In-reservoir transformation of dissolved organic matter as a function of hydrological flow.

Reservoirs are vital to meet the ever-increasing demands for freshwater in a warming climate. Dissolved organic matter (DOM) represents an important pool of carbon and can be a major concern in drinking water sources. However, insights into DOM dynamics in temperate, semi-arid reservoirs remain limited. Therefore, we investigated the variations in DOM properties in Lake Diefenbaker, a large reservoir on the Canadian Prairies, by analyzing eight years of DOM concentrations and composition through linear mixed effect modeling. Contrary to expectations, reservoir dissolved organic carbon (DOC) concentration showed no correlation with inflow from the South Saskatchewan River (p = 0.12), while dissolved organic nitrogen (DON) increased with decreasing inflow (p = 0.002). DOM optical indices (SUVA254 and E4:E6 ratio) and DOC:DON ratio revealed a pronounced influence of inflow on reservoir DOM composition (p < 0.001), i.e., allochthonous characteristics increased with increasing flow, and autochthonous characteristics increased with declining flow. Travel time corrected comparison of approximately the same water parcel along the reservoir length revealed that increasing water residence time in downstream regions led to a significant transformation in DOM composition, favoring autochthonous characteristics (mean SUVA254 reduced by 0.52 L mg-C-1 m-1, and the E4:E6 and spectral slope ratio increased by 1.6 and 0.06, respectively). Autochthonous DOC inputs likely offset the allochthonous DOC losses, which resulted in a relatively stable DOC concentration throughout the reservoir (mean 3.7 mg L-1). Additionally, the effect of a large aquaculture operation on reservoir DOM properties was investigated, but no effect was detected. The results have significant implications for managing large river-reservoirs. Autochthonous DOM poses challenges to water processing, necessitating monitoring of DOM composition for reservoir drinking water quality. Insights on climate-induced changes in DOM properties will also assist with understanding changes to habitat conditions and contaminant transport.

Actions in Support of Newborn Screening for Critical Congenital Heart Disease - United States, 2011-2018.

In 2011, the U.S. Department of Health and Human Services added critical congenital heart disease (CCHD), which occurs in two of every 1,000 births, to the list of conditions recommended to states for universal newborn screening (1). Without early detection, infants with CCHD are at risk for substantial morbidity and death in the first weeks and months of life (2). Based on 2007-2013 data, deaths from CCHD and other cardiac causes in infants aged <6 months significantly declined in infants born in eight states after they had fully implemented mandated newborn CCHD screening policies by June 2013 (3). CDC collaborated with the American Academy of Pediatrics (AAP) and the Association of Public Health Laboratories' Newborn Screening Technical Assistance and Evaluation Program (NewSTEPs) to update a 2015 report (4) on states' actions toward adopting and implementing policies supporting CCHD newborn screening. In 2018, all 50 states and the District of Columbia (DC) had implemented CCHD screening policies, and, with one exception, all states mandated that screening be done (California mandates that screening be offered). However, not all states had data systems in place for tracking all screening results and outcomes. Ongoing evaluation activities, which rely on screening data, could help identify program improvement opportunities and monitor the impact of early identification of CCHD.

State Legislation, Regulations, and Hospital Guidelines for Newborn Screening for Critical Congenital Heart Defects - United States, 2011-2014.

Critical congenital heart defects (CCHD) occur in approximately two of every 1,000 live births. Newborn screening provides an opportunity for reducing infant morbidity and mortality. In September 2011, the U.S. Department of Health and Human Services (HHS) Secretary endorsed the recommendation that critical congenital heart defects be added to the Recommended Uniform Screening Panel (RUSP) for all newborns. In 2014, CDC collaborated with the American Academy of Pediatrics (AAP) Division of State Government Affairs and the Newborn Screening Technical Assistance and Evaluation Program (NewSTEPs) to assess states' actions for adopting newborn screening for CCHD. Forty-three states have taken action toward newborn screening for CCHD through legislation, regulations, or hospital guidelines. Among those 43, 32 (74%) are collecting or planning to collect CCHD screening data; however, the type of data collected by CCHD newborn screening programs varies by state. State mandates for newborn screening for CCHD will likely increase the number of newborns screened, allowing for the possibility of early identification and prevention of morbidity and mortality. Data collection at the state level is important for surveillance, monitoring of outcomes, and evaluation of state CCHD newborn screening programs.

Effects of regional climate, hydrology and river impoundment on long-term patterns and characteristics of dissolved organic matter in semi-arid northern plains rivers.

Diverse environmental and anthropogenic factors, such as the ongoing reservoir constructions may influence riverine dissolved organic matter (DOM) properties. This has important implications for river water quality, particularly when reservoirs are a source of drinking water. Simultaneous studies of multidecadal trends in dissolved organic carbon (DOC) and dissolved organic nitrogen (DON) are scarce. We studied the patterns in DOC and DON concentration in two major rivers of the South Saskatchewan River (SSR) basin over a 42-year period (1978-2019). We also examined the impact of a large reservoir on riverine DOC properties. Contrary to many studies, we did not find a long-term increase in DOC and DON concentration, and DOC and DON patterns were not always synchronous. In an agriculture dominated watershed like the SSR basin, agricultural land use (e.g., nitrogen-fertilizer application) could influence DOC and DON concentration differently, potentially resulting in asynchronous patterns over time. River discharge was an important driver of DOM patterns. Regional precipitation in the lower SSR basin may also influence DOM patterns in locations where runoff contribution is greater. These regional factors explained greater variability in DOM compared to global scale indices (e.g., Pacific decadal oscillation) due to their direct control on DOM. A travel time corrected approach to account for the lengthy reservoir turnover time showed that a large reservoir caused a reduction in allochthonous DOC characteristics through photodegradation and perhaps, an increase in autochthonous characteristics. Our results illustrate: 1) the increase in DOM concentrations seen in the northern hemisphere is not present in semi-arid prairie rivers, 2) Controls on different DOM components could be different, and 3) large reservoirs may modify riverine DOC composition due to longer water residence time.

Investigating the combined effects of pH changes and UV radiation exposure on dissolved metal-humate complexes: an important process in aquatic systems.

An in vitro study was carried out to examine the impact of UV exposure on metal-dissolved humic material (M-DHM) complexes in aqueous systems at different pH. Complexation reactions of dissolved M (Cu, Ni, and Cd) with DHM increased with the increasing pH of the solution. Kinetically inert M-DHM complexes dominated at higher pH in the test solutions. Exposure to UV radiation did affect the chemical speciation of M-DHM complexes at different pH of the systems. The overall observation suggests that exposure to increasing UV radiation increased the lability, mobility, and bioavailability of M-DHM complexes in aquatic environments. The dissociation rate constant of Cu-DHM was found to be slower than Ni-DHM and Cd-DHM complexes (both before and after UV exposure). At a higher pH range, Cd-DHM complexes dissociated after exposure to UV radiation and a part of this dissociated Cd precipitated out from the system. No change in the lability of the produced Cu-DHM and Ni-DHM complexes after UV radiation exposure was observed. They did not appear to form new kinetically inert complexes even after 12 h of exposure. The outcome of this research has important global implications. The results of this study helped to understand DHM leachability from soil and its effect on dissolved metal concentrations in the Northern Hemisphere water bodies. The results of this study also facilitated to comprehend the fate of M-DHM complexes at photic depths (where pH changes are accompanied by high UV radiation exposure) in tropical marine/freshwater systems during summer.

Response of phytoplankton community composition to physicochemical and meteorological factors under different hydrological conditions in Lake Diefenbaker.

Changes in hydro-meteorological conditions due to warming climate and the operation of reservoirs may support algal blooms. Lake Diefenbaker is a large reservoir on the Canadian Prairies. Annual flow volume from its major tributary, the South Saskatchewan River (SSR), varies with precipitation and temperature in the Rocky Mountains. Furthermore, plans are underway to increase water abstraction from Lake Diefenbaker for irrigation. Therefore, we used a nine-year dataset that comprised a drought year (1984), four consecutive high flow years (2011 to 2014), and four subsequent low flow years (2015 to 2018) to investigate how these changes could affect the major phytoplankton groups and cyanobacterial community. Diatoms (38.5%) were the most abundant phytoplankton, followed by cryptomonads (28.9%) under low and high flow years. Diatoms were associated with greater mixing in late spring and fall, whereas the cryptomonads were related to the high nutrients from spring flow. Cyanobacteria (79.3%) contributed the greatest to the total phytoplankton biomass under drought; we hypothesized that the high abundance of cyanobacteria during drought was associated with thermocline deepening and subsequent internal loading of nutrients. Microcystis, a potential bloom-forming and toxin-producing genus, was dominant during the drought and correlated with reduced water level, increased air temperature, and moderate wind speed. Although its biomass was low, another potential bloom-forming and toxin-producing genus, Aphanizomenon, was present in low and high flow years. Aphanizomenon was correlated with decreased SSR flow and increased particulate carbon to particulate phosphorus ratios, which may be related to their ability to cope with P limitation. These results highlight that Lake Diefenbaker and other similar reservoirs are vulnerable to an increase in potential toxic cyanobacteria species with future expectations of climate warming and water abstraction.

In situ UVA exposure modulates change in the uptake of radiophosphate in size-fractionated plankton assemblages following UVR exposure.

We investigated the effect of ultraviolet radiation (UVR) on the uptake and partitioning of radiophosphate ((33)PO (4) (3-) ) in size-fractionated plankton assemblages (0.2-0.8, 0.8-2.0 and >2.0 µm) collected from nine freshwater lakes located in Saskatchewan, Canada. A significant (p < 0.05) reduction in (33)PO (4) (3-) uptake by plankton was observed in seven of the nine lakes. Plankton >2.0 µm were generally unaffected by UVR, whereas the 0.2-0.8 µm size fraction exhibited severe photoinhibition. The effect of UVR on the 0.8-2.0 µm size fraction was variable, ranging from significant reductions to significant increases in (33)PO (4) (3-) uptake. The >2.0 µm size fraction was composed of a diversity of phytoplankton genera, suggesting that P uptake mechanisms for a range of phytoplankton are resistant to UVR. Our ability to detect a UVR effect on specific plankton size fractions was confounded by the resolution of the analysis. That is, only examining the <2.0 and >2.0 µm size fractions concealed the effect of UVR on plankton <0.8 µm. The magnitude of decrease in P uptake by plankton <0.8 µm was significantly and negatively correlated with in situ UVA exposure. Our results underscore the need for studies to consider both the size resolution of their analysis (i.e., the size of target organisms) and the ambient light conditions under which organisms may have acclimated before generalizing results across limnetic systems.

Understanding the factors associated with long-term reconstructed turbidity in Lake Diefenbaker from Landsat-imagery.

Turbidity affects a variety of aquatic ecosystem processes. Turbidity events are dominated by suspended sediment in many systems. High levels of suspended sediment in lakes can occur during periods of high inflows from turbid tributaries or suspension of sediment from lake beds. This study reconstructed historic turbidity levels using Landsat-imagery on Lake Diefenbaker (LD), a large river-reservoir constructed in the late 1960's on the naturally turbid South Saskatchewan River (SSR). We examined the factors that were associated with it. Reconstructed turbidity levels, from Landsat-images, were similar to actual turbidity. The SSR flow and wind speed explained 64%, 54% and 69% of the variability in estimated turbidity levels at the riverine zone, the transition zone and the entire reservoir, respectively. The decrease in estimated turbidity from June to October and down the length of the reservoir is likely associated with the decline in the SSR flow and the settling of suspended sediments. The relationship between estimated turbidity and wind speed may be associated with the re-suspension of bottom sediment at the upper reach of LD. Wind speed and direction were related to estimated turbidity at the lacustrine zone (r2adj = 0.19, P < 0.05), which may be attributed to the persistence of sediments. We observed high turbidity in 2002 that exceeded other estimates of turbidity. Since 2002 was preceded by a prolonged drought, the high estimate turbidity may be related to an increase in sediment loads from the SSR flow and an increase in shoreline erosion from a rise in LD's water level. Hence, extreme events (drought and flooding) are associated with high turbidity in LD. As the Canadian Prairies continues to undergo climate change, lakes located in this region are predicted to experience more frequent extreme events. These extreme events will cause further deterioration of water quality.

Dissolved organic carbon in eastern Canadian lakes: Novel patterns and relationships with regional and global factors.

Long-term patterns in dissolved organic carbon (DOC) concentrations in 49 eastern Canadian lakes from four sites were re-examined with a ~ 35-year (~1980-2015) dataset. The study sites were Dorset (number of lakes, n = 8), Experimental Lakes Area (ELA, n = 4), Kejimkujik (n = 26) and Yarmouth (n = 11). Lake DOC patterns were synchronous within each site. However, comparisons of DOC patterns across sites showed that they were synchronous only between the Kejimkujik and Yarmouth locations. Hence, these two sites were pooled into a single Nova Scotia site (NS). Increases in DOC concentration were evident in Dorset, Ontario from 1988 (r2 = 0.78, p < 0.001) and NS from 2000 (r2 = 0.43, p = 0.006). DOC at the ELA in northwestern Ontario had a different pattern compared to the other sites, i.e., DOC had increased earlier (1983-2000), and then, unlike Dorset and NS, neither an increase nor decrease was detected between 2001 and 2015 (p = 0.78). Precipitation and sulfur deposition explained the greatest variance in DOC patterns at the Dorset and NS sites (i.e., precipitation: 21-49% and sulfur deposition: 24-54%). Precipitation was the most important driver of DOC at the ELA. Our results indicate that all the sites have gone through a process of increasing DOC, but at different times. The stabilizing pattern at the ELA since 2001 may suggest that DOC concentrations in ELA lakes have reached, or are approaching a new equilibrium, a phenomenon that was not observed at the other sites. Also, the increase in DOC was not always associated with declining sulfur deposition (e.g., ELA). Therefore, we conclude that there was considerable variation in DOC patterns across this large geographic region of Canada and potential drivers of these patterns were not consistent across these diverse sites.

Gay men who engage in group sex are at increased risk of HIV infection and onward transmission.

Among 746 participants in the Three or More Study (TOMS) of gay men who engaged in group sex in the previous 6 months, 22.4% reported unprotected anal intercourse (UAI) with any partners they did not know to be the same HIV serostatus as themselves. Not knowing oneself to be HIV-negative, not having a clear intention to use condoms, and more frequent group sex were independently associated with UAI. This study shows that gay men who engage in group sex represent an important priority for targeted HIV prevention activities and research.

Sediment plume model-a comparison between use of measured turbidity data and satellite images for model calibration.

In this study, we built a two-dimensional sediment transport model of Lake Diefenbaker, Saskatchewan, Canada. It was calibrated by using measured turbidity data from stations along the reservoir and satellite images based on a flood event in 2013. In June 2013, there was heavy rainfall for two consecutive days on the frozen and snow-covered ground in the higher elevations of western Alberta, Canada. The runoff from the rainfall and the melted snow caused one of the largest recorded inflows to the headwaters of the South Saskatchewan River and Lake Diefenbaker downstream. An estimated discharge peak of over 5200 m3/s arrived at the reservoir inlet with a thick sediment front within a few days. The sediment plume moved quickly through the entire reservoir and remained visible from satellite images for over 2 weeks along most of the reservoir, leading to concerns regarding water quality. The aims of this study are to compare, quantitatively and qualitatively, the efficacy of using turbidity data and satellite images for sediment transport model calibration and to determine how accurately a sediment transport model can simulate sediment transport based on each of them. Both turbidity data and satellite images were very useful for calibrating the sediment transport model quantitatively and qualitatively. Model predictions and turbidity measurements show that the flood water and suspended sediments entered upstream fairly well mixed and moved downstream as overflow with a sharp gradient at the plume front. The model results suggest that the settling and resuspension rates of sediment are directly proportional to flow characteristics and that the use of constant coefficients leads to model underestimation or overestimation unless more data on sediment formation become available. Hence, this study reiterates the significance of the availability of data on sediment distribution and characteristics for building a robust and reliable sediment transport model.

The effects of phosphorus additions on the sedimentation of contaminants in a uranium mine pit-lake.

We investigated the usefulness of phytoplankton for the removal of surface water contaminants. Nine large mesocosms (92.2m(3)) were suspended in the flooded DJX uranium pit at Cluff Lake (Saskatchewan, Canada), and filled with highly contaminated mine water. Each mesocosm was fertilized with a different amount of phosphorus throughout the 35 day experiment to stimulate phytoplankton growth, and to create a range in phosphorus load (g) to examine how contaminants may be affected by different nutrient regimes. Algal growth was rapid in fertilized mesocosms (as demonstrated by chlorophyll a profiles). As phosphorus loads increased there were significant declines (p<0.05) in the surface water concentrations of As, Co, Cu, Mn, Ni, and Zn. This decline was near significant for uranium (p=0.065). The surface water concentrations of Ra-226, Mo, and Se showed no relationship to phosphorus load. Contaminant concentrations in sediment traps suspended at the bottom of each mesocosm generally showed the opposite trend to that observed in the surface water, with most contaminants (As, Co, Cu, Mn, Ni, Ra-226, U, and Zn) exhibiting a significant positive relationship (p<0.05) with phosphorus load. Selenium and Mo did not respond to nutrient treatments. Our results suggest that phytoremediation has the potential to lower many surface water contaminants through the sedimentation of phytoplankton. Based on our results, we estimate that the Saskatchewan Surface Water Quality Objectives (SSWQO) for DJX pit would be met in approximately 45 weeks for Co, 65 weeks for Ni, 15 weeks for U, and 5 weeks for Zn.

Centralized assessment of dual-energy X-ray absorptiometry (DEXA) in multicenter studies of HIV-associated lipodystrophy.

BACKGROUND: The accurate measurement of total body and subcutaneous fat is essential if therapeutic interventions, aimed at preventing or reversing lipodystrophy syndrome, are to be adequately assessed. The aim of this study was to investigate the variability of dual-energy X-ray absorptiometry (DEXA) scans analysis performed at local sites compared to central analysis in a multicenter clinical trial. METHOD: The PIILR study was a multicenter randomized clinical trial in which 80 HIV-infected patients with physician-documented lipodystrophy had serial measurements of body composition performed with Lunar DEXA scans. Scans were analyzed at local sites and then were reanalyzed centrally. RESULTS: DEXA scans from 73 patients who completed 24 weeks study were compared. Greater variation in the locally analyzed results than in the centrally reanalyzed data was noted, with arm, leg, and combined limb fat being most divergent between the local and centralized assessments (ratio of local to central standard deviation was 1.28, 1.31, and 1.35, respectively). The magnitude of this variance was enough to alter statistically relevant differences between study populations. CONCLUSION: Quality assurance is an important issue in the use of DEXA scans to determine body fat composition in multicenter research studies. A central quality assurance site should be incorporated to reduce variability in results.

A comparison of phosphorus deficiency indicators with steady state phosphate in lakes.

A fundamental step in the management of nutrient impacted water bodies is the determination of the type and degree of nutrient limitation. However, nutrient deficiency indicators often provide inconsistent results. Recent advances in the measurement of phosphate concentrations may provide a better means to understand results from P deficiency indicators. With regards to phosphorus, deficiency indicators should predict P-limitation when phosphate concentrations are consistently low. We use this new understanding to examine the relationships between phosphate concentration and P deficiency. Patterns of steady state phosphate (ssPO(4)(3-)) concentrations and P deficiency were evaluated in 109 lakes located across Canada. Lakes encompassed a broad range in TP concentration (1.79-139.7 µg L(-1)). The relationships between ssPO(4)(3-) concentrations and simultaneously measured total P (TP), total dissolved P (TDP) and soluble reactive P (SRP) concentrations, particulate C:P and N:P ratios, alkaline phosphatase activities (APA) and phosphate turnover times (TT) were analyzed. ssPO(4)(3-) was positively correlated with TP and TDP. The ssPO(4)(3-) concentrations were 2-3 orders of magnitude lower than SRP concentrations. These two measures were only weakly correlated, suggesting that SRP is a major overestimate of PO(4)(3-). The ssPO(4)(3-) concentrations were negatively correlated with C:P and N:P ratios, and with APA, consistent with expectations. When only lakes with TT < 15 min were considered, TT was negatively correlated with TP, challenging the idea that nutrients become less limiting in more eutrophic systems. Overall, P deficiency indicators related to ssPO(4)(3-) in the expected manner. However, variability in relationships with APA and particulate stoichiometry emphasize the need for cautious interpretation of P deficiency measurements. We recommend simultaneous use of multiple techniques to confidently assess P deficiency.

The role of drugs during group sex among gay men in Australia.

BACKGROUND: Drug use has been associated with risk behaviour among gay men. We examined the use of drugs and sexual risk behaviour among homosexually-active men who engaged in group sex in Australia. METHODS: We used an anonymous, self-complete survey about participants' most recent occasion of group sex with other men and in-depth interviews with a small number of these survey participants. The 746 men who reported having engaged in group sex within the previous 6 months were included in these analyses. RESULTS: Among 746 men who engaged in group sex within the previous 6 months, 63.0% reported using illicit drugs at the group sex encounter. Men commonly reported using drugs specifically to enhance their sexual experience and to intensify the pleasure of that experience. After controlling for each drug type and other risk factors, only use of methamphetamine (odds ratio = 1.74, confidence interval = 1.06-2.88, P = 0.030) and having more than five drinks (odds ratio = 2.41, confidence interval = 1.34-4.33, P = 0.003) were independently associated with unprotected anal intercourse with non-HIV seroconcordant partners in multivariate analysis. CONCLUSION: Methamphetamine and heavy alcohol use are associated with increased sexual risk behaviour among men who engage in group sex. Within more 'adventurous' gay community subcultures, drug use is often for the explicit purpose of enhancing the sexual experience and this complex relationship may be key to understanding HIV risk among these men.

Sex comparison of hamstring structural and material properties.

BACKGROUND: Musculotendinous stiffness provides an estimate of resistance to joint perturbation, thus contributing to joint stability. Females demonstrate lesser hamstring stiffness than males, potentially contributing to the sex discrepancy in anterior cruciate ligament injury risk. However, it is unclear if the sex difference in hamstring stiffness is due to differences in muscle size or to inherent/material properties of the musculotendinous unit. It was hypothesized that hamstring stiffness, stress, strain, and elastic modulus would be greater in males than in females, and that hamstring stiffness would be positively correlated with muscle size. METHODS: Stiffness was assessed in 20 males and 20 females from the damping effect imposed by the hamstrings on oscillatory knee flexion/extension following joint perturbation. Hamstring length and change in length were estimated via motion capture, and hamstring cross-sectional area was estimated using ultrasound imaging. These characteristics were used to calculate hamstring material properties (i.e., stress, strain, and elastic modulus). FINDINGS: Stiffness was significantly greater in males than in females (P<0.001). However, stress, strain, and elastic modulus did not differ across sex (P>0.05). Stiffness was significantly correlated with cross-sectional area (r=0.395, P=0.039) and the linear combination of cross-sectional area and resting length (R(2)=0.156, P=0.043). INTERPRETATION: Male's hamstrings possess a greater capacity for resisting changes in length imposed via joint perturbation from a structural perspective, but this property is similar across sex from a material perspective. Females demonstrate lesser hamstring stiffness compared to males in response to standardized loading conditions, indicating a compromised ability to resist changes in length associated with joint perturbation, and potentially contributing to the higher female ACL injury risk. However, the difference in hamstring stiffness is attributable in large part to differences in muscle size.

Comparison of hamstring neuromechanical properties between healthy males and females and the influence of musculotendinous stiffness.

The hamstrings limit anterior cruciate ligament (ACL) loading, and neuromuscular control of these muscles is crucial for dynamic knee joint stability. Sex differences in electromechanical delay (EMD) and rate of force production (RFP) have been reported previously, and attributed to differences in musculotendinous stiffness (MTS). These characteristics define the neuromechanical response to joint perturbation, and sex differences in these characteristics may contribute to the greater female ACL injury risk. However, it is unclear if these differences exist in the hamstrings, and the relationship between MTS and neuromechanical function has not been assessed directly. Hamstring MTS, EMD, the time required to produce 50% peak force (Time50%), and RFP were assessed in 20 males and 20 females with no history of ACL injury. EMD did not differ significantly across sex (p=0.788). However, MTS (p<0.001) and RFP (p=0.003) were greater in males, Time50% (p=0.013) was shorter in males, and Time50% was negatively correlated with MTS (r=-0.332, p=0.039). These results suggest that neuromechanical hamstring function in females may limit dynamic knee joint stability, potentially contributing to the greater female ACL injury risk. However, future research is necessary to determine the direct influences of MTS and neuromechanical function on dynamic knee joint stability and ACL injury risk.

Abacavir substitution for nucleoside analogs in patients with HIV lipoatrophy: a randomized trial.

CONTEXT: Peripheral lipoatrophy may complicate antiretroviral therapy of human immunodeficiency virus (HIV) infection, often related to duration and type of nucleoside analog therapy, and may have a mitochondrial pathogenesis. No proven therapy exists for lipoatrophy, but abacavir is a nucleoside analog that may be less toxic to mitochondria. OBJECTIVE: To determine if substitution of stavudine or zidovudine with abacavir improves HIV lipoatrophy without affecting control of HIV replication. DESIGN: Randomized, open-label 24-week study. SETTING: Seventeen hospital HIV outpatient clinics and primary care centers in Australia and England, with randomization from June 2000 through January 2001. PARTICIPANTS: A total of 111 adults (109 men) with moderate or severe lipoatrophy who were receiving stavudine (n = 85) or zidovudine (n = 26) and had stable plasma HIV RNA levels below 400 copies/mL and no prior abacavir therapy. INTERVENTION: Patients were randomly assigned to switch from stavudine or zidovudine to abacavir, 300 mg twice per day, while continuing all other antiretroviral therapy (n = 54) or to continue all antiretroviral therapy (n = 57). MAIN OUTCOME MEASURES: The primary end point was limb fat mass, measured by dual-energy x-ray absorptiometry; key secondary end points were plasma HIV RNA levels, adverse events, physician-assessed (via subjective measures) lipodystrophy severity, total and central fat mass, and fasting metabolic (lipid, glycemic, and lactate) levels. RESULTS: There was a significant increase in limb fat in the abacavir group relative to the stavudine/zidovudine group (0.39 vs 0.08 kg; mean difference, 0.31; 95% confidence interval [CI], 0.06-0.57 kg), as well as significant relative increases in subcutaneous thigh (P =.01), arm (P<.001), and abdominal (P =.001) fat areas on computed tomography. Switching had no significant effect on secondary end points, including plasma HIV RNA (for unadjusted comparison between groups at week 24, odds ratio, 1.38; 95% CI, 0.48-3.96). Change in limb fat mass at week 24 did not correlate with change in subjectively determined perceived lipoatrophy severity (r = -0.06; P =.53 by Spearman correlation). Hypersensitivity to abacavir was seen in 5 patients (10%). CONCLUSIONS: In this sample of lipoatrophic HIV-infected adults, switching from stavudine or zidovudine to abacavir for 24 weeks led to significant, albeit modest, objectively measured increases in limb fat. Clinical lipoatrophy, as assessed subjectively, did not resolve, however, and at the rate of increase observed may take years to resolve with use of this strategy. Longer-term follow-up is needed.