Sample records for starting nevirapine-containing antiretroviral

  1. When to Start Antiretroviral Therapy

    MedlinePLUS

    ... circumstances. What factors influence the decision to start ART? When to start ART depends on the following ... an important factor in deciding when to start ART? A CD4 count measures the number of CD4 ...

  2. Antiretroviral therapy in Indian setting: When & what to start with, when & what to switch to?

    PubMed Central

    Kumarasamy, N.; Patel, Atul; Pujari, Sanjay

    2011-01-01

    With the rapid scale up of antiretroviral therapy, there is a dramatic decline in HIV related morbidity and mortality in both developed and developing countries. Several new safe antiretroviral, and newer class of drugs and monitoring assays are developed recently. As a result the treatment guideline for the management of HIV disease continue to change. This review focuses on evolving science on Indian policy - antiretroviral therapy initiation, which drugs to start with, when to change the initial regimen and what to change. PMID:22310814

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

    PubMed Central

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

    2012-01-01

    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

  4. Mortality of HIV-Infected Patients Starting Antiretroviral Therapy in Sub-Saharan Africa: Comparison with HIV-

    E-print Network

    Paris-Sud XI, Université de

    active antiretroviral therapy (ART) has declined in sub-Saharan Africa, but it is unclear how mortalityMortality of HIV-Infected Patients Starting Antiretroviral Therapy in Sub-Saharan Africa patients starting ART with non-HIV­related background mortality in four countries in sub- Saharan Africa

  5. Early loss to program in HIV-infected patients starting potent antiretroviral therapy in lower-income countries

    E-print Network

    Paris-Sud XI, Université de

    starting antiretroviral therapy (ART) is important to monitor clinical outcomes and evaluate program combination therapy (ART) has substantially improved the prognosis of HIV-infected patients in industrialized1 Early loss to program in HIV-infected patients starting potent antiretroviral therapy in lower

  6. Community perspective on the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial.

    PubMed

    Geffen, N; Aagaard, P; Corbelli, G M; Meulbroek, M; Peavy, D; Rappoport, C; Schwarze, S; Collins, S

    2015-04-01

    Determining when to start antiretroviral treatment (ART) is vitally important for people living with HIV. Yet the optimal point at which to start to maximize clinical benefit remains unknown. In the absence of randomized studies, current guidelines rely on conflicting observational data and expert opinion, and consequently diverge on this point. In the USA, ART is recommended irrespective of CD4 cell count. The World Health Organization now recommends starting ART at a CD4 cell count of 500?cells/?L, while the threshold for the UK and South Africa remains at 350?cells/?L. The Strategic Timing of AntiRetroviral Treatment (START) study, one of the largest clinical trials on the treatment of HIV infection, will answer this question. START compares two treatment strategies: immediate treatment at a CD4 cell count of 500?cells/?L or higher versus deferring treatment until the CD4 cell count decreases to 350?cells/?L or until AIDS develops. START includes seven substudies, five of which will clarify the relative contributions of HIV and ART in common comorbidities. START is fully enrolled and expected to be completed in 2016. HIV advocates support the study's design and have been involved from inception to enrolment. The trial will produce rigorous data on the benefits and risks of earlier treatment. It will inform policy and treatment advocacy globally, benefitting the health of HIV-positive people. PMID:25711318

  7. Agreement between physicians and non-physician clinicians in starting antiretroviral therapy in rural Uganda

    Microsoft Academic Search

    Ashwin Vasan; Kwonjune J Seung; Marion Achieng; Patrick Banura; Frank Lule; Megan Beems; Jim Todd; Elizabeth Madraa

    2009-01-01

    BACKGROUND: The scarcity of physicians in sub-Saharan Africa – particularly in rural clinics staffed only by non-physician health workers – is constraining access to HIV treatment, as only they are legally allowed to start antiretroviral therapy in the HIV-positive patient. Here we present a pilot study from Uganda assessing agreement between non-physician clinicians (nurses and clinical officers) and physicians in

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

    PubMed Central

    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

    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. PMID:23172344

  9. Mortality of HIV-Infected Patients Starting Antiretroviral Therapy in Sub-Saharan Africa: Comparison with HIV-Unrelated Mortality

    Microsoft Academic Search

    Martin W. G. Brinkhof; Andrew Boulle; Ralf Weigel; Eugčne Messou; Colin Mathers; Catherine Orrell; François Dabis; Margaret Pascoe; Matthias Egger

    2009-01-01

    Background: Mortality in HIV-infected patients who have access to highly active antiretroviral therapy (ART) has declined in sub-Saharan Africa, but it is unclear how mortality compares to the non-HIV-infected population. We compared mortality rates observed in HIV-1-infected patients starting ART with non-HIV-related background mortality in four countries in sub- Saharan Africa. Methods and Findings: Patients enrolled in antiretroviral treatment programmes

  10. Obesity Trends and Body Mass Index Changes After Starting Antiretroviral Treatment: The Swiss HIV Cohort Study

    PubMed Central

    Hasse, Barbara; Iff, Martin; Ledergerber, Bruno; Calmy, Alexandra; Schmid, Patrick; Hauser, Christoph; Cavassini, Matthias; Bernasconi, Enos; Marzolini, Catia; Tarr, Philip E.; Aubert, V.; Barth, J.; Battegay, M.; Bernasconi, E.; Böni, J.; Bucher, H.C.; Burton-Jeangros, C.; Calmy, A.; Cavassini, M.; Egger, M.; Elzi, L.; Fehr, J.; Fellay, J.; Furrer, H.; Fux, C.A.; Gorgievski, M.; Günthard, H.; Haerry, D.; Hasse, B.; Hirsch, H.H.; Hösli, I.; Kahlert, C.; Kaiser, L.; Keiser, O.; Klimkait, T.; Kouyos, R.; Kovari, H.; Ledergerber, B.; Martinetti, G.; Martinez de Tejada, B.; Metzner, K.; Müller, N.; Nadal, D.; Pantaleo, G.; Rauch, A.; Regenass, S.; Rickenbach, M.; Rudin, C.; Schöni-Affolter, F.; Schmid, P.; Schultze, D.; Schüpbach, J.; Speck, R.; Staehelin, C.; Tarr, P.; Telenti, A.; Trkola, A.; Vernazza, P.; Weber, R.; Yerly, S.

    2014-01-01

    Background ?The factors that contribute to increasing obesity rates in human immunodeficiency virus (HIV)-positive persons and to body mass index (BMI) increase that typically occurs after starting antiretroviral therapy (ART) are incompletely characterized. Methods ?We describe BMI trends in the entire Swiss HIV Cohort Study (SHCS) population and investigate the effects of demographics, HIV-related factors, and ART on BMI change in participants with data available before and 4 years after first starting ART. Results ?In the SHCS, overweight/obesity prevalence increased from 13% in 1990 (n = 1641) to 38% in 2012 (n = 8150). In the participants starting ART (n = 1601), mean BMI increase was 0.92 kg/m2 per year (95% confidence interval, .83–1.0) during year 0–1 and 0.31 kg/m2 per year (0.29–0.34) during years 1–4. In multivariable analyses, annualized BMI change during year 0–1 was associated with older age (0.15 [0.06–0.24] kg/m2) and CD4 nadir <199 cells/µL compared to nadir >350 (P < .001). Annualized BMI change during years 1–4 was associated with CD4 nadir <100 cells/µL compared to nadir >350 (P = .001) and black compared to white ethnicity (0.28 [0.16–0.37] kg/m2). Individual ART combinations differed little in their contribution to BMI change. Conclusions ?Increasing obesity rates in the SHCS over time occurred at the same time as aging of the SHCS population, demographic changes, earlier ART start, and increasingly widespread ART coverage. Body mass index increase after ART start was typically biphasic, the BMI increase in year 0–1 being as large as the increase in years 1–4 combined. The effect of ART regimen on BMI change was limited. PMID:25734114

  11. Immunodeficiency at the start of combination antiretroviral therapy in low-, middle- and high-income countries

    PubMed Central

    2013-01-01

    Objectives To describe the CD4 cell count at the start of combination antiretroviral therapy (cART) in low-income (LIC), lower middle-income (LMIC), upper middle-income (UMIC) and high-income (HIC) countries. Methods Patients aged ?16 years starting cART in a clinic participating in a multi-cohort collaboration spanning six continents (International epidemiological Databases to Evaluate AIDS and ART Cohort Collaboration) were eligible. Multi-level linear regression models were adjusted for age, gender and calendar year; missing CD4 counts were imputed. Findings 379,865 patients from nine LIC, four LMIC, four UMIC and six HIC were included. In LIC the median CD4 cell count at cART initiation increased by 83% from 80 to 145 cells/?l between 2002 and 2009. Corresponding increases in LMIC, UMIC and HIC were from 87 to 155 cells/?l (76% increase), 88 to 135 cells/?l (53%) and 209 to 274 cells/?l (31%). In 2009, compared to LIC, median counts were 13 cells/?l (95% CI -56 to +30) lower in LMIC, 22 cells/?l (-62 to +18) lower in UMIC and 112 /?l (+75 to +149) higher in HIC. They were 23 cells/?l (95% CI +18 to +28) higher in women than men. Median counts were 88 cells/?l (95% CI +35 to +141) higher in countries with an estimated national cART coverage >80%, compared to countries with <40% coverage. Conclusions Median CD4 cell counts at start of cART increased 2000-2009 but remained below 200 cells/?l in LIC and MIC and below 300 cells/?l in HIC. Earlier start of cART will require substantial efforts and resources globally. PMID:24419071

  12. Effects of nutritional supplementation for HIV patients starting antiretroviral treatment: randomised controlled trial in Ethiopia

    PubMed Central

    2014-01-01

    Objectives To determine the effects of lipid based nutritional supplements with either whey or soy protein in patients with HIV during the first three months of antiretroviral treatment (ART) and to explore effects of timing by comparing supplementation at the start of ART and after three months delay. Design Randomised controlled trial. Setting Three public ART facilities in Jimma, Oromia region, Ethiopia. Participants Adults with HIV eligible for ART with body mass index (BMI) >16. Intervention Daily supplementation with 200 g (4600 kJ) of supplement containing whey or soy during either the first three or the subsequent three months of ART. Outcome measures Primary: lean body mass assessed with deuterium dilution, grip strength measured with dynamometers, and physical activity measured with accelerometer and heart rate monitors. Secondary: viral load and CD4 counts. Auxiliary: weight and CD3 and CD8 counts. Results Of 318 patients enrolled, 210 (66%) were women, mean age was 33 (SD 9), and mean BMI was 19.5 (SD 2.4). At three months, participants receiving the supplements containing whey or soy had increased their lean body mass by 0.85 kg (95% confidence interval 0.16 kg to 1.53 kg) and 0.97 kg (0.29 kg to 1.64 kg), respectively, more than controls. This was accompanied by an increased gain of grip strength of 0.68 kg (?0.11 kg to 1.46 kg) for the whey supplement group and 0.93 kg (0.16 kg to 1.70 kg) for the soy supplement group. There were no effects on physical activity. Total weight gain increased by 2.05 kg (1.12 kg to 2.99 kg) and 2.06 kg (1.14 kg to 2.97 kg) for the whey and soy groups, respectively. In addition, in the whey supplement group overall CD3 counts improved by 150 cells/µL (24 to 275 cells/µL), of which 112 cells/µL (15 to 209 cells/µL) were CD8 and 25 cells/µL (?2 to 53 cells/µL) were CD4. Effects of the soy containing supplement on immune recovery were not significant. The effects of the two supplements, however, were not significantly different in direct comparison. Exploratory analysis showed that relatively more lean body mass was gained by patients with undetectable viral load at three months. Patients receiving delayed supplementation had higher weight gain but lower gains in functional outcomes. Conclusions Lipid based nutritional supplements improved gain of weight, lean body mass, and grip strength in patients with HIV starting ART. Supplements containing whey were associated with improved immune recovery. Trial registration Controlled-trials.com ISRCTN32453477. PMID:25134117

  13. Cost-effectiveness analysis of antiretroviral therapy in a cohort of HIV-infected patients starting first-line highly active antiretroviral therapy during 6 years of observation

    PubMed Central

    Maggiolo, Franco; Colombo, Giorgio L; Di Matteo, Sergio; Bruno, Giacomo M; Astuti, Noemi; Di Filippo, Elisa; Masini, Giulia; Bernardini, Claudia

    2015-01-01

    Objectives Costs may play a role in deciding how and when to start highly active antiretroviral therapy (HAART) in a naďve patient. The aim of the present study was to assess the cost- effectiveness of treatment with HAART in a large clinical cohort of naďve adults to determine the potential role of single-tablet regimens in the management of patients with human immunodeficiency virus (HIV). An incremental cost-effectiveness ratio analysis was performed, including a quality-adjusted life year approach. Results In total, 741 patients (females comprising 25.5%) were retrospectively included. The mean age was 39 years, the mean CD4 cell count was 266 cells/?L, and the mean viral load was 192,821 copies/mL. The most commonly used backbone was tenofovir + emtricitabine (77.6%); zidovudine + lamivudine was used in 10%, lamivudine + abacavir in 3%, and other nucleoside reverse transcriptase inhibitor (NRTI) or NRTI-free regimens in 9.4% of patients. NNRTIs were used in 52.8% of cases, boosted protease inhibitors in 44.1%, and unboosted protease inhibitors and integrase inhibitors in 0.7% and 2.4%, respectively. Starting therapy at CD4 >500 cells/?L and CD4 351–500 cells/?L rather than at <201 cells/?L was the more cost-effective approach. The same consideration was not true comparing current indications with the possibility to start HAART at any CD4 value (eg, >500 cells per ?L); in this case, the incremental cost-effectiveness ratio value was €199,130 per quality-adjusted life year gained, a higher value than the one suggested in guidelines. The single-tablet regimen (STR) invariably dominated any other therapeutic approach. Sensitivity analysis was performed, and starting right away with an STR was cost-effective even when compared with therapeutic strategies contemplating STR as simplification. Conclusion By integrating clinical data with economic variables, our study offers an estimate of the cost-effectiveness of the various first-line treatment strategies for patients infected with HIV and provides significant evidence to be used in future prospective pharmacoeconomic evaluations. PMID:25733942

  14. Women's reasons for not participating in follow up visits before starting short course antiretroviral prophylaxis for prevention of mother to child transmission of HIV: qualitative interview study

    Microsoft Academic Search

    Thomas M Painter; Kassamba L Diaby; Danielle M Matia; Lillian S Lin; Toussaint S Sibailly; Moise K Kouassi; Ehounou R Ekpini; Thierry H Roels; Stefan Z Wiktor

    2004-01-01

    Objective To find out why pregnant women who receive HIV-1 positive test results and are offered short course antiretroviral prophylaxis to prevent transmission of HIV from mother to child do not participate in necessary follow up visits before starting prophylaxis. Design Qualitative interview study. Setting A programme aiming to prevent transmission of HIV from mother to child at a public

  15. Is long term virological response related to CCR 5 32 deletion in HIV infected patients started on highly active antiretroviral therapy?

    E-print Network

    Boyer, Edmond

    Is long term virological response related to CCR 5 32 deletion in HIV infected patients started, antiretroviral therapy, CCR5 32 deletion, virological response Corresponding author : Dr. Jean to have a sustained virological response if all plasma HIV-RNA measurements between month 4 and years 3

  16. Predictors of mortality in HIV-infected patients starting antiretroviral therapy in a rural hospital in Tanzania

    PubMed Central

    Johannessen, Asgeir; Naman, Ezra; Ngowi, Bernard J; Sandvik, Leiv; Matee, Mecky I; Aglen, Henry E; Gundersen, Svein G; Bruun, Johan N

    2008-01-01

    Background Studies of antiretroviral therapy (ART) programs in Africa have shown high initial mortality. Factors contributing to this high mortality are poorly described. The aim of the present study was to assess mortality and to identify predictors of mortality in HIV-infected patients starting ART in a rural hospital in Tanzania. Methods This was a cohort study of 320 treatment-naďve adults who started ART between October 2003 and November 2006. Reliable CD4 cell counts were not available, thus ART initiation was based on clinical criteria in accordance with WHO and Tanzanian guidelines. Kaplan-Meier models were used to estimate mortality and Cox proportional hazards models to identify predictors of mortality. Results Patients were followed for a median of 10.9 months (IQR 2.9–19.5). Overall, 95 patients died, among whom 59 died within 3 months of starting ART. Estimated mortality was 19.2, 29.0 and 40.7% at 3, 12 and 36 months, respectively. Independent predictors of mortality were severe anemia (hemoglobin <8 g/dL; adjusted hazard ratio [AHR] 9.20; 95% CI 2.05–41.3), moderate anemia (hemoglobin 8–9.9 g/dL; AHR 7.50; 95% CI 1.77–31.9), thrombocytopenia (platelet count <150 × 109/L; AHR 2.30; 95% CI 1.33–3.99) and severe malnutrition (body mass index <16 kg/m2; AHR 2.12; 95% CI 1.06–4.24). Estimated one year mortality was 55.2% in patients with severe anemia, compared to 3.7% in patients without anemia (P < 0.001). Conclusion Mortality was found to be high, with the majority of deaths occurring within 3 months of starting ART. Anemia, thrombocytopenia and severe malnutrition were strong independent predictors of mortality. A prognostic model based on hemoglobin level appears to be a useful tool for initial risk assessment in resource-limited settings. PMID:18430196

  17. 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

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

    2004-01-01

    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

  18. Metabolic disorders and cardiovascular risk in treatment-naive HIV-infected patients of sub-saharan origin starting antiretrovirals: impact of westernized lifestyle.

    PubMed

    Eholié, Serge Paul; Lacombe, Karine; Krain, Alysa; Diallo, Zelica; Ouiminga, Mariama; Campa, Pauline; Bouchaud, Olivier; Bissagnene, Emmanuel; Girard, Pierre-Marie

    2015-04-01

    In a cohort of HIV-infected patients of sub-Saharan origin we describe the incidence of metabolic syndrome, insulin resistance, and lipodystrophy after 3 years of combined antiretroviral therapy, and model the 10-year risk of cardiovascular diseases, while taking into account environmental factors. This is a multinational, prospective cohort study conducted in HIV outpatient clinics from four tertiary care centers set in France and Côte d'Ivoire. The participants were HIV-infected, treatment-naive patients eligible to start antiretroviral treatment and were of sub-Saharan African origin. The main outcome measures were the incidence of metabolic syndrome, insulin resistance, and lipodystrophy, and the assessment of the 10-year risk of cardiovascular diseases using Framingham risk prediction, D.A.D. Cardiovascular Disease Risk, and WHO/ISH prediction charts. Of 245 patients followed for up to 3 years, the incidence of metabolic syndrome, insulin resistance, and lipodystrophy was 5.5, 8.5, and 6.8 per 100 person-years of follow-up (cumulative incidence: 14.4%, 19.2%, and 18.1%, respectively). Living in France as well as female gender and being overweight were risk factors for metabolic disorders as whole and only first generation protease inhibitors were marginally associated with metabolic syndrome. Cardiovascular risk as modeled through the three equations was high in all patients with the synergistic and deleterious effect of living in France compared to Côte d'Ivoire. This cohort study shows how the synergy between HIV, antiretroviral (ARV) exposure, and westernization of life style in a cohort of HIV-infected patients of sub-Saharan origin leads to a progressive increase in the risk of lipodystrophy, as well as metabolic syndrome and insulin resistance, all associated with increased cardiovascular risk. PMID:25707418

  19. Quality of Life Among Individuals with HIV Starting Antiretroviral Therapy in Diverse Resource-Limited Areas of the World

    PubMed Central

    Hendriksen, Ellen S.; Smeaton, Laura; Celentano, David D.; Hosseinipour, Mina C.; Barnett, Ronald; Guanira, Juan; Flanigan, Timothy; Kumarasamy, N.; Klingman, Karin; Campbell, Thomas

    2011-01-01

    As Antiretroviral Therapy (ART) is scaled up in low- and middle-income countries, it is important to understand Quality of Life (QOL) correlates including disease severity and person characteristics and to determine the extent of between-country differences among those with HIV. QOL and medical data were collected from 1,563 of the 1,571 participants at entry into a randomized clinical trial of ART conducted in the U.S. (n = 203) and 8 resource-limited countries (n = 1,360) in the Caribbean, South America, Asia, and Africa. Participants were interviewed prior to initiation of ART using a modified version of the ACTG SF-21, a health-related QOL measure including 8 subscales: general health perception, physical functioning, role functioning, social functioning, cognitive functioning, pain, mental health, and energy/fatigue. Other measures included demographics, CD4+ lymphocyte count, plasma HIV-1 RNA viral load. Higher quality of life in each of the 8 QOL subscales was associated with higher CD4+ lymphocyte category. General health perception, physical functioning, role functioning, and energy/fatigue varied by plasma HIV-1 RNA viral load categories. Each QOL subscale included significant variation by country. Only the social functioning subscale varied by sex, with men having greater impairments than women, and only the physical functioning subscale varied by age category. This was the first large-scale international ART trial to conduct a standardized assessment of QOL in diverse international settings, thus demonstrating that implementation of the behavioral assessment was feasible. QOL indicators at study entry varied with disease severity, demographics, and country. The relationship of these measures to treatment outcomes can and should be examined in clinical trials of ART in resource-limited settings using similar methodologies. PMID:21499794

  20. Gender differences in HIV disease progression and treatment outcomes among HIV patients one year after starting antiretroviral treatment (ART) in Dar es Salaam, Tanzania

    PubMed Central

    2013-01-01

    Background We investigated gender differences in treatment outcome during first line antiretroviral treatment (ART) in a hospital setting in Tanzania, assessing clinical, social demographic, virological and immunological factors. Methods We conducted a cohort study involving HIV infected patients scheduled to start ART and followed up to 1 year on ART. Structured questionnaires and patients file review were used to collect information and blood was collected for CD4 and viral load testing. Gender differences were assessed using Kruskal-Wallis test and chi-square test for continuous and categorical data respectively. Survival distributions for male and female patients were estimated using the Kaplan-Meier method and compared using Cox proportional hazards models. Results Of 234 patients recruited in this study, 70% were females. At baseline, women had significantly lower education level; lower monthly income, lower knowledge on ARV, less advanced HIV disease (33% women; 47% men started ART at WHO stage IV, p?=?0.04), higher CD4 cell count (median 149 for women, 102 for men, p?=?0.02) and higher BMI (p?=?0.002). After 1 year of standard ART, a higher proportion of females survived although this was not significant, a significantly higher proportion of females had undetectable plasma viral load (69% women, 45% men, p?=?0.003), however females ended at a comparable CD4 cell count (median CD4, 312 women; 321 men) signifying a worse CD4 cell increase (p?=?0.05), even though they still had a higher BMI (p?=?0.02). The unadjusted relative hazard for death for men compared to women was 1.94. After correcting for confounding factors, the Cox proportional hazards showed no significant difference in the survival rate (relative hazard 1.02). Conclusion We observed women were starting treatment at a less advanced disease stage, but they had a lower socioeconomical status. After one year, both men and women had similar clinical and immunological conditions. It is not clear why women lose their immunological advantage over men despite a better virological treatment response. We recommend continuous follow up of this and more cohorts of patients to better understand the underlying causes for these differences and whether this will translate also in longer term differences. PMID:23320567

  1. Estimating the cost-effectiveness of nutrition supplementation for malnourished, HIV-infected adults starting antiretroviral therapy in a resource-constrained setting

    PubMed Central

    2014-01-01

    Background Low body mass index (BMI) individuals starting antiretroviral therapy (ART) for HIV infection in sub-Saharan Africa have high rates of death and loss to follow-up in the first 6 months of treatment. Nutritional supplementation may improve health outcomes in this population, but the anticipated benefit of any intervention should be commensurate with the cost given resource limitations and the need to expand access to ART in the region. Methods We used Markov models incorporating historical data and program-wide estimates of treatment costs and health benefits from the Zambian national ART program to estimate the improvements in 6-month survival and program retention among malnourished adults necessary for a combined nutrition support and ART treatment program to maintain cost-effectiveness parity with ART treatment alone. Patients were stratified according to World Health Organization criteria for severe (BMI <16.0 kg/m2), moderate (16.00-16.99 kg/m2), and mild (17.00-18.49 kg/m2) malnutrition categories. Results 19,247 patients contributed data between May 2004 and October 2010. Quarterly survival and retention were lowest in the BMI <16.0 kg/m2 category compared to higher BMI levels, and there was less variation in both measures across BMI strata after 180 days. ART treatment was estimated to cost $556 per year and averted 7.3 disability-adjusted life years. To maintain cost-effectiveness parity with ART alone, a supplement needed to cost $10.99 per quarter and confer a 20% reduction in both 6-month mortality and loss to follow-up among BMI <16.0 kg/m2 patients. Among BMI 17.00-18.49 kg/m2 patients, supplement costs accompanying a 20% reduction in mortality and loss to follow-up could not exceed $5.18 per quarter. In sensitivity analyses, the maximum permitted supplement cost increased if the ART program cost rose, and fell if patients classified as lost to follow-up at 6 months subsequently returned to care. Conclusions Low BMI adults starting ART in sub-Saharan Africa are at high risk of early mortality and loss to follow-up. The expense of providing nutrition supplementation would require only modest improvements in survival and program retention to be cost-effective for the most severely malnourished individuals starting ART, but interventions are unlikely to be cost-effective among those in higher BMI strata. PMID:24839400

  2. Antiretroviral neurotoxicity.

    PubMed

    Robertson, Kevin; Liner, Jeff; Meeker, Rick B

    2012-10-01

    Combination antiretroviral therapy (CART) has proven to effectively suppress systemic HIV burden, however, poor penetration into the central nervous system (CNS) provides incomplete protection. Although the severity of HIV-associated neurocognitive disorders (HAND) has been reduced, neurological disease is expected to exert an increasing burden as HIV-infected patients live longer. Strategies to enhance penetration of antiretroviral compounds into the CNS could help to control HIV replication in this reservoir but also carries an increased risk of neurotoxicity. Efforts to target antiretroviral compounds to the CNS will have to balance these risks against the potential gain. Unfortunately, little information is available on the actions of antiretroviral compounds in the CNS, particularly at concentrations that provide effective virus suppression. The current studies evaluated the direct effects of 15 antiretroviral compounds on neurons to begin to provide basic neurotoxicity data that will serve as a foundation for the development of dosing and drug selection guidelines. Using sensitive indices of neural damage, we found a wide range of toxicities, with median toxic concentrations ranging from 2 to 10,000 ng/ml. Some toxic concentrations overlapped concentrations currently seen in the CSF but the level of toxicity was generally modest at clinically relevant concentrations. Highest neurotoxicities were associated with abacavir, efavarenz, etravirine, nevaripine, and atazanavir, while the lowest were with darunavir, emtracitabine, tenofovir, and maraviroc. No additive effects were seen with combinations used clinically. These data provide initial evidence useful for the development of treatment strategies that might reduce the risk of antiretroviral neurotoxicity. PMID:22811264

  3. Short communication: factors influencing time to CD4(+) T cell counts >200 cells/mm(3) in HIV-infected individuals with CD4(+) T cell <50 cells/mm(3) at the time of starting combination antiretroviral therapy.

    PubMed

    Ku, Nam Su; Song, Young Goo; Han, Sang Hoon; Kim, Sun Bean; Kim, Hye-won; Jeong, Su Jin; Kim, Chang Oh; Kim, June Myung; Choi, Jun Yong

    2012-12-01

    We evaluated factors influencing time to CD4(+) T cell counts >200 cells/mm(3) in HIV-infected individuals with CD4(+) T cell <50 cells/mm(3) starting combination antiretroviral therapy (cART). We included a total of 29 patients on successful cART for more than 1 year. In a logistic regression model, higher pre-cART CD4(+) T cell counts were significantly associated with shorter time to CD4(+) T cell counts >200cells/mm(3) in HIV-infected individuals with baseline CD4(+) T cell <50 cells/mm(3). In survival analysis, patients having higher pre-cART CD4(+) T cell counts, especially 40-49 cells/mm(3), were at significantly higher risk of achieving CD4(+) T cell counts >200 cells/mm(3). PMID:22632127

  4. Antiretroviral Treatment 2010: Progress and Controversies

    PubMed Central

    Gulick, Roy M.

    2011-01-01

    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. PMID:21045599

  5. Community outreach with weekly delivery of anti-retroviral drugs compared to cognitive-behavioural health care team-based approach to improve adherence among indigent women newly starting HAART

    Microsoft Academic Search

    F. Visnegarwala; M. C. Rodriguez-Barradass; E. A. Graviss; M. Caprio; M. Nykyforchyn; L. Laufman

    2006-01-01

    Sustained virological suppression requires adherence to >95% of doses of therapy. Overall there is paucity of data on adherence interventions among women and post-intervention outcomes. In this pilot study, we evaluated a novel strategy of weekly delivery of medications (Directly Delivered Therapy: DDT) for six months using an outreach worker (ORW), among ARV naďve indigent women starting HAART and compared

  6. Attitudes of People in the UK with HIV Who Are Antiretroviral (ART) Naďve to Starting ART at High CD4 Counts for Potential Health Benefit or to Prevent HIV Transmission

    PubMed Central

    Rodger, Alison J.; Phillips, Andrew; Speakman, Andrew; Gilson, Richard; Fisher, Martin; Wilkins, Ed; Anderson, Jane; Johnson, Margaret; O'Connell, Rebecca; Collins, Simon; Elford, Jonathan; Sherr, Lorraine; Lampe, Fiona C.

    2014-01-01

    Objective To assess if a strategy of early ART to prevent HIV transmission is acceptable to ART naďve people with HIV with high CD4 counts. Design ASTRA is a UK multicentre, cross sectional study of 3258 HIV outpatients in 2011/12. A self-completed questionnaire collected sociodemographic, behavioral and health data, and attitudes to ART; CD4 count was recorded from clinical records. Methods ART naďve participants with CD4 ?350 cells/µL (n?=?281) were asked to agree/disagree/undecided with the statements (i) I would want to start treatment now if this would slightly reduce my risk of getting a serious illness, and (ii) I would want to start treatment now if this would make me less infectious to a sexual partner, even if there was no benefit to my own health. Results Participants were 85% MSM, 76% white, 11% women. Of 281 participants, 49.5% and 45.2% agreed they would start ART for reasons (i) and (ii) respectively; 62.6% agreed with either (i) or (ii); 12.5% agreed with neither; 24.9% were uncertain. Factors independently associated (p<0.1) with agreement to (i) were: lower CD4, more recent HIV diagnosis, physical symptoms, not being depressed, greater financial hardship, and with agreement to (ii) were: being heterosexual, more recent HIV diagnosis, being sexually active. Conclusions A strategy of starting ART at high CD4 counts is likely to be acceptable to the majority of HIV-diagnosed individuals. Almost half with CD4 >350 would start ART to reduce infectiousness, even if treatment did not benefit their own health. However a significant minority would not like to start ART either for modest health benefit or to reduce infectivity. Any change in approach to ART initiation must take account of individual preferences. Transmission models of potential benefit of early ART should consider that ART uptake may be lower than that seen with low CD4 counts. PMID:24869805

  7. Fractures after antiretroviral initiation

    PubMed Central

    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

    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. PMID:22951635

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

    PubMed

    Kotzé, J E; McDonald, T

    2010-06-01

    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

  9. Antiretroviral therapy: 'the state of the art'.

    PubMed

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

    1999-03-01

    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

  10. Scaling up of highly active antiretroviral therapy in a rural district of Malawi: an effectiveness assessment

    Microsoft Academic Search

    Laurent Ferradini; Arnaud Jeannin; Loretxu Pinoges; Jacques Izopet; Didakus Odhiambo; Limangeni Mankhambo; Gloria Karungi; Elisabeth Szumilin; Serge Balandine; Gaëlle Fedida; M Patrizia Carrieri; Bruno Spire; Nathan Ford; Jean-Michel Tassie; Philippe J Guerin; Chris Brasher

    2006-01-01

    Methods We scaled up and simplifi ed HAART in this programme since August, 2002. We analysed survival indicators, CD4 count evolution, virological response, and adherence to treatment. We included adults who all started HAART 6 months or more before the analysis. HIV-1 RNA plasma viral load and self-reported adherence were assessed on a subsample of patients, and antiretroviral resistance mutations

  11. The Start of Head Start

    ERIC Educational Resources Information Center

    Neugebauer, Roger

    2010-01-01

    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…

  12. Brief report Tuberculosis following initiation of antiretroviral therapy

    E-print Network

    Paris-Sud XI, Université de

    -income countries Running title: Tuberculosis on antiretroviral therapy The ART-LINC Collaboration The Antiretroviral Therapy in Low-Income Countries (ART-LINC) Collaboration is a network of antiretroviral treatment1 Brief report Tuberculosis following initiation of antiretroviral therapy in low-income and high

  13. Start Young!

    ERIC Educational Resources Information Center

    Rubin, Penni

    2002-01-01

    Discusses the importance of early interest in science and how effective it is on career choice in adult stages of life. Recommends starting mathematics and science activities in preschool and kindergarten. Describes how to create a career-oriented learning center in the classroom with examples of kitchen chemistry, nutrition/botany, zoology,…

  14. Getting Started

    NSDL National Science Digital Library

    Marianne E. Krasny

    2001-01-01

    Before starting any of the activities in this guide, we strongly recommend that you read the information in this section. Here we cover the critically important issues of how to handle amphibians and reptiles, and safety issues concerning these animals and field activities in general. We also discuss permits and regulations relating to the collecting, handling, and raising of herps. This free selection also includes the Table of Contents, Preface, and Introduction.

  15. How does Antiretroviral Therapy Affect HIV Mutation?

    NSDL National Science Digital Library

    Devin Iimoto (Whittier College; )

    2005-06-11

    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.

  16. “Risk factors associated with virologic failure in HIV-infected patients receiving antiretroviral therapy at a public hospital in Peru”

    PubMed Central

    Jorge, Alave R; Jorge, Paz B; Elsa, Gonzalez L; Miguel, Campos S; Rodriguez, Martin; Willig, James; Juan, Echevarría Z

    2013-01-01

    OBJECTIVE To describe clinical and biological characteristics of subjects with virologic failure who participated in the sexually transmitted diseases HIV/AIDS National Program from a Peruvian public hospital. MATERIALS AND METHODS An exploratory descriptive study was performed with data from subjects older than 18 who started high activity antiretroviral therapy (HAART) between May 2004 and December 2009 and who had a viral load control after 24 weeks of HAART. Virologic failure was defined as a viral load value above 1000 copies/mL on follow up after 24 weeks on HAART. RESULTS Of 1 478 records of patients on HAART analized, the median age was 35 years [IQR, 29-41] and 69.6% were male. Also, virologic failure occurred in 24% and 3.7% died. Of subjects with virologic failure, 9.5% died. On multivariate analysis, age, history of antiretroviral use before starting HAART, change of antiretroviral therapy due to toxicity, opportunistic infections during HAART, level of CD4 + lymphocytes below 100 cells/ml at start of HAART, adherence and clinical stage were independently associated with virologic failure. In the group of patient with no history of antiretroviral use before starting HAART, age, opportunistic infections during HAART were associated with virologic failure. CONCLUSION This study identified factors associated with virologic failure. Further studies are needed to evaluate whether the use of these factors can help to identify prospectively patients at high risk of failure, and to design interventions aimed to reduce this risk. PMID:23450408

  17. [Drug interactions with antiretroviral agents].

    PubMed

    Furlan, V; Taburet, A M

    2001-01-01

    Concomitant administration of three or more antiretroviral drugs is the standard treatment for HIV-infected patients. I.p. and NNRT are metabolized by cytochrome P450 and are inhibitors or inducers of CYP3A4. Therefore a number of drug-drug interactions are likely to occur. Ritonavir, a potent CYP3A4 inhibitor, is coadministered with saquinavir, indinavir and amprenavir to enhance their plasma concentrations and their virological efficacy. In contrast, nevirapine and efavirenz are CYP3A4 inducers, which warrant an increase in i.p. dosing. These properties lead to interactions with other drugs metabolized by CYP3A4 and a knowledge or the route of biotransformation is useful to avoid side-effects or decrease efficacy (as in the case of statine coadministration). Some important interactions can lead to contraindications such as coadministration of rifampicine, astemizole, ergot derivates or cizapride, as a large decrease or increase in concentration can lead to inefficacy or to major side-effects. Clinical trials and notification of side-effects are important to detect unpredictable interactions and to propose guidelines; such an example is therapeutic drug monitoring of methadone to avoid withdrawal syndrome when coadministered with ritonavir or nelfinavir. PMID:11475806

  18. HIV-1 Antiretroviral Drug Therapy

    PubMed Central

    Arts, Eric J.; Hazuda, Daria J.

    2012-01-01

    The most significant advance in the medical management of HIV-1 infection has been the treatment of patients with antiviral drugs, which can suppress HIV-1 replication to undetectable levels. The discovery of HIV-1 as the causative agent of AIDS together with an ever-increasing understanding of the virus replication cycle have been instrumental in this effort by providing researchers with the knowledge and tools required to prosecute drug discovery efforts focused on targeted inhibition with specific pharmacological agents. To date, an arsenal of 24 Food and Drug Administration (FDA)-approved drugs are available for treatment of HIV-1 infections. These drugs are distributed into six distinct classes based on their molecular mechanism and resistance profiles: (1) nucleoside-analog reverse transcriptase inhibitors (NNRTIs), (2) non–nucleoside reverse transcriptase inhibitors (NNRTIs), (3) integrase inhibitors, (4) protease inhibitors (PIs), (5) fusion inhibitors, and (6) coreceptor antagonists. In this article, we will review the basic principles of antiretroviral drug therapy, the mode of drug action, and the factors leading to treatment failure (i.e., drug resistance). PMID:22474613

  19. The latest in antiretroviral therapy.

    PubMed

    Temesgen, Zelalem

    2006-10-01

    The XVI International AIDS Conference (AIDS 2006), organized by the International AIDS Society (IAS), took place August 12-18 in Toronto, Canada. It was attended by over 26,000 participants from more than 170 countries and featured more than 4,500 abstracts as well as an array of community and cultural activities. The theme of the meeting was "Time to deliver", emphasizing the continued need and urgency in bringing effective HIV prevention and treatment strategies to those living with and affected by HIV/AIDS. The meeting's agenda was broad and included policy and programmatic topics as well as scientific research. This report focuses on reports presented at the conference that directly deal with antiretroviral therapy. This is primarily because of the nature of the venue where it is intended to be published (Drug News & Perspectives) as well as the expertise of the author. It is not a lack of recognition of the other equally important topics and discussions that took place at AIDS 2006. The author is solely responsible for the selection of topics and presentations to be included in this report. PMID:17160151

  20. HIV-1 Antiretroviral Drug Therapy Eric J. Arts1

    E-print Network

    Levin, Judith G.

    HIV-1 Antiretroviral Drug Therapy Eric J. Arts1 and Daria J. Hazuda2 1 Ugandan CFAR Laboratories will review the basic principles of antiretroviral drug therapy, the mode of drug action, and the factors leading to treatment failure (i.e., drug resistance). BASIC PRINCIPLES OF ANTIRETROVIRAL THERAPY Before

  1. Antiretrovirals to Prevent HIV Infection: Pre- and Postexposure Prophylaxis

    PubMed Central

    Gay, Cynthia L.; Cohen, Myron S.

    2013-01-01

    More than 3 million people are now receiving antiretroviral therapy (ART) worldwide. Currently, the indications for ART depend primarily on CD4 count, blood viral burden, and clinical signs and symptoms suggesting advanced HIV disease. However, interest is increasing in ART’s preventive potential. Postexposure prophylaxis following both occupational and nonoccupational exposure to HIV is the standard-of-care in many settings. Observational and ecologic studies suggest that ART administered to HIV-infected people reduces transmission within serodiscordant couples. Pre-exposure prophylaxis to prevent HIV infection is a potentially safe and intermittent intervention for very high-risk people, and clinical trials to evaluate this preventive strategy are underway. The prevention benefits of ART may begin to affect the decision of when to start therapy and add a much-needed strategy to current HIV prevention efforts. PMID:18765106

  2. Recent progress in antiretrovirals – lessons from resistance

    PubMed Central

    Adamson, Catherine S.; Freed, Eric O.

    2008-01-01

    Recent failures in efforts to develop an effective vaccine against HIV-1 infection have emphasized the importance of antiretroviral therapy in treating HIV-1-infected patients. Thus far, inhibitors of two viral enzymes, reverse transcriptase and protease, have had a profoundly positive impact on the survival of HIV-1-infected patients. However, new inhibitors that act at diverse steps in the viral replication cycle are urgently needed because of the development of resistance to currently available antiretrovirals. This review summarizes recent progress in antiretroviral drug discovery and development by specifically focusing on novel inhibitors of three phases of replication: viral entry, integration of the viral DNA into the host cell genome and virus particle maturation. PMID:18468560

  3. How Do I Start?

    MedlinePLUS

    ... track of HIV disease. They are the viral load test and the CD4 cell test. The viral load test (see fact sheet 125 ) helps show how ... fact sheets on antiretroviral therapies, CD4 and viral load tests, opportunistic infections, and living with HIV. This ...

  4. Antiretroviral penetration into the CNS and incidence of AIDS-defining neurologic conditions

    PubMed Central

    Cain, Lauren E.; Justice, Amy; Tate, Janet; Logan, Roger; Sabin, Caroline; Winston, Alan; van Sighem, Ard; Miro, Jose M.; Podzamczer, Daniel; Olson, Ashley; Arribas, José Ramón; Moreno, Santiago; Meyer, Laurence; del Romero, Jorge; Dabis, François; Bucher, Heiner C.; Wandeler, Gilles; Vourli, Georgia; Skoutelis, Athanasios; Lanoy, Emilie; Gasnault, Jacques; Costagliola, Dominique; Hernán, Miguel A.

    2014-01-01

    Objective: The link between CNS penetration of antiretrovirals and AIDS-defining neurologic disorders remains largely unknown. Methods: HIV-infected, antiretroviral therapy–naive individuals in the HIV-CAUSAL Collaboration who started an antiretroviral regimen were classified according to the CNS Penetration Effectiveness (CPE) score of their initial regimen into low (<8), medium (8–9), or high (>9) CPE score. We estimated “intention-to-treat” hazard ratios of 4 neuroAIDS conditions for baseline regimens with high and medium CPE scores compared with regimens with a low score. We used inverse probability weighting to adjust for potential bias due to infrequent follow-up. Results: A total of 61,938 individuals were followed for a median (interquartile range) of 37 (18, 70) months. During follow-up, there were 235 cases of HIV dementia, 169 cases of toxoplasmosis, 128 cases of cryptococcal meningitis, and 141 cases of progressive multifocal leukoencephalopathy. The hazard ratio (95% confidence interval) for initiating a combined antiretroviral therapy regimen with a high vs low CPE score was 1.74 (1.15, 2.65) for HIV dementia, 0.90 (0.50, 1.62) for toxoplasmosis, 1.13 (0.61, 2.11) for cryptococcal meningitis, and 1.32 (0.71, 2.47) for progressive multifocal leukoencephalopathy. The respective hazard ratios (95% confidence intervals) for a medium vs low CPE score were 1.01 (0.73, 1.39), 0.80 (0.56, 1.15), 1.08 (0.73, 1.62), and 1.08 (0.73, 1.58). Conclusions: We estimated that initiation of a combined antiretroviral therapy regimen with a high CPE score increases the risk of HIV dementia, but not of other neuroAIDS conditions. PMID:24907236

  5. China: government issues licences for three antiretrovirals.

    PubMed

    Elliott, Richard

    2002-12-01

    The Chinese government has approved the production and sale of at least three generic antiretroviral drugs used in treating people living with HIV/AIDS. The first applications were filed in late 2001 and approved in August and September 2002. PMID:14743801

  6. Progress in antiretroviral drug delivery using nanotechnology

    PubMed Central

    Mallipeddi, Rama; Rohan, Lisa Cencia

    2010-01-01

    There are currently a number of antiretroviral drugs that have been approved by the Food and Drug Administration for use in the treatment of human immunodeficiency virus (HIV). More recently, antiretrovirals are being evaluated in the clinic for prevention of HIV infection. Due to the challenging nature of treatment and prevention of this disease, the use of nanocarriers to achieve more efficient delivery of antiretroviral drugs has been studied. Various forms of nanocarriers, such as nanoparticles (polymeric, inorganic, and solid lipid), liposomes, polymeric micelles, dendrimers, cyclodextrins, and cell-based nanoformulations have been studied for delivery of drugs intended for HIV prevention or therapy. The aim of this review is to provide a summary of the application of nanocarrier systems to the delivery of anti-HIV drugs, specifically antiretrovirals. For anti-HIV drugs to be effective, adequate distribution to specific sites in the body must be achieved, and effective drug concentrations must be maintained at those sites for the required period of time. Nanocarriers provide a means to overcome cellular and anatomical barriers to drug delivery. Their application in the area of HIV prevention and therapy may lead to the development of more effective drug products for combating this pandemic disease. PMID:20957115

  7. Bones, Fractures, Antiretroviral Therapy and HIV

    PubMed Central

    Battalora, Linda A.; Young, Ben; Overton, Edgar T.

    2014-01-01

    The course of HIV infection has been dramatically transformed by the success of antiretroviral therapy from a universally fatal infection to a manageable chronic disease. With these advances in HIV disease management, age-related comorbidities, including metabolic bone disease, have become more prominent in the routine care of persons living with HIV infection. Recent data have highlighted the role of HIV, initiation of antiretroviral therapy (ART), and hepatitis C virus (HCV) co-infection in bone mineral density (BMD) loss and fracture incidence. Additionally, the underlying mechanism for the development of metabolic bone disease in the setting of HIV has received considerable attention. This review will highlight recently published and presented data and synthesize the current state of the field. These data highlight the need for proactive prevention for fragility fractures. PMID:24535243

  8. The Promise of Antiretrovirals for HIV Prevention

    PubMed Central

    Flash, Charlene; Krakower, Douglas; Mayer, Kenneth H.

    2013-01-01

    With an estimated 2.6 million new HIV infections diagnosed annually, the world needs new prevention strategies to partner with condom use, harm reduction approaches for injection drug users, and male circumcision. Antiretrovirals can reduce the risk of mother-to-child HIV transmission and limit HIV acquisition after occupational exposure. Macaque models and clinical trials demonstrate efficacy of oral or topical antiretrovirals used prior to HIV exposure to prevent HIV transmission, ie pre-exposure prophylaxis (PrEP). Early initiation of effective HIV treatment in serodiscordant couples results in a 96% decrease in HIV transmission. HIV testing to determine serostatus and identify undiagnosed persons is foundational to these approaches. The relative efficacy of different approaches, adherence, cost and long-term safety will affect uptake and impact of these strategies. Ongoing research will help characterize the role for oral and topical formulations and help quantify potential benefits in sub-populations at risk for HIV acquisition. PMID:22351302

  9. Providing antiretroviral care in conflict settings

    Microsoft Academic Search

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

    2009-01-01

    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 Frontičres experience in a variety\\u000a of African settings and also local nongovernmental

  10. Complications of HIV disease and antiretroviral therapy.

    PubMed

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

    2012-01-01

    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

  11. Long-term outcome of second-line antiretroviral therapy in resource-limited settings.

    PubMed

    Osinusi-Adekanmbi, Olukemi; Stafford, Kristen; Ukpaka, Adiba; Salami, Donald; Ajayi, Samuel; Ndembi, Nicaise; Abimiku, Alash'le; Nwizu, Chidi; Gilliam, Bruce; Redfield, Robert; Amoroso, Anthony

    2014-01-01

    There is limited information on efficacy and durability of second-line antiretroviral therapy (2NL) beyond 12 months in resource-limited settings. A total of 73 patients were enrolled into a prospective 2NL observational cohort in Nigeria. Second-line antiretroviral therapy consisted of lopinavir/ritonavir plus nucleoside reverse transcriptase inhibitors. Time on 2NL ranged from 15 to 31 months. Genotypes were retrospectively done and not available to guide second-line regimen choice. At enrollment, median CD4 count was 121 cells/mm3, and median time on first-line antiretroviral therapy (ISL) was 24 months. At 6 to 9 months on 2NL, 72.6% (intention to treat [ITT]) and 88.3% (on treatment [OT]) had an undetectable viral load (UDVL). At 12 months, 65.8% (ITT) and 90.57% (OT) had UDVL. At >12 to 24 months and at >24 months, 57.5% (ITT) and 91.3% (OT) had UDVL. No statistically significant association was observed between CD4 at 2NL start, sex, genotypic sensitivity score of 2NL, or tenofovir (TDF) use in ISL and viral suppression. Two patients developed major protease inhibitor mutations while on 2NL. We observed a high degree of viral suppression at 12 months and little loss of viral suppression thereafter. PMID:25513035

  12. Long-term outcome of second-line antiretroviral therapy in resource-limited settings.

    PubMed

    Osinusi-Adekanmbi, Olukemi; Stafford, Kristen; Ukpaka, Adiba; Salami, Donald; Ajayi, Samuel; Ndembi, Nicaise; Abimiku, Alash'le; Nwizu, Chidi; Gilliam, Bruce; Redfield, Robert; Amoroso, Anthony

    2014-01-01

    There is limited information on efficacy and durability of second-line antiretroviral therapy (2NL) beyond 12 months in resource-limited settings. A total of 73 patients were enrolled into a prospective 2NL observational cohort in Nigeria. Second-line antiretroviral therapy consisted of lopinavir/ritonavir plus nucleoside reverse transcriptase inhibitors. Time on 2NL ranged from 15 to 31 months. Genotypes were retrospectively done and not available to guide second-line regimen choice. At enrollment, median CD4 count was 121 cells/mm3, and median time on first-line antiretroviral therapy (ISL) was 24 months. At 6 to 9 months on 2NL, 72.6% (intention to treat [ITT]) and 88.3% (on treatment [OT]) had an undetectable viral load (UDVL). At 12 months, 65.8% (ITT) and 90.57% (OT) had UDVL. At >12 to 24 months and at >24 months, 57.5% (ITT) and 91.3% (OT) had UDVL. No statistically significant association was observed between CD4 at 2NL start, sex, genotypic sensitivity score of 2NL, or tenofovir (TDF) use in ISL and viral suppression. Two patients developed major protease inhibitor mutations while on 2NL. We observed a high degree of viral suppression at 12 months and little loss of viral suppression thereafter. PMID:24668134

  13. Virologic and Immunologic Parameters that Predict Clinical Response of AIDS-Associated Kaposi's Sarcoma to Highly Active Antiretroviral Therapy

    Microsoft Academic Search

    C. Pellet; S. Chevret; L. Blum; C. Gauville; M. Hurault; G. Blanchard; F. Agbalika; C. Lascoux; D. Ponscarme; P. Morel; F. Calvo; C. Lebbe

    2001-01-01

    The purpose of the work was to assess the predictive value of biologic factors on the efficacy of highly active antiretroviral therapy alone or combined with chemotherapy on AIDS-associated Kaposi's sarcoma. Twenty-six AIDS?Kaposi's sarcoma patients who started therapy with protease inhibitors were investigated. No baseline chemotherapy was associated with less severe initial clinical status. Median follow-up was 652 d. The

  14. Antiretroviral Therapy Initiation Before, During, or After Pregnancy in HIV1Infected Women: Maternal Virologic, Immunologic, and Clinical Response

    Microsoft Academic Search

    Vlada V. Melekhin; Bryan E. Shepherd; Samuel E. Stinnette; Peter F. Rebeiro; Gema Barkanic; Stephen P. Raffanti; Timothy R. Sterling; Landon Myer

    2009-01-01

    BackgroundPregnancy has been associated with a decreased risk of HIV disease progression in the highly active antiretroviral therapy (HAART) era. The effect of timing of HAART initiation relative to pregnancy on maternal virologic, immunologic and clinical outcomes has not been assessed.MethodsWe conducted a retrospective cohort study from 1997–2005 among 112 pregnant HIV-infected women who started HAART before (N = 12),

  15. Antiretroviral pharmacokinetic profile: A review of sex differences

    Microsoft Academic Search

    Ighovwerha Ofotokun; Susan K. Chuck; Jane E. Hitti

    2007-01-01

    Background: Emerging evidence suggests that female sex may be associated with increased risk of developing antiretroviral toxicities. Although the mechanisms of sex-related antiretroviral pharmacodynamic differences remain poorly understood and may be multifactorial, they appear to be mediated through a common pathway of pharmacokinetic variability between the sexes.Objective: This article reviews sex differences in the pharmacokinetics of the major classes of

  16. Concise overview of the clinical pharmacokinetics of dideoxynucleoside antiretroviral agents

    Microsoft Academic Search

    David M. Burger; Pieter L. Meenhorst; Jos H. Beijnen

    1995-01-01

    In this paper aspects of the clinical pharmacokinetics of the antiretroviral agents zidovudine, didanosine and zalcitabine are reviewed. Special attention is paid to possibly altered pharmacokinetics in special circumstances, such as hepatic and renal dysfunction, pregnancy, stage of disease,etc. The dideoxynucleoside antiretroviral agents have some clinical pharmacokinetic properties in common (rapid absorption and elimination), but substantial differences exist in their

  17. KNOWLEDGE AQUIRED THROUGH INDEPENDENT RESEARCH Five Classes of Antiretroviral Drugs

    E-print Network

    Auerbach, Scott M.

    RESEARCH KNOWLEDGE AQUIRED THROUGH INDEPENDENT RESEARCH Five Classes of Antiretroviral Drugs CLASS DISCUSSION Algorithms to simulate the impact of drug combinations in HIV patients SCIENTIFIC Signaling Pathways of the Cell Effects of Antiretroviral Drugs in the Human Body Function of the Human

  18. Pharmacokinetics and drug–drug interactions of antiretrovirals: An update

    Microsoft Academic Search

    Laura Dickinson; Saye Khoo; David Back

    2010-01-01

    Current antiretroviral treatment has allowed HIV infection to become a chronic manageable condition with many HIV patients living longer. However, available antiretrovirals are not without limitations, for example the development of resistance and adverse effects. Consequently, new drugs in existing and novel classes are urgently required to provide viable treatment options to patients with few remaining choices. Darunavir, etravirine, maraviroc

  19. Update on antiretroviral therapy in paediatrics.

    PubMed

    Penazzato, Martina; Donŕ, Daniele; Wool, Pia-Sophie; Rampon, Osvalda; Giaquinto, Carlo

    2010-01-01

    This review provides an update on the most relevant issues concerning the current management of HIV infection in infants and children. Tremendous progress has been made over the last few years to diagnose and treat infants and children with HIV infection, yet much remains to be done. Every day there are nearly 1150 new infections in children under 15 years of age, more than 90% of them occurring in the developing world and most being the result of transmission from mother-to-child (WHO 2008). The comprehensive approach to preventing mother-to-child transmission (MTCT) has clearly reduced the number of children acquiring the infection in Western countries; while a further reduction of mother-to-child transmission should be aimed for personalized setting, specific intervention needs to be put in place and new efforts are now required in order to optimise treatment and care in HIV-infected children. The prompt initiation of treatment and a careful selection of first-line regimen, which considers potency as well as tolerability remain central. In addition, occurrence and prevention of opportunistic infections, adherence as well as long-term psychosocial consequences are becoming more and more relevant in the era of effective antiretroviral therapy. 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:19879898

  20. Antiretroviral drugs: Critical issues and recent advances

    PubMed Central

    Desai, Mira; Iyer, Geetha; Dikshit, R. K.

    2012-01-01

    Human immunodeficiency virus (HIV) infection is now recognized as a chronic illness. Although the success of highly active antiretroviral therapy is beyond question, several issues still persist. Since the drugs cannot eradicate the virus, cure is not yet possible, and patients have to maintain a lifelong adherence with the risk of toxic effects, drug-drug interactions and drug resistance. A clear understanding of the viral replication and its interaction with host cell factors has led to the development of a large number of effective antiretroviral drugs (ARVs). New drugs in the existing class such as apricitabine, elvucitabine and etravirine have shown promising results against HIV isolates resistant to first line drugs. These drugs have offered a new choice for patients with drug resistant disease. However, the impact of their long term use on safety is yet to be assessed. Novel drugs with unique mechanism of action such as CD4 receptor attachment inhibitors, maturation inhibitors, pharmacokinetic enhancers, capsid assembly inhibitors and lens epithelium derived growth factor inhibitors are still under development. Currently, ARVs, especially tenofovir and emtricitabine, are also being evaluated for prevention of sexual transmission of HIV-1. The initial results of an HIV prevention trial network are encouraging and have recommended the use of ARVs for pre-exposure prophylaxis. Thus, ARVs form the key component of HIV prevention and treatment strategy. This article discusses the challenges associated with HIV-1 treatment and updates several major advances in the development of ARVs. PMID:22701234

  1. Guidelines for antiretroviral therapy for HIV infection

    PubMed Central

    Rachlis, A R; Zarowny, D P

    1998-01-01

    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. PMID:9627563

  2. The Setpoint Study (ACTG A5217): Effect of Immediate Versus Deferred Antiretroviral Therapy on Virologic Set Point in Recently HIV-1–Infected Individuals

    PubMed Central

    DeGruttola, Victor; Sun, Xin; Fiscus, Susan A.; Del Rio, Carlos; Hare, C. Bradley; Markowitz, Martin; Connick, Elizabeth; Macatangay, Bernard; Tashima, Karen T.; Kallungal, Beatrice; Camp, Rob; Morton, Tia; Daar, Eric S.; Little, Susan

    2012-01-01

    (See the editorial commentary by Tossonian and Conway, on pages 10–12.) Background.?The benefits of antiretroviral therapy during early human immunodeficiency virus type 1 (HIV-1) infection remain unproved. Methods.?A5217 study team randomized patients within 6 months of HIV-1 seroconversion to receive either 36 weeks of antiretrovirals (immediate treatment [IT]) or no treatment (deferred treatment [DT]). Patients were to start or restart antiretroviral therapy if they met predefined criteria. The primary end point was a composite of requiring treatment or retreatment and the log10 HIV-1 RNA level at week 72 (both groups) and 36 (DT group). Results.?At the June 2009 Data Safety Monitoring Board (DSMB) review, 130 of 150 targeted participants had enrolled. Efficacy analysis included 79 individuals randomized ?72 weeks previously. For the primary end point, the IT group at week 72 had a better outcome than the DT group at week 72 (P = .005) and the DT group at week 36 (P = .002). The differences were primarily due to the higher rate of progression to needing treatment in the DT group (50%) versus the IT (10%) group. The DSMB recommended stopping the study because further follow-up was unlikely to change these findings. Conclusions.?Progression to meeting criteria for antiretroviral initiation in the DT group occurred more frequently than anticipated, limiting the ability to evaluate virologic set point. Antiretrovirals during early HIV-1 infection modestly delayed the need for subsequent treatment. Clinical Trials Registration.?NCT00090779. PMID:22180621

  3. Highly active antiretroviral treatment for the prevention of HIV transmission

    PubMed Central

    2010-01-01

    In 2007 an estimated 33 million people were living with HIV; 67% resided in sub-Saharan Africa, with 35% in eight countries alone. In 2007, there were about 1.4 million HIV-positive tuberculosis cases. Globally, approximately 4 million people had been given highly active antiretroviral therapy (HAART) by the end of 2008, but in 2007, an estimated 6.7 million were still in need of HAART and 2.7 million more became infected with HIV. Although there has been unprecedented investment in confronting HIV/AIDS - the Joint United Nations Programme on HIV/AIDS estimates $13.8 billion was spent in 2008 - a key challenge is how to address the HIV/AIDS epidemic given limited and potentially shrinking resources. Economic disparities may further exacerbate human rights issues and widen the increasingly divergent approaches to HIV prevention, care and treatment. HIV transmission only occurs from people with HIV, and viral load is the single greatest risk factor for all modes of transmission. HAART can lower viral load to nearly undetectable levels. Prevention of mother to child transmission offers proof of the concept of HAART interrupting transmission, and observational studies and previous modelling work support using HAART for prevention. Although knowing one's HIV status is key for prevention efforts, it is not known with certainty when to start HAART. Building on previous modelling work, we used an HIV/AIDS epidemic of South African intensity to explore the impact of testing all adults annually and starting persons on HAART immediately after they are diagnosed as HIV positive. This theoretical strategy would reduce annual HIV incidence and mortality to less than one case per 1000 people within 10 years and it would reduce the prevalence of HIV to less than 1% within 50 years. To explore HAART as a prevention strategy, we recommend further discussions to explore human rights and ethical considerations, clarify research priorities and review feasibility and acceptability issues. PMID:20205768

  4. Variable Impact on Mortality of AIDS-Defining Events Diagnosed during Combination Antiretroviral Therapy: Not All AIDS-Defining Conditions Are Created Equal

    PubMed Central

    2011-01-01

    Background The extent to which mortality differs following individual acquired immunodeficiency syndrome (AIDS)–defining events (ADEs) has not been assessed among patients initiating combination antiretroviral therapy. Methods We analyzed data from 31,620 patients with no prior ADEs who started combination antiretroviral therapy. Cox proportional hazards models were used to estimate mortality hazard ratios for each ADE that occurred in >50 patients, after stratification by cohort and adjustment for sex, HIV transmission group, number of anti-retroviral drugs initiated, regimen, age, date of starting combination antiretroviral therapy, and CD4+ cell count and HIV RNA load at initiation of combination antiretroviral therapy. ADEs that occurred in <50 patients were grouped together to form a “rare ADEs” category. Results During a median follow-up period of 43 months (interquartile range, 19–70 months), 2880 ADEs were diagnosed in 2262 patients; 1146 patients died. The most common ADEs were esophageal candidiasis (in 360 patients), Pneumocystis jiroveci pneumonia (320 patients), and Kaposi sarcoma (308 patients). The greatest mortality hazard ratio was associated with non-Hodgkin’s lymphoma (hazard ratio, 17.59; 95% confidence interval, 13.84–22.35) and progressive multifocal leukoencephalopathy (hazard ratio, 10.0; 95% confidence interval, 6.70–14.92). Three groups of ADEs were identified on the basis of the ranked hazard ratios with bootstrapped confidence intervals: severe (non-Hodgkin’s lymphoma and progressive multifocal leukoencephalopathy [hazard ratio, 7.26; 95% confidence interval, 5.55–9.48]), moderate (cryptococcosis, cerebral toxoplasmosis, AIDS dementia complex, disseminated Mycobacterium avium complex, and rare ADEs [hazard ratio, 2.35; 95% confidence interval, 1.76–3.13]), and mild (all other ADEs [hazard ratio, 1.47; 95% confidence interval, 1.08–2.00]). Conclusions In the combination antiretroviral therapy era, mortality rates subsequent to an ADE depend on the specific diagnosis. The proposed classification of ADEs may be useful in clinical end point trials, prognostic studies, and patient management. PMID:19275498

  5. Why Kids Start

    MedlinePLUS

    ... Home > Stop Smoking > About Smoking > Preventing Smoking Why Kids Start Almost 70% of adult smokers began smoking ... the time they turn 14. So why do kids start smoking in the first place? Their parents ...

  6. Starting Treatment in Pediatric HIV Infection: Try to Clarify a Gray Area.

    PubMed

    Prato, Manuela; Venturini, Elisabetta; Chiappini, Elena; de Martino, Maurizio; Galli, Luisa

    2015-05-01

    The introduction of combination antiretroviral therapy (ART) in HIV-infected children led to a dramatic reduction in HIV-related morbidity and mortality. The decision about which ART regimen to use on children and when to start the treatment needs to focus on assuring normal growth and neuropsychological development. According to the available treatment guidelines, all infants under 1 year of age with HIV should be started on an ART at diagnosis. It is difficult to balance between the benefits of providing treatment to asymptomatic children >1 year and the concerns about long-term resistance and antiretroviral drug side effects if the treatment is started too early. Current guidelines agree that the need for antiretroviral treatment among asymptomatic children >12 months depends on age-specific CD4+ T-cell count thresholds and viral loads. Recent studies showed that the introduction of combination ART during the first year of life preserves a good function of B-cell and T-cell compartments. Starting treatment earlier might have fundamental roles both in preserving the not yet depleted immune function and in preventing the progressive HIV encephalopathy. The comparison of the international guidelines available for starting HIV treatment in children in developed countries highlights a gray area. New randomized controlled studies are needed to clarify the appropriate approach in asymptomatic children between 2 and 5 years of age. PMID:25886774

  7. The Head Start Debates

    ERIC Educational Resources Information Center

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

    2004-01-01

    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…

  8. Nevada Head Start, 2002.

    ERIC Educational Resources Information Center

    Biagi, Kathy

    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,…

  9. Plasma and Intracellular Antiretroviral Concentrations in HIV-Infected Patients under Short Cycles of Antiretroviral Therapy

    PubMed Central

    Zehnacker, Laura; Abe, Emuri; Mathez, Dominique; Alvarez, Jean-Claude; Leibowitch, Jacques; Azoulay, Stéphane

    2014-01-01

    Study of plasma and intracellular concentrations of atazanavir, lopinavir, nevirapine, and efavirenz was conducted on 48 patients under short cycles of antiretroviral therapy. Intracellular concentrations (IC) were still measurable for all drugs after 85?h or 110?h drug intake despite the absence of drug in plasma for atazanavir and lopinavir. A linear relationship between plasma and intracellular efavirenz was observed. Further studies to fully understand the impact of IC in the intermittent antiviral treatment are required. PMID:25431661

  10. Starting Antiretroviral Treatment Early Improves Outcomes for HIV-Infected Individuals

    MedlinePLUS

    ... AIDS Treatment Network and government organizations based in Australia, Denmark, and the United Kingdom. The Medical Research ... the University of New South Wales in Sydney, Australia; and the Veterans Affairs Medical Center affiliated with ...

  11. [Mitochondrial hepatic toxicity associated with antiretroviral treatment].

    PubMed

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

    2005-09-01

    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

  12. Antiretroviral Drugs Used in the Treatment of HIV Infection

    MedlinePLUS

    ... Health and Human Services FDA U.S. Food and Drug Administration Protecting and Promoting Your Health A to ... Condition Information HIV/AIDS HIV/AIDS Treatment Antiretroviral drugs used in the treatment of HIV infection Drugs ...

  13. Microneedle delivery for improved efficacy of antiretroviral and antibiotic drugs

    E-print Network

    Stauber, Zachary Jason

    2012-01-01

    Two classes of drugs, antiretrovirals and antibiotics, could benefit greatly from delivery through microneedles. Microneedles (MN) offer an increase in efficacy for these drugs by providing delivery to the lymphatic system ...

  14. Stigma trajectories among people living with HIV (PLHIV) embarking on a life time journey with antiretroviral drugs in Jinja, Uganda

    E-print Network

    Mbonye, Martin; Nakamanya, Sarah; Birungi, Josephine; King, Rachel; Seeley, Janet; Jaffar, Shabbar

    2013-01-01

    on antiretroviral therapy (ART). We describe the stigmaroll out of antiretroviral therapy (ART) in many Sub-SaharanART adherence counselling should reflect changing causes and manifestations of stigma over time. Keywords: Stigma, Antiretroviral therapy,

  15. Sex Differences in Antiretroviral Therapy Initiation in Pediatric HIV Infection

    PubMed Central

    Swordy, Alice; Mori, Luisa; Laker, Leana; Muenchhoff, Maximilian; Matthews, Philippa C.; Tudor-Williams, Gareth; Lavandier, Nora; van Zyl, Anriette; Hurst, Jacob; Walker, Bruce D.; Ndung’u, Thumbi; Prendergast, Andrew; Goulder, Philip; Jooste, Pieter

    2015-01-01

    The incidence and severity of infections in childhood is typically greater in males. The basis for these observed sex differences is not well understood, and potentially may facilitate novel approaches to reducing disease from a range of conditions. We here investigated sex differences in HIV-infected children in relation to antiretroviral therapy (ART) initiation and post-treatment outcome. In a South African cohort of 2,101 HIV-infected children, we observed that absolute CD4+ count and CD4% were significantly higher in ART-naďve female, compared to age-matched male, HIV-infected children. Absolute CD4 count and CD4% were also significantly higher in HIV-uninfected female versus male neonates. We next showed that significantly more male than female children were initiated on ART (47% female); and children not meeting criteria to start ART by >5yrs were more frequently female (59%; p<0.001). Among ART-treated children, immune reconstitution of CD4 T-cells was more rapid and more complete in female children, even after adjustment for pre-ART absolute CD4 count or CD4% (p=0.011, p=0.030, respectively). However, while ART was initiated as a result of meeting CD4 criteria less often in females (45%), ART initiation as a result of clinical disease in children whose CD4 counts were above treatment thresholds occurred more often in females (57%, p<0.001). The main sex difference in morbidity observed in children initiating ART above CD4 thresholds, above that of TB disease, was as a result of wasting and stunting observed in females with above-threshold CD4 counts (p=0.002). These findings suggest the possibility that optimal treatment of HIV-infected children might incorporate differential CD4 treatment thresholds for ART initiation according to sex. PMID:26151555

  16. Head Start in Transition.

    ERIC Educational Resources Information Center

    Lubeck, Sally; And Others

    1997-01-01

    Explores history of Head Start and, to create another way of conceiving of the organization, shifting definitions and conflicting interpretations of parental involvement and staff development. Also draws on interviews with women involved with Head Start and concludes that the certainty and stability characterizing public policy since Enlightenment…

  17. Effect of Improved access to Antiretroviral Therapy on clinical characteristics of patients enrolled in the HIV care and treatment clinic, at Muhimbili National Hospital (MNH), Dar es Salaam, Tanzania

    Microsoft Academic Search

    Sabina F. Mugusi; Julius C. Mwita; Joel M. Francis; Said Aboud; Muhammad Bakari; Eric A. Aris; Andrew B. Swai; Ferdinand M. Mugusi; Kisali Pallangyo; Eric Sandstrom

    2010-01-01

    BACKGROUND: Sub-Saharan Africa has been severely affected by the HIV and AIDS pandemic. Global efforts at improving care and treatment has included scaling up use of antiretroviral therapy (ART). In Tanzania, HIV care and treatment program, including the provision of free ART started in 2004 with a pilot program at Muhimbili National Hospital in Dar es Salaam. This study describes

  18. [Antiretroviral treatment adherence and its association with TCD4+ lymphocyte subsets in children with HIV/AIDS].

    PubMed

    Balbaryski, Jeannette; Simonte, Karina; Urteneche, Inés; Candi, Marcela; Gaddi, Eduardo; Barboni, Graciela

    2013-01-01

    Human immunodeficiency virus infection causes a severe depletion of TCD4+ lymphocytes and a sustained immune activation state, hallmarks findings that led to numerical and phenotypic changes in the TCD4+ subsets. Highly active anti-retroviral therapy has substantially modified the course of HIV infection. Correct adherence to the treatment results in a decrease in viral load at undetectable levels and a significant increase in the number of peripheral T cell lymphocytes. In the present study association between changes in T cell subsets and treatment adherence was evaluated in 28 HIV (+) infected children, before and after 9 months on average, from starting anti-retroviral therapy. The group of 18 patients with good adherence, above 95%, showed a significant increase in CD4+CD45RA+CD62L+ naive cells percentual levels and a decrease in the CD4+CD45RA-CD62L+ central memory subset, between the two points of the follow-up period. Conversely, 10 children with failure in the adherence did not show significant differences in the percentual levels of both subsets. Improvement in the percentage of adherence among paediatric population, optimizing antiretroviral treatment, allows a quick and significant reduction of viral replication. This feature is associated with the progressive reconstitution of the immune system. PMID:23924530

  19. The Strategic Use of Antiretrovirals to Prevent HIV Infection: A Converging Agenda.

    PubMed

    Baggaley, Rachel; Doherty, Meg; Ball, Andrew; Ford, Nathan; Hirnschall, Gottfried

    2015-06-01

    There is a clear convergence toward an overarching strategic use of antiretroviral drugs to prevent human immunodeficiency virus (HIV) infection. Four interventions-immediate antiretroviral therapy (ART) for the infected partner in a serodiscordant couple, preexposure prophylaxis (PrEP), prevention of mother-to-child transmission (PMTCT), and postexposure prophylaxis (PEP)-are all strongly recommended by the World Health Organization as effective ways to prevent HIV infection. For HIV-infected individuals, ART to protect an HIV-uninfected partner and PMTCT are both part of an expanding list of recommendations for starting ART immediately to both treat and prevent HIV infection. For HIV-uninfected individuals, PrEP and PEP are increasingly being seen as related interventions, and there are compelling reasons to consider the provision of PEP as a potential gateway to PrEP. The effectiveness of each of these interventions depends on overcoming barriers to seeking services, adequate community understanding and engagement, high levels of access and uptake of services including HIV testing and counselling, and high levels of adherence. PMID:25972496

  20. Antiretroviral procurement and supply chain management.

    PubMed

    Ripin, David J; Jamieson, David; Meyers, Amy; Warty, Umesh; Dain, Mary; Khamsi, Cyril

    2014-01-01

    Procurement, the country-level process of ordering antiretrovirals (ARVs), and supply chain management, the mechanism by which they are delivered to health-care facilities, are critical processes required to move ARVs from manufacturers to patients. To provide a glimpse into the ARV procurement and supply chain, the following pages provide an overview of the primary stakeholders, principal operating models, and policies and regulations involved in ARV procurement. Also presented are key challenges that need to be addressed to ensure that the supply chain is not a barrier to the goal of universal coverage. This article will cover the steps necessary to order and distribute ARVs, including different models of delivery, key stakeholders involved, strategic considerations that vary depending on context and policies affecting them. The single drug examples given illustrate the complications inherent in fragmented supply and demand-driven models of procurement and supply chain management, and suggest tools for navigating these hurdles that will ultimately result in more secure and reliable ARV provision. Understanding the dynamics of ARV supply chain is important for the global health community, both to ensure full and efficient treatment of persons living with HIV as well as to inform the supply chain decisions for other public health products. PMID:25310145

  1. Cerebrospinal Fluid HIV Escape from Antiretroviral Therapy.

    PubMed

    Ferretti, Francesca; Gisslen, Magnus; Cinque, Paola; Price, Richard W

    2015-06-01

    CNS infection is a nearly constant facet of systemic CNS infection and is generally well controlled by suppressive systemic antiretroviral therapy (ART). However, there are instances when HIV can be detected in the cerebrospinal fluid (CSF) despite suppression of plasma viruses below the clinical limits of measurement. We review three types of CSF viral escape: asymptomatic, neuro-symptomatic, and secondary. The first, asymptomatic CSF escape, is seemingly benign and characterized by lack of discernable neurological deterioration or subsequent CNS disease progression. Neuro-symptomatic CSF escape is an uncommon, but important, entity characterized by new or progressive CNS disease that is critical to recognize clinically because of its management implications. Finally, secondary CSF escape, which may be even more uncommon, is defined by an increase of CSF HIV replication in association with a concomitant non-HIV infection, as a consequence of the local inflammatory response. Understanding these CSF escape settings not only is important for clinical diagnosis and management but also may provide insight into the CNS HIV reservoir. PMID:25860317

  2. Antiretroviral Activity of Ancestral TRIM5??

    PubMed Central

    Goldschmidt, Valérie; Ciuffi, Angela; Ortiz, Millan; Brawand, David; Muńoz, Miguel; Kaessmann, Henrik; Telenti, Amalio

    2008-01-01

    The antiretroviral protein TRIM5? is known to have evolved different restriction capacities against various retroviruses, driven by positive Darwinian selection. However, how these different specificities have evolved in the primate lineages is not fully understood. Here we used ancestral protein resurrection to estimate the evolution of antiviral restriction specificities of TRIM5? on the primate lineage leading to humans. We used TRIM5? coding sequences from 24 primates for the reconstruction of ancestral TRIM5? sequences using maximum-likelihood and Bayesian approaches. Ancestral sequences were transduced into HeLa and CRFK cells. Stable cell lines were generated and used to test restriction of a panel of extant retroviruses (human immunodeficiency virus type 1 [HIV-1] and HIV-2, simian immunodeficiency virus [SIV] variants SIVmac and SIVagm, and murine leukemia virus [MLV] variants N-MLV and B-MLV). The resurrected TRIM5? variant from the common ancestor of Old World primates (Old World monkeys and apes, ?25 million years before present) was effective against present day HIV-1. In contrast to the HIV-1 restriction pattern, we show that the restriction efficacy against other retroviruses, such as a murine oncoretrovirus (N-MLV), is higher for more recent resurrected hominoid variants. Ancestral TRIM5? variants have generally limited efficacy against HIV-2, SIVagm, and SIVmac. Our study sheds new light on the evolution of the intrinsic antiviral defense machinery and illustrates the utility of functional evolutionary reconstruction for characterizing recently emerged protein differences. PMID:18077724

  3. 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

    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

    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.

  4. The changing face of AIDS-related opportunism: Cryptococcosis in the highly active antiretroviral therapy (HAART) era. Case reports and literature review

    Microsoft Academic Search

    Roberto Manfredi; Federica Pieri; Stefano A. Pileri; Francesco Chiodo

    2000-01-01

    Only nine cases of AIDS-related cryptococcosis have been reported until now in patients receiving highly active antiretroviral therapy (HAART),all of them with abnormal clinical features. Two HIV-infected patients who experienced an atypical relapse of cryptococcosis shortly after the start of HAART and despite maintenance antifungal treatment, are described. Six different relapses of cryptococcal meningitis were observed in a 28-month period

  5. Start School Later

    NSDL National Science Digital Library

    Last month, Pediatrics, the official journal of the American Academy of Pediatrics (AAP), issued a formal policy statement concerning School Start Times for Adolescents (http://pediatrics.aappublications.org/content/early/2014/08/19/peds.2014-1697.abstract?sid=3f739b0e-a552-4a4a-bd0a-907809e20255). In essence, the AAP called for schools to start later, citing sleep deprivation among teenagers as â??an important public health issue.â?ť This site from Start School Later, a group advocating for â??health, safety and equity in education,â?ť provides good, if somewhat one-sided, information on the topic. If youâ??re unfamiliar, start with Research & Info, which provides links to a number of informative sites about adolescent sleep needs and the impact of early school start times. Success Stories takes readers to schools around the country that have experimented with, and benefited from, later start times. If you're inspired, you can also Get Involved. Whatever your position on the issue, this is an informative and interesting site.

  6. Appropriateness of antiretroviral therapy in clients of an HIV\\/AIDS case management organization

    Microsoft Academic Search

    W. C. Holmes; J. L. Pace; I. Frank

    2007-01-01

    We sought to assess appropriateness of antiretroviral therapy (ART) reported by clients of an HIV\\/AIDS case management organization and identify variables associated with appropriate ART receipt. A total of 295 such clients were mailed a survey asking them to identify antiretroviral medications they were taking.Of them 220 (75%) returned surveys; 201 (93%) were taking antiretrovirals. Of these, 159 were on

  7. HIV and Perceptions of Mortality Risk: Learning from the Provision of Antiretroviral Therapy

    E-print Network

    Mateo, Jill M.

    provision of antiretroviral therapies (ART), which dramatically slow the progression of the disease, has (CITE). Without receiving antiretroviral therapy (ART), a person who contracts HIV may live for 10HIV and Perceptions of Mortality Risk: Learning from the Provision of Antiretroviral Therapy

  8. AIDS . Author manuscript Switching to second-line antiretroviral therapy in resource-limited settings

    E-print Network

    Paris-Sud XI, Université de

    (VL) is routinely measured to detect failure of antiretroviral therapy (ART) and guide switching the prognosis of HIV infection has improved considerably since highly active antiretroviral therapy (ARTAIDS . Author manuscript Page /1 9 Switching to second-line antiretroviral therapy in resource

  9. Antiretroviral HIV treatment and care for injecting drug users: an evidence-based overview

    E-print Network

    Paris-Sud XI, Université de

    1 COMMENTARY Antiretroviral HIV treatment and care for injecting drug users: an evidence the advent of highly-active antiretroviral treatment (HAART). The overall benefit from antiretroviral HIV treatment has, however, been lesser in HIV-infected IDUs than in other patient groups (e.g. men who have sex

  10. Ophthalmic manifestations of HIV in the highly active anti-retroviral therapy era.

    PubMed

    Mowatt, L

    2013-01-01

    HIV-related eye disease can be classified as retinal HIV microangiopathy, opportunistic infections, neuro-ophthalmic manifestations and unusual malignancies. There is a 52-100% lifetime accumulative risk of HIV patients developing eye problems. Seventy-seven per cent of patients with ocular manifestations of HIV had CD4 counts < 200 cells/?L. Cytomegalovirus (CMV) is the most prevalent opportunistic infection, however, Africa has a low incidence of this, and more commonly squamous cell carcinoma, compared to the western hemisphere. Due to highly active antiretroviral therapy (HAART), the anti-CMV therapy may be discontinued if the CD4+ T cell count is > 100 cells/?L for a minimum of three months. Despite HAART, patients with a CD4 count < 50 cells/?L have a similar risk of developing CMV retinitis as compared to the pre-HAART era. Opportunistic infections include CMV, herpetic retinopathy (progressive outer retinal necrosis - PORN), less commonly toxoplasmosis, pneumocystis and cryptococcus. Malignancies associated with HIV include Kaposi's sarcoma and conjunctival squamous cell carcinoma. Cranial nerve palsies, optic disc swelling and atrophy are characteristic neuro-ophthalmic features. They usually occur secondary to meningitis/encephalitis (from cryptococcus and tuberculosis). With the advent of HAART, new complications have developed in CMV retinitis: immune recovery uveitis (IRU) and cystoid macula oedema (CMO). Immune recovery uveitis occurs in 71% of patients if HAART is started before the induction of the anti-CMV treatment. However, this is reduced to 31% if HAART is started after the induction treatment. Molluscum contagiosum and Kaposi's sarcoma can spontaneously resolve on HAART. Highly active anti-retroviral therapy has reduced the frequencies of opportunistic infections and improved the remission duration in HIV patients. PMID:24756590

  11. French 2013 guidelines for antiretroviral therapy of HIV-1 infection in adults

    PubMed Central

    Hoen, Bruno; Bonnet, Fabrice; Delaugerre, Constance; Delobel, Pierre; Goujard, Cécile; L’Hénaff, Marianne; Persiaux, Renaud; Rey, David; Rouzioux, Christine; Taburet, Anne-Marie; Morlat, Philippe

    2014-01-01

    Introduction These guidelines are part of the French Experts’ recommendations for the management of people living with HIV/AIDS, which were made public and submitted to the French health authorities in September 2013. The objective was to provide updated recommendations for antiretroviral treatment (ART) of HIV-positive adults. Guidelines included the following topics: when to start, what to start, specific situations for the choice of the first session of antiretroviral therapy, optimization of antiretroviral therapy after virologic suppression, and management of virologic failure. Methods Ten members of the French HIV 2013 expert group were responsible for guidelines on ART. They systematically reviewed the most recent literature. The chairman of the subgroup was responsible for drafting the guidelines, which were subsequently discussed within, and finalized by the whole expert group to obtain a consensus. Recommendations were graded for strength and level of evidence using predefined criteria. Economic considerations were part of the decision-making process for selecting preferred first-line options. Potential conflicts of interest were actively managed throughout the whole process. Results ART should be initiated in any HIV-positive person, whatever his/her CD4 T-cell count, even when >500/mm3. The level of evidence of the individual benefit of ART in terms of mortality or progression to AIDS increases with decreasing CD4 cell count. Preferred initial regimens include two nucleoside reverse transcriptase inhibitors (tenofovir/emtricitabine or abacavir/lamivudine) plus a non-nucleoside reverse transcriptase inhibitor (efavirenz or rilpivirine), or a ritonavir-boosted protease inhibitor (atazanavir or darunavir). Raltegravir, lopinavir/r, and nevirapine are recommended as alternative third agents, with specific indications and restrictions. Specific situations such as HIV infection in women, primary HIV infection, severe immune suppression with or without identified opportunistic infection, and person who injects drugs are addressed. Options for optimization of ART once virologic suppression is achieved are discussed. Evaluation and management of virologic failure are described, the aim of any intervention in such situation being to reduce plasma viral load to <50 copies/ml. Conclusion These guidelines recommend that any HIV-positive individual should be treated with ART. This recommendation was issued both for the patient’s own sake and for promoting treatment as prevention. PMID:24942364

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

    PubMed Central

    Broder, Samuel

    2010-01-01

    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. PMID:20018391

  13. The next generation of the World Health Organization's global antiretroviral guidance

    PubMed Central

    Hirnschall, Gottfried; Harries, Anthony D; Easterbrook, Philippa J; Doherty, Meg C; Ball, Andrew

    2013-01-01

    The 2013 World Health Organization’s (WHO) Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection provide more than 50 new recommendations across the continuum of HIV care, including recommendations on HIV testing, using antiretroviral drugs for prevention, linking individuals to HIV care and treatment services, initiating and maintaining antiretroviral therapy (ART) and monitoring treatment. Guidance is provided across all age groups and populations of adults, pregnant and breastfeeding women, adolescents and key populations. The guidelines are based on a public health approach to expanding the use of ARV drugs for HIV treatment and prevention, with a particular focus on resource-limited settings. The most important new clinical recommendations include: treating adults, adolescents and older children earlier – starting ART in all individuals with a CD4 cell count of 500 cells/mm3 or less (but giving priority to those with advanced clinical disease or a CD4 cell count less than 350 cells/mm3); starting ART at any CD4 cell count in certain populations, including those with active TB (existing recommendation), Hepatitis B infection and severe chronic liver disease, HIV-positive partners in serodiscordant couples (existing recommendation), pregnant and breastfeeding women, and children younger than 5 years of age; a preferred first-line ART regimen of Tenofovir+3TC or FTC+ Efavirenz as a once-daily fixed-dose combination for adults, pregnant women, and children aged 3 years and older; and the use of viral load testing as the preferred approach to monitoring the response to ART and to diagnose treatment failure. Guidance is also provided on enhancing the efficiency and effectiveness of HIV services, including strategies to improve retention in care, and adherence to ART; task-shifting to address human resource gaps; decentralizing delivery of ART to primary health care, and integrating ART services within maternal and child health, TB or drug dependency clinics. There is additional guidance for programme managers on how to plan HIV programmes and use resources most efficiently. PMID:23819908

  14. Antiretroviral Therapy as HIV Prevention: Status and Prospects

    PubMed Central

    Venkatesh, Kartik K.

    2010-01-01

    As antiretroviral treatment of HIV infection has become increasingly accessible, attention has focused on whether these drugs can used for prevention because of increased tolerability of newer medications, decreased cost, and the limitations of other approaches. We review the status of antiretroviral HIV prevention, including chemoprophylaxis, as well as the effects of treatment of infected individuals on prevention. It is possible that the life-saving agents that have transformed the natural history of AIDS can be a critical component of HIV prevention efforts, but their ultimate role in affecting HIV transmission dynamics remains to be defined. PMID:20724682

  15. In vivo assessment of antiretroviral therapy-associated side effects

    PubMed Central

    Ramos-Sanchez, Eduardo Milton; Goto, Hiro; Rivero, Dolores Helena Rodriguez Ferreira; Mauad, Thais; de Souza, Fernando Nogueira; Monteiro, Andrea Moreira; Gidlund, Magnus

    2014-01-01

    Antiretroviral therapy has been associated with side effects, either from the drug itself or in conjunction with the effects of human immunodeficiency virus infection. Here, we evaluated the side effects of the protease inhibitor (PI) indinavir in hamsters consuming a normal or high-fat diet. Indinavir treatment increased the hamster death rate and resulted in an increase in triglyceride, cholesterol and glucose serum levels and a reduction in anti-oxLDL auto-antibodies. The treatment led to histopathological alterations of the kidney and the heart. These results suggest that hamsters are an interesting model for the study of the side effects of antiretroviral drugs, such as PIs. PMID:25075786

  16. In vivo assessment of antiretroviral therapy-associated side effects.

    PubMed

    Ramos-Sanchez, Eduardo Milton; Goto, Hiro; Rivero, Dolores Helena Rodriguez Ferreira; Mauad, Thais; de Souza, Fernando Nogueira; Monteiro, Andrea Moreira; Gidlund, Magnus

    2014-07-01

    Antiretroviral therapy has been associated with side effects, either from the drug itself or in conjunction with the effects of human immunodeficiency virus infection. Here, we evaluated the side effects of the protease inhibitor (PI) indinavir in hamsters consuming a normal or high-fat diet. Indinavir treatment increased the hamster death rate and resulted in an increase in triglyceride, cholesterol and glucose serum levels and a reduction in anti-oxLDL auto-antibodies. The treatment led to histopathological alterations of the kidney and the heart. These results suggest that hamsters are an interesting model for the study of the side effects of antiretroviral drugs, such as PIs. PMID:25075786

  17. Antiretroviral activity of protease inhibitors against Toxoplasma gondii.

    PubMed

    Monzote, Lianet; Rodríguez, Marta; Alfonso, Yenisey; Cox, Raymundo

    2013-01-01

    The introduction of highly active antiretroviral therapy (HAART) has caused a marked reduction in the occurrence and severity of parasitic infections, including the toxoplasmic encephalitis (TE). These changes have been attributed to the restoration of cell-mediated immunity. This study was developed to examine the activity of six antiretroviral protease inhibitors (API) on Toxoplasma gondii tachyzoites. The six API showed anti-Toxoplasma activity, with IC50 value between 1.4 and 6.6 µg/mL. Further studies at the molecular level should be performed to clarify if the use of API could be beneficial or not for AIDS patients with TE. PMID:23328729

  18. Turning point Getting started

    E-print Network

    Uppsala Universitet

    Turning point Getting started To use clickers the program TurningPoint is used. TurningPoint is compatible with Powerpoint and to access TurningPoints functions simple open any powerpoint file through TurningPoint. You don't need to create the presentation in TurningPoint, apart from the questions. You can

  19. Getting started information)

    E-print Network

    Mumby, Peter J.

    in this workbook do not hesitate to ask your manager/supervisor. CASUAL INDUCTION WORKBOOK Print Services #12;Print Print Services What will you be doing? The type of tasks you will be carrying out will include. Page 2 Getting Started #12;Applying for shifts Page 3 Print Services Induction Workbook Please fill

  20. Start a Rock Collection

    NSDL National Science Digital Library

    American Museum of Natural History

    2012-06-26

    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.

  1. Starting in School

    ERIC Educational Resources Information Center

    Albertine, Susan

    2012-01-01

    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…

  2. "New Start at 45."

    ERIC Educational Resources Information Center

    Greenstein, Pearl

    1989-01-01

    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…

  3. Starting A Program.

    ERIC Educational Resources Information Center

    Costello, Phillip M.

    Many instructors and managers of adventure programs come to a time in their careers when they consider starting a program. In all cases, such a consideration begins with an idea. Evaluation of an idea's feasibility involves: (1) development of a program description that includes goals and objectives; (2) review of the proposal by others; (3)…

  4. StartMe

    NSDL National Science Digital Library

    The StartMe application gives Internet users the opportunity to create their own personal browser startpage with their favorite bookmarks and RSS feeds. The drag and drop interface is user-friendly, particularly for computer neophytes. Visitors can also incorporate extensions for popular browsers or tweak the appearance of their startpage as they see fit. This version is compatible with all operating systems.

  5. RESEARCH ARTICLE Open Access Prevalence, genetic diversity and antiretroviral

    E-print Network

    Paris-Sud XI, Université de

    -associated mutations among untreated HIV-1-infected pregnant women in Gabon, central Africa Mélanie Caron1 , Sonia to antiretroviral drugs, Untreated pregnant women, Gabon, Central Africa Background Human immunodeficiency virus described [2]. Previous studies showed that the HIV-1 pandemic originated in central Africa, where

  6. Evaluation of antiretrovirals in animal models of HIV infection

    Microsoft Academic Search

    Koen K. A. Van Rompay

    2010-01-01

    Animal models of HIV infection have played an important role in the development of antiretroviral drugs. Although each animal model has its limitations and never completely mimics HIV infection of humans, a carefully designed study allows experimental approaches that are not feasible in humans, but that can help to better understand disease pathogenesis and to provide proof-of-concept of novel intervention

  7. Clinical Pharmacokinetics of Antiretroviral Drugs in Older Persons

    PubMed Central

    Schoen, John C.; Erlandson, Kristine Mace

    2013-01-01

    Introduction Combination antiretroviral therapy has enabled HIV infected persons to reach older ages in high numbers. Hepatic and renal changes that normally occur with advancing age occur earlier and with higher incidence in HIV-infected individuals. A limited number of prospective controlled studies have demonstrated small reductions (17% to 41%) in lopinavir, atazanavir, and lamivudine clearance in older versus younger adults. A much larger number of retrospective studies in adults (age range ~20 to 60 years), including all antiretroviral drugs, have evaluated age as a covariate for pharmacokinetics. Most studies did not detect substantial associations between drug exposures and age. Areas Covered This review summarizes antiretroviral drug pharmacokinetics in older persons. The authors review articles from PubMed (search terms: elderly, antiretroviral, pharmacokinetics) in addition to the bibliographies of those selected. Expert Opinion The evidence to date does not support major pharmacokinetic changes in adults between ~20 and 60 years of age. However, additional prospective, well-controlled studies are needed in more persons > 60 years, including those with frailty and comorbidities, with assessment of unbound drug clearance, and incorporation of adherence, pharmacogenetics, and concomitant medications. Until then, guidelines for drug-drug interactions and dosing in renal and hepatic impairment should be followed in older HIV infected individuals. PMID:23514375

  8. Emergence of HIV-1 Drug Resistance During Antiretroviral Treatment

    E-print Network

    2007-04-20

    mune response in the emergence of drug resistance was investigated in (Shiri et al., ..... These coefficients measure the independent influence of each input pa- ..... exact same resources—uninfected target T cells, hence the resistant strain that becomes ...... the susceptibility of the virus to antiretroviral drugs in cell culture.

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

    PubMed Central

    2012-01-01

    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. PMID:18043315

  10. Early Antiretroviral Therapy in South African Children Reduces HIV-1-Infected Cells and Cell-Associated HIV-1 RNA in Blood Mononuclear Cells.

    PubMed

    van Zyl, Gert U; Bedison, Margaret A; van Rensburg, Anita Janse; Laughton, Barbara; Cotton, Mark F; Mellors, John W

    2015-07-01

    We measured cell-associated human immunodeficiency virus (HIV)-1 DNA (CAD) and RNA (CAR) and plasma HIV-1 RNA in blood samples from 20 children in the Children with HIV Early Antiretroviral (CHER) cohort after 7-8 years of suppressive combination antiretroviral therapy (cART). Children who initiated cART early (<2 months; n = 12) had lower HIV-1 CAD (median, 48 vs 216; P < .01) and CAR (median, 5 vs 436; P < .01) per million peripheral blood mononuclear cells than children who started later (?2 months; n = 8). Plasma HIV-1 RNA levels were not significantly lower in early-treated children (0.5 vs 1.2 copies/mL; P = .16). Early treatment at <2 months of age reduces the number of HIV-infected cells and HIV CAR. PMID:25538273

  11. A Start-up company to start your career

    E-print Network

    is not a `for-profit' business · But still must recoup costs · Harvard typically takes ~8% in equity · CompanyA Start-up company to start your career Professional Development Seminar March 6, 2013 #12;What is a start-up company? · Small, just started · Typically 1-5 years old · Often no products, no sales

  12. Systematic Review of Antiretroviral-Associated Lipodystrophy: Lipoatrophy, but Not Central Fat Gain, Is an Antiretroviral Adverse Drug Reaction

    PubMed Central

    de Waal, Reneé; Cohen, Karen; Maartens, Gary

    2013-01-01

    Background Lipoatrophy and/or central fat gain are observed frequently in patients on antiretroviral therapy (ART). Both are assumed to be antiretroviral adverse drug reactions. Methods We conducted a systematic review to determine whether fat loss or gain was more common in HIV-infected patients on ART than in uninfected controls; was associated with specific antiretrovirals; and would reverse after switching antiretrovirals. Results Twenty-seven studies met our inclusion criteria. One cohort study reported more lipoatrophy, less subcutaneous fat gain, but no difference in central fat gain in HIV-infected patients on ART than in controls. Randomised controlled trials (RCTs) showed more limb fat loss (or less fat gain) with the following regimens: stavudine (versus other nucleoside reverse transcriptase inhibitors (NRTIs)); efavirenz (versus protease inhibitors (PIs)); and NRTI-containing (versus NRTI-sparing). RCTs showed increased subcutaneous fat after switching to NRTI-sparing regimens or from stavudine/zidovudine to abacavir/tenofovir. There were no significant between-group differences in trunk and/or visceral fat gain in RCTs of various regimens, but results from efavirenz versus PI regimens were inconsistent. There was no significant between-group differences in central fat gain in RCTs switched to NRTI-sparing regimens, or from PI-containing regimens. Conclusions There is clear evidence of a causal relationship between NRTIs (especially thymidine analogues) and lipoatrophy, with concomitant PIs possibly having an ameliorating effect or efavirenz causing additive toxicity. By contrast, central fat gain appears to be a consequence of treating HIV infection, because it is not different from controls, is not linked to any antiretroviral class, and doesn't improve on switching. PMID:23723990

  13. Enhanced Antiretroviral Therapy in Rhesus Macaques Improves RT-SHIV Viral Decay Kinetics

    PubMed Central

    North, Thomas W.; Villalobos, Andradi; Hurwitz, Selwyn J.; Deere, Jesse D.; Higgins, Joanne; Chatterjee, Payel; Tao, Sijia; Kauffman, Robert C.; Luciw, Paul A.; Kohler, James J.

    2014-01-01

    Using an established nonhuman primate model, rhesus macaques were infected intravenously with a chimeric simian immunodeficiency virus (SIV) consisting of SIVmac239 with the human immunodeficiency virus type 1 (HIV-1) reverse transcriptase from clone HXBc2 (RT-SHIV). The impacts of two enhanced (four- and five-drug) highly active antiretroviral therapies (HAART) on early viral decay and rebound were determined. The four-drug combination consisted of an integrase inhibitor, L-870-812 (L-812), together with a three-drug regimen comprising emtricitabine [(?)-FTC], tenofovir (TFV), and efavirenz (EFV). The five-drug combination consisted of one analog for each of the four DNA precursors {using TFV, (?)-FTC, (?)-?-d-(2R,4R)-1,3-dioxolane-2,6-diaminopurine (amdoxovir [DAPD]), and zidovudine (AZT)}, together with EFV. A cohort treated with a three-drug combination of (?)-FTC, TFV, and EFV served as treated controls. Daily administration of a three-, four-, or five-drug combination of antiretroviral agents was initiated at week 6 or 8 after inoculation and continued up to week 50, followed by a rebound period. Plasma samples were collected routinely, and drug levels were monitored using liquid chromatography-tandem mass spectrometry (LC–MS-MS). Viral loads were monitored with a standard TaqMan quantitative reverse transcriptase PCR (qRT-PCR) assay. Comprehensive analyses of replication dynamics were performed. RT-SHIV infection in rhesus macaques produced typical viral infection kinetics, with untreated controls establishing persistent viral loads of >104 copies of RNA/ml. RT-SHIV loads at the start of treatment (V0) were similar in all treated cohorts (P > 0.5). All antiretroviral drug levels were measureable in plasma. The four-drug and five-drug combination regimens (enhanced HAART) improved suppression of the viral load (within 1 week; P < 0.01) and had overall greater potency (P < 0.02) than the three-drug regimen (HAART). Moreover, rebound viremia occurred rapidly following cessation of any treatment. The enhanced HAART (four- or five-drug combination) showed significant improvement in viral suppression compared to the three-drug combination, but no combination was sufficient to eliminate viral reservoirs. PMID:24777106

  14. StartUpNation

    NSDL National Science Digital Library

    It would seem that more and more people are interested in developing their own business, and a number of websites are dedicated to helping these persons achieve that goal. One valuable website in that realm is StartUpNation. Created by Jeff and Rich Sloan, the site contains a well-designed homepage that includes links to sections dedicated to areas of interest to the prospective entrepreneur, including those that deal with customer service and creating strategic marketing plans. A good place to start is the â??Lean from the Expertsâ?ť area, located on the left-hand side of the homepage. Here, visitors can learn from successful individuals, such as Glenn Coggeshell of Black Dot Coffee. Along the same side, visitors can also read about how to choose a business for themselves and also how to plan to make this business a reality. In keeping with the times, the site also affords users the opportunity to sign up for RSS feeds and the ability to listen (and download) a number of podcasts.

  15. Start Smart: Steps to Starting a Business Workshop Registration The Start Smart workshop will cover

    E-print Network

    Collins, Gary S.

    . ----------------------------------------------------------------------------------------------------------------------------------------------- START SMART REGISTRATION Name Daytime phone Address E-mail address City State Zip Optional: NameStart Smart: Steps to Starting a Business Workshop Registration The Start Smart workshop will cover and mail it with your check* or credit card information to: WSU Tri-Cities Business LINKS 2710 Crimson Way

  16. The obligation to provide antiretroviral treatment in HIV prevention trials.

    PubMed

    Lo, Bernard; Padian, Nancy; Barnes, Mark

    2007-06-19

    Providing antiretroviral therapy (ART) to participants who seroconvert during HIV prevention trials in developing countries is an ethical expectation. Promising treatment to the few seroconverters widens disparities within a resource-poor country and would be unjust. Such an assurance should be done in a way that also improves access to ART for others in the country. US funds for ART in poor countries from the PEPFAR should be available to all countries that host HIV prevention and clinical trials. PMID:17545698

  17. Antiretroviral Tissue Kinetics: In Vivo Imaging Using Positron Emission Tomography?

    PubMed Central

    Di Mascio, Michele; Srinivasula, Sharat; Bhattacharjee, Abesh; Cheng, Lily; Martiniova, Lucia; Herscovitch, Peter; Lertora, Juan; Kiesewetter, Dale

    2009-01-01

    Our current knowledge on the antiviral efficacy, dosing, and toxicity of available highly active antiretroviral therapy regimens is mostly derived from plasma or blood kinetics of anti-human immunodeficiency virus (anti-HIV) drugs. However, the blood comprises only 2% of the total target cells in the body. Tissue drug levels may differ substantially from corresponding plasma levels, and drug distribution processes may be characterized by high intertissue variability, leading to suboptimal target site concentrations and the potential risk for therapeutic failures. Positron emission tomography has greatly expanded the scope of the pharmacokinetic measurements that can be performed noninvasively in animal models or humans. We have prepared [18F]FPMPA, a fluorine-18-radiolabeled analogue of tenofovir, to study antiretroviral tissue kinetics in vivo noninvasively and tested the imaging probe in rats. The biodistribution of the fluorine-18 analogue closely follows that of nonfluorinated tenofovir. Compared to that in the blood, the levels of penetration of the antiretroviral drug were found to be significantly reduced in the spleen and submandibular lymph nodes (?2-fold), in the mesenteric lymph nodes and the testes (?4-fold), and in the brain compartment (?25-fold). Intersubject variability of the trough drug concentration (measured at 120 min) in certain tissues, like the colon (coefficient of variation, >100%), is not reflected by the intersubject variability in the blood compartment (coefficient of variation, 24%). Positron emission tomography imaging of the fluorine-18 analogue revealed the accumulation of the antiretroviral drug in the cortex of the kidneys, a potential correlate of tenofovir-induced nephrotoxicity observed in HIV-1-infected treated patients. Thus, [18F]FPMPA is a promising radiotracer for evaluation of tenofovir biodistribution under carefully controlled drug administration protocols. PMID:19667288

  18. Antiretroviral Outcomes in South African Prisoners: A Retrospective Cohort Analysis

    Microsoft Academic Search

    Natasha E. C. G. Davies; Alan S. Karstaedt

    2012-01-01

    Background and MethodsLittle is known about antiretroviral therapy (ART) outcomes in prisoners in Africa. We conducted a retrospective review of outcomes of a large cohort of prisoners referred to a public sector, urban HIV clinic. The review included baseline characteristics, sequential CD4 cell counts and viral load results, complications and co-morbidities, mortality and loss to follow-up up to 96 weeks

  19. Human Immunodeficiency Virus: Resistance to Antiretroviral Drugs in Developing Countries

    Microsoft Academic Search

    Rebecca F. Baggaley; Maya L. Petersen; Marcelo A. Soares; Marie-Claude Boily; Francisco I. Bastos

    \\u000a This chapter reviews issues central to understanding the emergence and transmission of drug-resistant human immunodeficiency\\u000a virus (HIV) and its impact on developing countries. We first give an overview of HIV, HIV treatment using antiretroviral drugs,\\u000a and access to treatment in developing countries. Then we review current understanding of the impact of adherence and treatment\\u000a interruption on the emergence of resistance

  20. [The pharmacoeconomics of antiretroviral drugs and the role of adherence].

    PubMed

    Bargiacchi, Olivia; Brondolo, Roberta; Rizzo, Giovanni; Garavelli, Pietro Luigi

    2012-12-01

    In the past decade health care expenses have increased by 50% in Italy, a country whose population mostly consists of people aged over 50 years old, the main users of health care services. Pharmaceutical expenditure is the main issue: monoclonal antibodies, biological immunosuppressants, antitumorals and antiretrovirals are the most expensive drugs. The cost of HIV/AIDS has remained constant during the last four years. Despite the increase in pharmaceutical costs, which made the infection chronic, hospitalization costs have been reduced. With sustainable economic development as a chiefly long-term target, a clinical governance system is nonetheless needed which also takes account of the adherence to antiretroviral therapy: thus poor adherence leads to a reduction in efficacy and at the same time an increase in welfare and community costs. Recently in SSvD "Prevention and cure of HIV infection and related syndromes" of "Maggiore della Caritŕ" University Hospital, Novara, adherence to antiretroviral therapy in 100 consecutive patients was evaluated. The results show that patients with high adherence to the treatment prescribed have a less expensive drug combination. Moreover, with better infection control and a higher immune recovery, they have less impact on social and health care costs. PMID:23299063

  1. Adverse effects of antiretroviral therapy for HIV infection.

    PubMed

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

    2004-01-20

    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

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

    PubMed Central

    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

    2013-01-01

    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

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

    PubMed Central

    2009-01-01

    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. PMID:19361855

  4. Prevalence of oral candidiasis in HIV/AIDS children in highly active antiretroviral therapy era. A literature analysis.

    PubMed

    Gaitán-Cepeda, Luis Alberto; Sánchez-Vargas, Octavio; Castillo, Nydia

    2015-08-01

    SummaryHighly active antiretroviral therapy has decreased the morbidity and mortality related to HIV infection, including oral opportunistic infections. This paper offers an analysis of the scientific literature on the epidemiological aspects of oral candidiasis in HIV-positive children in the combination antiretroviral therapy era. An electronic databases search was made covering the highly active antiretroviral therapy era (1998 onwards). The terms used were oral lesions, oral candidiasis and their combination with highly active antiretroviral therapy and HIV/AIDS children. The following data were collected from each paper: year and country in which the investigation was conducted, antiretroviral treatment, oral candidiasis prevalence and diagnostic parameters (clinical or microbiological). Prevalence of oral candidiasis varied from 2.9% in American HIV-positive children undergoing highly active antiretroviral therapy to 88% in Chilean HIV-positive children without antiretroviral therapy. With respect to geographical location and antiretroviral treatment, higher oral candidiasis prevalence in HIV-positive children on combination antiretroviral therapy/antiretroviral therapy was reported in African children (79.1%) followed by 45.9% reported in Hindu children. In HIV-positive Chilean children on no antiretroviral therapy, high oral candidiasis prevalence was reported (88%) followed by Nigerian children (80%). Oral candidiasis is still frequent in HIV-positive children in the highly active antiretroviral therapy era irrespective of geographical location, race and use of antiretroviral therapy. PMID:25156369

  5. Hydraulic type starting clutch

    SciTech Connect

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

    1987-07-14

    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 the input rotating member to the output rotating member; urging means interposed between the friction plates and the output rotating member for urging the friction plates to cause the transmission of torque from the input rotating member to the output rotating member; a hydraulic pressure chamber defined between the urging means and the output rotating member and disposed to be supplied with a hydraulic fluid for acting upon the urging means to urge the friction plates; a hydraulic fluid source for supplying the hydraulic fluid to the hydraulic pressure chamber; pressure regulating valve means for regulating the pressure of the hydraulic fluid in the hydraulic pressure chamber; and control means for controlling the pressure regulating valve means to regulate the pressure of the hydraulic fluid in the hydraulic pressure chamber so as to increase with an increase in the rotational speed of the input shaft, the control means.

  6. Maternal or Infant Antiretroviral Drugs to Reduce HIV-1 Transmission

    PubMed Central

    Chasela, Charles S.; Hudgens, Michael G.; Jamieson, Denise J.; Kayira, Dumbani; Hosseinipour, Mina C.; Kourtis, Athena P.; Martinson, Francis; Tegha, Gerald; Knight, Rodney J.; Ahmed, Yusuf I.; Kamwendo, Deborah D.; Hoffman, Irving F.; Ellington, Sascha R.; Kacheche, Zebrone; Soko, Alice; Wiener, Jeffrey B.; Fiscus, Susan A.; Kazembe, Peter; Mofolo, Innocent A.; Chigwenembe, Maggie; Sichali, Dorothy S.; van der Horst, Charles M.

    2012-01-01

    Background We evaluated the efficacy of a maternal triple-drug antiretroviral regimen or infant nevirapine prophylaxis for 28 weeks during breast-feeding to reduce postnatal transmission of human immunodeficiency virus type 1 (HIV-1) in Malawi. Methods We randomly assigned 2369 HIV-1–positive, breast-feeding mothers with a CD4+ lymphocyte count of at least 250 cells per cubic millimeter and their infants to receive a maternal antiretroviral regimen, infant nevirapine, or no extended postnatal antiretroviral regimen (control group). All mothers and infants received perinatal prophylaxis with single-dose nevirapine and 1 week of zidovudine plus lamivudine. We used the Kaplan–Meier method to estimate the cumulative risk of HIV-1 transmission or death by 28 weeks among infants who were HIV-1–negative 2 weeks after birth. Rates were compared with the use of the log-rank test. Results Among mother–infant pairs, 5.0% of infants were HIV-1–positive at 2 weeks of life. The estimated risk of HIV-1 transmission between 2 and 28 weeks was higher in the control group (5.7%) than in either the maternal-regimen group (2.9%, P = 0.009) or the infant-regimen group (1.7%, P<0.001). The estimated risk of infant HIV-1 infection or death between 2 and 28 weeks was 7.0% in the control group, 4.1% in the maternal-regimen group (P = 0.02), and 2.6% in the infant-regimen group (P<0.001). The proportion of women with neutropenia was higher among those receiving the antiretroviral regimen (6.2%) than among those in either the nevirapine group (2.6%) or the control group (2.3%). Among infants receiving nevirapine, 1.9% had a hypersensitivity reaction. Conclusions The use of either a maternal antiretroviral regimen or infant nevirapine for 28 weeks was effective in reducing HIV-1 transmission during breast-feeding. (ClinicalTrials.gov number, NCT00164736.) PMID:20554982

  7. Adherence to antiretroviral drug therapy in adult patients who are HIV-positive in Northwest Ethiopia: a study protocol

    PubMed Central

    Bezabhe, Woldesellassie M; Peterson, Gregory M; Bereznicki, Luke; Chalmers, Leanne; Gee, Peter

    2013-01-01

    Introduction Achievement of optimal medication adherence and management of antiretroviral toxicity pose great challenges among Ethiopian patients with HIV/AIDS. There is currently a lack of long-term follow-up studies that identify the barriers to, and facilitators of, adherence to antiretroviral therapy (ART) in the Ethiopian setting. Therefore, we aim to investigate the level of adherence to ART and a wide range of potential influencing factors, including adverse drug reactions occurring with ART. Methods and analysis We are conducting a 1-year prospective cohort study involving adult patients with HIV/AIDS starting on ART between December 2012 and March 2013. Data are being collected on patients’ appointment dates in the ART clinics. Adherence to ART is being measured using pill count, medication possession ratio and patient's self-report. The primary outcome of the study will be the proportion of patients who are adherent to their ART regimen at 3, 6 and 12?months using pill count. Taking 95% or more of the dispensed ART regimen using pill count at given points of time will be considered the optimal level of adherence in this study. Data will be analysed using descriptive and inferential statistical procedures. Ethics and dissemination Ethics approval was obtained from the Tasmania Health and Medical Human Research Ethics Committee and Bahir-Dar University's Ethics Committee. The results of the study will be reported in peer-reviewed scientific journals, conferences and seminar presentations. PMID:24176794

  8. Involving Parents in Head Start.

    ERIC Educational Resources Information Center

    Leik, Robert K.; Chalkley, Mary Anne

    1989-01-01

    The Head Start Family Impact Project involved a one-year study of 81 single mothers and their children from the Hennepin County Head Start Program. This program was planned to test the notion that parent-child interaction in the context of Head Start would be the most beneficial form of parental involvement. An assessment session, which measured…

  9. Maryland Early Head Start Initiative

    ERIC Educational Resources Information Center

    Center for Law and Social Policy, Inc. (CLASP), 2012

    2012-01-01

    Since 2000, Maryland has provided state supplemental funds to Head Start and Early Head Start (EHS) programs to improve access. Local EHS programs may use funds, through child care partnerships, to extend the EHS day or year. Maryland's approach to building on EHS includes: (1) Increase the capacity of existing Head Start and EHS programs to…

  10. High prevalence of lipoatrophy in pre-pubertal South African children on antiretroviral therapy: a cross-sectional study

    E-print Network

    2012-01-01

    of antiretroviral therapy (ART) in sub- Saharan Africa hasat antiretroviral therapy (ART) Median age at recruitment (Therapy For Hiv Infection In Adults And Adolescents; 2007. http://www.who.int/hiv/art/

  11. Impact of adherence counseling dose on antiretroviral adherence and HIV viral load among HIV-infected methadone maintained drug users

    Microsoft Academic Search

    Nina A. Cooperman; Moonseong Heo; Karina M. Berg; Xuan Li; Alain H. Litwin; Shadi Nahvi; Julia H. Arnsten

    2012-01-01

    Adherence counseling can improve antiretroviral adherence and related health outcomes in HIV-infected individuals. However, little is known about how much counseling is necessary to achieve clinically significant effects. We investigated antiretroviral adherence and HIV viral load relative to the number of hours of adherence counseling received by 60 HIV-infected drug users participating in a trial of directly observed antiretroviral therapy

  12. Uncertainty quantification for a model of HIV-1 patient response to antiretroviral therapy interruptions

    E-print Network

    with antiretroviral therapy (ART) can have disparate outcomes. A recent study showed that 11 HIV-1 patients maintained that are able to suppress HIV-1 after the termination of long-term ART therapy have low HIV-1 reservoirsUncertainty quantification for a model of HIV-1 patient response to antiretroviral therapy

  13. AIDS . Author manuscript Long-term immunologic response to antiretroviral therapy in low-income

    E-print Network

    Paris-Sud XI, Université de

    in resource-limited settings, where antiretroviral therapy (ART) is being scaled up using a public health to ART among patients remaining on therapy. Public health and programmatic interventions leading to antiretroviral therapy (ART) are important measures of the efficacy of ART in individual patients

  14. Evolution of Drug-resistant Viral Populations during Interruption of Antiretroviral Therapy

    E-print Network

    Ahlers, Guenter

    therapy (ART), some HIV-2 infected patients still fail treatment due to drug resistance, poor adherence1 Evolution of Drug-resistant Viral Populations during Interruption of Antiretroviral Therapy antiretroviral treatment (ART) interruption allows determination of the evolution of3 drug-resistant viruses

  15. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents

    E-print Network

    Levin, Judith G.

    therapy (ART). This new section provides an overview of costs as they relate to adherence, including important measure of response to ART, and should be monitored during therapy to assure consistent viral and Antiretroviral Therapy · In the past, this guideline has not formally discussed costs related to antiretroviral

  16. Transmission of HIV-1 minority resistant variants and response to first-line antiretroviral therapy

    E-print Network

    Paris-Sud XI, Université de

    of drug-resistant HIV-1 can impair the virological response to antiretroviral therapy (ART). Minority drugs (ARV) is one important factor limiting the effect of antiretroviral therapy (ART). In ART therapy O Peuchant 1 , R Thiébaut 2 , S Capdepont 1 , V Lavignolle-Aurillac 2 , D Neau 2,3 , P Morlat 3

  17. Early anthropometric and immunological success of antiretroviral therapy do not predict virological success in

    E-print Network

    Paris-Sud XI, Université de

    therapy (ART) is a critical step. In sub-Saharan Africa, few people have access to plasma viral load (VL of antiretroviral therapy (ART) is to suppress human immunodeficiency virus (HIV) replication. This is consideredPage 1 Early anthropometric and immunological success of antiretroviral therapy do not predict

  18. Evolution and recombination of genes encoding HIV-1 drug resistance and tropism during antiretroviral therapy

    E-print Network

    Suchard, Marc A.

    therapy (ART) is a high priority to improve understanding of HIV-1 pathogenesis and therapy. To understand antiretroviral therapy (ART) in some infected individuals resulting in the emergence of drug resistance mutations et al., 2008). Combination antiretroviral therapy (cART) has been successful in suppressing HIV-1

  19. What we know and what we do not know about factors associated with and interventions to promote antiretroviral adherence.

    PubMed

    Mannheimer, Sharon; Hirsch-Moverman, Yael

    2015-04-01

    Antiretroviral therapy (ART) adherence remains critical for achieving successful outcomes. Factors affecting ART adherence can occur at the individual level or be related to the treatment regimen, daily schedule, and/or interpersonal relationships. While treatment-related barriers have diminished with recent simplified ART regimens, guidelines still recommend considering regimen simplicity. ART readiness should be assessed prior to starting ART, with follow-up adherence assessments once ART is initiated, and at all subsequent clinical visits. Adherence interventions work best when multifaceted, targeted for at-risk and nonadherent participants, and tailored to individuals' needs. Successful interventions have included education and counseling, provision of social support, directly observed therapy, and financial incentives. Pillboxes and two-way short-text messaging service (SMS) reminders have been shown to be effective and are widely recommended tools for promoting ART adherence. Further research is needed to determine the optimal combination of adherence interventions, as well as generalizability, implementation, and cost-effectiveness. PMID:25860778

  20. Effect of pregnancy and the postpartum period on adherence to antiretroviral therapy among HIV-infected women established on treatment.

    PubMed

    Henegar, Cassidy E; Westreich, Daniel J; Maskew, Mhairi; Miller, William C; Brookhart, M Alan; Van Rie, Annelies

    2015-04-01

    : Among women who become pregnant after initiating highly active antiretroviral therapy (HAART), few data describe the effect of pregnancy and postpartum on adherence. We conducted a retrospective clinical cohort study among therapy-naive women (age, 18-45 years) initiating HAART in Johannesburg, South Africa. Among 7510 women in our analysis, 896 experienced a pregnancy after starting HAART. Compared with nonpregnant periods of follow-up, there was an increased risk of nonadherence during the postpartum period (weighted risk ratio: 1.46, 95% confidence interval: 1.17 to 1.82) but not during pregnancy itself (weighted risk ratio: 0.95, 95% confidence interval: 0.78 to 1.17). PMID:25559590

  1. Approaches to rationing antiretroviral treatment: ethical and equity implications.

    PubMed Central

    Bennett, Sara; Chanfreau, Catherine

    2005-01-01

    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

  2. Closing the Gap Antiretroviral Therapy for the Developing World

    NSDL National Science Digital Library

    Robin Pals-Rylaarsdam

    2003-01-01

    In this problem-based learning/role playing case, students apply their knowledge of the biology of HIV/AIDS and antiretroviral therapy to developing foreign aid policy for the HIV/AIDS crisis in sub-Saharan Africa. The case was created for a non-majors course in human biology taken mostly by juniors or seniors. It has also been used in a microbiology course for pre-nursing students and in an upper-level microbiology course for biology majors.

  3. Outcomes of antiretroviral treatment programmes in rural Lesotho: health centres and hospitals compared

    PubMed Central

    Labhardt, Niklaus Daniel; Keiser, Olivia; Sello, Motlalepula; Lejone, Thabo Ishmael; Pfeiffer, Karolin; Davies, Mary-Ann; Egger, Matthias; Ehmer, Jochen; Wandeler, Gilles

    2013-01-01

    Introduction Lesotho was among the first countries to adopt decentralization of care from hospitals to nurse-led health centres (HCs) to scale up the provision of antiretroviral therapy (ART). We compared outcomes between patients who started ART at HCs and hospitals in two rural catchment areas in Lesotho. Methods The two catchment areas comprise two hospitals and 12 HCs. Patients ?16 years starting ART at a hospital or HC between 2008 and 2011 were included. Loss to follow-up (LTFU) was defined as not returning to the facility for ?180 days after the last visit, no follow-up (no FUP) as not returning after starting ART, and retention in care as alive and on ART at the facility. The data were analysed using logistic regression, competing risk regression and Kaplan-Meier methods. Multivariable analyses were adjusted for sex, age, CD4 cell count, World Health Organization stage, catchment area and type of ART. All analyses were stratified by gender. Results Of 3747 patients, 2042 (54.5%) started ART at HCs. Both women and men at hospitals had more advanced clinical and immunological stages of disease than those at HCs. Over 5445 patient-years, 420 died and 475 were LTFU. Kaplan-Meier estimates for three-year retention were 68.7 and 69.7% at HCs and hospitals, respectively, among women (p=0.81) and 68.8% at HCs versus 54.7% at hospitals among men (p<0.001). These findings persisted in adjusted analyses, with similar retention at HCs and hospitals among women (odds ratio (OR): 0.89, 95% confidence interval (CI): 0.73–1.09) and higher retention at HCs among men (OR: 1.53, 95% CI: 1.20–1.96). The latter result was mainly driven by a lower proportion of patients LTFU at HCs (OR: 0.68, 95% CI: 0.51–0.93). Conclusions In rural Lesotho, overall retention in care did not differ significantly between nurse-led HCs and hospitals. However, men seemed to benefit most from starting ART at HCs, as they were more likely to remain in care in these facilities compared to hospitals. PMID:24267671

  4. Reduced Adherence to Antiretroviral Therapy among HIV-infected Tanzanians Seeking Cure from the Loliondo Healer

    PubMed Central

    Thielman, Nathan M.; Ostermann, Jan; Whetten, Kathryn; Whetten, Rachel; Itemba, Dafrosa; Maro, Venance; Pence, Brian; Reddy, Elizabeth

    2014-01-01

    The predictors for seeking alternative therapies for HIV-infection in sub-Saharan Africa are unknown. Among a prospective cohort of 442 HIV-infected patients in Moshi, Tanzania, 249 (56%) sought cure from a newly popularized religious healer in Loliondo (450 kilometers away), and their adherence to antiretrovirals (ARVs) dropped precipitously (OR=0.20, 95% CI, 0.09–0.44, p<0.001) following the visit. Compared to those not attending Loliondo, attendees were more likely to have been diagnosed with HIV more remotely (3.8 vs. 3.0 years prior, p<0.001), have taken ARVs longer (3.4 vs. 2.5 years, p<0.001), have higher median CD4+ lymphocyte counts (429 vs. 354 cells/mm3, p<0.001), be wealthier (wealth index 10.9 vs. 8.8, p = 0.034), and receive care at the private versus the public hospital (p=0.012). In multivariable logistic regression, only years since the start of ARVs remained significant (OR, 1.49, 95% CI, 1.23–1.80). Treatment fatigue may play a role in the lure of alternative healers. PMID:24525471

  5. Nevirapine versus efavirenz-based antiretroviral therapy regimens in antiretroviral-naive patients with HIV and tuberculosis infections in India: a pilot study

    PubMed Central

    2013-01-01

    Background Administration of rifampicin along with nevirapine reduces the plasma concentration of nevirapine in human immunodeficiency virus positive individuals with concomitant tuberculosis (HIV-TB patients). Nevirapine is a much cheaper drug than its alternative efavirenz, and might be beneficial in resource constrained settings. Methods A randomised open label trial was conducted at All India Institute of Medical Sciences, New Delhi, India. During the regimen of an antiretroviral therapy (ART), naive HIV-TB patients were randomly assigned to receive either nevirapine or efavirenz based ART with concomitant rifampicin based anti-tubercular therapy (ATT). Participants were followed for 24 months after starting ART. The end points were virological, immunological and clinical responses, and progression of HIV disease marked by failure of ART. Results Of the 135 HIV-TB patients, who were receiving rifampicin based ATT, 68 were selected randomly to receive efavirenz based ART and 67 to receive nevirapine based ART. The virological failure rates in the overall population, and the nevirapine and efavirenz groups were 14.1% (19/135); 14.9% (10/67) and 13.2% (9/68), respectively (p?=?0.94). No significant difference was found between the groups in the rate of clinical, immunological or virological failures. The overall mortality was 17% with no significant difference between the two groups. Except for the lead in period on day 14, the mean nevirapine concentration remained above 3 mg/L. No association was found between plasma levels of nevirapine and incidence of unfavourable outcomes in this group. Conclusions Outcome of ART in HIV-TB patients on rifampicin based ATT showed no significant difference, irrespective of whether efavirenz or nevirapine was used. Therefore, nevirapine based ART could be an alternative in the resource limited settings in patients with HIV and tuberculosis co-infection. Trial registration NCT No. 01805258. PMID:24134449

  6. A Multicenter Study of Initiation of Antiretroviral Therapy and Transmitted Drug Resistance in Antiretroviral-Naive Adolescents and Young Adults With HIV in New York City

    PubMed Central

    Gagliardo, Christina; Brozovich, Ava; Birnbaum, Jeffrey; Radix, Anita; Foca, Marc; Nelson, John; Saiman, Lisa; Yin, Michael; Carras-Terzian, Elektra; West, Emily; Neu, Natalie

    2014-01-01

    Background.?In December 2009, the Department of Health and Human Services guidelines for initiation of antiretroviral therapy (ART) changed to include patients with CD4 counts between 350 and 500 cells/µL. The aims of this study were to assess uptake of this recommendation in ART-naive youth with human immunodeficiency virus (HIV) and to describe the epidemiology of transmitted genotypic drug resistance mutations (DRMs) in this population. Methods.?A multicenter, retrospective cohort study of ART initiation in ART-naive youth was performed. Eligible subjects were 13–25 years of age, were diagnosed with HIV within 1 year of presentation to care at the study sites, and presented to care from January 2007 to June 2011. Results.?Of 685 potential subjects identified, 331 (49%) fulfilled inclusion criteria. Mean CD4 count at presentation to care was 452 cells/µL. Overall, 191 (58%) subjects started ART. The mean CD4 count at ART initiation was 261 cells/µL before and 363 cells/µL after the 2009 guideline change (P < .0001). Of 212 (64%) subjects with resistance testing available prior to ART initiation, 38 (18%) subjects had a major DRM and an increased proportion of resistance was seen in later study years. Conclusions.?Our study demonstrated an uptake in recently changed guideline recommendations to treat HIV-infected individuals at higher CD4 counts and reinforces the importance of performing resistance testing at entry into care, as 18% of our population had major DRMs prior to initiation of ART. PMID:24429431

  7. Photosensitization is required for antiretroviral activity of hypericin

    NASA Astrophysics Data System (ADS)

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

    1991-06-01

    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.

  8. Antiretroviral therapy in macrophages: implication for HIV eradication

    PubMed Central

    Gavegnano, Christina; Schinazi, Raymond F

    2010-01-01

    HIV type-1 (HIV-1) accounts for more than 25 million deaths and nearly 40 million people are infected worldwide. A significant obstacle in clearing virus from infected individuals is latently infected viral reservoirs. Latent HIV-1 can emerge with recrudescence as a productive infection later in disease progression and could provide a source for the emergence of resistant HIV-1. It is widely recognized that macrophages represent a latently infected viral reservoir and are a significant and critical HIV-1 target cell in vivo. Macrophages can be divided into multiple subsets of macrophage-like cells, all of which are susceptible to HIV-1 infection, including dendritic cells, Langerhans cells, alveolar macrophages, mucosal macrophages and microglial cells. Current antiretroviral therapy (ART) often displays differential antiviral activity in macrophages relative to CD4+ T-lymphocytes. Significant work has been performed to establish antiviral activity of many clinically approved ART in macrophages; however, a direct link between antiviral activity and specific mechanisms responsible for these antiviral effects are incompletely understood. This review identifies many understudied areas of research, along with topics for further research in the field of HIV therapy and eradication. Discussion focuses upon the known cellular pharmacology and antiviral activity of antiretroviral agents in macrophages and its relationship to latency, chronic HIV-1 infection and therapeutic strategies to eradicate systemic HIV-1 infection. PMID:19843977

  9. Antiretroviral chemoprophylaxis: state of evidence and the research agenda.

    PubMed

    Mayer, Kenneth H

    2014-07-01

    Oral antiretroviral preexposure prophylaxis (PrEP) has been shown to decrease human immunodeficiency virus (HIV) incidence in studies of men who have sex with men, heterosexual men and women, and injecting drug users. One study of pericoital tenofovir gel demonstrated that it reduced HIV incidence in South African women. However, other studies of African women failed to demonstrate protection with either oral tenofovir or tenofovir-emtricitabine, or daily tenofovir gel. The magnitude of PrEP protection appears to be highly correlated with medication adherence. New studies are evaluating whether different antiretrovirals, including dapivirine, rilpivirine, maraviroc, and new integrase inhibitors. Different formulations are also being evaluated, including gels, films, vaginal rings, and injectable medication. Although PrEP efficacy has been demonstrated, and several normative bodies (eg, the US Food and Drug Administration) have approved PrEP for clinical use, uptake has been slow. Reasons may include lack of sufficient provider and consumer education, residual concerns about costs, potential long-term toxicities, and behavioral disinhibition. Additional work is under way to determine how to best educate consumers and providers about optimal adherence and to use PrEP in conjunction with risk mitigation. PMID:24926034

  10. Practical and Conceptual Challenges in Measuring Antiretroviral Adherence

    PubMed Central

    Berg, Karina M.; Arnsten, Julia H.

    2010-01-01

    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. PMID:17133207

  11. Justice and HIV care in Africa--antiretrovirals in perspective.

    PubMed

    Houston, Stan

    2002-01-01

    The immense burden of HIV disease in sub-Saharan Africa has focused international interest on HIV care, especially on the lack of access to antiretroviral therapy (ART). Difficulties in implementing ART in Africa include drug costs, adequate long-term funding sources, assurance of drug quality, and rapid development of the human resources and healthcare infrastructure needed to deliver ART. Important questions requiring study are the minimum level of laboratory monitoring and clinical support consistent with good treatment outcomes, the impact of antiretroviral drug resistance on treated individuals and communities, and the effect of ART on transmission at a community level. There are some concerns and risks. First, a focus on treatment could compromise the commitment of individuals to risk-reduction, and of governments to prevention. Second, health equity could be reduced, by diverting scarce public funds from basic care for the poorest, to costly disease-suppressive care for a small and probably elite group. In conclusion, while prevention must be the first priority, care is also essential. The vast prevailing economic inequity between the world's rich and poor is the fundamental determinant of inequities in health and healthcare, including care for HIV. The global community of healthcare workers must focus its substantial influence on changing political and economic policies that foster injustice and AIDS. PMID:12942675

  12. A three-tier framework for monitoring antiretroviral therapy in high HIV burden settings

    PubMed Central

    Osler, Meg; Hilderbrand, Katherine; Hennessey, Claudine; Arendse, Juanita; Goemaere, Eric; Ford, Nathan; Boulle, Andrew

    2014-01-01

    The provision of antiretroviral therapy (ART) in low and middle-income countries is a chronic disease intervention of unprecedented magnitude and is the dominant health systems challenge for high-burden countries, many of which rank among the poorest in the world. Substantial external investment, together with the requirement for service evolution to adapt to changing needs, including the constant shift to earlier ART initiation, makes outcome monitoring and reporting particularly important. However, there is growing concern at the inability of many high-burden countries to report on the outcomes of patients who have been in care for various durations, or even the number of patients in care at a particular point in time. In many instances, countries can only report on the number of patients ever started on ART. Despite paper register systems coming under increasing strain, the evolution from paper directly to complex electronic medical record solutions is not viable in many contexts. Implementing a bridging solution, such as a simple offline electronic version of the paper register, can be a pragmatic alternative. This paper describes and recommends a three-tiered monitoring approach in low- and middle-income countries based on the experience implementing such a system in the Western Cape province of South Africa. A three-tier approach allows Ministries of Health to strategically implement one of the tiers in each facility offering ART services. Each tier produces the same nationally required monthly enrolment and quarterly cohort reports so that outputs from the three tiers can be aggregated into a single database at any level of the health system. The choice of tier is based on context and resources at the time of implementation. As resources and infrastructure improve, more facilities will transition to the next highest and more technologically sophisticated tier. Implementing a three-tier monitoring system at country level for pre-antiretroviral wellness, ART, tuberculosis and mother and child health services can be an efficient approach to ensuring system-wide harmonization and accurate monitoring of services, including long term retention in care, during the scale-up of electronic monitoring solutions. PMID:24780511

  13. Nebraska: Early Head Start Initiative

    ERIC Educational Resources Information Center

    Center for Law and Social Policy, Inc. (CLASP), 2012

    2012-01-01

    Since 1999, Nebraska's Early Head Start Infant/Toddler Quality Initiative has supported Early Head Start (EHS) and community child care partnerships to improve the quality and professionalism of infant and toddler care. EHS programs apply to receive funding to establish partnerships with center-based or home-based child care.The initiative has…

  14. Head Start Embraces Language Diversity

    ERIC Educational Resources Information Center

    David, Judy, Comp.

    2005-01-01

    Over its 40 years, Head Start has evolved from serving a population of primarily Spanish-speaking English-language learners to working with children and families who speak more than 140 different languages. In some Head Start classrooms, as many as 10 different languages are used by the children. In other classrooms, a majority of the…

  15. Kansas: Early Head Start Initiative

    ERIC Educational Resources Information Center

    Center for Law and Social Policy, Inc. (CLASP), 2012

    2012-01-01

    Kansas Early Head Start (KEHS) provides comprehensive services following federal Head Start Program Performance Standards for pregnant women and eligible families with children from birth to age 4. KEHS was implemented in 1998 using Child Care and Development Block Grant (CCDBG) quality set-aside dollars augmented by a transfer of federal…

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

    PubMed Central

    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

    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. PMID:24147059

  17. The journey to antiretroviral therapy in Karnataka, India: who was lost on the road?

    PubMed Central

    Shastri, Suresh; Sathyanarayna, Srinath; Nagaraja, Sharath Burugina; Kumar, Ajay MV; Rewari, Bharat; Harries, Anthony D; Zachariah, Rony

    2013-01-01

    Introduction One important operational challenge facing antiretroviral treatment (ART) programmes in low- and middle-income countries is the loss to follow-up between diagnosis of human immunodeficiency virus (HIV) and initiation of ART. This is a major obstacle to achieving universal access to ART. This study from Karnataka, India, tried to measure such losses by determining the number of HIV-positive individuals diagnosed, the number of them reaching ART centres, the number initiated on ART and the reasons for non-initiation of ART. Methods A review of records routinely maintained under the National AIDS Control Programme (NACP) was carried out in six districts of Karnataka. HIV-positive persons diagnosed during the months from January to June 2011 in 233 public HIV-testing sites were followed up until December 2011 based on the pre-ART registers. A chi-square test was used to assess statistical significance. Results Of 2291 HIV-positive persons diagnosed (52% male; mean age of 35 years), 1829 (80%) reached ART centres. Of the latter, 1166 (64%) were eligible for ART, and 959 (82%) were initiated on treatment. Overall losses (attrition) on the road between HIV diagnosis and ART initiation were 669 (29%). Deaths, migration and not willing to go to the ART centres were cited as the main known reasons for not reaching ART centres. For ART-eligible individuals who did not initiate ART, the most common known reasons for non-initiation included dying before initiation of ART and not being willing to start ART. Conclusions In a large state of India, eight in ten HIV-positive persons reached ART centres, and of those found ART eligible, 82% start treatment. Although this is an encouraging achievement, the programme needs to take further steps to improve the current performance by further reducing pre-ART attrition. We recommend online registering of diagnosed HIV-positive patients to track the patients more efficiently. PMID:23985346

  18. Effectiveness of first-line antiretroviral therapy in the IPEC cohort, Rio de Janeiro, Brazil

    PubMed Central

    2014-01-01

    Background While Brazil has had a long-standing policy of free access to antiretroviral therapy (ART) for all in need, the epidemiological impact of ART on human immunodeficiency virus (HIV) RNA suppression in this middle-income country has not been well evaluated. We estimate first-line ART effectiveness in a large Brazilian cohort and examine the socio-demographic, behavioral, clinical and structural factors associated with virologic suppression. Methods Virologic suppression on first-line ART at 6, 12, and 24 months from start of ART was defined as having a viral load measurement ?400 copies/mL without drug class modification and/or discontinuation. Drug class modification and/or discontinuation were defined based on the class of a particular drug. Quasi-Poisson regression was used to quantify the association of factors with virologic suppression. Results From January 2000 through June 2010, 1311 patients started first-line ART; 987 (75%) patients used NNRTI-based regimens. Virologic suppression was achieved by 77%, 76% and 68% of patients at 6, 12 and 24 months, respectively. Factors associated with virologic suppression at 12 months were: >8 years of formal education (compared to <4 years, risk ratio (RR) 1.13, 95% confidence interval (95% CI) 1.03-1.24), starting ART in 2005-2010 (compared to 2000-2004, RR 1.25 95% CI 1.15-1.35), and clinical trial participation (compared to no participation, RR 1.08 95% CI 1.01-1.16). Also at 12 months, women showed less virologic suppression compared to heterosexual men (RR 0.90 95% CI 0.82-0.99). For the 24-month endpoint, in addition to higher education, starting ART in the later period, and clinical trial participation, older age and an NNRTI-based regimen were also independently associated with virologic suppression. Conclusions Our results show that in Brazil, a middle-income country with free access to treatment, over three-quarters of patients receiving routine care reached virologic suppression on first-line ART by the end of the first year. Higher education, more recent ART initiation and clinical trial participation were associated with improved outcomes both for the 12-month and the 24-month endpoints, suggesting that further studies are needed to understand what aspects relating to these factors lead to higher virologic suppression. PMID:25206924

  19. Pharmacogenetics of antiretroviral drugs for the treatment of HIV-infected patients: an update.

    PubMed

    Cressey, Tim R; Lallemant, Marc

    2007-03-01

    Highly active antiretroviral therapy (HAART), a combination of at least three antiretroviral drugs, has dramatically improved the prognosis of HIV/AIDS. However, viral replication under therapy can lead to the selection of drug resistant viruses and subsequent virologic failure. While poor adherence is likely to be the main cause of treatment failure, individual pharmacokinetic variability can also play an important role. Drug-drug interactions, drug-food interactions, sex, age, renal/hepatic function and pregnancy are all sources of pharmacokinetic variability. Recent pharmacogenetic studies of antiretroviral drugs reported the influence of several genetic polymorphisms on antiretroviral drug exposure, toxicity and response to treatment. Initially, a single nucleotide polymorphism (SNP) in exon 26 (C3435T) of the multi-drug transporter gene (MDR1) was reported to be associated with low antiretroviral plasma drug levels but good initial immunological response; however, conflicting results have since been reported. Several studies on efavirenz, a commonly used antiretroviral drug, have reported higher plasma exposure and early side effects with the homozygous variant of the hepatic cytochrome P450 enzyme CYP2B6 G516T polymorphism, which are more frequently found in African-American subjects. However, despite its association with efavirenz exposure this polymorphism was not associated with time to virologic or toxicity-related failure. Genetic analysis has also proven to be a valuable predictor of antiretroviral drug hypersensitivity reactions; genetic screening of patients prior to initiation of specific antiretrovirals has proven to reduce the incidence of drug hypersensitivity in certain settings. The reasons for antiretroviral treatment failure are multi-factorial but as the individualization of HAART increases understanding the influence of specific genotypes on treatment success and toxicity could further optimize these life-saving treatments. PMID:17045554

  20. The START III bargaining space

    SciTech Connect

    Karas, T.H.

    1998-08-01

    The declining state of the Russian military and precarious Russian economic condition will give the US considerable advantages at the START III bargaining table. Taking the US-RF asymmetries into account, this paper discusses a menu of START III measures the US could ask for, and measures it could offer in return, in attempting to negotiate an equitable treaty. Measures the US might seek in a START III treaty include: further reductions in deployed strategic nuclear warheads, irreversibility of reductions through warhead dismantlement; beginning to bring theater nuclear weapons under mutual control, and increased transparency into the Russian nuclear weapons complex. The US may, however, wish to apply its bargaining advantages to attempting to achieve the first steps toward two long-range goals that would enhance US security: bringing theater nuclear weapons into the US-RF arms control arena, and increasing transparency into the Russian nuclear weapons complex. In exchange for measures relating to these objectives, the US might consider offering to Russia: Further strategic weapons reductions approaching levels at which the Russians believe they could maintain a degree of parity with the US; Measures to decrease the large disparities in potential deliver-system uploading capabilities that appear likely under current START II/START III scenarios; and Financial assistance in achieving START II/START III reductions as rapidly as is technically possible.

  1. Outcomes in Patients Waiting for Antiretroviral Treatment in the Free State Province, South Africa: Prospective Linkage Study

    PubMed Central

    INGLE, Suzanne; MAY, Margaret; UEBEL, Kerry; TIMMERMAN, Venessa; KOTZE, Eduan; BACHMANN, Max; STERNE, Jonathan A C; EGGER, Matthias; FAIRALL, Lara

    2011-01-01

    Objective In South Africa, many HIV-infected patients experience delays in accessing antiretroviral therapy (ART). We examined pre-treatment mortality and access to treatment in patients waiting for ART. Design Cohort of HIV-infected patients assessed for ART eligibility at 36 facilities participating in the Comprehensive HIV and AIDS Management (CHAM) program in the Free State Province. Methods Proportion of patients initiating ART, pre-ART mortality and risk factors associated with these outcomes were estimated using competing risks survival analysis. Results 44,844 patients enrolled in CHAM between May 2004 and December 2007, of whom 22,083 (49.2%) were eligible for ART; pre-ART mortality was 53.2 per 100 person-years (95% CI 51.8-54.7). Median CD4 count at eligibility increased from 87 cells/mm3 in 2004 to 101 cells/mm3 in 2007. Two years after eligibility an estimated 67.7% (67.1% – 68.4%) of patients had started ART, and 26.2% (25.6% - 26.9%) died before starting ART. Among patients with CD4 counts <25 cells/mm3 at eligibility, 48% died before ART and 51% initiated ART. Men were less likely to start treatment and more likely to die than women. Patients in rural clinics or clinics with low staffing levels had lower rates of starting treatment and higher mortality compared with patients in urban/ peri-urban clinics, or better staffed clinics. Conclusions Mortality is high in eligible patients waiting for ART in the Free State Province. The most immunocompromised patients had the lowest probability of starting ART and the highest risk of pre-ART death. Prioritization of these patients should reduce waiting times and pre-ART mortality. PMID:20935554

  2. HBV influence on Response to Antiretroviral Therapy in Horizontally HIV-HBV Coinfected Patient during Early Childhood

    PubMed Central

    Niculescu, Irina; Cup?a, A.M.; Stoian, Andreea Cristina; Dumitrescu, FLorentina; Giubelan, L.I.; Alexandru, D.O.

    2013-01-01

    Background: There are few studies on pediatric HIV-HBV coinfection, so evidences about relationships between the two viruses are scarce. Objectives: influence of HBV infection on virological and immunological response to antiretroviral therapy (ART) in antiretroviral-naďve horizontally HIV-HBV coinfected subjects during early childhood. Material and methods: observational study on 826 HIV+ subjects in evidence of Craiova Regional Centre (CRC); we analyzed the immunological and virological response at 6-12 months after starting first antiretroviral regimens compared in 2 groups: horizontally HIV-HBV coinfected subjects during early childhood (CoS) versus horizontally HIV infected subjects during early childhood without HBV infection (non-CoS). Results: Number of subjects: CoS-66 subjects, non-CoS-132 subjects. Demographic data: CoS-gender ratio F:M=0.886, the majority lived in rural area (57.58%), mean age on diagnosis-9.288±4.607 years, non-CoS-gender ratio F:M=0.859, the majority lived in urban area (53.79%), mean age on diagnosis-10.742±5.107 years. At baseline, HIV category was: CoS-A-1.52%, B-80.30%, C-18.18%, non-CoS-A-2.27%, B-70.45%, C-27.27% (p Chi2=0.332), the mean CD4+ cell count was: CoS-148.33±148.10 cells/ml, non-CoS-163.17±155.39 cells/ml (p Student=0.521) and the mean HIV viral load (HIV VL) was: CoS-5.06±0.80 lgcopies/ml (for 29 subjects), non-CoS-5.04±0.84 lgcopies/ml (for 61 subjects) (p Student=0.978). At the end of the studied period, the mean increase in CD4+ cell count was: CoS-177.068±141.676 cells/ml, non-CoS-176.015±191.751 cells/ml (p Student=0.969) and the mean decrease in HIV VL was: CoS-5.04±0.79 lgcopies/ml, non-COS-4.69±2.04 lgcopies/ml (p Student=0.911). Conclusions: The presence of HBV coinfection does not influence immunological or virological response to ART. PMID:24778861

  3. Antiretroviral Therapy-Associated Acute Motor and Sensory Axonal Neuropathy

    PubMed Central

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

    2011-01-01

    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. PMID:21327178

  4. Nanoformulation strategies for the enhanced oral bioavailability of antiretroviral therapeutics.

    PubMed

    Tatham, Lee M; Rannard, Steven P; Owen, Andrew

    2015-04-01

    The oral delivery of drugs with poor aqueous solubility is challenging and often results in poor bioavailability. Various nanoformulation platforms have demonstrated improved oral bioavailability of a range of drugs for different indications. The focus of this review is to provide an overview of the application of nanomedicine to oral antiretroviral therapy and outline how the current short-falls of this life-long therapy may be resolved using nanotechnology. As well as highlighting the rationale for a nanomedicine-based approach, the review focuses on the various strategies used to enhance oral bioavailability and describes the mechanisms of particle absorption across the GI tract. The recent advances in the development of long-acting formulations for both HIV treatment and pre-exposure prophylaxis are also discussed. PMID:25996045

  5. Antiretroviral-based HIV prevention strategies for women

    PubMed Central

    Chirenje, Z Mike; Marrazzo, Jeanne; Parikh, Urvi M.

    2015-01-01

    Almost three decades have elapsed since researchers identified HIV as the cause of AIDS, with current estimates from UNAIDS that 33.4 million adults were living with HIV/AIDS in 2008. Two-thirds of this burden of disease is in Sub-Saharan Africa, and 60% of those infected are women. The disease still remains incurable and current prevention strategies including abstinence, male/female condom use and male circumcision are only partially effective. New strategies to curb the epidemic are urgently needed. Scientists are diligently exploring HIV prevention methods that are safe, effective and affordable. These new biological interventions include oral pre- exposure prophylaxis using oral antiretroviral (ARV) drugs, ARV treatment in HIV-infected persons to reduce transmission and topical ARV-based microbicide formulations. PMID:20954882

  6. Methamphetamine use and neuropsychiatric factors are associated with antiretroviral nonadherence

    PubMed Central

    Moore, David J.; Blackstone, Kaitlin; Woods, Steven Paul; Ellis, Ronald J.; Atkinson, J. Hampton; Heaton, Robert K.; Grant, Igor

    2012-01-01

    The present study assesses the impact of methamphetamine (METH) on antiretroviral (ART) adherence among HIV+ persons, as well as examines the contribution of neurocognitive impairment and other neuropsychiatric factors (i.e., major depressive disorder (MDD), Antisocial Personality Disorder (ASPD), and Attention Deficit Disorder (ADHD)) for ART nonadherence. We examined HIV+ persons with DSM-IV-diagnosed lifetime history of METH abuse/dependence (HIV+/METH+; n = 67) as compared to HIV+ participants with no history of METH abuse/dependence (HIV+/METH?; n = 50). Ancillary analyses compared these groups with a small group of HIV+/METH+ persons with current METH abuse/dependence (HIV+/CU METH+; n = 8). Nonadherence was defined as self-report of any skipped ART dose in the last four days. Neurocognitive functioning was assessed with a comprehensive battery, covering seven neuropsychological domains. Lifetime METH diagnosis was associated with higher rates of detectable levels of plasma and CSF HIV RNA. When combing groups (i.e., METH+ and METH? participants), univariate analyses indicated co-occurring ADHD, ASPD, and MDD predicted ART nonadherence (p’s<0.10; not lifetime METH status or neurocognitive impairment). A significant multivariable model including these variables indicated that only MDD uniquely predicted ART nonadherence after controlling for the other variables (p<0.05). Ancillary analyses indicated that current METH users (use within 30 days) were significantly less adherent (50% prevalence of nonadherence) than lifetime METH+ users and HIV+/METH-participants, and that neurocognitive impairment was associated with nonadherence (p’s<0.05). METH use disorders are associated with worse HIV disease outcomes and ART medication nonadherence. Interventions often target substance use behaviors alone to enhance antiretroviral treatment outcomes; however, in addition to targeting substance use behaviors, interventions to improve ART adherence may also need to address coexisting neuropsychiatric factors and cognitive impairment to improve ART medication taking. PMID:22530794

  7. Fibrinolytic changes in pregnant women on highly active antiretroviral therapy

    PubMed Central

    Osime, Odaburhine E.; Ese-Onakewhor, Joseph U.; Kolade, Samson O.

    2015-01-01

    Objectives: To report on the changes in fibrinolytic activity in human immunodeficiency virus (HIV) infected pregnant women who are undergoing highly active antiretroviral therapy (HAART). Methods: Blood was collected from 50 HIV positive women on HAART (test subjects), and 50 HIV positive women not on HAART (controls). These women were attending the prevention of mother to child clinic (PMTCT) of the University of Benin Teaching Hospital, Benin City, Nigeria from January to June 2014. Standard manual techniques were used to estimate plasma fibrinogen concentration (PFC), euglobulin lysis time (ELT), packed cell volume (PCV), and plasma viscosity (PV). Results: The mean ± standard error of mean (SEM) of PFC was 4.02±0.13g/l and ELT from the test subjects was 378±15 mins was significantly higher (p<0.05) compared with the control subjects (PFC 3.46±0.12g/l and ELT 267±9.0mins). The PCV or hematocrit values in the test subject was 29.1±0.38%, which was significantly lower (p<0.05) compared with the control subject (31.3±0.43%). The PV in the test subject was 1.76±0.02 mPa/s, while the control subjects was higher (1.73±0.02 mPa/s). This increase was not statistically significant (p>0.05). There were differences in the various parameters investigated when the various trimesters were compared. These differences did not, however, follow a particular pattern. Conclusion: Highly active antiretroviral therapy can cause changes in fibrinolytic activity that may predispose pregnant women to hyperfibrinogenemia and anemia. PMID:25719585

  8. CD8+ Cell Anti-HIV Activity Rapidly Increases Upon Discontinuation of Early Antiretroviral Therapy

    E-print Network

    Killian, M. Scott; Roop, Jeremy; Ng, Sharon; Hecht, Frederick M.; Levy, Jay A.

    2009-01-01

    of initiating antiretroviral therapy (ART) very early in thetherapies that can preserve CNAR activity during early ART,therapy, for each of the 16 subjects studied, CNAR activity was measured during ART and

  9. Determinants of survival in adult HIV patients on antiretroviral therapy in Eastern Uttar Pradesh: A prospective study

    PubMed Central

    Chakravarty, Jaya; Tiwary, Narendra K.; Prasad, Shashi Ranjan; Shukla, Saurabh; Tiwari, Anurag; Mishra, Rabindra Nath; Sundar, Shyam

    2014-01-01

    Background & objectives: The National AIDS Control Organization (NACO) of India has been providing free ARV (antiretroviral) drugs since 2004. By 2012, 486,173 patients had received treatment through the antiretroviral therapy (ART) centres. The objective of this observational study was to assess the factors determining survival of patients on ART under routine programme conditions in an ART centre in north India five years after its inception. Methods: Treatment naive HIV positive patients who were enrolled in the ART centre between May 2009 and May 2010 and started on ART as per the Revised NACO guidelines 2009, were included in the study and outcome was assessed after two years of follow up. Results: A total of 1689 patients were included in the analysis, of whom 272 (16.10%) expired, 205 (12.13%) were lost to follow up (LFU), 526 (31.14%) were transferred out to other facilities and 686 (40.63%) were alive at the end of two years. Majority (92%) of the deaths occurred in the first six months of therapy. Age >30 yr, male gender, poor functional status, haemoglobin level <11 g/dl, body weight <45 kg and CD4 count <100/?l at baseline had significantly higher relative hazard of death. Most LFU also occurred in the first six months and these patients had significantly low CD4 count, weight, haemoglobin level and higher number of patients in Stages III and IV as compared to those who survived. Interpretation & conclusions: The study findings revealed poor survival in the first six months of therapy especially in those with severe immunosuppression. This emphasizes the need for early enrolment into the programme. The high LFU occurring early after initiation of therapy suggests the urgent need to build an efficient patient retrieval system in the programme. PMID:25488442

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

    PubMed Central

    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.

    2013-01-01

    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

  11. Neuropsychological Functioning and Antiretroviral Treatment in HIV\\/AIDS: A Review

    Microsoft Academic Search

    Lucette A. Cysique; Bruce J. Brew

    2009-01-01

    This article presents a review of studies that have investigated the neuropsychological effects of antiretroviral treatment\\u000a (ART) for HIV-1 infection. It provides a brief overview of the era of monotherapy, dual-therapy, and an extended overview\\u000a of the current era of combination antiretroviral therapy (CART). This review highlights that while CART has had a dramatic\\u000a effect on the incidence and the

  12. Adherence to antiretroviral therapy in a home-based AIDS care programme in rural Uganda

    Microsoft Academic Search

    Paul J Weidle; Nafuna Wamai; Peter Solberg; Cheryl Liechty; Sam Sendagala; Willy Were; Jonathan Mermin; Kate Buchacz; Prosper Behumbiize; Ray L Ransom; Rebecca Bunnell

    2006-01-01

    Summary Background Poverty and limited health services in rural Africa present barriers to adherence to antiretroviral therapy that necessitate innovative options other than facility-based methods for delivery and monitoring of such therapy. We assessed adherence to antiretroviral therapy in a cohort of HIV-infected people in a home-based AIDS care programme that provides the therapy and other AIDS care, prevention, and

  13. Long-term virological outcome in children on antiretroviral therapy in the UK and Ireland

    PubMed Central

    Duong, Trinh; Judd, Ali; Collins, Intira Jeannie; Doerholt, Katja; Lyall, Hermione; Foster, Caroline; Butler, Karina; Tookey, Pat; Shingadia, Delane; Menson, Esse; Dunn, David T.; Gibb, Di M.

    2014-01-01

    Objective: To assess factors at the start of antiretroviral therapy (ART) associated with long-term virological response in children. Design: Multicentre national cohort. Methods: Factors associated with viral load below 400?copies/ml by 12 months and virologic failure among children starting 3/4-drug ART in the UK/Irish Collaborative HIV Paediatric Study were assessed using Poisson models. Results: Nine hundred and ninety-seven children started ART at a median age of 7.7 years (inter-quartile range 2.9–11.7), 251 (25%) below 3 years: 411 (41%) with efavirenz and two nucleoside reverse transcriptase inhibitors (EFV?+?2NRTIs), 264 (26%) with nevirapine and two NRTIs (NVP?+?2NRTIs), 119 (12%; 106 NVP, 13 EFV) with non-nucleoside reverse transcriptase inhibitor and three NRTIs (NNRTI?+?3NRTIs), and 203 (20%) with boosted protease inhibitor-based regimens. Median follow-up after ART initiation was 5.7 (3.0–8.8) years. Viral load was less than 400?copies/ml by 12 months in 92% [95% confidence interval (CI) 91–94%] of the children. Time to suppression was similar across regimens (P?=?0.10), but faster over calendar time, with older age and lower baseline viral load. Three hundred and thirty-nine (34%) children experienced virological failure. Although progression to failure varied by regimen (P?

  14. Pharmacological interactions between rifampicin and antiretroviral drugs: challenges and research priorities for resource-limited settings.

    PubMed

    Semvua, Hadija H; Kibiki, Gibson S; Kisanga, Elton R; Boeree, Martin J; Burger, David M; Aarnoutse, Rob

    2015-02-01

    Coadministration of antituberculosis and antiretroviral therapy is often inevitable in high-burden countries where tuberculosis (TB) is the most common opportunistic infection associated with HIV/AIDS. Concurrent use of rifampicin and many antiretroviral drugs is complicated by pharmacokinetic drug-drug interactions. Rifampicin is a very potent enzyme inducer, which can result in subtherapeutic antiretroviral drug concentrations. In addition, TB drugs and antiretroviral drugs have additive (pharmacodynamic) interactions as reflected in overlapping adverse effect profiles. This review provides an overview of the pharmacological interactions between rifampicin-based TB treatment and antiretroviral drugs in adults living in resource-limited settings. Major progress has been made to evaluate the interactions between TB drugs and antiretroviral therapy; however, burning questions remain concerning nevirapine and efavirenz effectiveness during rifampicin-based TB treatment, treatment options for TB-HIV-coinfected patients with nonnucleoside reverse transcriptase inhibitor resistance or intolerance, and exact treatment or dosing schedules for vulnerable patients including children and pregnant women. The current research priorities can be addressed by maximizing the use of already existing data, creating new data by conducting clinical trials and prospective observational studies and to engage a lobby to make currently unavailable drugs available to those most in need. PMID:24943062

  15. Differences in access and patient outcomes across antiretroviral treatment clinics in the Free State province: prospective cohort study

    PubMed Central

    Ingle, Suzanne; May, Margaret; Uebel, Kerry; Timmerman, Venessa; Kotze, Eduan; Bachmann, Max; Sterne, Jonathan A C; Egger, Matthias; Fairall, Lara

    2010-01-01

    Objective To assess differences in access to antiretroviral treatment (ART) and patient outcomes across public-sector treatment facilities in the Free State Province, South Africa. Design Prospective cohort study with retrospective database linkage. We analysed data on patients enrolled in the treatment programme across 36 facilities between May 2004 and December 2007. We assessed percentage initiating ART and percentage dead, at one year after enrolment. Multivariable logistic regression was used to estimate associations of clinic-level and patient-level characteristics with both mortality and treatment status. Results Of 44,866 patients enrolled, 15,219 initiated treatment within one year. 8,778 died within one year, of whom 7,286 died before accessing ART. Outcomes at one year varied greatly across facilities and more variability was explained by clinic-level factors than by patient-level factors. The odds of starting treatment within one year improved over calendar time. Patients enrolled in facilities with treatment initiation available on site had higher odds of starting treatment and lower odds of death at one year compared to those enrolled in facilities that do not offer treatment initiation. Patients were less likely to start treatment if they were male, severely immunosuppressed (CD4 count <50 cells/ mm3), or underweight (< 50kg). Men were also more likely to die in the first year after enrolment. Conclusions Although increasing numbers of patients started ART between 2004 and 2007, many patients died before accessing ART. Patient outcomes could be improved by decentralisation of treatment services, fast-tracking the most immunodeficient patients and improving access especially for men. PMID:21080999

  16. Antiretroviral Drug Interactions: Overview of Interactions Involving New and Investigational Agents and the Role of Therapeutic Drug Monitoring for Management

    PubMed Central

    Rathbun, R. Chris; Liedtke, Michelle D.

    2011-01-01

    Antiretrovirals are prone to drug-drug and drug-food interactions that can result in subtherapeutic or supratherapeutic concentrations. Interactions between antiretrovirals and medications for other diseases are common due to shared metabolism through cytochrome P450 (CYP450) and uridine diphosphate glucuronosyltransferase (UGT) enzymes and transport by membrane proteins (e.g., p-glycoprotein, organic anion-transporting polypeptide). The clinical significance of antiretroviral drug interactions is reviewed, with a focus on new and investigational agents. An overview of the mechanistic basis for drug interactions and the effect of individual antiretrovirals on CYP450 and UGT isoforms are provided. Interactions between antiretrovirals and medications for other co-morbidities are summarized. The role of therapeutic drug monitoring in the detection and management of antiretroviral drug interactions is also briefly discussed. PMID:24309307

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

    PubMed Central

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

    2010-01-01

    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. PMID:20442769

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

    PubMed Central

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

    2012-01-01

    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. PMID:22943378

  19. T-Cell Subsets Predict Mortality in Malnourished Zambian Adults Initiating Antiretroviral Therapy

    PubMed Central

    Chisenga, Caroline C.; Filteau, Suzanne; Siame, Joshua; Chisenga, Molly; Prendergast, Andrew J.; Kelly, Paul

    2015-01-01

    Objective To estimate the prognostic value of T-cell subsets in Zambian patients initiating antiretroviral therapy (ART), and to assess the impact of a nutritional intervention on T-cell subsets. Methods This was a sub-study of a randomised clinical trial of a nutritional intervention for malnourished adults initiating ART. Participants in a randomised controlled trial (NUSTART trial) were enrolled between April and December 2012. Participants received lipid-based nutritional supplement either with or without additional vitamins and minerals. Immunophenotyping was undertaken at baseline and, in survivors, after 12 weeks of ART to characterize T-cell subsets using the markers CD3, CD4, CD8, CD45RA, CCR7, CD28, CD57, CD31, ?4?7, Ki67, CD25 and HLA-DR. Univariate and multivariate survival analysis was performed, and responses to treatment were analysed using the Wicoxon rank-sum test. Results Among 181 adults, 36 (20%) died by 12 weeks after starting ART. In univariate analysis, patients who died had fewer proliferating, more naďve and fewer gut homing CD4+ T-cells compared to survivors; and more senescent and fewer proliferating CD8+ T-cells. In a multivariate Cox regression model high naďve CD4+, low proliferating CD4+, high senescent CD8+ and low proliferating CD8+ subsets were independently associated with increased risk of death. Recent CD4+ thymic emigrants increased less between recruitment and 12 weeks of ART in the intervention group compared to the control group. Conclusions Specific CD4+ T-cell subsets are of considerable prognostic significance for patients initiating ART in Zambia, but only thymic output responded to this nutritional intervention. PMID:26083409

  20. Correlation between HIV disease and lipid metabolism in antiretroviral-naďve HIV-infected patients in Japan

    Microsoft Academic Search

    Fukuko OkaToshio; Toshio Naito; Miki Oike; Rino Imai; Mizue Saita; Akihiro Inui; Kazunori Mitsuhashi; Hiroshi Isonuma; Takuro Shimbo

    Antiretroviral therapy alters lipid metabolism in HIV-infected patients. However, interpreting the impact of HIV infection\\u000a on lipid metabolism is difficult because of various associated factors, including antiretroviral drugs and demographic characteristics.\\u000a A few studies have associated HIV infection with lipid metabolism in antiretroviral-naďve HIV-infected patients. Because there\\u000a were no data in this regard from Japan, the present study examined the

  1. HANDBOOK FOR PROJECT HEAD START.

    ERIC Educational Resources Information Center

    GRAHAM, JORY

    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…

  2. When Will I Start Developing?

    MedlinePLUS

    ... for Parents for Kids for Teens Teens Home Body Mind Sexual Health Food & Fitness Diseases & Conditions Infections Q&A School & Jobs Drugs & Alcohol Staying Safe Recipes En Espańol ... Guy's Guide to Body Image When Will I Start Developing? KidsHealth > Teens > ...

  3. Start Where Your Students Are

    ERIC Educational Resources Information Center

    Jackson, Robyn R.

    2010-01-01

    Starting where your students are means understanding how currencies are negotiated and traded in the classroom. Any behavior that students use to acquire the knowledge and skills needed in the classroom functions as currency. Teachers communicate the kinds of currencies they accept in their classrooms, such as getting good grades; students do…

  4. Head Start Dental Health Curriculum.

    ERIC Educational Resources Information Center

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

    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…

  5. Starting apparatus for internal combustion engines

    DOEpatents

    Dyches, G.M.; Dudar, A.M.

    1995-01-01

    This report is a patent description for a system to start an internal combustion engine. Remote starting and starting by hearing impaired persons are addressed. The system monitors the amount of current being drawn by the starter motor to determine when the engine is started. When the engine is started the system automatically deactivates the starter motor. Five figures are included.

  6. Central nervous system penetration of antiretroviral drugs: pharmacokinetic, pharmacodynamic and pharmacogenomic considerations.

    PubMed

    Decloedt, Eric H; Rosenkranz, Bernd; Maartens, Gary; Joska, John

    2015-06-01

    The prevalence of HIV-associated neurocognitive disorder (HAND) is increasing despite the widespread use of combination antiretroviral therapy (ART). Initial reports suggest that the use of antiretrovirals with good central nervous system (CNS) penetration leads to better neurocognitive outcomes, but this has not yet been confirmed in a large cohort study or randomised controlled trial. There is emerging evidence that high CNS concentrations of some antiretrovirals are potentially neurotoxic and may be associated with the development of HAND. Antiretroviral CNS exposure is ideally determined by determining the ratio of cerebrospinal fluid (CSF):plasma area under the curve of unbound drug, but usually only total drug concentrations are measured and the ratio of CSF:plasma drug concentration is done at a single time point, which can result in misclassifying CNS penetration ability. Efavirenz was previously thought to have poor CNS penetration, measured by the CSF:plasma ratio (0.87 %), but when unbound concentrations were measured it was found to have good CNS penetration (85 %). Indinavir and efavirenz are the only antiretroviral drugs for which CNS area under the concentration-time curves using unbound plasma and CSF concentrations has been calculated. Patient data to support the contribution of blood-brain barrier transporter polymorphisms to CNS antiretroviral concentrations are currently limited and lack power to detect true associations. Correlations between CNS antiretroviral exposure and effect is multifaceted, and to accurately predict CNS effects there is a need to develop a sophisticated intra-brain pharmacokinetic-pharmacodynamic-pharmacogenetic model that includes transporters as well as the influence of HIV. PMID:25777740

  7. Supporting children to adhere to anti-retroviral therapy in urban Malawi: multi method insights

    PubMed Central

    Weigel, Ralf; Makwiza, Ireen; Nyirenda, Jean; Chiunguzeni, Darles; Phiri, Sam; Theobald, Sally

    2009-01-01

    Background Ensuring good adherence is critical to the success of anti-retroviral treatment (ART). However, in resource-poor contexts, where paediatric HIV burden is high there has been limited progress in developing or adapting tools to support adherence for HIV-infected children on ART and their caregivers. We conducted formative research to assess children's adherence and to explore the knowledge, perceptions and attitudes of caregivers towards children's treatment. Methods All children starting ART between September 2002 and January 2004 (when ART was at cost in Malawi) were observed for at least 6 months on ART. Their adherence was assessed quantitatively by asking caregivers of children about missed ART doses during the previous 3 days at monthly visits. Attendance to clinic appointments was also monitored. In June and July 2004, four focus group discussions, each with 6 to 8 caregivers, and 5 critical incident narratives were conducted to provide complementary contextual data on caregivers' experiences on the challenges to and opportunities of paediatric ART adherence. Results We followed prospectively 47 children who started ART between 8 months and 12 years of age over a median time on ART of 33 weeks (2–91 weeks). 72% (34/47) never missed a single dose according to caregivers' report and 82% (327/401) of clinic visits were either as scheduled, or before or within 1 week after the scheduled appointment. Caregivers were generally knowledgeable about ART and motivated to support children to adhere to treatment despite facing multiple challenges. Caregivers were particularly motivated by seeing children begin to get better; but faced challenges in meeting the costs of medicine and transport, waiting times in clinic, stock outs and remembering to support children to adhere in the face of multiple responsibilities. Conclusion In the era of rapid scale-up of treatment for children there is need for holistic support strategies that focus on the child, the caregiver and the health worker and which are situated within the reality of fragile health systems. The findings highlight the need for cost-free and less complex paediatric ART regimes and culturally appropriate tools to support children's adherence. PMID:19602251

  8. 30 CFR 75.1913 - Starting aids.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...2010-07-01 2010-07-01 false Starting aids. 75.1913 Section 75.1913 Mineral Resources...Diesel-Powered Equipment § 75.1913 Starting aids. (a) Volatile fuel starting aids shall be used in accordance with...

  9. 30 CFR 75.1913 - Starting aids.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...2011-07-01 2011-07-01 false Starting aids. 75.1913 Section 75.1913 Mineral Resources...Diesel-Powered Equipment § 75.1913 Starting aids. (a) Volatile fuel starting aids shall be used in accordance with...

  10. 30 CFR 75.1913 - Starting aids.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...2013-07-01 2013-07-01 false Starting aids. 75.1913 Section 75.1913 Mineral Resources...Diesel-Powered Equipment § 75.1913 Starting aids. (a) Volatile fuel starting aids shall be used in accordance with...

  11. 30 CFR 75.1913 - Starting aids.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...2014-07-01 2014-07-01 false Starting aids. 75.1913 Section 75.1913 Mineral Resources...Diesel-Powered Equipment § 75.1913 Starting aids. (a) Volatile fuel starting aids shall be used in accordance with...

  12. 30 CFR 75.1913 - Starting aids.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...2012-07-01 2012-07-01 false Starting aids. 75.1913 Section 75.1913 Mineral Resources...Diesel-Powered Equipment § 75.1913 Starting aids. (a) Volatile fuel starting aids shall be used in accordance with...

  13. How Qualitative Methods Contribute to Understanding Combination Antiretroviral Therapy Adherence

    PubMed Central

    Sankar, Andrea; Golin, Carol; Simoni, Jane M.; Luborsky, Mark; Pearson, Cynthia

    2014-01-01

    Summary Strict adherence to medication regimens is generally required to obtain optimal response to combination antiretroviral therapy (ART). Yet, we have made limited progress in developing strategies to decrease the prevalence of nonadherence. As we work to understand adherence in developed countries, the introduction of ART in resource-poor settings raises novel challenges. Qualitative research is a scientific approach that uses methods such as observation, interviews, and verbal interactions to gather rich in-depth information about how something is experienced. It seeks to understand the beliefs, values, and processes underlying behavioral patterns. Qualitative methods provide powerful tools for understanding adherence. Culture-specific influences, medication beliefs, access, stigma, reasons for nonadherence, patterns of medication taking, and intervention fidelity and measurement development are areas ripe for qualitative inquiry. A disregard for the social and cultural context of adherence or the imposition of adherence models inconsistent with local values and practices is likely to produce irrelevant or ineffective interventions. Qualitative methods remain underused in adherence research. We review appropriate qualitative methods for and provide an overview of the qualitative research on ART nonadherence. We discuss the rationales for using qualitative methods, present 2 case examples illustrating their use, and discuss possible institutional barriers to their acceptance. PMID:17133205

  14. Antiretroviral treatment failure predicts mortality in rural Tanzania.

    PubMed

    Pettersen, Pernille S; Brox, Ida K; Naman, Ezra; Bruun, Johan N; Dyrhol-Riise, Anne M; Trřseid, Marius; Johannessen, Asgeir

    2015-08-01

    Virological monitoring of HIV-infected patients on antiretroviral treatment (ART) is rarely available in resource-limited settings and many patients experience unrecognized virological failure. We studied the long-term consequences of virological failure in rural Tanzania. Previously, virological efficacy was measured in a cohort treated with ART. In the present study, patients with virological failure (VF; HIV-RNA >400 copies/ml) were followed up and compared to those with virological response (VR; HIV-RNA <400 copies/ml) with regard to mortality, CD4 change and subsequent virological outcome. Fifty-six patients with VF had a median CD4 count of 358 cells/µl (interquartile range [IQR] 223-635) and a median HIV-RNA of 13,573 copies/ml (IQR 2326-129,736). Median CD4 count for those with VR was 499 cells/µl (IQR 290-636). During a median follow-up time of 39 months (IQR 18-42), 8 of 56 patients (14.3%) with VF died, compared to 1 of 63 patients (1.6%) with VR (p?=?0.009). All registered deaths were HIV-related. Of 55 patients with subsequent HIV-RNA measurements, only 12 of 30 (40%) patients with VF achieved virological suppression, compared to 20 of 25 (80%) patients with VR (p?=?0.003). Virological failure predicted death and subsequent virological failure in patients on ART in a resource-limited setting. PMID:25122578

  15. Namibian prisoners describe barriers to HIV antiretroviral therapy adherence.

    PubMed

    Shalihu, Nauyele; Pretorius, Louise; van Dyk, Agnes; Vander Stoep, Ann; Hagopian, Amy

    2014-01-01

    Little is available in scholarly literature about how HIV-positive prisoners, especially in low-income countries, access antiretroviral therapy (ART) medication. We interviewed 18 prisoners at a large prison in Namibia to identify barriers to medication adherence. The lead nurse researcher was a long-standing clinic employee at the prison, which afforded her access to the population. We identified six significant barriers to adherence, including (1) the desire for privacy and anonymity in a setting where HIV is strongly stigmatized; (2) the lack of simple supports for adherence, such as availability of clocks; (3) insufficient access to food to support the toll on the body of ingesting taxing ART medications; (4) commodification of ART medication; (5) the brutality and despair in the prison setting, generally leading to discouragement and a lack of motivation to strive for optimum health; and (6) the lack of understanding about HIV, how it is transmitted, and how it is best managed. Because most prisoners eventually transition back to communitysettings when their sentences are served, investments in prison health represent important investments in public health. PMID:24499371

  16. Long-acting injectable antiretrovirals for HIV treatment and prevention

    PubMed Central

    Spreen, William R.; Margolis, David A.; Pottage, John C.

    2013-01-01

    Purpose of review Long-acting antiretroviral (ARV) drugs may improve adherence to therapy and extend opportunities for therapeutic or prophylactic intervention to underserved patient populations. This review focuses on recent advances in the development of small molecule long-acting injectable ARV agents. Recent findings The need for combination ART and physicochemical and dosing limitations of current ARV drugs impede attempts to redevelop them as long-acting injectable formulations. However, the intrinsic properties of rilpivirine, a nonnucleoside reverse transcriptase inhibitor, and GSK1265744, an HIV-1 integrase strand transfer inhibitor, have enabled crystalline nanoparticle formulations to progress to clinical trials. Summary Investigational long-acting injectable nanoformulations of rilpivirine and GSK1265744 are clinical-stage development candidates. Complementary pharmacologic properties of both agents – different mechanisms of action, resistance profiles, metabolic pathways, lack of drug interactions and low daily oral doses – offer the potential for combination use. Phase I studies of the pharmacokinetics and safety of each long-acting formulation alone and in combination indicate that a monthly dosing regimen is possible for HIV treatment. An ongoing phase IIb trial of oral GSK1265744 and oral rilpivirine is evaluating this two-drug regimen for maintenance of virologic suppression; results will inform future studies using the injectable formulations. Additional preclinical and clinical studies indicate a potential use of each agent for HIV pre-exposure prophylaxis. PMID:24100877

  17. Synergistic vulnerabilities: Antiretroviral treatment among women in Uganda.

    PubMed

    Winchester, Margaret S

    2015-08-01

    Despite being an early success story in the reduction of HIV infection rates, Uganda faces myriad challenges in the recent era of accelerated antiretroviral treatment (ARV) scale-up. For those able to access treatment, ongoing vulnerabilities of poverty and violence compound treatment-related costs and concerns. This paper explores experiences of one particularly vulnerable population - women on ARVs who have also experienced intimate partner violence (IPV). Data were collected over 12 months in Uganda. They include ethnographic interviews (n = 40) drawn from a larger sample of women on ARV and semi-structured interviews with policy-makers and service providers (n = 42), examining the intersection of experiences and responses to treatment from multiple perspectives. Women's narratives show that due to treatment, immediate health concerns take on secondary importance, while other forms of vulnerability, including IPV and poverty, can continue to shape treatment experiences and the decision to stay in violent relationships. Providers likewise face difficulties in overburdened clinics, though they recognise women's concerns and the importance of considering other forms of vulnerability in treatment. This analysis makes the case for integrating treatment with other types of social services and demonstrates the importance of understanding the ways in which synergistic and compounding vulnerabilities confound treatment scale-up efforts. PMID:25647145

  18. Development of HIV Reservoir Targeted Long Acting Nanoformulated Antiretroviral Therapies

    PubMed Central

    Edagwa, Benson J; Zhou, Tian; McMillan, JoEllyn M; Liu, Xin-Ming; Gendelman, Howard E

    2014-01-01

    Human immunodeficiency virus (HIV) infection commonly results in a myriad of comorbid conditions secondary to immune deficiency. Infection also affects broad organ system function. Although current antiretroviral therapy (ART) reduces disease morbidity and mortality through effective control of peripheral viral load, restricted infection in HIV reservoirs including gut, lymphoid and central nervous system tissues, is not eliminated. What underlies these events is, in part, poor ART penetrance into each organ across tissue barriers, viral mutation and the longevity of infected cells. We posit that one means to improve these disease outcomes is through nanotechnology. To this end, this review discusses a broad range of cutting-edge nanomedicines and nanomedicine platforms that are or can be used to improve ART delivery. Discussion points include how polymer-drug conjugates, dendrimers, micelles, liposomes, solid lipid nanoparticles and polymeric nanoparticles can be harnessed to best yield cell-based delivery systems. When completely developed, such nanomedicine platforms have the potential to clear reservoirs of viral infection. PMID:25174930

  19. Alcohol use and antiretroviral adherence: Review and meta-analysis

    PubMed Central

    Hendershot, Christian S.; Stoner, Susan A.; Pantalone, David W.; Simoni, Jane M.

    2009-01-01

    Background Alcohol use is frequently implicated as a factor in nonadherence to highly active antiretroviral therapy (HAART). There have not been efforts to systematically evaluate findings across studies. This meta-analysis provides a quantitative evaluation of the alcohol-adherence association by aggregating findings across studies and examining potential moderators. Methods Literature searches identified 40 qualifying studies totaling over 25,000 participants. Studies were coded on several methodological variables. Results In the combined analysis, alcohol drinkers were approximately 50–60% as likely to be classified as adherent [OR = 0.548, 95% CI: 0.490–0.612] compared to abstainers (or those who drank relatively less). Effect sizes for problem drinking, defined as meeting the National Institute on Alcohol Abuse and Alcoholism (NIAAA) criteria for at-risk drinking or criteria for an alcohol use disorder, were greater [OR = 0.474, 95% CI = 0.408–0.550] than those reflecting any or global drinking [OR = 0.604, 95% CI = 0.531–0.687]. Several variables moderated the alcohol-adherence association. Conclusions Results support a significant and reliable association of alcohol use and medication nonadherence. Methodological variables appear to moderate this association and could contribute to inconsistencies across studies. Future research would benefit from efforts to characterize theoretical mechanisms as well as mediators and moderators of the alcohol-adherence association. PMID:19668086

  20. Continuing or adding IL-2 in patients treated with antiretroviral therapy (ACTG Protocol A5051, a rollover trial of ACTG Protocol A328)

    E-print Network

    Bosch, Ronald J; Pollard, Richard B; Landay, Alan; Aga, Evgenia; Fox, Lawrence; Mitsuyasu, Ronald

    2010-01-01

    to antiretroviral therapy (ART) alone or ART followed by IL-continue antiretroviral therapy (ART) alone or with eithertherapy and IL-2 in a pre- vious study, patients newly exposed to IL-2 after initial ART

  1. Antiretroviral drug resistance in HIV-1 therapy-naive patients in Cuba.

    PubMed

    Pérez, Lissette; Kourí, Vivian; Alemán, Yoan; Abrahantes, Yeisel; Correa, Consuelo; Aragonés, Carlos; Martínez, Orlando; Pérez, Jorge; Fonseca, Carlos; Campos, Jorge; Álvarez, Delmis; Schrooten, Yoeri; Dekeersmaeker, Nathalie; Imbrechts, Stijn; Beheydt, Gertjan; Vinken, Lore; Soto, Yudira; Álvarez, Alina; Vandamme, Anne-Mieke; Van Laethem, Kristel

    2013-06-01

    In Cuba, antiretroviral therapy rollout started in 2001 and antiretroviral therapy coverage has reached almost 40% since then. The objectives of this study were therefore to analyze subtype distribution, and level and patterns of drug resistance in therapy-naive HIV-1 patients. Four hundred and one plasma samples were collected from HIV-1 therapy-naive patients in 2003 and in 2007-2011. HIV-1 drug resistance genotyping was performed in the pol gene and drug resistance was interpreted according to the WHO surveillance drug-resistance mutations list, version 2009. Potential impact on first-line therapy response was estimated using genotypic drug resistance interpretation systems HIVdb version 6.2.0 and Rega version 8.0.2. Phylogenetic analysis was performed using Neighbor-Joining. The majority of patients were male (84.5%), men who have sex with men (78.1%) and from Havana City (73.6%). Subtype B was the most prevalent subtype (39.3%), followed by CRF20-23-24_BG (19.5%), CRF19_cpx (18.0%) and CRF18_cpx (10.3%). Overall, 29 patients (7.2%) had evidence of drug resistance, with 4.0% (CI 1.6%-4.8%) in 2003 versus 12.5% (CI 7.2%-14.5%) in 2007-2011. A significant increase in drug resistance was observed in recently HIV-1 diagnosed patients, i.e. 14.8% (CI 8.0%-17.0%) in 2007-2011 versus 3.8% (CI 0.9%-4.7%) in 2003 (OR 3.9, CI 1.5-17.0, p=0.02). The majority of drug resistance was restricted to a single drug class (75.8%), with 55.2% patients displaying nucleoside reverse transcriptase inhibitor (NRTI), 10.3% non-NRTI (NNRTI) and 10.3% protease inhibitor (PI) resistance mutations. Respectively, 20.7% and 3.4% patients carried viruses containing drug resistance mutations against NRTI+NNRTI and NRTI+NNRTI+PI. The first cases of resistance towards other drug classes than NRTI were only detected from 2008 onwards. The most frequent resistance mutations were T215Y/rev (44.8%), M41L (31.0%), M184V (17.2%) and K103N (13.8%). The median genotypic susceptibility score for the commonly prescribed first-line therapies was 2.5. This analysis emphasizes the need to perform additional surveillance studies to accurately assess the level of transmitted drug resistance in Cuba, as the extent of drug resistance might jeopardize effectiveness of first-line regimens prescribed in Cuba and might necessitate the implementation of baseline drug resistance testing. PMID:23416260

  2. Antiretroviral resistance among HIV type 1-infected women first exposed to antiretrovirals during pregnancy: plasma versus PBMCs.

    PubMed

    Soto-Ramirez, Luis E; Rodriguez-Diaz, Roberto; Durán, Adriana S; Losso, Marcelo H; Salomón, Horacio; Gómez-Carrillo, Manuel; Pampuro, Sandra; Harris, D Robert; Duarte, Geraldo; De Souza, Ricardo S; Read, Jennifer S

    2008-06-01

    Resistance-associated mutations (RAMs) in plasma samples from HIV-1-infected women who received antiretroviral (ARV) prophylaxis during pregnancy was assessed and correlated with the detection of RAMs in peripheral blood mononuclear cells (PMBCs). The study population was composed of HIV-1-infected women enrolled in a prospective cohort study in Latin America and the Caribbean (NISDI Perinatal Study) as of March 1, 2005, who were diagnosed with HIV-1 infection during the current pregnancy, who received ARVs during pregnancy for prevention of mother-to-child transmission of HIV-1, and who were followed through at least the 6-12 week postpartum visit. Plasma samples collected at enrollment during pregnancy and at 6-12 weeks postpartum were assayed for RAMs. Plasma results were compared to previously described PBMC results from the same study population. Of 819 enrolled subjects, 197 met the eligibility criteria. Nucleic acid amplification was accomplished in 123 plasma samples at enrollment or 6-12 weeks postpartum, and RAMs were detected in 22 (17.9%; 95%CI: 11.7-25.9%). Previous analyses had demonstrated detection of RAMs in PBMCs in 19 (16.1%). There was high concordance between RAMs detected in plasma and PBMC samples, with only eight discordant pairs. The prevalence of RAMs among these pregnant, HIV-1-infected women is high (15%). Rates of detection of RAMs in plasma and PBMC samples were similar. PMID:18507526

  3. Feasibility and benefits of scaling up antiretroviral treatment provision with the 2010 WHO antiretroviral therapy guidelines in rural Lesotho.

    PubMed

    Bygrave, Helen; Saranchuk, Peter; Makakole, Lipontso; Ford, Nathan

    2012-09-01

    The latest WHO guidelines (2010) for antiretroviral therapy (ART) in adults and adolescents recommend that countries should progressively reduce the use of stavudine in favour of tenofovir or zidovudine and that ART initiation commence at an earlier CD4 threshold of <350 cell/mm(3). In Lesotho, a high-burden, resource-limited setting, these two changes had been recommended since late 2007. A number of practical steps were taken to support implementation of Lesotho's national ART guidelines at the program level including: development of guidelines tailored to nurses working in primary care settings; training and clinical mentorship of different levels of health care workers; laboratory support; pharmacy support; and monitoring and evaluation. Clinical and programmatic benefits included decreased mortality, toxicity, and simplified patient management that was supportive of the decentralized, nurse-led model of care. This experience demonstrates that, despite limited resources, it was feasible to provide a standard of care similar to that of western guidelines and that these changes were supportive of simplified patient management. PMID:24029396

  4. Synergistic in vitro antiretroviral activity of a humanized monoclonal anti-CD4 antibody (TNX-355) and enfuvirtide (T-20).

    PubMed

    Zhang, Xing-Quan; Sorensen, Meredith; Fung, Michael; Schooley, Robert T

    2006-06-01

    Recently, antiretroviral agents directed at several steps involved in viral entry have been shown to reduce viral replication in vitro and in vivo. We have demonstrated a high level of in vitro synergistic antiretroviral activity for two entry inhibitors that are directed at sequential steps in the entry process. PMID:16723592

  5. Synergistic In Vitro Antiretroviral Activity of a Humanized Monoclonal Anti-CD4 Antibody (TNX-355) and Enfuvirtide (T-20)

    PubMed Central

    Zhang, Xing-Quan; Sorensen, Meredith; Fung, Michael; Schooley, Robert T.

    2006-01-01

    Recently, antiretroviral agents directed at several steps involved in viral entry have been shown to reduce viral replication in vitro and in vivo. We have demonstrated a high level of in vitro synergistic antiretroviral activity for two entry inhibitors that are directed at sequential steps in the entry process. PMID:16723592

  6. The Financial Burden of Morbidity in HIV-Infected Adults on Antiretroviral Therapy in Co^te d'Ivoire

    E-print Network

    Paris-Sud XI, Université de

    antiretroviral therapy (ART) in Co^te d'Ivoire. Methodology/Principal Findings: We conducted a crossThe Financial Burden of Morbidity in HIV-Infected Adults on Antiretroviral Therapy in Co^te d-sectional survey. After obtaining informed consent, we interviewed HIV-infected adults taking ART who had

  7. Cellular HIV-1 DNA load predicts HIV-RNA rebound and the outcome of highly active antiretroviral therapy

    E-print Network

    Cellular HIV-1 DNA load predicts HIV-RNA rebound and the outcome of highly active antiretroviral HIV-1 DNA prior to highly active antiretroviral therapy (HAART) initiation predicts its outcome initiation were available. Cellular HIV-1 DNA quantification was performed by a molecular beacon-based real

  8. Drug-Resistant Tuberculosis Treatment Complicated by Antiretroviral Resistance in HIV Coinfected Patients: A Report of Six Cases in Lesotho

    PubMed Central

    Satti, Hind; McLaughlin, Megan M.; Seung, Kwonjune J.

    2013-01-01

    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

  9. Drug-resistant tuberculosis treatment complicated by antiretroviral resistance in HIV coinfected patients: a report of six cases in Lesotho.

    PubMed

    Satti, Hind; McLaughlin, Megan M; Seung, Kwonjune J

    2013-07-01

    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

  10. Antiretroviral monocyte efficacy score linked to cognitive impairment in HIV

    PubMed Central

    Shikuma, Cecilia M; Nakamoto, Beau; Shiramizu, Bruce; Liang, Chin-Yuan; DeGruttola, Victor; Bennett, Kara; Paul, Robert; Kallianpur, Kalpana; Chow, Dominic; Gavegnano, Christina; Hurwitz, Selwyn J; Schinazi, Raymond F; Valcour, Victor G

    2013-01-01

    Background Monocytes transmigrating to the brain play a central role in HIV neuropathology. We hypothesized that the continued existence of neurocognitive impairment (NCI) despite potent antiretroviral (ARV) therapy is mediated by the inability of such therapy to control this monocyte/macrophage reservoir. Methods Cross-sectional and longitudinal analyses were conducted within a prospectively enrolled cohort. We devised a monocyte efficacy (ME) score based on the anticipated effectiveness of ARV medications against monocytes/macrophages using published macrophage in vitro drug efficacy data. We examined, within an HIV neurocognitive database, its association with composite neuropsychological test scores (NPZ8) and clinical cognitive diagnoses among subjects on stable ARV medications unchanged for >6 months prior to assessment. Results Among 139 subjects on ARV therapy, higher ME score correlated with better NPZ8 performance (r=0.23, P<0.01), whereas a score devised to quantify expected penetration effectiveness of ARVs into the brain (CPE score) did not (r=0.12, P=0.15). In an adjusted model (adjusted r2=0.12), ME score (?=0.003, P=0.02), CD4+ T-cell nadir (?=0.001, P<0.01) and gender (?=?0.456, P=0.02) were associated with NPZ8, whereas CPE score was not (?=0.003, P=0.94). A higher ME score was associated with better clinical cognitive status (P<0.01). With a range of 12.5–433.0 units, a 100-unit increase in ME score resulted in a 10.6-fold decrease in the odds of a dementia diagnosis compared with normal cognition (P=0.01). Conclusions ARV efficacy against monocytes/macrophages correlates with cognitive function in HIV-infected individuals on ARV therapy within this cohort. If validated, efficacy against monocytes/macrophages may provide a new target to improve HIV NCI. PMID:23018140

  11. Retention in HIV Care and Predictors of Attrition from Care among HIV-Infected Adults Receiving Combination Anti-Retroviral Therapy in Addis Ababa

    PubMed Central

    Mekuria, Legese A.; Prins, Jan M.; Yalew, Alemayehu W.; Sprangers, Mirjam A. G.; Nieuwkerk, Pythia T.

    2015-01-01

    Background Patient retention in chronic HIV care is a major challenge following the rapid expansion of combination antiretroviral therapy (cART) in Ethiopia. Objective To describe the proportion of patients who are retained in HIV care and characterize predictors of attrition among HIV-infected adults receiving cART in Addis Ababa. Method A retrospective analysis was conducted among 836 treatment naďve patients, who started cART between May 2009 and April 2012. Patients were randomly selected from ten health-care facilities, and their current status in HIV care was determined based on routinely available data in the medical records. Patients lost to follow-up (LTFU) were traced by telephone. Kaplan-Meier technique was used to estimate survival probabilities of retention and Cox proportional hazards regression was performed to identify the predictors of attrition. Results Based on individual patient data from the medical records, nearly 80% (95%CI: 76.7, 82.1) of the patients were retained in care in the first 3 and half years of antiretroviral therapy. After successfully tracing more than half of the LTFU patients, the updated one year retention in care estimate became 86% (95% CI: 83.41%, 88.17%). In the multivariate Cox regression analyses, severe immune deficiency at enrolment in care/or at cART initiation and ‘bed-ridden’ or ‘ambulatory’ functional status at the start of cART predicted attrition. Conclusion Retention in HIV care in Addis Ababa is comparable with or even better than previous findings from other resource-limited as well as EU/USA settings. However, measures to detect and enroll patients in HIV care as early as possible are still necessary. PMID:26114436

  12. 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

    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

    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. PMID:24086627

  13. Determinants of Survival in Adult HIV Clients on Antiretroviral Therapy in Lawra and Jirapa Districts of Upper West Region, Ghana.

    PubMed

    Okyere, Gabriel Asare; Alalbil, Paul Awinbil; Ping-Naah, Henry; Tifere, Yakubu

    2015-05-01

    We describe the rate of death and identify the determinants of survival in a cohort of adults starting antiretroviral therapy (ART) in 2 hospitals in Upper West Region, Ghana. Kaplan-Meier model was used to estimate the survival probability after ART initiation and Cox proportional hazard model used to assess the relationship between baseline variables and mortality. A total of 91 clients who were initiated on ART in both hospitals participated in the study. Clients staged in the World Health Organization (WHO) clinical stage III/IV had a higher risk of mortality than those staging I/II (hazard ratio [HR] of 3.93). Hemoglobin value at baseline with a cutoff ?12 g/dL for women (and ?13 for men) was strongly associated with mortality in participants with an HR of 3.87 (95% confidence interval [CI]: 0.71-21.19) for severe anemia, 2.11 (95% CI: 0.45-9.93) for moderate anemia, and 0.88 (95% CI: 0.16-4.82) for mild anemia. Anemia and WHO staging were independent predictors of mortality. PMID:24344253

  14. Predictors of Weight Change in Male HIV-Positive Injection Drug Users Initiating Antiretroviral Therapy in Hanoi, Vietnam

    PubMed Central

    Tang, Alice M.; Sheehan, Heidi B.; Jordan, Michael R.; Duong, Dang Van; Terrin, Norma; Dong, Kimberly; Lien, Trinh Thi Minh; Trung, Nguyen Vu; Wanke, Christine A.; Hien, Nguyen Duc

    2011-01-01

    We examined clinical and nutritional predictors of weight change over two consecutive 6-month intervals among 99 HIV-positive male injection drug users initiating antiretroviral therapy (ART) in Hanoi, Vietnam. The average weight gain was 3.1 ± 4.8?kg in the first six months after ART and 0.8 ± 3.0?kg in the following six months. Predictors of weight change differed by interval. In the first interval, CD4 < 200?cells/?L, excellent/very good adherence to ART, bothersome nausea, and liquid supplement use were all associated with positive weight changes. Moderate to heavy alcohol use and tobacco smoking were associated with negative weight changes. In the second interval, having a CD4 count <200?cells/?L at the beginning of the interval and tobacco smoking were the only significant predictors and both were associated with negative weight changes. We identified several potential areas for interventions to promote weight gain immediately after starting ART in this population. Studies are needed to determine whether improving weight prior to, or at, ART initiation will result in improved outcomes on ART. PMID:21776380

  15. Two-year outcome of first-line antiretroviral therapy among HIV-1 vertically infected children in Hanoi, Vietnam.

    PubMed

    Pham, Hv; Ishizaki, A; Nguyen, Lv; Phan, Ctt; Phung, Ttb; Takemoto, K; Pham, An; Bi, X; Khu, Dtk; Ichimura, H

    2014-10-19

    A retrospective analysis of 86 HIV-1 vertically infected Vietnamese children with a follow-up period >24 months after initiating antiretroviral therapy (ART) was performed from 2008 to 2012, to assess the outcome of first-line ART in resource-limited settings. Of the 86 children, 68 (79.1%) were treated successfully (plasma HIV-1 load [VL] <1000 copies/ml), and 63 (73.3%) had full viral suppression (VL <400 copies/ml) after 24 months of ART. No significant difference between successfully treated patients and failure groups was observed in VL, CD4(+) T-cell count or clinical stage at baseline; age at ART start; or ART regimen. All 14 children with VL >5000 copies/ml, one of four children with VL 1000-5000 copies/ml and none with VL <1000 copies/ml developed reverse-transcriptase inhibitor (RTI)-resistance mutations by 24 months of ART. Y181C and M184V/I were the most dominant non-nucleoside and nucleoside RTI-resistance mutations, respectively (13/15, 86.7%). These findings suggest that VL testing after 24 months of ART can be used to efficiently differentiate ART failures among HIV-1 vertically infected children in resource-limited settings. PMID:25332224

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

    PubMed Central

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

    2011-01-01

    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. PMID:21390948

  17. Differences in Response to Antiretroviral Therapy by Sex and Hepatitis C Infection Status.

    PubMed

    Marcus, Julia L; Leyden, Wendy A; Chao, Chun R; Xu, Lanfang; Quesenberry, Charles P; Tien, Phyllis C; Klein, Daniel B; Towner, William J; Horberg, Michael A; Silverberg, Michael J

    2015-07-01

    Hepatitis C virus (HCV) co-infection and biological sex may each affect response to antiretroviral therapy (ART), yet no studies have examined HIV-associated outcomes by both HCV status and sex. We conducted a cohort study of HIV-infected adults initiating ART in Kaiser Permanente California during 1996-2011. We used piecewise linear regression to assess CD4 changes by sex and HCV status over 5 years. We used Cox regression to estimate hazard ratios (HR) by sex and HCV status for HIV RNA <500 copies/mL over 1 year, and for AIDS and death over the follow-up period. Among 12,865 subjects, there were 154 HIV/HCV-co-infected women, 1000 HIV/HCV-co-infected men, 1088 HIV-mono-infected women, and 10,623 HIV-mono-infected men. CD4 increases were slower in the first year for HIV/HCV-co-infected women (75 cells/?L) and men (70 cells/?L) compared with HIV-mono-infected women (145 cells/?L) and men (120 cells/?L; p<0.001). After 5 years, women had higher CD4 than men in both HIV-mono-infected (598 vs. 562 cells/?L, p=0.003) and HIV/HCV-co-infected individuals (567 vs. 509 cells/?L, p=0.003). Regardless of sex, HIV/HCV co-infection was associated with 40% higher mortality [95% confidence interval (CI): 1.2-1.6] compared with HIV mono-infection, but was not associated with AIDS (HR 1.1, 95% CI: 0.9-1.3) or achieving HIV RNA <500 copies/mL (HR 1.0, 95% CI: 0.9-1.1). HIV/HCV-co-infected men and women have slower CD4 recovery after starting ART and have increased mortality compared with HIV-mono-infected men and women. HCV should be aggressively treated in HIV/HCV-co-infected adults, regardless of sex. PMID:26061798

  18. Heterosexual HIV-1 infectiousness and antiretroviral use: Systematic review of prospective studies of discordant couples

    PubMed Central

    Baggaley, Rebecca F; White, Richard G; Hollingsworth, T Déirdre; Boily, Marie-Claude

    2015-01-01

    Background Recent studies have estimated the reduction in HIV-1 infectiousness with antiretroviral therapy (ART), but high-quality studies such as randomized control trials, accompanied by rigorous adherence counselling, are likely to overestimate the effectiveness of treatment-as-prevention in real-life settings. Methods We attempted to summarize the effect of ART on HIV transmission by undertaking a systematic review and meta-analysis of HIV-1 infectiousness per heterosexual partnership (incidence rate and cumulative incidence over study follow-up) estimated from prospective studies of discordant couples. We used random-effects Poisson regression models to obtain summary estimates. When possible, the analyses were further stratified by direction of transmission (man-to-woman or woman-to-man) and economic setting (high- or low-income countries). Potential causes of heterogeneity of estimates were explored through subgroup analyses. Results Fifty publications were included. Nine allowed comparison between ART and non-ART users within studies (ART-stratified studies), where summary incidence rates were 3.6/100 person-years (95% confidence interval= 2.0-6.5) and 0.2/100 person-years (0.07-0.7) for non-ART- and ART-using couples, respectively (p<0.001), constituting a 91% (79%-96%) reduction in per-partner HIV-1 incidence rate with ART use. The 41 studies that did not stratify by ART use provided estimates with high levels of heterogeneity (I2 statistic) and few reported levels of ART use, making interpretation difficult. Nevertheless, estimates tended to be lower with than without ART use. Infectiousness tended to be higher for low-income than high-income settings, but there was no clear pattern by direction of transmission (man-to-woman and woman-to-man). Conclusions ART substantially reduces HIV-1 infectiousness within discordant couples, based on observational studies, and could play a major part in HIV-1 prevention efforts. However the non-zero risk from partners receiving ART demonstrates that appropriate counselling and other risk reduction strategies for discordant couples are still required. Additional estimates of ART effectiveness by adherence level from real-life settings will be important, especially for persons starting treatment early without symptoms. PMID:23222513

  19. Masculine attitudes of superiority deter men from accessing antiretroviral therapy in Dar es Salaam, Tanzania

    PubMed Central

    Nyamhanga, Tumaini M.; Muhondwa, Eustace P.Y.; Shayo, Rose

    2013-01-01

    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

  20. Uptake of WHO Recommendations for First-Line Antiretroviral Therapy in Kenya, Uganda, and Zambia

    PubMed Central

    Duber, Herbert C.; Dansereau, Emily; Masters, Samuel H.; Achan, Jane; Burstein, Roy; DeCenso, Brendan; Gasasira, Anne; Ikilezi, Gloria; Kisia, Caroline; Masiye, Felix; Njuguna, Pamela; Odeny, Thomas; Okiro, Emelda; Roberts, D. Allen; Gakidou, Emmanuela

    2015-01-01

    Introduction Antiretroviral therapy (ART) guidelines were significantly changed by the World Health Organization in 2010. It is largely unknown to what extent these guidelines were adopted into clinical practice. Methods This was a retrospective observational analysis of first-line ART regimens in a sample of health facilities providing ART in Kenya, Uganda, and Zambia between 2007-2008 and 2011-2012. Data were analyzed for changes in regimen over time and assessed for key patient- and facility-level determinants of tenofovir (TDF) utilization in Kenya and Uganda using a mixed effects model. Results Data were obtained from 29,507 patients from 146 facilities. The overall percentage of patients initiated on TDF-based therapy increased between 2007-2008 and 2011-2012 from 3% to 37% in Kenya, 2% to 34% in Uganda, and 64% to 87% in Zambia. A simultaneous decrease in stavudine (d4T) utilization was also noted, but its use was not eliminated, and there remained significant variation in facility prescribing patterns. For patients initiating ART in 2011-2012, we found increased odds of TDF use with more advanced disease at initiation in both Kenya (odds ratio [OR]: 2.78; 95% confidence interval [CI]: 1.73-4.48) and Uganda (OR: 2.15; 95% CI: 1.46-3.17). Having a CD4 test performed at initiation was also a significant predictor in Uganda (OR: 1.43; 95% CI: 1.16-1.76). No facility-level determinants of TDF utilization were seen in Kenya, but private facilities (OR: 2.86; 95% CI: 1.45-5.66) and those employing a doctor (OR: 2.86; 95% CI: 1.48-5.51) were more likely to initiate patients on TDF in Uganda. Discussion d4T-based ART has largely been phased out over the study period. However, significant in-country and cross-country variation exists. Among the most recently initiated patients, those with more advanced disease at initiation were most likely to start TDF-based treatment. No facility-level determinants were consistent across countries to explain the observed facility-level variation. PMID:25807553

  1. Prevalence of transmitted HIV-1 antiretroviral resistance among patients initiating antiretroviral therapy in Brazil: a surveillance study using dried blood spots

    PubMed Central

    de Moraes Soares, Celina M P; Vergara, Tania R C; Brites, Carlos; Brito, Jose D U; Grinberg, Gorki; Caseiro, Marcos M; Correa, Carlos; Suffert, Theodoro A; Pereira, Flavio R; Camargo, Michelle; Janini, Luiz M; Komninakis, Shirley; Sucupira, Maria C A; Diaz, Ricardo S

    2014-01-01

    Introduction In Brazil, the use of antiretrovirals is widespread: more than 260,000 individuals are currently undergoing treatment. We conducted a survey targeting antiretroviral-naďve individuals who were initiating antiretroviral therapy (ART) according to local guidelines. This survey covered five Brazilian regions. Methods The HIV Threshold Survey methodology (HIV-THS) of the World Health Organization was utilized, and subjects were selected from seven highly populated cities representative of all Brazilian macro-regions. Dried blood spots (DBS) were collected on SS903 collection cards and were transported by regular mail at room temperature to a single central laboratory for genotyping. Results We analysed samples from 329 individuals initiating highly active antiretroviral therapy (HAART), 39 (11.8%) of whom were harbouring transmitted drug resistance (TDR). The mean CD4+ T cell count was 253 cells/µL, and the mean viral load was 142,044 copies/mL. The regional prevalence of resistance was 17.0% in the Northeast, 12.8% in the Southeast, 10.6% in the Central region, 8.5% in the North and 8.5% in the South. The inhibitor-specific TDR prevalence was 6.9% for nucleoside reverse transcriptase inhibitors, 4.9% for non-nucleoside reverse transcriptase inhibitors and 3.9% for protease inhibitors; 3.6% of individuals presented resistance to more than one class of inhibitors. Overall, there were trends towards higher prevalences of subtype C towards the South and subtype F towards the North. Of the DBS samples collected, 9.3% failed to provide reliable results. Discussion We identified variable TDR prevalence, ranging from intermediate to high levels, among individuals in whom HIV disease progressed, thus implying that resistance testing before initiating ART could be effective in Brazil. Our results also indicate that the use of DBS might be especially valuable for providing access to testing in resource-limited and remote settings. PMID:25249214

  2. Does short-term virologic failure translate to clinical events in antiretroviral-naďve patients initiating antiretroviral therapy in clinical practice?

    PubMed Central

    The Antiretroviral Cohort Collaboration (ART-CC); Mugavero, Michael J.; May, Margaret; Harris, Ross; Saag, Michael S.; Costagliola, Dominique; Egger, Matthias; Phillips, Andrew; Günthard, Huldrych F.; Dabis, Francois; Hogg, Robert; De Wolf, Frank; Fatkenheuer, Gerd; John Gill, M.; Justice, Amy; D'Arminio Monforte, Antonella; Lampe, Fiona; Miró, Jose M.; Staszewski, Schlomo; Sterne, Jonathan A. C.

    2008-01-01

    Objective To determine if differences in short-term virologic failure among commonly used ART regimens translate to differences in clinical events in antiretroviral-naďve patients initiating ART. Design Observational cohort study of patients initiating ART between January 2000 and December 2005. Setting The Antiretroviral Therapy Cohort Collaboration (ART-CC) is a collaboration of 15 HIV cohort studies from Canada, Europe, and the United States. Subjects, participants A total of 13,546 antiretroviral-naďve HIV-positive patients initiating ART with efavirenz (EFV), nevirapine (NVP), lopinavir/ritonavir (LPV/r), nelfinavir (NFV), or abacavir (ABC) as third drugs in combination with a zidovudine and lamivudine NRTI backbone. Main outcome measures Short-term (24-week) virologic failure (>500 copies/mL) and clinical events within 2 years of ART initiation (incident AIDS-defining event, death, and a composite measure of these two outcomes). Results Compared with EFV as initial third drug, short-term virologic failure was more common with all other third drugs evaluated; NVP (adjusted odds ratio=1.87, 95%CI=1.58,2.22), LPV/r (1.32, 95%CI=1.12–1.57), NFV (3.20, 95%CI=2.74,3.74), and ABC (2.13, 95%CI=1.82,2.50). However, the rate of clinical events within 2 years of ART initiation appeared higher only with NVP (adjusted hazard ratio for composite outcome measure 1.27, 95%CI=1.04,1.56) and ABC (1.22, 95%CI=1.00,1.48). Conclusions Among antiretroviral-naďve patients initiating therapy, between-ART regimen differences in short-term virologic failure do not necessarily translate to differences in clinical outcomes. Our results should be interpreted with caution because of the possibility of residual confounding by indication. PMID:19005271

  3. Early changes in inflammatory and pro-thrombotic biomarkers in patients initiating antiretroviral therapy with abacavir or tenofovir

    PubMed Central

    2011-01-01

    Background Abacavir has been associated with an increased risk of acute myocardial infarction, but the pathogenic mechanisms remain unknown. We evaluated longitudinal changes in pro-atherosclerotic biomarkers in patients initiating abacavir or tenofovir. Methods Consecutive patients initiating antiretroviral therapy (ART) with abacavir/lamivudine or tenofovir/emtricitabine were included. Plasma levels of high sensitivity C reactive protein (hsCRP), interleukin-6 (IL-6), intercellular adhesion molecule-1, vascular cell adhesion molecule-1 (sVCAM-1) and plasminogen activator inhibitor-1 (PAI-1) were measured at baseline and at different time points throughout 48 weeks. Comparisons were adjusted for age, sex, ART status at inclusion, viral load, lipodystrophy, Framingham score and hepatitis C virus co-infection status. Results 50 patients were analyzed, 28 initiating abacavir and 22 tenofovir. The endothelial biomarker sVCAM-1 declined significantly in both treatment groups. hsCRP tended to increase soon after starting therapy with abacavir, a trend that was not seen in those initiating tenofovir. IL-6 significantly increased only at week 24 from baseline in patients on abacavir (+225%, p < 0.01) although the differences were not significant between groups. The procoagulant biomarker PAI-1 plasma levels increased from baseline at week 12 (+57%; p = 0.017), week 24 (+72%; p = 0.008), and week 48 (+149%; p < 0.001) in patients on tenofovir, but differences between groups were not statistically significant. Conclusion Changes in biomarkers of inflammation, coagulation, and endothelial function are not different in viremic patients starting ART with abacavir/lamivudine or tenofovir/emtricitabine. These changes occur in the early phases of treatment and include anti- and pro-atherosclerotic effects with both drugs. PMID:21294867

  4. Disparities in Antiretroviral Treatment: A Comparison of Behaviorally-HIV-Infected Youth and Adults in the HIV Research Network

    PubMed Central

    Agwu, AL; Fleishman, JA; Korthuis, PT; Siberry, GK; Ellen, JM; Gaur, AH; Rutstein, R; Gebo, KA

    2011-01-01

    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-naďve 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-naďve, 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. PMID:21637114

  5. Effects on Anthropometry and Appetite of Vitamins and Minerals Given in Lipid Nutritional Supplements for Malnourished HIV-Infected Adults Referred for Antiretroviral Therapy: Results From the NUSTART Randomized Controlled Trial

    PubMed Central

    Rehman, Andrea M.; Woodd, Susannah; PrayGod, George; Chisenga, Molly; Siame, Joshua; Koethe, John R.; Heimburger, Douglas C.; Kelly, Paul; Friis, Henrik

    2015-01-01

    Background: The evidence base for effects of nutritional interventions for malnourished HIV-infected patients starting antiretroviral therapy (ART) is limited and inconclusive. Objective: We hypothesized that both vitamin and mineral deficiencies and poor appetite limit weight gain in malnourished patients starting ART and that vitamin and mineral supplementation would improve appetite and permit nutritional recovery. Design: The randomized controlled Nutritional Support for Africans Starting Antiretroviral Therapy trial was conducted in Mwanza, Tanzania, and Lusaka, Zambia. ART-naive adults referred for ART and with body mass index <18.5 kg/m2 received lipid-based nutritional supplements either without (LNS) or with added vitamins and minerals (LNS-VM), beginning before ART initiation. Participants were given 30 g/d LNS from recruitment until 2 weeks after starting ART and 250 g/d from weeks 2 to 6 of ART. Results: Of 1815 patients recruited, 365 (20%) died during the study and 813 (45%) provided data at 12 weeks. Controlling for baseline values, anthropometric measures were consistently higher at 12-week ART in the LNS-VM than in the LNS group but statistically significant only for calf and mid-upper arm circumferences and triceps skinfold. Appetite did not differ between groups. Using piecewise mixed-effects quadratic models including all patients and time points, the main effects of LNS-VM were seen after starting ART and were significant for weight, body mass index, and mid-upper arm circumference. Conclusions: Provision of high levels of vitamins and minerals to patients referred for ART, delivered with substantial macronutrients, increased nutritional recovery but did not seem to act through treatment group differences in appetite. PMID:25501607

  6. Research Start-up Request Form Please use this form for all start-up requests.

    E-print Network

    Thomas, Andrew

    Research Start-up Request Form Please use this form for all start-up requests. All requests must: Department: College: Date of Offer: Start Date: Year 1 Year 2 Year 3 Fiscal Year: Equipment: Amount of Start-up of Start-up Provided by Dept. or College Year 1 Year 2 Year 3 Amount: Planned Use: EVP/Provost Signature

  7. Presence of an Inducible HIV1 Latent Reservoir during Highly Active Antiretroviral Therapy

    Microsoft Academic Search

    Tae-Wook Chun; Lieven Stuyver; Stephanie B. Mizell; Linda A. Ehler; Jo Ann M. Mican; Michael Baseler; Alun L. Lloyd; Martin A. Nowak; Anthony S. Fauci

    1997-01-01

    Although highly active antiretroviral therapy (HAART) in the form of triple combinations of drugs including protease inhibitors can reduce the plasma viral load of some HIV-1-infected individuals to undetectable levels, it is unclear what the effects of these regimens are on latently infected CD4+ T cells and what role these cells play in the persistence of HIV-1 infection in individuals

  8. Atazanavir/ritonavir-based combination antiretroviral therapy for treatment of HIV-1 infection in adults

    PubMed Central

    Achenbach, Chad J; Darin, Kristin M; Murphy, Robert L; Katlama, Christine

    2011-01-01

    In the past 15 years, improvements in the management of HIV infection have dramatically reduced morbidity and mortality. Similarly, rapid advances in antiretroviral medications have resulted in the possibility of life-long therapy with simple and tolerable regimens. Protease inhibitors have been important medications in regimens of combination antiretroviral therapy for the treatment of HIV. One of the recommended and commonly used therapies in this class is once-daily-administered atazanavir, pharmacologically boosted with ritonavir (atazanavir/r). Clinical studies and practice have shown these drugs, in combination with other antiretroviral agents, to be potent, safe and easy to use in a variety of settings. Atazanavir/r has minimal short-term toxicity, including benign bilirubin elevation, and has less potential for long-term complications of hyperlipidemia and insulin resistance compared with other protease inhibitors. A high genetic barrier to resistance and a favorable resistance profile make it an excellent option for initial HIV treatment or as the first drug utilized in the protease inhibitors class. Atazanavir/r is also currently being studied in novel treatment strategies, including combinations with new classes of antiretrovirals to assess nucleoside reverse transcriptase inhibitor-sparing regimens. In this article we review atazanavir/r as a treatment for HIV infection and discuss the latest information on its pharmacology, efficacy and toxicity. PMID:21731578

  9. Sex issues in HIV1-infected persons during highly active antiretroviral therapy: a systematic review

    Microsoft Academic Search

    Emanuele Nicastri; Sebastiano Leone; Claudio Angeletti; Lucia Palmisano; Loredana Sarmati; Antonio Chiesi; Andrea Geraci; Stefano Vella; Pasquale Narciso; Angela Corpolongo; Massimo Andreoni

    2007-01-01

    Background: Since the introduction of highly active antiretroviral therapy (HAART), morbidity and mortality rates have sharply decreased among HIV-infected patients. Studies of possible differences between men and women in the course of HIV infection give conflicting results. The objective of this study was to assess sex differences during HAART. Methods: A literature search by using the MEDLINE database between March

  10. HIV-associated renal diseases and highly active antiretroviral therapy-induced nephropathy.

    PubMed

    Röling, J; Schmid, H; Fischereder, M; Draenert, R; Goebel, F D

    2006-05-15

    Renal disease is becoming an increasingly prevalent entity in human immunodeficiency virus (HIV)-infected patients; it occurs in a variety of clinical settings and is associated with histopathological changes. HIV-related renal impairment can present as acute or chronic kidney disease; it can be caused directly or indirectly by HIV and/or by drug-related effects that are directly nephrotoxic or lead to changes in renal function by inducing metabolic vaculopathy and renal damage. Acute renal failure is frequently caused by the toxic effects of antiretroviral therapy or nephrotoxic antimicrobial substances used in the treatment of opportunistic infections. Chronic renal disease can be caused by multiple pathophysiological mechanisms, leading to HIV-associated nephropathy, a form of collapsing focal glomerulosclerosis, thrombotic microangiopathy, and various forms of immune complex glomerulonephritis. The increase in life expectancy and alteration of lipid metabolism due to receipt of highly active antiretroviral therapy are expected to result in an increased prevalence of diabetes and hypertension and, thus, to secondary diabetic and hypertensive renal damage. Antiretroviral agents, such as indinavir and tenofovir, have been associated with nephrotoxic drug effects that have been shown to be reversible in most cases. In this article, we review the current knowledge about acute and chronic HIV-associated renal disease, metabolic alterations and related nephropathies, and toxic drug effects of combination antiretroviral pharmacotherapy. PMID:16619164

  11. The antiretroviral protease inhibitor ritonavir accelerates glutathione export from cultured primary astrocytes.

    PubMed

    Arend, Christian; Brandmann, Maria; Dringen, Ralf

    2013-04-01

    Antiretroviral protease inhibitors are a class of important drugs that are used for the treatment of human immunodeficiency virus infections. Among those compounds, ritonavir is applied frequently in combination with other antiretroviral protease inhibitors, as it has been reported to boost their therapeutic efficiency. To test whether ritonavir affects the viability and the glutathione (GSH) metabolism of brain cells, we have exposed primary astrocyte cultures to this protease inhibitor. Application of ritonavir in low micromolar concentrations did not compromise cell viability, but caused a time- and concentration-dependent loss of GSH from the cells which was accompanied by a matching increase in the extracellular GSH content. Half-maximal effects were observed for ritonavir in a concentration of 3 ?M. The ritonavir-induced stimulated GSH export from astrocytes was completely prevented by MK571, an inhibitor of the multidrug resistance protein 1. In addition, continuous presence of ritonavir was essential to maintain the stimulated GSH export, since removal of ritonavir terminated the stimulated GSH export. Ritonavir was more potent to stimulate GSH export from astrocytes than the antiretroviral protease inhibitors indinavir and nelfinavir, but combinations of ritonavir with indinavir or nelfinavir did not further stimulate astrocytic GSH export compared to a treatment with ritonavir alone. The strong effects of ritonavir and other antiretroviral protease inhibitors on the GSH metabolism of astrocytes suggest that a chronic treatment of patients with such compounds may affect their brain GSH metabolism. PMID:23341120

  12. Antiretroviral protease inhibitors accelerate glutathione export from viable cultured rat neurons.

    PubMed

    Brandmann, Maria; Hohnholt, Michaela C; Petters, Charlotte; Dringen, Ralf

    2014-05-01

    Antiretroviral protease inhibitors are crucial components of the antiretroviral combination therapy that is successfully used for the treatment of patients with HIV infection. To test whether such protease inhibitors affect the glutathione (GSH) metabolism of neurons, cultured cerebellar granule neurons were exposed to indinavir, nelfinavir, lopinavir or ritonavir. In low micromolar concentrations these antiretroviral protease inhibitors did not acutely compromise the cell viability, but caused a time- and concentration-dependent increase in the accumulation of extracellular GSH which was accompanied by a matching loss in cellular GSH. The stimulating effect by indinavir, lopinavir and ritonavir on GSH export was immediately terminated upon removal of the protease inhibitors, while the nelfinavir-induced stimulated GSH export persisted after washing the cells. The stimulation of neuronal GSH export by protease inhibitors was completely prevented by MK571, an inhibitor of the multidrug resistance protein 1, suggesting that this transporter mediates the accelerated GSH export during exposure of neurons to protease inhibitors. These data suggest that alterations in brain GSH metabolism should be considered as potential side-effects of a treatment with antiretroviral protease inhibitors. PMID:24664418

  13. Patients' Ways of Speaking about Antiretroviral Medications and Possible Implications for Adherence

    ERIC Educational Resources Information Center

    Delbene, Roxana

    2012-01-01

    The medical literature reports that antiretrovirals (ARVs) are considered attitudinal objects (Dunbar-Jacob, 1995). Drawing on the pragmatics of emotion (Caffi & Janney, 1994), this study analyzes how patients' stances about their ARTs shape their emotional relationships with their treatments. The data, collected in a public hospital in Uruguay,…

  14. Immune recovery uveitis in patients with AIDS and cytomegalovirus retinitis after highly active antiretroviral therapy

    Microsoft Academic Search

    Quan Dong Nguyen; John H Kempen; Stephen G Bolton; James P Dunn; Douglas A Jabs

    2000-01-01

    PURPOSE: To estimate the incidence and describe the characteristics of immune recovery uveitis in patients with acquired immunodeficiency syndrome (AIDS) and cytomegalovirus retinitis treated with highly active antiretroviral therapy.METHODS: The records of all patients with AIDS and cytomegalovirus retinitis from 1995 to 1998 seen at the AIDS Ophthalmology Service of the Johns Hopkins Medical Institutions were reviewed. Eighty-two patients with

  15. Outcomes after two years of providing antiretroviral treatment in Khayelitsha, South Africa

    Microsoft Academic Search

    David Coetzee; Katherine Hildebrand; Andrew Boulle; Gary Maartens; Francoise Louis; Veliswa Labatala; Hermann Reuter; Nonthutuzelo Ntwana; Eric Goemaere

    2004-01-01

    Background: A community-based antiretroviral therapy (ART) programme was estab- lished in 2001 in a South African township to explore the operational issues involved in providing ART in the public sector in resource-limited settings and demonstrate the feasibility of such a service. Methods: Data was analysed on a cohort of patients with symptomatic HIV disease and a CD4 lymphocyte count ,

  16. Computed CD4 percentage as a low-cost method for determining pediatric antiretroviral treatment eligibility

    Microsoft Academic Search

    Steven FJ Callens; Faustin Kitetele; Jean Lusiama; Nicole Shabani; Samuel Edidi; Robert Colebunders; Frieda Behets; Annelies Van Rie

    2008-01-01

    BACKGROUND: The performance of the WHO recommendations for pediatric antiretroviral treatment (ART) in resource poor settings is insufficiently documented in routine care. METHODS: We compared clinical and immunological criteria in 366 children aged 0 to 12 years in Kinshasa and evaluated a simple computation to estimate CD4 percent, based on CD4 count, total white blood cell count and percentage lymphocytes.

  17. What Happens to Patients on Antiretroviral Therapy Who Transfer Out to Another Facility?

    Microsoft Academic Search

    Joseph Kwong-Leung Yu; Teck-Siang Tok; Jih-Jin Tsai; Wu-Shou Chang; Rose K. Dzimadzi; Ping-Hsiang Yen; Simon D. Makombe; Amon Nkhata; Erik J. Schouten; Kelita Kamoto; Anthony D. Harries; Beatriz Grinsztejn

    2008-01-01

    BackgroundLong term retention of patients on antiretroviral therapy (ART) in Africa's rapidly expanding programmes is said to be 60% at 2 years. Many reports from African ART programmes make little mention of patients who are transferred out to another facility, yet Malawi's national figures show a transfer out of 9%. There is no published information about what happens to patients

  18. Barriers to Antiretroviral Medication Adherence in Young HIV-Infected Children

    ERIC Educational Resources Information Center

    Roberts, Kathleen Johnston

    2005-01-01

    The purpose of this exploratory study was to examine, from the perspectives of both HIV-infected children and such children's primary guardians, the barriers children face in adhering to combination antiretroviral therapies. Nine HIV-infected young children and 14 guardians of HIV-positive children were interviewed about what the children's lives…

  19. Modelling HIV epidemics in the antiretroviral era: the UNAIDS Estimation and Projection package 2009

    E-print Network

    Raftery, Adrian

    Modelling HIV epidemics in the antiretroviral era: the UNAIDS Estimation and Projection package for country-level estimation and short-term projection of HIV/AIDS epidemics based on fitting observed HIV of ART on incidence and the resulting increases in HIV prevalence in populations with high ART coverage

  20. Future HIV Therapy Priority paper evaluation Antiretroviral therapy among HIV-infected breastfeeding mothers

    E-print Network

    Paris-Sud XI, Université de

    Future HIV Therapy Priority paper evaluation 1/10 Antiretroviral therapy among HIV-infected breastfeeding mothers: a promising strategy to prevent HIV transmission through breastmilk in Africa Renaud-00177039,version1-10Nov2009 Author manuscript, published in "Future HIV Therapy 2007;1(1):17-21" DOI : 10

  1. Cost-Effectiveness of Screening for HIV in the Era of Highly Active Antiretroviral Therapy

    Microsoft Academic Search

    Gillian D. Sanders; Ahmed M. Bayoumi; Vandana Sundaram; S. Pinar Bilir; Christopher P. Neukermans; Chara E. Rydzak; Lena R. Douglass; Laura C. Lazzeroni; Mark Holodniy; Douglas K. Owens

    2005-01-01

    background The costs, benefits, and cost-effectiveness of screening for human immunodeficiency virus (HIV) in health care settings during the era of highly active antiretroviral therapy (HAART) have not been determined. methods We developed a Markov model of costs, quality of life, and survival associated with an HIV-screening program as compared with current practice. In both strategies, sympto- matic patients were

  2. Factors associated with discontinuation of antiretroviral therapy in HIV-infected patients with alcohol problems

    Microsoft Academic Search

    T. W. Kim; A. Palepu; D. M. Cheng; H. Libman; R. Saitz; J. H. Samet

    2007-01-01

    Although mortality rates among HIV-infected populations have declined with the advent of combination antiretroviral therapy (ART), patients with substance use disorders have benefited less from these therapies. While adherence to ART has been well studied, less is known about factors associated with discontinuation of ART. The aim of this study is to investigate predictors of discontinuation of ART in HIV-infected

  3. Peyronie's disease in men with HIV responding to highly active antiretroviral therapy.

    PubMed

    Rogers, G D; French, M A

    2004-05-01

    The pathogenesis of Peyronie's disease (induratio penis plastica) is unclear, but immune phenomena appear likely to be involved. Two cases are presented where the condition developed in temporal association with a virological response to highly active antiretroviral therapy (HAART) in men with HIV infection. It is suggested that this may represent another manifestation of immune restoration disease. PMID:15139986

  4. Barriers to Adherence to Antiretroviral TreatmentThe Perspectives of Patient Advocates

    Microsoft Academic Search

    Ashraf Kagee; Tracey Delport

    2010-01-01

    Patient advocates were asked for their perspectives on the structural barriers to adherence to antiretroviral treatment among patients living with HIV. Poverty-related barriers were transport difficulties, food insecurity and patients’ receipt of a disability grant. Institutional barriers were long waiting times at clinics, negative experiences with clinic staff, low levels of health literacy and poor access to substance abuse treatment.

  5. Stigma trajectories among people living with HIV (PLHIV) embarking on a life time journey with antiretroviral drugs in Jinja, Uganda

    PubMed Central

    2013-01-01

    Background Stigma is a barrier to HIV prevention and treatment. There is a limited understanding of the types of stigma facing people living with HIV (PLHIV) on antiretroviral therapy (ART). We describe the stigma trajectories of PLHIV over a 5-year period from the time they started ART. Methods Longitudinal qualitative in-depth interviews were conducted with 41 members of The AIDS Support Organisation (TASO) from 2005 to 2008 in Jinja, Uganda, who were part of a pragmatic cluster-randomised trial comparing two different modes of ART delivery (facility and home). Participants were stratified by gender, ART delivery arm and HIV stage (early or advanced) and interviewed at enrolment on to ART and then after 3, 6, 18 and 30 months. Interviews focused on stigma and ART experiences. In 2011, follow-up interviews were conducted with 24 of the participants who could be traced. Transcribed texts were translated, coded and analyzed thematically. Results Stigma was reported to be very high prior to starting ART, explained by visible signs of long-term illnesses and experiences of discrimination and abuse. Early coping strategies included: withdrawal from public life, leaving work due to ill health and moving in with relatives. Starting ART led to a steady decline in stigma and allowed the participants to take control of their illness and manage their social lives. Better health led to resumption of work and having sex but led to reduced disclosure to employers, colleagues and new sexual partners. Some participants mentioned sero-sorting in order to avoid questions around HIV sero-status. A rise in stigma levels during the 18 and 30 month interviews may be correlated with decreased disclosure. By 2011, ART-related stigma was even more pronounced particularly among those who had started new sexual relationships, gained employment and those who had bodily signs from ART side-effects. Conclusion This study has shown that while ART comes with health benefits which help individuals to get rid of previously stigmatising visible signs, an increase in stigma may be noticed after about five years on ART, leading to reduced disclosure. ART adherence counselling should reflect changing causes and manifestations of stigma over time. PMID:24010761

  6. 30 CFR 57.10010 - Starting precautions.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 2011-07-01 false Starting precautions. 57.10010 Section 57.10010...SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-UNDERGROUND METAL AND NONMETAL MINES...Aerial Tramways § 57.10010 Starting precautions. Where possible, aerial...

  7. 30 CFR 57.10010 - Starting precautions.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 2012-07-01 false Starting precautions. 57.10010 Section 57.10010...SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-UNDERGROUND METAL AND NONMETAL MINES...Aerial Tramways § 57.10010 Starting precautions. Where possible, aerial...

  8. 30 CFR 57.10010 - Starting precautions.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 2014-07-01 false Starting precautions. 57.10010 Section 57.10010...SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-UNDERGROUND METAL AND NONMETAL MINES...Aerial Tramways § 57.10010 Starting precautions. Where possible, aerial...

  9. 30 CFR 57.10010 - Starting precautions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 2010-07-01 false Starting precautions. 57.10010 Section 57.10010...SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-UNDERGROUND METAL AND NONMETAL MINES...Aerial Tramways § 57.10010 Starting precautions. Where possible, aerial...

  10. 30 CFR 57.10010 - Starting precautions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 2013-07-01 false Starting precautions. 57.10010 Section 57.10010...SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-UNDERGROUND METAL AND NONMETAL MINES...Aerial Tramways § 57.10010 Starting precautions. Where possible, aerial...

  11. Northwestern Investigator's Guide to Starting a Company

    E-print Network

    ? ......................................................................... 6 For-profit or non-profit1 Northwestern Investigator's Guide to Starting a Company acknowledgment to the University of Georgia for permission to use material from "Start

  12. Engine management during NTRE start up

    NASA Astrophysics Data System (ADS)

    Bulman, Mel; Saltzman, Dave

    The topics are presented in viewgraph form and include the following: total engine system management critical to successful nuclear thermal rocket engine (NTRE) start up; NERVA type engine start windows; reactor power control; heterogeneous reactor cooling; propellant feed system dynamics; integrated NTRE start sequence; moderator cooling loop and efficient NTRE starting; analytical simulation and low risk engine development; accurate simulation through dynamic coupling of physical processes; and integrated NTRE and mission performance.

  13. A pilot study to determine the impact on dyslipidemia of adding tenofovir to stable background antiretroviral therapy: ACTG 5206.

    PubMed

    Tungsiripat, Marisa; Kitch, Douglas; Glesby, Marshall J; Gupta, Samir K; Mellors, John W; Moran, Laura; Jones, Lynne; Alston-Smith, Beverly; Rooney, James F; Aberg, Judith A

    2010-07-17

    Several studies have reported improvement in lipids after antiretroviral therapy switches to tenofovir disoproxil fumarate (TDF)-containing regimens. We assessed lipid-lowering effects of TDF by adding it to a stable antiretroviral therapy regimen in this double-blind, placebo-controlled crossover study. We demonstrated that nonhigh-density lipoprotein cholesterol, low-density lipoprotein cholestrol, and total cholestrol improved significantly over TDF vs. placebo treatment in HIV-infected individuals with dyslipidemia. Adding TDF to stable, virologically suppressive antiretroviral therapy regimens improved lipid parameters, supporting a lipid-lowering effect of TDF. PMID:20495438

  14. Therapy planning as constraint satisfaction: a computer-based antiretroviral therapy advisor for the management of HIV.

    PubMed Central

    Smith, D. S.; Park, J. Y.; Musen, M. A.

    1998-01-01

    We applied the Protégé methodology for building knowledge-based systems to the domain of antiretroviral therapy. We modeled the task of prescribing drug therapy for HIV, abstracting the essential characteristics of the problem solving. We mapped our model of the antiretroviral-therapy domain to the class of constraint-satisfaction problems, and reused the propose-and-revise problem-solving method, from the Protégé library of methods, to build an antiretroviral therapy advisor, ART Critic. Careful modeling and using Protégé allowed us to build a useful and extensible knowledge-based application rapidly. PMID:9929295

  15. Head Start--Hopes and Disappointments.

    ERIC Educational Resources Information Center

    Hymes, James L., Jr.

    1985-01-01

    James L. Hymes, Jr., former President of NAEYC and member of the original Head Start Planning Committee, is interviewed about his hopes for and disappointments with Head Start during the past 20 years. Highlights Head Start's initial benefits to families, children, and the early childhood profession; program quality; and continued lack of federal…

  16. JumpStart III Final Report.

    ERIC Educational Resources Information Center

    Cohen, Arthur M.; Brawer, Florence B.; Kozeracki, Carol A.

    This final report for the JumpStart III program presents a summary of the entrepreneurship training programs developed by each of the four JumpStart III partners selected in March 1997. Grants for the colleges totaled $354,546 over 2 years. The Jumpstart funding has been only a starting point for these and the other 12 Jumpstart partners in…

  17. 76 FR 14841 - Head Start Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-18

    ...investigation, GAO followed up on received allegations...involving two Head Start grantees, including...2) of the Head Start Act. Up to 10 percent of the...the lack of clear up-to-date rules...regulations exposes the Head Start and Early Head...

  18. Head Start of North Dakota. [Videotape].

    ERIC Educational Resources Information Center

    Kingsley, Kranzler

    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…

  19. Antiretroviral Agents Effectively Block HIV Replication after Cell-to-Cell Transfer

    PubMed Central

    Permanyer, Marc; Ballana, Ester; Ruiz, Alba; Badia, Roger; Riveira-Munoz, Eva; Gonzalo, Encarna; Clotet, Bonaventura

    2012-01-01

    Cell-to-cell transmission of HIV has been proposed as a mechanism contributing to virus escape to the action of antiretrovirals and a mode of HIV persistence during antiretroviral therapy. Here, cocultures of infected HIV-1 cells with primary CD4+ T cells or lymphoid cells were used to evaluate virus transmission and the effect of known antiretrovirals. Transfer of HIV antigen from infected to uninfected cells was resistant to the reverse transcriptase inhibitors (RTIs) zidovudine (AZT) and tenofovir, but was blocked by the attachment inhibitor IgGb12. However, quantitative measurement of viral DNA production demonstrated that all anti-HIV agents blocked virus replication with similar potency to cell-free virus infections. Cell-free and cell-associated infections were equally sensitive to inhibition of viral replication when HIV-1 long terminal repeat (LTR)-driven green fluorescent protein (GFP) expression in target cells was measured. However, detection of GFP by flow cytometry may incorrectly estimate the efficacy of antiretrovirals in cell-associated virus transmission, due to replication-independent Tat-mediated LTR transactivation as a consequence of cell-to-cell events that did not occur in short-term (48-h) cell-free virus infections. In conclusion, common markers of virus replication may not accurately correlate and measure infectivity or drug efficacy in cell-to-cell virus transmission. When accurately quantified, active drugs blocked proviral DNA and virus replication in cell-to-cell transmission, recapitulating the efficacy of antiretrovirals in cell-free virus infections and in vivo. PMID:22696642

  20. Effects of Hydroxychloroquine on Immune Activation and Disease Progression Among HIV-Infected Patients Not Receiving Antiretroviral Therapy A Randomized Controlled Trial

    PubMed Central

    Paton, Nicholas I.; Goodall, Ruth L.; Dunn, David T.; Franzen, Samuel; Collaco-Moraes, Yolanda; Gazzard, Brian G.; Williams, Ian G.; Fisher, Martin J.; Winston, Alan; Fox, Julie; Orkin, Chloe; Herieka, Elbushra A.; Ainsworth, Jonathan G.; Post, Frank A.; Wansbrough-Jones, Mark; Kelleher, Peter

    2013-01-01

    Context Therapies to decrease immune activation might be of benefit in slowing HIV disease progression. Objective To determine whether hydroxychloroquine decreases immune activation and slows CD4 cell decline. Design, Setting, and Patients Randomized, double-blind, placebo-controlled trial performed at 10 HIV outpatient clinics in the United Kingdom between June 2008 and February 2011. The 83 patients enrolled had asymptomatic HIV infection, were not taking antiretroviral therapy, and had CD4 cell counts greater than 400 cells/?L. Intervention Hydroxychloroquine, 400 mg, or matching placebo once daily for 48 weeks. Main Outcome Measures The primary outcome measure was change in the proportion of activated CD8 cells (measured by the expression of CD38 and HLA-DR surface markers), with CD4 cell count and HIV viral load as secondary outcomes. Analysis was by intention to treat using mixed linear models. Results There was no significant difference in CD8 cell activation between the 2 groups (?4.8% and ?4.2% in the hydroxychloroquine and placebo groups, respectively, at week 48; difference, ?0.6%; 95% CI, ?4.8% to 3.6%; P=.80). Decline in CD4 cell count was greater in the hydroxychloroquine than placebo group (?85 cells/?L vs ?23 cells/?L at week 48; difference, ?62 cells/?L; 95% CI, ?115 to ?8; P=.03). Viral load increased in the hydroxychloroquine group compared with placebo (0.61 log10 copies/mL vs 0.23 log10 copies/mL at week 48; difference, 0.38 log10 copies/mL; 95% CI, 0.13 to 0.63; P=.003). Antiretroviral therapy was started in 9 patients in the hydroxychloroquine group and 1 in the placebo group. Trial medication was well tolerated, but more patients reported influenza-like illness in the hydroxychloroquine group compared with the placebo group (29% vs 10%; P=.03). Conclusion Among HIV-infected patients not taking antiretroviral therapy, the use of hydroxychloroquine compared with placebo did not reduce CD8 cell activation but did result in a greater decline in CD4 cell count and increased viral replication. Trial Registration isrctn.org Identifier: ISRCTN30019040 PMID:22820788

  1. Increased soluble vascular cell adhesion molecule-1 plasma levels and soluble intercellular adhesion molecule-1 during antiretroviral therapy interruption and retention of elevated soluble vascular cellular adhesion molecule-1 levels following resumption of antiretroviral therapy

    PubMed Central

    Papasavvas, Emmanouil; Azzoni, Livio; Pistilli, Maxwell; Hancock, Aidan; Reynolds, Griffin; Gallo, Cecile; Ondercin, Joe; Kostman, Jay R.; Mounzer, Karam; Shull, Jane; Montaner, Luis J.

    2009-01-01

    Objective We investigated the effect of short viremic episodes on soluble markers associated with endothelial stress and cardiovascular disease risk in chronically HIV-1-infected patients followed during continuous antiretroviral therapy, antiretroviral therapy interruption and antiretroviral therapy resumption. Design and methods We assessed changes in plasma levels of von Willebrand factor, soluble vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 by enzyme-linked immunosorbent assay, as well as T-cell activation (CD8+/CD38+, CD8+/HLA-DR+ and CD3+/CD95+) by flow cytometry, in 36 chronically HIV-1-infected patients participating in a randomized study. Patients were divided into the following three groups: a, on continuous antiretroviral therapy; b, on a 6-week antiretroviral therapy interruption; or c, on antiretroviral therapy interruption extended to the achievement of viral set point. Results Although all measurements remained stable over a 40-week follow-up on antiretroviral therapy, plasma levels of soluble vascular cell adhesion molecule-1 (P < 0.0001) and soluble intercellular adhesion molecule-1 (P = 0.003) increased during treatment interruption in correlation with viral rebound and T-cell activation. No significant changes in von Willebrand factor were observed in any of the groups. After resuming antiretroviral therapy, soluble vascular cell adhesion molecule-1 levels remained elevated even after achievement of viral suppression to less than 50 copies/ml. Conclusion The prompt rise in plasma soluble vascular cell adhesion molecule-1 and soluble intercellular adhesion molecule-1 upon viral rebound suggests an acute increase in endothelial stress upon treatment interruption, which may persists after viral resuppression of virus. Thus, viral replication during short-term treatment interruption may increase the overall cardiovascular risk during and beyond treatment interruption. PMID:18525261

  2. Impact of HIV1 Subtype and Antiretroviral Therapy on Protease and Reverse Transcriptase Genotype: Results of a Global Collaboration

    Microsoft Academic Search

    Rami Kantor; David A. Katzenstein; Brad Efron; Ana Patricia Carvalho; Brian Wynhoven; Patricia Cane; John Clarke; Sunee Sirivichayakul; Marcelo A. Soares; Joke Snoeck; Candice Pillay; Hagit Rudich; Rosangela Rodrigues; Africa Holguin; Koya Ariyoshi; Maria Belen Bouzas; Pedro Cahn; Wataru Sugiura; Vincent Soriano; Luis F. Brigido; Zehava Grossman; Lynn Morris; Anne-Mieke Vandamme; Amilcar Tanuri; Praphan Phanuphak; Jonathan N. Weber; Deenan Pillay; P. Richard Harrigan; Ricardo Camacho; Jonathan M. Schapiro; Robert W. Shafer

    2005-01-01

    Background The genetic differences among HIV-1 subtypes may be critical to clinical management and drug resistance surveillance as antiretroviral treatment is expanded to regions of the world where diverse non-subtype-B viruses predominate.

  3. Detection of HIV-1 DNA resistance mutations by a sensitive assay at initiation of antiretroviral therapy is associated with virologic failure

    PubMed Central

    Jourdain, Gonzague; Wagner, Thor Andrew; Ngo-Giang-Huong, Nicole; Sirungsi, Wasna; Klinbuayaem, Virat; Fregonese, Federica; Nantasen, Issaren; Techpornroong, Malee; Halue, Guttiga; Nilmanat, Ampaipith; Wittayapraparat, Pakorn; Chalermpolprapa, Veeradet; Pathipvanich, Panita; Yuthavisuthi, Prapap; Frenkel, Lisa M.; Lallemant, Marc

    2010-01-01

    Background Antiretroviral therapy (ART) has become more available throughout the developing world during the past five years. The World Health Organization recommends nonnucleoside reverse transcriptase inhibitor-based regimens as initial ART. However, their efficacy may be compromised by resistance mutations selected by single-dose nevirapine (sdNVP) used to prevent mother-to-child-transmission of HIV-1 (PMTCT). There is no simple and efficient method to detect such mutations at initiation of ART. Methods 181 women participating in a PMTCT clinical trial who started NVP-ART after they had received sdNVP or placebo were tested for nevirapine-resistance point-mutations (K103N, Y181C, and G190A) using 100 copies of HIV-1 DNA with a sensitive oligonucleotide ligation assay (OLA) able to detect mutants at low concentrations (?5% of the viral population). Virologic failure was defined as plasma HIV-1 RNA confirmed >50 copies/mL between 6–18 months of NVP-ART. Results At initiation of NVP-ART, resistance mutations were identified in 26% of 148 participants given sdNVP (K103N-13%, Y181C-5%, G190A-19%; ?2 mutations-10%) at a median 9.3 months after sdNVP. The risk of virologic failure was .62 (95% confidence interval (CI), 0.46–0.77) in women with ?1 resistance mutation, compared to 0.25 (95% CI, 0.17–0.35) in those without detectable resistance mutations (P<.0001). Failure was independently associated with resistance, an interval of <6 months between sdNVP and NVP-ART initiation, and a viral load above the median at NVP-ART initiation. Conclusions Access to simple and inexpensive assays to detect low-concentrations of NVP-resistant HIV-1 DNA prior to the initiation of ART could help improve the outcome of first-line antiretroviral therapy. PMID:20377404

  4. Determinants of Highly Active Antiretroviral Therapy Duration in HIV-1-Infected Children and Adolescents in Madrid, Spain, from 1996 to 2012

    PubMed Central

    Palladino, Claudia; Briz, Verónica; Bellón, José María; Climent, Francisco J.; de Ory, Santiago J.; Mellado, María José; Navarro, María Luisa; Ramos, José T.; Taveira, Nuno; de José, María Isabel; Muńoz-Fernández, María Ángeles

    2014-01-01

    Objectives To investigate the duration of sequential HAART regimens and predictors of first-line regimen discontinuation among HIV-1 vertically infected children and adolescents. Design Multicentre survey of antiretroviral-naďve patients enrolled in the HIV-Paediatric Cohor,t CoRISpeS-Madrid Cohort, Spain. Methods Patients with a follow-up of ?1 month spent on HAART, with available baseline CD4 count and HIV-viral load (VL) were included. Time spent on sequential HAART regimens was estimated and multivariable regression was used to identify predictors of time to first-line regimen discontinuation. Results 104 patients were followed for a median 8 years after starting HAART among 1996–2012; baseline %CD4 was 21.5 (12.3–34.0)and viral load was 5.1 (4.6–5.6) log10 copies/mL. Patients received a mean of 1.9 regimens. Median time on first-line HAART (n?=?104) was 64.5 months; second HAART (n?=?56) 69.8 months; and third HAART (n?=?21) 66.5 months. Eleven (11%) patients were lost to follow-up while on first-line HAART and 54% discontinued (cumulative incidence of 16% and 38% by 1 and 3-year, respectively). The main predictor of first-line regimen discontinuation was suboptimal adherence to antiretrovirals (AHR: 2.60; 95% CI: 1.44–4.70). Conclusions Adherence to therapy was the main determinant of the duration of the first-line HAART regimen in children. It is important to identify patients at high risk for non-adherence, such as very young children and adolescents, in provide special care and support to those patients. PMID:24788034

  5. Association between medication possession ratio, virologic failure and drug resistance in HIV-1 infected adults on antiretroviral therapy in Côte d’Ivoire

    PubMed Central

    Messou, Eugčne; Chaix, Marie-Laure; Gabillard, Delphine; Minga, Albert; Losina, Elena; Yapo, Vincent; Kouakou, Martial; Danel, Christine; Sloan, Caroline; Rouzioux, Christine; Freedberg, Kenneth A.; Anglaret, Xavier

    2011-01-01

    Background Adherence is a strong determinant of viral suppression with antiretroviral therapy (ART), but measuring it is challenging. Medication delivery can be measured accurately in settings with computerized prescription databases. We studied the association between Medication Possession Ratio (MPR), virologic suppression, and resistance to ART in Côte d’Ivoire. Methods We conducted a prospective cohort study of HIV-1 infected adults initiating ART in three clinics using computerized monitoring systems. Patients had viral load (VL) tests at month 6 (M6) and month 12 (M12) after ART initiation, and genotype tests if VL was detectable (?300 copies/ml). MPR was defined as the number of daily doses of antiretroviral drug actually provided divided by the total number of follow-up days since ART initiation. Results Overall, 1,573 patients started ART with stavudine/zidovudine plus lamivudine plus nevirapine/efavirenz. At M6 and M12, 996 and 942 patients were in active follow-up; 20% (M6) and 25% (M12) of patients had detectable VL, including 7% (M6) and 11% (M12) with ?1 resistance mutation. Among patients with MPR ?95%, 80–94%, 65–79%, 50–64% and <50% at M12, the proportion with detectable VL [resistance] was 9% [4%], 17% [7%], 45% [24%], 67% [31%], and 85% [37%]. Among patients with ?1 mutation at M12, 86% were resistant to lamivudine/emtricitabine and/or nevirapine/efavirenz but not to other drugs. Conclusion MPR was strongly associated with virologic outcomes. Half of those with detectable VL at M12 had no resistance mutations. MPR should be used at M6 to identify patients who might benefit from early interventions to reinforce adherence. PMID:21191309

  6. Should highly active antiretroviral therapy be prescribed in critically ill HIV-infected patients during the ICU stay? A retrospective cohort study

    PubMed Central

    2012-01-01

    Background The impact of highly active antiretroviral therapy (HAART) in HIV-infected patients admitted to the intensive care unit (ICU) remains controversial. We evaluate impact of HAART prescription in HIV-infected patients admitted to the ICU of Tourcoing Hospital from January 2000 to December 2009. Results There were 91 admissions concerning 85 HIV-infected patients. Reasons for ICU admission were an AIDS-related diagnosis in 46 cases (51%). Fifty two patients (57%) were on HAART at the time of ICU admission, leading to 21 immunovirologic successes (23%). During the ICU stay, HAART was continued in 29 patients (32%), and started in 3 patients (3%). Only one patient experienced an adverse event related to HAART. Mortality rate in ICU and 6 months after ICU admission were respectively 19% and 27%. Kaplan-Meier estimates of the cumulative unajusted survival probability over 6 months were higher in patients treated with HAART during the ICU stay (Log rank: p?=?0.04). No benefit of HAART in ICU was seen in the adjusted survival proportion at 6 months or during ICU stay. Prescription of HAART during ICU was associated with a trend to lower incidence of new AIDS-related events at 6 months (respectively 17% and 34% with and without HAART, p?=?0.07), and with higher incidence of antiretroviral resistance after ICU stay (respectively 25% and 7% with and without HAART, p?=?0.02). Conclusions Our results suggest a lower death rate over 6 months in critically ill HIV-infected patients taking HAART during ICU stay. The optimal time to prescribe HAART in critically ill patients needs to be better defined. PMID:23020962

  7. Low rate of virological failure and maintenance of susceptibility to HIV-1 protease inhibitors with first-line lopinavir/ritonavir-based antiretroviral treatment in clinical practice.

    PubMed

    Prosperi, Mattia C F; Zazzi, Maurizio; Punzi, Grazia; Monno, Laura; Colao, Grazia; Corsi, Paola; Di Giambenedetto, Simona; Meini, Genny; Ghisetti, Valeria; Bonora, Stefano; Pecorari, Monica; Gismondo, Maria Rita; Bagnarelli, Patrizia; Carli, Tiziana; De Luca, Andrea

    2010-12-01

    Protease inhibitor (PI)-resistant HIV-1 has hardly ever been detected at failed boosted PI-based first-line antiretroviral regimens in clinical trials. However, this phenomenon has not been investigated in clinical practice. To address this gap, data from patients starting a first-line lopinavir/ritonavir (LPV/rtv)-based therapy with available baseline HIV-1 RNA load, a viral genotype and follow-up viral load after 3 and 6 months of treatment were extracted from the Italian Antiretroviral Resistance Cohort Analysis (ARCA) observational database. Based on survival analysis, 39 (7.1%) and 43 (7.8%) of the 548 examined patient cases had an HIV-1 RNA >500 and >50 copies/ml, respectively, after 6 months of treatment. Cox proportional hazard models detected baseline HIV-1 RNA (RH 1.79, 95%CI 1.10-2.92 per 1-log(10) increase, P=0.02) and resistance to the nucleoside backbone (RH 1.04, 95%CI 1.02-1.06 per 10-point increase using the Stanford HIVdb algorithm, P<0.001) as independent predictors of HIV-1 RNA at >500 copies/ml, but not at the >50 copies/ml cutoff criteria. Higher baseline viral load, older patient age, heterosexual route of infection and use of tenofovir/emtricitabine were predictors of failure at month 3 using the 50-copy and/or 500-copy threshold. Resistance to LPV/rtv did not occur or increase in any of the available 36 follow-up HIV-1 genotypes. Resistance to the nucleoside backbone (M184V) developed in four cases. Despite the likely differences in patient population and adherence, both the low rate of virological failure and the lack of development of LPV/rtv resistance documented in clinical trials are thus confirmed in clinical practice. PMID:20981785

  8. Factors associated with poor adherence to anti-retroviral therapy in patients attending a rural health centre in South Africa

    Microsoft Academic Search

    V. G. Bhat; M. Ramburuth; M. Singh; O. Titi; A. P. Antony; L. Chiya; E. M. Irusen; P. P. Mtyapi; M. E. Mofoka; A. Zibeke; L. A. Chere-Sao; N. Gwadiso; N. C. Sethathi; S. R. Mbondwana; M. Msengana

    2010-01-01

    South Africa has a very high HIV disease burden and proper patient adherence to anti-retroviral therapy (ART) is crucial in\\u000a achieving optimal treatment outcomes. Factors influencing adherence include demographic and psychosocial factors, medication-related\\u000a issues and other patient-related matters. This study was carried out in order to determine factors associated with poor compliance\\u000a to anti-retroviral (ARV) medications in a rural setting.

  9. The impact of herbal remedies on adverse effects and quality of life in HIV-infected individuals on antiretroviral therapy

    PubMed Central

    Bepe, Nyasha; Madanhi, Nathan; Mudzviti, Tinashe; Gavi, Samuel; Maponga, Charles Chiedza; Morse, Gene D

    2012-01-01

    Introduction Use of herbal remedies among HIV-infected individuals in Africa increased in the past decade, mainly due to traditional beliefs and at times inconsistent access to antiretroviral drugs. In Zimbabwe, accessibility and availability of antiretroviral drugs has increased in recent years; however, the use of herbal remedies remains high. This study was conducted to determine the impact of concomitant use of herbal remedies with antiretroviral drugs on adverse events and on quality of life. Methodology A convenient sample of HIV positive patients at Parirenyatwa group of hospitals' Family Care Clinic (Harare, Zimbabwe) was enrolled. A questionnaire was used to collect data on the adverse event experiences of the patients using herbal remedies for their HIV, as well as the types of herbal remedy used. Quality of life index was measured using an HIV/AIDS targeted quality of life (HAT-QOL) tool developed by the World Health Organization. Results Abdominal pain (odds ratio = 2.7, p-value = 0.01) and rash (odds ratio = 2.5, p-value = 0.02) had significant associations with using herbal remedies during antiretroviral therapy. Improved quality of life index was not significantly associated with herbal remedy use during antiretroviral therapy. Conclusions There is evidence to suggest that some traditional herbal remedies used in Zimbabwe may increase incidence of certain types of adverse events when used in combination with antiretroviral drugs. Use of herbal drugs in combination with antiretroviral therapy does not significantly improve quality of life index in comparison to antiretroviral drug use only. PMID:21330740

  10. The relation of price of antiretroviral drugs and foreign assistance with coverage of HIV treatment in Africa: retrospective study

    PubMed Central

    2010-01-01

    Objective To determine the association of reductions in price of antiretroviral drugs and foreign assistance for HIV with coverage of antiretroviral treatment. Design Retrospective study. Setting Africa. Participants 13 African countries, 2003-8. Main outcome measures A price index of first line antiretroviral therapy with data on foreign assistance for HIV was used to estimate the associations of prices and foreign assistance with antiretroviral coverage (percentage of people with advanced HIV infection receiving antiretroviral therapy), controlling for national public health spending, HIV prevalence, governance, and fixed effects for countries and years. Results Between 2003 and 2008 the annual price of first line antiretroviral therapy decreased from $1177 (Ł733; €844) to $96 and foreign assistance for HIV per capita increased from $0.4 to $13.8. At an annual price of $100, a $10 decrease was associated with a 0.16% adjusted increase in coverage (95% confidence interval 0.11% to 0.20%; 0.19% unadjusted, 0.14% to 0.24%). Each additional $1 per capita in foreign assistance for HIV was associated with a 1.0% adjusted increase in coverage (0.7% to 1.2%; 1.4% unadjusted, 1.1% to 1.6%). If the annual price of antiretroviral therapy stayed at $100, foreign assistance would need to quadruple to $64 per capita to be associated with universal coverage. Government effectiveness and national public health expenditures were also positively associated with increasing coverage. Conclusions Reductions in price of antiretroviral drugs were important in broadening coverage of HIV treatment in Africa from 2003 to 2008, but their future role may be limited. Foreign assistance and national public health expenditures for HIV seem more important in expanding future coverage. PMID:21088074

  11. 46 CFR 112.50-5 - Electric starting.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...Generator Sets § 112.50-5 Electric starting. An electric starting system must have a starting battery with sufficient capacity for at least six consecutive starts. A second, separate source of starting energy may provide...

  12. Wireless "Jump" Starts for Partly Disabled Equipment

    NASA Technical Reports Server (NTRS)

    Castle, K. D.

    1986-01-01

    Equipment activated when normal remote starting does not work Beam from nearby station first carries raw energy and then subsystemactivating signals to equipment crippled by discharged storage batteries. Operators start up equipment without approaching it under hazardous conditions. Potential terrestrial applications for scheme include starting of robots on such remotely-controlled hazardous tasks as handling of explosives or retrieval or deposition of objects in hostile environments.

  13. Start II, red ink, and Boris Yeltsin

    SciTech Connect

    Arbatov, A.

    1993-04-01

    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.

  14. START ships lipids across interorganelle space.

    PubMed

    Alpy, Fabien; Tomasetto, Catherine

    2014-01-01

    The family of StAR related lipid transfer proteins (START) is so-named based on the distinctive capacity for these proteins to transport lipids between membranes. The START domain is a module of about 210 residues, which binds lipids such as glycerolipids, sphingolipids and sterols. This domain has a deep lipid-binding pocket - which shields the hydrophic ligand from the external aqueous environment - covered by a lid. Based on their homology, the fifteen START proteins in mammals have been allocated to six distinct subfamilies, each subfamily being more specialized in the transport and/or sensing of a lipid ligand species. However within the same subgroup, their expression profile and their subcellular localization distinguish them and are critical for their different biological functions. Indeed, START proteins act in a variety of distinct physiological processes, such as lipid transfer between intracellular compartments, lipid metabolism and modulation of signaling events. Mutation or deregulated expression of START proteins is linked to pathological processes, including genetic disorders, autoimmune diseases and cancers. Besides the common single START domain, which is always located at the carboxy-terminal end in mammals, most START proteins harbor additional domains predicted to be critical in favoring lipid exchange. Evidence from well characterized START proteins indicates that these additional domains might be tethering machineries able to bring distinct organelles together and create membrane contact sites prone to lipid exchange via the START domain. PMID:24076129

  15. Long-Term Survival of HIV-Infected Children Receiving Antiretroviral Therapy in Thailand: A 5-Year Observational Cohort Study

    PubMed Central

    Collins, Intira J.; Jourdain, Gonzague; Hansudewechakul, Rawiwan; Kanjanavanit, Suparat; Hongsiriwon, Suchat; Ngampiyasakul, Chaiwat; Sriminiphant, Somboon; Technakunakorn, Pornchai; Ngo-Giang-Huong, Nicole; Duong, Trinh; Le Coeur, Sophie; Jaffar, Shabbar; Lallemant, Marc

    2010-01-01

    Background. There are scarce data on the long-termsurvival of human immunodeficiency virus (HIV)—infected children receiving antiretroviral therapy (ART) in lower-middle income countries beyond 2 years of follow-up. Methods. Previously untreated children who initiated ART on meeting immunological and/or clinical criteria were followed in a prospective cohort in Thailand. The probability of survival up to 5 years from initiation was estimated using Kaplan-Meier methods, and factors associated with mortality were assessed using Cox regression analyses. Results. Five hundred seventy-eight children received ART; of these, 111 (19.2%) were followed since birth. At start of ART (baseline), the median age was 6.7 years, 128 children (22%) were aged <2 years, and the median CD4 cell percentage was 7%. Median duration of follow-up was 53 months; 42 children (7%) died, and 38 (7%) were lost to follow-up. Age <12 months, low CD4 cell percentage, and low weight-for-height z score at ART initiation were independently associated with mortality (P < .001). The probability of survival among infants aged <12 months at baseline was 84.3% at 1 year and 76.7% at 5 years of ART, compared with 95.7% and 94.8%, respectively, among children aged ?1 year. Low CD4 cell percentage and wasting at baseline had a strong association with mortality among older children but weak or no association among infants. Conclusions. Children who initiated ART as infants after meeting immunological and/or clinical criteria had a high risk of mortality which persisted beyond the first year of therapy. Among older children, those with severe wasting or low CD4 cell percentage at treatment initiation were at high risk of mortality during the first 6 months of therapy. These findings support the scale-up of early HIV diagnosis and immediate treatment in infants, before advanced disease progression in older children. PMID:21054181

  16. Results of Antiretroviral Treatment Interruption and Intensification in Advanced Multi-Drug Resistant HIV Infection from the OPTIMA Trial

    PubMed Central

    Holodniy, Mark; Brown, Sheldon T.; Cameron, D. William; Kyriakides, Tassos C.; Angus, Brian; Babiker, Abdel; Singer, Joel; Owens, Douglas K.; Anis, Aslam; Goodall, Ruth; Hudson, Fleur; Piaseczny, Mirek; Russo, John; Schechter, Martin; Deyton, Lawrence; Darbyshire, Janet

    2011-01-01

    Background Guidance is needed on best medical management for advanced HIV disease with multidrug resistance (MDR) and limited retreatment options. We assessed two novel antiretroviral (ARV) treatment approaches in this setting. Methods and Findings We conducted a 2×2 factorial randomized open label controlled trial in patients with a CD4 count ?300 cells/µl who had ARV treatment (ART) failure requiring retreatment, to two options (a) re-treatment with either standard (?4 ARVs) or intensive (?5 ARVs) ART and b) either treatment starting immediately or after a 12-week monitored ART interruption. Primary outcome was time to developing a first AIDS-defining event (ADE) or death from any cause. Analysis was by intention to treat. From 2001 to 2006, 368 patients were randomized. At baseline, mean age was 48 years, 2% were women, median CD4 count was 106/µl, mean viral load was 4.74 log10 copies/ml, and 59% had a prior AIDS diagnosis. Median follow-up was 4.0 years in 1249 person-years of observation. There were no statistically significant differences in the primary composite outcome of ADE or death between re-treatment options of standard versus intensive ART (hazard ratio 1.17; CI 0.86–1.59), or between immediate retreatment initiation versus interruption before re-treatment (hazard ratio 0.93; CI 0.68–1.30), or in the rate of non-HIV associated serious adverse events between re-treatment options. Conclusions We did not observe clinical benefit or harm assessed by the primary outcome in this largest and longest trial exploring both ART interruption and intensification in advanced MDR HIV infection with poor retreatment options. Trial Registration Clinicaltrials.gov NCT00050089 PMID:21483491

  17. Incomplete Reconstitution of T Cell Subsets on Combination Antiretroviral Therapy in the AIDS Clinical Trials Group Protocol 384

    PubMed Central

    Robbins, Gregory K.; Spritzler, John G.; Chan, Ellen S.; Asmuth, David M.; Gandhi, Rajesh T.; Rodriguez, Benigno A.; Skowron, Gail; Skolnik, Paul R.; Shafer, Robert W.; Pollard, Richard B.

    2009-01-01

    Background Initiation of combination antiretroviral therapy (ART) results in higher total CD4 cell counts, a surrogate for immune reconstitution. Whether the baseline CD4 cell count affects reconstitution of immune cell subsets has not been well characterized. Methods Using data from 978 patients (621 with comprehensive immunological assessments) from the AIDS [Acquired Immunodeficiency Syndrome] Clinical Trials Group protocol 384, a randomized trial of initial ART, we compared reconstitution of CD4+, CD4+ naive and memory, CD4+ activation, CD8+, CD8+ activation, B, and natural killer cells among patients in different baseline CD4+ strata. Reference ranges for T cell populations in control patients negative for human immunodeficiency virus (HIV) infection were calculated using data from AIDS Clinical Trials Group protocol A5113. Results Patients in the lower baseline CD4+ strata did not achieve total CD4+ cell counts similar to those of patients in the higher strata during 144 weeks of ART, although CD4+ cell count increases were similar. Ratios of CD4+ naive-memory cell counts and CD4+:CD8+ cell counts remained significantly reduced in patients with lower baseline CD4+ cell counts (?350 cells/mm3). These immune imbalances were most notable for those initiating ART with a baseline CD4+ cell count ?200 cells/mm3, even after adjustment for baseline plasma HIV RNA levels. Conclusions After nearly 3 years of ART, T cell subsets in patients with baseline CD4+ cell counts >350 cells/mm3 achieved or approached the reference range those of control individuals without HIV infection. In contrast, patients who began ART with ?350 CD4+ cells/mm3 generally did not regain normal CD4+ naive-memory cell ratios. These results support current guidelines to start ART at a threshold of 350 cells/mm3 and suggest that there may be immunological benefits associated with initiating therapy at even higher CD4+ cell counts. PMID:19123865

  18. Pharmacodynamics of folic acid receptor targeted antiretroviral nanotherapy in HIV-1-infected humanized mice.

    PubMed

    Puligujja, Pavan; Araínga, Mariluz; Dash, Prasanta; Palandri, Diana; Mosley, R Lee; Gorantla, Santhi; Poluektova, Larisa; McMillan, JoEllyn; Gendelman, Howard E

    2015-08-01

    Long-acting nanoformulated antiretroviral therapy (nanoART) can sustain plasma drug levels and improve its biodistribution. Cell targeted-nanoART can achieve this and bring drug efficiently to viral reservoirs. However, whether such improvements affect antiretroviral responses remains unknown. To these ends, we tested folic acid (FA)-linked poloxamer407-coated ritonavir-boosted atazanavir (FA-nanoATV/r) nanoparticles for their ability to affect chronic HIV-1 infection in humanized mice. Following three, 100mg/kg FA-nanoATV/r intramuscular injections administered every other week to infected animals, viral RNA was at or below the detection limit, cell-associated HIV-1p24 reduced and CD4+ T cell counts protected. The dosing regimen improved treatment outcomes more than two fold from untargeted nanoATV/r. We posit that these nanoformulations have potential for translation to human use. PMID:26026666

  19. Unplanned antiretroviral treatment interruptions in southern Africa: how should we be managing these?

    PubMed

    Veenstra, Nina; Whiteside, Alan; Lalloo, David; Gibbs, Andrew

    2010-01-01

    Adherence to antiretroviral therapy is essential for maximising individual treatment outcomes and preventing the development of drug resistance. It is, however, frequently compromised due to predictable, but adverse, scenarios in the countries most severely affected by HIV/AIDS. This paper looks at lessons from three specific crises in southern Africa: the 2008 floods in Mozambique, the ongoing political and economic crisis in Zimbabwe, and the 2007 public sector strike in South Africa. It considers how these crises impacted on the delivery of antiretroviral therapy and looks at some of the strategies employed to mitigate any adverse effects. Based on this it makes recommendations for keeping patients on treatment and limiting the development of drug resistance where treatment interruptions are inevitable. PMID:20356383

  20. Relationship between antiretrovirals used as part of a cART regimen and CD4 cell count increases in patients with suppressed viremia

    Microsoft Academic Search

    Amanda Mocroft; Andrew N Phillips; Bruno Ledergerber; Christine Katlama; Antonio Chiesi; Frank-Detlef Goebel; Brygioa Knysz; Francisco Antunes; Peter Reiss; Jens D Lundgren

    2006-01-01

    Background: It is unknown if the CD4 cell count response differs according to antiretroviral drugs used in combination antiretroviral therapy (cART) in patients with maximal virological suppression [viral load (VL) < 50 copies\\/ml]. Objectives: To compare the change in CD4 cell count over consecutive measurements with VL < 50 copies\\/ml at both time-points according to nucleoside backbones and other antiretrovirals

  1. Adherence to antiretroviral therapy among a conflict-affected population in Northeastern Uganda: a qualitative study.

    PubMed

    Olupot-Olupot, Peter; Katawera, Andrew; Cooper, Curtis; Small, Will; Anema, Aranka; Mills, Edward

    2008-09-12

    We aimed to determine patient and health worker concerns regarding antiretroviral adherence in a conflict-affected population using focus groups (n = 40) and semi-structured interviews (n = 11). Patient concerns include security attending clinics, food security, distance to health centers and access to health providers. During periods of famine and flooding, the lack of food security and only single daily meals makes taking multiple doses impossible. Possible facilitating strategies included mobile teams, increased security and regularity of drug stocks. PMID:18753867

  2. The Effects of Intermittent, CD4-guided Antiretroviral Therapy on Body Composition and Metabolic Parameters

    PubMed Central

    MARTINEZ, Esteban; VISNEGARWALA, Fehmida; GRUND, Birgit; THOMAS, Avis; GIBERT, Cynthia; SHLAY, Judith; DRUMMOND, Fraser; PEARCE, Daniel; EDWARDS, Simon; REISS, Peter; EL-SADR, Wafaa; CARR, Andrew

    2010-01-01

    Objective To assess the effects of decreased antiretroviral therapy exposure on body fat and metabolic parameters. Design Sub-study of the SMART study in which participants were randomized to intermittent CD4-guided (DC group) or to continuous (VS group) antiretroviral therapy. Methods Participants at 33 sites were co-enrolled in the SMART Body Composition Sub-study. Regional fat was assessed annually by whole-body dual-energy X-ray absorptiometry and abdominal computed tomography. Fasting metabolic parameters were assessed at months 4, 8, and annually. Treatment groups were compared for changes in fat and metabolic markers using longitudinal mixed models. Results Two hundred seventy-five patients were randomized to the DC (n=142) or VS (n=133) groups, and followed for a median of 2.0 years. By month 12, limb fat (DC-VS difference 9.8%, 95% confidence interval [CI] 3.5 to 16.1; P=0.003) and subcutaneous abdominal fat (DC-VS difference 14.3 cm2, 95% CI ?0.1 to 28.7; P=0.05) increased in the DC group. There was no treatment difference on visceral abdominal fat (DC-VS difference ?2.1%, 95% CI ?13.5 to 9.4; P=0.72). Lipids significantly decreased in the DC group by month 4 and treatment differences persisted throughout follow-up (P?0.001). By 12 months, hemoglobin A1C increased in the DC (+0.3%) and remained stable in the VS group (P=0.003); the treatment difference remained significant through follow-up (P=0.02). Conclusions After 12 months, intermittent antiretroviral therapy increased subcutaneous fat, had no effect on visceral abdominal fat, decreased plasma lipids, and increased hemoglobin A1C compared with continuous antiretroviral therapy. PMID:20057309

  3. Transgenic mitochondrial superoxide dismutase and mitochondrially targeted catalase prevent antiretroviral-induced oxidative stress and cardiomyopathy

    Microsoft Academic Search

    James J Kohler; Ioan Cucoranu; Earl Fields; Elgin Green; Stanley He; Amy Hoying; Rodney Russ; Allison Abuin; David Johnson; Seyed H Hosseini; C Michael Raper; William Lewis

    2009-01-01

    Transgenic mice (TG) were used to define mitochondrial oxidative stress and cardiomyopathy (CM) induced by zidovudine (AZT), an antiretroviral used to treat HIV\\/AIDS. Genetically engineered mice either depleted or overexpressed mitochondrial superoxide dismutase (SOD2+\\/? KOs and SOD2-OX, respectively) or expressed mitochondrially targeted catalase (mCAT). TGs and wild-type (WT) littermates were treated (oral AZT, 35 days). Cardiac mitochondrial H2O2, aconitase activity,

  4. Viral Excretion in Cervicovaginal Secretions of HIV1Infected Women Receiving Antiretroviral Therapy

    Microsoft Academic Search

    M. Debiaggi; F. Zara; A. Spinillo; A. De Santolo; R. Maserati; R. Bruno; P. Sacchi; G. Achilli; A. Pistorio; E. Romero; G. Filice

    2001-01-01

    A longitudinal study was conducted to evaluate the viral shedding present in cervicovaginal secretions of HIV-1-seropositive\\u000a women receiving antiretroviral therapy. A total of 128 paired cervicovaginal and blood samples was obtained from 37 women\\u000a during a median follow-up period of 21 months. A sensitive, competitive, polymerase chain reaction and a reverse transcription\\u000a polymerase chain reaction were used for the simultaneous

  5. Aging exacerbates extrapyramidal motor signs in the era of highly active antiretroviral therapy

    Microsoft Academic Search

    Victor Valcour; Michael R. Watters; Andrew E. Williams; Ned Sacktor; Aaron McMurtray; Cecilia Shikuma

    2008-01-01

    The phenotype of human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) in the developed world has\\u000a changed with the broad institution of highly active antiretroviral theray (HAART) and with aging of the HIV+ population. Extrapyramidal\\u000a motor signs were a prominent feature of HAND as defined in the early stages of the epidemic but has not been reevaluated in\\u000a the era of

  6. Cliniconeuropathologic correlates of human immunodeficiency virus in the era of antiretroviral therapy

    Microsoft Academic Search

    I. Everall; F. Vaida; N. Khanlou; D. Lazzaretto; C. Achim; S. Letendre; D. Moore; R. Ellis; M. Cherner; B. Gelman; S. Morgello; E. Singer; I. Grant; E. Masliah

    2009-01-01

    The objective of this study was to examine the spectrum of human immunodeficiency virus (HIV) brain pathology and its clinical\\u000a correlates in the antiretroviral era. We carried out a cross-sectional survey, analyzing prospective clinical and neuropathological\\u000a data collected by the National NeuroAIDS Tissue Consortium (NNTC), comprising 589 brain samples from individuals with advanced\\u000a HIV disease collected from 1999 onwards. We

  7. Comprehensive In Vitro Analysis of Simian Retrovirus Type 4 Susceptibility to Antiretroviral Agents

    PubMed Central

    Togami, Hiroaki; Okamoto, Munehiro; Yoshikawa, Rokusuke; Miyazawa, Takayuki; Matsuoka, Masao

    2013-01-01

    Simian retrovirus type 4 (SRV-4), a simian type D retrovirus, naturally infects cynomolgus monkeys, usually without apparent symptoms. However, some infected monkeys presented with an immunosuppressive syndrome resembling that induced by simian immunodeficiency virus infection. Antiretrovirals with inhibitory activity against SRV-4 are considered to be promising agents to combat SRV-4 infection. However, although some antiretrovirals have been reported to have inhibitory activity against SRV-1 and SRV-2, inhibitors with anti-SRV-4 activity have not yet been studied. In this study, we identified antiretroviral agents with anti-SRV-4 activity from a panel of anti-human immunodeficiency virus (HIV) drugs using a robust in vitro luciferase reporter assay. Among these, two HIV reverse transcriptase inhibitors, zidovudine (AZT) and tenofovir disoproxil fumarate (TDF), potently inhibited SRV-4 infection within a submicromolar to nanomolar range, which was similar to or higher than the activities against HIV-1, Moloney murine leukemia virus, and feline immunodeficiency virus. In contrast, nonnucleoside reverse transcriptase inhibitors and protease inhibitors did not exhibit any activities against SRV-4. Although both AZT and TDF effectively inhibited cell-free SRV-4 transmission, they exhibited only partial inhibitory activities against cell-to-cell transmission. Importantly, one HIV integrase strand transfer inhibitor, raltegravir (RAL), potently inhibited single-round infection as well as cell-free and cell-to-cell SRV-4 transmission. These findings indicate that viral expansion routes impact the inhibitory activity of antiretrovirals against SRV-4, while only RAL is effective in suppressing both the initial SRV-4 infection and subsequent SRV-4 replication. PMID:23365453

  8. Comprehensive in vitro analysis of simian retrovirus type 4 susceptibility to antiretroviral agents.

    PubMed

    Togami, Hiroaki; Shimura, Kazuya; Okamoto, Munehiro; Yoshikawa, Rokusuke; Miyazawa, Takayuki; Matsuoka, Masao

    2013-04-01

    Simian retrovirus type 4 (SRV-4), a simian type D retrovirus, naturally infects cynomolgus monkeys, usually without apparent symptoms. However, some infected monkeys presented with an immunosuppressive syndrome resembling that induced by simian immunodeficiency virus infection. Antiretrovirals with inhibitory activity against SRV-4 are considered to be promising agents to combat SRV-4 infection. However, although some antiretrovirals have been reported to have inhibitory activity against SRV-1 and SRV-2, inhibitors with anti-SRV-4 activity have not yet been studied. In this study, we identified antiretroviral agents with anti-SRV-4 activity from a panel of anti-human immunodeficiency virus (HIV) drugs using a robust in vitro luciferase reporter assay. Among these, two HIV reverse transcriptase inhibitors, zidovudine (AZT) and tenofovir disoproxil fumarate (TDF), potently inhibited SRV-4 infection within a submicromolar to nanomolar range, which was similar to or higher than the activities against HIV-1, Moloney murine leukemia virus, and feline immunodeficiency virus. In contrast, nonnucleoside reverse transcriptase inhibitors and protease inhibitors did not exhibit any activities against SRV-4. Although both AZT and TDF effectively inhibited cell-free SRV-4 transmission, they exhibited only partial inhibitory activities against cell-to-cell transmission. Importantly, one HIV integrase strand transfer inhibitor, raltegravir (RAL), potently inhibited single-round infection as well as cell-free and cell-to-cell SRV-4 transmission. These findings indicate that viral expansion routes impact the inhibitory activity of antiretrovirals against SRV-4, while only RAL is effective in suppressing both the initial SRV-4 infection and subsequent SRV-4 replication. PMID:23365453

  9. Discontinuing anticytomegalovirus therapy in patients with immune reconstitution after combination antiretroviral therapy

    Microsoft Academic Search

    Douglas A. Jabs; Stephen G. Bolton; J. P. Dunn; Alan G. Palestine

    1998-01-01

    PURPOSE: To describe our experience with discontinuation of anticytomegalovirus maintenance therapy in patients who have had immune reconstitution after initiation of highly active antiretroviral therapy.METHODS: Fifteen patients with treated cytomegalovirus retinitis, who had immune reconstitution after initiation of highly active retroviral therapy, had anticytomegalovirus maintenance therapy discontinued. Patients were followed closely for relapse of retinitis.RESULTS: Median nadir CD4+ T-cell count,

  10. Polymorphisms and Splice Variants Influence the Antiretroviral Activity of Human APOBEC3H

    Microsoft Academic Search

    Ariana Harari; Marcel Ooms; Lubbertus C. F. Mulder; Viviana Simon

    2009-01-01

    Human APOBEC3H belongs to the APOBEC3 family of cytidine deaminases that potently inhibit exogenous and endogenous retroviruses. The impact of single nucleotide polymorphisms (SNP) and alternative splicing on the antiretroviral activity of human APOBEC3H is currently unknown. In this study, we show that APOBEC3H transcripts derived from human peripheral blood mononuclear cells are polymorphic in sequence and subject to alternative

  11. Measuring adherence to highly active antiretroviral therapy: Implications for research and practice

    Microsoft Academic Search

    Thomas Kerr; John Walsh; Elisa Lloyd-Smith; Evan Wood

    2005-01-01

    Highly active antiretroviral therapy (HAART) has radically changed the course of HIV disease, producing substantial reductions\\u000a in both HIV-related morbidity and mortality. However, the complexity of the typical daily HAART regimen is substantial, and\\u000a high levels of adherence are essential for complete and long-term viral suppression and the avoidance of drug resistance.\\u000a The complexity of HAART has made the assessment

  12. Brain localization of Kaposi’s sarcoma in a patient treated by combination antiretroviral therapy

    PubMed Central

    2013-01-01

    Background Central nervous system is a very rare site of Kaposi’s sarcoma in acquired immunodeficiency syndrome. Kaposi’s sarcoma, a neoplasm of endothelial origin, occurs mainly in the skin, but can involve many tissues, especially in patients with a poor immunity. Combination antiretroviral therapy, highly active against human immunodeficiency virus type-1, has caused a dramatic reduction of cutaneous and visceral involvements. No report of central nervous system localization of Kaposi’s sarcoma is described since the introduction of combination antiretroviral therapy in the late 90’s. Case presentation A 42 year-old Caucasian man affected by human immunodeficiency virus type-1 infection treated with combination antiretroviral therapy and showing relatively preserved immunity with low viral load presented gingival squamous cell carcinoma and visceral (lungs and lymph nodes) Kaposi’s sarcoma. Chemotherapy and radiotherapy were performed with improvement of both neoplasms. Afterwards, a magnetic resonance imaging showed focal lesions of the brain. Despite new chemotherapy and radiotherapy the patient died. Histology after autopsy revealed brain lesions due to Kaposi’s sarcoma with the detection of Human Herpesvirus 8 on tissue samples. Conclusions This is the first report in the combination antiretroviral therapy era of a very rare complication of Kaposi’s sarcoma, such as that of brain localization, in a patient with a relatively good control of human immunodeficiency virus infection. Therefore, Kaposi’s sarcoma should be considered in differential diagnosis with other intracranial mass lesions that can occur in human immunodeficiency virus infected-patients focusing the issue of appropriate treatment for central nervous system involvement. PMID:24359263

  13. [Severe psychosis in an African woman due to the antiretroviral agent efavirenz].

    PubMed

    van Twillert, G; van Santen, G; Godfried, M H

    2005-11-26

    A 34-year-old woman originally from Ghana was given efavirenz as antiretroviral therapy. One week later she was found to be in a psychotic state with paranoid hallucinations and anxiety; she then stabbed a nurse. The literature indicates that female patients of African origin appear to be more susceptible to the side effects of efavirenz due to genetically reduced clearance and therefore higher serum levels. PMID:16358620

  14. Depo-medroxyprogesterone in Women on Antiretroviral Therapy: Effective Contraception and Lack of Clinically Significant Interactions

    Microsoft Academic Search

    S E Cohn; J-G Park; D H Watts; A Stek; J Hitti; P A Clax; S Yu; J J L Lertora

    2007-01-01

    We conducted an open-label, steady-state pharmacokinetic (PK) study of drug interactions among HIV-infected women treated with depo-medroxyprogesterone acetate (DMPA) while on nucleoside analogues plus nelfinavir (N=21), efavirenz (N=17), or nevirapine (N=16); or nucleosides only or no antiretroviral therapy as a control group (N=16). PK parameters were estimated using non-compartmental analysis, with between-group comparisons of medroxyprogesterone acetate (MPA) PKs and within-subject

  15. Antiretroviral Non-Adherence is Associated With a Retrieval Profile of Deficits in Verbal Episodic Memory.

    PubMed

    Obermeit, Lisa C; Morgan, Erin E; Casaletto, Kaitlin B; Grant, Igor; Woods, Steven Paul

    2015-02-01

    HIV-associated deficits in verbal episodic memory are commonly associated with antiretroviral non-adherence; however, the specific aspects of memory functioning (e.g., encoding, consolidation, or retrieval) that underlie this established relationship are not well understood. This study evaluated verbal memory profiles of 202 HIV+ participants who underwent a 30-day electronic monitoring of antiretroviral adherence. At the group level, non-adherence was significantly associated with lower scores on immediate and delayed passage recall and word list learning. Retention and recognition of passages and word lists were not related to adherence. Participants were then classified as having either a normal verbal memory profile, a "subcortical" retrieval profile (i.e., impaired free recall with relatively spared recognition), or a "cortical" encoding profile (e.g., cued recall intrusions) based on the Massman et al. ( 1990 ) algorithm for the California Verbal Learning Test. HIV+ participants with a classic retrieval deficit had significantly greater odds of being non-adherent than participants with a normal or encoding profile. These findings suggest that adherence to prescribed antiretroviral regimens may be particularly vulnerable to disruption in HIV+ individuals due to deficits in the complex process of efficiently accessing verbal episodic information with minimal cues. A stronger relationship between non-adherence and passage (vs. word list) recall was also found and may reflect the importance of contextual features in remembering to take medications. Targeted interventions for enhancing and supporting episodic memory retrieval processes may improve antiretroviral adherence and overall health outcomes among persons living with HIV. PMID:25781903

  16. Effect of highly active antiretroviral therapy on diagnoses of sexually transmitted diseases in people with AIDS

    Microsoft Academic Search

    Susan Scheer; Priscilla Lee Chu; Jeffrey D Klausner; Mitchell H Katz; Sandra K Schwarcz

    Summary Background There has been an increase in high-risk sexual behaviour and sexually transmitted diseases (STD) during the time period when highly active antiretroviral therapy (HAART) became widely available. We examined whether taking HAART increased the risk of acquiring an STD—an epidemiological marker of unsafe sex—in people with AIDS. Methods We did a computerised match of people in the San

  17. Highly active antiretroviral therapy and hospital readmission: comparison of a matched cohort

    Microsoft Academic Search

    Bohdan Nosyk; Huiying Sun; Xin Li; Anita Palepu; Aslam H Anis

    2006-01-01

    BACKGROUND: Despite the known efficacy of highly active antiretroviral therapy (HAART), a large proportion of potentially-eligible HIV-infected patients do not access, and may stand to benefit from this treatment. In order to quantify these benefits in terms of reductions in hospitalizations and hospitalization costs, we sought to determine the impact of HAART on hospital readmission among HIV-infected patients hospitalized at

  18. Assessing resistance costs of antiretroviral therapies via measures of future drug options.

    PubMed

    Jiang, Hongyu; Deeks, Steven G; Kuritzkes, Daniel R; Lallemant, Marc; Katzenstein, David; Albrecht, Mary; DeGruttola, Victor

    2003-10-01

    The emergence of drug-resistant human immunodeficiency virus (HIV) type 1 in the setting of antiretroviral therapy failure limits the number of drugs available for use in subsequent therapy regimens. To quantify the relative HIV-1-resistance costs associated with various antiretroviral therapy strategies, we developed 2 related measures of future drug options (FDOs) by use of rule-based genotype-interpretation systems. The FDO1 metric assesses the number of drug classes that remain useful; the FDO2 metric assesses the number of drug classes that remain useful and the number of active drugs within each class. Application of these methods is illustrated with data from a randomized study of 3 therapy regimens in nucleoside analog-experienced patients. Each therapy regimen resulted in a unique pattern of drug-resistance (and cross-resistance) mutations. The regimen with the highest virologic failure rate preserved greater future drug options. Quantification of future drug options as an outcome of antiretroviral therapy trials may complement traditional clinical, virologic, and immunologic end points, thereby providing novel insights. PMID:14513420

  19. Systemic and topical drugs for the prevention of HIV infection: antiretroviral pre-exposure prophylaxis

    PubMed Central

    Baeten, Jared; Celum, Connie

    2013-01-01

    Pre-exposure prophylaxis (PrEP), in which HIV uninfected persons use oral or topical antiretroviral medications to protect against HIV acquisition, is a promising new HIV prevention strategy. The biologic rationale for evaluation of PrEP for sexual HIV prevention included non-human primate models and antiretroviral prophylaxis for HIV-exposed infants. Proof-of-concept that PrEP protects against sexual HIV acquisition has been demonstrated in four clinical trials, which used the antiretroviral medication tenofovir, either as a vaginal gel or as daily oral tenofovir disoproxil fumarate, alone or co-formulated with emtricitabine. Importantly, however, two trials failed to demonstrate HIV protection with PrEP, with low adherence to daily use of PrEP the leading hypothesis for lack of efficacy. Next steps in the field include rigorous evaluation of uptake and adherence to PrEP in implementation settings and research into ‘next-generation’ PrEP agents with longer half-life and less user-dependence. PMID:23020883

  20. Depression and patterns of self-reported adherence to antiretroviral therapy in Rwanda.

    PubMed

    Wroe, Emily B; Hedt-Gauthier, Bethany L; Franke, Molly F; Nsanzimana, Sabin; Turinimana, Jean Bosco; Drobac, Peter

    2015-03-01

    We determined the prevalence of depression in HIV-infected adults on antiretroviral therapy in rural Rwanda and measured the association of depression with non-adherence. In all, 292 patients on antiretroviral therapy for ?6 months were included. Adherence was self-reported by four-day recall, two- and seven-day treatment interruptions, and the CASE Index, which is a composite score accounting for difficulty taking medications on time, the average number of days per week a dose is missed, and the most recent missed dose. A total of 84% and 87% of participants reported good adherence by the four-day recall and CASE Index, respectively; 13% of participants reported two-day treatment interruptions; and 11% were depressed. Depression was significantly associated with two-day treatment interruptions but not with other measures of non-adherence. Self-reported adherence to antiretroviral therapy in rural Rwanda is high. Adherence assessments that do not consider treatment interruptions may miss important patterns of non-adherence, which may be especially prevalent among depressed individuals. Mental health interventions incorporated into routine HIV care may lead to improvements in mental health and adherence. PMID:24828554

  1. The Phenomenon of Business Start-Ups.

    ERIC Educational Resources Information Center

    Melis, Africa

    1990-01-01

    A study of four European countries (France, United Kingdom, Italy, and Spain) was conducted to gather data on the business start-up process and its impact on the generation of jobs, small business start-up support programs, training and counseling programs, and characteristics of successful business starters. (The original aim of the study was to…

  2. Report of First National Home Start Conference.

    ERIC Educational Resources Information Center

    Kapfer, Sherry

    The proceedings of the First National Home Start Conference are presented, based on reports of the sessions and activities of the meeting which was aimed at strengthening and supplementing child development in the home. Topics discussed include parent education, toy lending libraries, use of television, contributions of Head Start, early reading,…

  3. Starting Total Quality Management from ISO 9000

    Microsoft Academic Search

    Michael Bradley

    1994-01-01

    Some 20,000 companies have been registered as working to the International Quality Management Standard ISO 9000, but many have not achieved the improvements in their operations that can be obtained from managing on total quality management principles. ISO 9000 can be an excellent start to TQM, if it is interpreted in a way that encourages the company to start on

  4. NU Start: A Residential Learning Community.

    ERIC Educational Resources Information Center

    Bergstrom, Robert

    This paper describes NU Start, a summer learning community program at the University of Nebraska-Lincoln for first-year students of the English department and the University Library faculty. NU Start offered 4 sections of an Introduction to Literature course, each with 13 or 14 students. In addition, all students took a one-hour, self-paced…

  5. Getting Started: What's Your Fitness Level?

    MedlinePLUS

    Everyday Fitness Ideas from the National Institute on Aging at NIH www.nia.nih.gov/Go4Life Getting Started: What’s ... safe is to build slowly from your current fitness level. To find your starting point, answer the ...

  6. New Start Program: Second Year Report.

    ERIC Educational Resources Information Center

    Winchell, Anne

    Kingborough Community College's (KCC's) New Start Program was initiated in 1985 to give students who were unsuccessful at senior colleges a second chance at higher education. Following a very successful first year during which retention and academic performance were significantly improved, the New Start Program was expanded from 63 to 240 students…

  7. Digital MicrofilmTM Quick Start Guide

    E-print Network

    Olsen, Stephen L.

    Digital MicrofilmTM Quick Start Guide Getting Started ­ ProQuest Digital Microfilm is operable Adobe Reader Version 9 or higher JavaScript must be enabled #12;ProQuest Digital MicrofilmTM features corner of the page. ProQuest Support Center For answers to common Digital Microfilm support topics visit

  8. Administration for Children and Families: Head Start

    ERIC Educational Resources Information Center

    US Department of Health and Human Services, 2010

    2010-01-01

    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…

  9. When Do Start-Ups Make Sense?

    ERIC Educational Resources Information Center

    Langemeyer, Clement J.

    2005-01-01

    The start-up has received considerable attention in the last few years. While the National Research Council of Canada has generated many start-ups over its 88-year history, the creation of a formal entrepreneurship programme in the mid-1990s dramatically accelerated the pace at which they were created. Many factors come into play in the decision…

  10. Head Start Home-Based Resource Directory.

    ERIC Educational Resources Information Center

    Trans-Management Systems, Inc.

    A revision of the 1989 publication, this directory was compiled in order to help parents and professionals involved with Head Start home-based programming in meeting the needs of young children and families. The directory lists a broad range of guides and resources on topics related to Head Start home-based programs. Each listing provides the…

  11. START Analysis for ESAS Capability Needs Prioritization

    NASA Technical Reports Server (NTRS)

    Lincoln, William; Mrozinski, Joe; Hua, Hook; Merida, Sofia; Shelton, Kacie; Adumitroaie, Virgil; Weisbin, Charles R.; Derleth, Jason

    2006-01-01

    START is a tool to optimize research and development primarily for NASA missions. It was developed within the Strategic Systems Technology Program Office, a division of the Office of the Chief Technologist at NASA's Jet Propulsion Laboratory. START is capable of quantifying and comparing the risks, costs, and potential returns of technologies that are candidates for funding. START can be enormously helpful both in selecting technologies for development -- within the constraints of budget, schedule, and other resources -- and in monitoring their progress. START's methods are applicable to everything from individual tasks to multiple projects comprising entire programs of investigation. They can address virtually any technology assessment and capability prioritization issue. In this report, START is used to analyze the capability needs using data from NASA's Exploration Systems Architecture Study (ESAS).

  12. 78 FR 49372 - Notice of Availability of New Starts and Small Starts Policy Guidance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-14

    ...2013. The rule sets the framework for the New Starts and Small Starts evaluation and rating process; the policy guidance complements the rule by providing technical details about the methods for calculating the project justification and local financial...

  13. Starting Circuit For Erasable Programmable Logic Device

    NASA Technical Reports Server (NTRS)

    Cole, Steven W.

    1990-01-01

    Voltage regulator bypassed to supply starting current. Starting or "pullup" circuit supplies large inrush of current required by erasable programmable logic device (EPLD) while being turned on. Operates only during such intervals of high demand for current and has little effect any other time. Performs needed bypass, acting as current-dependent shunt connecting battery or other source of power more nearly directly to EPLD. Input capacitor of regulator removed when starting circuit installed, reducing probability of damage to transistor in event of short circuit in or across load.

  14. Training Head Start Coordinators for Workplace Preparedness. NCCU Head Start Monograph, October 1995.

    ERIC Educational Resources Information Center

    North Carolina Central Univ., Durham.

    This monograph summarizes results from academic capstone activities of graduate students and faculty advisors regarding issues consistent with Head Start national priorities and practice needs. The following theses are summarized: (1) "Multicultural Education in Head Start Programs in North Carolina" (S.K. Gant); (2) "The Impact of Head Start on…

  15. Michigan Middle Start Studies of Middle Start School Improvement, Lake Middle School: A Case Study.

    ERIC Educational Resources Information Center

    Gopalan, Pritha

    This case study documented the collaboration of Lake Middle School (pseudonym for a school in Michigan) with Middle Start, a middle-grades reform model and its progress and struggles implementing the model. Middle Start was coordinated by the Michigan Middle Start Partnership, and alliance that provided technical assistance, professional…

  16. Outcomes of Multidrug-Resistant Tuberculosis Treatment with Early Initiation of Antiretroviral Therapy for HIV Co-Infected Patients in Lesotho

    PubMed Central

    Satti, Hind; McLaughlin, Megan M.; Hedt-Gauthier, Bethany; Atwood, Sidney S.; Omotayo, David B.; Ntlamelle, Likhapha; Seung, Kwonjune J.

    2012-01-01

    Background Although the importance of concurrent treatment for multidrug-resistant tuberculosis (MDR-TB) and HIV co-infection has been increasingly recognized, there have been few studies reporting outcomes of MDR-TB and HIV co-treatment. We report final outcomes of comprehensive, integrated MDR-TB and HIV treatment in Lesotho and examine factors associated with death or treatment failure. Methods We reviewed clinical charts of all adult patients who initiated MDR-TB treatment in Lesotho between January 2008 and September 2009. We calculated hazard ratios (HR) and used multivariable Cox proportional hazards regression to identify predictors of poor outcomes. Results Of 134 confirmed MDR-TB patients, 83 (62%) were cured or completed treatment, 46 (34%) died, 3 (2%) transferred, 1 (1%) defaulted, and 1 (1%) failed treatment. Treatment outcomes did not differ significantly by HIV status. Among the 94 (70%) patients with HIV co-infection, 53% were already on antiretroviral therapy (ART) before MDR-TB treatment initiation, and 43% started ART a median of 16 days after the start of the MDR-TB regimen. Among HIV co-infected patients who died, those who had not started ART before MDR-TB treatment had a shorter median time to death (80 days vs. 138 days, p?=?0.065). In multivariable analysis, predictors of increased hazard of failure or death were low and severely low body mass index (HR 2.75, 95% confidence interval [CI] 1.27–5.93; HR 5.50, 95% CI 2.38–12.69), and a history of working in South Africa (HR 2.37, 95% CI 1.24–4.52). Conclusions Favorable outcomes can be achieved in co-infected patients using a community-based treatment model when both MDR-TB and HIV disease are treated concurrently and treatment is initiated promptly. PMID:23115633

  17. Association between apolipoprotein E4 genotype and human immunodeficiency virus-associated dementia in younger adults starting antiretroviral therapy in South Africa.

    PubMed

    Joska, John A; Combrinck, Marc; Valcour, Victor G; Hoare, Jacqueline; Leisegang, Felicity; Mahne, Anna Cecilia; Myer, Landon; Stein, Dan J

    2010-10-01

    It is not known whether the apolipoprotein E (ApoE) ?4 allelic variant is associated with human immunodeficiency virus (HIV)-associated dementia (HAD) in a South African population, where HIV clade C is predominant. ApoE genotyping was performed on 144 participants in a larger study of HIV-associated neurocognitive disorders (HAND). There was a lower frequency of the ?2 and ?3 alleles in the HIV-positive group, compared to a group of 300 community-based newborn infants. There were no differences in ApoE genotype across different categories of HAND. The ?4 allelic variant was less common in individuals with HAD than in those without HAD. These findings suggest that the ?4 allelic variant in HIV-positive individuals is not associated with the development of HAD in Southern Africa. PMID:20825268

  18. Association between apolipoprotein E4 genotype and human immunodeficiency virus-associated dementia in younger adults starting antiretroviral therapy in South Africa

    Microsoft Academic Search

    John A Joska; Marc Combrinck; Victor G Valcour; Jacqueline Hoare; Felicity Leisegang; Anna Cecilia Mahne; Landon Myer; Dan J Stein

    2010-01-01

    It is not known whether the apolipoprotein E (ApoE) ?4 allelic variant is associated with human immunodeficiency virus (HIV)-associated\\u000a dementia (HAD) in a South African population, where HIV clade C is predominant. ApoE genotyping was performed on 144 participants\\u000a in a larger study of HIV-associated neurocognitive disorders (HAND). There was a lower frequency of the ?2 and ?3 alleles\\u000a in

  19. Factors associated with high rates of antiretroviral medication adherence among youth living with perinatal HIV in Thailand.

    PubMed

    Kang, Ezer; Delzell, Darcie Ap; Chhabra, Manik; Oberdorfer, Peninnah

    2015-07-01

    Antiretroviral medication adherence behaviour among Thai youth with perinatal HIV in Thailand has received growing attention. However, few studies have examined individual predictors of antiretroviral adherence using multiple self-reports. A convenience sample of 89 Thai youth (interquartile range 14-16 years) with perinatal HIV at three paediatric programmes in Chiang Mai completed a structured questionnaire and reported their antiretroviral adherence in the past one, seven and 30 days using count-based recall and a visual analog scale. Mean self-reported adherence rates ranged from 83.5% (past 30 days) to 99.8% (yesterday) of the time. One-inflated beta regression models were used to examine the associations between antiretroviral adherence outcomes, treatment self-efficacy, depression, anxiety, social support and beliefs/attitudes about medications. Higher percentage of medications taken in the past 30 days was independently associated with higher treatment self-efficacy and fewer symptoms of depression. Adherence monitoring would benefit from focal assessment of youth depression and perceived capacity to follow their antiretroviral regimen. PMID:25080289

  20. HIV drug resistance in mothers and infants following use of antiretrovirals to prevent mother-to-child transmission.

    PubMed

    Ton, Quy; Frenkel, Lisa

    2013-03-01

    The purpose of this article is to review prominent studies on HIV drug-resistance in mothers and their infants after the use of antiretroviral drugs to prevent mother-to-child-transmission in resource-limited communities. The effects of drug-resistance on subsequent combination antiretroviral therapy are discussed, as are the probable mechanisms of acquisition and decay or persistence of drug-resistant mutants. Differences in the rates of HIV drug-resistance from interventions used to prevent mother-to-child-transmission in North America and Europe are contrasted to the simplified regimens used in resource-limited settings. Unresolved issues related to HIV drug-resistance are reviewed, including: whether maternal zidovudine monotherapy selects significant resistance; the clinical relevance of HIV drug-resistant variants selected by single-dose nevirapine that persist as minority viral variants and can affect the outcome of non-nucleoside reverse transcriptase inhibitor-based therapy; and the use of maternal combination antiretroviral therapy during breastfeeding. Finally, the current and upcoming strategies to reduce HIV drug-resistance related to use of antiretrovirals to prevent mother-to-child-transmission are discussed and contrasted with the challenges of financing and administering antiretrovirals to prevent mother-to-child-transmission in resource-limited communities. PMID:23432488

  1. Comparisons of anemia, thrombocytopenia, and neutropenia at initiation of HIV antiretroviral therapy in Africa, Asia, and the Americas

    PubMed Central

    Firnhaber, Cynthia; Smeaton, Laura; Saukila, Nasinuku; Flanigan, Timothy; Gangakhedkar, Raman; Kumwenda, Johnstone; La Rosa, Alberto; Kumarasamy, Nagalingeswaran; De Gruttola, Victor; Hakim, James Gita; Campbell, Thomas B.

    2010-01-01

    Summary Background Hematological abnormalities are common manifestations of advanced HIV-1 infection that could affect the outcomes of highly-active antiretroviral therapy (HAART). Although most HIV-1-infected individuals live in resource-constrained countries, there is little information about the frequency of hematological abnormalities such as anemia, neutropenia, and thrombocytopenia among individuals with advanced HIV-1 disease. Methods This study compared the prevalence of pre-antiretroviral therapy hematological abnormalities among 1571 participants in a randomized trial of antiretroviral efficacy in Africa, Asia, South America, the Caribbean, and the USA. Potential covariates for anemia, neutropenia, and thrombocytopenia were identified in univariate analyses and evaluated in separate multivariable models for each hematological condition. Results The frequencies of neutropenia (absolute neutrophil count ? 1.3 × 109/l), anemia (hemoglobin ? 10 g/dl), and thrombocytopenia (platelets ? 125 × 109/l) at initiation of antiretroviral therapy were 14%, 12%, and 7%, respectively, and varied by country (p < 0.0001 for each). In multivariable models, anemia was associated with gender, platelet count, and country; neutropenia was associated with CD4+ lymphocyte and platelet counts; and thrombocytopenia was associated with country, gender, and chronic hepatitis B infection. Conclusions Differences in the frequency of pretreatment hematological abnormalities could have important implications for the choice of antiretroviral regimen in resource-constrained settings. PMID:20961784

  2. 34 CFR 200.16 - Starting points.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...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...

  3. Starting to Exercise Again After a Break

    MedlinePLUS

    ... If Starting to Exercise Again after a Break Vacation? Flu? Out-of-town guests? Many things can ... breaks. Temporary Interruptions: l hen you’re on vacation, get out and see the sights on foot ...

  4. Why Your Child Might Start Drinking Alcohol

    MedlinePLUS

    ... Your Child Might Start Drinking Some children may experiment with alcohol as they approach their teen years ... 1-800-846-8517 Experienced a natural or human-caused disaster? Learn more about the Disaster Distress ...

  5. Ethereal: Getting Started CSCI 3171: Network Computing

    E-print Network

    Brooks, Stephen

    Ethereal: Getting Started CSCI 3171: Network Computing Introduction One's understanding of network," as shown in Figure 2.8 in the text. We will be using the Ethereal packet sniffer [http://www.ethereal

  6. Haptic Paddle: Getting Started University of Washington

    E-print Network

    1 Haptic Paddle: Getting Started University of Washington Department of Electrical Engineering Bio.....................................................................................................................2 Running the Example Code electronics for the haptic paddle. If you don't have a paddle sans firmware, please visit this link to learn

  7. Drug Abuse Prevention Starts with Parents

    MedlinePLUS

    ... Stages Listen Espańol Text Size Email Print Share Drug Abuse Prevention Starts with Parents Article Body Drugs, ... Learn the facts about the harmful effects of drugs. Talk with your child about the negative effects ...

  8. Getting Started Computing at the AI Lab

    E-print Network

    Stacy, Christopher C.

    1982-09-07

    This document describes the computing facilities at M.I.T. Artificial Intelligence Laboratory, and explains how to get started using them. It is intended as an orientation document for newcomers to the lab, and will be ...

  9. A New Start from Ground Zero?

    NASA Astrophysics Data System (ADS)

    Luisi, Pier Luigi

    2014-12-01

    It is pointed out that one of the main reasons of lack of real conceptual progress in the field may lie in the fact that questions concerning the biogenesis of macromolecules have never been asked or addressed in a proper way. We should start again research on the origin of life starting from "ground zero" and focusing on the prebiotic synthesis of ordered sequences of proteins and nucleic acids.

  10. New "starting points" for resources by subject.

    PubMed

    Prentice, Katherine A; Gaines, Julie K; Levy, Linda S

    2009-01-01

    The objective of the Starting Points Web page series at The University of Texas Health Science Center at San Antonio (UT HSC) Libraries is to provide specialized information resources in an organized online format. Highlighted resources include databases, journals, UT HSC campus information, funding sources, PubMed RSS article feeds, and information about professional associations. This paper discusses the development process, planning, challenges, and outcomes of the Starting Points series. PMID:19197747

  11. ,,START-UP BRACHFLCHE" Arbeitshilfe zur Erarbeitung von Projektplnen

    E-print Network

    Cirpka, Olaf Arie

    ,,START-UP BRACHFLÄCHE" Arbeitshilfe zur Erarbeitung von Projektplänen #12;#12;,,START-UP Preuß Volker Schrenk Kai Steffens Karolin Weber Stuttgart, April 2005 #12;START-UP-BRACHFLÄCHE Impressum;START-UP-BRACHFLÄCHE 3 Inhalt Abbildungsverzeichnis

  12. Title: First year lymphocyte T CD4+ response to antiretroviral therapy according to the HIV type in the IeDEA West Africa collaboration.

    E-print Network

    Paris-Sud XI, Université de

    ;Introduction As of 2007, it was estimated that the rapid scale-up of antiretroviral therapy (ART) in WestTitle: First year lymphocyte T CD4+ response to antiretroviral therapy according to the HIV type], but nonetheless leads to clinical AIDS in some instances [8, 9]. Unfortunately data on the ART response in HIV-2

  13. Massage Treatment in HIV1 Infected Dominican Children: A Preliminary Report on the Efficacy of Massage Therapy to Preserve the Immune System in Children Without Antiretroviral Medication

    Microsoft Academic Search

    Gail Shor-Posner; Maria-Jose Miguez; Maria Hernandez-Reif; Eddy Perez-Then; Maryann Fletcher

    2004-01-01

    Objectives: More than 1.4 million children are living with HIV and global access to antiretrovirals is not yet readily available. Massage therapy, which has been shown to improve immune function in HIVadults and adolescents, may provide an important complementary treatment to boost immune status in young chil- dren living with HIV disease, especially those without access to antiretroviral medications. No

  14. Cost analysis of initial highly active antiretroviral therapy regimens for managing human immunodeficiency virus-infected patients according to clinical practice in a hospital setting

    PubMed Central

    Colombo, Giorgio L; Castagna, Antonella; Di Matteo, Sergio; Galli, Laura; Bruno, Giacomo; Poli, Andrea; Salpietro, Stefania; Carbone, Alessia; Lazzarin, Adriano

    2014-01-01

    Objective In the study reported here, single-tablet regimen (STR) versus (vs) multi-tablet regimen (MTR) strategies were evaluated through a cost analysis in a large cohort of patients starting their first highly active antiretroviral therapy (HAART). Adult human immunodeficiency virus (HIV) 1-naďve patients, followed at the San Raffaele Hospital, Milan, Italy, starting their first-line regimen from June 2008 to April 2012 were included in the analysis. Methods The most frequently used first-line HAART regimens (>10%) were grouped into two classes: 1) STR of tenofovir disoproxil fumarate (TDF) + emtricitabine (FTC) + efavirenz (EFV) and 2) MTR including TDF + FTC + EFV, TDF + FTC + atazanavir/ritonavir (ATV/r), TDF + FTC + darunavir/ritonavir (DRV/r), and TDF + FTC + lopinavir/ritoavir (LPV/r). Data were analyzed from the point of view of the Lombardy Regional Health Service. HAART, hospitalizations, visits, medical examinations, and other concomitant non-HAART drug costs were evaluated and price variations included. Descriptive statistics were calculated for baseline demographic, clinical, and laboratory characteristics; associations between categorical variables and type of antiretroviral strategy (STR vs MTR) were examined using chi-square or Fisher’s exact tests. At multivariate analysis, the generalized linear model was used to identify the predictive factors of the overall costs of the first-line HAART regimens. Results A total of 474 naďve patients (90% male, mean age 42.2 years, mean baseline HIV-RNA 4.50 log 10 copies/mL, and cluster of differentiation 4 [CD4+] count of 310 cells/?L, with a mean follow-up of 28 months) were included. Patients starting an STR treatment were less frequently antibody-hepatitis C virus positive (4% vs 11%, P=0.040), and had higher mean CD4+ values (351 vs 297 cells/?L, P=0.004) than MTR patients. The mean annual cost per patient in the STR group was €9,213.00 (range: €6,574.71–€33,570.00) and €14,277.00 (range: €5,908.89–€82,310.30) among MTR patients. At multivariate analysis, after adjustment for age, sex, antibody-hepatitis C virus status, HIV risk factors, baseline CD4+, and HIV-RNA, the cost analysis was significantly lower among patients starting an STR treatment than those starting an MTR (adjusted mean: €12,096.00 vs €16,106.00, P=0.0001). Conclusion STR was associated with a lower annual cost per patient than MTR, thus can be considered a cost-saving strategy in the treatment of HIV patients. This analysis is an important tool for policy makers and health care professionals to make short- and long-term cost projections and thus assess the impact of these on available budgets. PMID:24379676

  15. 45 CFR 1308.21 - Parent participation and transition of children into Head Start and from Head Start to public...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...FAMILIES, HEAD START PROGRAM HEAD START PROGRAM PERFORMANCE STANDARDS ON...transition of children into Head Start and from Head Start to public school. (a) In...child's IEP. (4) Provide follow-up assistance and activities to...

  16. 45 CFR 1308.21 - Parent participation and transition of children into Head Start and from Head Start to public...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ...FAMILIES, HEAD START PROGRAM HEAD START PROGRAM PERFORMANCE STANDARDS ON...transition of children into Head Start and from Head Start to public school. (a) In...child's IEP. (4) Provide follow-up assistance and activities to...

  17. Should patents for antiretrovirals be waived in the developing world? Annual varsity medical debate - London, 21 January 2011

    PubMed Central

    2011-01-01

    The 2011 Varsity Medical Debate, between Oxford and Cambridge Universities, brought students and faculty together to discuss the waiving of patents for antiretroviral therapies in the developing world. With an estimated 29.5 million infected by Human Immunodeficiency Virus (HIV) in low- and middle-income countries and only 5.3 million of those being treated, the effective and equitable distribution of anti-retroviral therapy (ART) is an issue of great importance. The debate centred around three areas of contention. Firstly, there was disagreement about whether patents were the real barrier to the access of anti-retroviral therapy in the developing world. Secondly, there were differing views on the effectiveness of a patent pool. Thirdly, concerns were raised over the impact of waiving patents on research to produce new and better anti retro-viral drugs. PMID:21740573

  18. Small-Molecule Inhibition of HIV pre-mRNA Splicing as a Novel Antiretroviral Therapy to Overcome Drug Resistance

    PubMed Central

    Maire, Sophie; Ayadi, Lilia; Mahuteau-Betzer, Florence; Nguyen, Chi Hung; Mettling, Clément; Portales, Pierre; Grierson, David; Chabot, Benoit; Jeanteur, Philippe; Branlant, Christiane; Corbeau, Pierre; Tazi, Jamal

    2007-01-01

    The development of multidrug-resistant viruses compromises antiretroviral therapy efficacy and limits therapeutic options. Therefore, it is an ongoing task to identify new targets for antiretroviral therapy and to develop new drugs. Here, we show that an indole derivative (IDC16) that interferes with exonic splicing enhancer activity of the SR protein splicing factor SF2/ASF suppresses the production of key viral proteins, thereby compromising subsequent synthesis of full-length HIV-1 pre-mRNA and assembly of infectious particles. IDC16 inhibits replication of macrophage- and T cell–tropic laboratory strains, clinical isolates, and strains with high-level resistance to inhibitors of viral protease and reverse transcriptase. Importantly, drug treatment of primary blood cells did not alter splicing profiles of endogenous genes involved in cell cycle transition and apoptosis. Thus, human splicing factors represent novel and promising drug targets for the development of antiretroviral therapies, particularly for the inhibition of multidrug-resistant viruses. PMID:17967062

  19. The Complexity of HIV Persistence and Pathogenesis in the Lung Under Antiretroviral Therapy: Challenges Beyond AIDS

    PubMed Central

    2014-01-01

    Abstract Antiretroviral therapy (ART) represents a significant milestone in the battle against AIDS. However, we continue learning about HIV and confronting challenges 30 years after its discovery. HIV has cleverly tricked both the host immune system and ART. First, the many HIV subtypes and recombinant forms have different susceptibilities to antiretroviral drugs, which may represent an issue in countries where ART is just being introduced. Second, even under the suppressive pressures of ART, HIV still increases inflammatory mediators, deregulates apoptosis and proliferation, and induces oxidative stress in the host. Third, the preference of HIV for CXCR4 as a co-receptor may also have noxious outcomes, including potential malignancies. Furthermore, HIV still replicates cryptically in anatomical reservoirs, including the lung. HIV impairs bronchoalveolar T-lymphocyte and macrophage immune responses, rendering the lung susceptible to comorbidities. In addition, HIV-infected individuals are significantly more susceptible to long-term HIV-associated complications. This review focuses on chronic obstructive pulmonary disease (COPD), pulmonary arterial hypertension, and lung cancer. Almost two decades after the advent of highly active ART, we now know that HIV-infected individuals on ART live as long as the uninfected population. Fortunately, its availability is rapidly increasing in low- and middle-income countries. Nevertheless, ART is not risk-free: the developed world is facing issues with antiretroviral drug toxicity, resistance, and drug–drug interactions, while developing countries are confronting issues with immune reconstitution inflammatory syndrome. Several aspects of the complexity of HIV persistence and challenges with ART are discussed, as well as suggestions for new avenues of research. PMID:24797368

  20. Implementing a pharmacovigilance program to evaluate cutaneous adverse drug reactions in an antiretroviral access program

    PubMed Central

    Mudzviti, Tinashe; Sibanda, Marvelous; Gavi, Samuel; Maponga, Charles Chiedza; Morse, Gene D.

    2012-01-01

    Background Cutaneous adverse drug reactions (cADRs) can cause significant morbidity and distress in patients especially in the HIV infected population on antiretroviral therapy. Adverse Drug Reaction monitoring and ascertaining causality in resource limited settings still remains a challenge. This study was carried out to evaluate causality and measure incidence of cADRs in HIV infected patients on highly active antiretroviral therapy. The study was also designed to test a 3-step approach in the monitoring and evaluation of ADRs in resource limited settings. Methodology A retrospective patient medical records review was carried out at the Parirenyatwa Family Care Centre, (Harare, Zimbabwe). Cases of cADRs were reported to the Medicines Control Authority of Zimbabwe (Drug regulating body in Zimbabwe) for assessment and causality classification. Results Two hundred and twenty-one patient records were randomly selected and reviewed to determine if any diagnosis of cADRs was made by clinicians. Causality assessment revealed 13.1% of cADRs which were due to an offending agent in the antiretroviral therapy against an initial incidence of 17.6% which had been determined by the physicians. Conclusions cADRs had an incidence of 13.1% within the population under study due to non nucleoside reverse transcriptase inhibitors (NNRTIs). Most reactions were due to the NNRTIs which contributed 72.4 % of all cADRs. A panel of experts from the drug regulatory authority can be used as an implementation based mechanism in ascertaining causality objectively in settings where resources are constrained. PMID:23277506

  1. Durable Suppression of HIV-1 after Virologic Monitoring-Based Antiretroviral Adherence Counseling in Rakai, Uganda

    PubMed Central

    Billioux, Alexander; Nakigozi, Gertrude; Newell, Kevin; Chang, Larry W.; Quinn, Thomas C.; Gray, Ron H.; Ndyanabo, Anthony; Galiwango, Ronald; Kiggundu, Valerian; Serwadda, David; Reynolds, Steven J

    2015-01-01

    Objectives HIV viral load is recommended for monitoring antiretroviral treatment and identifying treatment failure. We assessed the durability of viral suppression after viral load-triggered adherence counseling among patients with HIV viremia 6 months after ART initiation. Design Observational cohort enrolled in an antiretroviral treatment program in rural Uganda. Methods Participants who underwent routine viral load determination every 24 weeks and had at least 48 weeks of follow-up were included in this analysis. Patients with viral loads >400 copies/ml at 24 weeks of treatment were given additional adherence counseling, and all patients were followed to assess the duration of viral suppression and development of virologic failure. Results 1,841 participants initiating antiretroviral therapy were enrolled in the Rakai Health Sciences Program between June 2005 and June 2011 and were followed with viral load monitoring every 24 weeks. 148 (8%) of patients did not achieve viral suppression at 24 weeks and were given additional adherence counseling. 85 (60%) of these patients had undetectable viral loads at 48 weeks, with a median duration of viral suppression of 240 weeks (IQR 193-288 weeks). Failure to achieve an undetectable viral load at 48 weeks was associated with age <30 years and 24 week viral load >2,000 copies/ml in multivariate logistic regression analysis. Conclusions The majority of patients with persistent viremia who were provided adherence counseling achieved robust viral suppression for a median 4.6 years. Access to virologic monitoring and adherence counseling is a priority in resource-limited settings. PMID:26011158

  2. Preclinical Pharmacokinetics and Tissue Distribution of Long-Acting Nanoformulated Antiretroviral Therapy

    PubMed Central

    Gautam, Nagsen; Roy, Upal; Balkundi, Shantanu; Puligujja, Pavan; Guo, Dongwei; Smith, Nathan; Liu, Xin-Ming; Lamberty, Benjamin; Morsey, Brenda; Fox, Howard S.; McMillan, JoEllyn; Gendelman, Howard E.

    2013-01-01

    Long-acting injectable nanoformulated antiretroviral therapy (nanoART) was developed with the explicit goal of improving medicine compliance and for drug targeting of viral tissue reservoirs. Prior nanoART studies completed in humanized virus-infected mice demonstrated sustained antiretroviral responses. However, the pharmacokinetics (PK) and tissue distribution of nanoART were not characterized. To this end, the PK and tissue distribution of nanoformulated atazanavir (ATV) and ritonavir (RTV) injected subcutaneously or intramuscularly in mice and monkeys were evaluated. Fourteen days after injection, ATV and RTV levels were up to 13-, 41-, and 4,500-fold higher than those resulting from native-drug administration in plasma, tissues, and at the site of injection, respectively. At nanoART doses of 10, 50, 100, and 250 mg/kg of body weight, relationships of more- and less-than-proportional increases in plasma and tissue levels with dose increases were demonstrated with ATV and RTV. Multiple-dose regimens showed serum and tissue concentrations up to 270-fold higher than native-drug concentrations throughout 8 weeks of study. Importantly, nanoART was localized in nonlysosomal compartments in tissue macrophages, creating intracellular depot sites. Reflective data were obtained in representative rhesus macaque studies. We conclude that nanoART demonstrates blood and tissue antiretroviral drug levels that are enhanced compared to those of native drugs. The sustained and enhanced PK profile of nanoART is, at least in part, the result of the sustained release of ATV and RTV from tissue macrophases and at the site of injection. PMID:23612193

  3. Technology-Based Self-Care Methods of Improving Antiretroviral Adherence: A Systematic Review

    PubMed Central

    Saberi, Parya; Johnson, Mallory O.

    2011-01-01

    Background As HIV infection has shifted to a chronic condition, self-care practices have emerged as an important topic for HIV-positive individuals in maintaining an optimal level of health. Self-care refers to activities that patients undertake to maintain and improve health, such as strategies to achieve and maintain high levels of antiretroviral adherence. Methodology/Principal Findings Technology-based methods are increasingly used to enhance antiretroviral adherence; therefore, we systematically reviewed the literature to examine technology-based self-care methods that HIV-positive individuals utilize to improve adherence. Seven electronic databases were searched from 1/1/1980 through 12/31/2010. We included quantitative and qualitative studies. Among quantitative studies, the primary outcomes included ARV adherence, viral load, and CD4+ cell count and secondary outcomes consisted of quality of life, adverse effects, and feasibility/acceptability data. For qualitative/descriptive studies, interview themes, reports of use, and perceptions of use were summarized. Thirty-six publications were included (24 quantitative and 12 qualitative/descriptive). Studies with exclusive utilization of medication reminder devices demonstrated less evidence of enhancing adherence in comparison to multi-component methods. Conclusions/Significance This systematic review offers support for self-care technology-based approaches that may result in improved antiretroviral adherence. There was a clear pattern of results that favored individually-tailored, multi-function technologies, which allowed for periodic communication with health care providers rather than sole reliance on electronic reminder devices. PMID:22140446

  4. Inadequacies in antiretroviral therapy use among Aboriginal and other Canadian populations.

    PubMed

    Miller, C L; Spittal, P M; Wood, E; Chan, K; Schechter, M T; Montaner, J S G; Hogg, R S

    2006-11-01

    We undertook this study to provide a profile of Aboriginal people initiating antiretroviral therapy and their response to treatment. Aboriginal peoples were identified through self-report. Baseline socio-demographics and risk factors were compared between Aboriginal and non-Aboriginal participants as were baseline factors associated with two consecutive plasma viral load measures below 500 copies/ml using contingency table analysis. Multivariate survival analysis of the prognostic factors associated with time to two consecutive plasma viral load measures below 500 copies/ml among eligible participants was undertaken to characterize response to antiretroviral therapy. There were 892 participants with available data for this analysis, of those 146 (16%) self-identified as Aboriginal. Aboriginal participants were more likely to be female (p < or = 0.001), have lower baseline plasma viral loads (p = 0.010), be co-infected with HCV (p < 0.001), live in unstable housing (p < or = 0.001), and report an income of >10K CDN (p < or = 0.001) per annum. Aboriginal people were less likely to report men who have sex with men (p < or = 0.001) and more likely to report injection drug use (p < or = 0.001) as a risk factor for HIV infection. Aboriginal participants were more likely to receive double versus triple combination antiretroviral therapy (p = 0.002), be less adherent in the first year on therapy (p = 0.001) and to have a physician less experienced with treating HIV (p < or = 0.001). When these factors were controlled for, Aboriginal people treated with triple combination therapy were as likely to respond and suppress their viral load below 500 copies. In the era of HAART, our results indicate that Aboriginal people living with HIV/AIDS were less likely to receive optimal therapy. However, when Aboriginals did receive triple drug therapy they suppressed just as well as non-Aboriginals. PMID:17012087

  5. Polyacrylamide Gel Treatment of Antiretroviral Therapy-induced Facial Lipoatrophy in HIV Patients

    Microsoft Academic Search

    Samreen Mansor; Vibeke Bro Breiting; Karin Dahlstrřm; Ĺse Bengĺrd Andersen; Ove Andersen; Lise Hanne Christensen

    Background  Today, highly active antiretroviral therapy is lifesaving for most HIV-infected patients, but the treatment can result in\\u000a facial lipoatrophy, which changes the face so radically that patients may develop severe psychological and social problems.\\u000a Since 2001 polyacrylamide gel (PAAG) has been used successfully in HIV patients abroad. This article describes the results\\u000a of a Danish study.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  Forty HIV patients recruited

  6. Improved case detection of active tuberculosis associated with an antiretroviral treatment program in Lesotho.

    PubMed

    Furin, J J; Rigodon, J; Cancedda, C; Keshavjee, S; Seung, K J; Letsie, M; Kim, J Y; Joseph, J K

    2007-10-01

    Tuberculosis (TB) remains the leading infectious killer of adults with human immunodeficiency virus (HIV) globally. Lesotho has the third highest prevalence of HIV and the fourth highest prevalence of TB worldwide, and the majority of TB patients are co-infected with HIV. This paper describes an antiretroviral treatment (ART) program instituted in a health center in a mountain region of Lesotho. Although the main goal of the program was to increase HIV detection and initiate ART for patients, the program also resulted in a ten-fold increase in the detection of TB among patients with and without HIV. PMID:17945074

  7. Influence of HCV or HBV coinfection on adverse drug reactions to antiretroviral drugs in HIV patients

    Microsoft Academic Search

    Emmanuelle Guitton; Jean-Louis Montastruc; Maryse Lapeyre-Mestre

    2006-01-01

    Objective  To compare the profile of adverse drug reactions (ADRs) to antiretroviral (ARV) drugs in patients coinfected with hepatitis\\u000a C virus (HCV) or hepatitis B virus (HBV) versus non-coinfected patients with human immunodeficiency virus (HIV) infection.\\u000a \\u000a \\u000a \\u000a Methods  We used the French Pharmacovigilance Database from 2000 to 2002. Selected patients were classified into four groups: HIV+HCV,\\u000a HIV+HBV, HIV+HBV+HCV and HIV patients. We compared

  8. Antiretroviral therapy adherence in persons with HIV/AIDS in Cuba.

    PubMed

    Aragonés, Carlos; Sánchez, Lizet; Campos, Jorge R; Pérez, Jorge

    2011-04-01

    INTRODUCTION Cuba has an HIV prevalence of 0.1% in the population aged 15 to 49 years, very low despite increased incidence in recent years. In 2001, domestically-produced generic antiretroviral therapy was introduced and there has been complete coverage since 2003. In 2006, 1986 people with HIV/AIDS were receiving ART; by 2009, that figure reached 5034. Adherence to antiretroviral therapy is fundamental: nonadherence leads to treatment failure, development of resistance, progression to AIDS, and death. OBJECTIVE Measure levels of treatment adherence and its predictive factors in persons with HIV/AIDS receiving antiretroviral therapy in 2006 in Cuba. METHODS A cross-sectional study was carried out in 2006 of Cuban HIV-positive individuals receiving antiretroviral therapy. A sample size of 876 was calculated using two-stage sampling (first by strata, and then by simple random sampling in each stratum). An anonymous structured questionnaire was administered to participants. Reporting of doses taken on each of the three days and in the week preceding the survey was recoded into five categories. Participants were considered highly adherent if they reported taking ?95.0% of their medication as prescribed. Reasons for nonadherence were described and logistic regression modeling used to develop hypotheses on associations between high adherence and its predictive factors. RESULTS Interviews were obtained with 847 individuals, 70.6% of whom self reported high adherence. There were no significant differences between highly adherent and less adherent patients with regard to sex, place of residence, treatment setting, time of diagnosis, or length of treatment. Variables associated with high adherence were communication with the specialist physician, change in treatment, memory, self-efficacy, as well as commitment to and opinions about treatment. CONCLUSIONS In Cuba, where treatment is free of charge to patients, adherence is good. Treatment adherence might be improved by achieving a closer doctor-patient relationship; taking measures to motivate patients and promote self-efficacy and commitment to treatment; publicizing treatment outcomes; and providing assistance to patients to help them remember their medication schedule. Further studies are required to determine current adherence levels; and longitudinal research to determine adherence over time. PMID:21654587

  9. Supporting Adherence to Antiretroviral Therapy with Mobile Phone Reminders: Results from a Cohort in South India

    PubMed Central

    Rodrigues, Rashmi; Shet, Anita; Antony, Jimmy; Sidney, Kristi; Arumugam, Karthika; Krishnamurthy, Shubha; D'Souza, George; DeCosta, Ayesha

    2012-01-01

    Background Adherence is central to the success of antiretroviral therapy. Supporting adherence has gained importance in HIV care in many national treatment programs. The ubiquity of mobile phones, even in resource-constrained settings, has provided an opportunity to utilize an inexpensive, contextually feasible technology for adherence support in HIV in these settings. We aimed to assess the influence of mobile phone reminders on adherence to antiretroviral therapy in South India. Participant experiences with the intervention were also studied. This is the first report of such an intervention for antiretroviral adherence from India, a country with over 800 million mobile connections. Methods Study design: Quasi-experimental cohort study involving 150 HIV-infected individuals from Bangalore, India, who were on antiretroviral therapy between April and July 2010. The intervention: All participants received two types of adherence reminders on their mobile phones, (i) an automated interactive voice response (IVR) call and (ii) A non-interactive neutral picture short messaging service (SMS), once a week for 6 months. Adherence measured by pill count, was assessed at study recruitment and at months one, three, six, nine and twelve. Participant experiences were assessed at the end of the intervention period. Results The mean age of the participants was 38 years, 27% were female and 90% urban. Overall, 3,895 IVRs and 3,073 SMSs were sent to the participants over 6 months. Complete case analysis revealed that the proportion of participants with optimal adherence increased from 85% to 91% patients during the intervention period, an effect that was maintained 6 months after the intervention was discontinued (p?=?0.016). Both, IVR calls and SMS reminders were considered non-intrusive and not a threat to privacy. A significantly higher proportion agreed that the IVR was helpful compared to the SMS (p<0.001). Conclusion Mobile phone reminders may improve medication adherence in HIV infected individuals in this setting, the effect of which was found to persist for at least 6 months after cessation of the intervention. PMID:22952574

  10. Youth, unemployment, and male gender predict mortality in AIDS patients started on HAART in Nigeria

    PubMed Central

    DeSilva, Malini B.; Merry, Stephen P.; Fischer, Philip R.; Rohrer, James E.; Isichei, Christian O.; Cha, Stephen S.

    2010-01-01

    This retrospective study identifies risk factors for mortality in a cohort of HIV-positive adult patients treated with highly active antiretroviral therapy (HAART) in Jos, Nigeria. We analyzed clinical data from a cohort of 1552 patients enrolled in a HIV/acquired immune deficiency syndrome treatment program and started on HAART between December 2004 and 30 April 2006. Death was our study endpoint. Patients were followed in the study until death, being lost to follow-up, or the end of data collection, 1 December 2006. Baseline patient characteristics were compared using Wilcoxon Rank Sum Test for continuous variables and Pearson Chi-Square test for categorical variables to determine if certain demographic factors were associated with more rapid progression to death. The Cox proportional hazard multivariate model analysis was used to find risk factors. As of 1 December 2006, a total of 104 cases progressed to death. In addition to the expected association of CD4 count less than 50 at initiation of therapy and active tuberculosis with mortality, the patient characteristics independently associated with a more rapid progression to death after initiation of HAART were male gender, age less than 30 years old, and unemployment or unknown occupation status. Future research is needed to identify the confounding variables that may be amenable to targeted interventions aimed at ameliorating these health disparities. PMID:19085222

  11. Plasma cytokine profiles in HIV-1 infected patients developing neuropathic symptoms shortly after commencing antiretroviral therapy: a case-control study

    PubMed Central

    2014-01-01

    Background In patients infected with human immunodeficiency virus 1 (HIV-1) neuropathic symptoms may develop within weeks of starting combination antiretroviral therapy (cART). This timing coincides with the occurrence of immune reconstitution inflammatory syndrome. Our objective was to investigate the longitudinal association of plasma cytokine and soluble receptor concentrations with incident neuropathic symptoms within 12 weeks of starting programme-based cART in a nested case-control study. Methods One hundred and twenty adults without neuropathic symptoms and about to initiate cART were followed longitudinally for 24 weeks after cART initiation. Subjects were examined for peripheral neuropathy at baseline (pre-cART) and 2-, 4-, 12- and 24 weeks thereafter. Individuals developing neuropathic symptoms within 12 weeks of starting cART were matched in a nested case-control design with those remaining symptom-free for at least 24 weeks. Plasma was collected at each visit. Cytokines and soluble receptors were quantified using multiplex immunometric assays. Results Incident neuropathic symptoms occurred in 32 (27%) individuals within 12 weeks of starting cART for the first time. Cytokine concentrations increased at 2 weeks, irrespective of symptom-status, returning to baseline concentrations at 12 weeks. Compared to the control group, the symptomatic group had higher baseline levels of interleukin-1 receptor (IL-1R)-antagonist. The symptomatic group also showed greater increases in soluble interleukin-2 receptor-alpha and tumour necrosis factor (TNF) receptor-II levels at week 2 and soluble interleukin-6 receptor levels at week 12. Ratios of pro-inflammatory- vs anti-inflammatory cytokines were higher for TNF-alpha/IL-4 (p?=?0.022) and interferon-gamma/IL-10 (p?=?0.044) in those developing symptoms. After 24 weeks of cART, the symptomatic group showed higher CD4+ counts (p?=?0.002). Conclusions The initiation of cART in previously treatment naďve individuals was associated with a cytokine 'burst’ between 2- and 4 weeks compared with pre-cART levels. Individuals developing neuropathic symptoms within 12 weeks of starting cART showed evidence of altered cytokine concentrations even prior to initiating cART, most notably higher circulating IL-1R-antagonist levels, and altered ratios of “pain-associated” cytokine and soluble receptors shortly after cART initiation. PMID:24512313

  12. Life expectancy of individuals on combination antiretroviral therapy in high-income countries: a collaborative analysis of 14 cohort studies

    PubMed Central

    2011-01-01

    Summary Background Combination antiretroviral therapy has led to significant increases in survival and quality of life, but at a population-level the effect on life expectancy is not well understood. Our objective was to compare changes in mortality and life expectancy among HIV-positive individuals on combination antiretroviral therapy. Methods The Antiretroviral Therapy Cohort Collaboration is a multinational collaboration of HIV cohort studies in Europe and North America. Patients were included in this analysis if they were aged 16 years or over and antiretroviral-naive when initiating combination therapy. We constructed abridged life tables to estimate life expectancies for individuals on combination antiretroviral therapy in 1996–99, 2000–02, and 2003–05, stratified by sex, baseline CD4 cell count, and history of injecting drug use. The average number of years remaining to be lived by those treated with combination antiretroviral therapy at 20 and 35 years of age was estimated. Potential years of life lost from 20 to 64 years of age and crude death rates were also calculated. Findings 18 587, 13 914, and 10 854 eligible patients initiated combination antiretroviral therapy in 1996–99, 2000–02, and 2003–05, respectively. 2056 (4·7%) deaths were observed during the study period, with crude death rates decreasing from 16·3 deaths per 1000 person-years in 1996–99 to 10·0 deaths per 1000 person-years in 2003–05. Potential years of life lost per 1000 person-years also decreased over the same time, from 366 to 189 years. Life expectancy at age 20 years increased from 36·1 (SE 0·6) years to 49·4 (0·5) years. Women had higher life expectancies than men. Patients with presumed transmission via injecting drug use had lower life expectancies than those from other transmission groups (32·6 [1·1] years vs 44·7 [0·3] years in 2003–05). Life expectancy was lower in patients with lower baseline CD4 counts than in those with higher baseline counts (32·4 [1·1] years for CD4 cell counts below 100 cells per ?L vs 50·4 [0·4] years for counts of 200 cells per ?L or more). Interpretation Life expectancy in HIV-infected patients treated with combination antiretroviral therapy increased between 1996 and 2005, although there is considerable variability in subgroups of patients. However, the average number of years remaining to be lived at age 20 years was about two-thirds of that in the general population in these countries. PMID:18657708

  13. Effects of a Phone Call Intervention to Promote Adherence to Antiretroviral Therapy and Quality of Life of HIV/AIDS Patients in Baoshan, China: A Randomized Controlled Trial

    PubMed Central

    Huang, Dongsheng; Sangthong, Rassamee; McNeil, Edward; Chongsuvivatwong, Virasakdi; Zheng, Weibin; Yang, Xuemei

    2013-01-01

    Background. Suboptimal adherence to antiretroviral therapy (ART) is still pervasive. The effect of using a mobile phone call intervention to improve patient adherence is currently not known. Objective. This study aims to investigate the effects of a phone call intervention on adherence to ART and quality of life (QOL) of treatment-naive and treatment-experienced patients. Methods. A randomized controlled trial was conducted in the three largest public hospitals. Adherence was measured by self-completed questionnaires. QOL was assessed by the WHOQOL-HIV BREF. Outcomes were assessed at day 15, at 1, 2, and 3 months after start of treatment for treatment-naive patients and at 3 months after study enrollment for treatment-experienced patients. Results. A total of 103 treatment-naive and 93 treatment-experienced HIV/AIDS patients were consecutively recruited. Results show that a phone call intervention could maintain high self-reported adherence among both treatment-naive and treatment-experienced patients. After three months, significant QOL improvements were observed in domains of physical health (P = 0.003), level of independence (P = 0.018), environment (P = 0.002), and spirituality/religion/personal beliefs (P = 0.021) among treatment-naive patients. Conclusion. A mobile phone call intervention to patients could maintain high adherence rates although no statistically significant differences were found. A phone call could improve some domains of QOL among treatment-naive patients. PMID:23401755

  14. Self-starting of passive mode locking.

    PubMed

    Gordon, Ariel; Gat, Omri; Fischer, Baruch; Kärtner, Franz X

    2006-11-13

    It has been recently understood that mode locking of lasers has the signification of a thermodynamic phase transition in a system of many interacting light modes subject to noise. In the same framework, self starting of passive mode locking has the thermodynamic significance of a noise-activated escape process across an entropic barrier. Here we present the first dynamical study of the light mode system. While accordant with the predictions of some earlier theories, it is the first to give precise quantitative predictions for the distribution of self-start times, in closed form expressions, resolving the long standing self starting problem. Numerical simulations corroborate these results, which are also in good agreement with experiments. PMID:19529528

  15. The feasibility of an intensive case management program for injection drug users on antiretroviral therapy in St. Petersburg, Russia

    PubMed Central

    2013-01-01

    Background The majority of HIV-infected individuals requiring antiretroviral therapy (ART) in Russia are Injection Drug Users (IDU). Substitution therapy used as part of a comprehensive harm reduction program is unavailable in Russia. Past data shows that only 16% of IDU receiving substance abuse treatment completed the course without relapse, and only 40% of IDU on ART remained on treatment at 6 months. Our goal was to determine if it was feasible to improve these historic outcomes by adding intensive case management (ICM) to the substance abuse and ART treatment programs for IDU. Methods IDU starting ART and able to involve a “supporter” who would assist in their treatment plan were enrolled. ICM included opiate detoxification, bi-monthly contact and counseling with the case, weekly group sessions, monthly contact with the “supporter” and home visits as needed. Full follow- up (FFU) was 8 months. Stata v10 (College Station, TX) was used for all analysis. Descriptive statistics were calculated for all baseline demographic variables, baseline and follow-up CD4 count, and viral load. Median baseline and follow-up CD4 counts and RNA levels were compared using the Kruskal-Wallis test. The proportion of participants with RNA?

  16. Predictors of Mortality among Adult Antiretroviral Therapy Users in Southeastern Ethiopia: Retrospective Cohort Study.

    PubMed

    Setegn, Tesfaye; Takele, Abulie; Gizaw, Tesfaye; Nigatu, Dabere; Haile, Demewoz

    2015-01-01

    Background. Although efforts have been made to reduce AIDS-related mortality by providing antiretroviral therapy (ART) services, still people are dying while they are on treatment due to several factors. This study aimed to investigate the predictors of mortality among adult antiretroviral therapy (ART) users in Goba Hospital, Southeast Ethiopia. Methods. The medical records of 2036 ART users who enrolled at Goba Hospital between 2007 and 2012 were reviewed and sociodemographic, clinical, and ART-related data were collected. Multivariable Cox proportional hazards regression model was used to measure risk of death and identify the independent predictors of mortality. Results. The overall mortality incidence rate was 20.3 deaths per 1000 person-years. Male, bedridden, overweight/obese, and HIV clients infected with TB and other infectious diseases had higher odds of death compared with their respective counterparts. On the other hand, ART clients with primary and secondary educational level and early and less advanced WHO clinical stage had lower odds of death compared to their counterparts. Conclusion. The overall mortality incidence rate was high and majority of the death had occurred in the first year of ART initiation. Intensifying and strengthening early ART initiation, improving nutritional status, prevention and control of TB, and other opportunistic infections are recommended interventions. PMID:25821596

  17. Magnetic resonance imaging evaluation of lipodystrophy in HIV-positive patients receiving highly active antiretroviral therapy.

    PubMed

    Eichler, K; Bickel, T M; Klauke, S; Eisen, J; Vogl, T J; Zangos, S

    2015-07-01

    We evaluated retrospectively an automated method for the separate detection of subcutaneous and visceral fat in the abdominal region by magnetic resonance studies in HIV-positive patients on highly active antiretroviral therapy. The patients were divided into four different groups: lipoatrophy, lipohypertrophy, mixed and the control group. The use of software for the automated detection of abdominal compartment visceral adipose tissue (VAT), total adipose tissue (TAT) and subcutaneous adipose tissue (SAT) was compared to manual evaluation methods (fuzzy C-mean). The results of ROC analysis showed that the parameters, particularly the VAT, are better than the VAT/TAT and at identifying patients with the symptoms of abdominal fat accumulation. A sensitivity of 80.3% and a specificity of 79.5% resulted from a threshold VAT value of >87?cm(2). Moreover, the manual evaluation method was shown to provide greater values for VAT and the VAT/TAT ratio than those given by the automated method. In the present study, a rapid MRI protocol for the detection and assessment of the course of lipodystrophy was presented and tested on a group of patients with signs of HALS, as well as on an antiretroviral naďve control group. PMID:25139003

  18. Comparative analysis of HIV type 1 genotypic resistance across antiretroviral trial treatment regimens.

    PubMed

    Gilbert, P B; Hanna, G J; De Gruttola, V; Martinez-Picado, J; Kuritzkes, D R; Johnson, V A; Richman, D D; D'Aquila, R T

    2000-09-20

    From data on HIV-1 genotypes collected from antiretroviral trial participants who fail virologically, we describe methods for comparing distributions of acquired HIV-1 mutations across different treatment regimens. Given a definition of a "mutational distance" that summarizes the genetic change of a subject's virus in a way that captures the resistance cost of exposure to an antiretroviral regimen, these comparative analyses inform about the relative treatability of emergent virus by next-line therapy directed to the same viral target. The utility of the methods is illustrated by application to data from AIDS Clinical Trials Group (ACTG) Study 241. We find that patients failing zidovudine/didanosine/nevirapine accumulated a 2.41-fold greater nonnucleoside reverse transcriptase inhibitor (RTI) mutational distance than patients failing zidovudine/didanosine [95% confidence interval (1.55, 5.26), p < 0.000001], quantitating expectations that adding a nonnucleoside RTI to a double nucleoside regimen may attenuate future effectiveness of nonnucleoside RTI therapy for nucleoside-experienced patients if viremia is not suppressed. We also find that persons with extensive prior experience with suboptimal nucleoside therapy who were virologically failing zidovudine/didanosine/nevirapine or zidovudine/didanosine accumulated a similar nucleoside RTI mutational distance, implying that the addition of the nonnucleoside RTI did not preserve future nucleoside options. PMID:11018852

  19. TRIM5{alpha} association with cytoplasmic bodies is not required for antiretroviral activity

    SciTech Connect

    Song, Byeongwoon [Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Division of AIDS, Harvard Medical School, Boston, MA 02115 (United States); Diaz-Griffero, Felipe [Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Division of AIDS, Harvard Medical School, Boston, MA 02115 (United States); Park, Do Hyun [Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Division of AIDS, Harvard Medical School, Boston, MA 02115 (United States); Rogers, Thomas [Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Division of AIDS, Harvard Medical School, Boston, MA 02115 (United States); Stremlau, Matthew [Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Division of AIDS, Harvard Medical School, Boston, MA 02115 (United States); Sodroski, Joseph [Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Division of AIDS, Harvard Medical School, Boston, MA 02115 (United States) and Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115 (United States)]. E-mail: joseph_sodroski@dfci.harvard.edu

    2005-12-20

    The tripartite motif (TRIM) protein, TRIM5{alpha}, restricts infection by particular retroviruses. Many TRIM proteins form cytoplasmic bodies of unknown function. We investigated the relationship between cytoplasmic body formation and the structure and antiretroviral activity of TRIM5{alpha}. In addition to diffuse cytoplasmic staining, the TRIM5{alpha} proteins from several primate species were located in cytoplasmic bodies of different sizes; by contrast, TRIM5{alpha} from spider monkeys did not form cytoplasmic bodies. Despite these differences, all of the TRIM5{alpha} proteins exhibited the ability to restrict infection by particular retroviruses. Treatment of cells with geldanamycin, an Hsp90 inhibitor, resulted in disappearance or reduction of the TRIM5{alpha}-associated cytoplasmic bodies, yet exerted little effect on the restriction of retroviral infection. Studies of green fluorescent protein-TRIM5{alpha} fusion proteins indicated that no TRIM5{alpha} domain is specifically required for association with cytoplasmic bodies. Apparently, the formation of cytoplasmic bodies is not required for the antiretroviral activity of TRIM5{alpha}.

  20. Human breast milk and antiretrovirals dramatically reduce oral HIV-1 transmission in BLT humanized mice.

    PubMed

    Wahl, Angela; Swanson, Michael D; Nochi, Tomonori; Olesen, Rikke; Denton, Paul W; Chateau, Morgan; Garcia, J Victor

    2012-01-01

    Currently, over 15% of new HIV infections occur in children. Breastfeeding is a major contributor to HIV infections in infants. This represents a major paradox in the field because in vitro, breast milk has been shown to have a strong inhibitory effect on HIV infectivity. However, this inhibitory effect has never been demonstrated in vivo. Here, we address this important paradox using the first humanized mouse model of oral HIV transmission. We established that reconstitution of the oral cavity and upper gastrointestinal (GI) tract of humanized bone marrow/liver/thymus (BLT) mice with human leukocytes, including the human cell types important for mucosal HIV transmission (i.e. dendritic cells, macrophages and CD4? T cells), renders them susceptible to oral transmission of cell-free and cell-associated HIV. Oral transmission of HIV resulted in systemic infection of lymphoid and non-lymphoid tissues that is characterized by the presence of HIV RNA in plasma and a gradual decline of CD4? T cells in peripheral blood. Consistent with infection of the oral cavity, we observed virus shedding into saliva. We then evaluated the role of human breast milk on oral HIV transmission. Our in vivo results demonstrate that breast milk has a strong inhibitory effect on oral transmission of both cell-free and cell-associated HIV. Finally, we evaluated the effect of antiretrovirals on oral transmission of HIV. Our results show that systemic antiretrovirals administered prior to exposure can efficiently prevent oral HIV transmission in BLT mice. PMID:22737068

  1. Remission of progressive multifocal leukoencephalopathy following highly active antiretroviral therapy in a man with AIDS

    PubMed Central

    Yoganathan, Katie; Brown, David; Yoganathan, Kathir

    2012-01-01

    A 43-year-old Caucasian homosexual man with AIDS presented with blurring of vision, change of personality, and memory loss in March 1999. He had first been admitted 2 months previously for treatment of Pneumocystis jiroveci pneumonia. A magnetic resonance imaging scan on admission showed multiple white matter lesions involving both subcortical cerebral hemispheres and cerebellar regions, with no mass effect or surrounding edema. JC virus was detected by nested polymerase chain reaction in the cerebrospinal fluid. These findings were diagnostic of progressive multifocal leukoencephalopathy (PML). His CD4 count was 34 cells/mL, and his HIV ribonucleic acid level was 800,789 copies/mL. He was treated with a combination antiretroviral therapy. He was last reviewed in October 2011. He was fully independent socially and mentally, but he still had some residual neurologic signs with right-sided homonymous hemianopia and visual agnosia. His HIV ribonucleic acid level was undetectable, and his CD4 count was 574 cells/mm3. Although the median survival of patients with PML was poor before the antiretroviral therapy era, our patient, who is now aged 55 years, is still alive 12 years after the diagnosis. The diagnosis of PML and differential diagnosis of focal neurologic signs in HIV-positive patients are discussed in this case report. PMID:22536089

  2. The charms and challenges of antiretroviral therapy in Uganda: the DART experience.

    PubMed

    Nyanzi-Wakholi, Barbara; Lara, Antonieta Medina; Munderi, Paula; Gilks, Charles

    2012-01-01

    Antiretroviral therapy (ART) improves the quality of life of people living with HIV/AIDS. However, adherence remains a challenge. A total of eight focus group discussions (FGD) were conducted with participants from a randomised controlled trial that monitored strategies for managing ART in African adults: Development of Antiretroviral Therapy. All FGD participants had received ART for at least one year. Perceived benefits of ART were key motivators for adherence. These benefits included improved physical health, restored self-esteem, acceptance in the community and hope for a longer and healthier life and reduced fear of HIV/AIDS-related death. Barriers to adherence included a high pill burden, ART side effects and socio-economic constraints, including lack of food and safe water for taking the pills. Visible ART side effects and involvement in an exclusively HIV/AIDS clinic could expose their HIV status, thus exacerbating stigma. Gender and socio-economic differences were found in the variety of strategies employed to ensure adherence. ART was perceived as improving the overall quality of life of recipients; however, it is crucial for ART programmes to be gender and socio-economic cognizant in order to enhance adherence to a lifelong therapy. PMID:21777081

  3. Antiretroviral Agents Used by HIV-Uninfected Persons for Prevention: Pre- and Postexposure Prophylaxis

    PubMed Central

    Grant, Robert M.

    2010-01-01

    Prophylactic use of antimicrobial agents and microbicides has been proven for many infections, including surgical, gastrointestinal, upper respiratory, and meningococcal infections. Antiretroviral therapy for pregnant women prevents mother-to-child transmission of human immunodeficiency virus (HIV), which has become rare in settings where access to therapy is widespread. Postexposure prophylaxis after needlestick injury or significant sexual exposure is recommended on the basis of animal studies and case-control observational studies, although use of these interventions is limited to those who recognize exposure, have access, and have the power to use the interventions. Clinical trials are evaluating whether regular or preexposure use of antiretroviral therapy provides additional protection for persons at high risk of infection who are also offered standard prevention care, including HIV testing, counseling, condoms, and management of sexually transmitted infections. Trials are evaluating topical or oral use. Concerns have arisen with regard to optimal dosing strategies, costs, access, drug resistance, risk behavior, and the role of communities. Future implementation, if warranted, will be guided by the results of clinical trials in progress and engagement of communities exposed to HIV. PMID:20397962

  4. Accelerated bone mineral loss in HIV-infected patients receiving potent antiretroviral therapy

    PubMed Central

    Tebas, Pablo; Powderly, William G.; Claxton, Sherry; Marin, Donna; Tantisiriwat, Woraphot; Teitelbaum, Steven L.; Yarasheski, Kevin E.

    2011-01-01

    Background The use of highly active antiretroviral therapy (HAART) has been associated with multiple metabolic complications whose pathogenesis is poorly understood at the present time. Methods We performed a cross-sectional analysis of whole-body, lumbar spine (L1 – L4) and proximal femur bone mineral density in 112 male subjects (HIV-infected patients on HAART that included a protease inhibitor, HIV-infected patients not receiving a protease inhibitor and healthy seronegative adults) using dual energy x-ray absorptiometry. Results Men receiving protease inhibitors had a higher incidence of osteopenia and osteoporosis according to World Health Organization definitions: relative risk = 2.19 (95% confidence interval 1.13–4.23) (P = 0.02). Subjects receiving protease inhibitors had greater central : appendicular adipose tissue ratios than the other two groups (P < 0.0001). There was no relationship between the central : appendicular fat ratio and the lumbar spine or proximal femur bone mineral density t- or z- scores, suggesting that osteoporosis and body fat redistribution are independent side effects of HAART. Conclusions Osteopenia and osteoporosis are unique metabolic complications associated with protease inhibitor-containing potent antiretroviral regimens, that appear to be independent of adipose tissue maldistribution. PMID:10770534

  5. Anti-retroviral drugs do not facilitate hepatitis C virus (HCV) infection in vitro.

    PubMed

    Sandmann, Lisa; Wilson, Matthew; Back, David; Wedemeyer, Heiner; Manns, Michael P; Steinmann, Eike; Pietschmann, Thomas; von Hahn, Thomas; Ciesek, Sandra

    2012-10-01

    An estimated 4 to 5 million people are co-infected with HIV/HCV worldwide. Recently observed outbreaks of acute HCV infection among HIV-positive men who have sex with men (MSM) have been linked to behavioral factors such as high risk sexual practices and recreational drug use. However, at the molecular level, many drugs such as glucocorticoids or cyclosporine A have been found to modulate viral replication. Thus, it is conceivable that drugs used in highly active antiretroviral therapy (HAART) may heighten susceptibility to HCV infection and contribute to the recent outbreaks. We therefore performed a comprehensive screen of antiretroviral drugs covering all available drug classes both individually and in typical combinations used during HAART to probe for direct effects on HCV cell entry, replication, new particle assembly and release. Importantly, no significant enhancement or inhibition of HCV cell entry, replication or new particle production was detected. While raltegravir and ritonavir boosted atazanavir reduce HCV replication, a tenfold reduction of HCVcc entry by the CCR5 antagonist maraviroc was observed. In conclusion, commonly used HAART agents do not specifically enhance HCV replication. Thus recent epidemic outbreaks of acute HCV in HIV-infected MSM are unlikely to be related to enhancing effects of HAART drugs. PMID:22842003

  6. Compulsory licensing often did not produce lower prices for antiretrovirals compared to international procurement.

    PubMed

    Beall, Reed F; Kuhn, Randall; Attaran, Amir

    2015-03-01

    Compulsory licensing has been widely suggested as a legal mechanism for bypassing patents to introduce lower-cost generic antiretrovirals for HIV/AIDS in developing countries. Previous studies found that compulsory licensing can reduce procurement prices for drugs, but it is unknown how the resulting prices compare to procurements through the Global Fund to Fight AIDS, Tuberculosis, and Malaria; UNICEF; and other international channels. For this study we systematically constructed a case-study database of compulsory licensing activity for antiretrovirals and compared compulsory license prices to those in the World Health Organization's (WHO's) Global Price Reporting Mechanism and the Global Fund's Price and Quality Reporting Tool. Thirty compulsory license cases were analyzed with 673 comparable procurements from WHO and Global Fund data. Compulsory license prices exceeded the median international procurement prices in nineteen of the thirty case studies, often with a price gap of more than 25 percent. Compulsory licensing often delivered suboptimal value when compared to the alternative of international procurement, especially when used by low-income countries to manufacture medicines locally. There is an ongoing need for multilateral and charitable actors to work collectively with governments and medicine suppliers on policy options. PMID:25732501

  7. Immune restoration after antiretroviral therapy: the pitfalls of hasty or incomplete repairs

    PubMed Central

    Wilson, Eleanor M.P.; Sereti, Irini

    2013-01-01

    Summary Antiretroviral therapy (ART) is a life-saving intervention in human immunodeficiency virus (HIV) infection. Immune restoration after ART dramatically reduces the incidence and severity of opportunistic diseases and death. On some occasions, immune restoration may be erratic, leading to acute inflammatory responses (known as immune reconstitution inflammatory syndrome) shortly after ART initiation, or incomplete with residual inflammation despite chronic treatment, leading to non-infectious morbidity and mortality. We propose that ART may not always restore the perfect balance of innate and adaptive immunity in strategic milieus, predisposing HIV-infected persons to complications of acute or chronic inflammation. The best current strategy for fully successful immune restoration is early antiretroviral therapy, which can prevent acquired immunodeficiency syndrome (AIDS)-associated events, restrict cell subset imbalances and dysfunction, while preserving structural integrity of lymphoid tissues. Future HIV research should capitalize on innovative techniques and move beyond the static study of T-cell subsets in peripheral blood or isolated tissues. Improved targeted therapeutic strategies could stem from a better understanding of how HIV perturbs the environmental niches and the mobility and trafficking of cells that affect the dynamic cell to cell interactions and determine the outcome of innate and adaptive immune responses. PMID:23772630

  8. Adherence of human immunodeficiency virus-infected patients to antiretroviral therapy.

    PubMed

    Singh, N; Berman, S M; Swindells, S; Justis, J C; Mohr, J A; Squier, C; Wagener, M M

    1999-10-01

    The impact of demographic, psychosocial, and medical regimen-related variables on adherence of 123 human immunodeficiency virus (HIV)-infected patients to antiretroviral therapy was assessed by means of refill methodology. Satisfaction with social support (P = .029), problem-focused coping (P = .027), and active-behavioral coping (P = .011) correlated significantly with adherence, whereas loss of motivation (P = .006), hopelessness (P = .16), and avoidant coping (p = .015) correlated with nonadherence. At the 6-month follow-up, the mean CD4 cell count differed significantly among adherent versus nonadherent patients (a mean increase of 78/mm3 vs. a mean decrease of 5/mm3; P = .018). Adherence did not correlate with the number of antiretroviral medications consumed per day (mean, 3.0 vs. 2.5). Non-Caucasian patients were more likely to be nonadherent than Caucasian patients (relative risk, 2.5; 95% confidence interval, 1.2-5.3; P = .013); this difference was not explained by age, education, employment, income, history of intravenous drug use, or medical regimen. Non-Caucasian patients, however, were less satisfied with their social support (P = .04) and informational support (P = .016) and were more likely to utilize emotion-focused coping (P = .01). Thus, satisfaction with social support and coping style significantly impacted adherence and likely accounted for the observed racial difference in adherence among HIV-infected patients. PMID:10589897

  9. Retention in medical care and antiretroviral treatment according to skin color in southern Brazil.

    PubMed

    Zubaran, Carlos; Michelim, Lessandra; Foresti, Katia; Medeiros, Gregory; May, William; Madi, José Mauro

    2014-01-01

    The aim of this study was to compare the retention in medical care and antiretroviral (ARV) treatment of individuals living with HIV and AIDS to antiretroviral therapy in southern Brazil according to their "race" or skin color. This study is part of a 225-day prospective trial, comprising 7 interviews, in which an intervention designed to improve adherence to treatment was tested. A convenience sample of 73 individuals living with HIV and/or AIDS enrolled in this follow-up procedure. The mean length of continuance in treatment was 161.5 (standard deviation [SD] = 18.6; 95% confidence interval [CI] = 125-198) and 138.4 (SD = 14.1; 95% C.I. = 111-166) days in the "nonwhite" and "white" categories, respectively. There was no significant difference between the 2 categories, ?(2)(1, n = 72) = 0.76, P = .38, which include similar levels of retention in medical care and treatment with ARV medications between groups of individuals categorized as white and nonwhite in this sample. PMID:23697777

  10. Predictors of Mortality among Adult Antiretroviral Therapy Users in Southeastern Ethiopia: Retrospective Cohort Study

    PubMed Central

    Setegn, Tesfaye; Takele, Abulie; Gizaw, Tesfaye; Nigatu, Dabere

    2015-01-01

    Background. Although efforts have been made to reduce AIDS-related mortality by providing antiretroviral therapy (ART) services, still people are dying while they are on treatment due to several factors. This study aimed to investigate the predictors of mortality among adult antiretroviral therapy (ART) users in Goba Hospital, Southeast Ethiopia. Methods. The medical records of 2036 ART users who enrolled at Goba Hospital between 2007 and 2012 were reviewed and sociodemographic, clinical, and ART-related data were collected. Multivariable Cox proportional hazards regression model was used to measure risk of death and identify the independent predictors of mortality. Results. The overall mortality incidence rate was 20.3 deaths per 1000 person-years. Male, bedridden, overweight/obese, and HIV clients infected with TB and other infectious diseases had higher odds of death compared with their respective counterparts. On the other hand, ART clients with primary and secondary educational level and early and less advanced WHO clinical stage had lower odds of death compared to their counterparts. Conclusion. The overall mortality incidence rate was high and majority of the death had occurred in the first year of ART initiation. Intensifying and strengthening early ART initiation, improving nutritional status, prevention and control of TB, and other opportunistic infections are recommended interventions. PMID:25821596

  11. Start safety apparatus for internal combustion engine

    Microsoft Academic Search

    H. Nakata; H. Souma

    1986-01-01

    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

  12. Jump Starting the Local Food Economy

    E-print Network

    Hall, Sharon J.

    Jump Starting the Local Food Economy Monday, September 26, 2011 12:00 - 1:30 p.m. (Lunch: "garbage, The Urban Farm Join Miguel Jardine and Greg Peterson as they outline three specific things you can do to contribute to your Local Food Economy and discuss the VermiSoks system. Miguel Jardine is the CEO and founder

  13. Does Head Start help hispanic children?

    Microsoft Academic Search

    Janet Currie; Duncan Thomas

    1999-01-01

    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

  14. Mental Health Services in Head Start

    ERIC Educational Resources Information Center

    Frey, Andy

    2008-01-01

    This dialog suggests that mental health services in Head Start should be more broadly defined than they currently are in many programs. Specifically, these services should emphasize the important role prevention (e.g., prereferral/identification) plays in promoting mental wellness. Additionally, this dialog briefly addresses the role of the mental…

  15. Desert Gardening 101: Steps to Starting a

    E-print Network

    Hall, Sharon J.

    Desert Gardening 101: Steps to Starting a Vegetable Garden Tuesday, September 27, 2011 9:00 ­ 10 Gardener Trish Yasolsky was certified a Master Gardener in 2009 and finished the Valley Permaculture plants, and vegetable gardening in Arizona. This class will give you the basic steps to begin a vegetable

  16. When Cars Start Gossiping Paolo Costa

    E-print Network

    Musolesi, Mirco

    When Cars Start Gossiping Paolo Costa Vrije Universiteit Amsterdam The Netherlands costa) where interacting nodes are computers embedded in cars. VANET applications aim at enhancing the driver, computers embedded in cars can rely on the vehicle's power supply and may have plenty of memory storage

  17. Psychiatric consultation for Project Head Start

    Microsoft Academic Search

    Saul L. Brown

    1966-01-01

    Psychiatric and\\/or “mental health” services for the Project Head Start program need to be adapted to the character of the population group to be dealt with. This requires special knowledge and skills, not only in relation to the psychopathology of the preschool-age child, but also to the subtleties of family pathology and the ways in which a disturbed child of

  18. Blackboard Quick Start Guides Measuring Student Performance

    E-print Network

    Blackboard Quick Start Guides Measuring Student Performance Evaluating what students have learned throughout the course can be accomplished in many ways, depending on the course objectives and how student performance will be measured. Homework, class participation papers and tests are all traditional methods

  19. Project Great Start Biennial Evaluation Report.

    ERIC Educational Resources Information Center

    Rudy, Dennis W.

    Project Great Start is designed to provide non-, limited-, and near-native English proficient students with improved, intensified, and increased learning opportunities for accelerated English acquisition and significant academic achievement. It focuses on three groups: students, parents, and school staff. Students and parents benefit from separate…

  20. Head Start Fathers' Involvement with Their Children

    ERIC Educational Resources Information Center

    Gorvine, Benjamin J.

    2010-01-01

    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…

  1. Analysis of False Starts in Spontaneous Speech.

    ERIC Educational Resources Information Center

    O'Shaughnessy, Douglas

    A primary difference between spontaneous speech and read speech concerns the use of false starts, where a speaker interrupts the flow of speech to restart his or her utterance. A study examined the acoustic aspects of such restarts in a widely-used speech database, examining approximately 1000 utterances, about 10% of which contained a restart.…

  2. Health&Safety PreventionStartsHere

    E-print Network

    Czarnecki, Krzysztof

    Health&Safety atWork PreventionStartsHere Workers have the right to: · Know about workplace hazards and what to do about them. · Participate in solving workplace health and safety problems. · Refuse work they believe is unsafe. Workers must: · Follow the law and workplace health and safety policies and procedures

  3. Monarch Kids Cub Run Start Times

    E-print Network

    Monarch Kids Cub Run Start Times: 1 Mile Fun Run: 9 AM 5K Walk/Run: 10 AM Parking: LOT 30­ next !! To REGISTER, SPONSOR, or make a DONATION go to: http://education.odu.edu/monarch kids April 12th­ 7:30AM-5 including, but not limited to, falls, contacts with other participants, the effects of the weather

  4. Starting mental health services in Cambodia

    Microsoft Academic Search

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

    1999-01-01

    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

  5. talk start all talks talk index ASTROPHYSICS

    E-print Network

    Rutten, Rob

    ­ Stellar evolution ­ Stellar nucleosynthesis ­ Stellar winds and mass loss ­ High-energy astrophysics evolution and stellar environments ­ structure and evolution of single and binary stars ­ nucleosynthesistalk start all talks talk index MASTER ASTROPHYSICS · content ­ evolution of stars and stellar

  6. Sure Start: A Guide for Trailblazers.

    ERIC Educational Resources Information Center

    Department for Education and Employment, London (England).

    Based on the evidence that early intervention and support can reduce family breakdown, strengthen children's school readiness, and benefit society in the long term, the Sure Start program in England is designed to offer support enabling parents to strengthen their relationship with their children and to access more fully local community services.…

  7. A climate change simulation starting from 1935

    Microsoft Academic Search

    U. Cubasch; G C Hegerl; A. Hellbach; H. Höck; U. Mikolajewicz; B D Santer; R. Voss

    1995-01-01

    Due to restrictions in the available computing resources and a lack of suitable observational data, transient climate change experiments with global coupled ocean-atmosphere models have been started from an initial state at equilibrium with the present day forcing. The historical development of greenhouse gas forcing from the onset of industrialization until the present has therefore been neglected. Studies with simplified

  8. Getting Started Advanced Search for Funding Opportunities

    E-print Network

    Duchowski, Andrew T.

    , scroll to bottom of page upon completing step 14 under "Advanced Search For Funding Opportunities" aboveGetting Started Advanced Search for Funding Opportunities For Assistance Delete Criteria to Update Search Funding ­ Finding Additional Sources Saving and Printing SPIN Search Results Past funding

  9. Advanced Research Computing Before We Start

    E-print Network

    Crawford, T. Daniel

    Advanced Research Computing Before We Start · Sign in · Copy files from the MIC directory Computing March 4, 2014 #12;Advanced Research Computing Outline · Background · The Intel Xeon Phi · Native Mode · Offloading ­ Automatic ­ Directives ­ Multiple MICs · MPI #12;Advanced Research Computing 4

  10. Quick Start Guide Blackboard 9.1

    E-print Network

    Galis, Frietson

    Quick Start Guide Blackboard 9.1 Student Manual 1 What is Blackboard? Blackboard is the online to help manage and improve student learning. Blackboard offers not only facilities to have structured and 9 are not supported! Accessing Blackboard Go to the following web page (note: without "www"!): http://blackboard

  11. Blackboard Quick Start Guides Keeping Students Informed

    E-print Network

    Oliver, Douglas L.

    Blackboard Quick Start Guides Keeping Students Informed Issues and answers Issue: I want to change. Add the What's New Module from the Community System to the Blackboard entry page by selecting Modify to every Blackboard course they are enrolled in since the last time they logged in, and provide them a link

  12. 34 CFR 200.16 - Starting points.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...starting points in reading/language arts and in mathematics...State's proficient level of academic achievement...students at the proficient level: (1) The percentage...proficient students in the lowest-achieving subgroup...students at the proficient level. The State must...

  13. CS Roo Quick Start January 20, 2014

    E-print Network

    Beveridge, Ross

    dates and days may be created automatically. · Dates and days are based on values in `config.php' · Page ... ­ a directory with on index.php file ­ term specific subdirectory. · The index.php file redirects to current. · Obviously this should be customized. CS Roo -Quick Start 5 Edit `config.php' · For customization

  14. Start-Up Success: Collection Development

    ERIC Educational Resources Information Center

    Awe, Susan C.

    2010-01-01

    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…

  15. The Start of a Tech Revolution

    ERIC Educational Resources Information Center

    Dyrli, Kurt O.

    2009-01-01

    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…

  16. Evaluation of Hawaii's Healthy Start Program

    Microsoft Academic Search

    Anne K. Duggan; Elizabeth C. McFarlane; Amy M. Windham; Charles A. Rohde; David S. Salkever; Loretta Fuddy; Leon A. Rosenberg; Sharon B. Buchbinder; Calvin C. J. Sia

    1999-01-01

    Hawaii's Healthy Start Program (HSP) is designed to prevent child abuse and neglect and to promote child health and development in newborns of families at risk for poor child outcomes. The program operates statewide in Hawaii and has inspired national and international adaptations, including Healthy Families America. This article describes HSP, its ongoing evaluation study, and evaluation findings at the

  17. School Start Time and Teen Sleep.

    ERIC Educational Resources Information Center

    Wahlstrom, Kyla L.

    2000-01-01

    Sleep studies have shown that teenagers' internal clocks are incompatible with most high schools' early hours. Research in two Minnesota districts indicates that later school starting times can benefit teens and everyone dealing with them. Student participation in sports and other afterschool activities remained high. (MLH)

  18. Getting Started with Microsoft Azure Virtual Machines

    E-print Network

    Narasayya, Vivek

    location to location with a tablet and then connect to a virtual machine using RDP or SSH to access yourGetting Started with Microsoft Azure Virtual Machines Introduction You can use a Microsoft Azure Virtual Machine when you need a scalable, cloud-based server running a Windows or Linux operating system

  19. Comprehensive Evaluation of Hawaii's Healthy Start Program.

    ERIC Educational Resources Information Center

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

    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…

  20. How to Start a Day Care Center.

    ERIC Educational Resources Information Center

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

    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…

  1. TRIP START TIME DISTRIBUTION Metro 1996

    E-print Network

    Toronto, University of

    APPENDIX B TRIP START TIME DISTRIBUTION #12;Metro 1996 0% 2% 4% 6% 8% 10% 12% 14% 430 530 630 730 hour window NHB HBO HBS HBW B.6 #12;Metro 1996 0% 2% 4% 6% 8% 10% 12% 14% 430 530 630 730 830 930 1030

  2. A Comparison of Initial Antiretroviral Therapy in the Swiss HIV Cohort Study and the Recommendations of the International AIDS Society-USA

    PubMed Central

    Wandeler, Gilles; Keiser, Olivia; Hirschel, Bernard; Günthard, Huldrych F.; Bernasconi, Enos; Battegay, Manuel; Clerc, Olivier; Vernazza, Pietro L.; Furrer, Hansjakob

    2011-01-01

    Background In order to facilitate and improve the use of antiretroviral therapy (ART), international recommendations are released and updated regularly. We aimed to study if adherence to the recommendations is associated with better treatment outcomes in the Swiss HIV Cohort Study (SHCS). Methods Initial ART regimens prescribed to participants between 1998 and 2007 were classified according to IAS-USA recommendations. Baseline characteristics of patients who received regimens in violation with these recommendations (violation ART) were compared to other patients. Multivariable logistic and linear regression analyses were performed to identify associations between violation ART and (i) virological suppression and (ii) CD4 cell count increase, after one year. Results Between 1998 and 2007, 4189 SHCS participants started 241 different ART regimens. A violation ART was started in 5% of patients. Female patients (adjusted odds ratio aOR 1.83, 95%CI 1.28–2.62), those with a high education level (aOR 1.49, 95%CI 1.07–2.06) or a high CD4 count (aOR 1.53, 95%CI 1.02–2.30) were more likely to receive violation ART. The proportion of patients with an undetectable viral load (<400 copies/mL) after one year was significantly lower with violation ART than with recommended regimens (aOR 0.54, 95% CI 0.37–0.80) whereas CD4 count increase after one year of treatment was similar in both groups. Conclusions Although more than 240 different initial regimens were prescribed, violations of the IAS-USA recommendations were uncommon. Patients receiving these regimens were less likely to have an undetectable viral load after one year, which strengthens the validity of these recommendations. PMID:22205931

  3. Has the Rate of CD4 Cell Count Decline before Initiation of Antiretroviral Therapy Changed over the Course of the Dutch HIV Epidemic among MSM?

    PubMed Central

    Gras, Luuk; Geskus, Ronald B.; Jurriaans, Suzanne; Bakker, Margreet; van Sighem, Ard; Bezemer, Daniela; Fraser, Christophe; Prins, Jan M.; Berkhout, Ben

    2013-01-01

    Introduction Studies suggest that the HIV-1 epidemic in the Netherlands may have become more virulent, leading to faster disease progression if untreated. Analysis of CD4 cell count decline before antiretroviral therapy (ART) initiation, a surrogate marker for disease progression, may be hampered by informative censoring as ART initiation is more likely with a steeper CD4 cell count decline. Methods Development of CD4 cell count from 9 to 48 months after seroconversion was analyzed using a mixed-effects model and 2 models that jointly modeled CD4 cell counts and time to censoring event (start ART, <100 CD4 cells/mm3, or AIDS) among therapy-naďve MSM HIV-1 seroconverters in the Netherlands. These models make different assumptions about the censoring process. Results All 3 models estimated lower median CD4 cell counts 9 months after seroconversion in later calendar years (623, 582, and 541 cells/mm3 for 1984–1995 [n?=?111], 1996–2002 [n?=?139], and 2003–2007 seroconverters [n?=?356], respectively, shared-parameter model). Only the 2 joint-models found a trend for a steeper decline of CD4 cell counts with seroconversion in later calendar years (overall p-values 0.002 and 0.06 for the pattern-mixture and the shared-parameter model, respectively). In the shared-parameter model the median decline from 9 to 48 months was 276 cellsmm3 for 1984–1995 seroconverters and 308 cells/mm3 for 2003–2007 seroconverters (difference in slope, p?=?0.045). Conclusion Mixed-effects models underestimate the CD4 cell decline prior to starting ART. Joint-models suggest that CD4 cell count declines more rapidly in patients infected between 2003 and 2007 compared to patients infected before 1996. PMID:23724048

  4. The impact of zidovudine on dementia-free survival in a population of HIV-positive men and women on antiretroviral therapy.

    PubMed

    Cornelisse, P G; Montessori, V; Yip, B; Craib, K J; O'Shaughnessy, M V; Montaner, J S; Hogg, R S

    2000-01-01

    Our objective was to characterize the effect of zidovudine therapy on AIDS dementia complex (dementia) free survival among HIV-infected men and women in a population-based cohort with free access to antiretroviral therapy in the province of British Columbia. Time to diagnosis of dementia among individuals was examined on the basis of zidovudine duration, CD4+ cell count at first treatment, gender, and transmission group [men having sex with men (MSM), intravenous drug users (IDU), heterosexuals]. We restricted the analysis to subjects with CD4+ cells counts within 12 months prior to treatment start date. Among 641 participants eligible for analysis, median duration of follow-up was 3.6 years, under which 86 (9.3%) events of dementia occurred. Participants were less likely to develop dementia with: increased zidovudine exposure (OR=0.26, 95% CI: 0.14-0.49), at least 260 CD4+ cells/mm3 (median) (OR=0.52, 95% CI: 0.34-0.78), and MSM risk group (OR=0.57, 95% CI: 0.35-0.94). Those infected through heterosexual contact had an increased risk (RR=2.04, 95% CI: 1.02-4.07). Using Cox's proportional hazards model, controlling for CD4+ cell count at treatment start date, independent predictors of dementia-free survival were: duration of zidovudine (OR=0.28, 95% CI: 0.15-0.52) and MSM transmission group (OR=0.61, 95% CI: 0.37-1.00). In this observational treatment cohort, factors associated with dementia-free survival include duration of zidovudine (AZT) therapy and MSM transmission group. It is not clear from these data whether the AZT protective effect is exclusive to this agent or whether other therapies might offer a similar protective effect. PMID:10667902

  5. Early versus Delayed Antiretroviral Therapy for HIV and Tuberculosis Co-Infected Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

    PubMed Central

    Yan, Shipeng; Chen, Lizhang; Wu, Wenqiong; Fu, Zhongxi; Zhang, Heng; Li, Zhanzhan; Fu, Chenchao; Mou, Jingsong; Xue, Jing; Hu, Yingyun

    2015-01-01

    Objective To compare important clinical outcomes between early and delayed initiation of antiretroviral therapy (ART) in adults who had a co-infection of human immunodeficiency virus (HIV) and tuberculosis (TB). Methods We performed a systematic search for relevant publications on PubMed, EMBASE, and the International Clinical Trials Registry Platform. We included randomized controlled trials (RCTs) that compared early ART initiation (within four weeks after anti-TB treatment starting) and delayed ART initiation (after eight weeks but less than twelve weeks of anti-TB treatment starting) in the course of TB treatment. Pooled estimates with corresponding 95% confidence interval (95%CI) were calculated with random-effects model. Sensitivity analysis was performed to investigate the stability of pooled estimates. Results A meta-analysis was evaluated from six RCTs with 2272 participants. Compared to delayed ART initiation, early ART initiation significantly reduces all-cause mortality in HIV-positive patients with TB [incidence rate ratio (IRR) 0.75, 95%CI 0.59 to 0.95; I2 = 0.00%; p = 0.67], even though there is an increased risk for IRD [IRR 2.29, 95%CI 1.81 to 2.91; I22 = 0.00%; p = 0.56]. Additionally, early ART initiation was not associated with an increased risk for grade 3-4 drug-related adverse events [IRR 0.99, 95%CI 0.83 to 1.18; I2 = 0.00%; p = 0.56]. Conclusions Although limited evidence, our results provide support for early ART initiation in the course of anti-TB treatment. However, more well-designed cohort or intervention studies are required to further confirm our findings. PMID:26000446

  6. The Effects of Head Start Health Services: Executive Summary of the Head Start Health Evaluation.

    ERIC Educational Resources Information Center

    Fosburg, Linda B.; And Others

    This report summarizes findings of an evaluation of Head Start health services. Chapter one presents an overview of the background of the evaluation project. Chapter two highlights findings for the major evaluation questions. These questions focus specifically on children's health status prior to entry into Head Start, health services subsequently…

  7. Tomorrow's answers start today FP7-tomorrow's answers start today -3

    E-print Network

    Scholl, Anthony J.

    FP7 Tomorrow's answers start today #12;#12;FP7- tomorrow's answers start today - 3 FP7 - European Research Council · Frontier research actions People - Human Potential, Marie Curie actions ( million) of FP7 Cooperation 32 365 Ideas: 7460 People: 4728 Capacities: 4217 Euratom: 2751 JRC: 1751

  8. Principios Multiculturales para los Programas Head Start (Multicultural Principles for Head Start Programs).

    ERIC Educational Resources Information Center

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

    This Spanish-language report outlines 10 multicultural principles for Head Start preschool programs and ancillary services. The report assets that Head Start programming should: (1) treat every child as an individual; (2) represent the cultural groups in the community; (3) emphasize accurate information about cultural groups and discard…

  9. Canterbury Bright Start Scholarships Page 1 of 2 CANTERBURY BRIGHT START SCHOLARSHIPS

    E-print Network

    Hickman, Mark

    Canterbury Bright Start Scholarships Page 1 of 2 CANTERBURY BRIGHT START SCHOLARSHIPS CANTERBURY Education Millennial Trust was established in 2001 to offer scholarships to students from the Canterbury acknowledges the generosity of The Canterbury Community Trust in funding the scholarships. 2. NAME The award

  10. Lack of association between dyslipidemia and insulin resistance in HIV-infected persons treated with highly active antiretroviral therapy

    Microsoft Academic Search

    Barbara Swanson; Joyce K. Keithley; Janice M. Zeller; Beverly E. Sha

    2004-01-01

    ObjectiveHighly active antiretroviral therapy has been implicated in the development of metabolic toxicities, including insulin resistance. Because it is “clinically silent,” insulin resistance is often undetected, thus precluding the initiation of treatments that may prevent progression to frank diabetes. Previous studies have documented associations between dyslipidemic profiles and insulin resistance in patients who do not have the human immunodeficiency virus

  11. Steep declines in population-level AIDS mortality following the introduction of antiretroviral therapy in Addis Ababa, Ethiopia

    Microsoft Academic Search

    Georges Reniers; Tekebash Araya; Gail Davey; Nico Nagelkerke; Yemane Berhane; Roel Coutinho; Eduard J Sanders

    2009-01-01

    Objectives: Assessments of population-level effects of antiretroviral therapy (ART) programmes in Africa are rare. We use data from burial sites to estimate trends in adult AIDS mortality and the mitigating effects of ART in Addis Ababa. ART has been available since 2003, and for free since 2005. Methods: To substitute for deficient vital registration, we use surveillance of burials at

  12. Affordable Antiretroviral Drugs for the UnderServed Markets: How to Expand Equitable Access Against the Backdrop of Challenging Scenarios?

    Microsoft Academic Search

    Daniele Dionisio; Yunzhen Cao; Lu Hongzhou; Krisana Kraisintu; Daniela Messeri

    2006-01-01

    BACKGROUND: Threats by enforced Intellectual Property (IP) rights to equitable HIV treatment access by poor populations are impending. India and China's policy directions in the field will be crucial in ultimately affecting the affordability and accessibility of antiretroviral (ARV) therapy in the under-served markets. These directions, together with the exploitation level of IP-bound flexibilities and the evolutionary modelling in partnerships

  13. Non-AIDS defining deaths and immunodeficiency in the era of combination antiretroviral therapy. CASCADE, 1996-2006.

    E-print Network

    Paris-Sud XI, Université de

    1 Title: Non-AIDS defining deaths and immunodeficiency in the era of combination antiretroviral therapy. CASCADE, 1996-2006. (102 characters) Running head: Non-AIDS causes of death and immunodeficiency Epidemiologia, Rome, Italy. inserm-00388946,version1-10Jan2012 Author manuscript, published in "AIDS 2009

  14. Optimizing treatment switch for virologic failure during first-line antiretroviral therapy in resource-limited settings.

    PubMed

    Adetunji, Adedotun A; Achenbach, Chad; Feinglass, Joseph; Darin, Kristin M; Scarsi, Kimberly K; Ekong, Ernest; Taiwo, Babafemi O; Adewole, Isaac F; Murphy, Robert

    2013-01-01

    We evaluated adult Nigerian patients with antiretroviral switch to second-line treatment with ritonavir-boosted protease inhibitor (PI/r)-based regimens due to virologic failure (confirmed HIV-1 RNA viral load [VL] >1000 copies/mL) during first-line antiretroviral therapy. Proportion of patients with VL >400 copies/mL and characteristics associated with nonsuppression during second-line treatment are described. Approximately 15% of patients (34 of 225) had VL >400 copies/mL at 1-year after treatment switch to PI/r-based regimens. In adjusted analyses, VL ?5 log10 copies/mL at treatment switch (odds ratio [OR] 2.90 [confidence interval (CI) 1.21-6.93]); duration of first-line treatment after virologic failure >180 days (OR 2.56 [CI 1.0-6.54]); and PI/r regimen adherence <90% (OR 3.27 [CI 1.39-7.68]) were associated with VL >400 copies/mL at 1 year of second-line treatment. We therefore recommend that the maximum permissible time between suspicion of virologic failure and completion of antiretroviral treatment switch should not exceed 6 months when patients develop first-line antiretroviral failure in resource-limited settings. PMID:23128403

  15. Effects of HIV disease on lipid, glucose and insulin levels: results from a large antiretroviral-naive cohort

    Microsoft Academic Search

    WM El-Sadr; CM Mullin; A Carr; C Gibert; C Rappoport; F Visnegarwala; C Grunfeld; SS Raghavan

    2005-01-01

    Objectives With the use of potent antiretroviral therapy in patients with HIV disease, changes in lipid parameters and glucose homeostasis have been noted. However, these effects have been difficult to interpret because of the varied demographic and treatment characteristics of the cohorts and the complexity of differentiating the effect of HIV disease from that of the drugs used in its

  16. The effect of AIDS defining conditions on immunological recovery among patients initiating antiretroviral therapy at Joint Clinical Research Centre, Uganda

    Microsoft Academic Search

    Brian K Kigozi; Samwel Sumba; Peter Mudyope; Betty Namuddu; Joan Kalyango; Charles Karamagi; Mathew Odere; Elly Katabira; Peter Mugyenyi; Francis Ssali

    2009-01-01

    BACKGROUND: Many HIV-infected patients only access health care once they have developed advanced symptomatic disease resulting from AIDS Defining Conditions (ADCs). We carried out a study to establish the effect of ADCs on immunological recovery among patients initiated on antiretroviral therapy (ART). METHODS: A retrospective cohort of 427 HIV-1 patients who were initiated on ART between January 2002 and December

  17. Economic and quality of life outcomes of antiretroviral therapy for HIV\\/AIDS in developing countries: a systematic literature review

    Microsoft Academic Search

    Jennifer Beard; Frank Feeley; Sydney Rosen

    2009-01-01

    The impacts of antiretroviral therapy (ART) on quality of life, mental health, labor productivity, and economic wellbeing for people living with HIV\\/AIDS in developing countries are only beginning to be measured. We conducted a systematic literature review to analyze the effect of ART on these economic and quality of life indicators in developing countries and assess the state of research

  18. Effects of HIV-related stigma among an early sample of patients receiving antiretroviral therapy in Botswana

    Microsoft Academic Search

    W. R. Wolfe; S. D. Weiser; D. R. Bangsberg; I. Thior; J. M. Makhema; D. B. Dickinson; K. F. Mompati; R. G. Marlink

    2006-01-01

    Botswana, with its estimated HIV prevalence of 37%, instituted a policy of universal access to antiretroviral therapy (ART) in 2002. Initial enrolment lagged behind expectations, with a shortfall in voluntary testing that observers have attributed to HIV-related stigma – although there are no published data on stigma among HIV-positive individuals in Botswana. We interviewed 112 patients receiving ART in 2000,

  19. Self-reported adherence to antiretroviral medications among participants in HIV clinical trials: The AACTG Adherence Instruments

    Microsoft Academic Search

    M. A. Chesney; J. R. Ickovics; D. B. Chambers; A. L. Gifford; J. Neidig; B. Zwickl; A. W. Wu

    2000-01-01

    This paper describes the AACTG Adherence Instruments, which are comprised of two self-report questionnaires for use in clinical trials conducted by the Adult AIDS Clinical Trials Group (AACTG). The questionnaires were administered to 75 patients at ten AACTG sites in the USA. All patients were taking combination antiretroviral therapy (ART), including at least one protease inhibitor. Eleven per cent of

  20. High-Performance Liquid Chromatography Methods to Simultaneous Determination of AntiRetroviral Drugs in Biological Matrices

    Microsoft Academic Search

    Cafer Saka

    2009-01-01

    Acquired immune deficiency syndrome or acquired immunodeficiency syndrome (AIDS or Aids) is symptoms and infections resulting from the damage to the human immune system. The purpose of this paper is to review the literature for high performance liquid chromatography methods to simultaneous determination of anti-retroviral drugs in biological matrices covering the articles mainly from 2001 to 2009. The biological matrix

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

    PubMed Central

    Mwango, Albert; Stringer, Jeffrey; Ledergerber, Bruno; Mulenga, Lloyd; Bucher, Heiner C.; Westfall, Andrew O.; Calmy, Alexandra; Boulle, Andrew; Chintu, Namwinga; Egger, Matthias; Chi, Benjamin H.

    2011-01-01

    Background Loss 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 Findings HIV-infected patients aged ?18 years who started ART 2004–2008 in observational cohorts in Zambia and Switzerland were included. We compared standard Kaplan-Meier curves with CR cumulative incidence. We calculated hazard ratios for LTFU across CD4 cell count strata using cause-specific Cox models, or Fine and Gray subdistribution models, adjusting for age, gender, body mass index and clinical stage. 89,339 patients from Zambia and 1,860 patients from Switzerland were included. 12,237 patients (13.7%) in Zambia and 129 patients (6.9%) in Switzerland were LTFU and 8,498 (9.5%) and 29 patients (1.6%), respectively, died. In Zambia, the probability of LTFU was overestimated in Kaplan-Meier curves: estimates at 3.5 years were 29.3% for patients starting ART with CD4 cells <100 cells/µl and 15.4% among patients starting with ?350 cells/µL. The estimates from CR cumulative incidence were 22.9% and 13.6%, respectively. Little difference was found between naďve and CR analyses in Switzerland since only few patients died. The results from Cox and Fine and Gray models were similar: in Zambia the risk of loss to follow-up and death increased with decreasing CD4 counts at the start of ART, whereas in Switzerland there was a trend in the opposite direction, with patients with higher CD4 cell counts more likely to be lost to follow-up. Conclusions In ART programmes in low-income settings the competing risk of death can substantially bias standard analyses of LTFU. The CD4 cell count and other prognostic factors may be differentially associated with LTFU in low-income and high-income settings. PMID:22205933

  2. Impact on life expectancy of HIV-1 positive individuals of CD4+ cell count and viral load response to antiretroviral therapy

    PubMed Central

    May, Margaret T.; Gompels, Mark; Delpech, Valerie; Porter, Kholoud; Orkin, Chloe; Kegg, Stephen; Hay, Phillip; Johnson, Margaret; Palfreeman, Adrian; Gilson, Richard; Chadwick, David; Martin, Fabiola; Hill, Teresa; Walsh, John; Post, Frank; Fisher, Martin; Ainsworth, Jonathan; Jose, Sophie; Leen, Clifford; Nelson, Mark; Anderson, Jane; Sabin, Caroline

    2014-01-01

    Objective: The objective of this study is to estimate life expectancies of HIV-positive patients conditional on response to antiretroviral therapy (ART). Methods: Patients aged more than 20 years who started ART during 2000–2010 (excluding IDU) in HIV clinics contributing to the UK CHIC Study were followed for mortality until 2012. We determined the latest CD4+ cell count and viral load before ART and in each of years 1–5 of ART. For each duration of ART, life tables based on estimated mortality rates by sex, age, latest CD4+ cell count and viral suppression (HIV-1 RNA <400?copies/ml), were used to estimate expected age at death for ages 20–85 years. Results: Of 21?388 patients who started ART, 961 (4.5%) died during 110?697 person-years. At start of ART, expected age at death [95% confidence interval (CI)] of 35-year-old men with CD4+ cell count less than 200, 200–349, at least 350?cells/?l was 71 (68–73), 78 (74–82) and 77 (72–81) years, respectively, compared with 78 years for men in the general UK population. Thirty-five-year-old men who increased their CD4+ cell count in the first year of ART from less than 200 to 200–349 or at least 350?cells/?l and achieved viral suppression gained 7 and 10 years, respectively. After 5 years on ART, expected age at death of 35-year-old men varied from 54 (48–61) (CD4+ cell count <200?cells/?l and no viral suppression) to 80 (76–83) years (CD4+ cell count ?350?cells/?l and viral suppression). Conclusion: Successfully treated HIV-positive individuals have a normal life expectancy. Patients who started ART with a low CD4+ cell count significantly improve their life expectancy if they have a good CD4+ cell count response and undetectable viral load. PMID:24556869

  3. 49 CFR 611.303 - Small Starts project justification criteria.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ...2013-10-01 2013-10-01 false Small Starts project justification criteria. 611.303 Section...TRANSPORTATION MAJOR CAPITAL INVESTMENT PROJECTS Small Starts § 611.303 Small Starts project justification criteria. (a) To...

  4. 49 CFR 611.307 - Overall Small Starts project ratings.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ...2013-10-01 false Overall Small Starts project ratings. 611.307 Section 611.307...TRANSPORTATION MAJOR CAPITAL INVESTMENT PROJECTS Small Starts § 611.307 Overall Small Starts project ratings. (a) The summary ratings...

  5. 49 CFR 611.303 - Small Starts project justification criteria.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...2014-10-01 2014-10-01 false Small Starts project justification criteria. 611.303 Section...TRANSPORTATION MAJOR CAPITAL INVESTMENT PROJECTS Small Starts § 611.303 Small Starts project justification criteria. (a) To...

  6. 49 CFR 611.307 - Overall Small Starts project ratings.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...2014-10-01 false Overall Small Starts project ratings. 611.307 Section 611.307...TRANSPORTATION MAJOR CAPITAL INVESTMENT PROJECTS Small Starts § 611.307 Overall Small Starts project ratings. (a) The summary ratings...

  7. Discontinuation of antiretroviral therapy causing progression to end-stage renal disease in an HIV patient diagnosed with immune complex ‘lupus-like’ glomerulonephritis

    PubMed Central

    Meyrier, A.; Shah, Silvi; Weber-Shrikant, Edit

    2012-01-01

    Immune complex ‘lupus-like glomerulonephritis’ is a type of renal injury seen infrequently in human immunodeficiency virus (HIV) patients and very little is known about the clinical course and treatment. Treatment options are limited but antiretroviral therapy and steroids have been tried with limited success. We report a case of a 21-year-old HIV-positive African American male with lupus-like glomerulonephritis who progressed to end-stage renal disease upon discontinuation of highly active antiretroviral therapy. This case illustrates the importance of antiretroviral therapy as an important treatment modality for immune complex lupus-like glomerulonephritis in HIV patients.

  8. Antiretroviral Effects on Host Lipoproteins Are Associated With Changes in Hepatitis C Virus (HCV) RNA Levels in Human Immunodeficiency Virus/HCV Coinfected Individuals

    PubMed Central

    Naggie, Susanna; Patel, Keyur; Yang, Lan-Yan; Chow, Shein-Chung; Johnson, Victoria; Guyton, John R.; Muir, Andrew J.; Sulkowski, Mark; Hicks, Charles

    2015-01-01

    We evaluated the impact of antiretroviral-induced dyslipidemia on hepatitis C virus (HCV) biogenesis in human immunodeficiency virus (HIV)/HCV coinfected patients. This study used serum samples from antiretroviral-naive HIV/HCV patients initiating their first regimen as part of AIDS Clinical Trials Group study protocols (A5142, A5202). Initiation of antiretrovirals increased most lipoproteins and apolipoproteins. In the multivariable model, changes in apolipoproteins were associated with changes in log10 HCV RNA from baseline to week-24 of therapy. Off-target lipogenic changes need to be considered in the context of liver and other metabolic disease in HIV/HCV patients.

  9. Key parameters of the swimming start and their relationship to start performance.

    PubMed

    Tor, Elaine; Pease, David L; Ball, Kevin A

    2015-07-01

    The swimming start is typically broken into three sub-phases; on-block, flight, and underwater phases. While overall start performance is highly important to elite swimming, the contribution of each phase and important technical components within each phase, particularly with the new kick-start technique, has not been established. The aim of this study was to identify technical factors associated with overall start performance, with a particular focus on the underwater phase. A number of parameters were calculated from 52 starts performed by elite freestyle and butterfly swimmers. These parameters were split into above-water and underwater groupings, before factor analysis was used to reduce parameter numbers for multiple regression. For the above-water phases, 81% of variance in start performance was accounted for by take-off horizontal velocity. For the underwater water phase, 96% of variance was accounted for with time underwater in descent, time underwater in ascent and time to 10 m. Therefore, developing greater take-off horizontal velocity and focussing on the underwater phase by finding the ideal trajectory will lead to improved start performance. PMID:25555171

  10. Starting Point: Teaching Entry Level Geoscience

    NSDL National Science Digital Library

    Starting Point, presented by the Science Education Research Center at Carleton College, is designed for faculty and graduate students who teach undergraduate entry-level geoscience courses. Each section "describes a teaching method, why/when it is useful, how it can be implemented, and a set of examples spanning the Earth system that can be used in your class." Here, visitors will find information about incorporating various teaching methods, such as role playing, teaching with geographic information systems, cooperative learning, and Socratic questioning. There are also a number of lesson examples which incorporate these methods. Topics for these lessons include the solar system, the atmosphere, climate, and earth history. Starting Point also encourages educators to submit their own teaching lessons that incorporate these methods to the collection.

  11. Starting apparatus for internal combustion engines

    DOEpatents

    Dyches, Gregory M. (Barnwell, SC); Dudar, Aed M. (Augusta, GA)

    1997-01-01

    An internal combustion engine starting apparatus uses a signal from a curt sensor to determine when the engine is energized and the starter motor should be de-energized. One embodiment comprises a transmitter, receiver, computer processing unit, current sensor and relays to energize a starter motor and subsequently de-energize the same when the engine is running. Another embodiment comprises a switch, current transducer, low-pass filter, gain/comparator, relay and a plurality of switches to energize and de-energize a starter motor. Both embodiments contain an indicator lamp or speaker which alerts an operator as to whether a successful engine start has been achieved. Both embodiments also contain circuitry to protect the starter and to de-energize the engine.

  12. Barriers to obesity prevention in Head Start.

    PubMed

    Hughes, Cayce C; Gooze, Rachel A; Finkelstein, Daniel M; Whitaker, Robert C

    2010-01-01

    Head Start provides early childhood education to nearly one million low-income children, through federal grants to more than 2,000 local programs. About one-third of children who enter Head Start are overweight or obese. But program directors face difficulty in implementing policies and practices to address obesity-and in our national survey, they identified the key barriers as lack of time, money, and knowledge. Also, parents and staff sometimes shared cultural beliefs that were inconsistent with preventing obesity, such as the belief that heavier children are healthier. Minimizing those barriers will require federal resources to increase staff training and technical assistance, develop staff wellness programs, and provide healthy meals and snacks. PMID:20194987

  13. Portuguese refiner starts up new gasoline complex

    SciTech Connect

    Not Available

    1995-03-13

    Petroleos de Portugal S.A. (Petrogal) has started up a new $85 million gasoline complex at its Sines, Portugal, refinery. The complex includes HF alkylation and Hydrisom units. The refinery also has completed an overall $650 million upgrade that includes a new visbreaker and vacuum column. Petrogal says the project has increased gasoline production to about 30,000 b/d. Major units constructed for the overall refinery expansion included: a 35,000 b/sd FCCU; a 26,000 b/sd visbreaker; a 45,000 b/sd vacuum distillation unit; two extractive mercaptan columns; an amylene treater; a sulfur-recovery system; and an 8,000 b/sd alkylation complex. The paper describes the gasoline complex, laboratory, safety, control room operation, and start-up.

  14. Evidence for persistent low-level viremia in individuals who control human immunodeficiency virus in the absence of antiretroviral therapy.

    PubMed

    Hatano, Hiroyu; Delwart, Eric L; Norris, Philip J; Lee, Tzong-Hae; Dunn-Williams, Joan; Hunt, Peter W; Hoh, Rebecca; Stramer, Susan L; Linnen, Jeffrey M; McCune, Joseph M; Martin, Jeffrey N; Busch, Michael P; Deeks, Steven G

    2009-01-01

    A subset of antiretroviral-untreated, human immunodeficiency virus (HIV)-infected individuals are able to maintain undetectable plasma HIV RNA levels in the absence of antiretroviral therapy. These "elite" controllers are of high interest as they may provide novel insights regarding host mechanisms of virus control. The degree to which these individuals have residual plasma viremia has not been well defined. We performed a longitudinal study of 46 elite controllers, defined as HIV-seropositive, antiretroviral-untreated individuals with plasma HIV RNA levels of <50 to 75 copies/ml. The median duration of HIV diagnosis was 13 years, the median baseline CD4(+) T-cell count was 753 cells/mm(3), and the median duration of follow-up was 16 months. Plasma and cellular HIV RNA levels were measured using the transcription-mediated amplification (TMA) assay (estimated limit of detection of <3.5 copies RNA/ml). A total of 1,117 TMA assays were performed (median of five time points/subject and four replicates/time point). All but one subject had detectable plasma HIV RNA on at least one time point, and 15 (33%) subjects had detectable RNA at all time points. The majority of controllers also had detectable cell-associated RNA and proviral DNA. A mixed-effect linear model showed no strong evidence of change in plasma RNA levels over time. In conclusion, the vast majority (98%) of elite controllers had measurable plasma HIV RNA, often at levels higher than that observed in antiretroviral-treated patients. This confirms the failure to eradicate the virus, even in these unique individuals who are able to reduce plasma viremia to very low levels without antiretroviral therapy. PMID:18945778

  15. Antiretroviral drug exposure in the female genital tract: implications for oral pre- and post-exposure prophylaxis

    PubMed Central

    Dumond, Julie B.; Yeh, Rosa F.; Patterson, Kristine B.; Corbett, Amanda H.; Jung, Byung Hwa; Rezk, Naser L.; Bridges, Arlene S.; Stewart, Paul W.; Cohen, Myron S.; Kashuba, Angela D.M.

    2010-01-01

    Objectives To describe first dose and steady state antiretroviral drug exposure in the female genital tract. Design Non-blinded, single center, open-label pharmacokinetic study in HIV-infected women. Method Twenty-seven women initiating combination antiretroviral therapy underwent comprehensive blood plasma and cervicovaginal fluid sampling for drug concentrations during the first dose of antiretroviral therapy and at steady-state. Drug concentrations were measured by validated HPLC/UV or HPLC-MS/MS methods. Pharmacokinetic parameters were estimated for 11 drugs by non-compartmental analysis. Descriptive statistics and 95% confidence intervals were generated using Intercooled STATA Release 8.0 (Stata Corporation, College Station, Texas, USA). Results For all antiretroviral drugs, genital tract concentrations were detected rapidly after the first dose. Drugs were stratified according to the genital tract concentrations achieved relative to blood plasma. Median rank order of highest to lowest genital tract concentrations relative to blood plasma at steady state were: lamivudine (concentrations achieved were 411% greater than blood plasma), emtricitabine (395%), zidovudine (235%) tenofovir (75%), ritonavir (26%), didanosine (21%), atazanavir (18%), lopinavir (8%), abacavir (8%), stavudine (5%), and efavirenz (0.4%). Conclusions This is the first study to comprehensively evaluate antiretroviral drug exposure in the female genital tract. These findings support the use of lamivudine, zidovudine, tenofovir and emtricitabine as excellent pre-exposure/post-exposure prophylaxis (PrEP/PEP) candidates. Atazanavir and lopinavir might be useful agents for these applications due to favorable therapeutic indices, despite lower genital tract concentrations. Agents such as stavudine, abacavir, and efavirenz that achieve genital tract exposures less than 10% of blood plasma are less attractive PrEP/PEP candidates. PMID:17721097

  16. Text Message Intervention Designs to Promote Adherence to Antiretroviral Therapy (ART): A Meta-Analysis of Randomized Controlled Trials

    PubMed Central

    Finitsis, David J.; Pellowski, Jennifer A.; Johnson, Blair T.

    2014-01-01

    Background The efficacy of antiretroviral therapy depends on patient adherence to a daily medication regimen, yet many patients fail to adhere at high enough rates to maintain health and reduce the risk of transmitting HIV. Given the explosive global growth of cellular-mobile phone use, text-messaging interventions to promote adherence are especially appropriate. This meta-analysis synthesized available text messaging interventions to promote antiretroviral therapy adherence in people living with HIV. Methods We performed Boolean searches of electronic databases, hand searches of recent year conference abstracts and reverse searches. Included studies (1) targeted antiretroviral therapy adherence in a sample of people living with HIV, (2) used a randomized-controlled trial design to examine a text messaging intervention, and (3) reported at least one adherence measurement or clinical outcome. Results Eight studies, including 9 interventions, met inclusion criteria. Text-messaging interventions yielded significantly higher adherence than control conditions (OR?=?1.39; 95% CI?=?1.18, 1.64). Sensitivity analyses of intervention characteristics suggested that studies had larger effects when interventions (1) were sent less frequently than daily, (2) supported bidirectional communication, (3) included personalized message content, and (4) were matched to participants’ antiretroviral therapy dosing schedule. Interventions were also associated with improved viral load and/or CD4+ count (k?=?3; OR?=?1.56; 95% CI?=?1.11, 2.20). Conclusions Text-messaging can support antiretroviral therapy adherence. Researchers should consider the adoption of less frequent messaging interventions with content and timing that is individually tailored and designed to evoke a reply from the recipient. Future research is needed in order to determine how best to optimize efficacy. PMID:24505411

  17. Extendable Product Traceability System from Small Start

    Microsoft Academic Search

    Shirou Wakayama; Yusuke Doi; Satoshi Ozaki; Atsushi Inoue

    2006-01-01

    A cost-effective and easy way to introduce a product traceability system is to start from a small system and gradually extend it to large-scale systems. Traceability systems used in existing field tests are unsuitable for large-scale deployment because they use a single, centralized database. This paper describes a extendable traceability system proposed by Toshiba that employs distributed databases and ID-hash

  18. Starting Science, Books One, Two and Three

    Microsoft Academic Search

    Jim Jardine

    1996-01-01

    Book One: 122 pp, price Ł7.50 ISBN 0 19 914235 1Book Two: 122 pp, price Ł7.50 ISBN 0 19 914241 6Book Three: 106 pp, price Ł7.50 ISBN 0 19 914374 9 Starting Science Book One This highly successful book, first published in 1985, has been so popular that it has had to be reprinted every year since! Although the new

  19. Multipurpose transportable missile-space complex 'Start'

    NASA Astrophysics Data System (ADS)

    Solomonov, Y.; Andryushin, V.

    1993-06-01

    Space-launcher of the Start family are reviewed focusing on differences between space-launchers and battle missiles, possible payload delivery schemes, and peculiarities of the fundamental and design schemes of a space launcher and ballistic missile. It is pointed out that a process of ICBM transformation into space launchers should be analyzed taking into account differences in operating conditions and the choice of the fundamental and design solutions.

  20. Starting out - Take up the challenge.

    PubMed

    Kirwan, Lisa

    2015-04-01

    I AM BACK in Ireland after my seven-week voluntary experience in China, and the realisation that I am now a fully qualified nurse is only just hitting me. I am preparing to move to London to start working as a children's nurse soon. This is something I am looking forward to but I am also apprehensive about it and unsure what to expect. PMID:25858402

  1. Exercise starts and ends in the brain.

    PubMed

    Kayser, Bengt

    2003-10-01

    Classically the limit to endurance of exercise is explained in terms of metabolic capacity. Cardio-respiratory capacity and muscle fatigue are thought to set the limit and the majority of studies on factors limiting endurance exercise discuss issues such as maximal oxygen uptake (VO2max), aerobic enzyme capacity, cardiac output, glycogen stores, etc. However, this paradigm does not explain the limitation to endurance exercise with large muscle groups at altitude, when at exhaustion exercise is ended without limb locomotor muscle fatigue and with sub-maximal cardiac output. A simple fact provides a basis for an explanation. Voluntary exercise starts and ends in the brain. It starts with spatial and temporal recruitment of motor units and ends with their de-recruitment. A conscious decision precedes a voluntary effort. The end of effort is again volitional and a forced conscious decision to stop precedes it, but it is unknown what forces the off-switch of recruitment at exhaustion although sensation of exertion certainly plays a role. An alternative model explaining the limitation of exercise endurance thus proposes that the central nervous system integrates input from various sources all related to the exercise and limits the intensity and duration of recruitment of limb skeletal muscle to prevent jeopardizing the integrity of the organism. This model acknowledges the cardio-respiratory and muscle metabolic capacities as prime actors on the performance scene, while crediting the central nervous system for its pivotal role as the ultimate site where exercise starts and ends. PMID:12883902

  2. on TB therapy, which they usually need more urgently, and then give them antiretroviral

    E-print Network

    Cai, Long

    , the debate has boiled down to timing: when should those with TB start taking HIV drugs? Start too early, and they might develop this bizarre syndrome. Start too late, and they might die. "If you were to ask five." Scientists are just beginning to grapple with this syndrome, which they've dubbed IRIS for immune

  3. 76 FR 37174 - Capital Investment Program-New Starts and Small Starts Program Funds

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-24

    ...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,...

  4. Efficacy of Initial Antiretroviral Therapy for HIV-1 Infection in Adults: A Systematic Review and Meta-Analysis of 114 Studies with up to 144 Weeks' Follow-Up

    PubMed Central

    Lee, Frederick J.; Amin, Janaki; Carr, Andrew

    2014-01-01

    Background A comprehensive assessment of initial HIV-1 treatment success may inform study design and treatment guidelines. Methods Group-based, systematic review and meta-analysis of initial antiretroviral therapy studies, in adults, of ?48 weeks duration, reported through December 31, 2012. Size-weighted, intention-to-treat efficacy was calculated. Parameters of study design/eligibility, participant and treatment characteristics were abstracted. Multivariable, random effects, linear regression models with backwards, stepwise selection were then used to identify variables associated with efficacy. Outcome Measures Antiviral efficacy (undetectable plasma viral load) and premature cessation of therapy. Results 114 studies were included (216 treatment groups; 40,124 participants; mean CD4 count 248 cells/µL [SD 81]; mean HIV-1 plasma viral load log10 4.9 [SD 0.2]). Mean efficacy across all groups was 60% (SD 16) over a mean 82 weeks' follow-up (SD 38). Efficacy declined over time: 66% (SD 16) at 48 weeks, 60% (SD 16) at 96 weeks, 52% (SD 18) at 144 weeks. The most common reason for treatment cessation was participant decision (11%, SD 6.6). Efficacy was higher with ‘Preferred’ than ‘Alternative’ regimens (as defined by 2013 United States antiretroviral guidelines): 75% vs. 65%, respectively, difference 10%; 95%CI 7.6 to 15.4; p<0.001. In 98 groups (45%) reporting efficacy stratified by pre-treatment viral load (< or ?100,000 copies/mL), efficacy was greater for the lower stratum (70% vs. 62%, respectively, difference 8.4%; 95%CI 6.0 to 10.9; p<0.001). This difference persisted within ‘Preferred’ regimens. Greatest efficacy was associated with use of tenofovir-emtricitabine (vs. other nucleoside analogue backbones) and integrase strand transfer inhibitors (vs. other third drug classes). Conclusion Initial antiretroviral treatments for HIV-1 to date appear to have suboptimal long-term efficacy, but are more effective when commenced at plasma viral loads <100,000 copies/mL. Rising viral load should be considered an indication for starting treatment. Integrase inhibitors offer a treatment advantage (vs. other third drug classes). PMID:24830290

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

    PubMed Central

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

    2007-01-01

    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 distribution of health professionals. Methods We obtained data on the total number of patients on highly active antiretroviral treatment program from the Malawi National AIDS Commission and Ministry of Health, HIV Unit, and the number of registered health professionals from the relevant regulatory bodies. We also estimated number of health professionals required to deliver highly active antiretroviral therapy (HAART) using estimates of human resources from the literature. We also obtained data from the Ministry of Health on the actual number of nurses, clinical officers and medical doctors providing services in HAART clinics. We then made comparisons between the human resources situation on the ground and the theoretical estimates based on explicit assumptions. Results There were 610 clinicians (396 clinical officers and 214 physicians), 44 pharmacists and 98 pharmacy technicians and 7264 nurses registered in Malawi. At the end of March 2007 there were 85 clinical officer and physician full-time equivalents (FTEs) and 91 nurse FTEs providing HAART to 95,674 patients. The human resources used for the delivery of HAART comprised 13.9% of all clinical officers and physicians and 1.1% of all nurses. Using the estimated numbers of health professionals from the literature required 15.7–31.4% of all physicians and clinical officers, 66.5–199.3% of all pharmacists and pharmacy technicians and 2.6 to 9.2% of all the available nurses. To provide HAART to all the 170,000 HIV infected persons estimated as clinically eligible would require 4.7% to 16.4% of the total number of nurses, 118.1% to 354.2% of all the available pharmacists and pharmacy technicians and 27.9% to 55.7% of all clinical officers and physicians. The actual number of health professionals working in the delivery of HAART in the clinics represented 44% to 88.8% (for clinical officers and medical doctors) and 13.6% and 47.6% (for nurses), of what would have been needed based on the literature estimation. Conclusion HAART provision is a labour intensive exercise. Although these data are insufficient to determine whether HAART scale-up has resulted in the weakening or strengthening of the health systems in Malawi, the human resources requirements for HAART scale-up are significant. Malawi is using far less human resources than would be estimated based on the literature from other settings. The impact of HAART scale-up on the overall delivery of health services should be assessed. PMID:18093318

  6. Critical illness in HIV-infected patients in the era of combination antiretroviral therapy.

    PubMed

    Akgün, Kathleen M; Huang, Laurence; Morris, Alison; Justice, Amy C; Pisani, Margaret; Crothers, Kristina

    2011-06-01

    As HIV-infected persons on combination antiretroviral therapy (ART) are living longer and rates of opportunistic infections have declined, serious non-AIDS-related diseases account for an increasing proportion of deaths. Consistent with these changes, non-AIDS-related illnesses account for the majority of ICU admissions in more recent studies, in contrast to earlier eras of the AIDS epidemic. Although mortality after ICU admission has improved significantly since the earliest HIV era, it remains substantial. In this article, we discuss the current state of knowledge regarding the impact of ART on incidence, etiology, and outcomes of critical illness among HIV-infected patients. In addition, we consider issues related to administration of ART in the ICU and identify important areas of future research. PMID:21653532

  7. Critical Illness in HIV-Infected Patients in the Era of Combination Antiretroviral Therapy

    PubMed Central

    Akgün, Kathleen M.; Huang, Laurence; Morris, Alison; Justice, Amy C.; Pisani, Margaret; Crothers, Kristina

    2011-01-01

    As HIV-infected persons on combination antiretroviral therapy (ART) are living longer and rates of opportunistic infections have declined, serious non–AIDS-related diseases account for an increasing proportion of deaths. Consistent with these changes, non–AIDS-related illnesses account for the majority of ICU admissions in more recent studies, in contrast to earlier eras of the AIDS epidemic. Although mortality after ICU admission has improved significantly since the earliest HIV era, it remains substantial. In this article, we discuss the current state of knowledge regarding the impact of ART on incidence, etiology, and outcomes of critical illness among HIV-infected patients. In addition, we consider issues related to administration of ART in the ICU and identify important areas of future research. PMID:21653532

  8. Prevention of HIV-1 Infection with Early Antiretroviral Therapy: Treatment as -

    NASA Astrophysics Data System (ADS)

    Gilada, Ishwar; Gilada, T.

    2014-07-01

    There are 34.2 million living with HIV/AIDS globally according to the UNAIDS. The incidence is 2.5 million new infections every year. Out of the 24.8 million patients eligible for antiretroviral treatment, only 8 million are actually receiving it. Nearly 1.7 million people (4658 per day) die of the disease every year i.e., 4658/day, making HIV/AIDS a planetary emergency. The most disturbing fact is that more than 50% of the infected people do not reveal their HIV status to their sexual partners. The UN Sec-Gen Ban Ki-moon suggested "3 Zeros"--Zero Infection, Zero Stigma, Zero AIDS-deaths in 2008...

  9. Antiretroviral Treatment Interruptions Induced by the Kenyan Postelection Crisis Are Associated With Virological Failure

    PubMed Central

    Kemboi, Emmanuel; Mambo, Fidelis; Rono, Mary; Injera, Wilfred; Delong, Allison; Schreier, Leeann; Kaloustian, Kara W.; Sidle, John; Buziba, Nathan; Kantor, Rami

    2014-01-01

    Background Antiretroviral treatment interruptions (TIs) cause suboptimal clinical outcomes. Data on TIs during social disruption are limited. Methods We determined effects of unplanned TIs after the 2007–2008 Kenyan postelection violence on virological failure, comparing viral load (VL) outcomes in HIV-infected adults with and without conflict-induced TI. Results Two hundred and one patients were enrolled, median 2.2 years after conflict and 4.3 years on treatment. Eighty-eight patients experienced conflict-related TIs and 113 received continuous treatment. After adjusting for preconflict CD4, patients with TIs were more likely to have detectable VL, VL >5,000 and VL >10,000. Conclusions Unplanned conflict-related TIs are associated with increased likelihood of virological failure. PMID:24047971

  10. [Are immunomodulators capable to improve the activity of nucleoside antiretroviral agents?].

    PubMed

    Sinet, M; Pocidalo, J J

    1993-10-01

    Synthetic polyribonucleotides stimulate cells to produce interferons and other cytokines and increase both humoral and cell-mediated immunity. The polynucleotide complexes affect host defense system and may have antiviral properties. Studies in animal models of experimental viral infection may therefore be performed to define a possible strategy for their use in human disease. Antiviral properties of polyribonucleotides have been demonstrated in animals, especially in murine models of retroviral infection. In the early treatment of Friend virus infection, the antiretroviral effect of zidovudine is enhanced by combination with poly I poly C or poly A poly U. Polyribonucleotides also enhance the inhibitory effect of zidovudine on HIV replication in lymphocyte T or macrophage cultures. Therefore this class of compounds could be used in combination with antiviral agents in the treatment of HIV infection, especially when they induce no significant toxicity as it is the case for poly A poly U. PMID:8309723

  11. HIV reservoir dynamics in the face of highly active antiretroviral therapy.

    PubMed

    Costiniuk, Cecilia T; Jenabian, Mohammad-Ali

    2015-02-01

    Upon discontinuation of highly active antiretroviral therapy (HAART), human immunodeficiency virus (HIV)-infected individuals experience a brisk rebound in blood plasma viremia due to the exodus of HIV from various body reservoirs. Assessment of HIV dynamics during HAART and following treatment discontinuation is essential to better understand HIV persistence. Here we will first provide a brief overview of the molecular mechanisms involved in HIV reservoir formation and persistence. After a summary of HAART-mediated HIV decay within peripheral blood, we discuss findings from clinical studies examining the effects of HAART initiation and interruption on HIV reservoir dynamics in major anatomical compartments, including lymph nodes and spleen, gut associated lymphoid tissue, reproductive organs, the central nervous system, and the lungs. Features contributing to these reservoirs as distinct compartments, including anatomical features, the presence of drug transporters, and the effect of co-infection, are also discussed. PMID:25412339

  12. Evolution and recombination of genes encoding HIV-1 drug resistance and tropism during antiretroviral therapy.

    PubMed

    Shi, Binshan; Kitchen, Christina; Weiser, Barbara; Mayers, Douglas; Foley, Brian; Kemal, Kimdar; Anastos, Kathryn; Suchard, Marc; Parker, Monica; Brunner, Cheryl; Burger, Harold

    2010-08-15

    Characterization of residual plasma virus during antiretroviral therapy (ART) is a high priority to improve understanding of HIV-1 pathogenesis and therapy. To understand the evolution of HIV-1 pol and env genes in viremic patients under selective pressure of ART, we performed longitudinal analyses of plasma-derived pol and env sequences from single HIV-1 genomes. We tested the hypotheses that drug resistance in pol was unrelated to changes in coreceptor usage (tropism), and that recombination played a role in evolution of viral strains. Recombinants were identified by using Bayesian and other computational methods. High-level genotypic resistance was seen in approximately 70% of X4 and R5 strains during ART. There was no significant association between resistance and tropism. Each patient displayed at least one recombinant encompassing env and representing a change in predicted tropism. These data suggest that, in addition to mutation, recombination can play a significant role in shaping HIV-1 evolution. PMID:20451945

  13. Potential effect of pharmacogenetics on maternal, fetal and infant antiretroviral drug exposure during pregnancy and breastfeeding.

    PubMed

    Olagunju, Adeniyi; Owen, Andrew; Cressey, Tim R

    2012-10-01

    Mother-to-child-transmission rates of HIV in the absence of any intervention range between 20 and 45%. However, the provision of antiretroviral drugs (ARVs) during pregnancy, delivery and breastfeeding can reduce HIV transmission to less than 2%. Physiological changes during pregnancy can influence ARV disposition. Associations between SNPs in genes coding for metabolizing enzymes, and/or transporters, and ARVs disposition are well described; however, relatively little is known about the influence of these SNPs on ARV pharmacokinetics during pregnancy and lactation as well as their effect on distribution into the fetal compartment and breast milk excretion. Differences in maternal, fetal and infant ARV exposure due to SNPs may affect the efficacy and safety of ARVs used to prevent mother-to-child-transmission. The aim of this review is to provide an update on the effect of pregnancy-induced changes on the pharmacokinetics of ARVs and highlight the potential role of pharmacogenetics. PMID:23057550

  14. Work-Related Barriers and Facilitators to Antiretroviral Therapy Adherence in Persons Living with HIV Infection

    PubMed Central

    Torres-Madriz, Gilberto; Lerner, Debra; Ruthazer, Robin; Rogers, William H.; Wilson, Ira B.

    2013-01-01

    Little is known about how the structure of work affects adherence to HIV antiretroviral therapy. We surveyed participants in an adherence intervention study to learn more about job characteristics, including measures of psychological demand and control, and job accommodations. Adherence was assessed using the Medication Event Monitoring System (MEMS). Of 156 trial subjects, 69 were employed, and these 69 made 229 study visits. Psychological demands and control were unrelated to adherence, but the presence of workplace accommodations was significantly associated with adherence (p <0.05). In multivariable models adjusting for clustering, those who reported having received an accommodation were 12% more adherent than those who did not receive an accommodation. Adherence was unrelated to experiencing side effects affecting work performance. Having the ability to institute job accommodations was more important to adherence than the psychosocial structure of the work. These potential benefits of requesting modifications need to be weighed against the possible risks of workplace disclosure. PMID:20091340

  15. A case of atypical progressive outer retinal necrosis after highly active antiretroviral therapy.

    PubMed

    Woo, Se Joon; Yu, Hyeong Gon; Chung, Hum

    2004-06-01

    This is a report of an atypical case of progressive outer retinal necrosis (PORN) and the effect of highly active antiretroviral therapy (HAART) on the clinical course of viral retinitis in an acquired immunodeficiency syndrome (AIDS) patient. A 22-year-old male patient infected with human immunodeficiency virus (HIV) presented with unilaterally reduced visual acuity and a dense cataract. After cataract extraction, retinal lesions involving the peripheral and macular areas were found with perivascular sparing and the mud-cracked, characteristic appearance of PORN. He was diagnosed as having PORN based on clinical features and was given combined antiviral treatment. With concurrent HAART, the retinal lesions regressed, with the regression being accelerated by further treatment with intravenous acyclovir and ganciclovir. This case suggests that HAART may change the clinical course of PORN in AIDS patients by improving host immunity. PORN should be included in the differential diagnosis of acute unilateral cataract in AIDS patients. PMID:15255240

  16. Causes of Death on Antiretroviral Therapy: A Post-Mortem Study from South Africa

    PubMed Central

    Wong, Emily B.; Omar, Tanvier; Setlhako, Gosetsemang J.; Osih, Regina; Feldman, Charles; Murdoch, David M.; Martinson, Neil A.; Bangsberg, David R.; Venter, W. D. F.

    2012-01-01

    Background Mortality in the first months of antiretroviral therapy (ART) is a significant clinical problem in sub-Saharan Africa. To date, no post-mortem study has investigated the causes of mortality in these patients. Methods HIV-positive adults who died as in-patients at a Johannesburg academic hospital underwent chart-review and ultrasound-guided needle autopsy for histological and microbiological examination of lung, liver, spleen, kidney, bone marrow, lymph node, skin and cerebrospinal fluid. A clinico-pathologic committee considered all available data and adjudicated immediate and contributing causes of death. Results Thirty-nine adults were enrolled: 14 pre-ART, 15 early-ART (7–90 days), and 10 late-ART (>90 days). Needle sampling yielded adequate specimen in 100% of kidney, skin, heart and cerebrospinal fluid samples, 97% of livers and lungs, 92% of bone marrows, 87% of spleens and 68% of lymph nodes. Mycobacterial infections were implicated in 69% of deaths (26 of 27 of these due to M. tuberculosis), bacterial infections in 33%, fungal infections in 21%, neoplasm in 26%, and non-infectious organ failure in 26%. Immune reconstitution inflammatory syndrome (IRIS) was implicated in 73% of early-ART deaths. Post-mortem investigations revealed previously undiagnosed causes of death in 49% of cases. Multiple pathologies were common with 62% of subjects with mycobacterial infection also having at least one other infectious or neoplastic cause of death. Conclusions Needle biopsy was efficient and yielded excellent pathology. The large majority of deaths in all three groups were caused by M. tuberculosis suggesting an urgent need for improved diagnosis and expedited treatment prior to and throughout the course of antiretroviral therapy. Complex, unrecognized co-morbidities pose an additional challenge. PMID:23094059

  17. Metabolic and body composition effects of newer antiretrovirals in HIV-infected patients.

    PubMed

    Srinivasa, Suman; Grinspoon, Steven K

    2014-05-01

    In the absence of a cure, HIV-infected patients are being successfully treated with antiretroviral therapies (ART) and living longer. Indeed, an increasing number of HIV-infected patients are living beyond the age of 50 years, and in that regard, the use of ART has transformed HIV into a chronic medical condition. As more HIV-infected patients are virologically controlled and living longer, the trajectory of disease morbidity has shifted, however, primarily from opportunistic infections and immune dysfunction to metabolic complications. Evidence suggests that HIV-infected patients acquire significant metabolic risks, including lipodystrophic changes, subclinical atherosclerosis, and insulin resistance. The etiology of these metabolic complications specifically in HIV-infected patients is not entirely clear but may be related to a complex interaction between long-term consequences of infection and HIV itself, chronic use of antiretrovirals, and underlying inflammatory processes. Previous classes of ART, such as protease inhibitors (PIs) and reverse transcriptase inhibitors, have been implicated in altering fat redistribution and lipid and glucose homeostasis. Advances in drug development have introduced newer ART with strategies to target novel mechanisms of action and improve patient adherence with multi-class drug combinations. In this review, we will focus on these newer classes of ART, including selected entry inhibitors, integrase inhibitors, and multi-class drug combinations, and two newer PIs, and the potential of these newer agents to cause metabolic complications in HIV-infected patients. Taken together, further reduction of morbidity in HIV-infected patients will require increasing awareness of the deleterious metabolic complications of ART with subsequent management to mitigate these risks. PMID:24523497

  18. Patterns of Geographic Mobility Predict Barriers to Engagement in HIV Care and Antiretroviral Treatment Adherence

    PubMed Central

    Reyes, Emily; Levine, Elizabeth A.; Khan, Shah Z.; Garduńo, L. Sergio; Donastorg, Yeycy; Hammer, Scott M.; Brudney, Karen; Hirsch, Jennifer S.

    2014-01-01

    Abstract Migration and geographic mobility increase risk for HIV infection and may influence engagement in HIV care and adherence to antiretroviral therapy. Our goal is to use the migration-linked communities of Santo Domingo, Dominican Republic, and New York City, New York, to determine the impact of geographic mobility on HIV care engagement and adherence to treatment. In-depth interviews were conducted with HIV+Dominicans receiving antiretroviral therapy, reporting travel or migration in the past 6 months and key informants (n=45). Mobility maps, visual representations of individual migration histories, including lifetime residence(s) and all trips over the past 2 years, were generated for all HIV+ Dominicans. Data from interviews and field observation were iteratively reviewed for themes. Mobility mapping revealed five distinct mobility patterns: travel for care, work-related travel, transnational travel (nuclear family at both sites), frequent long-stay travel, and vacation. Mobility patterns, including distance, duration, and complexity, varied by motivation for travel. There were two dominant barriers to care. First, a fear of HIV-related stigma at the destination led to delays seeking care and poor adherence. Second, longer trips led to treatment interruptions due to limited medication supply (30-day maximum dictated by programs or insurers). There was a notable discordance between what patients and providers perceived as mobility-induced barriers to care and the most common barriers found in the analysis. Interventions to improve HIV care for mobile populations should consider motivation for travel and address structural barriers to engagement in care and adherence. PMID:24839872

  19. Short Communication: Transmitted HIV Drug Resistance in Antiretroviral-Naive Pregnant Women in North Central Nigeria

    PubMed Central

    Sagay, Atiene S.; Chaplin, Beth; Chebu, Philippe; Musa, Jonah; Okpokwu, Jonathan; Hamel, Donald J.; Pam, Ishaya C.; Agbaji, Oche; Samuels, Jay; Meloni, Seema; Sankale, Jean-Louis; Okonkwo, Prosper; Kanki, Phyllis

    2014-01-01

    Abstract The World Health Organization (WHO) recommends periodic surveillance of transmitted drug resistance (TDR) in communities in which antiretroviral therapy (ART) has been scaled-up for greater than 3 years. We conducted a survey of TDR mutations among newly detected HIV-infected antiretroviral (ARV)-naive pregnant women. From May 2010 to March 2012, 38 ARV-naive pregnant women were recruited in three hospitals in Jos, Plateau state, north central Nigeria. Eligible subjects were recruited using a modified version of the binomial sequential sampling technique recommended by WHO. HIV-1 genotyping was performed and HIV-1 drug resistance mutations were characterized according to the WHO 2009 surveillance drug resistance mutation (SDRM) list. HIV subtypes were determined by phylogenetic analysis. The women's median age was 25.5 years; the median CD4+ cell count was 317 cells/?l and the median viral load of 16 was 261 copies/ml. Of the 38 samples tested, 34 (89%) were successfully genotyped. The SDRM rate was <5% for all ART drug classes, with 1/34 (2.9%) for NRTIs/NNRTIs and none for protease inhibitors 0/31 (0%). The specific SDRMs detected were M41L for nucleoside reverse transcriptase inhibitors (NRTIs) and G190A for nonnucleoside reverse transcriptase inhibitors (NNRTIs). HIV-1 subtypes detected were CRF02_AG (38.2%), G? (41.2%), G (14.7%), CRF06-CPX (2.9%), and a unique AG recombinant form (2.9%). The single ARV-native pregnant woman with SDRMs was infected with HIV-1 subtype G?. Access to ART has been available in the Jos area for over 8 years. The prevalence of TDR lower than 5% suggests proper ART administration, although continued surveillance is warranted. PMID:24164431

  20. Trauma History and Depression Predict Incomplete Adherence to Antiretroviral Therapies in a Low Income Country

    PubMed Central

    Whetten, Kathryn; Shirey, Kristen; Pence, Brian Wells; Yao, Jia; Thielman, Nathan; Whetten, Rachel; Adams, Julie; Agala, Bernard; Ostermann, Jan; O'Donnell, Karen; Hobbie, Amy; Maro, Venance; Itemba, Dafrosa; Reddy, Elizabeth

    2013-01-01

    Background As antiretroviral therapy (ART) for HIV becomes increasingly available in low and middle income countries (LMICs), understanding reasons for lack of adherence is critical to stemming the tide of infections and improving health. Understanding the effect of psychosocial experiences and mental health symptomatology on ART adherence can help maximize the benefit of expanded ART programs by indicating types of services, which could be offered in combination with HIV care. Methodology The Coping with HIV/AIDS in Tanzania (CHAT) study is a longitudinal cohort study in the Kilimanjaro Region that included randomly selected HIV-infected (HIV+) participants from two local hospital-based HIV clinics and four free-standing voluntary HIV counselling and testing sites. Baseline data were collected in 2008 and 2009; this paper used data from 36 month follow-up interviews (N?=?468). Regression analyses were used to predict factors associated with incomplete self-reported adherence to ART. Results Incomplete ART adherence was significantly more likely to be reported amongst participants who experienced a greater number of childhood traumatic events: sexual abuse prior to puberty and the death in childhood of an immediate family member not from suicide or homicide were significantly more likely in the non-adherent group and other negative childhood events trended toward being more likely. Those with incomplete adherence had higher depressive symptom severity and post-traumatic stress disorder (PTSD). In multivariable analyses, childhood trauma, depression, and financial sacrifice remained associated with incomplete adherence. Discussion This is the first study to examine the effect of childhood trauma, depression and PTSD on HIV medication adherence in a low income country facing a significant burden of HIV. Allocating spending on HIV/AIDS toward integrating mental health services with HIV care is essential to the creation of systems that enhance medication adherence and maximize the potential of expanded antiretroviral access to improve health and reduce new infections. PMID:24124455

  1. Antiretroviral treatment of HIV-1 prevents transmission of HIV-1: where do we go from here?

    PubMed

    Cohen, Myron S; Smith, M Kumi; Muessig, Kathryn E; Hallett, Timothy B; Powers, Kimberly A; Kashuba, Angela D

    2013-11-01

    Antiretroviral drugs that inhibit viral replication were expected to reduce transmission of HIV by lowering the concentration of HIV in the genital tract. In 11 of 13 observational studies, antiretroviral therapy (ART) provided to an HIV-infected index case led to greatly reduced transmission of HIV to a sexual partner. In the HPTN 052 randomised controlled trial, ART used in combination with condoms and counselling reduced HIV transmission by 96·4%. Evidence is growing that wider, earlier initiation of ART could reduce population-level incidence of HIV. However, the full benefits of this strategy will probably need universal access to very early ART and excellent adherence to treatment. Challenges to this approach are substantial. First, not all HIV-infected individuals can be located, especially people with acute and early infection who are most contagious. Second, the ability of ART to prevent HIV transmission in men who have sex with men (MSM) and people who use intravenous drugs has not been shown. Indeed, the stable or increased incidence of HIV in MSM in some communities where widespread use of ART has been established emphasises the concern that not enough is known about treatment as prevention for this crucial population. Third, although US guidelines call for immediate use of ART, such guidelines have not been embraced worldwide. Some experts do not believe that immediate or early ART is justified by present evidence, or that health-care infrastructure for this approach is sufficient. These concerns are very difficult to resolve. Ongoing community-based prospective trials of early ART are likely to help to establish the population-level benefit of ART, and-if successful-to galvanise treatment as prevention. PMID:24152938

  2. Modulation of HCV Replication After Combination Antiretroviral Therapy in HCV/HIV Coinfected Patients

    PubMed Central

    Sherman, Kenneth E.; Guedj, Jeremie; Shata, Mohamed Tarek; Blackard, Jason T.; Rouster, Susan D.; Castro, Mario; Feinberg, Judith; Sterling, Richard K.; Goodman, Zachary; Aronow, Bruce J.; Perelson, Alan S.

    2015-01-01

    The hepatitis C virus (HCV) is an important contributor to morbidity and mortality in patients coinfected with human immunodeficiency virus (HIV). Coinfection results in increased HCV replication and more rapid rates of liver disease progression. The effect of HIV combination antiretroviral therapy (cART) on HCV replication has not been studied in depth. To address this issue, we enrolled a small cohort of HCV/HIV coinfected patients into a cART initiation trial, and used dynamic modeling combined with evaluation of immune responses and microarray profiles to determine how effective treatment of HIV affects HCV. Treatment with cART resulted in HCV flare and alanine aminotransferase (ALT) increase (2× or more increase from baseline) in a subset of treated patients. Subjects with evidence of hepatic injury (increased ALT) were more likely to have HCV-specific immune responses directed against HCV epitopes. Over time, HCV viral loads declined. Reproducible and biologically important gene expression changes occurred in patients who underwent successful cART, particularly with respect to downregulation of genes with known antiviral roles. Our findings suggest that the effective suppression of HIV by cART initiates a cascade of early and late events in treated patients with HCV. Early events involving downregulation of interferon-stimulated genes may lead to transiently increased viral replication and hepatic injury. At later time points, HCV viral load declines to levels comparable to those seen in the setting of HCV monoinfection. These findings support early antiretroviral therapy in those with HCV/HIV coinfection. PMID:25101888

  3. Short communication: Transmitted HIV drug resistance in antiretroviral-naive pregnant women in north central Nigeria.

    PubMed

    Imade, Godwin E; Sagay, Atiene S; Chaplin, Beth; Chebu, Philippe; Musa, Jonah; Okpokwu, Jonathan; Hamel, Donald J; Pam, Ishaya C; Agbaji, Oche; Samuels, Jay; Meloni, Seema; Sankale, Jean-Louis; Okonkwo, Prosper; Kanki, Phyllis

    2014-02-01

    The World Health Organization (WHO) recommends periodic surveillance of transmitted drug resistance (TDR) in communities in which antiretroviral therapy (ART) has been scaled-up for greater than 3 years. We conducted a survey of TDR mutations among newly detected HIV-infected antiretroviral (ARV)-naive pregnant women. From May 2010 to March 2012, 38 ARV-naive pregnant women were recruited in three hospitals in Jos, Plateau state, north central Nigeria. Eligible subjects were recruited using a modified version of the binomial sequential sampling technique recommended by WHO. HIV-1 genotyping was performed and HIV-1 drug resistance mutations were characterized according to the WHO 2009 surveillance drug resistance mutation (SDRM) list. HIV subtypes were determined by phylogenetic analysis. The women's median age was 25.5 years; the median CD4(+) cell count was 317 cells/?l and the median viral load of 16 was 261 copies/ml. Of the 38 samples tested, 34 (89%) were successfully genotyped. The SDRM rate was <5% for all ART drug classes, with 1/34 (2.9%) for NRTIs/NNRTIs and none for protease inhibitors 0/31 (0%). The specific SDRMs detected were M41L for nucleoside reverse transcriptase inhibitors (NRTIs) and G190A for nonnucleoside reverse transcriptase inhibitors (NNRTIs). HIV-1 subtypes detected were CRF02_AG (38.2%), G' (41.2%), G (14.7%), CRF06-CPX (2.9%), and a unique AG recombinant form (2.9%). The single ARV-native pregnant woman with SDRMs was infected with HIV-1 subtype G'. Access to ART has been available in the Jos area for over 8 years. The prevalence of TDR lower than 5% suggests proper ART administration, although continued surveillance is warranted. PMID:24164431

  4. Implication of TRIMalpha and TRIMCyp in interferon-induced anti-retroviral restriction activities

    PubMed Central

    Carthagena, Laetitia; Parise, Mélanie C; Ringeard, Mathieu; Chelbi-Alix, Mounira K; Hazan, Uriel; Nisole, Sébastien

    2008-01-01

    Background TRIM5? is a restriction factor that interferes with retroviral infections in a species-specific manner in primate cells. Although TRIM5? is constitutively expressed, its expression has been shown to be up-regulated by type I interferon (IFN). Among primates, a particular case exists in owl monkey cells, which express a fusion protein between TRIM5 and cyclophilin A, TRIMCyp, specifically interfering with HIV-1 infection. No studies have been conducted so far concerning the possible induction of TRIMCyp by IFN. We investigated the consequences of IFN treatment on retroviral restriction in diverse primate cells and evaluated the implication of TRIM5? or TRIMCyp in IFN-induced anti-retroviral activities. Results First, we show that human type I IFN can enhance TRIM5? expression in human, African green monkey and macaque cells, as well as TRIMCyp expression in owl monkey cells. In TRIM5?-expressing primate cell lines, type I IFN has little or no effect on HIV-1 infection, whereas it potentates restriction activity against N-MLV in human and African green monkey cells. In contrast, type I IFN treatment of owl monkey cells induces a great enhancement of HIV-1 restriction, as well as a strain-tropism independent restriction of MLV. We were able to demonstrate that TRIM5? is the main mediator of the IFN-induced activity against N-MLV in human and African green monkey cells, whereas TRIMCyp mediates the IFN-induced HIV-1 restriction enhancement in owl monkey cells. In contrast, the type I IFN-induced anti-MLV restriction in owl monkey cells is independent of TRIMCyp expression. Conclusion Together, our observations indicate that both TRIM5? and TRIMCyp are implicated in IFN-induced anti-retroviral response in primate cells. Furthermore, we found that type I IFN also induces a TRIMCyp-independent restriction activity specific to MLV in owl monkey cells. PMID:18613956

  5. Attitude towards antiretroviral pre-exposure prophylaxis (PrEP) prescription among HIV specialists

    PubMed Central

    2013-01-01

    Background To investigate perceptions and attitude to prescribe Pre-Exposure Prophylaxis (PrEP) among HIV specialists. Methods A questionnaire developed through a Focus Group and literature review was administered to a convenience sample of HIV specialists during educational courses in two Regions and an online survey in February-May 2012. Participants were classified as having a positive or negative attitude according to their willingness to prescribe PrEP. Demographic and working information, experience with HIV-infected patients, information and provision of antiretrovirals to uninfected persons, self-reported knowledge, perceptions and concerns regarding PrEP were assessed. The association between a different attitude towards PrEP prescription and selected characteristics was assessed through univariate and multivariate regression analysis. Results Of 311 specialists, 70% would prescribe PrEP, mainly to serodiscordant partners (64%) but also to people at ongoing, high risk of HIV infection (56%); 66% advocated public support of costs. A negative attitude towards PrEP was significantly associated with lack of provision of information on, and prescription of, antiretroviral post-exposure prophylaxis; specialists with a negative attitude believed behavioural interventions to be more effective than PrEP and were more concerned about toxicity. Overall, 90% of specialists disagreed regarding a lack of time for engaging in prevention counselling and PrEP monitoring; 79% would welcome formal guidelines, while those with a negative attitude did not consider this advisable. Conclusions Although conflicting attitudes appear evident, most specialists seem to be willing, with guidance from normative bodies, to promote PrEP within multiple prevention strategies among vulnerable populations. More scientific evidence regarding effectiveness could overcome resistance. PMID:23672424

  6. Cystatin C-Based Renal Function Changes After Antiretroviral Initiation: A Substudy of a Randomized Trial

    PubMed Central

    Gupta, Samir K.; Kitch, Douglas; Tierney, Camlin; Daar, Eric S.; Sax, Paul E.; Melbourne, Kathleen; Ha, Belinda; McComsey, Grace A.

    2014-01-01

    Background. ?The effects of antiretrovirals on cystatin C-based renal function estimates are unknown. Methods. ?We analyzed changes in renal function using creatinine and cystatin C-based estimating equations in 269 patients in A5224s, a substudy of study A5202, in which treatment-naive patients were randomized to abacavir/lamivudine or tenofovir/emtricitabine with open-label atazanavir/ritonavir or efavirenz. Results. ?Changes in renal function significantly improved (or declined less) with abacavir/lamivudine treatment compared with tenofovir/emtricitabine using the Cockcroft-Gault formula (P = .016) and 2009 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI; P = .030) and 2012 CKD-EPI cystatin C-creatinine (P = .025). Renal function changes significantly improved (or declined less) with efavirenz compared with atazanavir/ritonavir (P < .001 for all equations). Mean (95% confidence interval) renal function changes specifically for tenofovir/emtricitabine combined with atazanavir/ritonavir were ?8.3 (?14.0, ?2.6) mL/min with Cockcroft-Gault; ?14.9 (?19.7, ?10.1) mL/min per 1.732 with Modification of Diet in Renal Disease; ?12.8 (?16.5, ?9.0) mL/min per 1.732 with 2009 CKD-EPI; +8.9 (4.2, 13.7) mL/min per 1.732 with 2012 CKD-EPI cystatin C; and ?1.2 (?5.1, 2.6) mL/min per 1.732 with 2012 CKD-EPI cystatin C-creatinine. Renal function changes for the other treatment arms were more favorable but similarly varied by estimating equation. Conclusions. ?Antiretroviral-associated changes in renal function vary in magnitude and direction based on the estimating equation used. PMID:25734077

  7. Plasma Sclerostin in HIV-Infected Adults on Effective Antiretroviral Therapy.

    PubMed

    Erlandson, Kristine M; O'Riordan, MaryAnn; Hileman, Corrilynn O; Rapaport, Eric; Labbato, Danielle; Campbell, Thomas B; McComsey, Grace A

    2015-07-01

    Sclerostin is linked to bone physiology and cardiovascular disease through the Wnt/?-catenin signaling pathway. The goal of this study was to determine if sclerostin is related to bone physiology and cardiovascular disease during antiretroviral treatment in HIV-infected persons. This was a cross-sectional analysis from study entry into the Stopping Atherosclerosis and Treating Unhealthy bone with RosuvastatiN in HIV (SATURN) trial, an ongoing randomized trial comparing rosuvastatin to placebo in HIV-infected adults on antiretroviral therapy. Plasma sclerostin was measured at study entry by ELISA from participants with available samples. Spearman correlation and multivariable linear regression were used to test relationships between sclerostin and bone density or bone turnover and cardiovascular disease. Among 139 HIV-infected participants (median age 46 years, CD4 lymphocyte count 614 cells/?l), the median plasma sclerostin level was 444.1 (IQR 330.3, 570.1) pg/ml. Correlations were detected between sclerostin and age (r=0.26), lumbar spine Z-score (r=0.31), RANKL (r=-0.21), carotid intima-media thickness (CIMT, r=0.19), and sVCAM-1 (r=0.27), p<0.05. No significant correlations were detected between sclerostin and current (r=0.006) or nadir CD4 count (r=0.11). While associations between sclerostin, lumbar spine Z-score, and sVCAM-1 were robust to covariate adjustment (p<0.01), association with CIMT was no longer significant (p=0.08). Our findings provide preliminary support for a relationship between sclerostin and bone mineral density in HIV-infected persons. The Wnt/?-catenin pathway should be investigated as a potential mechanism for loss of bone mineral density in treated HIV infection. PMID:25919636

  8. Artemether-lumefantrine co-administration with antiretrovirals: population pharmacokinetics and dosing implications

    PubMed Central

    Hoglund, Richard M; Byakika-Kibwika, Pauline; Lamorde, Mohammed; Merry, Concepta; Ashton, Michael; Hanpithakpong, Warunee; Day, Nicholas P J; White, Nicholas J; Äbelö, Angela; Tarning, Joel

    2015-01-01

    AIM Drug–drug interactions between antimalarial and antiretroviral drugs may influence antimalarial treatment outcomes. The aim of this study was to investigate the potential drug–drug interactions between the antimalarial drugs, lumefantrine, artemether and their respective metabolites desbutyl-lumefantrine and dihydroartemisinin, and the HIV drugs efavirenz, nevirapine and lopinavir/ritonavir. METHOD Data from two clinical studies, investigating the influence of the HIV drugs efavirenz, nevirapine and lopinavir/ritonavir on the pharmacokinetics of the antimalarial drugs lumefantrine, artemether and their respective metabolites, in HIV infected patients were pooled and analyzed using a non-linear mixed effects modelling approach. RESULTS Efavirenz and nevirapine significantly decreased the terminal exposure to lumefantrine (decrease of 69.9% and 25.2%, respectively) while lopinavir/ritonavir substantially increased the exposure (increase of 439%). All antiretroviral drugs decreased the total exposure to dihydroartemisinin (decrease of 71.7%, 41.3% and 59.7% for efavirenz, nevirapine and ritonavir/lopinavir, respectively). Simulations suggest that a substantially increased artemether-lumefantrine dose is required to achieve equivalent exposures when co-administered with efavirenz (250% increase) and nevirapine (75% increase). When co-administered with lopinavir/ritonavir it is unclear if the increased lumefantrine exposure compensates adequately for the reduced dihydroartemisinin exposure and thus whether dose adjustment is required. CONCLUSION There are substantial drug interactions between artemether-lumefantrine and efavirenz, nevirapine and ritonavir/lopinavir. Given the readily saturable absorption of lumefantrine, the dose adjustments predicted to be necessary will need to be evaluated prospectively in malaria-HIV co-infected patients. PMID:25297720

  9. A systematic review of treatment fatigue among HIV-infected patients prescribed antiretroviral therapy.

    PubMed

    Claborn, Kasey R; Meier, Ellen; Miller, Mary Beth; Leffingwell, Thad R

    2015-01-01

    HIV treatment requires lifelong adherence to medication regimens that comprise inconvenient scheduling, adverse side effects, and lifestyle changes. Antiretroviral adherence and treatment fatigue have been inextricably linked. Adherence in HIV-infected populations has been well investigated; however, little is known about treatment fatigue. This review examines the current state of the literature on treatment fatigue among HIV populations and provides an overview of its etiology and potential consequences. Standard systematic research methods were used to gather published papers on treatment fatigue and HIV. Five databases were searched using PRISMA criteria. Of 1557 studies identified, 21 met the following inclusion criteria: (a) study participants were HIV-infected; (b) participants were prescribed antiretroviral medication; (c) the article referenced treatment fatigue; (d) the article was published in a peer-reviewed journal; and (e) text was available in English. Only seven articles operationally defined treatment fatigue, with three themes emerging throughout the definitions: (1) pill burden; (2) loss of desire to adhere to the regimen; and (3) nonadherence to regimens as a consequence of treatment fatigue. Based on these studies, treatment fatigue may be defined as "decreased desire and motivation to maintain vigilance in adhering to a treatment regimen among patients prescribed long-term protocols." The cause and course of treatment fatigue appear to vary by developmental stage. To date, only structured treatment interruptions have been examined as an intervention to reduce treatment fatigue in children and adults. No behavioral interventions have been developed to reduce treatment fatigue. Further, only qualitative studies have examined treatment fatigue conceptually. Studies designed to systematically assess treatment fatigue are needed. Increased understanding of the course and duration of treatment fatigue is expected to improve adherence interventions, thereby improving clinical outcomes for individuals living with HIV. PMID:25110152

  10. Endosomal Trafficking of Nanoformulated Antiretroviral Therapy Facilitates Drug Particle Carriage and HIV Clearance

    PubMed Central

    Guo, Dongwei; Zhang, Gang; Wysocki, Tadeusz A.; Wysocki, Beata J.; Gelbard, Harris A.; Liu, Xin-Ming; McMillan, JoEllyn M.

    2014-01-01

    ABSTRACT Limitations of antiretroviral therapy (ART) include poor patient adherence, drug toxicities, viral resistance, and failure to penetrate viral reservoirs. Recent developments in nanoformulated ART (nanoART) could overcome such limitations. To this end, we now report a novel effect of nanoART that facilitates drug depots within intracellular compartments at or adjacent to the sites of the viral replication cycle. Poloxamer 407-coated nanocrystals containing the protease inhibitor atazanavir (ATV) were prepared by high-pressure homogenization. These drug particles readily accumulated in human monocyte-derived macrophages (MDM). NanoATV concentrations were ?1,000 times higher in cells than those that could be achieved by the native drug. ATV particles in late and recycling endosome compartments were seen following pulldown by immunoaffinity chromatography with Rab-specific antibodies conjugated to magnetic beads. Confocal microscopy provided cross validation by immunofluorescent staining of the compartments. Mathematical modeling validated drug-endosomal interactions. Measures of reverse transcriptase activity and HIV-1 p24 levels in culture media and cells showed that such endosomal drug concentrations enhanced antiviral responses up to 1,000-fold. We conclude that late and recycling endosomes can serve as depots for nanoATV. The colocalization of nanoATV at endosomal sites of viral assembly and its slow release sped antiretroviral activities. Long-acting nanoART can serve as a drug carrier in both cells and subcellular compartments and, as such, can facilitate viral clearance. IMPORTANCE The need for long-acting ART is significant and highlighted by limitations in drug access, toxicity, adherence, and reservoir penetrance. We propose that targeting nanoformulated drugs to infected tissues, cells, and subcellular sites of viral replication may improve clinical outcomes. Endosomes are sites for human immunodeficiency virus assembly, and increasing ART concentrations in such sites enhances viral clearance. The current work uncovers a new mechanism by which nanoART can enhance viral clearance over native drug formulations. PMID:24920821

  11. A Prospective Study of Predictors of Adherence to Combination Antiretroviral Medication

    PubMed Central

    Golin, Carol E; Liu, Honghu; Hays, Ron D; Miller, Loren G; Beck, C Keith; Ickovics, Jeanette; Kaplan, Andrew H; Wenger, Neil S

    2002-01-01

    OBJECTIVE Adherence to complex antiretroviral therapy (ART) is critical for HIV treatment but difficult to achieve. The development of interventions to improve adherence requires detailed information regarding barriers to adherence. However, short follow-up and inadequate adherence measures have hampered such determinations. We sought to assess predictors of long-term (up to 1 year) adherence to newly initiated combination ART using an accurate, objective adherence measure. DESIGN A prospective cohort study of 140 HIV-infected patients at a county hospital HIV clinic during the year following initiation of a new highly active ART regimen. MEASURES AND MAIN RESULTS We measured adherence every 4 weeks, computing a composite score from electronic medication bottle caps, pill count and self-report. We evaluated patient demographic, biomedical, and psychosocial characteristics, features of the regimen, and relationship with one's HIV provider as predictors of adherence over 48 weeks. On average, subjects took 71% of prescribed doses with over 95% of patients achieving suboptimal (<95%) adherence. In multivariate analyses, African-American ethnicity, lower income and education, alcohol use, higher dose frequency, and fewer adherence aids (e.g., pillboxes, timers) were independently associated with worse adherence. After adjusting for demographic and clinical factors, those actively using drugs took 59% of doses versus 72% for nonusers, and those drinking alcohol took 66% of doses versus 74% for nondrinkers. Patients with more antiretroviral doses per day adhered less well. Participants using no adherence aids took 68% of doses versus 76% for those in the upper quartile of number of adherence aids used. CONCLUSIONS Nearly all patients' adherence levels were suboptimal, demonstrating the critical need for programs to assist patients with medication taking. Interventions that assess and treat substance abuse and incorporate adherence aids may be particularly helpful and warrant further study. PMID:12390551

  12. NEUROCOGNITIVE FUNCTIONING IN ANTIRETROVIRAL THERAPY-NAĎVE YOUTH WITH BEHAVIORALLY ACQUIRED HIV

    PubMed Central

    Nichols, Sharon L.; Bethel, James; Garvie, Patricia A.; Patton, Doyle E; Thornton, Sarah; Kapogiannis, Bill G.; Ren, Weijia; Major-Wilson, Hanna; Puga, Ana; Woods, Steven P.

    2013-01-01

    Purpose Youth living with HIV account for over one-third of new HIV infections and are at high risk of adverse psychosocial, everyday living, and health outcomes. HIV-associated neurocognitive disorders (HAND) are known to affect health outcomes of HIV-infected adults even in the era of combination antiretroviral therapy (cART). Thus, the current study aimed to characterize the prevalence and clinical correlates of HAND in youth living with HIV. Here we report baseline neurocognitive data for behaviorally HIV-infected youth enrolled in a prospective study evaluating strategies of antiretroviral treatment initiation and use. Methods Two hundred twenty participants, age 18-24, naďve to treatment (except for prevention of mother to child HIV transmission; n=3), completed a comprehensive neurocognitive, substance use, and behavioral health assessment battery. Results 64.7% of youth met criteria for HAND (96.4% asymptomatic, 3.5% syndromic), with deficits in episodic memory and fine-motor skills emerging as the most commonly affected ability areas. Multivariable models showed that lower CD4 count, longer time since HIV diagnosis, and high risk alcohol use were uniquely associated with neurocognitive deficits. Conclusions Over two-thirds of youth with behaviorally acquired HIV evidence neurocognitive deficits, which have modest associations with more advanced HIV disease as well as other factors. Research is needed to determine the impact of such neuropsychiatric morbidity on mental health and HIV disease treatment outcomes (e.g., non-adherence) and transition to independent living responsibilities in HIV-infected youth, as well as its long-term trajectory and possible responsiveness to cognitive rehabilitation and pharmacotherapy. PMID:23972941

  13. Antiretroviral drug supply challenges in the era of scaling up ART in Malawi.

    PubMed

    Schouten, Erik J; Jahn, Andreas; Ben-Smith, Anne; Makombe, Simon D; Harries, Anthony D; Aboagye-Nyame, Francis; Chimbwandira, Frank

    2011-01-01

    The number of people receiving antiretroviral treatment (ART) has increased considerably in recent years and is expected to continue to grow in the coming years. A major challenge is to maintain uninterrupted supplies of antiretroviral (ARV) drugs and prevent stock outs. This article discusses issues around the management of ARVs and prevention of stock outs in Malawi, a low-income country with a high HIV/AIDS burden, and a weak procurement and supply chain management system. This system for ARVs, paid for by the Global Fund to Fight AIDS, Tuberculosis and Malaria, and bypassing the government Central Medical Stores, is in place, using the United Nations Children's Fund's (UNICEF's) procurement services. The system, managed by a handful of people who spend limited time on supply management, is characterized by a centrally coordinated quantification based on verified data from all national ART clinics, parallel procurement through UNICEF, and direct distribution to ART clinics. The model worked well in the first years of the ART programme with a single first-line ARV regimen, but with more regimens becoming available (e.g., alternative first-line, second-line and paediatric regimens), it has become more difficult to administer. Managing supplies through a parallel system has the advantage that weaknesses in the national system have limited influence on the ARV procurement and supply chain management system. However, as the current system operates without a central warehouse and national buffer stock capacity, it diminishes the ability to prevent ARV stock outs. The process of ordering ARVs, from the time that estimates are made to the arrival of supplies in health facilities, takes approximately one year. Addressing the challenges involved in maintaining ARVs through an efficient procurement and supply chain management system that prevents ARV stock outs through the establishment of a dedicated procurement team, a central warehouse and/or national buffer stock is a priority. PMID:21967844

  14. Antiretroviral Treatment Interruptions Predict Female Genital Shedding of Genotypically Resistant HIV-1 RNA

    PubMed Central

    GRAHAM, Susan M.; JALALIAN-LECHAK, Zahra; SHAFI, Juma; CHOHAN, Vrasha; DEYA, Ruth W.; JAOKO, Walter; MANDALIYA, Kishor N.; PESHU, Norbert M.; OVERBAUGH, Julie; MCCLELLAND, R. Scott

    2012-01-01

    Objectives Resistant viruses may emerge in the female genital tract during antiretroviral therapy (ART). Our objective was to identify predictors of drug-resistant HIV-1 RNA in genital secretions after initiation of non-nucleoside reverse transcriptase inhibitor (NNRTI)-based therapy. Design We conducted a prospective cohort study with periodic evaluation of plasma and genital swab samples for HIV-1 RNA levels and antiretroviral resistance mutations. Methods First-line ART was initiated in 102 women. Plasma and genital HIV-1 RNA levels were measured at months 0, 3, 6, and 12. Genotypic resistance testing was performed for samples from all participants with RNA >1,000 copies/mL at month 6 or 12. Cox regression analysis was used to identify factors associated with incident genital tract resistance. Results Detectable genital tract resistance developed in 5 women, all with detectable plasma resistance (estimated incidence, 5.5/100 person-years of observation). Treatment interruption >48 hours, adherence by pill count, adherence by visual analog scale, and baseline plasma viral load were associated with incident genital tract resistance. In multivariate analysis, only treatment interruption was associated with risk of detectable genital tract resistance (adjusted hazard ratio 14.2, 95% CI 1.3–158.4). Conclusions Treatment interruption >48 hours during NNRTI-based therapy led to a significantly increased risk of detecting genotypically resistant HIV-1 RNA in female genital tract secretions. Patient- and program-level interventions to prevent treatment interruptions could reduce the risk of shedding resistant HIV-1 during ART. PMID:22592588

  15. Patterns of geographic mobility predict barriers to engagement in HIV care and antiretroviral treatment adherence.

    PubMed

    Taylor, Barbara S; Reyes, Emily; Levine, Elizabeth A; Khan, Shah Z; Garduńo, L Sergio; Donastorg, Yeycy; Hammer, Scott M; Brudney, Karen; Hirsch, Jennifer S

    2014-06-01

    Migration and geographic mobility increase risk for HIV infection and may influence engagement in HIV care and adherence to antiretroviral therapy. Our goal is to use the migration-linked communities of Santo Domingo, Dominican Republic, and New York City, New York, to determine the impact of geographic mobility on HIV care engagement and adherence to treatment. In-depth interviews were conducted with HIV+Dominicans receiving antiretroviral therapy, reporting travel or migration in the past 6 months and key informants (n=45). Mobility maps, visual representations of individual migration histories, including lifetime residence(s) and all trips over the past 2 years, were generated for all HIV+ Dominicans. Data from interviews and field observation were iteratively reviewed for themes. Mobility mapping revealed five distinct mobility patterns: travel for care, work-related travel, transnational travel (nuclear family at both sites), frequent long-stay travel, and vacation. Mobility patterns, including distance, duration, and complexity, varied by motivation for travel. There were two dominant barriers to care. First, a fear of HIV-related stigma at the destination led to delays seeking care and poor adherence. Second, longer trips led to treatment interruptions due to limited medication supply (30-day maximum dictated by programs or insurers). There was a notable discordance between what patients and providers perceived as mobility-induced barriers to care and the most common barriers found in the analysis. Interventions to improve HIV care for mobile populations should consider motivation for travel and address structural barriers to engagement in care and adherence. PMID:24839872

  16. Alternative starting materials for industrial processes.

    PubMed Central

    Mitchell, J W

    1992-01-01

    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 PMID:11607260

  17. Prenflo gasifier starts up in August

    SciTech Connect

    Not Available

    1986-12-01

    Operation of the PRENFLO coal gasification test unit at Fuerstenhausen, West Germany was started on August 12, 1986. The basic design features incorporated in the PRENFLO process include: pressurized entrained-flow coal gasification; dry coal dust feeding; operating pressure range between 20 and 60 bar; and standardized capacity of 1000 metric tons of coal per day, with a potential increase of up to 2500 metric tons per day. Presently, the product gas is sent to an adjacent coke oven plant where it is mixed with the coke oven gas, desulfurized and used to underfire the coke ovens. Preliminary performance data and coal gas composition are given. 3 figures, 2 tables.

  18. K.CC Start-Stop Counting

    NSDL National Science Digital Library

    2012-05-01

    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...

  19. Prospective Immune Dynamics during the First 24 Weeks of Efavirenz Based-Antiretroviral Therapy in HIV-1-Infected Subjects, According to CD4+ T-Cell Counts at Presentation: The IMMUNEF Clinical Trial

    PubMed Central

    Soria, Alessandro; Trabattoni, Daria; Squillace, Nicola; Rainone, Veronica; Gnudi, Federica; Clerici, Mario; Gori, Andrea; Bandera, Alessandra

    2015-01-01

    Background Longitudinal characterization of immune recovery in the first-phase of antiretroviral therapy (ART) is poorly described. We compared immune kinetics in individuals who were diagnosed early or late with HIV-1 infection, (thus commencing ART with different CD4+ T-cell counts), in order to investigate possible mechanisms involved in subsequent poor immune recovery. Methods Immunophenotyping, immune activation, proliferation, apoptosis, regulatory T-cells and intracellular cytokine production were compared at baseline and during 24-week follow-up in two groups of HIV-1-infected patients initiating the same ART (tenofovir/emtricitabine/efavirenz) and divided according to baseline CD4+ T-cell counts (late: ?200/?L; early: >200/?L). Wilcoxon-rank sum test and analysis for repeated measures were used to evaluate differences between groups over time. Results Twenty-four out of 30 enrolled subjects were evaluable for the analysis, 13 late and 11 early presenters. Significantly lower CD4+ naďve and memory T-cells, and higher plasma viral load, as well as augmented percentages of activated (CD4+/CD25+ cells), apoptotic (CD4+/AnnexinV+/7AAD?, CD4+/caspase 8+ and CD4+/caspase 9+), and proliferating (CD8+/Ki67+ cells) lymphocytes were present at baseline in late presenters; ART resulted in a reduction of apoptotic and proliferating lymphocytes within the follow-up period. Conclusions A skewing towards memory/activated/apoptotic phenotype is seen in HIV-1-infected subjects starting ART at low CD4+ T-cell counts; ART results in early (24 weeks) trend towards normalization of these parameters. Antiretroviral therapy may play a role in rapidly limiting aberrant immune exhaustion even in late presenters, while requiring more time for re-population of highly depleted naďve T-cells. Trial Registration EU Clinical Trial Register EUDRACT number 2008-006188-35 https://www.clinicaltrialsregister.eu/ctr-search/trial/2008-006188-35/IT PMID:25671649

  20. A QuickStart Guide to printing a

    E-print Network

    A QuickStart Guide to printing a 3D model starting from a block of bytes Bridget CarragherStart Guide to printing a 3D model starting from a block of bytes This is currently a three step process. (1 and selecting a new size (of 3 inches for example). Once you have done this, choose Print from the File menu

  1. Head Start Goes to School: 1995-96 Evaluation Report.

    ERIC Educational Resources Information Center

    Mulholland, Lori; Shaw, Kathleen; Heffernon, Rick; Stafford, Mary E.

    The Arizona Head Start--Public School Transition Project is 1 of 31 demonstration projects designed to test whether advances by Head Start children could be maintained by continuing Head Start-type services into kindergarten through the third grade, and to identify, develop, and implement transition practices to bridge the gap between Head Start

  2. College Of Geosciences New Faculty Start-Up Funds Policy

    E-print Network

    including discussion of salary, space, and start-up needs. No start-up funds offer will be made without to the College. (3) Start-up funds may be used for graduate assistant salaries, but may not be used for post- doctoral research associate salaries. (4) Start-up funds may be used for a maximum of one month of summer

  3. 40 CFR 1065.525 - Engine starting, restarting, and shutdown.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...engine starting, start the engine using one of the following methods: (1) Start the engine as recommended in the owners...charged battery, a suitable power supply, or a suitable compressed air...the dynamometer to start the engine. To do this, motor the...

  4. 40 CFR 1065.525 - Engine starting, restarting, and shutdown.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...engine starting, start the engine using one of the following methods: (1) Start the engine as recommended in the owners...charged battery, a suitable power supply, or a suitable compressed air...the dynamometer to start the engine. To do this, motor the...

  5. 40 CFR 1065.525 - Engine starting, restarting, and shutdown.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...engine starting, start the engine using one of the following methods: (1) Start the engine as recommended in the owners...charged battery, a suitable power supply, or a suitable compressed air...the dynamometer to start the engine. To do this, motor the...

  6. Evaluation of a training program to increase the capacity of health care providers to provide antiretroviral therapy to pediatric patients in sub-Saharan Africa

    Microsoft Academic Search

    Harrison N Kamiru

    2006-01-01

    More than 810,000 people from sub-Saharan Africa had accessed antiretroviral therapy by the end of 2005. This represented a marked scale up in provision of antiretroviral therapy (ART) in sub-Saharan Africa but there are still many challenges in delivering ART especially to children. Baylor International Pediatric AIDS Initiative (BIPAI) offered the Swaziland government this service for the pediatric population. ^

  7. CD4 Response Up to 5 Years After Combination Antiretroviral Therapy in Human Immunodeficiency Virus-Infected Patients in Latin America and the Caribbean

    PubMed Central

    Luz, Paula M.; Belaunzarán-Zamudio, Pablo F.; Crabtree-Ramírez, Brenda; Caro-Vega, Yanink; Hoces, Daniel; Rebeiro, Peter F.; Blevins, Meridith; Pape, Jean W.; Cortes, Claudia P.; Padgett, Denis; Cahn, Pedro; Veloso, Valdilea G.; McGowan, Catherine C.; Grinsztejn, Beatriz; Shepherd, Bryan E.

    2015-01-01

    We describe CD4 counts at 6-month intervals for 5 years after combination antiretroviral therapy initiation among 12 879 antiretroviral-naive human immunodeficiency virus-infected adults from Latin America and the Caribbean. Median CD4 counts increased from 154 cells/mm3 at baseline (interquartile range [IQR], 60–251) to 413 cells/mm3 (IQR, 234–598) by year 5. PMID:26180829

  8. Gender Inequities in Quality of Care among HIV-Positive Individuals Initiating Antiretroviral Treatment in British Columbia, Canada (2000–2010)

    PubMed Central

    Carter, Allison; Eun Min, Jeong; Chau, William; Lima, Viviane D.; Kestler, Mary; Pick, Neora; Money, Deborah; Montaner, Julio S G.; Hogg, Robert S.; Kaida, Angela

    2014-01-01

    Objectives We measured gender differences in “Quality of Care” (QOC) during the first year after initiation of antiretroviral therapy and investigated factors associated with poorer QOC among women. Design QOC was estimated using the Programmatic Compliance Score (PCS), a validated metric associated with all-cause mortality, among all patients (?19 years) who initiated ART in British Columbia, Canada (2000–2010). Methods PCS includes six indicators of non-compliance with treatment initiation guidelines at baseline (not having drug resistance testing before treatment; starting on a non-recommended regimen; starting therapy at CD4<200 cells/mm3) and during first-year follow-up (receiving <3 CD4 tests; receiving <3 viral load tests; not achieving viral suppression within six months). Summary scores range from 0–6; higher scores indicate poorer QOC. Multivariable ordinal logistic regression was used to measure if female gender was an independent predictor of poorer QOC and factors associated with poorer QOC among women. Results QOC was determined for 3,642 patients (20% women). At baseline: 42% of women (34% men) did not have resistance testing before treatment; 17% of women (9% men) started on a non-recommended regimen (all p<0.001). At follow-up: 17% of women (11% men) received <3 CD4; 17% of women (11% men) received <3 VL; 50% of women (41% men) did not achieve viral suppression (all p<0.001). Overall, QOC was better among men (mean PSC?=?1.54 (SD?=?1.30)) compared with women (mean?=?1.89 (SD?=?1.37); p<0.001). In the multivariable model, female gender (AOR?=?1.16 [95% CI: 0.99–1.35]; p?=?0.062) remained associated with poorer QOC after covariate adjustment. Among women, those with injection drug use history, of Aboriginal ancestry, from Vancouver Island, and who initiated ART in earlier years were more likely to have poorer QOC. Conclusions Poorer QOC among women, especially from marginalized communities, demands that barriers undermining women's access to high-quality care be addressed to improve treatment and health for women with HIV. PMID:24642949

  9. The GlueX Start Counter

    NASA Astrophysics Data System (ADS)

    Pooser, Eric; GlueX Collaboration

    2014-09-01

    The GlueX experiment will study meson photoproduction with unprecedented precision. This experiment will use the coherent bremsstrahlung technique to produce a 9 GeV linearly polarized photon beam incident on a liquid H2 target. A Start Counter detector has been fabricated to identify the accelerator electron beam buckets, approximately 2 ns apart, and to provide accurate timing information which is used in the level-1 trigger of the experiment. This detector is designed to operate at photon intensities of up to 108 ? / s in the coherent peak and provide a timing resolution <350 ps so as to provide successful identification of the electron beam buckets to within 99% accuracy. Furthermore, the Start Counter detector will provide excellent solid angle coverage, ~90% of 4? hermeticity, and a high degree of segmentation for background rejection. It consists of a cylindrical array of 30 scintillators with pointed ends that bend towards the beam at the downstream end. Silicon PhotoMultiplier (SiPM) detectors have been selected as the readout system. The physical properties of the scintillators, have been studied extensively at FIU. The results of these studies are discussed.

  10. The GlueX Start Counter

    NASA Astrophysics Data System (ADS)

    Llodra, Anthony; Pooser, Eric; GlueX Collaboration

    2015-04-01

    The GlueX experiment, which is online as of October of 2014, will study meson photo production with unprecedented precision. This experiment will use the coherent bremsstrahlung technique to produce a 9 GeV linearly polarized photon beam incident on a liquid H2 target kept at a few degrees Kelvin. A Start Counter detector has been fabricated to identify the accelerator electron beam buckets, approximately 2 nanoseconds apart, and to provide accurate timing information. This detector is designed to operate at photon intensities of up to 108 ?/s in the coherent peak and provide a timing resolution of less than 350 picoseconds so as to provide successful identification of the electron beam buckets. It consists of a cylindrical array of 30 scintillators with pointed ends that bend towards the beam at the downstream end. The EJ-200 scintillator is best suited for the Start Counter due to its fast decay time on the order of 2 nanoseconds and long attenuation length. Silicon Photo Multiplier (SiPM) detectors have been selected as the readout system and are to be placed as close as possible, less than 300 micron, to the upstream end of each scintillator. The methods/details of the assembly and the optimization of the surface quality of scintillator paddles are discussed. This work was supported in part by DoE Contracts DE-FG02-99ER41065 and DE-AC05-06OR23177.

  11. Analyses of HIV-1 Drug-Resistance Profiles Among Infected Adolescents Experiencing Delayed Antiretroviral Treatment Switch After Initial Nonsuppressive Highly Active Antiretroviral Therapy

    PubMed Central

    Agwu, Allison; Lindsey, Jane C.; Ferguson, Kimberly; Zhang, Haili; Spector, Stephen; Rudy, Bret J.; Ray, Stuart C.; Douglas, Steven D.; Flynn, Patricia M.

    2008-01-01

    Abstract Treatment failure and drug resistance create obstacles to long-term management of HIV-1 infection. Nearly 60% of infected persons fail their first highly active antiretroviral therapy (HAART) regimen, partially because of nonadherence, requiring a switch to a second regimen to prevent drug resistance. Among HIV-infected youth, a group with rising infection rates, treatment switch is often delayed; virologic and immunologic consequences of this delay are unknown. We conducted a retrospective, longitudinal study of drug resistance outcomes of initial HAART in U.S. youth enrolled between 1999–2001 in a multicenter, observational study and experiencing delayed switch in their first nonsuppressive treatment regimen for up to 3 years. HIV-1 genotyping was performed on plasma samples collected longitudinally, and changes in drug resistance mutations, CD4+ T cell numbers and viral replication capacity were assessed. Forty-four percent (n = 18) of youth in the parent study experiencing virologic nonsuppression were maintained on their initial HAART regimen for a median of 144 weeks. Drug resistance was detected in 61% (11/18) of subjects during the study. Subjects on non-nucleoside reverse transcriptase inhibitor (NNRTI) regimens developed more (8/10) drug resistance mutations than those on protease-inhibitor (PI) regimens (2/7) (p = 0.058). Subjects developing NNRTI-resistance (NNRTI-R), showed a trend toward lower CD4+ T cell gains (median:??6?cells/mm3 per year) than those without detectable NNRTI-R (median:?+149?cells/mm3 per year) (p = 0.16). HIV-1–infected youth maintained on initial nonsuppressive NNRTI-based HAART regimens are more likely to develop drug-resistant viremia than with PI-based HAART. This finding may have implications for initial treatment regimens and transmission risk in HIV-infected youth, a group with rising infection rates. PMID:18479228

  12. Rapid scaling-up of antiretroviral therapy in 10,000 adults in Côte d’Ivoire: two-year outcomes and determinants

    PubMed Central

    Toure, Siaka; Kouadio, Bertin; Seyler, Catherine; Traore, Moussa; Dakoury-Dogbo, Nicole; Duvignac, Julien; Diakite, Nafissatou; Karcher, Sophie; Grundmann, Christophe; Marlink, Richard; Dabis, François; Anglaret, Xavier

    2013-01-01

    Objective To assess the rates and determinants of mortality, loss-to-follow-up (LTFU) and immunological failure in a non governmental organization implemented program of access to antiretroviral treatment (ART) in Côte d’Ivoire. Methods In each new treatment center, professionals were trained in HIV care, and a computerized data system was implemented. Individual patient and program level determinants of survival, LTFU and immunological failure were assessed by multivariate analysis. Results Between May 2004 and February 2007, 10,211 patients started ART in 19 clinics (median pre-ART CD4 count 123/mm3, initial regimen ZDV-3TC-EFV 20%, d4T-3TC-EFV 22%, d4T-3TC-NVP 52%). At 18 months on ART, the median gain in CD4 cells was +202/mm3, the probability of death was 0.15 and the probability of being LTFU was 0.21. In addition to the commonly reported determinants of impaired outcomes (low CD4 count, low body mass index, low hemoglobin, advanced clinical stage, older age and poor adherence), two factors were also shown to independently jeopardize prognosis: (i) male sex (men vs. women: hazard ratio [HR]=1.52 for death, HR=1.27 for LTFU, HR=1.31 for immunological failure); and (ii) attending a recently opened clinic (unexperienced vs. experienced centres: HR=1.40 for death, HR=1.58 for LTFU). None of the three outcomes was associated with the drug regimen. Discussion In this rapidly scaling-up programme: survival and immune reconstitution were good; women and patients followed-up in centres with longer experience had better outcomes; outcomes were similar in ZDV/d4t-based regimens and in EFV/NVP-based regimens. Decreasing the rate of LTFU should now be the top priority in ART roll-out. PMID:18427206

  13. Mortality trends in the era of antiretroviral therapy: evidence from the Network for Analysing Longitudinal Population based HIV/AIDS data on Africa (ALPHA)

    PubMed Central

    Reniers, Georges; Slaymaker, Emma; Nakiyingi-Miiro, Jessica; Nyamukapa, Constance; Crampin, Amelia Catharine; Herbst, Kobus; Urassa, Mark; Otieno, Fred; Gregson, Simon; Sewe, Maquins; Michael, Denna; Lutalo, Tom; Hosegood, Victoria; Kasamba, Ivan; Price, Alison; Nabukalu, Dorean; Mclean, Estelle; Zaba, Basia

    2014-01-01

    Background: The rollout of antiretroviral therapy (ART) is one of the largest public health interventions in Eastern and Southern Africa of recent years. Its impact is well described in clinical cohort studies, but population-based evidence is rare. Methods: We use data from seven demographic surveillance sites that also conduct community-based HIV testing and collect information on the uptake of HIV services. We present crude death rates of adults (aged 15–64) for the period 2000–2011 by sex, HIV status, and treatment status. Parametric survival models are used to estimate age-adjusted trends in the mortality rates of people living with HIV (PLHIV) before and after the introduction of ART. Results: The pooled ALPHA Network dataset contains 2.4 million person-years of follow-up time, and 39114 deaths (6893 to PLHIV). The mortality rates of PLHIV have been relatively static before the availability of ART. Mortality declined rapidly thereafter, with typical declines between 10 and 20% per annum. Compared with the pre-ART era, the total decline in mortality rates of PLHIV exceeds 58% in all study sites with available data, and amounts to 84% for women in Masaka (Uganda). Mortality declines have been larger for women than for men; a result that is statistically significant in five sites. Apart from the early phase of treatment scale up, when the mortality of PLHIV on ART was often very high, mortality declines have been observed in PLHIV both on and off ART. Conclusion: The expansion of treatment has had a large and pervasive effect on adult mortality. Mortality declines have been more pronounced for women, a factor that is often attributed to women's greater engagement with HIV services. Improvements in the timing of ART initiation have contributed to mortality reductions in PLHIV on ART, but also among those who have not (yet) started treatment because they are increasingly selected for early stage disease. PMID:25406756

  14. Predictors of CD4:CD8 Ratio Normalization and Its Effect on Health Outcomes in the Era of Combination Antiretroviral Therapy

    PubMed Central

    Leung, Victor; Gillis, Jennifer; Raboud, Janet; Cooper, Curtis; Hogg, Robert S.; Loutfy, Mona R.; Machouf, Nima; Montaner, Julio S. G.; Rourke, Sean B.; Tsoukas, Chris; Klein, Marina B.

    2013-01-01

    Background HIV leads to CD4:CD8 ratio inversion as immune dysregulation progresses. We examined the predictors of CD4:CD8 normalization after combination antiretroviral therapy (cART) and determined whether normalization is associated with reduced progression to AIDS-defining illnesses (ADI) and death. Methods A Canadian cohort of HIV-positive adults with CD4:CD8<1.2 prior to starting cART from 2000–2010 were analyzed. Predictors of (1) reaching a CD4:CD8 ?1.2 on two separate follow-up visits >30 days apart, and (2) ADI and death from all causes were assessed using adjusted proportional hazards models. Results 4206 patients were studied for a median of 2.77 years and 306 (7.2%) normalized their CD4:CD8 ratio. Factors associated with achieving a normal CD4:CD8 ratio were: baseline CD4+ T-cells >350 cells/mm3, baseline CD8+ T-cells <500 cells/mm3, time-updated HIV RNA suppression, and not reporting sex with other men as a risk factor. There were 213 ADIs and 214 deaths in 13476 person-years of follow-up. Achieving a normal CD4:CD8 ratio was not associated with time to ADI/death. Conclusions In our study, few individuals normalized their CD4:CD8 ratios within the first few years of initiating modern cART. This large study showed no additional short-term predictive value of the CD4:CD8 ratio for clinical outcomes after accounting for other risk factors including age and HIV RNA. PMID:24204912

  15. Nine-year follow-up of HIV-infected Romanian children and adolescents receiving lopinavir/ritonavir-containing highly active antiretroviral therapy

    PubMed Central

    Wanless, Richard S.B.; Rugin?, Sorin; Ru??, Simona Maria; Dumitru, Irina-Magdalena; Cernat, Roxana Carmen; Schwarzwald, Heidi L.; Calles, Nancy R.; Schutze, Gordon E.; Schweitzer, Ana-Maria; Draper, Heather R.; Kline, Mark W.

    2013-01-01

    Introduction Many Romanian children were infected nosocomially with human immunodeficiency virus (HIV) in the late 1980s. The Romanian-American Children's Center of Excellence in Constan?a continues to follow approximately 450 of these patients. In 2001, 414 of these patients were initiated on triple therapy including lopinavir/ritonavir. Data from this cohort treated through August 2006 were published in April 2007 demonstrating that the treatment was well tolerated, with 337 children (81%) remaining on therapy after a median duration of >4 years. The current article describes the results of continued analysis of this cohort through end 2010. The objective of the study was to determine the long-term clinical outcomes of children and adolescents commenced on antiretroviral therapy (ART) including lopinavir/ritonavir. Methods Data were extracted retrospectively from the charts of the 336 patients remaining on lopinavir/ritonavir in August 2006. The following outcomes were analyzed: mortality, current patient status, viral load (VL), CD4 counts and reasons for discontinuation of lopinavir/ritonavir. Results The median age at initiation of lopinavir/ritonavir was 14.0 years (range 5.4 to 20.0 years). The median time on lopinavir/ritonavir treatment was 7.5 years (interquartile range 5.7 to 8.6 years). Overall mortality was 13.5%. Of the original 414 patients started on lopinavir/ritonavir in 2001, 199 (48.1%) remained on this therapy at the end of 2010 and of these 63.8% had undetectable viral load. Conclusion Despite initial suboptimal ART, a significant proportion of patients subsequently treated with a lopinavir/ritonavir based regimen remained on this therapy for up to nine years. PMID:24432292

  16. Multicentric Castleman’s Disease and Kaposi’s Sarcoma in a HIV-Positive Patient on Highly Active Antiretroviral Therapy

    PubMed Central

    Ortega, Lauro; Cooper, Chad J.; Otoukesh, Salman; Mojtahedzadeh, Mona; Didia, Claudia S.; Torabi, Alireza; Nahleh, Zeina

    2014-01-01

    Castleman’s disease is a group of rare lymphoproliferative disorders. The plasmablastic multicentric Castleman’s disease is frequently discovered in HIV-infected individuals in association with Kaposi sarcoma (HHV-8). Thirty-five year old male presented to our care with the main compliant of severe back pain for one week. His past medical problems include acquired immune deficiency syndrome diagnosed 12 years prior and Kaposi sarcoma, currently on highly active antiretroviral therapy (HAART). Radiographic imaging revealed hepatomegaly and diffuse lymphadenopathy. The HIV viral load was <20 polymerase chain reaction copies/mL, absolute CD4 count was 453 cells/mcL (490-1740 cells/mcL) and CD8 count was 4142 cells/mcL (180-1170 cells/ mcL). Excisional biopsy of the left supraclavicular lymph node was performed with pathological findings of HHV8+ Kaposi sarcoma in the background of multicentric Castleman’s disease (plasmacytic variant). No evidence of transformation into large B-cell or plasmablastic lymphoma was noted. He was discharged on HAART and follow up to receive chemotherapy with cyclophosphamide, adriamycin, vincristine plus prednisone was started and rituximab plus prophylaxis for pneumocystis carinii. Multicentric Castleman’s disease has become more relevant in recent years due to its association with HIV and HHV-8 (Kaposi sarcoma) and its potential to progress into plasmablastic B-cell lymphoma. The progression of MCD to B-cell lymphoma is a concern, especially in patients with HIV infection because it precludes the worst outcome and a high mortality, despite treatment. The most intriguing part of this case is that MCD occurred in a HIV-positive on HAART. This case signals a warning that a high suspicion for MCD can be justified even in those HIV-positive patients on HAART because the possibly of progression to plasmablastic B-cell lymphoma. PMID:25276327

  17. Expanded access to highly active antiretroviral therapy: a potentially powerful strategy to curb the growth of the HIV epidemic.

    PubMed

    Lima, Viviane D; Johnston, Karissa; Hogg, Robert S; Levy, Adrian R; Harrigan, P Richard; Anema, Aranka; Montaner, Julio S G

    2008-07-01

    We developed a mathematical model using a multiple source of infection framework to assess the potential effect of the expansion of highly active antiretroviral therapy (HAART) coverage among those in medical need on the number of individuals testing newly positive for human immunodeficiency virus (HIV) and on related costs in British Columbia, Canada, over the next 25 years. The model was calibrated using retrospective data describing antiretroviral therapy utilization and individuals testing newly positive for HIV in the province. Different scenarios were investigated on the basis of varying assumptions regarding drug resistance, adherence to HAART, therapeutic guidelines, degree of HAART coverage, and the timing of HAART uptake. Expansion of HAART lead to substantial reductions in the growth of the HIV epidemic and related costs. These results provide powerful additional motivation to accelerate the roll out of HAART programs aggressively targeting those in medical need, both for their own benefit and as a means of decreasing new HIV infections. PMID:18498241

  18. Antiretroviral therapy for adults infected with HIV: Guidelines for health care professionals from the Quebec HIV care committee

    PubMed Central

    Rouleau, Danielle; Fortin, Claude; Trottier, Benoît; Lalonde, Richard; Lapointe, Normand; Côté, Pierre; Routy, Jean-Pierre; Matte, Marie-France; Tsarevsky, Irina; Baril, Jean-Guy

    2011-01-01

    The appropriate use of antiretrovirals reduces morbidity and mortality caused by HIV infection. The present article provides health care professionals with a practical guide for the use of antiretrovirals. Therapy should be initiated based predominantly on clinical presentation and CD4 count, and should consist of three active drugs or at least two active drugs when this is not possible, as in cases of some treatment-experienced patients. This is the most effective way to achieve long-term suppression of viral replication. Selection of individual drugs in the regimen should consider the weight of the evidence supporting these choices, as well as their tolerability profiles and ease of use, the patients’ comorbidities and treatment history. Treatment interruption is not recommended, either in aviremic patients or in those who have experienced virological failure. Instead, the therapeutic regimen should be adjusted to minimize side effects, promote adherence and suppress viral replication. PMID:22654926

  19. The structure of compressible starting vortices

    NASA Astrophysics Data System (ADS)

    Lee, S.; Bershader, D.

    1994-02-01

    The structures of highly two-dimensional shock-induced compressible starting vortices were investigated. Density distributions across the vortex were measured by dual-pulsed holographic interferometry. Pressure profiles of the vortex were measured by fast-response miniature Kulite transducers. From these two independent measurements the velocity profile was calculated using the radial momentum equation. The detailed vortex structure is similar to that from the tip of a wing and consists of four well-defined regions: a core region, a logarithmic region, a transition region, and an inviscid region. The distribution of circulation of the vortices can be expressed by a set of empirical formulae. The proportionality constants of the logarithmic region were found to be 0.43±0.01 for three different two-dimensional vortices.

  20. Independent to start gas flow in Moldova

    SciTech Connect

    NONE

    1997-02-03

    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.