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Introduction The risk of HIV-1 mother-to-child transmission (MTCT) is associated mainly with gestational age at which antiretroviral therapy begins and the HIV-1 RNA plasma viral load at delivery. Regimens with integrase inhibitors (INI) are increasing in high-risk pregnant women. The objective was to review the experience with INI in a Madrid Cohort of mother-infant pairs. Patients and methods Retrospective, multicentric, observational study, of HIV-infected pregnant women exposed to INI. Patients of 9 hospitals were included (2000–2017). Results Sixty-seven pregnant women exposed to INI (cohort: 1423) and 68 children (17.6% premature babies, 34.3% with combined postexposure prophylaxis). There were no cases of MTCT. Of 24 women with no previous antiretroviral therapy, 20 were diagnosed in current pregnancy. Of 43 women with antiretroviral therapy before pregnancy, 65% received INI before conception. Raltegravir was the most used (80.5%). There was a statistically significant increase (p = 0.02) of mothers with undetectable viral load at delivery. INI were well tolerated. In 11.7% of exposed children minor congenital anomalies were detected. Conclusions INI seem safe and effective in the prevention of MTCT. Our findings support their use as intensification regimens in pregnant women with high risk of MTCT.

Resumen Introduccion El riesgo de transmision vertical (TV) del VIH depende fundamentalmente de la edad gestacional de inicio del tratamiento antirretroviral y la carga viral materna al parto. Son crecientes las pautas con inhibidores de integrasa (INI) en embarazadas con situaciones de riesgo. Nuestro objetivo fue revisar la experiencia con INI en la Cohorte de Madrid de madres-ninos. Pacientes y metodos Estudio retrospectivo, multicentrico, observacional, de gestantes con infeccion por VIH-1 expuestas a INI de 9 hospitales publicos durante 2000-2017. Resultados Hubo 67 gestantes (cohorte: 1.423) y 68 neonatos (el 17,6% prematuros, el 34,3% con profilaxis combinada). No hubo casos de TV. Veinte mujeres se diagnosticaron en la gestacion actual. De 43 con tratamiento antirretroviral previo a gestacion, el 65% recibia INI preconcepcional. El mas empleado fue raltegravir (80,5%). Aumento significativamente (p = 0,02) la proporcion de madres con carga viral indetectable al parto. La tolerancia a INI fue adecuada. Hubo anomalias congenitas menores en el 11,7% de los ninos. Conclusiones Los INI parecen seguros y eficaces como prevencion de TV. Nuestros hallazgos refuerzan su utilidad como intensificacion en gestantes que llegan al tercer trimestre con pauta no supresora.

HIV infection continues to be a worldwide public health problem. After the introduction of effective preventive measures, perinatal transmission dramatically decreased. Our aim was to assess the sociodemographic changes in pregnant women living with HIV infection and trends in perinatal transmission rates over time.The Madrid cohort of HIV-infected mother-infant pairs is a multicenter, prospective, observational, and cohort study that collects information on HIV-infected pregnant women and their children.Information on clinical-epidemiological characteristics of HIV-infected pregnant women until delivery and their children from 9 public hospitals was included. Data were collected from a standardized questionnaire from medical records. The results were classified in 3 periods: period 1 (P1) 2000-2006, period 2 (P2) 2007-2013, and period 3 (P3) 2014-2020.A total of 1521 women living with HIV and 1548 newborns were included. In P1, most mothers (75.8%) were Spanish, whereas in P2 and P3 there was a predominance of foreign origin [62.8% and 70.5% respectively ( P0.01)]. The percentage of women with antiretroviral treatment before pregnancy increased significantly in P3 ( P0.01). The proportion of Caesarean sections decreased over time ( P0.01): 66.2% (n = 472) in P1, 54.9% (n = 245) in P2, and 46.7% (n = 141) in P3. The percentage of preterm and low birth weight newborns showed a statistically significant decrease. Even though there were no statistically significant differences ( P = 0.154), a decrease in cases of perinatal infection was observed (1.6% in P1, 1.3% in P2 and 0.3% in P3).The epidemiologic characteristics of pregnant women with HIV infection have changed over time in our setting, with an increase of non-Caucasian, heterosexual, and perinatally infected mothers. Although there are still perinatal infections, especially in vulnerable populations such as immigrant women, transmission rate has markedly decreased in recent years and is still of major concern. Prevention measures should be reinforced in the most socially disadvantaged groups.

Resumen Introduccion El contacto sexual es actualmente en Espana la primera via de contagio de VIH. Pese a los descensos en el numero 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 jovenes en Espana. Metodos Se realizo un estudio observacional descriptivo transversal utilizando un cuestionario sobre salud sexual y conocimiento sobre el VIH adaptado del Instituto Nacional de Estadistica. El grupo estuvo compuesto por jovenes no infectados por VIH. Se incluyo la variable riesgo sexual (alto y bajo), siendo de riesgo alto los sujetos que habian tenido tres o mas parejas y no utilizaban preservativo en todas las relaciones. Resultados Se encuestaron 243 jovenes (65,6% mujeres) de entre 16 y 36 anos (media = 25,7; DE = 4,1) (16-24 anos: 134 sujetos; 25-29 anos, 60 sujetos; mas de 30 anos, 47 sujetos). El 40,9% contestaron que utilizaban el preservativo en todas sus relaciones y el 61% que no perciben ningun riesgo de infeccion. De forma mayoritaria no se encuentran diferencias significativas en conocimiento sobre vias de transmision entre los grupos de alto y de bajo riesgo. Los metodos de proteccion 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 Conclusiones El principal resultado del estudio es la infravaloracion personal de riesgo indicado segun las diferencias encontradas entre la valoracion personal y el indice de riesgo sexual. Se encuentran resultados tanto positivos como negativos en cuanto al conocimiento sobre el VIH.

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.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.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).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.

Immune recovery after prolonged highly active antiretroviral therapy (HAART) with lopinavir/ritonavir has been reported in adults but not in children. Our study aimed at evaluating the long-term use of lopinavir/ritonavir among children in a clinical setting.We carried out a retrospective study on 69 protease inhibitor (PI)-experienced vertically HIV-infected children on HAART containing lopinavir/ritonavir. We analysed the changes in percentage CD4+ cell count (%CD4+) and viral load (VL) and identified prognostic factors to achieve CD4+25% and undetectable VL (uVL) (or=400 copies/mL) by logistic regression.During the first 2 years, we found an increase in the %CD4+ in children with baseline CD4+ between 0% and 15% and those with baseline VL30,000 copies/mL. We found a decrease in VL in all groups of children. From second to fourth year, we found an increase in %CD4+ in all the children who had CD4+25% and in those with baseline VL100,000 copies/mL. We found that %CD4+ at baseline had a strong positive association with achieving CD4+25% at 6, 12, 18, 24, 36 and 48 months of follow-up. We also found that length of PI use had a negative association with reaching CD4+25% at 24 and 48 months and achieving uVL at 12 and 24 months. VL at baseline had a negative association with achieving uVL at 18 and 24 months.Our study demonstrates ongoing immune recovery among children on HAART with lopinavir/ritonavir after 4 years of follow-up. Lopinavir/ritonavir, when given as part of a salvage regimen, is safe and well tolerated in HIV-infected children.

We carried out a retrospective study to analyze the long-term response to highly active antiretroviral therapy of 19 vertically human immunodeficiency virus type 1/hepatitis C virus (HCV-1/HIV) coinfected children. The clinical, immunologic, viral, and biochemical variables were assayed at 0, 1, 2, 3, 4, 5, and 6 years of follow-up. Our data suggest that CD4 T-cell recovery and viral load control during long-term highly active antiretroviral therapy among HIV-1/HCV children were similar to those described in HIV-1 monoinfected children, but hepatic function was significantly altered in HIV-1/HCV children.

Fundamento y objetivo: Evaluar la capacidad del tratamiento antirretroviral de gran actividad (TARGA) para reconstituir totalmente el sistema inmunologico en un nino infectado por el virus de la inmunodefiencia humana (VIH) con sida grave y profunda inmunodepresion. Paciente y metodo: La respuesta proliferativa y la produccion de citocinas de las celulas mononucleares de sangre periferica (CMSP) frente a fitohemoglotinina (PHA) fueron evaluadas por incorporacion de [3H]-timidina y enzimoinmunoanalisis, respectivamente. Las subpoblaciones linfocitarias T se cuantificaron por citometria de flujo y la produccion timica de celulas T, mediante la cuantificacion de TCR rearrangement excision circles (TREC). Resultados: En sus primeros anos de vida, el nino presento otitis recurrente por Pneumococcus. A los 2-3 anos de edad, las celulas T CD4+ descendieron de 822 a 154 celulas x 106/l, iniciandose tratamiento con zidovudina (AZT), aunque nunca supero las 350 celulas T CD4+ x 106/l. A los 6 anos de edad, la cifra de celulas T CD4+ era inferior a 15 x 106/l, y se administro estavudina (d4T) junto a lamivudina (3TC) sin recuperar las celulas T CD4+. A los 7 anos de edad, la cifra de celulas T CD4+ era del 0,8% y la carga viral (CV) de 32.000 copias/ml. Este estado coincidio con un leiomioma plantar que fue extirpado y una neumonia por Pneumocystis carinii. Tras 6 meses de TARGA (con d4T, 3TC, viracept y efavirenz) alcanzo valores de celulas T CD4+ del 25%, celulas T CD4 de 597 x 106/l, y CV indetectable. Ademas se produjo un incremento del numero absoluto de celulas virgenes y valores de TREC. Tras el TARGA aumentaron la respuesta linfoproliferativa a PHA y la produccion de interferon gamma (IFN-?). Actualmente el paciente esta asintomatico. Conclusion: La recuperacion inmunologica y clinica del nino infectado por el VIH en fases muy avanzadas de la enfermedad fue posible gracias al TARGA, lo que demuestra la plasticidad de su sistema inmunitario.

We evaluated the evolution over time of once-daily antiretroviral therapy in HIV-infected children and its relationship with adherence. An increase on the prevalence of once-daily antiretroviral therapy was observed over time (from 0.9% in 2002 to 44.2% in 2011). There was no difference in adherence regarding once-daily or BID regimens in 2011. Adherence was related to age and pill burden.

We studied HIV coreceptor tropism in vertically HIV-infected children and adolescents with the objective of predicting the proportion of children and adolescents that could be treated with CCR5 (R5) antagonists.One hundred eighteen multidrug-resistant pediatric patients (36 children and 82 adolescents) were enrolled in a cross-sectional study. Viral tropism was assessed using the new phenotypic HIV-1 tropism coreceptor assay information and Trofile.Of 118 antiretroviral-experienced HIV-infected children and adolescents, 49 (57.0%) had dual-tropic and 20 (23.3%) had X4-tropic viruses by tropism coreceptor assay information testing. Only 17 (19.7%) showed R5-tropic variants. HIV-1 coreceptor usage was not detectable in 32 of 118 (27%) patients. Among 24 children and 62 adolescents with tropism coreceptor assay information results, 17 (70.8%) children and 51 (82.2%) adolescents showed viruses with dual-tropic or X4-tropic variants. Additionally, Trofile (ES) was performed in 42 of 118 patients with HIV-1 RNA1000 copies/mL. No patient showed X4-tropic variants; dual-tropic viruses were observed in 12 (28.6%) patients. In 6 (14.3%) patients, HIV tropism could not be determined. X4-tropic variants were more common in children (P = 0.031). CD4 T cell percentage was significantly lower in children (P = 0.011) and adolescents (P = 0.027) with R5-tropic viruses than in those with X4-tropic viruses.The presence of X4-tropic variants in more than 80% of our cohort of antiretroviral-experienced children and adolescents with vertical HIV-1 infection indicates a very limited role for CCR5 antagonists as part of salvage regimens for highly treatment-experienced vertically HIV-1-infected patients with extensive antiretroviral drug resistance and limited treatment options.

One of the principal techniques for evaluating the surface hydrophobicity of biological samples is contact angle. This method, applied readily to flat-smooth-inert surfaces, gives rise to an important debate when implemented with microbial lawns. After its initial description, in 1984, several authors have carried out modifications of the technique but the results obtained have not been previously judged. This work focuses on the particularities of contact angle measurements on bacterial lawns and enhances the idea of the impossibility of using water contact angle as a universal measurement of bacterial hydrophobicity. Contact angles can only be used as relative indicators of hydrophobicity, in a similar way to tests based on microbial adhesion to solvents. The strong dependence of contact angles on dried bacterial lawns with measuring time and environmental conditions (e.g. pH of the media) preclude the estimation of their absolute values, and so, of the cells surface Gibbs energy. Yet, for a given measuring time, it is found that the hydrophobicity and the apparent bacterial surface Gibbs energy components are qualitatively related to the bacterial surface electrical potential. In particular, a hydrophobic increase is always accompanied by an increase of the cells Lifshitz-Van der Waals component and a decrease of their acid-base component and absolute zeta potential. Therefore, the present study shows that the physico-chemical surface properties that characterize bacteria are not independent, and one of them can be qualitatively described in terms of the others when measuring contact angles at a fixed time after the drying of the microbial beds.

Thirty two HIV-infected children, on highly active antiretroviral therapy (HAART) and500 CD4+ T cells/mm3, were rated according to the time-course of viral load (VL) during the whole follow-up period (18 months) in a longitudinal retrospective study. (a) uVL group: 15 children with VL below 400 copies/mL; (b) dVL group: 17 children with higher VL. The uVL group showed higher memory (CD4+CD45RO+) T cells than did dVL group, and higher number of memory activated CD4+CD45RO+HLA-DR+ than did control group (healthy age-matched uninfected children), whereas CD4+CD45RA(hi)+CD62L+ was similar. However, TCR rearrangement excision circles (TRECs) were higher in uVL group than in dVL group. uVL Group showed CD8+CD45RO+ and CD8+CD45RO+CD38- higher number than the control group, but lower than the dVL group. The percentage of CD8+CD45RA(hi)+CD62L+, CD8+CD45RA+, CD8+CD62L-, and CD8+CD28+ was higher in uVL group than in dVL group, and lower than in control group. The uVL group showed higher number of activated (HLA-DR+CD38+, HLA-DR+, HLA-DR+CD38-) CD4+ T cells and lower percentages of CD4+HLA-DR-CD38+ than dVL group. In activated CD8- T cell, the uVL group had lower CD8+HLA-DR+CD38+, CD8+HLA-DR+, and CD8+CD38+ than the dVL group. Preeffector (CD8+CD57-CD28- and CD8+CD45RA-CD62L-) T cells were lower in the uVL group than in dVL group. In the effector (CD8+CD57+, CD8+CD57+CD28-, and CD8+CD45RA+CD62L-) T cells, HIV-infected-children had higher values than control group. HIV-infected-children who respond to HAART had TRECs reconstitution, decreased immune activation, and lower effector CD8+ T cells. Moreover, successful HAART allow the increment of activated CD4+ T cells.

The aim of this study was to evaluate the ability of long-term highly active antiretroviral therapy (HAART) to fully reconstitute the immune system in children with severe AIDS.Lymphoproliferative responses (LPR) were evaluated by incorporation of [3H]-thymidine. Cytokine production in culture (IFN- gamma, IL-5) was quantified using commercially available specific ELISA assays. T-cells subsets were determined by 3-color flow cytometry and thymic production of T-cells was assessed by quantification of TCR rearrangement excision circles (TRECs).We present a vertically HIV-1-infected child at clinical category C, with long-standing CD4+ T-cells below 50/l, who was monitored during 3-years after starting HAART by quantifying the viral load (VL), naïve, memory, and activated T-cell subsets, and thymical function as well as clinical events. VL was suppressed to undetectable levels since the beginning of HAART with d4T, 3TC, nelfinavir, and efavirenz resulting in a dramatic immune reconstitution, achieving normal CD4+ T-cells counts after 6 months (25%, 597 CD4+ T-cells/l) and perdurable undetectable VL levels. Naïve CD4 and CD8 T-cells increased in parallel to TCR rearrangement excision circles (TRECs) levels, with a concomitant decrease in T-cell activation markers. Interestingly, the patient showed an increase in the lymphoproliferative responses to PHA; the IFN-gamma production by PBMCs increased with HAART while the production of IL-5 diminished, thus indicating a switch of type 2 to type 1 response. He recovered clinically and immunologically (up to normal levels) and remains asymptomatic at present.This report demonstrates that at least in these children, an immune and clinical recovery from an advanced stage of HIV-disease can be possible throught HAART.