Outcomes of the South African National Antiretroviral Treatment Programme for children: the IeDEA Southern Africa collaboration

OBJECTIVES: To assess paediatric antiretroviral treatment (ART) outcomes and their associations from a collaborative cohort representing 20% of the South African national treatment programme. DESIGN AND SETTING: Multi-cohort study of 7 public sector paediatric ART programmes in Gauteng, Western Cape and KwaZulu-Natal provinces. SUBJECTS: ART-naive children (< or = 16 years) who commenced treatment with > or = 3 antiretroviral drugs before March 2008. OUTCOME MEASURES: Time to death or loss to follow-up were assessed using the Kaplan-Meier method. Associations between baseline characteristics and mortality were assessed with Cox proportional hazards models stratified by site. Immune status, virological suppression and growth were described in relation to duration of ART. RESULTS: The median (interquartile range) age of 6 078 children with 9 368 child-years of follow-up was 43 (15 - 83) months, with 29% being < 18 months. Most were severely ill at ART initiation. More than 75% of children were appropriately monitored at 6-monthly intervals with viral load suppression (< 400 copies/ml) being 80% or above throughout 36 months of treatment. Mortality and retention in care at 3 years were 7.7% (95% confidence interval 7.0 - 8.6%) and 81.4% (80.1 - 82.6%), respectively. Together with young age, all markers of disease severity (low weight-for-age z-score, high viral load, severe immune suppression, stage 3/4 disease and anaemia) were independently associated with mortality. CONCLUSIONS: Dramatic clinical benefit for children accessing the national ART programme is demonstrated. Higher mortality in infants and those with advanced disease highlights the need for early diagnosis of HIV infection and commencement of ART.

Climatic change and contemporaneous land-use phases north and south of the Alps 2300 BC to 800 AD

Fluctuations in the Δ14C curve and subsequent gaps of archaeological findings at 800–650 and 400–100 BC in western and central Europe may indicate major climate-driven land-abandonment phases. To address this hypothesis radiocarbon-dated sediments from four lakes in Switzerland were studied palynologically. Pollen analysis indicates contemporaneous phases of forest clearances and of intensified land-use at 1450–1250 BC, 650–450 BC, 50 BC–100 AD and around 700 AD. These land-use expansions coincided with periods of warm climate as recorded by the Alpine dendroclimatic and Greenland oxygen isotope records. Our results suggest that harvest yields would have increased synchronously over wide areas of central and southern Europe during periods of warm and dry climate. Combined interpretation of palaeoecological and archaeological findings suggests that higher food production led to increased human populations. Positive long-term trends in pollen values of Cerealia and Plantago lanceolata indicate that technical innovations during the Bronze and Iron Age (e.g. metal ploughs, scythes, hay production, fertilising methods) gradually increased agricultural productivity. The successful adoption of yield-increasing advances cannot be explained by climatic determinism alone. Combined with archaeological evidence, our results suggest that despite considerable cycles of spatial and demographic reorganisation (repeated land abandonments and expansions, as well as large-scale migrations and population decreases), human societies were able to shift to lower subsistence levels without dramatic ruptures in material culture. However, our data imply that human societies were not able to compensate rapidly for harvest failures when climate deteriorated. Agriculture in marginal areas was abandoned, and spontaneous reforestations took place on abandoned land south and north of the Alps. Only when the climate changed again to drier and warmer conditions did a new wide-spread phase of forest clearances and field extensions occur, allowing the reoccupation of previously abandoned areas. Spatial distribution of cereal cultivation and growth requirements of Cerealia species suggest that increases in precipitation were far more decisive in driving crop failures over central and southern Europe than temperature decreases.