Treatment with highly active antiretroviral therapy in human immunodeficiency virus type 1-infected children is associated with a sustained effect on growth

INTRODUCTION: Growth failure is a common feature of children with human immunodeficiency virus type 1 (HIV-1) infection. Children who are treated with mono or dual nucleoside analogue reverse transcriptase inhibitor (NRTI) therapy show a temporary increase in weight gain and linear growth rate. In adults, protease-inhibitor-containing antiretroviral therapy is associated with a sustained weight gain and increased body mass index (BMI). Experience with protease inhibitors and growth in children is still limited. The data mainly deal with short-term effects on growth. OBJECTIVE: To evaluate the effect of highly active antiretroviral therapy (HAART) on growth in children with HIV-1 infection. DESIGN AND METHODS: We analyzed selected growth parameters, clinical data, and laboratory results as part of a prospective, open, uncontrolled, multicenter study to evaluate the clinical, immunologic, and virologic response to HAART consisting of indinavir, zidovudine, and lamivudine in children with HIV-1 infection. Height and weight were measured at 0, 12, 24, 36, 48, 60, 72, 84, and 96 weeks after initiation of HAART. Information about the children's growth before enrollment in the study was retrieved from the hospital medical records and/or the school doctor or health center. BMI was calculated. z Scores were used to express the standard deviation (SD) in SD units from the Dutch reference curves for age and gender. Viral loads and CD4+ T-cell counts were examined prospectively and related to these growth parameters. z Scores were also calculated for CD4+ T-cell counts to correct for age-related differences. A z score of 0 represents the P50, which is exactly the age/sex-appropriate median. A height z score of -1 indicates that a child's height is 1 SD below the age- and gender-specific median height for the normal population. Virologic responders were defined as those who either reached an undetectable viral load (1.5 log reduction in viral load compared with baseline at week 12 after the initiation of HAART, which was maintained during the follow-up period. RESULTS. PATIENTS: Twenty-four patients were included (age: 0.4-16.3 years at baseline), with a median HIV-1 RNA load of 105 925 copies/mL (5.03 log), a median CD4+ T-cell count of 0.586 x 10(9)/L (median z score: -2.28 SD), a median height z score of -1.22, a median weight z score of -0.74, and a median baseline BMI z score of -0.32. Eleven patients were naive to antiretroviral therapy, and 13 patients had received previous treatment with NRTI monotherapy. Twenty children used indinavir and 4 children used nelfinavir as part of HAART. VIROLOGIC AND IMMUNOLOGIC RESPONSES TO HAART: Seventeen children were virologic responders, and 7 children were virologic nonresponders. In patients naive to NRTIs, median baseline viral loads were significantly higher than in pretreated patients. However, at weeks 48 and 96, there was no significant difference between the viral loads of both groups. At baseline, there was no significant difference in CD4+a T-cell z scores between virologic responders and nonresponders or between naive and pretreated patients. During 96 weeks of HAART, the increase of CD4+ T-cell z score was significantly higher in responders than in nonresponders. The increase in CD4+ T-cell z score was not significantly different for naive and pretreated patients. HEIGHT, WEIGHT, AND BMI z SCORE CHANGES: We found that

Fetal Metabolic Stress Disrupts Immune Homeostasis and Induces Proinflammatory Responses in Human Immunodeficiency Virus Type 1-and Combination Antiretroviral Therapy-Exposed Infants

Analytical BioScience

Has the Rate of CD4 Cell Count Decline before Initiation of Antiretroviral Therapy Changed over the Course of the Dutch HIV Epidemic among MSM?

Introduction:Studies suggest that the HIV-1 epidemic in the Netherlands may have become more virulent, leading to faster disease progression if untreated. Analysis of CD4 cell count decline before antiretroviral therapy (ART) initiation, a surrogate marker for disease progression, may be hampered by informative censoring as ART initiation is more likely with a steeper CD4 cell count decline.Methods:Development of CD4 cell count from 9 to 48 months after seroconversion was analyzed using a mixed-effects model and 2 models that jointly modeled CD4 cell counts and time to censoring event (start ART

Non-AIDS defining cancers in the D:A:D Study-time trends and predictors of survival : a cohort study

BACKGROUND:Non-AIDS defining cancers (NADC) are an important cause of morbidity and mortality in HIV-positive individuals. Using data from a large international cohort of HIV-positive individuals, we described the incidence of NADC from 2004-2010, and described subsequent mortality and predictors of these.METHODS:Individuals were followed from 1st January 2004/enrolment in study, until the earliest of a new NADC, 1st February 2010, death or six months after the patient's last visit. Incidence rates were estimated for each year of follow-up, overall and stratified by gender, age and mode of HIV acquisition. Cumulative risk of mortality following NADC diagnosis was summarised using Kaplan-Meier methods, with follow-up for these analyses from the date of NADC diagnosis until the patient's death, 1st February 2010 or 6 months after the patient's last visit. Factors associated with mortality following NADC diagnosis were identified using multivariable Cox proportional hazards regression.RESULTS:Over 176,775 person-years (PY), 880 (2.1%) patients developed a new NADC (incidence: 4.98/1000PY [95% confidence interval 4.65, 5.31]). Over a third of these patients (327, 37.2%) had died by 1st February 2010. Time trends for lung cancer, anal cancer and Hodgkin's lymphoma were broadly consistent. Kaplan-Meier cumulative mortality estimates at 1, 3 and 5 years after NADC diagnosis were 28.2% [95% CI 25.1-31.2], 42.0% [38.2-45.8] and 47.3% [42.4-52.2], respectively. Significant predictors of poorer survival after diagnosis of NADC were lung cancer (compared to other cancer types), male gender, non-white ethnicity, and smoking status. Later year of diagnosis and higher CD4 count at NADC diagnosis were associated with improved survival. The incidence of NADC remained stable over the period 2004-2010 in this large observational cohort.CONCLUSIONS:The prognosis after diagnosis of NADC, in particular lung cancer and disseminated cancer, is poor but has improved somewhat over time. Modifiable risk factors, such as smoking and low CD4 counts, were associated with mortality following a diagnosis of NADC

De dupe van beschermende regels. Verruim de voorwaarden boot fase-I-onderzoek met kinderen.

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Reductie van verticale transmissie door perinatale profylaxe bij een HIV-1 geëxposeerde in Nederland geboren kinderen in de periode 1995-2000.

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