Unfortunately no trends in retention in care were

Unfortunately, no trends in retention in care were presented by Nsanzimana and colleagues, and the method used to estimate life expectancy—the abridged life table method—is not well suited to answering questions about trends in quality of care, because it src inhibitors allows little scope for multivariate analysis. Using an alternative method—the relative survival model—we have recently shown that some improvement in life expectancy is likely to have occurred in South Africa, after controlling for both differences in baseline CD4 count and antiretroviral therapy duration across different calendar years. However, the improvement was small when compared with the more substantial improvements reported in studies from high-income countries and the Rwandan study, which did not fully control for baseline CD4 count and duration of antiretroviral therapy (). Finally, as the investigators point out, the improvements in life expectancy in Rwanda might partly be due to improvements in non-HIV mortality.
An estimated 305 800 newborn babies have sickle cell anemia, and about two-thirds of these babies are born in Africa. The burden of disease is expected to rise as a result of improved survival in high-prevalence low-income and middle-income countries. Since the first clinical description of sickle-cell anaemia more than 100 years ago, only one drug, hydroxyurea, has been shown to have proven efficacy for amelioration of symptoms. Human stem-cell transplantation remains the only cure but is not available in many developing countries where the burden of disease is highest. Attention must therefore focus on the use of the relatively more accessible hydroxyurea. However, a few critical questions remain about the applicability of this simple regimen in low-resource, high-burden settings. Evidence suggests that widespread implementation of hydroxyurea for the management of sickle-cell anaemia in these settings might be a leap in the dark. In November, 2014, the US National Heart, Lung, and Blood Institute announced the end of a hydroxyurea efficacy trial because of unequivocal results of efficacy in children. The TWiTCH (Transcranial doppler With Transfusions Changing to Hydroxyurea) study was a clinical phase 3 randomised trial at 25 medical centres in the USA and Canada that compared monthly erythrocyte transfusions (standard therapy) with daily hydroxyurea (the alternative) for 121 children between 4–16 years of age with sickle-cell anaemia and abnormally elevated transcranial doppler velocities, and thus at high risk of stroke. Follow-up was originally scheduled for 24 months, but the study was terminated after only half the children completed the treatment phase owing to overwhelming evidence of benefit in the hydroxyurea-treated group. In a previous multicentre, randomised, double-blind, placebo-controlled trial of hydroxyurea in infants and young children, Wang and colleagues assessed the effect of a fixed dose (20 mg/kg) of hydroxyurea in children aged 9–18 months with haemoglobin SS or haemoglobin Sβ(0)thalassaemia. The investigators reported clinical benefits of hydroxyurea, including lower rates of pain and dactylitis, admission to hospital, and transfusion. However, benefits on renal, splenic, and neurological function were inconclusive. Mild-to-moderate neutropenia was found, but there were no associated increase in infections. In a subgroup of children, naive and memory T-cell subsets and antibody responses to pneumococcal, measles, mumps, and rubella vaccines were measured. The hydroxyurea-treated group had significantly lower total CD4 lymphocyte and memory T-cell count than did the control group. Although antibody concentrations between the two groups were equivalent at study exit, aggregates took longer to reach an antibody peak in the hydroxyurea-treated group. The practical implication of this finding in measles-endemic settings with suboptimum immunisation coverage is unknown. Clearly, this scenario could pose a public health concern in the event of disease outbreaks, such as is often the case with measles in most developing countries.