Characteristics of foot fractures in HIV-infected patients previously treated with tenofovir versus non-tenofovir-containing highly active antiretroviral therapy

Arash A Horizon1, Robert J Joseph2, Qiming Liao3, Steven T Ross3, Gary E Pakes31Center for Rheumatology, 2Surgical Podiatry, Los Angeles, CA, USA; 3GlaxoSmithKline, Research Triangle Park, NC, USASummary: In a retrospective case series study, medical records were evaluated for all male patients infected with human immunodeficiency virus (HIV) diagnosed over a one-year period with foot fractures (n = 30) confirmed by magnetic resonance imaging at a Los Angeles outpatient private practice rheumatology clinic. Proportionally more patients had received tenofovir prefracture (17 [57%]) than those who had not (13 [43%]). At fracture diagnosis, these two groups were similar in median age (49 versus 48 years), HIV-1 RNA (both 1.7 log10 copies/mL), CD4 count (300 versus 364/mm3), time between HIV diagnosis and foot fracture (both 17 years), family history of degenerative bone disease (24% versus 23%), prevalence of malabsorption syndrome, renal failure, calcium deficiency, or vitamin D deficiency, and concurrent use of bisphosphonates, calcitonin, and diuretics. However, more tenofovir-treated patients had osteoporosis (35% versus 8%), stress-type fractures (53% versus 31%), concurrent fractures (12% versus 0%), wasting syndrome (29% versus 15%), truncal obesity (18% versus 8%), smoked cigarettes (more than one pack/day for more than one year; 35% versus 8%), dual energy X-ray absorptiometry (DEXA) T scores <–2.4 (denoting osteoporosis) at the femur (24% versus 9%) and spine (47% versus 36%), and had received protease inhibitors (71% versus 46%), non-nucleoside reverse transcriptase inhibitors (24% versus 0%), prednisone (24% versus 0%), testosterone (47% versus 23%), and teriparatide (29% versus 8%). Median time from tenofovir initiation until fracture was 2.57 (range 1.17–5.69) years. In conclusion, more foot fractures were observed in tenofovir-treated patients than in non-tenofovir-treated patients with HIV infection. Comorbidities and/or coadministered drugs may have been contributory.Keywords: HIV infection, fractures, antiretroviral therapy, tenofovi

Response by gender of HIV-1-infected subjects treated with abacavir/lamivudine plus atazanavir, with or without ritonavir, for 144 weeks

Kathleen E Squires,1 Benjamin Young,2,3 Lizette Santiago,4 Robin H Dretler,5 Sharon L Walmsley,6 Henry H Zhao,7 Gary E Pakes,8 Lisa L Ross,8 Mark S Shaefer8 On behalf of the ARIES Study Team 1Thomas Jefferson University, Philadelphia, PA, 2Apex Family Medicine and Research, Denver, CO, 3International Association of Physicians in AIDS Care, Washington DC, USA; 4HOPE Clinic and Wellness Center, San Juan, Puerto Rico; 5ID Specialists of Atlanta, Decatur, GA, USA; 6University Health Network, Toronto, ON, Canada; 7GlaxoSmithKline, 8ViiV Healthcare, Research Triangle Park, NC, USA Purpose: The 144-week results of the open-label, multicenter Atazanavir/Ritonavir Induction with Epzicom Study (ARIES) were stratified by gender to compare treatment responses.Methods: A total of 369 HIV-infected, antiretroviral-naïve subjects receiving once-daily abacavir/lamivudine + atazanavir/ritonavir (ATV/r) whose HIV-1 RNA was <50 copies/mL by week 30 were randomized 1:1 at week 36 to maintain or discontinue ritonavir for 108 subsequent weeks. Between- and within-treatment gender-related efficacy and safety differences were analyzed.Results: Subjects were 85% male; 64% white; and had a mean age of 39 years, baseline median HIV-1 RNA of 114,815 copies/mL, and median CD4+ cell count of 198 cells/mm3. Gender (ATV [n=189]: 29 females/160 males; ATV/r [n=180]: 25 females/155 males) and most other demographics were similar between groups; more females than males were black (65% vs 25%) and fewer females had baseline HIV-1 RNA ≥100,000 copies/mL (41% vs 58%). At week 144, no significant differences between genders were observed in proportion maintaining HIV-1 RNA <50 copies/mL (ATV, 79% vs 77%; ATV/r, 60% vs 75%) or <400 copies/mL (ATV, 83% vs 84%; ATV/r, 68% vs 82%) (intent-to-treat-exposed: time to loss of virologic response analysis); median CD4+ change from baseline (ATV, +365 vs +300 cells/mm3; ATV/r, +344 vs +301 cells/mm3); proportion with treatment-related grade 2–4 adverse events (baseline to week 144: ATV, 41% vs 31%; ATV/r, 36% vs 43%; weeks 36 to 144: ATV, 14% vs 13%; ATV/r, 24% vs 23%); or proportion developing fasting lipid changes. Female and male virologic failure rates (ATV, 0 vs 5; ATV/r, 2 vs 4) and proportions completing the study were similar during the extension phase. Primary withdrawal reasons were loss to follow-up and pregnancy for females and loss to follow-up and other for males.Conclusion: Over 144 weeks, no significant gender differences were observed in efficacy, safety, or fasting lipid changes with abacavir/lamivudine +ATV or abacavir/lamivudine +ATV/r. Keywords: ARIES, HIV-infected, gender, virologic efficacy&nbsp

Operationalisation of the 25% policy target for desiccation; measures, costs and effects. Background document with respect to the National Environmental Outlook 1993-2015 and the Water Policy Evaluation Document

In dit onderzoek is getracht aan te geven welke maatregelen (type, sterkte en locatie) nodig zijn om de 25% reductie van het verdroogde areaal conform de doelstelling binnen bereik te brengen. Tevens is aangegeven wat de kosten zijn die met de maatregelen samenhangen en tot welke natuurwinst de maatregelen zullen leiden. Ten behoeve van het onderzoek is in nauwe samenwerking met de provincies in betrekkelijk korte tijd een nieuwe, landsdekkende inventarisatie van het verdroogde areaal uitgevoerd ; deze actie heeft geleid tot de 'Indicatieve kaart van verdroogde gebieden met een natuurfunctie'. Het blijkt dat binnen een gebied van ruim 400.000 ha gebiedsdelen voorkomen die deel uit maken van deze aangewezen natuurgebieden en die als verdroogd worden aangemerkt. Met deze kaart als uitgangspunt is vervolgens een maatregelenpakket samengesteld, dat bij uitvoering zou moeten leiden tot opheffing van de hydrologische verdroging in ca 25% van het verdroogde areaal, zoals het verhogen van het polderpeil in peilbeheerste gebieden, het verhogen van het beek- en stuwpeil in vrij afwaterende gebieden, het verhogen van de drainagebasis en de drainageweerstand in vrij afwaterende gebieden en het reduceren c.q. staken van een aantal grondwaterwinningen voor de openbare drinkwatervoorziening. De hydrologische effecten van de maatregelen zijn berekend met het Landelijk Grondwater Model LGM en met DEMGEN. De effecten op de natuur zijn berekend met het Dosis Effect Model NAtuur Terrestrisch, afgekort DEMNAT. Uit de berekeningen met het LGM blijkt, dat in ruim 1000 km2 van het verdroogde areaal de GVG voldoende omhoog komt om de hydrologische verdroging op te heffen. Daarmee voldoet dit maatregelenpakket juist aan de 25%-doelstelling. De consequenties voor de drinkwatervoorziening zijn doorgerekend met het model DRISIM. Ten gevolge van de maatregelen zal de natuurwaarde in het modelgebied met ca 42.000 nwe toenemen, hetgeen (toevalligerwijs) ook 25% is van de actuele natuurwaarde binnen het modelgebied (162.000 nwe). Uit het onderzoek blijkt voorts dat: het theoretisch en technisch mogelijk is de 25%-doelstelling te realiseren. Gezien de omvang van de maatregelen en de problemen waar dat in de praktijk op zal stuiten, is het niet waarschijnlijk dat de doelstelling in 2000 zal worden gerealiseerd ; om de 25%-doelstelling te realiseren niet volstaan kan worden met lokale kleinschalige maatregelen binnen de gebieden met bestemming natuur, maar dat ook maatregelen in de regio, aansluitend aan de natuurgebieden, noodzakelijk zijn; specifieke gebiedsgerichte maatregelen effectiever zijn dan generieke maatregelen, met andere woorden de bestrijding van de verdroging vraagt om maatwerk ; in het algemeen waterhuishoudkundige maatregelen ten opzichte van het reduceren of realloceren van grondwaterwinningen veel effectiever zijn, alhoewel in bepaalde regio's specifieke plaatselijke omstandigheden tot andere conclusies kunnen leiden.In 1990 the policy target was stated to reduce the area occupied by nature reserves showing signs of desiccation by 25% in 2000 with respect to the 1985 situation. In the survey described in this report the measures (type, force and location) necessary to reach the target have been elaborated, along with the costs and the ecological benefits of the package of measures calculated. In close cooperation with the provinces, a new inventory has been made of nature reserves showing signs of desiccation. An area of about 4000 km2 was identified as nature reserve territory containing large or small apparently desiccated parts. This overall area of 4000 km2 turned out to be far more than presumed to date. In about 2500 km2 of the desiccated area these measures were calculated with a hydrological-numerical model. About half (1200 km2) of the area is desiccated ; the rest is found in the transition zone. In all cases extra water supply emanating from external areas realizing the higher surface water levels was assumed not done because of the negative effects of the poor water quality in most cases. Furthermore, there is evidence that: it is theoretically possible to realize the 25% policy target but when the extent of the measures to be taken is considered, it will not be possible before 2000 ; to realize the 25% target it will not be sufficient to take locally scaled measures only ; regional scale measures have also to be taken; measures specific to an area are more effective than generic measures, so abating desiccation needs tailormade solutions; measures with respect to the surfacewater system are far more effective than the reduction and/or abandoning of groundwater withdrawals.DGM/DWL R