Neighborhood environmental factors linked to hospitalizations of older people for viral lower respiratory tract infections in Spain: a case-crossover study.

BACKGROUND: Lower respiratory tract viral infection (LRTI) is a significant cause of morbidity-mortality in older people worldwide. We analyzed the association between short-term exposure to environmental factors (climatic factors and outdoor air pollution) and hospital admissions with a viral LRTI diagnosis in older adults. METHODS: We conducted a bidirectional case-crossover study in 6367 patients over 65 years of age with viral LRTI and residential zip code in the Spanish Minimum Basic Data Set. Spain's State Meteorological Agency was the source of environmental data. Associations were assessed using conditional logistic regression. P-values were corrected for false discovery rate (q-values). RESULTS: Almost all were hospital emergency admissions (98.13%), 18.64% were admitted to the intensive care unit (ICU), and 7.44% died. The most frequent clinical discharge diagnosis was influenza (90.25%). LRTI hospital admissions were more frequent when there were lower values of temperature and O3 and higher values of relative humidity and NO2. The regression analysis adjusted by temperatures and relative humidity showed higher concentrations at the hospital admission for NO2 [compared to the lag time of 1-week (q-value< 0.001) and 2-weeks (q-value< 0.001)] and O3 [compared to the lag time of 3-days (q-value< 0.001), 1-week (q-value< 0.001), and 2-weeks (q-value< 0.001)] were related to a higher odds of hospital admissions due to viral LRTI. Moreover, higher concentrations of PM10 at the lag time of 1-week (q-value = 0.023) and 2-weeks (q-value = 0.002), and CO at the lag time of 3-days (q-value = 0.023), 1-week (q-value< 0.001) and 2-weeks (q-value< 0.001)], compared to the day of hospitalization, were related to a higher chances of hospital admissions with viral LRTI. CONCLUSION: Unfavorable environmental factors (low temperatures, high relative humidity, and high concentrations of NO2, O3, PM10, and CO) increased the odds of hospital admissions with viral LRTI among older people, indicating they are potentially vulnerable to these environmental factors.

Environmental factors linked to hospital admissions in young children due to acute viral lower respiratory infections: A bidirectional case-crossover study.

OBJECTIVE: This study evaluated the association of the short-term exposure to environmental factors (relative humidity, temperature, NO2, SO2, O3, PM10, and CO) with hospital admissions due to acute viral lower respiratory infections (ALRI) in children under two years before the COVID-19 era. METHODS: We performed a bidirectional case-crossover study in 30,445 children with ALRI under two years of age in the Spanish Minimum Basic Data Set (MBDS) from 2013 to 2015. Environmental data were obtained from Spain's State Meteorological Agency (AEMET). The association was assessed by conditional logistic regression. RESULTS: Lower temperature one week before the day of the event (hospital admission) (q-value = 0.012) and higher relative humidity one week (q-value = 0.003) and two weeks (q-value<0.001) before the day of the event were related to a higher odds of hospital admissions. Higher NO2 levels two weeks before the event were associated with hospital admissions (q-value<0.001). Moreover, higher concentrations on the day of the event for SO2 (compared to lag time of 1-week (q-value = 0.026) and 2-weeks (q-value<0.001)), O3 (compared to lag time of 3-days (q-value<0.001), 1-week (q-value<0.001), and 2-weeks (q-value<0.001)), and PM10 (compared to lag time of 2-weeks (q-value<0.001)) were related to an increased odds of hospital admissions for viral ALRI. CONCLUSION: Short-term exposure to environmental factors (climatic conditions and ambient air contaminants) was linked to a higher likelihood of hospital admissions due to ALRI. Our findings emphasize the importance of monitoring environmental factors to assess the odds of ALRI hospital admissions and plan public health resources.

Environmental factors are associated with hospital admissions for sepsis-related pneumonia: A bidirectional case-crossover design.

OBJECTIVE: Pneumonia is a common cause of morbidity and sepsis worldwide, mainly in the elderly. We evaluated the impact of short-term exposure to environmental factors on hospital admissions for sepsis-related pneumonia in a nationwide study in Spain. METHODS: We conducted a bidirectional case-crossover study in patients who had sepsis-related pneumonia in 2013. Data were obtained from the Minimum Basic Data Set (MBDS) and the State Meteorological Agency (AEMET) of Spain. Conditional logistic regressions were used to evaluate the association between environmental factors (temperature, relative humidity, NO2, SO2, O3, PM10, and CO) and hospital admissions with sepsis-related pneumonia. RESULTS: A total of 3,262,758 hospital admissions were recorded in the MBDS, of which, 253,467 were patients with sepsis. Among those, 67,443 had sepsis-related pneumonia and zip code information. We found inverse associations [adjusted odds ratio (aOR) values < 1] between short-term exposure to temperature and hospital admissions for sepsis-related pneumonia. Moreover, short-term exposure to higher levels of relative humidity, NO2, SO2, O3, PM10, and CO were directly associated (aOR values > 1) with a higher risk of hospital admissions for sepsis-related pneumonia. Overall, the impact of environmental factors was more prominent with increasing age, mainly among the elderly aged 65 or over. CONCLUSION: Short-term exposure to environmental factors (temperature, relative humidity, NO2, SO2, O3, CO, and PM10) was associated with a higher risk of hospital admissions for sepsis-related pneumonia. Our findings support the role of environmental factors in monitoring the risk of hospital admissions for sepsis-related pneumonia and can help plan and prepare public health resources.

Environmental Factors Related to Pulmonary Tuberculosis in HIV-Infected Patients in the Combined Antiretroviral Therapy (cART) Era.

The aim of our study was to evaluate the seasonal variations and whether short-term exposure to environmental risk factors, such as climate and air pollution, is associated with PTB-related hospital admissions in human immunodeficiency virus (HIV)-infected patients in Spain during the era of combined antiretroviral therapy (cART). A retrospective study was carried out using data from the Minimum Basic Data Set (MBDS) and the State Meteorological Agency (AEMET) of Spain. The primary outcome variable was hospital admissions with PTB diagnosis. The environmental risk factors evaluated were season, temperature, humidity, NO2, SO2, O3, PM10, and CO. Overall, HIV-infected patients had a lower frequency of PTB-related hospital admissions in summer (22.8%) and autumn (22.4%), but higher values in winter (26.6%) and spring (28.2%). Using a Bayesian temporal model, PTB-related hospital admissions were less frequent in summer-autumn and more abundant in winter-spring during the first years of follow-up. During the later years of follow-up, the seasonal trends continued resulting in the lowest values in autumn and the highest in spring. When considering short-term exposure to environmental risk factors, lower temperatures at 1 week (odds ratio (OR) = 1.03; p = 0.008), 1.5 weeks (OR = 1.03; p<0.001), 2 weeks (OR = 1.04; p<0.001), and 3 weeks (OR = 1.03; p<0.001) prior to PTB admission. In addition, higher concentration of NO2 at the time of admission were significantly associated with higher likelihoods of PTB-related hospital admission in HIV-infected patients when 1.5 weeks (OR = 1.1; p = 0.044) and 2 weeks (OR = 1.21; p<0.001) were used as controls. Finally, higher concentration of SO2 at 1.5 weeks prior to PTB admission was significantly associated with a higher likelihood of PTB-related hospital admissions (OR = 0.92; p = 0.029). In conclusion, our data suggest an apparent seasonal variation in hospital admissions of HIV-infected patients with a PTB diagnosis (summer/autumn vs. winter/spring), as well as a link to short-term exposure to environmental risk factors, such as temperature and ambient NO2 and SO2.

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

INTRODUCTION: 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. METHODS: We carried out a retrospective study. Data were collected from the National Hospital Discharge Database and the State Meteorological Agency of Spain. A case-crossover analysis was applied to identify environmental risk factors related to hospitalizations and deaths. For each patient, climatic factors and pollution levels were assigned based on readings from the nearest meteorological station to his or her postal code. RESULTS: There were 13,139 new PCP diagnoses and 1754 deaths in hospitalized HIV-positive patients from 1997 to 2011. The PCP incidence (events per 1000 person-years) dropped from 11.6 in 1997 to 2000, to 5.4 in 2004 to 2011 (p<0.001). The mortality (events per 10,000 person-years) also decreased from 14.3 in 1997 to 2000, to 7.5 in 2004 to 2011 (p<0.001). Most hospital admissions and deaths occurred in the winter season and the fewest occurred in the summer, overlapping respectively with the lowest and highest temperatures of the year in Spain. Moreover, lower temperatures prior to PCP admission, as well as higher concentrations of NO2 and particulate matter up to 10 m in size (PM10) at the time of admission were associated with higher likelihoods of hospital admission due to PCP when two weeks, one month, 1.5 months or two months were used as controls (p<0.01). Furthermore, higher concentrations of ozone at one month (p=0.007), 1.5 months (p<0.001) and two months (p=0.006) prior to admission were associated with higher likelihoods of hospital admission with PCP. For PCP-related deaths, lower temperatures prior to admission and higher concentrations of atmospheric PM10 at the time of admission were related to higher likelihood of death when two weeks, one month and 1.5 months were used as controls (p<0.05). CONCLUSIONS: PCP was a significant health problem in the cART era (1997 to 2011), and PCP epidemiology was adversely influenced by colder climatological factors and higher ambient air pollution levels.

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.

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 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.

[Viral load in HIV-infected children on high activity antiretroviral therapy]. / Carga viral plasmática en niños infectados por el virus de la inmunodeficiencia humana que reciben tratamiento antirretroviral de gran actividad.

BACKGROUND AND OBJECTIVE: To determine whether viral load (VL) prior to undetectable VL has predictive value on the re-emergence of VL (> 400 copies/ml, > 5,000 copies/ml and > 30,000 copies/ml). PATIENTS AND METHOD: Retrospective study carried out on 81 vertically human immunodeficiency virus (HIV)-infected children on antiretroviral therapy who were distributed in 3 groups according to their median value of VL one year before reaching undetectable VL: A-group: VL < 5,000 copies/ml; B-group: VL between 5,000 and 30,000 copies/ml, and C-group: VL > 30,000 copies/ml. RESULTS: During the whole follow-up period, 63 (77.8%) children had a rebound of VL > 400 copies/ml. Forty-two (51.8%) children had a rebound of VL > 5,000 copies/ml. Twenty-seven (33.3%) children had a rebound of VL > 30,000 copies/ml. HIV-children of B-group had values of hazard ratio (HR) statistically significant for a rebound of VL > 5,000 copies/ml. Moreover, HIV-children of C-group had values of HR greater and statistically significant for a rebound of VL > 500, > 5,000 and > 30,000 copies/ml. For a rebound of VL > 30,000 copies/ml, the C-group had values of RR > 12. CONCLUSIONS: High VL levels prior to undetectable VL can be a useful prognostic marker of virological failure in HIV-infected children.

Carga viral plasmática en niños infectados por el virus de la inmunodeficiencia humana que reciben tratamiento antirretroviral de gran actividad / Viral load in HIV-infected children on high activity antiretroviral therapy

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 niños 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 método: Se ha realizado un estudio retrospectivo. Los niños se dividieron en 3 grupos según la mediana de CV un año antes de alcanzar la CV indetectable: grupo A, formado por 15 niños con CV inferior a 5.000 copias/ml; grupo B, constituido por 32 niños con CV de 5.000 a 30.000 copias/ml, y grupo C, compuesto por 34 niños con CV mayor de 30.000 copias/ml. Resultados: Un total de 63 niños (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 niños del grupo C se obtuvieron valores de la razón de riesgo (RR) estadísticamente significativos con respecto a los niños 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 niños del grupo B tuvieron valores de RR estadísticamente significativos sólo para el rebote de CV mayor de 5.000 copias/ml. Conclusiones: La CV elevada previa a conseguir la CV indetectable es un factor pronóstico de rebote de la CV en niños infectados por el VIH que reciben antirretrovirales de gran actividad

Background and objective: To determine whether viral load (VL) prior to undetectable VL has predictive value on the re-emergence of VL (> 400 copies/ml, > 5,000 copies/ml and > 30,000 copies/ml). Patients and method: Retrospective study carried out on 81 vertically human immunodeficiency virus (HIV)-infected children on antiretroviral therapy who were distributed in 3 groups according to their median value of VL one year before reaching undetectable VL: A-group: VL 30,000 copies/ml. Results: During the whole follow-up period, 63 (77.8%) children had a rebound of VL > 400 copies/ml. Forty-two (51.8%) children had a rebound of VL > 5,000 copies/ml. Twenty-seven (33.3%) children had a rebound of VL > 30,000 copies/ml. HIV-children of B-group had values of hazard ratio (HR) statistically significant for a rebound of VL > 5,000 copies/ml. Moreover, HIV-children of C-group had values of HR greater and statistically significant for a rebound of VL > 500, > 5,000 and > 30,000 copies/ml. For a rebound of VL > 30,000 copies/ml, the C-group had values of RR > 12. Conclusions: High VL levels prior to undetectable VL can be a useful prognostic marker of virological failure in HIV-infected children

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.

BACKGROUND: Antiretroviral 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. METHODS: Forty-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. RESULTS: Very 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. CONCLUSION: NFV is a safe drug with a good profile and able to achieve an adequate response in children.

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 /=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.

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.

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

BACKGROUND: The 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. METHODS: We 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 < or = 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). RESULTS: We 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 (> or = 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+ > or = 25% than the Non-Responders group (p < 0.05) after month 12. CONCLUSION: Long-term VL suppression in turn induces large beneficial effects in immunological responses. However, it is not indispensable to recover CD4+ levels.

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.

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.

The effects on infants of potent antiretroviral therapy during pregnancy: a report from Spain.

BACKGROUND: The purpose of our study was to assess the effects on infants of protease inhibitor (PI)-based antiretroviral therapy (ART) given to their HIV-positive mothers during pregnancy. MATERIAL/METHODS: A multicenter observational study was carried out at 11 centers in Spain, involving 124 HIV-1-infected pregnant women under ART and their infants. The mothers were classified according to the ART protocols used during pregnancy into two groups: group A, 52 women with > or =2 nucleoside reverse transcriptase inhibitors (NRTI) with or without NNRTI, for a mean time of 4.7+/-2.2 months; and group B, 72 women on protease inhibitor (PI)-based regimens for 5.4+/-2.6 months. RESULTS: Maternal therapy was well tolerated, with no serious adverse effects on pregnancy course. No newborn was infected with HIV-1. There were two deaths at birth (group B), both with extreme prematurity. Among the 126 ART-exposed infants (4 siblings), the most common toxicity was anemia (29%), without significant differences between the two groups. Low birthweight and prematurity were also common (21% and 14%, respectively). CONCLUSIONS: Optimal management of HIV-1 infection in women, regardless of their pregnancy status, can be recommended in more developed countries, without adverse effects on pregnancy outcome, and dramatically decreasing vertical transmission. HAART with PI versus potent ART during pregnancy was effective and safe for infants throughout the 12-month follow-up. In the light of recent advances in anti-HIV-1 pregnancy therapy, the long-term safety of these prophylactic and therapeutical strategies should be studied.