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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.

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.

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.

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.