Rosa Resino

Impact on weight and height with the use of HAART in HIV-infected children.

Background: There are few data on long-term effects of highly active antiretroviral therapy (HAART) on weight and height in HIV-infected children. Objectives: Our objective was to assess the effect of HAART on the weight and height of HIV-infected children over time in the Madrid cohort, and analyze possible factors associated with the effect. Patients and methods: This was a retrospective study of HIV-infected children starting HAART in 1997 or later. Serial measurements of weight, height and body mass index (BMI) were performed and converted to z-scores using the Spanish revised reference data. Changes from baseline in weight, height and BMI at 12, 24, 36, 48 and 60 months were determined. Associations of z-scores at the last visit with immunologic (CD4% above 25%) and virologic responses (more than 50% of samples below 400 copies/mL), CDC (Centers for Disease Control) clinical category, and the presence and type of lipodystrophy (lipoatrophy or lipohypertrophy) were evaluated. Results: Twelve hundred and twelve children, 97% of them vertically-infected, received HAART starting in 1997 for a median of 71 months (4–102 months). Median age at initiation of HAART was 6 years (1 month–18 years). Thirty-nine percentage were antiretroviral naive and 61% had received NRTI therapy previously. Thirty-two percentage and 53% had CDC class C and immunologic class 3, respectively. At the final evaluation, 24% of children remained on their first combination therapy, 39% on the second and 37% had received at least 3 different HAART regimens. Fifty-one percentage were classified as virologic responders. Thirty-nine percentage of children in this study were diagnosed with lipodystrophy. At baseline, median z-score for weight, height and BMI were −0.45, −0.60 and −0.33, respectively. HAART was associated with significant increases in z-scores of weight and height but not BMI at the different time-points analyzed. Virologic nonresponders had significantly lower z-scores for weight and height but not for BMI. CDC class C was associated with lower z-scores for height. No differences in final measurements were observed for baseline CD4, immunologic response or lipoatrophy. Children with lipohypertophy had a significantly higher BMI at the last visit. Conclusions: HIV-infected children experienced a continued catch-up in weight and height 5 years after starting HAART. Virologic control is related to sustained growth.

Long-term effects of highly active antiretroviral therapy in pretreated, vertically HIV type 1-infected children : 6 years of follow-up

BACKGROUND Several studies of children with human immunodeficiency virus (HIV) type 1 infection have demonstrated sustained increases in CD4+ cell count, even when virological failure has occurred after receipt of highly active antiretroviral therapy (HAART), but these studies were of limited duration. Moreover, the CD4+ cell count threshold at which antiretroviral treatment should be initiated is still unsettled. The aim of this study was to define the long-term impact of HAART on CD4+ cell percentage and viral load according to CD4+ cell percentages before HAART was initiated. METHODS We conducted a retrospective study of 113 pretreated HIV-1-infected children stratified by pre-HAART CD4+ cell percentage (<5%, 5%-15%, 15%-25%, and >25%). The inclusion criteria were as follows: initiating HAART with a protease inhibitor, having 6 years of follow-up after starting HAART, having a CD4+ cell count or viral load recorded before initiation of HAART, and having received mono- or dual-nucleoside therapy before starting HAART. RESULTS During the first 2 years of HAART, HIV-1-infected children experienced a significant increase in CD4+ cell percentage and a decrease in viral load (P<.05). During their last 4 years of receiving HAART, we found a significant decrease in viral load but not an increase in CD4+ cell percentage, because the CD4+ cell percentage reached a plateau after the second year of HAART. Moreover, children with CD4+ cell percentages of <5% at baseline did not achieve CD4+ cell percentages of >25% after 6 years of HAART. Children with CD4+ cell percentages of 5%-25% at baseline had a strong negative association with achieving CD4+ cell percentages of >30% for at least 6 and 12 months but not with achieving CD4+ cell percentages of >30% for at least 24 months. CONCLUSIONS Long-term HAART allowed for restoration of CD4+ cell counts and control of viral loads in HIV-1-infected children. However, initiating HAART after severe immunosuppression has occurred is detrimental for the restoration of the CD4+ cell count.

Clinical Outcomes Improve with Highly Active Antiretroviral Therapy in Vertically HIV Type-1–Infected Children

Background. Use of antiretroviral therapy has resulted in a decrease in morbidity and mortality rates in human immunodeficiency virus type 1 (HIV-1)-infected children.Methods. We performed a retrospective study involving 427 children to determine the effectiveness of different antiretroviral therapy protocols on clinical outcome. The follow-up period was divided into 5 calendar periods (CPs): CP1 (1980-1989), before antiretroviral therapy was administered; CP2 (1990-1993), when monotherapy was administered; CP3 (1994-1996), when combined therapy was administered; CP4 (1997-1998), when </=50% of children were receiving highly active antiretroviral therapy (HAART); and CP5 (1999-2003), when >/=60% of children were receiving HAART.Results. Children experienced a progressive increase in the CD4(+) cell count and decrease in the viral load from 1997 onwards. A lower number of AIDS cases and deaths occurred during CP5 than during the other CPs (P<.01), with a relative risk of an absence of AIDS of >20 and a relative risk of survival of >30. The AIDS rate was >50% in CP1; we observed a very strong decrease to 14% in CP2, to 16% in CP3, to 7% in CP4, and to 2% in CP5. The mortality rates in CP2 and CP3 were >6% and thereafter decreased to 0.5% in CP5. The relative risks for no hospital admission in CP4 and CP5 were >3.5. The total rates of hospital admission in CP1, CP2, and CP3 were >30%; we observed a decrease in CP4 and CP5. The duration of hospitalization decreased during the follow-up period, and it was higher in CP1 (~30 days) than in the other periods.Conclusions. We observed that HAART produces a decrease in adverse clinical outcomes (i.e., hospital admission, AIDS, and death) in children with vertical HIV-1 infection in Madrid, Spain.

Extensive implementation of highly active antiretroviral therapy shows great effect on survival and surrogate markers in vertically HIV-infected children.

We performed a retrospective observational study of 253 children vertically infected with human immunodeficiency virus (1994-2001) to assess the effectiveness of antiretroviral therapies (ARTs) on survival and surrogate markers at the population level. Children were divided into 3 groups according to the ART protocols used during the follow-up period: calendar period (CP) 1 (1994-1996) received combined therapy with 2 nucleoside reverse transcriptase inhibitors (NRTIs); CP2 (1997-1998) received implementation of highly active ART (HAART) with 3 drugs (NRTIs, protease inhibitors, and non-NRTIs); and CP3 (1999-2001) received extensive HAART. The children in the CP3 group had statistically significant longer survival periods, lower virus load (VL), highest undetectable VL proportion, and highest CD4+ T cell counts. HAART is effective at the population level at decreasing VL, increasing CD4+ T cells, and increasing the survival in a higher percentage of HIV-infected children.

Spatial pattern of HIV-1 mother-to-child-transmission in Madrid (Spain) from 1980 till now: demographic and socioeconomic factors.

Objective:To evaluate any possible association between indicators of social inequalities and the geographical distribution of HIV-1 mother-to-child transmission (MTCT) cases in Madrid. Methods:We carried out an observational survey of 224 HIV-1 vertically infected children born in 1980–2006 living in Madrid. We elaborated maps representing the prevalence of HIV-1 MTCT cases. We assessed the association between indicators of social inequalities and the spatial distribution of MTCT cases. Poisson univariate and multivariate analysis of risk factors for MTCT were performed. Results:We identified core areas of transmission mainly in southern Madrid until 2006. The prevalence of MTCT cases was significantly correlated to the percentage of immigrants, illiterates, unemployed women and the income in 1996 and 2000/2001. The risk of MTCT increased in the periods up to 1996 compared with the calendar period 1980–1989, whereas the risk decreased in 1999–2006 [relative risk, 0.08; 95% confidence interval (CI), 0.03–0.18; P < 0.001]. The risk was especially high in the districts of Usera (absolute relative risk, 11.4; 95% CI, 2.6–49.5; P = 0.001), Puente de Vallecas (absolute relative risk, 14.0; 95% CI, 3.4–57.9; P < 0.001) and San Blas (absolute relative risk, 12.5; 95% CI, 2.9–53.6; P = 0.001). The percentage of illiterates was the indicator that explained the risk of MTCT (absolute relative risk, 1.07; 95% CI, 1.05–1.10; P = 0.001). Conclusion:We observed a geographic heterogeneity of the HIV-1 vertical transmission with the highest prevalence in disadvantaged districts. What is described in the present review is the HIV-1 vertical transmission within a social context; this approach could be relevant in analysing the pattern of HIV-1 transmission in other Western cities or highlighting the distribution of other infectious diseases.

Impact of long-term viral suppression in CD4+ recovery of HIV-children on Highly Active Antiretroviral Therapy

BackgroundThe effects of HAART may differ between children and adults because children have a developing immune system, and the long-term immunological outcome in HIV-infected children on HAART is not well-known. A major aim of our study was to determine CD4+ evolution associated with long-term VL control during 4 years of observation on HAART.MethodsWe carried out a retrospective study on a cohort of 160 vertically HIV-infected children. It was carried out from 1996 to 2004 in six large Spanish pediatric referral hospitals. We compared 33 children who had long-term VL suppression (VL ≤400 copies/ml) in the first 12 months of follow-up and maintained that level throughout follow-up (Responders-group), and 127 children with persistently detectable VL in spite of ART switches (Non-Responders-group).ResultsWe observed a quick initial and significant increase in CD4+ counts from the baseline to 12 months on HAART in both groups (p < 0.01). The Non-Responders group sustained CD4+ increases and most of these children maintained high CD4+ level counts (≥25%). The Non-Responders group reached a plateau between 26% and 27% CD4+ at the first 12 months of follow-up that remained stable during the following 3 years. However, the Responders group reached a plateau between 30% and 32% CD4+ at 24, 36 and 48 months of follow-up. We found that the Responders group had higher CD4+ count values and higher percentages of children with CD4+ ≥25% than the Non-Responders group (p < 0.05) after month 12.ConclusionLong-term VL suppression in turn induces large beneficial effects in immunological responses. However, it is not indispensable to recover CD4+ levels.

Effects of highly active antiretroviral therapy with nelfinavir in vertically HIV-1 infected children: 3 years of follow-up. Long-term response to nelfinavir in children

BackgroundAntiretroviral treatment (ART) in children has special features and consequently, results obtained from clinical trials with antiretroviral drugs in adults may not be representative of children. Nelfinavir (NFV) is an HIV-1 Protease Inhibitor (PI) which has become as one of the first choices of PI for ART in children. We studied during a 3-year follow-up period the effects of highly active antiretroviral therapy with nelfinavir in vertically HIV-1 infected children.MethodsForty-two vertically HIV-infected children on HAART with NFV were involved in a multicentre prospective study. The children were monitored at least every 3 months with physical examinations, and blood sample collection to measure viral load (VL) and CD4+ cell count. We performed a logistic regression analysis to determinate the odds ratio of baseline characteristics on therapeutic failure.ResultsVery important increase in CD4+ was observed and VL decreased quickly and it remained low during the follow-up study. Children with CD4+ <25% at baseline achieved CD4+ >25% at 9 months of follow-up. HIV-infected children who achieved undetectable viral load (uVL) were less than 40% in each visit during follow-up. Nevertheless, HIV-infected children with VL >5000 copies/ml were less than 50% during the follow-up study. Only baseline VL was an important factor to predict VL control during follow-up. Virological failure at defined end-point was confirmed in 30/42 patients. Along the whole of follow-up, 16/42 children stopped HAART with NFV. Baseline characteristics were not associated with therapeutic change.ConclusionNFV is a safe drug with a good profile and able to achieve an adequate response in children.

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.

Pneumocystis pneumonia in HIV-positive patients in Spain: epidemiology and environmental risk factors.

Specific environmental factors may play a role in the development of Pneumocystis pneumonia (PCP) in HIV‐positive patients. The aim of this study was to estimate the PCP incidence and mortality in hospitalized HIV‐positive patients in Spain during the combination antiretroviral therapy (cART) era (1997 to 2011), as well as to analyze the climatological factors and air pollution levels in relation to hospital admissions and deaths.

Carga viral plasmática en niños infectados por el virus de la inmunodeficiencia humana que reciben tratamiento antirretroviral de gran actividad

Fundamento y objetivo Determinar si la carga viral (CV) previa a conseguir un valor de 400 copias/ml o menor (CV indetectable) en una cohorte de 81 ninos infectados por el virus de la inmunodeficiencia humana (VIH) que reciben tratamiento antirretroviral de gran actividad predice distintos niveles de rebote de la CV. Pacientes y metodo Se ha realizado un estudio retrospectivo. Los ninos se dividieron en 3 grupos segun la mediana de CV un ano antes de alcanzar la CV indetectable: grupo A, formado por 15 ninos con CV inferior a 5.000 copias/ml; grupo B, constituido por 32 ninos con CV de 5.000 a 30.000 copias/ml, y grupo C, compuesto por 34 ninos con CV mayor de 30.000 copias/ml. Resultados Un total de 63 ninos (77,8%) tuvieron una CV mayor de 400 copias/ml, 42 (51,8%) tuvieron una CV mayor de 5.000 copias/ml y 27 (33,3%) tuvieron una CV mayor de 30.000 copias/ml. En los ninos del grupo C se obtuvieron valores de la razon de riesgo (RR) estadisticamente significativos con respecto a los ninos del grupo A para el repunte de CV mayor de 500 copias/ml, mayor de 5.000 copias/ml y mayor de 30.000 copias/ml, con un valor de RR superior a 12 para el repunte de CV mayor de 30.000 copias/ml. Los ninos del grupo B tuvieron valores de RR estadisticamente significativos solo para el rebote de CV mayor de 5.000 copias/ml. Conclusiones La CV elevada previa a conseguir la CV indetectable es un factor pronostico de rebote de la CV en ninos infectados por el VIH que reciben antirretrovirales de gran actividad.