HSIL was 24.8%. The majority (60.1%) reported sexual intercourse with both men and women in their lifetime. At least 36.7% had 1 or more oncogenic HPV types. Four variables were independently associated with the presence of LSIL/HSIL in multivariate analysis: history of sex with both men and women (odds ratio [OR] = 4.8) or men only (OR = 6.2) compared with those having sex with women only; current cigarette smoking (OR = 2.2); current CD4(+) level between 200 and 500 cells/mm(3) (OR = 2.9) or below 200 cells/mm(3) (OR = 3.8) compared with CD4(+) level above 500 cells/mm(3); and presence of oncogenic anal HPV infection (OR = 9.6). CONCLUSIONS: We found a high prevalence of AIN among HIV-positive men in Brazil. This population may serve as an important bridge population to women with implications for anogenital HPV infection in both men and women. Our findings confirm the need to assess screening programs for AIN among high-risk groups, similar to those used to prevent cervical cancer.
Assuntos
Neoplasias do Ânus/epidemiologia , Carcinoma in Situ/epidemiologia , Infecções por HIV/complicações , Adolescente , Adulto , Brasil/epidemiologia , Estudos Transversais , DNA Viral/isolamento & purificação , Histocitoquímica , Humanos , Masculino , Pessoa de Meia-Idade , Técnicas de Diagnóstico Molecular , Papillomaviridae/isolamento & purificação , Prevalência , Fatores de Risco , Adulto JovemRESUMO
The aim of this study was to classify the diversity of anal HPV and non-HPV sexually transmitted infections (STIs) and compare the concordance between anal and genital infections in HIV-infected and uninfected women living in the Tapajós region, Amazon, Brazil. A cross-sectional study was performed with 112 HIV-uninfected and 41 HIV-infected nonindigenous women. Anal and cervical scrapings were collected and analyzed for HPV, Chlamydia trachomatis (CT), Neisseria gonorrheae (NG), Trichomonas vaginalis (TV), Mycoplasma genitalium (MG), and Human alphaherpesvirus 2 (HSV-2). The Kappa test evaluated the concordance between anal and genital infections. The overall prevalence of anal HPV infection was 31.3% in HIV-uninfected and 97.6% in HIV-infected women. The most frequent anal high-risk HPV (hrHPV) types were HPV18 and HPV16 in HIV-uninfected women and HPV51, HPV59, HPV31, and HPV58 in HIV-infected women. Anal HPV75 Betapapillomavirus was also identified. Anal non-HPV STIs were identified in 13.0% of all participants. The concordance analysis was fair for CT, MG, and HSV-2, almost perfect agreement for NG, moderate for HPV, and variable for the most frequent anal hrHPV types. Thus, a high prevalence of anal HPV infection with moderate and fair concordance between anal and genital HPV and non-HPV STIs was observed in our study.
Assuntos
Infecções por Chlamydia , Infecções por HIV , Infecções por Papillomavirus , Infecções Sexualmente Transmissíveis , Humanos , Feminino , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/epidemiologia , Brasil/epidemiologia , Estudos Transversais , Infecções Sexualmente Transmissíveis/complicações , Infecções Sexualmente Transmissíveis/epidemiologia , Chlamydia trachomatis , Colo do Útero , Neisseria gonorrhoeae , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Prevalência , Infecções por Chlamydia/complicações , Infecções por Chlamydia/epidemiologiaRESUMO
IMPORTANCE: The study provides valuable insights into the sociodemographic characteristics, clinical outcomes, and humoral immune response of those affected by the virus that has devastated every field of human life since 2019; the COVID-19 patients. Firstly, the association among clinical manifestations, comorbidities, and the production of neutralizing antibodies (Nabs) against SARS-CoV-2 is explored. Secondly, varying levels of Nabs among patients are revealed, and a significant correlation between the presence of Nabs and a shorter duration of hospitalization is identified, which highlights the potential role of Nabs in predicting clinical outcomes. Lastly, a follow-up conducted 7 months later demonstrates the progression and persistence of Nabs production in recovered unvaccinated individuals. The study contributes essential knowledge regarding the characteristics of the study population, the early humoral immune response, and the dynamics of Nabs production over time. These findings have significant implications for understanding the immune response to COVID-19 and informing clinical management approaches.
Assuntos
COVID-19 , Humanos , Formação de Anticorpos , SARS-CoV-2 , Anticorpos Antivirais , Anticorpos Neutralizantes , HospitalizaçãoRESUMO
The present study describes a follow-up of a prospective and observational cohort of patients infected with HIV-1 and treated with raltegravir for salvage therapy in Brazil. Two groups of patients were analyzed: switching from T20 to RAL (Group 1, n = 9) and salvage therapy containing RAL (Group 2, n = 10). Blood samples were drawn for CD4(+) T-cell counts and HIV-1 viral load determinations. Protease, reverse transcriptase, and integrase genotyping were performed at baseline and at the time of virologic failure. CD4(+) T-cells increased at 6 and 12 months in both groups; HIV-1 viral load was continuously suppressed for Group 1, and for Group 2 it significantly decreased after starting a RAL-containing regimen. Three out of 10 patients from Group 2 could not suppress HIV-1 viral load. The mutations Q148H + G140S were observed for two patients and for the third patient only mutations to PR/RT inhibitors were detected. The genotypic sensitivity score (GSS) was analyzed for all patients of Group 2 and both patients who developed resistance to raltegravir presented a GSS < 2.0 for the RAL-containing scheme, which could be associated to the lack of effectiveness of the proposed scheme. The present study describes, for the first time in Brazil, the close follow-up of a series of patients using a raltegravir-containing HAART, showing the safety of the enfuvirtide switch to RAL and the effectiveness of a therapeutic regimen with RAL in promoting immune reconstitution and suppressing HIV replication, as well as documenting the occurrence of resistance to integrase inhibitors in the country.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Farmacorresistência Viral/genética , Infecções por HIV/tratamento farmacológico , HIV-1/genética , Pirrolidinonas/uso terapêutico , Terapia de Salvação/métodos , Terapia Antirretroviral de Alta Atividade , Brasil/epidemiologia , Contagem de Linfócito CD4 , Cicloexanos/uso terapêutico , Enfuvirtida , Seguimentos , Técnicas de Genotipagem , Proteína gp41 do Envelope de HIV/uso terapêutico , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Integrase de HIV/genética , Protease de HIV/genética , Transcriptase Reversa do HIV/genética , HIV-1/enzimologia , HIV-1/fisiologia , Humanos , Maraviroc , Mutação , Fragmentos de Peptídeos/uso terapêutico , Estudos Prospectivos , RNA Viral/sangue , Raltegravir Potássico , Resultado do Tratamento , Triazóis/uso terapêutico , Carga Viral , Replicação ViralRESUMO
The extent to which perinatally HIV-infected children, following cART initiation, develop a low proviral reservoir burden over time, as measured by HIV DNA droplet-digital polymerase chain reaction (ddPCR) and the effect on HIV antibody is not well characterized. We measured proviral HIV DNA and plasma RNA virus load (VL) in 37 perinatally HIV-infected children at 6 months of age who initiated stable cART. At 6-11 years of age, HIV proviral DNA, HIV VL (RNA), and HIV antibody by Western Blot (WB) were assessed. CART was initiated before 6 months of age in 13 children and after 6 months in 24. At school age, the HIV DNA levels did not differ by the timing of cART, and the HIV DNA levels were lower in children with negative/indeterminate WB (p = 0.0256). Children with undetectable HIV RNA VL > 50% of the time since cART initiation had lower median DNA VL than children with undetectable VL < 50% of the time (p = 0.07). Long-term viral suppression in perinatally HIV-infected children is associated with a decrease in HIV antibodies and reduced HIV reservoirs.
Assuntos
Infecções por HIV , HIV-1 , Criança , Humanos , Lactente , Provírus/genética , Anticorpos Anti-HIV , HIV-1/genética , Carga Viral , Infecções por HIV/tratamento farmacológico , DNA Viral/análise , RNARESUMO
Background: Tuberculosis (TB) and AIDS are the leading causes of infectious diseases death worldwide. Here, we investigated the relationship between from single nucleotide polymorphisms (SNPs) of the NLRP3, CARD8, AIM2, CASP-1, IFI16, and IL-1ß inflammasome genes, as well as the profiles of secreted proinflammatory cytokines (e.g., IL-1ß, IL-18, IL-33, and IL-6) with the TB clinical profiles, TB-HIV coinfection, and IRIS onset. Methods: The individuals were divided into four groups: TB-HIV group (n=88; 11 of them with IRIS), HIV-1 group (n=20), TB group (n=24) and healthy volunteers (HC) group (n=10), and were followed up at INI/FIOCRUZ and HGNI (Rio de Janeiro/Brazil) from 2006 to 2016. Real-time PCR was used to determine the genotypes of the Single Nucleotide Polymorphism (SNPs), and ELISA was used to measure the plasma cytokine levels. Unconditional logistic regression models were used to perform risk estimations. Results: A higher risk for extrapulmonary TB was associated with the TT genotype (aOR=6.76; P=0.026) in the NLRP3 rs4612666 Single Nucleotide Polymorphism (SNP) and the C-C-T-G-C haplotype (aOR=4.99; P= 0.017) in the NLRP3 variants. This same Single Nucleotide Polymorphism (SNP) was associated with lower risk against extrapulmonary TB when the carrier allele C (aOR=0.15; P=0.021) was present. Among those with HIV-1 infections, a higher risk for TB onset was associated with the GA genotype (aOR=5.5; P=0.044) in the IL1-ß rs1143634 Single Nucleotide Polymorphism (SNP). In contrast, lower risk against TB onset was associated with the A-G haplotype (aOR=0.17; P= 0.026) in the CARD8 variants. Higher IL-6 and IL-33 levels were observed in individuals with TB. A higher risk for IRIS onset was associated with CD8 counts ≤ 500 cells/mm3 (aOR=12.32; P=0.010), the presence of extrapulmonary TB (aOR=6.6; P=0.038), and the CT genotype (aOR=61.06; P=0.026) or carrier allele T (aOR=61.06; P=0.026) in the AIM2 rs2276405 Single Nucleotide Polymorphism (SNP), whereas lower risk against IRIS onset was associated with the AT genotype (aOR=0.02; P=0.033) or carrier allele T (aOR=0.02; P=0.029) in the CARD8 rs2043211 Single Nucleotide Polymorphism (SNP) and the T-G haplotype (aOR=0.07; P= 0.033) in the CARD8 variants. No other significant associations were observed. Conclusions: Our results depict the involvement of genetic polymorphisms of crucial innate immunity genes and proinflammatory cytokines in the clinical outcomes related to TB-HIV coinfection.