High prevalence of X4/DM-tropic variants in children and adolescents infected with HIV-1 by vertical transmission.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 RNA > 1000 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. CONCLUSIONS: 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.

Long-term efficacy and safety of fosamprenavir in human immunodeficiency virus-infected pediatric patients.

Fosamprenavir (FPV) efficacy in human immunodeficiency virus (HIV)-infected pediatric patients is still being evaluated in ongoing clinical trials. The long-term efficacy and safety of FPV boosted with ritonavir (FPV/r) was evaluated in 20 antiretroviral-naive and antiretroviral-experienced HIV-vertically infected pediatric patients. Analyses of CD4(+) T-cells, HIV-ribonucleic acid (RNA), and clinical status were performed during a median of 180 weeks. Initially, median HIV-RNA was 4.6 log(10) in naive and 4.4 log(10) in pretreated patients. Median CD4(+) T-cell was 17% and 31%, respectively. After FPV/r treatment, 18 of 20 patients achieved undetectable HIV-RNA and 4 of 20 experienced adverse events. To date, FPV/r treatment has shown sustained antiviral response and immunologic improvement in our 20 patients.

Impact of highly active antiretroviral therapy (HAART) on AIDS and death in a cohort of vertically HIV type 1-infected children: 1980-2006.

We evaluated the population effectiveness of highly active antiretroviral therapy (HAART) on the risk of AIDS and death in a multicenter cohort of 346 HIV-1 vertically infected children born between 1980 and 2006 in the Comunidad Autónoma de Madrid (CAM), Spain. Risks of AIDS and death in patients with the same duration of HIV infection were compared in different calendar periods [CP1: 1980-1989, CP2: 1990-1993 (reference), CP3: 1994-1996, CP4: 1997-1998, CP5: 1999-2006] through cumulative incidence curves and Cox proportional hazards models, allowing for late entry, that included the calendar period as the time-dependent covariate and adjusting for gender and mother's transmission category. The median follow-up was 11.8 years [interquartile range (IQR), 6.3-15.9]. Median CD4+ T cell percentage increased up to 26.5 in CP5 (IQR, 19.5-36.7) while the viral load decreased (median log(10) copies/ml in CP5, 3.66; IQR, 3.07-4.22). Multivariate analysis showed significant reduction in the risk of death since 1997 onward [CP4: adjusted hazard ratios (AHR), 0.29; 95% confidence interval (CI), 0.12-0.69; CP5: AHR, 0.06; 95% CI, 0.03-0.15]. Reduction in progression to AIDS reached borderline significance in CP4 (AHR, 0.49; 95% CI, 0.23-1.05) and was more marked in the last period (CP5: AHR, 0.30; 95% CI, 0.16-0.59). The reductions in the incidence of AIDS and death observed since 1996 were largely attributable to HAART.

Immunological recovery and metabolic disorders in severe immunodeficiency HIV type 1-infected children on highly active antiretroviral therapy.

Little is known about immunologic reconstitution in children on highly active antiretroviral treatment (HAART) during very long-term periods. A retrospective study was carried out to assess the effectiveness and development of metabolic disorders after very long-term periods on HAART in HIV-infected children with severe immunodeficiency. We included 55 children who were stratified into three groups according to %CD4(+) pre-HAART and rate of immunologic recovery: (1) S1-Rec: CD4(+) < or =5% at baseline and slow immunologic recovery; (2) S2-Rec: CD4(+) 5-15% at baseline and slow immunologic recovery; (3) R-Rec: CD4(+) < or =15% at baseline and rapid immunologic recovery (reference group). An adequate immune recovery after 8 years on HAART was achieved by only 25% of children. S1-Rec never achieved a mean of CD4(+) > or =25% after 8 years on HAART. All children had a significant increase in plasma cholesterol levels during the first 2 years. Afterward, cholesterol levels reached a plateau and remained stable until year 8 of follow-up. Higher rates of lipodystrophy were found in the R-Rec group [14 (100%)] than in the S1-Rec group [9/19 (47.4%)] or the S2-Rec group [13/20 (65%)] at the end of the study (p = 0.006). Overall, having a low nadir of CD4(+) hindered immune reconstitution; however, children with rapid immunologic recovery showed a higher prevalence of the lipodystrophy syndrome.

Long-term response to highly active antiretroviral therapy with lopinavir/ritonavir in pre-treated vertically HIV-infected children.

BACKGROUND: 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. METHODS: 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) ( 100,000 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. CONCLUSIONS: 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.

Slow progression of human immunodeficiency virus and hepatitis C virus disease in a cohort of coinfected children.

We carried out a retrospective study to determine the evolution of 23 vertically HIV-1/HCV coinfected children and 30 vertically HIV-1 infected children (control group). Six out of 23 HIV-1/HCV coinfected children developed AIDS versus 20 out of 30 HIV-1 children (P < 0.05). HIV-1/HCV children had a good evolution in relation to CD4 and HIV-RNA viral load. They presented higher CD8 counts than HIV-1 children during long periods, and slower progression of HCV liver disease.

[Changes in vertical HIV transmission: comparison between 1994 and 2004]. / Cambios en la transmisión vertical del virus de la inmunodeficiencia humana: comparación de los años 1994 y 2004.

BACKGROUND AND OBJECTIVE: Vertical transmission (VT) is the main route of human immunodeficiency virus (HIV) infection in children. Since the publication of PACTG 076 study in 1994, several preventive methods against the vertical transmission of the HIV have been developed. In this study, we compare the clinical and epidemiological profile of HIV-infected pregnant women and the VT rate in the years 1994 and 2004. PATIENTS AND METHOD: We looked at maternal, obstetric and pediatric variables of HIV-infected women and their children, born in 1994 and 2004, who were followed in Hospital La Paz. RESULTS: We included 40 mother-infant couples in 1994 and 35 couples in 2004. The HIV vertical transmission rate was 35% in 1994 and 0% in 2004. We did not find changes in Hepatitis C virus (HCV) vertical transmission. In 1994, HIV-infected mothers had a more advanced HIV-disease and the major route of HIV-transmission was the intravenous drug use. Vaginal delivery was more frequent and rupture of membranes was longer than in 2004. The main route of maternal HIV infection in 2004 was sexual contact. In this same year, the use of combination antiretroviral therapy, even during pregnancy, was generalized, the elective cesarean section was the most frequent form of delivery, and every newborn received zidovudine. CONCLUSIONS: In the last decade, there have been important epidemiological changes in HIV-infected mothers in our society. The administration of antiretroviral therapy during pregnancy and to the newborn, as well as other obstetric strategies, can prevent HIV vertical transmission. Nevertheless, we did not find any change in the risk of HCV vertical transmission.

Immunological changes after highly active antiretroviral therapy with lopinavir-ritonavir in heavily pretreated HIV-infected children.

We evaluated the effect of salvage antiretroviral therapy with lopinavir/ritonavir (LPV/r) on the immune system of heavily antiretroviral pretreated HIV-infected children. We carried out a longitudinal study in 20 antiretroviral experienced HIV-infected children to determine the changes in several immunological parameters (T cell subsets, thymic function) every 3 months during 18 months of follow-up on salvage therapy with LPV/r. Statistical analyses were performed with the Wilcoxon test, taking as a reference the basal value at the entry in the study. HIV-infected children showed an increase of CD4+ T cells, a decrease in CD8+ T cells, and an increase in T cell rearrangement excision circle (TRECs) levels. The percentage of HIV children with undetectable viral load (VL < or = 400 copies/ml) increased significantly (p = 0.007) and the percentage with SI viral phenotype decreased significantly (p = 0.002) at the end of the study. Thus, the viral phenotype changed to NSI/R5 after salvage therapy with LPV/r. Interestingly, we observed a significant decrease of memory (CD4+ CD45RO+) and a moderate decrease of activated (CD4+ HLA-DR+, CD4+ HLA-DR+CD38, CD4+, CD45RO+HLA-DR+) CD4+ T cells during the follow-up. On the other hand, memory (CD8+ CD45RO+ and CD8+ CD45RO+CD38+), activated (CD8+ HLA-DR+CD38+, CD8+ HLA-DR+, CD8+ CD38+), and effector (CD8+ CD57+, CD8+ CD28(-)CD57+) CD8+ T cells had a very significant decrease during follow-up. Our data indicate an immune system reconstitution in heavily pretreated HIV-infected children in response to salvage therapy with LPV/r as a consequence of a decrease in immune system activation and an increase in thymic function.

Impact of highly active antiretroviral therapy on CD4+ T cells and viral load of children with AIDS: a population-based study.

In this study, we sought to characterize the changes over time at the population level on CD4(+) T cells and plasma viral load (VL) levels of HIV-1-infected children with or without AIDS. We carried out a retrospective study in 114 HIV-infected children during the calendar period that a highly active antiretroviral therapy (HAART) protocol was used. The HAART protocol consisted of three drugs: nucleoside analogue HIV-1 reverse transcriptase inhibitors, and/or HIV protease inhibitors, and/or nonnucleoside analogue HIV-1 reverse transcriptase inhibitors. The mean of CD4(+) T cells percentage and log(10) VL per calendar year were stratified by AIDS diagnostic. As new HAART strategies become available, an increase of CD4(+) T cells and a decrease of VL were observed over time, in children with and without AIDS. In 2001, children with AIDS reached values of CD4(+) T cells and VL similar to children without AIDS. In conclusion, our study shows that the generalized use of HAART has permitted improvement in immunological and virological status of HIV-infected children without AIDS, and more importantly in children with AIDS.