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1

When to start antiretroviral therapy.  

PubMed

Antiretrovirals perform superbly in combating HIV infection. But when to initiate therapy in asymptomatic, nonpregnant, hepatitis-free, HIV-infected persons is not securely established. Of two completed randomized trials using modern therapy, a Haitian trial demonstrated a benefit to initiating therapy between 200 and 350 CD4 cells/mm(3) as compared with less than 200 CD4 cells/mm(3) and an international trial demonstrated a benefit to starting at greater than 350 CD4 cells/mm(3) as compared with less than 250 CD4 cells/mm(3). Many observational cohorts support initiating treatment at less than 350 CD4 cells/mm(3). Of these, three large studies supported initiation at less than 350 cells/mm(3), less than 450 CD4 cells/mm(3), and less than 500 CD4 cells/mm(3), respectively, but only the last supported starting at higher counts. Such studies are not probative, given the problem of confounding. No conventional antiretroviral regimen is free of long-term adverse effects, especially over decades of use. All are expensive and require expensive monitoring. When resources are restricted, initiation of antiretrovirals for persons with high CD4 count diverts treatment from more needy persons. Pathophysiological considerations favor universal treatment because antiretrovirals mitigate systemic inflammation, which aggravates atherosclerosis. There are suggestions that HIV hastens the natural decline of cognitive, renal, and pulmonary function as well as bone mineral loss; the mechanism(s) are uncertain, as is the ability of antiretrovirals to counteract the probable acceleration. The four major guideline panels, although all have issued updates in the past year, are not consistent in recommendations for treatment of HIV-infected persons with counts greater than 350 CD4 cells/mm(3). PMID:21308456

Rhame, Frank S

2011-02-01

2

Should antiretroviral therapy be started earlier?  

Microsoft Academic Search

Current treatment guidelines recommend that antiretroviral therapy be deferred until the CD4 count has fallen into the 200\\u000a to 350 cells\\/mm3 range. However, treatment has become simpler, less toxic, and more forgiving of missed doses. Longer-term follow-up data\\u000a from clinical cohorts are now showing better outcomes when therapy is started at higher CD4 cell counts. Therapy initiated\\u000a early has better

Joel E. Gallant

2007-01-01

3

Central Nervous System Strongyloidiasis and Cryptococcosis in an HIV-Infected Patient Starting Antiretroviral Therapy.  

PubMed

We report a case of Strongyloides stercoralis hyperinfection syndrome with central nervous system involvement, in a patient with late human immunodeficiency virus (HIV) infection starting antiretroviral therapy, in whom Strongyloides stercoralis larvae and Cryptococcus neoformans were isolated antemortem from cerebrospinal fluid. Our patient was not from an endemic region for the parasite, so strongyloidiasis was not originally suspected. For this reason, we conclude that Strongyloides stercoralis infection should be suspected in HIV-infected patients starting antiretroviral therapy in order to avoid potential fatal outcomes. PMID:22924046

Rodríguez, Mónica; Flores, Paúl; Ahumada, Víctor; Vázquez-Vázquez, Lorena; Alvarado-de la Barrera, Claudia; Reyes-Terán, Gustavo

2012-08-08

4

Adherence, virological and immunological outcomes for HIV-infected veterans starting combination antiretroviral therapies  

PubMed Central

Objectives We aimed to determine adherence, virological, and immunological outcomes one year after starting a first combination antiretroviral therapy (ART) regimen. Design Observational; synthesis of administrative, laboratory, and pharmacy data. Antiretroviral regimens were divided into efavirenz, nevirapine, boosted protease inhibitor (PI), and single PI categories. Propensity scores were used to control for confounding by treatment assignment. Adherence was estimated from pharmacy refill records. Setting Veterans Affairs Healthcare System, all sites. Participants HIV-infected individuals starting combination ART with a low likelihood of previous antiretroviral exposure. Interventions None. Outcomes The proportion of antiretroviral prescriptions filled as prescribed, a change in log HIV-RNA, the proportion with log HIV-RNA viral suppression, a change in CD4 cell count. Results A total of 6394 individuals unlikely to have previous antiretroviral exposure started combination ART between 1996 and 2004, and were eligible for analysis. Adherence overall was low (63% of prescriptions filled as prescribed), and adherence with efavirenz (67%) and nevirapine (65%) regimens was significantly greater than adherence with boosted PI (59%) or single PI (61%) regimens (P < 0.001). Efavirenz regimens were more likely to suppress HIV-RNA at one year (74%) compared with nevirapine (62%), boosted PI (63%), or single PI (53%) regimens (all P < 0.001), and this superiority was maintained when analyses were adjusted for baseline clinical characteristics and propensity for treatment assignment. Efavirenz also yielded more favorable immunological outcomes. Conclusion HIV-infected individuals initiating their first combination ART using an efavirenz-based regimen had improved virological and immunological outcomes and greater adherence levels.

Braithwaite, R. Scott; Kozal, Michael J.; Chang, Chung Chou H.; Roberts, Mark S.; Fultz, Shawn L.; Goetz, Matthew Bidwell; Gibert, Cynthia; Rodriguez-Barradas, Maria; Mole, Larry; Justice, Amy C.

2012-01-01

5

Estimated mortality of adult HIV-infected patients starting treatment with combination antiretroviral therapy  

PubMed Central

Objective To provide estimates of mortality among HIV-infected patients starting combination antiretroviral therapy. Methods We report on the death rates from 122?925 adult HIV-infected patients aged 15?years or older from East, Southern and West Africa, Asia Pacific and Latin America. We use two methods to adjust for biases in mortality estimation resulting from loss from follow-up, based on double-sampling methods applied to patient outreach (Kenya) and linkage with vital registries (South Africa), and apply these to mortality estimates in the other three regions. Age, gender and CD4 count at the initiation of therapy were the factors considered as predictors of mortality at 6, 12, 24 and >24?months after the start of treatment. Results Patient mortality was high during the first 6?months after therapy for all patient subgroups and exceeded 40 per 100 patient years among patients who started treatment at low CD4 count. This trend was seen regardless of region, demographic or disease-related risk factor. Mortality was under-reported by up to or exceeding 100% when comparing estimates obtained from passive monitoring of patient vital status. Conclusions Despite advances in antiretroviral treatment coverage many patients start treatment at very low CD4 counts and experience significant mortality during the first 6?months after treatment initiation. Active patient tracing and linkage with vital registries are critical in adjusting estimates of mortality, particularly in low- and middle-income settings.

Yiannoutsos, Constantin Theodore; Johnson, Leigh Francis; Boulle, Andrew; Musick, Beverly Sue; Gsponer, Thomas; Balestre, Eric; Law, Matthew; Shepherd, Bryan E; Egger, Matthias

2012-01-01

6

The effect of efavirenz versus nevirapine-containing regimens on immunologic, virologic and clinical outcomes in a prospective observational study  

PubMed Central

Objective To compare regimens consisting of either efavirenz or nevirapine and two or more nucleoside reverse transcriptase inhibitors (NRTIs) among HIV-infected, antiretroviral-naive, and AIDS-free individuals with respect to clinical, immunologic, and virologic outcomes. Design Prospective studies of HIV-infected individuals in Europe and the US included in the HIV-CAUSAL Collaboration. Methods Antiretroviral therapy-naive and AIDS-free individuals were followed from the time they started an NRTI, efavirenz or nevirapine, classified as following one or both types of regimens at baseline, and censored when they started an ineligible drug or at 6 months if their regimen was not yet complete. We estimated the ‘intention-to-treat’ effect for nevirapine versus efavirenz regimens on clinical, immunologic, and virologic outcomes. Our models included baseline covariates and adjusted for potential bias introduced by censoring via inverse probability weighting. Results A total of 15 336 individuals initiated an efavirenz regimen (274 deaths, 774 AIDS-defining illnesses) and 8129 individuals initiated a nevirapine regimen (203 deaths, 441 AIDS-defining illnesses). The intention-to-treat hazard ratios [95% confidence interval (CI)] for nevirapine versus efavirenz regimens were 1.59 (1.27, 1.98) for death and 1.28 (1.09, 1.50) for AIDS-defining illness. Individuals on nevirapine regimens experienced a smaller 12-month increase in CD4 cell count by 11.49 cells/?l and were 52% more likely to have virologic failure at 12 months as those on efavirenz regimens. Conclusions Our intention-to-treat estimates are consistent with a lower mortality, a lower incidence of AIDS-defining illness, a larger 12-month increase in CD4 cell count, and a smaller risk of virologic failure at 12 months for efavirenz compared with nevirapine.

2013-01-01

7

Variability of Growth in Children Starting Antiretroviral Treatment in Southern Africa  

PubMed Central

BACKGROUND: Poor growth is an indication for antiretroviral therapy (ART) and a criterion for treatment failure. We examined variability in growth response to ART in 12 programs in Malawi, Zambia, Zimbabwe, Mozambique, and South Africa. METHODS: Treatment naïve children aged <10 years were included. We calculated weight for age z scores (WAZs), height for age z scores (HAZs), and weight for height z scores (WHZs) up to 3 years after starting ART, by using the World Health Organization standards. Multilevel regression models were used. RESULTS: A total of 17?990 children (range, 238–8975) were followed for 36?181 person-years. At ART initiation, most children were underweight (50%) and stunted (66%). Lower baseline WAZ, HAZ, and WHZ were the most important determinants of faster catch-up growth on ART. WAZ and WHZ increased rapidly in the first year and stagnated or reversed thereafter, whereas HAZ increased continuously over time. Three years after starting ART, WAZ ranged from ?2.80 (95% confidence interval [CI]: ?3.66 to ?2.02) to ?1.98 (95% CI: ?2.41 to ?1.48) in children with a baseline z score < ?3 and from ?0.79 (95% CI: ?1.62 to 0.02) to 0.05 (95% CI: ?0.42 to 0.51) in children with a baseline WAZ ? ?1. For HAZ, the corresponding range was ?2.33 (95% CI: ?2.62 to ?2.02) to ?1.27 (95% CI: ?1.58 to ?1.00) for baseline HAZ < ?3 and ?0.24 (95% CI: ?0.56 to 0.15) to 0.84 (95% CI: 0.53 to 1.16) for HAZ ? ?1. CONCLUSIONS: Despite a sustained growth response and catch-up growth in children with advanced HIV disease treated with ART, normal weights and heights are not achieved over 3 years of ART.

Gsponer, Thomas; Weigel, Ralf; Davies, Mary-Ann; Bolton, Carolyn; Moultrie, Harry; Vaz, Paula; Rabie, Helena; Technau, Karl; Ndirangu, James; Eley, Brian; Garone, Daniela; Wellington, Maureen; Giddy, Janet; Ehmer, Jochen; Egger, Matthias

2012-01-01

8

Nonadherence Increases the Risk of Hospitalization Among HIV-Infected Antiretroviral Naïve Patients Started on HAART  

Microsoft Academic Search

Background. Since the advent of highly active antiretroviral therapy (HAART), AIDS-related hospitalizations have decreased. The objective of this study was to assess the impact of adherence on hospitalization among antiretroviral-naïve HIV-infected persons initiating HAART. Methods. Analysis was based on a cohort of individuals initiating HAART between 1996 and 2001. The primary outcome was hospitalization for one or more days. Survival

Sarah J. Fielden; Melanie L. A. Rusch; Benita Yip; Evan Wood; Kate Shannon; Adrian R. Levy; Julio S. G. Montaner; Robert S. Hogg

2008-01-01

9

Considerations in the rationale, design and methods of the Strategic Timing of AntiRetroviral Treatment (START) study  

PubMed Central

Background Untreated human immunodeficiency virus (HIV) infection is characterized by progressive depletion of CD4+ T lymphocyte (CD4) count leading to the development of opportunistic diseases (acquired immunodeficiency syndrome (AIDS)), and more recent data suggest that HIV is also associated with an increased risk of serious non-AIDS (SNA) diseases including cardiovascular, renal, and liver diseases and non-AIDS-defining cancers. Although combination antiretroviral treatment (ART) has resulted in a substantial decrease in morbidity and mortality in persons with HIV infection, viral eradication is not feasible with currently available drugs. The optimal time to start ART for asymptomatic HIV infection is controversial and remains one of the key unanswered questions in the clinical management of HIV-infected individuals. Purpose In this article, we outline the rationale and methods of the Strategic Timing of AntiRetroviral Treatment (START) study, an ongoing multicenter international trial designed to assess the risks and benefits of initiating ART earlier than is currently practiced. We also describe some of the challenges encountered in the design and implementation of the study and how these challenges were addressed. Methods A total of 4000 study participants who are HIV type 1 (HIV-1) infected, ART naïve with CD4 count > 500 cells/?L are to be randomly allocated in a 1:1 ratio to start ART immediately (early ART) or defer treatment until CD4 count is <350 cells/ ?L (deferred ART) and followed for a minimum of 3 years. The primary outcome is time to AIDS, SNA, or death. The study had a pilot phase to establish feasibility of accrual, which was set as the enrollment of at least 900 participants in the first year. Results Challenges encountered in the design and implementation of the study included the limited amount of data on the risk of a major component of the primary endpoint (SNA) in the study population, changes in treatment guidelines when the pilot phase was well underway, and the complexities of conducting the trial in a geographically wide population with diverse regulatory requirements. With the successful completion of the pilot phase, more than 1000 participants from 100 sites in 23 countries have been enrolled. The study will expand to include 237 sites in 36 countries to reach the target accrual of 4000 participants. Conclusions START is addressing one of the most important questions in the clinical management of ART. The randomization provided a platform for the conduct of several substudies aimed at increasing our understanding of HIV disease and the effects of antiretroviral therapy beyond the primary question of the trial. The lessons learned from its design and implementation will hopefully be of use to future publicly funded international trials.

Babiker, Abdel G; Emery, Sean; Fatkenheuer, Gerd; Gordin, Fred M; Grund, Birgit; Lundgren, Jens D; Neaton, James D; Pett, Sarah L; Phillips, Andrew; Touloumi, Giota; Vjecha, Michael J

2012-01-01

10

Endothelial Function in HIV-Infected Antiretroviral Na?ve Subjects Before and After Starting Potent Antiretroviral Therapy: AIDS Clinical Trials Group Study 5152s  

PubMed Central

Objectives This study evaluated the effects of three class-sparing antiretroviral therapy (ART) regimens on endothelial function in HIV-infected subjects participating in a randomized trial. Background Endothelial dysfunction has been observed in patients receiving ART for human immunodeficiency virus (HIV) infection. Methods This was a prospective, multicenter study of treatment-naïve subjects who were randomly assigned to receive a protease inhibitor-sparing regimen of nucleoside reverse transcriptase inhibitors (NRTIs) + efavirenz, a non-nucleoside reverse transcriptase inhibitor-sparing regimen of NRTIs + lopinavir/ritonavir, or a NRTI-sparing regimen of efavirenz + lopinavir/ritonavir. NRTIs were lamivudine + stavudine, zidovudine, or tenofovir. Brachial artery flow-mediated dilation (FMD) was determined by B-mode ultrasound before starting on ART, then after 4 and 24 weeks. Results There were 82 subjects (median age 35 years, 91% men, 54% white). Baseline CD4 cell counts and plasma HIV RNA values were 245 cells/mm3 and 4.8 log10 copies/ml, respectively. At baseline, FMD was 3.68% (interquartile range 1.98 – 5.51%). After 4 and 24 weeks of ART, plasma HIV RNA decreased by 2.1 and 3.0 log10 copies/mL, respectively. FMD increased by 0.74% (?0.62 – +2.74, p=0.003) and 1.48% (?0.20 – +4.30%, p< 0.001), respectively, with similar changes in each arm (pKW>0.600). The decrease in plasma HIV RNA at 24 weeks was associated with greater FMD (rs=? 0.30, p=0.017). Conclusions Among treatment-naïve individuals with HIV, three different ART regimens rapidly improved endothelial function. Benefits were similar for all ART regimens, appeared quickly, and persisted at 24 weeks. Condensed Abstract Among 82 treatment-naïve HIV-infected subjects participating in a prospective, multicenter study of three class-sparing antiretroviral therapy regimens, flow-mediated dilation of the brachial artery improved after 4 (+0.74%, p=0.003) and 24 weeks (+1.48%, p< 0.001), with similar changes in each arm (pKW>0.600).

Torriani, Francesca J.; Komarow, Lauren; Parker, Robert A.; Cotter, Bruno R.; Currier, Judith S.; Dube, Michael P.; Fichtenbaum, Carl J.; Gerschenson, Mariana; Mitchell, Carol K.C.; Murphy, Robert L.; Squires, Kathleen; Stein, James H.

2008-01-01

11

Retention in Care of HIV-Infected Children from HIV Test to Start of Antiretroviral Therapy: Systematic Review  

PubMed Central

Background In adults it is well documented that there are substantial losses to the programme between HIV testing and start of antiretroviral therapy (ART). The magnitude and reasons for loss to follow-up and death between HIV diagnosis and start of ART in children are not well defined. Methods We searched the PubMed and EMBASE databases for studies on children followed between HIV diagnosis and start of ART in low-income settings. We examined the proportion of children with a CD4 cell count/percentage after after being diagnosed with HIV infection, the number of treatment-eligible children starting ART and predictors of loss to programme. Data were extracted in duplicate. Results Eight studies from sub-Saharan Africa and two studies from Asia with a total of 10,741 children were included. Median age ranged from 2.2 to 6.5 years. Between 78.0 and 97.0% of HIV-infected children subsequently had a CD4 cell count/percentage measured, 63.2 to 90.7% of children with an eligibility assessment met the eligibility criteria for the particular setting and time and 39.5 to 99.4% of the eligible children started ART. Three studies reported an association between low CD4 count/percentage and ART initiation while no association was reported for gender. Only two studies reported on pre-ART mortality and found rates of 13 and 6 per 100 person-years. Conclusion Most children who presented for HIV care met eligibility criteria for ART. There is an urgent need for strategies to improve the access to and retention to care of HIV-infected children in resource-limited settings.

Mugglin, Catrina; Wandeler, Gilles; Estill, Janne; Egger, Matthias; Bender, Nicole; Davies, Mary-Ann; Keiser, Olivia

2013-01-01

12

Mortality of HIV-infected patients starting potent antiretroviral therapy: comparison with the general population in nine industrialized countries  

PubMed Central

Background Mortality in HIV-infected patients has declined substantially with combination antiretroviral therapy (ART), but it is unclear whether it has reached that of the general population. We compared mortality in patients starting ART in nine countries of Europe and North America with the corresponding general population, taking into account their response to ART. Methods Eligible patients were enrolled in prospective cohort studies participating in the ART Cohort Collaboration. We calculated the ratio of observed to expected deaths from all causes [standardized mortality ratio (SMR)], measuring time from 6 months after starting ART, according to risk group, clinical stage at the start of ART and CD4 cell count and viral load at 6 months. Expected numbers of deaths were obtained from age-, sex- and country-specific mortality rates. Results Among 29 935 eligible patients, 1134 deaths were recorded in 131 510 person-years of follow-up. The median age was 37 years, 8162 (27%) patients were females, 4400 (15%) were injecting drug users (IDUs) and 6738 (23%) had AIDS when starting ART. At 6 months, 23 539 patients (79%) had viral load measurements ?500 copies/ml. The lowest SMR, 1.05 [95% confidence interval (CI) 0.82–1.35] was found for men who have sex with men (MSM) who started ART free of AIDS, reached a CD4 cell count of ?350 cells/?L and suppressed viral replication to ?500 copies/ml by the sixth month. In contrast, the SMR was 73.7 (95% CI 46.4–116.9) in IDUs who failed to suppress viral replication and had CD4 cell counts <50 cells/?L at 6 months. The percentage of patients with SMRs <2 was 46% for MSM, 42% for heterosexually infected patients and 0% for patients with a history of injection drug use. Corresponding percentages for SMRs >10 were 4, 14 and 47%. Conclusions In industrialized countries, the mortality experience of HIV-infected patients who start ART and survive the first 6 months continues to be higher than in the general population, but for many patients excess mortality is moderate and comparable with patients having other chronic conditions. Much of the excess mortality might be prevented by earlier diagnosis of HIV followed by timely initiation of ART.

2009-01-01

13

Development and Validation of Decision Rules to Guide Frequency of Monitoring CD4 Cell Count in HIV1 Infection before Starting Antiretroviral Therapy  

Microsoft Academic Search

BackgroundAlthough CD4 cell count monitoring is used to decide when to start antiretroviral therapy in patients with HIV-1 infection, there are no evidence-based recommendations regarding its optimal frequency. It is common practice to monitor every 3 to 6 months, often coupled with viral load monitoring. We developed rules to guide frequency of CD4 cell count monitoring in HIV infection before

Thierry Buclin; Amalio Telenti; Rafael Perera; Chantal Csajka; Hansjakob Furrer; Jeffrey K. Aronson; Paul P. Glasziou; Landon Myer

2011-01-01

14

Health-related quality of life and patient–provider relationships in HIV-infected patients during the first three years after starting PI-containing antiretroviral treatment  

Microsoft Academic Search

The aim of this study was to investigate factors associated with better health-related quality of life (HRQL) during the first three years after starting PI-containing antiretroviral treatment. Clinical, social and behavioural data from the APROCO cohort enabled us to analyze simultaneously the association between HRQL and patients’ relationships with their health care providers. A self-administered questionnaire collected information about HRQL

M. Préau; C. Leport; D. Salmon-ceron; P. Carrieri; H. Portier; G. Chene; B. Spire; P. Choutet; F. Raffi; M. Morin

2004-01-01

15

Predicting hospitalization among HIV-infected antiretroviral naïve patients starting HAART: Determining clinical markers and exploring social pathways  

Microsoft Academic Search

In the era of highly active antiretroviral therapy (HAART), hospitalization as a measure of morbidity has become of increasing interest. The objectives of this study were to determine clinical predictors of hospitalization among HIV-infected persons initiating HAART and to explore the impact of gender and drug use on hospitalization. The analysis was based on a cohort of HIV-positive individuals initiating

Sarah J. Fielden; Melanie L. A. Rusch; Adrian R. Levy; Benita Yip; Evan Wood; Richard P. Harrigan; Irene Goldstone; Silvia Guillemi; Julio S. Montaner; Robert S. Hogg

2008-01-01

16

Antiretroviral Treatment Start-Time during Primary SIVmac Infection in Macaques Exerts a Different Impact on Early Viral Replication and Dissemination  

PubMed Central

Background The time of infection is rarely known in human cases; thus, the effects of delaying the initiation of antiretroviral therapy (ART) on the peripheral viral load and the establishment of viral reservoirs are poorly understood. Methodology/Principal Findings Six groups of macaques, infected intravenously with SIVmac251, were given placebo or antiretroviral therapy to explore reservoir establishment; macaques were treated for 2 weeks, with treatment starting 4 hours, 7 or 14 days after infection. Viral replication and dissemination were measured in the gut (rectum), in the lung and in blood and lymphoid tissues (peripheral lymph nodes), by quantifying viral RNA, DNA and 2LTR circles. We used immunohistochemistry (CD4 and CD68) to assess the impact of these treatments on the relative amount of virus target cells in tissue. Treatment that was started 4 hours post-infection (pi) decreased viral replication and dissemination in blood and tissue samples, which were assessed on day 14 (RNA/DNA/2LTR circles). The virus remained detectable and lymphoid tissues were activated in LN and the gut in both placebo- and ART-treated animals. Viral RNA in plasma continued to be lower in macaques treated seven days after infection; however, this was not the case for viral DNA in peripheral blood mononuclear cells. There was a small but significant difference in RNA and DNA levels in tissues between placebo- and ART-treated animals on day 21. When started 14 days after infection, treatment resulted in a limited decrease in the plasma viral load. Conclusions Treatment that was started 4 hours after infection significantly reduced viral replication and dissemination. When started 7 days after infection, it was of slight virological benefit in peripheral blood and in tissues, and treatment was even less effective if started 14 days pi. These data favor starting ART no longer than one week after intravenous SIVmac251 exposure.

Sellier, Pierre; Mannioui, Abdelkrim; Bourry, Olivier; Dereuddre-Bosquet, Nathalie; Delache, Benoit; Brochard, Patricia; Calvo, Julien; Prevot, Sophie; Roques, Pierre

2010-01-01

17

Gender Differences in Survival among Adult Patients Starting Antiretroviral Therapy in South Africa: A Multicentre Cohort Study  

PubMed Central

Background Increased mortality among men on antiretroviral therapy (ART) has been documented but remains poorly understood. We examined the magnitude of and risk factors for gender differences in mortality on ART. Methods and Findings Analyses included 46,201 ART-naïve adults starting ART between January 2002 and December 2009 in eight ART programmes across South Africa (SA). Patients were followed from initiation of ART to outcome or analysis closure. The primary outcome was mortality; secondary outcomes were loss to follow-up (LTF), virologic suppression, and CD4+ cell count responses. Survival analyses were used to examine the hazard of death on ART by gender. Sensitivity analyses were limited to patients who were virologically suppressed and patients whose CD4+ cell count reached >200 cells/µl. We compared gender differences in mortality among HIV+ patients on ART with mortality in an age-standardised HIV-negative population. Among 46,201 adults (65% female, median age 35 years), during 77,578 person-years of follow-up, men had lower median CD4+ cell counts than women (85 versus 110 cells/µl, p<0.001), were more likely to be classified WHO stage III/IV (86 versus 77%, p<0.001), and had higher mortality in crude (8.5 versus 5.7 deaths/100 person-years, p<0.001) and adjusted analyses (adjusted hazard ratio [AHR] 1.31, 95% CI 1.22–1.41). After 36 months on ART, men were more likely than women to be truly LTF (AHR 1.20, 95% CI 1.12–1.28) but not to die after LTF (AHR 1.04, 95% CI 0.86–1.25). Findings were consistent across all eight programmes. Virologic suppression was similar by gender; women had slightly better immunologic responses than men. Notably, the observed gender differences in mortality on ART were smaller than gender differences in age-standardised death rates in the HIV-negative South African population. Over time, non-HIV mortality appeared to account for an increasing proportion of observed mortality. The analysis was limited by missing data on baseline HIV disease characteristics, and we did not observe directly mortality in HIV-negative populations where the participating cohorts were located. Conclusions HIV-infected men have higher mortality on ART than women in South African programmes, but these differences are only partly explained by more advanced HIV disease at the time of ART initiation, differential LTF and subsequent mortality, and differences in responses to treatment. The observed differences in mortality on ART may be best explained by background differences in mortality between men and women in the South African population unrelated to the HIV/AIDS epidemic. Please see later in the article for the Editors' Summary.

Cornell, Morna; Schomaker, Michael; Garone, Daniela Belen; Giddy, Janet; Hoffmann, Christopher J.; Lessells, Richard; Maskew, Mhairi; Prozesky, Hans; Wood, Robin; Johnson, Leigh F.; Egger, Matthias; Boulle, Andrew; Myer, Landon

2012-01-01

18

Clinical Differences between Younger and Older Adults with HIV/AIDS Starting Antiretroviral Therapy in Uganda and Zimbabwe: A Secondary Analysis of the DART Trial  

PubMed Central

Objective Clinical and immunological data about HIV in older adults from low and middle income countries is scarce. We aimed to describe differences between younger and older adults with HIV starting antiretroviral therapy in two low–income African countries. Methods Setting: HIV clinics in Uganda and Zimbabwe. Design: Secondary exploratory cross-sectional analysis of the DART randomized controlled trial. Outcome Measures: Clinical and laboratory characteristics were compared between adults aged 18-49 years (younger) and ? 50 years (older), using two exploratory multivariable logistic regression models, one with HIV viral load (measured in a subset pre-ART) and one without. Results A total of 3316 eligible participants enrolled in DART were available for analysis; 219 (7%) were ? 50 years and 1160 (35%) were male. Across the two adjusted regression models, older adults had significantly higher systolic blood pressure, lower creatinine clearance and were consistently less likely to be females compared to younger adults with HIV. Paradoxically, the models separately suggested that older adults had statistically significant (but not clinically important) higher CD4+ cell counts and higher plasma HIV–1 viral copies at initiation. Crude associations between older age and higher baseline hemoglobin, body mass index, diastolic blood pressure and lower WHO clinical stage were not sustained in the adjusted analysis. Conclusions Our study found clinical and immunological differences between younger and older adults, in a cohort of Africans starting antiretroviral therapy. Further investigations should explore how these differences could be used to ensure equity in service delivery and affect outcomes of antiretroviral therapy.

Parikh, Sujal M.; Obuku, Ekwaro A.; Walker, Sarah A.; Semeere, Aggrey S.; Auerbach, Brandon J.; Hakim, James G.; Mayanja-Kizza, Harriet; Mugyenyi, Peter N.; Salata, Robert A.; Kityo, Cissy M.

2013-01-01

19

Supplementary feeding with either ready-to-use fortified spread or corn-soy blend in wasted adults starting antiretroviral therapy in Malawi: randomised, investigator blinded, controlled trial  

PubMed Central

Objective To investigate the effect of two different food supplements on body mass index (BMI) in wasted Malawian adults with HIV who were starting antiretroviral therapy. Design Randomised, investigator blinded, controlled trial. Setting Large, public clinic associated with a referral hospital in Blantyre, Malawi. Participants 491 adults with BMI <18.5. Interventions Ready-to-use fortified spread (n=245) or corn-soy blend (n=246). Main outcome measures Primary outcomes: changes in BMI and fat-free body mass after 3.5 months. Secondary outcomes: survival, CD4 count, HIV viral load, quality of life, and adherence to antiretroviral therapy. Results The mean BMI at enrolment was 16.5. After 14 weeks, patients receiving fortified spread had a greater increase in BMI and fat-free body mass than those receiving corn-soy blend: 2.2 (SD 1.9) v 1.7 (SD 1.6) (difference 0.5, 95% confidence interval 0.2 to 0.8), and 2.9 (SD 3.2) v 2.2 (SD 3.0) kg (difference 0.7 kg, 0.2 to 1.2 kg), respectively. The mortality rate was 27% for those receiving fortified spread and 26% for those receiving corn-soy blend. No significant differences in the CD4 count, HIV viral load, assessment of quality of life, or adherence to antiretroviral therapy were noted between the two groups. Conclusion Supplementary feeding with fortified spread resulted in a greater increase in BMI and lean body mass than feeding with corn-soy blend. Trial registration Current Controlled Trials ISRCTN67515515.

2009-01-01

20

Development and Validation of Decision Rules to Guide Frequency of Monitoring CD4 Cell Count in HIV-1 Infection before Starting Antiretroviral Therapy  

PubMed Central

Background Although CD4 cell count monitoring is used to decide when to start antiretroviral therapy in patients with HIV-1 infection, there are no evidence-based recommendations regarding its optimal frequency. It is common practice to monitor every 3 to 6 months, often coupled with viral load monitoring. We developed rules to guide frequency of CD4 cell count monitoring in HIV infection before starting antiretroviral therapy, which we validated retrospectively in patients from the Swiss HIV Cohort Study. Methodology/Principal Findings We built up two prediction rules (“Snap-shot rule” for a single sample and “Track-shot rule” for multiple determinations) based on a systematic review of published longitudinal analyses of CD4 cell count trajectories. We applied the rules in 2608 untreated patients to classify their 18 061 CD4 counts as either justifiable or superfluous, according to their prior ?5% or <5% chance of meeting predetermined thresholds for starting treatment. The percentage of measurements that both rules falsely deemed superfluous never exceeded 5%. Superfluous CD4 determinations represented 4%, 11%, and 39% of all actual determinations for treatment thresholds of 500, 350, and 200×106/L, respectively. The Track-shot rule was only marginally superior to the Snap-shot rule. Both rules lose usefulness for CD4 counts coming near to treatment threshold. Conclusions/Significance Frequent CD4 count monitoring of patients with CD4 counts well above the threshold for initiating therapy is unlikely to identify patients who require therapy. It appears sufficient to measure CD4 cell count 1 year after a count >650 for a threshold of 200, >900 for 350, or >1150 for 500×106/L, respectively. When CD4 counts fall below these limits, increased monitoring frequency becomes advisable. These rules offer guidance for efficient CD4 monitoring, particularly in resource-limited settings.

Buclin, Thierry; Telenti, Amalio; Perera, Rafael; Csajka, Chantal; Furrer, Hansjakob; Aronson, Jeffrey K.; Glasziou, Paul P.

2011-01-01

21

Toxicity-related antiretroviral drug treatment modifications in individuals starting therapy: A cohort analysis of time patterns, sex, and other risk factors  

PubMed Central

Background Modifications to combination antiretroviral drug therapy (CART) regimens can occur for a number of reasons, including adverse drug effects. We investigated the frequency of and reasons for antiretroviral drug modifications (ADM) during the first 3 years after initiation of CART, in a closed cohort of CART-naïve adult patients who started treatment in the period 1998–2007 in Croatia. Material/Methods We calculated differential toxicity rates by the Poisson method. In multivariable analysis, we used a discrete-time regression model for repeated events for the outcome of modification due to drug toxicity. Results Of 321 patients who started CART, median age was 40 years, 19% were women, baseline CD4 was <200 cells/mm3 in 71%, and viral load was ?100 000 copies/mL in 69%. Overall, 220 (68.5%) patients had an ADM; 124 (56%) of these had ?1 ADM for toxicity reasons. Only 12.7% of individuals starting CART in the period 1998–2002 and 39.4% in the period 2003–2007 remained on the same regimen after 3 years. The following toxicities caused ADM most often: lipoatrophy (22%), gastrointestinal symptoms (20%), and neuropathy (18%). Only 5% of drug changes were due to virologic failure. Female sex (hazard ratio [HR], 2.42 95%; confidence intervals, 1.39–4.24) and older age (HR, 1.42 per every 10 years) were associated with toxicity-related ADM in the first 3 months of a particular CART regimen, but after 3 months of CART they were not. Conclusions Less toxic and better-tolerated HIV treatment options should be available and used more frequently in Croatia.

Mihanovic, Marta Perovic; Haque, Najm S.; Rutherford, George W.; Zekan, Sime; Begovac, Josip

2013-01-01

22

HIV Replication, Inflammation, and the Effect of Starting Antiretroviral Therapy on Plasma Asymmetric Dimethylarginine, a Novel Marker of Endothelial Dysfunction  

PubMed Central

Background HIV infection is associated with premature development of cardiovascular disease (CVD). Understanding the effects of HIV replication on endothelial dysfunction and platelet activation may identify treatment targets to reduce CVD risk. Methods A subgroup of HIV-infected participants in the Strategies for Management of Antiretroviral Therapy (SMART) study off antiretroviral therapy (ART) at entry enabled a randomized comparison of immediate versus deferred ART initiation of changes in asymmetric dimethylarginine (ADMA), soluble CD40L and P-selectin levels. Results At study entry, median (IQR) levels of ADMA, sCD40L, and P-selectin were 0.57 (0.49-0.66) ?g/mL, 251 (135-696) ?mol/L, and 34 (28-44) pg/mL. Compared to those randomized to deferral of ART (n=114), participants randomized to immediate ART (n=134) had 10.3% lower ADMA levels (p=0.003) at 12 months; treatment differences in sCD40L (95% CI:-17 to 44%; p=0.53) and P-selectin (95% CI:-10 to 10%; p=0.95) were not significant. The difference in ADMA for those assigned immediate ART compared to those assigned ART deferral was greater among younger patients and those with higher levels of hsCRP and D-dimer (p?0.05 for interaction for both), but not HIV RNA level at baseline (p=0.51). Discussion ART initiation leads to declines in ADMA levels, a marker of nitric-oxide-mediated endothelial dysfunction. Improvement in ADMA levels was related to the degree of inflammation and coagulation, suggesting that up-regulation of these pathways contributes to premature vascular disease among individuals with HIV infection. Whether declines in ADMA levels impact risk of disease requires further research.

Baker, Jason V.; Neuhaus, Jacqueline; Duprez, Daniel; Freiberg, Matthew; Bernardino, Jose I.; Badley, Andrew D.; Nixon, Daniel E.; Lundgren, Jens D.; Tracy, Russell P.; Neaton, James D.

2012-01-01

23

Loss to Follow-Up and Mortality Rates in HIV-1-Infected Patients in Curaçao Before and After the Start of Combination Antiretroviral Therapy.  

PubMed

Abstract We estimated the impact of loss to follow-up (LTFU) on the mortality rate among HIV-1-infected patients in Curaçao. A total of 214 therapy-naive HIV-1-infected patients aged 15 years or older upon entering into HIV care between January 2005 and July 2009 were included. Persons who discontinued follow-up for more than 365 days were defined as LTFU and traced with the aim of registering their vital status. If no personal contact could be made, data were matched with the Curaçao National Death Registry. Mortality rates were estimated before and after starting combination antiretroviral therapy (cART). We used log-rank tests to compare survival rates among patients LTFU and patients who experienced continuous follow-up. Pre-cART mortality in patients LTFU was similar to pre-cART mortality in those with continuous follow-up (p=0.79). All pre-cART deaths occurred within 6 months after entry. Low CD4 cell count was predictive of a shorter time to death after entry. Adjusting for those who were LTFU, the mortality rate after starting cART increased from 4.3 to 5.5 per 100 person years of observation (p=0.06). Mortality after starting cART was highest in the first 2 months after starting cART, especially for those who had late disease stage. Mortality rates were lower in patients with continuous follow-up compared to LTFUs (p<0.001). Mortality rates in HIV-1-infected patients who have started cART in Curaçao are underestimated as a result of inefficient patient administration combined with people starting cART at a very late disease stage. Monitoring HIV treatment could help in reducing the risk of LTFU and may improve the effect of treatment. PMID:23927464

Hermanides, Hillegonda; Holman, Rebecca; Gras, Luuk; Winkel, Carel; Gerstenbluth, Izzy; de Wolf, Frank; Duits, Ashley

2013-08-31

24

Treatment Response and Mortality among Patients Starting Antiretroviral Therapy with and without Kaposi Sarcoma: A Cohort Study  

PubMed Central

Background Improved survival among HIV-infected individuals on antiretroviral therapy (ART) has focused attention on AIDS-related cancers including Kaposi sarcoma (KS). However, the effect of KS on response to ART is not well-described in Southern Africa. We assessed the effect of KS on survival and immunologic and virologic treatment responses at 6- and 12-months after initiation of ART. Methods We analyzed prospectively collected data from a cohort of HIV-infected adults initiating ART in South Africa. Differences in mortality between those with and without KS at ART initiation were estimated with Cox proportional hazard models. Log-binomial models were used to assess differences in CD4 count response and HIV virologic suppression within a year of initiating treatment. Results Between January 2001–January 2008, 13,847 HIV-infected adults initiated ART at the study clinics. Those with KS at ART initiation (n?=?247, 2%) were similar to those without KS (n?=?13600,98%) with respect to age (35 vs. 35yrs), presenting CD4 count (74 vs. 85cells/mm3) and proportion on TB treatment (37% vs. 30%). In models adjusted for sex, baseline CD4 count, age, treatment site, tuberculosis and year of ART initiation, KS patients were over three times more likely to have died at any time after ART initiation (hazard ratio[HR]: 3.62; 95% CI: 2.71–4.84) than those without KS. The increased risk was highest within the first year on ART (HR: 4.05; 95% CI: 2.95–5.55) and attenuated thereafter (HR: 2.30; 95% CI: 1.08–4.89). Those with KS also gained, on average, 29 fewer CD4 cells (95% CI: 7–52cells/mm3) and were less likely to increase their CD4 count by 50 cells from baseline (RR: 1.43; 95% CI: 0.99–2.06) within the first 6-months of treatment. Conclusions HIV-infected adults presenting with KS have increased risk of mortality even after initiation of ART with the greatest risk in the first year. Among those who survive the first year on therapy, subjects with KS demonstrated a poorer immunologic response to ART than those without KS.

Maskew, Mhairi; Fox, Matthew P.; van Cutsem, Gilles; Chu, Kathryn; MacPhail, Patrick; Boulle, Andrew; Egger, Matthias; Africa, for IeDEA Southern

2013-01-01

25

Patients' worries before starting antiretroviral therapy and their association with treatment adherence and outcomes: a prospective study in rural Uganda, 2004 - 2009  

PubMed Central

Background In HIV-infected persons, good adherence to antiretroviral therapy (ART) is essential for successful treatment outcomes. Patients’ worries before starting ART may affect their ART adherence and treatment outcomes. Methods Between 2004 and 2009, HIV-infected individuals in a prospective cohort study in rural Uganda were assessed for ART eligibility. A counsellor explained the ART eligibility criteria, adherence and side effects, and recorded the patients’ worries related to ART. Every quarter, patients who initiated ART had clinical, immunological (CD4 cell counts) and virological (viral loads) assessments, and data were collected on ART adherence using patients’ self-reports and pill counts. We describe the patients’ worries and examine their association with ART adherence, and immunological and virological outcomes. Results We assessed 421 patients, 271 (64%) were females, 318 (76%) were aged 30 years and above and 315 (75%) were eligible for ART. 277 (66%) reported any worry, and the proportions were similar by sex, age group and ART eligibility status. The baseline median CD4 counts and viral loads were similar among patients with any worry and those with no worry. The commonest worries were: fear of HIV serostatus disclosure; among 69 (16%) participants, lack of food when appetite improved after starting ART; 50 (12%), concurrent use of other medications; 33 (8%), adherence to ART; 28 (7%) and problems concerning condom use; 27 (6%). After 24 months or more on ART, patients who reported any worry had made more scheduled ART refill visits than patients who reported no worry (p<0.01), but the annual CD4 cell increases were similar (p=0.12). After one year on ART, patients who reported any worry had greater virological suppression than patients who reported no worry (p<0.05). Conclusions Despite the lack of significant associations of worries with unfavourable ART outcomes, physicians and counsellors should assist patients in overcoming their worries that can cause stress and discomfort. Food supplements may be desirable for some patients initiating ART.

2013-01-01

26

Prognosis of HIV-1 infected patients starting antiretroviral therapy in sub-Saharan Africa: a collaborative analysis of scale-up programmes  

PubMed Central

Background Prognostic models have been developed for HIV-1 infected patients who start combination antiretroviral therapy (ART) in high-income countries, but not for patients treated in sub-Saharan Africa. Methods We included 10,331 adult patients who started ART between 2004 and 2007 in ART scale-up programmes in Côte d’Ivoire, South Africa and Malawi. Data were analysed by intention-to-continue-treatment, ignoring treatment changes and interruptions. We used Weibull survival models to construct two prognostic models: one that included baseline CD4 count and one that did not, since in many African settings CD4 count is not routinely measured. Findings During the first year after starting ART, 912 (8.2%) patients died. Baseline CD4 cell count (adjusted hazard ratio 0.21 [95% CI 0.17–0.27] comparing ?200 with <25 cells/?L), WHO clinical stage (3.45 [2.43–4.90] comparing stages III/IV with I/II), body weight (0.23 [0.18–0.30] comparing ?60 with <45kg) and anaemia (0.27 [0.20–0.36] comparing none with severe) were strongly associated with mortality. Other independent risk factors were low total lymphocyte count, advanced age and male sex. The CD4 model included CD4 count, clinical stage, body weight, age and sex (160 risk strata). In the alternative model CD4 count was replaced by total lymphocyte count and degree of anaemia (288 risk strata). With the CD4 model the probability of death ranged from 0.9% (95% CI 0.6–1.4) in patients in the lowest risk stratum to 53% (44–62) in patients in the highest risk stratum. The corresponding probabilities for the total lymphocyte/haemoglobin model were 0.9% (0.5–1.4) and 60% (48–71). Interpretation Prognostic models based on the CD4 cell count, or total lymphocytes and haemoglobin provide similarly strong discrimination in predicting early mortality in patients starting ART in sub-Saharan Africa. These models are useful for counselling patients, planning health services and predicting outcomes at the population level.

May, Margaret; Boulle, Andrew; Phiri, Sam; Messou, Eugene; Myer, Landon; Wood, Robin; Keiser, Olivia; Sterne, Jonathan A C; Dabis, Francois; Egger, Matthias

2011-01-01

27

The Presence of CXCR4-Using HIV-1 Prior to Start of Antiretroviral Therapy Is an Independent Predictor of Delayed Viral Suppression  

PubMed Central

The emergence of CXCR4-using HIV variants (X4-HIV) is associated with accelerated disease progression in the absence of antiretroviral therapy. However, the effect of X4-HIV variants on the treatment response remains unclear. Here we determined whether the presence of X4-HIV variants influenced the time to undetectable viral load and CD4+ T cell reconstitution after initiation of cART in 732 patients. The presence of X4-HIV variants was determined by MT-2 assay prior to cART initiation and viral load and CD4+ T cell counts were analyzed every 3 to 6 months during a three year follow-up period. Kaplan-Meier and Cox proportional hazard analyses were performed to compare time to viral suppression and the absolute CD4+ T cell counts and increases in CD4+ T cell counts during follow-up were compared for patients with and without X4-HIV at start of cART. Patients harboring X4-HIV variants at baseline showed a delay in time to achieve viral suppression below the viral load detection limit. This delay in viral suppression was independently associated with high viral load and the presence of X4-HIV variants. Furthermore, the absolute CD4+ T cell counts were significantly lower in patients harboring X4-HIV variants at all time points during follow-up. However, no differences were observed in the increase in absolute CD4+ T cell numbers after treatment initiation, indicating that the reconstitution of CD4+ T cells is independent of the presence of X4-HIV variants. The emergence of X4-HIV has been associated with an accelerated CD4+ T cell decline during the natural course of infection and therefore, patients who develop X4-HIV variants may benefit from earlier treatment initiation in order to obtain faster reconstitution of the CD4+ T cell population to normal levels.

Gijsbers, Esther F.; van Sighem, Ard; Harskamp, Agnes M.; Welkers, Matthijs R. A.; de Wolf, Frank; Brinkman, Kees; Prins, Jan M.; Schuitemaker, Hanneke; van 't Wout, Angelique B.; Kootstra, Neeltje A.

2013-01-01

28

When to start antiretroviral therapy  

Microsoft Academic Search

The current literature is controversial in providing evidence to determine the optimal time to initiate therapy among patients\\u000a with HIV. However, there is evidence that initiating early treatment might provide benefits by treating primary HIV infection,\\u000a preserving normal immune function, suppressing HIV viral replication, deferring clinical progression, and reducing HIV transmission.\\u000a The biggest challenges in initiating treatment early are issues

Cunlin Wang; Saba W. Masho; Daniel E. Nixon

2006-01-01

29

HIV drug resistance early warning indicators in cohorts of individuals starting antiretroviral therapy between 2004 and 2009: World Health Organization global report from 50 countries.  

PubMed

The World Health Organization developed a set of human immunodeficiency virus drug resistance (HIVDR) early warning indicators (EWIs) to assess antiretroviral therapy clinic and program factors associated with HIVDR. EWIs are monitored by abstracting data routinely recorded in clinical records, and the results enable clinics and program managers to identify problems that should be addressed to minimize preventable emergence of HIVDR in clinic populations. As of June 2011, 50 countries monitored EWIs, covering 131 686 patients initiating antiretroviral treatment between 2004 and 2009 at 2107 clinics. HIVDR prevention is associated with patient care (appropriate prescribing and patient monitoring), patient behavior (adherence), and clinic/program management efforts to reduce treatment interruptions (follow up, retention on first-line ART, procurement and supply management of antiretroviral drugs). EWIs measure these factors and the results have been used to optimize patient and population treatment outcomes. PMID:22544188

Bennett, Diane E; Jordan, Michael R; Bertagnolio, Silvia; Hong, Steven Y; Ravasi, Giovanni; McMahon, James H; Saadani, Ahmed; Kelley, Karen F

2012-05-01

30

HIV Drug Resistance Early Warning Indicators in Cohorts of Individuals Starting Antiretroviral Therapy Between 2004 and 2009: World Health Organization Global Report From 50 Countries  

PubMed Central

The World Health Organization developed a set of human immunodeficiency virus drug resistance (HIVDR) early warning indicators (EWIs) to assess antiretroviral therapy clinic and program factors associated with HIVDR. EWIs are monitored by abstracting data routinely recorded in clinical records, and the results enable clinics and program managers to identify problems that should be addressed to minimize preventable emergence of HIVDR in clinic populations. As of June 2011, 50 countries monitored EWIs, covering 131 686 patients initiating antiretroviral treatment between 2004 and 2009 at 2107 clinics. HIVDR prevention is associated with patient care (appropriate prescribing and patient monitoring), patient behavior (adherence), and clinic/program management efforts to reduce treatment interruptions (follow up, retention on first-line ART, procurement and supply management of antiretroviral drugs). EWIs measure these factors and the results have been used to optimize patient and population treatment outcomes.

Jordan, Michael R.; Bertagnolio, Silvia; Hong, Steven Y.; Ravasi, Giovanni; McMahon, James H.; Saadani, Ahmed; Kelley, Karen F.

2012-01-01

31

High Levels of Risk Behavior Among People Living with HIV Initiating and Waiting to Start Antiretroviral Therapy in Cape Town South Africa  

Microsoft Academic Search

Baseline data were collected in Cape Town during 2006 to study if patients on combination antiretroviral therapy (ART) experience\\u000a decreased inhibition to avoid risky sexual behavior. A total of 924 HIV-positive individuals were recruited; 520 who initiated\\u000a ART within 3 months and 404 waiting for ART. Nearly half of men (40.1%) and women (46.3%) reported having unprotected sex\\u000a their last time.

Thomas P. Eisele; Catherine Mathews; Mickey Chopra; Lisanne Brown; Eva Silvestre; Vanessa Daries; Carl Kendall

2008-01-01

32

Efficacy and durability of nevirapine in antiretroviral drug näive patients.  

PubMed

Nevirapine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) that was first reported in the scientific literature in 1990. Varying doses of nevirapine (NVP) and a number of regimens containing this NNRTI have been studied in antiretroviral (ARV) näive patients. Four key studies have compared the efficacy and safety of triple drug regimens containing NVP in ARV näive, HIV-1 infected patients. The INCAS study was the first demonstration of how to use NVP in an effective and durable manner: as a component of a triple drug regimen. The COMBINE Study was a comparison of protease inhibitor (PI)-based and NVP-based triple regimens. The Atlantic Study is comparing the safety and efficacy of three triple drug regimens in ARV näive patients. In this study, treatment consists of a divergent drug regimen (PI and nucleoside reverse transcriptase inhibitors, NRTIs) targeting both HIV-1 protease and reverse transcriptase or a convergent regimen targeting reverse transcriptase alone (three NRTIs or two NRTIs plus a NNRTI). A clinical endpoint study (BI 1090) compared the efficacy and durability of multi-drug regimens in ARV näive patients with high baseline plasma HIV-1 RNA levels (pVLs) and low peripheral blood CD4+ lymphocyte counts. Data from these studies confirm that triple regimens containing NVP suppressed viral replication for up to one year, even when the ARV näive patients had low CD4+ cell counts at baseline. Nevirapine-containing regimens suppressed pVLs to < 50 copies/ mL in approximately 50% of patients in the studies discussed (Intent to Treat analyses). Data from 96 weeks of follow up in the Atlantic Study demonstrates that the regimens containing didanosine and stavudine plus indinavir or NVP were significantly more successful in suppressing pVLs to < 50 copies/mL during this period than a regimen composed of these NRTIs and lamivudine (p < or = 0.001). As with other ARV drugs, NVP should always be used as part of a fully suppressive ARV regimen. When used in this way, it is an effective ARV drug, which contributes to durable virological and immunological responses in approximately half of all treated patients. Nevirapine-containing regimens are effective in patients with advanced HIV-1 infection, i.e., low CD4+ cell counts. Data will soon be available from the 2NN Study that compares the efficacy and safety of four different regimens using NVP once daily, NVP twice daily, efavirenz once daily or a combination of NVP and efavirenz. All four arms of the study include a backbone of stavudine and lamivudine. PMID:14562857

Lange, Joep M A

2003-09-01

33

Antiretroviral Treatment 2010: Progress and Controversies  

PubMed Central

Effective antiretroviral therapy (ART) changes the clinical course of HIV infection. There are 25 antiretroviral drugs approved for the treatment of HIV infection, and current antiretroviral drug regimens are highly effective, convenient, and relatively nontoxic. ART regimens should be chosen in consideration of a patient’s particular clinical situation. Successful treatment is associated with durable suppression of HIV viremia over years, and consequently, ART reduces the risk of clinical progression. In fact, current models estimate that an HIV-infected individual appropriately treated with antiretroviral drugs has a life expectancy that approaches that of the general HIV-uninfected population, although some patient groups such as injection drug users do less well. Despite these advances, continued questions about ART persist: What is the optimal time to start ART? What is the best regimen to start? When is the optimal time to change ART? What is the best regimen to change to? In addition, newer antiretroviral agents are in development, both in existing classes and in new classes such as the CD4 receptor attachment inhibitors and the maturation inhibitors. Further research will help optimize current antiretroviral treatments and strategies.

Gulick, Roy M.

2011-01-01

34

AIDS and Non-AIDS Morbidity and Mortality Across the Spectrum of CD4 Cell Counts in HIV-Infected Adults Before Starting Antiretroviral Therapy in C?te d'Ivoire  

PubMed Central

Background.?In Western Europe, North America, and Australia, large cohort collaborations have been able to estimate the short-term CD4 cell count–specific risk of AIDS or death in untreated human immunodeficiency virus (HIV)–infected adults with high CD4 cell counts. In sub–Saharan Africa, these CD4 cell count–specific estimates are scarce. Methods.?From 1996 through 2006, we followed up 2 research cohorts of HIV-infected adults in Côte d’Ivoire. This included follow-up off antiretroviral therapy (ART) across the entire spectrum of CD4 cell counts before the ART era, and only in patients with CD4 cell counts >200?cells/?L once ART became available. Data were censored at ART initiation. We modeled the CD4 cell count decrease using an adjusted linear mixed model. CD4 cell count–specific rates of events were obtained by dividing the number of first events occurring in a given CD4 cell count stratum by the time spent in that stratum. Results.?Eight hundred sixty patients were followed off ART over 2789 person-years (PY). In the ?650, 500–649, 350–499, 200–349, 100–199, 50–99, and 0–49?cells/?L CD4 cell count strata, the rates of AIDS or death were 0.9, 1.7, 3.7, 10.4, 30.9, 60.8, and 99.9 events per 100 PY, respectively. In patients with CD4 cell counts ?200 CD4?cells/?L, the most frequent AIDS-defining disease was tuberculosis (decreasing from 4.0 to 0.6 events per 100 PY for 200–349 and ?650 cells/?L, respectively), and the most frequent HIV non-AIDS severe diseases were visceral bacterial diseases (decreasing from 9.1 to 3.6 events per 100 PY). Conclusions.?Rates of AIDS or death, tuberculosis, and invasive bacterial diseases are substantial in patients with CD4 cell counts ?200 cells/?L. Tuberculosis and bacterial diseases should be the most important outcomes in future trials of early ART in sub–Saharan Africa.

Minga, Albert; Gabillard, Delphine; Ouassa, Timothee; Messou, Eugene; Morris, Brandon; Traore, Moussa; Coulibaly, Ali; Freedberg, Kenneth A.; Lewden, Charlotte; Menan, Herve; Abo, Yao; Dakoury-Dogbo, Nicole; Toure, Siaka; Seyler, Catherine

2012-01-01

35

Antiretroviral drug resistance testing.  

PubMed

While antiretroviral drugs, those approved for clinical use and others under evaluation, attempt in lowering viral load and boost the host immune system, antiretroviral drug resistance acts as a major impediment in the management of human immune deficiency virus type-1 (HIV-1) infection. Antiretroviral drug resistance testing has become an important tool in the therapeutic management protocol of HIV-1 infection. The reliability and clinical utilities of genotypic and phenotypic assays have been demonstrated. Understanding of complexities of interpretation of genotyping assay, along with updating of lists of mutation and algorithms and determination of clinically relevant cut-offs for phenotypic assays are of paramount importance. The assay results are to be interpreted and applied by experienced HIV practitioners, after taking into consideration the clinical profile of the patient. This review sums up the methods of assay currently available for measuring resistance to antiretroviral drugs and outlines the clinical utility and limitations of these assays. PMID:16855319

Sen, Sourav; Tripathy, S P; Paranjape, R S

36

The Start of Head Start  

ERIC Educational Resources Information Center

|The creation of the Head Start program occurred at break-neck speed with many dramatic turns and many colorful players. No one tells the story better than Edward Zigler in "Head Start: The Inside Story of America's Most Successful Educational Experiment"--a detailed and personal, behind the scenes look at the program's inception. From this…

Neugebauer, Roger

2010-01-01

37

Use of antiretrovirals during pregnancy and breastfeeding in low-income and middle-income countries  

PubMed Central

Purpose of review The purpose of the study was to review recent evidence on the use of antiretrovirals during pregnancy and breastfeeding in low-income and middle-income settings. Recent findings Access to antiretroviral prophylaxis strategies for HIV-infected pregnant women has increased globally, but two-thirds of women in need still do not receive even the simplest regimen for the prevention of mother-to-child transmission of HIV, and most pregnant women in need of antiretroviral treatment do not receive it. The use of combination antiretroviral treatment in pregnancy in low-resource settings is safe and effective, and increasing evidence supports starting ongoing antiretroviral treatment at a CD4 cell count below 350/?l in pregnant women. The use of appropriate short-course antiretroviral prophylactic regimens is effective for prevention of mother-to-child transmission of HIV in women with higher CD4 cell counts. New data on the use of antiretroviral prophylaxis to prevent transmission through breastfeeding demonstrate that both maternal antiretroviral treatment and extended infant prophylaxis are effective. Summary Antiretroviral use in pregnancy can benefit mothers in need of treatment and reduce the risk of mother-to-child transmission. Emerging evidence of the effectiveness of antiretroviral prophylaxis in preventing transmission through breastfeeding is encouraging and likely to influence practice in the future.

McIntyre, James

2010-01-01

38

Highly active antiretroviral therapy outcomes in a primary care clinic  

Microsoft Academic Search

This paper compares antiretroviral outcomes of patients at a primary care clinic with those previously reported at HIV specialty clinics and examines risk factors for treatment failure. A retrospective medical record review was undertaken at an academic primary care practice in Baltimore, Maryland. One hundred and twenty-three patients were included who had not previously received HAART and who were started

D. A. Rastegar; M. I. Fingerhood; D. R. Jasinski

2003-01-01

39

Start Young!  

NSDL National Science Digital Library

A person, place, or thing is what usually sparks those first memorable childhood impressions. Of course, we often do not study our newfound interests from the time of our personal enlightenment to adulthood, but early childhood interests are strong and they can have a powerful hold on us. Children usually show interest in many areas, though one interest usually resurfaces as they get older. Often, it seems this interest--usually one from childhood--is the one that leads to a profession. This free selection from Start Young! Early Childhood Science Activities also includes a Contents, Introduction, and Index section, along with a Quick Reference Chart.

Rubin, Penni

2006-01-01

40

Maternal antiretroviral prophylaxis and breastfeeding.  

PubMed

The prevention of mother-to-child transmission of HIV-1 during breastfeeding is a major concern in resource-poor settings where alternatives to breast milk may be unaffordable, unsafe and limited by social stigma. The use of triple-drug antiretroviral regimens initiated during pregnancy and continued throughout breastfeeding is being studied as a means to prevent transmission by reducing HIV-1 viral load in the maternal serum and breast milk. Studies characterizing the exposure of antiretroviral agents in breast milk and in the breastfed infant are important to understand the dynamics of HIV-1 replication in breast milk and to establish the safety profiles of antiretroviral drugs. PMID:22910400

Marzolini, Catia; Gray, Glenda E

2012-08-21

41

Individualization of antiretroviral therapy  

PubMed Central

Antiretroviral therapy (ART) has evolved considerably over the last three decades. From the early days of monotherapy with high toxicities and pill burdens, through to larger pill burdens and more potent combination therapies, and finally, from 2005 and beyond where we now have the choice of low pill burdens and once-daily therapies. More convenient and less toxic regimens are also becoming available, even in resource-poor settings. An understanding of the individual variation in response to ART, both efficacy and toxicity, has evolved over this time. The strong association of the major histocompatibility class I allele HLA-B*5701 and abacavir hypersensitivity, and its translation and use in routine HIV clinical practice as a predictive marker with 100% negative predictive value, has been a success story and a notable example of the challenges and triumphs in bringing pharmacogenetics to the clinic. In real clinical practice, however, it is going to be the exception rather than the rule that individual biomarkers will definitively guide patient therapy. The need for individualized approaches to ART has been further increased by the importance of non-AIDS comorbidities in HIV clinical practice. In the future, the ideal utilization of the individualized approach to ART will likely consist of a combined approach using a combination of knowledge of drug, virus, and host (pharmacogenetic and pharmacoecologic [factors in the individual’s environment that may be dynamic over time]) information to guide the truly personalized prescription. This review will focus on our knowledge of the pharmacogenetics of the efficacy and toxicity of currently available antiretroviral agents and the current and potential utility of such information and approaches in present and future HIV clinical care.

Pavlos, Rebecca; Phillips, Elizabeth J

2012-01-01

42

Fractures after antiretroviral initiation  

PubMed Central

Background Bone mineral density declines by 2–6% within 1–2 years after initiation of antiretroviral therapy (ART); however, it is uncertain whether this results in an immediate or cumulative increase in fracture rates. Methods We evaluated the incidence and predictors of fracture in 4640 HIV-positive participants from 26 randomized ART studies followed in the AIDS Clinical Trials Group (ACTG) Longitudinal-Linked Randomized Trial study for a median of 5 years. Fragility and nonfragility fractures were recorded prospectively at semiannual visits. Incidence was calculated as fractures/total person-years. Cox proportional hazards models evaluated effects of traditional fracture risks, HIV disease characteristics, and ART exposure on fracture incidence. Results Median (interquartile range) age was 39 (33, 45) years; 83% were men, 48% white, and median nadir CD4 cell count was 187 (65, 308) cells/?l. Overall, 116 fractures were reported in 106 participants with median time-to-first fracture of 2.3 years. Fracture incidence was 0.40 of 100 person-years among all participants and 0.38 of 100 person-years among 3398 participants who were ART naive at enrollment into ACTG parent studies. Among ART-naive participants, fracture rates were higher within the first 2 years after ART initiation (0.53/100 person-years) than subsequent years (0.30/100 person-years). In a multivariate analysis of ART-naive participants, increased hazard of fracture was associated with current smoking and glucocorticoid use but not with exposure to specific antiretrovirals. Conclusion Fracture rates were higher within the first 2 years after ART initiation, relative to subsequent years. However, continuation of ART was not associated with increasing fracture rates in these relatively young HIV-positive individuals.

Yin, Michael T.; Kendall, Michelle A.; Wu, Xingye; Tassiopoulos, Katherine; Hochberg, Marc; Huang, Jeannie S.; Glesby, Marshall J.; Bolivar, Hector; McComsey, Grace A.

2013-01-01

43

Monitoring of HIV type 1 DNA load and drug resistance in peripheral blood mononuclear cells during suppressive antiretroviral therapy does not predict virologic failure.  

PubMed

Our objective was to determine whether monitoring HIV-1 DNA concentration or new resistance mutations in peripheral blood mononuclear cells (PBMCs) during effective antiretroviral therapy (ART) predicts virologic failure. A retrospective analysis used blood specimens and clinical data from three nevirapine containing arms of a four-arm, open-label, randomized trial comparing ART regimens in HIV-1-infected children who had failed mono- or dual-nucleoside therapy. Sensitive assays compared cell-associated HIV-1 DNA concentrations and nevirapine (NVP) and lamivudine (3TC) resistance mutations in children with plasma HIV-1 RNA <400 copies(c)/ml who did or did not experience subsequent virologic failure. Forty-six children were analyzed through the last available follow-up specimen, collected at 48 (n=16) or 96 (n=30) weeks of ART. Thirty-five (76%) had sustained viral suppression and 11 (24%) had plasma viral rebound to ? 400 c/ml (virologic failure detected at a median of 36 weeks). HIV-1 DNA levels at baseline, 24, 48, and 96 weeks of ART were similar in children who did vs. did not experience virologic failure (p=0.82). HIV-1 DNA levels did not increase prior to viral rebound. NVP resistance mutations were detected in 91% of subjects in the failure group vs. 3% in the suppressed group (p <0.0001). Among nine evaluable children, NVP mutations were first detected prior to virologic failure in two (22%), at viral rebound in five (56%), and after failure in two (22%) children. HIV-1 DNA concentrations did not predict virologic failure in this cohort. New drug resistance mutations were detected in the PBMCs of a minority of virologically suppressed children who subsequently failed ART. PMID:22081867

Beck, Ingrid A; Jang, Minyoung; McKernan-Mullin, Jennifer; Bull, Marta; Wagner, Thor; Huang, Sharon; Song, Lin-Ye; Nachman, Sharon; Krogstad, Paul; Eshleman, Susan H; Wiznia, Andrew; Frenkel, Lisa M

2012-01-27

44

Monitoring of HIV Type 1 DNA Load and Drug Resistance in Peripheral Blood Mononuclear Cells During Suppressive Antiretroviral Therapy Does Not Predict Virologic Failure  

PubMed Central

Abstract Our objective was to determine whether monitoring HIV-1 DNA concentration or new resistance mutations in peripheral blood mononuclear cells (PBMCs) during effective antiretroviral therapy (ART) predicts virologic failure. A retrospective analysis used blood specimens and clinical data from three nevirapine containing arms of a four-arm, open-label, randomized trial comparing ART regimens in HIV-1-infected children who had failed mono- or dual-nucleoside therapy. Sensitive assays compared cell-associated HIV-1 DNA concentrations and nevirapine (NVP) and lamivudine (3TC) resistance mutations in children with plasma HIV-1 RNA <400 copies(c)/ml who did or did not experience subsequent virologic failure. Forty-six children were analyzed through the last available follow-up specimen, collected at 48 (n=16) or 96 (n=30) weeks of ART. Thirty-five (76%) had sustained viral suppression and 11 (24%) had plasma viral rebound to ?400?c/ml (virologic failure detected at a median of 36 weeks). HIV-1 DNA levels at baseline, 24, 48, and 96 weeks of ART were similar in children who did vs. did not experience virologic failure (p=0.82). HIV-1 DNA levels did not increase prior to viral rebound. NVP resistance mutations were detected in 91% of subjects in the failure group vs. 3% in the suppressed group (p <0.0001). Among nine evaluable children, NVP mutations were first detected prior to virologic failure in two (22%), at viral rebound in five (56%), and after failure in two (22%) children. HIV-1 DNA concentrations did not predict virologic failure in this cohort. New drug resistance mutations were detected in the PBMCs of a minority of virologically suppressed children who subsequently failed ART.

Beck, Ingrid A.; Jang, Minyoung; McKernan-Mullin, Jennifer; Bull, Marta; Wagner, Thor; Huang, Sharon; Song, Lin-Ye; Nachman, Sharon; Krogstad, Paul; Eshleman, Susan H.; Wiznia, Andrew

2012-01-01

45

Introducing antiretroviral therapy.  

PubMed

This paper discusses the introduction of antiretroviral (ARV) therapy to HIV-infected patients. ARV therapy is treatment with drugs that fight the HIV virus and keep the HIV-infected patient healthy. Treatment may involve only one ARV (monotherapy) or a combination of two or more ARVs (combination therapy). The increasing availability of ARVs in many countries has caused dangerous side effects to develop quickly in patients due to the improper use of drug combinations. Some life-threatening side effects of ARV misuse include vomiting, diarrhea, fever, diabetes, and pancreatitis. People who experience these symptoms need to change their drug combination; a drug must be taken with strict instructions to prevent unpleasant side effects and its reaction with other drugs (protease inhibitors, for example, react with the tuberculosis drug rifampicin). An ARV should also be closely monitored to ensure its continuous effectiveness using CD4 and viral load counts at least every 3-6 months. A change in drug combination is required when CD4 count is dropping or the viral load is not reduced or maintained. PMID:12349194

46

[Interactions with antiretroviral drugs].  

PubMed

Drug-drug interactions are frequently encountered in the therapy of HIV-infected patients, since the highly active antiretroviral therapy always contains several drugs. Drugs against opportunistic infections and concomitant diseases are added frequently. All protease inhibitors are inhibitors of CYP3A, which is important in the metabolism of approximately 50% of all drugs, e.g. simvastatin, atorvastatin, sildenafil, and clarithromycin. Among the protease inhibitors, ritonavir is the strongest inhibitor of CYP3A activity. This inhibition is also used to enhance ("boost") the bioavailability of other protease inhibitors. The nonnucleoside reverse transcriptase inhibitors (NNRTI) efavirenz and nevirapine lead to an increase in CYP3A activity during long-term treatment. To prevent interactions, doses of CYP3A substrates have to be adapted in the beginning and at the end of CYP3A activity-modifying treatments. Interactions can also be a result of modifications in the activities of glucuronosyltransferases and of transport proteins. Ritonavir is an inhibitor of P-glycoprotein, which leads to increased expositions towards many antineoplastic drugs. PMID:19943026

Ceschi, A; Curkovic, I; Kirchheiner, J; Kullak-Ublick, G A; Jetter, A

2010-01-01

47

Comparison among antiretroviral adherence questions  

PubMed Central

Our objective was to compare antiretroviral adherence questions. Among 53 methadone maintained HIV-infected drug users, we compared five measures, including two single item measures using qualitative Likert-type responses, one measure of percent adherence, one visual analog scale, and one measure that averaged responses across antiretrovirals. Responses were termed inconsistent if respondents endorsed the highest adherence level on at least one measure but middle levels on others. We examined ceiling effects, concordance, and correlations with VL. Response distributions differed markedly between measures. A ceiling effect was less pronounced for the single-item measures than for the measure that averaged responses for each antiretroviral: the proportion with 100% adherence varied from 22% (single item measure) to 58% (multi-item measure). Overall agreement between measures ranged from fair to good; 49% of participants had inconsistent responses. Though responses correlated with VL, single-item measures had higher correlations. Future studies should compare single-item questions to objective measures.

Berg, Karina M.; Wilson, Ira B.; Li, Xuan; Arnsten, Julia H.

2013-01-01

48

When to start, what to start and other treatment controversies in pediatric HIV infection.  

PubMed

Over the last decade there have been dramatic changes in the management of pediatric HIV infection. Whilst observational studies and several randomized control trials (RCTs) have addressed some questions about when to start antiretroviral therapy (ART) in children and what antiretrovirals to start, many others remain unanswered. In infants, early initiation of ART greatly reduces mortality and disease progression. Treatment guidelines now recommend ART in all infants younger than 1 or 2 years of age depending on geographical setting. In children >1 year of age, US, European (Paediatric European Network for Treatment of AIDS; PENTA) and WHO guidelines differ and debate is ongoing. Recent data from an RCT in Thailand in children with moderate immune suppression indicate that it is safe to monitor asymptomatic children closely without initiating ART, although earlier treatment was associated with improved growth. Untreated HIV progression in children aged over 5 years is similar to that in adults, and traditionally adult treatment thresholds are applied. Recent adult observational and modeling studies showed a survival advantage and reduction of age-associated complications with early treatment. The current US guidelines have lowered CD4+ cell count thresholds for ART initiation for children aged >5 years to 500?cells/mm3. Co-infections influence the choice of drugs and the timing of starting ART. Drug interactions, overlapping toxicities and adherence problems secondary to increased pill burden are important issues. Rapid changes in the pharmacokinetics of antiretrovirals in the first years of life, limited pharmacokinetic data in children and genetic variation in metabolism of many antiretrovirals make correct dosing difficult. Adherence should always be addressed prior to starting ART or switching regimens. The initial ART regimen depends on previous exposure, including perinatal administration for prevention of mother to child transmission (PMTCT), adherence, co-infections, drug availability and licensing. A European cohort study in infants indicated that treatment with four drugs produced superior virologic suppression and immune recovery. Protease inhibitor (PI)-based ART has the advantage of a high barrier to viral resistance. A recent RCT conducted in several African countries showed PI-based ART to be advantageous in children aged <3 years compared with nevirapine-based ART irrespective of previous nevirapine exposure. Another trial in older children from resource rich settings showed both regimens were equally effective. Treatment interruption remains a controversial issue in children, but one study in Europe demonstrated no short-term detrimental effects. ART in children is a rapidly evolving area with many new antiretrovirals being developed and undergoing trials. The aim of ART has shifted from avoiding mortality and morbidity to achieving a normal life expectancy and quality of life, minimizing toxicities and preventing early cancers and age-related illnesses. PMID:23013459

Turkova, Anna; Webb, Rachel H; Lyall, Hermione

2012-12-01

49

Incidence of hyperlipidaemia in a cohort of 212 HIV-infected patients receiving a protease inhibitor-based antiretroviral therapy  

Microsoft Academic Search

Two hundred and twelve HIV-positive patients who started a new protease inhibitor (PI)-based antiretroviral regimen between January 1998 and December 2000 in our tertiary care centre were prospectively followed-up during a 12-month study period, in order to assess the incidence of hyperlipidaemia and related clinical adverse events. At the end of 1-year follow-up, PI-containing antiretroviral treatment led to a statistically

Leonardo Calza; Roberto Manfredi; Barbara Farneti; Francesco Chiodo

2003-01-01

50

Complications of Antiretroviral Therapy Initiation in Hospitalised Patients with HIV-Associated Tuberculosis  

PubMed Central

Background HIV-associated tuberculosis is a common coinfection in Sub-Saharan Africa, which causes high morbidity and mortality. A sub-set of HIV-associated tuberculosis patients require prolonged hospital admission, during which antiretroviral therapy initiation may be required. The aim of this study was to document the causes of clinical deterioration of hospitalised patients with HIV-associated tuberculosis starting antiretroviral therapy in order to inform healthcare practice in low- to middle-income countries. Methods Prospective, observational cohort study of adult inpatients with HIV-associated tuberculosis starting antiretroviral therapy in a dedicated tuberculosis hospital in Cape Town, South Africa. Causes of clinical deterioration and outcome were recorded in the first 12 weeks of antiretroviral therapy. Patients with rifampicin-resistant tuberculosis were excluded. Results Between May 2009 and November 2010, 112 patients (60% female), with a median age of 32 years were enrolled. At baseline the median CD4 count was 55 cells/mm3 (IQR 31–106) and HIV viral load 5.6 log copies/mL. All patients had significant comorbidity: 82% were bed-bound, 65% had disseminated tuberculosis and 27% had central nervous system tuberculosis. Seventy six patients (68%) developed 144 clinical events after starting antiretroviral therapy. TB-IRIS, hospital-acquired infections and significant drug toxicities occurred in 42%, 20.5% and 15% of patients respectively. A new opportunistic disease occurred in 15% of patients and a thromboembolic event in 8%. Mortality during the 12 week period was 10.6%. Conclusions High rates of TB-IRIS, hospital-acquired infections and drug toxicities complicate the course of patients with HIV-associated tuberculosis starting antiretroviral therapy in hospital. Despite the high morbidity, mortality was relatively low. Careful clinical management and adequate resources are needed in hospitalised HIV-TB patients in the 1st three months following ART initiation.

van der Plas, Helen; Meintjes, Graeme; Schutz, Charlotte; Goliath, Rene; Myer, Landon; Baatjie, Dorothea; Wilkinson, Robert J.; Maartens, Gary; Mendelson, Marc

2013-01-01

51

An information system to manage the rollout of the antiretroviral treatment programme in the Free State.  

PubMed

The Acquired Immune Deficiency Syndrome epidemic, caused by the Human Immunodeficiency Virus, is a global crisis which threatens development gains, economies, and societies. Within sub-Saharan Africa, where the epidemic began the earliest and the HIV prevalence is the highest, African countries have death rates not seen before. In South Africa the epidemic has a devastating impact which creates profound suffering on individuals and their families, and the impact on the socio-economic level is of great concern. The eradication of HIV/AIDS represents one of humanity's greatest challenges, which requires co-operation and comprehensive collaboration between many different role players. In this endeavour clinical information plays a major role. To combat the effect of the disease, the Free State Department of Health started with the provisioning of antiretroviral therapy in the public health sector. The objective of this paper was to address the challenges they faced in order to develop and implement an information system to manage the rollout of antiretroviral treatment effectively. They started with a paper-based system to collect vital information. It was followed by a palm computer project that was initiated to electronically capture the data collected by the paper-based system. This system was then replaced by a comprehensive Hospital and Clinic Information System which was acquired and customised for the antiretroviral data collection process. Research partners developed a standalone antiretroviral data warehouse for collecting information associated with the monitoring and evaluation of the Free State antiretroviral and HIV/ AIDS treatment programme. The data warehouse successfully produced several management information reports to the antiretroviral management team. A need was identified to design a comprehensive antiretroviral data warehouse that will integrate data from several operational sources which are all associated with HIV/AIDS. PMID:21469517

Kotzé, J E; McDonald, T

2010-06-01

52

Hepatotoxicity with antiretroviral treatment of pregnant women  

Microsoft Academic Search

BACKGROUND:Hepatotoxicity in adults with human immunodeficiency virus (HIV) infection has been associated with all classes of antiretroviral drugs and coinfection with hepatitis B and C virus. We treated two HIV-infected pregnant women in whom hepatotoxicity developed after initiating antiretroviral therapy.CASES:The first woman developed icterus, jaundice, hyperbilirubinemia, and elevated serum aminotransferase levels approximately 5 months after beginning combination antiretroviral therapy with

James B. Hill; Jeanne S. Sheffield; Gerda G. Zeeman; George D. Wendel

2001-01-01

53

Antiretroviral therapy: 'the state of the art'.  

PubMed

The field of antiretroviral therapy is evolving at a very rapid pace. At this time, the initiation and optimization of antiretroviral therapy is based on serial plasma viral load determinations which aim to suppress viral replication to as low as possible for as long as possible, thus preventing disease progression. Currently available antiretrovirals require combination therapy with at least three agents to achieve this goal. Increasing availability of newer and more potent antiretroviral regimens will continue to enhance and simplify the number of therapeutic options available in the not too distant future. PMID:10337460

Montaner, J S; Montessori, V; Harrigan, R; O'Shaughnessy, M; Hogg, R

1999-03-01

54

Reactive arthritis responding to antiretroviral therapy in an HIV-1-infected individual.  

PubMed

Reactive arthritis (ReA) is an autoimmune seronegative spondyloarthropathy that occurs in response to a urogenital or enteric infection. Several studies have reported a link between ReA and HIV infection. We report a case of an HIV-1-infected patient diagnosed with a disabling ReA who failed to respond to conventional therapy but whose symptoms resolved rapidly after starting antiretroviral therapy (ART). Clinicians may not be cognizant to this phenomenon and so this case report serves to remind clinicians that initiation of antiretroviral therapy should be considered in HIV-infected patients with ReA who are refractory to standard therapy. PMID:22648898

Scott, C; Brand, A; Natha, M

2012-05-01

55

Determinants of access to experimental antiretroviral drugs in an Italian cohort of patients with HIV: a multilevel analysis  

PubMed Central

Background Identification of the determinants of access to investigational drugs is important to promote equity and scientific validity in clinical research. We aimed to analyze factors associated with the use of experimental antiretrovirals in Italy. Methods We studied participants in the Italian Cohort of Antiretroviral-Naive Patients (ICoNA). All patients 18 years or older who had started cART (? 3 drugs including at least two NRTI) after their enrolment and during 1997-2007 were included in this analysis. We performed a random effect logistic regression analysis to take into account clustering observations within clinical units. The outcome variable was the use of an experimental antiretroviral, defined as an antiretroviral started before commercial availability, in any episode of therapy initiation/change. Use of an experimental antiretroviral obtained through a clinical trial or an expanded access program (EAP) was also analyzed separately. Results A total of 9,441 episodes of therapy initiation/change were analyzed in 3,752 patients. 392 episodes (360 patients) involved an experimental antiretroviral. In multivariable analysis, factors associated with the overall use of experimental antiretrovirals were: number of experienced drugs (? 8 drugs versus "naive": adjusted odds ratio [AOR] = 3.71) or failed antiretrovirals(3-4 drugs and ? 5 drugs versus 0-2 drugs: AOR = 1.42 and 2.38 respectively); calendar year (AOR = 0.80 per year) and plasma HIV-RNA copies/ml at therapy change (? 4 log versus < 2 log: AOR = 1.55). The probability of taking an experimental antiretroviral through a trial was significantly lower for patients suffering from liver co-morbidity(AOR = 0.65) and for those who experienced 3-4 drugs (vs naive) (AOR = 0.55), while it increased for multi-treated patients(AOR = 2.60). The probability to start an experimental antiretroviral trough an EAP progressively increased with the increasing number of experienced and of failed drugs and also increased for patients with liver co-morbidity (AOR = 1.44; p = 0.053). and for male homosexuals (vs heterosexuals: AOR = 1.67). Variability of the random effect associated to clinical units was statistically significant (p < 0.001) although no association was found with specific characteristics of clinical unit examined. Conclusions Among patients with HIV infection in Italy, access to experimental antiretrovirals seems to be influenced mainly by exhaustion of treatment options and not by socio-demographic factors.

2012-01-01

56

The Head Start Debates  

ERIC Educational Resources Information Center

The future of Head Start depends on how well people learn from and apply the lessons from its past. That's why everyone involved in early education needs this timely, forward-thinking book from the leader of Head Start. The first book to capture the Head Start debates in all their complexity and diversity, this landmark volume brings together the…

Zigler, Edward, Ed.; Styfco, Sally J., Ed.

2004-01-01

57

Head Start Facilities Manual.  

ERIC Educational Resources Information Center

|A quality Head Start facility should provide a physical environment responsive both to the needs of the children and families served and to the needs of staff, volunteers, and community agencies that share space with Head Start. This manual is a tool for Head Start grantees and delegate agencies for assessing existing facilities, making…

Research Assessment Management, Inc., Silver Spring, MD.

58

Sprint start instrumentation  

Microsoft Academic Search

A prototype instrument has been developed to measure the forces generated on the starting blocks and the speed of a sprinter at the start of a sprint event. The starting block forces can be resolved into horizontal and vertical components for each foot, or the various combinations of these four forces can be calculated and displayed along with the resultant

R. E. Gander; J. D. McClements; L. K. Sanderson; B. A. Rostad; K. E. Josephson; A. J. Pratt

1994-01-01

59

The Head Start Debates  

ERIC Educational Resources Information Center

|The future of Head Start depends on how well people learn from and apply the lessons from its past. That's why everyone involved in early education needs this timely, forward-thinking book from the leader of Head Start. The first book to capture the Head Start debates in all their complexity and diversity, this landmark volume brings together the…

Zigler, Edward, Ed.; Styfco, Sally J., Ed.

2004-01-01

60

Nevada Head Start, 2002.  

ERIC Educational Resources Information Center

This pamphlet describes the current services of the Nevada Head Start program. Information is provided on program eligibility requirements, the number of children and families served during the 2001-2002 program year, the counties served by Head Start programs, health services provided, demographic characteristics of families served by Head Start,…

Biagi, Kathy

61

Timing of initiation of antiretroviral therapy in AIDS-free HIV1-infected patients: a collaborative analysis of 18 HIV cohort studies  

Microsoft Academic Search

Background The CD4 cell count at which combination antiretroviral therapy should be started is a central, unresolved issue in the care of HIV-1-infected patients. in the absence of randomised trials, we examined this question in prospective cohort studies. Methods We analysed data from 18 cohort studies of patients with HIV. Antiretroviral-naive patients from 15 of these studies were eligible for

J. A. C. Sterne; M. May; D. Costagliola; Wolf de F; A. N. Phillips; R. Harris; M. J. Funk; R. B. Geskus; J. Gill; F. Dabis; J. M. Miro; A. C. Justice; B. Ledergerber; G. Faetkenheuer; R. S. Hogg; A. d'Arminio Monforte; M. Saag; C. Smith; S. Staszewski; M. Egger; S. R. Cole

2009-01-01

62

Starting School in August  

ERIC Educational Resources Information Center

|In this article, the author discusses the controversial decision of the school board from the Broward County, Florida to start the school year on August 9. School boards across the country that are grappling with the idea of starting school earlier in the year are increasingly running up against strong opposition from parents. In many districts,…

Chmelynski, Carol

2006-01-01

63

Head Start. Fact Sheet.  

ERIC Educational Resources Information Center

Head Start is a national program that provides comprehensive developmental services for preschool children (ages 3 to 5) from low-income families and social services for their families. Approximately 1,400 community-based nonprofit organizations and school systems develop programs to meet specific needs. Head Start began in 1965 in the Office of…

Administration for Children, Youth, and Families (DHHS), Washington, DC.

64

Smart Start News, 1999.  

ERIC Educational Resources Information Center

|Smart Start is a comprehensive public-private initiative to help all North Carolina children enter school healthy and ready to succeed, and provides children from birth to age five access to high-quality and affordable child care, health care, and other critical services. This document comprises the first two issues of "Smart Start News," a…

Harris, Monica, Ed.

1999-01-01

65

Bacterial start site prediction  

Microsoft Academic Search

With the growing number of completely sequenced bacterial genes, accurate gene prediction in bacterial genomes remains an important problem. Although the existing tools predict genes in bacterial genomes with high overall accuracy, their ability to pinpoint the translation start site remains unsatisfactory. In this paper, we present a novel approach to bacterial start site prediction that takes into account multiple

Sridhar S. Hannenhalli; William S. Hayes; Artemis G. Hatzigeorgiou; James W. Fickett

1999-01-01

66

Starting School in August  

ERIC Educational Resources Information Center

In this article, the author discusses the controversial decision of the school board from the Broward County, Florida to start the school year on August 9. School boards across the country that are grappling with the idea of starting school earlier in the year are increasingly running up against strong opposition from parents. In many districts,…

Chmelynski, Carol

2006-01-01

67

Aboriginal Head Start.  

ERIC Educational Resources Information Center

|In Canada, about 100 Aboriginal Head Start (AHS) programs provide Aboriginal preschool children with a start in preparing for elementary school and an understanding of their Native culture. The involvement of parents, communities, and elders is key to the success of AHS. The AHS mission statement and seven guiding principles are presented. (SV)|

Dunning, Paula

2000-01-01

68

How does Antiretroviral Therapy Affect HIV Mutation?  

NSDL National Science Digital Library

You are a physician who works with people who are infected with HIV. You study HIV-1 protease and reverse transcriptase to determine which anti-retroviral drugs might be effective and which drugs might be ineffective.

Devin Iimoto (Whittier College;)

2005-06-11

69

Electric starting apparatus  

SciTech Connect

An electric starting system is described for cranking an engine comprising, a source of voltage, an electric starter comprising an electric cranking motor and a solenoid having pull-in and hold-in coils and a shiftable plunger, a pinion that is shifted by movement of the plunger that is adapted to mesh with the ring gear of the engine, switch means having first and second contacts that are at times electrically connected by a contactor shiftable by movement of the plunger, a manually operable start switch, means connecting the start switch and the hold-in coil in series and across the voltage source whereby the hold-in coil is energized when the start switch is closed and is deenergized when the start switch is opened, means connecting one side of the voltage source to the first contact, means connecting an opposite side of the voltage source to one side of the cranking motor, a circuit connecting the first contact to an opposite side of the cranking motor comprising in a series connection the pull-in coil and the current carrying electrodes of a semiconductor switch, a circuit connecting the second contact to the opposite side of the cranking motor, and means connecting a control electrode of the semiconductor switch to the start switch such that the semiconductor switch is biased conductive between its current carrying electrodes to energize the pull-in coil when the start switch is closed.

Raver, L.J.

1986-05-06

70

The CLAS Start Counter  

SciTech Connect

The design, construction, and performance of a hexagonal-nose-cone shaped plastic scintillation counter system is described. This ''Start Counter'' is used as part of the trigger and to measure event start times for photon beam running with CLAS in Hall B at the Thomas Jefferson National Accelerator Facility. The Start Counter is constructed of three 3-mm thick coupled paddle scintillators and achieves a software-corrected time resolution of 260 ps. Each coupled-paddle scintillator operated without appreciable sagging up to {approx}1.2 MHz rate.

S. Taylor; S. Ahmad; J. Distelbrink; G. S. Mutchler; E. Smith; T. Smith

2001-08-01

71

Derivation of parameters used in Spectrum for eligibility for antiretroviral therapy and survival on antiretroviral therapy  

PubMed Central

Background The Spectrum projection package uses estimates of national HIV incidence, demographic data and other assumptions to describe the consequences of the HIV epidemic in low and middle-income countries. The default parameters used in Spectrum are updated every 2?years as new evidence becomes available to inform the model. This paper reviews the default parameters that define the course of HIV progression among adults and children in Spectrum. Methods For adults, data available from published and grey literature and data from the ART-LINC International epidemiologic Database to Evaluate AIDS (IeDEA) collaboration were combined to estimate survival among those who started antiretroviral therapy (ART). For children, a review of published material on survival on ART and survival on ART and cotrimoxazole was used to derive survival probabilities. Historical data on the distribution of CD4 cell counts and CD4 cell percentages by age among children who were not treated (before treatment was available) were used to progress children from seroconversion to different CD4 cell levels. Results Based on the updated evidence estimated survival among adults aged over 15?years in the first year on ART was 86%, while in subsequent years survival was estimated at 90%. Survival among children during the first year on ART was estimated to be 85% and for subsequent years 93%. Discussion The revised default parameters based on additional data will make Spectrum estimates more accurate than previous rounds of estimates.

Lewden, Charlotte; Brinkhof, Martin W G; Dabis, Francois; Tassie, Jean-Michel; Souteyrand, Yves; Stover, John

2010-01-01

72

Linkage to HIV Care and Antiretroviral Therapy in Cape Town, South Africa  

Microsoft Academic Search

BackgroundAntiretroviral therapy (ART) has been scaled-up rapidly in Africa. Programme reports typically focus on loss to follow-up and mortality among patients receiving ART. However, little is known about linkage and retention in care of individuals prior to starting ART.MethodologyData on adult residents from a periurban community in Cape Town were collected at a primary care clinic and hospital. HIV testing

Katharina Kranzer; Jennifer Zeinecker; Philip Ginsberg; Catherine Orrell; Nosindiso N. Kalawe; Stephen D. Lawn; Linda-Gail Bekker; Robin Wood; David Joseph Diemert

2010-01-01

73

Cost-Effectiveness of Antiretroviral Therapy for Multidrug-Resistant HIV: Past, Present, and Future  

PubMed Central

In the early years of the highly active antiretroviral therapy (HAART) era, HIV with resistance to two or more agents in different antiretroviral classes posed a significant clinical challenge. Multidrug-resistant (MDR) HIV was an important cause of treatment failure, morbidity, and mortality. Treatment options at the time were limited; multiple drug regimens with or without enfuvirtide were used with some success but proved to be difficult to sustain for reasons of tolerability, toxicity, and cost. Starting in 2006, data began to emerge supporting the use of new drugs from the original antiretroviral classes (tipranavir, darunavir, and etravirine) and drugs from new classes (raltegravir and maraviroc) for the treatment of MDR HIV. Their availability has enabled patients with MDR HIV to achieve full and durable viral suppression with more compact and cost-effective regimens including at least two and often three fully active agents. The emergence of drug-resistant HIV is expected to continue to become less frequent in the future, driven by improvements in the convenience, tolerability, efficacy, and durability of first-line HAART regimens. To continue this trend, the optimal rollout of HAART in both rich and resource-limited settings will require careful planning and strategic use of antiretroviral drugs and monitoring technologies.

Harris, Marianne; Nosyk, Bohdan; Harrigan, Richard; Lima, Viviane Dias; Cohen, Calvin; Montaner, Julio

2012-01-01

74

Cost-Effectiveness of Antiretroviral Therapy for Multidrug-Resistant HIV: Past, Present, and Future.  

PubMed

In the early years of the highly active antiretroviral therapy (HAART) era, HIV with resistance to two or more agents in different antiretroviral classes posed a significant clinical challenge. Multidrug-resistant (MDR) HIV was an important cause of treatment failure, morbidity, and mortality. Treatment options at the time were limited; multiple drug regimens with or without enfuvirtide were used with some success but proved to be difficult to sustain for reasons of tolerability, toxicity, and cost. Starting in 2006, data began to emerge supporting the use of new drugs from the original antiretroviral classes (tipranavir, darunavir, and etravirine) and drugs from new classes (raltegravir and maraviroc) for the treatment of MDR HIV. Their availability has enabled patients with MDR HIV to achieve full and durable viral suppression with more compact and cost-effective regimens including at least two and often three fully active agents. The emergence of drug-resistant HIV is expected to continue to become less frequent in the future, driven by improvements in the convenience, tolerability, efficacy, and durability of first-line HAART regimens. To continue this trend, the optimal rollout of HAART in both rich and resource-limited settings will require careful planning and strategic use of antiretroviral drugs and monitoring technologies. PMID:23193464

Harris, Marianne; Nosyk, Bohdan; Harrigan, Richard; Lima, Viviane Dias; Cohen, Calvin; Montaner, Julio

2012-11-08

75

Preferred antiretroviral drugs for the next decade of scale up  

PubMed Central

Global commitments aim to provide antiretroviral therapy (ART) to 15 million people living with HIV by 2015, and recent studies have demonstrated the potential for widespread ART to prevent HIV transmission. Increasingly, countries are adapting their national guidelines to start ART earlier, for both clinical and preventive benefits. To maximize the benefits of ART in resource-limited settings, six key principles need to guide ART choice: simplicity, tolerability and safety, durability, universal applicability, affordability and heat stability. Currently available drugs, combined with those in late-stage clinical development, hold great promise to simplify treatment in the short term. Over the longer term, newer technologies, such as long-acting formulations and nanotechnology, could radically alter the treatment paradigm. This commentary reviews recommendations made in an expert consultation on treatment scale up in resource-limited settings.

Andrieux-Meyer, Isabelle; Calmy, Alexandra; Cahn, Pedro; Clayden, Polly; Raguin, Gilles; Katlama, Christine; Vitoria, Marco; Levin, Andrew; Lynch, Sharonann; Goemaere, Eric; Ford, Nathan

2012-01-01

76

Starting Trees from Cuttings.  

ERIC Educational Resources Information Center

|Describes a procedure for starting tree cuttings from woody plants, explaining "lag time," recommending materials, and giving step-by-step instructions for rooting and planting. Points out species which are likely candidates for cuttings and provides tips for teachers for developing a unit. (JM)|

Kramer, David C.

1983-01-01

77

Head Start Curriculum Guide.  

ERIC Educational Resources Information Center

|One of a series of guides for preschool teachers and aides, the book offers a Head Start curriculum guide to help achieve goals regarding social behavior, general attitudes, academic skills, health, and parent development. Information on curriculum is divided into areas of bloc time outline, classroom arrangement, building concepts (such as…

Smith, Clare Coe; And Others

78

Start a Rock Collection  

NSDL National Science Digital Library

Learners follow a three-step process to start their own rock collection. Learners will collect rocks, record information about each rock on a Rock Chart, observe and sort their rocks, and create a rock display. This activity also includes a book list with resources for rock classification.

History, American M.

2012-06-26

79

Electric starting apparatus  

Microsoft Academic Search

An electric starting system is described for cranking an engine comprising, a source of voltage, an electric starter comprising an electric cranking motor and a solenoid having pull-in and hold-in coils and a shiftable plunger, a pinion that is shifted by movement of the plunger that is adapted to mesh with the ring gear of the engine, switch means having

Raver

1986-01-01

80

Starting in School  

ERIC Educational Resources Information Center

|Through its signature initiative, Liberal Education and America's Promise (LEAP), the Association of American Colleges and Universities (AAC&U) is promoting a vision for learning that begins in school: Starting in School . . . Rigorous and rich curriculum focused on the essential learning outcomes; comprehensive, individualized, and…

Albertine, Susan

2012-01-01

81

Starting in School  

ERIC Educational Resources Information Center

Through its signature initiative, Liberal Education and America's Promise (LEAP), the Association of American Colleges and Universities (AAC&U) is promoting a vision for learning that begins in school: Starting in School . . . Rigorous and rich curriculum focused on the essential learning outcomes; comprehensive, individualized, and…

Albertine, Susan

2012-01-01

82

"New Start at 45."  

ERIC Educational Resources Information Center

New Start at 45, operated by Fujitsu Ltd. in Japan, is a management development course for 45-year-old adults in management or supervisory positions. Two components are a 6-week liberal arts curriculum and a 2-week, intensive course in either international management, sales management, or subsidiaries management. Benefits include increased…

Greenstein, Pearl

1989-01-01

83

Project Right Start.  

ERIC Educational Resources Information Center

|The University-Urban Interface Program (UUIP) is a federally-funded project to study an urban university's community relations efforts and innovations, their successes and failures. This is a study of one of the UUIP areas of priority, Project Right Start, a plan for creating a facility for the detection and treatment of psychological problems in…

Jameson, Barbara B.

84

Hydraulic type starting clutch  

Microsoft Academic Search

This patent describes a hydraulic type starting clutch comprising: an input shaft; an input rotating member arranged for rotation in unison with the input shaft; an output shaft; an output rotating member arranged for rotation in unison with the output shaft; friction plates interposed between the input rotating member and the output rotating member for engagement to transmit torque from

K. Ohzono; K. Hayashi; M. Saito; M. Kato; Y. Yoshida

1987-01-01

85

Early Antiretroviral Therapy reduces the incidence of otorrhea in a randomized study of early and deferred antiretroviral therapy: Evidence from the Children with HIV Early Antiretroviral Therapy (CHER) Study  

PubMed Central

Background Although otorrhea occurs commonly in HIV-infected infants, there are few data. We compared the incidence of otorrhea in infants receiving early vs deferred ART in the Children with HIV Early Antiretroviral (CHER) trial. Infants aged 6 to 12 weeks of age with confirmed HIV infection and a CD4 percentage greater than or equal to 25% were randomized to early or deferred ART at two sites in South Africa. Medical records from one study site were reviewed for otorrhea. Findings Data were reviewed from the start of the trial in July 2005 until 20 June 2007, when the Data Safety Monitoring Board recommended that randomization to the deferred arm should stop and that all infants in this arm be reviewed for commencing antiretroviral therapy. Infants entered the study at a median of 7.4 weeks of age. Eleven of 38 (29%) on deferred therapy and 7 of 75 (9%) in the early-therapy group developed otorrhea (risk ratio 3.1, 95% confidence interval (CI) 1.31-7.36; p = 0.01). Conclusions Early initiation of antiretroviral therapy is associated with significantly less otorrhea than when a deferred strategy is followed. Trial registration NCT00102960. ClinicalTrials.Gov

2011-01-01

86

Antiretroviral treatment of maternal HIV infection.  

PubMed Central

QUESTION: One of my pregnant patients tested positive for human immunodeficiency virus. Will HIV therapy put her pregnancy outcome at risk? ANSWER: The biggest risk is vertical transmission of HIV to her baby. She should be treated with combination therapy; triple therapy is required to reduce vertical transmission. Zidovudine is not teratogenic in humans, but information on other antiretroviral drugs is incomplete.

Talaie, Haleh; Nava-Ocampo, Alejandro A.; Koren, Gideon

2004-01-01

87

Antiretroviral drug-related toxicities - clinical spectrum, prevention, and management.  

PubMed

Introduction: The number of HIV patients receiving antiretroviral therapy is increasing worldwide, as new infections continue to occur and access to drugs is scaling up in most developing regions. Due to the efficacious nature of combination antiretroviral therapy in most drug-adherent patients, the concerns on the safety profile of these lifelong medicines have attracted great attention. Areas covered: Side effects of antiretroviral agents can be clinically symptomatic or manifest only as laboratory abnormalities. Drug-related toxicities can be grouped by antiretroviral drug class or damage of distinct body organs/systems. By mechanism, antiretroviral-associated adverse events generally result from hypersensitivity reactions, direct cytopathic effect, or idiosyncratic phenomena. Expert opinion: A good knowledge of the toxicity profile of antiretroviral agents is warranted for HIV care providers in order to prevent and avoid unwanted complications. PMID:23730950

Fernandez-Montero, Jose V; Eugenia, Eugenia; Barreiro, Pablo; Labarga, Pablo; Soriano, Vicente

2013-06-04

88

Drug Interactions with New and Investigational Antiretrovirals  

PubMed Central

More than 20 individual and fixed-dose combinations of antiretrovirals are approved for the treatment of human immunodeficiency virus (HIV) infection. However, owing to the ongoing limitations of drug resistance and adverse effects, new treatment options are still required. A number of promising new agents in existing or new drug classes are in development or have recently been approved by the US FDA. Since these agents will be used in combination with other new and existing antiretrovirals, understanding the potential for drug interactions between these compounds is critical to their appropriate use. This article summarizes the drug interaction potential of new and investigational protease inhibitors (darunavir), non-nucleoside reverse transcriptase inhibitors (etravirine and rilpivirine), chemokine receptor antagonists (maraviroc, vicriviroc and INCB 9471), integrase inhibitors (raltegravir and elvitegravir) and maturation inhibitors (bevirimat).

Brown, Kevin C.; Paul, Sunita; Kashuba, Angela D.M.

2010-01-01

89

Negatively buoyant starting jets  

NASA Astrophysics Data System (ADS)

The initial development of negatively buoyant jets has been investigated experimentally and numerically, focusing on the role played by gravity in the evolution of the leading vortex ring. Under the experimental conditions considered in this work, the densimetric Froude number, Fr=?jUj2/[(?0-?j)gD], which represents the ratio between the jet momentum and the buoyancy forces, emerges as the most relevant parameter characterizing the dynamics of the flow. Two different flow regimes have been observed depending on the Froude number: for sufficiently small Fr, the vortex ring generated initially is pushed radially away by gravity forces before it has time to detach from the shear layer originating at the orifice. On the other hand, when the Froude number is larger than a critical value, Fr>Frc~1, the vortex ring detaches from the injection orifice and propagates downstream into the stagnant ambient followed by a trailing jet until it eventually reaches a maximum penetration depth. In order to clarify the mechanisms leading to the transition between the two regimes, and to gain physical understanding of the formation dynamics of negatively buoyant starting jets, the total and the vortex circulation, as well as the trajectory of the vortex center, have been measured and compared to the case of neutrally buoyant jets. Finally, based on the experimental measurements and on the results of the numerical computations, a kinematic model that successfully describes the evolution of both total circulation and vortex trajectory is proposed.

Marugán-Cruz, C.; Rodríguez-Rodríguez, J.; Martínez-Bazán, C.

2009-11-01

90

Drug Interactions With Antiretrovirals for HIV Infection  

Microsoft Academic Search

More than 20 years of research in human immunodeficiency virus (HIV) infection has led to remarkable scientific breakthroughs\\u000a in drug development. Although the use of highly active antiretroviral therapy (HAART) has dramatically altered survival rates,\\u000a these complex regimens remain challenging to use, even to the experienced practitioner. In no other disease state does the\\u000a management and exploitation of drug interactions

Kimberly A. Struble; Stephen C. Piscitelli

91

[CBO guidelines 'Antiretroviral therapy in the Netherlands'].  

PubMed

In collaboration with the Dutch Institute for Health Care Improvement (CBO) and on the basis of recent developments, new guidelines have been developed for the diagnosis and treatment of HIV-infected patients. The most important recommendations are: Treatment of adult patients is indicated if HIV load > 30,000 RNA copies/ml, or when CD4+ cell count is < 350 x 10(6) cells/l. Treatment of children is indicated if HIV load > 5,000 copies/ml, even when CD4+ cell count is > 500 x 10(6) cells/l. Optimal antiretroviral treatment consists of a combination of two nucleoside reverse transcriptase inhibitors (NRTIs) and one protease inhibitor, or a combination of two NRTIs and one non-nucleoside reverse transcriptase inhibitor. Patients on antiretroviral treatment should be monitored every 3 months. Undetectable HIV load should be the target of first- or second-line antiretroviral treatment. In order to prevent HIV transmission from mother to child, prescription of antiretroviral drugs after the first three months of pregnancy is indicated in pregnant women with a detectable HIV load. Prophylaxis of opportunistic infections can be discontinued if CD4+ cell count recovers above 200 x 10(6)/l. In case of exposure to HIV due to a needle or other occupational accident or unsafe sexual contact, post-exposure prophylaxis should be offered after careful risk evaluation. Preferably, vaccination to prevent pneumococci infections, influenza, hepatitis A or hepatitis B should be given when CD4+ cell count is > 200 x 10(6)/l. PMID:11534375

Borleffs, J C; Danner, S A; Lange, J M; van Everdingen, J J

2001-08-18

92

Antiretroviral Therapy for HIV2 Infected Patients  

Microsoft Academic Search

Objectives: To evaluate clinical and RNA load response to antiretroviral therapy amongst patients infected with HIV-2 and to study the development of drug resistance.Methods: Seven HIV-2 seropositive patients were monitored with clinical examination, CD4 cell count and HIV-2 viral RNA load. Viruses from four subjects were genotyped and in vitro recovery of virus by co-cultivation with PBMCs and HVS T-cells

N. A. Smith; T. Shaw; N. Berry; C. Vella; L. Okorafor; D. Taylor; J. Ainsworth; A. Choudhury; R. S. Daniels; S. El-Gadi; A. Fakoya; G. Moyle; J. Oxford; R. Tedder; S. O'Shea; A. de Ruiter; J. Breuer

2001-01-01

93

Providing antiretroviral care in conflict settings  

Microsoft Academic Search

There has been an historic expectation that delivering combination antiretroviral therapy (cART) to populations affected by\\u000a violent conflict is untenable due to population movement and separation of drug supplies. There is now emerging evidence that\\u000a cART provision can be successful in these populations. Using examples from Médecins Sans Frontières experience in a variety\\u000a of African settings and also local nongovernmental

Edward J. Mills; Nathan Ford; Sonal Singh; Oghenowede Eyawo

2009-01-01

94

Pediatric adherence to HIV antiretroviral therapy  

Microsoft Academic Search

More than 2 million children are infected with HIV globally. Pediatric antiretroviral therapy (ART) adherence is complex,\\u000a and current levels are often suboptimal. As established treatment programs in developed settings struggle with chronic therapy\\u000a and nascent treatment programs in resource-limited settings expand, the importance and challenges of good adherence to ART\\u000a are becoming ever more clear. Adherence behavior is influenced

Jessica Haberer; Claude Mellins

2009-01-01

95

Pilot Controlled Trial of the Adherence Readiness Program: An Intervention to Assess and Sustain HIV Antiretroviral Adherence Readiness.  

PubMed

To pilot the adherence readiness program, 60 patients planning to start HIV antiretrovirals were assigned to usual care (n = 31) or the intervention (n = 29), of whom 54 started antiretrovirals and were followed for up to 24 weeks. At week 24, the intervention had a large effect (50.0 % vs. 16.7 %, d = 0.75) on optimal dose-timing (85+ % doses taken on time) and small effect (54.2 % vs. 43.3 %, d = 0.22) on optimal dose-taking (85+ % doses taken) electronically monitored adherence, and medium effect on undetectable viral load (62 % 0.5 % vs. 43.4 %, d = 0.41), compared to usual care. These intervention benefits on adherence and viral suppression warrant further investigation. PMID:23904145

Wagner, Glenn J; Lovely, Paul; Schneider, Stefan

2013-11-01

96

Pilot Controlled Trial of the Adherence Readiness Program: An Intervention to Assess and Sustain HIV Antiretroviral Adherence Readiness  

PubMed Central

To pilot the Adherence Readiness Program, 60 patients planning to start HIV antiretrovirals were assigned to usual care (n=31) or the intervention (n=29), of whom 54 started antiretrovirals and were followed for up to 24 weeks. At Week 24, the intervention had a large effect (50.0% vs. 16.7%, d=.75) on optimal dose-timing (85+% doses taken on time) and small effect (54.2% vs. 43.3%, d=.22) on optimal dose-taking (85+% doses taken) electronically monitored adherence, and medium effect on undetectable viral load (62%.5% vs. 43.4%, d= .41), compared to usual care. These intervention benefits on adherence and viral suppression warrant further investigation.

Wagner, Glenn J.; Lovely, Paul; Schneider, Stefan

2013-01-01

97

Antiretroviral medications during pregnancy for therapy or prophylaxis  

Microsoft Academic Search

The use of combination antiretroviral therapy during pregnancy has enabled us to decrease perinatal HIV transmission to less\\u000a than 1%, in areas with adequate resources. Questions remain regarding the safety of these medications for the mother, fetus,\\u000a and child. Recent publications present conflicting data about associations between antiretrovirals and prematurity and other\\u000a adverse pregnancy outcomes, and if highly active antiretroviral

Alice Marie Stek

2009-01-01

98

Metabolic abnormalities associated with HIV infection and antiretroviral therapy  

Microsoft Academic Search

Although noted early in the HIV epidemic, metabolic abnormalities came to prominence when potent combination antiretroviral\\u000a therapy was introduced. Complications associated with HIV infection and antiretroviral therapy include cardiovascular disease,\\u000a lipid disorders, glucose metabolism disorders, adipose tissue disorders, bone metabolism disorders, and lactic acidosis. Metabolic\\u000a complications have driven the discovery of new agents and classes of antiretrovirals, and have shaped

Carl J. Fichtenbaum

2009-01-01

99

Complications of HIV disease and antiretroviral therapy.  

PubMed

Studies on the efficacy of and drug interactions with the hepatitis C virus (HCV) direct-acting antivirals (DAAs) in HCV/ HIV coinfection were a highlight of the 2012 Conference on Retroviruses and Opportunistic Infections. The addition of an HCV protease inhibitor (PI) to pegylated interferon alfa/ribavirin increased HCV cure rates by 30% to 35% in HCV genotype 1 treatment-naive HIV-coinfected patients, an increase similar to that observed in HIV-uninfected HCV-infected patients. Drug interactions with antiretrovirals can be complex, and DAAs are recommended for use only with antiretroviral drugs for which pharmacokinetic data are available. Further drug interaction and clinical data are needed to ensure the safe coadminstration of DAAs with antiretroviral therapy. The conference placed continued emphasis on pathogenesis, management, and prevention of the long-term complications of HIV disease and its therapies, including cardiovascular disease, lipodystrophy, renal disease, alterations in bone metabolism, and vitamin D deficiency, along with a growing focus on biomarkers to predict development of end-organ disease. HIV has increasingly been recognized as a disease of accelerated aging, manifested by increased progression of vascular disease, cellular markers of aging, and a heightened risk of certain non-AIDS-defining malignancies. This year's conference also highlighted data on diagnosis, prevention, and complications of tuberculosis coinfection as well as the treatment and prevention of coinfections that are common with HIV, including cryptococcal meningitis, influenza, and varicella zoster. PMID:22710907

Luetkemeyer, Anne F; Havlir, Diane V; Currier, Judith S

100

Challenges in initiating antiretroviral therapy in 2010  

PubMed Central

Many clinical trials have shown that initiating antiretroviral therapy (ART) at higher rather than lower CD4 T cell-positive counts results in survival benefit. Early treatment can help prevent end-organ damage associated with HIV replication and can decrease infectivity. The mainstay of treatment is either a non-nucleoside reverse transcriptase inhibitor or a ritonavir-boosted protease inhibitor in combination with two nucleoside reverse transcriptase inhibitors. While effective at combating HIV, ART can produce adverse alterations of lipid parameters, with some studies suggesting a relationship between some anti-retroviral agents and cardiovascular disease. As the HIV-positive population ages, issues such as hypertension and diabetes must be taken into account when initiating ART. Adhering to ART can be difficult; however, nonoptimal adherence to ART can result in the development of resistance; thus, drug characteristics and the patient’s preparedness to begin therapy must be considered. Reducing the pill burden through the use of fixed-dose antiretroviral drug combinations can facilitate adherence.

Tremblay, Cecile L; Baril, Jean-Guy; Fletcher, David; Kilby, Donald; MacPherson, Paul; Shafran, Stephen D; Tyndall, Mark W

2010-01-01

101

From Head Start to Sure Start: Reflections on Policy Transfer  

ERIC Educational Resources Information Center

|This article uses the history of debates over the US Head Start programme (1965), Early Head Start (1994) and the UK Sure Start initiative (1998), as a window on to policy transfer. In all the three, the aim was that early intervention could offer a means of boosting children's educational attainment and of countering the wider effects of poverty…

Welshman, John

2010-01-01

102

Manual for Head Start Administrators. Volume I: Head Start Requirements.  

ERIC Educational Resources Information Center

|Head Start Administrators must be fully knowledgeable of all applicable Federal requirements and skilled in applying these requirements in the daily operation of their program, whether starting a new program or striving to maintain a high quality program. This manual provides Head Start administrators with a compilation of the program…

Administration for Children, Youth, and Families (DHHS), Washington, DC. Head Start Bureau.

103

Too Smart to Start: Families  

MedlinePLUS

... e-Cards Push Play Resources Did You Know? Families Welcome to Too Smart To Start, your Web ... help young people be too smart to start. Families While many teens drink alcohol, underage alcohol use ...

104

Evaluating Sure Start, Head Start, and Early Head Start: Finding Their Signals Amidst Methodological Static  

ERIC Educational Resources Information Center

|Evaluations of three national early childhood programs--Sure Start in England and Head Start and Early Head Start in the United States--are examined to determine what their respective methodological strengths and weaknesses are and to detect impacts or signals common to all of these evaluations. These shared signals include improved family…

Allen, Benjamin L.

2008-01-01

105

Evaluating Sure Start, Head Start, and Early Head Start: Finding Their Signals Amidst Methodological Static  

Microsoft Academic Search

Evaluations of three national early childhood programs–Sure Start in England and Head Start and Early Head Start in the United States–are examined to determine what their respective methodological strengths and weaknesses are and to detect impacts or signals common to all of these evaluations. These shared signals include improved family functioning and parenting practices and strong signs of parental and

Benjamin L. Allen

2008-01-01

106

Evaluating Sure Start, Head Start, and Early Head Start: Finding Their Signals Amidst Methodological Static  

ERIC Educational Resources Information Center

Evaluations of three national early childhood programs--Sure Start in England and Head Start and Early Head Start in the United States--are examined to determine what their respective methodological strengths and weaknesses are and to detect impacts or signals common to all of these evaluations. These shared signals include improved family…

Allen, Benjamin L.

2008-01-01

107

Pharmacogenetics of Adverse Effects Due To Antiretroviral Drugs  

Microsoft Academic Search

The availability of highly active antiretroviral therapy has markedly improved the survival rate and quality of life in patients infected with HIV. At present, however, there is still no cure for HIV and those undergoing treatment have to do so for life. The use of antiretroviral drugs has been associated with several toxicities that limit their success. Some acute and

Francesc Vidal; Félix Gutiérrez; Mar Gutiérrez; Montserrat Olona; Victoria Sánchez; Gracia Mateo; Joaquim Peraire; Consuelo Viladés; Sergi Veloso; Miguel López-Dupla; Pere Domingo

2010-01-01

108

Cold-start vs. warm-start miss ratios  

Microsoft Academic Search

In a two-level computer storage hierarchy, miss ratio measurements are often made from a “cold start”, that is, made with the first-level store initially empty. For large capacities the effect on the measured miss ratio of the misses incurred while filling the first-level store can be significant, even for long reference strings. Use of “warm-start” rather than “cold-start” miss ratios

Malcolm C. Easton; Ronald Fagin

1978-01-01

109

Antiretroviral treatment in the private sector in Namibia.  

PubMed

Antiretroviral treatment (ART) has been available in the private sector in Namibia since 1998. National guidelines were developed by the Ministry of Health and clinicians of the public and private sector in 2003 and launched at the start of the public sector ART programme by the Ministry of Health. The Namibian HIV Clinicians Society was established around this period to promote adherence to the national guidelines and to provide comprehensive training for health professionals. To monitor adherence to national ART guidelines, in 2003, the Society requested access to anonymized data on ART dispensing from the medical insurance industry. Dispensing data from all Namibian medical insurance companies were obtained. ART regimens were categorized as recommended (non-nucleoside reverse transcriptase inhibitor-based and boosted protease inhibitor [PI]-based), not recommended (non-boosted PI-based or stavudine/didanosine-containing regimens), ineffective (dual therapy) and second line or salvage regimens. This analysis was repeated in 2004, 2005 and 2008. In 2003, only 2306 adult private patients received ART, of which only 1527 (66%) were recommended regimens. In 2008, 7010 private patients received ART, of which 6372 (91%) were recommended regimens. The private sector covered about 15% of the total number of 46,732 reported ART patients reported in the year 2008. Many of these private patients might not have accessed ART in the public sector. PMID:21998178

Van der Veen, F; Mugala-Mukungu, F; Kangudi, M; Feris, A; Katjitae, I; Colebunders, R

2011-10-01

110

Cost-Effectiveness of Antiretroviral Therapy for Prevention  

PubMed Central

Recent empirical studies and analyses have heightened interest in the use of expanded antiretroviral therapy (ART) for prevention of HIV transmission. However, ART is expensive, approximately $600 per person per year, raising issues of the cost and cost-effectiveness of ambitious ART expansion. The goal of this review is to equip the reader with the conceptual tools and substantive background needed to understand and evaluate the policy and programmatic implications of cost-effectiveness assessments of ART for prevention. We provide this review in six sections. We start by introducing and explaining basic concepts of health economics as they relate to this issue, including resources, costs, health metrics (such as Disability-Adjusted Life Years), and different types of economic analysis. We then review research on the cost and cost-effectiveness of ART as treatment, and on the cost-effectiveness of traditional HIV prevention. We describe critical issues in the epidemic impact of ART, such as suppression of transmission and the role of the acute phase of infection. We then present a conceptual model for conducting and interpreting cost-effectiveness analyses of ART as prevention, and review the existing preliminary estimates in this area. We end with a discussion of future directions for programmatic demonstrations and evaluation.

Kahn, James G; Marseille, Elliot A; Bennett, Rod; Williams, Brian G; Granich, Reuben

2011-01-01

111

Establishing a workplace antiretroviral therapy programme in South Africa.  

PubMed

Ways to expand access to antiretroviral treatment (ART) in low income settings are being sought. We describe an HIV care programme including ART in an industrial setting in South Africa. The programme uses guidelines derived from local and international best practice. The training component aims to build capacity among health care staff. Nurses and doctors are supported by experienced HIV clinicians through telephone consultation and site visits. Patients undergo a three-stage counselling procedure prior to starting ART. Drug regimens and monitoring are standardised and prophylaxis against opportunistic infections (isoniazid and cotrimoxazole) is offered routinely. Laboratory and pharmacy services, using named-patient dispensing, are centralized. The programme is designed to ensure that data on clinical and economic outcomes will be available for programme evaluation. Between November 2002-December 2004, ART delivery has been established at 70 ART workplace ART sites. The sites range from 200 to 12000 employees, and from small occupational health clinics and general practitioner rooms to larger hospital clinics. During this period, 2456 patients began ART. Of those on treatment for at least three months, 1728 (78%) have been retained on the programme and only 38 (1.7%) patients have failed the first-line ART regimen. This model for delivery of ART is feasible and successful in an industrial setting. The model may be generalizable to other employment health services in settings of high HIV prevalence, and as a model for implementing ART in other types of health-care settings. PMID:17129856

Charalambous, S; Grant, A D; Day, J H; Pemba, L; Chaisson, R E; Kruger, P; Martin, D; Wood, R; Brink, B; Churchyard, G J

2007-01-01

112

Basic health care package without antiretroviral therapy?  

Microsoft Academic Search

Background  Antiretroviral therapy (ART) for HIV\\/AIDS patients has become a standard in developed countries and a generally accepted objective\\u000a in developing countries. Major funding agencies, such as USAID and the Global Fund to Fight AIDS, Tuberculosis and Malaria,\\u000a are supporting ART programmes in developing countries as a non-negotiable element of a basic health care package.\\u000a \\u000a \\u000a \\u000a Aim  Recently a few papers have challenged

Steffen Flessa

2008-01-01

113

CD4+ Count-Guided Interruption of Antiretroviral Treatment The Strategies for Management of Antiretroviral Therapy (SMART) Study Group  

Microsoft Academic Search

Methods We randomly assigned persons infected with HIV who had a CD4+ cell count of more than 350 per cubic millimeter to the continuous use of antiretroviral therapy (the viral suppression group) or the episodic use of antiretroviral therapy (the drug con- servation group). Episodic use involved the deferral of therapy until the CD4+ count decreased to less than 250

W. M. El-Sadr; J. D. Lundgren; J. D. Neaton; F. Gordin; D. Abrams; R. C. Arduino; A. Babiker; W. Burman; N. Clumeck; C. J. Cohen; D. Cohn

2006-01-01

114

Comparative efficacy versus effectiveness of initial antiretroviral therapy in clinical trials versus routine care  

PubMed Central

Summary The generalizability of clinical trial findings (efficacy) to routine care (effectiveness) may be limited. The present study found similar first year virologic and CD4 outcomes among antiretroviral-naïve patients treated through routine care vs. those participating in clinical trials. Background The generalizability of clinical trial findings (efficacy) to routine care (effectiveness) may be limited due to study eligibility criteria and volunteer bias. While well chronicled in many conditions, the efficacy vs. effectiveness of antiretroviral therapy (ART) remains understudied. Methods A retrospective study of the UAB 1917 Clinic Cohort evaluated naïve patients starting ART between 1/1/00–12/31/06. Patients received ART through clinical trials or routine care. Multivariable logistic and linear regression models were fit to evaluate factors associated with virologic failure (VF=VL>50 copies/mL) and change from baseline CD4 count 6 and 12 months after ART initiation. Sensitivity analyses evaluated the impact of missing data on outcomes. Results Among 570 patients starting ART during the study period, 121 (21%) enrolled in clinical trials vs. 449 (79%) receiving ART via routine care. ART receipt through routine care was not associated with VF at either 6 (OR=1.00;95%CI=0.54–1.86) or 12 (OR=1.56;95%CI=0.80–3.05) months in primary analyses. No significant differences in CD4 count responses at 6 and 12 months were observed. Conclusions Though marked differences in efficacy vs. effectiveness have been observed in the therapeutic outcomes of other conditions, our analyses found no evidence of such divergence among our patients initiating antiretroviral therapy for HIV.

Routman, Justin S.; Willig, James H.; Westfall, Andrew O.; Abroms, Sarah R.; Varshney, Mohit; Adusumilli, Sunil; Allison, Jeroan J.; Savage, Karen G.; Saag, Michael S.; Mugavero, Michael J.

2009-01-01

115

Safety and Tolerability of Antiretrovirals during Pregnancy  

PubMed Central

Combination antiretroviral therapy (CART) dramatically decreases mother-to-child HIV-1 transmission (MTCT), but maternal adverse events are not infrequent. A review of 117 locally followed pregnancies revealed 7 grade ?3 AEs possibly related to antiretrovirals, including 2 hematologic, 3 hepatic, and 2 obstetric cholestasis cases. A fetal demise was attributed to obstetric cholestasis, but no maternal deaths occurred. The drugs possibly associated with these AE were zidovudine, nelfinavir, lopinavir/ritonavir, and indinavir. AE or intolerability required discontinuation/substitution of nevirapine in 16% of the users, zidovudine in 10%, nelfinavir in 9%, lopinavir/ritonavir in 1%, but epivir and stavudine in none. In conclusion, nevirapine, zidovudine, and nelfinavir had the highest frequency of AE and/or the lowest tolerability during pregnancy. Although nevirapine and nelfinavir are infrequently used in pregnancy at present, zidovudine is included in most MTCT preventative regimens. Our data emphasize the need to revise the treatment recommendations for pregnant women to include safer and better-tolerated drugs.

Weinberg, Adriana; Forster-Harwood, Jeri; Davies, Jill; McFarland, Elizabeth J.; Pappas, Jennifer; Kinzie, Kay; Barr, Emily; Paul, Suzanne; Salbenblatt, Carol; Soda, Elizabeth; Vazquez, Anna; Levin, Myron J.

2011-01-01

116

Guidelines for antiretroviral therapy for HIV infection  

PubMed Central

OBJECTIVE: To develop guidelines for health care providers and their HIV-positive patients on the clinical use of antiretroviral agents for HIV infection. OPTIONS: Recommendations published in 1996 by an international panel. OUTCOMES: Improvement in clinical outcomes or in surrogate markers of disease activity. EVIDENCE AND VALUES: The Canadian HIV Trials Network held a workshop on Oct. 19-20, 1996, to develop Canadian guidelines that incorporate information from recent basic and clinical research. RECOMMENDATIONS: Recommendations for the use of antiretroviral drugs in HIV infection are provided for initial therapy, continuing therapy, primary infection, vertical transmission, pediatric therapy and postexposure prophylaxis. VALIDATION: The guidelines are based on consensus of the participants attending the workshop: Canadian investigators, clinicians and invited representatives from the community, government and the pharmaceutical industry. They are subject to review and updating as new information on clinical benefits is published. SPONSORS: The workshop was organized by the National Centre of the Canadian HIV Trials Network. Unrestricted educational grants were provided by 8 pharmaceutical companies. Additional support was provided from the National AIDS Strategy of Health Canada.

Rachlis, A R; Zarowny, D P

1998-01-01

117

Mitochondrial DNA haplogroups and incidence of lipodystrophy in HIV-infected patients on long-term antiretroviral therapy.  

PubMed

We investigated the rates of lipodystrophy events, according to mitochondrial DNA haplogroup, in 187 patients starting combination antiretroviral therapy and following it. Incidence rates of lipoatrophy and fat accumulation were 8.2 and 4.8 per 100 person-years of follow-up, respectively. In multivariable models, patients with haplogroup K were at higher risk of any lipodystrophy [adjusted relative risk (aRR) 4.02, P = 0.0009], lipoatrophy (competing-risk aRR 2.42, P = 0.09; cause-specific aRR 2.99, P = 0.031), and fat accumulation (competing-risk aRR, 2.63, P = 0.11; cause-specific aRR 5.27, P = 0.019) than those with haplogroup H. Mitochondrial haplogroups may explain part of the genetic predisposition to lipodystrophy during combination antiretroviral therapy. PMID:22245716

De Luca, Andrea; Nasi, Milena; Di Giambenedetto, Simona; Cozzi-Lepri, Alessandro; Pinti, Marcello; Marzocchetti, Angela; Mussini, Cristina; Fabbiani, Massimiliano; Bracciale, Laura; Cauda, Roberto; Cossarizza, Andrea

2012-02-01

118

Antiretroviral-based HIV-1 prevention: antiretroviral treatment and pre-exposure prophylaxis.  

PubMed

Antiretroviral-based HIV-1 prevention strategies - including antiretroviral treatment (ART) to reduce the infectiousness of individuals with HIV-1 and oral and topical pre-exposure prophylaxis (PrEP) for uninfected individuals to prevent HIV-1 acquisition - are the most promising new approaches for decreasing HIV-1 spread. Observational studies among HIV-1 serodiscordant couples have associated ART initiation with a reduction in HIV-1 transmission risk of 80-92%, and a recent randomized trial demonstrated that earlier initiation of ART (that is, at CD4(+) T-cell counts between 350 and 550 cells/mm(3)), in the context of virological monitoring and adherence support, resulted in a 96% reduction in HIV-1 transmission. A number of ongoing and recently-completed clinical trials have assessed the efficacy of PrEP for HIV-1 prevention as pericoitally administered or daily-administered 1% tenofovir gel and daily oral tenofovir disoproxil fumarate (TDF) and combination emtricitabine (FTC)/TDF. Completed studies have demonstrated HIV-1 protection efficacies ranging from 39% to 75%. However, two trials in African women have shown no HIV-1 protection with TDF and FTC/TDF PrEP; the reasons for lack of efficacy in those trials are being investigated. Adherence is likely the key to efficacy of antiretrovirals for HIV-1 prevention, both as ART and PrEP. Critical unanswered questions for successful delivery of antiretroviral-based HIV-1 prevention include how to target ART and PrEP to realize maximum population benefits, whether HIV-1-infected individuals at earlier stages of infection would accept ART to reduce their risk for transmitting HIV-1 and whether highest-risk HIV-1-negative persons would use PrEP, and whether high adherence could be sustained to achieve high effectiveness. PMID:23221365

Celum, Connie; Baeten, Jared M

2012-12-07

119

[Mitochondrial hepatic toxicity associated with antiretroviral treatment].  

PubMed

Highly active antiretroviral therapy (HAART) has become the gold standard treatment of HIV/AIDS infection. NRTI-related mitochondrial toxicity has been recognized as a serious adverse effect of HAART. The mechanisms underlying NRTI-induced mitochondriopathy involve the inhibition of the human DNA polymerase gamma mtDNA mutations and oxidative stress. The clinical spectrum of NRTI-related toxicity ranges from a subclinical disease e.g. mild hepatic abnormalities, to a rare life-threatening condition with lactic acidosis and hepatic insufficiency. In the latter, liver histology shows massive steatosis. Ultrastructural assessment of mitochondrial abnormalities may be of help to address the NRTI toxicity in poorly symptomatic patients. Efforts have been recently made to assess the clinical relevance of non-invasive tests including the evaluation of mtDNA or mitochondrial functions in peripheral blood mononuclear cells for the diagnosis of NRTI-associated toxicity. PMID:16327656

Duong Van Huyen, Jean-Paul; Batisse, Dominique; Bélair, Marie-France; Bruneval, Patrick

2005-09-01

120

Taking Antiretroviral Therapy for HIV Infection  

PubMed Central

OBJECTIVE To describe how people with HIV understand and experience the problem of adhering to antiretroviral medication regimens. DESIGN We performed a qualitative study based on interviews with HIV-infected patients, including 46 clients of AIDS service organizations, who were sampled according to age, ethnicity, and injection drug use history, and a convenience sample of 15 patients. Interviews were conducted in English or Spanish and were audiotaped and transcribed. PARTICIPANTS Of 52 respondents who had prescriptions for antiretroviral therapy, 25 were randomly selected for in-depth analysis. Of these, 5 reported having an AIDS diagnosis, 15 reported symptoms they attributed to HIV, and 5 reported having no symptoms of HIV disease. MEASUREMENTS AND MAIN RESULTS Investigators prepared structured abstracts of interviews to extract adherence-related data. One investigator compared the abstracts with the original transcripts to confirm the interpretations, and used the abstracts to organize and classify the findings. Most subjects (84%) reported recent nonadherent behavior, including ceasing treatment, medication “holidays,” sleeping through doses, forgetting doses, skipping doses due to side effects, and following highly asymmetric schedules. Initially, most reported that they were not significantly nonadherent, and many did not consider their behavior nonadherent. Only a minority clearly understood the possible consequences of missing doses. Most said they had not discussed their nonadherence with their physicians. CONCLUSIONS Many people rationalize their difficulty in adhering to HIV treatment by deciding that the standard of adherence they can readily achieve is appropriate. Physicians should inquire about adherence-related behavior in specific detail, and ensure that patients understand the consequences of not meeting an appropriate standard.

Laws, M Barton; Wilson, Ira B; Bowser, Diana M; Kerr, Sarah E

2000-01-01

121

Too Smart to Start: Teens  

MedlinePLUS

... Smart To Start, your Web site on avoiding underage alcohol use and its consequences. We’re glad that ... affects your body and your behavior. Facts About Underage Drinking : Learn about alcohol facts, myths, consequences, and more. ...

122

Head Start Dental Health Curriculum.  

National Technical Information Service (NTIS)

There are many ways to provide meaningful learning experiences about dental health that can help Head Start children develop good attitudes and habits. Learning about good dental health care at an early age can help children throughout their lives. Dental...

1997-01-01

123

Design of the START experiment  

SciTech Connect

The START experiment (Small Tight Aspect Ratio Tokamak) is a low-budget device under construction that is specifically intended to investigate MHD behavior at extremely tight aspect ratios (as low as R/a-1.2) as well as the effectiveness of a major radius compression technique to produce high toroidal current in such plasmas. The main components of the START assembly are described along with the mode of operation.

Smith, R.T.C. [UKAEA Fusion, Culham UK; Peng, Yueng Kay Martin [ORNL

1989-01-01

124

Early Antiretroviral Therapy and Mortality among HIV-Infected Infants  

PubMed Central

Background In countries with a high seroprevalence of human immunodeficiency virus type 1 (HIV-1), HIV infection contributes significantly to infant mortality. We investigated antiretroviral-treatment strategies in the Children with HIV Early Antiretroviral Therapy (CHER) trial. Methods HIV-infected infants 6 to 12 weeks of age with a CD4 lymphocyte percentage (the CD4 percentage) of 25% or more were randomly assigned to receive antiretroviral therapy (lopinavir–ritonavir, zidovudine, and lamivudine) when the CD4 percentage decreased to less than 20% (or 25% if the child was younger than 1 year) or clinical criteria were met (the deferred antiretroviral-therapy group) or to immediate initiation of limited antiretroviral therapy until 1 year of age or 2 years of age (the early antiretroviral-therapy groups). We report the early outcomes for infants who received deferred antiretroviral therapy as compared with early antiretroviral therapy. Results At a median age of 7.4 weeks (interquartile range, 6.6 to 8.9) and a CD4 percentage of 35.2% (interquartile range, 29.1 to 41.2), 125 infants were randomly assigned to receive deferred therapy, and 252 infants were randomly assigned to receive early therapy. After a median follow-up of 40 weeks (interquartile range, 24 to 58), antiretroviral therapy was initiated in 66% of infants in the deferred-therapy group. Twenty infants in the deferred-therapy group (16%) died versus 10 infants in the early-therapy groups (4%) (hazard ratio for death, 0.24; 95% confidence interval [CI], 0.11 to 0.51; P<0.001). In 32 infants in the deferred-therapy group (26%) versus 16 infants in the early-therapy groups (6%), disease progressed to Centers for Disease Control and Prevention stage C or severe stage B (hazard ratio for disease progression, 0.25; 95% CI, 0.15 to 0.41; P<0.001). Stavudine was substituted for zidovudine in four infants in the early-therapy groups because of neutropenia in three infants and anemia in one infant; no drugs were permanently discontinued. After a review by the data and safety monitoring board, the deferred-therapy group was modified, and infants in this group were all reassessed for initiation of antiretroviral therapy. Conclusions Early HIV diagnosis and early antiretroviral therapy reduced early infant mortality by 76% and HIV progression by 75%. (ClinicalTrials.gov number, NCT00102960.)

Violari, Avy; Cotton, Mark F.; Gibb, Diana M.; Babiker, Abdel G.; Steyn, Jan; Madhi, Shabir A.; Jean-Philippe, Patrick; McIntyre, James A.

2010-01-01

125

Facilitating Compound Progression of Antiretroviral Agents via Modeling and Simulation  

Microsoft Academic Search

Pharmacotherapy in human immunodeficiency virus (HIV)-infected patients and the development of safe and effective antiretroviral\\u000a dosing regimens has been hindered by numerous issues, including the rapid development of viral resistance to drug therapy,\\u000a the narrow therapeutic window of the drug compounds, and lack of fundamental knowledge concerning the sources of variation\\u000a in exposure and response to antiretroviral agents. Sources of

Jeffrey S. Barrett

2007-01-01

126

Cardiometabolic risk factors among HIV patients on antiretroviral therapy  

PubMed Central

Background HIV and combination antiretroviral therapy (cART) may increase cardiovascular disease (CVD) risk. We assessed the early effects of cART on CVD risk markers in a population with presumed low CVD risk. Methods Adult patients (n=118) in Lusaka, Zambia were recruited at the time of initiation of cART for HIV/AIDS. Cardiometabolic risk factors were measured before and 90?days after starting cART. Participants were grouped according to cART regimens: Zidovudine + Lamivudine + Nevirapine (n=58); Stavudine + Lamivudine + Nevirapine (n=43); and ‘other’ (Zidovudine + Lamivudine + Efavirenz, Stavudine + Lamivudine + Efavirenz, Tenofovir + Emtricitabine + Efavirenz or Tenofovir + Emtricitabine + Nevirapine, n=17). ANOVA was used to test whether changes in cardiometabolic risk markers varied by cART regimen. Results From baseline to 90?days after initiation of cART, the prevalence of low levels of high-density lipoprotein cholesterol (<1.04?mmol/L for men and <1.30?mmol/L for women) significantly decreased (78.8% vs. 34.8%, P<0.001) while elevated total cholesterol (TC ?5.18?mmol/L, 5.1% vs. 11.9%, P=0.03) and the homeostasis model assessment of insulin resistance ?3.0 (1.7% vs. 17.0%, P<0.001) significantly increased. The prevalence of TC:HDL-c ratio ?5.0 significantly decreased (44.9% vs. 6.8%, P<0.001). These changes in cardiometabolic risk markers were independent of the cART regimen. Conclusion Our results suggest that short-term cART is associated with a cardioprotective lipid profile in Zambia and a tendency towards insulin resistance regardless of the cART regimen.

2013-01-01

127

Five Year Outcomes of the China National Free Antiretroviral Treatment Program  

PubMed Central

Background China's National Free Antiretroviral Treatment Program began in 2002 and, by August 2008, included over 52,000 patients. Objective To report five year outcomes on adult mortality and immunological treatment failure rates and risk factors. Design Open cohort analysis of prospectively collected observational database. Patients All patients in national treatment database from June 2002-August 2008. Patients excluded if not started on triple therapy or had missing treatment regimen information. Intervention Antiretroviral therapy per Chinese national treatment guidelines. Measurements Mortality rate and immunologic treatment failure rate using World Health Organization criteria. Results Of 52,191 total patients, 48,785 were included. Median age was 38 years, 58% were male, 53% were infected through plasma/blood, and median baseline CD4 cell count was 118/?L. Mortality was greatest during the first three months of treatment (22.6/100 person-years) but declined to a steady rate of 4-5/100 person-years after six months and maintained over the subsequent 4½ years. Baseline CD4 cell count <50/?L (adjusted hazard ratio [HR] 3.3, 95% confidence interval [CI] 2.9-3.8, compared to ?200/?L) and having 4-5 baseline symptom categories (adjusted HR 3.4, 95% CI 2.9-4.0, compared to no baseline symptoms) were the strongest mortality risk factors. Treatment failure was determined among 31,070 with ?1 follow-up CD4 cell count. Overall, 25% (12.0/100 person-years) failed treatment with the cumulative treatment failure rate increasing to 50% at five years. Limitation Immunologic treatment failure does not necessarily correlate well with virologic treatment failure. Conclusions The National Free Antiretroviral Treatment Program reduced mortality among adult AIDS patients in China to rates comparable to other low or middle-income countries. A cumulative immunological treatment failure rate of 50% after five years, with limited availability of second-line regimens, is of great concern.

Zhang, Fujie; Dou, Zhihui; Ma, Ye; Zhao, Yan; Liu, Zhongfu; Bulterys, Marc; Chen, Ray Y.

2009-01-01

128

Antiretroviral drug concentrations in semen of HIV-1 infected men  

PubMed Central

website extra A table detailing antiretroviral drugs appears on the STI website. www.sextransinf.com Because semen is a major vehicle for the sexual transmission of HIV-1, control of viral replication within the sanctuary of the male genital tract should be a goal of antiretroviral therapy. Local immune responses, virus specific factors, and the degree of viral and cellular trafficking all appear to be important in controlling viral replication and evolution. However, the most important factor influencing viral replication and evolution within the male genital tract may be the disposition of antiretroviral agents into genital tissues and fluids. This review proposes possible mechanisms of antiretroviral distribution into the male genital tract by using other sanctuary barriers; such as the placenta, renal tubules, and blood-brain barrier; as models. In addition, this review summarises recent clinical studies regarding the disposition of currently available antiretroviral drugs into the seminal plasma and discusses some of the difficulties in interpreting drug concentration in the genital tract. Key Words: HIV; semen; antiretrovirals; drug concentrations; pharmacokinetics; protein binding

Taylor, S.; Pereira, A.

2001-01-01

129

Long-term outcome of patients after a single interruption of antiretroviral therapy: a cohort study  

PubMed Central

Background To describe the long term outcome of patients who interrupted highly active antiretroviral therapy (HAART) once, identify the variables associated with earlier need to re-start HAART, and the response when therapy was resumed. A retrospective observational cohort of 66 adult patients with HIV-1 infection who interrupted HAART with a CD4+cell count ?350 cells/?L and undetectable viral load (VL) was performed. The pre-established CD4+ cell count for restarting therapy was 300cells/?L. Cox regression was used to analyse the variables associated with earlier HAART reinitiation. Results The median follow-up was 209 weeks (range, 64–395). Rates of HIV-related or possible HIV-related events were 0.37 (one case of acute retroviral syndrome) and 1.49 per 100 patient-years, respectively. Two patients died after re-starting therapy and having reached undetectable VL. Three patients suffered a sexually transmitted disease while off therapy. Fifty patients (76%) resumed therapy after a median of 97 weeks (range, 17–267). Age, a nadir of CD4+ <250 cells/?L, and a mean VL during interruption of >10,000 copies/ml were independent predictors for earlier re-start. The intention-to-treat success rate of the first HAART resumed regimen was 85.4%. There were no differences by regimen used, nor between regimens that were the same as or different from the one that had been interrupted. Conclusions Our data suggest highly active antiretroviral therapy may be interrupted in selected patients because in these patients, when the HAART is restarted, the viral and clinical response may be achieved.

2012-01-01

130

New strategies for lowering the costs of antiretroviral treatment and care for people with HIV/AIDS in the United Kingdom.  

PubMed

In the UK, the annual cost of treatment and care for people with human immunodeficiency virus (HIV)/acquired immune deficiency virus (AIDS) rose by over 600% from £104 million in 1997 to £762 million in 2010; approximately two-thirds of the £762 million cost of treatment and care in 2010 was for the procurement of antiretrovirals and other related drugs. The number of people accessing care for HIV/AIDS rose from 22,000 in 2000 to 65,000 in 2009. Adoption of "test and treat" guidelines for treating all HIV-infected people with antiretrovirals would further increase the burden of costs. Given the current economic situation, there is now a new focus on strategies for treatment and care of people with HIV-1 infection which can maintain efficacy but at a lower cost. In this review, we propose three strategies which could potentially lower the costs of treatment and care, ie, stopping testing CD4 counts for patients with full HIV RNA suppression on antiretroviral treatment and recent CD4 counts above 350 cells/?L; more widespread use of generic antiretrovirals as replacements for patients currently taking patented versions; and use of darunavir-ritonavir monotherapy as a switch option for patients with full HIV RNA suppression on other antiretrovirals and no history of virological failure. However, it is important that high standards of clinical care are maintained despite cost-saving measures. Antiretrovirals with generic alternatives may have toxicity issues, eg, zidovudine and nevirapine. There could be ethical issues in starting patients on these drugs if they are currently tolerating other treatments. The use of darunavir-ritonavir monotherapy is not consistently recommended in international HIV treatment guidelines. PMID:22888265

Gazzard, Brian; Moecklinghoff, Christiane; Hill, Andrew

2012-07-12

131

New strategies for lowering the costs of antiretroviral treatment and care for people with HIV/AIDS in the United Kingdom  

PubMed Central

In the UK, the annual cost of treatment and care for people with human immunodeficiency virus (HIV)/acquired immune deficiency virus (AIDS) rose by over 600% from £104 million in 1997 to £762 million in 2010; approximately two-thirds of the £762 million cost of treatment and care in 2010 was for the procurement of antiretrovirals and other related drugs. The number of people accessing care for HIV/AIDS rose from 22,000 in 2000 to 65,000 in 2009. Adoption of “test and treat” guidelines for treating all HIV-infected people with antiretrovirals would further increase the burden of costs. Given the current economic situation, there is now a new focus on strategies for treatment and care of people with HIV-1 infection which can maintain efficacy but at a lower cost. In this review, we propose three strategies which could potentially lower the costs of treatment and care, ie, stopping testing CD4 counts for patients with full HIV RNA suppression on antiretroviral treatment and recent CD4 counts above 350 cells/?L; more widespread use of generic antiretrovirals as replacements for patients currently taking patented versions; and use of darunavir-ritonavir monotherapy as a switch option for patients with full HIV RNA suppression on other antiretrovirals and no history of virological failure. However, it is important that high standards of clinical care are maintained despite cost-saving measures. Antiretrovirals with generic alternatives may have toxicity issues, eg, zidovudine and nevirapine. There could be ethical issues in starting patients on these drugs if they are currently tolerating other treatments. The use of darunavir-ritonavir monotherapy is not consistently recommended in international HIV treatment guidelines.

Gazzard, Brian; Moecklinghoff, Christiane; Hill, Andrew

2012-01-01

132

Parents Should Start Talking Before They Start Drinking  

Microsoft Academic Search

Most Oakland County youth who drink alcohol usually began drinking in the seventh, eighth or ninth grades. When youth drink alcohol at such young ages, serious harm begins. More children are killed by alcohol than all illegal drugs combined. In addition, children who begin drinking alcohol before the age of 15 are 5 times more likely than those who start

Donnis Reese

133

Estimating the Impact and Cost of the WHO 2010 Recommendations for Antiretroviral Therapy.  

PubMed

In July 2010, WHO published new recommendations on providing antiretroviral therapy to adults and adolescents, including starting ART earlier, usually at a CD4 count of 350 or lower, specific regimens for first- and second-line therapies, and other recommendations. This paper estimates the potential impact and cost of the revised guidelines by first, calculating the number of people that would be in need of antiretroviral therapy (ART) with different eligibility criteria, and second, calculating the costs associated with the potential impact. Results indicate that switching the eligibility criterion from CD4 count <200 to <350 increases the need for ART in low- and middle-income countries (country-level) by 50% (range 34% to 70%). The costs of ART programs only to increase coverage to 80% by 2015 would be 44% more (range 29% to 63%) when switching the eligibility criterion to CD4 count <350. When testing and outreach costs are included, total costs increase by 62%, from US$26.3 billion under the previous eligibility criterion of treating those with CD4 <200 to US$42.5 billion using the revised eligibility criterion of treating those with CD4 <350. PMID:21490782

Stover, John; Bollinger, Lori; Avila, Carlos

2010-11-29

134

Dynamics of the HIV infection under antiretroviral therapy: A cellular automata approach  

NASA Astrophysics Data System (ADS)

The dynamics of human immunodeficiency virus infection under antiretroviral therapy is investigated using a cellular automata model where the effectiveness of each drug is self-adjusted by the concentration of CD4+  T infected cells present at each time step. The effectiveness of the drugs and the infected cell concentration at the beginning of treatment are the control parameters of the cell population's dynamics during therapy. The model allows describing processes of mono and combined therapies. The dynamics that emerges from this model when considering combined antiretroviral therapies reproduces with fair qualitative agreement the phases and different time scales of the process. As observed in clinical data, the results reproduce the significant decrease in the population of infected cells and a concomitant increase of the population of healthy cells in a short timescale (weeks) after the initiation of treatment. Over long time scales, early treatment with potent drugs may lead to undetectable levels of infection. For late treatment or treatments starting with a low density of CD4+  T healthy cells it was observed that the treatment may lead to a steady state in which the T cell counts are above the threshold associated with the onset of AIDS. The results obtained are validated through comparison to available clinical trial data.

González, Ramón E. R.; Coutinho, Sérgio; Zorzenon dos Santos, Rita Maria; de Figueirêdo, Pedro Hugo

2013-10-01

135

Integration of Antiretroviral Therapy with Tuberculosis Treatment  

PubMed Central

Background We previously reported that integrating antiretroviral therapy (ART) with tuberculosis treatment reduces mortality. However, optimal time to initiate ART during tuberculosis treatment remains contentious. Methods To address this, we conducted a 3-arm, open-label randomized controlled trial in South Africa in acid-fast bacilli smear positive patients (n=642) with HIV and CD4+ counts <500 cells/mm3. Findings on the early therapy group (ART initiated within 4 weeks of tuberculosis treatment initiation, n=214) and late therapy group (ART initiated within the first 4 weeks of the continuation phase of tuberculosis treatment, n=215) are presented here. Results Median CD4+ count and viral load at baseline was 150 cells/mm3 and 161000 copies/ml, being similar in both groups. Incidence rate of AIDS or death was 6.9 (18/259.4) and 7.8 (19/244.2) per 100 person-years in the early and late therapy groups respectively (Incidence Rate Ratio (IRR)=0.89; 95%Confidence Interval (95%CI): 0.44,1.79; P=0.73). However, in patients with CD4+ counts <50 cells/mm3, the incidence rates of AIDS or death were 8.5 (early) and 26.3 (late) per 100 person-years (IRR=0.32; 95%CI: 0.07,1.13; P=0.06). Immune reconstitution inflammatory syndrome (IRIS) incidence rates were 20.2 (early) and 7.7 (late) per 100 person-years (IRR=2.62; 95%CI: 1.48,4.82; P<0.001). Adverse events requiring antiretroviral drug switches occurred in 10 (early) and 1 (late) patients (P=0.006). Conclusions The benefits of AIDS-free survival balanced against the risks of IRIS and ART-related adverse events, support early ART initiation in patients with CD4+ counts <50 cells/mm3 and deferred ART initiation to the continuation phase of tuberculosis treatment when CD4+ counts are higher.

Abdool Karim, Salim S.; Naidoo, Kogieleum; Grobler, Anneke; Padayatchi, Nesri; Baxter, Cheryl; Gray, Andrew L.; Gengiah, Tanuja; Gengiah, Santhanalakshmi; Naidoo, Anushka; Jithoo, Niraksha; Nair, Gonasagrie; El-Sadr, Wafaa M.; Friedland, Gerald; Abdool Karim, Quarraisha

2011-01-01

136

Trends in CD4 counts in HIV-infected patients with HIV viral load monitoring while on combination antiretroviral treatment: results from The TREAT Asia HIV Observational Database  

Microsoft Academic Search

BACKGROUND: The aim of this study was to examine the relationship between trends in CD4 counts (slope) and HIV viral load (VL) after initiation of combination antiretroviral treatment (cART) in Asian patients in The TREAT Asia HIV Observational Database (TAHOD). METHODS: Treatment-naive HIV-infected patients who started cART with three or more and had three or more CD4 count and HIV

Jialun Zhou; Thira Sirisanthana; Sasisopin Kiertiburanakul; Yi-Ming A Chen; Ning Han; Nagalingeswaran Kumarasamy; Jun Yong Choi; Tuti Parwati Merati; Evy Yunihastuti; Shinichi Oka; Adeeba Kamarulzaman; Praphan Phanuphak; Christopher KC Lee; Patrick CK Li; Sanjay Pujari; Vanthanak Saphonn; Matthew G Law

2010-01-01

137

Estimating Loss to Follow-Up in HIV-Infected Patients on Antiretroviral Therapy: The Effect of the Competing Risk of Death in Zambia and Switzerland  

Microsoft Academic Search

BackgroundLoss to follow-up (LTFU) is common in antiretroviral therapy (ART) programmes. Mortality is a competing risk (CR) for LTFU; however, it is often overlooked in cohort analyses. We examined how the CR of death affected LTFU estimates in Zambia and Switzerland.Methods and FindingsHIV-infected patients aged ?18 years who started ART 2004–2008 in observational cohorts in Zambia and Switzerland were included.

Franziska Schöni-Affolter; Olivia Keiser; Albert Mwango; Jeffrey Stringer; Bruno Ledergerber; Lloyd Mulenga; Heiner C. Bucher; Andrew O. Westfall; Alexandra Calmy; Andrew Boulle; Namwinga Chintu; Matthias Egger; Benjamin H. Chi

2011-01-01

138

Suboptimal CD4 reconstitution despite viral suppression in an urban cohort on Antiretroviral Therapy (ART) in sub-Saharan Africa: Frequency and clinical significance  

Microsoft Academic Search

BACKGROUND: A proportion of individuals who start antiretroviral therapy (ART) fail to achieve adequate CD4 cell reconstitution despite sustained viral suppression. We determined the frequency and clinical significance of suboptimal CD4 reconstitution despite viral suppression (SO-CD4) in an urban HIV research cohort in Kampala, Uganda METHODS: We analyzed data from a prospective research cohort of 559 patients initiating ART between

Damalie Nakanjako; Agnes Kiragga; Fowzia Ibrahim; Barbara Castelnuovo; Moses R Kamya; Philippa J Easterbrook

2008-01-01

139

Steady-state nevirapine, lamivudine and stavudine levels in Malawian HIV-infected children on antiretroviral therapy using split Triomune 30 tablets  

Microsoft Academic Search

BACKGROUND: Children remain under-represented in national antiretroviral treatment (ART) programmes in settings with limited resources and high HIV prevalence. In Malawi, an increasing number of HIV-infected children have been started on ART with split tablets of an adult fixed-dose combination drug in the past few years. In 2006, the national paediatric ART regime was changed from Triomune 40 (T40) to

Goenke Poerksen; Louisa Pollock; Peter Moons; Emily Chesshyre; David Burger; Saye Khoo; Elizabeth Molyneux

2010-01-01

140

Preparing for highly active antiretroviral therapy rollout in rural South Africa: an assessment using the information, motivation, and behavioral skills model  

Microsoft Academic Search

Following a controversial history and before South Africa started the world's largest highly active antiretroviral therapy (HAART) rollout, little was known about community-level information, motivation, and behavioral skills (IMB) regarding HAART in high-HIV-prevalence rural communities. The IMB model has been shown to predict behaviors that are associated with desirable HAART outcomes. We conducted an anonymous, cross-sectional “HAART-Felt Prospects” survey among

Margo D. Simon; Frederick L. Altice; Anthony P. Moll; Mbuso Shange; Gerald H. Friedland

2010-01-01

141

Early versus delayed initiation of antiretroviral therapy for Indian HIV-Infected individuals with tuberculosis on antituberculosis treatment  

PubMed Central

Background For antiretroviral therapy (ART) naive human immunodeficiency virus (HIV) infected adults suffering from tuberculosis (TB), there is uncertainty about the optimal time to initiate highly active antiretroviral therapy (HAART) after starting antituberculosis treatment (ATT), in order to minimize mortality, HIV disease progression, and adverse events. Methods In a randomized, open label trial at All India Institute of Medical Sciences, New Delhi, India, eligible HIV positive individuals with a diagnosis of TB were randomly assigned to receive HAART after 2-4 or 8-12?weeks of starting ATT, and were followed for 12?months after HAART initiation. Participants received directly observed therapy short course (DOTS) for TB, and an antiretroviral regimen comprising stavudine or zidovudine, lamivudine, and efavirenz. Primary end points were death from any cause, and progression of HIV disease marked by failure of ART. Findings A total of 150 patients with HIV and TB were initiated on HAART: 88 received it after 2-4?weeks (early ART) and 62 after 8-12?weeks (delayed ART) of starting ATT. There was no significant difference in mortality between the groups after the introduction of HAART. However, incidence of ART failure was 31% in delayed versus 16% in early ART arm (p?=?0.045). Kaplan Meier disease progression free survival at 12?months was 79% for early versus 64% for the delayed ART arm (p?=?0.05). Rates of adverse events were similar. Interpretation Early initiation of HAART for patients with HIV and TB significantly decreases incidence of HIV disease progression and has good tolerability. Trial registration CTRI/2011/12/002260

2012-01-01

142

Head Start Center Design Guide.  

ERIC Educational Resources Information Center

|This guide contains suggested criteria for planning, designing, and renovating Head Start centers so that they are safe, child-oriented, developmentally appropriate, beautiful, environmentally sensitive, and functional. The content is based on the U.S. General Services Administration's Child Care Center Design Guide, PBS-P140, which was intended…

Administration for Children, Youth, and Families (DHHS), Washington, DC. Head Start Bureau.

143

Head Start Center Design Guide.  

National Technical Information Service (NTIS)

This design guide contains suggested criteria for planning, designing, and renovating Head Start centers. The centent is based on the U.S. Gneral Services Administration's Child Care Center Design Guide, PBS-P140, which was intended for use in developing ...

2000-01-01

144

Head Start Dental Health Curriculum.  

ERIC Educational Resources Information Center

|This curriculum for Head Start programs provides preschool learning experiences that teach about dental health. The majority of the curriculum guide is devoted to the following lesson plans: (1) "Introduction of 'Smiley the Super Pup'," an optional puppet character which may be used to review the concepts covered in each lesson; (2) "Visiting the…

Administration for Children, Youth, and Families (DHHS), Washington, DC. Head Start Bureau.

145

HANDBOOK FOR PROJECT HEAD START.  

ERIC Educational Resources Information Center

THIS BOOKLET WAS DESIGNED TO MEET SOME IMMEDIATE NEEDS FOR THE FIRST SUMMER SESSION OF PROJECT HEAD START. IT CONTAINS SOME OF THE MOST WORKABLE AND PROMISING TEACHING METHODS IN THE ENTIRE FIELD OF COMPENSATORY EDUCATIONS, METHODS THAT HAVE BEEN USED IN PRIVATELY SPONSORED CENTERS AND HAVE PROVED VALUABLE IN COPING WITH PROBLEMS ENCOUNTERED IN…

GRAHAM, JORY

146

Commentary on project head start  

Microsoft Academic Search

Conclusion Head Start is in a position to evaluate its successes and failures of the last 20 years, to assess the needs of low-income children and their families in the eighties and nineties, and to plan ahead for another 20 years of successful operation. We must take this challenge seriously, because if we don't our program will not meet the

Francis Wardle

1986-01-01

147

Running Start Research and Discussion.  

ERIC Educational Resources Information Center

|This report discusses several studies of Running Start, a dual-enrollment program for high school juniors and seniors in Washington. The program was created in 1990 by the Washington State Legislature to expand educational choices for high school students. In 1991-1992, there were less than 1,000 students participating; in 1998-1999 there were…

Meld, Andrea

148

Near Field of Starting Plumes  

Microsoft Academic Search

Although steady jets and plumes have been studied extensively in the past, there is relatively little known about the initial stages of starting buoyant jets. The present investigation examined buoyancy-driven flows resulting from cylindrical containers w ith length to diameter ratios (L\\/D) between 2 and 13. Density ratios up to ten percent were utilized. A technique was developed to release

H. Johari; M. Gharib; D. Dabiri

1997-01-01

149

Maintenance Posture for Quick Start.  

National Technical Information Service (NTIS)

Quick Start is an aircraft modification which installed cartridge starters on all engines of the B-52G/H and non-fan KC-135 aircraft. Routine peacetime use of the modification was suspended due to an excessive amount of smoke and toxic gases created by th...

J. M. Connolly

1981-01-01

150

Self start flyback power supply  

SciTech Connect

A switching regulator power supply operates at a variable high frequency with low power dissipation and a minimum of complexity. The transformer primary windings are included as part of a self starting circuit which starts a pulse generator having a fixed pulse width and variable frequency. During a first cycle of operation, the self starting circuit in response to the input rectified AC power after a predetermined period of time applies sufficient voltage which enables the pulse generator to begin generating a first output pulse of fixed pulse width. This causes the primary windings to store energy and feedback energy to the self starting circuit which increases the voltage applied to the generator causing it to begin normal operation at maximum frequency. An error circuit coupled to the secondary winding compares the output DC supply voltage to a reference voltage and generates an error signal which is applied through a DC coupling circuit for adjusting the frequency of the pulse generator to existing line and load conditions.

Fenter, W.S.

1983-08-23

151

Increases in Pediatric Antiretroviral Treatment, South Africa 2005-2010  

PubMed Central

Background In South Africa in 2010, about 340,000 children under the age of 15 were infected with HIV. We describe the increase in the treatment of South African pediatric HIV-infected patients assisted by the President’s Emergency Plan for AIDS Relief (PEPFAR) from 2004 to 2010. Methods We reviewed routine program data from PEPFAR-funded implementing partners among persons receiving antiretroviral treatment age 15 years old and less. Data quality was assessed during the reporting period by program officials through routine analysis of trends and logic checks. Based on UNAIDS estimated mortality rates of untreated HIV-infected children, we calculated the number of deaths averted and life-years gained in children under five receiving PEPFAR-assisted antiretroviral treatment. Results From October 2004 through September 2010, the number of children newly initiated on antiretroviral treatment in PEPFAR-assisted programs increased from 154 to 2,641 per month resulting in an increase from 2,412 children on antiretroviral treatment in September 2005 to 79,416 children in September 2010. Of those children who initiated antiretroviral treatment before September 2009, 0–4 year olds were 1.4 (95% CI: 1.3–1.5) times as likely to transfer out of the program or die as 5–14 year olds; males were 1.3 (95% CI: 1.0–1.7) times as likely to stop treatment as females. Approximately 27,548 years of life were added to children under-five years old from PEPFAR-assisted antiretroviral treatment. Conclusions Pediatric antiretroviral treatment in South Africa has increased substantially. However, additional case-finding and a further acceleration in the implementation of pediatric care and treatment services is required to meet the current treatment need.

Patel, Sandeep D.; Larson, Elysia; Mbengashe, Thobile; O'Bra, Heidi; Brown, J. W.; Golman, Thurma M.; Klausner, Jeffrey D.

2012-01-01

152

Conceptualizing Antiretroviral Adherence in Beijing, China  

PubMed Central

International health experts agree that China is on the verge of an AIDS crisis. In response, the Chinese government initiated the “Four Frees and One Care” policy in 2003 to decrease economic barriers and increase access to antiretroviral therapies for people with HIV. However, long-term treatment success requires not only access, but high rates of medication adherence. This qualitative interview study with 29 persons receiving HIV care at Beijing’s Ditan Hospital identified barriers to and facilitators of medication adherence. The interviews were guided by an a priori conceptual model of adherence with four components: access, knowledge about medications, motivation, and proximal cues to action. Barriers to adherence were related to stigma and fear of discrimination; the medications themselves (including side effects and complicated dosing regimens); and other economic issues (i.e., costs of transportation, lab tests, and hospitalizations). Facilitators included participants’ strong will to live, use of electronic reminders, and family support. These results support the conceptual model and suggest that successful interventions must minimize stigma as it negatively affects all components of the model for adherence.

Starks, Helene; Simoni, Jane; Zhao, Hongxin; Huang, Bu; Fredriksen-Goldsen, Karen; Pearson, Cynthia; Chen, Wei-Ti; Lu, Lianhe; Zhang, Fujie

2012-01-01

153

Outcomes of antiretroviral therapy in the Swiss HIV Cohort Study: latent class analysis.  

PubMed

An in-depth understanding of the different groups that make up the HIV-infected population should inform prevention and care. Using latent class analysis (LCA) we identified seven groups with similar socio-demographic and behavioral characteristics at enrolment in the Swiss HIV Cohort Study: older gay men, younger gay men, older heterosexual men, injection drug users, single migrants, migrant women in partnerships and heterosexual men and women. Outcomes of combination antiretroviral therapy (ART) were analyzed in 1,633 patients starting ART. Compared to older gay men, the probability of a virologic response to ART was reduced in single migrants, in older heterosexual men and in IDUs. Loss to follow-up was higher in single migrants and IDUs, and mortality was increased in older heterosexual men and IDUs. Socio-behavioral groups identified by LCA allow insights above what can be gleaned from traditional transmission groups, and may identify patients who could benefit from targeted interventions. PMID:21630013

Keiser, Olivia; Spycher, Ben; Rauch, Andri; Calmy, Alexandra; Cavassini, Matthias; Glass, Tracy R; Nicca, Dunja; Ledergerber, Bruno; Egger, Matthias

2012-02-01

154

Head Start Impact Study: First Year Findings  

ERIC Educational Resources Information Center

|The Congressionally-mandated Head Start Impact Study is being conducted across 84 nationally representative grantee/delegate agencies. Approximately 5,000 newly entering 3- and 4-year-old children applying for Head Start were randomly assigned to either a Head Start group that had access to Head Start program services or to a non-Head Start group…

Puma, Michael; Bell, Stephen; Cook, Ronna; Heid, Camilla; Lopez, Michael

2005-01-01

155

Strategies for Optimizing Adherence to Highly Active Antiretroviral Therapy: Lessons from Research and Clinical Practice  

Microsoft Academic Search

Successful treatment of human immunodeficiency virus infection\\/acquired immunodeficiency syndrome (HIV\\/AIDS) with highly active antiretroviral therapy (HAART) requires that patients maintain nearly perfect adherence to the prescribed regimen. Suboptimal adherence to antiretroviral therapy is clearly the most common cause of virologic failure of HAART regimens. Given the critical role of adherence in successful antiretroviral therapy, it is essential that providers of

2001-01-01

156

The development of antiretroviral therapy and its impact on the HIV-1/AIDS pandemic  

PubMed Central

In the last 25 years, HIV-1, the retrovirus responsible for the Acquired Immunodeficiency Syndrome (AIDS), has gone from being an “inherently untreatable” infectious agent to one eminently susceptible to a range of approved therapies. During a five-year period, starting in the mid-1980s, my group at the National Cancer Institute played a role in the discovery and development of the first generation of antiretroviral agents, starting in 1985 with Retrovir® (zidovudine, AZT) in a collaboration with scientists at the Burroughs-Wellcome Company (now GlaxoSmithKline). We focused on AZT and related congeners in the dideoxynucleoside family of nucleoside reverse transcriptase inhibitors (NRTIs), taking them from the laboratory to the clinic in response to the pandemic of AIDS, then a terrifying and lethal disease. These drugs proved, above all else, that HIV-1 infection is treatable, and such proof provided momentum for new therapies from many sources, directed at a range of viral targets, at a pace that has rarely if ever been matched in modern drug development. Antiretroviral therapy has brought about a substantial decrease in the death rate due to HIV-1 infection, changing it from a rapidly lethal disease into a chronic manageable condition, compatible with very long survival. This has special implications within the classic boundaries of public health around the world, but at the same time in certain regions may also affect a cycle of economic and civil instability in which HIV-1/AIDS is both cause and consequence. Many challenges remain, including 1.) the life-long duration of therapy; 2.) the ultimate role of pre-exposure prophylaxis (PrEP); 3.) the cardiometabolic side effects or other toxicities of long-term therapy; 4.) the emergence of drug-resistance and viral genetic diversity (non-B subtypes); 5.) the specter of new cross-species transmissions from established retroviral reservoirs in apes and Old World monkeys; and 6.) the continued pace of new HIV-1 infections in many parts of the world. All of these factors make refining current therapies and developing new therapeutic paradigms essential priorities, topics covered in articles within this special issue of Antiviral Research. Fortunately, there are exciting new insights into the biology of HIV-1, its interaction with cellular resistance factors, and novel points of attack for future therapies. Moreover, it is a short journey from basic research to public health benefit around the world. The current science will lead to new therapeutic strategies with far-reaching implications in the HIV-1/AIDS pandemic. This article forms part of a special issue of Antiviral Research marking the 25th anniversary of antiretroviral drug discovery and development, Vol 85, issue 1, 2010.

Broder, Samuel

2010-01-01

157

Comparative manufacture and cell-based delivery of antiretroviral nanoformulations  

PubMed Central

Nanoformulations of crystalline indinavir, ritonavir, atazanavir, and efavirenz were manufactured by wet milling, homogenization or sonication with a variety of excipients. The chemical, biological, immune, virological, and toxicological properties of these formulations were compared using an established monocyte-derived macrophage scoring indicator system. Measurements of drug uptake, retention, release, and antiretroviral activity demonstrated differences amongst preparation methods. Interestingly, for drug cell targeting and antiretroviral responses the most significant difference among the particles was the drug itself. We posit that the choice of drug and formulation composition may ultimately affect clinical utility.

Balkundi, Shantanu; Nowacek, Ari S; Veerubhotla, Ram S; Chen, Han; Martinez-Skinner, Andrea; Roy, Upal; Mosley, R Lee; Kanmogne, Georgette; Liu, Xinming; Kabanov, Alexander V; Bronich, Tatiana; McMillan, JoEllyn; Gendelman, Howard E

2011-01-01

158

Impact of African herbal medicines on antiretroviral metabolism.  

PubMed

We examined the effects of two African herbal medicines recommended for HIV/AIDS patients on antiretroviral metabolism. Extracts from Hypoxis and Sutherlandia showed significant effects on cytochrome P450 3A4 metabolism and activated the pregnane X receptor approximately twofold. P-glycoprotein expression was inhibited, with Hypoxis showing 42-51% and Sutherlandia showing 19-31% of activity compared with verapamil. Initiating policies to provide herbal medicines with antiretroviral agents may put patients at risk of treatment failure, viral resistance or drug toxicity. PMID:15627040

Mills, Edward; Foster, Brian C; van Heeswijk, Rolf; Phillips, Elizabeth; Wilson, Kumanan; Leonard, Blair; Kosuge, Kazuhiro; Kanfer, Isadore

2005-01-01

159

Starting a High School newspaper  

NSDL National Science Digital Library

This Website will provide some resources to help you create a high school newspaper. You will see the connection of education and news, see some methods for creation and be able to see available resources i n helping you out Newspapers are very important part of everyday life. Although there are many new forms of media around, newspapers continue to stand the test of time. They can also be very important in the classroom. On this page you will find some valuable resources to help you start a campus paper or ...

Dart, Greg

2007-10-19

160

Rapid starting methanol reactor system  

DOEpatents

The invention relates to a methanol-to-hydrogen cracking reactor for use with a fuel cell vehicular power plant. The system is particularly designed for rapid start-up of the catalytic methanol cracking reactor after an extended shut-down period, i.e., after the vehicular fuel cell power plant has been inoperative overnight. Rapid system start-up is accomplished by a combination of direct and indirect heating of the cracking catalyst. Initially, liquid methanol is burned with a stoichiometric or slightly lean air mixture in the combustion chamber of the reactor assembly. The hot combustion gas travels down a flue gas chamber in heat exchange relationship with the catalytic cracking chamber transferring heat across the catalyst chamber wall to heat the catalyst indirectly. The combustion gas is then diverted back through the catalyst bed to heat the catalyst pellets directly. When the cracking reactor temperature reaches operating temperature, methanol combustion is stopped and a hot gas valve is switched to route the flue gas overboard, with methanol being fed directly to the catalytic cracking reactor. Thereafter, the burner operates on excess hydrogen from the fuel cells.

Chludzinski, Paul J. (38 Berkshire St., Swampscott, MA 01907); Dantowitz, Philip (39 Nancy Ave., Peabody, MA 01960); McElroy, James F. (12 Old Cart Rd., Hamilton, MA 01936)

1984-01-01

161

Importance of Baseline Prognostic Factors With Increasing Time Since Initiation of Highly Active Antiretroviral Therapy  

PubMed Central

Background The extent to which the prognosis for AIDS and death of patients initiating highly active antiretroviral therapy (HAART) continues to be affected by their characteristics at the time of initiation (baseline) is unclear. Methods We analyzed data on 20,379 treatment-naive HIV-1–infected adults who started HAART in 1 of 12 cohort studies in Europe and North America (61,798 person-years of follow-up, 1844 AIDS events, and 1005 deaths). Results Although baseline CD4 cell count became less prognostic with time, individuals with a baseline CD4 count <25 cells/µL had persistently higher progression rates than individuals with a baseline CD4 count >350 cells/µL (hazard ratio for AIDS = 2.3, 95% confidence interval [CI]: 1.0 to 2.3; mortality hazard ratio = 2.5, 95% CI: 1.2 to 5.5, 4 to 6 years after starting HAART). Rates of AIDS were persistently higher in individuals who had experienced an AIDS event before starting HAART. Individuals with presumed transmission by means of injection drug use experienced substantially higher rates of AIDS and death than other individuals throughout follow-up (AIDS hazard ratio = 1.6, 95% CI: 0.8 to 3.0; mortality hazard ratio = 3.5, 95% CI: 2.2 to 5.5, 4 to 6 years after starting HAART). Conclusions Compared with other patient groups, injection drug users and patients with advanced immunodeficiency at baseline experience substantially increased rates of AIDS and death up to 6 years after starting HAART.

2012-01-01

162

Public-Health and Individual Approaches to Antiretroviral Therapy: Township South Africa and Switzerland Compared  

PubMed Central

Background The provision of highly active antiretroviral therapy (HAART) in resource-limited settings follows a public health approach, which is characterised by a limited number of regimens and the standardisation of clinical and laboratory monitoring. In industrialized countries doctors prescribe from the full range of available antiretroviral drugs, supported by resistance testing and frequent laboratory monitoring. We compared virologic response, changes to first-line regimens, and mortality in HIV-infected patients starting HAART in South Africa and Switzerland. Methods and Findings We analysed data from the Swiss HIV Cohort Study and two HAART programmes in townships of Cape Town, South Africa. We included treatment-naïve patients aged 16 y or older who had started treatment with at least three drugs since 2001, and excluded intravenous drug users. Data from a total of 2,348 patients from South Africa and 1,016 patients from the Swiss HIV Cohort Study were analysed. Median baseline CD4+ T cell counts were 80 cells/?l in South Africa and 204 cells/?l in Switzerland. In South Africa, patients started with one of four first-line regimens, which was subsequently changed in 514 patients (22%). In Switzerland, 36 first-line regimens were used initially, and these were changed in 539 patients (53%). In most patients HIV-1 RNA was suppressed to 500 copies/ml or less within one year: 96% (95% confidence interval [CI] 95%–97%) in South Africa and 96% (94%–97%) in Switzerland, and 26% (22%–29%) and 27% (24%–31%), respectively, developed viral rebound within two years. Mortality was higher in South Africa than in Switzerland during the first months of HAART: adjusted hazard ratios were 5.90 (95% CI 1.81–19.2) during months 1–3 and 1.77 (0.90–3.50) during months 4–24. Conclusions Compared to the highly individualised approach in Switzerland, programmatic HAART in South Africa resulted in similar virologic outcomes, with relatively few changes to initial regimens. Further innovation and resources are required in South Africa to both achieve more timely access to HAART and improve the prognosis of patients who start HAART with advanced disease.

Keiser, Olivia; Orrell, Catherine; Egger, Matthias; Wood, Robin; Brinkhof, Martin W. G; Furrer, Hansjakob; van Cutsem, Gilles; Ledergerber, Bruno; Boulle, Andrew

2008-01-01

163

The emergence of drug resistant HIV variants and novel anti-retroviral therapy.  

PubMed

After its identification in 1980s, HIV has infected more than 30 million people worldwide. In the era of highly active anti-retroviral therapy, anti-retroviral drug resistance results from insufficient anti-retroviral pressure, which may lead to treatment failure. Preliminary studies support the idea that anti-retroviral drug resistance has evolved largely as a result of low-adherence of patients to therapy and extensive use of anti-retroviral drugs in the developed world; however, a highly heterogeneous horde of viral quasi-species are currently circulating in developing nations. Thus, the prioritizing of strategies adopted in such two worlds should be quite different considering the varying anti-retroviral drug resistance prevalence. In this article, we explore differences in anti-retroviral drug resistance patterns between developed and developing countries, as they represent two distinct ecological niches of HIV from an evolutionary standpoint. PMID:23835806

Paydary, Koosha; Khaghani, Parisa; Emamzadeh-Fard, Sahra; Alinaghi, Seyed Ahmad Seyed; Baesi, Kazem

2013-07-01

164

The emergence of drug resistant HIV variants and novel anti-retroviral therapy  

PubMed Central

After its identification in 1980s, HIV has infected more than 30 million people worldwide. In the era of highly active anti-retroviral therapy, anti-retroviral drug resistance results from insufficient anti-retroviral pressure, which may lead to treatment failure. Preliminary studies support the idea that anti-retroviral drug resistance has evolved largely as a result of low-adherence of patients to therapy and extensive use of anti-retroviral drugs in the developed world; however, a highly heterogeneous horde of viral quasi-species are currently circulating in developing nations. Thus, the prioritizing of strategies adopted in such two worlds should be quite different considering the varying anti-retroviral drug resistance prevalence. In this article, we explore differences in anti-retroviral drug resistance patterns between developed and developing countries, as they represent two distinct ecological niches of HIV from an evolutionary standpoint.

Paydary, Koosha; Khaghani, Parisa; Emamzadeh-Fard, Sahra; Alinaghi, Seyed Ahmad Seyed; Baesi, Kazem

2013-01-01

165

Three Generic Nevirapine-Based Antiretroviral Treatments in Chinese HIV/AIDS Patients: Multicentric Observation Cohort  

PubMed Central

Background The purpose of this study was to evaluate the efficacy and safety of three nevirapine-based antiretroviral treatments for adult antiretroviral-naïve Chinese patients with HIV-1 infection. Methodology This was a prospective, multicenter study. 198 antiretroviral-naïve HIV-1 positive subjects with CD4 lymphocyte counts between 100/ul and 350/ul and plasma HIV-1 RNA levels more than 500 copies/ml were randomized to start three NVP-based antiretroviral treatments: group A, NVP+AZT+ddI; group B, NVP+3TC+d4T; group C, NVP+AZT+3TC. Viral responses, immunologic responses, adverse events and drug resistence were monitored at baseline and the end of week 4, 12, 24, 36, 52. Viralogical response and immunological response were also comparaed in different strata of baseline CD4 T lymphocyte counts and plasma HIV-1 RNA concentrations. At baseline, the plasma HIV-1 RNA was 4.44±0.68, 4.52±0.71 and 4.41±0.63 lg copies/ml in group A, B and C respectively (p?=?0.628). At the end of the study, the plasma viral load reached 2.54±1.11, 1.89±0.46 and 1.92±0.58 lg copies/ml in group A, B and C respectively (p<0.001). At week 52, suppression of plasma HIV-1 RNA to less than 50 copies/ml was achieved in more patients in group B and C than in group A (68.2%, 69% vs. 39.7%; p<0.001). In planned subgroup analyses, the decrease of viral response rate was seen in group A when CD4 cell count >200/ul (subgroup H). But in subgroup L, viral response rate of three groups has no significant statistic difference. There were no statistically significant differences among three groups in immunological response wthin any of the CD4 or pVL strata. 3 out of 193 patients with available genotype at baseline showed primary drug resistant. Of 26 patients with virologic failure, 17 patients showed secondary drug resistant, 16 subjects in group A and 1 subject in group B. Logistic regression analysis indicated that presence of hepatotoxicity was associated with HCV-Ab positive (OR?=?2.096, 95%CI: 1.106–3.973, P?=?0.023) and higher CD4 baseline (CD4 count >250/ul)(OR?=?2.096, 95%CI: 1.07–4.107, P?=?0.031). Conclusion Our findings strongly support the use of 3TC+d4T and 3TC+AZT as the nucleoside analogue combination in NVP-based antiretroviral therapy. The regimen of AZT+ddI+NVP produced poor virological response especially in the stratum of CD4 count more than 200/ul. More patients showed secondary drug resistant in this arm too. Patients with HCV-Ab+ and CD4 count >250/ul appear to have significantly high risk of hepatoxicity. Trial Registration ClinicalTrials.gov NCT00618176

Li, Taisheng; Dai, Yi; Kuang, Jiqiu; Jiang, Jingmei; Han, Yang; Qiu, Zhifeng; Xie, Jing; Zuo, Lingyan; Li, Yanling

2008-01-01

166

77 FR 3838 - Notice of Availability of Proposed New Starts/Small Starts Policy Guidance  

Federal Register 2010, 2011, 2012, 2013

...FTA-2010-0009] Notice of Availability of Proposed New Starts/Small Starts Policy Guidance AGENCY: Federal Transit Administration...Administration's (FTA) Proposed Policy Guidance on New Starts/Small Starts and requests your comments on it....

2012-01-25

167

Ingredients: where pet food starts.  

PubMed

Every clinician is asked "What should I feed my pet?" Understanding the ingredients in pet food is an important part of making the best recommendation. Pet food can be as simple as one ingredient or as complicated as containing more than 60 ingredients. Pet food and its ingredients are regulated by the Food and Drug Administration and state feed officials. Part of that regulation is the review and definition of ingredients. Existing ingredients change and new ingredients become available so the need for ingredient definitions grows. Ingredients for product formulations are chosen based on their nutrient content, digestibility, palatability, functionality, availability, and cost. As an example, a typical, nutritionally complete dry dog food with 42 ingredients is examined and the ingredients are discussed here. Safe, healthy pet food starts with safe ingredients sourced from well-monitored suppliers. The ultimate goal of both veterinarians and pet food manufacturers is the same--long healthy lives for dogs and cats. PMID:18656839

Thompson, Angele

2008-08-01

168

Starting a TALEN Core Facility  

PubMed Central

Targeted gene modifications have been advanced by the use of engineered nucleases that make a double strand break (DSB) in genomic DNA. When the cell responds to the DSB by either the imperfect repair process of non-homologous end joining (NHEJ) or by homologous recombination (HR) from a donor template, a targeted modification can result. Since the first engineered nucleases were made in 1996 by fusing a zinc finger DNA binding domain to a FokI cleavage domain, Zinc Finger Nucleases (ZFNs) have progressed considerably to the point of clinical trials for HIV. More recently in 2009, a DNA binding motif called Transcription Activator Like Effector (TALE) was discovered to have a simple code for sequence recognition. Using the same concept as in ZFNs, TALEs were fused to a FokI cleavage domain to engineer Transcription Activator Like Effector Nucleases (TALENs). Although ZFNs are several years ahead of TALENs on research and optimization, TALENs are quickly proving to be capable of similar performance but with a much simpler design. There are commercial vendors as well as core facilities producing ZFNs and TALENs and multiple TALEN assembly kits that have been made publicly available. These TALEN assembly kits can be used to construct a custom nuclease for virtually any genome region of interest. With the idea of starting a TALEN core facility service for a private institution, a comparison of the assembly methods was made to determine which method was best suited. This presentation will introduce the TALEN structure, compare assembly methods from a core facility perspective and highlight the first experiences of starting a TALEN core facility.

Delventhal, Kym

2013-01-01

169

Stevens-Johnson syndrome caused by the antiretroviral drug nevirapine  

Microsoft Academic Search

Nevirapine is a non-nucleoside reverse transcriptase inhibitor widely used in combination with other antiretroviral agents for the treatment of HIV infection. Severe rash, including the Stevens-Johnson syndrome (SJS), is the major toxicity of nevirapine and is described in the package labeling with a prominent, boxed warning. Though physicians treating large populations of patients with HIV are well aware of this

Denise W. Metry; Christopher J. Lahart; Kathryn L. Farmer; Adelaide A. Hebert

2001-01-01

170

Running a tightrope: regulatory challenges in the development of antiretrovirals.  

PubMed

Since the approval of Retrovir, (zidovudine, AZT) in 1987 by the Food and Drug Administration, a number of regulatory initiatives were codified into regulation which contributed to the rapid development of new treatments for HIV-1 infection. These initiatives are a testament to the efforts of AIDS activists and regulators to improve access to drugs for serious and life-threatening diseases. Currently, 28 antiretroviral drugs and combinations of antiretrovirals are available to treat HIV-1 infection. The broadening armamentarium of approved antiretroviral drugs provides new options and more choices for physicians and HIV patients. Importantly, the introduction of these newly approved HIV drugs has shown that the majority of HIV-1-infected treatment-naïve and treatment-experienced patients can achieve maximal virologic suppression (less than 50 copies/mL HIV-1 RNA). This article describes the past and current regulatory challenges in the development of new HIV treatments and provides an overview of the drug regulations that were required for the approval of HIV drugs. This article forms part of a special issue of Antiviral Research marking the 25th anniversary of antiretroviral drug discovery and development, Vol 85, issue 1, 2010. PMID:19665489

Naeger, Lisa K; Struble, Kimberly A; Murray, Jeffrey S; Birnkrant, Debra B

2009-08-07

171

Susceptibility of the human retrovirus XMRV to antiretroviral inhibitors  

Microsoft Academic Search

BACKGROUND: XMRV (xenotropic murine leukemia virus-related virus) is the first known example of an exogenous gammaretrovirus that can infect humans. A limited number of reports suggest that XMRV is intrinsically resistant to many of the antiretroviral drugs used to treat HIV-1 infection, but is sensitive to a small subset of these inhibitors. In the present study, we used a novel

Robert A Smith; Geoffrey S Gottlieb; A Dusty Miller

2010-01-01

172

Factors Influencing Adherence to Antiretroviral Medication in Ilorin, Nigeria  

Microsoft Academic Search

Background: Good adherence to highly active antiretroviral therapy (HAART) is required for viral suppression and prevention of drug resistance. Patients’ adherence to HAART has not been determined since the commencement of HAART at the University of Ilorin Teaching Hospital (UITH), Ilorin, Nigeria, over 5 years ago. Objectives: To determine the adherence level of people living with HIV\\/AIDS (PLWHA) to HAART

Alakija Kazeem Salami; Abayomi Fadeyi; James A Ogunmodede; Olufemi Desalu

2010-01-01

173

Early development of non-hodgkin lymphoma following initiation of newer class antiretroviral therapy among HIV-infected patients - implications for immune reconstitution  

PubMed Central

Background In the HAART era, the incidence of HIV-associated non-Hodgkin lymphoma (NHL) is decreasing. We describe cases of NHL among patients with multi-class antiretroviral resistance diagnosed rapidly after initiating newer-class antiretrovirals, and examine the immunologic and virologic factors associated with potential IRIS-mediated NHL. Methods During December 2006 to January 2008, eligible HIV-infected patients from two affiliated clinics accessed Expanded Access Program antiretrovirals of raltegravir, etravirine, and/or maraviroc with optimized background. A NHL case was defined as a pathologically-confirmed tissue diagnosis in a patient without prior NHL developing symptoms after starting newer-class antiretrovirals. Mean change in CD4 and log10 VL in NHL cases compared to controls was analyzed at week 12, a time point at which values were collected among all cases. Results Five cases occurred among 78 patients (mean incidence = 64.1/1000 patient-years). All cases received raltegravir and one received etravirine. Median symptom onset from newer-class antiretroviral initiation was 5 weeks. At baseline, the median CD4 and VL for NHL cases (n = 5) versus controls (n = 73) were 44 vs.117 cells/mm3 (p = 0.09) and 5.2 vs. 4.2 log10 (p = 0.06), respectively. The mean increase in CD4 at week 12 in NHL cases compared to controls was 13 (n = 5) vs. 74 (n = 50)(p = 0.284). Mean VL log10 reduction in NHL cases versus controls at week 12 was 2.79 (n = 5) vs. 1.94 (n = 50)(p = 0.045). Conclusions An unexpectedly high rate of NHL was detected among treatment-experienced patients achieving a high level of virologic response with newer-class antiretrovirals. We observed trends toward lower baseline CD4 and higher baseline VL in NHL cases, with a significantly greater decline in VL among cases by 12 weeks. HIV-related NHL can occur in the setting of immune reconstitution. Potential immunologic, virologic, and newer-class antiretroviral-specific factors associated with rapid development of NHL warrants further investigation.

2010-01-01

174

Cold start fuel enrichment circuit  

SciTech Connect

A cold start and knock prevention circuit is described having an output node providing a fuel enrichment signal for an internal combustion engine, comprising in combination: transducer means sensing audio signals indicative of engine combustion and occurring within a combustion chamber of the engine and converting the audio signals into an electrical output voltage including a portion representing background noise and a portion representing detonation; means for adjust the amplitude of the transducer output voltage; means sampling the portion of the transducer output voltage representing background noise and controlling the adjusting means to decrease the amplitude of the transducer output voltage for increased sensed background noise and to increase the amplitude of the transducer output voltage for decreased sensed background noise; detonation threshold means responsive to a predetermined increase in the amplitude of the portion of the transducer output voltage representing detonation above the amplitude of the portion of the transducer output voltage representing background noise, and outputting a fuel enrichment signal to the output node; a thermistor connected to the output node and sensing engine temperature; a voltage source biasing the thermistor such that the voltage across the thermistor varies with engine temperature and provides an output fuel enrichment signal at the output node.

Staerzi, R.E.; Radtke, N.H.; Hummel, L.S.

1988-08-16

175

Triple class experience after initiation of combination antiretroviral treatment in Australia: survival and projections  

PubMed Central

Background Patients who have become triple class experienced (TCE) are at a high risk of exhausting available treatment options. This study aims to investigate factors associated with becoming TCE and to explore the effect of becoming TCE on survival. We also project the prevalence of TCE in Australia to 2012. Methods Patients were defined as TCE when they stopped a combination antiretroviral treatment (cART) that introduced the third of the three major antiretroviral classes. Cox proportional hazards models were used to investigate factors associated with TCE and the effect of TCE on survival. To project TCE prevalence, we used predicted rates of TCE by fitting a Poisson regression model, together with the estimated number of patients who started cART in each year in Australia, assuming a mortality rate of 1.5 per 100 person-years. Results Of the 1498 eligible patients, 526 became TCE. Independent predictors of a higher risk of TCE included current CD4 counts below 200 cells µL?1 and earlier calendar periods. No significant difference in survival was observed between those who were TCE and those who were not yet TCE. An increasing number of patients are using cART in Australia and if current trends continue, the number of patients who are TCE is estimated to increase from 2800 in 2003 to 5000 in 2012. Conclusion Our results suggest that the prevalence of TCE in Australia is estimated to plateau after 2003. However, as an increasing number of patients are becoming TCE, it is necessary to develop new drugs that come from new classes or do not have overlapping resistance.

Pour, Sadaf Marashi; Woolley, Ian; Canavan, Peter; Chuah, John; Russell, Darren B.; Law, Matthew; Petoumenos, Kathy

2012-01-01

176

EXPANDING ANTIRETROVIRAL OPTIONS IN RESOURCE-LIMITED SETTINGS - A COSTEFFECTIVENESS ANALYSIS  

PubMed Central

Background Current World Health Organization (WHO) guidelines for treatment of HIV in resource-limited settings call for two antiretroviral regimens. The effectiveness and cost-effectiveness of increasing the number of antiretroviral regimens is unknown. Methods Using a simulation model, we compared the survival and costs of current WHO regimens with two 3-regimen strategies: an initial regimen of three nucleoside reverse transcriptase inhibitors followed by the WHO regimens; and the WHO regimens followed by a regimen with a second-generation boosted protease inhibitor (2bPI). We evaluated monitoring with CD4 counts only and with both CD4 counts and viral load. We used cost and effectiveness data from Cape Town, and tested all assumptions in sensitivity analyses. Results Over the lifetime of the cohort, 25.6% of individuals failed both WHO regimens by virologic criteria. However, when patients were monitored using CD4 counts alone, only 6.5% were prescribed additional HAART, due to missed and delayed detection of failure. The life expectancy gain for individuals who took a 2bPI was 6.7–8.9 months, depending on the monitoring strategy. When CD4 alone was available, adding a regimen with a 2bPI was associated with an incremental cost-effectiveness ratio of $2,581 per year-of-life gained, and when viral load was available, the ratio was $6,519 per year-of-life gained. Strategies with triple-NRTI regimens in initial therapy were dominated. Results were sensitive to the price of 2bPIs. Conclusions About 1 in 4 individuals who start HAART in sub-Saharan Africa will fail currently recommended regimens. At current prices, adding a regimen with a 2bPI is cost-effective for South Africa and other middle-income countries by WHO standards.

Bendavid, Eran; Wood, Robin; Katzenstein, David A.; Bayoumi, Ahmed M.; Owens, Douglas K.

2009-01-01

177

Early antiretroviral treatment reduces risk of bacille Calmette-Gu?rin immune reconstitution adenitis  

PubMed Central

Setting Two centres in Soweto and Cape Town, South Africa. Objective To assess the effects of timing of initiation of antiretroviral treatment (ART) and other factors on the risk of bacille Calmette-Guérin (BCG) related regional adenitis due to immune reconstitution inflammatory syndrome (BCG-IRIS) in human immunodeficiency virus (HIV) infected infants. Design HIV-infected infants aged 6–12 weeks with CD4 count ?25% enrolled in the Children with HIV Early Antiretroviral Therapy (CHER) Trial received early (before 12 weeks) or deferred (after immunological or clinical progression) ART; infants with CD4 count <25% all received early ART. All received BCG vaccination after birth. Reactogenicity to BCG was assessed prospectively during routine study follow-up. Results Of 369 infants, 32 (8.7%) developed BCG-IRIS within 6 months of starting ART, 28 (88%) within 2 months after ART initiation. Of the 32 cases, 30 (93.8%) had HIV-1 RNA > 750 000 copies/ml at initiation. Incidence of BCG-IRIS was 10.9 and 54.3 per 100 person-years (py) among infants with CD4 count ?25% at enrolment receiving early (at median age 7.4 weeks) vs. deferred (23.2 weeks) ART, respectively (HR 0.24, 95%CI 0.11–0.53, P < 0.001). Infants with CD4 count <25% receiving early ART had intermediate incidence (41.7/100 py). Low CD4 counts and high HIV-1 RNA at initiation were the strongest independent risk factors for BCG-IRIS. Conclusions Early ART initiation before immunological and/or clinical progression substantially reduces the risk of BCG-IRIS regional adenitis.

Rabie, H.; Violari, A.; Duong, T.; Madhi, S. A.; Josipovic, D.; Innes, S.; Dobbels, E.; Lazarus, E.; Panchia, R.; Babiker, A. G.; Gibb, D. M.; Cotton, M. F.

2011-01-01

178

Timing of initiation of antiretroviral therapy in AIDS-free HIV-1-infected patients: a collaborative analysis of 18 HIV cohort studies  

PubMed Central

Summary Background The CD4 cell count at which combination antiretroviral therapy should be started is a central, unresolved issue in the care of HIV-1-infected patients. In the absence of randomised trials, we examined this question in prospective cohort studies. Methods We analysed data from 18 cohort studies of patients with HIV. Antiretroviral-naive patients from 15 of these studies were eligible for inclusion if they had started combination antiretroviral therapy (while AIDS-free, with a CD4 cell count less than 550 cells per ?L, and with no history of injecting drug use) on or after Jan 1, 1998. We used data from patients followed up in seven of the cohorts in the era before the introduction of combination therapy (1989–95) to estimate distributions of lead times (from the first CD4 cell count measurement in an upper range to the upper threshold of a lower range) and unseen AIDS and death events (occurring before the upper threshold of a lower CD4 cell count range is reached) in the absence of treatment. These estimations were used to impute completed datasets in which lead times and unseen AIDS and death events were added to data for treated patients in deferred therapy groups. We compared the effect of deferred initiation of combination therapy with immediate initiation on rates of AIDS and death, and on death alone, in adjacent CD4 cell count ranges of width 100 cells per ?L. Findings Data were obtained for 21?247 patients who were followed up during the era before the introduction of combination therapy and 24?444 patients who were followed up from the start of treatment. Deferring combination therapy until a CD4 cell count of 251–350 cells per ?L was associated with higher rates of AIDS and death than starting therapy in the range 351–450 cells per ?L (hazard ratio [HR] 1·28, 95% CI 1·04–1·57). The adverse effect of deferring treatment increased with decreasing CD4 cell count threshold. Deferred initiation of combination therapy was also associated with higher mortality rates, although effects on mortality were less marked than effects on AIDS and death (HR 1·13, 0·80–1·60, for deferred initiation of treatment at CD4 cell count 251–350 cells per ?L compared with initiation at 351–450 cells per ?L). Interpretation Our results suggest that 350 cells per ?L should be the minimum threshold for initiation of antiretroviral therapy, and should help to guide physicians and patients in deciding when to start treatment. Funding UK Medical Research Council.

2009-01-01

179

Does Head Start Make a Difference?  

Microsoft Academic Search

The impact of participation in Head Start is investigated using a national sample of children. Comparisons are drawn between siblings to control for selection. Head Start is associated with large and significant gains in test scores among both whites and African-Americans. However, among African-Americans, these gains are quickly lost. Head Start significantly reduces the probability that a white child will

Janet Currie; Duncan Thomas

1995-01-01

180

Exploration into the Head Start Fade Phenomenon  

Microsoft Academic Search

The Head Start fade effect, documented since the 1970s, finds that students who make gains in I.Q. and social skills in the Head Start program later see those positive effects diminish in the early years of schooling and disappear altogether by the end of third grade. The hypothesis proposed in this study was as follows: Group I Head Start students

Deborah Tenjeras Clarke

2007-01-01

181

Head Start on Science Preliminary Findings.  

ERIC Educational Resources Information Center

For many Head Start teachers and staff, the word "science" conjures up uncomfortable feelings and memories. The purpose of this project--a collaborative effort of California State University, Long Beach and the Head Start Program of Long Beach Unified School District (LBUSD)--was to prepare Head Start staff to become more capable, comfortable,…

Ritz, William C.; Von Blum, Ruth

182

Does Head Start Help Hispanic Children?  

Microsoft Academic Search

Poor educational attainment is a persistent problem among Latino children, relative to non-Latinos. This paper examines the effects of participation in the Head Start program on Latinos. We find that large and significant benefits accrue to Head Start children when we compare them to siblings who did not participate in the program. On average, Head Start closes at least 1\\/4

Janet Currie; Duncan Thomas

1996-01-01

183

Head Start of North Dakota. [Videotape].  

ERIC Educational Resources Information Center

The Head Start program is a comprehensive child development program designed to increase the social competence of children in low-income families and children with disabilities and to improve their chances of school success. This 9-minute videotape describes the Head Start and Early Head Start programs in North Dakota. The tape features parents…

Kingsley, Kranzler

184

Alaska Head Start Annual Program Report, 1999.  

ERIC Educational Resources Information Center

|This annual report details the accomplishments of the Alaska Head Start Program for fiscal year 1999. The report begins with a description of the Head Start program and its core values, and delineates the administrative and program partners of Head Start, its service population, eligibility requirements, funding sources, service models, and…

Alaska State Dept. of Education and Early Devolopment, Juneau. Head Start State Collaboration Office.

185

Happy 30th Birthday Head Start.  

ERIC Educational Resources Information Center

|On Head Start's 30th anniversary, highlights its components of parent involvement and family support, commitment to meeting local needs, training and technical assistance support, and collaborative approach. Also discusses the Head Start Reauthorization Act and the special advisory committee's recommendations for the improvement of the Head Start

Kerr, Tom

1995-01-01

186

Adherence to antiretroviral therapy among HIV-infected prisoners.  

PubMed

Adherence, the act of following a course of medication in exactly the manner prescribed, is critical for the success of therapy. Adherence is influenced by many behavioural and social factors and incarceration might be one such factor. This study determined the level of adherence and reasons for non-adherence to antiretroviral therapy among 93 HIV-infected prisoners. Up to 56% of these patients had poor adherence. A similar rate of adherence was detected in prisoners after release. Problems with antiretroviral adherence among prisoners appear to be mostly linked to their deviant behaviour. Inmates with poor adherence had higher HIV-related morbidity and mortality. Age and country of origin were also associated to adherence. PMID:24008850

Paparizos, Vassilios; Kourkounti, Sofia; Leuow, Kirsten; Georgoulas, Stergios; Kyriakis, Kyriakos; Antoniou, Christina

2013-09-01

187

Dangerous medicines: Unproven AIDS cures and counterfeit antiretroviral drugs  

PubMed Central

Background Increasing access to antiretroviral therapy (ART) is a critical goal endorsed by the United Nations and all of its member states. At the same time, anecdotal accounts suggest that the promotion of unproven AIDS 'cures' and remedies are widespread, and in the case of The Gambia, Iran and South Africa, have been promoted by governments directly. Although a range of legislative and regulatory measures have been adopted by some governments, and technical assistance has been provided by international agencies to address counterfeit medicines generally, the threat of counterfeit antiretroviral drugs is not being addressed. Discussion Countries, charged with fulfilling the right to health and committed to expanding access to ART must explicitly recognize their obligation to combat unproven AIDS treatments and ensure the availability of a safe and efficacious drugs supply. International donors must help support and coordinate these efforts.

Amon, Joseph J

2008-01-01

188

HIV-1 Neuroimmunity in the Era of Antiretroviral Therapy  

PubMed Central

Human immunodeficiency virus type one (HIV-1) associated neurocognitive disorders (HAND) can affect < 50% of infected people during the disease course. While antiretroviral therapies have substantively increased the quality of life and reduced HIV-1 associated dementia, less severe minor cognitive and motor deficits continue. Trafficking of HIV-1 into the central nervous system (CNS), peripheral immune activation, dysregulated glial immunity, and diminished homeostatic responses are the disease-linked pathobiologic events. Monocyte-macrophage passage into the CNS remains an underlying force for disease severity. Monocyte phenotypic may change at an early stage of cell maturation and immune activation of hematopoietic stem cells. Activated monocytes are pulled into the brain in response to chemokines made as a result of glial inflammatory processes, which in turn cause secondary functional deficits in neurons. Current therapeutic approaches are focused on adjunctive and brain-penetrating antiretroviral therapies. These may attenuate virus-associated neuroinflammatory activities thereby decreasing the severity and frequency of HAND.

Kraft-Terry, Stephanie D.; Stothert, Andrew R.; Buch, Shilpa; Gendelman, Howard E.

2010-01-01

189

Anaemia and zidovudine-containing antiretroviral therapy in paediatric antiretroviral programmes in the IeDEA Paediatric West African Database to evaluate AIDS.  

PubMed

Introduction: There is a risk of anaemia among HIV-infected children on antiretroviral therapy (ART) containing zidovudine (ZDV) recommended in first-line regimens in the WHO guidelines. We estimated the risk of severe anaemia after initiation of a ZDV-containing regimen in HIV-infected children included in the IeDEA West African database. Methods: Standardized collection of data from HIV-infected children (positive PCR<18 months or positive serology ?18 months) followed up in HIV programmes was included in the regional IeDEA West Africa collaboration. Ten clinical centres from seven countries contributed (Benin, Burkina Faso, Côte d'Ivoire, Gambia, Ghana, Mali and Senegal) to this collection. Inclusion criteria were age <16 years and starting ART. We explored the data quality of haemoglobin documentation over time and the incidence and predictors of severe anaemia (Hb<7g/dL) per 100 child-years of follow-up over the duration of first-line antiretroviral therapy. Results: As of December 2009, among the 2933 children included in the collaboration, 45% were girls, median age was five years; median CD4 cell percentage was 13%; median weight-for-age z-score was-2.7; and 1772 (60.4%) had a first-line ZDV-containing regimen. At baseline, 70% of the children with a first-line ZDV-containing regimen had a haemoglobin measure available versus 76% in those not on ZDV (p?0.01): the prevalence of severe anaemia was 3.0% (n=38) in the ZDV group versus 10.2% (n=89) in those without (p<0. 01). Over the first-line follow-up, 58.9% of the children had ?1 measure of haemoglobin available in those exposed to ZDV versus 60.4% of those not (p=0.45). Severe anaemia occurred in 92 children with an incidence of 2.47 per 100 child-years of follow-up in those on a ZDV-containing regimen versus 4.25 in those not (p?0.01). Adjusted for age at ART initiation and first-line regimen, a weight-for-age z-score ?-3 was a strong predictor associated with a 5.59 times risk of severe anaemia (p<0.01). Conclusions: Severe anaemia is frequent at baseline and guides the first-line ART prescription, but its incidence seems rare among children on ART. Severe malnutrition at baseline is a strong predictor for development of severe anaemia, and interventions to address this should form an integral component of clinical care. PMID:24047928

Renner, Lorna A; Dicko, Fatoumata; Kouéta, Fla; Malateste, Karen; Gueye, Ramatoulaye D; Aka, Edmond; Eboua, Tanoh K; Azondékon, Alain; Okomo, Uduok; Touré, Pety; Ekouévi, Didier; Leroy, Valeriane

2013-09-17

190

Anaemia and zidovudine-containing antiretroviral therapy in paediatric antiretroviral programmes in the IeDEA Paediatric West African Database to evaluate AIDS  

PubMed Central

Introduction There is a risk of anaemia among HIV-infected children on antiretroviral therapy (ART) containing zidovudine (ZDV) recommended in first-line regimens in the WHO guidelines. We estimated the risk of severe anaemia after initiation of a ZDV-containing regimen in HIV-infected children included in the IeDEA West African database. Methods Standardized collection of data from HIV-infected children (positive PCR<18 months or positive serology ?18 months) followed up in HIV programmes was included in the regional IeDEA West Africa collaboration. Ten clinical centres from seven countries contributed (Benin, Burkina Faso, Côte d'Ivoire, Gambia, Ghana, Mali and Senegal) to this collection. Inclusion criteria were age <16 years and starting ART. We explored the data quality of haemoglobin documentation over time and the incidence and predictors of severe anaemia (Hb<7g/dL) per 100 child-years of follow-up over the duration of first-line antiretroviral therapy. Results As of December 2009, among the 2933 children included in the collaboration, 45% were girls, median age was five years; median CD4 cell percentage was 13%; median weight-for-age z-score was ?2.7; and 1772 (60.4%) had a first-line ZDV-containing regimen. At baseline, 70% of the children with a first-line ZDV-containing regimen had a haemoglobin measure available versus 76% in those not on ZDV (p?0.01): the prevalence of severe anaemia was 3.0% (n=38) in the ZDV group versus 10.2% (n=89) in those without (p<0. 01). Over the first-line follow-up, 58.9% of the children had ?1 measure of haemoglobin available in those exposed to ZDV versus 60.4% of those not (p=0.45). Severe anaemia occurred in 92 children with an incidence of 2.47 per 100 child-years of follow-up in those on a ZDV-containing regimen versus 4.25 in those not (p?0.01). Adjusted for age at ART initiation and first-line regimen, a weight-for-age z-score ??3 was a strong predictor associated with a 5.59 times risk of severe anaemia (p<0.01). Conclusions Severe anaemia is frequent at baseline and guides the first-line ART prescription, but its incidence seems rare among children on ART. Severe malnutrition at baseline is a strong predictor for development of severe anaemia, and interventions to address this should form an integral component of clinical care.

Renner, Lorna A; Dicko, Fatoumata; Koueta, Fla; Malateste, Karen; Gueye, Ramatoulaye D; Aka, Edmond; Eboua, Tanoh K; Azondekon, Alain; Okomo, Uduok; Toure, Pety; Ekouevi, Didier; Leroy, Valeriane

2013-01-01

191

Antiretroviral treatment interruptions and risk of non-opportunistic diseases  

Microsoft Academic Search

Structured treatment interruptions have been studied as a strategy to reduce antiretroviral toxicities and expenditures in\\u000a the treatment of HIV-infected individuals. Paradoxically, in addition to the increased incidence of death and opportunistic\\u000a infections, these interruptions in therapy have resulted in the development of a number of non-opportunistic diseases, including\\u000a cardiovascular events, renal insufficiency, hepatic failure, and non-AIDS-defining malignancies. Hypotheses regarding

Kenneth A. Lichtenstein

2009-01-01

192

Emergence of HIV1 Drug Resistance During Antiretroviral Treatment  

Microsoft Academic Search

Treating HIV-infected patients with a combination of several antiretroviral drugs usually contributes to a substantial decline\\u000a in viral load and an increase in CD4+ T cells. However, continuing viral replication in the presence of drug therapy can lead to the emergence of drug-resistant\\u000a virus variants, which subsequently results in incomplete viral suppression and a greater risk of disease progression. In

Libin Rong; Zhilan Feng; Alan S. Perelson

2007-01-01

193

Active site remodeling switches HIV specificity of antiretroviral TRIMCyp  

Microsoft Academic Search

TRIMCyps are primate antiretroviral proteins that potently inhibit HIV replication. Here we describe how rhesus macaque TRIMCyp (RhTC) has evolved to target and restrict HIV-2. We show that the ancestral cyclophilin A (CypA) domain of RhTC targets HIV-2 capsid with weak affinity, which is strongly increased in RhTC by two mutations (D66N and R69H) at the expense of HIV-1 binding.

Amanda J Price; Flavia Marzetta; Michael Lammers; Laura M J Ylinen; Torsten Schaller; Sam J Wilson; Greg J Towers; Leo C James

2009-01-01

194

The impact of host pharmacogenetics on antiretroviral drug disposition  

Microsoft Academic Search

The ability to predict efficacy and toxicity during antiretroviral therapy for HIV would be of obvious advantage. The substantial\\u000a variability between patients in terms of bioavailability and distribution of current regimens is likely driven by genetic\\u000a and environmental factors. Protease inhibitors and nucleoside\\/nucleotide reverse transcriptase inhibitors are metabolized\\u000a by cytochrome P450 enzymes. Their bioavailability and excretion may also be affected

Andrew Owen

2006-01-01

195

Making Markets for Merit Goods: The Political Economy of Antiretrovirals  

Microsoft Academic Search

This paper examines the role of policy entrepreneurs and global activists in shaping the international market for antiretroviral drugs to combat HIV\\/AIDS. When ARVs first came on the market in the 1990s they were exceedingly expensive; the cost of treatment was upwards of $10,000 per year. These drugs were thus accessible only to those patients who had high incomes. But

Ethan B. Kapstein; Josh Busby

2009-01-01

196

Therapeutic Drug Monitoring of Antiretroviral Drugs with HPLC-MS  

Microsoft Academic Search

Prospective and retrospective studies have provided some evidence of the clinical and virological benefit of incorporating TDM into routine patient care. Because antiretroviral therapy consists always of a combination of different drugs, analysis can be simplified if different drugs are measured at the same time. Therefore, LC-MS or LC-MS\\/MS is nowadays the analytical method of choice. In 2003 we have

Ursula Gutteck-Amsler; Katharina M. Rentsch

197

Molecular evolution of the antiretroviral TRIM5 gene  

Microsoft Academic Search

In 2004, the first report of TRIM5? as a cellular antiretroviral factor triggered intense interest among virologists, particularly\\u000a because some primate orthologs of TRIM5? have activity against HIV. Since that time, a complex and eventful evolutionary history\\u000a of the TRIM5 locus has emerged. A review of the TRIM5 literature constitutes a veritable compendium of evolutionary phenomena, including elevated rates of

Welkin E. Johnson; Sara L. Sawyer

2009-01-01

198

Combination antiretroviral drugs in PLGA nanoparticle for HIV-1  

PubMed Central

Background Combination antiretroviral (AR) therapy continues to be the mainstay for HIV treatment. However, antiretroviral drug nonadherence can lead to the development of resistance and treatment failure. We have designed nanoparticles (NP) that contain three AR drugs and characterized the size, shape, and surface charge. Additionally, we investigated the in vitro release of the AR drugs from the NP using peripheral blood mononuclear cells (PBMCs). Methods Poly-(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) containing ritonavir (RTV), lopinavir (LPV), and efavirenz (EFV) were fabricated using multiple emulsion-solvent evaporation procedure. The nanoparticles were characterized by electron microscopy and zeta potential for size, shape, and charge. The intracellular concentration of AR drugs was determined over 28 days from NPs incubated with PBMCs. Macrophages were imaged by fluorescent microscopy and flow cytometry after incubation with fluorescent NPs. Finally, macrophage cytotoxicity was determined by MTT assay. Results Nanoparticle size averaged 262 ± 83.9 nm and zeta potential -11.4 ± 2.4. AR loading averaged 4% (w/v). Antiretroviral drug levels were determined in PBMCs after 100 ?g of NP in 75 ?L PBS was added to media. Intracellular peak AR levels from NPs (day 4) were RTV 2.5 ± 1.1; LPV 4.1 ± 2.0; and EFV 10.6 ± 2.7 ?g and continued until day 28 (all AR ? 0.9 ?g). Free drugs (25 ?g of each drug in 25 ?L ethanol) added to PBMCs served as control were eliminated by 2 days. Fluorescence microscopy and flow cytometry demonstrated phagocytosis of NP into monocytes-derived macrophages (MDMs). Cellular MTT assay performed on MDMs demonstrated that NPs are not significantly cytotoxic. Conclusion These results demonstrated AR NPs could be fabricated containing three antiretroviral drugs (RTV, LPV, EFV). Sustained release of AR from PLGA NP show high drug levels in PBMCs until day 28 without cytotoxicity.

2009-01-01

199

Assessing relationships between health-related quality of life and adherence to antiretroviral therapy  

Microsoft Academic Search

Objective: To investigate associations between health-related quality of life (HRQoL), as assessed using the multidimensional quality of life-HIV (MQOL-HIV) questionnaire, and adherence to antiretroviral treatment in HIV-infected subjects. Design: Multicentre cross-sectional study in three institutional tertiary hospitals in northwest Spain. Patients and methods: The MQOL-HIV was completed by 235 HIV-infected adults undergoing antiretroviral treatment. Adherence to antiretroviral therapy was assessed

E. Carballo; C. Cadarso-Suárez; I. Carrera; J. Fraga; J. de la Fuente; A. Ocampo; R. Ojea; A. Prieto

2004-01-01

200

Antiretroviral therapy for human immunodeficiency virus infection in 1997.  

PubMed Central

It has become clear that the acquired immunodeficiency syndrome follows continuous replication of the human immunodeficiency virus (HIV) and a decrease in immune capability, most obviously a decline in the number of CD4 lymphocytes. An understanding of key elements in the infectious life cycle of HIV has led to the development of potent antiretroviral drugs selectively targeting unique reverse transcriptase and protease enzymes of the virus. Completed clinical trials have shown that antiretroviral therapy for HIV infection, begun early, reduces viral replication and reverses the decline in CD4 lymphocyte numbers. Recent studies of combination therapies have shown that decreases in plasma HIV viremia to low levels and sustained increases in CD4 cell numbers are associated with longer survival. Potent combination regimens including protease inhibitors and non-nucleoside reverse transcriptase inhibitors suppress detectable viral replication and have demonstrated clinical benefits in patients with advanced disease. Progress in antiretroviral therapy and methods to monitor responses to treatment are providing new hope in the treatment of HIV infection.

Katzenstein, D A

1997-01-01

201

Adverse effects of antiretroviral therapy for HIV infection.  

PubMed

Long-term remission of HIV-1 disease can be readily achieved by combinations of antiretroviral agents. The suppression of plasma viral loads to less than the limit of quantification of the most sensitive commercially available assays (i.e., less than 50 copies/mL) and the coincident improvement in CD4 T cell counts is associated with resolution of established opportunistic infections and a decrease in the risk of new opportunistic infections. However, prolonged treatment with combination regimens can be difficult to sustain because of problems with adherence and toxic effects. All antiretroviral drugs can have both short-term and long-term adverse events. The risk of specific side effects varies from drug to drug, from drug class to drug class, and from patient to patient. A better understanding of the adverse effects of antiretroviral agents is of interest not only for HIV specialists as they try to optimize therapy, but also for other physicians who care for HIV-positive patients. PMID:14734438

Montessori, Valentina; Press, Natasha; Harris, Marianne; Akagi, Linda; Montaner, Julio S G

2004-01-20

202

Adverse effects of antiretroviral therapy for HIV infection  

PubMed Central

LONG-TERM REMISSION OF HIV-1 DISEASE CAN BE READILY ACHIEVED by combinations of antiretroviral agents. The suppression of plasma viral loads to less than the limit of quantification of the most sensitive commercially available assays (i.e., less than 50 copies/mL) and the coincident improvement in CD4 T cell counts is associated with resolution of established opportunistic infections and a decrease in the risk of new opportunistic infections. However, prolonged treatment with combination regimens can be difficult to sustain because of problems with adherence and toxic effects. All antiretroviral drugs can have both short-term and long-term adverse events. The risk of specific side effects varies from drug to drug, from drug class to drug class, and from patient to patient. A better understanding of the adverse effects of antiretroviral agents is of interest not only for HIV specialists as they try to optimize therapy, but also for other physicians who care for HIV-positive patients.

Montessori, Valentina; Press, Natasha; Harris, Marianne; Akagi, Linda; Montaner, Julio S.G.

2004-01-01

203

Renal impairment in a rural African antiretroviral programme  

PubMed Central

Background There is little knowledge regarding the prevalence and nature of renal impairment in African populations initiating antiretroviral treatment, nor evidence to inform the most cost effective methods of screening for renal impairment. With the increasing availability of the potentially nephrotixic drug, tenofovir, such information is important for the planning of antiretroviral programmes Methods (i) Retrospective review of the prevalence and risk factors for impaired renal function in 2189 individuals initiating antiretroviral treatment in a rural African setting between 2004 and 2007 (ii) A prospective study of 149 consecutive patients initiating antiretrovirals to assess the utility of urine analysis for the detection of impaired renal function. Severe renal and moderately impaired renal function were defined as an estimated GFR of ? 30 mls/min/1.73 m2 and 30–60 mls/min/1.73 m2 respectively. Logistic regression was used to determine odds ratio (OR) of significantly impaired renal function (combining severe and moderate impairment). Co-variates for analysis were age, sex and CD4 count at initiation. Results (i) There was a low prevalence of severe renal impairment (29/2189, 1.3% 95% C.I. 0.8–1.8) whereas moderate renal impairment was more frequent (287/2189, 13.1% 95% C.I. 11.6–14.5) with many patients having advanced immunosuppression at treatment initiation (median CD4 120 cells/?l). In multivariable logistic regression age over 40 (aOR 4.65, 95% C.I. 3.54–6.1), male gender (aOR 1.89, 95% C.I. 1.39–2.56) and CD4<100 cells/ul (aOR 1.4, 95% C.I. 1.07–1.82) were associated with risk of significant renal impairment (ii) In 149 consecutive patients, urine analysis had poor sensitivity and specificity for detecting impaired renal function. Conclusion In this rural African setting, significant renal impairment is uncommon in patients initiating antiretrovirals. Urine analysis alone may be inadequate for identification of those with impaired renal function where resources for biochemistry are limited.

2009-01-01

204

Pharmacodynamic and antiretroviral activities of combination nanoformulated antiretrovirals in HIV-1-infected human peripheral blood lymphocyte-reconstituted mice.  

PubMed

Lack of adherence, inaccessibility to viral reservoirs, long-term drug toxicities, and treatment failures are limitations of current antiretroviral therapy (ART). These limitations lead to increased viral loads, medicine resistance, immunocompromise, and comorbid conditions. To this end, we developed long-acting nanoformulated ART (nanoART) through modifications of existing atazanavir, ritonavir, and efavirenz suspensions in order to establish cell and tissue drug depots to achieve sustained antiretroviral responses. NanoART's abilities to affect immune and antiviral responses, before or following human immunodeficiency virus type 1 infection were tested in nonobese severe combined immune-deficient mice reconstituted with human peripheral blood lymphocytes. Weekly subcutaneous injections of drug nanoformulations at doses from 80 mg/kg to 250 mg/kg, 1 day before and/or 1 and 7 days after viral exposure, elicited drug levels that paralleled the human median effective concentration, and with limited toxicities. NanoART treatment attenuated viral replication and preserved CD4(+) Tcell numbers beyond that seen with orally administered native drugs. These investigations bring us one step closer toward using long-acting antiretrovirals in humans. PMID:22811299

Roy, Upal; McMillan, JoEllyn; Alnouti, Yazen; Gautum, Nagsen; Smith, Nathan; Balkundi, Shantanu; Dash, Prasanta; Gorantla, Santhi; Martinez-Skinner, Andrea; Meza, Jane; Kanmogne, Georgette; Swindells, Susan; Cohen, Samuel M; Mosley, R Lee; Poluektova, Larisa; Gendelman, Howard E

2012-07-17

205

Family Connections: Helping Early Head Start/Head Start Staff and Parents Address Mental Health Challenges  

ERIC Educational Resources Information Center

|Early Head Start/Head Start teachers and staff encounter parents who have wrestled with depression and other adversities every day. This article describes an innovative program of trainings for and consultation to Early Head Start/Head Start staff to help them effectively deal with mental heath challenges faced by parents and children. The…

Beardslee, William R.; Avery, Mary Watson; Ayoub, Catherine; Watts, Caroline L.

2009-01-01

206

Head start teaching center: Evaluation of a new approach to head start staff development  

Microsoft Academic Search

Head Start Teaching Centers are a national demonstration project designed to provide participatory training in all Head Start component areas within the context of an exemplary Head Start program. Each Teaching Center employs an independent evaluation to study this alternative approach to Head Start staff development. This paper presents the results of the outcome evaluation for the first year of

Diane M. Horm-Wingerd; David A. Caruso; Sheryl Gomes-Atwood; Julianna Golas

1997-01-01

207

Family Connections: Helping Early Head Start/Head Start Staff and Parents Address Mental Health Challenges  

ERIC Educational Resources Information Center

Early Head Start/Head Start teachers and staff encounter parents who have wrestled with depression and other adversities every day. This article describes an innovative program of trainings for and consultation to Early Head Start/Head Start staff to help them effectively deal with mental heath challenges faced by parents and children. The program…

Beardslee, William R.; Avery, Mary Watson; Ayoub, Catherine; Watts, Caroline L.

2009-01-01

208

A line-start permanent magnet motor with gentle starting behavior  

Microsoft Academic Search

The line-start permanent magnet motor combines a permanent magnet rotor for best motor efficiency and an induction motor squirrel-cage rotor to permit starting on a conventional AC power source. Three new concepts have been introduced to improve starting performance by eliminating objectionable torque pulsations during the starting interval. A new rotor concept, called the divided magnet rotor, has been devised

Charles M. Stephens; Gerald B. Kliman; John Boyd

1998-01-01

209

ANALYSIS OF AZEOTROPIC DISTILLATION SEQUENCES START UP  

Microsoft Academic Search

The optimal start-up of a two-distillation tower process involving multiple steady states is a very complex task, since a rigorous dynamic optimization is necessary. Searching for optimal start-up strategies for tower sequences is far from trivial. Besides of the multiplicity of solutions, one of the complicating factors is the activation of the recycle stream, which severely constrains the possible start-up

Nicolás J. Scenna; Sonia J. Benz; Nestor H. Rodríguez; Juan Ignacio Klaric

210

Start II, red ink, and Boris Yeltsin  

SciTech Connect

Apart from the vulnerability implied by the START II treaty, it will bear the burden of the general political opposition to the Yeltsin administration. START II will be seen as part of an overall Yeltsin-Andrei Kozyrev foreign policy that is under fire for selling out Russian national interests in Yugoslavia, the Persian Gulf, and elsewhere. This article discusses public opinion concerning START II, the cost of its implementation, and the general purpose of the treaty.

Arbatov, A.

1993-04-01

211

Virological response and HIV drug resistance 12 months after antiretroviral therapy initiation at 2 clinics in Nigeria.  

PubMed

This report describes a pilot study, conducted in Nigeria, of the World Health Organization protocol for monitoring human immunodeficiency virus (HIV) drug resistance (HIVDR) and associated program factors among patients receiving first-line antiretroviral therapy (ART). In 2008, 283 HIV-infected patients starting ART were consecutively enrolled at 2 ART clinics in Abuja. Twelve months after ART initiation, 62% were alive and on first-line ART, 3% had died, 1% had transferred out of the program, and 34% were lost to follow-up. Among patients on first-line ART at 12 months, 90% had viral suppression. However, in view of the high loss to follow-up rate (34%), strategies for patient retention and tracking are critical to minimize possible HIVDR and optimize treatment outcomes. PMID:22544206

Ugbena, Richard; Aberle-Grasse, John; Diallo, Karidia; Bassey, Orji; Jelpe, Tapdiyel; Rottinghaus, Erin; Azeez, Aderemi; Akpan, Raphael; Muhammad, Mukhtar; Shanmugam, Vedapuri; Singh, Satvinder; Yang, Chunfu

2012-05-01

212

Changes in Inflammatory and Coagulation Biomarkers: A Randomized Comparison of Immediate Versus Deferred Antiretroviral Therapy in Patients with HIV Infection  

PubMed Central

Ojectives Among a subgroup of participants in the Strategies for Management of Antiretroviral Therapy (SMART) Trial that were naïve to antiretroviral therapy (ART) or off ART (?6 months) at study entry, risk of AIDS and serious non-AIDS events was increased for participants who deferred ART compared to those randomized to (re)initiate ART immediately. Our objective was to determine whether ART initiation in this group reduced markers of inflammation and coagulation that have been associated with increased mortality risk in SMART. Changes in these biomarkers have been described after stopping ART, but not after starting ART in SMART. Methods Stored specimens for 254 participants (126 DC and 128 VS) who were naïve to ART or off ART (?6 months) were analyzed for interleukin-6 (IL-6), high sensitivity C-reactive protein (hsCRP) and D-dimer at baseline and months 2 and 6. Results At month 6, 62% of VS group had HIV RNA <400copies/mL and median CD4 count was 190 cells/mm3 higher than for the DC group (590 vs. 400 cells/mm3). Compared with DC, the VS group had 32% (95%CI: 19 to 43%) lower D-dimer levels at month 6 (p<0.001); differences were not significant for hsCRP or IL-6 levels. Conclusions In this randomized comparison of immediate versus delayed ART initiation, D-dimer, but not IL-6 and hsCRP, declined significantly after starting ART. Further studies are needed to determine whether improvements in D-dimer are associated with reduced risk of clinical disease, and whether adjunct treatments used in combination with ART can reduce inflammation among individuals with HIV infection.

Baker, Jason V; Neuhaus, Jacqueline; Duprez, Daniel; Kuller, Lewis H.; Tracy, Russell; Belloso, Waldo H.; De Wit, Stephane; Drummond, Fraser; Lane, H. Clifford; Ledergerber, Bruno; Lundgren, Jens; Nixon, Daniel E.; Paton, Nicholas I.; Neaton, James D.

2010-01-01

213

Baseline cellular HIV DNA load predicts HIV DNA decline and residual HIV plasma levels during effective antiretroviral therapy.  

PubMed

Cellular human immunodeficiency virus type 1 (HIV-1) DNA may be considered a marker of disease progression with significant predictive power, but published data on its correlation with plasma HIV RNA levels and CD4 counts in acute and chronic patients are not conclusive. We evaluated a cohort of 180 patients naïve for antiretroviral therapy before the beginning of treatment and after a virological response in order to define the indicators correlated with HIV DNA load decrease until undetectability. The following variables were evaluated as continuous variables: age, CD4 cell count and log(10) HIV DNA level at baseline and follow-up, and baseline log(10) HIV RNA level. Primary HIV infection at the start of therapy, an HIV RNA level at follow-up of <2.5 copies/ml, origin, gender, and transmission risk were evaluated as binary variables. The decline of HIV DNA values during effective therapy was directly related to baseline HIV DNA and HIV RNA values, to an increase in the number of CD4 cells, and to the achievement of an HIV RNA load of <2.5 copies/ml. An undetectable cellular HIV DNA load was achieved by 21.6% of patients at the follow-up time point and correlated significantly with lower baseline cellular HIV DNA values and with being in the primary stage of infection when therapy started. In conclusion, early treatment facilitated the achievement of undetectable levels of plasma viremia and cellular HIV DNA and a better recovery of CD4 lymphocytes. HIV DNA levels before and during highly active antiretroviral therapy may be used as a new tool for monitoring treatment efficacy. PMID:22135262

Parisi, Saverio Giuseppe; Andreis, Samantha; Mengoli, Carlo; Scaggiante, Renzo; Ferretto, Roberto; Manfrin, Vinicio; Cruciani, Mario; Giobbia, Mario; Boldrin, Caterina; Basso, Monica; Andreoni, Massimo; Palù, Giorgio; Sarmati, Loredana

2011-11-30

214

Inflammation Predicts Changes in High-Density Lipoprotein Particles and Apolipoprotein A1 Following Initiation of Antiretroviral Therapy  

PubMed Central

Background The effects of HIV infection and antiretroviral therapy (ART) on usual lipid levels have been reported. The effects of initiating versus deferring ART on high- and low-density lipoprotein particle concentrations (HDL-P and LDL-P) and apolipoprotein (Apo) levels are not well described. Methods In a subgroup of participants not taking ART at study entry who were randomized in the Strategies for Management of Antiretroviral Therapy (SMART) to immediately initiate ART (‘VS group’) or to defer it (‘DC group’), lipoprotein particle concentrations and ApoA1 and ApoB levels were measured at baseline and at 2 and 6 months following randomization. Results Compared to DC group (n=126), HDL-P and ApoA1 levels increased among VS participants (n=128) after starting ART. At 6 months, VS participants had 13% higher total HDL-P (p < 0.001) and 9% higher ApoA1 (p < 0.001). LDL-P, VLDL-P, and ApoB did not differ significantly between the VS and DC groups. Among VS participants, predictors of HDL-P and ApoA1 increases included baseline levels of hsCRP and IL-6, but not HIV RNA level, CD4 count or traditional CVD risk factors. The effect of starting ART on changes in HDL-P and ApoA1 was greater for those with higher versus lower baseline levels of IL-6 (p=0.001 and 0.08, respectively, for interaction) or hsCRP (p=0.01 and 0.04, respectively, for interaction). Conclusion HDL-P and ApoA1 increase following ART initiation, to a degree that depends on the degree of inflammation present at entry. These findings suggest that activation of inflammatory pathways contribute to HIV-associated changes in HDL.

Baker, Jason V.; Neuhaus, Jacqueline; Duprez, Daniel; Cooper, David A.; Hoy, Jennifer; Kuller, Lewis; Lampe, Fiona C.; Liappis, Angelike; Friis-Moller, Nina; Otvos, Jim; Paton, Nicholas I.; Tracy, Russell; Neaton, James D.

2012-01-01

215

Osteopenia in HIV-infected Women Prior to Highly Active Antiretroviral Therapy  

Microsoft Academic Search

Background and objectives: Multiple endocrine and metabolic consequences of human immunodeficiency (HIV) infection exist that alter bone metabolism in patients with acquired immune deficiency syndrome (AIDS). Osteopenia in AIDS patients has been associated with antiretroviral therapy particulary with protease inhibitors. However, there is very little data on bone metabolism in female subjects with AIDS prior to highly active antiretroviral therapy.Methods:

J Teichmann; E Stephan; U Lange; T Discher; G Friese; J Lohmeyer; H Stracke; R. G Bretzel

2003-01-01

216

Progress of the National Pediatric Free Antiretroviral Therapy program in China  

Microsoft Academic Search

In 2003, the Chinese Government initiated a free antiretroviral therapy (ART) program focusing on adult AIDS patients. Pediatric antiretroviral (ARV) formulations were yet unavailable. It was not until July 2005, with the initiation of a two-stage program implemented by the Chinese Ministry of Health, that pediatric formulations became accessible in China. Initially, the pediatric ART program was piloted in six

Yan Zhao; Xin Sun; Yun He; Zhirong Tang; Guoping Peng; Aiwen Liu; Xiaochun Qiao; Huiqin Li; Zhiqiang Chen; Zhihui Dou; Ye Ma; Zhongfu Liu; Fujie Zhang

2010-01-01

217

Strategies for Living with the Challenges of HIV and Antiretroviral Use in Zambia  

ERIC Educational Resources Information Center

This study sought to identify strategies for living with the challenges of HIV and antiretroviral (ARV) use among new medication users in urban Zambia. Participants (n = 160) were recruited from urban Lusaka, Zambia. Qualitative Data was drawn from monthly ARV treatment education intervention groups addressing HIV and antiretroviral use. Themes…

Jones, Deborah; Zulu, Isaac; Mumbi, Miriam; Chitalu, Ndashi; Vamos, Szonja; Gomez, Jacqueline; Weiss, Stephen M.

2009-01-01

218

Human resources requirements for highly active antiretroviral therapy scale-up in Malawi  

Microsoft Academic Search

BACKGROUND: Twelve percent of the adult population in Malawi is estimated to be HIV infected. About 15% to 20% of these are in need of life saving antiretroviral therapy. The country has a public sector-led antiretroviral treatment program both in the private and public health sectors. Estimation of the clinical human resources needs is required to inform the planning and

Adamson S Muula; John Chipeta; Seter Siziya; Emmanuel Rudatsikira; Ronald H Mataya; Edward Kataika

2007-01-01

219

Antiretroviral Drug Resistance Mutations Sustain or Enhance CTL Recognition of Common HIV1 Pol Epitopes  

Microsoft Academic Search

Antiretroviral drug resistance and escape from CTL are major obstacles to effective control of HIV replication. To investigate the possibility of combining drug and immune-based selective pressures against HIV, we studied the effects of antiretroviral drug resistance mutations on CTL recognition of five HIV-1 Pol epitopes presented by common HLA molecules. We found that these common drug resistance mutations sustain

Rosemarie D. Mason; M. Ian Bowmer; Constance M. Howley; Maureen Gallant; Jennifer C. E. Myers; Michael D. Grant

220

A Program to Provide Antiretroviral Therapy to Residents of an Urban Slum in Nairobi, Kenya  

Microsoft Academic Search

Objective: To evaluate retention in care and response to therapy for patients enrolled in an antiretroviral treatment program in a severely resource-constrained setting. Methods: We evaluated patients enrolled between February 26, 2003, and February 28, 2005, in a community clinic in Kibera, an informal settlement, in Nairobi, Kenya. Midlevel providers offered simplified, standardized antiretroviral therapy (ART) regimens and monitored patients

Barbara J. Marston; Doris K. Macharia; Lucy Nganga; Mary Wangai; Festus Ilako; Odylia Muhenje; Mette Kjaer; Anthony Isavwa; Andrea Kim; Kenneth Chebet; Kevin M. DeCock; Paul J. Weidle

2007-01-01

221

Measuring adherence to antiretroviral treatment in resource-poor settings: The clinical validity of key indicators  

Microsoft Academic Search

BACKGROUND: Access to antiretroviral therapy has dramatically expanded in Africa in recent years, but there are no validated approaches to measure treatment adherence in these settings. METHODS: In 16 health facilities, we observed a retrospective cohort of patients initiating antiretroviral therapy. We constructed eight indicators of adherence and visit attendance during the first 18 months of treatment from data in

Dennis Ross-Degnan; Marsha Pierre-Jacques; Fang Zhang; Hailu Tadeg; Lillian Gitau; Joseph Ntaganira; Robert Balikuddembe; John Chalker; Anita K Wagner

2010-01-01

222

Impact of a Rural Village Women (Asha) Intervention on Adherence to Antiretroviral Therapy in Southern India  

PubMed Central

Background Despite the increased prevalence of HIV in the rural female population of India, adherence to antiretroviral therapy continues to be low due to several barriers which discourage rural women. Objectives To assess the effectiveness of an intervention (Asha-Life) delivered by Accredited Social Health Activists to improve antiretroviral therapy adherence of rural women living with AIDS in India compared to that of a usual care group. Method A total of 68 rural women living with AIDS, aged 18–45 years, participated in a prospective, randomized pilot clinical trial and were assessed for several factors affecting adherence, such as sociodemographic characteristics, health history, CD4 cell count, enacted stigma, depressive symptomology, help getting antiretroviral therapy, and perceived therapy benefits. Results Findings at 6 months revealed that, while both groups improved their adherence to antiretroviral therapy, there was greater improvement in the Asha-Life group (p < .001), who reported a greater reduction in barriers to antiretroviral therapy than those in the usual care group. Discussion Antiretroviral therapy adherence showed significant increase in the Asha-Life cohort, in which basic education on HIV/AIDS, counseling on antiretroviral therapy, financial assistance, and better nutrition was provided. The Asha-Life intervention may have great potential in improving antiretroviral therapy adherence and decreasing barriers among rural women living with AIDS in India.

Nyamathi, Adeline; Hanson, Alecia Y.; Salem, Benissa E.; Sinha, Sanjeev; Ganguly, Kalyan K.; Leake, Barbara; Yadav, Kartik; Marfisee, Mary

2012-01-01

223

Antiretroviral therapy in the lives of women of colour with HIV  

Microsoft Academic Search

Non-adherence to antiretroviral medication is associated with adverse patient outcomes. Considerable research and clinical work has focused on issues surrounding patient compliance to prescribed regimens. Few studies have explored the essence of antiretroviral medications in the lives of women of colour with HIV. A qualitative study of HIV-infected women of colour was undertaken in response to the question: What is

A. Wayson Locher; K. Pargament; J. Duggan

2007-01-01

224

Prevalence of adverse events associated with potent antiretroviral treatment: Swiss HIV Cohort Study  

Microsoft Academic Search

Summary Background Data on adverse events to antiretroviral treatment have been recorded in clinical trials, post- marketing analyses, and anecdotal reports. Such data might not be an up-to-date or comprehensive assessment of all possible treatment combinations defined as potent antiretroviral treatment. Methods Using a standard clinical and laboratory method, we assessed prevalence of adverse events in 1160 patients who were

Jacques Fellay; Bruno Ledergerber; Enos Bernasconi; Hansjakob Furrer; Manuel Battegay; Bernard Hirschel; Pietro Vernazza; Patrick Francioli; Gilbert Greub; Markus Flepp; Amalio Telenti

2001-01-01

225

Cell-to-cell spread of HIV permits ongoing replication despite antiretroviral therapy  

Microsoft Academic Search

Latency and ongoing replication have both been proposed to explain the drug-insensitive human immunodeficiency virus (HIV) reservoir maintained during antiretroviral therapy. Here we explore a novel mechanism for ongoing HIV replication in the face of antiretroviral drugs. We propose a model whereby multiple infections per cell lead to reduced sensitivity to drugs without requiring drug-resistant mutations, and experimentally validate the

Alex Sigal; Jocelyn T. Kim; Alejandro B. Balazs; Erez Dekel; Avi Mayo; Ron Milo; David Baltimore

2011-01-01

226

Disseminated rhodococcus equi infection in HIV infection despite highly active antiretroviral therapy  

PubMed Central

Background Rhodococcus equi (R.equi) is an acid fast, GRAM + coccobacillus, which is widespread in the soil and causes pulmonary and extrapulmonary infections in immunocompromised people. In the context of HIV infection, R.equi infection (rhodococcosis) is regarded as an opportunistic disease, and its outcome is influenced by highly active antiretroviral therapy (HAART). Case presentation We report two cases of HIV-related rhodococcosis that disseminated despite suppressive HAART and anti-rhodococcal treatment; in both cases there was no immunological recovery, with CD4+ cells count below 200/?L. In the first case, pulmonary rhodococcosis presented 6 months after initiation of HAART, and was followed by an extracerebral intracranial and a cerebral rhodococcal abscess 1 and 8 months, respectively, after onset of pulmonary infection. The second case was characterized by a protracted course with spread of infection to various organs, including subcutaneous tissue, skin, colon and other intra-abdominal tissues, and central nervous system; the spread started 4 years after clinical resolution of a first pulmonary manifestation and progressed over a period of 2 years. Conclusions Our report highlights the importance of an effective immune recovery, despite fully suppressive HAART, along with anti-rhodococcal therapy, in order to clear rhodococcal infection.

2011-01-01

227

Screening HIV-infected adults in Malawi for anaemia: impact on eligibility for antiretroviral therapy  

PubMed Central

Summary Clinical staging determines antiretroviral therapy (ART) eligibility when CD4 count is not available. Haemoglobin (Hb) ?8 g/dL is an indication for the treatment. We measured Hb in HIV-positive Malawian adults undergoing clinical assessment for ART eligibility and calculated the percentage of patients with CD4 ? 350 cells/?L deemed eligible for ART by clinical staging with and without Hb measurement, using the existing threshold and an alternative proposed after comparing Hb values to CD4 counts. Three hundred and thirty-eight patients had CD4 counts measured and 226 (67%) had CD4 ? 350 cells/?L. Thirty-six (16%) patients with low CD4 count were eligible for ART by clinical assessment alone, 48 (21%) when Hb was also measured with a threshold of ?8 g/dL and 74 (34%) with a threshold of ?10 g/dL. Measuring Hb alongside clinical assessment could increase the number of patients with CD4 ? 350 cells/?L starting ART by 33% using a threshold of Hb ? 8 g/dL or 114% with a threshold of ?10g/dL.

Page, I D; McKew, S J; Kudzala, A G; Fullwood, C; van Oosterhout, J J; Bates, I

2013-01-01

228

Where to Start Browsing the Web?  

Microsoft Academic Search

Both human users and crawlers face the problem of finding good start pages to explore some topic. We show how to assist in qualifying pages as start nodes by link-based ranking algorithms. We introduce a class of hub ranking methods based on counting the short search paths of the Web. Somewhat surpris- ingly, the Page Rank scores computed on the

Dániel Fogaras

2003-01-01

229

JobStart: The Road to Independence.  

ERIC Educational Resources Information Center

|Family Friends is an intergenerational program that brings senior volunteers into the lives of children with disabilities or chronic illnesses. JobStart is a training program in which volunteers help children with disabilities who are 10 years of age or older prepare to enter the world of work. A JobStart team is formed for each child in the…

National Council on the Aging, Inc., Washington, DC.

230

Administration for Children and Families: Head Start  

ERIC Educational Resources Information Center

This paper presents an overview of the Head Start program. Under the American Recovery and Reinvestment Act (Recovery Act), $1 billion will be provided to the Office of Head Start to promote the school readiness of low-income children, including children on federally-recognized reservations and children of migratory farm workers, by enhancing…

US Department of Health and Human Services, 2010

2010-01-01

231

Head Start as a National Laboratory  

Microsoft Academic Search

Project Head Start was initiated during an optimistic era when many believed that intelligence could be vastly improved through environmental input. This extreme position holds many dangers. The search for the brief periods in development when intervention will yield life-long benefits has also been misleading; all stages of life deserve their own program focus. Head Start has held a unique

Edward Zigler; Victoria Seitz

1982-01-01

232

Report of Melt Plant start-up  

Microsoft Academic Search

This report covers the start-up of facilities in the 314 Bldg. at Hanford Engineering Development Laboratory for casting from scrap. The period covered is from January 19, 1948, the time of starting the outgassing in the South (B) furnace through February 4, 1948, the time of completion of the third production run in that furnace. 3 tabs.

Jochen

1948-01-01

233

Trident SSBNS in START. Final report  

SciTech Connect

This report advocates not agreeing to ballistic missile warhead sublimits in START in order to place maximum reliance on the Trident/D-5 strategic weapon system. With reduced numbers in our post-START inventory, it is mandatory to emphasize our most survivable, capable, flexible and affordable systems for deterrence and defense.

Ackley, R.T.

1990-04-30

234

START: System Testability Analysis and Research Tool  

Microsoft Academic Search

START, a software package for automatic test sequencing and testability analysis of complex, hierarchically described modular systems, is described, and its use in modeling systems is examined. START uses algorithms based on information theory, heuristic search, and graph theory to solve various faces of the test sequencing and testability analysis problems. A system is modeled in the failure space as

Kriihna R. Pattipati; Somnath Deb; Mahesh Dontamsetty; Amit Maitra

1991-01-01

235

Drug Abuse Prevention Starts with Parents  

MedlinePLUS

... Contact Us My Cart Healthy Children > Ages & Stages > Teen > Substance Abuse > Drug Abuse Prevention Starts with Parents Ages & Stages Listen Drug Abuse Prevention Starts with Parents Article ... alcohol, are easily available to children and adolescents. As a parent, you have a major impact ...

236

Head StartChallenges and Training Needs  

Microsoft Academic Search

Head Start is the largest program providing comprehensive educational, health, and social services to young children and their families in poverty and is an important player in the early childhood service delivery system. This article summarizes the results of a needs assessment of Head Start programs in one region in the nation. Three important challenges were identified: (a) serving young

LEAH BUSCEMI; TESS BENNETT; DAWN THOMAS; DEBORAH A. DELUCA

1996-01-01

237

The Texas Head Start Metro Models.  

ERIC Educational Resources Information Center

|The Texas Metro Network (TMN) is an informal group of Head Start Directors and Executive Directors organized for the purposes of improving the delivery of training and technical assistance and for assisting communication between large scale Head Start programs in the metropolitan areas of Texas. In pursuit of these aims, each member unit of the…

Riley, Mary Tom, Ed.; Flores, Alfredo R., Ed.

238

Longer Term Effects of Head Start.  

National Technical Information Service (NTIS)

Little is known about the long-term effects of participation in Head Start. This paper draws on unique non-experimental data from the Panel Study of Income Dynamics to provide new evidence on the effects of participation in Head Start on schooling attainm...

E. Garces D. Thomas J. Currie

2000-01-01

239

The Head Start Classroom of the Future.  

ERIC Educational Resources Information Center

|Describes the Head Start Classroom of the Future project, which is being introduced into inner-city centers in Grand Rapids, Michigan; a classroom for children of Hispanic migrant farmworkers in Holland, Michigan; and a classroom for Native American children at the Isleta Pueblo Head Start near Albuquerque, New Mexico. (BB)|

Taylor, Anne; And Others

1990-01-01

240

What motivates ecopreneurs to start businesses?  

Microsoft Academic Search

Purpose – Ecopreneurs are those entrepreneurs who start for-profit businesses with strong underlying green values and who sell green products or services. This is an emerging field where research is still in its infancy. Research has been called for to understand the factors that motivate these ecopreneurs to start businesses – and that is the focus of this study. The

Jodyanne Kirkwood; Sara Walton

2010-01-01

241

Medication Possession Ratio Predicts Antiretroviral Regimens Persistence in Peru  

PubMed Central

Objectives In developing nations, the use of operational parameters (OPs) in the prediction of clinical care represents a missed opportunity to enhance the care process. We modeled the impact of multiple measurements of antiretroviral treatment (ART) adherence on antiretroviral treatment outcomes in Peru. Design And Methods Retrospective cohort study including ART naïve, non-pregnant, adults initiating therapy at Hospital Nacional Cayetano Heredia, Lima-Peru (2006-2010). Three OPs were defined: 1) Medication possession ratio (MPR): days with antiretrovirals dispensed/days on first-line therapy; 2) Laboratory monitory constancy (LMC): proportion of 6 months intervals with ?1 viral load or CD4 reported; 3) Clinic visit constancy (CVC): proportion of 6 months intervals with ?1 clinic visit. Three multi-variable Cox proportional hazard (PH) models (one per OP) were fit for (1) time of first-line ART persistence and (2) time to second-line virologic failure. All models were adjusted for socio-demographic, clinical and laboratory variables. Results 856 patients were included in first-line persistence analyses, median age was 35.6 years [29.4-42.9] and most were male (624; 73%). In multivariable PH models, MPR (per 10% increase HR=0.66; 95%CI=0.61-0.71) and LMC (per 10% increase 0.83; 0.71-0.96) were associated with prolonged time on first-line therapies. Among 79 individuals included in time to second-line virologic failure analyses, MPR was the only OP independently associated with prolonged time to second-line virologic failure (per 10% increase 0.88; 0.77-0.99). Conclusions The capture and utilization of program level parameters such as MPR can provide valuable insight into patient-level treatment outcomes.

Westfall, Andrew O.; Paz, Jorge; Moran, Fiorella; Carbajal-Gonzalez, Danny; Callacondo, David; Avalos, Odalie; Rodriguez, Martin; Gotuzzo, Eduardo; Echevarria, Juan; Willig, James H.

2013-01-01

242

Antiretroviral Adherence During Pregnancy and Postpartum in Latin America  

PubMed Central

Abstract Adherence to antiretrovirals by pregnant women (and postpartum women if breastfeeding) is crucial to effectively decrease maternal viral load and decrease the risk of mother-to-child transmission of HIV. Our objectives were to describe self-reported adherence to antiretrovirals during the antepartum (after 22 weeks of pregnancy) and postpartum periods (6–12 weeks and 6 months), and identify predictors of adherence among HIV-infected women enrolled and followed in a prospective cohort study from June 2008 to June 2010 at multiple sites in Latin America. Adherence was evaluated using the number of missed and expected doses during the 3 days before the study visit. At the pre-delivery visit, 340 of 376 women (90%) reported perfect adherence. This rate significantly decreased by 6–12 weeks (171/214 [80%]) and 6 months postpartum (163/199 [82%], p<0.01). The odds for less than perfect adherence at the pre-delivery visit was significantly higher for pregnant women with current tobacco use (odds ratio [OR]=2.9, 95% confidence interval [CI]: 1.46–6.14; p=0.0029). At 6–12 weeks postpartum, the probability of non-perfect adherence increased by 6% for each 1 year increase in age (OR=1.06, 95% CI: 1.00–1.12, p=0.0497). At 6 months postpartum, the odds of nonperfect adherence was higher for those who were currently using alcohol (OR=3.04, 95% CI: 1.34–6.90; p=0.0079). Although a self-report measure of adherence based on only 3 days may lead to overestimation of actual adherence over time, women with perfect adherence had lower viral loads and higher CD4 counts. Adherence to antiretrovirals decreased significantly postpartum. Interventions should target women at high risk for lower adherence during pregnancy and postpartum, including tobacco and alcohol users.

Harris, D. Robert; Kakehasi, Fabiana; Haberer, Jessica E.; Cahn, Pedro; Losso, Marcelo; Teles, Elizabete; Pilotto, Jose H.; Hofer, Cristina B.; Read, Jennifer S.

2012-01-01

243

Approaches to rationing antiretroviral treatment: ethical and equity implications.  

PubMed Central

Despite a growing global commitment to the provision of antiretroviral therapy (ART), its availability is still likely to be less than the need. This imbalance raises ethical dilemmas about who should be granted access to publicly-subsidized ART programmes. This paper reviews the eligibility and targeting criteria used in four case-study countries at different points in the scale-up of ART, with the aim of drawing lessons regarding ethical approaches to rationing. Mexico, Senegal, Thailand and Uganda have each made an explicit policy commitment to provide antiretrovirals to all those in need, but are achieving this goal in steps--beginning with explicit rationing of access to care. Drawing upon the case-studies and experiences elsewhere, categories of explicit rationing criteria have been identified. These include biomedical factors, adherence to treatment, prevention-driven factors, social and economic benefits, financial factors and factors driven by ethical arguments. The initial criteria for determining eligibility are typically clinical criteria and assessment of adherence prospects, followed by a number of other factors. Rationing mechanisms reflect several underlying ethical theories and the ethical underpinnings of explicit rationing criteria should reflect societal values. In order to ensure this alignment, widespread consultation with a variety of stakeholders, and not only policy-makers or physicians, is critical. Without such explicit debate, more rationing will occur implicitly and this may be more inequitable. The effects of rationing mechanisms upon equity are critically dependent upon the implementation processes. As antiretroviral programmes are implemented it is crucial to monitor who gains access to these programmes.

Bennett, Sara; Chanfreau, Catherine

2005-01-01

244

Approaches to rationing antiretroviral treatment: ethical and equity implications.  

PubMed

Despite a growing global commitment to the provision of antiretroviral therapy (ART), its availability is still likely to be less than the need. This imbalance raises ethical dilemmas about who should be granted access to publicly-subsidized ART programmes. This paper reviews the eligibility and targeting criteria used in four case-study countries at different points in the scale-up of ART, with the aim of drawing lessons regarding ethical approaches to rationing. Mexico, Senegal, Thailand and Uganda have each made an explicit policy commitment to provide antiretrovirals to all those in need, but are achieving this goal in steps--beginning with explicit rationing of access to care. Drawing upon the case-studies and experiences elsewhere, categories of explicit rationing criteria have been identified. These include biomedical factors, adherence to treatment, prevention-driven factors, social and economic benefits, financial factors and factors driven by ethical arguments. The initial criteria for determining eligibility are typically clinical criteria and assessment of adherence prospects, followed by a number of other factors. Rationing mechanisms reflect several underlying ethical theories and the ethical underpinnings of explicit rationing criteria should reflect societal values. In order to ensure this alignment, widespread consultation with a variety of stakeholders, and not only policy-makers or physicians, is critical. Without such explicit debate, more rationing will occur implicitly and this may be more inequitable. The effects of rationing mechanisms upon equity are critically dependent upon the implementation processes. As antiretroviral programmes are implemented it is crucial to monitor who gains access to these programmes. PMID:16175829

Bennett, Sara; Chanfreau, Catherine

2005-07-01

245

Evaluation of HIV/AIDS patients' knowledge on antiretroviral drugs.  

PubMed

Lack of information on antiretroviral drugs or the misunderstanding of available information can facilitate incorrect use of such drugs. This can result in non-adherence to the prescribed regimen, leading to a great possibility of a therapeutic failure. The aim of this study was to know which information HIV/AIDS patients, who receive their medicines at the pharmacy of a reference hospital in the northeast Brazil, have on the drugs they use, the source of this information and whether there is a need for additional information. A total of 195 HIV/AIDS patients, who were using either zidovudina + lamivudina 300+150 mg (AZT+3TC), efavirenz 600 mg (EFZ) or lopinavir/ritonavir 133.33/33 mg (LPV/r), were interviewed. The mean age was 41 years (SD = 9.55) and 70.8% were males. Of the total, 55.4% didn't know the effect of the drug in the organism; 35.9% were unaware of the necessity of taking antiretroviral drugs for the rest of their lives; only 14.4% knew how to proceed when a dosage was missed; 22.1% said they could die and the same number of individuals believed in aggravation of the disease in case of treatment interruption. The majority, 68.2%, considered it very necessary to receive drug information. The results show that there is an apparent lack of general information among users of antiretroviral drugs, and at the same time a need for it. It is necessary that all professionals involved in the health care of the patients agree that an efficient supply of information on prescribed drugs is an ethical component of the treatment that favors and fosters its adherence. PMID:20191194

Almeida, Regina Flávia de Castro; Vieira, Anya Pimentel Gomes Fernandes

2009-06-01

246

Effect of Antiretroviral Therapy on HIV Reservoirs in Elite Controllers.  

PubMed

Elite controllers suppress human immunodeficiency virus (HIV) viremia to below the limit of detection in the absence of antiretroviral therapy (ART). However, precise frequencies of CD4(+) T cells carrying replication-competent HIV and/or the dynamics of the infectious viral reservoirs in response to initiation and discontinuation of ART in elite controllers are unknown. We show that the size of the pool of CD4(+) T cells harboring infectious HIV diminished significantly after initiation of ART and rebounded to baseline upon cessation of therapy. Our data provide compelling evidence that persistent viral replication occurs in untreated elite controllers even in the absence of detectable plasma viremia. PMID:23847057

Chun, Tae-Wook; Shawn Justement, J; Murray, Danielle; Kim, Connie J; Blazkova, Jana; Hallahan, Claire W; Benko, Erika; Costiniuk, Cecilia T; Kandel, Gabor; Ostrowski, Mario; Kaul, Rupert; Moir, Susan; Casazza, Joseph P; Koup, Richard A; Kovacs, Colin; Fauci, Anthony S

2013-07-11

247

The effect of antiretrovirals on Plasmodium falciparum liver stages.  

PubMed

HIV and malaria overlap geographically, but the full impact of different antiretrovirals on malaria remains poorly understood. We examined the antimalarial activity of the HIV protease inhibitors lopinavir and saquinavir and the non-nucleoside reverse transcriptase inhibitor nevirapine on Plasmodium falciparum liver stages. Our results demonstrate that the HIV PI lopinavir inhibits liver stage parasites at clinically relevant concentrations, that is, at drug levels achieved in HIV-infected patients on standard dosing regimens. Because drugs that inhibit liver stages target parasites when they are present in lower numbers, these results might have implications for eradication efforts. PMID:23907270

Hobbs, Charlotte V; De La Vega, Patricia; Penzak, Scott R; Van Vliet, Jillian; Krzych, Urszula; Sinnis, Photini; Borkowsky, William; Duffy, Patrick E

2013-06-19

248

Where Does the Motivation for the Antiretroviral Therapy Come From? Assessing Existential Meaning, Personal Growth, and Motivation Toward Antiretroviral Therapy in People Affected by HIV\\/AIDS  

Microsoft Academic Search

\\u000a The present study examines the relations between personal growth, perception of meaningful life, and motivation toward antiretroviral\\u000a (ARV) therapy in 117 patients affected by HIV\\/AIDS. The subjects were recruited from antiretroviral treatment programs offered\\u000a at 23 care houses “Case Alloggio,” in 13 regions of Italy. Overall, the results reveal that internalized motivation toward\\u000a ARV therapy is explained by personal positive

Krzysztof Szadejko; Gabriele Covotta

249

Structural Barriers to Timely Initiation of Antiretroviral Treatment in Vietnam: Findings from Six Outpatient Clinics  

PubMed Central

In Vietnam, premature mortality due to AIDS-related conditions is commonly associated with late initiation to antiretroviral therapy (ART). This study explores reasons for late ART initiation among people living with HIV (PLHIV) from the perspectives of health care providers and PLHIV. The study was undertaken in six clinics from five provinces in Vietnam. Baseline CD4 counts were collected from patient records and grouped into three categories: very late initiators (?100 cells/mm3 CD4), late initiators (100–200 cells/mm3) and timely initiators (200–350 cells/mm3). Thirty in-depth interviews with patients who started ART and 15 focus group discussions with HIV service providers were conducted and thematic analysis of the content performed. Of 934 patients, 62% started ART very late and 11% initiated timely treatment. The proportion of patients for whom a CD4 count was obtained within six months of their HIV diagnosis ranged from 22% to 72%. The proportion of patients referred to ART clinics by voluntary testing and counselling centres ranged from 1% to 35%. Structural barriers to timely ART initiation were poor linkage between HIV testing and HIV care and treatment services, lack of patient confidentiality and a shortage of HIV/AIDS specialists. If Vietnam’s treatment practice is to align with WHO recommendations then the connection between voluntary counselling and testing service and ART clinics must be improved. Expansion and decentralization of HIV/AIDS services to allow implementation at the community level increased task sharing between doctors and nurses to overcome limited human resources, and improved patient confidentiality are likely to increase timely access to HIV treatment services for more patients.

Tran, Dam Anh; Shakeshaft, Anthony; Ngo, Anh Duc; Rule, John; Wilson, David P.; Zhang, Lei; Doran, Christopher

2012-01-01

250

Tuberculosis in Antiretroviral Treatment Programs in Lower Income Countries: Availability and Use of Diagnostics and Screening  

PubMed Central

Objectives In resource-constrained settings, tuberculosis (TB) is a common opportunistic infection and cause of death in HIV-infected persons. TB may be present at the start of antiretroviral therapy (ART), but it is often under-diagnosed. We describe approaches to TB diagnosis and screening of TB in ART programs in low- and middle-income countries. Methods and findings We surveyed ART programs treating HIV-infected adults in sub-Saharan Africa, Asia and Latin America in 2012 using online questionnaires to collect program-level and patient-level data. Forty-seven sites from 26 countries participated. Patient-level data were collected on 987 adult TB patients from 40 sites (median age 34.7 years; 54% female). Sputum smear microscopy and chest radiograph were available in 47 (100%) sites, TB culture in 44 (94%), and Xpert MTB/RIF in 23 (49%). Xpert MTB/RIF was rarely available in Central Africa and South America. In sites with access to these diagnostics, microscopy was used in 745 (76%) patients diagnosed with TB, culture in 220 (24%), and chest X-ray in 688 (70%) patients. When free of charge culture was done in 27% of patients, compared to 21% when there was a fee (p?=?0.033). Corresponding percentages for Xpert MTB/RIF were 26% and 15% of patients (p?=?0.001). Screening practices for active disease before starting ART included symptom screening (46 sites, 98%), chest X-ray (38, 81%), sputum microscopy (37, 79%), culture (16, 34%), and Xpert MTB/RIF (5, 11%). Conclusions Mycobacterial culture was infrequently used despite its availability at most sites, while Xpert MTB/RIF was not generally available. Use of available diagnostics was higher when offered free of charge.

Fenner, Lukas; Ballif, Marie; Graber, Claire; Nhandu, Venerandah; Dusingize, Jean Claude; Cortes, Claudia P.; Carriquiry, Gabriela; Anastos, Kathryn; Garone, Daniela; Jong, Eefje; Gnokoro, Joachim Charles; Sued, Omar; Ajayi, Samuel; Diero, Lameck; Wools-Kaloustian, Kara; Kiertiburanakul, Sasisopin; Castelnuovo, Barbara; Lewden, Charlotte; Durier, Nicolas; Sterling, Timothy R.; Egger, Matthias

2013-01-01

251

Immunological failure despite virological suppression in HIV seropositive individuals on antiretroviral therapy  

PubMed Central

Background: Some individuals experience a discordant response during antiretroviral therapy (ART), with a blunted CD4+ cell count response despite low HIV-1 RNA plasma levels. Materials and Methods: CD4 counts and viral load of 251 individuals on ART referred to the center were analysed for immunological failure. The viral load tests of 28 patients revealed a discordant response, characterized by low CD4 counts despite viral suppression (<47 copies in 23, <5000 in 4 patients and <10000 in one patient). Univariate and multiple regression analysis was done to determine factors associated with immunological failure in patients with viral suppression. Results: Twenty-eight patients developed immunological failure over a duration of 3.7±1.14 years despite viral suppression. In univariate analysis of discordant patients, low CD4 counts(<100cells/?l) at start of ART(P=0.0261), less than 50% gain in CD4 count (P=0.048) after one year of start of ART and duration on ART for more than 3 years (P=0.0436) were associated with immunological failure. In multiple regression, duration on ART, age and nadir CD4 count (lowest ever) on treatment were predictors of immunological failure in these patients. Overall females (n=8) demonstrated much higher CD4 counts of 136±72 than males (n=20) 79±38 cells/?l at the time of diagnosis of immunological failure. Conclusions: Discordance was observed in 13.59% of patients. Detection of failure to first line therapy based on immunologic criteria, without viral load testing, can result in unnecessary switches to 2nd line therapy.

Prabhakar, B.; Banu, Asima; Pavithra, H. B.; Chandrashekhara, P.; Sasthri, Suresh

2011-01-01

252

The Combined Effect of Modern Highly Active Antiretroviral Therapy Regimens and Adherence on Mortality Over Time  

PubMed Central

Objective To characterize the impact of longitudinal adherence on survival in drug-naive individuals starting currently recommended highly active antiretroviral therapy (HAART) regimens. Methods Eligible study participants initiated HAART between January 2000 and November 2004 and were followed until November 2005 (N = 903). HAART regimens contained efavirenz, nevirapine, or ritonavir-boosted atazanavir or lopinavir. Marginal structural modeling was used to address our objective. Results The all-cause mortality was 11%. Individual adherence decreased significantly over time, with the mean adherence shifting from 79% within the first 6 months of starting HAART to 72% within the 24- to 30-month period (P value < 0.01). Nonadherence over time (<95%) was strongly associated with higher risk of mortality (hazard ratio: 3.13; 95% confidence interval (CI): 1.95 to 5.05). Nonadherent (<95%) patients on nonnucleoside reverse transcriptase inhibitor (NNRTI)–based and boosted protease inhibitor–based regimens were, respectively, 3.61 times (95% CI: 2.15 to 6.06) and 3.25 times (95% CI: 1.63 to 6.49) more likely to die than adherent patients. Within the NNRTI-based regimens, nonadherent individuals on efavirenz were at a higher risk of mortality. Conclusions Incomplete adherence to modern HAART over time was strongly associated with increased mortality, and patients on efavirenz-based NNRTI therapies were particularly at a higher risk if nonadherent. These results highlight the need to develop further strategies to help sustain high levels of adherence on a long-term basis.

Lima, Viviane D.; Harrigan, Richard; Bangsberg, David R.; Hogg, Robert S.; Gross, Robert; Yip, Benita; Montaner, Julio S. G.

2013-01-01

253

Barriers and outcomes: TB patients co-infected with HIV accessing antiretroviral therapy in rural Zambia.  

PubMed

The vulnerabilities that underlie barriers faced by the rural poor whilst trying to access and adhere to "free" antiretroviral treatment (ART) demand more attention. This paper highlights barriers that poor rural Zambians co-infected with tuberculosis (TB) and HIV and their households faced in accessing ART between September 2006 and July 2007, and accounts for patient outcomes by the end of TB treatment and (more sporadically) beyond October 2009. The analysis draws on findings from wider anthropological fieldwork on the converging impact of TB, HIV and food insecurity, focusing for the purpose of this paper on ethnographic case-studies of seven newly diagnosed TB patients co-infected with HIV and their six households (one household had two TB patients). Economic barriers included being pushed into deeper poverty by managing TB, rural location, absence of any external assistance, and mustering time and extended funds for transport and "special food" during and beyond the end of TB. In the case of death, funeral costs were astronomical. Social barriers included translocation, broken marriages, a sub-ordinate household position, gender relations, denial, TB/HIV stigma and the difficulty of disclosure. Health facility barriers involved understaffing, many steps, lengthy procedures and inefficiencies (lost blood samples, electricity cuts). By the end of TB treatment, outcomes were mixed; two co-infected patients had died, three had started ART and two had yet to start ART. The three on ART underwent a striking transformation in the short term. By October 2009, two more had died and three were doing well. The study advocates nutritional support and other material support (especially transport funds) for co-infected TB patients until ART is accessed and livelihood regained. More prompt diagnosis of TB and reducing steps and increasing the reach of the ART programme in rural areas are also recommended. PMID:20680860

Chileshe, Muatale; Bond, Virginia Anne

2010-01-01

254

HIV-1 transmission among HIV-1 discordant couples before and after the introduction of antiretroviral therapy  

PubMed Central

Objective To evaluate the impact of antiretroviral therapy (ART) on HIV-1 transmission rates among HIV-1 discordant couples in Rakai, Uganda. Design Observational cohort study. Methods HIV-1 discordant couples were retrospectively identified between 2004 and 2009. Study participants underwent annual screening for HIV-1 and were interviewed to evaluate risk behaviors. Participants were offered voluntary counseling and testing and provided with risk reduction counseling. Free ART was offered to participants with a CD4 cell count of 250 cells/?l or less or WHO stage IV disease. HIV-1 incidence and sexual risk behaviors were compared before and after the HIV-1-positive index partners started ART. Results Two hundred and fifty HIV-1 discordant couples were followed between 2004 and 2009 and 32 HIV-1-positive partners initiated ART. Forty-two HIV-1 transmissions occurred over 459.4 person-years prior to ART initiation, incidence 9.2/100 person-years [95% confidence interval (CI) 6.59–12.36]. In 32 couples in which the HIV-1 index partners started ART, no HIV-1 transmissions occurred during 53.6 person-years. The 95% CI for the incidence rate difference was ?11.91 to ?6.38 (P=0.0097). Couples reported more consistent condom use during ART use, but there was no significant difference in the number of sexual partners or other risk behaviors. Viral load was markedly reduced in persons on ART. Conclusion HIV-1 transmission may be reduced among HIV-1 discordant couples after initiation of ART due to reductions in HIV-1 viral load and increased consistent condom use.

Reynolds, Steven J.; Makumbi, Frederick; Nakigozi, Gertrude; Kagaayi, Joseph; Gray, Ronald H.; Wawer, Maria; Quinn, Thomas C.; Serwadda, David

2012-01-01

255

Antiretroviral treatment switch strategies for lowering the costs of antiretroviral therapy in subjects with suppressed HIV-1 viremia in Spain  

PubMed Central

Background The current economic recession in European countries has forced governments to design emergency measures to reduce spending on drugs, including antiretroviral therapy (ART). Switching antiretroviral drugs for others that have the same efficacy and safety profile at a lower cost (cost-reduction measures, CRM) could prove to be a valid means of generating savings. Methods Descriptive study of prospective consensus-based CRM undertaken in 2011 in a Catalonian hospital HIV unit among patients with prolonged plasma HIV-1 RNA <50 copies/mL. Results During the study period, we made 673 switches (87.5% more than the previous year), of which 378 (56.2%) were CRM (16% of all patients treated), leading to a savings of €87,410/month. Switching tenofovir/emtricitabine for abacavir/lamivudine was the most common CRM (129, 31.3%), followed by simplification to boosted protease inhibitor monotherapy (bPImono, 102, 26%). The CRM that generated the greatest saving were switching to bPImono (38%), withdrawal or replacement of raltegravir (24%), switching tenofovir/emtricitabine for abacavir/lamivudine (13%), and switching to nevirapine (5%). Cost savings with CRM were slightly higher than those achieved with medication paid for by clinical trial sponsors (€80,333/month) or through discount arrangements (€76,389/month). Conclusion Proactively switching antiretroviral therapy in selected treated patients with sustained virological suppression can generate significant cost savings in pharmacy spending in developed countries. These findings have implications for decision makers in designing safe strategies that maintain HIV-1 suppression at lower costs.

Llibre, Josep M; Cardona, Gloria; Santos, Jose R; Andreu, Angels; Estrada, Josep O; Ara, Jordi; Bonafont, Xavier; Clotet, Bonaventura

2013-01-01

256

Profound Depletion of HIV-1 Transcription in Patients Initiating Antiretroviral Therapy during Acute Infection  

PubMed Central

Background Although combination antiretroviral therapy (cART) initiated in the acute phase of HIV-1 infection may prevent expansion of the latent reservoir, its benefits remain controversial. In the current study, HIV-1 RNA transcription patterns in peripheral blood mononuclear cells (PBMC) were monitored during acute cART to assess the effect of early treatment on cellular viral reservoirs. Methodology/Principal Findings Acutely HIV-1 infected patients (n?=?24) were treated within 3–15 weeks after infection. Patients elected to cease treatment after ?1 year of therapy. HIV-1 DNA (vDNA), HIV-1 RNA species expressed both in latently and productively infected cells, unspliced (UsRNA), multiply spliced (MsRNA-tatrev; MsRNA-nef), and PBMC-associated extracellular virion RNA (vRex), expressed specifically by productively infected cells, were quantified in PBMC by patient matched real-time PCR prior, during and post cART. In a matched control-group of patients on successful cART started during chronic infection (n?=?15), UsRNA in PBMC and vDNA were measured cross-sectionally. In contrast to previous reports, PBMC-associated HIV-1 RNAs declined to predominantly undetectable levels on cART. After cART cessation, UsRNA, vRex, and MsRNA-tatrev rebounded to levels not significantly different to those at baseline (p>0.1). In contrast, MsRNA-nef remained significantly lower as compared to pretreatment (p?=?0.015). UsRNA expressed at the highest levels of all viral RNAs, was detectable on cART in 42% of patients with cART initiated during acute infection as opposed to 87% of patients on cART initiated during chronic infection (Fisher's exact test; p?=?0.008). Accordingly, UsRNA levels were 105–fold lower in the acute as compared to the chronic group. Conclusion Early intervention resulted in profound depletion of PBMC expressing HIV-1 RNA. This is contrary to chronically infected patients who predominantly showed continuous UsRNA expression on cART. Thus, antiretroviral treatment initiated during the acute phase of infection prevented establishment or expansion of long-lived transcriptionally active viral cellular reservoirs in peripheral blood.

von Wyl, Viktor; Metzner, Karin J.; Scherrer, Alexandra U.; Niederost, Barbara; Althaus, Claudia F.; Rieder, Philip; Grube, Christina; Joos, Beda; Weber, Rainer; Fischer, Marek; Gunthard, Huldrych F.

2010-01-01

257

Factors Influencing Adherence to Antiretroviral Treatment in Nepal: A Mixed-Methods Study  

PubMed Central

Background Antiretroviral therapy (ART) is a lifesaver for individual patients treated for Human Immunodeficiency Virus (HIV) and Acquired Immune Deficiency Syndrome (AIDS). Maintaining optimal adherence to antiretroviral drugs is essential for HIV infection management. This study aimed to understand the factors influencing adherence amongst ART-prescribed patients and care providers in Nepal. Methods A cross-sectional mixed-methods study surveying 330 ART-prescribed patients and 34 in-depth interviews with three different types of stakeholders: patients, care providers, and key people at policy level. Adherence was assessed through survey self-reporting and during the interviews. A multivariate logistic regression model was used to identify factors associated with adherence, supplemented with a thematic analysis of the interview transcripts. Results A total of 282 (85.5%) respondents reported complete adherence, i.e. no missed doses in the four-weeks prior to interview. Major factors influencing adherence were: non-disclosure of HIV status (OR?=?17.99, p?=? 0.014); alcohol use (OR?=?12.89, p?=?<0.001), being female (OR?=?6.91, p?=?0.001), being illiterate (OR?=?4.58, p?=?0.015), side-effects (OR?=?6.04, p?=?0.025), ART started ?24 months (OR?=?3.18, p?=?0.009), travel time to hospital >1 hour (OR?=?2.84, p?=?0.035). Similarly, lack of knowledge and negative perception towards ART medications also significantly affected non-adherence. Transport costs (for repeat prescription), followed by pills running out, not wanting others to notice, side-effects, and being busy were the most common reasons for non-adherence. The interviews also revealed religious or ritual obstacles, stigma and discrimination, ART-associated costs, transport problems, lack of support, and side-effects as contributing to non-adherence. Conclusion Improving adherence requires a supportive environment; accessible treatment; clear instructions about regimens; and regimens tailored to individual patients’ lifestyles. Healthcare workers should address some of the practical and cultural issues around ART medicine whilst policy-makers should develop appropriate social policy to promote adherence among ART-prescribed patients.

Wasti, Sharada P.; Simkhada, Padam; Randall, Julian; Freeman, Jennifer V.; van Teijlingen, Edwin

2012-01-01

258

Physics of Tokamak Plasma Start-up  

NASA Astrophysics Data System (ADS)

This tutorial describes and reviews the state-of-art in tokamak plasma start-up and its importance to next step devices such as ITER, a Fusion Nuclear Science Facility and a Tokamak/ST demo. Tokamak plasma start-up includes breakdown of the initial gas, ramp-up of the plasma current to its final value and the control of plasma parameters during those phases. Tokamaks rely on an inductive component, typically a central solenoid, which has enabled attainment of high performance levels that has enabled the construction of the ITER device. Optimizing the inductive start-up phase continues to be an area of active research, especially in regards to achieving ITER scenarios. A new generation of superconducting tokamaks, EAST and KSTAR, experiments on DIII-D and operation with JET's ITER-like wall are contributing towards this effort. Inductive start-up relies on transformer action to generate a toroidal loop voltage and successful start-up is determined by gas breakdown, avalanche physics and plasma-wall interaction. The goal of achieving steady-sate tokamak operation has motivated interest in other methods for start-up that do not rely on the central solenoid. These include Coaxial Helicity Injection, outer poloidal field coil start-up, and point source helicity injection, which have achieved 200, 150 and 100 kA respectively of toroidal current on closed flux surfaces. Other methods including merging reconnection startup and Electron Bernstein Wave (EBW) plasma start-up are being studied on various devices. EBW start-up generates a directed electron channel due to wave particle interaction physics while the other methods mentioned rely on magnetic helicity injection and magnetic reconnection which are being modeled and understood using NIMROD code simulations.

Mueller, Dennis

2012-10-01

259

Physicists: A Start-Ups's Secret Weapon  

NASA Astrophysics Data System (ADS)

High-tech start-ups have been a magnet for engineers, MBAs, and money. However, the vital and rewarding role of physicists in these ventures is often overlooked. This talk will focus on the essential contributions physicists make and the various positions physicists hold "behind the scenes" in high-tech start-ups. As the high-tech economy continues to heat up, especially in telecommunications, the opportunities for physicists continue to expand. This is truely a time for physicists to make their mark in the start-up world.

Smoliar, Laura

2001-03-01

260

Practical and Conceptual Challenges in Measuring Antiretroviral Adherence  

PubMed Central

Accurate measurement of antiretroviral adherence is essential for targeting and rigorously evaluating interventions to improve adherence and prevent viral resistance. Across diseases, medication adherence is an individual, complex, and dynamic human behavior that presents unique measurement challenges. Measurement of medication adherence is further complicated by the diversity of available measures, which have different utility in clinical and research settings. Limited understanding of how to optimize existing adherence measures has hindered progress in adherence research in both HIV and other diseases. Though self-report is the most widely used adherence measure and the most promising for use in clinical care and resource limited settings, adherence researchers have yet to develop evidence-based standards for self-reported adherence. In addition, the use of objective measures, such as electronic drug monitoring or pill counts, is limited by poor understanding of the source and magnitude of error biasing these measures. To address these limitations, research is needed to evaluate methods of combining information from different measures. The goals of this review are to describe the state of the science of adherence measurement, to discuss the advantages and disadvantages of common adherence measurement methods, and to recommend directions for improving antiretroviral adherence measurement in research and clinical care.

Berg, Karina M.; Arnsten, Julia H.

2010-01-01

261

Antimalaria action of antiretroviral drugs on Plasmodium berghei in mice.  

PubMed

Malaria parasitemia enhances replication of human immunodeficiency virus. Antiretroviral drugs that possess antiplasmodial activity may reverse such an effect. Activity of the antiretroviral drugs lamivudine (L), zidovudine (Z), nevirapine (N), and stavudine (S) against Plasmodium berghei inoculated into 70 adult albino mice was investigated. Eight groups of five animals each were treated with different drugs as either curative or prophylactic regimens. These regimens were also given to four groups as L/Z/N or L/S/N. Z therapy alone and L/Z/N eliminated malaria parasites as follows: curative and prophylactic Z groups, mean ± SEM = 62,132.87 ± 22,816.1 parasites/?L and 62,474.85 ± 14,639.1 parasites/?L, respectively on day 4 and 0 parasites/?L on day 26; curative L/Z/N group, 31,583.53 ± 6,361.67 parasites/?L, and 0 parasites/?L (days 4 and 18, respectively); prophylactic L/Z/N group, 41,138.1 ± 3,528.03 parasites/?L, and 0 parasites/?L (days 4, and 20 respectively). Peters four-day suppressive values were 67-82.2%. Zidovudine or L/Z/N therapy may modify the epidemiology of malaria and therefore the pandemic of human immunodeficiency virus infection. PMID:23208888

Akinyede, Akinwumi; Akintonwa, Alade; Awodele, Olufunsho; Olayemi, Sunday; Oreagba, Ibrahim; Okany, Charles; Aina, Oluwagbemiga; Akindele, Samuel

2012-12-03

262

HIV and antiretroviral therapy: Impact on the central nervous system  

PubMed Central

Summary The HIV pandemic represents a major source of neurological morbidity worldwide. Emerging data from diverse populations indicate that HIV leads to significant neurocognitive impairments that reduce individuals' ability to contribute to the well being of their families and society. HIV affects vulnerable populations with many comorbidities, but the virus contributes to neurocognitive impairment independent of these conditions. The neuropathological substrate of HIV neurocognitive disorders is damage to synapses and dendrites, without major neuronal loss. This suggests the potential for substantial reversibility if synaptodendritic function can be restored. In the developed world, combination antiretroviral therapy (CART) leads to improved neurocognitive function as well as morbidity and mortality in HIV. CART is being used in increasing numbers of individuals in resource limited settings. New cases of severe dementia are now rare in populations where effective CART has been deployed. While some degree of neurocognitive improvement with CART is almost universal, many individuals do not achieve full restoration of their premorbid neurocognitive status, and milder degrees of impairment remain quite prevalent. Optimizing neurocognitive recovery is likely to require the development of better CNS penetrating antiretroviral regimens and the use of neuroprotective agents.

Ellis, Ronald

2010-01-01

263

HIV-Antiretroviral Therapy Induced Liver, Gastrointestinal, and Pancreatic Injury  

PubMed Central

The present paper describes possible connections between antiretroviral therapies (ARTs) used to treat human immunodeficiency virus (HIV) infection and adverse drug reactions (ADRs) encountered predominantly in the liver, including hypersensitivity syndrome reactions, as well as throughout the gastrointestinal system, including the pancreas. Highly active antiretroviral therapy (HAART) has a positive influence on the quality of life and longevity in HIV patients, substantially reducing morbidity and mortality in this population. However, HAART produces a spectrum of ADRs. Alcohol consumption can interact with HAART as well as other pharmaceutical agents used for the prevention of opportunistic infections such as pneumonia and tuberculosis. Other coinfections that occur in HIV, such as hepatitis viruses B or C, cytomegalovirus, or herpes simplex virus, further complicate the etiology of HAART-induced ADRs. The aspect of liver pathology including liver structure and function has received little attention and deserves further evaluation. The materials used provide a data-supported approach. They are based on systematic review and analysis of recently published world literature (MedLine search) and the experience of the authors in the specified topic. We conclude that therapeutic and drug monitoring of ART, using laboratory identification of phenotypic susceptibilities, drug interactions with other medications, drug interactions with herbal medicines, and alcohol intake might enable a safer use of this medication.

Neuman, Manuela G.; Schneider, Michelle; Nanau, Radu M.; Parry, Charles

2012-01-01

264

Photosensitization is required for antiretroviral activity of hypericin  

NASA Astrophysics Data System (ADS)

In a seminal series of papers, Meruelo and co-workers have described the potent antiretroviral effect of hypericin. Interestingly, hypericin was found to inhibit not only the production of infectious virus from chronically infected cells, but was also shown to directly inhibit reverse transcriptase activity of mature virions. The effect of hypericin on cells chronically infected with equine infectious anemia virus (EIAV), a retrovirus genetically related to HIV, is demonstrated. At concentrations of 10 (mu) g/ml, hypericin reduced production of infectious EIAV by 99.99% without causing obvious cytopathic effects. Interestingly, the results indicated that the antiretroviral activity of hypericin was wholly dependent on the presence of light. No decrease in viral infectivity was observed when hypericin and virus were incubated in the dark. Moreover, it appeared that light was an absolute requirement for the antiviral activity, as even high concentrations of hypericin (10 (mu) g/ml) were unable to reduce infectivity of as few as 100 infectious virions.

Carpenter, Susan; Tossberg, John; Kraus, George A.

1991-06-01

265

A Systematic Review Comparing Antiretroviral Adherence Descriptive and Intervention Studies  

PubMed Central

We examined the extent to which studies aimed at testing interventions to improve antiretroviral adherence have targeted the facilitators of and barriers known to affect adherence. Of the 88 reports reviewed, 41 were reports of descriptive studies conducted with U.S. HIV-positive women and 47 were reports of intervention studies conducted with U.S. HIV-positive persons. We extracted from the descriptive studies all findings addressing any factor linked to antiretroviral adherence and from the intervention studies, information on the nature of the intervention, the adherence problem targeted, the persons targeted for the intervention, and the intervention outcomes desired. We discerned congruence between the prominence of substance abuse as a factor identified in the descriptive studies as a barrier to adherence and its prominence as the problem most addressed in those reports of intervention studies that specified the problems targeted for intervention. We also discerned congruence between the prominence of family and provider support as factors identified in the descriptive studies as facilitators of adherence and the presence of social support as an intervention component and outcome variable. Less discernible in the reports of intervention studies was specific attention to other factors prominent in the descriptive studies, which may be due to the complex nature of the problem, individualistic and rationalist slant of interventions, or simply the ways interventions were presented. Our review raises issues about niche standardization and intervention tailoring, targeting, and fidelity.

Sandelowski, Margarete; Voils, Corrine I.; Chang, Yunkyung; Lee, Eun-Jeong

2009-01-01

266

Head start teaching center: Describing the initiation of a new approach to head start staff development  

Microsoft Academic Search

This paper provides a description of the program and formative evaluation of the New England Head Start Teaching Center, one\\u000a of fourteen funded nationally to study alternative approaches to Head Start staff development. Head Start Teaching Centers\\u000a are a national demonstration project created to provide participatory training in all Head Start component areas within the\\u000a context of an exemplary Head

David A. Caruso; Diane M. Horm-Wingerd; Lynda Dickinson

1996-01-01

267

National Head Start Association Position Paper: A Vision for Head Start and State Collaboration.  

ERIC Educational Resources Information Center

|Based on the view that coordinated efforts among Head Start programs, child care programs and other prekindergarten programs, and states can be enhanced without devolving Head Start and its high quality standards to the states, this position paper draws on a Bush Administration report and the Head Start Program Performance Standards to…

Ryan, Joel; Allen, Ben

268

Head Start 2010: Fulfilling the Promise. Report of the Head Start 2010 National Advisory Panel.  

ERIC Educational Resources Information Center

In anticipation of the 35th anniversary of Project Head Start, the National Head Start Association (NHSA) launched a national initiative to discover how Head Start can best serve children and families in the new millennium. A series of hearings and open forums were conducted throughout the country in 1999, along with a special session featuring…

National Head Start Association, Alexandria, VA.

269

A Review of Head Start Research Since 1970. Head Start Evaluation, Synthesis and Utilization Project.  

ERIC Educational Resources Information Center

|This review attempts to summarize the major findings concerning the impact of Head Start that have been reported in the literature published since 1970, and to communicate these results to policymakers, researchers, Head Start program staff, and others. The review constitutes an update of "A Review of Head Start Research since 1969 and an…

Hubbell, Ruth

270

Which starting style is faster in sprint running--standing or crouch start?  

PubMed

The purpose of this study was to further understand the biomechanical differences between the standing and crouch starting methods, and to investigate whether one of the starting styles provides better acceleration and proves to be faster. Six university track team sprinters performed 2 x 3 x 50 m trials. Digitised video, photocell timing, and velocity data revealed that during the first steps of the performance the standing start produced higher body centre of mass horizontal velocity than the crouch start. This may be due to the longer distance between the feet in the standing start, which caused longer push-off phases, and the work against gravity in the crouch start. However, this advantage in horizontal velocity disappeared by the 10 m mark, where similar velocities were recorded with both start styles. Further, there was no statistically significant difference between the two starting styles in horizontal velocity at the 25 m mark, nor in the time to reach the 25 m or 50 m mark. Regarding relay running, where athletes need to decide to adopt either a crouch start without starting blocks or a standing start, there seems to be no specific reason for outgoing athletes to use a crouch start, although this area warrants further investigation. PMID:15079987

Salo, Aki; Bezodis, Ian

2004-01-01

271

Head Start/EPSDT Collaboration Evaluation.  

National Technical Information Service (NTIS)

The first year evaluation of the Head Start - Medicaid Early Periodic Screening, Diagnosis, and Treatment (EPSDT) Collaborative Effort is described in this report. The effort was initiated in 1974 by the Office of Child Development as a demonstration prog...

1976-01-01

272

Start small and build toward business intelligence.  

PubMed

To use business intelligence effectively, healthcare organizations should start small, align organizationally, and leverage success. Organizations should determine which measures they need and how to present them. Organizations should reinvest savings to continually improve. PMID:19161037

Kirby, Sean; Robertson, Brian

2009-01-01

273

34 CFR 200.16 - Starting points.  

Code of Federal Regulations, 2013 CFR

...Using data from the 2001-2002 school year, each State must establish starting points in reading/language arts and in mathematics for measuring the percentage of students meeting or exceeding the State's proficient level of academic...

2013-07-01

274

Start at the Store: Prevent Foodborne Illness  

MedlinePLUS Videos and Cool Tools

... Most Popular Searches Home Food Drugs Medical Devices Radiation-Emitting Products Vaccines, Blood & Biologics Animal & Veterinary Cosmetics ... Cosmetics Dietary Supplements Drugs Food Medical Devices Nutrition Radiation-Emitting Products Tobacco Products Vaccines, Blood & Biologics Start ...

275

Head Start/EPSDT Collaboration Evaluation.  

National Technical Information Service (NTIS)

This nontechnical report is based on the final report of the evaluation of the Head Start - Medicaid Early Periodic Screening, Diagnosis, and Treatment (EPSDT) Collaborative Effort. The collaborative effort, a demonstration project initiated in 1974 by th...

G. McMurray R. Sims

1976-01-01

276

The physics of tokamak start-up  

NASA Astrophysics Data System (ADS)

Tokamak start-up on present-day devices usually relies on inductively induced voltage from a central solenoid. In some cases, inductive startup is assisted with auxiliary power from electron cyclotron radio frequency heating. International Thermonuclear Experimental Reactor, the National Spherical Torus Experiment Upgrade and JT60, now under construction, will make use of the understanding gained from present-day devices to ensure successful start-up. Design of a spherical tokamak (ST) with DT capability for nuclear component testing would require an alternative to a central solenoid because the small central column in an ST has insufficient space to provide shielding for the insulators in the solenoid. Alternative start-up techniques such as induction using outer poloidal field coils, electron Bernstein wave start-up, coaxial helicity injection, and point source helicity injection have been used with success, but require demonstration of scaling to higher plasma current.

Mueller, D.

2013-05-01

277

Why Your Child Might Start Drinking Alcohol  

MedlinePLUS

UNDERAGE DRINKING PREVENTION NATIONAL MEDIA CAMPAIGN WHY YOUR CHILD MIGHT START DRINKING ALCOHOL As children approach their teen years, they begin to experience many emotional and physical changes, and ...

278

The Physics of Tokamak Start-up  

SciTech Connect

Tokamak start-up on present-day devices usually relies on inductively induced voltage from a central solenoid. In some cases inductive startup is assisted with auxiliary power from electron cyclotron radio frequency heating. ITER, the National Spherical Torus eXperiment Upgrade and JT60, now under construction, will make use of the understanding gained from present-day devices to ensure successful start-up. Design of a spherical tokamak (ST) with DT capability for nuclear component testing would require an alternative to a central solenoid because the small central column in an ST has insufficient space to provide shielding for the insulators in the solenoid. Alternative start-up techniques such as induction using outer poloidal field coils, electron Bernstein wave start-up, coaxial helicity injection and point source helicity injection have been used with success, but require demonstration of scaling to higher plasma current.

D. Mueller

2012-11-13

279

Pellet injection on START and MAST  

Microsoft Academic Search

Cryogenic pellet injection has been used in START and it is under commissioning for MAST for fuelling and diagnostics. In START NBI, heated plasmas fuelled with deuterium pellets, high normalized density (Greenwald number NG?1.1) with good energy confinement time (?E\\/?EelmfITER97?1.3) both at high beta (?T?25%, ?N?4.9) have been obtained for time scales close to the energy confinement time (??E). In

C Ribeiro; R Akers; F Alladio; K Axon; L Baylor; G. F Counsell; J Dowling; S Fielding; L Garzotti; M Gryaznevich; W. E Han; P Innocente; I Jenkins; J deKloe; R Martin; P Micozzi; B Sass; A Sykes; D Terranova; T. N Todd; P Twynam; M Wakatani; M. J Walsh; S You

2001-01-01

280

Choice of Initial Combination Antiretroviral Therapy in Individuals With HIV Infection: Determinants and Outcomes.  

PubMed

BACKGROUND Current guidelines give recommendations for preferred combination antiretroviral therapy (cART). We investigated factors influencing the choice of initial cART in clinical practice and its outcome. METHODS We analyzed treatment-naive adults with human immunodeficiency virus (HIV) infection participating in the Swiss HIV Cohort Study and starting cART from January 1, 2005, through December 31, 2009. The primary end point was the choice of the initial antiretroviral regimen. Secondary end points were virologic suppression, the increase in CD4 cell counts from baseline, and treatment modification within 12 months after starting treatment. RESULTS A total of 1957 patients were analyzed. Tenofovir-emtricitabine (TDF-FTC)-efavirenz was the most frequently prescribed cART (29.9%), followed by TDF-FTC-lopinavir/r (16.9%), TDF-FTC-atazanavir/r (12.9%), zidovudine-lamivudine (ZDV-3TC)-lopinavir/r (12.8%), and abacavir/lamivudine (ABC-3TC)-efavirenz (5.7%). Differences in prescription were noted among different Swiss HIV Cohort Study sites (P < .001). In multivariate analysis, compared with TDF-FTC-efavirenz, starting TDF-FTC-lopinavir/r was associated with prior AIDS (relative risk ratio, 2.78; 95% CI, 1.78-4.35), HIV-RNA greater than 100 000 copies/mL (1.53; 1.07-2.18), and CD4 greater than 350 cells/?L (1.67; 1.04-2.70); TDF-FTC-atazanavir/r with a depressive disorder (1.77; 1.04-3.01), HIV-RNA greater than 100 000 copies/mL (1.54; 1.05-2.25), and an opiate substitution program (2.76; 1.09-7.00); and ZDV-3TC-lopinavir/r with female sex (3.89; 2.39-6.31) and CD4 cell counts greater than 350 cells/?L (4.50; 2.58-7.86). At 12 months, 1715 patients (87.6%) achieved viral load less than 50 copies/mL and CD4 cell counts increased by a median (interquartile range) of 173 (89-269) cells/?L. Virologic suppression was more likely with TDF-FTC-efavirenz, and CD4 increase was higher with ZDV-3TC-lopinavir/r. No differences in outcome were observed among Swiss HIV Cohort Study sites. CONCLUSIONS Large differences in prescription but not in outcome were observed among study sites. A trend toward individualized cART was noted suggesting that initial cART is significantly influenced by physician's preference and patient characteristics. Our study highlights the need for evidence-based data for determining the best initial regimen for different HIV-infected persons. PMID:22892835

Elzi, Luigia; Erb, Stefan; Furrer, Hansjakob; Ledergerber, Bruno; Cavassini, Matthias; Hirschel, Bernard; Vernazza, Pietro; Bernasconi, Enos; Weber, Rainer; Battegay, Manuel

2012-09-24

281

Broadening the use of antiretroviral therapy: the case for feline leukemia virus  

PubMed Central

Antiretroviral drugs have saved and extended the lives of millions of individuals infected with HIV. The major classes of anti-HIV drugs include reverse transcriptase inhibitors, protease inhibitors, integrase inhibitors, and entry/fusion inhibitors. While antiretroviral drug regimens are not commonly used to treat other types of retroviral infections, there are instances where there is a perceived need for re-evaluation of the benefits of antiretroviral therapy. One case in point is that of feline leukemia virus (FeLV), an infection of companion felines. While vaccines exist to prevent FeLV infection and spread, they have not eliminated FeLV infection. For FeLV-infected felines and their human companions, antiretroviral therapy would be desirable and of practical importance if good options were available. Here, we discuss FeLV biology and current treatment options, and propose that there is a need for antiretroviral treatment options for FeLV infection. The comparative use and analysis of antiretroviral therapy can provide new insights into the mechanism of antiretroviral drug action.

Greggs, Willie M; Clouser, Christine L; Patterson, Steven E; Mansky, Louis M

2011-01-01

282

Direct-to-consumer advertisements for HIV antiretroviral medications: a progress report.  

PubMed

Direct-to-consumer (DTC) prescription drug advertisements for HIV anti-retrovirals are controversial and have been criticized in the past for including deceptive images and underplaying HIV drug limitations. We sought to describe the state of recent DTC ads for HIV antiretrovirals in popular magazines by performing a content analysis of all complete DTC ads for antiretroviral medications appearing in eight national magazines during a one-year period. Current ads appear to have addressed previous concerns, but important problems still exist, such as failing to specify the medication's role in current treatment, to quantify drug efficacy, or to highlight life-threatening side effects. PMID:17848450

Kallen, Alexander; Woloshin, Steven; Shu, Jennifer; Juhl, Ellen; Schwartz, Lisa

283

Antiretroviral and anti-hepatitis C virus direct-acting antiviral-related hepatotoxicity.  

PubMed

Antiretroviral-related hepatotoxicity occurs commonly in patients with human immunodeficiency virus (HIV). Liver injury ranges from unconjugated hyperbilirubinemia and nodular regenerative hyperplasia to lactic acidosis and toxic hepatitis. Effective antiretroviral therapy has changed coinfected patients' primary morbidities and mortality to chronic liver disease rather than complications from HIV. Treatment for hepatitis C virus (HCV) is strongly encouraged early in all coinfected patients. However, drug-drug interactions must be considered to ensure safe and tolerable use alone or in combination with antiretroviral therapies. The first-generation and newer HCV direct-acting antivirals are promising in coinfected patients, with minimal side effects and hepatotoxicity. PMID:24099023

Han, Hyosun; Agarwal, Ritu; Martel-Laferriere, Valerie; Dieterich, Douglas T

2013-09-04

284

Predictors of first-line antiretroviral therapy discontinuation due to drug-related adverse events in HIV-infected patients: a retrospective cohort study  

PubMed Central

Background Drug-related toxicity has been one of the main causes of antiretroviral treatment discontinuation. However, its determinants are not fully understood. Aim of this study was to investigate predictors of first-line antiretroviral therapy discontinuation due to adverse events and their evolution in recent years. Methods Patients starting first-line antiretroviral therapy were retrospectively selected. Primary end-point was the time to discontinuation of therapy due to adverse events, estimating incidence, fitting Kaplan-Meier and multivariable Cox regression models upon clinical/demographic/chemical baseline patients’ markers. Results 1,096 patients were included: 302 discontinuations for adverse events were observed over 1,861 person years of follow-up between 1988 and 2010, corresponding to an incidence (95% CI) of 0.16 (0.14-0.18). By Kaplan-Meier estimation, the probabilities (95% CI) of being free from an adverse event at 90 days, 180 days, one year, two years, and five years were 0.88 (0.86-0.90), 0.85 (0.83-0.87), 0.79 (0.76-0.81), 0.70 (0.67-0.74), 0.55 (0.50-0.61), respectively. The most represented adverse events were gastrointestinal symptoms (28.5%), hematological (13.2%) or metabolic (lipid and glucose metabolism, lipodystrophy) (11.3%) toxicities and hypersensitivity reactions (9.3%). Factors associated with an increased hazard of adverse events were: older age, CDC stage C, female gender, homo/bisexual risk group (vs. heterosexual), HBsAg-positivity. Among drugs, zidovudine, stavudine, zalcitabine, didanosine, full-dose ritonavir, indinavir but also efavirenz (actually recommended for first-line regimens) were associated to an increased hazard of toxicity. Moreover, patients infected by HIV genotype F1 showed a trend for a higher risk of adverse events. Conclusions After starting antiretroviral therapy, the probability of remaining free from adverse events seems to decrease over time. Among drugs associated with increased toxicity, only one is currently recommended for first-line regimens but with improved drug formulation. Older age, CDC stage, MSM risk factor and gender are also associated with an increased hazard of toxicity and should be considered when designing a first-line regimen.

2012-01-01

285

45 CFR 1311.1 - Head Start Fellows Program Purpose.  

Code of Federal Regulations, 2010 CFR

...Welfare 4 2009-10-01 2009-10-01 false Head Start Fellows Program Purpose. 1311.1 Section 1311...ADMINISTRATION FOR CHILDREN, YOUTH AND FAMILIES, HEAD START PROGRAM HEAD START FELLOWS PROGRAM § 1311.1 Head Start...

2009-10-01

286

45 CFR 1311.1 - Head Start Fellows Program Purpose.  

Code of Federal Regulations, 2010 CFR

...Welfare 4 2010-10-01 2010-10-01 false Head Start Fellows Program Purpose. 1311.1 Section 1311...ADMINISTRATION FOR CHILDREN, YOUTH AND FAMILIES, HEAD START PROGRAM HEAD START FELLOWS PROGRAM § 1311.1 Head Start...

2010-10-01

287

Antiretroviral genotypic resistance in plasma RNA and whole blood DNA in HIV-1 infected patients failing HAART.  

PubMed

The extent to which HIV-1 proviral DNA mutations cause clinically relevant antiretroviral resistance is still controversial. Paired plasma HIV-1 RNA and whole blood DNA were compared in patients failing HAART to investigate if the additional knowledge of archived mutations could improve the selection of potentially active drugs. Seventy-three HIV-1-infected patients with first/second HAART failure were studied before starting a new regimen based on RNA genotyping. Follow-up data after a 12-week therapy were available. DNA genotyping was retrospectively performed on stored whole blood samples and mutational profiles were compared to those from RNA. The mean number of IAS pol mutations was significantly higher in RNA (4.45 +/- 2.76) than in DNA (2.88 +/- 2.47) (P < 0.001). DNA genotyping provided a 6% increase in detection of resistance-associated mutations. Among 64/73 patients showing discordant DNA/RNA profiles, 54 (84%) also differed for predicted active drugs. 16/73 (22%) patients had >or=1 mutation revealed by DNA genotyping alone, probably affecting therapy success in 2/16. However, neither RNA/DNA discordance nor detection of isolated DNA mutations were statistically associated with outcome. In conclusion, plasma RNA remains the elective choice for HIV genotyping in patients with therapy failure, even if the detection of proviral resistance-associated mutations, not simultaneously found in RNA, is a frequent event. Therefore, in some cases DNA plus RNA genotyping might assist in choosing more accurately subsequent antiretroviral regimens. PMID:18712823

Saracino, Annalisa; Gianotti, Nicola; Marangi, Marianna; Cibelli, Donatella C; Galli, Andrea; Punzi, Grazia; Monno, Laura; Lazzarin, Adriano; Angarano, Gioacchino

2008-10-01

288

Racial Differences in Response to Antiretroviral Therapy for HIV Infection: An AIDS Clinical Trials Group (ACTG) Study Analysis.  

PubMed

Background.?In the United States, black individuals infected with human immunodeficiency virus (HIV) have higher rates of virologic failure on antiretroviral therapy (ART) and of death compared to white individuals. The cause for these disparities is uncertain. We sought to examine differences in virologic outcomes among antiretroviral-naive clinical trial participants starting randomized ART and to investigate factors to explain the differences. Methods.?Individual-level data from participants initiating ART in 5 AIDS Clinical Trials Group studies were analyzed. Included studies were those conducted during 1998-2006 with a primary outcome of virologic failure. The primary outcome measure was time to virologic failure, regardless of ART changes. Results.?A total of 2495 individuals (1151 black; 1344 white) were included with a median follow-up of 129 weeks. Compared to whites, blacks had an increased hazard of virologic failure (hazard ratio [HR]; 1.7; 95% confidence interval [CI], 1.4-1.9; P < .001), with no evidence of heterogeneity across regimens (P = .97); the association remained after adjustment for measured confounders (HR, 1.4; 95% CI, 1.2-1.6; P < .001). Increased hazard of virologic failure was associated with younger age, higher pretreatment HIV type 1 RNA level, lower pretreatment CD4 cell count, hepatitis C antibody, less education, and recent nonadherence to treatment. Sensitivity analyses with different endpoint definitions demonstrated similar results. Conclusions.?In this analysis, blacks had a 40% higher virologic failure risk than whites that was not explained by measured confounders. The observation was consistent over a range of regimens, suggesting that the difference may be driven by social factors; however, biological factors cannot be ruled out. Further research should identify the sources of racial disparities and develop strategies to reduce them. PMID:24046302

Ribaudo, Heather J; Smith, Kimberly Y; Robbins, Gregory K; Flexner, Charles; Haubrich, Richard; Chen, Yun; Fischl, Margaret A; Schackman, Bruce R; Riddler, Sharon A; Gulick, Roy M

2013-09-17

289

HIV, dementia and antiretroviral drugs: 30 years of an epidemic.  

PubMed

Neurological complications due to the HIV itself became apparent early on in the course of the AIDS epidemic. The most feared were the cognitive and motor complications termed AIDS dementia complex or HIV-associated dementia. With the introduction of combination antiretroviral therapy, the incidence of HIV-associated dementia has been dramatically reduced. However, the prevalence of less severe forms of the disorder remains around 20%. There is controversy about whether some patients may continue with progressive cognitive decline despite adequate suppression of the HIV. The salient issues are those of cerebrospinal fluid (CSF) drug penetration, drug neurotoxicity and persistent immune activation and inflammation. This review will also discuss other newly encountered complications, including the compartmentalisation (or CSF escape) and immune reconstitution inflammatory syndromes. PMID:23378642

Manji, Hadi; Jäger, H R; Winston, Alan

2013-02-01

290

Initiating antiretrovirals during tuberculosis treatment: a drug safety review  

PubMed Central

Introduction Integrating HIV and TB treatment can reduce mortality substantially. Practical barriers to treatment integration still exist and include safety concerns related to concomitant drug use because of drug interactions and additive toxicities. Altered therapeutic concentrations may influence the chances of treatment success or toxicity. Areas covered The available data on drug-drug interactions between the rifamycin class of anti-mycobacterials and the non-nucleoside reverse transcriptase inhibitor and the protease inhibitor classes of anti-retrovirals are discussed with recommendations for integrated use. Additive drug toxicities, the impact of immune reconstitution inflammatory syndrome (IRIS) and the latest data on survival benefits of integrating treatment are elucidated. Expert opinion Deferring treatment of HIV to avoid drug-interactions with TB treatment or the occurrence of IRIS is not necessary. In the integrated management of TB/HIV co-infection, rational drug combinations aimed at reducing toxicities while effecting TB cure and suppressing HIV viral load are possible.

Gengiah, Tanuja N.; Gray, Andrew L.; Naidoo, Kogieleum; Karim, Quarraisha Abdool

2011-01-01

291

African Mitochondrial DNA Subhaplogroups and Peripheral Neuropathy during Antiretroviral Therapy  

PubMed Central

Susceptibility to peripheral neuropathy during antiretroviral therapy with nucleoside reverse transcriptase inhibitors (NRTIs) was previously associated with a European mitochondrial DNA (mtDNA) haplogroup among non-Hispanic white persons. To determine if NRTI-associated peripheral neuropathy was related to mtDNA variation in non-Hispanic black persons, we sequenced mtDNA of participants from AIDS Clinical Trials Group study 384. Of 156 non-Hispanic blacks with genomic data, 51 (33%) developed peripheral neuropathy. In a multivariate model, African mtDNA subhaplogroup L1c was an independent predictor of peripheral neuropathy (OR=3.7, 95% CI 1.1-12.0). An African mtDNA subhaplogroup is for the first time implicated in susceptibility to NRTI-associated toxicity.

Canter, Jeffrey A.; Robbins, Gregory K.; Selph, Doug; Clifford, David B.; Kallianpur, Asha R.; Shafer, Robert; Levy, Shawn; Murdock, Deborah G.; Ritchie, Marylyn D.; Haas, David W.; Hulgan, Todd

2010-01-01

292

Antiretroviral Therapy-Associated Acute Motor and Sensory Axonal Neuropathy  

PubMed Central

Guillain-Barré syndrome (GBS) has been reported in HIV-infected patients in association with the immune reconstitution syndrome whose symptoms can be mimicked by highly active antiretroviral therapy (HAART)-mediated mitochondrial toxicity. We report a case of a 17-year-old, HIV-infected patient on HAART with a normal CD4 count and undetectable viral load, presenting with acute lower extremity weakness associated with lactatemia. Electromyography/nerve conduction studies revealed absent sensory potentials and decreased compound muscle action potentials, consistent with a diagnosis of acute motor and sensory axonal neuropathy. Lactatemia resolved following cessation of HAART; however, neurological deficits minimally improved over several months in spite of immune modulatory therapy. This case highlights the potential association between HAART, mitochondrial toxicity and acute axonal neuropathies in HIV-infected patients, distinct from the immune reconstitution syndrome.

Capers, Kimberly N.; Turnacioglu, Sinan; Leshner, Robert T.; Crawford, John R.

2011-01-01

293

Outcomes of Universal Access to Antiretroviral Therapy (ART) in Georgia  

PubMed Central

Since 2004, Georgia achieved universal access to free antiretroviral therapy (ART). A retrospective cohort study was conducted to evaluate the outcomes of Georgia's ART program. The study included adult patients enrolled in the ART program from 2004 through 2009. Of 752 patients, 76% were men, 60% were injection drug users (IDU), 59% had a history of an AIDS-defining illness, and 53% were coinfected with hepatitis C. The median baseline CD4 cell count was 141?cells/mm3. During followup, 152 (20%) patients died, with the majority of deaths occurring within 12 months of ART initiation. Mortality was associated with advanced immunodeficiency or the presence of incurable disease at baseline. Among patients remaining on treatment, the median CD4 gain was 216?cell/mm3 and 86% of patients had viral load <400 copies/ml at the last clinical visit. The Georgia ART program has been successful in treating injection drug users infected with HIV.

Tsertsvadze, Tengiz; Chkhartishvili, Nikoloz; Sharvadze, Lali; Dvali, Natia; Chokoshvili, Otar; Gabunia, Pati; Abutidze, Akaki; Nelson, Kenrad; DeHovitz, Jack; del Rio, Carlos

2011-01-01

294

Gender Differences in Factors Associated with Adherence to Antiretroviral Therapy  

PubMed Central

OBJECTIVE To identify gender differences in social and behavioral factors associated with antiretroviral adherence. DESIGN Prospective cohort study. SETTING Methadone maintenance program. PARTICIPANTS One hundred thirteen HIV-seropositive current or former opioid users. MEASUREMENTS AND MAIN RESULTS Participants were surveyed at baseline about social and behavioral characteristics and at monthly research visits about drug and alcohol use and medication side effects. Electronic monitors (MEMS) were used to measure antiretroviral adherence. Median adherence among women was 27% lower than among men (46% vs. 73%; P < .05). In gender-stratified multivariate models, factors associated with worse adherence in men included not belonging to an HIV support group (P < .0001), crack/cocaine use (P < .005), and medication side effects (P = .01). Among women, alcohol use (P = .005), heroin use (P < .05), and significant medication side effects (P < .005) were independently associated with worse adherence. In a model including both men and women, worse adherence was associated with lack of long-term housing (P < .005), not belonging to any HIV support groups (P < .0005), crack or cocaine use (P < .01), and medication side effects (P < .0005). In addition, worse adherence was associated with the interaction between female gender and alcohol use (P ? .05). CONCLUSIONS In this cohort of current and former opioid users, gender-stratified analysis demonstrated that different social and behavioral factors are associated with adherence in men and women. Among both men and women, worse adherence was associated with lack of long-term housing, not belonging to an HIV support group, crack/cocaine use, and medication side effects. Among women only, alcohol use was associated with worse adherence.

Berg, Karina M; Demas, Penelope A; Howard, Andrea A; Schoenbaum, Ellie E; Gourevitch, Marc N; Arnsten, Julia H

2004-01-01

295

Cohort profile: Antiretroviral Therapy Cohort Collaboration (ART-CC).  

PubMed

The advent of effective combination antiretroviral therapy (ART) in 1996 resulted in fewer patients experiencing clinical events, so that some prognostic analyses of individual cohort studies of human immunodeficiency virus-infected individuals had low statistical power. Because of this, the Antiretroviral Therapy Cohort Collaboration (ART-CC) of HIV cohort studies in Europe and North America was established in 2000, with the aim of studying the prognosis for clinical events in acquired immune deficiency syndrome (AIDS) and the mortality of adult patients treated for HIV-1 infection. In 2002, the ART-CC collected data on more than 12,000 patients in 13 cohorts who had begun combination ART between 1995 and 2001. Subsequent updates took place in 2004, 2006, 2008, and 2010. The ART-CC data base now includes data on more than 70 000 patients participating in 19 cohorts who began treatment before the end of 2009. Data are collected on patient demographics (e.g. sex, age, assumed transmission group, race/ethnicity, geographical origin), HIV biomarkers (e.g. CD4 cell count, plasma viral load of HIV-1), ART regimen, dates and types of AIDS events, and dates and causes of death. In recent years, additional data on co-infections such as hepatitis C; risk factors such as smoking, alcohol and drug use; non-HIV biomarkers such as haemoglobin and liver enzymes; and adherence to ART have been collected whenever available. The data remain the property of the contributing cohorts, whose representatives manage the ART-CC via the steering committee of the Collaboration. External collaboration is welcomed. Details of contacts are given on the ART-CC website (www.art-cohort-collaboration.org). PMID:23599235

May, Margaret T; Ingle, Suzanne M; Costagliola, Dominique; Justice, Amy C; de Wolf, Frank; Cavassini, Matthias; D'Arminio Monforte, Antonella; Casabona, Jordi; Hogg, Robert S; Mocroft, Amanda; Lampe, Fiona C; Dabis, François; Fätkenheuer, Gerd; Sterling, Timothy R; Del Amo, Julia; Gill, M John; Crane, Heidi M; Saag, Michael S; Guest, Jodie; Brodt, Hans-Reinhard; Sterne, Jonathan Ac

2013-04-18

296

Head Start: It Works for Indiana Children and Families!  

Microsoft Academic Search

This technical report summarizes new and existing data to address the question, “Does Head Start work for Indiana children, families, and communities?” Data sources consulted in this study include the state Head Start Program Information Report, local Indiana Head Start and Early Head Start Programs, existing national studies of Head Start and Early Head Start, and local and national data

Jennifer Dobbs-Oates; James Elicker; Volker Thomas

2010-01-01

297

Sex after ART: sexual partnerships established by HIV-infected persons taking anti-retroviral therapy in Eastern Uganda.  

PubMed

This paper explores the social contexts that influence the formation and nature of sexual partnerships among people on anti-retroviral therapy (ART). We draw on the findings of a qualitative, longitudinal study of 70 people (36 women and 34 men) who have been participating in a home-based ART programme for over three years in Eastern Uganda. Since initiating ART, 32 (18 men and 14 women) participants reported having had a new partner. Five participants (4 men and 1 woman) renewed relationships with spouses with whom they had been prior to starting ART. Overall, 37 of the 70 participants had had a sexual partner after starting ART. Companionship, material support, social and cultural norms, as well as a desire for sex and children, are drivers of new relationships. The opportunity that ART brings for people to get on with their lives brings with it a reinstatement into a social world that places a value on marriage and child-bearing. The sexual rights of those living with HIV and on ART need to be taken seriously and safer sex facilitated. PMID:19544115

Seeley, Janet; Russell, Steven; Khana, Kenneth; Ezati, Enoch; King, Rachel; Bunnell, Rebecca

2009-10-01

298

Long-acting parenteral nanoformulated antiretroviral therapy: interest and attitudes of HIV-infected patients.  

PubMed

Aim: To gauge patient interest in receiving long-acting injectable nanoformulated antiretroviral therapy. Methods: Four hundred adult HIV-infected patients currently prescribed antiretroviral therapy were surveyed. ?(2) tests were used for comparisons of interest across groups. Results: Respondents were 68% male and 53% African-American, with a mean age of 47 years. Overall, 73% of patients indicated that they would definitely or probably try injectable nanoformulated antiretroviral therapy; 61% with weekly dosing; 72% every 2 weekly; and 84% monthly. In total, 48% indicated that they were very concerned about the possible side effects and 35% were very concerned about needle use. Conclusion: The majority of respondents indicated that they definitely or probably would try parenteral nanoformulated antiretroviral therapy. Original submitted 24 May 2012; Revised submitted 2 November 2012; Published online 23 April 2013. PMID:23611617

Williams, Jennifer; Sayles, Harlan R; Meza, Jane L; Sayre, Patrick; Sandkovsky, Uriel; Gendelman, Howard E; Flexner, Charles; Swindells, Susan

2013-04-23

299

ROLE OF PLACENTAL ATP-BINDING CASSETTE (ABC) TRANSPORTERS IN ANTIRETROVIRAL THERAPY DURING PREGNANCY  

PubMed Central

Highly Active Anti-Retroviral Therapy (HAART) is used to treat HIV-infected patients and involves administration of multiple antiretroviral drugs acting at different steps of the HIV life cycle. In treating HIV-infected pregnant patients, the aim of therapy is not only to treat the mother but also to prevent the transmission of the virus to the fetus. Among the antiretroviral drugs used, there are differences in the extent of transfer of these drugs across the placenta; HIV protease inhibitors are particularly poorly transferred. Activities of ABC transporters expressed in the human placenta as well as differences in plasma protein binding may account for the poor transplacental transfer of certain drugs. This review discusses factors affecting the extent of placental transfer of antiretroviral drugs during pregnancy. These issues may also apply to drugs in other therapeutic categories.

Gulati, Abhishek; Gerk, Phillip M.

2010-01-01

300

Correlates of antiretroviral and antidepressant adherence among depressed HIV-infected patients.  

PubMed

Although crucial for efficacy of pharmacotherapy, adherence to prescribed medication regimens for both antiretrovirals and antidepressants is often suboptimal. As many depressed HIV-infected individuals are prescribed both antiretrovirals and antidepressants, it is important to know whether correlates of nonadherence are similar or different across type of regimen. The HIV Translating Initiatives for Depression into Effective Solutions (HI-TIDES) study was a single-blinded, longitudinal, randomized controlled effectiveness trial comparing collaborative care to usual depression care at three Veterans Affairs HIV clinics. The current investigation utilized self-report baseline interview and chart-abstracted data. Participants were 225 depressed HIV-infected patients who were prescribed an antidepressant (n=146), an antiretroviral (n=192), or both (n=113). Treatment adherence over the last 4 days was dichotomized as "less than 90% adherence" or "90% or greater adherence." After identifying potential correlates of nonadherence, we used a seemingly unrelated regression (SUR) bivariate probit model, in which the probability of adherence to HIV medications and the probability of adherence to antidepressant medications are modeled jointly. Results indicated that 75.5% (n=146) of those prescribed antiretrovirals reported 90%-plus adherence to their antiretroviral prescription and 76.7% (n=112) of those prescribed antidepressants reported 90%-plus adherence to their antidepressant prescription, while 67% of those prescribed both (n=113) reported more than 90% adherence to both regimens. SUR results indicated that education, age, and HIV symptom severity were significant correlates of antiretroviral medication adherence while gender and generalized anxiety disorder diagnosis were significant correlates of adherence to antidepressant medications. In addition, antiretroviral adherence did not predict antidepressant adherence (?=1.62, p=0.17), however, antidepressant adherence did predict antiretroviral adherence (?=2.30, p<0.05). PMID:22536930

Bottonari, Kathryn A; Tripathi, Shanti P; Fortney, John C; Curran, Geoff; Rimland, David; Rodriguez-Barradas, Maria; Gifford, Allen L; Pyne, Jeffrey M

2012-03-21

301

Combination antiretroviral therapy in human immunodeficiency virus–infected pregnant women  

Microsoft Academic Search

Objective: To describe the safety, efficacy, and perinatal transmission rates of human immunodeficiency virus (HIV) with combination antiretroviral therapy in pregnancy.Methods: Retrospective study of all HIV-infected pregnant women treated with combination antiretroviral therapy after September 1, 1996, and who delivered by September 1, 1998, at Bronx-Lebanon Hospital Center.Results: Thirty women received combination therapy, 13 with protease inhibitor. Median baseline CD4

Joseph P McGowan; Marilyn Crane; Andrew A Wiznia; Steve Blum

1999-01-01

302

Sources of motivation and frustration among healthcare workers administering antiretroviral treatment for HIV in rural Zimbabwe  

Microsoft Academic Search

The roll-out of accessible and affordable antiretroviral (ARV) drugs for people living with HIV in low-income countries is drastically changing the nature of HIV-related healthcare. The Zimbabwean Ministry of Health has renewed efforts to make antiretroviral treatment (ART) for HIV free and publically available across the country. This paper describes the findings from a multi-method qualitative study including interviews and

C. Campbell; K. Scott; C. Madenhire; C. Nyamukapa; S. Gregson

2011-01-01

303

How individual can personalized antiretroviral treatment be? Deep salvage in an HIV-1-infected patient.  

PubMed

We present an HIV-1-infected male (who is now 52 years old) with a multi-drug-resistant virus and discuss the considerations finally leading to an antiretroviral regimen resulting in long-term viral suppression and excellent immunological response in a deep salvage situation. Even in a desperate situation with high-level multi-class resistance, highly individual, personalized antiretroviral regimes can be tailor-made to achieve unexpected improvements in the health status of a patient. PMID:22286888

Jensen, Bjoern; Esser, Stefan; Kaiser, Rolf; Luebke, Nadine; Häussinger, Dieter

2012-01-24

304

Start-Up Success: Collection Development  

ERIC Educational Resources Information Center

|All those who dream of working for themselves and being their own boss, whether they are fresh college graduates, recently unemployed, or newly retired from one career, have a thousand questions about where and how to begin. New entrepreneurs especially will need professional, expert help to start and run a small business effectively and…

Awe, Susan C.

2010-01-01

305

How to Start a Day Care Center.  

ERIC Educational Resources Information Center

|This publication describes the necessary steps a day care planner should follow from his or her initial thoughts of starting a day care center through to opening the door to care for children. The following steps are suggested: (1) consult appropriate offices to obtain licensing regulations, and zoning codes, as well as information on major…

Day Care and Child Development Council of America, Inc., Washington, DC.

306

SP100 start-up control strategy  

Microsoft Academic Search

A control analysis was performed to evaluate the reference and two alternative reactor start-up control strategies for the SP-100, using a detailed nonlinear model of the reactor. The analysis results show that the reference control strategy for the SP-100 adequately meets the current requirements. The two alternative control strategies provide tighter control than the reference strategy. Use of the measured

Raymond A. Meyer; Sang K. Rhow; Kwok K. Wong; Frank J. Halfen

1991-01-01

307

Transgulf Conversion Project to start soon  

Microsoft Academic Search

The Transgulf Pipeline Conversion Project is close to starting construction after more than 11 years of regulatory proceeding and legal battles. The project will convert 890 miles of Florida Gas Transmission Company's system between Baton Rouge and Fort Lauderdale to products service. New construction includes 361 miles of 24-, 26-, and 30-inch pipe to maintain gas deliverability of 725 million

1985-01-01

308

Exploring start-up event sequences  

Microsoft Academic Search

This research analyzed new venture start-up activities undertaken by 71 nascent entrepreneurs. Nascent entrepreneurs are individuals who were identified as taking steps to found a new business but who had not yet succeeded in making the transition to new business ownership. Longitudinal data for the study comes from a secondary data analysis of two representative samples, one of 683 adult

Paul D. Reynolds; William B. Gartner

1996-01-01

309

Getting-Started Strategies and Cooperative Learning.  

ERIC Educational Resources Information Center

Offers several strategies for implementing cooperative learning in the classroom. Suggests sample exercises including (1) a scavenger hunt; (2) a reaction wheel; (3) cooperative brainstorming and classification; (4) a "pair of pairs" exercise; and (5) a three-step interview. Explains that the examples are starting points that have been used in…

Myers, John J.; And Others

1991-01-01

310

Addressing Tooth Decay in Head Start Children  

ERIC Educational Resources Information Center

|Tooth decay is the most prevalent chronic disease of childhood. Oral health education and dental services are crucial to reducing the number of children afflicted with dental cavities. Due to limited access to preventative care, Head Start children are particularly vulnerable to tooth decay. This article outlines practical implications of a…

Knowlden, Adam P.; Hill, Lawrence F.; Alles-White, Monica L.; Cottrell, Randall R.

2012-01-01

311

Stirring and structure in mantle starting plumes  

Microsoft Academic Search

Simple arguments show that ascending thermal plumes will entrain their surroundings as the result of coupling between conduction of heat and laminar stirring driven by the plume motion. In the initial stages of ascent of a plume fed by a continuous buoyancy flux (a starting plume) the plume consists of a large buoyant head followed by a narrow vertical conduit.

Ross W. Griffiths; Ian H. Campbell

1990-01-01

312

Philadelphia's Independence Starts Here: Disability Arts Festival  

ERIC Educational Resources Information Center

In tribute to Philadelphia's world-changing past, Festival partners dubbed the month-long Disability Arts Festival "Independence Starts Here." Through it, they hoped to begin to change the future for over 675,000 people with disabilities in the area and their families. Led by Amaryllis Theatre Company, which now also serves as VSA arts of…

Smith, Mimi Kenney

2008-01-01

313

Even Start: Facilitating Transitions to Kindergarten.  

ERIC Educational Resources Information Center

|The federal Even Start program was implemented to improve the educational opportunities of low-income children and adults by integrating early childhood education, adult education, and parent education into a unified family literacy initiative. Because children's first formal educational experiences may significantly influence the course of their…

Riedinger, Susan Allin

314

Physicists: A Start-Ups's Secret Weapon  

Microsoft Academic Search

High-tech start-ups have been a magnet for engineers, MBAs, and money. However, the vital and rewarding role of physicists in these ventures is often overlooked. This talk will focus on the essential contributions physicists make and the various positions physicists hold \\

Laura Smoliar

2001-01-01

315

National Home Start Evaluation: Field Procedures Manual.  

ERIC Educational Resources Information Center

This field procedures manual for community interviewers and site coordinators, one of a series of documents on the evaluation of the National Home Start program (NHS), describes specific testing procedures for collecting family data. A federally funded demonstration program, NHS is aimed at providing home-based services (such as health, education,…

Nauta, Marrit J.

316

Head Start Fathers' Involvement with Their Children  

ERIC Educational Resources Information Center

|Until recently, fathers have been underexamined relative to mothers in research on parenting. Fathers in poverty, as well as stepfathers and nonresidential fathers, have been a particularly understudied group. This study explores Head Start fathers' involvement with their children. Fathers are defined to include stepfathers as well as…

Gorvine, Benjamin J.

2010-01-01

317

New Hugoton gas plant starts up  

Microsoft Academic Search

Earlier this summer, Amoco Production Co. started up its new Hugoton Jayhawk gas-processing plant in the Hugoton field of southwest Kansas. The plant is positioned to be a regional processing hub, not only for Hugoton gas, but for gas produced in Oklahoma, Colorado, and the Texas Panhandle. Hugoton Jayhawk is designed to recover more than 80% of the Câ and

S. Ruehle; L. Coalmer

1998-01-01

318

Thorstein Veblen: A Marxist Starting Point  

Microsoft Academic Search

As existing literature attests, in spite of methodological differences Marx and Veblen draw strikingly similar conclusions regarding production, conflict, and alienation in modern existence. We here attempt to establish that similarity in conclusion stems from similarity in approach. After reviewing the existing literature on a Marx-Veblen methodological reconciliation, we recapitulate Marx’s method, making the mediated starting point the locus of

2011-01-01

319

Head Start Fathers' Involvement with Their Children  

ERIC Educational Resources Information Center

Until recently, fathers have been underexamined relative to mothers in research on parenting. Fathers in poverty, as well as stepfathers and nonresidential fathers, have been a particularly understudied group. This study explores Head Start fathers' involvement with their children. Fathers are defined to include stepfathers as well as…

Gorvine, Benjamin J.

2010-01-01

320

Starting with "I": Personal Essays by Teenagers.  

ERIC Educational Resources Information Center

|In personal essays, teenagers express their views on serious subjects like violence, racism, and teen parenting, and discuss common teen experiences like dating, getting a job, and starting college. This collection contains the following: (1) "Brotherly Love" (Jessica Vicuna); (2) "How To Survive Shopping with Mom" (Chris Kanarick); (3) "A…

Estepa, Andrea, Ed.; Kay, Philip, Ed.

321

Comprehensive Evaluation of Hawaii's Healthy Start Program.  

ERIC Educational Resources Information Center

|This conference paper discusses the results of a study that investigated the characteristics and needs of mothers participating in Hawaii's Healthy Start Program (HSP). The HSP is a screening and outreach program with two components: (1) the early identification component, which consists of community-based screening to identify newborns at…

Duggan, Anne K.; Buchbinder, Sharon B.; Fuddy, Loretta; Sia, Calvin; Young, Elizabeth

322

Teacher Questionnaire [ETS Head Start Longitudinal Study].  

ERIC Educational Resources Information Center

This 147-item questionnaire was used to collect data on those Head Start and other preschool teachers who were teaching Longitudinal Study target children. Areas of requested information included: demographic characteristics, education and experience, attitudes toward minority-groups and economically disadvanted children's motivation and learning…

Educational Testing Service, Princeton, NJ.

323

Shift mechanism for engine starting apparatus  

Microsoft Academic Search

This patent describes a shift lever mechanism for translating axial movement of the plunger of a starter solenoid into axial movement of a pinion of an engine starting apparatus. This apparatus consists of, a starter solenoid having an axially shiftable plunger and a coil winding, a spring opposing pull-in movement of the plunger and a solenoid switch operated to a

J. A. Colvin; R. G. Colvill; A. L. Smock

1986-01-01

324

How to Start Intergenerational Programs in Communities.  

ERIC Educational Resources Information Center

|This document is designed for use by community organizers in creating, developing and maintaining an intergenerational program. Starting with a brief overview of the Maryland Intergenerational Coalition, the document describes (in short, bulleted entries) the activities and accomplishments of various intergenerational programs in Maryland, such…

2002

325

The Start of a Tech Revolution  

ERIC Educational Resources Information Center

|We are at the start of a revolution in the use of computers, one that analysts predict will rival the development of the PC in its significance. Companies such as Google, HP, Amazon, Sun Microsystems, Sony, IBM, and Apple are orienting their entire business models toward this change, and software maker SAS has announced plans for a $70 million…

Dyrli, Kurt O.

2009-01-01

326

Starting mental health services in Cambodia  

Microsoft Academic Search

Cambodia has undergone massive psychosocial trauma in the last few decades, but has had virtually no western-style mental health services. For the first time in Cambodia a number of mental health clinics in rural areas have been started. This experience is used to discuss the risks and opportunities in introducing these services in the present war-torn situation. Basic statistics from

Daya J. Somasundaram; Willem A. C. M. van de Put; Maurice Eisenbruch

1999-01-01

327

High starting torque for AC SCR controller  

Microsoft Academic Search

A control strategy is proposed for AC thyristor controllers. The main feature of the proposed technique is that motors can start with high torque, while using an economical design. This allows the use of AC thyristor controllers for a wide range of applications, where they have not been used before. The method employs the AC thyristor controller as a discrete

Antonio Ginart; Rosana Esteller; A. Maduro; R. Piiiero; R. Moncada

1999-01-01

328

Structural model of head start classroom quality  

Microsoft Academic Search

The purpose of this research study was to develop, test, and validate a model that identifies the characteristics and beliefs of teachers and aides, and the classroom structural dimensions associated with Head Start classroom quality. The quality of classroom teaching practices was collected using the Assessment Profile for Early Childhood Programs: Research Version. Classroom structural characteristics were collected by observers.

Martha Abbott-Shim; Richard Lambert; Frances McCarty

2000-01-01

329

Does Head Start help hispanic children?  

Microsoft Academic Search

Poor educational attainment is a persistent problem among US hispanic children, relative to non-hispanics. Many of these children are immigrants and\\/or come from households that use a minority language in the home. This paper examines the effects of participation in a government sponsored preschool program called Head Start on these children. We find that large and significant benefits accrue to

Janet Currie; Duncan Thomas

1999-01-01

330

Adolescent Sleep Needs and School Starting Times.  

ERIC Educational Resources Information Center

A key task for schools is to ensure that the conditions in which learning is to take place address the biological needs of the learners. This book examines sleep needs of adolescents and discusses the implications of these needs for school starting times. This book is a collection of five articles that appeared in a special section of the Phi…

Wahlstrom, Kyla L., Ed.

331

Attachment relationships in Early Head Start families  

Microsoft Academic Search

The remarkable papers in this Special Issue underscore the importance of applied research on families in poverty, the opportunities to developmental science of the Early Head Start National Research and Evaluation Project, and the mutual benefits from collaborations between research scientists and program practitioners. This commentary highlights the insights of these papers concerning the consequences of maternal attachment style and

Ross A. Thompson

2011-01-01

332

Starting Salary Outcomes of Cooperative Education Graduates.  

ERIC Educational Resources Information Center

|Comparison of 370 engineering co-op graduates with 1,037 nonco-op engineering graduates showed that co-op participants had higher starting salaries; 5 or fewer terms of co-op had better effects. Women, especially electrical, mechanical, or chemical majors, had substantially better salaries with co-op experience. (SK)|

Gardner, Philip D.; And Others

1992-01-01

333

Depression and posttraumatic stress disorder among HIV-infected Gambians on antiretroviral therapy.  

PubMed

Mood disorders are more frequent among people with HIV infection than among non-HIV-infected individuals of the same age, socioeconomic status, and HIV risks. They have been associated with worse adherence and clinical outcomes, yet remain underdiagnosed and undertreated in sub-Saharan Africa. We explored the relationship between mood disorders using the 10-item depression scale of the Centers for Epidemiological Studies (CES-D10) and the 22-item Impact of Events Scale-Revised (IES-R) for posttraumatic stress disorder, and a range of demographic and HIV-related variables among 252 consecutive subjects on antiretroviral therapy (ART). The study was conducted in the Genito-Urinary Medicine Clinic of the Medical Research Council's Gambia Unit. These screening tests were positive in 7% and 30%, respectively, of the patients, with higher scores (more depression or more post-traumatic stress) associated with female gender, more advanced WHO clinical stage, and lower Karnofsky Perfomance Scale rating. Higher CES-D10 scores were also seen among those on their second ART regimen. No relationship was seen with age, time on ART, viral load, or CD4 cell count. Compared to an earlier study at the same site in subjects prior to starting ART, the prevalence of depression in those stabilized on ART was dramatically reduced (by 34%, from 41%) while that of PTSD dropped less (by 13%, from 43%). Integrating the CES-D10 or a similar instrument into patient preparation for ART is recommended in order to identify those who may benefit from further mental health investigations, specific therapy, or closer follow-up during early ART. PMID:22989270

Peterson, Kevin; Togun, Toyin; Klis, Sandor; Menten, Joris; Colebunders, Robert

2012-09-18

334

Kinetics of Microbial Translocation Markers in Patients on Efavirenz or Lopinavir/r Based Antiretroviral Therapy  

PubMed Central

Objectives We investigated whether there are differences in the effects on microbial translocation (MT) and enterocyte damage by different antiretroviral therapy (ART) regimens after 1.5 years and whether antibiotic use has impact on MT. In a randomized clinical trial (NCT01445223) on first line ART, patients started either lopinavir/r (LPV/r) (n?=?34) or efavirenz (EFV) containing ART (n?=?37). Lipopolysaccharide (LPS), sCD14, anti-flagellin antibodies and intestinal fatty acid binding protein (I-FABP) levels were determined in plasma at baseline (BL) and week 72 (w72). Results The levels of LPS and sCD14 were reduced from BL to w72 (157.5 pg/ml vs. 140.0 pg/ml, p?=?0.0003; 3.13 ug/ml vs. 2.85 ug/ml, p?=?0.005, respectively). The levels of anti-flagellin antibodies had decreased at w72 (0.35 vs 0.31 [OD]; p<0.0004), although significantly only in the LPV/r arm. I-FABP levels increased at w72 (2.26 ng/ml vs 3.13 ng/ml; p<0.0001), although significantly in EFV treated patients only. Patients given antibiotics at BL had lower sCD14 levels at w72 as revealed by ANCOVA compared to those who did not receive (??=??0.47 µg/ml; p?=?0.015). Conclusions Markers of MT and enterocyte damage are elevated in untreated HIV-1 infected patients. Long-term ART reduces the levels, except for I-FABP which role as a marker of MT is questionable in ART-experienced patients. Why the enterocyte damage seems to persist remains to be established. Also antibiotic usage may influence the kinetics of the markers of MT. Trial Registration ClinicalTrials.gov NCT01445223

Vesterbacka, Jan; Nowak, Piotr; Barqasho, Babilonia; Abdurahman, Samir; Nystrom, Jessica; Nilsson, Staffan; Funaoka, Hiroyuki; Kanda, Tatsuo; Andersson, Lars-Magnus; Gisslen, Magnus; Sonnerborg, Anders

2013-01-01

335

Mortality in an antiretroviral therapy programme in Jinja, south-east Uganda: a prospective cohort study  

PubMed Central

Background There have been few reports of long-term survival of HIV-infected patients on antiretroviral therapy (ART) in Africa managed under near normal health service conditions. Methods Participants starting ART between February 2005 and December 2006 in The AIDS Support (TASO) clinic in Jinja, Uganda, were enrolled into a cluster-randomised trial of home versus facility-based care and followed up to January 2009. The trial was integrated into normal service delivery with patients managed by TASO staff according to national guidelines. Rates of survival, virological failure, hospital admissions and CD4 count over time were similar between the two arms. Data for the present analysis were analysed using Cox regression analyses. Results 1453 subjects were enrolled with baseline median count of 108 cells/?l. Over time, 119 (8%) withdrew and 34 (2%) were lost to follow-up. 197/1453 (14%) died. Mortality rates (95% CI) per 100 person-years were 11.8 (10.1, 13.8) deaths in the first year and 2.4 (1.8, 3.2) deaths thereafter. The one, two and three year survival probabilities (95% CI) were 0.89 (0.87 - 0.91), 0.86 (0.84 - 0.88) and 0.85 (0.83 - 0.87) respectively. Low baseline CD4 count, low body weight, advanced clinical condition (WHO stages III and IV), not being on cotrimoxazole prophylaxis and male gender were associated independently with increased mortality. Tuberculosis, cryptococcal meningitis and diarrhoeal disease were estimated to be major causes of death. Conclusion Practical and affordable interventions are needed to enable earlier initiation of ART and to reduce mortality risk among those who present late for treatment with advanced disease.

2011-01-01

336

Long-Term Antiretroviral Treatment Outcomes in Seven Countries in the Caribbean  

PubMed Central

Objectives To report long-term HIV treatment outcomes in 7 Caribbean countries. Design Observational cohort study. Methods We report outcomes for all antiretroviral therapy (ART) naïve adult patients enrolled on ART from program inception until study closing for cohorts in Barbados, the Dominican Republic, Haiti, Jamaica, Martinique, Trinidad, and Puerto Rico. Incidence and predictors of mortality were analyzed by time-to-event approaches. Results 8,203 patients started ART from 1998 to 2008. Median follow-up time was 31 months (interquartile range: 14 to 50 months). Mortality was 13% overall: 6% in Martinique, 8% in Jamaica, 11% in Trinidad, 13% in Haiti, 15% in the Dominican Republic, 15% in Barbados, and 24% in Puerto Rico. Mortality was associated with male gender (HR 1.58; 95% CI: 1.33 – 1.87), body weight (HR 0.85 per 10 pounds; 95% CI: 0.82 – 0.89), hemoglobin (HR 0.84 per g/dl; 95% CI: 0.80 – 0.88), CD4 cell count (0.90 per 50 CD4 cells; 95% CI: 0.86 – 0.93), concurrent TB (HR 1.58; 95% CI: 1.25 – 2.01) and age (HR 1.19 per 10 years; 95% CI: 1.11 – 1.28). After controlling for these variables, mortality in Martinique, Jamaica, Trinidad and Haiti was not significantly different. A total of 75% of patients remained alive and in-care at the end of the study period. Conclusions Long-term mortality rates vary widely across the Caribbean. Much of the difference can be explained by disease severity at ART initiation, nutritional status, and concurrent TB. Earlier ART initiation will be critical to improve outcomes.

KOENIG, Serena P; RODRIGUEZ, Luis A; BARTHOLOMEW, Courtenay; EDWARDS, Alison; CARMICHAEL, Tracie E; BARROW, Geoff; CABIE, Andre; HUNTER, Robert; VASQUEZ-MORA, Giselle; QUAVA-JONES, Avion; ADOMAKOH, Nicholas; FIGUEROA, J Peter; LIAUTAUD, Bernard; TORRES, Magaly; PAPE, Jean W

2012-01-01

337

Antiretroviral therapy uptake and coverage in four HIV community cohort studies in sub-Saharan Africa  

PubMed Central

Objective To compare socio-demographic patterns in access to antiretroviral therapy (ART) across four community HIV cohort studies in Africa. Methods Data on voluntary counselling and testing and ART use among HIV-infected persons were analysed from Karonga (Malawi), Kisesa (Tanzania), Masaka (Uganda) and Manicaland (Zimbabwe), where free ART provision started between 2004 and 2007. ART coverage was compared across sites by calculating the proportion on ART among those estimated to need treatment, by age, sex and educational attainment. Logistic regression was used to identify socio-demographic characteristics associated with undergoing eligibility screening at an ART clinic within 2 years of being diagnosed with HIV, for three sites with information on diagnosis and screening dates. Results Among adults known to be HIV-infected from serological surveys, the proportion who knew their HIV status was 93% in Karonga, 37% in Kisesa, 46% in Masaka and 25% in Manicaland. Estimated ART coverage was highest in Masaka (68%) and lowest in Kisesa (2%). The proportion of HIV-diagnosed persons who were screened for ART eligibility within 2 years of diagnosis ranged from 14% in Kisesa to 84% in Masaka, with the probability of screening uptake increasing with age at diagnosis in all sites. Conclusions Higher HIV testing rates among HIV-infected persons in the community do not necessarily correspond with higher uptake of ART, nor more equitable treatment coverage among those in need of treatment. In all sites, young adults tend to be disadvantaged in terms of accessing and initiating ART, even after accounting for their less urgent need.

Wringe, Alison; Floyd, Sian; Kazooba, Patrick; Mushati, Phyllis; Baisley, Kathy; Urassa, Mark; Molesworth, Anna; Schumacher, Christina; Todd, Jim; Zaba, Basia

2012-01-01

338

Antiretroviral Therapy Responses among Children Attending a Large Public Clinic in Soweto, South Africa  

PubMed Central

Background Antiretroviral therapy access with successful outcomes for children is expanding in resource limited countries. The aim of this study was to determine treatment responses of children in a routine setting where first line therapy with lopinavir/ritonavir is routinely included for young children. Methods Outpatient records of children who initiated ART between April 2004 and March 2008 at a government clinic in Soweto were reviewed. Children <3 years initiated ART with lopinavir/ritonavir- and those ? 3 years efavirenz-containing regimens Results ART was initiated at median age 4.3 years, 28.6% also received TB treatment. During 3155 child-years of follow-up (median follow-up 17 months), 132 (6%) children died giving a mortality rate of 4.2 (95%CI: 3.5, 5.0) deaths per 100 child-years. By 12 and 24 months, 84% and 96% of children achieved virologic suppression. The proportion of children with viral rebound rose from 5.4% to 16.3% at 24 and 36 months from start of ART. Younger children (receiving lopinavir/ritonavir-based first-line therapy) with higher viral loads, suppressed more slowly and were more likely to die. Children given TB treatment at the time of viral suppression were more likely to have virologic rebound. Conclusion Despite good treatment outcomes overall, children with advanced disease at ART initiation had poorer outcomes, particularly those < 3 years of age, most of whom were treated with LPV/r-containing therapy. The increasing risk of viral rebound over time for the whole cohort is concerning given currently limited available treatment options for children.

MEYERS, TAMMY; YOTEIENG, MARCEL; KUHN, LOUISE; MOULTRIE, HARRY

2011-01-01

339

Frequency of HIV-1 Viral Load Monitoring of Patients Initially Successfully Treated with Combination Antiretroviral Therapy  

PubMed Central

Background Although considered an essential tool for monitoring the effect of combination antiretroviral treatment (CART), HIV-1 RNA (viral load, VL) testing is greatly influenced by cost and availability of resources. Objectives To examine whether HIV infected patients who were initially successfully treated with CART have less frequent monitoring of VL over time and whether CART failure and other HIV-disease and sociodemographic characteristics are associated with less frequent VL testing. Methods The study included patients who started CART in the period 1999–2004, were older than 18 years, CART naive, had two consecutive viral load measurements of <400 copies/ml after 5 months of treatment and had continuous CART during the first 15 months. The time between two consecutive visits (days) was the outcome and associated factors were assessed using linear mixed models. Results We analyzed a total of 128 patients with 1683 visits through December 2009. CART failure was observed in 31 (24%) patients. When adjusted for the follow-up time, the mean interval between two consecutive VL tests taken in patients before CART failure (155.2 days) was almost identical to the interval taken in patients who did not fail CART (155.3 days). On multivariable analysis, we found that the adjusted estimated time between visits was 150.9 days before 2003 and 177.6 in 2008/2009. A longer time between visits was observed in seafarers compared to non-seafarers; the mean difference was 30.7 days (95% CI, 14.0 to 47.4; p<0.001); and in individuals who lived more than 160 kilometers from the HIV treatment center (mean difference, 16 days, p?=?0.010). Conclusions Less frequent monitoring of VL became common in recent years and was not associated with failure. We identified seafarers as a population with special needs for CART monitoring and delivery.

Romih, Vanja; Zidovec Lepej, Snjezana; Gedike, Kornelija; Lukas, Davorka; Begovac, Josip

2010-01-01

340

Food Insecurity as a Barrier to Sustained Antiretroviral Therapy Adherence in Uganda  

PubMed Central

Background Food insecurity is emerging as an important barrier to antiretroviral (ARV) adherence in sub-Saharan Africa and elsewhere, but little is known about the mechanisms through which food insecurity leads to ARV non-adherence and treatment interruptions. Methodology We conducted in-depth, open-ended interviews with 47 individuals (30 women, 17 men) living with HIV/AIDS recruited from AIDS treatment programs in Mbarara and Kampala, Uganda to understand how food insecurity interferes with ARV therapy regimens. Interviews were transcribed, coded for key themes, and analyzed using grounded theory. Findings Food insecurity was common and an important barrier to accessing medical care and ARV adherence. Five mechanisms emerged for how food insecurity can contribute to ARV non-adherence and treatment interruptions or to postponing ARV initiation: 1) ARVs increased appetite and led to intolerable hunger in the absence of food; 2) Side effects of ARVs were exacerbated in the absence of food; 3) Participants believed they should skip doses or not start on ARVs at all if they could not afford the added nutritional burden; 4) Competing demands between costs of food and medical expenses led people either to default from treatment, or to give up food and wages to get medications; 5) While working for food for long days in the fields, participants sometimes forgot medication doses. Despite these obstacles, many participants still reported high ARV adherence and exceptional motivation to continue therapy. Conclusions While reports from sub-Saharan Africa show excellent adherence to ARVs, concerns remain that these successes are not sustainable in the presence of widespread poverty and food insecurity. We provide further evidence on how food insecurity can compromise sustained ARV therapy in a resource-limited setting. Addressing food insecurity as part of emerging ARV treatment programs is critical for their long-term success.

Frongillo, Edward A.; Senkungu, Jude; Mukiibi, Nozmu; Bangsberg, David R.

2010-01-01

341

Factors affecting antiretroviral pharmacokinetics in HIV-infected women with virologic suppression on combination antiretroviral therapy: a cross-sectional study  

PubMed Central

Background Although some studies show higher antiretroviral concentrations in women compared to men, data are limited. We conducted a cross-sectional study of HIV-positive women to determine if protease inhibitor (PI) and non-nucleoside reverse transcriptase inhibitor (NNRTI) Cmin and Cmax values were significantly different than historical general population (predominantly male) averages and to evaluate correlates of higher concentrations. Methods HIV-positive women with virologic suppression (viral load < 50copies/mL) on their first antiretroviral regimen were enrolled. Timed blood samples for Cmin and Cmax were drawn weekly for 3 weeks. The ratio of each individual’s median Cmin and Cmax to the published population mean values for their PI or NNRTI was calculated and assessed using Wilcoxon sign-rank. Intra- and inter-patient variability of antiretroviral drug levels was assessed using coefficient of variation and intra-class correlation. Linear regression was used to identify correlates of the square root-transformed Cmin and Cmax ratios. Results Data from 82 women were analyzed. Their median age was 41 years (IQR=36-48) and duration of antiretrovirals was 20 months (IQR=9-45). Median antiretroviral Cmin and Cmax ratios were 1.21 (IQR=0.72-1.89, p=0.003) (highest ratios for nevirapine and lopinavir) and 0.82 (IQR=0.59-1.14, p=0.004), respectively. Nevirapine and efavirenz showed the least and unboosted atazanavir showed the most intra- and inter-patient variability. Higher CD4+ count correlated with higher Cmin. No significant correlates for Cmax were found. Conclusions Compared to historical control data, Cmin in the women enrolled was significantly higher whereas Cmax was significantly lower. Antiretroviral Cmin ratios were highly variable within and between participants. There were no clinically relevant correlates of drug concentrations. Trial registration NCT00433979

2013-01-01

342

Predictors of Change in CD4 Lymphocyte Count and Weight among HIV Infected Patients on Anti-Retroviral Treatment in Ethiopia: A Retrospective Longitudinal Study  

PubMed Central

Background Antiretroviral treatment (ART) has been introduced in Ethiopia a decade ago and continues to be scaled up. However, there is dearth of literature on the impact of ART on changes in CD4 lymphocyte count and weight among patients on treatment. Objective To determine the predictors of change in CD4 lymphocyte count and weight among HIV/AIDS infected patients taking antiretroviral treatment in eastern Ethiopia. Methods A retrospective cohort study was conducted among HIV/AIDS patients taking ART from 2005 to 2010. A sample of 1540 HIV infected adult patients who started antiretroviral therapy in hospitals located in eastern Ethiopia were included in the study. The primary outcomes of interest were changes in CD4 count and weight. Descriptive statistics and multivariable regression analyses were performed to examine the outcomes among the cohort. Results Both the median CD4 lymphocyte counts and weight showed improvements in the follow up periods. The multivariate analysis shows that the duration of ART was an important predictor of improvements in CD4 lymphocyte count (beta 7.91; 95% CI 7.48–8.34; p 0.000) and weight (beta 0.15; 95% CI 0.13–0.18; p 0.000). Advanced WHO clinical stage, lower baseline CD4 cell count, and baseline hemoglobin levels were factors associated with decline in weight. Actively working patients had higher CD4 lymphocyte count and weight compared to those that were ambulatory (p<0.05). Conclusion We detected a substantial increment in weight and CD4 lymphocyte count among the patients who were taking ART in eastern Ethiopia. Patients who are of older age, with low initial CD4 lymphocyte count, late stage of the WHO clinical stages and lower hemoglobin level may need special attention. The reasons for the improved findings on CD4 count and weight throughout the five years of follow up merit further investigation.

Reda, Ayalu A.; Biadgilign, Sibhatu; Deribew, Amare; Gebre, Betemariam; Deribe, Kebede

2013-01-01

343

The public health approach to identify antiretroviral therapy failure: high-level nucleoside reverse transcriptase inhibitor resistance among Malawians failing first-line antiretroviral therapy  

PubMed Central

Background Over 150 000 Malawians have started antiretroviral therapy (ART), in which first-line therapy is stavudine/lamivudine/nevirapine. We evaluated drug resistance patterns among patients failing first-line ART on the basis of clinical or immunological criteria in Lilongwe and Blantyre, Malawi. Methods Patients meeting the definition of ART failure (new or progressive stage 4 condition, CD4 cell count decline more than 30%, CD4 cell count less than that before treatment) from January 2006 to July 2007 were evaluated. Among those with HIV RNA of more than 1000 copies/ml, genotyping was performed. For complex genotype patterns, phenotyping was performed. Results Ninety-six confirmed ART failure patients were identified. Median (interquartile range) CD4 cell count, log10 HIV-1 RNA, and duration on ART were 68 cells/?l (23–174), 4.72 copies/ml (4.26–5.16), and 36.5 months (26.6–49.8), respectively. Ninety-three percent of samples had nonnucleoside reverse transcriptase inhibitor mutations, and 81% had the M184V mutation. The most frequent pattern included M184V and nonnucleoside reverse transcriptase inhibitor mutations along with at least one thymidine analog mutation (56%). Twenty-three percent of patients acquired the K70E or K65R mutations associated with tenofovir resistance; 17% of the patients had pan-nucleoside resistance that corresponded to K65R or K70E and additional resistance mutations, most commonly the 151 complex. Emergence of the K65R and K70E mutations was associated with CD4 cell count of less than 100 cells/?l (odds ratio 6.1) and inversely with the use of zidovudine (odds ratio 0.18). Phenotypic susceptibility data indicated that the nucleoside reverse transcriptase inhibitor backbone with the highest activity for subsequent therapy was zidovudine/lamivudine/tenofovir, followed by lamivudine/tenofovir, and then abacavir/didanosine. Conclusion When clinical and CD4 cell count criteria are used to monitor first-line ART failure, extensive nucleoside reverse transcriptase inhibitor and nonnucleoside reverse transcriptase inhibitor resistance emerges, with most patients having resistance profiles that markedly compromise the activity of second-line ART.

Hosseinipour, Mina C.; van Oosterhout, Joep J.G.; Weigel, Ralf; Phiri, Sam; Kamwendo, Debbie; Parkin, Neil; Fiscus, Susan A.; Nelson, Julie A.E.; Eron, Joseph J.; Kumwenda, Johnstone

2010-01-01

344

Early Head Start Research and Evaluation Project: Early Head Start Works  

ERIC Educational Resources Information Center

|The upcoming Congressional reauthorization of the Early Head Start program provides an opportunity to focus on what can be done to achieve even greater impacts for infants, toddlers, and families in Early Head Start. In this policy brief, the Zero to Three Policy Center presents its recommendations for Congressional action and discusses…

ZERO TO THREE, 2007

2007-01-01

345

The Starting and Managing Series. Volume 17. Starting and Managing a Small Retail Camera Store.  

National Technical Information Service (NTIS)

The booklet is offered as a starting point for the person thinking of going into photographic retailing. It doesn't pretend to tell the reader all he needs to know in order to get his business off to a good start; it does point out some of the problems an...

M. Bragin

1969-01-01

346

The National Evaluation of Early Head Start: Early Head Start Works. Policy Brief.  

ERIC Educational Resources Information Center

Congress created Early Head Start in 1995 to support healthy prenatal outcomes and enhance intellectual, social, and emotional development of infants and toddlers to promote later success in school and in life. This policy brief summarizes findings of the Congressionally mandated National Evaluation of Early Head Start and offers policy…

Zero to Three: National Center for Infants, Toddlers and Families, Washington, DC.

347

Early Head Start Research and Evaluation Project: Early Head Start Works  

ERIC Educational Resources Information Center

The upcoming Congressional reauthorization of the Early Head Start program provides an opportunity to focus on what can be done to achieve even greater impacts for infants, toddlers, and families in Early Head Start. In this policy brief, the Zero to Three Policy Center presents its recommendations for Congressional action and discusses scientific…

ZERO TO THREE, 2007

2007-01-01

348

Cold-start hydrocarbon emissions control  

SciTech Connect

This article describes an effective, energy-efficient strategy for dealing with this problem using HC traps and heat-exchange related catalyst beds that have been successfully tested. The worldwide regulatory climate for continued and dramatic reductions in vehicle exhaust emissions will continue unabated for some time. The best known of these mandates includes California Air Resources Board`s Low Emission Vehicle (CARB LEV) program, the Ozone Transport Commission`s recent petition to the EPA for partial adoption of CARB`s LEV program, and the European Economic Community`s proposed staged multi-tier approach to reduce auto exhaust pollution. Since up to 70% of hydrocarbon tailpipe emissions occur during the cold-start portion of the Federal Test Procedure (FTP), significant reductions in total FTP HC emissions must include a cold-start HC abatement strategy.

NONE

1995-10-01

349

Timing to start controlling a dynamic stall  

NASA Astrophysics Data System (ADS)

The appropriate timing to start controlling a dynamic stall was studied to find a way to reduce the total amount of energy to suppress separation. The dynamic stall of an airfoil in pitching-up motion was adopted because the time when separation occurs can be determined beforehand. The angle of attack was increased from 0 to 30 degrees at a constant angular velocity. The timing of control was defined as the interval from the start of control to the onset of separation without control. A wall jet ejected from a thin slit near the leading edge at a constant velocity was used to suppress the separation. Many combinations of timing of the ejection and velocity of the jet were tested to determine the optimum amount of energy required to suppress the stall. It was found that, within the limits of our experimental conditions, there exists an optimum combination.

Mochizuki, Osamu; Kumano, Satoshi; Kiya, Masaru

1999-11-01

350

Nursing in project Head Start: improving health.  

PubMed

The purpose of this study was to evaluate the effectiveness of a nurse-directed health promotion program in decreasing upper respiratory illness symptoms and injury rates in preschool children attending a Head Start (HS) program. The health promotion program presented to the Head Start staff consisted of signs and symptoms of childhood illnesses, infection control, injury prevention and first aid. The 47 children had their health evaluated by a registered nurse once per week for 4 weeks before the program and once per week for 4 weeks after the program. The children's health was evaluated using the Child Health Assessment Inventory. Symptoms of upper respiratory illness were significantly decreased after the intervention of the program. Injury rates increased, but further data analysis determined that 88% of the injuries had occurred at home. PMID:9119718

Ulione, M S; Donovan, E

351

Verifying START: From satellites to suspect sites  

SciTech Connect

When applied together, NTM (national technical means), inspections, and cooperative measures will have a synergistic effect, giving the United States high confidence that it can detect any militarily significant START (Strategic Arms Reduction Talks) violation. Give the large strategic retaliatory capability both sides will retain under a START treaty, only large-scale cheating would be militarily significant, and there is little doubt such cheating could be easily detected. While counting mobile ICBMs (inter-continental ballistic missiles) will be more difficult than monitoring fixed silos, the web of verification provisions now agreed upon will answer the challenge. A large number of ICBMs cannot be maintained and operated without a massive supporting infrastructure, including command and control, deployment, maintenance, and testing facilities. The large covert infrastructure needed to deploy even a few hundred illegal mobile ICBM warheads would surely be detected. Further, the United States should be able to detect any recurring pattern of small violations.

Lockwood, D. (Arms Control Association, Washington, DC (USA))

1990-10-01

352

Computation of Cold-Start Miss Ratios  

Microsoft Academic Search

Cold-start miss ratios are miss ratios that are measured with an initially empty first-level store. The values obtained depend on C, the first-level storage capacity, and on T, the number of references. These miss ratios, measured for various values of T, are useful in evaluating the effect of task switching on cache miss ratios when the cache capacity is C.

Malcolm C. Easton

1978-01-01

353

A Starting Point for Analyzing Basketball Statistics  

Microsoft Academic Search

The quantitative analysis of sports is a growing branch of science and, in many ways one that has developed through non-academic and non-traditionally peer-reviewed work. The aim of this paper is to bring to a peer-reviewed journal the generally accepted basics of the analysis of basketball, thereby providing a common starting point for future research in basketball. The possession concept,

Justin Kubatko; Dean Oliver; Kevin Pelton; Dan T. Rosenbaum

2007-01-01

354

Does Head Start Make a Difference?  

Microsoft Academic Search

Although there is a broad hi-partisan support for Head Start, the evidence of positive longterm effects of the program is not overwhelming. Using data from the National Longitudinal Survey's Child-Mother file, we examine the impact of the program on a range of child outcomes. We compare non-parametric estimates of program effects with estimates from parametric models that control for selection

Janet Currie; Duncan Thomas

1993-01-01

355

Getting Started with Actionscript 3.0  

Microsoft Academic Search

\\u000a Here you stand (or sit or lie) at the very start of a long and perilous journey to becoming an ActionScript developer. Well,\\u000a OK, maybe not all that perilous—it’s not like there are any dragons, angry trolls, or even anything as dangerous as a mildly\\u000a annoyed snail—but you can get some pretty nasty finger aches from all the typing.

Steve Webster; Todd Yard

356

Financing Start-ups: Advising vs. Competing  

Microsoft Academic Search

High-tech start-ups get external finance and guidance mostly from venture capitalists and\\/or business angels. We identify a simultaneous double moral hazard for the management style of entrepreneurs and the decision to advise the firm for financiers. We embed this relationship into the financial competition where strategic choices are equity shares, liquidation rights and quality of advising. We show that the

Nicolas Boccard

2001-01-01

357

Utilization of antiretroviral treatment in Ethiopia between February and December 2006: spatial, temporal, and demographic patterns  

PubMed Central

Background In 2003, the Ethiopian Ministry of Health (MOH) started to implement a national antiretroviral treatment (ART) program. Using data in the monthly HIV/AIDS Updates issued by the MOH, this paper examines the spatial and temporal distribution of ART on a population basis for Ethiopian towns and administrative zones and regions for the period February to December 2006. Results The 101 public ART hospitals treated 44,446 patients and the 91 ART health centers treated 1,599 patients in December 2006. The number of patients currently receiving ART doubled between February and December 2006 and the number of female patients aged 15 years and older surpassed male patients, apparently due to increased awareness and provision of free ART. Of 58,405 patients who ever started ART in December 2006, 46,045 (78.8%) were adhering to treatment during that month. Population coverage of ART was highest in the three urban administrative regions of Addis Ababa, Harari and Dire Dawa, in regional centers with referral hospitals, and in several small road side towns that had former mission or other NGO-operated hospitals. Hospitals in Addis Ababa had the largest patient loads (on average 850 patients) and those in SNNPR (Southern Nations and Nationalities Peoples Republic) (212 patients) and Somali (130 patients) regions the fewest patients. In bivariate tests, number of patients receiving treatment was significantly correlated with population size of towns, urban population per zone, number of hospitals per zone, and duration of ART services in 2006 (all p < 0.001). The stronger relationship with urban than total zonal populations (p < 0.001 versus p = 0.014) and the positive correlation between distance from 44 health centers to the nearest ART hospital and patients receiving treatment at these health centers may be due to a combination of differential accessibility of ART sites, patient knowledge and health-seeking behavior. Conclusion The sharp increase in ART uptake in 2006 is largely due to the rapid increase in the provision of free treatment at more sites. The marked variation in ART utilization patterns between urban and rural communities and among zones and regions requires further studies. Recommendations are made for further expansion and sustainability of the ART scale-up.

Kloos, Helmut; Assefa, Yibeltal; Adugna, Aynalem; Mulatu, Mesfin Samuel; Mariam, Damen Haile

2007-01-01

358

Alternative starting materials for industrial processes.  

PubMed Central

In the manufacture of chemical feedstocks and subsequent processing into derivatives and materials, the U.S. chemical industry sets the current standard of excellence for technological competitiveness. This world-class leadership is attributed to the innovation and advancement of chemical engineering process technology. Whether this status is sustained over the next decade depends strongly on meeting increasingly demanding challenges stimulated by growing concerns about the safe production and use of chemicals without harmful impacts on the environment. To comply with stringent environmental regulations while remaining economically competitive, industry must exploit alternative benign starting materials and develop environmentally neutral industrial processes. Opportunities are described for development of environmentally compatible alternatives and substitutes for some of the most abundantly produced, potentially hazardous industrial chemicals now labeled as "high-priority toxic chemicals." For several other uniquely important commodity chemicals where no economically competitive, environmentally satisfactory, nontoxic alternative starting material exists, we advocate the development of new dynamic processes for the on-demand generation of toxic chemicals. In this general concept, which obviates mass storage and transportation of chemicals, toxic raw materials are produced in real time, where possible, from less-hazardous starting materials and then chemically transformed immediately into the final product. As a selected example for semiconductor technology, recent progress is reviewed for the on-demand production of arsine in turnkey electrochemical generators. Innovation of on-demand chemical generators and alternative processes provide rich areas for environmentally responsive chemical engineering processing research and development for next-generation technology. Images

Mitchell, J W

1992-01-01

359

Start-up of laminar pipe flow  

NASA Astrophysics Data System (ADS)

The transient flow in a pipe following the sudden opening of a valve is considered. The axisymmetric Navier-Stokes equations in primitive variables are solved numerically using finite-difference techniques. Predicted variations with time of the axial velocity component and the pressure field are presented for different values of the start-up flow parameter M. The computed velocity profiles for M = 38.25 compare favorably with the measurements of van de Sande et al. (1980). In the long pipe limit M = 0 the numerical solution differs by less than 1 percent from the exact analytic solution due to Szymanksi. For the shorter pipes, it is observed that the start-up time period and the resulting steady-state flow rate are significantly reduced due to the entrance region effects. For M = 0.5, for instance, the start-up time and the ultimate flow rate are reduced by about 55 and 40 percent, respectively, as compared with Szymanski's (1932) infinitely long pipe solution. The time variation of the apparent friction factor is provided for some different cases.

Andersson, H. I.; Kristoffersen, R.

360

Antiretroviral Treatment for Children with Peripartum Nevirapine Exposure  

PubMed Central

BACKGROUND Single-dose nevirapine is the cornerstone of the regimen for prevention of mother-to-child transmission of human immunodeficiency virus (HIV) in resource-limited settings, but nevirapine frequently selects for resistant virus in mothers and children who become infected despite prophylaxis. The optimal antiretroviral treatment strategy for children who have had prior exposure to single-dose nevirapine is unknown. METHODS We conducted a randomized trial of initial therapy with zidovudine and lamivudine plus either nevirapine or ritonavir-boosted lopinavir in HIV-infected children 6 to 36 months of age, in six African countries, who qualified for treatment according to World Health Organization (WHO) criteria. Results are reported for the cohort that included children exposed to single-dose nevirapine prophylaxis. The primary end point was virologic failure or discontinuation of treatment by study week 24. Enrollment in this cohort was terminated early on the recommendation of the data and safety monitoring board. RESULTS A total of 164 children were enrolled. The median percentage of CD4+ lymphocytes was 19%; a total of 56% of the children had WHO stage 3 or 4 disease. More children in the nevirapine group than in the ritonavir-boosted lopinavir group reached a primary end point (39.6% vs. 21.7%; weighted difference, 18.6 percentage-points; 95% confidence interval, 3.7 to 33.6; nominal P = 0.02). Baseline resistance to nevirapine was detected in 18 of 148 children (12%) and was predictive of treatment failure. No significant between-group differences were seen in the rate of adverse events. CONCLUSIONS Among children with prior exposure to single-dose nevirapine for perinatal prevention of HIV transmission, antiretroviral treatment consisting of zidovudine and lamivudine plus ritonavir-boosted lopinavir resulted in better outcomes than did treatment with zidovudine and lamivudine plus nevirapine. Since nevirapine is used for both treatment and perinatal prevention of HIV infection in resource-limited settings, alternative strategies for the prevention of HIV transmission from mother to child, as well as for the treatment of HIV infection, are urgently required. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00307151.)

Palumbo, Paul; Lindsey, Jane C.; Hughes, Michael D.; Cotton, Mark F.; Bobat, Raziya; Meyers, Tammy; Bwakura-Dangarembizi, Mutsawashe; Chi, Benjamin H.; Musoke, Philippa; Kamthunzi, Portia; Schimana, Werner; Purdue, Lynette; Eshleman, Susan H.; Abrams, Elaine J.; Millar, Linda; Petzold, Elizabeth; Mofenson, Lynne M.; Jean-Philippe, Patrick; Violari, Avy

2010-01-01

361

Three Postpartum Antiretroviral Regimens to Prevent Intrapartum HIV Infection  

PubMed Central

Background The safety and efficacy of adding antiretroviral drugs to standard zidovudine prophylaxis in infants of mothers with human immunodeficiency virus (HIV) infection who did not receive antenatal antiretroviral therapy (ART) because of late identification are unclear. We evaluated three ART regimens in such infants. Methods Within 48 hours after their birth, we randomly assigned formula-fed infants born to women with a peripartum diagnosis of HIV type 1 (HIV-1) infection to one of three regimens: zidovudine for 6 weeks (zidovudine-alone group), zidovudine for 6 weeks plus three doses of nevirapine during the first 8 days of life (two-drug group), or zidovudine for 6 weeks plus nelfinavir and lamivudine for 2 weeks (three-drug group). The primary outcome was HIV-1 infection at 3 months in infants uninfected at birth. Results A total of 1684 infants were enrolled in the Americas and South Africa (566 in the zidovudine-alone group, 562 in the two-drug group, and 556 in the three-drug group). The overall rate of in utero transmission of HIV-1 on the basis of Kaplan–Meier estimates was 5.7% (93 infants), with no significant differences among the groups. Intra-partum transmission occurred in 24 infants in the zidovudine-alone group (4.8%; 95% confidence interval [CI], 3.2 to 7.1), as compared with 11 infants in the two-drug group (2.2%; 95% CI, 1.2 to 3.9; P = 0.046) and 12 in the three-drug group (2.4%; 95% CI, 1.4 to 4.3; P = 0.046). The overall transmission rate was 8.5% (140 infants), with an increased rate in the zidovudine-alone group (P = 0.03 for the comparisons with the two- and three-drug groups). On multivariate analysis, zidovudine monotherapy, a higher maternal viral load, and maternal use of illegal substances were significantly associated with transmission. The rate of neutropenia was significantly increased in the three-drug group (P<0.001 for both comparisons with the other groups). Conclusions In neonates whose mothers did not receive ART during pregnancy, prophylaxis with a two- or three-drug ART regimen is superior to zidovudine alone for the prevention of intrapartum HIV transmission; the two-drug regimen has less toxicity than the three-drug regimen. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development [NICHD] and others; ClinicalTrials.gov number, NCT00099359.)

Nielsen-Saines, Karin; Watts, D. Heather; Veloso, Valdilea G.; Bryson, Yvonne J.; Joao, Esau C.; Pilotto, Jose Henrique; Gray, Glenda; Theron, Gerhard; Santos, Breno; Fonseca, Rosana; Kreitchmann, Regis; Pinto, Jorge; Mussi-Pinhata, Marisa M.; Ceriotto, Mariana; Machado, Daisy; Bethel, James; Morgado, Marisa G.; Dickover, Ruth; Camarca, Margaret; Mirochnick, Mark; Siberry, George; Grinsztejn, Beatriz; Moreira, Ronaldo I.; Bastos, Francisco I.; Xu, Jiahong; Moye, Jack; Mofenson, Lynne M.

2013-01-01

362

Association of isoniazid preventive therapy with lower early mortality in individuals on antiretroviral therapy in a workplace programme in South Africa  

PubMed Central

Objective To describe the association between isoniazid preventive therapy (IPT) and mortality among individuals starting antiretroviral therapy (ART) in a workplace programme in South Africa where tuberculosis incidence is very high. Methods ART-naïve individuals starting ART from January 2004 to December 2007 were followed for up to 12 months. Deaths were ascertained from clinic and human resources data. The association between IPT and mortality was assessed using Cox regression. Results 3,270 individuals were included (median age 45; 93% male; median baseline CD4 155 cells/mm3 (IQR:87–221); 45% WHO stage 3/4). 922(28%) individuals started IPT either prior to, or within three months of, starting ART. Individuals who started IPT tended to have less advanced HIV disease at ART initiation. 259 (7.9%) deaths were observed, overall mortality rate 8.9/100 person years [pyrs] (95%CI:7.9–10.6). The unadjusted mortality rate was lower among those who received IPT vs. not (3.7/100 pyrs versus 11.1/100 pyrs respectively, hazard ratio (HR) 0.34 [95%CI:0.24–0.49]); this association remained after adjustment for age, baseline CD4, baseline WHO stage, year of ART start and individual company (HR 0.51, 95%CI 0.32–0.80). In sensitivity analyses restricted to those with no previous history of TB (n=3036) or with no TB symptoms at ART initiation (n=2251), IPT remained associated with reduced mortality (adjusted HRs 0.51 (95%CI: 0.32 – 0.81) and 0.48 (95%CI: 0.24–0.96) respectively). Conclusions Mortality was lower among individuals receiving IPT with or prior to ART start. These results support routine use of IPT in conjunction with ART.

Charalambous, S; Grant, AD; Innes, C; Hoffmann, CJ; Dowdeswell, R; Pienaar, J; Fielding, KL; Churchyard, GJ

2013-01-01

363

Head Start Impact Study: First Year Findings. Executive Summary  

ERIC Educational Resources Information Center

|The Congressionally-mandated Head Start Impact Study is being conducted across 84 nationally representative grantee/delegate agencies. Approximately 5,000 newly entering 3- and 4-year-old children applying for Head Start were randomly assigned to either a Head Start group that had access to Head Start program services or to a non-Head Start group…

Puma, Michael; Bell, Stephen; Cook, Ronna; Heid, Camilla; Lopez, Michael

2005-01-01

364

Adverse effects of highly active antiretroviral therapy in developing countries.  

PubMed

Recent increases in access to highly active antiretroviral therapy (HAART) have made the management of drug toxicities an increasingly crucial component of human immunodeficiency virus (HIV) care in developing countries. The spectrum of adverse effects related to HAART in developing countries may differ from that in developed countries because of the high prevalence of conditions such as anemia, malnutrition, and tuberculosis and frequent initial presentation with advanced HIV disease. The severity of adverse effects may vary as a result of host genetics and diagnostic delays attributable to inadequate laboratory monitoring. This article reviews current knowledge about toxicities related to HAART in resource-limited regions, which are in the process of rapid treatment scale-up. We conclude that initiating HAART before advanced immunosuppression, titrating doses in single-pill drug combinations to differences in patients' body weights, providing more intensive laboratory monitoring during the initial months of therapy, and providing access to less-toxic nucleoside reverse-transcriptase inhibitors may decrease the incidence of toxicities related to HAART in resource-limited regions. PMID:17879931

Subbaraman, Ramnath; Chaguturu, Sreekanth Krishna; Mayer, Kenneth H; Flanigan, Timothy P; Kumarasamy, Nagalingeswaran

2007-09-06

365

Treatment of antiretroviral-drug-resistant HIV-1 infection.  

PubMed

Drug-resistant HIV-1 is a cause of growing clinical and public-health concern. In many patients, combination antiretroviral therapy fails to achieve complete viral suppression (virological failure). Continuing viral replication during therapy leads to the accumulation of drug-resistance mutations, resulting in increased viral load and a greater risk of disease progression. Patients with drug-resistant HIV-1 infection have three therapeutic options: a change to a salvage regimen with the aim of fully suppressing viral replication; interruption of therapy; or continuation of a partially effective regimen. The first strategy is preferred for most patients failing their first or perhaps their second regimen. However, the best approach remains unclear for patients who have failed multiple treatment regimens and who have limited options for complete viral suppression. The management of such patients requires a careful understanding of the pathogenesis of drug-resistant HIV-1, the clinical consequences of virological failure, the potential benefits and limitations of diagnostic assays, and the likelihood that agents in development will be effective. PMID:14683662

Deeks, Steven G

2003-12-13

366

Hospitalization risk following initiation of highly active antiretroviral therapy  

PubMed Central

Objectives While highly active antiretroviral therapy (HAART) decreases long-term morbidity and mortality, its short-term effect on hospitalization rates is unknown. The primary objective of this study was to determine hospitalization rates over time in the year after HAART initiation for virological responders and nonresponders. Methods Hospitalizations among 1327 HAART-naïve subjects in an urban HIV clinic in 1997–2007 were examined before and after HAART initiation. Hospitalization rates were stratified by virological responders (? 1 log10 decrease in HIV-1 RNA within 6 months after HAART initiation) and nonresponders. Causes were determined through International Classification of Diseases, 9th Revision (ICD-9) codes and chart review. Multivariate negative binomial regression was used to assess factors associated with hospitalization. Results During the first 45 days after HAART initiation, the hospitalization rate of responders was similar to their pre-HAART baseline rate [75.1 vs. 78.8/100 person-years (PY)] and to the hospitalization rate of nonresponders during the first 45 days (79.4/100 PY). The hospitalization rate of responders fell significantly between 45 and 90 days after HAART initiation and reached a plateau at approximately 45/100 PY from 91 to 365 days after HAART initiation. Significant decreases were seen in hospitalizations for opportunistic and nonopportunistic infections. Conclusions The first substantial clinical benefit from HAART may be realized by 90 days after HAART initiation; providers should keep close vigilance at least until this time.

Berry, SA; Manabe, YC; Moore, RD; Gebo, KA

2011-01-01

367

Barriers to Sustaining Antiretroviral Treatment in Kisesa, Tanzania  

PubMed Central

Two years after the introduction of free antiretroviral therapy (ART) in Tanzania and in spite of the logistical support provided to facilitate clinic attendance, a considerable level of attrition from the program was identified among clients from a semi-rural ward. Qualitative research on ART patients’ health-seeking behavior identified factors affecting sustained attendance at treatment clinics. A mix of methods was used for data collection including semi-structured interviews with 42 clients and 11 service providers and 4 participatory group activities conducted with members of a post-test group between October and December 2006. A socio-ecological framework guided data analysis to categorize facilitators and barriers into individual, social, programmatic, and structural level influences, and subsequently explored their interaction and relative significance in shaping ART clients’ behavior. Our findings suggest that personal motivation and self-efficacy contribute to program retention, and are affected by other individual-level experiences such as perceived health benefits or disease severity. However, these determinants are influenced by others’ opinions and beliefs in the community, and constrained by programmatic and structural barriers. Individuals can develop the requisite willingness to sustain strict treatment requirements in a challenging context, but are more likely to do so within supportive family and community environments. Effectiveness and sustainability of ART roll-out could be strengthened by strategic intervention at different levels, with particular attention to community-level factors such as social networks’ influence and support.

Roura, Maria; Busza, Joanna; Wringe, Alison; Mbata, Doris; Urassa, Mark; Zaba, Basia

2009-01-01

368

Predictors of Adherence to Antiretroviral Therapy in Rural Zambia  

PubMed Central

Background/Objective Antiretroviral therapy (ART) adherence levels of ?95% optimize outcomes and minimize HIV drug resistance. As such, identifying barriers to adherence is essential. We sought to assess travel to point-of-care for ART as a potential barrier to adherence in rural Zambia, within the context of patient demographics, perceived stigma, and selected clinical indices. Methods We studied 424 patients receiving ART from the Macha Mission Hospital (MMH). Interviews ascertained age, gender, education, perceived stigma, nearest rural health facility (RHF), and mode/cost/time of transport for each study participant. Motorcycle odometer and global positioning system way-points measured distance from the MMH to each of the RHFs, estimating patients’ home-to-MMH travel distances. Body mass index, World Health Organization HIV/AIDS stage, and pill counts were assessed from review of patients’ medical and pharmacy records. Results At least 95% adherence was documented for 83.7% of the patients in their first months of ART. Travel-related factors did not predict adherence. Adherence was higher for those on ART for a longer time (odds ratio = 1.04 per day; P = 0.002). Conclusions Patients in rural Zambia can achieve adherence rates compatible with good clinical outcomes despite long travel distances. The MMH was able to provide quality HIV/AIDS care by implementing programmatic features selecting for a highly adherent population in this resource-limited setting.

Carlucci, James G.; Kamanga, Aniset; Sheneberger, Robb; Shepherd, Bryan E.; Jenkins, Cathy A.; Spurrier, John; Vermund, Sten H.

2009-01-01

369

Real-Time Adherence Monitoring for HIV Antiretroviral Therapy  

PubMed Central

Current adherence assessments typically detect missed doses long after they occur. Real-time, wireless monitoring strategies for antiretroviral therapy may provide novel opportunities to proactively prevent virologic rebound and treatment failure. Wisepill, a wireless pill container that transmits a cellular signal when opened, was pilot tested in ten Ugandan individuals for 6 months. Adherence levels measured by Wisepill, unannounced pill counts, and self-report were compared with each other, prior standard electronic monitoring, and HIV RNA. Wisepill data was initially limited by battery life and signal transmission interruptions. Following device improvements, continuous data was achieved with median (interquartile range) adherence levels of 93% (87–97%) by Wisepill, 100% (99–100%) by unannounced pill count, 100% (100–100%) by self-report, and 92% (79–98%) by prior standard electronic monitoring. Four individuals developed transient, low-level viremia. After overcoming technical challenges, real-time adherence monitoring is feasible for resource-limited settings and may detect suboptimal adherence prior to viral rebound.

Kahane, Josh; Kigozi, Isaac; Emenyonu, Nneka; Hunt, Peter; Martin, Jeffrey; Bangsberg, David R.

2010-01-01

370

Prospective Antiretroviral Treatment of Asymptomatic, HIV-1 Infected Controllers  

PubMed Central

The study of HIV-infected “controllers” who are able to maintain low levels of plasma HIV RNA in the absence of antiretroviral therapy (ART) may provide insights for HIV cure and vaccine strategies. Despite maintaining very low levels of plasma viremia, controllers have elevated immune activation and accelerated atherosclerosis. However, the degree to which low-level replication contributes to these phenomena is not known. Sixteen asymptomatic controllers were prospectively treated with ART for 24 weeks. Controllers had a statistically significant decrease in ultrasensitive plasma and rectal HIV RNA levels with ART. Markers of T cell activation/dysfunction in blood and gut mucosa also decreased substantially with ART. Similar reductions were observed in the subset of “elite” controllers with pre-ART plasma HIV RNA levels below conventional assays (<40 copies/mL). These data confirm that HIV replication persists in controllers and contributes to a chronic inflammatory state. ART should be considered for these individuals (ClinicalTrials.gov NCT01025427).

Hatano, Hiroyu; Yukl, Steven A.; Ferre, April L.; Graf, Erin H.; Somsouk, Ma; Sinclair, Elizabeth; Abdel-Mohsen, Mohamed; Liegler, Teri; Harvill, Kara; Hoh, Rebecca; Palmer, Sarah; Bacchetti, Peter; Hunt, Peter W.; Martin, Jeffrey N.; McCune, Joseph M.; Tracy, Russell P.; Busch, Michael P.; O'Doherty, Una; Shacklett, Barbara L.; Wong, Joseph K.; Deeks, Steven G.

2013-01-01

371

Early loss of bone mineral density is correlated with a gain of fat mass in patients starting a protease inhibitor containing regimen: the prospective Lipotrip study  

PubMed Central

Background HIV-infected patients starting antiretroviral treatment (ART) experience deep and early disorders in fat and bone metabolism, leading to concomitant changes in fat mass and bone mineral density. Methods We conducted a prospective study in treatment-naive HIV-infected patients randomized to receive two nucleoside reverse transcriptase inhibitors in combination with either a protease inhibitor (PI) or a non-nucleosidic reverse transcriptase inhibitor (NNRTI), to evaluate early changes in body composition, bone mineral density and metabolic markers as differentially induced by antiretroviral therapies. We measured changes in markers of carbohydrate, of fat and bone metabolism, and, using dual-emission X-ray absorptiometry (DXA), body composition and bone mineral density (BMD). Complete data on changes between baseline and after 21 months treatment were available for 35 patients (16 in the PI group and 19 in the NNRTI group). Results A significant gain in BMI and in total and lower limb fat mass was recorded only in patients receiving PI. A loss of lumbar BMD was observed in both groups, being higher with PI. Plasma markers of bone metabolism (alkaline phosphatase, osteocalcin, collagen crosslaps) and levels of parathormone and of 1,25diOH-vitamin D3 significantly increased in both groups, concomitant with a decline in 25OH-vitamin D3. Lipids and glucose levels increased in both groups but rise in triglyceride was more pronounced with PI. A correlation between loss of BMD and gain of fat mass is observed in patients starting PI. Conclusions We evidenced an early effect of ART on lipid and bone metabolisms. PI lead to a significant gain in fat mass correlated with a sharp drop in BMD but active bone remodelling is evident with all antiretroviral treatments, associated with low vitamin D levels and hyperparathyroidism. In parallel, signs of metabolic restoration are evident. However, early increases in lean and fat mass, triglycerides, waist circumference and leptin are much more pronounced with PI.

2013-01-01

372

76 FR 37174 - Capital Investment Program-New Starts and Small Starts Program Funds  

Federal Register 2010, 2011, 2012, 2013

...INFORMATION CONTACT: For general program information on the New Starts, contact Eric Hu, Office of Program Management, at (202) 366-0870, e-mail: Eric.Hu@dot.gov mailto:, for project specific issues, contact Elizabeth Day,...

2011-06-24

373

Moving Forward: Head Start Children, Families, and Programs in 2003. Head Start Series. CLASP Policy Brief No. 5  

ERIC Educational Resources Information Center

This policy brief is the fifth of a series of analyses of Head Start Program Information Report (PIR) data by CLASP (Center for Law and Social Policy). It describes the picture for Head Start and Early Head Start children, families, and programs in the 2002-2003 program year. In this brief, "Head Start" refers to all Head Start programs, including…

Hart, Katherine; Schumacher, Rachel

2004-01-01

374

5 CFR 9701.351 - Setting an employee's starting pay.  

Code of Federal Regulations, 2013 CFR

...2013-01-01 false Setting an employee's starting pay. 9701.351 Section...9701.351 Setting an employee's starting pay. DHS will, after coordination...regarding the starting rate of pay for an employee, includingâ (a)...

2013-01-01

375

Oral Health Activities of Early Head Start and Migrant and Seasonal Head Start Programs  

Microsoft Academic Search

Guidelines recommend that Migrant and Seasonal Head Start programs (MSHS) address the dental needs of children of migrant and seasonal farmworkers. This study describes parent- and child-oriented oral health activities of North Carolina’s MSHS programs and compares them with non-migrant Early Head Start (EHS) programs using data collected from a questionnaire completed by teachers and family services staff. Migrant and

Ashley M. Kranz; R. Gary Rozier; Leslie P. Zeldin; John S. Preisser

2012-01-01

376

K.CC Start-Stop Counting  

NSDL National Science Digital Library

This is a task from the Illustrative Mathematics website that is one part of a complete illustration of the standard to which it is aligned. Each task has at least one solution and some commentary that addresses important asects of the task and its potential use. Here are the first few lines of the commentary for this task: Have students form a circle and sit facing in toward each other. The teacher selects a range of the number sequence to practice. Start with the teacher...

377

The Fragile Success of Team Start-ups  

Microsoft Academic Search

This article describes the benefits and pitfalls of starting a firm with an entrepreneurial team, drawing on a longitudinal empirical analysis of the life course of 90 team start-ups and 1196 solo start-ups in the Netherlands. In the first three years of their existence, team start-ups perform better than solo start-ups on several success indicators. However, after this start phase,

Veronique Schutjens; Erik Stam

378

Assessment of antiretroviral therapy knowledge and willingness of persons with HIV to support its uptake in Uganda  

PubMed Central

Background Access to care and treatment services for human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) are hampered by human resource constraints and knowledge gaps about antiretroviral therapy. Training people with HIV/AIDS (PWA) as educators on antiretroviral therapy may help in the expansion of antiretroviral therapy-related knowledge in Africa. The aim of this study was to assess the antiretroviral therapy-specific knowledge, beliefs, and attitudes of PWA as well as their proactive communication with community members and to explore their willingness to serve as support personnel. Methods Data were obtained from a large randomized trial of PWA. We analyzed qualitative and quantitative data from 524 PWA aged 18 years and over who initiated home-based antiretroviral therapy in 2003. We assessed knowledge and communication of HIV prevention and treatment messages by PWA to communities using structured messages complemented with other knowledge questions and the willingness of PWA to serve as support persons. Descriptive bivariate associations and logistic regression statistical methods were performed. In addition, qualitative data analysis was used. Results The level of knowledge about antiretroviral therapy was high among all PWA on several technical attributes. Overall, 90% of PWA reported that they had been consulted by community members for informed opinions on antiretroviral therapy, 70% felt they were opinion leaders on aspects of antiretroviral therapy within the communities, and approximately 70% were willing to be engaged as community support persons. Those who were classified as opinion leaders reported being approached more regularly by community members for expert advice about antiretroviral therapy compared with nonopinion leaders (odds ratio [OR] 11.7; 95% confidence interval [CI] 7.3–18.6), and opinion leaders were significantly more informed on most technical attributes of antiretroviral therapy, such as “who qualifies for antiretroviral therapy based on CD4 count” (OR 1.6, 95% CI 1.1–2.0) and “the need to be evaluated for antiretroviral therapy” (OR 1.8, 95% CI 1.2–2.0). Conclusion Opinion leaders demonstrated correct knowledge and willingness to provide information on antiretroviral therapy care and treatment issues and were, in turn, consulted more frequently for antiretroviral therapy advice compared with nonopinion leaders. Training opinion leaders to work as community support personnel may increase knowledge about antiretroviral therapy in underserved communities.

Batamwita, Richard; Moore, David M; King, Rachel; Mills, Edward; Stangl, Anne L

2011-01-01

379

ACTG A5095: Three- vs Four-Drug Antiretroviral Regimens for the Initial Treatment of HIV-1 Infection, A Randomized Controlled Trial (on CD-ROM).  

National Technical Information Service (NTIS)

Context: Three-drug antiretroviral regimens are standard of care for initial treatment of human immunodeficiency virus 1 (HIV-1) infection, but a 4-drug regimen could improve antiretroviral activity and be more effective than a 3-drug regimen. Objective: ...

2006-01-01

380

ACTG 388: A Randomized Trial of 2 Different 4-Drug Antiretroviral Regimens Versus a 3-Drug Regimen in Advanced Human Immunodeficiency Virus (on CD-ROM).  

National Technical Information Service (NTIS)

The CD-ROM compares long-term virologic benefits of antiretroviral regimens in persons with advanced human immunodeficiency virus, a randomized, open-label study was conducted of 517 subjects with no or limited prior experience with antiretroviral therapy...

2005-01-01

381

Utilization patterns and projected demand of antiretroviral drugs in low- and middle-income countries.  

PubMed

Background. The rapid scale-up of antiretroviral therapy in resource-limited settings has greatly increased demand for antiretroviral medicines and raised the importance of good forward planning, especially in the context of the new 2010 WHO treatment guidelines. Methods. Forecasting of the number of people receiving antiretroviral therapy from 2010 to 2012 was produced using three approaches: linear projection, country-set targets, and a restricted scenario. Two additional scenarios were then used to project the demand for various antiretroviral medicines under a fast and slower phase-out of stavudine. Results. We projected that between 7.1 million and 8.4 million people would be receiving ART by the end of 2012. Of these, 6.6% will be on second-line therapy. High variation in forecast includes reductions in the demand for d4T and d4T increases in the demand for tenofovir, emtricitabine followed by efavirenz, ritonavir, zidovudine and lopinavir; lamivudine, atazanavir, and nevirapine. Conclusion. Despite the global economic crisis and in response to the revised treatment guidelines, our model forecasts an increasing and shifting demand for antiretrovirals in resource-limited settings not only to provide treatment to new patients, but also to those switching to less toxic regimens. PMID:21490783

Renaud-Théry, Françoise; Avila-Figueroa, Carlos; Stover, John; Thierry, Sigrid; Vitoria, Marco; Habiyambere, Vincent; Souteyrand, Yves

2011-03-24

382

Status of the START neutral beam project  

SciTech Connect

A major advantage of spherical tokamaks is their potential for achieving high beta and high plasma density in modest sized plasmas using low magntic field. Given this combination of low field and high density, neutral beam injection can provide effective auxiliary heating for the next generation of spherical tokamaks. A neutral beam injector, shipped recently from Oak Ridge National Laboratory as part of an ongoing collaboration on spherical tokamak research, has now been installed onto the START (Small Tight Aspect Ratio Tokamak) experiment at Culham Laboratory. This should provide the first experimental test of neutral injectino into spherical tokamak plasmas, and allow the effects of neutral beam heating on energy confinement and beta values to be assessed at low aspect ratios. This experiment also extends the data base of confinement scaling for tokamaks in general. Modifications to START have included in-situ machining of a new 31 cm diameter port for NBI, plus the installation of a new graphite neutral beam stop equipped with thermocouples to provide beam profile and shinethrough diagnosis. The major modification to the NBI beamline has been the installation of an optical fiber coupled control and instrumentation system. The injector will be operated without cryopumps in a 'volume pumped' configuration, and should provide 0.5 MW of injected hydrogen neutral power at a beam energy of 40 keV for 20 ms pulses. The status of the installation and commissioning program is reported.

Nightingale, M. P. S. [Association EURATOM-CCFE, Abingdon, UK; Peng, Yueng Kay Martin [ORNL

1995-01-01

383

[Correlation between CD4 T-cell counts and HIV-1 RNA plasma levels in HIV-1 patients receiving highly active antiretroviral therapy (HAART)  

PubMed

The prognostic value of plasma HIV-1 RNA baseline levels in patients who are going to receive HAART has been recently questioned. In the present study the authors correlated the baseline counts of viremy and CD4 with the viral suppression induced by HAART in an ongoing cohort of HIV-1 positive patients. Data resulting from the study suggest that the HAART effect on CD4 T-cells depends both on the immunological status before starting therapy and on the degree of viral suppression. After briefly discussing about the possible causes of disconnection between CD4 T-cells count and plasma HIV-1 RNA levels, authors conclude that the viral suppression is the desired goal of antiretroviral treatment and that the maximum effect of HAART can be achieved by carefully clinically evaluating patients and individuating the best therapy. PMID:12748445

Maggiolo, F.; Bottura, P.; Capra, R.; Pravettoni, G.; Suter, F.

1999-01-01

384

Hemophagocytic syndrome as a presenting sign of transformation of smoldering to acute adult T-cell leukemia/lymphoma: efficacy of anti-retroviral and interferon therapy.  

PubMed

A 55-year-old Caribbean woman with a 6-year history of smoldering adult T-cell leukemia/lymphoma presented with clinical and biological symptoms of hemophagocytic syndrome. An extensive search for infectious diseases was negative. A lymph node biopsy showing large T-cell lymphoma (CD4-, CD25+) and findings of high LDH count and severe lymphocytosis led to the diagnosis of acute adult T-cell leukemia/lymphoma. Anti-retroviral therapy combining zidovudine, lamivudine, and interferon-alpha was started, resulting in rapid control of both hemophagocytic syndrome and symptoms of acute adult T-cell leukemia/lymphoma. Thus, we propose that adult T-cell leukemia/lymphoma must be added to the spectrum of etiologies of hemophagocytic syndrome. PMID:15164389

Aouba, Achille; Lambotte, Olivier; Vasiliu, Viorel; Divine, Marine; Valensi, Françoise; Varet, Bruno; Bazarbachi, Ali; Hermine, Olivier

2004-06-01

385

Mortality and loss-to-follow-up during the pre-treatment period in an antiretroviral therapy programme under normal health service conditions in Uganda  

PubMed Central

Background In many HIV programmes in Africa, patients are assessed clinically and prepared for antiretroviral treatment over a period of 4–12 weeks. Mortality rates following initiation of ART are very high largely because patients present late with advanced disease. The rates of mortality and retention during the pre-treatment period are not well understood. We conducted an observational study to determine these rates. Methods HIV-infected subjects presenting at The AIDS Support Clinic in Jinja, SE Uganda, were assessed for antiretroviral therapy (ART). Eligible subjects were given information and counselling in 3 visits done over 4–6 weeks in preparation for treatment. Those who did not complete screening were followed-up at home. Survival analysis was done using poisson regression. Results 4321 HIV-infected subjects were screened of whom 2483 were eligible for ART on clinical or immunological grounds. Of these, 637 (26%) did not complete screening and did not start ART. Male sex and low CD4 count were associated independently with not completing screening. At follow-up at a median 351 days, 181 (28%) had died, 189 (30%) reported that they were on ART with a different provider, 158 (25%) were alive but said they were not on ART and 109 (17%) were lost to follow-up. Death rates (95% CI) per 100 person-years were 34 (22, 55) (n.18) within one month and 37 (29, 48) (n.33) within 3 months. 70/158 (44%) subjects seen at follow-up said they had not started ART because they could not afford transport. Conclusion About a quarter of subjects eligible for ART did not complete screening and pre-treatment mortality was very high even though patients in this setting were well informed. For many families, the high cost of transport is a major barrier preventing access to ART.

Amuron, Barbara; Namara, Geoffrey; Birungi, Josephine; Nabiryo, Christine; Levin, Jonathan; Grosskurth, Heiner; Coutinho, Alex; Jaffar, Shabbar

2009-01-01

386

Are They Really Lost? "True" Status and Reasons for Treatment Discontinuation among HIV Infected Patients on Antiretroviral Therapy Considered Lost to Follow Up in Urban Malawi  

PubMed Central

Introduction Patients who are lost to follow-up (LTFU) while on antiretroviral therapy (ART) pose challenges to the long-term success of ART programs. We describe the extent to which patients considered LTFU are misclassified as true disengagement from care when they are still alive on ART and explain reasons for ART discontinuation using our active tracing program to further improve ART retention programs and policies. Methods We identified adult ART patients who missed clinic appointment by more than 3 weeks between January 2006 and December 2010, assuming that such patients would miss their doses of antiretroviral drugs. Patients considered LTFU who consented during ART registration were traced by phone or home visits; true ART status after tracing was documented. Reasons for ART discontinuation were also recorded for those who stopped ART. Results Of the 4,560 suspected LTFU cases, 1,384 (30%) could not be traced. Of the 3,176 successfully traced patients, 952 (30%) were dead and 2,224 (70%) were alive, of which 2,183 (99.5%) started ART according to phone-based self-reports or physical verification during in-person interviews. Of those who started ART, 957 (44%) stopped ART and 1,226 (56%) reported still taking ART at the time of interview by sourcing drugs from another clinic, using alternative ART sources or making brief ART interruptions. Among 940 cases with reasons for ART discontinuations, failure to remember (17%), too weak/sick (12%), travel (46%), and lack of transport to the clinic (16%) were frequently cited; reasons differed by gender. Conclusion The LTFU category comprises sizeable proportions of patients still taking ART that may potentially bias retention estimates and misdirect resources at the clinic and national levels if not properly accounted for. Clinics should consider further decentralization efforts, increasing drug allocations for frequent travels, and improving communication on patient transfers between clinics to increase retention and adherence.

Tweya, Hannock; Feldacker, Caryl; Estill, Janne; Jahn, Andreas; Ng'ambi, Wingston; Ben-Smith, Anne; Keiser, Olivia; Bokosi, Mphatso; Egger, Matthias; Speight, Colin; Gumulira, Joe; Phiri, Sam

2013-01-01

387

Community-based treatment of advanced HIV disease: introducing DOT-HAART (directly observed therapy with highly active antiretroviral therapy)  

Microsoft Academic Search

In 2000, acquired immunodeficiency syndrome (AIDS) overtook tuberculosis (TB) as the world's leading infectious cause of adult deaths. In affluent countries, however, AIDS mortality has dropped sharply, largely because of the use of highly active antiretroviral therapy (HAART). Antiretroviral agents are not yet considered essential medications by international public health experts and are not widely used in the poor countries

Paul Farmer; Fernet Leandre; Joia Mukherjee; Rajesh Gupta; Laura Tarter; Jim Yong Kim

388

Growth, immune and viral responses in HIV infected African children receiving highly active antiretroviral therapy: a prospective cohort study  

Microsoft Academic Search

BACKGROUND: Scale up of paediatric antiretroviral therapy in resource limited settings continues despite limited access to routine laboratory monitoring. We documented the weight and height responses in HIV infected Ugandan children on highly active antiretroviral therapy and determined clinical factors associated with successful treatment outcomes. METHODS: A prospective cohort of HIV infected children were initiated on HAART and followed for

Philippa M Musoke; Peter Mudiope; Linda N Barlow-Mosha; Patrick Ajuna; Danstan Bagenda; Michael M Mubiru; Thorkild Tylleskar; Mary G Fowler

2010-01-01

389

Barriers to adherence to antiretroviral medications among patients living with HIV in southern China: a qualitative study  

Microsoft Academic Search

Although China's government is rapidly expanding access to antiretroviral therapy, little is known about barriers to adherence among Chinese HIV-infected patients, particularly among injection drug users. To better understand barriers to antiretroviral treatment adherence, we conducted a qualitative research study, using both focus group and key informant methods, among 36 HIV-positive men and women in Dali, in southwestern China. All

Lora L. Sabin; Mary Bachman Desilva; Davidson H. Hamer; Xu Keyi; Yuan Yue; Fan Wen; Li Tao; Harald K. Heggenhougen; Lewis Seton; Ira B. Wilson; Christopher J. Gill

2008-01-01

390

Tenofovir Disoproxil Fumarate and an Optimized Background Regimen of Antiretroviral Agents as Salvage Therapy for Pediatric HIV Infection  

Microsoft Academic Search

Objectives. Highly active antiretroviral therapy has altered the course of HIV infection among children, but new antiretroviral agents are needed for treatment-experienced children with drug-resistant vi- rus. Tenofovir disoproxil fumarate (DF) is a promising agent for use in pediatric salvage therapy, because of its tolerability, efficacy, and resistance profile. We designed this study to provide preliminary pediatric safety and dosing

Rohan Hazra; Rachel I. Gafni; Frank Maldarelli; Frank M. Balis; Antonella N. Tullio; Ellen DeCarlo; Carol J. Worrell; Seth M. Steinberg; John Flaherty; Kitty Yale; Brian P. Kearney; Steven L. Zeichner

2006-01-01

391

Resistance in pediatric patients experiencing virologic failure with first-line and second-line antiretroviral therapy.  

PubMed

We examined HIV-1 resistance in children failing first-line and second-line antiretroviral therapy in South Africa, all with clade C virus. Those exposed to full-dose ritonavir had multiple protease resistance mutations. Nineteen percent had wild-type virus. Appropriate antiretroviral therapy sequencing in sub-Saharan African children is essential for prolong treatment options. PMID:23303240

Orrell, Catherine; Levison, Julie; Ciaranello, Andrea; Bekker, Linda-Gail; Kuritzkes, Daniel R; Freedberg, Kenneth A; Wood, Robin

2013-06-01

392

ABC for people with HIV: responses to sexual behaviour recommendations among people receiving antiretroviral therapy in Jinja, Uganda  

PubMed Central

People living with HIV who are taking antiretroviral therapy (ART) are increasingly involved in ‘positive prevention’ initiatives. These are generally oriented to promoting abstinence, ‘being faithful’ (partner reduction) and condom use (ABC). We conducted a longitudinal qualitative study with people living with HIV using ART, who were provided with adherence education and counselling support by a Ugandan nongovernmental organisation, The AIDS Support Organisation (TASO). Forty people were selected sequentially as they started ART, stratified by sex, ART delivery mode (clinic- or home-based) and HIV progression stage (early or advanced) and interviewed at enrolment and at 3, 6, 18 and 30 months. At initiation of ART, participants agreed to follow TASO's positive-living recommendations. Initially poor health prevented sexual activity. As health improved, participants prioritised resuming economic production and support for their children. With further improvements, sexual desire resurfaced and people in relationships cemented these via sex. The findings highlight the limitations of HIV prevention based on medical care/personal counselling. As ART leads to health improvements, social norms, economic needs and sexual desires increasingly influence sexual behaviour. Positive prevention interventions need to seek to modify normative and economic influences on sexual behaviour, as well as to provide alternatives to condoms.

Allen, Caroline; Mbonye, Martin; Seeley, Janet; Birungi, Josephine; Wolff, Brent; Coutinho, Alex; Jaffar, Shabbar

2011-01-01

393

Sexual risk taking among patients on antiretroviral therapy in an urban informal settlement in Kenya: a cross-sectional survey  

PubMed Central

Background Our intention was to analyze demographic and contextual factors associated with sexual risk taking among HIV-infected patients on antiretroviral treatment (ART) in Africa's largest informal urban settlement, Kibera in Nairobi, Kenya. Methods We used a cross-sectional survey in a resource-poor, urban informal settlement in Nairobi; 515 consecutive adult patients on ART attending the African Medical and Research Foundation clinic in Kibera in Nairobi were included in the study. Interviewers used structured questionnaires covering socio-demographic characteristics, time on ART, number of sexual partners during the previous six months and consistency of condom use. Results Twenty-eight percent of patients reported inconsistent condom use. Female patients were significantly more likely than men to report inconsistent condom use (aOR 3.03; 95% CI 1.60-5.72). Shorter time on ART was significantly associated with inconsistent condom use. Multiple sexual partners were more common among married men than among married women (adjusted OR 4.38; 95% CI 1.82-10.51). Conclusions Inconsistent condom use was especially common among women and patients who had recently started ART, i.e., when the risk of HIV transmission is higher. Having multiple partners was quite common, especially among married men, with the potential of creating sexual networks and an increased risk of HIV transmission. ART needs to be accompanied by other preventive interventions to reduce the risk of new HIV infections among sero-discordant couples and to increase overall community effectiveness.

2011-01-01

394

D-dimer and CRP levels are elevated prior to antiretroviral treatment in patients who develop IRIS  

PubMed Central

Biomarkers could be useful in evaluating immune reconstitution inflammatory syndrome (IRIS). A cohort of 45 HIV-1-infected, antiretroviral treatment (ART)-naïve patients with baseline CD4 T cell counts ?100 cells/?L who were started on ART, suppressed HIV-RNA to <50 copies/mL, and seen every 1-3 months for 1 year were retrospectively evaluated for suspected or confirmed IRIS. D-dimer, C-reactive protein (CRP), and selected autoantibodies were analyzed at baseline, 1 and 3 months post-ART in cryopreserved plasma. Median differences between cases and controls were compared with Mann-Whitney and Fischer's exact tests. Sixteen patients (35.6%) developed IRIS (median of 35 days post-ART initiation): unmasking=8, paradoxical=7, autoimmune=1. Pre-ART D-dimer and CRP were higher in IRIS cases versus controls (D-dimer: 0.89mg/L versus 0.66mg/L, p=0.037; CRP: 0.74mg/L versus 0.39mg/L, p=0.022), while D-dimer was higher in unmasking cases at IRIS onset (2.04mg/L versus 0.36mg/L, p=0.05). These biomarkers may be useful in identifying patients at risk for IRIS.

Porter, Brian O.; Ouedraogo, G. Laissa; Hodge, Jessica; Smith, Margo; Pau, Alice; Roby, Gregg; Kwan, Richard; Bishop, Rachel; Rehm, Catherine; Mican, JoAnn; Sereti, Irini

2010-01-01

395

Method and apparatus for starting supersonic compressors  

DOEpatents

A supersonic gas compressor with bleed gas collectors, and a method of starting the compressor. The compressor includes aerodynamic duct(s) situated for rotary movement in a casing. The aerodynamic duct(s) generate a plurality of oblique shock waves for efficiently compressing a gas at supersonic conditions. A convergent inlet is provided adjacent to a bleed gas collector, and during startup of the compressor, bypass gas is removed from the convergent inlet via the bleed gas collector, to enable supersonic shock stabilization. Once the oblique shocks are stabilized at a selected inlet relative Mach number and pressure ratio, the bleed of bypass gas from the convergent inlet via the bypass gas collectors is effectively eliminated.

Lawlor, Shawn P

2013-08-06

396

Start safety apparatus for internal combustion engine  

SciTech Connect

A start safety apparatus of an engine adapted for a multipurpose power tool is described which consists of: an engine, an exciter coil generating alternate electromotive force in synchronism with rotation of the engine; an ignition coil having primary and secondary windings; a spark plug connected to the secondary winding of the ignition coil; a capacitor connected to the primary winding of the ignition coil the capacitor being charged with a positive half-cycle of the electromotive force; ignition timing control means for controlling discharge of the capacitor; a throttle control latch for setting a throttle valve of the engine in a predetermined throttle angle; a tool driven by the engine; and a centrifugal clutch transferring engine power to the tool when an engine speed exceeds a clutch-in speed.

Nakata, H.; Souma, H.

1986-09-09

397

Independent to start gas flow in Moldova  

SciTech Connect

A small independent operator hopes to start gas production this year in the eastern European republic of Moldova, which imports all oil and gas, mainly from Russia. Redeco Ltd. LLC, Oklahoma City, is seeking commercial customers in the town of Baimaclia for gas from a planned 5 km sales pipeline from nearby Victorovca field. The company is affiliated with Redexco ltd., Calgary, and Costilla Energy Inc., Midland, Tex. Redeco`s Victorovca 302 workover well in Cantemir County flowed 500 Mcfd of gas in December from 1,976--86 ft in the Miocene Sarmat formation. The well is in the eastern Carpathian basin. Most wells in Victorovca field are 30--45 years old, but Redeco believes it could economically redrill the field. Victorovca field extends about 12 km east-west and 4 km north-south.

NONE

1997-02-03

398

Cryopump and method of starting the cryopump  

SciTech Connect

A method of starting a cryopump is described comprising: providing a first stage cryopanel and a second stage cryopanel in a pumping volume, providing a close cycle refrigerator having a first stage and a second, colder stage in an insulating volume, and thermally isolating the refrigerator from the cryopanels and from the pumping volume by means of a vacuum in the insulating volume; operating the refrigerator to cool it to cryopumping temperatures; thereafter providing a thermal coupling between the refrigerator first stage and the first stage cryopanel to cool the first stage cryopanel and thereby condense gases thereon from the pumping volume; and thereafter providing a thermal coupling between the refrigerator second stage and the second stage cryopanel to cool the second stage cryopanel and thereby condense additional gases thereon from the pumping volume.

Olsen, D.A.

1988-08-16

399

Getting Started in Qualitative Physics Education Research  

NSDL National Science Digital Library

In this article, we introduce strategies and procedures for collecting and analyzing qualitative data and discuss other aspects of qualitative research such as the role of theory. There are multiple traditions of qualitative research, each with its own methods and terminology. Here, we provide a generic approach to qualitative research that is consistent with most qualitative research traditions. This article consists of nine sections: 1) Introduction, 2) Research Questions and Study Design, 3) Collecting Data, 4) Processing Data, 5) Coding and Analyzing Data, 6) Multiple Representations and Making Inferences, 7) Theoretical perspectives, 8) An Illustration of the Research Process and 9) Validity and Reliability in Qualitative Research. Throughout this article, strategies and examples are provided to help researchers that are both new and veterans to Physics Education Research (PER) to get started in qualitative PER.

Otero, Valerie K.; Harlow, Danielle

2009-06-11

400

Siberian company starts up modular refinery  

SciTech Connect

Uraineftegas, a subsidiary of Russian oil giant Lukoil, has started up Siberia`s first modular crude distillation unit. The 2,000 b/d refinery was designed and manufactured by Ventech Engineers Inc., Pasadena, Tex. Uraineftegas is based in Urai, Siberia. Located in the Tyumen region on the Konda river, the remote town is accessible only by air and water. Most of Urai`s crude production--about 50,000 b/d, according to Ventech president Bill Stanley--is shipped by pipeline to the refining centers at Ufa and Omsk. Because there are no products pipelines in which to ship fuels back to Urai, the town needed a small refinery in order to produce its own fuels. This report briefly describes the design ad operation of these modular units. It describes construction techniques and temperature control equipment used to maintain an operational environment under severe winter weather.

NONE

1996-03-18

401

Stages of change for adherence to antiretroviral medications.  

PubMed

Abstract Providers do not predict reliably which of their HIV-positive patients are having difficulty adhering to antiretroviral therapy (ART). The transtheoretical, or stages of change model, may be a useful tool to help providers identify patients who are having difficulty with ART adherence. The objective of the current study was to determine the relationship between stages of change and ART adherence among patients who were actively taking ART. Data from a randomized trial of a provider-focused intervention were used to examine the relationship between the stages of change and adherence, measured using electronic monitoring devices in the 30 days following the stages of change assessment. Individuals were eligible for inclusion if they were taking ART and had detectable plasma viral load (HIV-RNA). Repeated measures analysis of covariance was used to determine the impact of stages of change on adherence after controlling for potential confounders. The sample of 137 participants was 22% female, 48% white, 28% African-American, with a mean age of 42 years. Fifty-eight percent reported sex with a man as an HIV risk factor, while 13% reported sex with a woman, 14% reported injecting drugs and 15% reported other risk factors. In adjusted models, those in earlier stages of change (i.e., contemplation and preparation) had significantly lower adherence (-9.8%, p=0.04) compared to those in the action and maintenance phases. No demographic characteristics predicted adherence. The stages of change model may function as a screening tool for clinicians to discover patients at-risk of lower adherence. PMID:24093810

Genberg, Becky L; Lee, Yoojin; Rogers, William H; Willey, Cynthia; Wilson, Ira B

2013-10-01

402

The HIV Antiretroviral Drug Efavirenz has LSD-Like Properties.  

PubMed

Anecdotal reports have surfaced concerning misuse of the HIV antiretroviral medication efavirenz ((4S)-6-chloro-4-(2-cyclopropylethynyl)-4-(trifluoromethyl)-2,4-dihydro-1H-3,1-benzoxazin-2-one) by HIV patients and non-infected teens who crush the pills and smoke the powder for its psychoactive effects. Molecular profiling of the receptor pharmacology of efavirenz pinpointed interactions with multiple established sites of action for other known drugs of abuse including catecholamine and indolamine transporters, and GABAA and 5-HT2A receptors. In rodents, interaction with the 5-HT2A receptor, a primary site of action of lysergic acid diethylamine (LSD), appears to dominate efavirenz's behavioral profile. Both LSD and efavirenz reduce ambulation in a novel open-field environment. Efavirenz occasions drug-lever responding in rats discriminating LSD from saline, and this effect is abolished by selective blockade of the 5-HT2A receptor. Similar to LSD, efavirenz induces head-twitch responses in wild-type, but not in 5-HT2A-knockout, mice. Despite having GABAA-potentiating effects (like benzodiazepines and barbiturates), and interactions with dopamine transporter, serotonin transporter, and vesicular monoamine transporter 2 (like cocaine and methamphetamine), efavirenz fails to maintain responding in rats that self-administer cocaine, and it fails to produce a conditioned place preference. Although its molecular pharmacology is multifarious, efavirenz's prevailing behavioral effect in rodents is consistent with LSD-like activity mediated via the 5-HT2A receptor. This finding correlates, in part, with the subjective experiences in humans who abuse efavirenz and with specific dose-dependent adverse neuropsychiatric events, such as hallucinations and night terrors, reported by HIV patients taking it as a medication. PMID:23702798

Gatch, Michael B; Kozlenkov, Alexey; Huang, Ren-Qi; Yang, Wenjuan; Nguyen, Jacques D; González-Maeso, Javier; Rice, Kenner C; France, Charles P; Dillon, Glenn H; Forster, Michael J; Schetz, John A

2013-05-24

403

The MOTIVATE trials: maraviroc therapy in antiretroviral treatment-experienced HIV-1-infected patients.  

PubMed

Although the use of combination antiretroviral therapy has resulted in spectacular improvements in morbidity and mortality of HIV-1 infected patients, a need for the development of antiretroviral compounds with new mechanisms of action remains. Maraviroc (Celsentri(®); ViiV Healthcare, Middlesex, UK) is the only drug of the class of chemokine (C-C motif) receptor 5 antagonists registered for treatment for HIV-1-infected antiretroviral therapy-experienced patients. Registration was based on the MOTIVATE-1 and -2 studies, which compared the efficacy and tolerability of maraviroc in combination with optimized background therapy with placebo. The aim of this paper is to review the MOTIVATE studies and to discuss issues related to maraviroc therapy in clinical practice such as assessment of HIV-1 coreceptor tropism. PMID:23113664

van Lelyveld, Steven F L; Wensing, Annemarie M J; Hoepelman, Andy I M

2012-10-31

404

Outcome of pregnancy in HIV-positive women planned for vaginal delivery under effective antiretroviral therapy.  

PubMed

This retrospective cohort study was conducted at Newham University Hospital, London to investigate maternal outcome of planned vaginal delivery as well as rate of maternal-to-child transmission. Between June 2004 and June 2006, 23 (16%) women of 144 HIV-infected pregnant women opted for planned vaginal delivery. Offer of vaginal delivery was based on maternal HIV RNA count <50 cells/ml around 36 weeks' gestation. All women received antiretroviral therapy. Fifteen (65%) women achieved vaginal delivery. Babies were followed up over 18 months. All babies had antiretroviral prophylaxis. No babies were breast-fed. There was no report of maternal-to-child transmission in any of these babies. Our study suggests that planned vaginal delivery could be safe with antiretroviral therapy in pregnancy, optimal intrapartum care, viral load of <1000 copies/ml at delivery, retroviral prophylaxis for babies and avoidance of breast-feeding. PMID:20121502

Islam, S; Oon, V; Thomas, P

2010-01-01

405

A Patient with Multiple Immune Reconstitution Inflammatory Syndrome (IRIS) Following Initiation of Antiretroviral Therapy  

PubMed Central

The Immune Reconstitution Inflammatory Syndrome (IRIS) is an exaggerated pathological inflammatory reaction which occurs after the initiation of the antiretroviral therapy, due to the exuberant immune responses to the occult or the apparent opportunistic infections. The hallmark of the syndrome is the paradoxical worsening of an existing infection or a disease process or the appearance of a new infection or a disease process soon after the initiation of the antiretroviral therapy. The most common forms of IRIS occur in association with tuberculosis and chronic viral and invasive fungal infections. Multiple IRIS in a patient is extremely rare. Our patient had multiple manifestations of IRIS, in the form of cryptococcal meningitis, toxoplasmosis and Cytomegalovirus (CMV) retinitis after the initiation of highly active antiretroviral therapy.

Achappa, Basavaprabhu; Madi, Deepak; Shetty, Nishitha; Mahalingam, Soundarya

2012-01-01

406

Kinetics and Determining Factors of the Virologic Response to Antiretrovirals during Pregnancy  

PubMed Central

HIV-infected pregnant women with undetectable plasma HIV RNA concentrations at delivery pose a minimal risk of vertical transmission. We studied the kinetics and the determinants of the virologic response to antiretroviral therapy in 117 consecutive pregnancies. Patients who initiated therapy during pregnancy had a VL decrease of 2 and 2.5 log10 after 4 and 24 weeks, respectively. Therapeutic drug monitoring (TDM) of the protease inhibitors administered in doses recommended for nonpregnant adults resulted in below-target concentrations in 29%, 35%, and 44% of 1st, 2nd, and 3rd trimester measurements, respectively, but low drug concentrations did not correlate with virologic failure. Demographic characteristics, antiretroviral experience prior to pregnancy, baseline VL, or use of specific antiretrovirals did not affect the virologic response. Adherence to ?95% of prescribed doses and utilization of psychosocial services were associated with undetectable plasma HIV RNA at delivery. In conclusion, the virologic responses of pregnant and nonpregnant adults share similar charactersitics.

Weinberg, Adriana; Harwood, Jeri E. F.; McFarland, Elizabeth J.; Pappas, Jennifer; Davies, Jill; Kinzie, Kay; Barr, Emily; Paul, Suzanne; Salbenblatt, Carol; Soda, Elizabeth; Vazquez, Anna; Peloquin, Charles A.; Levin, Myron J.

2009-01-01

407

Immune reconstitution in HIV-1 infected subjects treated with potent antiretroviral therapy  

PubMed Central

The introduction of potent antiretroviral drug regimens contributed to a decline in HIV-1 associated morbidity and mortality. Clinical observations of spontaneous remission of previously untreatable opportunistic infections in subjects on highly active antiretroviral therapy (HAART) reflect the substantial degree of immune reconstitution which can be achieved by those therapies. A biphasic increase of CD4+ T lymphocytes has been reported including naive (CD45RA+) and memory (CD45RO+) cell subsets. Proliferative lymphocyte responses to recall antigens and mitogens are enhanced over time, while T lymphocyte activation is largely reduced and T cell receptor (TCR) repertoires are partly restored. Proliferative lymphocyte responses specific to HIV-1 antigens, in contrast, remain weak. A complete normalisation of HIV-1 associated immunological alterations has not been reported so far, but the observation period of subjects on potent antiretroviral therapies is still relatively short. ???

Kaufmann, G. R.; Zaunders, J.; Cooper, D. A.

1999-01-01

408

HIV-Associated Nephropathy: Clinical Presentation, Pathology, and Epidemiology in the Era of Antiretroviral Therapy  

PubMed Central

The classic kidney disease of Human Immunodeficiency Virus (HIV) infection, HIV-associated nephropathy, is characterized by progressive acute renal failure, often accompanied by proteinuria and ultrasound findings of enlarged, echogenic kidneys. Definitive diagnosis requires kidney biopsy, which demonstrates collapsing focal segmental glomerulosclerosis with associated microcystic tubular dilatation and interstitial inflammation. Podocyte proliferation is a hallmark of HIV-associated nephropathy, although this classic pathology is observed less frequently in antiretroviral-treated patients. The pathogenesis of HIV-associated nephropathy involves direct HIV infection of renal epithelial cells, and the widespread introduction of combination antiretroviral therapy has had a significant impact on the natural history and epidemiology of this unique disease. These observations have established antiretroviral therapy as the cornerstone of treatment for HIV-associated nephropathy, in the absence of prospective clinical trials. Adjunctive therapy for HIV-associated nephropathy includes ACE inhibitors or angiotensin receptor blockers, as well as corticosteroids in selected patients with significant interstitial inflammation or rapid progression.

Wyatt, Christina M.; Klotman, Paul E.; D'Agati, Vivette D.

2008-01-01

409

Drug-resistant tuberculosis treatment complicated by antiretroviral resistance in HIV coinfected patients: a report of six cases in Lesotho.  

PubMed

Treating drug-resistant tuberculosis (DR-TB) is particularly challenging in high human immunodeficiency virus (HIV) prevalence settings. Neither antiretroviral resistance testing nor viral load monitoring is widely available in sub-Saharan Africa, and antiretroviral resistance can complicate the clinical management for DR-TB/HIV coinfected patients. We describe six cases of antiretroviral resistance in DR-TB patients with HIV coinfection in Lesotho. Two patients died before or immediately after antiretroviral resistance was detected by genotyping; the remaining four patients were switched to effective antiretroviral therapy (ART) regimens. Favorable DR-TB treatment outcomes in coinfected patients require successful management of their HIV infection, including treatment with an effective ART regimen. Coinfected patients undergoing DR-TB treatment may require closer monitoring of their response to ART, including routine viral load testing, to ensure that they receive an effective ART regimen concurrent with DR-TB treatment. PMID:23669229

Satti, Hind; McLaughlin, Megan M; Seung, Kwonjune J

2013-05-13

410

Induction of p-glycoprotein by antiretroviral drugs in human brain microvessel endothelial cells.  

PubMed

The membrane-associated drug transporter P-glycoprotein (P-gp) plays an essential role in drug efflux from the brain. Induction of this protein at the blood-brain barrier (BBB) could further affect the ability of a drug to enter the brain. At present, P-gp induction mediated by antiretroviral drugs at the BBB has not been fully investigated. Since P-gp expression is regulated by ligand-activated nuclear receptors, i.e., human pregnane X receptor (hPXR) and human constitutive androstane receptor (hCAR), these receptors could represent potential pathways involved in P-gp induction by antiretroviral drugs. The aims of this study were (i) to determine whether antiretroviral drugs currently used in HIV pharmacotherapy are ligands for hPXR or hCAR and (ii) to examine P-gp function and expression in human brain microvessel endothelial cells treated with antiretroviral drugs identified as ligands of hPXR and/or hCAR. Luciferase reporter gene assays were performed to examine the activation of hPXR and hCAR by antiretroviral drugs. The hCMEC/D3 cell line, which is known to display several morphological and biochemical properties of the BBB in humans, was used to examine P-gp induction following 72 h of exposure to these agents. Amprenavir, atazanavir, darunavir, efavirenz, ritonavir, and lopinavir were found to activate hPXR, whereas abacavir, efavirenz, and nevirapine were found to activate hCAR. P-gp expression and function were significantly induced in hCMEC/D3 cells treated with these drugs at clinical concentrations in plasma. Together, our data suggest that P-gp induction could occur at the BBB during chronic treatment with antiretroviral drugs identified as ligands of hPXR and/or hCAR. PMID:23836171

Chan, Gary N Y; Patel, Rucha; Cummins, Carolyn L; Bendayan, Reina

2013-07-08

411

Female gender predicts lower access and adherence to antiretroviral therapy in a setting of free healthcare  

PubMed Central

Background Barriers to HIV treatment among injection drug users (IDU) are a major public health concern. However, there remain few long-term studies investigating key demographic and behavioral factors - and gender differences in particular - that may pose barriers to antiretroviral therapy (ART), especially in settings with universal healthcare. We evaluated access and adherence to ART in a long-term cohort of HIV-positive IDU in a setting where medical care and antiretroviral therapy are provided free of charge through a universal healthcare system. Methods We evaluated baseline antiretroviral use and subsequent adherence to ART among a Canadian cohort of HIV-positive IDU. We used generalized estimating equation logistic regression to evaluate factors associated with 95% adherence to antiretroviral therapy estimated based on prescription refill compliance. Results Between May 1996 and April 2008, 545 IDU participants were followed for a median of 23.8 months (Inter-quartile range: 8.5 - 91.6), among whom 341 (63%) were male and 204 (37%) were female. Within the six-month period prior to the baseline interview, 133 (39%) men and 62 (30%) women were on ART (p = 0.042). After adjusting for clinical characteristics as well as drug use patterns measured longitudinally throughout follow-up, female gender was independently associated with a lower likelihood of being 95% adherent to ART (Odds Ratio [OR] = 0.70; 95% Confidence Interval: 0.53-0.93). Conclusions Despite universal access to free HIV treatment and medical care, female IDU were less likely to access and adhere to antiretroviral therapy, a finding that was independent of drug use and clinical characteristics. These data suggest that interventions to improve access to HIV treatment among IDU must be tailored to address unique barriers to antiretroviral therapy faced by female IDU.

2011-01-01

412

Repeated assessments of food security predict CD4 change in the setting of antiretroviral therapy  

PubMed Central

Food insecurity is highly prevalent in HIV-infected populations, and analyses utilizing multiple assessments of food security to predict CD4 change are lacking. 592 patients with ? 4 food security assessments were followed prospectively. In the final model, for patients using antiretroviral therapy, increases in CD4 counts were on average 99.5 cells less for individuals with at least one episode of food insecurity compared to those consistently food secure (P < 0.001). Other sociodemographic factors were not predictive. Repeated assessments of food security are potent predictors of treatment response notwithstanding antiretroviral therapy use. Potential mechanisms for this association are proposed.

McMahon, James H.; Wanke, Christine A.; Elliott, Julian H.; Skinner, Sally; Tang, Alice M.

2011-01-01

413

How well do clinicians estimate patients’ adherence to combination antiretroviral therapy?  

Microsoft Academic Search

OBJECTIVE: Adherence to combination antiretroviral therapy is critical for clinical and virologic success in HIV-infected patients.\\u000a To combat poor adherence, clinicians must identify nonadherent patients so they can implement interventions. However, little\\u000a is known about the accuracy of these assessments. We sought to describe the accuracy of clinicians’ estimates of patients’\\u000a adherence to combination antiretroviral therapy.\\u000a \\u000a \\u000a SETTING: Public HIV clinic.

Loren G. Miller; Honghu Liu; Ron D. Hays; Carol E. Golin; C. Keith Beck; Steven M. Asch; Yingying Ma; Andrew H. Kaplan; Neil S. Wenger

2002-01-01

414

Starting winding optimization in single-phase induction motor design  

Microsoft Academic Search

This paper presents algorithms for the optimal design of the starting winding and\\/or the starting capacitor for split-phase motors and capacitor start motors by optimizing the starting performance. By means of the circle diagram, the two-dimensional optimization problem becomes a one-dimensional problem. For capacitor start and run motors, two strategies are introduced for the design of the auxiliary winding, the

D. Lin; P. Zhou; N. Lambert

2010-01-01

415

Disparities in Antiretroviral Treatment: A Comparison of Behaviorally-HIV-Infected Youth and Adults in the HIV Research Network  

PubMed Central

Objectives Increasing numbers of youth are becoming HIV-infected and need highly active antiretroviral therapy (HAART). We hypothesized that behaviorally HIV-infected youth (BIY) ages 18–24 are less likely than adults (?25 years) to receive HAART and once initiated, more likely to discontinue their first HAART regimen. Methods Longitudinal analysis of treatment-naïve patients (age ?18) meeting criteria for HAART and followed at HIVRN sites (2002–2008). Time from meeting criteria to HAART initiation and duration on first regimen were assessed using Cox proportional hazards regression. Results 3,127 (268 youth, 2,859 adult) treatment-naïve, HIV-infected patients met criteria. BIY were more likely to be Black (66.8% vs. 51.1%; p<.01) and less likely to identify injection drug use (IDU) HIV risk (1.1% vs. 8.8%; p<.01) than adults ? 25 years. Nearly 69% of BIY started HAART, versus 79% of adults; p<.001. Adults 25–29 (Adjusted Hazards Ratio (AHR) 1.39 [95% CI: 1.12–1.73]) and ?50 (AHR 1.24 [95% CI 1.00–1.54]), but not 30–49 years (AHR 1.19 [95% CI 0.99–1.44]) were more likely to initiate HAART than BIY. Attending ?4 HIV provider visits within one year of meeting criteria was associated with HAART initiation (AHR 1.91 [1.70–2.14]). CD4 200–350 vs. <200 cells/mm3 (AHR 0.57 (95% CI 0.52–0.63]) and IDU (AHR 0.80 [95% CI 0.69–0.92]) were associated with a lower likelihood of HAART initiation. There were no age-related differences in duration of first regimen. Conclusion BIY are less likely to start HAART when meeting treatment criteria. Addressing factors associated with this disparity is critical to improving care for youth.

Agwu, AL; Fleishman, JA; Korthuis, PT; Siberry, GK; Ellen, JM; Gaur, AH; Rutstein, R; Gebo, KA

2011-01-01

416

Long-term increase in CD4+ T-cell counts during combination antiretroviral therapy for HIV-1 infection  

PubMed Central

Objective To inform guidelines concerning when to initiate combination antiretroviral therapy (ART), we investigated whether CD4+ T-cell counts (CD4 counts) continue to increase over long periods of time on ART. Losses-to-follow-up and some patients discontinuing ART at higher CD4 counts hamper such evaluation, but novel statistical methods can help address these issues. We estimated the long-term CD4 count trajectory accounting for losses-to-follow-up and treatment discontinuations. Design The study population included 898 U.S. patients first initiating ART in a randomized trial (ACTG 384); 575 were subsequently prospectively followed in an observational study (ALLRT). Methods Inverse probability of censoring weighting statistical methods were used to estimate the CD4 count trajectory accounting for losses-to-follow-up and ART-discontinuations, overall and for pre-treatment CD4 count categories ? 200, 201–350, 351–500, and >500 cells/mm3. Results Median CD4 count increased from 270 cells/mm3 pre-ART to an estimated 556 at three and 532 cells/mm3 at seven years after starting ART in analyses ignoring treatment discontinuations; and to 570 and 640 cells/mm3, respectively, had all patients continued ART. However, even had ART been continued, an estimated 25%, 9%, 3% and 2% of patients with pre-treatment CD4 counts of ? 200, 201–350, 351–500, and >500 cells/mm3 would have had CD4 counts ?350 cells/mm3 after seven years. Conclusions If patients remain on ART, CD4 counts increase in most patients for at least seven years. However, the substantial percentage of patients starting therapy at low CD4 counts who still had low CD4 counts after seven years provides support for ART initiation at higher CD4 counts.

Lok, Judith J; Bosch, Ronald J; Benson, Constance A; Collier, Ann C; Robbins, Gregory K; Shafer, Robert W; Hughes, Michael D

2010-01-01

417

Long-Term Survival in HIV Positive Patients with up to 15 Years of Antiretroviral Therapy  

PubMed Central

Background Life expectancy has increased for newly diagnosed HIV patients since the inception of combination antiretroviral treatment (cART), but there remains a need to better understand the characteristics of long-term survival in HIV-positive patients. We examined long-term survival in HIV-positive patients receiving cART in the Australian HIV Observational Database (AHOD), to describe changes in mortality compared to the general population and to develop longer-term survival models. Methods Data were examined from 2,675 HIV-positive participants in AHOD who started cART. Standardised mortality ratios (SMR) were calculated by age, sex and calendar year across prognostic characteristics using Australian Bureau of Statistics national data as reference. SMRs were examined by years of duration of cART by CD4 and similarly by viral load. Survival was analysed using Cox-proportional hazards and parametric survival models. Results The overall SMR for all-cause mortality was 3.5 (95% CI: 3.0–4.0). SMRs by CD4 count were 8.6 (95% CI: 7.2–10.2) for CD4<350 cells/µl; 2.1 (95% CI: 1.5–2.9) for CD4?=?350–499 cells/µl; and 1.5 (95% CI: 1.1–2.0) for CD4?500 cells/µl. SMRs for patients with CD4 counts <350 cells/µL were much higher than for patients with higher CD4 counts across all durations of cART. SMRs for patients with viral loads greater than 400 copies/ml were much higher across all durations of cART. Multivariate models demonstrated improved survival associated with increased recent CD4, reduced recent viral load, younger patients, absence of HBVsAg-positive ever, year of HIV diagnosis and incidence of ADI. Parametric models showed a fairly constant mortality risk by year of cART up to 15 years of treatment. Conclusion Observed mortality remained fairly constant by duration of cART and was modelled accurately by accepted prognostic factors. These rates did not vary much by duration of treatment. Changes in mortality with age were similar to those in the Australian general population.

McManus, Hamish; O'Connor, Catherine C.; Boyd, Mark; Broom, Jennifer; Russell, Darren; Watson, Kerrie; Roth, Norman; Read, Phillip J.; Petoumenos, Kathy; Law, Matthew G.

2012-01-01

418

Masculine attitudes of superiority deter men from accessing antiretroviral therapy in Dar es Salaam, Tanzania.  

PubMed

Background: This article presents part of the findings from a larger study that sought to assess the role that gender relations play in influencing equity regarding access and adherence to antiretroviral therapy (ART). Review of the literature has indicated that, in Southern and Eastern Africa, fewer men than women have been accessing ART, and the former start using ART late, after HIV has already been allowed to advance. The main causes for this gender gap have not yet been fully explained. Objective: To explore how masculinity norms limit men's access to ART in Dar es Salaam. Design: This article is based on a qualitative study that involved the use of focus group discussions (FGDs). The study employed a stratified purposive sampling technique to recruit respondents. The study also employed a thematic analysis approach. Results: Overall, the study's findings revealed that men's hesitation to visit the care and treatment clinics signifies the superiority norm of masculinity that requires men to avoid displaying weakness. Since men are the heads of families and have higher social status, they reported feeling embarrassed at having to visit the care and treatment clinics. Specifically, male respondents indicated that going to a care and treatment clinic may raise suspicion about their status of living with HIV, which in turn may compromise their leadership position and cause family instability. Because of this tendency towards 'hiding', the few men who register at the public care and treatment clinics do so late, when HIV-related signs and symptoms are already far advanced. Conclusion: This study suggests that the superiority norm of masculinity affects men's access to ART. Societal expectations of a 'real man' to be fearless, resilient, and emotionally stable are in direct conflict with expectations of the treatment programme that one has to demonstrate health-promoting behaviour, such as promptness in attending the care and treatment clinic, agreeing to take HIV tests, and disclosing one's status of living with HIV to at least one's spouse or partner. Hence, there is a need for HIV control agencies to design community-based programmes that will stimulate dialogue on the deconstruction of masculinity notions. PMID:24152373

Nyamhanga, Tumaini M; Muhondwa, Eustace P Y; Shayo, Rose

2013-10-22

419

Masculine attitudes of superiority deter men from accessing antiretroviral therapy in Dar es Salaam, Tanzania  

PubMed Central

Background This article presents part of the findings from a larger study that sought to assess the role that gender relations play in influencing equity regarding access and adherence to antiretroviral therapy (ART). Review of the literature has indicated that, in Southern and Eastern Africa, fewer men than women have been accessing ART, and the former start using ART late, after HIV has already been allowed to advance. The main causes for this gender gap have not yet been fully explained. Objective To explore how masculinity norms limit men's access to ART in Dar es Salaam. Design This article is based on a qualitative study that involved the use of focus group discussions (FGDs). The study employed a stratified purposive sampling technique to recruit respondents. The study also employed a thematic analysis approach. Results Overall, the study's findings revealed that men's hesitation to visit the care and treatment clinics signifies the superiority norm of masculinity that requires men to avoid displaying weakness. Since men are the heads of families and have higher social status, they reported feeling embarrassed at having to visit the care and treatment clinics. Specifically, male respondents indicated that going to a care and treatment clinic may raise suspicion about their status of living with HIV, which in turn may compromise their leadership position and cause family instability. Because of this tendency towards ‘hiding’, the few men who register at the public care and treatment clinics do so late, when HIV-related signs and symptoms are already far advanced. Conclusion This study suggests that the superiority norm of masculinity affects men's access to ART. Societal expectations of a ‘real man’ to be fearless, resilient, and emotionally stable are in direct conflict with expectations of the treatment programme that one has to demonstrate health-promoting behaviour, such as promptness in attending the care and treatment clinic, agreeing to take HIV tests, and disclosing one's status of living with HIV to at least one's spouse or partner. Hence, there is a need for HIV control agencies to design community-based programmes that will stimulate dialogue on the deconstruction of masculinity notions.

Nyamhanga, Tumaini M.; Muhondwa, Eustace P.Y.; Shayo, Rose

2013-01-01

420

Outcomes of Antiretroviral Therapy in Vietnam: Results from a National Evaluation  

PubMed Central

Objectives Vietnam has significantly scaled up its national antiretroviral therapy (ART) program since 2005. With the aim of improving Vietnam’s national ART program, we conducted an outcome evaluation of the first five years of the program in this concentrated HIV epidemic where the majority of persons enrolled in HIV care and treatment services are people who inject drugs (PWID). The results of this evaluation may have relevance for other national ART programs with significant PWID populations. Design Retrospective cohort analysis of patients at 30 clinics randomly selected with probability proportional to size among 120 clinics with at least 50 patients on ART. Methods Charts of patients whose ART initiation was at least 6 months prior to the study date were abstracted. Depending on clinic size, either all charts or a random sample of 300 charts were selected. Analyses were limited to treatment-naïve patients. Multiple imputations were used for missing data. Results Of 7,587 patient charts sampled, 6,875 were those of treatment-naïve patients (74.4% male, 95% confidence interval [CI]: 72.4–76.5, median age 30, interquartile range [IQR]: 26–34, 62.0% reported a history of intravenous drug use, CI: 58.6–65.3). Median baseline CD4 cell count was 78 cells/mm3 (IQR: 30–162) and 30.4% (CI: 25.8–35.1) of patients were at WHO stage IV. The majority of patients started d4T/3TC/NVP (74.3%) or d4T/3TC/EFV (18.6%). Retention rates after 6, 12, 24, and 36 months were 88.4% (CI: 86.8–89.9), 84.0% (CI: 81.8–86.0), 78.8% (CI: 75.7–81.6), and 74.6% (CI: 69.6–79.0). Median CD4 cell count gains after 6, 12, 24, and 36 months were 94 (IQR: 45–153), 142 (IQR: 78–217), 213 (IQR: 120–329), and 254 (IQR: 135–391) cells/mm3. Patients who were PWID showed significantly poorer retention. Conclusions The study showed good retention and immunological response to ART among a predominantly PWID group of patients despite advanced HIV infections at baseline.

Nguyen, Duc Bui; Do, Nhan Thi; Shiraishi, Ray W.; Le, Yen Ngoc; Tran, Quang Hong; Huu Nguyen, Hai; Medland, Nicholas; Nguyen, Long Thanh; Struminger, Bruce Baird

2013-01-01

421

Impact of Previous Virological Treatment Failures and Adherence on the Outcome of Antiretroviral Therapy in 2007  

PubMed Central

Background Combination antiretroviral treatment (cART) has been very successful, especially among selected patients in clinical trials. The aim of this study was to describe outcomes of cART on the population level in a large national cohort. Methods Characteristics of participants of the Swiss HIV Cohort Study on stable cART at two semiannual visits in 2007 were analyzed with respect to era of treatment initiation, number of previous virologically failed regimens and self reported adherence. Starting ART in the mono/dual era before HIV-1 RNA assays became available was counted as one failed regimen. Logistic regression was used to identify risk factors for virological failure between the two consecutive visits. Results Of 4541 patients 31.2% and 68.8% had initiated therapy in the mono/dual and cART era, respectively, and been on treatment for a median of 11.7 vs. 5.7 years. At visit 1 in 2007, the mean number of previous failed regimens was 3.2 vs. 0.5 and the viral load was undetectable (<50 copies/ml) in 84.6% vs. 89.1% of the participants, respectively. Adjusted odds ratios of a detectable viral load at visit 2 for participants from the mono/dual era with a history of 2 and 3, 4, >4 previous failures compared to 1 were 0.9 (95% CI 0.4–1.7), 0.8 (0.4–1.6), 1.6 (0.8–3.2), 3.3 (1.7–6.6) respectively, and 2.3 (1.1–4.8) for >2 missed cART doses during the last month, compared to perfect adherence. From the cART era, odds ratios with a history of 1, 2 and >2 previous failures compared to none were 1.8 (95% CI 1.3–2.5), 2.8 (1.7–4.5) and 7.8 (4.5–13.5), respectively, and 2.8 (1.6–4.8) for >2 missed cART doses during the last month, compared to perfect adherence. Conclusions A higher number of previous virologically failed regimens, and imperfect adherence to therapy were independent predictors of imminent virological failure.

Ballif, Marie; Ledergerber, Bruno; Battegay, Manuel; Cavassini, Matthias; Bernasconi, Enos; Schmid, Patrick; Hirschel, Bernard; Furrer, Hansjakob; Rickenbach, Martin

2009-01-01

422

Elimination of HIV in South Africa through Expanded Access to Antiretroviral Therapy: A Model Comparison Study  

PubMed Central

Background Expanded access to antiretroviral therapy (ART) using universal test and treat (UTT) has been suggested as a strategy to eliminate HIV in South Africa within 7 y based on an influential mathematical modeling study. However, the underlying deterministic model was criticized widely, and other modeling studies did not always confirm the study's finding. The objective of our study is to better understand the implications of different model structures and assumptions, so as to arrive at the best possible predictions of the long-term impact of UTT and the possibility of elimination of HIV. Methods and Findings We developed nine structurally different mathematical models of the South African HIV epidemic in a stepwise approach of increasing complexity and realism. The simplest model resembles the initial deterministic model, while the most comprehensive model is the stochastic microsimulation model STDSIM, which includes sexual networks and HIV stages with different degrees of infectiousness. We defined UTT as annual screening and immediate ART for all HIV-infected adults, starting at 13% in January 2012 and scaled up to 90% coverage by January 2019. All models predict elimination, yet those that capture more processes underlying the HIV transmission dynamics predict elimination at a later point in time, after 20 to 25 y. Importantly, the most comprehensive model predicts that the current strategy of ART at CD4 count ?350 cells/µl will also lead to elimination, albeit 10 y later compared to UTT. Still, UTT remains cost-effective, as many additional life-years would be saved. The study's major limitations are that elimination was defined as incidence below 1/1,000 person-years rather than 0% prevalence, and drug resistance was not modeled. Conclusions Our results confirm previous predictions that the HIV epidemic in South Africa can be eliminated through universal testing and immediate treatment at 90% coverage. However, more realistic models show that elimination is likely to occur at a much later point in time than the initial model suggested. Also, UTT is a cost-effective intervention, but less cost-effective than previously predicted because the current South African ART treatment policy alone could already drive HIV into elimination. Please see later in the article for the Editors' Summary

Hontelez, Jan A. C.; Lurie, Mark N.; Barnighausen, Till; Bakker, Roel; Baltussen, Rob; Tanser, Frank; Hallett, Timothy B.; Newell, Marie-Louise; de Vlas, Sake J.

2013-01-01

423

Starting Points: Challenging the "Quiet Crisis". A Description of the Starting Points Sites.  

ERIC Educational Resources Information Center

|In 1994, the Carnegie Corporation released "Starting Points: Meeting the Needs of Our Youngest Children," which called for an action agenda to promote responsible parenthood, guarantee quality child care choices, ensure good health and protection, and mobilize communities to support young children and families. In 1996, the Carnegie Corporation…

Knitzer, Jane; Collins, Ann; Oshinsky, Carole; Stout, Laura; Weiss, Heather; Schilder, Diane; Riel, Elizabeth; Smith, Jennifer C.; Groak, Chris; Howell, Julia; Mitchell, Cheryl; Sherman, Annie; Winslow, Becky