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1.
J Viral Hepat ; 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31515866

RESUMO

HIV co-infection has been suggested to play a deleterious role on the pathogenesis of liver fibrosis among vertically HCV-infected children. The aim of this study was to describe the longitudinal evolution of vertically acquired HIV/HCV co-infection in youths, in comparison with HCV infection alone. This was a retrospective, multicentre study including vertically HIV/HCV-co-infected patients and age- and sex-matched vertically HCV-mono-infected patients. Progression to advanced liver fibrosis, defined as F3 or more by elastography or METAVIR biopsy staging, and response to treatment were compared by means of univariate and multivariate regression analyses and Cox regression models. Sixty-seven co-infected patients were compared with 67 matched HCV-mono-infected patients. No progression to advanced liver disease was observed during the first decade. At a median age of 20.0 [19.0, 22.0] years, 26.7% co-infected vs 20% mono-infected had progressed to advanced fibrosis (P = .617). Peg-IFN/RBV for HCV treatment was given to 37.9% vs 86.6% (P-value < .001). At treatment initiation, co-infected patients were older (16.9 ± 4.1 vs 11.7 ± 4.5 years, P < .001), and 47.1% vs 7.1% showed advanced fibrosis (P < .003), with no differences in hard-to-treat genotype distribution. Sustained viral response was comparable between groups (43.5% vs 44.0%, P = .122). In vertically HIV/HCV-co-infected patients, the progression to liver fibrosis was rare during childhood. At the end of adolescence, over 25% of patients displayed advanced liver disease. Response to Peg-IFN/RBV was poor and comparable in both groups, supporting the need for fast access to early treatment with direct-acting antivirals against HCV for vertically co-infected patients.

2.
Artigo em Inglês | MEDLINE | ID: mdl-30929024

RESUMO

Data for a total of 57 patients vertically coinfected with human immunodeficiency virus (HIV)/hepatitis C virus (HCV) and 365 HIV-monoinfected patients were compared until their transition to adult care. No differences regarding the dynamics of CD4 and/or CD8 T-cell counts during childhood were found. The coexistence of HCV does not increase the risk of disease progression in vertically HIV-infected patients.

3.
Enferm. infecc. microbiol. clín. (Ed. impr.) ; 37(3): 176-182, mar. 2019. tab
Artigo em Espanhol | IBECS | ID: ibc-181302

RESUMO

Introducción: El contacto sexual es actualmente en España la primera vía de contagio de VIH. Pese a los descensos en el número de nuevas infecciones en mujeres y consumo de drogas, en hombres se mantiene estable. El presente estudio pretende evaluar conductas de riesgo y conocimientos sobre VIH en una muestra de jóvenes en España. Métodos: Se realizó un estudio observacional descriptivo transversal utilizando un cuestionario sobre salud sexual y conocimiento sobre el VIH adaptado del Instituto Nacional de Estadística. El grupo estuvo compuesto por jóvenes no infectados por VIH. Se incluyó la variable riesgo sexual (alto y bajo), siendo de riesgo alto los sujetos que habían tenido tres o más parejas y no utilizaban preservativo en todas las relaciones. Resultados: Se encuestaron 243 jóvenes (65,6% mujeres) de entre 16 y 36 años (media = 25,7; DE = 4,1) (16-24 años: 134 sujetos; 25-29 años, 60 sujetos; más de 30 años, 47 sujetos). El 40,9% contestaron que utilizaban el preservativo en todas sus relaciones y el 61% que no perciben ningún riesgo de infección. De forma mayoritaria no se encuentran diferencias significativas en conocimiento sobre vías de transmisión entre los grupos de alto y de bajo riesgo. Los métodos de protección que se asociaron significativamente con las diferencias en riesgo sexual fueron lavarse tras las relaciones sexuales, tener pocas parejas, uso de espermicidas y carga viral indetectable (p < 0,05). Conclusiones: El principal resultado del estudio es la infravaloración personal de riesgo indicado según las diferencias encontradas entre la valoración personal y el índice de riesgo sexual. Se encuentran resultados tanto positivos como negativos en cuanto al conocimiento sobre el VIH


Introduction: Sexual intercourse is currently the main route of HIV infection in Spain. Despite decreases in new infections among women and drug users, the rate remains stable in men. The aim of this study was to assess risk behaviour and HIV awareness in a sample of young adults in Spain. Methods: A cross-sectional, observational, descriptive study was performed on a non-HIV infected sample, using a questionnaire on sexual health and HIV awareness adapted from the Spanish National Institute of Statistics. A sexual risk variable was included (high and low), which was classified as high if subjects had had three or more sexual partners and did not always use a condom in all their sexual encounters. Results: 243 subjects were included (65.6% women) aged between 16 and 36 years (mean = 25.7; SD = 4.1) (16-24 years: 134 subjects; 25-29 years: 60 subjects; over 30 years: 47 subjects). Approximately 40.9% said that they used a condom in all sexual relations and 61% did not perceive any risk of infection. There were no significant differences in awareness of infection routes between the high and low risk profiles. Washing after sex, having few partners, spermicide use and having undetectable viral load were protective measures significantly associated with differences in sexual risk (P < .05). Conclusions: The main finding of the study was the underestimation of risk of infection, analysed after differences found between self-assessment and sexual risk. Both positive and negative results were found concerning HIV awareness


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto Jovem , Adulto , Assunção de Riscos , Infecções por HIV/epidemiologia , Comportamento Sexual , Infecções por HIV/microbiologia , Infecções por HIV/prevenção & controle , Espanha/epidemiologia , Indicadores Básicos de Saúde , Análise de Dados
4.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-30017259

RESUMO

INTRODUCTION: Sexual intercourse is currently the main route of HIV infection in Spain. Despite decreases in new infections among women and drug users, the rate remains stable in men. The aim of this study was to assess risk behaviour and HIV awareness in a sample of young adults in Spain. METHODS: A cross-sectional, observational, descriptive study was performed on a non-HIV infected sample, using a questionnaire on sexual health and HIV awareness adapted from the Spanish National Institute of Statistics. A sexual risk variable was included (high and low), which was classified as high if subjects had had three or more sexual partners and did not always use a condom in all their sexual encounters. RESULTS: 243 subjects were included (65.6% women) aged between 16 and 36years (mean=25.7; SD=4.1) (16-24years: 134 subjects; 25-29years: 60 subjects; over 30years: 47 subjects). Approximately 40.9% said that they used a condom in all sexual relations and 61% did not perceive any risk of infection. There were no significant differences in awareness of infection routes between the high and low risk profiles. Washing after sex, having few partners, spermicide use and having undetectable viral load were protective measures significantly associated with differences in sexual risk (P<.05). CONCLUSIONS: The main finding of the study was the underestimation of risk of infection, analysed after differences found between self-assessment and sexual risk. Both positive and negative results were found concerning HIV awareness.

5.
Sci Rep ; 8(1): 2347, 2018 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-29403002

RESUMO

This pilot study evaluates in pediatric patients the impact of HIV/HCV coinfection in the molecular evolution of the HIV-1 subtype B protease (HIV-1BPR). For this study, HIV-1B/HCV coinfected (15) and HIV-1B monoinfected (56) patients with available HIV-1B pol sequences were enrolled. Both groups of patients had comparable gender frequencies and average age, time of infection, antiretroviral treatment (ART) exposure and time under ART. Prevalence of drug resistance mutations (DRM), genetic diversity, number of synonymous (dS) and non-synonymous (dN) mutations per site and selection pressures (dN - dS) in the HIV-1BPR were estimated and compared between mono- and coinfected patients. Both HIV-1B populations presented similar genetic diversity (0.050 ± 0.02 vs. 0.045 ± 0.01) and dS (0.074 ± 0.03 vs. 0.078 ± 0.04). In turn, in coinfected patients the HIV-1BPR had higher dN (0.045 ± 0.01 vs. 0.024 ± 0.01) and dN-dS (-0.026 ± 0.02 vs. -0.048 ± 0.04) values, and less amino acid sites under purifying selection (4.2% vs. 42.1%) than in monoinfected patients. Accordingly, in co-infection with HCV, the HIV-1BPR sites 50, 53, 82, 84 and 88 - associated with resistance to PIs - were under neutral evolution, whereas these sites were under purifying selection in monoinfected patients. This pilot study suggests that HIV-1B may evolve differently in the presence than in the absence of HCV.

7.
PLoS One ; 12(8): e0183558, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28841701

RESUMO

BACKGROUND: An increasing number of perinatally HIV-infected women (PHIV) are reaching adulthood and becoming pregnant. Most PHIV women have been exposed to a high number of antiretroviral regimens, and they may have difficulties to achieve viral suppression. Psychosocial problems are not uncommon and could be an important barrier for treatment adherence. The effects of chronic HIV infection and long-term exposure to antiretroviral treatment of PHIV women cause concerns on the developing fetus. The aims of this study were to describe the prevention of mother-to-child transmission strategies in PHIV women and the infant outcomes in the Madrid Cohort of HIV-infected mother-infant pairs. METHODS: All PHIV pregnant women registered in the Cohort that gave birth from 2000 to 2015 were included in the study. RESULTS: Twenty-eight pregnancies in twenty-two perinatally infected women were registered. Most women were Caucasian and heavily treatment-experienced. Nine cases (32.1%) were at high risk of HIV mother-to-child transmission. Maternal HIV-1 viral load was detectable close to delivery in four women (14.3%). The management of these cases was described, and the treatment strategies were discussed. None of the newborns acquired HIV infection. Eight infants (28.6%) were small for gestational age. CONCLUSIONS: This study included a large series of pregnancies among PHIV women attended according to a youth-centered care model. The challenges in the management of this population by health-care providers were described. Specific strategies to minimize perinatal transmission risks should be addressed in future collaborative studies.


Assuntos
Infecções por HIV/fisiopatologia , Complicações Infecciosas na Gravidez , Resultado da Gravidez , Adolescente , Adulto , Fármacos Anti-HIV/uso terapêutico , Feminino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Espanha/epidemiologia , Carga Viral , Adulto Jovem
8.
Pediatr Res ; 81(1-1): 80-87, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27653084

RESUMO

BACKGROUND: Early infant diagnosis (EID) of HIV-1 is necessary to reduce HIV-related mortality. As maternal antibodies transferred across the placenta may persist up to 18 mo, commercial virological assays (CVAs) are needed. This study compares four CVAs for EID using dried blood specimens (DBS) from HIV-1-exposed infants. METHODS: DBS from 68 infants born to HIV-1-infected women were collected from November 2012 to December 2013 in Equatorial Guinea. Four CVAs were performed: Siemens VERSANT HIV-1 RNA 1.0 kPCR assay, Roche CAP/CTM Quantitative Test v2.0, CAP/CTM Qualitative Tests v1.0 and v2.0. Definitive diagnosis was established following World Health Organization (WHO) recommendations. RESULTS: Two HIV-1-infected infants (2.9%) were detected by the four CVAs while 49 (72%) resulted negative. Discordant results were observed in 17 (25%) infants and HIV-1 infection was excluded in 14 patients when virological and serological testing was performed in additional DBS. Different false-positive rates HIV-1 were observed with Roche assays. CONCLUSION: CVAs using DBS were useful for EID, although discrepant results were common. Further research is required to reduce false-positive results that could result in wrong diagnosis and unneeded treatment. We propose caution with low viral load (VL) values when using VL assays. Clear guidelines are required for EID of HIV-exposed infants with discrepant virological results.


Assuntos
Infecções por HIV/diagnóstico , Infecções por HIV/virologia , HIV-1 , Adulto , Bioensaio/métodos , Teste em Amostras de Sangue Seco/métodos , Diagnóstico Precoce , Guiné Equatorial , Reações Falso-Positivas , Feminino , Infecções por HIV/transmissão , HIV-1/genética , HIV-1/isolamento & purificação , Humanos , Lactente , Recém-Nascido , Transmissão Vertical de Doença Infecciosa , Masculino , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Complicações Infecciosas na Gravidez/virologia , RNA Viral/sangue , RNA Viral/genética , Virologia/métodos , Adulto Jovem
9.
PLoS One ; 11(10): e0165333, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27798676

RESUMO

OBJECTIVES: This is the first study describing drug resistance mutations (DRM) and HIV-1 variants among infected pregnant women in Equatorial Guinea (GQ), a country with high (6.2%) and increasing HIV prevalence. METHODS: Dried blood spots (DBS) were collected from November 2012 to December 2013 from 69 HIV-1 infected women participating in a prevention of mother-to-child transmission program in the Hospital Regional of Bata and Primary Health Care Centre María Rafols, Bata, GQ. The transmitted (TDR) or acquired (ADR) antiretroviral drug resistance mutations at partial pol sequence among naive or antiretroviral therapy (ART)-exposed women were defined following WHO or IAS USA 2015 lists, respectively. HIV-1 variants were identified by phylogenetic analyses. RESULTS: A total of 38 of 69 HIV-1 specimens were successfully amplified and sequenced. Thirty (79%) belonged to ART-experienced women: 15 exposed to nucleoside reverse transcriptase inhibitors (NRTI) monotherapy, and 15 to combined ART (cART) as first regimen including two NRTI and one non-NRTI (NNRTI) or one protease inhibitor (PI). The TDR rate was only found for PI (3.4%). The ADR rate was 37.5% for NNRTI, 8.7% for NRTI and absent for PI or NRTI+NNRTI. HIV-1 group M non-B variants caused most (97.4%) infections, mainly (78.9%) recombinants: CRF02_AG (55.2%), CRF22_A101 (10.5%), subtype C (10.5%), unique recombinants (5.3%), and A3, D, F2, G, CRF06_cpx and CRF11_cpx (2.6% each). CONCLUSIONS: The high rate of ADR to retrotranscriptase inhibitors (mainly to NNRTIs) observed among pretreated pregnant women reinforces the importance of systematic DRM monitoring in GQ to reduce HIV-1 resistance transmission and to optimize first and second-line ART regimens when DRM are present.


Assuntos
Farmacorresistência Viral/genética , HIV-1/genética , Mutação/genética , Guiné Equatorial/epidemiologia , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/genética , Infecções por HIV/virologia , Humanos , Gravidez , Adulto Jovem
10.
Enferm. infecc. microbiol. clín. (Ed. impr.) ; 34(9): 566-570, nov. 2016. graf, tab
Artigo em Espanhol | IBECS | ID: ibc-157123

RESUMO

Antecedentes: En los últimos años se han realizado grandes esfuerzos en el programa de prevención de la transmisión de la madre al hijo (PTMH) de VIH en Guinea Ecuatorial (GE). El objetivo de este estudio fue describir los resultados del programa de PTMH en 2 centros sanitarios de Guinea Ecuatorial. Métodos: Estudio observacional prospectivo realizado en el Hospital Regional de Bata y Centro de Salud María Rafols en Bata, GE. Se analizaron las características epidemiológicas, clínicas y microbiológicas de las madres infectadas por el VIH-1 y de sus hijos. Se recogieron muestras sanguíneas en papel de filtro (DBS) en los lactantes expuestos (noviembre de 2012-diciembre de 2013) y se analizaron con la técnica Siemens VERSANT HIV-1 RNA v1.0 (kPCR). Resultados: Sesenta y ocho pares de madres y niños fueron incluidos. La mayoría de las mujeres estaban asintomáticas (88,2% con estadio clínicoI de la OMS). Cuarenta y siete mujeres (69,2%) recibieron tratamiento antirretroviral durante el embarazo. Cuarenta y cinco niños (66,1%) recibieron profilaxis posnatal con antirretrovirales. La mediana de edad en el momento de inclusión fue de 2,4meses (rango 1,2-4,9). Se confirmó la infección en 2 niños, y un niño falleció antes de poder descartarse la infección. La tasa de transmisión del VIH-1 fue del 2,9% (IC95%: 0,2-10,5). Conclusiones: Este estudio ha permitido evaluar el programa de PTMH en base a las técnicas de diagnóstico precoz. La identificación precoz de los pacientes infectados por el VIH-1 es fundamental para el inicio oportuno del tratamiento y evitar la mortalidad asociada a la infección (AU)


Background: Great efforts have been made in the last few years in order to implement the prevention of mother-to-child transmission (PMTCT) program in Equatorial Guinea (GQ). The aim of this study was to evaluate the rates of mother-to-child HIV transmission based on an HIV early infant diagnosis (EID) program. Methods: A prospective observational study was performed in the Regional Hospital of Bata and Primary Health Care Centre Maria Rafols, Bata, GQ. Epidemiological, clinical, and microbiological characteristics of HIV-1-infected mothers and their exposed infants were recorded. Dried blood spots (DBS) for HIV-1 EID were collected from November 2012 to December 2013. HIV-1 genome was detected using Siemens VERSANT HIV-1 RNA 1.0 kPCR assay. Results: Sixty nine pairs of women and infants were included. Sixty women (88.2%) had WHO clinical stage 1. Forty seven women (69.2%) were on antiretroviral treatment during pregnancy. Forty five infants (66.1%) received postnatal antiretroviral prophylaxis. Age at first DBS analysis was 2.4 months (IQR 1.2-4.9). One infant died before a HIV-1 diagnosis could be ruled out. Two infants were HIV-1 infected and started HAART before any symptoms were observed. The rate of HIV-1 transmission observed was 2.9% (95%CI 0.2-10.5). Conclusions: The PMTCT rate was evaluated for the first time in GQ based on EID. EID is the key for early initiation of antiretroviral therapy and to reduce the mortality associated with HIV infection (AU)


Assuntos
Humanos , Criança , Infecções por HIV/diagnóstico , HIV-1/isolamento & purificação , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Infecções por HIV/epidemiologia , Diagnóstico Precoce , Estudos Prospectivos , Antirretrovirais/administração & dosagem
11.
Enferm Infecc Microbiol Clin ; 34(9): 566-570, 2016 Nov.
Artigo em Espanhol | MEDLINE | ID: mdl-26778797

RESUMO

BACKGROUND: Great efforts have been made in the last few years in order to implement the prevention of mother-to-child transmission (PMTCT) program in Equatorial Guinea (GQ). The aim of this study was to evaluate the rates of mother-to-child HIV transmission based on an HIV early infant diagnosis (EID) program. METHODS: A prospective observational study was performed in the Regional Hospital of Bata and Primary Health Care Centre Maria Rafols, Bata, GQ. Epidemiological, clinical, and microbiological characteristics of HIV-1-infected mothers and their exposed infants were recorded. Dried blood spots (DBS) for HIV-1 EID were collected from November 2012 to December 2013. HIV-1 genome was detected using Siemens VERSANT HIV-1 RNA 1.0 kPCR assay. RESULTS: Sixty nine pairs of women and infants were included. Sixty women (88.2%) had WHO clinical stage 1. Forty seven women (69.2%) were on antiretroviral treatment during pregnancy. Forty five infants (66.1%) received postnatal antiretroviral prophylaxis. Age at first DBS analysis was 2.4 months (IQR 1.2-4.9). One infant died before a HIV-1 diagnosis could be ruled out. Two infants were HIV-1 infected and started HAART before any symptoms were observed. The rate of HIV-1 transmission observed was 2.9% (95%CI 0.2-10.5). CONCLUSIONS: The PMTCT rate was evaluated for the first time in GQ based on EID. EID is the key for early initiation of antiretroviral therapy and to reduce the mortality associated with HIV infection.


Assuntos
Diagnóstico Precoce , Infecções por HIV/diagnóstico , Infecções por HIV/transmissão , HIV-1 , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Adulto , Guiné Equatorial , Feminino , Humanos , Lactente , Gravidez , Estudos Prospectivos
12.
J Infect ; 71(3): 368-76, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26033694

RESUMO

OBJECTIVES: Viral load (VL) testing is used for early HIV diagnosis in infants (EID) and for detecting early therapeutic failure events, but can be affected by HIV genetic variability. Dried blood samples (DBS) increase VL access and EID in remote settings and when low blood volume is available. METHODS: This study compares VL values using Siemens VERSANT HIV-1 RNA 1.0 kPCR assay (kPCR) and Roche CAP/CTM Quantitative test v2.0 (CAP/CTM v2.0) in 176 DBS carrying different HIV-1 variants collected from 69 Equatoguinean mothers and their infants with known HIV-1 status (71 infected, 105 uninfected). RESULTS: CAP/CTM v2.0 provided false positive VLs in 11 (10.5%) cases. VL differences above 0.5 log10 were observed in 42/49 (87.5%) DBS, and were above 1 log10 in 18 cases. CAP/CTM v2.0 quantified all the 41 specimens with previously inferred HIV-1 variant by phylogenetic analysis (68.3% recombinants) whereas kPCR only identified 90.2% of them, and was unable to detect 14.3% of 21 CRF02_AG viruses. CAP/CTM v2.0 showed higher sensitivity than kPCR (95.8% vs. 70.1%), quantifying a higher rate of viruses in infected DBS from subjects under antiretroviral exposure at sampling time compared to kPCR (94.7% vs. 96.2%, p-value<0.001). kPCR showed maximum specificity (100%) whereas for CAP/CTM v2.0 was 89.5%. CONCLUSIONS: VL assays should increase their sensitivity and specificity to avoid overestimated HIV-1 quantifications, which could be interpreted as virological failure events, or false negative diagnostic results due to genetic variability. We recommend using the same VL technique for each patient during antiretroviral therapy monitoring.


Assuntos
Erros de Diagnóstico , Infecções por HIV/diagnóstico , HIV-1/isolamento & purificação , HIV-1/fisiologia , Carga Viral/métodos , Adulto , Teste em Amostras de Sangue Seco , Reações Falso-Positivas , Feminino , Infecções por HIV/virologia , HIV-1/genética , Humanos , Lactente , Mães , Filogenia , Reação em Cadeia da Polimerase , RNA Viral/genética , Kit de Reagentes para Diagnóstico , Sensibilidade e Especificidade , Manejo de Espécimes , Adulto Jovem
13.
J Clin Virol ; 63: 66-9, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25600609

RESUMO

BACKGROUND: Confirmatory assays for HIV diagnosis are not well implemented in low-income countries with limited infrastructures. Geenius™ HIV 1/2 Confirmatory Assay is a single-use immunochromatographic test for the confirmation and differentiation of individual HIV-1/2 antibodies validated in venous whole blood, serum and plasma. However, dried blood specimens (DBS) are easier to collect, store and transport than plasma/serum in remote settings from limited resource countries and mobile populations. OBJECTIVES: To evaluate the confirmatory assay Geenius™ HIV 1/2 for HIV diagnosis using DBS specimens. STUDY DESIGN: We collected DBS from 70 Guinean women previously diagnosed as HIV-1 infected by rapid tests using whole blood samples in Equatorial Guinea and from 25 HIV-negative Guinean women and HIV-exposed infants diagnosed by molecular testing in Madrid. Geenius HIV 1/2 was performed by eluting two drops of dried blood from each patient and following the manufacturer instructions for the assay but using 40µl of the eluted blood as specimen. The results obtained were confirmed by western blot. RESULTS: Geenius™ HIV 1/2 successfully confirmed the HIV-1 positive and negative infection in all tested DBS specimens, providing 100% specificity [95% Confidence Interval (CI): 86.2%-100%]. No HIV 1/2 coinfections were found in the study cohort. This is the first report that proves a good performance of Geenius™ HIV 1/2 for the HIV-1 infection confirmation using only two drops of dried blood. CONCLUSIONS: Our results approve the utility of this confirmatory assay using DBS when a lack of adequate infrastructure to collect, store or transport plasma/serum is found. DBS are a practical alternative to plasma/serum for HIV serological diagnosis.


Assuntos
Sangue/virologia , Cromatografia de Afinidade/métodos , Anticorpos Anti-HIV/sangue , Infecções por HIV/diagnóstico , HIV-1/imunologia , Manejo de Espécimes/métodos , Dessecação , Feminino , Guiné , Humanos , Lactente , Espanha
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