A randomized controlled trial of genotypic HIV drug resistance testing in HIV-1-infected children: the PERA (PENTA 8) trial.

OBJECTIVE: To evaluate the longer-term utility of genotypic resistance testing in HIV-1-infected children with virological failure. METHODS: Children aged 3 months-18 years switching antiretroviral therapy (ART) with HIV-1 RNA > 2,000 copies/ml were randomized between genotypic testing (Virtual Phenotype) and no testing at baseline and subsequent virological failures. Children were followed to at least 96 weeks. RESULTS: One hundred and seventy eligible children, from 24 clinical centres in six countries, were randomized to resistance testing (n = 87) or no testing (n = 83) between June 2000-July 2003. At baseline, mean HIV-1 RNA and CD4+ T-cell percentage were 4.7 log10 copies/ml and 20%, respectively. Children had taken ART for a mean of 5 years; 24% had received all three classes, 53% nucleoside reverse transcriptase inhibitors (NRTIs)+protease inhibitors (PIs), 9% NRTIs+non-nucleoside reverse transcriptase inhibitors (NNRTIs) and 14% NRTIs only. There was no difference between the arms in the drug classes or the individual PIs/NNRTIs prescribed. However, 49% in the resistance test arm (RT) versus 19% in the no-test arm (NT) continued at least one NRTI from their failing regimen; 56% versus 19% were prescribed didanosine+stavudine as their NRTI backbone. Adjusting for baseline HIV-1 RNA, mean reductions in HIV-1 RNA at 48 weeks were 1.51 log10 copies/ml in the RT arm and 1.23 in the NT arm (P = 0.3); the difference between the arms was smaller at week 96 (RT: 1.50, NT: 1.47; P = 0.9). CONCLUSION: In this first paediatric trial of resistance testing, we observed a substantial difference in NRTI-prescribing behaviour across arms. However statistically significant evidence of a long-term virological or immunological benefit was not observed. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN14367816.

Haematological risk factors for pregnancy outcome in Jamaican women with homozygous sickle cell disease

OBJECTIVE; To examine the association between fetal outcome and the steady state haematology of mothers with homozygous sickle cell disease. DESIGN; A retrospective observational study. The data were taken from the dockets, kept at the Sickle Cell Clinic at the University Hospital of the West Indies or two peripheral clinics operated by the staff of the MRC Laboratories. SUBJECTS; All women aged 14 years or older with homozygous sickle cell disease who had experienced at least one pregnancy in the period 1977 to 1986. MAIN OUTCOME MEASURES; Three fetal outcomes including miscarriages, perinatal deaths, and birthweight. RESULTS; There were 270 singleton pregnancies in 175 women with an overall fetal wastage of 32.2 percent. There was a significant increased risk of perinatal death with low maternal fetal haemoglobin level, but there was no haematological associations with miscarriages or birthweight. CONCLUSIONS: These data suggest that maternal steady-state haemoglobin has little influence on fetal outcome, with the exception that mothers with high HbF levels are less prone to perinatal deaths. Further study is required to investigate acute haematological changes associated with pregnancy. (AU)

The haematology of homozygous sickle-cell disease - abstract

The purpose of the study was to investigate age- and sex-related variations in the haematology of older patients with SS disease, in order to determine haematological characteristics possibly favouring survival. Steady state haematology was available in 181 patients aged 40-73 years. There appeared to be no consistent sex differences in any of the indices examined. Longitudinal analyses were performed for the 133 patients with at least two observations, using analysis of covariance (ANCOVA) methods. Highly significant declines in total haemoglobin (Hb), platelet counts and absolute reticulocyte count were displayed in both sexes. Overall, Hb levels decreased by approximately 0.076 gm/dl/year in females and 0.113 gm/dl/year in males. Significant increases occurred in HbA, HbF and MCV in females only. The total nucleated count (NBC) fell with age, although the decline was only significant in females. These observations are consistent with a progressive bone marrow failure which is not explained by the commonly occurring renal impairment in older SS patients since the changes persisted in analyses confined to the 84 patients with normal creatinine levels (C=120 æmol/l). The mechanism for this bone marrow failure is currently unknown. The prevalence of homozygous alpha thalassaemia in the study group (4.4 percent) was similar to that in the overall SS population, providing no evidence that this may lead to improved survival, as has been suggested (AU)

Risk factors for proliferative sickle retinopathy

The prevalence, incidence, and risk factors associated with proliferative sickle retinopathy (PSR) were investigated in 786 patients with homozygous sickle cell (SS) disease and 533 patients with sickle cell hemo globin C (SC) disease. PSR was more common in SC disease, in which there was a significant predominance of males, and it increased with age in both genotypes. In SC disease the risk of developing PSR was highest between 15 and 24 years in males, between 20 and 39 years in females, and in SS disease between 25 and 39 years in both sexes. PSR tended to be bilateral, especially in SC disease. There was no evidence of familial clustering of PSR in SC siblings, and insufficient numbers of SS siblings were available to test for clustering. Haematological risk factors associated with PSR in SS disease were a high haemoglobin in males and a low fetal haemoglobin in both sexes and in SC disease, a high mean cell volume, and a low fetal haemoglobinin females. (AU)

Diabetic maculopathy in a Jamaican population

Maculopathy is the commonest cause of severe visual loss diabetic retinopathy in Jamaica [5]. Ophthalmic assessment of 158 black Jamaican maturity onset diabetics referred randomly from the primary and secondary health centres, demonstrated maculopathy in 48 percent of patients. Duration of diabetes was a strong risk factor for maculopathy (p less than 0.0010). Poor compliance with diabetic and hypertensive therapy may infleunce the prevalence of maculopathy (AU)

Gallstones in Jamaican children with homozygous sickle-cell disease - abstract

Gallstones were detected by ultrasonography in 30/226 (13 per cent) children with SS disease, aged 5-13 years, participating in a cohort study from birth. Children with gallstones had significantly lower total haemoglobin and foetal haemoglobin and higher bilirubin levels. Further analysis revealed that the apparent effects of Hb and HbF were secondary to their relationship with bilirubin levels. Abdominal pain crises were significantly associated with gallstones but both factors appeared to reflect an increased clinical severity and were probably not casually related. No patient had symptoms specific for gallstones. An association with abdominal pain crisis should not, of itself, be considered an indication for surgery (AU)

Abnormal thyroid hormone and thyrotropin levels in homozygous sickle cell disease

Male patients with SS disease had significantly lower T3 and higher TSH levels than a comparison group. Stimulation with TRH in 10 male sibling pairs showed highly significant increases in T3 and TSH in both patients and sibling controls although the increase in TSH was significantly greater in SS disease. The interpretation of these findings unclear although the thyroid indices indicate an abnormal pituitary-thyroid axis most consistent with a modest primary thyroid failure

The painful crisis of homozygous sickle cell disease: a study of the risk factors

Some epidemiologic features of the painful crisis in homozygous sickle cell disease were examined in a retrospective study of 995 painful crises. Previously reported associations with cold weather and pregnancy were confirmed. There was a striking increase in painful crises in male patients between the ages of 15 and 25 years, whereas female patients showed little age-related change. The frequency of painful crises correlated positively with hemoglobin levels and reticulocyte counts in female patients. There was a striking increase in painful crises in male patients with hemoglobin levels above 8.5 g/dL (>85 g/L). High hemoglobin levels appear to be an important risk factor for painful crises.(AU)