Biomedical subjects
Publications and source records attributed to Hemophilia Growth and Development Study.
Hepatitis C virus (HCV) infection may be associated with neurocognitive deficits. The Hemophilia Growth and Development Study enrolled HIV-infected and HIV-uninfected patients and a group of nonhemophiliac siblings. After controlling for multiple factors, HCV monoinfection was not associated with deficits in adaptive behavior, intelligence, or attention/concentration.
This study used a well characterized cohort of human immunodeficiency virus type 1 (HIV-1)-infected hemophiliacs to define the relationship between the SDF1-3'A allele, the plasma HIV-1 coreceptor tropism, and the natural history of HIV-1 disease. Subjects heterozygous or homozygous for the SDF1-3'A allele experienced higher rates of decline in CD4+ T cell counts over time than did those without the allele (P=.009). Moreover, they had an increased risk of progression to acquired immunodeficiency syndrome and death, a relationship that persisted even when baseline plasma HIV-1 RNA levels and CD4+ T cell counts or CCR5 Delta 32 and CCR2-64I genotype were controlled for. This relationship was even stronger in a subgroup of subjects for whom tropism data were available. Subjects with the SDF1-3'A allele were also more likely to have detectable X4-tropic viruses (P=.012), and, when tropism was included in the survival analyses, the effect of the SDF1-3'A allele on disease progression was no longer significant. Therefore, the increased frequency of X4-tropic viruses in subjects carrying the SDF1-3'A allele may explain the observed adverse effect that this allele has on the natural history of HIV-1 disease.
OBJECTIVE: To determine the influence of pol replication capacity on the natural history of HIV-1 infection. DESIGN: Pol replication capacity was measured using a recombinant virus single cycle assay on baseline plasma specimens from subjects enrolled in the Hemophilia Growth and Development Study. SETTING: Children and adolescents with hemophilia and HIV-1 infection were enrolled at multiple sites across the USA into a natural history study. PARTICIPANTS: The Hemophilia Growth and Development Study enrolled 207 HIV-1-infected hemophiliacs between 6 and 19 years of age in 1989 and 1990. Subjects were followed every 6 months through 1997 with pol replication capacity measurements available from 128 of the subjects. MAIN OUTCOME MEASURES: A univariate model defined the relationship between pol replication capacity and HIV-1 RNA and CD4 T-cell number. A random effects model assessed the ability of this measure to predict CD4 T-cell decline over time and a Cox proportional hazards model and Kaplan-Meier analyses defined how it predicts clinical progression. RESULTS: Pol replication capacity measures correlated with baseline HIV-1 RNA, R = 0.189 (P = 0.03) and CD4 T-cell number, -0.197 (P = 0.03). It also independently predicted CD4 T-cell decline over time and progression to AIDS. CONCLUSIONS: This study demonstrates that pol replication capacity independently influences the natural history of HIV-1 infection.
The relationship between hepatitis C virus (HCV) genotype and HCV and human immunodeficiency virus (HIV) type 1 disease is not well defined. The present study analyzed data from a cohort of 207 HIV-1-infected and 126 HIV-1-uninfected children and adolescents with hemophilia who enrolled in the Hemophilia Growth and Development Study and were followed for 7 years. The mean HCV RNA level was higher in the participants in the HCV genotype 1 group than in the participants the HCV non-genotype 1 group, among both the HIV-1-infected (difference, +0.33 log(10) copies/mL; P=.038) and HIV-1-uninfected (difference, +0.59 log(10) copies/mL; P=.008) participants. Although HCV genotype was not associated with differences in HIV-1 RNA level, a significantly lower mean CD4(+) T cell count (difference, -127 cells/ microL; P=.026) and percentage of CD4(+) T cells (difference, -4.3%; P=.027) were observed in the participants in the HCV genotype 1 group, compared with those in the participants in the HCV non-genotype 1 group. In addition, the participants in the HCV genotype 1 group were at increased risk for progression to AIDS-related mortality (hazard ratio, 2.44; P=.037). The present study suggests that HCV infection and genotype may influence the natural history of HCV and HIV-1 disease.
The aim of the study is to determine the causes and frequency of hospitalization in HIV-negative boys and adolescents with haemophilia and evaluate their impact on academic achievement. One hundred and twenty-six HIV-negative boys and adolescents were followed prospectively from 1989-96, at 14 comprehensive haemophilia treatment centres. One hundred and fifteen participants with haemophilia A or B were included in the investigation. These participants contributed an average of 57.8 months of follow-up. There were 203 hospitalizations in 65 participants and 50 participants were never hospitalized. Haemarthroses and soft tissue bleeds accounted for 46 and 44 causes of hospitalization. Central line infection was the third most common cause. Participants with inhibitor had the majority of central line infections and hospitalizations. Intracranial haemorrhage resulted in five hospitalizations in two participants. Other causes of bleeding accounted for 22% of hospitalizations. The median number of hospitalizations per year was 0.18. Duration of hospital stay was significantly related to lower spelling scores. Acute and chronic joint problems and soft tissue bleeds still account for the majority of hospitalizations. Positive inhibitor status was associated with higher numbers of hospitalizations and central line infections. Academic achievement was affected, to some degree, by length of hospital stay.
OBJECTIVE: To quantify practice effects associated with annual administrations of WISC-R and WAIS-R in children and adolescents with and without hemophilia. METHODS: Participants were young men (age: 7-19; 80 with hemophilia, 30 siblings) enrolled in the Hemophilia Growth and Development Study. Participants with hemophilia completed age-appropriate Wechsler scales at baseline and at four annual follow-ups; the siblings, at baseline and one 2-year follow-up. Regression analyses were used to quantify average changes in scores, adjusting for variables related to test performance. RESULTS: Consecutive annual evaluations were free of significant practice effects for 4 years with the Verbal Scale and for 2 years with the Performance Scale. VIQ decreased, and PIQ increased over time. Baseline VIQ was related to changes in VIQ; baseline PIQ and number of test-specific retests were related to changes in PIQ. CONCLUSIONS: The findings support use of Wechsler scales for annual evaluations to monitor cognitive development in children and adolescents.
Coinfection with hepatitis C virus (HCV) and HIV-1 is common in patients with hemophilia and in intravenous drug users. Little, however, is known about the relation between HIV-1 and HCV coinfection and the effects on HCV clearance and pathogenesis. We examined data from 207 HIV-1-infected and 126 HIV-1-uninfected patients with hemophilia enrolled in the multicenter Hemophilia Growth and Development Study. Participants were observed during prospective follow-up for approximately 7 years with annual measurements of alanine aminotransferase (ALT), CD4+ cells, and HCV and HIV-1 RNA levels. Clearance of HCV was more likely to occur in those uninfected with HIV-1 (14.3 versus 2.5%; odds ratio [OR] 4.79; 95% confidence interval [CI], 1.63-14.08, p =.005) and was more common with decreasing age (OR, 1.23; 95% CI, 1.04-1.47; p =.017). HCV RNA levels were higher throughout the 7 years of follow-up in those HIV-1-infected (p <.001). In the HIV-1-infected participants, baseline CD4+ cells were inversely related to HCV RNA with every 100-cell increase associated with a 0.19 log10 copy/ml decrease in HCV RNA (p =.002), and HIV-1 and HCV RNA levels were directly related (p =.008). Increasing HCV RNA levels were also associated with significantly higher ALT levels regardless of HIV-1 infection status. These results demonstrate that HIV-1/HCV co-infection is associated with a reduced likelihood of HCV clearance and that higher levels of HCV RNA are associated with increased hepatic inflammation.
Hepatitis C virus (HCV) and human immunodeficiency virus type 1 (HIV-1) coinfection is common in hemophiliacs and injection drug users. To assess the interaction between HCV load and HIV-1 disease progression, we examined 207 HIV-1/HCV-coinfected patients. Patients were followed prospectively for approximately 7 years, and annual measurements of CD4(+) cell counts and HCV and HIV-1 loads were obtained. Survival analysis was used to define the independent effects of HCV load on HIV-1 progression. After controlling for CD4(+) cell count and HIV-1 RNA level, every 10-fold increase in baseline HCV RNA was associated with a relative risk (RR) for clinical progression to acquired immunodeficiency syndrome (AIDS) of 1.66 (95% confidence interval [CI], 1.10-2.51; P=.016) and an RR for AIDS-related mortality of 1.54 (95% CI, 1.03-2.30; P=.036). These findings emphasize the need for further research regarding the use of HIV-1- and HCV-specific therapy in coinfected individuals.
OBJECTIVE: The investigation examined the associations of plasma human immunodeficiency virus (HIV) RNA and CD4(+) T lymphocytes with height, weight, skeletal maturation, testosterone levels, and height velocity for hemophilic children and adolescents with HIV infection in the Hemophilia Growth and Development Study. STUDY DESIGN: Two hundred seven participants were evaluated over 7 years. RESULTS: A threefold increment in baseline plasma HIV RNA was associated with a 0.98-cm decrease in height and a 1.67-kg decrease in weight; 100-cells/microL decrements in baseline CD4(+) were associated with a 2.51-cm decrease in height and a 3.83-kg decrease in weight. Participants with high plasma HIV RNA (>3125 copies/mL) experienced significant delay in achieving maximum height velocity and lower maximum velocity compared with those with low viral load. The high CD4(+) (>243)/low plasma HIV RNA group had earlier age at maximum height velocity compared with the other 3 groups and higher maximum height velocity compared with the low CD4(+)/high plasma HIV RNA and low CD4(+)/low plasma HIV RNA groups. Decrements in CD4(+) were associated with decreases in bone age and testosterone level. CONCLUSIONS: CD4(+) and HIV RNA were important in predicting growth outcomes.
OBJECTIVE: To assess differences in caregiver report of youth and family psychosocial adjustment associated with HIV infection and greater immune compromise in youths with hemophilia. METHODS: Caregivers of 162 boys with hemophilia 8 to 20 years old completed three youth and family questionnaires (Personality Inventory for Children, Revised [PIC-R]; Questionnaire on Resources and Stress [QRS]; Family Environment Scale). RESULTS: Caregivers of HIV positive (HIV+) youths reported greater health concerns, social withdrawal (PIC-R), physical and adaptive limitations associated with illness (QRS) in their sons, and more pessimism about their sons' future and negative attitudes about parenting (QRS). Caregivers of HIV+ youths with greater immune compromise reported greater concerns about their sons' health and greater pessimism about their futures, as well as lower levels of family integration and more limited family opportunities. CONCLUSIONS: Results suggest caregivers perceive psychosocial problems in HIV+ youths with hemophilia and their families; some problems are specifically associated with greater immune compromise.