Science.gov

Sample records for starting nevirapine-containing antiretroviral

  1. Artemether-Lumefantrine Exposure in HIV-Infected Nigerian Subjects on Nevirapine-Containing Antiretroviral Therapy.

    PubMed

    Parikh, Sunil; Fehintola, Fatai; Huang, Liusheng; Olson, Alexander; Adedeji, Waheed A; Darin, Kristin M; Morse, Gene D; Murphy, Robert L; Taiwo, Babafemi O; Akinyinka, Olusegun O; Adewole, Isaac F; Aweeka, Francesca T; Scarsi, Kimberly K

    2015-12-01

    Coadministration of nevirapine-based antiretroviral therapy (ART) and artemether-lumefantrine is reported to result in variable changes in lumefantrine exposure. We conducted an intensive pharmacokinetic study with 11 HIV-infected adults who were receiving artemether-lumefantrine plus nevirapine-based ART, and we compared the results with those for 16 HIV-negative adult historical controls. Exposure to artemether and lumefantrine was significantly lower and dihydroartemisinin exposure was unchanged in subjects receiving nevirapine-based ART, compared with controls. Nevirapine exposure was unchanged before and after artemether-lumefantrine administration. PMID:26392500

  2. Disposition of amodiaquine and desethylamodiaquine in HIV-infected Nigerian subjects on nevirapine-containing antiretroviral therapy

    PubMed Central

    Scarsi, Kimberly K.; Fehintola, Fatai A.; Ma, Qing; Aweeka, Francesca T.; Darin, Kristin M.; Morse, Gene D.; Akinola, Ibrahim Temitope; Adedeji, Waheed A.; Lindegardh, Niklas; Tarning, Joel; Ojengbede, Oladosu; Adewole, Isaac F.; Taiwo, Babafemi; Murphy, Robert L.; Akinyinka, Olusegun O.; Parikh, Sunil

    2014-01-01

    Objectives Artesunate plus amodiaquine is used for malaria treatment in regions with overlapping HIV endemicity. Co-administration of artesunate/amodiaquine with antiretroviral therapy (ART) may result in drug–drug interactions, but minimal data exist. This study evaluated the impact of nevirapine-based ART, containing a backbone of zidovudine and lamivudine, on the disposition of amodiaquine and its active metabolite, desethylamodiaquine (DEAQ). Methods This was an open-label, parallel-group pharmacokinetic comparison between HIV-infected, adult subjects receiving steady-state nevirapine-based ART (n?=?10) and ART-naive subjects (control group, n?=?11). All subjects received a loose formulation of artesunate/amodiaquine (200/600 mg) daily for 3 days, with serial pharmacokinetic sampling over 96 h following the final dose of artesunate/amodiaquine. Amodiaquine and DEAQ were quantified using a validated HPLC method with UV detection. Pharmacokinetic parameters were determined using standard non-compartmental methods. Results Exposures to both amodiaquine and DEAQ were significantly lower in the nevirapine-based ART group compared with the control group (amodiaquine AUC0–24 145 versus 204 ng·h/mL, P?=?0.02; DEAQ AUC0–96 14?571 versus 21?648 ng·h/mL, P?

  3. When to Start Antiretroviral Therapy

    MedlinePLUS

    HIV Treatment When to Start Antiretroviral Therapy (Last updated 4/28/2015; last reviewed 4/28/2015) Key Points Antiretroviral therapy (ART) is the use ... make adherence difficult. When is it time to start treatment with HIV medicines? Treatment with HIV medicines ( ...

  4. Case Report: Stevens-Johnson syndrome following a single double dosing of nevirapine-containing regimen once in an HIV-infected woman on long-term antiretroviral therapy.

    PubMed Central

    Kakande, Betty; Isaacs, Thuraya; Muloiwa, Rudzani; Dlamini, Sipho; Lehloenya, Rannakoe

    2015-01-01

    A 31-year old HIV-infected African woman on nevirapine, tenofovir and lamivudine for more than 4 years presented with an 8-day history of symptoms and signs of Stevens-Johnson syndrome. She was on no other medication. Her viral load was undetectable and she had maintained a CD4 count of between 356 and 387cells/mm 3 in the preceding 2½ years. She missed her antiretrovirals 10 days before the onset of her symptoms and subsequently doubled her daily dose the following day. She had been on no other medication in the preceding 8 weeks. Her ARVs were stopped and she fully re-epithelialized with the exception of the lips, over the following 10 days. She was started on a daily single tablet of Odimune® (a fixed drug combination antiretroviral containing tenofovir, emtricitabine and efavirenz). Nevirapine is the most common offender in cases of antiretroviral-associated SJS in published literature. Lamivudine is very rarely implicated while there are no similar reports with tenofovir.  We concluded that nevirapine was by far the most likely offender in this case. Nevirapine toxicity is associated with high CD4 counts, undetectable viral load and high drug plasma level. We postulate that the sudden increase of the plasma levels of nevirapine in a patient with a high CD4 count and undetectable viral load created a perfect storm for the development of SJS in our patient, who had been on the NVP-containing regimen for many years. Clinicians should be aware that severe adverse drug reactions are dynamic and can occur even when the drug has been in use for a long time.

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

    PubMed Central

    2013-01-01

    Objective To compare regimens consisting of either efavirenz or nevirapine and two or more nucleoside reverse transcriptase inhibitors (NRTIs) among HIV-infected, antiretroviral-naive, and AIDS-free individuals with respect to clinical, immunologic, and virologic outcomes. Design Prospective studies of HIV-infected individuals in Europe and the US included in the HIV-CAUSAL Collaboration. Methods Antiretroviral therapy-naive and AIDS-free individuals were followed from the time they started an NRTI, efavirenz or nevirapine, classified as following one or both types of regimens at baseline, and censored when they started an ineligible drug or at 6 months if their regimen was not yet complete. We estimated the ‘intention-to-treat’ effect for nevirapine versus efavirenz regimens on clinical, immunologic, and virologic outcomes. Our models included baseline covariates and adjusted for potential bias introduced by censoring via inverse probability weighting. Results A total of 15 336 individuals initiated an efavirenz regimen (274 deaths, 774 AIDS-defining illnesses) and 8129 individuals initiated a nevirapine regimen (203 deaths, 441 AIDS-defining illnesses). The intention-to-treat hazard ratios [95% confidence interval (CI)] for nevirapine versus efavirenz regimens were 1.59 (1.27, 1.98) for death and 1.28 (1.09, 1.50) for AIDS-defining illness. Individuals on nevirapine regimens experienced a smaller 12-month increase in CD4 cell count by 11.49 cells/?l and were 52% more likely to have virologic failure at 12 months as those on efavirenz regimens. Conclusions Our intention-to-treat estimates are consistent with a lower mortality, a lower incidence of AIDS-defining illness, a larger 12-month increase in CD4 cell count, and a smaller risk of virologic failure at 12 months for efavirenz compared with nevirapine. PMID:22546987

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

    PubMed Central

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

    2012-01-01

    Background Untreated human immunodeficiency virus (HIV) infection is characterized by progressive depletion of CD4+ T lymphocyte (CD4) count leading to the development of opportunistic diseases (acquired immunodeficiency syndrome (AIDS)), and more recent data suggest that HIV is also associated with an increased risk of serious non-AIDS (SNA) diseases including cardiovascular, renal, and liver diseases and non-AIDS-defining cancers. Although combination antiretroviral treatment (ART) has resulted in a substantial decrease in morbidity and mortality in persons with HIV infection, viral eradication is not feasible with currently available drugs. The optimal time to start ART for asymptomatic HIV infection is controversial and remains one of the key unanswered questions in the clinical management of HIV-infected individuals. Purpose In this article, we outline the rationale and methods of the Strategic Timing of AntiRetroviral Treatment (START) study, an ongoing multicenter international trial designed to assess the risks and benefits of initiating ART earlier than is currently practiced. We also describe some of the challenges encountered in the design and implementation of the study and how these challenges were addressed. Methods A total of 4000 study participants who are HIV type 1 (HIV-1) infected, ART naïve with CD4 count > 500 cells/?L are to be randomly allocated in a 1:1 ratio to start ART immediately (early ART) or defer treatment until CD4 count is <350 cells/ ?L (deferred ART) and followed for a minimum of 3 years. The primary outcome is time to AIDS, SNA, or death. The study had a pilot phase to establish feasibility of accrual, which was set as the enrollment of at least 900 participants in the first year. Results Challenges encountered in the design and implementation of the study included the limited amount of data on the risk of a major component of the primary endpoint (SNA) in the study population, changes in treatment guidelines when the pilot phase was well underway, and the complexities of conducting the trial in a geographically wide population with diverse regulatory requirements. With the successful completion of the pilot phase, more than 1000 participants from 100 sites in 23 countries have been enrolled. The study will expand to include 237 sites in 36 countries to reach the target accrual of 4000 participants. Conclusions START is addressing one of the most important questions in the clinical management of ART. The randomization provided a platform for the conduct of several substudies aimed at increasing our understanding of HIV disease and the effects of antiretroviral therapy beyond the primary question of the trial. The lessons learned from its design and implementation will hopefully be of use to future publicly funded international trials. PMID:22547421

  7. Young age at start of antiretroviral therapy and negative HIV antibody results in HIV-infected children when suppressed

    PubMed Central

    Kuhn, Louise; Schramm, Diana B.; Shiau, Stephanie; Strehlau, Renate; Pinillos, Francoise; Technau, Karl; Coovadia, Ashraf; Abrams, Elaine J.; Puren, Adrian; Tiemessen, Caroline T.

    2015-01-01

    Background Negative results on standard HIV antibody tests have been described among HIV-infected children suppressed on antiretroviral therapy (ART) started early in life. Here we describe the frequency and predictors of this phenomenon in a well-characterized cohort of treated children. Methods We selected samples from 103 HIV-infected children who started ART ? 14 months of age and from 122 children who started ? 6 months of age followed as part of two sequential clinical trials in Johannesburg, South Africa. Children had attained viral suppression on ART and had received ART for between 3 and 6.4 years (mean 4.3 years) when tested for HIV antibody using a standard ELISA (Genescreen™ HIV1/2 version 2; Bio-rad). Results Only children ?6 months of age when ART was started had negative antibody results when tested after suppression on ART several years later. Negative or low-positive antibody results were observed in 40.0%, 37.0% and 27.8% of children starting ART <2 months of age, or starting during month 2 or 3, respectively. This dropped to 5.9%, 3.5%, and 5.3% if ART was started during month 4, 5, and 6, respectively. Higher CD4 percentage prior to ART initiation and no recorded intermittent viremia also predicted negative antibody results. Conclusion Testing negative on standard HIV antibody tests occurs fairly commonly among HIV-infected children who started ART ? 3 months of age and are virally-suppressed. It would be prudent in clinical practice to avoid HIV antibody tests among virally-suppressed, early-treated children to prevent unnecessary confusion. PMID:25870988

  8. Site-nurse initiated Adherence and Symptom Support Telephone Calls for HIV-positive individuals starting antiretroviral therapy, ACTG 5031, a substudy of ACTG 384.

    PubMed Central

    Robbins, Gregory K.; Testa, Marcia A.; Su, Max; Safren, Steven A.; Morse, Gene; Lammert, Sara; Shafer, Robert W.; Reynolds, Nancy R.; Chesney, Margaret A.

    2013-01-01

    Background: Effective and easy to implement interventions to improve adherence to antiretroviral therapy are needed. Objective: To compare a site-nurse initiated adherence and symptom support telephone calls for HIV-positive individuals starting antiretroviral therapy compare to the study site’s standard of care. Methods: A randomized controlled trial of site-nurse initiated adherence and symptom support telephone calls for HIV-positive individuals starting antiretrovirals. Subjects were randomized to receive site-nurse initiated telephone calls (intervention) or no additional calls above the site’s standard of care (control). Subjects received calls 1-3 days after initiating antiretrovirals, weeks 1, 2, 3, 6, 10, 14, 18, 22, 26, and every 8 weeks thereafter. Self-reported adherence was captured during study visits. Results: A total of 333 subjects starting antiretrovirals as part of ACTG 384 were co-enrolled into ACTG 5031. Subjects were followed for up to 160 weeks and were contacted for 74% of scheduled calls. There was no significant difference in proportion of patients with >95% mean Total Adherence, 87.9% and 91.2% (p=0.34) and mean self-reported Total Adherence, 97.9% and 98.4% in the intervention and control, respectively, or in symptom distress and clinical endpoints. Conclusions: In the context of a clinical trial, where self-reported adherence was exceptionally high, the site-nurse initiated telephone calls did not further improve self-reported adherence, symptom distress or clinical outcomes. PMID:24144900

  9. Supplementary feeding with either ready-to-use fortified spread or corn-soy blend in wasted adults starting antiretroviral therapy in Malawi: Randomised, Investigator Blinded, Controlled Trial

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To investigate the effect of two different food supplements on body mass index (BMI) in wasted Malawian adults with HIV who were starting antiretroviral therapy. A randomised, investigator blinded, controlled trial was used in a large, public clinic associated with a referral hospital in Blantyre, M...

  10. Laboratory adverse events and discontinuation of therapy according to CD4+ cell count at the start of antiretroviral therapy

    PubMed Central

    Jose, Sophie; Quinn, Killian; Hill, Teresa; Leen, Clifford; Walsh, John; Hay, Phillip; Fisher, Martin; Post, Frank; Nelson, Mark; Gompels, Mark; Johnson, Margaret; Chadwick, David; Gilson, Richard; Sabin, Caroline; Fidler, Sarah

    2014-01-01

    Objective: Few data describe antiretroviral treatment (ART)-related adverse events when treatment is initiated at CD4+ cell counts more than 350?cells/?l. We compared rates of laboratory-defined adverse events (LDAEs) according to CD4+ cell count at ART initiation. Design: Analysis of on-going cohort study. Methods: ART-naive persons initiating ART from 2000 to 2010 were included. Chi-square, analysis of variance (ANOVA) and Kruskal–Wallis tests compared characteristics among those starting ART with a CD4+ cell count of 350 or less, 351–499 and at least 500?cells/?l. Time-updated Poisson regression compared rates of LDAE in the three CD4+ cell strata. Cox proportional hazard models compared risk of ART discontinuation. Results: Nine thousand, four hundred and six individuals were included: median age 37 years, 61% white, 80% men, median viral load 4.8?log copies/ml. Four hundred and forty-seven (4.9%) and 1099 (11.7%) started ART with a CD4+ cell count at least 500 and 351–499?cells/?l, respectively. One thousand, two hundred and eighty-three (13.6%) patients experienced at least one LDAE. The rate of LDAE did not differ between those starting ART with a CD4+ cell count 351–499 and less than 350?cells/?l [relative rate 0.90, 95% confidence interval (CI) 0.74–1.09)], but an increased risk of ART discontinuation was observed (hazard ratio 1.58, 95% CI 1.10–2.27). Those starting ART at CD4+ cell count at least 500?cells/?l had an increased rate of LDAE (relative rate 1.44, 95% CI 1.13–1.82) but were not more likely to discontinue ART (hazard ratio 1.15, 95% CI 0.64–2.09). Conclusion: This study demonstrates the need to consider ART-related toxicities when initiating therapy at CD4+ cell counts at least 500?cells/?l. Whilst evidence from randomized controlled trials is awaited, the timing of ART initiation in terms of benefits and risks of ART remains an important question. PMID:24583670

  11. Loss to follow-up and mortality rates in HIV-1-infected patients in Curaçao before and after the start of combination antiretroviral therapy.

    PubMed

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

    2013-10-01

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

  12. Factors Informing HIV Providers’ Decisions to Start Antiretroviral Therapy for Young People Living with Behaviorally Acquired HIV

    PubMed Central

    Lee, Lana; Rand, Cynthia; Ellen, Jonathan M.; Agwu, Allison L.

    2014-01-01

    Purpose Young people with behaviorally acquired HIV (BHIV) are less likely than adults to initiate antiretroviral therapy (ART) despite meeting treatment criteria. We explored critical factors involved in healthcare providers’ decision-making regarding ART initiation for young people with BHIV (ages 12–24). Methods Semi-structured interviews were conducted with 23 HIV providers from diverse training backgrounds caring for youth with BHIV at 4 adult clinics and 1 pediatric clinic in a high prevalence urban city. Interview domains probed clinical and non-clinical patient characteristics, the role of adherence, and provider attitudes working with youth to establish decision-making priorities for ART initiation. The constant comparative approach was used to develop grounded theory on providers’ decision-making on ART initiation. Results Clinical criteria, particularly the CD4 count, and the public health implications of HIV transmission determined the urgency for ART initiation. However, patient-related concerns regarding treatment readiness and adherence hampered the decision to initiate, especially at higher CD4 counts. Providers who acknowledged developmental characteristics of youth (e.g. evolving adult identity and self-efficacy around health management) appeared more cautious in assessing future ART adherence and responded with intensive clinical support. Extensive involvement of multidisciplinary teams was identified as an important strategy to retain youth in care, whereas strengthening youth-targeted approaches may be an unmet need in adult clinics. Conclusion Evaluation of providers’ awareness of the developmental features of youth and characteristics of youth-targeted approaches in clinics caring for youth with BHIV may inform interventions to increase youth engagement in care and subsequent decisions to successfully initiate ART. PMID:24794054

  13. 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

  14. Rising Obesity Prevalence and Weight Gain Among Adults Starting Antiretroviral Therapy in the United States and Canada.

    PubMed

    Koethe, John R; Jenkins, Cathy A; Lau, Bryan; Shepherd, Bryan E; Justice, Amy C; Tate, Janet P; Buchacz, Kate; Napravnik, Sonia; Mayor, Angel M; Horberg, Michael A; Blashill, Aaron J; Willig, Amanda; Wester, C William; Silverberg, Michael J; Gill, John; Thorne, Jennifer E; Klein, Marina; Eron, Joseph J; Kitahata, Mari M; Sterling, Timothy R; Moore, Richard D

    2016-01-01

    The proportion of overweight and obese adults in the United States and Canada has increased over the past decade, but temporal trends in body mass index (BMI) and weight gain on antiretroviral therapy (ART) among HIV-infected adults have not been well characterized. We conducted a cohort study comparing HIV-infected adults in the North America AIDS Cohort Collaboration on Research and Design (NA-ACCORD) to United States National Health and Nutrition Examination Survey (NHANES) controls matched by sex, race, and age over the period 1998 to 2010. Multivariable linear regression assessed the relationship between BMI and year of ART initiation, adjusting for sex, race, age, and baseline CD4(+) count. Temporal trends in weight on ART were assessed using a generalized least-squares model further adjusted for HIV-1 RNA and first ART regimen class. A total of 14,084 patients from 17 cohorts contributed data; 83% were male, 57% were nonwhite, and the median age was 40 years. Median BMI at ART initiation increased from 23.8 to 24.8?kg/m(2) between 1998 and 2010 in NA-ACCORD, but the percentage of those obese (BMI ?30?kg/m(2)) at ART initiation increased from 9% to 18%. After 3 years of ART, 22% of individuals with a normal BMI (18.5-24.9?kg/m(2)) at baseline had become overweight (BMI 25.0-29.9 kg/m(2)), and 18% of those overweight at baseline had become obese. HIV-infected white women had a higher BMI after 3 years of ART as compared to age-matched white women in NHANES (p?=?0.02), while no difference in BMI after 3 years of ART was observed for HIV-infected men or non-white women compared to controls. The high prevalence of obesity we observed among ART-exposed HIV-infected adults in North America may contribute to health complications in the future. PMID:26352511

  15. Outcomes in a Cohort of Patients Started on Antiretroviral Treatment and Followed up for a Decade in an Urban Clinic in Uganda

    PubMed Central

    Castelnuovo, Barbara; Kiragga, Agnes; Musaazi, Joseph; Sempa, Joseph; Mubiru, Frank; Wanyama, Jane; Wandera, Bonnie; Kamya, Moses Robert; Kambugu, Andrew

    2015-01-01

    Background Short-medium term studies from sub-Saharan Africa show that, despite high early mortality, substantial loss to program, and high rates toxicity, patients on antiretroviral treatment have achieved outcomes comparable to those in developed settings. However, these studies were unable to account for long term outcomes of patients as they stayed longer on treatment. Objectives We aim to describe ten years outcomes of one of the first cohort of HIV positive patients started on antiretroviral treatment (ART) in Sub-Saharan Africa. Methods We report 10-years outcomes including mortality, retention, CD4-count response, virological outcomes, ART regimens change from a prospective cohort of 559 patients initiating ART and followed up for 10 years Uganda. Results Of 559 patients, 69.1% were female, median age (IQR) was 38 (33–44) years, median CD4-count (IQR) 98 (21–163) cell/?L; 74% were started on stavudine, lamivudine and nevirapine, 26% on zidovudine, lamivudine and efavirenz. After 10 years 361 (65%) patients were still in the study; 127 (22.7%) had died; 30 (5%) were lost to follow-up; 27 (5%) transferred; 18 (3%) withdrew consent. The probability of death was high in the first year (0.15, 95%, CI 0.12–0.18). The median CD4 count increased from 98 to 589 cell/?L (IQR: 450–739 cell/?L) with a median increase of 357 cells/?L (IQR: 128–600 cells/?L); 7.4% never attained initial viral suppression and of those who did 31.7% experienced viral failure. Three hundred and two patients had at least one drug substitution while on first line after a median of 40 months; 66 (11.9%) of the patients were switched to a second line PI-based regimen due to confirmed treatment failure. Conclusions Despite the high rate of early mortality due to advanced disease at presentation the outcomes from this cohort are encouraging, particularly the remarkable and incremental immune-recovery and a satisfactory rate of virologic suppression. PMID:26642214

  16. "I will start treatment when I think the time is right": HIV-positive gay men talk about their decision not to access antiretroviral therapy.

    PubMed

    Gold, R S; Ridge, D T

    2001-12-01

    In a qualitative study, 20 HIV-infected Australian gay men were interviewed about their decision not to access antiretroviral drug therapy. The main reasons given for the decision were fear of side effects; fear of long-term damage to body organs; the inconvenience of the treatment regimens; belief that the regimen's demands would be a threat to morale; and belief that there was no reason to start therapy in the absence of AIDS-related symptoms. Actions taken by the men to monitor and maintain their health included seeing a doctor regularly; having regular T-cell and viral load tests; and trying to maintain a positive outlook by not letting HIV/AIDS 'take over' their lives. Almost half the men considered they had been subjected to unreasonable pressure to access therapy and there was considerable pride at having resisted this pressure. The findings suggest that the men disagreed with the biomedical model for managing HIV/AIDS only on the question of if and when to access therapy. They also suggest that underlying the men's dissent from the biomedical model was a different mode of thinking than is required by the model: while the model demands thinking that is abstract, the men focused strongly on factors close to the 'here and now' of immediate experience. The practical implications of the findings are explored. PMID:11720640

  17. Mortality in Patients with HIV-1 Infection Starting Antiretroviral Therapy in South Africa, Europe, or North America: A Collaborative Analysis of Prospective Studies

    PubMed Central

    Boulle, Andrew; Schomaker, Michael; May, Margaret T.; Hogg, Robert S.; Shepherd, Bryan E.; Monge, Susana; Keiser, Olivia; Lampe, Fiona C.; Giddy, Janet; Ndirangu, James; Garone, Daniela; Fox, Matthew; Ingle, Suzanne M.; Reiss, Peter; Dabis, Francois; Costagliola, Dominique; Castagna, Antonella; Ehren, Kathrin; Campbell, Colin; Gill, M. John; Saag, Michael; Justice, Amy C.; Guest, Jodie; Crane, Heidi M.; Egger, Matthias; Sterne, Jonathan A. C.

    2014-01-01

    Background High early mortality in patients with HIV-1 starting antiretroviral therapy (ART) in sub-Saharan Africa, compared to Europe and North America, is well documented. Longer-term comparisons between settings have been limited by poor ascertainment of mortality in high burden African settings. This study aimed to compare mortality up to four years on ART between South Africa, Europe, and North America. Methods and Findings Data from four South African cohorts in which patients lost to follow-up (LTF) could be linked to the national population register to determine vital status were combined with data from Europe and North America. Cumulative mortality, crude and adjusted (for characteristics at ART initiation) mortality rate ratios (relative to South Africa), and predicted mortality rates were described by region at 0–3, 3–6, 6–12, 12–24, and 24–48 months on ART for the period 2001–2010. Of the adults included (30,467 [South Africa], 29,727 [Europe], and 7,160 [North America]), 20,306 (67%), 9,961 (34%), and 824 (12%) were women. Patients began treatment with markedly more advanced disease in South Africa (median CD4 count 102, 213, and 172 cells/µl in South Africa, Europe, and North America, respectively). High early mortality after starting ART in South Africa occurred mainly in patients starting ART with CD4 count <50 cells/µl. Cumulative mortality at 4 years was 16.6%, 4.7%, and 15.3% in South Africa, Europe, and North America, respectively. Mortality was initially much lower in Europe and North America than South Africa, but the differences were reduced or reversed (North America) at longer durations on ART (adjusted rate ratios 0.46, 95% CI 0.37–0.58, and 1.62, 95% CI 1.27–2.05 between 24 and 48 months on ART comparing Europe and North America to South Africa). While bias due to under-ascertainment of mortality was minimised through death registry linkage, residual bias could still be present due to differing approaches to and frequency of linkage. Conclusions After accounting for under-ascertainment of mortality, with increasing duration on ART, the mortality rate on HIV treatment in South Africa declines to levels comparable to or below those described in participating North American cohorts, while substantially narrowing the differential with the European cohorts. Please see later in the article for the Editors' Summary PMID:25203931

  18. Antiretroviral nephrotoxicities.

    PubMed

    Atta, Mohamed G; Deray, Gilbert; Lucas, Gregory M

    2008-11-01

    With the introduction of combination antiretroviral therapy, there have been substantial declines in both morbidity and mortality associated with human immunodeficiency virus (HIV)-1 infection. However, data increasingly indicate that HIV-1-infected individuals are faced with accelerated rates of chronic diseases that afflict the general population such as diabetes mellitus, hypertension, and dyslipidemia, as well as cardiovascular, liver, and kidney diseases. Furthermore, this population is exposed to a variety of adverse effects from long-term use of antiretroviral medications, which may cause clinically important renal toxicities. However, it often is challenging to distinguish antiretroviral-related renal toxicity from either direct effects of HIV-1 on the kidney or from a multitude of non-HIV-related kidney diseases. A timely and coordinated effort by the HIV primary provider and a nephrologist is likely to facilitate the evaluation of HIV-1-infected patients with new kidney problems. PMID:19013327

  19. Utility of Cryptococcal Antigen Screening and Evolution of Asymptomatic Cryptococcal Antigenemia among HIV-Infected Women Starting Antiretroviral Therapy in Thailand.

    PubMed

    Kwan, Candice K; Leelawiwat, Wanna; Intalapaporn, Poj; Anekthananon, Thanomsak; Raengsakulrach, Boonyos; Peters, Philip J; McNicholl, Janet M; Park, Benjamin J; McConnell, Michelle S; Weidle, Paul J

    2014-09-01

    Cryptococcal meningitis (CM) remains a significant HIV-associated opportunistic infection in Southeast Asia and Africa, with a high burden of disease and a high mortality rate despite the availability of antiretroviral therapy (ART). We retrospectively examined the utility of cryptococcal antigen screening to identify risk for CM among 211 Thai women initiating ART. Antigenemia prevalence was 11% (n = 9) among 84 women with a CD4 count <100 cells/mm(3). Screening identified all women who later developed CM. Cryptococcal antigen titers decreased over time with ART. Our study confirmed findings from previous studies in Thailand and South Africa and provided novel observational data regarding the course of cryptococcal antigenemia in patients initiating ART and the poor efficacy of low-dose fluconazole prophylaxis in preventing CM among patients with antigenemia. PMID:24003059

  20. Short communication: emerging transmitted HIV type 1 drug resistance mutations among patients prior to start of first-line antiretroviral therapy in middle and low prevalence sites in China.

    PubMed

    Wang, Xia; He, Cui; Xing, Hui; Liao, Lingjie; Xu, Xiaoqin; He, Jianmei; Liu, Yong; Ling, Hua; Liang, Shu; Hsi, Jenny H; Ruan, Yuhua; Shao, Yiming

    2012-12-01

    It is known that transmitted drug resistance (TDR) will most likely emerge in regions where antiretroviral therapy (ART) has been widely available for years. However, after a decade of rapid scale-up of ART in China, there are few data regarding TDR among HIV-infected patients prior to initiating first-line ART in China. A prospective, observational cohort study was performed at sentinel sites in five provinces or municipalities. Study participants were recruited at the county- or city-level centers for disease control (CDCs), during routine monitoring visits following referral from diagnosing parties (e.g., hospitals). Each province or municipality recruited 140 patients through sequential sampling throughout the 2011 calendar year. A total of 627 eligible subjects were included in the analysis. the median CD4(+) cell count was 206 cells/ml at the baseline survey. The majority of patients (93.5%) had plasma HIV viral load ?1,000 copies/ml. Of the 627 patients, 17 (2.7%) had drug resistance mutations for any type of HIV drugs. The prevalence of drug resistance mutations to nonnucleoside reverse transcriptase inhibitor (NNRTI) drugs (8/627, 1.3%) was higher than to nucleoside reverse transcriptase inhibitor (NRTI) drugs (5/627, 0.8%) and protease inhibitor (PI) drugs (4/627, 0.6%). A logistic regression model showed that the only predictive factor was the route of infection through homosexual intercourse, i.e., men who have sex with men (MSM) status. As HIV prevalence is rising rapidly among Chinese MSM, it is essential to continue surveying this risk group and related high-risk populations with low awareness of HIV, and to develop new public health interventions that help to reduce the spread of drug-resistant HIV. PMID:22822770

  1. Attitudes of People in the UK with HIV Who Are Antiretroviral (ART) Naïve 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 naïve 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 naïve 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

  2. New wave antiretrovirals.

    PubMed

    Smart, T

    1996-09-01

    Researchers are investigating aspects of the life cycle of HIV that can be exploited by new drugs. Promising compounds include those that block the fusion of HIV to cells; dextran sulfate is an example of such a drug. Reverse transcriptase inhibitors continue to receive attention, with the focus placed on dealing with the resistance that HIV develops to this class of drugs. Other studies are targeting HIV integrase, an enzyme that integrates HIV genetic material into the host cell's DNA, as the next important target of antiretroviral therapy. Two zinc finger inhibitors are currently in clinical trials, one of which is about to enter phase I/II dose-ranging studies. Finally, several novel protease inhibitors are in development. Pharmacia and Upjohn are developing a protease inhibitor that is relatively easy to make and is active against HIV. PMID:11363838

  3. Individualization of antiretroviral therapy.

    PubMed

    Pavlos, Rebecca; Phillips, Elizabeth J

    2012-01-01

    Antiretroviral therapy (ART) has evolved considerably over the last three decades. From the early days of monotherapy with high toxicities and pill burdens, through to larger pill burdens and more potent combination therapies, and finally, from 2005 and beyond where we now have the choice of low pill burdens and once-daily therapies. More convenient and less toxic regimens are also becoming available, even in resource-poor settings. An understanding of the individual variation in response to ART, both efficacy and toxicity, has evolved over this time. The strong association of the major histocompatibility class I allele HLA-B*5701 and abacavir hypersensitivity, and its translation and use in routine HIV clinical practice as a predictive marker with 100% negative predictive value, has been a success story and a notable example of the challenges and triumphs in bringing pharmacogenetics to the clinic. In real clinical practice, however, it is going to be the exception rather than the rule that individual biomarkers will definitively guide patient therapy. The need for individualized approaches to ART has been further increased by the importance of non-AIDS comorbidities in HIV clinical practice. In the future, the ideal utilization of the individualized approach to ART will likely consist of a combined approach using a combination of knowledge of drug, virus, and host (pharmacogenetic and pharmacoecologic [factors in the individual's environment that may be dynamic over time]) information to guide the truly personalized prescription. This review will focus on our knowledge of the pharmacogenetics of the efficacy and toxicity of currently available antiretroviral agents and the current and potential utility of such information and approaches in present and future HIV clinical care. PMID:23226059

  4. Macrophage endocytic trafficking of antiretroviral nanoparticles

    PubMed Central

    Kadiu, Irena; Nowacek, Ari; McMillan, JoEllyn; Gendelman, Howard E

    2011-01-01

    Aim Nanoformulated antiretroviral therapy can improve drug compliance for people infected with HIV. Additional benefits would include specific drug deliveries to viral reservoirs and reduction in systemic toxicities. Methods In this article, we describe mechanisms of crystalline antiretroviral nanoparticle (NP) uptake, intracellular trafficking and release in human monocyte-derived macrophages. Results Following clathrin-dependent endocytosis NPs bypassed lysosomal degradation by sorting from early endosomes to recycling endosome pathways. Disruption of this pathway by siRNAs or brefeldin-A impaired particle release. Proteomic and biological analysis demonstrated that particle recycling was primarily Rab11 regulated. Particles were released intact and retained complete antiretroviral efficacy. Conclusion These results suggest possible pathways of subcellular transport of antiretroviral nanoformulations that preserve both particle integrity and antiretroviral activities demonstrating the potential utility of this approach for targeted drug delivery. PMID:21417829

  5. 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…

  6. Challenges of malnutrition care among HIV-infected children on antiretroviral treatment in Africa.

    PubMed

    Jesson, J; Leroy, V

    2015-05-01

    More than 90% of the estimated 3.2 million children with HIV worldwide, at the end of 2013, were living in sub-Saharan Africa. The management of these children was still difficult in 2014 despite the progress in access to antiretroviral drugs. A great number of HIV-infected children are not diagnosed at 6 weeks and start antiretroviral treatment late, at an advanced stage of HIV disease complicated by other comorbidities such as malnutrition. Malnutrition is a major problem in the sub-Saharan Africa global population; it is an additional burden for HIV-infected children because they do not respond as well as non-infected children to the usual nutritional care. HIV infection and malnutrition interact, creating a vicious circle. It is important to understand the relationship between these 2 conditions and the effect of antiretroviral treatment on this circle to taking them into account for an optimal management of pediatric HIV. An improved monitoring of growth during follow-up and the introduction of a nutritional support among HIV-infected children, especially at antiretroviral treatment initiation, are important factors that could improve response to antiretroviral treatment and optimize the management of pediatric HIV in resource-limited countries. PMID:25861689

  7. 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,…

  8. Use of Third Line Antiretroviral Therapy in Latin America

    PubMed Central

    Cesar, Carina; Shepherd, Bryan E.; Jenkins, Cathy A.; Ghidinelli, Massimo; Castro, Jose Luis; Veloso, Valdiléa Gonçalves; Cortes, Claudia P.; Padgett, Denis; Crabtree-Ramirez, Brenda; Gotuzzo, Eduardo; Fink, Valeria; Duran, Adriana; Sued, Omar; McGowan, Catherine C.; Cahn, Pedro

    2014-01-01

    Background Access to highly active antiretroviral therapy (HAART) is expanding in Latin America. Many patients require second and third line therapy due to toxicity, tolerability, failure, or a combination of factors. The need for third line HAART, essential for program planning, is not known. Methods Antiretroviral-naïve patients ?18 years who started first HAART after January 1, 2000 in Caribbean, Central and South America Network (CCASAnet) sites in Argentina, Brazil, Honduras, Mexico, and Peru were included. Clinical trials participants were excluded. Third line HAART was defined as use of darunavir, tipranavir, etravirine, enfuvirtide, maraviroc or raltegravir. Need for third line HAART was defined as virologic failure while on second line HAART. Results Of 5853 HAART initiators followed for a median of 3.5 years, 310 (5.3%) failed a second line regimen and 44 (0.8%) received a third line regimen. Cumulative incidence of failing a 2nd or starting a 3rd line regimen was 2.7% and 6.0% three and five years after HAART initiation, respectively. Predictors at HAART initiation for failing a second or starting a third line included female sex (hazard ratio [HR]?=?1.54, 95% confidence interval [CI] 1.18–2.00, p?=?0.001), younger age (HR?=?2.76 for 20 vs. 40 years, 95% CI 1.86–4.10, p<0.001), and prior AIDS (HR?=?2.17, 95% CI 1.62–2.90, p<0.001). Conclusions Third line regimens may be needed for at least 6% of patients in Latin America within 5 years of starting HAART, a substantial proportion given the large numbers of patients on HAART in the region. Improved accessibility to third line regimens is warranted. PMID:25221931

  9. Press Start

    NASA Astrophysics Data System (ADS)

    Harteveld, Casper

    This level sets the stage for the design philosophy called “Triadic Game Design” (TGD). This design philosophy can be summarized with the following sentence: it takes two to tango, but it takes three to design a meaningful game or a game with a purpose. Before the philosophy is further explained, this level will first delve into what is meant by a meaningful game or a game with a purpose. Many terms and definitions have seen the light and in this book I will specifically orient at digital games that aim to have an effect beyond the context of the game itself. Subsequently, a historical overview is given of the usage of games with a serious purpose which starts from the moment we human beings started to walk on our feet till our contemporary society. It turns out that we have been using games for all kinds of non-entertainment purposes for already quite a long time. With this introductory material in the back of our minds, I will explain the concept of TGD by means of a puzzle. After that, the protagonist of this book, the game Levee Patroller, is introduced. Based on the development of this game, the idea of TGD, which stresses to balance three different worlds, the worlds of Reality, Meaning, and Play, came into being. Interested? Then I suggest to quickly “press start!”

  10. “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

  11. [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

  12. Starting motor

    SciTech Connect

    Tanaka, T.; Hamano, I

    1989-05-23

    This patent describes a starting motor having a housing, planetary reduction gears including an internal gear in the housing. The improvement consists of an elastic member having a first annular portion mounted in engagement with a fixed annular member of the housing and a plurality of protruding axially extending elastic portions providing a corrugated surface pressed into engagement with an end portion of the internal gear, the elastic member being sandwiched between the internal gear and the housing member, the protruding axially extending elastic portions providing resilient means which flex and incline circumferentially under turning force from the internal gear and exert reactive thrust on the internal gear elastically so that the frictional force at the abutting surfaces of the protruding portions holds the internal gear in resilient engagement with the elastic member and the resilient means acts as a buffer to absorb rotary impact force developing in the planetary reduction gears.

  13. Hidden costs of antiretroviral treatment: the public health efficiency of drug packaging

    PubMed Central

    Andreu-Crespo, Àngels; Llibre, Josep M; Cardona-Peitx, Glòria; Sala-Piñol, Ferran; Clotet, Bonaventura; Bonafont-Pujol, Xavier

    2015-01-01

    While the overall percentage of unused antiretroviral medicines returned to the hospital pharmacy is low, their cost is quite high. Adverse events, treatment failure, pharmacokinetic interactions, pregnancy, or treatment simplification are common reasons for unplanned treatment changes. Socially inefficient antiretroviral packages prevent the reuse of drugs returned to the hospital pharmacy. We defined antiretroviral package categories based on the excellence of drug packaging and analyzed the number of pills and costs of drugs returned during a period of 1 year in a hospital-based HIV unit attending to 2,413 treated individuals. A total of 6,090 pills (34% of all returned antiretrovirals) – with a cost of 47,139.91€ – would be totally lost, mainly due to being packed up in the lowest efficiency packages. Newer treatments are packaged in low-excellence categories of packages, thus favoring the maintenance of these hidden costs in the near future. Therefore, costs of this low-efficiency drug packaging, where medication packages are started but not completed, in high-cost medications are substantial and should be properly addressed. Any improvement in the packaging by the manufacturer, and favoring the choice of drugs supplied through efficient packages (when efficacy, toxicity, and convenience are similar), should minimize the treatment expenditures paid by national health budgets. PMID:26273190

  14. Antiretroviral therapy in children: recent advances.

    PubMed

    Lodha, Rakesh; Manglani, Mamta

    2012-12-01

    Availability and successful use of various antiretroviral drugs has transformed HIV/AIDS from an incurable to a treatable chronic condition. The antiretroviral therapy can successfully suppress viral replication and preserve the immune system for many years. The implementation of antiretroviral therapy program in resource limited settings using the 'public health approach' of the World Health Organization has had a dramatic impact on the lives of millions of HIV infected individuals. Antiretroviral therapy (ART) in children has many challenges: use of appropriate formulations, regular need for modification of doses as the child grows, adherence issues, etc. To reduce the high morbidity and mortality in HIV infected children, it is currently recommended that all HIV infected children less than 24 mo should receive ART; in older children the indications are based on clinical and/or immunological criteria. Highly active antiretroviral therapy regimens include at least 3 antiretroviral drugs. The first line therapy recommended for children is a combination of two nucleoside reverse transcriptase inhibitors and a non-nucleoside reverse transcriptase inhibitor. Infants who have had exposure to nevirapine should receive a combination of two nucleoside reverse transcriptase inhibitors and a protease inhibitor; the protease inhibitor of choice is ritonavir boosted lopinavir. The success of therapy is dependent on >95 % adherence. The second line regimen, used when the first line therapy fails, is based on a protease inhibitor. The ongoing research focuses on simplification of regimen, discovery of more potent drugs, availability of more pediatric formulations, treatment of drug resistant strains etc. The optimal indications for initiation of therapy in children, are also being studied. PMID:23184329

  15. 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

  16. 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

  17. Dosing antiretroviral medication when crossing time zones: a review.

    PubMed

    Lewis, Joseph M; Volny-Anne, Alain; Waitt, Catriona; Boffito, Marta; Khoo, Saye

    2016-01-01

    International tourism continues to increase worldwide, and people living with HIV and their clinicians are increasingly confronted with the problem of how to dose antiretroviral therapy during transmeridian air travel across time zones. No guidance on this topic currently exists. This review is a response to requests from patient groups for clear, practical and evidence-based guidance for travelling on antiretroviral therapy; we present currently available data on the pharmacokinetic forgiveness and toxicity of various antiretroviral regimens, and synthesize this data to provide guidelines on how to safely dose antiretrovirals when travelling across time zones. PMID:26684823

  18. Virological Response and Antiretroviral Drug Resistance Emerging during Antiretroviral Therapy at Three Treatment Centers in Uganda

    PubMed Central

    Kaleebu, Pontiano; Kirungi, Wilford; Watera, Christine; Asio, Juliet; Lyagoba, Fred; Lutalo, Tom; Kapaata, Anne A.; Nanyonga, Faith; Parry, Chris M.; Magambo, Brian; Nazziwa, Jamirah; Nannyonjo, Maria; Hughes, Peter; Hladik, Wolfgang; Ruberantwari, Anthony; Namuwenge, Norah; Musinguzi, Joshua; Downing, Robert; Katongole-Mbidde, Edward

    2015-01-01

    Background With the scale-up of antiretroviral therapy (ART), monitoring programme performance is needed to maximize ART efficacy and limit HIV drug resistance (HIVDR). Methods We implemented a WHO HIVDR prospective survey protocol at three treatment centers between 2012 and 2013. Data were abstracted from patient records at ART start (T1) and after 12 months (T2). Genotyping was performed in the HIV pol region at the two time points. Results Of the 425 patients enrolled, at T2, 20 (4.7%) had died, 66 (15.5%) were lost to follow-up, 313 (73.6%) were still on first-line, 8 (1.9%) had switched to second-line, 17 (4.0%) had transferred out and 1 (0.2%) had stopped treatment. At T2, 272 out of 321 on first and second line (84.7%) suppressed below 1000 copies/ml and the HIV DR prevention rate was 70.1%, just within the WHO threshold of ?70%. The proportion of participants with potential HIVDR was 20.9%, which is higher than the 18.8% based on pooled analyses from African studies. Of the 35 patients with mutations at T2, 80% had M184V/I, 65.7% Y181C, and 48.6% (54.8% excluding those not on Tenofovir) had K65R mutations. 22.9% had Thymidine Analogue Mutations (TAMs). Factors significantly associated with HIVDR prevention at T2 were: baseline viral load (VL) <100,000 copies/ml [Adjusted odds ratio (AOR) 3.13, 95% confidence interval (CI): 1.36–7.19] and facility. Independent baseline predictors for HIVDR mutations at T2 were: CD4 count <250 cells/?l (AOR 2.80, 95% CI: 1.08–7.29) and viral load ?100,000 copies/ml (AOR 2.48, 95% CI: 1.00–6.14). Conclusion Strengthening defaulter tracing, intensified follow-up for patients with low CD4 counts and/or high VL at ART initiation together with early treatment initiation above 250 CD4 cells/ul and adequate patient counselling would improve ART efficacy and HIVDR prevention. The high rate of K65R and TAMs could compromise second line regimens including NRTIs. PMID:26700639

  19. 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

  20. 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

  1. Tropism distribution among antiretroviral-naive HIV-2-infected patients.

    PubMed

    Visseaux, Benoit; Charpentier, Charlotte; Ozanne, Alexandra; Nizard, Alexis; Drumard, Suzon; Fagard, Catherine; Glohi, David; Damond, Florence; Brun-Vézinet, Françoise; Matheron, Sophie; Descamps, Diane

    2015-10-23

    The aim of this study was to describe HIV-2 R5/X4-tropism distribution in antiretroviral-naive HIV-2-infected patients. Population sequencing of the gp105 region was performed on peripheral blood mononuclear cells issued from 151 antiretroviral-naive patients. Tropism was successfully determined in 46 of 151 samples (30%) with six of 46 (13%) X4-tropic viruses. X4-tropism was associated with lower CD4 cell count (337 vs. 551/mm; P?=?0.032) but not with plasma viral load. Thus, X4-tropism prevalence in HIV-2 antiretroviral-naive patients is similar to that observed in HIV-1. PMID:26544584

  2. Current Perspectives on HIV-1 Antiretroviral Drug Resistance

    PubMed Central

    Iyidogan, Pinar; Anderson, Karen S.

    2014-01-01

    Current advancements in antiretroviral therapy (ART) have turned HIV-1 infection into a chronic and manageable disease. However, treatment is only effective until HIV-1 develops resistance against the administered drugs. The most recent antiretroviral drugs have become superior at delaying the evolution of acquired drug resistance. In this review, the viral fitness and its correlation to HIV-1 mutation rates and drug resistance are discussed while emphasizing the concept of lethal mutagenesis as an alternative therapy. The development of resistance to the different classes of approved drugs and the importance of monitoring antiretroviral drug resistance are also summarized briefly. PMID:25341668

  3. Pediatric Adherence to HIV Antiretroviral Therapy

    PubMed Central

    Mellins, Claude

    2010-01-01

    More than two million children are infected with HIV globally. Pediatric ART adherence is complex and current levels are often suboptimal. As established treatment programs in developed settings struggle with chronic therapy and nascent treatment programs in resource-limited settings expand, the importance and challenges of good adherence to antiretroviral therapy are becoming ever more clear. Adherence behavior is influenced by many factors, which may be categorized as characteristics of the child, the caregiver(s) and family, the regimen, and society and culture. Many of these influences complicate measurement of pediatric adherence and there is no gold standard. This article provides a conceptual framework and evidence-based look at the factors influencing ART adherence in children and aims to identify areas for intervention for this vulnerable population in need. PMID:19849962

  4. 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 ...

  5. 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 Share ...

  6. Antiretroviral drug concentrations in semen of HIV-1 infected men.

    PubMed

    Taylor, S; Pereira, A S

    2001-02-01

    Because semen is a major vehicle for the sexual transmission of HIV-1, control of viral replication within the sanctuary of the male genital tract should be a goal of antiretroviral therapy. Local immune responses, virus specific factors, and the degree of viral and cellular trafficking all appear to be important in controlling viral replication and evolution. However, the most important factor influencing viral replication and evolution within the male genital tract may be the disposition of antiretroviral agents into genital tissues and fluids. This review proposes possible mechanisms of antiretroviral distribution into the male genital tract by using other sanctuary barriers; such as the placenta, renal tubules, and blood-brain barrier; as models. In addition, this review summarises recent clinical studies regarding the disposition of currently available antiretroviral drugs into the seminal plasma and discusses some of the difficulties in interpreting drug concentration in the genital tract. PMID:11158684

  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. 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-naïve 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

  9. The Survival Benefits of Antiretroviral Therapy in South Africa

    PubMed Central

    April, Michael D.; Wood, Robin; Berkowitz, Bethany K.; Paltiel, A. David; Anglaret, Xavier; Losina, Elena; Freedberg, Kenneth A.; Walensky, Rochelle P.

    2014-01-01

    Background.?We sought to quantify the survival benefits attributable to antiretroviral therapy (ART) in South Africa since 2004. Methods.?We used the Cost-Effectiveness of Preventing AIDS Complications–International model (CEPAC) to simulate 8 cohorts of human immunodeficiency virus (HIV)–infected patients initiating ART each year during 2004–2011. Model inputs included cohort-specific mean CD4+ T-cell count at ART initiation (112–178 cells/µL), 24-week ART suppressive efficacy (78%), second-line ART availability (2.4% of ART recipients), and cohort-specific 36-month retention rate (55%–71%). CEPAC simulated survival twice for each cohort, once with and once without ART. The sum of the products of per capita survival differences and the total numbers of persons initiating ART for each cohort yielded the total survival benefits. Results.?Lifetime per capita survival benefits ranged from 9.3 to 10.2 life-years across the 8 cohorts. Total estimated population lifetime survival benefit for all persons starting ART during 2004–2011 was 21.7 million life-years, of which 2.8 million life-years (12.7%) had been realized by December 2012. By 2030, benefits reached 17.9 million life-years under current policies, 21.7 million life-years with universal second-line ART, 23.3 million life-years with increased linkage to care of eligible untreated patients, and 28.0 million life-years with both linkage to care and universal second-line ART. Conclusions.?We found dramatic past and potential future survival benefits attributable to ART, justifying international support of ART rollout in South Africa. PMID:24307741

  10. Sexual behaviors during antiretroviral therapy among HIV-infected patients, Thailand.

    PubMed

    Lertpiriyasuwat, Cheewanan; Pradipasen, Mandhana; Thiangtham, Weena; Kaewduangjai, Punthip

    2007-05-01

    An increasing trend in sexual risk behavior has occurred in the era of antiretroviral therapy (ART) in Thailand. This study was conducted to identify sexual risk behavior and examine relationships between unprotected sex and CD4 levels among HIV-infected patients receiving ART in the National Antiretroviral Program. A cross-sectional survey was conducted in 460 HIV-infected patients age 18-49 years who visited the out-patient clinic of Bamrasnaradura Infectious Diseases Institute in February 2006 by using a standardized self-administered questionnaire. The results show that 60.4% of participants were men. The median most recent CD4 cell count during the prior 6 months was 261 cells/mm3. Twenty-three percent of the participants who had no sexual activity after they knew their HIV positive status started having sex again after receiving ART with a 12-week median duration period from starting ART to having first sex. There was a significant difference between the number of those having sexual activity before and after starting ART (p-value=0.013). Fifty-six percent of participants had sex during the previous 6 months. Of these, 26.5% had sex with commercial partners and 28.4% with non-regular partners. Inconsistent condom use, with commercial partners or non-regular partners, in females (35.3-36.8%) was higher than in males (7.8-11.1%). Participants with a known HIV-negative regular partner were 0.25 times more likely to have unprotected sex than those with a known HIV-positive regular partner (adjusted OR, 0.25; 95%CI, 0.09-0.73). No association between unprotected sex and CD4 levels was found. The findings support the need for reinforcing risk reduction programs among HIV-infected persons, particularly couple counseling, and promoting awareness of risk of acquirring sexually transmitted infections and drug-resistant strains of HIV. PMID:17877219

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

    NASA Astrophysics Data System (ADS)

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

    2013-10-01

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

  12. Smart Start News, 1999.

    ERIC Educational Resources Information Center

    Harris, Monica, Ed.

    1999-01-01

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

  13. Factors influencing global antiretroviral procurement prices

    PubMed Central

    2009-01-01

    Background Antiretroviral medicines (ARVs) are one of the most costly parts of HIV/AIDS treatment. Many countries are struggling to provide universal access to ARVs for all people living with HIV and AIDS. Although substantial price reductions of ARVs have occurred, especially between 2002 and 2008, achieving sustainable access for the next several decades remains a major challenge for most low- and middle-income countries. The objectives of the present study were twofold: first, to analyze global ARV prices between 2005 and 2008 and associated factors, particularly procurement methods and key donor policies on ARV procurement efficiency; second, to discuss the options of procurement processes and policies that should be considered when implementing or reforming access to ARV programs. Methods An ARV-medicines price-analysis was carried out using the Global Price Reporting Mechanism from the World Health Organization. For a selection of 12 ARVs, global median prices and price variation were calculated. Linear regression models for each ARV were used to identify factors that were associated with lower procurement prices. Logistic regression models were used to identify the characteristics of those countries which procure below the highest and lowest direct manufactured costs. Results Three key factors appear to have an influence on a country's ARV prices: (a) whether the product is generic or not; (b) the socioeconomic status of the country; (c) whether the country is a member of the Clinton HIV/AIDS Initiative. Factors which did not influence procurement below the highest direct manufactured costs were HIV prevalence, procurement volume, whether the country belongs to the least developed countries or a focus country of the United States President's Emergency Plan For AIDS Relief. Conclusion One of the principal mechanisms that can help to lower prices for ARV over the next several decades is increasing procurement efficiency. Benchmarking prices could be one useful tool to achieve this. PMID:19922690

  14. Vaginal Cytomegalovirus Shedding Before and After Initiation of Antiretroviral Therapy in Rakai, Uganda.

    PubMed

    Gianella, Sara; Redd, Andrew D; Grabowski, Mary K; Tobian, Aaron A R; Serwadda, David; Newell, Kevin; Patel, Eshan U; Kalibbala, Sarah; Ssebbowa, Paschal; Gray, Ronald H; Quinn, Thomas C; Reynolds, Steven J

    2015-09-15

    Vaginal shedding of cytomegalovirus (CMV) DNA was determined longitudinally among 96 women coinfected with human immunodeficiency virus (HIV), herpes simplex virus 2, and CMV starting antiretroviral therapy (ART) during a placebo-controlled trial of HSV-2 suppression with acyclovir in Rakai, Uganda. Vaginal CMV was detected in 75 of 96 women (78.0%) and 379 of 1080 individual visits (35.1%). ART status, higher HIV RNA viral load before ART initiation, and younger age were significantly associated with increased frequency of CMV shedding (P < .01). Compared to pre-ART, CMV shedding peaked from month 2 to month 4 after ART initiation, suggesting possible immune reconstitution inflammatory syndrome. Further studies need to determine the clinical significance of asymptomatic CMV shedding. PMID:25743428

  15. Comparative manufacture and cell-based delivery of antiretroviral nanoformulations

    PubMed Central

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

    2011-01-01

    Nanoformulations of crystalline indinavir, ritonavir, atazanavir, and efavirenz were manufactured by wet milling, homogenization or sonication with a variety of excipients. The chemical, biological, immune, virological, and toxicological properties of these formulations were compared using an established monocyte-derived macrophage scoring indicator system. Measurements of drug uptake, retention, release, and antiretroviral activity demonstrated differences amongst preparation methods. Interestingly, for drug cell targeting and antiretroviral responses the most significant difference among the particles was the drug itself. We posit that the choice of drug and formulation composition may ultimately affect clinical utility. PMID:22267924

  16. 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

  17. 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

  18. 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

  19. 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

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

    PubMed Central

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

    2013-01-01

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

  1. Clinically relevant drug-drug interactions between antiretrovirals and antifungals

    PubMed Central

    Vadlapatla, Ramya Krishna; Patel, Mitesh; Paturi, Durga K; Pal, Dhananjay; Mitra, Ashim K

    2015-01-01

    Introduction Complete delineation of the HIV-1 life cycle has resulted in the development of several antiretroviral drugs. Twenty-five therapeutic agents belonging to five different classes are currently available for the treatment of HIV-1 infections. Advent of triple combination antiretroviral therapy has significantly lowered the mortality rate in HIV patients. However, fungal infections still represent major opportunistic diseases in immunocompromised patients worldwide. Areas covered Antiretroviral drugs that target enzymes and/or proteins indispensable for viral replication are discussed in this article. Fungal infections, causative organisms, epidemiology and preferred treatment modalities are also outlined. Finally, observed/predicted drug-drug interactions between antiretrovirals and antifungals are summarized along with clinical recommendations. Expert opinion Concomitant use of amphotericin B and tenofovir must be closely monitored for renal functioning. Due to relatively weak interactive potential with the CYP450 system, fluconazole is the preferred antifungal drug. High itraconazole doses (> 200 mg/day) are not advised in patients receiving booster protease inhibitor (PI) regimen. Posaconazole is contraindicated in combination with either efavirenz or fosamprenavir. Moreover, voriconazole is contraindicated with high-dose ritonavir-boosted PI. Echino-candins may aid in overcoming the limitations of existing antifungal therapy. An increasing number of documented or predicted drug-drug interactions and therapeutic drug monitoring may aid in the management of HIV-associated opportunistic fungal infections. PMID:24521092

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

    PubMed Central

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

    2008-01-01

    Background The purpose of this study was to evaluate the efficacy and safety of three nevirapine-based antiretroviral treatments for adult antiretroviral-naïve Chinese patients with HIV-1 infection. Methodology This was a prospective, multicenter study. 198 antiretroviral-naïve HIV-1 positive subjects with CD4 lymphocyte counts between 100/ul and 350/ul and plasma HIV-1 RNA levels more than 500 copies/ml were randomized to start three NVP-based antiretroviral treatments: group A, NVP+AZT+ddI; group B, NVP+3TC+d4T; group C, NVP+AZT+3TC. Viral responses, immunologic responses, adverse events and drug resistence were monitored at baseline and the end of week 4, 12, 24, 36, 52. Viralogical response and immunological response were also comparaed in different strata of baseline CD4 T lymphocyte counts and plasma HIV-1 RNA concentrations. At baseline, the plasma HIV-1 RNA was 4.44±0.68, 4.52±0.71 and 4.41±0.63 lg copies/ml in group A, B and C respectively (p?=?0.628). At the end of the study, the plasma viral load reached 2.54±1.11, 1.89±0.46 and 1.92±0.58 lg copies/ml in group A, B and C respectively (p<0.001). At week 52, suppression of plasma HIV-1 RNA to less than 50 copies/ml was achieved in more patients in group B and C than in group A (68.2%, 69% vs. 39.7%; p<0.001). In planned subgroup analyses, the decrease of viral response rate was seen in group A when CD4 cell count >200/ul (subgroup H). But in subgroup L, viral response rate of three groups has no significant statistic difference. There were no statistically significant differences among three groups in immunological response wthin any of the CD4 or pVL strata. 3 out of 193 patients with available genotype at baseline showed primary drug resistant. Of 26 patients with virologic failure, 17 patients showed secondary drug resistant, 16 subjects in group A and 1 subject in group B. Logistic regression analysis indicated that presence of hepatotoxicity was associated with HCV-Ab positive (OR?=?2.096, 95%CI: 1.106–3.973, P?=?0.023) and higher CD4 baseline (CD4 count >250/ul)(OR?=?2.096, 95%CI: 1.07–4.107, P?=?0.031). Conclusion Our findings strongly support the use of 3TC+d4T and 3TC+AZT as the nucleoside analogue combination in NVP-based antiretroviral therapy. The regimen of AZT+ddI+NVP produced poor virological response especially in the stratum of CD4 count more than 200/ul. More patients showed secondary drug resistant in this arm too. Patients with HCV-Ab+ and CD4 count >250/ul appear to have significantly high risk of hepatoxicity. Trial Registration ClinicalTrials.gov NCT00618176 PMID:19081791

  3. 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

  4. PHP: Getting Started Introduction

    E-print Network

    Vander Zanden, Brad

    PHP: Getting Started Introduction This document describes: 1. the basic syntax for PHP code, 2. how to execute PHP scripts, 3. methods for sending output to the browser, 4. the handling of whitespace, and 5. how to comment your code. Basic PHP syntax PHP code typically resides in a plaintext file with a .php

  5. Starting Material Silicon substrate

    E-print Network

    Healy, Kevin Edward

    Starting Material Silicon substrate 150 mm, p-type, , 36-63 ohm-cm Attila Horvath 2005 #12;Pad Oxidation and Nitride Deposition Silicon substrate Pad oxide = 250A Silicon nitride = 2200A Attila Horvath 2005 #12;N-Well Photo and Nitride Etch Silicon substrate Pad oxide Silicon nitride Photo resist Attila

  6. Timing of Initiation of Antiretroviral Therapy in Human Immunodeficiency Virus (HIV)–Associated Tuberculous Meningitis

    PubMed Central

    Török, M. Estee; Yen, Nguyen Thi Bich; Chau, Tran Thi Hong; Mai, Nguyen Thi Hoang; Phu, Nguyen Hoan; Mai, Pham Phuong; Dung, Nguyen Thi; Van Vinh Chau, Nguyen; Bang, Nguyen Duc; Tien, Nguyen Anh; Minh, N. H.; Hien, Nguyen Quang; Thai, Phan Vuong Khac; Dong, Doan The; Anh, Do Thi Tuong; Thoa, Nguyen Thi Cam; Hai, Nguyen Ngoc; Lan, Nguyen Ngoc; Lan, Nguyen Thi Ngoc; Quy, Hoang Thi; Dung, Nguyen Huy; Hien, Tran Tinh; Chinh, Nguyen Tran; Simmons, Cameron Paul; de Jong, Menno; Wolbers, Marcel; Farrar, Jeremy James

    2015-01-01

    Background The optimal time to initiate antiretroviral therapy (ART) in human immunodeficiency virus (HIV)–associated tuberculous meningitis is unknown. Methods We conducted a randomized, double-blind, placebo-controlled trial of immediate versus deferred ART in patients with HIV-associated tuberculous meningitis to determine whether immediate ART reduced the risk of death. Antiretroviral drugs (zidovudine, lamivudine, and efavirenz) were started either at study entry or 2 months after randomization. All patients were treated with standard antituberculosis treatment, adjunctive dexamethasone, and prophylactic co-trimoxazole and were followed up for 12 months. We conducted intention-to-treat, per-protocol, and prespecified subgroup analyses. Results A total of 253 patients were randomized, 127 in the immediate ART group and 126 in the deferred ART group; 76 and 70 patients died within 9 months in the immediate and deferred ART groups, respectively. Immediate ART was not significantly associated with 9-month mortality (hazard ratio [HR], 1.12; 95% confidence interval [CI], .81–1.55; P = .50) or the time to new AIDS events or death (HR, 1.16; 95% CI, .87–1.55; P = .31). The percentage of patients with severe (grade 3 or 4) adverse events was high in both arms (90% in the immediate ART group and 89% in the deferred ART group; P = .84), but there were significantly more grade 4 adverse events in the immediate ART arm (102 in the immediate ART group vs 87 in the deferred ART group; P = .04). Conclusions Immediate ART initiation does not improve outcome in patients presenting with HIV-associated tuberculous meningitis. There were significantly more grade 4 adverse events in the immediate ART arm, supporting delayed initiation of ART in HIV-associated tuberculous meningitis. Clinical Trials Registration ISRCTN63659091. PMID:21596680

  7. HIV Antiretroviral Resistance Mutations Among Antiretroviral Treatment-Naive and -Experienced Patients in South Korea

    PubMed Central

    Kim, Min Hyung; Song, Je Eun; Ahn, Jin Young; Kim, Yong Chan; Oh, Dong Hyun; Choi, Heun; Ann, Hea Won; Kim, Jae Kyoung; Kim, Sun Bean; Jeong, Su Jin; Ku, Nam Su; Han, Sang Hoon; Song, Young Goo; Kim, June Myung

    2013-01-01

    Abstract The purpose of this study was to assess the prevalence and characteristics of HIV drug resistance mutations among antiretroviral therapy (ART)-naive and ART-experienced patients in South Korea. A total of 50 ART-naive and 34 ART-experienced Korean HIV-1-infected patients who visited an urban hospital from February 2007 to March 2011 were included. Most patients (86.9%) were infected with clade B HIV-1. Six (12%) ART-naive and 22 (64.7%) ART-experienced patients had HIV strains with resistance mutations. Among ART-naive patients, V179D was the most common mutation, being found in five ART-naive patients. Among ART-experienced patients, M184V was the most common mutation. Eight of 34 ART-experienced patients had thymidine analogue mutations (TAMs). The prevalence of drug-resistant HIV-1 in ART-naive patients was higher than in previous reports, and 50% of patients with virologic failure harbored strains with multiple resistance mutations. HIV drug resistance testing should be recommended to guide therapy of ART-naive patients in South Korea. PMID:23952717

  8. Long-Term Antiretroviral Treatment Initiated at Primary HIV-1 Infection Affects the Size, Composition, and Decay Kinetics of the Reservoir of HIV-1-Infected CD4 T Cells

    PubMed Central

    Buzon, Maria J.; Martin-Gayo, Enrique; Pereyra, Florencia; Ouyang, Zhengyu; Sun, Hong; Li, Jonathan Z.; Piovoso, Michael; Shaw, Amy; Dalmau, Judith; Zangger, Nadine; Martinez-Picado, Javier; Zurakowski, Ryan; Yu, Xu G.; Telenti, Amalio; Walker, Bruce D.; Rosenberg, Eric S.

    2014-01-01

    ABSTRACT Initiation of antiretroviral therapy during the earliest stages of HIV-1 infection may limit the seeding of a long-lasting viral reservoir, but long-term effects of early antiretroviral treatment initiation remain unknown. Here, we analyzed immunological and virological characteristics of nine patients who started antiretroviral therapy at primary HIV-1 infection and remained on suppressive treatment for >10 years; patients with similar treatment duration but initiation of suppressive therapy during chronic HIV-1 infection served as controls. We observed that independently of the timing of treatment initiation, HIV-1 DNA in CD4 T cells decayed primarily during the initial 3 to 4 years of treatment. However, in patients who started antiretroviral therapy in early infection, this decay occurred faster and was more pronounced, leading to substantially lower levels of cell-associated HIV-1 DNA after long-term treatment. Despite this smaller size, the viral CD4 T cell reservoir in persons with early treatment initiation consisted more dominantly of the long-lasting central-memory and T memory stem cells. HIV-1-specific T cell responses remained continuously detectable during antiretroviral therapy, independently of the timing of treatment initiation. Together, these data suggest that early HIV-1 treatment initiation, even when continued for >10 years, is unlikely to lead to viral eradication, but the presence of low viral reservoirs and durable HIV-1 T cell responses may make such patients good candidates for future interventional studies aiming at HIV-1 eradication and cure. IMPORTANCE Antiretroviral therapy can effectively suppress HIV-1 replication to undetectable levels; however, HIV-1 can persist despite treatment, and viral replication rapidly rebounds when treatment is discontinued. This is mainly due to the presence of latently infected CD4 T cells, which are not susceptible to antiretroviral drugs. Starting treatment in the earliest stages of HIV-1 infection can limit the number of these latently infected cells, raising the possibility that these viral reservoirs are naturally eliminated if suppressive antiretroviral treatment is continued for extremely long periods of time. Here, we analyzed nine patients who started on antiretroviral therapy within the earliest weeks of the disease and continued treatment for more than 10 years. Our data show that early treatment accelerated the decay of infected CD4 T cells and led to very low residual levels of detectable HIV-1 after long-term therapy, levels that were otherwise detectable in patients who are able to maintain a spontaneous, drug-free control of HIV-1 replication. Thus, long-term antiretroviral treatment started during early infection cannot eliminate HIV-1, but the reduced reservoirs of HIV-1 infected cells in such patients may increase their chances to respond to clinical interventions aiming at inducing a drug-free remission of HIV-1 infection. PMID:24965451

  9. Vibrational spectra and quantum mechanical calculations of antiretroviral drugs: Nevirapine

    NASA Astrophysics Data System (ADS)

    Ayala, A. P.; Siesler, H. W.; Wardell, S. M. S. V.; Boechat, N.; Dabbene, V.; Cuffini, S. L.

    2007-02-01

    Nevirapine (11-cyclopropyl-5,11-dihydro-4-methyl-6H-dipyrido[3,2-b:2',3'e][1,4]diazepin-6-one) is an antiretroviral drug belonging to the class of the non-nucleoside inhibitors of the HIV-1 virus reverse transcriptase. As most of this kind of antiretroviral drugs, nevirapine displays a butterfly-like conformation which is preserved in complexes with the HIV-1 reverse transcriptase. In this work, we present a detailed vibrational spectroscopy investigation of nevirapine by using mid-infrared, near-infrared, and Raman spectroscopies. These data are supported by quantum mechanical calculations, which allow us to characterize completely the vibrational spectra of this compound. Based on these results, we discuss the correlation between the vibrational modes and the crystalline structure of the most stable form of nevirapine.

  10. HIV-1 Neuroimmunity in the Era of Antiretroviral Therapy

    PubMed Central

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

    2010-01-01

    Human immunodeficiency virus type one (HIV-1) associated neurocognitive disorders (HAND) can affect < 50% of infected people during the disease course. While antiretroviral therapies have substantively increased the quality of life and reduced HIV-1 associated dementia, less severe minor cognitive and motor deficits continue. Trafficking of HIV-1 into the central nervous system (CNS), peripheral immune activation, dysregulated glial immunity, and diminished homeostatic responses are the disease-linked pathobiologic events. Monocyte-macrophage passage into the CNS remains an underlying force for disease severity. Monocyte phenotypic may change at an early stage of cell maturation and immune activation of hematopoietic stem cells. Activated monocytes are pulled into the brain in response to chemokines made as a result of glial inflammatory processes, which in turn cause secondary functional deficits in neurons. Current therapeutic approaches are focused on adjunctive and brain-penetrating antiretroviral therapies. These may attenuate virus-associated neuroinflammatory activities thereby decreasing the severity and frequency of HAND. PMID:20044002

  11. Combination antiretroviral drugs in PLGA nanoparticle for HIV-1

    PubMed Central

    2009-01-01

    Background Combination antiretroviral (AR) therapy continues to be the mainstay for HIV treatment. However, antiretroviral drug nonadherence can lead to the development of resistance and treatment failure. We have designed nanoparticles (NP) that contain three AR drugs and characterized the size, shape, and surface charge. Additionally, we investigated the in vitro release of the AR drugs from the NP using peripheral blood mononuclear cells (PBMCs). Methods Poly-(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) containing ritonavir (RTV), lopinavir (LPV), and efavirenz (EFV) were fabricated using multiple emulsion-solvent evaporation procedure. The nanoparticles were characterized by electron microscopy and zeta potential for size, shape, and charge. The intracellular concentration of AR drugs was determined over 28 days from NPs incubated with PBMCs. Macrophages were imaged by fluorescent microscopy and flow cytometry after incubation with fluorescent NPs. Finally, macrophage cytotoxicity was determined by MTT assay. Results Nanoparticle size averaged 262 ± 83.9 nm and zeta potential -11.4 ± 2.4. AR loading averaged 4% (w/v). Antiretroviral drug levels were determined in PBMCs after 100 ?g of NP in 75 ?L PBS was added to media. Intracellular peak AR levels from NPs (day 4) were RTV 2.5 ± 1.1; LPV 4.1 ± 2.0; and EFV 10.6 ± 2.7 ?g and continued until day 28 (all AR ? 0.9 ?g). Free drugs (25 ?g of each drug in 25 ?L ethanol) added to PBMCs served as control were eliminated by 2 days. Fluorescence microscopy and flow cytometry demonstrated phagocytosis of NP into monocytes-derived macrophages (MDMs). Cellular MTT assay performed on MDMs demonstrated that NPs are not significantly cytotoxic. Conclusion These results demonstrated AR NPs could be fabricated containing three antiretroviral drugs (RTV, LPV, EFV). Sustained release of AR from PLGA NP show high drug levels in PBMCs until day 28 without cytotoxicity. PMID:20003214

  12. Practical guidelines to interpret plasma concentrations of antiretroviral drugs.

    PubMed

    Kappelhoff, Bregt S; Crommentuyn, Kristel M L; de Maat, Monique M R; Mulder, Jan W; Huitema, Alwin D R; Beijnen, Jos H

    2004-01-01

    Several relationships have been reported between antiretroviral drug concentrations and the efficacy of treatment, and toxicity. Therefore, therapeutic drug monitoring (TDM) may be a valuable tool in improving the treatment of HIV-1-infected patients in daily practice. In this regard, several measures of exposure have been studied, e.g. trough and maximum concentrations, concentration ratios and the inhibitory quotient. However, it has not been unambiguously established which pharmacokinetic parameter should be monitored to maintain optimal viral suppression. Each pharmacokinetic parameter has its pros and cons. Many factors can affect the pharmacokinetics of antiretroviral agents, resulting in variability in plasma concentrations between and within patients. Therefore, plasma concentrations should be considered on several occasions. In addition, the interpretation of the drug concentration of a patient should be performed on an individual basis, taking into account the clinical condition of the patient. Important factors herewith are viral load, immunology, occurrence of adverse events, resistance pattern and comedication. In spite of the described constraints, the aim of this review is to provide a practical guide for TDM of antiretroviral agents. This article outlines pharmacokinetic target values for the HIV protease inhibitors amprenavir, atazanavir, indinavir, lopinavir, nelfinavir, ritonavir and saquinavir, and the non-nucleoside reverse transcriptase inhibitors efavirenz and nevirapine. Detailed advice is provided on how to interpret the results of TDM of these drugs. PMID:15509183

  13. Enceladus: Starting Hydrothermal Activity

    NASA Technical Reports Server (NTRS)

    Matson, D. L.; Castillo-Rogez, J. C.; Johnson, T. V.; Lunine, J. I.; Davies, A. G.

    2011-01-01

    We describe a process for starting the hydrothermal activity in Enceladus' South Polar Region. The process takes advantage of fissures that reach the water table, about 1 kilometer below the surface. Filling these fissures with fresh ocean water initiates a flow of water up from an ocean that can be self-sustaining. In this hypothesis the heat to sustain the thermal anomalies and the plumes comes from a slightly warm ocean at depth. The heat is brought to the surface by water that circulates up, through the crust and then returns to the ocean.

  14. 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

  15. 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

  16. Missouri: Early Head Start Initiative

    ERIC Educational Resources Information Center

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

    2012-01-01

    Missouri's Early Head Start/Child Care Partnership Project expands access to Early Head Start (EHS) services for children birth to age 3 by developing partnerships between federal Head Start, EHS contractors, and child care providers. Head Start and EHS contractors that participate in the initiative provide services through community child care…

  17. Minnesota: Early Head Start Initiatiive

    ERIC Educational Resources Information Center

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

    2012-01-01

    Minnesota provides supplemental state funding to existing federal Head Start and Early Head Start (EHS) grantees to increase their capacity to serve additional infants, toddlers, and pregnant women. The initiative was started in 1997 when the state legislature earmarked $1 million of the general state Head Start supplemental funds for children…

  18. 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

  19. Directly Administered Antiretroviral Therapy for HIV-Infected Drug Users Does Not Have an Impact on Antiretroviral Resistance

    PubMed Central

    Maru, Duncan Smith-Rohrberg; Kozal, Michael J.; Bruce, R. Douglas; Springer, Sandra A.

    2009-01-01

    Background Directly administered antiretroviral therapy (DAART) is an effective intervention that improves clinical outcomes among HIV-infected drug users. Its effects on antiretroviral drug resistance, however, are unknown. Methods We conducted a community-based, prospective, randomized controlled trial of DAART compared with self-administered therapy (SAT). We performed a modified intention-to-treat analysis among 115 subjects who provided serum samples for HIV genotypic resistance testing at baseline and at follow-up. The main outcomes measures included total genotypic sensitivity score, future drug options, number of new drug resistance mutations (DRMs), and number of new major International AIDS Society (IAS) mutations. Results The adjusted probability of developing at least 1 new DRM did not differ between the 2 arms (SAT: 0.41 per person-year [PPY], DAART: 0.49 PPY; adjusted relative risk [RR] = 1.04; P = 0.90), nor did the number of new mutations (SAT: 0.76 PPY, DAART: 0.83 PPY; adjusted RR = 0.99; P = 0.99) or the probability of developing new major IAS new drug mutations (SAT: 0.30 PPY, DAART: 0.33 PPY; adjusted RR = 1.12; P = 0.78). On measures of GSS and FDO, the 2 arms also did not differ. Conclusion In this trial, DAART provided on-treatment virologic benefit for HIV-infected drug users without affecting the rate of development of antiretroviral medication resistance. PMID:18193497

  20. START High Performance Discharges

    NASA Astrophysics Data System (ADS)

    Gates, D. A.

    1997-11-01

    Improvements to START (Small Tight Aspect Ratio Tokamak), the first spherical tokamak in the world to achieve high plasma temperature with both a significant pulse length and confinement time, have been ongoing since 1991. Recent modifications include: expansion of the existing capacitor banks allowing plasma currents as high as 300kA, an increase in the available neutral beam heating power ( ~ 500kW), and improvements to the vacuum system. These improvements have led to the achievement of the world record plasma ? (? 2?_0 /B^2) of ~ 30% in a tokamak. The normalised ? ( ?N ? ? aB/I_p) reached 4.5 with q_95 = 2.3. Properties of the reconstructed equilibrium will be discussed in detail. The theoretical limit to ? is higher in a spherical tokamak than in a conventional machine, due to the higher values of normalised current (IN ? I_p/aB) achievable at low aspect ratio. The record ? was achieved with IN ~ 8 while conventional tokamaks are limited to IN ~ 3, or less. Calculations of the ideal MHD stability of the record discharge indicate high ? low-n kink modes are stable, but that the entire profile is at or near marginal stability for high-n ballooning modes. The phenomenology of the events leading up to the plasma termination is discussed. An important aspect of the START program is to explore the physics of neutral beam absorption at low aspect ratio. A passive neutral particle analyser has been used to study the temporal and spatial dependence of the fast hydrogen beam ions. These measurements have been used in conjunction with a single particle orbit code to estimate the fast ion losses due to collisions with slow neutrals from the plasma edge. Numerical analysis of neutral beam power deposition profiles are compared with the data from an instrumented beam stop. The global energy confinement time ?E in beam heated discharges on START is similar to that obtained in Ohmic discharges, even though the input power has roughly doubled over the Ohmic case. Analysis of the confinement properties of the discharge and a discussion of the scaling of confinement with global plasma parameters will be presented. Comparisons are made between the predictions of neoclassical transport theory and ion temperature measurements from a charge exchange spectrometer. These results indicate the ability of spherical tokamaks to support high ? operation with good confinement. Experiments in the MAST (Mega Amp Spherical Tokamak) device, currently under construction, will demonstrate spherical tokamak operations for significantly longer pulse lengths at high ( ~1-2MA) plasma current.

  1. Antiretroviral treatment in pregnancy: a six-year perspective on recent trends in prescription patterns, viral load suppression, and pregnancy outcomes.

    PubMed

    Baroncelli, Silvia; Tamburrini, Enrica; Ravizza, Marina; Dalzero, Serena; Tibaldi, Cecilia; Ferrazzi, Enrico; Anzidei, Gianfranco; Fiscon, Marta; Alberico, Salvatore; Martinelli, Pasquale; Placido, Giuseppina; Guaraldi, Giovanni; Pinnetti, Carmela; Floridia, Marco

    2009-07-01

    The aim of the study was to describe the recent trends in antiretroviral treatment in late pregnancy and the sociodemographic changes among pregnant women with HIV over the last 6 years. Data from the National Program on Surveillance on Antiretroviral Treatment in Pregnancy in Italy were grouped per calendar year, and changes in antiretroviral treatment, population characteristics, maternal immunovirologic status and newborn clinical parameters were analyzed. A total of 981 HIV-infected mothers who delivered between 2002 and 2008 were evaluated. The proportion of women receiving at least three antiretroviral drugs at delivery increased significantly from 63.0% in 2002 to 95.5% in 2007-2008, paralleled by a similar upward trend in the proportion of women who achieved complete viral suppression at third trimester (from 37.3 in 2002 to 80.9 in 2007-2008; p < 0.001). The co-formulation of zidovudine plus lamivudine remained the most common nucleoside backbone in pregnancy, even if a significant increase in the use of tenofovir plus emtricitabine was observed in more recent years. Starting from 2003, nevirapine prescription declined, paralleled by a significant rise in the use of protease inhibitors (PI), which were present in more than 60% of regimens administered in 2007-2008. Nelfinavir was progressively replaced by ritonavir-boosted PIs, mainly lopinavir. No significant changes in preterm delivery, Apgar score, birth weight, and birth defects were observed during the study period, and the rate of HIV transmission remained below 2%. These data demonstrate a significant evolution in the treatment of HIV in pregnancy. Constant improvements in the rates of HIV suppression were observed, probably driven by the adoption of stronger and more effective regimens and by the increasing options available for combination treatment. PMID:19530956

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

    ERIC Educational Resources Information Center

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

    2009-01-01

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

  3. From Head Start to Sure Start: Reflections on Policy Transfer

    ERIC Educational Resources Information Center

    Welshman, John

    2010-01-01

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

  4. Start and bomber survivability

    SciTech Connect

    Speed, R.D.

    1989-05-01

    The survivability of the strategic bombers, while important today, is likely to be viewed as being of even greater importance in the 1990s if the US makes drastic cuts in its strategic forces as proposed in START and possible follow-on treaties. The analysis in this paper indicates that the Soviets with only a few SSBNs could pose a serious threat to the survivability of the strategic bombers (as presently based) if they moved these SSBNs close to the coasts or developed short-time-of-flight trajectories for their SLBMs. In searching for ways to improve bomber survivability, the use of the proposed LPS (Limited Protection System) ABM to defend bomber bases was examined, but found to offer marginal improvement, at best. However, a significant improvement in survivability against even severe threats could be achieved if the alert bomber forces were rebased at a large number (preferably 40 or more) of separate bases distributed in a region in the interior of the country with the closest base being at least 500 nmi from the coasts.

  5. Starting physiology: bioelectrogenesis.

    PubMed

    Baptista, Vander

    2015-12-01

    From a Cartesian perspective of rational analysis, the electric potential difference across the cell membrane is one of the fundamental concepts for the study of physiology. Unfortunately, undergraduate students often struggle to understand the genesis of this energy gradient, which makes the teaching activity a hard task for the instructor. The topic of bioelectrogenesis encompasses multidisciplinary concepts, involves several mechanisms, and is a dynamic process, i.e., it never turns off during the lifetime of the cell. Therefore, to improve the transmission and acquisition of knowledge in this field, I present an alternative didactic model. The design of the model assumes that it is possible to build, in a series of sequential steps, an assembly of proteins within the membrane of an isolated cell in a simulated electrophysiology experiment. Initially, no proteins are inserted in the membrane and the cell is at a baseline energy state; the extracellular and intracellular fluids are at thermodynamic equilibrium. Students are guided through a sequence of four steps that add key membrane transport proteins to the model cell. The model is simple at the start and becomes progressively more complex, finally producing transmembrane chemical and electrical gradients. I believe that this didactic approach helps instructors with a more efficient tool for the teaching of the mechanisms of resting membrane potential while helping students avoid common difficulties that may be encountered when learning this topic. PMID:26628666

  6. Air jump start system

    SciTech Connect

    Kettler, E.H.

    1986-05-20

    An apparatus is described for jump starting the internal combustion engine of a motor vehicle equipped with an air starter comprising in combination: An engine air pressure starter tank mounted on the motor vehicle; A tire carried by the vehicle having an inflation valve; starter tank air inlet means connected in fluid relationship with the tank including a check valve member connected in fluid relationship to the tank, the check valve member normally biased in closed position to prevent air under pressure from discharging from the tank, and operable to be opened to allow pressurized air to enter the tank, and a first air inlet hose coupling connected in closed fluid communication with the check valve member; and starter tank air recharging means including a second hose coupling sealingly connected releasably in fluid relation to the first hose coupling, a length of flexible tubing connected in sealed air tight relation to the first hose coupling at one end thereof, and a coupling sealingly connected at the other end of the tubing operable to be sealingly connected to the inflation valve of the tire and to compress the valve stem thereof to open the inflation valve to allow pressurized air from the tire to enter the air starter tank through the check valve.

  7. Computational models for prediction of response to antiretroviral therapies.

    PubMed

    Prosperi, Mattia C F; De Luca, Andrea

    2012-01-01

    This review describes the state-of-the-art in statistical, machine learning, and expert-advised computational methods for the evaluation and optimization of combination antiretroviral therapy, with respect to the virologic outcomes in HIV-1-infected patients. Currently employed methodologies are based on the paradigm for which mutations present in patient viral genotypes, selected either by treatment or already transmitted to the patient as resistant mutants, are the major drivers of virologic outcomes. Genotypic interpretation systems have been designed with the prime objective of characterizing the resistance to individual drugs, deriving scores from the association of viral genotypes with in vitro phenotypic drug susceptibility or in vivo response to treatment. Nevertheless, the very large range of possible drug combinations and of viral mutational patterns leads to an extremely complex scenario, making prediction of in vivo treatment response extremely challenging. To deal with such complexity, machine learning methods are being increasingly explored, thanks to the availability of exponentially growing HIV data bases in recent years. The combination of genotypic interpretation systems with other laboratory markers, treatment history, past clinical events, and the usage of data-driven techniques has dramatically raised the confidence in predicting virologic outcomes. A few of these systems have been implemented as free web-services, indicating ranks of suitable combination antiretroviral therapy regimens given a patient's clinical background. Future perspectives in the field foresee the extension of therapy optimization systems to newly approved antiretroviral drug targets and the prediction of other clinical outcomes, rather than the sole virologic response. PMID:22627610

  8. [Clinical and immunological profile of HIV-infected patients at the initiation of antiretroviral therapy in Douala].

    PubMed

    Essomba, N E; Mbatchou Ngahane, B H; Nida, M; Temfack, E; Mapoure Njankouo, Y; Abeng, R L; Fokalbo, Z Kobe; Achu Joko, H; Mbenoun, M; Meledie, A P; Halle, M P; Malongue, A; Tchente, C; Nana Njamen, T; Halle Ekane, G; Ngwane, S; Barla, E; Abena, P; Ndobo, P; Moungo Kuidjeu, C; Adiogo, D; Mouelle Sone, A; Luma Namme, H; Coppieters, Y

    2015-10-01

    The aim of this study was to describe the clinical and immunological profile of patients infected with HIV after initiation of antiretroviral therapy. Sociodemographic characteristics, clinical and immunological patients were recorded. Chi square test and Mann-Whitney were used to compare variables. The multivariate regression model identified risk factors. So that, 936 (56.2%) patients were in stages III and IV of the WHO and 65.2% at an advanced stage of the disease. Factors associated with initiation at an advanced stage, were male sex (p = 0.007) and time to diagnosis (p = 0.005). In 2/3 cases, treatment is started at an advanced stage of disease. It is therefore important to intensify awareness campaigns for early detection and encourage patients to ensure regular medical follow-up screening. PMID:26296430

  9. Response to antiretroviral therapy (ART): comparing women with previous use of zidovudine monotherapy (ZDVm) in pregnancy with ART naïve women

    PubMed Central

    2014-01-01

    Background Short-term zidovudine monotherapy (ZDVm) remains an option for some pregnant HIV-positive women not requiring treatment for their own health but may affect treatment responses once antiretroviral therapy (ART) is subsequently started. Methods Data were obtained by linking two UK studies: the UK Collaborative HIV Cohort (UK CHIC) study and the National Study of HIV in Pregnancy and Childhood (NSHPC). Treatment responses were assessed for 2028 women initiating ART at least one year after HIV-diagnosis. Outcomes were compared using logistic regression, proportional hazards regression or linear regression. Results In adjusted analyses, ART-naïve (n?=?1937) and ZDVm-experienced (n?=?91) women had similar increases in CD4 count and a similar proportion achieving virological suppression; both groups had a low risk of AIDS. Conclusions In this setting, antenatal ZDVm exposure did not adversely impact on outcomes once ART was initiated for the woman’s health. PMID:24593018

  10. Epidemiology and Management of Antiretroviral-Associated Cardiovascular Disease

    PubMed Central

    Chastain, Daniel B; Henderson, Harold; Stover, Kayla R

    2015-01-01

    Risk and manifestations of cardiovascular disease (CVD) in patients infected with human immunodeficiency virus (HIV) will continue to evolve as improved treatments and life expectancy of these patients increases. Although initiation of antiretroviral (ARV) therapy has been shown to reduce this risk, some ARV medications may induce metabolic abnormalities, further compounding the risk of CVD. In this patient population, both pharmacologic and nonpharmacologic strategies should be employed to treat and reduce further risk of CVD. This review summarizes epidemiology data of the risk factors and development of CVD in HIV and provides recommendations to manage CVD in HIV-infected patients. PMID:25866592

  11. Generic antiretroviral drugs in developing countries: friends or foes?

    PubMed

    Zucman, David; Camara, Seydou; Gravisse, Jérome; Dimi, Svetlane; Vasse, Marc; Goudjo, Abdon; Choquet, Marion; Peytavin, Gilles

    2014-02-20

    Although second-line generic antiretroviral drugs are of great value in developing countries, there are concerns regarding their quality. We studied a generic Lopinavir/ritonavir (200/50 ?mg; Arga-L, India) marketed in the Republic of Congo but not prequalified by WHO. Despite adequate quantitative and qualitative drug content, Arga-L had a bio-availablility of 10% compared with Kaletra. To avoid selection of drug-resistant HIV, rigorous pharmacological monitoring of generic drugs not prequalified by WHO must be a priority. PMID:24378755

  12. People with AIDS (PWA) since highly active antiretroviral therapy, 1996.

    PubMed

    Dunbar, Deanne

    2011-06-01

    Although clarity about HIV transmission biology and effective therapy should mean that an AIDS diagnosis is more socially acceptable today, for some groups the cultural stigma of HIV infection has changed little in the last 30 years. This paper will examine why representations of HIV-positive gay men suggest they pose a special civic risk and how these conceptualizations have harnessed cultural anxieties about racial and sexual minorities to shape public policy and behavior since the advent of Highly Active Antiretroviral Therapy (HAART) in 1996. PMID:21243415

  13. Thailand: successful challenge to invalid patent claim on antiretrovirals.

    PubMed

    Kaplan, Karyn

    2002-12-01

    Thai people living with HIV/AIDS made legal history on 1 October 2002, when they won a lawsuit against the pharmaceutical giant Bristol Myers-Squibb (BMS). The plaintiffs, two people living with HIV/AIDS and a local NGO, the AIDS Access Foundation, lodged a complaint against BMS and Thailand's Department of Intellectual Property (DIP) in Thailand's Central Intellectual Property and International Trade Court (CIPITC). They claimed that the BMS patent registration for its buffered tablet formulation of the antiretroviral AIDS drug, dideoxy purine nucleoside (ddI, brand name Videx), was illegally amended in an attempt to claim a wider monopoly than the patent description justified. PMID:14740606

  14. 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…

  15. Postexposure Prophylactic Effect of Hepatitis B Virus (HBV)-Active Antiretroviral Therapy against HBV Infection

    PubMed Central

    Watanabe, Tsunamasa; Hamada-Tsutsumi, Susumu; Yokomaku, Yoshiyuki; Imamura, Junji; Sugiura, Wataru

    2014-01-01

    Retrospective study indicates that hepatitis B virus (HBV)-active nucleoside (nucleotide) analogues (NAs) used for antiretroviral therapy reduce the incidence of acute HBV infections in human immunodeficiency virus (HIV)-infected patients. Learning from HIV postexposure prophylaxis (PEP), we explored the possibility of using NAs in PEP following HBV exposure, if preexposure prophylaxis is feasible clinically. Using freshly isolated primary human hepatocytes cultured in vitro, we analyzed the effect of HBV-active tenofovir and lamivudine in primary HBV infection and also the effect of treatment with these NAs after HBV infection. HBV-active NAs applied from 24 h before inoculation could not prevent the secretion of hepatitis B surface antigen into the culture medium, and cessation of the NAs after inoculation allowed the cells to establish an apparent HBV infection. In contrast, hepatitis B immune globulin was able to prevent HBV infection completely. NA treatment before infection, however, can control the spread of HBV infection, as detected by immunohistochemistry. Practically, starting NA treatment within 2 days of primary HBV infection inhibited viral spread effectively, as well as preexposure treatment. We demonstrated that preexposure NA treatment was not able to prevent the acquisition of HBV infection but prevented viral spread by suppressing the production of mature progeny HBV virions. The effect of postexposure treatment within 2 days was similar to the effect of preexposure treatment, suggesting the possibility of HBV PEP using HBV-active NAs in HIV- and HBV-susceptible high-risk groups. PMID:25512419

  16. Reduced adherence to antiretroviral therapy among HIV-infected Tanzanians seeking cure from the Loliondo healer.

    PubMed

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

    2014-03-01

    : 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 km away), and their adherence to antiretrovirals (ARVs) dropped precipitously (odds ratio = 0.20, 95% confidence interval: 0.09 to 0.44, P < 0.001) after the visit. Compared with those not attending Loliondo, attendees were more likely to have been diagnosed with HIV more remotely (3.8 vs. 3.0 years before, 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/mm, 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 (odds ratio = 1.49, 95% confidence interval: 1.23 to 1.80). Treatment fatigue may play a role in the lure of alternative healers. PMID:24525471

  17. 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

  18. Antiretroviral Chemoprophylaxis: State of Evidence and the Research Agenda

    PubMed Central

    Mayer, Kenneth H.

    2014-01-01

    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

  19. HPLC analysis of generic antiretroviral drugs purchased in Rwanda.

    PubMed

    Schuman, Marc; Schneider, Serge; Omes, Christine; Wennig, Robert; Fundira, Léon; Tayari, Jean-Claude; Arendt, Vic

    2005-01-01

    A reversed phase HPLC method using photo diode array detection for the simultaneous quantification of lamivudine, stavudine, nevirapine, zidovudine, methyl paraben and propyl paraben in solid and liquid drug formulations was developed and validated. The separation was achieved using a Waters Symmetry C8 column, using a mobile phase gradient comprising 50 mM NaH2PO4 (pH 3.8) and acetonitrile (95:5 to 45:55, v/v) and a flow gradient (0.5 to 1.0 ml/min). The limits of detection and quantification were below 19 ng/ml and 55 ng/ml respectively. The intra- and inter-day assay precisions were within 4.4% relative standard deviations. The developed method was applied to 12 different generic antiretroviral medications, consisting of tablets, capsules and solutions, produced by two Indian manufacturers and purchased by the Central Agency of Essential Drug Procurement of Rwanda for the ESTHER project in Rwanda. The average content of the antiretroviral agent(s) compared to the labeled amount(s) was 101.4%. Methyl paraben and propyl paraben, added to solutions as preservatives, were within the FDA recommended limits. PMID:17176547

  20. Trends and economic stress: a challenge to universal access to antiretroviral treatment in India.

    PubMed

    Dhamija, P; Bansal, D; Medhi, B

    2009-07-01

    The prospects for expanded access to antiretroviral therapy (ART) in resource-poor settings have greatly improved as a result of global and national efforts to reduce the cost of antiretroviral drugs (ARV), growing availability of cheaper generics, and increased financing available from the Global Funds like Medicines Sans Frontieres. Indian health set-up provides drugs free-of-cost to HIV infected patients through government network and also through open-market to those who intend to have personalized care. Post-2005, implementation of WTO agreement on TRIPS is expected to have a significant impact on pricing and availability of generic ARV. The study has been planned to explore the trends and gaps in availability & accessibility of ARV in India. The trends in per-patient-per-year (PPPY) cost of individual ARV and treatment regimes were also explored. The epidemiological data demonstrated stabilization of the epidemic in India. Most ARV are available in India by the generic manufacturers with a median drug lag period of 2.05 years (Range 0.75-6.51 years). There is a significant price difference in drugs available from generic and originator companies. Prices for patented and generic ARV in India reflect price negotiations that have taken place since the introduction of drugs in the country, still most of the ARVs are available at a much higher cost in the market [median 2.6 times (range 1-7)]. The per-patient per year (PPPY) cost of providing first-line regime in 2008 has decreased 2.75 times from that in 2003. The analysis shows the stabilization of prices of all drugs after 2006. HIV spending in India has seen a growth of 26 percent and 28 percent in 2005-06 and 2006-07 respectively. Still, the expected expenditure to cover the whole patient population needing therapy is considerably higher than the actual expenditure incurred for providing ARV. Despite the price reductions and availability of ARV at a lower cost through agencies like MSF, there is a large gap in the expenditure incurred and patient population covered. These trends may foreshadow future AIDS treatment cost trends in the country as more people start treatment, AIDS patients live longer and move from first-line to second and third-line treatment, AIDS treatment becomes more complex, generic competition emerges, and newer patented drugs become available. PMID:19601776

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

    PubMed Central

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

    2010-01-01

    Background Although combination antiretroviral therapy (cART) initiated in the acute phase of HIV-1 infection may prevent expansion of the latent reservoir, its benefits remain controversial. In the current study, HIV-1 RNA transcription patterns in peripheral blood mononuclear cells (PBMC) were monitored during acute cART to assess the effect of early treatment on cellular viral reservoirs. Methodology/Principal Findings Acutely HIV-1 infected patients (n?=?24) were treated within 3–15 weeks after infection. Patients elected to cease treatment after ?1 year of therapy. HIV-1 DNA (vDNA), HIV-1 RNA species expressed both in latently and productively infected cells, unspliced (UsRNA), multiply spliced (MsRNA-tatrev; MsRNA-nef), and PBMC-associated extracellular virion RNA (vRex), expressed specifically by productively infected cells, were quantified in PBMC by patient matched real-time PCR prior, during and post cART. In a matched control-group of patients on successful cART started during chronic infection (n?=?15), UsRNA in PBMC and vDNA were measured cross-sectionally. In contrast to previous reports, PBMC-associated HIV-1 RNAs declined to predominantly undetectable levels on cART. After cART cessation, UsRNA, vRex, and MsRNA-tatrev rebounded to levels not significantly different to those at baseline (p>0.1). In contrast, MsRNA-nef remained significantly lower as compared to pretreatment (p?=?0.015). UsRNA expressed at the highest levels of all viral RNAs, was detectable on cART in 42% of patients with cART initiated during acute infection as opposed to 87% of patients on cART initiated during chronic infection (Fisher's exact test; p?=?0.008). Accordingly, UsRNA levels were 105–fold lower in the acute as compared to the chronic group. Conclusion Early intervention resulted in profound depletion of PBMC expressing HIV-1 RNA. This is contrary to chronically infected patients who predominantly showed continuous UsRNA expression on cART. Thus, antiretroviral treatment initiated during the acute phase of infection prevented establishment or expansion of long-lived transcriptionally active viral cellular reservoirs in peripheral blood. PMID:20967271

  2. 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

  3. 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

  4. Start Date End Date Start Time End Time

    E-print Network

    Nicholson, Bruce J.

    in advance of the event. A $50 administration fee will be assessed to any event submitted less than 10 days prior to the event. hh:mm mm/dd/yyyy Est # of Vehicles Submit Form Clear Fields 000 - None Enter #s onlyEvent Name Start Date End Date Start Time End Time Event Location Building Room Other Est

  5. Insurability of HIV-positive people treated with antiretroviral therapy in Europe: collaborative analysis of HIV cohort studies

    PubMed Central

    Kaulich-Bartz, Josee; Dam, Wayne; May, Margaret T.; Lederberger, Bruno; Widmer, Urs; Phillips, Andrew N.; Grabar, Sophie; Mocroft, Amanda; Vilaro, Josep; van Sighem, Ard; Moreno, Santiago; Dabis, François; Monforte, Antonella D’Arminio; Teira, Ramon; Ingle, Suzanne M.; Sterne, Jonathan A.C.

    2013-01-01

    Objective: To increase equitable access to life insurance for HIV-positive individuals by identifying subgroups with lower relative mortality. Design: Collaborative analysis of cohort studies. Methods: We estimated relative mortality from 6 months after starting antiretroviral therapy (ART), compared with the insured population in each country, among adult patients from European cohorts participating in the ART Cohort Collaboration (ART-CC) who were not infected via injection drug use, had not tested positive for hepatitis C, and started triple ART between 1996–2008. We used Poisson models for mortality, with the expected number of deaths according to age, sex and country specified as offset. Results: There were 1236 deaths recorded among 34?680 patients followed for 174?906 person-years. Relative mortality was lower in patients with higher CD4 cell count and lower HIV-1 RNA 6 months after starting ART, without prior AIDS, who were older, and who started ART after 2000. Compared with insured HIV-negative lives, estimated relative mortality of patients aged 20–39 from France, Italy, United Kingdom, Spain and Switzerland, who started ART after 2000 had 6-month CD4 cell count at least 350?cells/?l and HIV-1 RNA less than104?copies/ml and without prior AIDS was 459%. The proportion of exposure time with relative mortality below 300, 400, 500 and 600% was 28, 43, 61 and 64%, respectively, suggesting that more than 50% of patients (those with lower relative mortality) could be insurable. Conclusion: The continuing long-term effectiveness of ART implies that life insurance with sufficiently long duration to cover a mortgage is feasible for many HIV-positive people successfully treated with ART for more than 6 months. PMID:23449349

  6. 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…

  7. Maine: Early Head Start Initiatives

    ERIC Educational Resources Information Center

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

    2012-01-01

    Maine has two initiatives that build on Early Head Start (EHS). The first initiative, Fund for a Healthy Maine, has since 2001 provided tobacco settlement money to existing Head Start and EHS programs to expand the number of children who receive full-day, full-year services. Local programs have the option of using these funds for EHS, depending on…

  8. 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…

  9. Antiretroviral Therapy Adherence Among Transgender Women Living with HIV

    PubMed Central

    Sevelius, Jae M.; Carrico, Adam; Johnson, Mallory O.

    2010-01-01

    Despite disproportionate rates of HIV among transgender women and evidence that medication adherence is necessary for treatment success and increased likelihood of survival, there has been little investigation into antiretroviral treatment (ART) adherence issues among transgender women. This study examined rates of self-reported ART adherence among transgender women on ART (n = 35) and well-established correlates of nonadherence including depression, adherence self-efficacy, patient perceptions of interactions with their providers, and perceived adverse side effects of ART compared to other respondents (n = 2,770). Transgender women on ART were less likely to report 90% adherence rates or higher and reported less confidence in their abilities to integrate treatment regimens into their daily lives. When transgender women were compared to other respondents, regardless of the current medication regimen, they reported significantly fewer positive interactions with their health care providers. Training for providers and integration of hormone therapy into HIV care is recommended. PMID:20347342

  10. [Policy dilemmas in providing antiretroviral treatment in Brazil].

    PubMed

    do Lago, Regina Ferro; Costa, Nilson do Rosário

    2010-11-01

    This paper addresses institutional constraints that have affected Brazilian politics regarding provision of anti-retroviral treatment (ART) to HIV/Aids patients. We analyzed the normative conflict resulting from international agreements on intellectual property rights, especially patent protection, and the constitutional rights of Brazilian patients to universal and free access to ART. These constraints have not substantially changed the Brazilian public policy yet, but they may impact the future sustainability of this policy. As the main barrier to the production of patented drugs is not technological but institutional, Brazilian government faces a dilemma. It may either abide by existing monopolistic restrictions or it may incite competitiveness of domestic industries and developing countries in the pharmaceutical market. PMID:21120341

  11. Antiretroviral therapy-associated acute motor and sensory axonal neuropathy.

    PubMed

    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

  12. Determinants of antiretroviral therapy coverage in Sub-Saharan Africa

    PubMed Central

    Hoque, Mohammad Zahirul

    2015-01-01

    Among 35 million people living with the human immunodeficiency virus (HIV) in 2013, only 37% had access to antiretroviral therapy (ART). Despite global concerted efforts to provide the universal access to the ART treatment, the ART coverage varies among countries and regions. At present, there is a lack of systematic empirical analyses on factors that determine the ART coverage. Therefore, the current study aimed to identify the determinants of the ART coverage in 41 countries in Sub-Saharan Africa. It employed statistical analyses for this purpose. Four elements, namely, the HIV prevalence, the level of national income, the level of medical expenditure and the number of nurses, were hypothesised to determine the ART coverage. The findings revealed that among the four proposed determinants only the HIV prevalence had a statistically significant impact on the ART coverage. In other words, the HIV prevalence was the sole determinant of the ART coverage in Sub-Saharan Africa. PMID:26664812

  13. Antiretroviral Treatment Regimen Outcomes Among HIV-Infected Prisoners

    PubMed Central

    Springer, Sandra A.; Friedland, Gerald H.; Doros, Gheorghe; Pesanti, Edward; Altice, Frederick L.

    2008-01-01

    Background Despite the high prevalence of HIV in correctional settings, the duration of therapy and response to various highly active antiretroviral therapy (HAART) regimens in this setting is unknown. Method Using a retrospective cohort study (1997?2002) of HIV-infected prisoners in Connecticut that linked demographic, pharmacy, and laboratory data, we compared HIV-1 RNA (VL) and CD4 lymphocyte responses to four treatment strategies at baseline and at the end of incarceration. Results Using an analysis of 1,044 incarceration periods or 1,099 subjects for whom ?6 months of continuous data were available, HAART regimens that included a triple NRTI, two NRTIs + either a PI or NNRTI, or a three-class (NRTI+NNRTI+PI) strategy demonstrated no difference in virological and immunological outcomes. The proportion of subjects who were initiated with NRTI, NNRTI, PI, or three-class regimens were 14%, 32%, 46%, and 8%, respectively. For all study groups, the mean change from baseline in CD4 and VL was +74 cells/?L and ?0.93 log10 copies/mL (p < .0001), respectively. Overall, 59% of subjects had an HIV-1 RNA level below the level of detection (<400 copies/mL) by the end of their incarceration. Using Kaplan-Meier curves to examine the time to change in the initial HAART strategy over the incarceration period, the three-class strategy was significantly more likely to be changed earlier than all others (p < .05). Conclusion Although the three-class strategy was less durable, initiating HAART with any strategy resulted in similar and impressive virological and immunological outcomes by the end of incarceration, further supporting prison as an important site for the initiation and provision of effective antiretroviral therapy. PMID:17720660

  14. Alcohol consumption enhances antiretroviral painful peripheral neuropathy by mitochondrial mechanisms

    PubMed Central

    Ferrari, Luiz F.; Levine, Jon D.

    2010-01-01

    A major dose-limiting side effect of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) chemotherapies, such as the nucleoside reverse transcriptase inhibitors (NRTIs), is a small-fiber painful peripheral neuropathy, mediated by its mitochondrial toxicity. Co-morbid conditions may also contribute to this dose-limiting effect of HIV/AIDS treatment. Alcohol abuse, which alone also produces painful neuropathy, is one of the most important co-morbid risk factors for peripheral neuropathy in patients with HIV/AIDS. Despite the prevalence of this problem and its serious impact on the quality of life and continued therapy in HIV/AIDS patients, the mechanisms by which alcohol abuse exacerbates highly active antiretroviral therapy (HAART)-induced neuropathic pain has not been demonstrated. In this study, performed in rats, we investigated the cellular mechanism by which consumed alcohol impacts antiretroviral-induced neuropathic pain. NRTI 2',3'-dideoxycytidine (ddC) (50 mg/kg) neuropathy was mitochondrial dependent and PKC? independent, and alcohol-induced painful neuropathy, PKC? dependent and mitochondrial independent. At low doses, ddC (5 mg/kg) and alcohol (6.5% ethanol diet for one week), which alone do not affect nociception, together produce profound mechanical hyperalgesia. This hyperalgesia is mitochondrial dependent but PKC? independent. These experiments, which provide the first model for studying the impact of co-morbidity in painful neuropathy, support the clinical impression that alcohol consumption enhances HIV/AIDS therapy neuropathy, and provide evidence for a role of mitochondrial mechanisms underlying this interaction. PMID:20726883

  15. Highly active antiretroviral therapy: Does it Sound toxic?

    PubMed Central

    Khoza-Shangase, Katijah

    2011-01-01

    Objective The main objective of the current study is to monitor the auditory status in a group of adults with AIDS, receiving Highly Active Antiretroviral Therapy (HAART) (3TC -lamivudine, D4T – stavudine, and efavirenz) in a hospital outpatient clinic in Gauteng. A total sample of 54 adults (between the ages of 18 and 50 years) in the experimental group and 16 in the control group were assessed prospectively following a repeated measures design. All participants were assessed at baseline at three months, and at six months into the treatment. Materials and Methods The participants underwent case history interviews and medical record reviews, otoscopy, and tympanometry, as well as conventional pure tone audiometry and distortion product otoacoustic emission testing. Both descriptive and inferential statistics were used to analyze the data. Results On audiological monitoring, statistically significant changes (P<0.05) were established, only in the experimental group, for pure tone audiometry — with clinically significant changes found at high frequencies. Statistically significant changes with clinically significant changes were obtained for distortion product otoacoustic emissions (DPOAEs) in the experimental group, particularly at high frequencies — implying subclinical hearing function changes; while lack of statistically significant changes with no clinically significant changes were found in the control group. The subclinical hearing changes in the experimental group were also evident in the findings of the subclinical hearing loss group, who, although they had normal pure tone function after six months of follow up, presented with clinical changes on DPOAEs at 6 and 8 kHz. Conclusions Findings highlight the need for closer monitoring of the effects of antiretroviral drugs (ARVs) on hearing, through the use of more sensitive tools of assessment when conducting drug trials. PMID:21430965

  16. 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-naïve 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

  17. Life extended : the intimate politics of the antiretroviral era in Northern Nigeria 

    E-print Network

    Kingsley, Peter Alden

    2014-11-27

    For more than thirty years, the HIV pandemic has caused immense harm across sub-Saharan Africa. From the middle of the last decade, however, a treatment revolution has been underway, as effective antiretroviral drugs (ARVs) ...

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

    PubMed Central

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

    2014-01-01

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

  19. 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

  20. VIROLOGIC AND IMMUNOLOGIC OUTCOMES IN HIV-INFECTED CAMBODIAN CHILDREN AFTER 18 MONTHS OF HIGHLY ACTIVE ANTIRETROVIRAL THERAPY (HAART)

    PubMed Central

    Sophan, Sam; Meng, Chhour Y; Pean, Polidy; Harwell, Joseph; Hutton, Elizabeth; Trzmielina, Sonia; Somasundaran, Mohan; Luzuriaga, Katherine; Pugatch, David

    2010-01-01

    This observational cohort study was conducted among HIV-infected, antiretroviral therapy (ART) naive children in Phnom Penh, Cambodia, to evaluate the feasibility and efficacy of highly active antiretroviral therapy (HAART) delivered using a modified directly observed therapy (MDOT) protocol. From August 2004 to March 2006, 26 children were enrolled and started on a first-line HAART regimen, which was continued for 18 months. The study included a directly observed therapy phase (months 1–3) and a medication self–administration phase (months 4–18). CD4 percentage (CD4%) and HIV-1 RNA plasma viral load (PVL) were measured at baseline and at months 6, 12, and 18. At baseline, the median age was 5.5 years (range: 13 months–12 years), the median CD4% was 4, and the median PVL was 7.5×105 copies/ml. At 18 months, 23 (88%) children were alive and participating in the study. Of these children, 20 (87%) had a PVL <400 copies/ml and 12 (52%) had PVL <50 copies/ml. The median CD4% increased to 23, while the median change in height-for-weight z-score was 0.64. Genotypic resistance typing in 2 children with PVL >400 copies/ml at 18 months demonstrated mutations associated with resistance to lamivudine (M184V) and non-nucleoside reverse transcriptase inhibitors (Y181C and G190A). The virologic and immunologic outcomes achieved in this study compare favorably with those reported by other pediatric HIV treatment programs worldwide. The study results suggest that MDOT may be effective for HAART administration in limited-resource settings like Cambodia. PMID:20578491

  1. Evaluation of improvement of onychomycosis in HIV-infected patients after initiation of combined antiretroviral therapy without antifungal treatment.

    PubMed

    Ruíz-López, Patricia; Moreno-Coutiño, Gabriela; Fernández-Martínez, Ramón; Espinoza-Hernández, Jessica; Rodríguez-Zulueta, Patricia; Reyes-Terán, Gustavo

    2015-09-01

    Onychomycosis in HIV-infected patients has a prevalence of 20-44% and is more frequently seen with CD4(+) T cell counts ?450 cel ?l(-1). There are case reports of improvement in onychomycosis after initiation of combined antiretroviral therapy (cART), but there are no prospective studies that prove the existence and frequency of this phenomenon. The aim of this study was to evaluate if HIV-infected patients with onychomycosis who begin cART improve and/or cure without antifungal treatment. We included HIV-infected patients with onychomycosis who had not started cART and nor received antifungal therapy during 6 months prior to the study. We evaluated affected the nails with the Onychomycosis Severity Index (OSI); nail scrapings were collected and direct microscopy with potassium hydroxide (KOH) as well as mycological culture were performed. We repeated these procedures at 3 and 6 months to assess changes. CD4 T cell counts and HIV viral load were obtained. A total of 16 patients were included, with male gender predominance (68.7%); distal and lateral subungual onychomycosis (DLSO) was the most common form (31.3%). Trichophyton rubrum was the most frequently isolated microorganism. OSI decreased 21.5% at 3 months and 40% at 6 months after initiation of antiretrovirals (P = 0.05). We found a non-significant tendency towards improvement with higher CD4(+) T cell counts and with viral loads <100 000 copies ml(-1). This could be due to the increase in CD4(+) T cells, decreased percentage of Treg (CD4(+)CD25(+)) among CD4(+) Tcells and/or a decreased viral load; further studies are necessary to prove these hypothesis. PMID:26155930

  2. Hydrazine engine start system air start performance and controls sizing

    SciTech Connect

    Johnson, A.T.

    1992-01-01

    Hydrazine has been used as an energy source in many applications to fuel in-flight main engine starting. In a current application, an existing hydrazine engine start system (ESS) design was adapted to meet new fuel control requirements. This paper presents a brief system description, historical context, and the motivating factors for the hydrazine controls changes and three case studies of controls design and analysis from the ESS program. 4 refs.

  3. 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.

  4. Pharmacokinetics of Antiretrovirals In Genital Secretions and Anatomic Sites of HIV Transmission: Implications for HIV Prevention

    PubMed Central

    Trezza, Christine R.; Kashuba, Angela D. M.

    2014-01-01

    The incidence of HIV remains alarmingly high in many parts of the world. Prophylactic use of antiretrovirals, capable of concentrating in the anatomical sites of transmission, may reduce the risk of infection after an unprotected sexual exposure. To date, orally and topically administered antiretrovirals have exhibited variable success in preventing HIV transmission in large-scale clinical trials. Antiretroviral mucosal pharmacokinetics may help explain the outcomes of these investigations. Penetration and accumulation of antiretrovirals into sites of transmission can influence dosing strategies and pre-exposure prophylaxis clinical trial design. Antiretroviral tissue distribution varies widely within and between drug classes, attributed in part to their physicochemical properties and tissue-specific drug transporter expression. Nucleoside (-tide) reverse transcriptase inhibitors, the CCR5 antagonist maraviroc, and the integrase inhibitor raltegravir demonstrate the highest penetration into the male and female reproductive tracts and colorectal tissue relative to blood. This review will describe antiretroviral exposure in anatomic sites of transmission, and place these findings in context with the prevention of HIV and the efficacy of pre-exposure prophylactic strategies. PMID:24859035

  5. 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?

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

    PubMed

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

    2012-10-01

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

  7. Incidence of pregnancy following antiretroviral therapy initiation and associated factors in eight West African countries

    PubMed Central

    Burgos-Soto, Juan; Balestre, Eric; Minga, Albert; Ajayi, Samuel; Sawadogo, Adrien; Zannou, Marcel D.; Leroy, Valériane; Ekouevi, Didier K.; Dabis, François; Becquet, Renaud

    2014-01-01

    Introduction This study aimed at estimating the incidence of pregnancy after antiretroviral therapy (ART) initiation in eight West African countries over a 10-year period. Methods A retrospective analysis was conducted within the international database of the IeDEA West Africa Collaboration. All HIV-infected women aged <50 years and starting ART for their own health between 1998 and 2011 were eligible. Pregnancy after ART initiation was the main outcome and was based on clinical reporting. Poisson regression analysis accounting for country heterogeneity was computed to estimate first pregnancy incidence post-ART and to identify its associated factors. Pregnancy incidence rate ratios were adjusted on country, baseline CD4 count and clinical stage, haemoglobin, age, first ART regimen and calendar year. Results Overall 29,425 HIV-infected women aged 33 years in median [Inter Quartile Range: 28–38] contributed for 84,870 women-years of follow-up to this analysis. The crude incidence of first pregnancy (2,304 events) was 2.9 per 100 women-years [95% confidence interval [CI]: 2.7–3.0], the highest rate being reported among women aged 25–29 years: 4.7 per 100 women-years; 95% CI: 4.3–5.1. The overall Kaplan-Meier probability of pregnancy occurrence by the fourth year on ART was 10.9% (95% CI: 10.4–11.4) and as high as 28.4% (95% CI: 26.3–30.6) among women aged 20–29 years at ART initiation. Conclusion The rate of pregnancy occurrence after ART initiation among HIV-infected women living in the West Africa region was high. Family planning services tailored to procreation needs should be provided to all HIV-infected women initiating ART and health consequences carefully monitored in this part of the world. PMID:25216079

  8. New indicators for delay in initiation of antiretroviral treatment: estimates for Cameroon

    PubMed Central

    Ndawinz, Jacques DA; Anglaret, Xavier; Delaporte, Eric; Koulla-Shiro, Sinata; Gabillard, Delphine; Minga, Albert; Costagliola, Dominique

    2015-01-01

    Abstract Objective To propose two new indicators for monitoring access to antiretroviral treatment (ART) for human immunodeficiency virus (HIV); (i) the time from HIV seroconversion to ART initiation, and (ii) the time from ART eligibility to initiation, referred to as delay in ART initiation. To estimate values of these indicators in Cameroon. Methods We used linear regression to model the natural decline in CD4+ T-lymphocyte (CD4+ cell) numbers in HIV-infected individuals over time. The model was fitted using data from a cohort of 351 people in Côte d’Ivoire. We used the model to estimate the time from seroconversion to ART initiation and the delay in ART initiation in a representative sample of 4154 HIV-infected people who started ART in Cameroon between 2007 and 2010. Findings In Cameroon, the median CD4+ cell counts at ART initiation increased from 140 cells/?l (interquartile range, IQR: 66 to 210) in 2007–2009 to 163 cells/?l (IQR: 73 to 260) in 2010. The estimated average time from seroconversion to ART initiation decreased from 10.4 years (95% confidence interval, CI: 10.3 to 10.5) to 9.8 years (95% CI: 9.6 to 10.0). Delay in ART initiation increased from 3.4 years (95% CI: 3.1 to 3.7) to 5.8 years (95% CI: 5.6 to 6.2). Conclusion The estimated time to initiate ART and the delay in ART initiation indicate that progress in Cameroon is insufficient. These indicators should help monitor whether public health interventions to accelerate ART initiation are successful. PMID:26478609

  9. Initiation of antiretroviral therapy at high CD4+ cell counts is associated with positive treatment outcomes

    PubMed Central

    Lima, Viviane D.; Reuter, Anja; Harrigan, P. Richard; Lourenço, Lillian; Chau, William; Hull, Mark; Mackenzie, Lauren; Guillemi, Silvia; Hogg, Robert S.; Barrios, Rolando; Montaner, Julio S.G.

    2015-01-01

    Objective There is limited research investigating the possible mechanisms of how starting combination antiretroviral therapy (cART) at a higher CD4+ cell count decreases mortality. This study investigated the association between initiating cART with short-term and long-term achievement of viral suppression; emergence of any drug resistance and of an AIDS-defining illness (ADI); long-term treatment adherence; and all-cause mortality. Methods This retrospective cohort study included 4120 naive patients who initiated cART between 2000 and 2012. Patients were followed until 2013, death or until the last contact date (varied by outcome). The main exposure was the interaction between period of cART initiation (2000–2006 and 2007–2012) and CD4+ cell count at cART initiation (<500 versus ?500 cells/?l). We considered both baseline and longitudinal covariates. We fitted different multivariable models using cross-sectional and longitudinal statistical methods, depending on the outcome. Results Patients who initiated cART with a CD4+ cell count at least 500 cells/?l in 2007–2012 had an increased likelihood of achieving viral suppression at 9 months and of maintaining an adherence level of at least 95% over time, and the lowest probability of developing any resistance and an ADI during follow-up. These patients were not the ones with the highest likelihood of maintaining viral suppression over time, most likely due to viral load blips experienced during the follow-up. Conclusion The outcomes in this study likely play an important role in explaining the positive impact of early cART initiation on mortality. These results should alleviate some of the concerns clinicians may have when initiating cART in patients with high CD4+s as recommended by current treatment guidelines. PMID:26165354

  10. Effects of Antiretroviral Therapy on Autonomic Function in Early HIV Infection: A Preliminary Report

    PubMed Central

    Chow, Dominic; Kocher, Morgan; Shikuma, Cecilia; Parikh, Nisha; Grandinetti, Andrew; Nakamoto, Beau; Seto, Todd; Low, Phillip

    2012-01-01

    Background: A prospective study was conducted in human immunodeficiency virus (HIV)-infected patients as they undergo alterations in their antiretroviral therapy (ART) to determine the effect of ART on autonomic function. Methods: HIV-infected subjects who were either 1) naïve to ART and initiating ART, or 2) receiving ART and in HIV virologic failure for at least 4 months and were about to switch ART were enrolled in this study. Autonomic function assessment (cardiovagal, adrenergic, and sudomotor tests) was performed prior to and 4 months after initiating the new ART. Changes in clinical autonomic symptoms and virologic assessment were assessed. Results: Twelve subjects completed the study: 92% male; median age (Q1, Q3) was 41.0 (28.0, 48.2) years; and 50% White/Non-Hispanic. Seventy-five percent were ART naïve while 25% were failing their ART regimen. The median CD4 count was 336.5 (245.3, 372.3) cells/mm3. All subjects achieved an undetectable HIV viral load by the 4-month follow-up visit. The majority of naïve subjects were started on an ART regimen of tenofovir / emtricitabine / efavirenz. There were no significant differences in autonomic function assessment, as measured by cardiovagal, adrenergic, and sudomotor tests, with regards to ART initiation. Conclusion: This is the first study to examine the effects of initiating ART on autonomic function in early HIV infection. This study found no appreciable differences of ART on the autonomic nervous system when ART is initiated early in the course of HIV disease. ART may not contribute to short-term changes in autonomic function. PMID:22859899

  11. Effect of antiretroviral therapy on patients’ economic well being: five-year follow-up

    PubMed Central

    Rosen, Sydney; Larson, Bruce; Rohr, Julia; Sanne, Ian; Mongwenyana, Constance; Brennan, Alana T.; Galárraga, Omar

    2014-01-01

    Objective: Evaluate the effect of antiretroviral therapy (ART) on South African HIV patients’ economic well being, as indicated by symptoms, normal activities, employment, and external support, during the first 5 years on treatment. Methods: Prospective cohort study of 879 adult patients at public or nongovernmental clinics enrolled before ART initiation or on ART less than 6 months and followed for 5.5 years or less. Patients were interviewed during routine clinic visits. Outcomes were estimated using population-averaged logistic regression and reported as proportions of the cohort experiencing outcomes by duration on ART. Results: For patients remaining in care, outcomes improved continuously and substantially, with all differences between baseline and 5 years statistically significant (P?starting ART to 17% after 5 years on ART and fatigue from 62 to 7%. The probability of not being able to perform normal activities in the previous week fell from 47 to 5% and of being employed increased from 32 to 44%; difficulty with job performance among those employed fell from 56 to 6%. As health improved, the probability of relying on a caretaker declined from 81 to less than 1%, and receipt of a disability grant, which initially increased, fell slightly over time on ART. Conclusion: Results from one of the longest prospective cohorts tracking economic outcomes of HIV treatment in Africa suggest continuous improvement during the first 5 years on treatment, confirming the sustained economic benefits of providing large-scale treatment. PMID:24076660

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

    PubMed Central

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

    2012-01-01

    Objectives To report long-term HIV treatment outcomes in 7 Caribbean countries. Design Observational cohort study. Methods We report outcomes for all antiretroviral therapy (ART) naïve adult patients enrolled on ART from program inception until study closing for cohorts in Barbados, the Dominican Republic, Haiti, Jamaica, Martinique, Trinidad, and Puerto Rico. Incidence and predictors of mortality were analyzed by time-to-event approaches. Results 8,203 patients started ART from 1998 to 2008. Median follow-up time was 31 months (interquartile range: 14 to 50 months). Mortality was 13% overall: 6% in Martinique, 8% in Jamaica, 11% in Trinidad, 13% in Haiti, 15% in the Dominican Republic, 15% in Barbados, and 24% in Puerto Rico. Mortality was associated with male gender (HR 1.58; 95% CI: 1.33 – 1.87), body weight (HR 0.85 per 10 pounds; 95% CI: 0.82 – 0.89), hemoglobin (HR 0.84 per g/dl; 95% CI: 0.80 – 0.88), CD4 cell count (0.90 per 50 CD4 cells; 95% CI: 0.86 – 0.93), concurrent TB (HR 1.58; 95% CI: 1.25 – 2.01) and age (HR 1.19 per 10 years; 95% CI: 1.11 – 1.28). After controlling for these variables, mortality in Martinique, Jamaica, Trinidad and Haiti was not significantly different. A total of 75% of patients remained alive and in-care at the end of the study period. Conclusions Long-term mortality rates vary widely across the Caribbean. Much of the difference can be explained by disease severity at ART initiation, nutritional status, and concurrent TB. Earlier ART initiation will be critical to improve outcomes. PMID:22240464

  13. 76 FR 70009 - Head Start Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-09

    ...This final rule amends the Head Start Program regulations to implement statutory provisions of the Improving Head Start for School Readiness Act of 2007 to establish a system of designation renewal to determine if Head Start and Early Head Start agencies are delivering high-quality and comprehensive Head Start and Early Head Start programs that meet the educational, health, nutritional, and......

  14. START Background Report START, April 2015 1 BACKGROUND REPORT

    E-print Network

    Hill, Wendell T.

    -Shabaab, which emerged from the Islamic Courts Union (ICU) in 2007, was among the most active terrorist groups in the world in 2014, according to preliminary data from START's Global Terrorism Database (GTD). While al to military missions in Somalia and hosts large numbers of Somali refugees. Since it emerged from the Islamic

  15. Immune recovery after starting ART in HIV-infected patients presenting and not presenting with tuberculosis in South Africa.

    PubMed

    Schomaker, Michael; Egger, Matthias; Maskew, Mhairi; Garone, Daniela; Prozesky, Hans; Hoffmann, Christopher J; Boulle, Andrew; Fenner, Lukas

    2013-05-01

    We studied the immune response after starting antiretroviral treatment (ART) in 15,646 HIV-infected patients with or without tuberculosis (TB) at presentation in 3 ART programs in South Africa between 2003 and 2010. Patients presenting with TB had similar increases in CD4 cells compared with all other patients (adjusted difference 4.9 cells/µL per 6 months, 95% confidence interval: 0.2 to 9.7). Younger age, advanced clinical stage, female sex, and lower CD4 cell count at ART start were all associated with steeper CD4 slopes. In South Africa, HIV-infected patients presenting with TB experience immune recovery after starting ART that is no worse than in other patients. PMID:23364513

  16. The risk of viral rebound in the year after delivery in women remaining on antiretroviral therapy

    PubMed Central

    Huntington, Susie; Thorne, Claire; Newell, Marie-Louise; Anderson, Jane; Taylor, Graham P.; Pillay, Deenan; Hill, Teresa; Tookey, Pat A.; Sabin, Caroline

    2015-01-01

    Objective: The objective of this study is to assess the risk of viral rebound in postpartum women on suppressive combination antiretroviral therapy (cART). Methods: Using data from the UK Collaborative HIV Cohort (UK CHIC) study and the UK and Ireland National Study of HIV in Pregnancy and Childhood (NSHPC), women with HIV-RNA 50?copies/ml or less at delivery in 2006–2011, who started life-long cART during pregnancy (n?=?321) or conceived on cART (n?=?618), were matched by age, duration on cART and time period, with at least one control (non-postpartum). The cumulative probability of viral rebound (HIV-RNA >200?copies/ml) was assessed by Kaplan–Meier analysis; adjusted hazard ratios (aHRs) for the 0–3 and 3–12 months postdelivery (cases)/pseudo-delivery (controls) were calculated in Cox proportional hazards models. Results: In postpartum women who conceived on cART, 5.9% [95% confidence interval (95% CI) 4.0–7.7] experienced viral rebound by 3 months, and 2.2% (1.4–3.0%) of their controls. The risk of viral rebound was higher in postpartum women than in controls during the first 3 months [aHR 2.63 (1.58–4.39)] but not during the 3–12 months postdelivery/pseudo-delivery. In postpartum women who started cART during pregnancy, 27% (22–32%) experienced viral rebound by 3 months, and 3.0% (1.6–4.4%) of their controls. The risk of viral rebound was higher in postpartum women than in controls during both postdelivery/pseudo-delivery periods [<3 months: aHR 6.63 (3.58–12.29); 3–12 months: aHR 4.05 (2.03–8.09)]. Conclusion: In women on suppressive cART, the risk of viral rebound is increased following delivery, especially in the first 3 months, which may be related to reduced adherence, indicating the need for additional adherence support for postpartum women. PMID:26544700

  17. Antiretroviral treatment induced catatonia in 16-year-old boy.

    PubMed

    Lingeswaran, Anand

    2014-01-01

    We present a 16-year-old boy, who had presented to us with catatonic features of mutism, withdrawal, passive negativism, grimacing, gesturing, echopraxia, and excitement of 5 days duration while taking antiretroviral therapy (ART) for a period of 2 years. He had history of birth asphyxia and acquired HIV infection from his father when the same syringe and needle was used on both of them in a medical setting where the father and son had consulted for treatment of pyrexia of unknown origin. He was the eldest of a three children family in which the biologic father had acquired HIV through extramarital sexual contact with HIV-infected sex workers but was unaware of his HIV positive status till our patient, the 16-year-old was admitted and treated for pulmonary tuberculosis at 14 years of age. The boy's mother had only acquired HIV after having three children with the HIV-positive husband, thus leaving the other two children HIV negative. The catatonia completely resolved within 2 days after the ART was withheld, and risperidone 1 mg twice a day was prescribed. This case highlights the risks of ART and breach of universal precautions. PMID:25624940

  18. Barriers to Sustaining Antiretroviral Treatment in Kisesa, Tanzania

    PubMed Central

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

    2009-01-01

    Two years after the introduction of free antiretroviral therapy (ART) in Tanzania and in spite of the logistical support provided to facilitate clinic attendance, a considerable level of attrition from the program was identified among clients from a semi-rural ward. Qualitative research on ART patients’ health-seeking behavior identified factors affecting sustained attendance at treatment clinics. A mix of methods was used for data collection including semi-structured interviews with 42 clients and 11 service providers and 4 participatory group activities conducted with members of a post-test group between October and December 2006. A socio-ecological framework guided data analysis to categorize facilitators and barriers into individual, social, programmatic, and structural level influences, and subsequently explored their interaction and relative significance in shaping ART clients’ behavior. Our findings suggest that personal motivation and self-efficacy contribute to program retention, and are affected by other individual-level experiences such as perceived health benefits or disease severity. However, these determinants are influenced by others’ opinions and beliefs in the community, and constrained by programmatic and structural barriers. Individuals can develop the requisite willingness to sustain strict treatment requirements in a challenging context, but are more likely to do so within supportive family and community environments. Effectiveness and sustainability of ART roll-out could be strengthened by strategic intervention at different levels, with particular attention to community-level factors such as social networks’ influence and support. PMID:19866538

  19. Novel drug delivery approaches on antiviral and antiretroviral agents

    PubMed Central

    Sharma, Pooja; Chawla, Anuj; Arora, Sandeep; Pawar, Pravin

    2012-01-01

    Viruses have the property to replicate very fast in host cell. It can attack any part of host cell. Therefore, the clinical efficacy of antiviral drugs and its bioavailability is more important concern taken into account to treat viral infections. The oral and parenteral routes of drug administration have several shortcomings, however, which could lead to the search for formulating better delivery systems. Now, a day's novel drug delivery systems (NDDS) proved to be a better approach to enhance the effectiveness of the antivirals and improve the patient compliance and decrease the adverse effect. The NDDS have reduced the dosing frequency and shorten the duration of treatment, thus, which could lead the treatment more cost-effective. The development of NDDS for antiviral and antiretroviral therapy aims to deliver the drug devoid of toxicity, with high compatibility and biodegradability, targeting the drug to specific sites for viral infection and in some instances it also avoid the first pass metabolism effect. This article aims to discuss the usefulness of novel delivery approaches of antiviral agents such as niosomes, microspheres, microemulsions, nanoparticles that are used in the treatment of various Herpes viruses and in human immunodeficiency virus (HIV) infections. PMID:23057001

  20. 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

  1. 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

  2. Evolving Human Rights and the Science of Antiretroviral Medicine.

    PubMed

    Kavanagh, Matthew; Cohn, Jennifer; Mabote, Lynette; Meier, Benjamin Mason; Williams, Brian; Russell, Asia; Sikwese, Kenly; Baker, Brook

    2015-01-01

    Recent years have seen significant advances in the science of using antiretroviral medicines (ARVs) to fight HIV. Where not long ago ARVs were used late in disease to prevent sick people from dying, today people living with HIV can use ARVs to achieve viral suppression early in the course of disease. This article reviews the mounting new scientific evidence of major clinical and prevention ARV benefits. This has changed the logic of the AIDS response, eliminating competition between "treatment" and "prevention" and encouraging early initiation of treatment for individual and public health benefit. These breakthroughs have implications for the health-related human rights duties of States. With medical advance, the "highest attainable standard" of health has taken a leap, and with it the rights obligations of States. We argue that access to early treatment for all is now a core State obligation and restricting access to, or failing to provide accurate information about, it violates both individual and collective rights. In a context of real political and technical challenges, however, in this article we review the policy implications of evolving human rights obligations given the new science. National and international legal standards require action on budget, health and intellectual property policy, which we outline. PMID:26204587

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

    PubMed

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

    2011-01-01

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

  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. Off to a Good Start.

    ERIC Educational Resources Information Center

    Hoffman, Carl

    1994-01-01

    Caring Start is a mobile-clinic program that provides prenatal care, well-baby clinics, childhood immunizations, counseling services, and contraceptives to rural poor families in northwest Pennsylvania. Before the mobile clinic, many rural women (mostly teenagers) went without prenatal health care due to lack of transportation. (LP)

  6. Rigor Made Easy: Getting Started

    ERIC Educational Resources Information Center

    Blackburn, Barbara R.

    2012-01-01

    Bestselling author and noted rigor expert Barbara Blackburn shares the secrets to getting started, maintaining momentum, and reaching your goals. Learn what rigor looks like in the classroom, understand what it means for your students, and get the keys to successful implementation. Learn how to use rigor to raise expectations, provide appropriate…

  7. Starting with the Business Basics.

    ERIC Educational Resources Information Center

    Hoffman, Carl

    1999-01-01

    A nonprofit community action agency, BusinesStart, provides business training and small loans to entrepreneurs in 18 rural counties in southwestern Virginia and northeastern Tennessee. The entrepreneurs, many with no previous business experience, cite the agency's basic business training as key to their success. (SV)

  8. Head Start Planned Variation Program.

    ERIC Educational Resources Information Center

    Klein, Jenny

    There is little agreement concerning which methods of preschool intervention are most effective. In order to evaluate several approaches to early childhood education, Project Head Start, in conjunction with Project Follow Through, has initiated the Planned Variation program. This year only a pilot project is underway with eight schools…

  9. Employment Obtaining and Business Starting

    ERIC Educational Resources Information Center

    Lan, Jian

    2009-01-01

    The implementation of business starting education in higher vocational colleges is of important and realistic meanings for cultivating advanced technology application-type talents and for releasing the employment obtaining pressure of higher vocational students. Based on the analysis on the employment situation of higher vocational graduates, this…

  10. 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…

  11. 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

  12. Research as a path to wide-scale implementation of antiretroviral therapy in Africa.

    PubMed

    Sanne, Ian; van der Horst, Charles

    2004-09-01

    Although some would deny the importance of research in resource-poor countries, the benefits of research to implementation of treatment for HIV infection are innumerable. These benefits include the development of infrastructure, training of staff, creation and validation of algorithms appropriate for the setting, and answering questions necessary for a safe and effective roll-out of therapy. This was true in the USA in 1986, 1 year after the antibody test for HIV was developed, and is true in Africa today. Shortly after the development of the HIV antibody test and before any antiretroviral therapy, few physicians or centres were willing to provide care for HIV patients and fewer had adequate facilities to do so. At that time it was not known how to make an adequate diagnosis of many of the opportunistic infections nor was there a clear idea of how to treat the patients. No-one knew either the best or most cost-effective method to prevent infections. Even as roll-out of therapy proceeded in early 1987 with the approval of zidovudine by the US Food and Drug Administration, physicians were clueless as to when to start treatment. With the addition of other medications in the armamentarium, clinicians began to make mistakes in their ignorance, adding on medications one at a time as they were approved, which led to accumulation of resistance mutations for a generation of patients. These mutations were transmitted to partners and children. What single-handedly helped advance treatment in the USA and Europe in the 1980s was the willingness of respective governing authorities to create clinical research groups not only to develop new drugs but to help create cost-effective ways to use them. All the current treatment guidelines were developed from that research. Over the years these research groups provided care, including medications, laboratory tests and physician and nurse time, for thousands of patients. Medical centres, where these indigent patients were receiving their care, were encouraged to open their doors, creating state of the art clinics and inpatient wards. A generation of clinicians was trained at these research centres where the bulk of US HIV patients were treated. They provided care as they were conducting research. The ability of resource-poor countries to deliver large-scale roll-out plans is dependent on the development of leadership and skills to implement the programmes. South Africa, despite a delay in initiating a national treatment programme, is an example of a country where the research conducted in the period 1996 to 2004 has enabled a skilled set of clinicians, pharmacists and paramedical staff to provide leadership in the scale up of antiretroviral therapy programmes. Guideline development, training and implementation have been led by treatment experts who learned their skills in the research arena. PMID:15534564

  13. 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

  14. Head Start Impact Study: First Year Findings

    ERIC Educational Resources Information Center

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

    2005-01-01

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

  15. 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.

  16. Implementation of antiretroviral therapy guidelines for under-five children in Tanzania: translating recommendations into practice

    PubMed Central

    Nuwagaba-Biribonwoha, Harriet; Wang, Chunhui; Kilama, Bonita; Jowhar, Farhat K; Antelman, Gretchen; Panya, Milembe F; Abrams, Elaine J

    2015-01-01

    Introduction Paediatric antiretroviral therapy (ART) guidelines have been updated several times in recent years. We assessed implementation of ART guidelines among under-five children to inform the transition to universal paediatric ART in Tanzania. Methods We conducted a retrospective cohort analysis of infants (0 to 11 months) and children (12 to 59 months) enrolled between 2010 and 2012 using routinely collected data. Infants and children were initiated on ART according to the 2008 World Health Organization (WHO) recommendations/2009 Tanzania guidelines (universal ART for infants). Cumulative ART initiation incidence and correlates of ART initiation were examined using competing risk methods accounting for attrition (death or loss to follow-up). Kaplan-Meier methods and Cox regression models were used to examine attrition on ART and its correlates. Results A total of 1679 children were enrolled at 69 clinics: 469 (28%) infants and 1210 (74%) children. Infant cumulative ART initiation incidence was 59.6, 71.3 and 78.0% at one, three and six months of follow-up. Infants were more likely to start ART if enrolled in 2012 [adjusted sub-hazard ratio (AsHR)=2.2, 95% confidence interval (CI): 1.7 to 2.8] or 2011 (AsHR=1.8, 95% CI: 1.4 to 2.3) compared to 2010; they were more likely to start ART from prevention of mother-to-child HIV transmission (AsHR=1.6, 95% CI: 1.3 to 2.1) and inpatient wards (AsHR=1.5, 95% CI: 1.2 to 2.0) versus being enrolled from voluntary counselling and testing centres. Attrition at 12 months on ART was 33.9% and was more likely among infants with WHO Stage 4 [adjusted hazard ratio (AHR)=3.1. 95% CI: 1.8 to 5.2] and severe malnutrition (AHR=1.4, 95% CI: 1.0 to 1.9). Among 599 children eligible for ART at enrolment, cumulative ART initiation incidence was 51.8, 68.6 and 76.1% at one, three, and six months. Children were more likely to start ART if enrolled in 2012 (AsHR=1.8, 95% CI: 1.4 to 2.3) or 2011 (AsHR=1.5, 95% CI: 1.2 to 1.8) compared to 2010; they were more likely to start ART at primary health facilities (AsHR=1.5, 95% CI: 1.1 to 2.0) and less likely at urban facilities (AsHR=0.6, 95% CI: 0.5 to 0.9) and facilities without CD4 testing on site (AsHR=0.7, 95% CI: 0.5 to 0.9). Attrition at 12 months on ART was 23.1% and was more likely with severe malnutrition (AHR=1.8, 95% CI: 1.1 to 3.0), WHO Stage 4 (AHR=3.0, 95% CI: 1.0 to 8.5) and outpatient enrolees (AHR=1.7, 95% CI: 1.1 to 2.7). Conclusions Our findings suggest the gradual adoption of guidelines over calendar time. Interventions to expedite ART initiation and support retention on ART are needed. PMID:26690303

  17. Cellular Responses and Tissue Depots for Nanoformulated Antiretroviral Therapy.

    PubMed

    Martinez-Skinner, Andrea L; Araínga, Mariluz A; Puligujja, Pavan; Palandri, Diana L; Baldridge, Hannah M; Edagwa, Benson J; McMillan, JoEllyn M; Mosley, R Lee; Gendelman, Howard E

    2015-01-01

    Long-acting nanoformulated antiretroviral therapy (nanoART) induces a range of innate immune migratory, phagocytic and secretory cell functions that perpetuate drug depots. While recycling endosomes serve as the macrophage subcellular depots, little is known of the dynamics of nanoART-cell interactions. To this end, we assessed temporal leukocyte responses, drug uptake and distribution following both intraperitoneal and intramuscular injection of nanoformulated atazanavir (nanoATV). Local inflammatory responses heralded drug distribution to peritoneal cell populations, regional lymph nodes, spleen and liver. This proceeded for three days in male Balb/c mice. NanoATV-induced changes in myeloid populations were assessed by fluorescence-activated cell sorting (FACS) with CD45, CD3, CD11b, F4/80, and GR-1 antibodies. The localization of nanoATV within leukocyte cell subsets was determined by confocal microscopy. Combined FACS and ultra-performance liquid chromatography tandem mass-spectrometry assays determined nanoATV carriages by cell-based vehicles. A robust granulocyte, but not peritoneal macrophage nanoATV response paralleled zymosan A treatment. ATV levels were highest at sites of injection in peritoneal or muscle macrophages, dependent on the injection site. The spleen and liver served as nanoATV tissue depots while drug levels in lymph nodes were higher than those recorded in plasma. Dual polymer and cell labeling demonstrated a nearly exclusive drug reservoir in macrophages within the liver and spleen. Overall, nanoART induces innate immune responses coincident with rapid tissue macrophage distribution. Taken together, these works provide avenues for therapeutic development designed towards chemical eradication of human immunodeficiency viral infection. PMID:26716700

  18. Reforming antiretroviral price negotiations and public procurement: the Mexican experience.

    PubMed

    Adesina, Adebiyi; Wirtz, Veronika J; Dratler, Sandra

    2013-01-01

    Since antiretroviral (ARV) medicines represent one of the most costly components of therapy for HIV in middle-income countries, ensuring their efficient procurement is highly relevant. In 2008, Mexico created a national commission for the negotiation of ARV prices to achieve price reductions for their public HIV treatment programmes. The objective of this study is to assess the immediate impact of the creation of the Mexican Commission for Price Negotiation on ARV prices and expenditures. A longitudinal retrospective analysis of procurement prices, volumes and type of the most commonly prescribed ARVs procured by the two largest providers of HIV/AIDS care in Mexico between 2004 and 2009 was carried out. These analyses were combined with 26 semi-structured key informant interviews to identify changes in the procurement process. Prices for ARVs dropped by an average of 38% after the first round of negotiations, indicating that the Commission was successful in price negotiations. However, when compared with other upper-middle-income countries, Mexico continues to pay an average of six times more for ARVs. The Commission's negotiations were successful in achieving lower ARV prices. However, price reduction in upper-middle-income countries suggests that the price decrease in Mexico cannot be entirely attributed to the Commission's first round of negotiations. In addition, key informants identified inefficiencies in the forecasting and procurement processes possibly affecting the efficiency of the negotiation process. A comprehensive approach to improving efficiency in the purchasing and delivery of ARVs is necessary, including a better clarification in the roles and responsibilities of the Commission, improving supply data collection and integration in forecasting and procurement, and the creation of a support system to monitor and provide feedback on patient ARV use. PMID:22375026

  19. The HIV antiretroviral drug efavirenz has LSD-like properties.

    PubMed

    Gatch, Michael B; Kozlenkov, Alexey; Huang, Ren-Qi; Yang, Wenjuan; Nguyen, Jacques D; González-Maeso, Javier; Rice, Kenner C; France, Charles P; Dillon, Glenn H; Forster, Michael J; Schetz, John A

    2013-11-01

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

  20. Leptin expression in HIV-infected patients during antiretroviral therapy

    PubMed Central

    Tiliscan, C?t?lin; Aram?, Victoria; Mih?ilescu, Raluca; Munteanu, Daniela Ioana; Streinu-Cercel, Adrian; Ion, Daniela Adriana; R?dulescu, Mihaela Andreea; Popescu, Cristina; Lobodan, Alina Elena; Negru, Anca Ruxandra; Aram?, ?tefan Sorin

    2015-01-01

    Background Leptin is an adipokine with complex metabolic, neuroendocrine and immune functions. Our objective was to evaluate leptin serum levels in a cohort of Romanian HIV-infected patients undergoing antiretroviral therapy in relation to their immune-virological status, lipid and glucose metabolic abnormalities and the presence of metabolic syndrome (MS). Methods We enrolled consecutive non-diabetic HIV-infected patients aged 18 and over on stable cART for at least 6 months. Blood samples were tested for: leptin, CD4 T cells count, HIV viral load and lipid panel. Results A total of 90 HIV-infected patients were included in the study: 50 males (55.6%) with a mean age of 33.3 years and 40 females with a mean age of 30.4 years. Most patients (74.4%) had HIV viral load below the limit of detection and the median CD4 count for the cohort was 476 (410) cells/cmm. More than one third of the patients (41.1%) had hypoleptinemia. The prevalence of MS was 13.3%. Hypoleptinemia was significantly more frequent in men. In a subset of patients with undetectable HIV viral load, the median leptin value was 0.6 (6.07) ng/mL in patients with poor immune recovery (CD4 count ? 200/cmm) compared to 2 (3.07) ng/mL for those with better immune response (CD4 count > 200/cmm), without statistical significance. The median values of leptin were similar for persons with and without MS criteria. HDL-cholesterol values were positively correlated to leptin values in a linear regression model. Conclusion A significant proportion of patients in our study presented low levels of leptin; this finding was not associated with immune and virological parameters or the presence of MS. Hypoleptinemia was significantly correlated with lower levels of HDL-cholesterol, a key cardiovascular risk factor. PMID:26405677

  1. Antiretroviral drugs do not interfere with bryostatin-mediated HIV-1 latency reversal.

    PubMed

    Martínez-Bonet, Marta; Clemente, Maria Isabel; Álvarez, Susana; Díaz, Laura; García-Alonso, Dolores; Muñoz, Eduardo; Moreno, Santiago; Muñoz-Fernández, Maria Ángeles

    2015-11-01

    Although an effective combination of antiretroviral therapy (cART) controls HIV-1 viraemia in infected patients, viral latency established soon after infection hinders HIV-1 eradication. It has been shown that bryostatin-1 (BRY) inhibits HIV-infection in vitro and reactivates the latent virus through the protein kinase C-NF-?B pathway. We determined the in vitro potential effect of BRY in combination with currently used antiretroviral drugs. BRY alone or in combination with maraviroc (MVC)/Atripla (ATP) was tested for its capacity to reactivate latent virus and inhibit new infections. JLTRG-R5 cells and two latent HIV-1-infected cell lines, J89GFP and THP89GFP, were used as latency models. To quantify HIV infection, the reporter cell line TZM-bl was used. We found that BRY reactivates HIV-1 even in combination with MVC or ATP. Antiretroviral combinations with BRY do not interfere with BRY activity (i.e., the reactivation of latently infected cells) or with the antiviral activity of antiretroviral drugs. In addition, BRY-mediated down-modulation of surface CD4 and CXCR4 was not affected when it was used in combination with other antiretrovirals, and no hyperactivation or high-proliferation effects were observed in primary T cells. Moreover, the BRY treatment was able to reactivate HIV-1 in CD4+ T cells from HIV-1-infected patients under cART. Thus, we propose the use of BRY to purge the viral reservoir and recommend its combination with current antiretroviral treatments. PMID:26427554

  2. Induction of P-Glycoprotein by Antiretroviral Drugs in Human Brain Microvessel Endothelial Cells

    PubMed Central

    Chan, Gary N. Y.; Patel, Rucha; Cummins, Carolyn L.

    2013-01-01

    The membrane-associated drug transporter P-glycoprotein (P-gp) plays an essential role in drug efflux from the brain. Induction of this protein at the blood-brain barrier (BBB) could further affect the ability of a drug to enter the brain. At present, P-gp induction mediated by antiretroviral drugs at the BBB has not been fully investigated. Since P-gp expression is regulated by ligand-activated nuclear receptors, i.e., human pregnane X receptor (hPXR) and human constitutive androstane receptor (hCAR), these receptors could represent potential pathways involved in P-gp induction by antiretroviral drugs. The aims of this study were (i) to determine whether antiretroviral drugs currently used in HIV pharmacotherapy are ligands for hPXR or hCAR and (ii) to examine P-gp function and expression in human brain microvessel endothelial cells treated with antiretroviral drugs identified as ligands of hPXR and/or hCAR. Luciferase reporter gene assays were performed to examine the activation of hPXR and hCAR by antiretroviral drugs. The hCMEC/D3 cell line, which is known to display several morphological and biochemical properties of the BBB in humans, was used to examine P-gp induction following 72 h of exposure to these agents. Amprenavir, atazanavir, darunavir, efavirenz, ritonavir, and lopinavir were found to activate hPXR, whereas abacavir, efavirenz, and nevirapine were found to activate hCAR. P-gp expression and function were significantly induced in hCMEC/D3 cells treated with these drugs at clinical concentrations in plasma. Together, our data suggest that P-gp induction could occur at the BBB during chronic treatment with antiretroviral drugs identified as ligands of hPXR and/or hCAR. PMID:23836171

  3. Managing Sure Start in partnership.

    PubMed

    Hassan, Lamiece; Spencer, Joy; Hogard, Elaine

    2006-08-01

    In March 2006, Sure Start programmes were mainstreamed, becoming 'Children's Centres' for which local authorities have assumed strategic responsibility. This paper describes an evaluation of a Sure Start local programme Management Board which was conducted in preparation for this transition. Focusing on practices relating to partnership working and community involvement, a distinctive trident evaluation model was used to explore outcomes, processes and multiple stakeholder perspectives through a multi-method approach (incorporating interviews, questionnaires and documentary analysis). This revealed that an effective, collaborative style of working had been fostered between board members, resulting in synergy. Furthermore, a number of governance arrangements were identified that specifically supported partnership developments, including quorum regulations and adherence to decision-making by consensus. A series of recommendations are presented that were made with the aim of strengthening the community voice on the board and preserving the most effective and empowering elements of practice following the transition. PMID:16922033

  4. Why I Started Studying Prejudice

    E-print Network

    Dovidio, John F.

    2005-01-01

    for local classroom use, whether in readers or reprinted volumes or other use, must contact the editors for permission. Why I Started Studying Prejudice John F. Dovidio I was born in 1951, and since then the United States has wrestled with profound... our society. Soon after, I entered graduate school. Sam Gaertner, who was studying aversive racism—racism among the well-intentioned—was my advisor. This confluence of personal experience, recent insights, new academic opportunities, and the support...

  5. 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...

  6. 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...

  7. 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...

  8. 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...

  9. 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...

  10. Perception of Antiretroviral Generic Medicines: One-Day Survey of HIV-Infected Patients and Their Physicians in France

    PubMed Central

    Jacomet, Christine; Allavena, Clotilde; Peyrol, Fleur; Pereira, Bruno; Joubert, Laurence Morand; Bagheri, Haleh; Cotte, Laurent; Garaffo, Rodolphe; Gerbaud, Laurent; Dellamonica, Pierre

    2015-01-01

    Background In the interest of cost effectiveness, switching antiretroviral brand name medications to generics is recommended in France since 2013. The study objective was to evaluate the perception of generics per se and antiretroviral generics in HIV-infected patients and their hospital physicians Methods and Findings 556 out of 703 (79%) adult HIV+ outpatients and 116 physicians in 33 clinics were included in a multicentric cross-sectional survey performed in September 2013. Patients completed a self-questionnaire on their perception and acceptability of generics. Physicians completed a questionnaire on their acceptability of switching antiretroviral to generic. Socio-demographic data, medical history and HIV history were collected. Among the 556 patients with a median HIV duration of 13 years, 77% were France native, 59% in active employment, 100% covered by social insurance, 95% on antiretroviral therapy. Seventy-six percent of the patients accepted generics and 55% trusted them overall. Antiretroviral generics were accepted by 44% of them but only by 17% if the pill burden was going to increase. The factor significantly associated with acceptability of antiretroviral generics was acceptance of generics per se (p<0.001). Among the 116 physicians following a median of 100 HIV-patients/year, 75% would prescribe generics, dropping to 26% if the combo had to be broken. Factors significantly associated with willingness to prescribe antiretroviral generics were the absence of concern regarding the chemical entity (OR = 0.33), being aware that the patient would accept generics for other pathologies (OR = 2.04) and would accept antiretroviral generics (OR = 1.94). No factor related to sociodemographic conditions, HIV status or comorbidities was associated with the acceptability of antiretroviral generics. Conclusions Acceptability of antiretroviral generics in this French population was mostly dictated by the patient’s and physician’s knowledge and use of generics overall. It should be improved with an efficient information of both patients and physicians. PMID:25658627

  11. School start times for adolescents.

    PubMed

    2014-09-01

    The American Academy of Pediatrics recognizes insufficient sleep in adolescents as an important public health issue that significantly affects the health and safety, as well as the academic success, of our nation's middle and high school students. Although a number of factors, including biological changes in sleep associated with puberty, lifestyle choices, and academic demands, negatively affect middle and high school students' ability to obtain sufficient sleep, the evidence strongly implicates earlier school start times (ie, before 8:30 am) as a key modifiable contributor to insufficient sleep, as well as circadian rhythm disruption, in this population. Furthermore, a substantial body of research has now demonstrated that delaying school start times is an effective countermeasure to chronic sleep loss and has a wide range of potential benefits to students with regard to physical and mental health, safety, and academic achievement. The American Academy of Pediatrics strongly supports the efforts of school districts to optimize sleep in students and urges high schools and middle schools to aim for start times that allow students the opportunity to achieve optimal levels of sleep (8.5-9.5 hours) and to improve physical (eg, reduced obesity risk) and mental (eg, lower rates of depression) health, safety (eg, drowsy driving crashes), academic performance, and quality of life. PMID:25156998

  12. 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 naïve 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

  13. 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

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

    PubMed Central

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

    2010-01-01

    Biomarkers could be useful in evaluating immune reconstitution inflammatory syndrome (IRIS). A cohort of 45 HIV-1-infected, antiretroviral treatment (ART)-naïve patients with baseline CD4 T cell counts ?100 cells/?L who were started on ART, suppressed HIV-RNA to <50 copies/mL, and seen every 1-3 months for 1 year were retrospectively evaluated for suspected or confirmed IRIS. D-dimer, C-reactive protein (CRP), and selected autoantibodies were analyzed at baseline, 1 and 3 months post-ART in cryopreserved plasma. Median differences between cases and controls were compared with Mann-Whitney and Fischer's exact tests. Sixteen patients (35.6%) developed IRIS (median of 35 days post-ART initiation): unmasking=8, paradoxical=7, autoimmune=1. Pre-ART D-dimer and CRP were higher in IRIS cases versus controls (D-dimer: 0.89mg/L versus 0.66mg/L, p=0.037; CRP: 0.74mg/L versus 0.39mg/L, p=0.022), while D-dimer was higher in unmasking cases at IRIS onset (2.04mg/L versus 0.36mg/L, p=0.05). These biomarkers may be useful in identifying patients at risk for IRIS. PMID:20227921

  15. Regional Anthropometry Changes in Antiretroviral-Naïve Persons Initiating a Zidovudine-Containing Regimen in Mbarara, Uganda

    PubMed Central

    Thompson, Vanessa; Medard, Bitekyerezo; Taseera, Kabanda; Chakera, Ali J.; Andia, Irene; Emenyonu, Nneka; Hunt, Peter W.; Martin, Jeffrey; Scherzer, Rebecca; Weiser, Sheri D.; Bangsberg, David R.

    2011-01-01

    Abstract Lipodystrophy is commonly reported in Africa after antiretroviral therapy (ART) is initiated, but few studies have objectively measured changes in body composition. Body composition was determined in 76 HIV-infected participants from Mbarara, Uganda after starting a thymidine-analog regimen, and annual change was determined using repeated measures analysis. We measured skinfolds (tricep, thigh, subscapular, and abdomen), circumferences (arm, hip, thigh, waist), and total lean and fat mass (using bioelectric impedance analysis). A cross-sectional sample of 49 HIV-uninfected participants was studied for comparison. At baseline, most body composition measures were lower in HIV-infected than uninfected participants, but waist circumference was similar. After 12 months on ART, there was little difference in body composition measures between HIV-infected and uninfected participants; median waist circumference appeared higher in HIV-infected participants (79 vs. 75?cm; p?=?0.090). Among HIV-infected participants, increases were observed in total lean and fat mass, circumference, and skinfold measures; only the increase in tricep skinfold did not reach statistical significance (+1.05?mm; 95% confidence interval: ?0.24, 2.34; p?=?0.11). Regional anthropometry in peripheral and central body sites increased over 12 months after ART initiation in HIV-infected persons from southwestern Uganda, suggesting a restoration to health. Gains in the tricep skinfold, a reliable marker of subcutaneous fat, appeared blunted, which could indicate an inhibitory effect of zidovudine on peripheral subcutaneous fat recovery. PMID:21128866

  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. Macrophage Folate Receptor-Targeted Antiretroviral Therapy Facilitates Drug Entry, Retention, Antiretroviral Activities and Biodistribution for Reduction of Human Immunodeficiency Virus Infections

    PubMed Central

    Puligujja, Pavan; McMillan, JoEllyn; Kendrick, Lindsey; Li, Tianyuzi; Balkundi, Shantanu; Smith, Nathan; Veerubhotla, Ram S.; Edagwa, Benson J.; Kabanov, Alexander V.; Bronich, Tatiana; Gendelman, Howard E.; Liu, Xin-Ming

    2013-01-01

    Macrophages serve as vehicles for the carriage and delivery of polymer-coated nanoformulated antiretroviral therapy (nanoART). Although superior to native drug, high drug concentrations are required for viral inhibition. Herein, folate-modified atazanavir/ritonavir (ATV/r)-encased polymers facilitated macrophage receptor targeting for optimizing drug dosing. Folate coating of nanoART ATV/r significantly enhanced cell uptake, retention and antiretroviral activities without altering cell viability. Enhanced retentions of folate-coated nanoART within recycling endosomes provided a stable subcellular drug depot. Importantly, five-fold enhanced plasma and tissue drug levels followed folate-coated formulation injection in mice. Folate polymer encased ATV/r improves nanoART pharmacokinetics bringing the technology one step closer to human use. PMID:23680933

  18. 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

  19. Psychosocial Factors Affecting Medication Adherence Among HIV-1 Infected Adults Receiving Combination Antiretroviral Therapy (cART) in Botswana

    PubMed Central

    Do, Natalie T.; Phiri, Kelesitse; Bussmann, Hermann; Gaolathe, Tendani; Marlink, Richard G.

    2010-01-01

    Abstract As increasing numbers of persons are placed on potentially life-saving combination antiretroviral therapy (cART) in sub-Saharan Africa, it is imperative to identify the psychosocial and social factors that may influence antiretroviral (ARV) medication adherence. Using an 87 question survey, the following data were collected from patients on cART in Botswana: demographics, performance (Karnofsky) score, perceived stigma and level of HIV disclosure, attitudes and beliefs concerning HIV/AIDS, substance and/or drug use, depression, and pharmacy and healthcare provider-related factors. Overall adherence rates were determined by patient self-report, institutional adherence, and a culturally modified Morisky scale. Three hundred adult patients were recruited between April and May 2005. The overall cART adherence rate was 81.3% based on 4 day and 1 month patient recall and on clinic attendance for ARV medication refills during the previous 3 months. Adults receiving cART for 1–6 months were the least adherent (77%) followed by those receiving cART for greater than 12 months (79%). Alcohol use, depression, and nondisclosure of positive HIV status to their partner were predictive of poor adherence rates (p value <0.02). A significant proportion (81.3%) of cART-treated adults were adherent to their prescribed treatment, with rates superior to those reported in resource-rich settings. Adherence rates were poorest among those just starting cART, most likely due to the presence of ARV-related toxicity. Adherence was lower among those who have been treated for longer periods of time (greater than 1 year), suggesting complacency, which may become a significant problem, especially among these long-term cART-treated patients who return to improved physical and mental functioning and may be less motivated to adhere to their ARV medications. Healthcare providers should encourage HIV disclosure to “at-risk” partners and provide ongoing counseling and education to help patients recognize and overcome HIV-associated stigma, alcohol abuse, and depression. PMID:20518649

  20. Maximizing the benefits of antiretroviral therapy for key affected populations

    PubMed Central

    Grubb, Ian R; Beckham, Sarah W; Kazatchkine, Michel; Thomas, Ruth M; Albers, Eliot R; Cabral, Mauro; Lange, Joep; Vella, Stefano; Kurian, Manoj; Beyrer, Chris

    2014-01-01

    Introduction Scientific research has demonstrated the clinical benefits of earlier initiation of antiretroviral treatment (ART), and that ART can markedly reduce HIV transmission to sexual partners. Ensuring universal access to ART for those who need it has long been a core principle of the HIV response, and extending the benefits of ART to key populations is critical to increasing the impact of ART and the overall effectiveness of the HIV response. However, this can only be achieved through coordinated efforts to address political, social, legal and economic barriers that key populations face in accessing HIV services. Discussion Recent analyses show that HIV prevalence levels among key populations are far higher than among the general population, and they experience a range of biological and behavioural factors, and social, legal and economic barriers that increase their vulnerability to HIV and have resulted in alarmingly low ART coverage. World Health Organization 2014 consolidated guidance on HIV among key populations offers the potential for increased access to ART by key populations, following the same principles as for the general adult population. However, it should not be assumed that key populations will achieve greater access to ART unless stigma, discrimination and punitive laws, policies and practices that limit access to ART and other HIV interventions in many countries are addressed. Conclusions Rights-based approaches and investments in critical enablers, such as supportive legal and policy environments, are essential to enable wider access to ART and other HIV interventions for key populations. The primary objective of ART should always be to treat the person living with HIV; prevention is an important, additional benefit. ART should be provided only with informed consent. The preventive benefits of treatment must not be used as a pretext for failure to provide other necessary HIV programming for key populations, including comprehensive harm reduction and other prevention interventions tailored to meet the needs of key populations. An end to AIDS is only possible if we overcome the barriers of criminalization, stigma and discrimination that remain key drivers of the HIV epidemics among key populations. PMID:25043380

  1. Host and Viral Determinants of Mx2 Antiretroviral Activity

    PubMed Central

    Busnadiego, Idoia; Kane, Melissa; Rihn, Suzannah J.; Preugschas, Hannah F.; Hughes, Joseph; Blanco-Melo, Daniel; Strouvelle, Victoria P.; Zang, Trinity M.; Willett, Brian J.; Boutell, Chris

    2014-01-01

    ABSTRACT Myxovirus resistance 2 (Mx2/MxB) has recently been uncovered as an effector of the anti-HIV-1 activity of type I interferons (IFNs) that inhibits HIV-1 at an early stage postinfection, after reverse transcription but prior to proviral integration into host DNA. The mechanistic details of Mx2 antiviral activity are not yet understood, but a few substitutions in the HIV-1 capsid have been shown to confer resistance to Mx2. Through a combination of in vitro evolution and unbiased mutagenesis, we further map the determinants of sensitivity to Mx2 and reveal that multiple capsid (CA) surfaces define sensitivity to Mx2. Intriguingly, we reveal an unanticipated sensitivity determinant within the C-terminal domain of capsid. We also report that Mx2s derived from multiple primate species share the capacity to potently inhibit HIV-1, whereas selected nonprimate orthologs have no such activity. Like TRIM5?, another CA targeting antiretroviral protein, primate Mx2s exhibit species-dependent variation in antiviral specificity against at least one extant virus and multiple HIV-1 capsid mutants. Using a combination of chimeric Mx2 proteins and evolution-guided approaches, we reveal that a single residue close to the N terminus that has evolved under positive selection can determine antiviral specificity. Thus, the variable N-terminal region can define the spectrum of viruses inhibited by Mx2. IMPORTANCE Type I interferons (IFNs) inhibit the replication of most mammalian viruses. IFN stimulation upregulates hundreds of different IFN-stimulated genes (ISGs), but it is often unclear which ISGs are responsible for inhibition of a given virus. Recently, Mx2 was identified as an ISG that contributes to the inhibition of HIV-1 replication by type I IFN. Thus, Mx2 might inhibit HIV-1 replication in patients, and this inhibitory action might have therapeutic potential. The mechanistic details of how Mx2 inhibits HIV-1 are currently unclear, but the HIV-1 capsid protein is the likely viral target. Here, we determine the regions of capsid that specify sensitivity to Mx2. We demonstrate that Mx2 from multiple primates can inhibit HIV-1, whereas Mx2 from other mammals (dogs and sheep) cannot. We also show that primate variants of Mx2 differ in the spectrum of lentiviruses they inhibit and that a single residue in Mx2 can determine this antiviral specificity. PMID:24760893

  2. Glucose Metabolism Disorders, HIV and Antiretroviral Therapy among Tanzanian Adults

    PubMed Central

    Maganga, Emmanuel; Smart, Luke R.; Kalluvya, Samuel; Kataraihya, Johannes B.; Saleh, Ahmed M.; Obeid, Lama; Downs, Jennifer A.; Fitzgerald, Daniel W.; Peck, Robert N.

    2015-01-01

    Introduction Millions of HIV-infected Africans are living longer due to long-term antiretroviral therapy (ART), yet little is known about glucose metabolism disorders in this group. We aimed to compare the prevalence of glucose metabolism disorders among HIV-infected adults on long-term ART to ART-naïve adults and HIV-negative controls, hypothesizing that the odds of glucose metabolism disorders would be 2-fold greater even after adjusting for possible confounders. Methods In this cross-sectional study conducted between October 2012 and April 2013, consecutive adults (>18 years) attending an HIV clinic in Tanzania were enrolled in 3 groups: 153 HIV-negative controls, 151 HIV-infected, ART-naïve, and 150 HIV-infected on ART for ? 2 years. The primary outcome was the prevalence of glucose metabolism disorders as determined by oral glucose tolerance testing. We compared glucose metabolism disorder prevalence between each HIV group vs. the control group by Fisher’s exact test and used multivariable logistic regression to determine factors associated with glucose metabolism disorders. Results HIV-infected adults on ART had a higher prevalence of glucose metabolism disorders (49/150 (32.7%) vs.11/153 (7.2%), p<0.001) and frank diabetes mellitus (27/150 (18.0%) vs. 8/153 (5.2%), p = 0.001) than HIV-negative adults, which remained highly significant even after adjusting for age, gender, adiposity and socioeconomic status (OR = 5.72 (2.78–11.77), p<0.001). Glucose metabolism disorders were significantly associated with higher CD4+ T-cell counts. Awareness of diabetes mellitus was <25%. Conclusions HIV-infected adults on long-term ART had 5-fold greater odds of glucose metabolism disorders than HIV-negative controls but were rarely aware of their diagnosis. Intensive glucose metabolism disorder screening and education are needed in HIV clinics in sub-Saharan Africa. Further research should determine how glucose metabolism disorders might be related to immune reconstitution. PMID:26287742

  3. 77 FR 3838 - Notice of Availability of Proposed New Starts/Small Starts Policy Guidance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-25

    ... Federal Transit Administration Notice of Availability of Proposed New Starts/Small Starts Policy Guidance... Policy Guidance on New Starts/Small Starts and requests your comments on it. This document compliments... measures proposed for evaluation of projects seeking New Starts and Small Starts funding and the way...

  4. Long-term increase in CD4+ T-cell counts during combination antiretroviral therapy for HIV-1 infection

    PubMed Central

    Lok, Judith J; Bosch, Ronald J; Benson, Constance A; Collier, Ann C; Robbins, Gregory K; Shafer, Robert W; Hughes, Michael D

    2010-01-01

    Objective To inform guidelines concerning when to initiate combination antiretroviral therapy (ART), we investigated whether CD4+ T-cell counts (CD4 counts) continue to increase over long periods of time on ART. Losses-to-follow-up and some patients discontinuing ART at higher CD4 counts hamper such evaluation, but novel statistical methods can help address these issues. We estimated the long-term CD4 count trajectory accounting for losses-to-follow-up and treatment discontinuations. Design The study population included 898 U.S. patients first initiating ART in a randomized trial (ACTG 384); 575 were subsequently prospectively followed in an observational study (ALLRT). Methods Inverse probability of censoring weighting statistical methods were used to estimate the CD4 count trajectory accounting for losses-to-follow-up and ART-discontinuations, overall and for pre-treatment CD4 count categories ? 200, 201–350, 351–500, and >500 cells/mm3. Results Median CD4 count increased from 270 cells/mm3 pre-ART to an estimated 556 at three and 532 cells/mm3 at seven years after starting ART in analyses ignoring treatment discontinuations; and to 570 and 640 cells/mm3, respectively, had all patients continued ART. However, even had ART been continued, an estimated 25%, 9%, 3% and 2% of patients with pre-treatment CD4 counts of ? 200, 201–350, 351–500, and >500 cells/mm3 would have had CD4 counts ?350 cells/mm3 after seven years. Conclusions If patients remain on ART, CD4 counts increase in most patients for at least seven years. However, the substantial percentage of patients starting therapy at low CD4 counts who still had low CD4 counts after seven years provides support for ART initiation at higher CD4 counts. PMID:20467286

  5. The Home Start Demonstration Program: An Overview.

    ERIC Educational Resources Information Center

    Office of Child Development (DHEW), Washington, DC.

    Following a discussion of the Home Start program and its evaluation plan, the 16 Office of Child Development-funded Home Start projects in the United States are described. Home start is a 3-year Head Start demonstration program, aimed at the 3-5 years of age range, which focuses on enhancing the quality of children's lives by building upon…

  6. 30 CFR 75.1913 - Starting aids.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Starting aids. 75.1913 Section 75.1913 Mineral... SAFETY STANDARDS-UNDERGROUND COAL MINES Diesel-Powered Equipment § 75.1913 Starting aids. (a) Volatile fuel starting aids shall be used in accordance with recommendations provided by the starting...

  7. 30 CFR 75.1913 - Starting aids.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Starting aids. 75.1913 Section 75.1913 Mineral... SAFETY STANDARDS-UNDERGROUND COAL MINES Diesel-Powered Equipment § 75.1913 Starting aids. (a) Volatile fuel starting aids shall be used in accordance with recommendations provided by the starting...

  8. 30 CFR 75.1913 - Starting aids.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Starting aids. 75.1913 Section 75.1913 Mineral... SAFETY STANDARDS-UNDERGROUND COAL MINES Diesel-Powered Equipment § 75.1913 Starting aids. (a) Volatile fuel starting aids shall be used in accordance with recommendations provided by the starting...

  9. 30 CFR 75.1913 - Starting aids.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Starting aids. 75.1913 Section 75.1913 Mineral... SAFETY STANDARDS-UNDERGROUND COAL MINES Diesel-Powered Equipment § 75.1913 Starting aids. (a) Volatile fuel starting aids shall be used in accordance with recommendations provided by the starting...

  10. 30 CFR 75.1913 - Starting aids.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Starting aids. 75.1913 Section 75.1913 Mineral... SAFETY STANDARDS-UNDERGROUND COAL MINES Diesel-Powered Equipment § 75.1913 Starting aids. (a) Volatile fuel starting aids shall be used in accordance with recommendations provided by the starting...

  11. Rapid starting methanol reactor system

    DOEpatents

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

    1984-01-01

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

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

    E-print Network

    Suchard, Marc A.

    Evolution and recombination of genes encoding HIV-1 drug resistance and tropism during HIV-1 recombination HIV-1 tropism Characterization of residual plasma virus during antiretroviral the hypotheses that drug resistance in pol was unrelated to changes in coreceptor usage (tropism

  13. 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…

  14. Altered Oligodendrocyte Maturation and Myelin Maintenance: The Role of Antiretrovirals in HIV-Associated Neurocognitive Disorders.

    PubMed

    Jensen, Brigid K; Monnerie, Hubert; Mannell, Maggie V; Gannon, Patrick J; Espinoza, Cagla Akay; Erickson, Michelle A; Bruce-Keller, Annadora J; Gelman, Benjamin B; Briand, Lisa A; Pierce, R Christopher; Jordan-Sciutto, Kelly L; Grinspan, Judith B

    2015-11-01

    Despite effective viral suppression through combined antiretroviral therapy (cART), approximately half of HIV-positive individuals have HIV-associated neurocognitive disorders (HAND). Studies of antiretroviral-treated patients have revealed persistent white matter abnormalities including diffuse myelin pallor, diminished white matter tracts, and decreased myelin protein mRNAs. Loss of myelin can contribute to neurocognitive dysfunction because the myelin membrane generated by oligodendrocytes is essential for rapid signal transduction and axonal maintenance. We hypothesized that myelin changes in HAND are partly due to effects of antiretroviral drugs on oligodendrocyte survival and/or maturation. We showed that primary mouse oligodendrocyte precursor cell cultures treated with therapeutic concentrations of HIV protease inhibitors ritonavir or lopinavir displayed dose-dependent decreases in oligodendrocyte maturation; however, this effect was rapidly reversed after drug removal. Conversely, nucleoside reverse transcriptase inhibitor zidovudine had no effect. Furthermore, in vivo ritonavir administration to adult mice reduced frontal cortex myelin protein levels. Finally, prefrontal cortex tissue from HIV-positive individuals with HAND on cART showed a significant decrease in myelin basic protein compared with untreated HIV-positive individuals with HAND or HIV-negative controls. These findings demonstrate that antiretrovirals can impact myelin integrity and have implications for myelination in juvenile HIV patients and myelin maintenance in adults on lifelong therapy. PMID:26469251

  15. 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

  16. EDITORIAL REVIEW The antiretroviral rollout and drug-resistant HIV in

    E-print Network

    Blower, Sally

    EDITORIAL REVIEW The antiretroviral rollout and drug-resistant HIV in Africa: insights from in Africa is likely to generate an epidemic of drug-resistant strains of HIV. We review what has occurred, and the emergence and transmission of drug-resistant HIV. We also review how mathematical models have been used

  17. 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,…

  18. 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

  19. Antiretroviral effect of lovastatin on HIV-1-infected individuals without highly active antiretroviral therapy (The LIVE study): a phase-II randomized clinical trial

    PubMed Central

    Montoya, Carlos J; Jaimes, Fabian; Higuita, Edwin A; Convers-Páez, Sandra; Estrada, Santiago; Gutierrez, Francisco; Amariles, Pedro; Giraldo, Newar; Peñaloza, Cristina; Rugeles, Maria T

    2009-01-01

    Background Highly active antiretroviral therapy produces a significant decrease in HIV-1 replication and allows an increase in the CD4 T-cell count, leading to a decrease in the incidence of opportunistic infections and mortality. However, the cost, side effects and complexity of antiretroviral regimens have underscored the immediate need for additional therapeutic approaches. Statins exert pleiotropic effects through a variety of mechanisms, among which there are several immunoregulatory effects, related and unrelated to their cholesterol-lowering activity that can be useful to control HIV-1 infection. Methods/design Randomized, double-blinded, placebo controlled, single-center, phase-II clinical trial. One hundred and ten chronically HIV-1-infected patients, older than 18 years and naïve for antirretroviral therapy (i.e., without prior or current management with antiretroviral drugs) will be enrolled at the outpatient services from the most important centres for health insurance care in Medellin-Colombia. The interventions will be lovastatin (40 mg/day, orally, for 12 months; 55 patients) or placebo (55 patients). Our primary aim will be to determine the effect of lovastatin on viral replication. The secondary aim will be to determine the effect of lovastatin on CD4+ T-cell count in peripheral blood. As tertiary aims we will explore differences in CD8+ T-cell count, expression of activation markers (CD38 and HLA-DR) on CD4 and CD8 T cells, cholesterol metabolism, LFA-1/ICAM-1 function, Rho GTPases function and clinical evolution between treated and not treated HIV-1-infected individuals. Discussion Preliminary descriptive studies have suggested that statins (lovastatin) may have anti HIV-1 activity and that their administration is safe, with the potential effect of controlling HIV-1 replication in chronically infected individuals who had not received antiretroviral medications. Considering that there is limited clinical data available on this topic, all these findings warrant further evaluation to determine if long-term administration of statins may benefit the virological and immunological evolution in HIV-1-infected individuals before the use of antiretroviral therapy is required. Trial registration Registration number NCT00721305. PMID:19538732

  20. Predicted savings to the UK National Health Service from switching to generic antiretrovirals, 2014–2018

    PubMed Central

    Hill, Andrew; Hill, Teresa; Jose, Sophie; Pozniak, Anton

    2014-01-01

    Introduction In other disease areas, generic drugs are normally used after patent expiry. Patents on zidovudine, lamivudine, nevirapine and efavirenz have already expired. Patents will expire for abacavir in late 2014, lopinavir/r in 2016, and tenofovir, darunavir and atazanavir in 2017. However, patents on single-tablet regimens do not expire until after 2026. Methods The number of people taking each antiretroviral in the UK was estimated from 23,655 individuals in the UK CHIC cohort (2012 database). Costs of patented drugs were taken from the British National Formulary database, assuming a 30% discount. Costs of generic antiretrovirals were estimated using an 80% discount from patented prices, or actual costs where available. Two options were analysed: 1 – all patients use single-tablet regimens and patented versions of drugs; prices remain stable over time; 2 – all people switch from patented to generic drugs when available, after patent expiry (dates shown above). Results There were an estimated 67,000 people taking antiretrovirals in the UK in 2014, estimated to rise by 8% per year until 2018 (in line with previous rises). The most widely used antiretrovirals in the CHIC cohort were tenofovir (TDF) (75%), emtricitabine (FTC) (69%), efavirenz (EFV) (39%), lamivudine (3TC) (23%), abacavir (ABC) (18%), darunavir (DRV) (21%) and atazanavir (ATV) (16%). The predicted annual UK cost of generic ABC/3TC/EFV (three generic tablets once daily) was £1018 per person-year. Costs of patented single-tablet regimens ranged from £5000 to £7500 per person-year. Assuming continued use of patented antiretrovirals in the UK, the predicted total national costs of antiretroviral treatment were predicted to rise from £425 million in 2014 to £459 m in 2015, £495 m in 2016, £536 m in 2017 and £578 m in 2018. With a 100% switch to generics, total predicted costs were £337 m in 2014, £364 m in 2015, £382 m in 2016, £144 m in 2017 and £169 m in 2018. The total predicted saving over five years from a switch to generics was £1.1 billion. Conclusions Systematic switching from patented to generic antiretrovirals could potentially save approximately £1.1 billion in the UK over the next five years, compared with continued use of patented versions: this money could be spent on urgently needed HIV prevention programmes. Similar savings are feasible for other European countries, given parallel patent expiry dates. More detailed economic evaluation is required to show when patented single-tablet regimens provide value for money, compared to bioequivalent generic versions of 3–4 pills once daily. PMID:25394006

  1. Influence of HIV antiretrovirals on methadone N-demethylation and transport.

    PubMed

    Campbell, Scott D; Gadel, Sarah; Friedel, Christina; Crafford, Amanda; Regina, Karen J; Kharasch, Evan D

    2015-05-15

    Drug interactions involving methadone and/or HIV antiretrovirals can be problematic. Mechanisms whereby antiretrovirals induce clinical methadone clearance are poorly understood. Methadone is N-demethylated to 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) by CYP2B6 and CYP3A4 in vitro, but by CYP2B6 in vivo. This investigation evaluated human hepatocytes as a model for methadone induction, and tested the hypothesis that methadone and EDDP are substrates for human drug transporters. Human hepatocyte induction by several antiretrovirals of methadone N-demethylation, and CYP2B6 and CYP3A4 transcription, protein expression and catalytic activity, and pregnane X receptor (PXR) activation were evaluated. Methadone and EDDP uptake and efflux by overexpressed transporters were also determined. Methadone N-demethylation was generally not significantly increased by the antiretrovirals. CYP2B6 mRNA and activity (bupropion N-demethylation) were induced by several antiretrovirals, as were CYP3A4 mRNA and protein expression, but only indinavir increased CYP3A activity (alfentanil dealkylation). CYP upregulation appeared related to PXR activation. Methadone was not a substrate for uptake (OCT1, OCT2, OCT3, OATP1A2, OATP1B1, OATP1B3, OATP2B1) or efflux (P-gp, BCRP) transporters. EDDP was a good substrate for P-gp, BCRP, OCT1, OCT3, OATP1A2, and OATP1B1. OATP1A2- and OCT3-mediated EDDP uptake, and BCRP-mediated EDDP efflux transport, was inhibited by several antiretrovirals. Results show that hepatocyte methadone N-demethylation resembles expressed and liver microsomal metabolism more than clinical metabolism. Compared with clinical studies, hepatocytes underreport induction of methadone metabolism by HIV drugs. Hepatocytes are not a good predictive model for clinical antiretroviral induction of methadone metabolism and not a substitute for clinical studies. EDDP is a transporter substrate, and is susceptible to transporter-mediated interactions. PMID:25801005

  2. Lipid and Glucose Alterations in HIV-Infected Children Beginning or Changing Antiretroviral Therapy

    PubMed Central

    Chantry, Caroline J.; Hughes, Michael D.; Alvero, Carmelita; Cervia, Joseph S.; Meyer, William A.; Hodge, Janice; Borum, Peggy; Moye, Jack

    2009-01-01

    OBJECTIVE The objective of this study was to describe lipid profiles and glucose homeostasis in HIV-positive children after initiating or changing antiretroviral therapy and their associations with viral, immune, antiretroviral therapy, and growth factor parameters. METHODS Ninety-seven prepubertal HIV-positive children aged 1 month to <13 years were observed for 48 weeks after beginning or changing antiretroviral therapy. Fasting lipid panels, serum glucose, insulin, insulin-like growth factor-1 and binding proteins-1 and -3, plasma viral load, and CD4% were measured. Each child was matched on age, gender, and race/ethnicity to children from the National Health and Nutrition Examination Survey, used to give z scores for each child’s lipid values. Multivariate regression was used to evaluate the association of changes in z scores over 48 weeks with suppression of HIV-1 RNA, change in CD4% and growth factors, and antiretroviral therapy, adjusted for entry z score, CD4%, log10 HIV-1 RNA, Centers for Disease Control and Prevention category, and total fat and cholesterol dietary intake. RESULTS Lipid, apolipoprotein, and insulin levels all increased significantly by 48 weeks. Multivariate analysis of changes demonstrated that increased HDL and decreased total-HDL cholesterol ratio were associated with CD4% increase and with insulin-like growth factor-1, which increased to normal (versus remained stable or became low) over 48 weeks. Total cholesterol levels increased among children who achieved HIV-1 RNA of <400 copies per mL. Antiretroviral therapy regimens that included both a protease inhibitor and a non–nucleoside reverse transcriptase inhibitor were associated with greater increases in total-HDL cholesterol ratio than regimens that contained a protease inhibitor or a non–nucleoside reverse transcriptase inhibitor but not both. CONCLUSIONS In these HIV-positive children with predominantly mild-to-moderate disease, initiation or change in antiretroviral therapy was associated with significant increases in multiple lipid measures and insulin resistance. Favorable lipid changes were associated with CD4% increases, suggesting a protective effect of immune reconstitution on atherosclerosis, and with increased insulin-like growth factor-1 levels, supporting the theory that reduced growth hormone resistance may be a mechanism by which lipid profiles are improved. Finally, antiretroviral therapy regimens that contain both a non–nucleoside reverse transcriptase inhibitor and a protease inhibitor are associated with worse lipid profiles than regimens that contain 1 but not both of these drug classes. PMID:18519448

  3. 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

  4. Prevalence of Potential Drug-Drug Interactions Involving Antiretroviral Drugs in a Large Kenyan Cohort

    PubMed Central

    Kigen, Gabriel; Kimaiyo, Sylvester; Nyandiko, Winstone; Faragher, Brian; Sang, Edwin; Jakait, Beatrice; Owen, Andrew; Back, David; Gibbons, Sara; Seden, Kay; Khoo, Saye H.

    2011-01-01

    Background Clinically significant drug-drug interactions (CSDIs) involving antiretrovirals are frequent and under-recognized in developed countries, but data are lacking for developing countries. Methodology and Principal Findings To investigate the prevalence of CSDIs between antiretrovirals and coadministered drugs, we surveyed prescriptions dispensed in a large HIV clinic in Kenya. Of 1040 consecutive patients screened, 996 were eligible for inclusion. CSDIs were defined as ‘major’ (capable of causing severe or permanent damage, contraindicated, avoid or not recommended by the manufacturer, or requiring dose modification) or ‘moderate’ (manufacturers advise caution, or close monitoring, or capable of causing clinical deterioration). A total of 334 patients (33.5%) were at risk for a CSDI, potentially lowering antiretroviral drug concentrations in 120 (12%) patients. Major interactions most frequently involved rifampicin (12.4%, mostly with efavirenz) and azoles (2.7%) whereas moderate interactions were frequently azoles (13%), steroids (11%), and antimalarials (3%). Multivariable analyses suggested that patients at risk for CSDIs had lower CD4 counts (P?=?0.006) and baseline weight (P?=?0.023) and WHO Stage 3 or 4 disease (P?0.007). Risk for CSDIs was not associated with particular regimens, although only 116 (11.6%) patients were receiving WHO second line regimens. Conclusions One in three patients receiving antiretrovirals in our programme were at risk of CSDIs. Strategies need to be urgently developed to avoid important drug interactions, to identify early markers of toxicity and to manage unavoidable interactions safely in order to reduce risk of harm, and to maximize the effectiveness of mass antiretroviral deployment in Africa. PMID:21373194

  5. Preventing obesity starts with breastfeeding.

    PubMed

    Spatz, Diane L

    2014-01-01

    Preventing obesity starts with breastfeeding. An infant's nutrition at birth affects not only short-term health outcomes but also the health of that person as a child, adolescent, and adult. This article examines major findings that all conclude that any breastfeeding will help protect an infant from obesity and overweight. Research supports that the more exclusive and longer a child is breastfed, the more protection from overweight and obesity is conferred. Mechanisms of action are explored in this article. It is of paramount importance to provide evidence-based lactation support and care to families to improve the incidence, exclusivity, and duration of breastfeeding. Breastfeeding is one concrete method to address the obesity epidemic that is growing worldwide. PMID:24476651

  6. Geneva summit: a fresh start

    SciTech Connect

    Reagan, R.

    1985-01-01

    This address by the President occurred just after his return to the US following his talks with USSR General Secretary Gorbachev in Geneva. After briefly presenting the history and context of the summit, he notes that both he and Mr. Gorbachev were eager that their meeting give a push to important talks occurring then (in Geneva) on reducing nuclear weapons. He recouents their confronting the major issues, emphasizing his explanations to Mr. Gorbachev of our SDI. He notes the barriers to communications between the US and Soviet societies and the efforts necessary to dispel them and build a more stable relationship. Finally, he concludes that the summit was worthwhile - a good start - that a new realism spawned the summit, and now our byword must be: steady as we go.

  7. Virologic Response in Children Treated with Abacavir Compared with Stavudine-Based Antiretroviral Treatment – A South African Multi-Cohort Analysis

    PubMed Central

    Technau, Karl-Günter; Schomaker, Michael; Kuhn, Louise; Moultrie, Harry; Coovadia, Ashraf; Eley, Brian; Rabie, Helena; Wood, Robin; Cox, Vivian; Vizcaya, Luisa Salazar; Muchiri, Evans; Davies, Mary-Ann

    2014-01-01

    Background Initiation criteria and pediatric antiretroviral treatment (ART) regimens have changed over the past few years in South Africa. We reported worse early virological outcomes associated with the use abacavir (ABC)-based regimens at one large site: here we expand this analysis to multiple sites in the IeDEA-Southern Africa collaboration. Methods Data for 9543 ART-naïve children <16 years at treatment initiation started on either stavudine/lamivudine (d4T/3TC) or ABC/3TC with efavirenz (EFV) or ritonavir-boosted lopinavir (LPV/r) treated at six clinics in Johannesburg and Cape Town, South Africa, were analysed with Chi-square tests and logistic regression to evaluate viral suppression at six and twelve months. Results Prevalence of viral suppression at six months in 2174 children started on a d4T-based LPV/r regimen was greater (70%) than among 438 children started on an ABC-based LPV/r regimen (54%, p<0.0001). Among 3189 children started on a d4T-based EFV regimen a higher proportion (86%) achieved suppression at six months compared to 391 children started on ABC-containing EFV regimens (78%, p<0.0001). Relative benefit of d4T vs. ABC on six month suppression remained in multivariate analysis after adjustment for pre-treatment characteristics, cohort and year of program (LPV/r – OR 0.57 [CI: 0.46–0.72]; EFV – OR 0.46 [CI: 0.32–0.65]). Conclusion This expanded analysis is consistent with our previous report of worse virological outcomes after ABC was introduced as part of first-line ART in South Africa. Whether due to the drug itself or coincident with other changes over time, continued monitoring and analyses must clarify causes and prevent suboptimal long term outcomes. PMID:24378944

  8. Enhanced normalisation of CD4/CD8 ratio with early antiretroviral therapy in primary HIV infection

    PubMed Central

    Thornhill, John; Inshaw, Jamie; Oomeer, Soonita; Kaleebu, Pontiano; Cooper, David; Ramjee, Gita; Schechter, Mauro; Tambussi, Giuseppe; Fox, Julie; Maria Miro, Jose; Weber, Jonathan; Babiker, Abdel; Porter, Kholoud; Fidler, Sarah

    2014-01-01

    Introduction Despite normalization of total CD4 counts, ongoing immune dysfunction is noted amongst those on antiretroviral therapy (ART). Low CD4/CD8 ratio is associated with a high risk of AIDS and non-AIDS events and may act as a marker of immune senescence [1]. This ratio is improved by ART although normalization is uncommon (~7%) [2]. The probability of normalization of CD4 count is improved with immediate ART initiation in primary HIV infection (PHI) [3]. We examined whether CD4/CD8 ratio similarly normalized in immediate vs. deferred ART at PHI. Material and Methods Using data from the SPARTAC trial and the UK Register of HIV Seroconverters, we examined the effect of ART with time (continuous) from HIV seroconversion (SC) on CD4/CD8 ratio (?1) adjusted for sex, risk group, ethnicity, enrolment from an African site and both CD4 count and age at ART initiation. We also examined that effect by dichotomizing HIV duration at ART initiation (ART started within six months of SC: early ART; ART initiated>six months after SC: deferred). We also considered time to CD4 count normalization (?900 cells/mm3). Results In total, 353 initiated ART with median (IQR) 97.9 (60.5, 384.5) days from estimated seroconversion; 253/353 early ART, 100 deferred ART. At one year after starting ART, 114/253 (45%) early ART had normalized CD4/8 ratio, compared with 11/99 (11%) in the deferred group, whilst 83/253 (33%) of early ART had normalized CD4 counts, compared with 3/99 (3%) in the deferred group. Individuals initiating within six months of PHI were significantly more likely to reach normal ratio than those initiating later (HR, 95% CI 2.96, 1.75 – 5.01, p<0.001). The longer after SC ART was initiated, the reduced likelihood of achieving normalization of CD4/CD8 ratio (HR 0.98, 95% CI 0.96 – 0.99 for each 30-day increase). CD4 count at ART initiation was also associated with normalization, as expected (HR 1.002, 95% CI 1.001 – 1.002, p<0.001). There was an association between normal CD4/CD8 ratio and being virally suppressed (<400 copies HIV RNA/ml) p<0.001. CD4 count normalization was also significantly more likely for those initiating early (HR 5.00, 95% CI 1.52 – 16.41, p=0.008). Conclusions The likelihood of achieving normalization of CD4/CD8 ratios was increased if ART was initiated within six months of PHI. Higher CD4/CD8 ratio may reflect a more “normal” immune phenotype conferring enhanced prognosis and predict post-treatment control. PMID:25393989

  9. Optimization of antiretroviral therapy for HIV infected patients by simultaneous analysis of immune restoration and serious side effects 

    E-print Network

    Velez Vega, Camilo

    2002-01-01

    . Continuous administration of antiretroviral drugs has led to serious drug toxicity and side effects resulting in forced therapy cease and consequent viral rebound. As a result, clinicians encounter an optimization problem: how to best control viral...

  10. 76 FR 37174 - Capital Investment Program-New Starts and Small Starts Program Funds

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-24

    ... Federal Transit Administration Capital Investment Program--New Starts and Small Starts Program Funds... Investment (New Starts and Small Starts) program funds. The funds will be used for construction of new fixed... Starts, contact Eric Hu, Office of Program Management, at (202) 366-0870, e-mail: Eric.Hu@dot.gov...

  11. Cold start fuel enrichment circuit

    SciTech Connect

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

    1988-08-16

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

  12. Immunomodulation of antiretroviral drug-suppressed chronic HIV-1 infection in an oral probiotic double-blind placebo-controlled trial.

    PubMed

    Yang, Otto O; Kelesidis, Theodoros; Cordova, Robert; Khanlou, Homayoon

    2014-10-01

    A putative source of inappropriate immune activation that drives human immunodeficiency virus (HIV)-1 immunopathogenesis is the gastrointestinal tract. Even with effective antiretroviral treatment, residual activation persists. We hypothesized that an oral probiotic could improve the residual immune activation in chronic treated HIV-1 infection, and tested a Bacillus coagulans GBI-30, 6086 capsule probiotic in HIV-1-infected persons with suppressed viremia on stable antiretroviral therapy in a 3-month double-blind placebo-controlled trial (10 probiotic, 7 placebo). The Gastrointestinal Symptom Rating Scale (GSRS) was administered monthly. Blood was tested at the start and end of placebo/probiotic administration for viremia, CD4(+) T cell percentage/concentration, soluble (s)CD14, soluble intestinal fatty acid binding protein, sCD163, D-dimer, C-reactive protein (CRP), interleukin-8, and tumor necrosis factor-?. All participants maintained viremia <40 RNA copies/ml. The probiotic was safe and well tolerated, and appeared to improve chronic gastrointestinal symptoms. Its administration was associated with a significant increase in the percentage of blood CD4(+) T cells compared to placebo (+2.8% versus -1.8%, p=0.018) although CD4(+) T cell concentrations were generally unchanged in both groups. None of the biomarkers showed significant changes on probiotic treatment or between-group differences in change (although significance was borderline for a greater sCD163 drop in the probiotic versus placebo group, p=0.05). Some biomarkers showed significant correlations to each other, particularly D-dimer with CRP and sCD14 with tumor necrosis factor (TNF)-?. These data demonstrate the safety and possible benefit of this probiotic for residual inflammation in treated HIV-1 infection, although further study will be required to determine the immune pathways involved. PMID:25127924

  13. 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

  14. Antiretroviral Regimens and CD4/CD8 Ratio Normalization in HIV-Infected Patients during the Initial Year of Treatment: A Cohort Study

    PubMed Central

    De Salvador-Guillouët, F.; Sakarovitch, C.; Durant, J.; Risso, K.; Demonchy, E.; Roger, P. M.; Fontas, E.

    2015-01-01

    Background As CD4/CD8 ratio inversion has been associated with non-AIDS morbidity and mortality, predictors of ratio normalization after cART need to be studied. Here, we aimed to investigate the association of antiretroviral regimens with CD4/CD8 ratio normalization within an observational cohort. Methods We selected, from a French cohort at the Nice University Hospital, HIV-1 positive treatment-naive patients who initiated cART between 2000 and 2011 with a CD4/CD8 ratio <1. Association between cART and ratio normalization (>1) in the first year was assessed using multivariate logistic regression models. Specific association with INSTI-containing regimens was examined. Results 567 patients were included in the analyses; the median CD4/CD8 ratio was 0.36. Respectively, 52.9%, 29.6% and 10.4% initiated a PI-based, NNRTI-based or NRTI-based cART regimens. About 8% of the population started an INSTI-containing regimen. 62 (10.9%) patients achieved a CD4/CD8 ratio ?1 (N group). cART regimen was not associated with normalization when coded as PI-, NNRTI- or NRTI-based regimen. However, when considering INSTI-containing regimens alone, there was a strong association with normalization [OR, 7.67 (2.54–23.2)]. Conclusions Our findings suggest an association between initiation of an INSTI-containing regimen and CD4/CD8 ratio normalization at one year in naïve patients. Should it be confirmed in a larger population, it would be another argument for their use as first-line regimen as it is recommended in the recent update of the “Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents”. PMID:26485149

  15. 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

  16. Antiretroviral-Free HIV-1 Remission and Viral Rebound Following Allogeneic Stem Cell Transplantation: A Report of Two Cases

    PubMed Central

    Henrich, Timothy J.; Hanhauser, Emily; Marty, Francisco M.; Sirignano, Michael N.; Keating, Sheila; Lee, Tzong-Hae; Robles, Yvonne P.; Davis, Benjamin T.; Li, Jonathan Z.; Heisey, Andrea; Hill, Alison L.; Busch, Michael P.; Armand, Philippe; Soiffer, Robert J.; Altfeld, Marcus; Kuritzkes, Daniel R.

    2014-01-01

    Background It is unknown if the reduction in HIV-1 reservoirs observed following allogeneic hematopoietic stem cell transplantation (HSCT) with susceptible donor cells is sufficient to achieve sustained HIV-1 remission. Objective To characterize HIV-1 reservoirs in blood and tissues, and to perform analytical antiretroviral treatment interruptions to determine the potential for allogeneic HSCT to lead to sustained antiretroviral-free HIV-1 remission. Design Characterization of HIV-1 reservoirs and immunity before and after antiretroviral interruption. Setting Tertiary care center. Patients Two HIV-infected men with undetectable HIV-1 following allogeneic HSCT for hematologic malignancies. Measurements Quantification of HIV-1 in various tissues after HSCT and the duration of antiretroviral-free HIV-1 remission after treatment interruption. Results No HIV-1 was detected from peripheral blood or rectal mucosa prior to analytical treatment interruption. Plasma HIV-1 RNA and cell-associated HIV-1 DNA remained undetectable until 12 to 32 weeks after antiretroviral cessation. Both patients experienced rebound viremia with the development of acute retroviral syndrome within one to two weeks of the most recent negative viral load measurement. One patient developed new efavirenz resistance after re-initiation of antiretroviral therapy. Re-initiation of active therapy led to viral decay and resolution of symptoms in both patients. Limitations The study was limited to 2 patients. Conclusions Allogeneic HSCT may lead to loss of detectable HIV-1 from blood and gut tissue and variable periods of antiretroviral-free HIV-1 remission, but viral rebound can occur despite a minimum 3-log10 reduction in reservoir size. Long-lived tissue reservoirs may have contributed to viral persistence. Defining the nature and half-life of such reservoirs is essential in order to achieve durable antiretroviral-free HIV-1 remission. PMID:25047577

  17. Engine management during NTRE start up

    NASA Technical Reports Server (NTRS)

    Bulman, Mel; Saltzman, Dave

    1993-01-01

    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.

  18. 76 FR 14841 - Head Start Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-18

    ...and the legal consequences of committing fraud. The intent of this rule is to reduce...Head Start: Undercover Testing Finds Fraud and Abuse at Selected Head Start Centers...discussed new findings related to specific fraud allegations at two Head Start...

  19. 30 CFR 56.10010 - Starting precautions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Starting precautions. 56.10010 Section 56.10010 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE... Starting precautions. Where possible, aerial tramways shall not be started until the operator...

  20. 30 CFR 57.10010 - Starting precautions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Starting precautions. 57.10010 Section 57.10010 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE....10010 Starting precautions. Where possible, aerial tramways shall not be started until the operator...

  1. 34 CFR 200.16 - Starting points.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false Starting points. 200.16 Section 200.16 Education... Programs Operated by Local Educational Agencies Adequate Yearly Progress (ayp) § 200.16 Starting points. (a) Using data from the 2001-2002 school year, each State must establish starting points in...

  2. Starting or building your business / social enterprise

    E-print Network

    Chittka, Lars

    , evaluate and test my idea? Researching the market is an important starting point. Consider your competitors begin to test the market, get feedback and refine your idea. Consider applying for the QM `Try it.uk/starting-up-a-business/start-with-an-idea and www.gov.uk/market-research-business What should I include in my business plan? To help consolidate

  3. HIV-1 Genital Shedding is Suppressed in the Setting of High Genital Antiretroviral Drug Concentrations Throughout the Menstrual Cycle

    PubMed Central

    Sheth, Anandi N.; Evans-Strickfaden, Tammy; Haaland, Richard; Martin, Amy; Gatcliffe, Chelsea; Adesoye, Adebola; Omondi, Michael W.; Lupo, L. Davis; Danavall, Damien; Easley, Kirk; Chen, Cheng-Yen; Pau, Chou-Pong; Hart, Clyde; Ofotokun, Igho

    2014-01-01

    Background.?It is not known if fluctuations in genital tract antiretroviral drug concentrations correlate with genital virus shedding in human immunodeficiency virus (HIV)–infected women on antiretroviral therapy (ART). Methods.?Among 20 HIV-infected women on ART (tenofovir [TFV], emtricitabine [FTC], and ritonavir-boosted atazanavir [ATV]) with suppressed plasma virus loads, blood and cervicovaginal samples collected twice weekly for 3 weeks were tested for antiretroviral concentrations, HIV-1 RNA, and proviral DNA. Results.?Cervicovaginal:plasma antiretroviral concentration ratios were highest for FTC (11.9, 95% confidence interval [CI], 8.66–16.3), then TFV (3.52, 95% CI, 2.27–5.48), and ATV (2.39, 95% CI, 1.69–3.38). Within- and between-person variations in plasma and genital antiretroviral concentrations were observed. Low amounts of genital HIV-1 RNA (<50 copies/mL) were detected in 45% of women at 16% of visits. Genital HIV-1 DNA was detected in 70% of women at 35% of visits. Genital virus detection was associated with higher concentrations of mucosal leukocytes but not with genital antiretroviral concentrations, menstrual cycle phase, bacterial vaginosis, genital bleeding, or plasma virus detection. Conclusions.?Standard doses of ART achieved higher genital than plasma concentrations across the menstrual cycle. Therapeutic ART suppresses genital virus shedding throughout the menstrual cycle, even in the presence of factors reported to increase virus shedding. PMID:24643223

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

    PubMed Central

    Lert, France; Kazatchkine, Michel D.

    2007-01-01

    AIDS-related mortality and the rate of progression to AIDS have dramatically decreased since 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 with men). Poorer outcomes in HIV-infected IDUs are related to a variety of factors, including increased rates of non-HIV related deaths, hepatitis C, delayed access to effective treatment, lower adherence to care and treatment regimens, continuation of illicit drug use, depression and negative life events. The available evidence strongly suggests the need for the large-scale implementation of comprehensive treatment and care strategies for IDUs that include both treatment of drug-dependence and HAART. PMID:17689373

  5. 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

  6. Hybrid data capture for monitoring patients on highly active antiretroviral therapy (HAART) in urban Botswana.

    PubMed Central

    Bussmann, Hermann; Wester, C. William; Ndwapi, Ndwapi; Vanderwarker, Chris; Gaolathe, Tendani; Tirelo, Geoffrey; Avalos, Ava; Moffat, Howard; Marlink, Richard G.

    2006-01-01

    Individual patient care and programme evaluation are pivotal for the success of antiretroviral treatment programmes in resource-limited countries. While computer-aided documentation and data storage are indispensable for any large programme, several important issues need to be addressed including which data are to be collected, who collects it and how it is entered into an electronic database. We describe a patient-monitoring approach, which uses patient encounter forms (in hybrid paper + electronic format) based on optical character recognition, piloted at Princess Marina Hospital in Gaborone, Botswana's first public highly active antiretroviral therapy (HAART) outpatient clinic. Our novel data capture approach collects "key" data for tracking patient and programme outcomes. It saves physician time and does not detract from clinical care. PMID:16501730

  7. Persistent HIV-1 replication is associated with lower antiretroviral drug concentrations in lymphatic tissues

    PubMed Central

    Fletcher, Courtney V.; Staskus, Kathryn; Wietgrefe, Stephen W.; Rothenberger, Meghan; Reilly, Cavan; Chipman, Jeffrey G.; Beilman, Greg J.; Khoruts, Alexander; Thorkelson, Ann; Schmidt, Thomas E.; Anderson, Jodi; Perkey, Katherine; Stevenson, Mario; Perelson, Alan S.; Douek, Daniel C.; Haase, Ashley T.; Schacker, Timothy W.

    2014-01-01

    Antiretroviral therapy can reduce HIV-1 to undetectable levels in peripheral blood, but the effectiveness of treatment in suppressing replication in lymphoid tissue reservoirs has not been determined. Here we show in lymph node samples obtained before and during 6 mo of treatment that the tissue concentrations of five of the most frequently used antiretroviral drugs are much lower than in peripheral blood. These lower concentrations correlated with continued virus replication measured by the slower decay or increases in the follicular dendritic cell network pool of virions and with detection of viral RNA in productively infected cells. The evidence of persistent replication associated with apparently suboptimal drug concentrations argues for development and evaluation of novel therapeutic strategies that will fully suppress viral replication in lymphatic tissues. These strategies could avert the long-term clinical consequences of chronic immune activation driven directly or indirectly by low-level viral replication to thereby improve immune reconstitution. PMID:24469825

  8. Factors Influencing Adherence to Antiretroviral Therapy for HIV-Infected Female Inmates

    PubMed Central

    Roberson, Donna W.; White, Becky L.; Fogel, Catherine I.

    2015-01-01

    New HIV cases are increasing among women, especially women of color. Moreover, the rate of infection for incarcerated women is twice that of incarcerated men. With advances in medication therapy, HIV has become a chronic illness that can be successfully treated, provided the patient is able to achieve adherence with the prescribed antiretroviral medication regimen. Incarcerated women, however, frequently come from environments burdened with violence, substance and physical abuse, homelessness, child-care issues, and mental illness. Such burdens negatively affect the ability of these women to adhere to the medication plan. This study explored incarcerated HIV-infected women’s barriers to and facilitators of adherence to antiretroviral therapy (ART), the role of health care provider relationships in adherence, and the ways in which issues of medical privacy influence ability or desire to adhere while incarcerated. A secondary analysis of an existing set of qualitative interviews with HIV-infected female inmates was conducted. PMID:19118771

  9. Suicide mortality among people accessing highly active antiretroviral therapy for HIV/AIDS in British Columbia: a retrospective analysis

    PubMed Central

    Gurm, Jasmine; Samji, Hasina; Nophal, Adriana; Ding, Erin; Strehlau, Verena; Zhu, Julia; Montaner, Julio S.G.; Hogg, Robert S.

    2015-01-01

    Background Suicide rates have been reported at elevated levels among people living with HIV/AIDS. We sought to characterize longitudinal suicide rates among people living with HIV/AIDS who are accessing free highly active antiretroviral treatment (HAART) in British Columbia and evaluate the sociodemographic, clinical and behavioural factors associated with suicide in this population. Methods Retrospective analysis of all patients in the HAART Observational Medical Evaluation and Research (HOMER) cohort who were 19 years of age and older who started treatment between August 1996 and June 2012. The primary outcome variable was death due to suicide. Data on deaths were obtained monthly through a linkage with the British Columbia Ministry of Health Vital Statistics Agency. Logistic regression and Cox proportional hazards models were used to identify factors independently associated with suicide mortality. Results A total of 993 deaths among 5229 patients accessing treatment were recorded, of which 82 (8.2%) were caused by suicide. Death from suicide peaked at 961 deaths per 100 000 person-years in 1998 and declined to 2.81 deaths per 100 000 person-years in 2010. Cox regression analysis showed that a history of injection drug use (adjusted hazard ratio [AHR] = 3.95, 95% confidence interval [CI] 1.99–7.86) or having no experience with an AIDS-defining illness (AHR = 4.45, 95% CI 1.62–12.25) were factors independently associated with suicide. This model showed a 51% reduction (AHR = 0.49, 95% CI 0.45–0.54) in the suicide rate per calendar year. Interpretation Deaths from suicide declined substantially over time, and factors other than progression of HIV disease, such as injection drug use, may be important targets for intervention to reduce suicide risk. PMID:26389091

  10. Impact of antiretroviral therapy on quality of life in HIV-infected Southeast Asian children in the PREDICT study.

    PubMed

    Bunupuradah, Torsak; Kosalaraksa, Pope; Vibol, Ung; Hansudewechakul, Rawiwan; Sophonphan, Jiratchaya; Kanjanavanit, Suparat; Ngampiyaskul, Chaiwat; Wongsawat, Jurai; Luesomboon, Wicharn; Vonthanak, Saphonn; Ananworanich, Jintanat; Ruxrungtham, Kiat; Puthanakit, Thanyawee

    2013-11-01

    Quality of life (QOL) is an important antiretroviral treatment (ART) outcome. We compared QOL among 299 Thai and Cambodian children ages 1-12 years-old, CD4 15-24% randomized to early (ART at week 0, N=149) versus deferred groups (ART when at CD4 <15%, N=150) and also compared with QOL data from age-matched healthy controls (N=275). Primary caregivers completed PACTG QOL questionnaires at week 0 and every 24 weeks until 144 weeks. Children were enrolled during March 2006 to September 2008. Mean (SD) age of children was 6.3 (2.8) years, 58% were female, 60% were Thai, %CDC N:A:B:C was 2:62:36:0%. During 144 weeks, all children in the early-group and 69 (46%) of deferred-group children started ART. There was no significant difference of QOL scores between treatment groups at baseline (all p>0.05) and at week 144 (all p>0.05). By multivariate analysis, the early-group had higher QOL score changes in five domains, including health perception (p=0.04), physical resilience (p=0.02), psychosocial well-being (p=0.04), social and role functioning (p<0.01), and symptoms (p=0.01) compared to the deferred group. QOL of HIV-infected children in both groups were lower than healthy control in all 7 domains at baseline (all p<0.05) and 5 of 7 domains at weeks 144 (p<0.01). In conclusion, no significant difference of QOL scores between treatment groups. Early ART commencement associated with greater increase of QOL scores over 144 weeks. QOL scores in HIV-infected children were lower than healthy controls. PMID:24191673

  11. Acupuncture and the relaxation response for treating gastrointestinal symptoms in HIV patients on highly active antiretroviral therapy

    PubMed Central

    Chang, Bei-Hung; Sommers, Elizabeth

    2011-01-01

    Objectives To examine the effect of acupuncture and the relaxation response (RR) for treating gastrointestinal (GI) symptoms in HIV patients who are using highly active antiretroviral therapy (HAART). Methods The authors conducted a 4-arm 2×2 double-blind randomised controlled trial in an acupuncture clinic in the USA. Sham acupuncture and health education were used as the control conditions of real acupuncture and RR elicitation, respectively. Enrolled patients were randomised to real acupuncture+RR (AR), sham acupuncture+RR (SR), real acupuncture+health education (AE) or sham acupuncture+health education (SE) study arm. Participants listened to CDs with RR-eliciting instructions or health education while receiving acupuncture intervention. Interventions were provided twice weekly for 4 weeks and once weekly for another 4 weeks. Participants used daily diaries to record GI symptom severity ratings (0–10). The authors estimated the intervention effect as the changes in symptom rating per intervention session increase using a mixed-effects regression model. Results A total of 130 people with HIV/AIDS who were on HAART and had persistent GI symptoms were enrolled and 115 started the study intervention. The AR group had greater intervention effects for loose stools symptoms than the other three groups (?=?0.149, ?0.151 and ?0.144, p value=0.013, 0.013 and 0.018 comparing AR to AE, SR and SE, respectively). The AR group also had significant intervention effects on reducing nausea symptoms when the intervention was given twice per week (?=?0.218, p=0.001). Conclusions Our trial provided preliminary data demonstrating the potential synergistic effects of acupuncture and RR for treating GI symptoms in HIV patients on HAART. PMID:21705396

  12. Impact of Antiretroviral Therapy on Quality of Life in HIV-Infected Southeast Asian Children in the PREDICT Study

    PubMed Central

    Bunupuradah, Torsak; Kosalaraksa, Pope; Vibol, Ung; Hansudewechakul, Rawiwan; Sophonphan, Jiratchaya; Kanjanavanit, Suparat; Ngampiyaskul, Chaiwat; Wongsawat, Jurai; Luesomboon, Wicharn; Vonthanak, Saphonn; Ananworanich, Jintanat; Ruxrungtham, Kiat

    2013-01-01

    Abstract Quality of life (QOL) is an important antiretroviral treatment (ART) outcome. We compared QOL among 299 Thai and Cambodian children ages 1–12 years-old, CD4 15–24% randomized to early (ART at week 0, N=149) versus deferred groups (ART when at CD4 <15%, N=150) and also compared with QOL data from age-matched healthy controls (N=275). Primary caregivers completed PACTG QOL questionnaires at week 0 and every 24 weeks until 144 weeks. Children were enrolled during March 2006 to September 2008. Mean (SD) age of children was 6.3 (2.8) years, 58% were female, 60% were Thai, %CDC N:A:B:C was 2:62:36:0%. During 144 weeks, all children in the early-group and 69 (46%) of deferred-group children started ART. There was no significant difference of QOL scores between treatment groups at baseline (all p>0.05) and at week 144 (all p>0.05). By multivariate analysis, the early-group had higher QOL score changes in five domains, including health perception (p=0.04), physical resilience (p=0.02), psychosocial well-being (p=0.04), social and role functioning (p<0.01), and symptoms (p=0.01) compared to the deferred group. QOL of HIV-infected children in both groups were lower than healthy control in all 7 domains at baseline (all p<0.05) and 5 of 7 domains at weeks 144 (p<0.01). In conclusion, no significant difference of QOL scores between treatment groups. Early ART commencement associated with greater increase of QOL scores over 144 weeks. QOL scores in HIV-infected children were lower than healthy controls. PMID:24191673

  13. Recent trends in the spectrum of opportunistic infections in human immunodeficiency virus infected individuals on antiretroviral therapy in South India

    PubMed Central

    Shahapur, Praveen R.; Bidri, Rajendra C.

    2014-01-01

    Background: Opportunistic infections (OI) are the major cause of morbidity and mortality among human immunodeficiency virus (HIV) infected individuals. The pattern of OIs differs widely, hence it is necessary to correlate spectrum of OIs and CD4 counts among HIV infected individuals in specific localities. Materials and Methods: The present study describes the clinical and laboratory profiles of different OIs among 55 HIV seropositive patients. CD4 count was estimated and antiretroviral therapy (ART) was started in 27 patients as per National Acquired Immunodeficiency Syndrome Control Organization guidelines. These 27 patients were classified into stage 1, stage 2 and stage 3 based on CD4 counts of >500 cells/?l, 200-499 cells/?l and <200 cells/?l respectively. The OIs presented by respective groups were documented. Results: Pulmonary tuberculosis was found to be the most common OI constituting 43.6% of all cases followed by candidiasis (30.9%), cryptosporidial diarrhea (21.8%), herpes zoster (16.3%), cryptococcal meningitis (3.63%), Pneumocystis jirovecii pneumonia (1.81%), and other miscellaneous infections (23.6%). Only 1 patient was found in stage I while 13 patients each were grouped in stage II or stage III. The mean CD4 count in our study population who were on ART was 230 ± 150 cells/µl. Conclusion: The pattern of OIs among our study group did not differ significantly from patients not receiving ART. The effect of ART on CD4 count differs from patient to patient based on the degree of depletion of CD4 count before the initiation of ART, drug adherence, concomitant OIs and their treatment. PMID:25097422

  14. 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

  15. Persisting high prevalence of pneumococcal carriage among HIV-infected adults receiving antiretroviral therapy in Malawi: a cohort study

    PubMed Central

    Heinsbroek, Ellen; Tafatatha, Terence; Phiri, Amos; Ngwira, Bagrey; Crampin, Amelia C.; Read, Jonathan M.; French, Neil

    2015-01-01

    Objective: HIV-infected adults have high rates of pneumococcal carriage and invasive disease. We investigated the effect of antiretroviral therapy (ART) on pneumococcal carriage in HIV-infected adults prior to infant pneumococcal conjugate vaccine (PCV) rollout. Design: Observational cohort study. Methods: We recruited HIV-infected adults newly attending a rural HIV clinic in northern Malawi between 2008 and 2010. Nasopharyngeal samples were taken at baseline and after 6, 12, 18 and 24 months. We compared pneumococcal carriage by ART status using generalized estimated equation models adjusted for CD4+ cell count, sex, seasonality, and other potential confounders. Results: In total, 336 individuals were included, of which 223 individuals started ART during follow-up. Individuals receiving ART had higher pneumococcal carriage than individuals not receiving ART (25.9 vs. 19.8%, P?=?0.03) particularly for serotypes not included in PCV13 (16.1 vs. 9.6% P?=?0.003). Following adjustment, increased carriage of non-PCV13 serotypes was still observed for individuals on ART, but results for all serotypes were nonsignificant [all serotypes: adjusted risk ratio (aRR) 1.22 (0.95–1.56); non-PCV13 serotypes: aRR 1.72, 95% CI 1.13–2.62]. Conclusion: Pneumococcal carriage in HIV-infected adults in Malawi remained high despite use of ART, consistent with failure of mucosal immune reconstitution in the upper respiratory tract. There was evidence of increased carriage of non-PCV13 serotypes. HIV-infected adults on ART could remain an important reservoir for pneumococcal diversity post infant pneumococcal vaccine introduction. Control of pneumococcal disease in African HIV remains a priority. PMID:26218599

  16. Pubertal Onset in HIV-infected Children in the Era of Combination Antiretroviral Treatment

    PubMed Central

    WILLIAMS, Paige L.; ABZUG, Mark J.; JACOBSON, Denise L.; WANG, Jiajia; VAN DYKE, Russell B.; HAZRA, Rohan; PATEL, Kunjal; DIMEGLIO, Linda A.; MCFARLAND, Elizabeth J.; SILIO, Margarita; BORKOWSKY, William; SEAGE, George R.; OLESKE, James M.; GEFFNER, Mitchell E.

    2014-01-01

    Objective To evaluate associations of perinatal HIV infection (PHIV), HIV disease severity, and combination antiretroviral treatment with age at pubertal onset. Design Analysis of data from two U.S. longitudinal cohort studies [IMPAACT 219C and PHACS AMP], conducted 2000–2012, including PHIV and HIV-exposed uninfected (HEU) youth. Tanner stage assessments of pubertal status (breast and pubic hair in girls; genitalia and pubic hair in boys) were conducted annually. Methods We compared the timing of pubertal onset (Tanner stage ?2) between PHIV and HEU youth using interval-censored models. For PHIV youth, we evaluated associations of HIV disease severity and combination antiretroviral treatment with age at pubertal onset, adjusting for race/ethnicity and birth cohort. Results The mean age at pubertal onset was significantly later for the 2086 PHIV youth compared to 453 HEU children (10.3 vs 9.6, 10.5 vs 10.0, 11.3 vs 10.4, and 11.5 vs 10.7 years according to female breast, female pubic hair, male genitalia, and male pubic hair staging, respectively, all p<0.001). PHIV youth with HIV-1 RNA viral load >10,000 copies/mL (vs ?10,000 copies/mL) or CD4% <15% (vs ?15%) had significantly later pubertal onset (by 4–13 months). Each additional year of combination antiretroviral treatment was associated with a 0.6- to1.2-month earlier mean age at pubertal onset, but this trend did not persist after adjustment for birth cohort. Conclusions Pubertal onset occurs significantly later in PHIV than in HEU youth, especially among those with more severe HIV disease. However, in the current era, combination antiretroviral treatment may result in more normal timing of pubertal onset. PMID:24145244

  17. Mycobacterium xenopi pulmonary infection in an HIV infected patient under highly active antiretroviral treatment

    PubMed Central

    Bachmeyer, C; Blum, L; Stelianides, S; Benchaa, B; Gruat, N; Danne, O

    2001-01-01

    Highly active antiretroviral therapy (HAART) is responsible for a striking reduction in AIDS related morbidity and mortality by partly restoring immune function. However, HAART can also precipitate the development of clinically apparent opportunistic infections in patients with latent infections. We report a case of an HIV infected patient who developed granulomatous nodular and cavitatory lesions of the lungs due to Mycobacterium xenopi as a manifestation of the immune restoration syndrome.?? PMID:11713363

  18. Healthcare Worker Perceived Barriers to Early Initiation of Antiretroviral and Tuberculosis Therapy among Tanzanian Inpatients

    PubMed Central

    Wajanga, Bahati M. K.; Peck, Robert N.; Kalluvya, Samuel; Fitzgerald, Daniel W.; Smart, Luke R.; Downs, Jennifer A.

    2014-01-01

    Setting Clinical trials have shown that early initiation of antiretroviral therapy in HIV-infected patients with tuberculosis saves lives, but models for implementation of this new strategy have been under-studied in real-world settings. Objective To identify the barriers and possible solutions for implementing concurrent early treatment with antiretroviral and anti-tuberculosis therapy in a large East African referral hospital where the prevalence of both infections is high. Design In-depth interviews among hospital administrators, laboratory technicians, nurses, pharmacists, and physicians. Results Twenty-six hospital staff identified six key barriers and corresponding solutions to promote rapid initiation of antiretroviral therapy in HIV-infected inpatients with tuberculosis. These include revising systems of medication delivery, integrating care between inpatient and outpatient systems, training hospital nurses to counsel and initiate medications in inpatients, and cultivating a team approach to consistent guideline implementation. Conclusion Most barriers identified by hospital staff were easily surmountable with reorganization, training, and policy changes at minimal cost. Efforts to reduce mortality for HIV and tuberculosis co-infected patients in accordance with new World Health Organization guidelines are currently hampered by implementation barriers in real-world settings. Our findings suggest that these can be overcome with strategic enactment of simple, realistic interventions to promote early dual treatment for HIV/tuberculosis co-infected patients. PMID:24551061

  19. Can antiretroviral therapy be tailored to each human immunodeficiency virus-infected individual? Role of pharmacogenomics.

    PubMed

    Asensi, Victor; Collazos, Julio; Valle-Garay, Eulalia

    2015-08-12

    Pharmacogenetics refers to the effect of single nucleotide polymorphisms (SNPs) within human genes on drug therapy outcome. Its study might help clinicians to increase the efficacy of antiretroviral drugs by improving their pharmacokinetics and pharmacodynamics and by decreasing their side effects. HLAB*5701 genotyping to avoid the abacavir-associated hypersensitivity reaction (HSR) is a cost-effective diagnostic tool, with a 100% of negative predictive value, and, therefore, it has been included in the guidelines for treatment of human immunodeficiency virus (HIV) infection. HALDRB*0101 associates with nevirapine-induced HSR. CYP2B6 SNPs modify efavirenz plasma levels and their genotyping help decreasing its central nervous system, hepatic and HSR toxicities. Cytokines SNPs might influence the development of drug-associated lipodystrophy. APOA5, APOB, APOC3 and APOE SNPs modify lipids plasma levels and might influence the coronary artery disease risk of HIV-infected individuals receiving antiretroviral therapy. UGT1A1*28 and ABCB1 (MDR1) 3435C > T SNPs modify atazanavir plasma levels and enhance hyperbilirubinemia. Much more effort needs to be still devoted to complete large prospective studies with multiple SNPs genotyping in order to reveal more clues about the role played by host genetics in antiretroviral drug efficacy and toxicity. PMID:26279978

  20. Can antiretroviral therapy be tailored to each human immunodeficiency virus-infected individual? Role of pharmacogenomics

    PubMed Central

    Asensi, Victor; Collazos, Julio; Valle-Garay, Eulalia

    2015-01-01

    Pharmacogenetics refers to the effect of single nucleotide polymorphisms (SNPs) within human genes on drug therapy outcome. Its study might help clinicians to increase the efficacy of antiretroviral drugs by improving their pharmacokinetics and pharmacodynamics and by decreasing their side effects. HLAB*5701 genotyping to avoid the abacavir-associated hypersensitivity reaction (HSR) is a cost-effective diagnostic tool, with a 100% of negative predictive value, and, therefore, it has been included in the guidelines for treatment of human immunodeficiency virus (HIV) infection. HALDRB*0101 associates with nevirapine-induced HSR. CYP2B6 SNPs modify efavirenz plasma levels and their genotyping help decreasing its central nervous system, hepatic and HSR toxicities. Cytokines SNPs might influence the development of drug-associated lipodystrophy. APOA5, APOB, APOC3 and APOE SNPs modify lipids plasma levels and might influence the coronary artery disease risk of HIV-infected individuals receiving antiretroviral therapy. UGT1A1*28 and ABCB1 (MDR1) 3435C > T SNPs modify atazanavir plasma levels and enhance hyperbilirubinemia. Much more effort needs to be still devoted to complete large prospective studies with multiple SNPs genotyping in order to reveal more clues about the role played by host genetics in antiretroviral drug efficacy and toxicity. PMID:26279978

  1. Conspiracy Beliefs about HIV Are Related to Antiretroviral Treatment Nonadherence among African American Men with HIV

    PubMed Central

    Bogart, Laura M.; Wagner, Glenn; Galvan, Frank H.; Banks, Denedria

    2009-01-01

    Background Medical mistrust is prevalent among African Americans and may influence health care behaviors such as treatment adherence. We examined whether a specific form of medical mistrust – HIV conspiracy beliefs (e.g., HIV is genocide against African Americans) – was associated with antiretroviral treatment nonadherence among African American men with HIV. Methods On baseline surveys, 214 African American men with HIV reported their agreement with 9 conspiracy beliefs, socio-demographic characteristics, depression symptoms, substance use, disease characteristics, medical mistrust, and health care barriers. Antiretroviral medication adherence was monitored electronically for one-month post-baseline among 177 men in the baseline sample. Results Confirmatory factor analysis revealed two distinct conspiracy belief subscales: genocidal beliefs (e.g., HIV is manmade) and treatment-related beliefs (e.g., people who take antiretroviral treatments are human guinea pigs for the government). Both subscales were related to nonadherence in bivariate tests. In a multivariate logistic regression, only treatment-related conspiracies were associated with a lower likelihood of optimal adherence at one-month follow-up (Odds ratio = 0.60, 95% confidence interval = 0.37 to 0.96, p < 0.05). Conclusions HIV conspiracy beliefs, especially those related to treatment mistrust, can contribute to health disparities by discouraging appropriate treatment behavior. Adherence-promoting interventions targeting African Americans should openly address such beliefs. PMID:19952767

  2. 78 FR 49372 - Notice of Availability of New Starts and Small Starts Policy Guidance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-14

    ... Projects promulgated in January 2013. The rule sets the framework for the New Starts and Small Starts... and Small Starts projects. The final policy guidance sets forth breakpoints for determining whether a... Federal Transit Administration 49 CFR Part 611 Notice of Availability of New Starts and Small...

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

    ERIC Educational Resources Information Center

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

    2009-01-01

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

  4. Interactions of antiretroviral drugs with the SLC22A1 (OCT1) drug transporter

    PubMed Central

    Moss, Darren M.; Liptrott, Neill J.; Siccardi, Marco; Owen, Andrew

    2015-01-01

    The SLC22A1 influx transporter is expressed on the basolateral membrane of hepatocytes and is involved in the excretion of numerous cations. Inhibition of SLC22A1 by several antiretrovirals, such as the protease inhibitor darunavir, has not previously been determined. In order to better understand and predict drug-SLC22A1 interactions, a range of antiretrovirals were screened for SLC22A1-associated inhibition and transport. Stable SLC22A1-expressing KCL22 cells were produced previously by nucleofection. Control KCL22 cells were transfected with the empty vector pcDNA3.1. Accumulation of tetraethylammonium (5.5 ?M, 30 min) was determined in SLC22A1-expressing and mock-transfected cells with and without 50 ?M of SLC22A1 inhibitor prazosin, or 50 ?M of each antiretroviral drug. SLC22A1 IC50 values for efavirenz, darunavir, and prazosin were determined. Cellular accumulation of efavirenz and darunavir was also assessed in SLC22A1-expressing KCL22 cells and reversibility of this accumulation was assessed using prazosin. Tetraethylammonium accumulation was higher in SLC22A1-expressing cells compared to mock-transfected cells (10.6 ± 0.8 ?M vs. 0.3 ± 0.004 ?M, p = 0.009) and was significantly reduced in SLC22A1-expressing cells when co-incubated with all antiretrovirals tested except atazanavir, lamivudine, tenofovir, zidovudine, and raltegravir. Particularly noticeable was the predominance of SLC22A1 inhibitors in the protease inhibitor and non-nucleoside reverse transcriptase inhibitor classes. Absolute SLC22A1 IC50 values for efavirenz, darunavir, and prazosin were 21.8, 46.2, and 2.8 ?M, respectively. Efavirenz accumulation was higher in SLC22A1-expressing cells compared to mock-transfected cells (17% higher, p = 0.009) which was reversed using prazosin, whereas no difference was observed for darunavir (p = 0.86). These data inform the mechanistic basis for disposition, drug-drug interactions and pharmacogenetic candidate gene selection for antiretroviral drugs. PMID:25914645

  5. Microcomputer controlled soft start of motor

    NASA Astrophysics Data System (ADS)

    Gao, Miao; Wang, Yanpeng; Li, Shian

    2005-12-01

    Improving the starting characteristics of a motor is an important part of the motor control. An intelligent soft starting technique was adopted in the starter and used in the present study because of its many advantages compared with conventional starting processes. The core of the soft starter was a single chip (Atmel 8098), its soul was the software and its control object was a Silicon Controlled Rectifier (SCR). The starter achieved not only current-limit starting, but also closed-loop control with a stator current detection circuit. In conclusion, as a result of digital control, starting characteristic can be conveniently chosen according to the load. In addition the starter is of small size, and starting is smooth and reliable due to current feedback.

  6. 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.

  7. 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 Start Time - Midpoint of 1 hour Window NHB HBO HBS HBW B.1 #12;Durham 1996 0% 2% 4% 6% 8% 10% 12% 14 2530 2630 2730 Start Time - Midpoint of 1 hour Window NHB HBO HBS HBW B.2 #12;York 1996 0% 2% 4% 6% 8

  8. 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.

  9. Retention in Care of Adult HIV Patients Initiating Antiretroviral Therapy in Tigray, Ethiopia: A Prospective Observational Cohort Study

    PubMed Central

    Bucciardini, Raffaella; Fragola, Vincenzo; Abegaz, Teshome; Lucattini, Stefano; Halifom, Atakilt; Tadesse, Eskedar; Berhe, Micheal; Pugliese, Katherina; Binelli, Andrea; De Castro, Paola; Terlizzi, Roberta; Fucili, Luca; Di Gregorio, Massimiliano; Mirra, Marco; Olivieri, Erika; Teklu, Tsigemariam; Zegeye, Teame; Haile, Amanuel; Vella, Stefano; Abraham, Loko; Godefay, Hagos

    2015-01-01

    Introduction Although Ethiopia has been scaling up the antiretroviral therapy (ART) services, low retention in care of patients remains one of the main obstacles to treatment success. We report data on retention in care and its associated determinants in Tigray, Ethiopia. Methods We used data from the CASA project, a prospective observational and multi-site study of a cohort of HIV-infected patients who initiated ART for the first time in Tigray. Four participating health facilities (HFs) located in the South of Tigray were considered for this study. Patients were followed for one year after ART initiation. The main outcome measure was represented by the current retention in care, defined as the proportion of patients who were alive and receiving ART at the same HF one year after ART initiation. Patients who started ART between January 1, 2013 and December 31, 2013 were included in this analysis. Patients were followed for one year after ART initiation. The determinants of retention were analysed using univariate and multivariate Cox Proportional Hazards model with robust sandwich estimates to account for within HF correlation. Results The four participating HFs in Tigray were able to retain overall 85.1% of their patients after one year from starting ART. Loss to follow-up (5.5%) and transfers to other HF (6.6) were the main determinant of attrition. A multivariate analysis shows that the factors significantly associated with retention were the type of HF, gender and active TB. Alamata health center was the HF with the highest attrition rate (HR 2.99, 95% CI: 2.77–3.23). Active TB (HR 1.72, 95% CI: 1.23–2.41) and gender (HR 1.64, 95% CI: 1.10–2.56) were also significantly associated with attrition. Conclusions Although Ethiopia has significantly improved access to the ART program, achieving and maintaining a satisfactory long-term retention rate is a future goal. This is difficult because of different retention rates among HFs. Moreover specific interventions should be directed to people of different sex to improve retention in care in male population. PMID:26340271

  10. Outcomes of antiretroviral therapy in children in Asia and Africa: a comparative analysis of the IeDEA pediatric multiregional collaboration

    PubMed Central

    Leroy, Valeriane; Malateste, Karen; Rabie, Helena; Lumbiganon, Pagakrong; Ayaya, Samuel; Dicko, Fatoumata; Davies, Mary-Ann; Kariminia, Azar; Wools-Kaloustian, Kara; Aka, Edmond; Phiri, Samuel; Aurpibul, Linda; Yiannoutsos, Constantin; Signaté-Sy, Haby; Mofenson, Lynne; Dabis, François

    2013-01-01

    Background We investigated 18-month incidence and determinants of death and loss-to-follow-up of children after antiretroviral therapy (ART) initiation in a multiregional collaboration in lower-income countries. Methods HIV-infected children (positive PCR <18 months or positive serology ?18 months) from IeDEA cohorts, <16 years, initiating ART were eligible. A competing risk regression model was used to analyze the independent risk of two failure types: death and loss-to-follow-up (>6 months). Findings Data on 13611 children, from Asia (N=1454), East-Africa (N=3114), Southern-Africa (N=6212) and West-Africa (N=2881) contributed 20,417 person-years of follow-up. At 18 months, the adjusted risk of death was 4.3% in East-Africa, 5.4% in Asia, 5.7% in Southern-Africa and 7.4% in West-Africa (P=0.01). Age<24 months, WHO stage 4, CD4<10%, attending a private sector clinic, larger cohort size and living in West-Africa were independently associated with poorer survival. The adjusted risk of loss-to-follow-up was 4.1% in Asia, 9.0% in Southern-Africa, 14.0% in East-Africa, and 21.8% in West-Africa (P <0.01). Age<12 months, non NNRTI-based ART regimen, WHO stage 4 at ART start, ART initiation after 2005, attending a public sector or a non-urban clinic, having to pay for laboratory tests or antiretroviral drugs, larger cohort size, and living in East or West-Africa were significantly associated with higher loss-to-follow-up. Conclusion Findings differed substantially across regions but raise overall concerns about delayed ART start, low access to free HIV-services for children, and increased workload on program retention in lower-income countries. Universal free access to ART services and innovative approaches are urgently needed to improve pediatric outcomes at program level. PMID:23187940

  11. The Evolving Genotypic Profile of HIV-1 Mutations Related to Antiretroviral Treatment in the North Region of Brazil

    PubMed Central

    Lopes, Carmen Andréa F.; Soares, Marcelo A.; Falci, Diego R.; Sprinz, Eduardo

    2015-01-01

    HIV related mutations can be associated with decreased susceptibility to antiretrovirals and treatment failures. There is scarce information about HIV mutations in persons failing HIV treatment in North of Brazil. Our aim was to evaluate evolution of HIV subtypes and mutations patterns related to antiretroviral therapy in this region. We investigated HIV resistance profile in adults failing antiretroviral regimen in Northern Brazil from January, 2004, through December, 2013. Genotype data was evaluated through Stanford University algorithm. There were 377 genotypes from different individuals to evaluate. Resistance mutations were similar to worldwide reports and related to antiretroviral exposure. Most prevalent mutations in the reverse transcriptase gene were M184V (80.1%) and K130N (40.6%). Thymidine associated mutations were more frequent in multiexperienced patients. Most common protease mutations were M46I, V82A, I54V, L90M, I84V, M46L, and L76V. Subtype B was the most prevalent (90.7%). There were differences between subtypes B and non-B mutations. We documented for the first time subtypes and patterns of HIV associated mutations in Northern Brazil. A1 subtype was identified for the first time in this area. Depending on drug regimen and how experienced the patient is, an empirical switch of a failing antiretroviral treatment could be a reasonable option. PMID:26543866

  12. 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

  13. Evolution of Antiretroviral Drug Costs in Brazil in the Context of Free and Universal Access to AIDS Treatment

    PubMed Central

    Nunn, Amy S; Fonseca, Elize M; Bastos, Francisco I; Gruskin, Sofia; Salomon, Joshua A

    2007-01-01

    Background Little is known about the long-term drug costs associated with treating AIDS in developing countries. Brazil's AIDS treatment program has been cited widely as the developing world's largest and most successful AIDS treatment program. The program guarantees free access to highly active antiretroviral therapy (HAART) for all people living with HIV/AIDS in need of treatment. Brazil produces non-patented generic antiretroviral drugs (ARVs), procures many patented ARVs with negotiated price reductions, and recently issued a compulsory license to import one patented ARV. In this study, we investigate the drivers of recent ARV cost trends in Brazil through analysis of drug-specific prices and expenditures between 2001 and 2005. Methods and Findings We compared Brazil's ARV prices to those in other low- and middle-income countries. We analyzed trends in drug expenditures for HAART in Brazil from 2001 to 2005 on the basis of cost data disaggregated by each ARV purchased by the Brazilian program. We decomposed the overall changes in expenditures to compare the relative impacts of changes in drug prices and drug purchase quantities. We also estimated the excess costs attributable to the difference between prices for generics in Brazil and the lowest global prices for these drugs. Finally, we estimated the savings attributable to Brazil's reduced prices for patented drugs. Negotiated drug prices in Brazil are lowest for patented ARVs for which generic competition is emerging. In recent years, the prices for efavirenz and lopinavir–ritonavir (lopinavir/r) have been lower in Brazil than in other middle-income countries. In contrast, the price of tenofovir is US$200 higher per patient per year than that reported in other middle-income countries. Despite precipitous price declines for four patented ARVs, total Brazilian drug expenditures doubled, to reach US$414 million in 2005. We find that the major driver of cost increases was increased purchase quantities of six specific drugs: patented lopinavir/r, efavirenz, tenofovir, atazanavir, enfuvirtide, and a locally produced generic, fixed-dose combination of zidovudine and lamivudine (AZT/3TC). Because prices declined for many of the patented drugs that constitute the largest share of drug costs, nearly the entire increase in overall drug expenditures between 2001 and 2005 is attributable to increases in drug quantities. Had all drug quantities been held constant from 2001 until 2005 (or for those drugs entering treatment guidelines after 2001, held constant between the year of introduction and 2005), total costs would have increased by only an estimated US$7 million. We estimate that in the absence of price declines for patented drugs, Brazil would have spent a cumulative total of US$2 billion on drugs for HAART between 2001 and 2005, implying a savings of US$1.2 billion from price declines. Finally, in comparing Brazilian prices for locally produced generic ARVs to the lowest international prices meeting global pharmaceutical quality standards, we find that current prices for Brazil's locally produced generics are generally much higher than corresponding global prices, and note that these prices have risen in Brazil while declining globally. We estimate the excess costs of Brazil's locally produced generics totaled US$110 million from 2001 to 2005. Conclusions Despite Brazil's more costly generic ARVs, the net result of ARV price changes has been a cost savings of approximately US$1 billion since 2001. HAART costs have nevertheless risen steeply as Brazil has scaled up treatment. These trends may foreshadow future AIDS treatment cost trends in other developing countries as more people start treatment, AIDS patients live longer and move from first-line to second and third-line treatment, AIDS treatment becomes more complex, generic competition emerges, and newer patented drugs become available. The specific application of the Brazilian model to other countries will depend, however, on the strength of their health systems, intellectual property regulations, epidemiologic

  14. 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…

  15. Head Start. What Works Clearinghouse Intervention Report

    ERIC Educational Resources Information Center

    What Works Clearinghouse, 2015

    2015-01-01

    "Head Start" is a national, federally funded program that provides services to promote school readiness for children from birth to age 5 from predominantly low-income families. Based on a review of the research, the WWC found "Head Start" to have potentially positive effects on general reading achievement and no discernible…

  16. GETTING STARTED IN PER: GENDER AND

    E-print Network

    Wu, Mingshen

    Just as PER started with figuring out student misconceptions, gender in PER started with gender gaps on conceptual tests 1994 gender part of article introducing TUG-K 1996 AAPT talk on gender gap on FCI in university students 2004 DIRECT gender gap noted in article introducing test 2006 CLASS survey article noted

  17. JobStart: The Road to Independence.

    ERIC Educational Resources Information Center

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

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

  18. 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…

  19. Head Start Impact Study. Final Report

    ERIC Educational Resources Information Center

    Puma, Michael; Bell, Stephen; Cook, Ronna; Heid, Camilla; Shapiro, Gary; Broene, Pam; Jenkins, Frank; Fletcher, Philip; Quinn, Liz; Friedman, Janet; Ciarico, Janet; Rohacek, Monica; Adams, Gina; Spier, Elizabeth

    2010-01-01

    This report addresses the following four questions by reporting on the impacts of Head Start on children and families during the children's preschool, kindergarten, and 1st grade years: (1) What difference does Head Start make to key outcomes of development and learning (and in particular, the multiple domains of school readiness) for low-income…

  20. Head Start Impact Study. Technical Report

    ERIC Educational Resources Information Center

    Puma, Michael; Bell, Stephen; Cook, Ronna; Heid, Camilla; Shapiro, Gary; Broene, Pam; Jenkins, Frank; Fletcher, Philip; Quinn, Liz; Friedman, Janet; Ciarico, Janet; Rohacek, Monica; Adams, Gina; Spier, Elizabeth

    2010-01-01

    This Technical Report is designed to provide technical detail to support the analysis and findings presented in the "Head Start Impact Study Final Report" (U.S. Department of Health and Human Services, January 2010). Chapter 1 provides an overview of the Head Start Impact Study and its findings. Chapter 2 provides technical information on the…

  1. Werkcollege from 9 September start mysql server

    E-print Network

    Peletier, Reynier

    Werkcollege from 9 September Tasks: start mysql server create a database download data from 2MASS and USNO-A2 ingest data into database cross-identify 2MASS and USNO-A2 regions 1 Start MySQL server In your home directory (/Users/users/belikov through this example) create a subdirectory for MySQL data storage

  2. 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).

  3. Pre-Antiretroviral Therapy Serum Selenium Concentrations Predict WHO Stages 3, 4 or Death but not Virologic Failure Post-Antiretroviral Therapy

    PubMed Central

    Shivakoti, Rupak; Gupte, Nikhil; Yang, Wei-Teng; Mwelase, Noluthando; Kanyama, Cecilia; Tang, Alice M.; Pillay, Sandy; Samaneka, Wadzanai; Riviere, Cynthia; Berendes, Sima; Lama, Javier R.; Cardoso, Sandra W.; Sugandhavesa, Patcharaphan; Semba, Richard D.; Christian, Parul; Campbell, Thomas B.; Gupta, Amita

    2014-01-01

    A case-cohort study, within a multi-country trial of antiretroviral therapy (ART) efficacy (Prospective Evaluation of Antiretrovirals in Resource Limited Settings (PEARLS)), was conducted to determine if pre-ART serum selenium deficiency is independently associated with human immunodeficiency virus (HIV) disease progression after ART initiation. Cases were HIV-1 infected adults with either clinical failure (incident World Health Organization (WHO) stage 3, 4 or death by 96 weeks) or virologic failure by 24 months. Risk factors for serum selenium deficiency (<85 ?g/L) pre-ART and its association with outcomes were examined. Median serum selenium concentration was 82.04 ?g/L (Interquartile range (IQR): 57.28–99.89) and serum selenium deficiency was 53%, varying widely by country from 0% to 100%. In multivariable models, risk factors for serum selenium deficiency were country, previous tuberculosis, anemia, and elevated C-reactive protein. Serum selenium deficiency was not associated with either clinical failure or virologic failure in multivariable models. However, relative to people in the third quartile (74.86–95.10 ?g/L) of serum selenium, we observed increased hazards (adjusted hazards ratio (HR): 3.50; 95% confidence intervals (CI): 1.30–9.42) of clinical failure but not virologic failure for people in the highest quartile. If future studies confirm this relationship of high serum selenium with increased clinical failure, a cautious approach to selenium supplementation might be needed, especially in HIV-infected populations with sufficient or unknown levels of selenium. PMID:25401501

  4. Cholelithiasis and Nephrolithiasis in HIV-Positive Patients in the Era of Combination Antiretroviral Therapy

    PubMed Central

    Lin, Kuan-Yin; Liao, Sih-Han; Liu, Wen-Chun; Cheng, Aristine; Lin, Shu-Wen; Chang, Sui-Yuan; Tsai, Mao-Song; Kuo, Ching-Hua; Wu, Mon-Ro; Wang, Hsiu-Po; Hung, Chien-Ching; Chang, Shan-Chwen

    2015-01-01

    Objectives This study aimed to describe the epidemiology and risk factors of cholelithiasis and nephrolithiasis among HIV-positive patients in the era of combination antiretroviral therapy. Methods We retrospectively reviewed the medical records of HIV-positive patients who underwent routine abdominal sonography for chronic viral hepatitis, fatty liver, or elevated aminotransferases between January 2004 and January 2015. Therapeutic drug monitoring of plasma concentrations of atazanavir was performed and genetic polymorphisms, including UDP-glucuronosyltransferase (UGT) 1A1*28 and multidrug resistance gene 1 (MDR1) G2677T/A, were determined in a subgroup of patients who received ritonavir-boosted or unboosted atazanavir-containing combination antiretroviral therapy. Information on demographics, clinical characteristics, and laboratory testing were collected and analyzed. Results During the 11-year study period, 910 patients who underwent routine abdominal sonography were included for analysis. The patients were mostly male (96.9%) with a mean age of 42.2 years and mean body-mass index of 22.9 kg/m2 and 85.8% being on antiretroviral therapy. The anchor antiretroviral agents included non-nucleoside reverse-transcriptase inhibitors (49.3%), unboosted atazanavir (34.4%), ritonavir-boosted lopinavir (20.4%), and ritonavir-boosted atazanavir (5.5%). The overall prevalence of cholelithiasis and nephrolithiasis was 12.5% and 8.2%, respectively. Among 680 antiretroviral-experienced patients with both baseline and follow-up sonography, the crude incidence of cholelithiasis and nephrolithiasis was 4.3% and 3.7%, respectively. In multivariate analysis, the independent factors associated with incident cholelithiasis were exposure to ritonavir-boosted atazanavir for >2 years (adjusted odds ratio [AOR], 6.29; 95% confidence interval [CI], 1.12–35.16) and older age (AOR, 1.04; 95% CI, 1.00–1.09). The positive association between duration of exposure to ritonavir-boosted atazanavir and incident cholelithiasis was also found (AOR, per 1-year exposure, 1.49; 95% CI, 1.05–2.10). The associated factors with incident nephrolithiasis were hyperlipidemia (AOR, 3.97; 95% CI, 1.32–11.93), hepatitis B or C coinfection (AOR, 3.41; 95% CI, 1.09–10.62), and exposure to abacavir (AOR, 12.01; 95% CI, 1.54–93.54). Of 180 patients who underwent therapeutic drug monitoring of plasma atazanavir concentrations and pharmacogenetic investigations, we found that the atazanavir concentrations and UGT 1A1*28 and MDR1 G2677T/A polymorphisms were not statistically significantly associated with incident cholelithiasis and nephrolithiasis. Conclusions In HIV-positive patients in the era of combination antiretroviral therapy, a high prevalence of cholelithiasis and nephrolithiasis was observed, and exposure to ritonavir-boosted atazanavir for >2 years was associated with incident cholelithiasis. PMID:26360703

  5. 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

  6. Start 2: Thinking one move ahead

    SciTech Connect

    Gaines, L.L.

    1991-11-01

    At their summit meeting in the spring of 1990, Presidents Bush and Gorbachev issued a joint statement expressing their intentions to continue the process of strategic arms control beyond the Strategic Arms Reduction Treaty (START), which was eventually signed in July 1991, toward agreement on further reductions. They set general goals for negotiation of a follow-on treaty to START, which has been called START II. President Bush's historic speech on September 27, 1991, reinforced those goals and specified several actions the US would take. It is the purpose of this report to examine possible provisions of START II and the implications of those provisions for achievement of the goals set at the 1990 summit, for verifiability, and for US force planning. This look ahead will contribute to advance planning of appropriate negotiating positions, verification research and development (R D), and force modernization and restructuring. This report describes the goals for a START II treaty and possible means for achieving them. It postulates one set of provisions for such a treaty, while it examines force structures for the US that could result from adoption of a treaty with these provisions. The adequacy of methods for verifying START II are examined and the implications of a START II treaty are postulated.

  7. Start 2: Thinking one move ahead

    SciTech Connect

    Gaines, L.L.

    1991-11-01

    At their summit meeting in the spring of 1990, Presidents Bush and Gorbachev issued a joint statement expressing their intentions to continue the process of strategic arms control beyond the Strategic Arms Reduction Treaty (START), which was eventually signed in July 1991, toward agreement on further reductions. They set general goals for negotiation of a follow-on treaty to START, which has been called START II. President Bush`s historic speech on September 27, 1991, reinforced those goals and specified several actions the US would take. It is the purpose of this report to examine possible provisions of START II and the implications of those provisions for achievement of the goals set at the 1990 summit, for verifiability, and for US force planning. This look ahead will contribute to advance planning of appropriate negotiating positions, verification research and development (R&D), and force modernization and restructuring. This report describes the goals for a START II treaty and possible means for achieving them. It postulates one set of provisions for such a treaty, while it examines force structures for the US that could result from adoption of a treaty with these provisions. The adequacy of methods for verifying START II are examined and the implications of a START II treaty are postulated.

  8. Healthy start lessons learned on interconception care.

    PubMed

    Badura, Maribeth; Johnson, Kay; Hench, Karen; Reyes, Madelyn

    2008-01-01

    The Federal Healthy Start program was started in 1991 to address the factors that contribute to the Nation's high infant mortality rate, particularly among populations with disproportionately high rates of adverse perinatal health outcomes. The goals of Healthy Start are to reduce disparities in access to and utilization of health services by using a lifespan approach, improving the local health care system, and increasing consumer and community input into health care decisions. In 2007, Healthy Start served 99 communities in 38 states, the District of Columbia, and Puerto Rico. Most Healthy Start grantees are nonprofit organizations. Since 2005, all 97 Healthy Start grantees (and the 2 additional grantees funded in 2007) have been required to include an interconception care component. Three quarters of grantees enrolled the majority of their interconception clients during the prenatal period. Most grantees used care coordination and case management as the primary approach to improving interconception health care. In 2007, 93 interconception projects reported that 9 out of 10 women had an ongoing source of primary care. Grantees screened to detect health conditions and risks, as well as provided an opportunity to provide vital information to women about their risks for chronic conditions such as obesity, hypertension, and diabetes. The Healthy Start interconception components demonstrate a critical need for and the potential impact of a strong interconception care program for high-risk populations such as women living in poverty, in medically underserved communities, and without health coverage. PMID:19059550

  9. 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

  10. 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

  11. HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy

    PubMed Central

    Heaton, R.K.; Clifford, D.B.; Franklin, D.R.; Woods, S.P.; Ake, C.; Vaida, F.; Ellis, R.J.; Letendre, S.L.; Marcotte, T.D.; Atkinson, J.H.; Rivera-Mindt, M.; Vigil, O.R.; Taylor, M.J.; Collier, A.C.; Marra, C.M.; Gelman, B.B.; McArthur, J.C.; Morgello, S.; Simpson, D.M.; McCutchan, J.A.; Abramson, I.; Gamst, A.; Fennema-Notestine, C.; Jernigan, T.L.; Wong, J.; Grant, I.

    2010-01-01

    Objectives: This is a cross-sectional, observational study to determine the frequency and associated features of HIV-associated neurocognitive disorders (HAND) in a large, diverse sample of infected individuals in the era of combination antiretroviral therapy (CART). Methods: A total of 1,555 HIV-infected adults were recruited from 6 university clinics across the United States, with minimal exclusions. We used standardized neuromedical, psychiatric, and neuropsychological (NP) examinations, and recently published criteria for diagnosing HAND and classifying 3 levels of comorbidity (minimal to severe non-HIV risks for NP impairment). Results: Fifty-two percent of the total sample had NP impairment, with higher rates in groups with greater comorbidity burden (40%, 59%, and 83%). Prevalence estimates for specific HAND diagnoses (excluding severely confounded cases) were 33% for asymptomatic neurocognitive impairment, 12% for mild neurocognitive disorder, and only 2% for HIV-associated dementia (HAD). Among participants with minimal comorbidities (n = 843), history of low nadir CD4 was a strong predictor of impairment, and the lowest impairment rate on CART occurred in the subset with suppressed plasma viral loads and nadir CD4 ?200 cells/mm3 (30% vs 47% in remaining subgroups). Conclusions: The most severe HAND diagnosis (HAD) was rare, but milder forms of impairment remained common, even among those receiving CART who had minimal comorbidities. Future studies should clarify whether early disease events (e.g., profound CD4 decline) may trigger chronic CNS changes, and whether early CART prevents or reverses these changes. GLOSSARY ANI = asymptomatic neurocognitive impairment; CART = combination antiretroviral therapy; CHARTER = CNS HIV Antiretroviral Therapy Effects Research; CIDI = Composite International Diagnostic Interview; CLIA = Clinical Laboratory Improvement Amendments; CPE = CNS penetration effectiveness; HAD = HIV-associated dementia; HAND = HIV-associated neurocognitive disorder; IADL = instrumental activities of daily living; LP = lumbar puncture; MND = mild neurocognitive disorder; NP = neuropsychological; PAOFI = Patient's Assessment of Own Functioning Inventory. PMID:21135382

  12. Analysis of the Ex Vivo and In Vivo Antiretroviral Activity of Gemcitabine

    PubMed Central

    Clouser, Christine L.; Holtz, Colleen M.; Mullett, Mary; Crankshaw, Duane L.; Briggs, Jacquie E.; Chauhan, Jay; VanHoutan, Ilze Matise; Patterson, Steven E.; Mansky, Louis M.

    2011-01-01

    Replication of retroviral and host genomes requires ribonucleotide reductase to convert rNTPs to dNTPs, which are then used as substrates for DNA synthesis. Inhibition of ribonucleotide reductase by hydroxyurea (HU) has been previously used to treat cancers as well as HIV. However, the use of HU as an antiretroviral is limited by its associated toxicities such as myelosuppression and hepatotoxicity. In this study, we examined the ribonucleotide reductase inhibitor, gemcitabine, both in cell culture and in C57Bl/6 mice infected with LP-BM5 murine leukemia virus (LP-BM5 MuLV, a murine AIDS model). Gemcitabine decreased infectivity of MuLV in cell culture with an EC50 in the low nanomolar range with no detectable cytotoxicity. Similarly, gemcitabine significantly decreased disease progression in mice infected with LP-BM5. Specifically, gemcitabine treatment decreased spleen size, plasma IgM, and provirus levels compared to LP-BM5 MuLV infected, untreated mice. Gemcitabine efficacy was observed at doses as low as 1 mg/kg/day in the absence of toxicity. Higher doses of gemcitabine (3 mg/kg/day and higher) were associated with toxicity as determined by a loss in body mass. In summary, our findings demonstrate that gemcitabine has antiretroviral activity ex vivo and in vivo in the LP-BM5 MuLV model. These observations together with a recent ex vivo study with HIV-1[1], suggest that gemcitabine has broad antiretroviral activity and could be particularly useful in vivo when used in combination drug therapy. PMID:21264291

  13. 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

  14. Rationale, design, and sample characteristics of a randomized controlled trial of directly observed antiretroviral therapy delivered in methadone clinics

    PubMed Central

    Berg, Karina M.; Mouriz, Jennifer; Li, Xuan; Duggan, Elise; Goldberg, Uri; Arnsten, Julia H.

    2009-01-01

    Background Directly observed therapy (DOT) programs for HIV treatment have demonstrated feasibility, acceptability, and improved viral suppression, but few have been rigorously tested. We describe a randomized controlled trial testing the efficacy of an antiretroviral DOT program in methadone maintenance clinics. Our objective was to determine if DOT is more efficacious than self-administered antiretroviral therapy for reducing HIV viral load, improving adherence, and reducing drug resistance among opioid dependent drug users receiving methadone treatment. Methods Participants were randomized to treatment as usual (TAU) or antiretroviral DOT for the 24-week intervention. TAU participants received standard adherence counseling, and DOT participants received standard adherence counseling plus directly observed antiretroviral therapy, which was delivered at the same time as they received daily methadone. Assessments occurred at baseline, weekly for 8 weeks, and then monthly for 4 months. Our primary outcomes were between group changes from baseline to the end of the intervention in: HIV viral load, antiretroviral adherence, and number of viral mutations. Results Between June 2004 and August 2007, we screened 3,231 methadone maintained patients and enrolled 77; 39 participants were randomized to DOT and 38 to TAU. 65 completed the 24-week intervention. Conclusions Our trial will allow rigorous evaluation of the efficacy of directly observed antiretroviral therapy delivered in methadone clinics for improving adherence and clinical outcomes. This detailed description of trial methodology can serve as a template for the development of future DOT programs and can guide protocols for studies among HIV-infected drug users receiving methadone for opioid dependence. PMID:19505589

  15. 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.

  16. Prevalence of Dyslipidemia Among Antiretroviral-Naive HIV-Infected Individuals in China

    PubMed Central

    Shen, Yinzhong; Wang, Jiangrong; Wang, Zhenyan; Qi, Tangkai; Song, Wei; Tang, Yang; Liu, Li; Zhang, Renfang; Lu, Hongzhou

    2015-01-01

    Abstract Little is known about the epidemiological features of dyslipidemia among antiretroviral-naive HIV-infected individuals in China. We used a cross-sectional study design to estimate the prevalence of dyslipidemia in this population, and to identify risk factors associated with the presence of dyslipidemia. One thousand five hundred and eighteen antiretroviral-naive HIV-infected individuals and 347 HIV-negative subjects in China were enrolled during 2009 to 2010. Demographics and medical histories were recorded. After an overnight fast, serum samples were collected to measure lipid levels. Factors associated with the presence of dyslipidemia were analyzed by logistic regression. Mean total cholesterol (TC), low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL) levels were lower in HIV-positive than HIV-negative subjects, but mean triglyceride (TG) was higher in HIV-positive subjects. The overall prevalence of dyslipidemia in HIV-positive and HIV-negative groups did not differ (75.6% vs. 73.7%, P?=?0.580). However, the prevalence of high TC (8.4% vs. 28.2%, P?antiretroviral-naive HIV-infected Chinese adults, there was a high prevalence of dyslipidemia characterized by high TG and low HDL, which was associated with lower CD4 counts. These data support the assessment of lipid profiles before and after initiation of antiretroviral therapy regardless of age. PMID:26632908

  17. Engagement in human immunodeficiency virus care: linkage, retention, and antiretroviral therapy adherence.

    PubMed

    Eaton, Ellen F; Saag, Michael S; Mugavero, Michael

    2014-09-01

    Effective human immunodeficiency virus (HIV) care in the modern antiretroviral therapy (ART) era requires early entry into and retention in care. Early initiation and adherence to ART therapy improves outcomes. Many evidence-based tools and behavioral interventions are available to optimize adherence to care and ART and can be implemented in clinical settings. Monitoring care engagement and ART adherence creates the opportunity to intervene and prevent virologic failure or loss to follow up. Special HIV-infected populations, such as pregnant and mentally ill patients, require enhanced surveillance and care. PMID:25151561

  18. New antiretroviral strategies: interview with Marcus Conant, M.D. Interview by John S. James.

    PubMed

    Conant, M

    1995-08-01

    Dr. Marcus Conant presents his views on new antiretroviral strategies in an interview with AIDS Treatment News. Dr. Conant discusses the diagnostic advances in determining the stage of HIV infection, including viral load testing; explains which initial antiviral therapies he would use first when confronted with disease progression, particularly the changes in use of AZT and 3TC; describes the danger points he watches for in CD4 percent and why percent is a better measurement than CD4 count; and reveals where he believes AIDS treatment is going in the near future. PMID:11362623

  19. Antiretroviral medication diversion among HIV-positive substance abusers in South Florida.

    PubMed

    Surratt, Hilary L; Kurtz, Steven P; Cicero, Theodore J; O'Grady, Catherine; Levi-Minzi, Maria A

    2013-06-01

    The high cost of life-saving antiretroviral (ARV) therapy for HIV represents an expense that impedes accessibility and affordability by patients. This price structure also appears to motivate the diversion of ARVs and the targeting of HIV-positive patients by pill brokers in the illicit market. Our field research with indigent, HIV-positive substance abusers links ARV diversion to high levels of competing needs, including psychiatric disorders, HIV stigma, and homelessness. Interventions to reduce diversion must address the needs of highly vulnerable patients. PMID:23597362

  20. 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…

  1. Mid South Middle Start: Studies of Three Middle Start Schools in the Mid South Delta

    ERIC Educational Resources Information Center

    Rose, Lea Williams; Cheney, Nancy

    2005-01-01

    These three case studies highlight the implementation and impact of Mid South Middle Start by: (1) contributing toward an in-depth understanding of what it means to be a school implementing Middle Start; (2) describing a holistic portrait of the schools' participation in Mid South Middle Start; and (3) assisting the Academy for Educational…

  2. Hematologic, hepatic, renal, and lipid laboratory monitoring after initiation of combination antiretroviral therapy in the United States, 2000-2010.

    PubMed

    Yanik, Elizabeth L; Napravnik, Sonia; Ryscavage, Patrick; Eron, Joseph J; Koletar, Susan L; Moore, Richard D; Zinski, Anne; Cole, Stephen R; Hunt, Peter; Crane, Heidi M; Kahn, James; Mathews, William C; Mayer, Kenneth H; Taiwo, Babafemi O

    2013-06-01

    We assessed laboratory monitoring after combination antiretroviral therapy initiation among 3678 patients in a large US multisite clinical cohort, censoring participants at last clinic visit, combination antiretroviral therapy change, or 3 years. Median days (interquartile range) to first hematologic, hepatic, renal, and lipid tests were 30 (18-53), 31 (19-56), 33 (20-59), and 350 (96-1106), respectively. At 1 year, approximately 80% received more than 2 hematologic, hepatic, and renal tests consistent with guidelines. However, only 40% received 1 or more lipid tests. Monitoring was more frequent in specific subgroups, likely reflecting better clinic attendance or clinician perception of higher susceptibility to toxicities. PMID:23446495

  3. 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

  4. 34 CFR 200.16 - Starting points.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...EDUCATION, DEPARTMENT OF EDUCATION TITLE I-IMPROVING THE ACADEMIC ACHIEVEMENT OF THE DISADVANTAGED Improving Basic Programs...students meeting or exceeding the State's proficient level of academic achievement. (b) Each starting point must be...

  5. 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 ...

  6. GETTING STARTED IN MATH AND THE SCIENCES

    E-print Network

    Bucci, David J.

    GETTING STARTED IN MATH AND THE SCIENCES Some beginning advice.... #12 in math, sciences, etc.,) and your strengths · Not the same as high school (in or Science · Concern about Math/Science preparation · Less than 700 on the SATI

  7. 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...

  8. The Physics of Tokamak Start-up

    SciTech Connect

    D. Mueller

    2012-11-13

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

  9. A new start from ground zero?

    PubMed

    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. PMID:25618540

  10. Baseline characteristics, response to and outcome of antiretroviral therapy among patients with HIV-1, HIV-2 and dual infection in Burkina Faso.

    PubMed

    Harries, Katie; Zachariah, Rony; Manzi, Marcel; Firmenich, Peter; Mathela, Richard; Drabo, Joseph; Onadja, G; Arnould, Line; Harries, Anthony

    2010-02-01

    In an urban district hospital in Burkina Faso we investigated the relative proportions of HIV-1, HIV-2 and HIV-1/2 among those tested, the baseline sociodemographic and clinical characteristics, and the response to and outcome of antiretroviral therapy (ART). A total of 7368 individuals (male=32%; median age=34 years) were included in the analysis over a 6 year period (2002-2008). The proportions of HIV-1, HIV-2 and dual infection were 94%, 2.5% and 3.6%, respectively. HIV-1-infected individuals were younger, whereas HIV-2-infected individuals were more likely to be male, have higher CD4 counts and be asymptomatic on presentation. ART was started in 4255 adult patients who were followed up for a total of 8679 person-years, during which time 469 deaths occurred. Mortality differences by serotype were not statistically significant, but were generally worse for HIV-2 and HIV-1/2 after controlling for age, CD4 count and WHO stage. Among severely immune-deficient patients, mortality was higher for HIV-2 than HIV-1. CD4 count recovery was poorest for HIV-2. HIV-2 and dually infected patients appeared to do less well on ART than HIV-1 patients. Reasons may include differences in age at baseline, lower intrinsic immune recovery in HIV-2, use of ineffective ART regimens (inappropriate prescribing) by clinicians, and poor drug adherence. PMID:19783268

  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. ETHICAL USE OF ANTIRETROVIRAL RESOURCES FOR HIV PREVENTION IN RESOURCE POOR SETTINGS

    PubMed Central

    RENNIE, STUART

    2015-01-01

    The effectiveness of antiretroviral regimes (ARVs) to reduce risk of HIV transmission from mother to child and as post-exposure prophylaxis has been known for almost two decades. Recent research indicates ARVs can also reduce the risk of HIV transmission via sexual intercourse in two other ways. With pre-exposure prophylaxis (PrEP), ARVs are used to reduce risk of HIV acquisition among persons who are HIV negative and significantly exposed to the virus. With treatment as prevention (TasP), ARVs are used to reduce risk of HIV transmission from persons who are already HIV positive. The development of these new prevention strategies raises a rationing problem: given the chronic shortage of ARVs for HIV-infected persons in need of treatment, is it ethically justified to allocate ARVs for PrEP and/or TasP? This article examines the intuitively appealing view that allocation of ARVs for treatment should be the highest priority, the use of ARVs for TasP should be a secondary priority, and that utilizing ARVs for PrEP would be unethical. I will argue that selective, evidence-based allocation of ARVs for prevention in certain cases could be ethically justified even when there is insufficient anti-retroviral access for all those needing it for treatment. PMID:23724978

  13. A Systematic Review of Antiretroviral Adherence Interventions for HIV-Infected People Who Use Drugs

    PubMed Central

    CampBinford, Meredith; Kahana, Shoshana Y.; Altice, Frederick L.

    2012-01-01

    HIV-infected persons who use drugs (PWUDs) are particularly vulnerable for suboptimal combination antiretroviral therapy (cART) adherence. A systematic review of interventions to improve cART adherence and virologic outcomes among HIV-infected PWUDs was conducted. Among the 45 eligible studies, randomized controlled trials suggested directly administered antiretroviral therapy, medication-assisted therapy (MAT), contingency management, and multi-component, nurse-delivered interventions provided significant improved short-term adherence and virologic outcomes, but these effects were not sustained after intervention cessation. Cohort and prospective studies suggested short-term increased cART adherence with MAT. More conclusive data regarding the efficacy on cART adherence and HIV treatment outcomes using cognitive behavioral therapy, motivational interviewing, peer-driven interventions and the integration of MAT into HIV clinical care are warranted. Of great concern was the virtual lack of interventions with sustained post-intervention adherence and virologic benefits. Future research directions, including the development of interventions that promote long-term improvements in adherence and virologic outcomes, are discussed. PMID:22936463

  14. Coumarins as Potential Inhibitors of DNA Polymerases and Reverse Transcriptases. Searching New Antiretroviral and Antitumoral Drugs.

    PubMed

    Garro, Hugo A; Pungitore, Carlos R

    2015-01-01

    Human Immunodeficiency Virus (HIV) is the viral agent of Acquired Immunodeficiency Syndrome (AIDS), and at present, there is no effective vaccine against HIV. Reverse Transcriptase (RT) is an essential enzyme for retroviral replication, such as HIV as well as for other RNA infectious viruses like Human T lymphocyte virus. Polymerases act in DNA metabolism, modulating different processes like mitosis, damage repair, transcription and replication. It has been widely documented that DNA Polymerases and Reverse Transcriptases serve as molecular targets for antiviral and antitumoral chemotherapy. Coumarins are oxygen heterocycles that are widely distributed throughout the plant kingdom. Natural coumarins have attraction due to their bioactive properties such as tumor promotion inhibitory effects, and anti-HIV activity. Coumarins and derivates exhibit potent inhibitory effects on HIV-1 replication in lymphocytes and compounds isolated from Calophyllum inophyllum or DCK derivates showed inhibitory activity against human RT. Furthermore, natural isocoumarins isolated from cultures of fungi or hydroxycoumarins were able to inhibit human DNA polymerase. In view of their importance as drugs and biologically active natural products, and their medicinally useful properties, extensive studies have been carried out on the synthesis of coumarin compounds in recent years. Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs), a class of antiretroviral chemotherapeutic agents, act by binding to an allosteric pocket showing, generally, low toxicity. This work tries to summarize the investigation about natural and synthetic coumarins with the ability to inhibit key enzymes that play a crucial role in DNA metabolism and their possible application as antiretroviral and antitumoral agents. PMID:26179474

  15. Global patient safety and antiretroviral drug-drug interactions in the resource-limited setting.

    PubMed

    Seden, Kay; Khoo, Saye H; Back, David; Byakika-Kibwika, Pauline; Lamorde, Mohammed; Ryan, Mairin; Merry, Concepta

    2013-01-01

    Scale-up of HIV treatment services may have contributed to an increase in functional health facilities available in resource-limited settings and an increase in patient use of facilities and retention in care. As more patients are reached with medicines, monitoring patient safety is increasingly important. Limited data from resource-limited settings suggest that medication error and antiretroviral drug-drug interactions may pose a significant risk to patient safety. Commonly cited causes of medication error in the developed world include the speed and complexity of the medication use cycle combined with inadequate systems and processes. In resource-limited settings, specific factors may contribute, such as inadequate human resources and high disease burden. Management of drug-drug interactions may be complicated by limited access to alternative medicines or laboratory monitoring. Improving patient safety by addressing the issue of antiretroviral drug-drug interactions has the potential not just to improve healthcare for individuals, but also to strengthen health systems and improve vital communication among healthcare providers and with regulatory agencies. PMID:22915459

  16. Physical activity and capacity at initiation of antiretroviral treatment in HIV patients in Ethiopia.

    PubMed

    Olsen, M F; Kæstel, P; Tesfaye, M; Abdissa, A; Yilma, D; Girma, T; Mølgaard, C; Faurholt-Jepsen, D; Christensen, D L; Brage, S; Andersen, Å B; Friis, H

    2015-04-01

    SUMMARY We described levels of habitual physical activity and physical capacity in HIV patients initiating antiretroviral treatment in Ethiopia and assessed the role of HIV and nutritional indicators on these outcomes. Physical activity energy expenditure (PAEE) and activity levels were measured with combined heart rate and movement sensors. Physical capacity was assessed by grip strength, sleeping heart rate and heart rate economy. Grip strength data was also available from a sex- and age-matched HIV-negative reference group. Median PAEE was 27.9 (interquartile range 17.4-39.8) kJ/kg per day and mean ± s.d. grip strength was 23.6 ± 6.7 kg. Advanced HIV disease predicted reduced levels of both physical activity and capacity; e.g. each unit viral load [log(1+copies/ml)] was associated with -15% PAEE (P < 0.001) and -1.0 kg grip strength (P < 0.001). Grip strength was 4.2 kg lower in patients compared to HIV-negative individuals (P < 0.001). Low body mass index (BMI) predicted poor physical activity and capacity independently of HIV status, e.g. BMI <16 was associated with -42% PAEE (P < 0.001) and -6.8 kg grip strength (P < 0.001) compared to BMI ?18.5. The study shows that advanced HIV and malnutrition are associated with considerably lower levels of physical activity and capacity in patients at initiation of antiretroviral treatment. PMID:25034136

  17. Drug interactions between antineoplastic and antiretroviral therapies: Implications and management for clinical practice.

    PubMed

    Mounier, Nicolas; Katlama, Christine; Costagliola, Dominique; Chichmanian, Rose-Marie; Spano, Jean-Philippe

    2009-10-01

    Despite the impact of combined antiretroviral therapy (cART) on human immunodeficiency virus (HIV)-related mortality, malignancies remain the second most common cause of death in HIV infection in developed countries. In addition to the AIDS-defining malignancies, other cancers such as Hodgkin's lymphoma and anal cancer, are more frequent in HIV-infected patients who survive longer even though they do not have complete immune restoration The use of concomitant antineoplastic chemotherapy and cART have been demonstrated to be feasible and effective in patients with HIV-related malignancies; however, many drugs used in cART regimens have the potential for causing drug interactions as a result of their ability to either inhibit or induce the cytochrome P450 (CYP) enzyme system. Since many antineoplastic drugs are also metabolised by the CYP system, co-administration with cART could result in either drug accumulation and possible toxicity, or rapid drug metabolism and decreased efficacy. Unfortunately, very limited prospective interaction data are available to safely guide the combined use of cART and chemotherapy. This paper reviews the potential drug interactions and therapeutic considerations of the antiretroviral agents used to treat HIV and the most common anticancer agents used in the treatment of malignancies found in patients with HIV infection. PMID:19070506

  18. Birth defects among a cohort of infants born to HIV-infected women on antiretroviral medication

    PubMed Central

    Watts, D. Heather; Huang, Sharon; Culnane, Mary; Kaiser, Kathleen A.; Scheuerle, Angela; Mofenson, Lynne; Stanley, Kenneth; Newell, Marie-Louise; Mandelbrot, Laurent; Delfraissy, Jean-Francois; Cunningham, Coleen K.

    2011-01-01

    Objective To determine rate of and risk factors for birth defects in infants born to HIV-infected women receiving nucleoside and protease inhibitor antiretroviral (ARV) therapy. Methods Birth defects were evaluated among infants on the Pediatric AIDS Clinical Trials Group 316 trial that studied addition of peripartum nevirapine to established ARV regimen for prevention of mother-to-child transmission. Maternal therapy was categorized by trimester of earliest exposure. Birth defects were coded using conventions of the Antiretroviral Pregnancy Registry. Results Birth defects were detected in 60/1414 (4.2%; 95% CI 3.3–5.4%) infants including 30/636 (4.7%; 95% CI 3.2–6.7%) with first trimester ARV exposure and 30/778 (3.9%; 95% CI 2.6–5.5%) with exposure only after the first trimester (P=0.51). Rates of classes of defects were similar between first trimester compared to later exposure groups except heart defects which occurred in 16 (2.5%; 95% CI 1.4–4.1%) with first trimester ARV exposure and in six (0.8%; 95% CI 0.3–1.7%) infants with later exposure (P=0.02). Exposure to ARV was not associated with specific types of heart defects. Two cases of cardiomyopathy were noted. Conclusion ARV use in early pregnancy was not associated with an increased risk of birth defects overall. The possible association of ARV exposure with heart defects requires further surveillance. PMID:21142844

  19. Zoonotic Cryptosporidium Species and Enterocytozoon bieneusi Genotypes in HIV-Positive Patients on Antiretroviral Therapy

    PubMed Central

    Wang, Lin; Zhang, Hongwei; Zhao, Xudong; Zhang, Longxian; Zhang, Guoqing; Guo, Meijin; Liu, Lili; Xiao, Lihua

    2013-01-01

    Molecular diagnostic tools have been used increasingly in the characterization of the transmission of cryptosporidiosis and microsporidiosis in developing countries. However, few studies have examined the distribution of Cryptosporidium species and Enterocytozoon bieneusi genotypes in AIDS patients receiving antiretroviral therapy. In the present study, 683 HIV-positive patients in the National Free Antiretroviral Therapy Program in China and 683 matched HIV-negative controls were enrolled. Cryptosporidium species and subtypes and Enterocytozoon bieneusi genotypes were detected and differentiated by PCR and DNA sequencing. The infection rates were 1.5% and 0.15% for Cryptosporidium and 5.7% and 4.2% for E. bieneusi in HIV-positive and HIV-negative participants, respectively. The majority (8/11) of Cryptosporidium cases were infections by zoonotic species, including Cryptosporidium meleagridis (5), Cryptosporidium parvum (2), and Cryptosporidium suis (1). Prevalent E. bieneusi genotypes detected, including EbpC (39), D (12), and type IV (7), were also potentially zoonotic. The common occurrence of EbpC was a feature of E. bieneusi transmission not seen in other areas. Contact with animals was a risk factor for both cryptosporidiosis and microsporidiosis. The results suggest that zoonotic transmission was significant in the epidemiology of both diseases in rural AIDS patients in China. PMID:23224097

  20. Poor functional immune recovery in aged HIV-1-infected patients following successfully treatment with antiretroviral therapy.

    PubMed

    Kasahara, Taissa M; Hygino, Joana; Andrade, Regis M; Monteiro, Clarice; Sacramento, Priscila M; Andrade, Arnaldo F B; Bento, Cleonice A M

    2015-10-01

    Aging is now a well-recognized characteristic of the HIV-infected population and both AIDS and aging are characterized by a deficiency of the T-cell compartment. The objective of the present study was to evaluate the impact of antiretroviral (ARV) therapy in recovering functional response of T cells to both HIV-1-specific ENV peptides (ENV) and tetanus toxoid (TT), in young and aged AIDS patients who responded to ARV therapy by controlling virus replication and elevating CD4(+) T cell counts. Here, we observed that proliferative response of T-cells to either HIV-1-specific Env peptides or tetanus toxoid (TT) was significantly lower in older antiretroviral (ARV)-treated patients. With regard to cytokine profile, lower levels of IFN-?, IL-17 and IL-21, associated with elevated IL-10 release, were produced by Env- or TT-stimulated T-cells from older patients. The IL-10 neutralization by anti-IL-10 mAb did not elevate IFN-? and IL-21 release in older patients. Finally, even after a booster dose of TT, reduced anti-TT IgG titers were quantified in older AIDS patients and it was related to both lower IL-21 and IFN-? production and reduced frequency of central memory T-cells. Our results reveal that ARV therapy, despite the adequate recovery of CD4(+) T cell counts and suppression of viremia, was less efficient in recovering adequate immune response in older AIDS patients. PMID:26429325

  1. Pregnancy outcomes following exposure to efavirenz-based antiretroviral therapy in the Republic of Congo.

    PubMed

    Bisio, Francesca; Nicco, Elena; Calzi, Anna; Giacobbe, Daniele Roberto; Mesini, Alessio; Banguissa, Hubert; Vividila, Nicole Edith; Mahoungou, Pélagie; Boumba, Jean Denis; Mboungou, Franc Astyanax Mayinda; Bruzzone, Bianca; Ratto, Sandra; Icardi, Giancarlo; Viscoli, Claudio; Bruzzi, Paolo

    2015-04-01

    WHO recently recommended efavirenz (EFV) use for HIV infection through pregnancy, breastfeeding and childbearing age. However the use of EFV during pregnancy remains of concern and not all national guidelines reflect WHO advice. Few data are available concerning pregnancy outcomes. The objective of our study was to evaluate pregnancy outcomes in a cohort of women who conceived on EFV. A retrospective, multicenter cohort study was conducted in Pointe Noire, Republic of Congo (September 2005- June 2012). The following adverse pregnancy outcomes were considered: births defects, low birth weight, premature delivery, stillbirth and abortion, stratified by antiretroviral exposure at the time of conception. During the study period, 188 women conceived on antiretrovirals: 35 (18.6%) on EFV-based regimens and 153 (81.4%) on nevirapine-based regimens. Adverse pregnancy outcomes were observed in 17/35 (48.6%, 95% CI 33.0-64.4%) women in the EFV group and in 43/153 (28.1%, 95% CI 21.6-35.7%) in the non-EFV group (p=0.019). No birth defect was observed in either group. An increased incidence of adverse pregnancy outcomes was observed in the EFV group. As WHO is promoting a widespread use of EFV also for women in childbearing age, our study emphasizes the importance of launching large prospective cohort studies investigating pregnancy outcomes in exposed women. PMID:25938743

  2. RISUG: a potential candidate for the entry inhibitor group of antiretroviral drugs.

    PubMed

    Banerjee, Shubhadeep; Guha, Sujoy K

    2009-08-01

    Entry inhibitors are a group of antiretroviral drug which prevents HIV from entering human immune cells. They include both fusion and attachment inhibitors. A hypothesis is put forward in which a new male contraceptive drug with proven antimicrobial property is proposed as a possible candidate for the entry inhibitor group of antiretroviral drugs. The proposed mechanism of action involves (i) interaction with gp120 and thereby preventing binding to CD4 and (ii) competitive binding with the viral glycoprotein and inhibit the glycoprotein - cell surface glyocosaminoglycan Heparan Sulfate (HS) interaction. A new drug RISUG (Reversible Inhibition of Sperm Under Guidance) presently undergoing Phase III clinical trials throughout India for its contraceptive effect in male has also antimicrobial actions. RISUG is a chemical complex of styrene maleic anhydride (SMA(AN)) and dimethyl sulfoxide. On injection into the vas deferens, it reacts with the components of intravas fluid, the spermatic fluid and gets converted to styrene maleic acid (SMA(AC)) and breakdown products like mandelic acid. An anti HIV activity of RISUG is likely due to its electrical charge and mandelic acid generation. For experimental validation HIV in vitro assays can be performed which will involve infectivity assays, luciferase assay and soluble gp120 assays. A positive result from the studies will validate the hypothesis. PMID:19409721

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

    SciTech Connect

    Song, Byeongwoon; Diaz-Griffero, Felipe; Park, Do Hyun; Rogers, Thomas; Stremlau, Matthew; Sodroski, Joseph . 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}.

  4. Sequencing paediatric antiretroviral therapy in the context of a public health approach

    PubMed Central

    Boerma, Ragna S; Boender, T Sonia; van Hensbroek, Michael Boele; Rinke de Wit, Tobias F; Sigaloff, Kim CE

    2015-01-01

    Introduction As access to prevention of mother-to-child transmission (PMTCT) efforts has increased, the total number of children being born with HIV has significantly decreased. However, those children who do become infected after PMTCT failure are at particular risk of HIV drug resistance, selected by exposure to maternal or paediatric antiretroviral drugs used before, during or after birth. As a consequence, the response to antiretroviral therapy (ART) in these children may be compromised, particularly when non-nucleoside reverse transcriptase inhibitors (NNRTIs) are used as part of the first-line regimen. We review evidence guiding choices of first- and second-line ART. Discussion Children generally respond relatively well to ART. Clinical trials show the superiority of protease inhibitor (PI)- over NNRTI-based treatment in young children, but observational reports of NNRTI-containing regimens are usually favourable as well. This is reassuring as national guidelines often still recommend the use of NNRTI-based treatment for PMTCT-unexposed young children, due to the higher costs of PIs. After failure of NNRTI-based, first-line treatment, the rate of acquired drug resistance is high, but HIV may well be suppressed by PIs in second-line ART. By contrast, there are currently no adequate alternatives in resource-limited settings (RLS) for children failing either first- or second-line, PI-containing regimens. Conclusions Affordable salvage treatment options for children in RLS are urgently needed. PMID:26639116

  5. Persistent Peripheral Nervous System Damage in Simian Immunodeficiency Virus-Infected Macaques Receiving Antiretroviral Therapy.

    PubMed

    Dorsey, Jamie L; Mangus, Lisa M; Hauer, Peter; Ebenezer, Gigi J; Queen, Suzanne E; Laast, Victoria A; Adams, Robert J; Mankowski, Joseph L

    2015-11-01

    Human immunodeficiency virus (HIV)-induced peripheral neuropathy is the most common neurologic complication associated with HIV infection. In addition to virus-mediated injury of the peripheral nervous system (PNS), treatment of HIV infection with combination antiretroviral therapy (cART) may induce toxic neuropathy as a side effect. Antiretroviral toxic neuropathy is clinically indistinguishable from the sensory neuropathy induced by HIV; in some patients, these 2 processes are likely superimposed. To study these intercurrent PNS disease processes, we first established a simian immunodeficiency virus (SIV)/pigtailed macaque model in which more than 90% of animals developed PNS changes closely resembling those seen in HIV-infected individuals with distal sensory neuropathy. To determine whether cART alters the progression of SIV-induced PNS damage, dorsal root ganglia and epidermal nerve fibers were evaluated in SIV-infected macaques after long-term suppressive cART. Although cART effectively suppressed SIV replication and reduced macrophage activation in the dorsal root ganglia, PGP 9.5 immunostaining and measurements of epidermal nerve fibers in the plantar surface of the feet of treated SIV-infected macaques clearly showed that cART did not normalize epidermal nerve fiber density. These findings illustrate that significant PNS damage persists in SIV-infected macaques on suppressive cART. PMID:26426267

  6. Trends in First-Line Antiretroviral Therapy in Asia: Results from the TREAT Asia HIV Observational Database

    PubMed Central

    Boettiger, David Charles; Kerr, Stephen; Ditangco, Rossana; Merati, Tuti Parwati; Pham, Thuy Thi Thanh; Chaiwarith, Romanee; Kiertiburanakul, Sasisopin; Li, Chung Ki Patrick; Kumarasamy, Nagalingeswaran; Vonthanak, Saphonn; Lee, Christopher; Van Kinh, Nguyen; Pujari, Sanjay; Wong, Wing Wai; Kamarulzaman, Adeeba; Zhang, Fujie; Yunihastuti, Evy; Choi, Jun Yong; Oka, Shinichi; Ng, Oon Tek; Kantipong, Pacharee; Mustafa, Mahiran; Ratanasuwan, Winai; Sohn, Annette; Law, Matthew

    2014-01-01

    Background Antiretroviral therapy (ART) has evolved rapidly since its beginnings. This analysis describes trends in first-line ART use in Asia and their impact on treatment outcomes. Methods Patients in the TREAT Asia HIV Observational Database receiving first-line ART for ?6 months were included. Predictors of treatment failure and treatment modification were assessed. Results Data from 4662 eligible patients was analysed. Patients started ART in 2003–2006 (n?=?1419), 2007–2010 (n?=?2690) and 2011–2013 (n?=?553). During the observation period, tenofovir, zidovudine and abacavir use largely replaced stavudine. Stavudine was prescribed to 5.8% of ART starters in 2012/13. Efavirenz use increased at the expense of nevirapine, although both continue to be used extensively (47.5% and 34.5% of patients in 2012/13, respectively). Protease inhibitor use dropped after 2004. The rate of treatment failure or modification declined over time (22.1 [95%CI 20.7–23.5] events per 100 patient/years in 2003–2006, 15.8 [14.9–16.8] in 2007–2010, and 11.6 [9.4–14.2] in 2011–2013). Adjustment for ART regimen had little impact on the temporal decline in treatment failure rates but substantially attenuated the temporal decline in rates of modification due to adverse event. In the final multivariate model, treatment modification due to adverse event was significantly predicted by earlier period of ART initiation (hazard ratio 0.52 [95%CI 0.33–0.81], p?=?0.004 for 2011–2013 versus 2003–2006), older age (1.56 [1.19–2.04], p?=?0.001 for ?50 years versus <30years), female sex (1.29 [1.11–1.50], p?=?0.001 versus male), positive hepatitis C status (1.33 [1.06–1.66], p?=?0.013 versus negative), and ART regimen (11.36 [6.28–20.54], p<0.001 for stavudine-based regimens versus tenofovir-based). Conclusions The observed trends in first-line ART use in Asia reflect changes in drug availability, global treatment recommendations and prescriber preferences over the past decade. These changes have contributed to a declining rate of treatment modification due to adverse event, but not to reductions in treatment failure. PMID:25184314

  7. High rates of baseline antiretroviral resistance among HIV-infected pregnant women in an HIV referral centre in Rio de Janeiro, Brazil.

    PubMed

    de Lourdes Teixeira, Maria; Nafea, Shamim; Yeganeh, Nava; Santos, Edwiges; Isabel Gouvea, Maria; Joao, Esau; Ceci, Loredana; Bressan, Clarisse; Leticia Cruz, Maria; Claude Sidi, Leon; Nielsen-Saines, Karin

    2015-11-01

    In order to understand antiretroviral resistance during pregnancy and its impact on HIV vertical transmission, we performed a cross-sectional analysis of 231 HIV-infected pregnant women who fulfilled Brazilian guidelines for antiretroviral testing and had antiretroviral genotypic testing performed between April 2010 and October 2012. At entry into prenatal care, the mean CD4 cell count for this cohort of patients was 406 cells/mm(3) (95% CI: 373-438 cells/mm(3)), while the mean HIV RNA was 24,394 copies/ml (95% CI: 18,275-30,513 copies/ml). Thirty-six women (16%) had detectable antiretroviral-resistant mutations. By 34 weeks gestation, 75% had achieved HIV RNA <400 copies/ml. Our logistic regression model showed the odds of harbouring antiretroviral-resistant virus with a baseline CD4 cell count of <200 cells/mm(3) was eight times that of subjects with CD4 cell counts >500 CD4 cells/mm(3) (95% CI 1.5-42.73). Six infants were HIV infected, four born to mothers with detectable viraemia at 34 weeks and two born to mothers who were lost to follow up. Antiretroviral resistance is common in prenatal care but did not increase vertical transmission if viral load was appropriately suppressed. Genotyping should be considered in Brazil in order to assist initiation of appropriate combination antiretroviral therapy during pregnancy to suppress viral load to avoid vertical transmission. PMID:25504831

  8. Knowledge, Stigma, and Behavioral Outcomes among Antiretroviral Therapy Patients Exposed to Nalamdana's Radio and Theater Program in Tamil Nadu, India

    ERIC Educational Resources Information Center

    Nambiar, Devaki; Ramakrishnan, Vimala; Kumar, Paresh; Varma, Rajeev; Balaji, Nithya; Rajendran, Jeeva; Jhona, Loretta; Chandrasekar, Chokkalingam; Gere, David

    2011-01-01

    Arts-based programs have improved HIV-related knowledge, attitudes, and behavior in general and at-risk populations. With HIV transformed into a chronic condition, this study compares patients at consecutive stages of receiving antiretroviral treatment, coinciding with exposure to a radio-and-theater-based educational program (unexposed [N = 120],…

  9. Optimizing treatment switch for virologic failure during first-line antiretroviral therapy in resource-limited settings

    PubMed Central

    Adetunji, Adedotun A.; Achenbach, Chad; Feinglass, Joseph; Darin, Kristin M.; Scarsi, Kimberly K.; Ekong, Ernest; Taiwo, Babafemi O.; Adewole, Isaac F.; Murphy, Robert

    2015-01-01

    We evaluated adult Nigerian patients with antiretroviral switch to second-line treatment with protease inhibitor (PI/r)-based regimens due to virologic failure (confirmed HIV-1 RNA viral load >1000 copies/mL) during first-line antiretroviral therapy. Proportion of patients with viral load (VL) >400 copies/mL and characteristics associated with non-suppression during second-line treatment are described. Approximately 15% of patients (34/225) 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 (OR 2.90 [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

  10. 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

  11. Low bone mass in behaviorally HIV-infected young men on antiretroviral therapy: adolescent trials network (ATN) study 021B

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Peak bone mass is achieved in adolescence/early adulthood and is the key determinant of bone mass in adulthood. We evaluated the association of bone mass with HIV infection and antiretroviral therapy (ART) during this critical period among behaviorally HIV infected young men and seronegative control...

  12. Decreased human immunodeficiency virus type 1 plasma viremia during antiretroviral therapy reflects downregulation of viral replication in lymphoid tissue.

    PubMed Central

    Cohen, O J; Pantaleo, G; Holodniy, M; Schnittman, S; Niu, M; Graziosi, C; Pavlakis, G N; Lalezari, J; Bartlett, J A; Steigbigel, R T

    1995-01-01

    Although several immunologic and virologic markers measured in peripheral blood are useful for predicting accelerated progression of human immunodeficiency virus (HIV) disease, their validity for evaluating the response to antiretroviral therapy and their ability to accurately reflect changes in lymphoid organs remain unclear. In the present study, changes in certain virologic markers have been analyzed in peripheral blood and lymphoid tissue during antiretroviral therapy. Sixteen HIV-infected individuals who were receiving antiretroviral therapy with zidovudine for > or = 6 months were randomly assigned either to continue on zidovudine alone or to add didanosine for 8 weeks. Lymph node biopsies were performed at baseline and after 8 weeks. Viral burden (i.e., HIV DNA copies per 10(6) mononuclear cells) and virus replication in mononuclear cells isolated from peripheral blood and lymph node and plasma viremia were determined by semiquantitative polymerase chain reaction assays. Virologic and immunologic markers remained unchanged in peripheral blood and lymph node of patients who continued on zidovudine alone. In contrast, a decrease in virus replication in lymph nodes was observed in four of six patients who added didanosine to their regimen, and this was associated with a decrease in plasma viremia. These results indicate that decreases in plasma viremia detected during antiretroviral therapy reflect downregulation of virus replication in lymphoid tissue. Images Fig. 1 Fig. 2 Fig. 3 PMID:7597072

  13. Early antiretroviral therapy in children perinatally infected with HIV: a unique opportunity to implement immunotherapeutic approaches to prolong viral remission.

    PubMed

    Klein, Nigel; Palma, Paolo; Luzuriaga, Katherine; Pahwa, Savita; Nastouli, Eleni; Gibb, Diane M; Rojo, Pablo; Borkowsky, William; Bernardi, Stefania; Zangari, Paola; Calvez, Vincent; Compagnucci, Alexandra; Wahren, Britta; Foster, Caroline; Munoz-Fernández, María Ángeles; De Rossi, Anita; Ananworanich, Jintanat; Pillay, Deenan; Giaquinto, Carlo; Rossi, Paolo

    2015-09-01

    From the use of antiretroviral therapy to prevent mother-to-child transmission to the possibility of HIV cure hinted at by the Mississippi baby experience, paediatric HIV infection has been pivotal to our understanding of HIV pathogenesis and management. Daily medication and indefinite antiretroviral therapy is recommended for children infected with HIV. Maintenance of life-long adherence is difficult and the incidence of triple-class virological failure after initiation of antiretroviral therapy increases with time. This challenge shows the urgent need to define novel strategies to provide long-term viral suppression that will allow safe interruption of antiretroviral therapy without viral rebound and any associated complications. HIV-infected babies treated within a few days of birth have a unique combination of a very small pool of integrated viruses, a very high proportion of relatively HIV resistant naive T cells, and an unparalleled capacity to regenerate an immune repertoire. These features make this group the optimum model population to investigate the potential efficacy of immune-based therapies. If successful, these investigations could change the way we manage HIV infection. PMID:26187030

  14. Reconstitution of naive T cells during antiretroviral treatment of HIV-infected adults is dependent on age

    E-print Network

    de Boer, Rob J.

    . Conclusion: These observations suggest that the thymus contributes considerably to the regeneration of naive the regeneration of the naive T cells during highly active antiretroviral therapy (HAART) to thymus describing the loss of functional thymus tissue in human adults [9]. Methods The recovery of naive and memory

  15. S. Blower, et al.: Forecasting the Future of HIV Epidemics: the Impact of Antiretroviral Therapies & Imperfect Vaccines AIDSREVIEWS

    E-print Network

    Blower, Sally

    & Imperfect Vaccines AIDSREVIEWS 113 Forecasting the Future of HIV Epidemics: the Impact of Antiretroviral Therapies & Imperfect Vaccines S. Blower1*, E.J. Schwartz1 and J. Mills2 1 AIDS Institute & Department (ART) and (ii) imperfect vaccines. In particular, we discuss how models have been used to predict

  16. Directly observed antiretroviral therapy improves adherence and viral load in drug users attending methadone maintenance clinics: a randomized controlled trial*

    PubMed Central

    BERG, KARINA M.; LITWIN, ALAIN; LI, XUAN; HEO, MOONSEONG; ARNSTEN, JULIA H.

    2010-01-01

    Objective To determine if directly observed antiretroviral therapy (DOT) is more efficacious than self-administered therapy for improving adherence and reducing HIV viral load (VL) among methadone-maintained opioid users. Design Two-group randomized trial. Setting Twelve methadone maintenance clinics with on-site HIV care in the Bronx, New York. Participants HIV-infected adults prescribed combination antiretroviral therapy. Intervention 24 weeks of DOT. Main outcomes measures Between group differences at 4 assessment points from baseline to week 24 in: (1) antiretroviral adherence measured by pill count, (2) VL, and (3) proportion with undetectable VL (< 75 copies/ml). Results Between June 2004 and August 2007, we enrolled 77 participants. Adherence in the DOT group was higher than in the control group at all post-baseline assessment points; by week 24 mean DOT adherence was 86% compared to 56% in the control group (p<0.0001). Group differences in mean adherence remained significant after stratifying by baseline VL (detectable versus undetectable). In addition, during the 24-week intervention, the proportion of DOT participants with undetectable VL increased from 51% to 71%. Conclusions Among HIV-infected opioid users, antiretroviral DOT administered in methadone clinics was efficacious for improving adherence and decreasing VL, and these improvements were maintained over a 24-week period. DOT should be more widely available to methadone patients. PMID:20832196

  17. 76 FR 50813 - Major Capital Investment Projects; Guidance on News Starts/Small Starts Policies and Procedures

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-16

    ... Federal Transit Administration Major Capital Investment Projects; Guidance on News Starts/Small Starts... on the New Starts and Small Starts programs. FTA is required by statute to publish policy guidance every two years on the New Starts and Small Starts programs. This notice serves to notify the...

  18. Alcohol cold starting - A theoretical study

    NASA Technical Reports Server (NTRS)

    Browning, L. H.

    1983-01-01

    Two theoretical computer models have been developed to study cold starting problems with alcohol fuels. The first model, a droplet fall-out and sling-out model, shows that droplets must be smaller than 50 microns to enter the cylinder under cranking conditions without being slung-out in the intake manifold. The second model, which examines the fate of droplets during the compression process, shows that the heat of compression can be used to vaporize small droplets (less than 50 microns) producing flammable mixtures below freezing ambient temperatures. While droplet size has the greater effect on startability, a very high compression ratio can also aid cold starting.

  19. 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. PMID:26110167

  20. Adherence to extended postpartum antiretrovirals is associated with decreased breastmilk HIV-1 transmission: Results of the BAN study

    PubMed Central

    DAVIS, Nicole L.; MILLER, William C.; HUDGENS, Michael G.; CHASELA, Charles S.; SICHALI, Dorothy; KAYIRA, Dumbani; NELSON, Julie A. E.; STRINGER, Jeffrey S. A.; ELLINGTON, Sascha R.; KOURTIS, Athena P.; JAMIESON, Denise J; VAN DER HORST, Charles

    2015-01-01

    Objective Estimate association between postpartum antiretroviral adherence and breastmilk HIV-1 transmission Design Prospective cohort study Methods Mother-infant pairs were randomized after delivery to immediately begin receiving 28 weeks of either triple maternal antiretrovirals (zidovudine, lamivudine, and either nevirapine, nelfinavir, or lopinavir-ritonavir) or daily infant nevirapine as part of the Breastfeeding, Antiretrovirals, and Nutrition study. Associations between postpartum antiretroviral adherence and rate of breastmilk HIV-1 transmission were estimated using Cox models. We measured adherence over four postpartum time intervals using pill count, suspension bottle weight, and maternal self-report. Adherence was categorized and lagged by one interval. Missing adherence measures were multiply imputed. Infant HIV-1 infection was determined by DNA PCR every 2-6 weeks. The primary endpoint was infant HIV-1 infection by 38 weeks of age among infants alive and uninfected at 5 weeks. Results Analyses included 1479 mother-infant pairs and 45 transmission events. Using pill count and bottle weight information, 22-40% of mother-infant pairs at any given interval were <90% adherent. Having ?90% adherence was associated with a 52% (95% CI 3-76%) relative reduction in the rate of breastmilk HIV-1 transmission, compared with having <90% adherence when controlling for study arm, breastfeeding status, and maternal characteristics. Complete case analysis rendered similar results (n=501; relative reduction 59%, 95% CI 6-82%). Conclusion Non-adherence to extended postpartum ART regimens in ‘real world’ settings is likely to be higher than that seen in BAN. Identifying mothers with difficulty adhering to antiretrovirals, and developing effective adherence interventions, will help maximize benefits of ARV provision throughout breastfeeding. PMID:25493600

  1. How to Start a Free University.

    ERIC Educational Resources Information Center

    Marsello, Greg

    Information on establishing and running a free university is presented in this handbook. A free university is defined as an organization offering ungraded, unaccredited classes, activities and programs to the general public. Information on starting the free university includes: how to determine the needs of your community; deciding on a name and…

  2. Verifying the INF and START treaties

    SciTech Connect

    Ifft, Edward

    2014-05-09

    The INF and START Treaties form the basis for constraints on nuclear weapons. Their verification provisions are one of the great success stories of modern arms control and will be an important part of the foundation upon which the verification regime for further constraints on nuclear weapons will be constructed.

  3. Start Spring `16 on the right track!

    E-print Network

    Wu, Chien H.

    Start Spring `16 on the right track! Sign up for an ASP course today! These courses are designed to help you sharpen your academic skills. Each class gives either two or three hours of non want to turn the spring semester into an exceptionally successful one and bring up your GPA? Register

  4. 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…

  5. Program Quick Facts Eligible Start-ups

    E-print Network

    Program Quick Facts Eligible Start-ups Businesses Small to Medium-sized Under 1,000 employees's, Doctoral, and Post-Doctoral Graduate Business Southern Ontario Locations Business Provide 6 months of paid Internship (GEI) program provides incentives to businesses in Southern Ontario to offer employment to recent

  6. Addressing Tooth Decay in Head Start Children

    ERIC Educational Resources Information Center

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

    2012-01-01

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

  7. Starting with "I": Personal Essays by Teenagers.

    ERIC Educational Resources Information Center

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

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

  8. 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…

  9. FIRE AND ELECTRICAL SAFETY How Fires Start ?

    E-print Network

    Haimovich, Alexander

    FIRE AND ELECTRICAL SAFETY #12; How Fires Start ? Fire is a chemical reaction that occurs when, such as gasoline, oil, solvents, and oil and based paints 3.Class C - energized electrical equipment- is a special mixture that creates a smothering blanket over the fire which cuts off the supply of oxygen

  10. Getting started with PEPA Jane Hillston

    E-print Network

    Hillston, Jane

    of Edinburgh Scotland 9th April 2013 #12;2/ 26 The PEPA Eclipse Plug-in processing the model #12;3/ 26 The PEPA1/ 26 Getting started with PEPA Jane Hillston LFCS, School of Informatics The University website http://www.dcs.ed.ac.uk/pepa From the website the PEPA Eclipse Plug-in and some other tools

  11. 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…

  12. Philadelphia's Independence Starts Here: Disability Arts Festival

    ERIC Educational Resources Information Center

    Smith, Mimi Kenney

    2008-01-01

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

  13. WHAT STARTS HERE CHANGES THE WORLD

    E-print Network

    Pillow, Jonathan

    WHAT STARTS HERE CHANGES THE WORLD #12;"My time in pharmacy school has really opened my eyes opportunities available at one of the world's leading public universities. The UT College of Pharmacy offers changes the world!" M. Lynn Crismon, Pharm.D. Dean #12;THE UNIVERSITY OF TEXAS AT AUSTIN One

  14. Arcjet power supply and start circuit

    NASA Technical Reports Server (NTRS)

    Gruber, Robert P. (inventor)

    1988-01-01

    A dc power supply for spacecraft arcjet thrusters has an integral automatic starting circuit and an output averaging inductor. The output averaging inductor, in series with the load, provides instantaneous current control, and ignition pulse and an isolated signal proportional to the arc voltage. A pulse width modulated converter, close loop configured, is also incorporated to give fast response output current control.

  15. GETTING STARTED Monday, July 6, 2009

    E-print Network

    GETTING STARTED Monday, July 6, 2009 Katzman Lounge, Vanier Hall Office of Faculty Recruitment of Windsor and the important role faculty will play in setting future strategic directions. It will also.m. Office of Human Resources (30 mins) Rita LaCivita, Executive Director Cheryl Paglione, Associate

  16. 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)

  17. 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.…

  18. Start Your Own Business. Interim Guide.

    ERIC Educational Resources Information Center

    Manitoba Dept. of Education and Training, Winnipeg.

    This guide is designed for use by instructors teaching a 12-unit course in starting a business. Presented first is a diagram illustrating the place of the course in Manitoba's business education curriculum. The academic, personal management, and teamwork skills that have been deemed critical employability skills required of the Canadian work force…

  19. Including Children with Significant Disabilities in Head Start. Training Guides for the Head Start Learning Community.

    ERIC Educational Resources Information Center

    Education Development Center, Inc., Newton, MA.

    Intended to help Head Start programs recruit and include children with significant disabilities and their families, this guide offers Head Start staff tools to work more collaboratively to plan and implement integrated services for all children, especially children with significant disabilities. Following an introductory section, the guide…

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

    ERIC Educational Resources Information Center

    ZERO TO THREE, 2007

    2007-01-01

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

  1. Improvement in HIV-associated motor slowing after antiretroviral therapy including protease inhibitors.

    PubMed

    Sacktor, N C; Skolasky, R L; Lyles, R H; Esposito, D; Selnes, O A; McArthur, J C

    2000-02-01

    A study of neuropsychological performance was conducted in 33 HIV+ patients initiating highly active antiretroviral therapy (HAART). Grooved Pegboard (GP) non-dominant hand performance improved in 23/33 (70%) subjects (P=0.002). Among 23 patients with motor slowing (GP non-dominant hand z score < -1.0) at baseline, 18 (78%) improved on the GP non-dominant hand test after initiating HAART (P=0.001). GP non-dominant hand performance improved longitudinally in HIV+ patients initiating HAART, while matched HIV+ controls not on HAART did not change (P=0.045). Significant improvement in motor performance can occur after HAART in HIV+ patients with impairment. PMID:10787000

  2. Substance abuse, adherence with antiretroviral therapy, and clinical outcomes among HIV-infected individuals

    PubMed Central

    Lucas, Gregory M.

    2010-01-01

    Substance abuse and addiction are highly prevalent in HIV-infected individuals. Substance abuse is an important comorbidity that affects the delivery and outcomes of HIV medical management. In this paper I will review data examining the associations between substance abuse and HIV treatment and potential strategies to improve outcomes in this population that warrant further investigation. Current - but not past - substance abuse adversely affects engagement in care, acceptance of antiretroviral therapy, adherence with therapy, and long-term persistence in care. Substance abuse treatment appears to facilitate engagement in HIV care, and access to evidence-based treatment for substance abuse is central to addressing the HIV epidemic. Strategies that show promise for HIV-infected substance abusers include integrated treatment models, directly observed therapy, and incentive-based interventions. PMID:20888839

  3. Early suppressive antiretroviral therapy in HIV infection is associated with measurable changes in the corpus callosum.

    PubMed

    Kelly, Sean G; Taiwo, Babafemi O; Wu, Ying; Bhatia, Ramona; Kettering, Casey S; Gao, Yi; Li, Suyang; Hutten, Ryan; Ragin, Ann B

    2014-10-01

    The purpose of this study was to examine the impact of early suppressive antiretroviral therapy (ART) on brain structure and neurocognitive outcomes. We conducted an observational study of subjects within 1 year of HIV infection. Ten ART-naïve and 10 ART-suppressed individuals were matched for age and infection duration and age-matched to 10 HIV-seronegative controls. Quantitative brain imaging and neurocognitive data were analyzed. Subjects on suppressive ART had diminished corpus callosum structural integrity on macromolecular and microstructural imaging, higher cerebrospinal fluid percent, higher depression scores, and lower functional performance. Early suppressive ART may alter the trajectory of neurological progression of HIV infection, particularly in the corpus callosum. PMID:24965253

  4. Antiretroviral therapy for the prevention of HIV transmission: what will it take?

    PubMed

    McNairy, Margaret L; El-Sadr, Wafaa M

    2014-04-01

    The evidence in support of use of antiretroviral therapy (ART) for prevention of human immunodeficiency virus (HIV) transmission is encouraging and has stimulated optimism for achieving a dramatic change in the trajectory of the HIV epidemic. Yet, there are substantial challenges that, if not addressed, could be the Achilles' heel for this concept. These challenges require strengthening every step of the HIV care continuum, including expansion of HIV testing to reach all those with HIV infection, effective linkage to and retention in care, timely initiation of ART, and high levels of treatment adherence with viral load suppression. Also important is the identification of individuals with acute HIV infection whose contribution to HIV transmission may be substantial. Implementation research is needed to identify strategies that address these challenges and to determine the efficacy of ART for prevention in key populations as well as to evaluate the effectiveness of combination strategies for HIV prevention at the population level. PMID:24429438

  5. Disfiguring molluscum contagiosum in a HIV-positive patient responding to antiretroviral therapy.

    PubMed

    Sen, Sumit; Goswami, Bidyut Krishna; Karjyi, Nabendu; Bhaumik, Parna

    2009-01-01

    Molluscum contagiosum (MC) is caused by a double stranded DNA virus belonging to the pox virus family. MC lesions are usually pearly, dome shaped, small, discrete lesions with central umbilication. In HIV-positive patients atypical varieties are found. They may be large or nonumbilicated. Individual papules may join to form the agminate variety. This form is rare. Lesions of MC in healthy immunocompetent patients may occur at any part of the body including face, trunk, and limbs. Sexually active adults have lesions usually on the genitalia, pubis, and inner thigh, rarely on the face and scalp. We present a case of agminate MC occurring in a patient with acquired immunodeficiency disease responding to highly active antiretroviral therapy. PMID:20101316

  6. 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...

  7. Preferences for characteristics of antiretroviral therapy provision in Johannesburg, South Africa: results of a conjoint analysis.

    PubMed

    Opuni, Marjorie; Bishai, David; Gray, Glenda E; McIntyre, James A; Martinson, Neil A

    2010-08-01

    A survey was administered to HIV-infected patients and a sample in Soweto and the Johannesburg inner city to measure preferences for antiretroviral therapy (ART) provision. The 25 to 49-year-old male and female respondents viewed 20 sets of three hypothetical ART clinic choices after reading information on ART. Each set had a permutation of four levels of: monthly ART price, clinic waiting times, HIV clinic branding and clinic staff attitudes. For each set, respondents selected the preferred mix of characteristics and indicated if they would pay for it. For every ZAR 100 (USD PPP 25) increase in price, the average probability of selecting a clinic decreased by 2.8 and 3.0% in the HIV patient and household samples, respectively. Cost as well as staff attitude, wait time, and clinic branding may constitute important barriers to ART uptake and adherence in resource-poor settings. PMID:19533322

  8. 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

  9. Determinants of Engagement in HIV Treatment and Care among Zambians new to Antiretroviral Therapy

    PubMed Central

    Jones, Deborah L.; Zulu, Isaac; Vamos, Szonja; Cook, Ryan; Chitalu, Ndashi; Weiss, Stephen M.

    2012-01-01

    This pilot study assessed the determinants of engagement in HIV care among Zambian patients new to antiretroviral (ARV) therapy, and the effect of an intervention to increase medication adherence. Participants (n = 160) were randomized to a 3-month group or individual intervention utilizing a crossover design. Psychophysiological (depression, cognitive functioning, health status), social (social support, disclosure, stigma), and structural (health care access, patient-provider communication) factors and treatment engagement (adherence to clinic visits and medication) were assessed. Participants initially receiving group intervention improved their adherence, but gains were not maintained following crossover to the individual intervention. Increased social support and patient-provider communication and decreased concern about HIV medications predicted increased clinic attendance across both arms. Results suggest that early participation in a group intervention may promote increased adherence among patients new to therapy, but long-term engagement in care may be sustained by both one-on-one and group interventions by health care staff. PMID:23009738

  10. Head Start Impact Study: First Year Findings. Executive Summary

    ERIC Educational Resources Information Center

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

    2005-01-01

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

  11. Barriers to acceptance and adherence of antiretroviral therapy in urban Zambian women: a qualitative study.

    PubMed

    Murray, Laura K; Semrau, Katherine; McCurley, Ellen; Thea, Donald M; Scott, Nancy; Mwiya, Mwiya; Kankasa, Chipepo; Bass, Judith; Bolton, Paul

    2009-01-01

    Sub-Saharan Africa contains over 60% of the world's HIV infections and Zambia is among the most severely affected countries in the region. As antiretroviral programs have been rapidly expanding, the long-term success of these programs depends on a good understanding of the behavioral determinants of acceptance and adherence to antiretroviral therapy (ART). The study used qualitative methods to gain local insight into potentially important factors affecting HIV-infected women's decision to accept or continue with ART. Some of the barriers identified by this study are consistent with factors cited in the existing adherence literature from both developed and developing nations such as side effects, hunger and stigma; other factors have not been previously reported. One major theme was unfamiliarity with the implications of having a chronic, potentially deadly disease. Other emerging themes from this study include the complicated effect of ART on interpersonal relationship, particularly between husbands and wives, the presence of depression and hopelessness, and lack of accurate information. The results suggest that the reasons for non-uptake of treatment include issues related to local cultural frameworks (e.g., illness ideology), mental and behavioral health (e.g., depression and/or interpersonal challenges), stigma, and motivating factors (e.g., values of church or marriage) of different cultures that affect the ability and willingness to take life-saving medicine for a long period of time. Qualitative studies are critical to better understand why ART eligible individuals are choosing not to initiate or continue treatment to achieve needed adherence levels. PMID:19085223

  12. Interactions of Papua New Guinea medicinal plant extracts with antiretroviral therapy

    PubMed Central

    Larson, Erica C.; Hathaway, Laura B.; Lamb, John G.; Pond, Chris D.; Rai, Prem P.; Matainaho, Teatulohi K.; Piskaut, Pius; Barrows, Louis R.; Franklin, Michael R.

    2014-01-01

    Ethnopharmacological relevance A substantial proportion of the population in Papua New Guinea (PNG) lives with human immunodeficiency virus (HIV). Treatment requires lifelong use of antiretroviral therapy (ART). The majority of people in PNG use traditional medicines (TM) derived from plants for all types of health promotions. Consequently, there is a concern that herb-drug interactions may impact the efficacy of ART. Herb-drug, or drug-drug, interactions occur at the level of metabolism through two major mechanisms: enzyme induction or enzyme inhibition. In this study, extracts of commonly-used medicinal plants from PNG were screened for herb-drug interactions related to cytochrome P450s (CYPs). Materials and Methods Sixty nine methanol extracts of TM plants were screened for their ability to induce CYPs by human aryl hydrocarbon receptor- (hAhR-) and human pregnane X receptor- (hPXR-) dependent mechanisms, utilizing a commercially available cell-based luciferase reporter system. Inhibition of three major CYPs, CYP1A2, CYP3A4, and CYP2D6, was determined using human liver microsomes and enzyme-selective model substrates. Results Almost one third of the TM plant extracts induced the hAhR-dependent expression of CYP1A2, the hPXR-dependent expression of CYP3A4, or both. Almost two thirds inhibited CYP1A2, CYP3A4, or CYP2D6, or combinations thereof. Many plant extracts exhibited both induction and inhibition properties. Conclusions We demonstrated that the potent and selective ability of extracts from PNG medicinal plants to affect drug metabolizing enzymes through induction and/or inhibition is a common phenomenon. Use of traditional medicines concomitantly with ART could dramatically alter the concentrations of antiretroviral drugs in the body; and their efficacy. PNG healthcare providers should counsel HIV patients because of this consequence. PMID:25138353

  13. 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

  14. Comparative Effectiveness of First Antiretroviral Regimens in Clinical Practice Using a Causal Approach

    PubMed Central

    Cuzin, Lise; Pugliese, Pascal; Allavena, Clotilde; Katlama, Christine; Cotte, Laurent; Cheret, Antoine; Cabié, André; Rey, David; Chirouze, Catherine; Bani-Sadr, Firouze; Flandre, Philippe

    2015-01-01

    Abstract The objective of this study was to estimate the cumulative incidences of failure by months 12 (M12) and 24 (M24) for the most prescribed first-line anti-retroviral regimens (ART). It is retrospective analysis of a prospectively collected database. All patients who initiated their first ART with the most prescribed regimens between 1st January 2004 and 30th June 2013 in 12 large HIV reference centers in France were included. The outcome was treatment failure—defined by any treatment modification for virological or tolerability reasons—and comparisons between regimens were carried out at M12 and M24. Adjusted and weighted methods via the propensity score (PS) were used to compare the effectiveness of the first antiretroviral regimens. Potential confounders of the treatment-outcome association were used to estimate PS with multinomial logistic regression. Overall, 3128 and 2690 patients were included in the M12 and M24 analyses, respectively. Patients received 5 different regimens (ABC/3TC with ATV/r or DRV/r, TDF/FTC with ATV/r, DRV/r, or EFV). Failure was reported in 25% and 42% at M12 and M24, respectively. Patients who received TDF/FTC/EFV had a significantly higher proportion of failure at M12 by comparison with TDF/FTC with DRV/r (reference), but not at M24. Patients in the 3 other groups had a trend toward a higher proportion of failure at M12 although not statistically significant. No difference was found at M24. Using data from a large prospective cohort, we found that boosted atazanavir and darunavir had comparable effectiveness, whatever the associated NRTIs, whereas efavirenz-based regimens were relatively less performing on the short term. PMID:26426666

  15. Trends in drug resistance mutations in antiretroviral-naïve intravenous drug users of Rio de Janeiro.

    PubMed

    Maia Teixeira, Sylvia Lopes; Bastos, Francisco Inácio; Hacker, Mariana A; Guimarães, Monick Lindenmeyer; Morgado, Mariza Gonçalves

    2006-06-01

    DNA sequencing of a pol gene fragment from drug-naive injecting drug users samples obtained at two time points of the Brazilian AIDS epidemic (Pre-HAART era: 1994 to early 1997, n = 27; post-HAART era: 1999-2001, n = 38) was undertaken to assess HIV-1 antiretroviral drug resistance mutations and subtyping profiles. Genotypic analysis revealed the presence of PR primary L90M, D30N, M46I, and V82A mutations in 7.9% of the post-HAART group, and a high frequency of secondary mutations (84.2%). Nucleoside RT-associated mutations were observed in 13.2%. In the pre-HAART group, a higher frequency of RT mutations was observed (22.2%) and no PR primary mutations were found, in agreement with the introduction of protease inhibitors (PIs) in therapy during the same period. The identification of 7.9% of drug-naive injecting drug users already bearing RT/PR primary resistance mutations in the post-HAART era group constitutes a major concern in terms of dissemination of drug resistant viruses. The resistance mutations profile of the individuals may reflect the context of antiretroviral treatment in Brazil at the sample collection periods (1994-1997 and 1999-2001). In spite of the differences observed in the drug resistance profiles, similar frequencies of subtype B (63.0 vs. 73.7%), F (22.2 vs. 10.5%), and recombinant B/F (14.8 vs. 15.8%) viruses were found, respectively, in the pre- and post-HAART groups. PMID:16628575

  16. Cognitive functioning during highly active antiretroviral therapy interruption in human immunodeficiency virus type 1 infection

    PubMed Central

    Childers, Meredith E; Woods, Steven Paul; Letendre, Scott; McCutchan, J Allen; Rosario, Debralee; Grant, Igor; Mindt, Monica Rivera; Ellis, Ronald J

    2015-01-01

    Although no longer considered therapeutically beneficial, antiretroviral treatment interruptions (TIs) still occur frequently among patients with human immunodeficiency virus (HIV) infection for a variety of reasons. TIs typically result in viral rebound and worsening immunosuppression, which in turn are risk factors for neurocognitive decline and dementia. We sought to determine the extent of neurocognitive risk with TIs and subsequent reintroduction of highly active antiretroviral therapy (HAART) by using a comprehensive, sensitive neuropsychological assessment and by concurrently determining changes in plasma and cerebrospinal fluid (CSF) viral load and CD4 counts. Prospective, serial, clinical evaluations including neuropsychological (NP) testing and measurement of plasma HIV RNA and CD4 count and mood state were performed on HIV-1–infected individuals (N=11) at three time points: (1) prior to a TI, while on HAART; (2) after TIs averaging 6 months; and (3) after reinitiating HAART therapy. During TI, plasma HIV RNA increased and CD4 counts declined significantly, but NP performance did not change. Following reinitiation of HAART, viral loads fell below pre-TI levels, and CD4 counts rose. Improved viral suppression and immune restoration with reinitiation of HAART resulted in significant improvement in neurocognitive performance. No changes on comprehensive questionnaires of mood state were observed in relation to TI. NP performance and mood state remained stable during TIs despite worsened viral loads and CD4 counts. Because “practice effects” are generally greatest between the first and second NP testing sessions, improvement at the third, post-TI time point was unlikely to be accounted for by practice. TIs of up to 6 months appear to be neurocognitively and psychiatrically safe for most patients. PMID:19016380

  17. Out-of-pocket costs of AIDS care in China: are free antiretroviral drugs enough?

    PubMed

    Moon, S; Van Leemput, L; Durier, N; Jambert, E; Dahmane, A; Jie, Y; Wu, G; Philips, M; Hu, Y; Saranchuk, P

    2008-09-01

    Financial access to HIV care and treatment can be difficult for many people in China, where the government provides free antiretroviral drugs but does not cover the cost of other medically necessary components, such as lab tests and drugs for opportunistic infections. This article estimates out-of-pocket costs for treatment and care that a person living with HIV/AIDS in China might face over the course of one year. Data comes from two treatment projects run by Médecins Sans Frontières in Nanning, Guangxi Province and Xiangfan, Hubei Province. Based on the national treatment guidelines, we estimated costs for seven different patient profiles ranging from WHO Clinical Stages I through IV. We found that patients face significant financial barriers to even qualify for the free ARV program. For those who do, HIV care and treatment can be a catastrophic health expenditure, with cumulative patient contributions ranging from approximately US$200-3939/year in Nanning and US$13-1179/year in Xiangfan, depending on the patient's clinical stage of HIV infection. In Nanning, these expenses translate as up to 340% of an urban resident's annual income or 1200% for rural residents; in Xiangfan, expenses rise to 116% of annual income for city dwellers and 295% in rural areas. While providing ARV drugs free of charge is an important step, the costs of other components of care constitute important financial barriers that may exclude patients from accessing appropriate care. Such barriers can also lead to undesirable outcomes in the future, such as impoverishment of AIDS-affected households, higher ARV drug-resistance rates and greater need for complex, expensive second-line antiretroviral drugs. PMID:18777223

  18. 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

  19. Clinical pharmacology quality assurance program: models for longitudinal analysis of antiretroviral proficiency testing for international laboratories.

    PubMed

    DiFrancesco, Robin; Rosenkranz, Susan L; Taylor, Charlene R; Pande, Poonam G; Siminski, Suzanne M; Jenny, Richard W; Morse, Gene D

    2013-10-01

    Among National Institutes of Health HIV Research Networks conducting multicenter trials, samples from protocols that span several years are analyzed at multiple clinical pharmacology laboratories (CPLs) for multiple antiretrovirals. Drug assay data are, in turn, entered into study-specific data sets that are used for pharmacokinetic analyses, merged to conduct cross-protocol pharmacokinetic analysis, and integrated with pharmacogenomics research to investigate pharmacokinetic-pharmacogenetic associations. The CPLs participate in a semiannual proficiency testing (PT) program implemented by the Clinical Pharmacology Quality Assurance program. Using results from multiple PT rounds, longitudinal analyses of recovery are reflective of accuracy and precision within/across laboratories. The objectives of this longitudinal analysis of PT across multiple CPLs were to develop and test statistical models that longitudinally: (1) assess the precision and accuracy of concentrations reported by individual CPLs and (2) determine factors associated with round-specific and long-term assay accuracy, precision, and bias using a new regression model. A measure of absolute recovery is explored as a simultaneous measure of accuracy and precision. Overall, the analysis outcomes assured 97% accuracy (±20% of the final target concentration of all (21) drug concentration results reported for clinical trial samples by multiple CPLs). Using the Clinical Laboratory Improvement Act acceptance of meeting criteria for ?2/3 consecutive rounds, all 10 laboratories that participated in 3 or more rounds per analyte maintained Clinical Laboratory Improvement Act proficiency. Significant associations were present between magnitude of error and CPL (Kruskal-Wallis P < 0.001) and antiretroviral (Kruskal-Wallis P < 0.001). PMID:24052065

  20. 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

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

    PubMed Central

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

    2012-01-01

    The roll-out of accessible and affordable antiretroviral (ARV) drugs for people living with HIV in low-income countries is drastically changing the nature of HIV-related healthcare. The Zimbabwean Ministry of Health has renewed efforts to make antiretroviral treatment (ART) for HIV free and publically available across the country. This paper describes the findings from a multi-method qualitative study including interviews and a focus group with healthcare workers (mostly nurses), totalling 25 participants, and field notes from over 100 hours of ethnographic observation in three rural Zimbabwean health centres. These health centres began providing free ARV drugs to HIV-positive people over one year prior to the research period. We examined sources of motivation and frustration among nurses administering ART in these resource-poor health centres. The findings suggest that healthcare workers administering ART in challenging circumstances are adept at drawing strength from the dramatic physical and emotional recoveries made possible by ART and from their personal memories of the suffering caused by HIV/AIDS among close friends or family. However, healthcare staff grappled with extreme resource shortages, which led to exhaustion and frustration. Surprisingly, only one year into ART provision, healthcare workers did not reference the professional challenges of their HIV work before ART became available, suggesting that medical breakthroughs such as ART rapidly come to be seen as a standard element of nursing. Our findings provide a basis for optimism that medical breakthroughs such as ART can reinvigorate healthcare workers in the short term. However, we caution that the daily challenges of nursing in poor environments, especially administering an ongoing and resource-intensive regime such as ART, must be addressed to enable nurses to continue delivering high-quality ART in sub-Saharan Africa. PMID:21400319

  2. 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.; Garduño, 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

  3. The pricing and procurement of antiretroviral drugs: an observational study of data from the Global Fund.

    PubMed Central

    Vasan, Ashwin; Hoos, David; Mukherjee, Joia S.; Farmer, Paul E.; Rosenfield, Allan G.; Perriëns, Joseph H.

    2006-01-01

    The Purchase price report released in August 2004 by the Global Fund to Fight AIDS, Tuberculosis, and Malaria (Global Fund) was the first publication of a significant amount of real transaction purchase data for antiretrovirals (ARVs). We did an observational study of the ARV transaction data in the Purchase price report to examine the procurement behaviour of principal recipients of Global Fund grants in developing countries. We found that, with a few exceptions for specific products (e.g. lamivudine) and regions (e.g. eastern Europe), prices in low-income countries were broadly consistent or lower than the lowest differential prices quoted by the research and development sector of the pharmaceutical industry. In lower middle-income countries, prices were more varied and in several instances (lopinavir/ritonavir, didanosine, and zidovudine/lamivudine) were very high compared with the per capita income of the country. In all low- and lower middle-income countries, ARV prices were still significantly high given limited local purchasing power and economic strength, thus reaffirming the need for donor support to achieve rapid scale-up of antiretroviral therapy. However, the price of ARVs will have to decrease to render scale-up financially sustainable for donors and eventually for governments themselves. An important first step in reducing prices will be to make available in the public domain as much ARV transaction data as possible to provide a factual basis for discussions on pricing. The price of ARVs has considerable implications for the sustainability of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) treatment in the developing world. PMID:16710550

  4. HIV related pulmonary arterial hypertension: epidemiology in Africa, physiopathology, and role of antiretroviral treatment.

    PubMed

    Bigna, Jean Joel R; Sime, Paule Sandra D; Koulla-Shiro, Sinata

    2015-01-01

    The development of HIV related pulmonary arterial hypertension (PAH) reduces the probability of survival by half as compared with HIV-infected individuals without HIV related PAH. HIV infected patients have a greater incidence of PAH compared to general population and have a 2500-fold increased risk of developing PAH. It is therefore important to have a recent overview of the problem in Africa, the most HIV affected part of the world (70 % of all HIV infection in the world). First, we discussed the epidemiology of HIV-related PAH in Africa. Second, the current understanding of the HIV-related PAH pathogenesis has been covered. Third, role of highly active antiretroviral therapy on HIV-related PAH has been revisited. There are few data concerning epidemiology of HIV related pulmonary hypertension in Africa leading to necessity to conduct further prospective large studies. The prevalence of PAH among HIV infected people in Africa varies from 5 to 13 %. The prevalence of HIV-related PAH in Africa is notably high compared to those in developed countries and in general population. The pathogenesis of PAH is clearly complex, and probably results from the interaction of multiple modulating genes with environmental factors. The physiopathology includes cytokines secretion increase which induces dysregulation of endothelial and vascular smooth muscle cell growth and imbalance of endogenous vasodilators and constrictors; HIV viral proteins which induces vascular oxidative stress, smooth myocyte proliferation and migration, and endothelial injury and genetic predisposition due to some major histocompatibility complex alleles, particularly HDL-DR6 and HLA-DR5. Histologically, HIV related PAH has the same characteristics with other types PAH. Antiretroviral therapy have a beneficial effect on the outcome of HIV related pulmonary hypertension, but it lacks evidence from large prospective studies. PMID:26566389

  5. Barriers to acceptance and adherence of antiretroviral therapy in urban Zambian women: a qualitative study

    PubMed Central

    Murray, Laura K.; Semrau, Katherine; McCurley, Ellen; Thea, Donald M.; Scott, Nancy; Mwiya, Mwiya; Kankasa, Chipepo; Bass, Judith; Bolton, Paul

    2009-01-01

    Sub-Saharan Africa contains over 60% of the world’s HIV infections and Zambia is among the most severely affected countries in the region. As antiretroviral programs have been rapidly expanding, the long-term success of these programs depends on a good understanding of the behavioral determinants of acceptance and adherence to antiretroviral therapy (ART). The study used qualitative methods to gain local insight into potentially important factors affecting HIV-infected women’s decision to accept or continue with ART. Some of the barriers identified by this study are consistent with factors cited in the existing adherence literature from both developed and developing nations such as side effects, hunger and stigma; other factors have not been previously reported. One major theme was unfamiliarity with the implications of having a chronic, potentially deadly disease. Other emerging themes from this study include the complicated effect of ART on interpersonal relationship, particularly between husbands and wives, the presence of depression and hopelessness, and lack of accurate information. The results suggest that the reasons for non-uptake of treatment include issues related to local cultural frameworks (e.g., illness ideology), mental and behavioral health (e.g., depression and/or interpersonal challenges), stigma, and motivating factors (e.g., values of church or marriage) of different cultures that affect the ability and willingness to take life-saving medicine for a long period of time. Qualitative studies are critical to better understand why ART eligible individuals are choosing not to initiate or continue treatment to achieve needed adherence levels. PMID:19085223

  6. 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

  7. Antiretroviral treatment of HIV-1 prevents transmission of HIV-1: where do we go from here?

    PubMed Central

    Cohen, Myron S; Smith, M Kumi; Muessig, Kathryn E; Hallett, Timothy B; Powers, Kimberly A; Kashuba, Angela D

    2013-01-01

    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

  8. Serious Adverse Events Are Uncommon with Combination Neonatal Antiretroviral Prophylaxis: A Retrospective Case Review

    PubMed Central

    Smith, Christiana; Forster, Jeri E.; Levin, Myron J.; Davies, Jill; Pappas, Jennifer; Kinzie, Kay; Barr, Emily; Paul, Suzanne

    2015-01-01

    Six weeks of zidovudine (ZDV) is recommended for postnatal prophylaxis of HIV-exposed infants, but combination antiretrovirals are indicated if HIV transmission risk is increased. We investigated the frequency and severity of adverse events (AE) in infants receiving multiple drug prophylaxis compared to ZDV alone. In this retrospective review of 148 HIV-exposed uninfected infants born between 1997–2009, we determined clinical and laboratory AE that occurred between days of life 8–42. Thirty-six infants received combination prophylaxis; among those, a three-drug regimen containing ZDV, lamivudine, and nevirapine was most common (53%). Rates of laboratory AE grade ?1 were as follows for the combination prophylaxis and ZDV alone groups, respectively: neutropenia 55% and 39%; anemia 50% and 39%; thrombocytopenia 0 and 3%; elevated aspartate aminotransferase 3% and 3%; elevated alanine aminotransferase 0 and 1%; hyperbilirubinemia 19% and 42%. Anemia occurred more frequently in infants who received three-drug prophylaxis compared to infants who received ZDV alone (63% vs. 39%, p = 0.04); all anemia AE were grade 1 or 2 in the three-drug prophylaxis group. Overall, 75% of infants on combination prophylaxis and 66% of infants on ZDV alone developed grade ?1 AE (p = 0.32), and 17% of infants in either group developed grade ?3 AE. Stavudine was substituted for ZDV in 23 infants due to anemia or neutropenia. After this antiretroviral change, 50% of evaluable infants demonstrated improvement in AE grade, and 25% had no change. In conclusion, low grade anemia, neutropenia, and hyperbilirubinemia occurred frequently regardless of the prophylactic regimen, but serious AE were uncommon. Although most AE were typical of ZDV toxicity, the combination of ZDV with lamivudine and nevirapine resulted in an increased frequency of low-grade anemia. Further studies are needed to identify prophylactic regimens with less toxicity for infants born to HIV-infected mothers. PMID:26000984

  9. Adverse Drug Reactions to Antiretroviral Therapy: Prospective Study in Children in Sikasso (Mali)

    PubMed Central

    Oumar, Aboubacar A.; Diallo, Korotoumou; Dembélé, Jean P.; Samaké, Lassana; Sidibé, Issa; Togo, Boubacar; Sylla, Mariam; Tounkara, Anatole; Dao, Sounkalo; Tulkens, Paul M.

    2012-01-01

    OBJECTIVES Adverse events during antiretroviral treatment are frequent and various. Their diagnosis incurs some various difficulties according to the geographic context. Our aim was to describe the frequency, nature, and preventability of adverse drug reactions (ADRs) due to antiretroviral treatment in Malian outpatient children. METHODS The study was a 6-month (June 1 to November 30, 2010) prospective, observational study of 92 children admitted to a pediatric hospital in Sikasso, Mali. The patients were treated with a generic drug and/or drug combinations. Prior to treatment initiation, demographic characteristics, clinical history, and biologic parameters, including CD4 cell counts, were collected for each patient. The World Health Organization's adverse drug reactions classification was used to characterize the side effects. Adverse effects and toxicities were graded 1, 2, and 3. Analysis of data was performed using SPSS Version 17.0 software. RESULTS Ninety-two human immunodeficiency virus–infected children met the criteria of inclusion. After 24 weeks of treatment, we observed that 14.1% of children had at least one side effect during our study. Side effects were many and varied, with the most frequent being cutaneous rash, nausea, vomiting, and diarrhea (38.5%, 23.1%, 15.4%, and 15.4%, respectively). Side effects were grade 1 in most cases. One case of grade 2 and one case of grade 3 were observed with rash. We observed one case of grade 3 side effects during our study. The treatment regimen was changed in 15.2% of cases, including one case because of side effects. CONCLUSION ADRs are not rare in Mali, particularly in children. These ADRs have an impact on quality of life for patients. We recommend a pharmacovigilance system for sustainable management of side effects in patients infected with human immunodeficiency virus in Mali. PMID:23411444

  10. Adherence to highly active antiretroviral therapy in a tertiary care hospital in West Bengal, India

    PubMed Central

    Saha, Rajib; Saha, Indranil; Sarkar, Aditya Prasad; Das, Dilip Kumar; Misra, Raghunath; Bhattacharya, Krishnadas; Roy, Rabindra Nath; Bhattacharya, Abantika

    2014-01-01

    INTRODUCTION The introduction of highly active antiretroviral therapy (HAART) for the treatment of human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS) has led to the reduction of mortality and the improvement of the quality of life of people living with HIV/AIDS (PLWHA). The present study was conducted to determine the pattern of adherence to HAART among PLWHA, and to assess the factor(s) affecting nonadherence, if any. METHODS This study was a hospital-based analytical, cross-sectional epidemiological study conducted between July and October 2011. A total of 370 adult HIV-positive patients registered in the Antiretroviral Therapy Centre of Burdwan Medical College and Hospital, West Bengal, India, were included. Nonadherence was defined as missing at least a single dose of medicine within the last four days. Data was analysed using the Statistical Package for the Social Sciences version 19.0 (IBM Corp, Armonk, NY, USA). RESULTS A total of 87.6% of patients were found to be adherent to HAART. Principal causes of nonadherence were forgetting to take medicine (70.2%), being away from home (65.2%), and busyness with other things (64.7%). Multivariate logistic regression analysis revealed that nonadherence was significantly associated with a positive family history of HIV/AIDS (odds ratio [OR] 16; 95% confidence interval [CI] 2.2–114.3; p = 0.01), occurrence of side effects with HAART (OR 9.81; 95% CI 1.9–51.7; p = 0.01) and employment (OR 5.93; 95% CI 1.5–23.2; p = 0.01). CONCLUSION Although overall adherence was high, the factors that affect nonadherence can be addressed with proper counselling and motivation of patients and their family members. Adherence to HAART could delay the progression of this lethal disease and minimise the risk of developing drug resistance. PMID:24570318

  11. 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

  12. Islamic perspectives on HIV/AIDS and antiretroviral treatment: the case of Nigeria.

    PubMed

    Balogun, Amusa Saheed

    2010-12-01

    Some religious reactions to the HIV epidemic in Africa unwittingly contributed to the expansion of the epidemic in its early years. This was because many religious people regarded the emergence of HIV and AIDS as divine punishment for man's sins as a result of people's sexual promiscuity. Some also opposed public promotion of the use of condoms for HIV prevention. However, religious bodies have made positive contributions to HIV/AIDS responses in many African countries in recent times. Though Christian bodies are taking the lead in faith-based responses to HIV and AIDS in Africa, Islamic bodies have also been major partners in HIV/AIDS interventions in several countries. Against this background, this article examines some Islamic perceptions of HIV and AIDS, and especially the impact of antiretroviral treatment (ART) for people living with HIV in Africa, with particular emphasis on Nigeria. In spite of the emergence of antiretroviral (ARV) drugs in Africa, Islam still emphasises the prevention of new infections and care for people living with HIV or AIDS. The article discusses basic issues associated with ARVs, such as health, sickness, life-prolongation and death, from an Islamic viewpoint, as well as some Islamic measures to prevent HIV-risk-taking behaviours in an era of ARVs. It also looks at the nature and extent of Islamic involvement in the national HIV/AIDS response in Nigeria. The paper concludes that while Islam sees HIV and AIDS and other diseases as 'tests' from Allah, the religion is not opposed to ART. Thus, efforts need to be intensified by Islamic bodies and Muslim leaders in Nigeria for an improved response to HIV and AIDS in the country. PMID:25875894

  13. Who takes the medicine? Adherence to antiretroviral therapy in Southern Ethiopia

    PubMed Central

    Teshome, Wondu; Belayneh, Mihretu; Moges, Mathewos; Endriyas, Misganu; Mekonnen, Emebet; Ayele, Sinafiksh; Misganaw, Tebeje; Shiferaw, Mekonnen; Chinnakali, Palanivel; Hinderaker, Sven Gudmund; Kumar, Ajay MV

    2015-01-01

    Background Treatment adherence is critical for the success of antiretroviral therapy (ART) for people living with HIV. There is limited representative information on ART drug adherence and its associated factors from Southern Ethiopia. We aimed at estimating the level of adherence to ART among people living with HIV and factors associated with it in 20 randomly selected ART clinics of Southern Ethiopia. Methods In this cross-sectional study, we interviewed consecutive HIV patients on first-line antiretroviral regimen attending the clinics in June 2014 using a pretested and structured questionnaire. For measuring adherence, we used 4-day recall method based on “The AIDS Clinical Trial Group adherence assessment tool”. Patients were classified as “Incomplete adherence” if they missed any of the doses in the last 4 days. Data were singly entered using EpiData and descriptive analysis, and unadjusted odds ratios were calculated using EpiDataStat software. Multivariate logistic regression analysis was performed using Stata v12.0. Results Of 974 patients interviewed, 539 (56%) were females, and mean age was 35 years. The proportion of patients with incomplete adherence was 13% (95% confidence interval: 11%–15%). In multivariate analysis, factors significantly associated with incomplete adherence included young age, being Protestant Christian, consuming alcohol, being single, and being a member of an HIV association. Psychosocial factors like stigma, depression, and satisfaction to care were not associated with incomplete adherence in the current context. Conclusion The overall adherence to ART was good. However, there were certain subgroups with incomplete adherence who need special attention. The health care providers (especially counselors) need to be aware of these subgroups and tailor their counseling to improve adherence among these groups. Exploratory qualitative studies may help uncover the exact reasons for incomplete adherence. PMID:26604706

  14. 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

  15. Effectiveness of Patient Adherence Groups as a Model of Care for Stable Patients on Antiretroviral Therapy in Khayelitsha, Cape Town, South Africa

    E-print Network

    Hernan, Miguel Angel

    Abstract: Background: Innovative models of care are required to cope with the ever-increasing number of patients on antiretroviral therapy in the most affected countries. This study, in Khayelitsha, South Africa, evaluates ...

  16. Pharmacogenetics of non-nucleoside reverse transcriptase inhibitors (NNRTIs) in resource-limited settings: Influence on antiretroviral therapy response and concomitant anti-tubercular, antimalarial and contraceptive treatments.

    PubMed

    Russo, Gianluca; Paganotti, Giacomo Maria; Soeria-Atmadja, Sandra; Haverkamp, Miriam; Ramogola-Masire, Doreen; Vullo, Vincenzo; Gustafsson, Lars Lennart

    2016-01-01

    The burden of human immunodeficiency virus (HIV) is mainly concentrated to resources-limited countries where the response to available antiretroviral therapy is often limited by the occurrence of toxicity or by the emergence of HIV drug resistance. Efavirenz and nevirapine are the antiretroviral drugs most prescribed in resources-limited countries as part of antiretroviral combination therapy. Their metabolism and conjugation are largely influenced by enzymatic genetic polymorphisms. The genetic variability of their metabolism could be associated to different metabolic phenotypes causing reduced patients' adherence because of toxicity or drug-drug interactions with concomitant therapies. The purpose of this review is to summarize published evidence on pharmacogenetic and pharmacokinetic aspects related to efavirenz and nevirapine, the influence of concomitant anti-tubercular, anti-malarial or contraceptive treatments, and the impact of human genetic variation and drug-drug interaction on the virologic and immunologic response to antiretroviral therapy in resources-limited countries. PMID:26602158

  17. 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+ naïve 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 naïve 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

  18. First-line antiretroviral treatment of HIV-infected children. A choice largely based on adult data.

    PubMed

    2011-04-01

    About 2 million children worldwide are infected with HIV.There are about 1500 HIV-infected children in France. This review examines the choice of first-line antiretroviral treatment for children under 12 years of age, based on a review of the literature using the standard Prescrire methodology. In children under 5 years of age, the percentage of CD4+ T lymphocytes among all circulating lymphocytes is more stable than the absolute count. The CD4+ T cell percentage is therefore used as a marker of immunological status in this age group. The decision to begin antiretroviral treatment in a child depends on the short or medium-term risk of progression to AIDS or death. Treatment is warranted for infants under 1 year of age, children under 6 years of age whose CD4+ T cell percentage is below 25%, and older children with a CD4+ T cell count below 350 per mm3. In Africa, antiretroviral treatment seems justified for all infected children under 2 years of age. First-line treatment for children is based on a combination of at least 3 antiretroviral drugs. Zidovudine and lamivudine remain the first-choice nucleoside reverse transcriptase inhibitors. The lopinavir + ritonavir combination is the first-choice HIV protease inhibitor, but the oral solution is poorly accepted by children because of its unpleasant taste and the high ethanol content of the ritonavir oral solution. As for the non-nucleoside reverse transcriptase inhibitors, efavirenz has not been assessed in children under 3 years of age; nevirapine can be used, but it has suboptimal antiviral activity. Antiretroviral drugs seem to have similar adverse effects in children and adults. Long-term data are lacking, however, especially on possible cardiac and metabolic effects. In view of the large number of children infected worldwide, more efforts are urgently needed to adapt first-line antiretroviral drugs to paediatric use. This means developing and assessing specific paediatric formulations and fixed-dose combinations. PMID:21648216

  19. 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.

  20. Verifying START: From satellites to suspect sites

    SciTech Connect

    Lockwood, D. )

    1990-10-01

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

  1. Key parameters of the swimming start and their relationship to start performance.

    PubMed

    Tor, Elaine; Pease, David L; Ball, Kevin A

    2015-01-01

    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

  2. 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.

  3. 40 CFR 86.136-90 - Engine starting and restarting.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...the engine (automatic and manual-choke engines) shall be started by depressing the accelerator pedal about half way and cranking the engine until it starts. (b) Diesel vehicles. The engine shall be started according to the...

  4. New START, Eyjafjallajökull, and Nuclear Winter

    NASA Astrophysics Data System (ADS)

    Robock, Alan

    2010-11-01

    On 8 April 2010, U.S. president Barack Obama and Russian president Dmitry Medvedev signed the Treaty Between the United States of America and the Russian Federation on Measures for the Further Reduction and Limitation of Strategic Offensive Arms, committing the United States and Russia to reducing their nuclear arsenals to levels less than 5% of the maximum during the height of the cold war in the 1980s. This treaty is called “New START,” as it is a follow-on to the 1991 Strategic Arms Reductions Treaty (START). On 14 April 2010 the Eyjafjallajökull volcano in Iceland began an explosive eruption phase that shut down air traffic in Europe for 6 days and continued to disrupt it for another month. What do these two events have in common? Nuclear weapons, when targeted at cities and industrial areas, would start fires, producing clouds of sooty smoke. Volcanic eruptions emit ash particles and sulfur dioxide (SO2), which forms sulfate aerosols in the atmosphere. Thus, both the use of nuclear weapons and volcanic eruptions produce particles that can be transported large distances from the source and can affect weather and climate.

  5. CD4+ and viral load outcomes of antiretroviral therapy switch strategies after virologic failure of combination antiretroviral therapy in perinatally HIV-infected youth in the United States

    PubMed Central

    Fairlie, Lee; Karalius, Brad; Patel, Kunjal; van Dyke, Russell B.; Hazra, Rohan; Hernán, Miguel A.; Siberry, George K.; Seage, George R.; Agwu, Allison; Wiznia, Andrew

    2015-01-01

    Objective: This study compared 12-month CD4+ and viral load outcomes in HIV-infected children and adolescents with virological failure, managed with four treatment switch strategies. Design: This observational study included perinatally HIV-infected (PHIV) children in the Pediatric HIV/AIDS Cohort Study (PHACS) and Pediatric AIDS Clinical Trials (PACTG) Protocol 219C. Methods: Treatment strategies among children with virologic failure were compared: continue failing combination antiretroviral therapy (cART); switch to new cART; switch to drug-sparing regimen; and discontinue all ART. Mean changes in CD4+% and viral load from baseline (time of virologic failure) to 12 months follow-up in each group were evaluated using weighted linear regression models. Results: Virologic failure occurred in 939 out of 2373 (40%) children. At 12 months, children switching to new cART (16%) had a nonsignificant increase in CD4+% from baseline, 0.59 percentage points [95% confidence interval (95% CI) ?1.01 to 2.19], not different than those who continued failing cART (71%) (?0.64 percentage points, P?=?0.15) or switched to a drug-sparing regimen (5%) (1.40 percentage points, P?=?0.64). Children discontinuing all ART (7%) experienced significant CD4+% decline ?3.18 percentage points (95% CI ?5.25 to ?1.11) compared with those initiating new cART (P?=?0.04). All treatment strategies except discontinuing ART yielded significant mean decreases in log10VL by 12 months, the new cART group having the largest drop (?1.15 log10VL). Conclusion: In PHIV children with virologic failure, switching to new cART was associated with the best virological response, while stopping all ART resulted in the worst immunologic and virologic outcomes and should be avoided. Drug-sparing regimens and continuing failing regimens may be considered with careful monitoring. PMID:26182197

  6. `If I am given antiretrovirals I will think I am nearing the grave': Kenyan HIV serodiscordant couples' attitudes regarding early initiation of antiretroviral therapy

    PubMed Central

    Curran, Kathryn; Ngure, Kenneth; Shell-Duncan, Bettina; Vusha, Sophie; Mugo, Nelly R.; Heffron, Renee; Celum, Connie; Baeten, Jared M.

    2014-01-01

    Objectives Early initiation of antiretroviral therapy (ART) – that is, at higher CD4+ cell counts (>350 cells/?l) – is a potent HIV prevention strategy. The WHO recommends ART initiation by all HIV-infected individuals in HIV serodiscordant relationships to prevent HIV transmission, yet the acceptability of early ART among couples has not been well studied. Design Qualitative study exploring HIV serodiscordant couples' attitudes toward early initiation of ART. Methods We conducted eight focus group discussions and 20 in-depth interviews with members of heterosexual HIV serodiscordant couples in Kenya. Investigators iteratively applied inductive and deductive codes, developed matrices to identify patterns in codes, and reached consensus on key attitudes (motivations and barriers) related to early ART and one central, emerging theme. Results Most participants expressed interest in early initiation of ART, with maintaining health and preventing HIV transmission as key benefits. However, many identified personal concerns and potential barriers to wider community acceptance, including side-effects, adherence to life-long treatment, and stigma. The meaning of ART emerged as a fundamental consideration, with initiating therapy perceived as emblematic of the final stage of AIDS, when one was `nearing the grave.' One particular challenge was what early ART might signify for someone who looks and feels healthy. Conclusion HIV serodiscordant couples recognized the potential benefits of early ART, but ART was frequently viewed as signifying AIDS and approaching mortality. Potential implementation of early ART presents challenges and an opportunity to reorientate individuals toward a new image of ART as health-preserving for patients and partners. PMID:24413310

  7. Anti-Retroviral Lectins Have Modest Effects on Adherence of Trichomonas vaginalis to Epithelial Cells In Vitro and on Recovery of Tritrichomonas foetus in a Mouse Vaginal Model

    PubMed Central

    Chatterjee, Aparajita; Ratner, Daniel M.; Ryan, Christopher M.; Johnson, Patricia J.; O’Keefe, Barry R.; Secor, W. Evan; Anderson, Deborah J.; Robbins, Phillips W.; Samuelson, John

    2015-01-01

    Trichomonas vaginalis causes vaginitis and increases the risk of HIV transmission by heterosexual sex, while Tritrichomonas foetus causes premature abortion in cattle. Our goals were to determine the effects, if any, of anti-retroviral lectins, which are designed to prevent heterosexual transmission of HIV, on adherence of Trichomonas to ectocervical cells and on Tritrichomonas infections in a mouse model. We show that Trichomonas Asn-linked glycans (N-glycans), like those of HIV, bind the mannose-binding lectin (MBL) that is part of the innate immune system. N-glycans of Trichomonas and Tritrichomonas bind anti-retroviral lectins (cyanovirin-N and griffithsin) and the 2G12 monoclonal antibody, each of which binds HIV N-glycans. Binding of cyanovirin-N appears to be independent of susceptibility to metronidazole, the major drug used to treat Trichomonas. Anti-retroviral lectins, MBL, and galectin-1 cause Trichomonas to self-aggregate and precipitate. The anti-retroviral lectins also increase adherence of ricin-resistant mutants, which are less adherent than parent cells, to ectocervical cell monolayers and to organotypic EpiVaginal tissue cells. Topical application of either anti-retroviral lectins or yeast N-glycans decreases by 40 to 70% the recovery of Tritrichomonas from the mouse vagina. These results, which are explained by a few simple models, suggest that the anti-retroviral lectins have a modest potential for preventing or treating human infections with Trichomonas. PMID:26252012

  8. 77 FR 3838 - Notice of Availability of Proposed New Starts/Small Starts Policy Guidance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-25

    ...Administration's (FTA) Proposed Policy Guidance on New Starts/Small...rating process, and the proposed policy guidance fills in the details...Title 49, U.S. Code, FTA is making available this proposed policy guidance for public...

  9. Spectrum of imaging appearances of intracranial cryptococcal infection in HIV/AIDS patients in the anti-retroviral therapy era.

    PubMed

    Offiah, Curtis E; Naseer, Aisha

    2016-01-01

    Cryptococcus neoformans infection is the most common fungal infection of the central nervous system (CNS) in advanced human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) patients, but remains a relatively uncommon CNS infection in both the immunocompromised and immunocompetent patient population, rendering it a somewhat elusive and frequently overlooked diagnosis. The morbidity and mortality associated with CNS cryptococcal infection can be significantly reduced by early recognition of the imaging appearances by the radiologist in order to focus and expedite clinical management and treatment. The emergence and evolution of anti-retroviral therapy have also impacted significantly on the imaging appearances, morbidity, and mortality of this neuro-infection. The constellation of varied imaging appearances associated with cryptococcal CNS infection in the HIV and AIDS population in the era of highly active anti-retroviral therapy (HAART) will be presented in this review. PMID:26564776

  10. Short Communication: The Relationship Between Mitochondrial Dysfunction and Insulin Resistance in HIV-Infected Children Receiving Antiretroviral Therapy

    PubMed Central

    Jacobson, Denise L.; Anderson, Lynn; Gerschenson, Mariana; Van Dyke, Russell B.; McFarland, Elizabeth J.; Miller, Tracie L.

    2013-01-01

    Abstract Mitochondrial abnormalities may lead to metabolic complications in HIV-infected children who have been receiving long-term antiretroviral treatment. We conducted a matched, case-control study comparing 21 HIV-infected children with insulin resistance (cases) to 21 HIV-infected children without insulin resistance (controls) to assess differences in mitochondrial DNA (mtDNA) copies/cell and oxidative phosphorylation NADH dehydrogenase (C1) and cytochrome c oxidase (C4) enzyme activities in peripheral blood mononuclear cells. MtDNA copies/cell tended to be lower in cases, and fasting serum glucose levels were inversely and significantly correlated with C1 enzyme activity, more so in cases. Larger pediatric studies should evaluate mitochondrial etiologies of insulin resistance and determine the role of antiretroviral therapies or HIV infection on mitochondrial dysfunction. PMID:23742635

  11. Self-Report Measures of Antiretroviral Therapy Adherence: A Review with Recommendations for HIV Research and Clinical Management

    PubMed Central

    Kurth, Ann E.; Pearson, Cynthia R.; Pantalone, David W.; Merrill, Joseph O.; Frick, Pamela A.

    2014-01-01

    A review of 77 studies employing self-report measures of antiretroviral adherence published 1/1996 through 8/2004 revealed great variety in adherence assessment item content, format, and response options. Recall periods ranged from 2 to 365 days (mode = 7 days). The most common cutoff for optimal adherence was 100% (21/48 studies, or 44%). In 27 of 34 recall periods (79%), self-reported adherence was associated with adherence as assessed with other indirect measures. Data from 57 of 67 recall periods (84%) indicated self-reported adherence was significantly associated with HIV-1 RNA viral load; in 16 of 26 (62%), it was associated with CD4 count. Clearly, the field would benefit from item standardization and a priori definitions and operationalizations of adherence. We conclude that even brief self-report measures of antiretroviral adherence can be robust, and recommend items and strategies for HIV research and clinical management. PMID:16783535

  12. Dutrebis (lamivudine and raltegravir) for use in combination with other antiretroviral products for the treatment of HIV-1 infection.

    PubMed

    Casado, José Luis; Bañón, Sara

    2015-11-01

    Raltegravir and lamivudine have been part of highly active therapy regimens throughout the past years of antiretroviral therapy. A fixed-dose, single-tablet regimen comprising a non-poloxamer formulation of the integrase inhibitor raltegravir and the transcriptase inhibitor lamivudine (raltegravir/lamivudine; Dutrebis(®)) has been recently licensed for the treatment of HIV-1 infection. In several Phase I pharmacokinetic studies, one Dutrebis (150 mg lamivudine/300 mg raltegravir) fixed-dose combination tablet showed a higher bioavailability but comparable lamivudine and 400 mg raltegravir poloxamer exposures. Thus, the co-administration of raltegravir together with lamivudine created a potent, effective, well-tolerated antiretroviral combination, which could be more convenient for the patient. However, the disadvantage of twice a day administration, and the existence of other fixed-dose combinations limit its widespread clinical use. This article reviews pharmacokinetics data and appraises their potential use in current and future HIV therapy. PMID:26517111

  13. Cellular automata approach for the dynamics of HIV infection under antiretroviral therapies: The role of the virus diffusion

    NASA Astrophysics Data System (ADS)

    González, Ramón E. R.; de Figueirêdo, Pedro Hugo; Coutinho, Sérgio

    2013-10-01

    We study a cellular automata model to test the timing of antiretroviral therapy strategies for the dynamics of infection with human immunodeficiency virus (HIV). We focus on the role of virus diffusion when its population is included in previous cellular automata model that describes the dynamics of the lymphocytes cells population during infection. This inclusion allows us to consider the spread of infection by the virus-cell interaction, beyond that which occurs by cell-cell contagion. The results show an acceleration of the infectious process in the absence of treatment, but show better efficiency in reducing the risk of the onset of AIDS when combined antiretroviral therapies are used even with drugs of low effectiveness. Comparison of results with clinical data supports the conclusions of this study.

  14. Short communication: The relationship between mitochondrial dysfunction and insulin resistance in HIV-infected children receiving antiretroviral therapy.

    PubMed

    Sharma, Tanvi S; Jacobson, Denise L; Anderson, Lynn; Gerschenson, Mariana; Van Dyke, Russell B; McFarland, Elizabeth J; Miller, Tracie L

    2013-09-01

    Mitochondrial abnormalities may lead to metabolic complications in HIV-infected children who have been receiving long-term antiretroviral treatment. We conducted a matched, case-control study comparing 21 HIV-infected children with insulin resistance (cases) to 21 HIV-infected children without insulin resistance (controls) to assess differences in mitochondrial DNA (mtDNA) copies/cell and oxidative phosphorylation NADH dehydrogenase (C1) and cytochrome c oxidase (C4) enzyme activities in peripheral blood mononuclear cells. MtDNA copies/cell tended to be lower in cases, and fasting serum glucose levels were inversely and significantly correlated with C1 enzyme activity, more so in cases. Larger pediatric studies should evaluate mitochondrial etiologies of insulin resistance and determine the role of antiretroviral therapies or HIV infection on mitochondrial dysfunction. PMID:23742635

  15. Late initiation of combination antiretroviral therapy in Canada: a call for a national public health strategy to improve engagement in HIV care

    PubMed Central

    Cescon, Angela; Patterson, Sophie; Davey, Colin; Ding, Erin; Raboud, Janet M; Chan, Keith; Loutfy, Mona R; Cooper, Curtis; Burchell, Ann N; Palmer, Alexis K; Tsoukas, Christos; Machouf, Nima; Klein, Marina B; Rourke, Sean B; Rachlis, Anita; Hogg, Robert S; Montaner, Julio SG

    2015-01-01

    Introduction Combination antiretroviral therapy (ART) significantly decreases morbidity, mortality and HIV transmission. We aimed to characterize the timing of ART initiation based on CD4 cell count from 2000 to 2012 and identify factors associated with late initiation of treatment. Methods Participants from the Canadian Observational Cohort (CANOC), a multi-site cohort of HIV-positive adults initiating ART naively after 1 January 2000, in three Canadian provinces (British Columbia, Ontario and Québec) were included. Late initiation was defined as a CD4 count <200 cells/mm3 or an AIDS-defining illness before ART initiation (baseline). Temporal trends were assessed using the Cochran–Armitage test, and independent correlates of late initiation were identified using logistic regression. Results In total, 8942 participants (18% female) of median age 40 years (Q1–Q3 33–47) were included. The median baseline CD4 count increased from 190 cells/mm3 (Q1–Q3 80–320) in 2000 to 360 cells/mm3 (Q1–Q3 220–490) in 2012 (p<0.001). Overall, 4274 participants (48%) initiated ART with a CD4 count <200 cells/mm3 or AIDS-defining illness. Late initiation was more common among women, non-MSM, older individuals, participants from Ontario and BC (vs. Québec), persons with injection drug use (IDU) history and individuals starting ART in earlier calendar years. In sub-analysis exploring recent (2008 to 2012) predictors using an updated CD4 criterion (<350 cells/mm3), IDU and residence in BC (vs. Québec) were no longer significant correlates of late initiation. Conclusions This analysis documents increasing baseline CD4 counts over time among Canadians initiating ART. However, CD4 counts at ART initiation remain below contemporary treatment guidelines, highlighting the need for strategies to improve earlier engagement in HIV care. PMID:26443752

  16. Use, perceptions, and acceptability of a ready-to-use supplementary food among adult HIV patients initiating antiretroviral treatment: a qualitative study in Ethiopia

    PubMed Central

    Olsen, Mette Frahm; Tesfaye, Markos; Kaestel, Pernille; Friis, Henrik; Holm, Lotte

    2013-01-01

    Objectives Ready-to-use supplementary foods (RUSF) are used increasingly in human immunodeficiency virus (HIV) programs, but little is known about how it is used and viewed by patients. We used qualitative methods to explore the use, perceptions, and acceptability of RUSF among adult HIV patients in Jimma, Ethiopia. Methods The study obtained data from direct observations and 24 in-depth interviews with HIV patients receiving RUSF. Results Participants were generally very motivated to take RUSF and viewed it as beneficial. RUSF was described as a means to fill a nutritional gap, to “rebuild the body,” and protect it from harmful effects of antiretroviral treatment (ART). Many experienced nausea and vomiting when starting the supplement. This caused some to stop supplementation, but the majority adapted to RUSF. The supplement was eaten separately from meal situations and only had a little influence on household food practices. RUSF was described as food with “medicinal qualities,” which meant that many social and religious conventions related to food did not apply to it. The main concerns about RUSF related to the risk of HIV disclosure and its social consequences. Conclusion HIV patients view RUSF in a context of competing livelihood needs. RUSF intake was motivated by a strong wish to get well, while the risk of HIV disclosure caused concerns. Despite the motivation for improving health, the preservation of social networks was prioritized, and nondisclosure was often a necessary strategy. Food sharing and religious fasting practices were not barriers to the acceptability of RUSF. This study highlights the importance of ensuring that supplementation strategies, like other HIV services, are compatible with the sociocultural context of patients. PMID:23766634

  17. Ten Years of Surveillance for Invasive Streptococcus pneumoniae during the Era of Antiretroviral Scale-Up and Cotrimoxazole Prophylaxis in Malawi

    PubMed Central

    Everett, Dean B.; Mukaka, Mavuto; Denis, Brigitte; Gordon, Stephen B.; Carrol, Enitan D.; van Oosterhout, Joep J.; Molyneux, Elizabeth M.; Molyneux, Malcolm; French, Neil; Heyderman, Robert S.

    2011-01-01

    Objective To document trends in invasive pneumococcal disease (IPD) in a central hospital in Malawi during the period of national scale-up of antiretroviral therapy (ART) and cotrimoxazole prophylaxis. Methods Between 1 January 2000 and 31 December 2009 almost 100,000 blood cultures and 40,000 cerebrospinal fluid (CSF) cultures were obtained from adults and children admitted to the Queen Elizabeth Central Hospital, Blantyre, Malawi with suspected severe bacterial infection. Results 4,445 pneumococcal isolates were obtained over the 10 year period. 1,837 were from children: 885 (19.9%) from blood and 952 (21.4%) from CSF. 2,608 were from adults: 1,813 (40.8%) from blood and 795 (17.9%) from CSF. At the start of the surveillance period cotrimoxazole resistance was 73.8% and at the end was 92.6%. Multidrug resistance (MDR) was present in almost one third of isolates and was constant over time. Free ART was introduced in Malawi in 2004. From 2005 onwards there was a decline in invasive pneumococcal infections with a negative correlation between ART scale-up and the decline in IPD (Pearson's correlation r?=??0.91; p<0.001). Conclusion During 2004–2009, national ART scale-up in Malawi was associated with a downward trend in IPD at QECH. The introduction of cotrimoxazole prophylaxis in HIV-infected groups has not coincided with a further increase in pneumococcal cotrimoxazole or multidrug resistance. These data highlight the importance of surveillance for high disease burden infections such as IPD in the region, which will be vital for monitoring pneumococcal conjugate vaccine introduction into national immunisation programmes. PMID:21423577

  18. Low Incidence of Renal Dysfunction among HIV-Infected Patients on a Tenofovir-Based First Line Antiretroviral Treatment Regimen in Myanmar

    PubMed Central

    Kyaw, Nang Thu Thu; Antierens, Annick; Soe, Kyi Pyar; Woodman, Mike; Das, Mrinalini; Zuu, Moe Khine Lwin; Htwe, Pyae Sone

    2015-01-01

    Background Since 2004, Médecins Sans Frontières-Switzerland has provided treatment and care for people living with HIV in Dawei, Myanmar. Renal function is routinely monitored in patients on tenofovir (TDF)-based antiretroviral treatment (ART), and this provides an opportunity to measure incidence and risk factors for renal dysfunction. Methods We used routinely collected program data on all patients aged ?15 years starting first-line TDF-based ART between January 2012 and December 2013. Creatinine clearance (CrCl) was assessed at base line and six-monthly, with renal dysfunction defined as CrCl < 50ml/min/1.73m2. We calculated incidence of renal dysfunction and used Cox regression analysis to identify associated risk factors. Results There were 1391 patients, of whom 1372 had normal renal function at baseline. Of these, 86 (6.3%) developed renal dysfunction during a median time of follow-up 1.14 years with an incidence rate of 5.4 per 100 person-years: 78 had CrCl between 30–50ml/min/1.73m2 and were maintained on TDF–based ART, but 5 were changed to another regimen: 4 because of CrCl <30ml/min/1.73m2. Risk factors for renal dysfunction included age ?45 years, diagnosed diabetes, underlying renal disease, underweight and CD4 count <200cells/mm3. There were 19 patients with baseline renal dysfunction and all continued on TDF-based ART: CrCl stayed between 30–49 ml/min/1.73m2 in five patients while the remainder regained normal renal function. Conclusions In a resource-poor country like Myanmar, the low incidence of renal toxicity in our patient cohort suggests that routine assessment of CrCl may not be needed and could be targeted to high risk groups if resources permit. PMID:26301416

  19. [Reasons for antiretroviral treatment change in HIV+ patients in Spain in 2010-2011. SWITCH AUDIT Study].

    PubMed

    Pedrol, Enric; Viciana, Pompeyo; Arranz, Alberto; Pasquau, Juan; Deig, Elisabeth; Tasias, Mariona

    2014-06-01

    Survey in 349 HIV infected subjects in 19 Spanish Hospitals in 2010-2011, to assess the reasons for antiretroviral treatment change. Simplification was the most frequent reason for change (37%), followed by toxicity (30%) and treatment failure (21%). There were statistically significant differences according to treatment line and transmission category. In conclusion, in many patients treatment is changed in order to obtain the benefits of a regimen easier to follow. PMID:24940888

  20. The design of single-arm clinical trials of combination antiretroviral regimens for treatment-naive HIV-infected patients.

    PubMed

    Zheng, Lu; Rosenkranz, Susan L; Taiwo, Babafemi; Para, Michael F; Eron, Joseph J; Hughes, Michael D

    2013-04-01

    Single-arm clinical trials are useful to evaluate antiretroviral regimens in certain populations of HIV-infected treatment-naive patients for whom a randomized controlled trial is not feasible or desirable. They can also be useful to establish initial estimates of efficacy and safety/tolerability of novel regimens to inform the design of large phase III trials. In this article, we discuss key design considerations for such single-arm studies. PMID:23228206

  1. The Design of Single-Arm Clinical Trials of Combination Antiretroviral Regimens for Treatment-Naive HIV-Infected Patients

    PubMed Central

    Rosenkranz, Susan L.; Taiwo, Babafemi; Para, Michael F.; Eron, Joseph J.; Hughes, Michael D.

    2013-01-01

    Abstract Single-arm clinical trials are useful to evaluate antiretroviral regimens in certain populations of HIV-infected treatment-naive patients for whom a randomized controlled trial is not feasible or desirable. They can also be useful to establish initial estimates of efficacy and safety/tolerability of novel regimens to inform the design of large phase III trials. In this article, we discuss key design considerations for such single-arm studies. PMID:23228206

  2. 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

  3. Turbojet-engine Starting and Acceleration

    NASA Technical Reports Server (NTRS)

    Mc Cafferty, R. J.; Straight, D. M.

    1956-01-01

    From considerations of safety and reliability in performance of gas-turbine aircraft, it is clear that engine starting and acceleration are of utmost importance. For this reason extensive efforts have been devoted to the investigation of the factors involved in the starting and acceleration of engines. In chapter III it is shown that certain basic combustion requirements must be met before ignition can occur; consequently, the design and operation of an engine must be tailored to provide these basic requirements in the combustion zone of the engine, particularly in the vicinity of the ignition source. It is pointed out in chapter III that ignition by electrical discharges is aided by high pressure, high temperature, low gas velocity and turbulence, gaseous fuel-air mixture, proper mixture strength, and-an optimum spark. duration. The simultaneous achievement of all these requirements in an actual turbojet-engine combustor is obviously impossible, yet any attempt to satisfy as many requirements as possible will result in lower ignition energies, lower-weight ignition systems, and greater reliability. These factors together with size and cost considerations determine the acceptability of the final ignition system. It is further shown in chapter III that the problem of wall quenching affects engine starting. For example, the dimensions of the volume to be burned must be larger than the quenching distance at the lowest pressure and the most adverse fuel-air ratio encountered. This fact affects the design of cross-fire tubes between adjacent combustion chambers in a tubular-combustor turbojet engine. Only two chambers in these engines contain spark plugs; therefore, the flame must propagate through small connecting tubes between the chambers. The quenching studies indicate that if the cross-fire tubes are too narrow the flame will not propagate from one chamber to another. In order to better understand the role of the basic factors in actual engine operation, many investigations have been conducted in single combustors from gas-turbine engines and in full-scale engines in altitude tanks and in flight. The purpose of the present chapter is to discuss the results of such studies and, where possible, to interpret these results qualitatively in terms of the basic requirements reported in chapter III. The discussion parallels the three phases of turbojet engine starting: (1) Ignition of the fuel-air mixture (2) Propagation of flame throughout the combustion zone (3) Acceleration of the engine to operating speed.

  4. Magnetic resonance imaging of folic acid-coated magnetite nanoparticles reflects tissue biodistribution of long-acting antiretroviral therapy

    PubMed Central

    Li, Tianyuzi; Gendelman, Howard E; Zhang, Gang; Puligujja, Pavan; McMillan, JoEllyn M; Bronich, Tatiana K; Edagwa, Benson; Liu, Xin-Ming; Boska, Michael D

    2015-01-01

    Regimen adherence, systemic toxicities, and limited drug penetrance to viral reservoirs are obstacles limiting the effectiveness of antiretroviral therapy (ART). Our laboratory’s development of the monocyte-macrophage-targeted long-acting nanoformulated ART (nanoART) carriage provides a novel opportunity to simplify drug-dosing regimens. Progress has nonetheless been slowed by cumbersome, but required, pharmacokinetic (PK), pharmacodynamics, and biodistribution testing. To this end, we developed a small magnetite ART (SMART) nanoparticle platform to assess antiretroviral drug tissue biodistribution and PK using magnetic resonance imaging (MRI) scans. Herein, we have taken this technique a significant step further by determining nanoART PK with folic acid (FA) decorated magnetite (ultrasmall superparamagnetic iron oxide [USPIO]) particles and by using SMART particles. FA nanoparticles enhanced the entry and particle retention to the reticuloendothelial system over nondecorated polymers after systemic administration into mice. These data were seen by MRI testing and validated by comparison with SMART particles and direct evaluation of tissue drug levels after nanoART. The development of alendronate (ALN)-coated magnetite thus serves as a rapid initial screen for the ability of targeting ligands to enhance nanoparticle-antiretroviral drug biodistribution, underscoring the value of decorated magnetite particles as a theranostic tool for improved drug delivery. PMID:26082630

  5. Magnetic resonance imaging of folic acid-coated magnetite nanoparticles reflects tissue biodistribution of long-acting antiretroviral therapy.

    PubMed

    Li, Tianyuzi; Gendelman, Howard E; Zhang, Gang; Puligujja, Pavan; McMillan, JoEllyn M; Bronich, Tatiana K; Edagwa, Benson; Liu, Xin-Ming; Boska, Michael D

    2015-01-01

    Regimen adherence, systemic toxicities, and limited drug penetrance to viral reservoirs are obstacles limiting the effectiveness of antiretroviral therapy (ART). Our laboratory's development of the monocyte-macrophage-targeted long-acting nanoformulated ART (nanoART) carriage provides a novel opportunity to simplify drug-dosing regimens. Progress has nonetheless been slowed by cumbersome, but required, pharmacokinetic (PK), pharmacodynamics, and biodistribution testing. To this end, we developed a small magnetite ART (SMART) nanoparticle platform to assess antiretroviral drug tissue biodistribution and PK using magnetic resonance imaging (MRI) scans. Herein, we have taken this technique a significant step further by determining nanoART PK with folic acid (FA) decorated magnetite (ultrasmall superparamagnetic iron oxide [USPIO]) particles and by using SMART particles. FA nanoparticles enhanced the entry and particle retention to the reticuloendothelial system over nondecorated polymers after systemic administration into mice. These data were seen by MRI testing and validated by comparison with SMART particles and direct evaluation of tissue drug levels after nanoART. The development of alendronate (ALN)-coated magnetite thus serves as a rapid initial screen for the ability of targeting ligands to enhance nanoparticle-antiretroviral drug biodistribution, underscoring the value of decorated magnetite particles as a theranostic tool for improved drug delivery. PMID:26082630

  6. Optimal time for initiating antiretroviral therapy (ART) in HIV-infected, treatment-naive children aged 2 to 5 years old

    PubMed Central

    Siegfried, Nandi; Davies, Mary-Ann; Penazzato, Martina; Muhe, Lulu M; Egger, Matthias

    2014-01-01

    Background The use of combination antiretroviral therapy (cART) comprising three antiretroviral medications from at least two classes of drugs is the current standard treatment for HIV infection in adults and children. Current World Health Organization (WHO) guidelines for antiretroviral therapy recommend early treatment regardless of immunologic thresholds or the clinical condition for all infants (less than one years of age) and children under the age of two years. For children aged two to five years current WHO guidelines recommend (based on low quality evidence) that clinical and immunological thresholds be used to identify those who need to start cART (advanced clinical stage or CD4 counts ? 750 cells/mm3 or per cent CD4 ? 25%). This Cochrane review will inform the current available evidence regarding the optimal time for treatment initiation in children aged two to five years with the goal of informing the revision of WHO 2013 recommendations on when to initiate cART in children. Objectives To assess the evidence for the optimal time to initiate cART in treatment-naive, HIV-infected children aged 2 to 5 years. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the AEGIS conference database, specific relevant conferences, www.clinicaltrials.gov, the World Health Organization International Clinical Trials Registry platform and reference lists of articles. The date of the most recent search was 30 September 2012. Selection criteria Randomised controlled trials (RCTs) that compared immediate with deferred initiation of cART, and prospective cohort studies which followed children from enrolment to start of cART and on cART. Data collection and analysis Two review authors considered studies for inclusion in the review, assessed the risk of bias, and extracted data on the primary outcome of death from all causes and several secondary outcomes, including incidence of CDC category C and B clinical events and per cent CD4 cells (CD4%) at study end. For RCTs we calculated relative risks (RR) or mean differences with 95% confidence intervals (95% CI). For cohort data, we extracted relative risks with 95% CI from adjusted analyses. We combined results from RCTs using a random effects model and examined statistical heterogeneity. Main results Two RCTs in HIV-positive children aged 1 to 12 years were identified. One trial was the pilot study for the larger second trial and both compared initiation of cART regardless of clinical-immunological conditions with deferred initiation until per cent CD4 dropped to <15%. The two trials were conducted in Thailand, and Thailand and Cambodia, respectively. Unpublished analyses of the 122 children enrolled at ages 2 to 5 years were included in this review. There was one death in the immediate cART group and no deaths in the deferred group (RR 2.9; 95% CI 0.12 to 68.9). In the subgroup analysis of children aged 24 to 59 months, there was one CDC C event in each group (RR 0.96; 95% CI 0.06 to 14.87) and 8 and 11 CDC B events in the immediate and deferred groups respectively (RR 0.95; 95% CI 0.24 to 3.73). In this subgroup, the mean difference in CD4 per cent at study end was 5.9% (95% CI 2.7 to 9.1). One cohort study from South Africa, which compared the effect of delaying cART for up to 60 days in 573 HIV-positive children starting tuberculosis treatment (median age 3.5 years), was also included. The adjusted hazard ratios for the effect on mortality of delaying ART for more than 60 days was 1.32 (95% CI 0.55 to 3.16). Authors’ conclusions This systematic review shows that there is insufficient evidence from clinical trials in support of either early or CD4-guided initiation of ART in HIV-infected children aged 2 to 5 years. Programmatic issues such as the retention in care of children in ART programmes in resource-limited settings will need to be considered when formulating WHO 2013 recommendations. PMID:24114324

  7. 46 CFR 112.50-7 - Compressed air starting.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 4 2012-10-01 2012-10-01 false Compressed air starting. 112.50-7 Section 112.50-7... air starting. A compressed air starting system must meet the following: (a) The starting, charging... air compressors addressed in paragraph (c)(3)(i) of this section. (b) The compressed air...

  8. 46 CFR 112.50-7 - Compressed air starting.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 4 2013-10-01 2013-10-01 false Compressed air starting. 112.50-7 Section 112.50-7... air starting. A compressed air starting system must meet the following: (a) The starting, charging... air compressors addressed in paragraph (c)(3)(i) of this section. (b) The compressed air...

  9. 46 CFR 112.50-7 - Compressed air starting.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 4 2011-10-01 2011-10-01 false Compressed air starting. 112.50-7 Section 112.50-7... air starting. A compressed air starting system must meet the following: (a) The starting, charging... air compressors addressed in paragraph (c)(3)(i) of this section. (b) The compressed air...

  10. 40 CFR 86.136-90 - Engine starting and restarting.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... the engine until it starts. (b) Diesel vehicles. The engine shall be started according to the... 40 Protection of Environment 19 2014-07-01 2014-07-01 false Engine starting and restarting. 86.136... Complete Heavy-Duty Vehicles; Test Procedures § 86.136-90 Engine starting and restarting. (a)...

  11. 40 CFR 1065.930 - Engine starting, restarting, and shutdown.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 32 2010-07-01 2010-07-01 false Engine starting, restarting, and... Systems § 1065.930 Engine starting, restarting, and shutdown. Unless the standard-setting part specifies otherwise, start, restart, and shut down the test engine for field testing as follows: (a) Start or...

  12. 40 CFR 1065.930 - Engine starting, restarting, and shutdown.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 33 2011-07-01 2011-07-01 false Engine starting, restarting, and... Systems § 1065.930 Engine starting, restarting, and shutdown. Unless the standard-setting part specifies otherwise, start, restart, and shut down the test engine for field testing as follows: (a) Start or...

  13. 40 CFR 86.536-78 - Engine starting and restarting.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 18 2010-07-01 2010-07-01 false Engine starting and restarting. 86.536... Regulations for 1978 and Later New Motorcycles; Test Procedures § 86.536-78 Engine starting and restarting. (a)(1) The engine shall be started according to the manufacturer's recommended starting procedures....

  14. 40 CFR 1065.930 - Engine starting, restarting, and shutdown.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Systems § 1065.930 Engine starting, restarting, and shutdown. Unless the standard-setting part specifies otherwise, start, restart, and shut down the test engine for field testing as follows: (a) Start or restart... 40 Protection of Environment 32 2010-07-01 2010-07-01 false Engine starting, restarting,...

  15. 7 CFR 3015.22 - Starting date of retention period.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 15 2010-01-01 2010-01-01 false Starting date of retention period. 3015.22 Section... Access Requirements § 3015.22 Starting date of retention period. (a) General. The retention period starts... funding period starts on the day the recipient submits to USDA its annual or final expenditure report...

  16. 46 CFR 112.50-3 - Hydraulic starting.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 4 2014-10-01 2014-10-01 false Hydraulic starting. 112.50-3 Section 112.50-3 Shipping... POWER SYSTEMS Emergency Diesel and Gas Turbine Engine Driven Generator Sets § 112.50-3 Hydraulic starting. A hydraulic starting system must meet the following: (a) The hydraulic starting system must be...

  17. 46 CFR 112.50-3 - Hydraulic starting.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 4 2013-10-01 2013-10-01 false Hydraulic starting. 112.50-3 Section 112.50-3 Shipping... POWER SYSTEMS Emergency Diesel and Gas Turbine Engine Driven Generator Sets § 112.50-3 Hydraulic starting. A hydraulic starting system must meet the following: (a) The hydraulic starting system must be...

  18. 46 CFR 112.50-3 - Hydraulic starting.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 4 2012-10-01 2012-10-01 false Hydraulic starting. 112.50-3 Section 112.50-3 Shipping... POWER SYSTEMS Emergency Diesel and Gas Turbine Engine Driven Generator Sets § 112.50-3 Hydraulic starting. A hydraulic starting system must meet the following: (a) The hydraulic starting system must be...

  19. 46 CFR 112.50-3 - Hydraulic starting.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 4 2011-10-01 2011-10-01 false Hydraulic starting. 112.50-3 Section 112.50-3 Shipping... POWER SYSTEMS Emergency Diesel and Gas Turbine Engine Driven Generator Sets § 112.50-3 Hydraulic starting. A hydraulic starting system must meet the following: (a) The hydraulic starting system must be...

  20. 46 CFR 112.50-3 - Hydraulic starting.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false Hydraulic starting. 112.50-3 Section 112.50-3 Shipping... POWER SYSTEMS Emergency Diesel and Gas Turbine Engine Driven Generator Sets § 112.50-3 Hydraulic starting. A hydraulic starting system must meet the following: (a) The hydraulic starting system must be...

  1. Locality Aware Concurrent Start for Stencil Applications

    SciTech Connect

    Shrestha, Sunil; Gao, Guang R.; Manzano Franco, Joseph B.; Marquez, Andres; Feo, John T.

    2015-02-10

    Stencil computations are at the heart of many physical simulations used in scientific codes. Thus, there exists a plethora of optimization efforts for this family of computations. Among these techniques, tiling techniques that allow concurrent start have proven to be very efficient in providing better performance for these critical kernels. Nevertheless, with many core designs being the norm, these optimization techniques might not be able to fully exploit locality (both spatial and temporal) on multiple levels of the memory hierarchy without compromising parallelism. It is no longer true that the machine can be seen as a homogeneous collection of nodes with caches, main memory and an interconnect network. New architectural designs exhibit complex grouping of nodes, cores, threads, caches and memory connected by an ever evolving network-on-chip design. These new designs may benefit greatly from carefully crafted schedules and groupings that encourage parallel actors (i.e. threads, cores or nodes) to be aware of the computational history of other actors in close proximity. In this paper, we provide an efficient tiling technique that allows hierarchical concurrent start for memory hierarchy aware tile groups. Each execution schedule and tile shape exploit the available parallelism, load balance and locality present in the given applications. We demonstrate our technique on the Intel Xeon Phi architecture with selected and representative stencil kernels. We show improvement ranging from 5.58% to 31.17% over existing state-of-the-art techniques.

  2. Stability starts with the purchase specification

    NASA Astrophysics Data System (ADS)

    Gould, Gerald

    1990-11-01

    Comprehensive Purchase Specification(s) must not merely define a generic type of material by chemistry and mechanical properties. It must be capable of specifying the method of material formation (i. e. rolled cast forged vacuum hot pressed etc. ) it''s grain size preferred orientation homogeneity etc and the method of material removal to minimize surface damage and/or work hardening. Starting out with heavily stressed material will in many instances negate the possibility of fabricating components which can be subsequently processed and heat treated to eliminate the residual stresses which cause components to change dimensionally and/or creep or experience premature micro-yielding - the anisotropy of work hardening Bauschinger Effect. . MATERIAL AND FORM SELECTION In order to produce parts or precision assemblies with maximum stability one must recognize the various forms that are available and the selection of alloys to choose from. The next step may be selecting a form with the best homogeneity or a form which will permit the subsequent processing to a condition of useable stability (minimum residual stress). Another vexing problem is the fabricating of parts from bar or plate for prototypes and the subsequent purchase of cast or powder compacted parts for production. Two very diverse material conditions. A brief familiarization (See Figure 1 and 2) with the forms available from a partial list is a starting point in the ultimate selection of form alloy condition and subsequent

  3. Predicting Malawian Women’s Intention to Adhere to Antiretroviral Therapy

    PubMed Central

    McKinney, Ogbochi; Modeste, Naomi N.; Lee, Jerry W.; Gleason, Peter C.

    2015-01-01

    Background With the increase in scaling up of antiretroviral therapy (ART), knowledge of the need for adherence to ART is pivotal for successful treatment outcomes. Design and Methods A cross-sectional study was carried out between October and December 2013. We administered theory of planned behaviour (TPB) and adherence questionnaires to 358 women aged 18-49 years, from a rural and urban ART-clinics in southern Malawi. Hierarchical linear regression models were used to predict intentions to adhere to ART. Results Regression models show that attitude (?=0.47), subjective norm (?=0.31) and perceived behavioural control (?=0.12) explain 55% of the variance in intentions to adhere to ART. The relationship between both food insecurity and perceived side effects with intentions to adhere to ART is mediated by attitude, subjective norm, and perceived behavioural control. Household (r=0.20) and individual (r=0.21) food insecurity were positively and significantly correlated with perceived behavioural control. Household food insecurity had a negative correlation with perceived side effects (r=-0.11). Perceived side effects were positively correlated with attitude (r=0.25). There was no statistically significant relationship between intentions to adhere to ART in the future and one month self-report of past month adherence. These interactions suggest that attitude predicted adherence only when food insecurity is high or perception of side effects is strong. Conclusions This study shows that modification might be needed when using TPB constructs in resource constraint environments. Significance for public health The knowledge of the rates of adherence to antiretroviral therapy (ART) could be used to evaluate planning and project, which could lead to better outcomes predicted by treatment efficacy data. In addition, knowledge of adherence behaviour could help the development of interventions focusing on collaboration between healthcare providers and Malawian government to provide food support for patients on ART. The interventions could also focus on providing better counselling support to improve beliefs regarding control over taking the medication and perceived versus real side effects. It is relevant for public health professors to understand factors influencing women’s ART adherence, in order to create interventions that are appropriate for increasing ART adherence, which may lead to improved outcomes among women with HIV living in endemic regions with limited treatment access. PMID:26425494

  4. Retained in HIV Care But Not on Antiretroviral Treatment: A Qualitative Patient-Provider Dyadic Study

    PubMed Central

    Christopoulos, Katerina A.; Olender, Susan; Lopez, Andrea M.; Lekas, Helen-Maria; Jaiswal, Jessica; Mellman, Will; Geng, Elvin; Koester, Kimberly A.

    2015-01-01

    Background Patients retained in HIV care but not on antiretroviral therapy (ART) represent an important part of the HIV care cascade in the United States. Even in an era of more tolerable and efficacious ART, decision making in regards to ART offer and uptake remains complex and calls for exploration of both patient and provider perspectives. We sought to understand reasons for lack of ART usage in patients meeting the Health Resources Services Administration definition of retention as well as what motivated HIV primary care appointment attendance in the absence of ART. Methods and Findings We conducted a qualitative study consisting of 70 in-depth interviews with ART-naïve and ART-experienced patients off ART and their primary care providers in two urban safety-net HIV clinics in San Francisco and New York. Twenty patients and their providers were interviewed separately at baseline, and 15 dyads were interviewed again after at least 3 mo and another clinic visit in order to understand any ART use in the interim. We applied dyadic analysis to our data. Nearly all patients were willing to consider ART, and 40% of the sample went on ART, citing education on newer antiretroviral drugs, acceptance of HIV diagnosis, social support, and increased confidence in their ability to adhere as facilitators. However, the strength of the provider recommendation of ART played an important role. Many patients had internalized messages from providers that their health was too good to warrant ART. In addition, providers, while demonstrating patient-centered care through sensitivity to patients experiencing psychosocial instability, frequently muted the offer of ART, at times unintentionally. In the absence of ART, lab monitoring, provider relationships, access to social services, opiate pain medications, and acute symptoms motivated care. The main limitations of this study were that treatment as prevention was not explored in depth and that participants were recruited from academic HIV clinics in the US, making the findings most generalizable to this setting. Conclusions Provider communication with regard to ART is a key focus for further exploration and intervention in order to increase ART uptake for those retained in HIV care. PMID:26263532

  5. Economic evaluation of initial antiretroviral therapy for HIV-infected patients: an update of Italian guidelines

    PubMed Central

    Colombo, Giorgio L; Di Matteo, Sergio; Antinori, Andrea; Medaglia, Massimo; Murachelli, Silvia; Rizzardini, Giuliano

    2013-01-01

    Introduction Highly active antiretroviral therapy (HAART) has allowed many HIV-infected patients to enjoy longer survival and a better quality of life. We performed an economic analysis to estimate the cost-effectiveness of HAART regimens in Italy for managing HIV-naïve infected patients with a viral load below 100,000 copies/mL. Patients and methods The population considered in the model consisted of adult subjects with an HIV viral load below 100,000 copies/mL who received antiretroviral HAART treatment for the first time, according to the Italian National Guidelines with recommendation grade A1. The incremental cost-effectiveness analysis of quality-adjusted life years (QALYs) was carried out by means of a Markov model. Both the outcomes (QALYs) and the costs were discounted by 3.5%. The time horizon adopted in the model was 10 years. The point of view of the analysis was that of the Italian national health service. Results The tenofovir (TDF)/emtricitabine (FTC)/rilpivirine (RPV) single-tablet regimen (STR) (€7,417.00) revealed the lowest mean treatment cost. TDF/FTC + raltegravir (RAL) showed a better quality of life (0.906 QALY/year), followed by TDF/FTC/RPV (STR; 0.900 QALY/year), TDF/FTC + RPV (multipill regimen) (0.889 QALY/year), and TDF/FTC + atazanavir (ATV/r) (0.886 QALY/year). TDF/FTC/RPV (STR) appeared to be the most cost-effective therapeutic choice (€13,655.00), followed by TDF/FTC + RPV (multipill regimen) (€15,803.00), and TDF/FTC + efavirenz (EFV) (€16,181.00). The sensitivity analysis on the main variables confirmed the validity of the base case scenario. Conclusion STR (TDF/FTC/RPV) is the most cost-effective treatment strategy compared with the other therapeutic regimens recommended by the Italian guidelines for the treatment of naïve patients with a viral load <100,000 copies/mL. The inclusion of adverse-event management of HIV-infected patients affects the cost-effectiveness ratio of all HAART regimens. PMID:24124383

  6. Oral health activities of Early Head Start and Migrant and Seasonal Head Start programs.

    PubMed

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

    2012-08-01

    Guidelines recommend that Migrant and Seasonal Head Start programs (MSHS) address the dental needs of children of migrant and seasonal farmworkers. This study describes parent- and child-oriented oral health activities of North Carolina's MSHS programs and compares them with non-migrant Early Head Start (EHS) programs using data collected from a questionnaire completed by teachers and family services staff. Migrant and Seasonal Head Start staff reported engaging in more oral health activities than EHS staff, which was confirmed by results of logit and ordered logit regression models. Despite promising findings about the engagement of MSHS staff, participation in oral health activities is lower than recommended. Differences between EHS and MSHS programs might be due to differing needs of enrolled children and families or to different approaches to meeting the needs of families. PMID:24212169

  7. Siberian company starts up modular refinery

    SciTech Connect

    1996-03-18

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

  8. Method and apparatus for starting supersonic compressors

    DOEpatents

    Lawlor, Shawn P

    2013-08-06

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

  9. Breakthrough seizures after starting vilazodone for depression.

    PubMed

    McKean, James; Watts, Hannah; Mokszycki, Robert

    2015-03-01

    Vilazodone is a new selective serotonin reuptake inhibitor (SSRI) and serotonin 5-HT1a partial agonist that is approved by the United States Food and Drug Administration to treat major depression. SSRI-induced seizures are rare and are more likely to be associated with larger doses and severe symptoms such as those present in serotonin syndrome. Several case reports have implicated SSRIs, buspirone, or the combination of these agents as the cause of seizures, but these reports were confounded with either coingestions or doses that exceeded FDA recommendations. We describe a 22-year-old woman with a history of seizure disorder who had been seizure free for the previous 8 years and experienced two breakthrough seizures shortly after starting vilazodone. Her dose of vilazodone had recently been titrated to 40 mg/day when she experienced the first seizure. She was instructed to taper vilazodone over the next several days, then discontinue the drug, and then follow up with her neurologist. Based on the patient's history, physical examination, and recent dose increase, it was plausible that vilazodone was the cause of the seizures. Use of the Naranjo adverse drug reaction probability scale indicated a possible relationship (score of 4) between her development of seizures and vilazodone therapy. The pharmacodynamics of this particular class of SSRI has both proconvulsive and anticonvulsive mechanisms. This is of particular concern in patients with a history of seizure disorder who are starting antidepressive therapy. In persons with epilepsy who are taking vilazodone and experience breakthrough seizures, practitioners should consider this drug as a potential cause of these seizures. Thus, until future research and experience with vilazodone can provide a definitive answer, clinicians should be cautious when prescribing this medication to treat depression in patients with a history of seizure disorder. PMID:25809181

  10. Predictors of Persistent Anaemia in the First Year of Antiretroviral Therapy: A Retrospective Cohort Study from Goma, the Democratic Republic of Congo

    PubMed Central

    Akilimali, Pierre Zalagile; Kashala-Abotnes, Espérance; Musumari, Patou Masika; Kayembe, Patrick Kalambayi; Tylleskar, Thorkild; Mapatano, Mala Ali

    2015-01-01

    Background Anaemia is associated with adverse outcomes including early death in the first year of antiretroviral therapy (ART). This study reports on the factors associated with persistent anaemia among HIV-infected patients initiating ART in the Democratic Republic of Congo (DR Congo). Methods We conducted a retrospective cohort study and analyzed data from patients receiving HIV care between January 2004 and December 2012 at two major hospitals in Goma, DR Congo. Haemoglobin concentrations of all patients on ART regimen were obtained prior to and within one year of ART initiation. A logistic regression model was used to identify the predictors of persistent anaemia after 12 months of ART. Results Of 756 patients, 69% of patients were anaemic (IC95%: 65.7–72.3) at baseline. After 12 months of follow up, there was a 1.2 g/dl average increase of haemoglobin concentration (P < 0.001) with differences depending on the therapeutic regimen. Patients who received zidovudine (AZT) gained less than those who did not receive AZT (0.99 g/dl vs 1.33 g/dl; p< 0.001). Among 445 patient who had anaemia at the beginning, 33% (147/445) had the condition resolved. Among patients with anaemia at ART initiation, those who did not receive cotrimoxazole prophylaxis before starting ART(AOR 3.89; 95% CI 2.09–7.25; P < 0.001) and a AZT initial regimen (AOR 2.19; 95% CI 1.36–3.52; P < 0.001) were significantly at risk of persistent anaemia. Conclusions More than two thirds of patients had anaemia at baseline. The AZT-containing regimen and absence of cotrimoxazole prophylaxis before starting ART were associated with persistent anaemia 12 months, after initiation of treatment. Considering the large proportion of patients with persistence of anaemia at 12 months, we suggest that it is necessary to conduct a large study to assess anaemia among HIV-infected patients in Goma. PMID:26474481

  11. A Prognostic Model for Estimating the Time to Virologic Failure in HIV-1 Infected Patients Undergoing a New Combination Antiretroviral Therapy Regimen

    PubMed Central

    2011-01-01

    Background HIV-1 genotypic susceptibility scores (GSSs) were proven to be significant prognostic factors of fixed time-point virologic outcomes after combination antiretroviral therapy (cART) switch/initiation. However, their relative-hazard for the time to virologic failure has not been thoroughly investigated, and an expert system that is able to predict how long a new cART regimen will remain effective has never been designed. Methods We analyzed patients of the Italian ARCA cohort starting a new cART from 1999 onwards either after virologic failure or as treatment-naïve. The time to virologic failure was the endpoint, from the 90th day after treatment start, defined as the first HIV-1 RNA > 400 copies/ml, censoring at last available HIV-1 RNA before treatment discontinuation. We assessed the relative hazard/importance of GSSs according to distinct interpretation systems (Rega, ANRS and HIVdb) and other covariates by means of Cox regression and random survival forests (RSF). Prediction models were validated via the bootstrap and c-index measure. Results The dataset included 2337 regimens from 2182 patients, of which 733 were previously treatment-naïve. We observed 1067 virologic failures over 2820 persons-years. Multivariable analysis revealed that low GSSs of cART were independently associated with the hazard of a virologic failure, along with several other covariates. Evaluation of predictive performance yielded a modest ability of the Cox regression to predict the virologic endpoint (c-index?0.70), while RSF showed a better performance (c-index?0.73, p < 0.0001 vs. Cox regression). Variable importance according to RSF was concordant with the Cox hazards. Conclusions GSSs of cART and several other covariates were investigated using linear and non-linear survival analysis. RSF models are a promising approach for the development of a reliable system that predicts time to virologic failure better than Cox regression. Such models might represent a significant improvement over the current methods for monitoring and optimization of cART. PMID:21672248

  12. Retention in care and medication adherence: current challenges to antiretroviral therapy success.

    PubMed

    Holtzman, Carol W; Brady, Kathleen A; Yehia, Baligh R

    2015-04-01

    Health behaviors such as retention in HIV medical care and adherence to antiretroviral therapy (ART) pose major challenges to reducing new HIV infections, addressing health disparities, and improving health outcomes. Andersen's Behavioral Model of Health Service Use provides a conceptual framework for understanding how patient and environmental factors affect health behaviors and outcomes, which can inform the design of intervention strategies. Factors affecting retention and adherence among persons with HIV include patient predisposing factors (e.g., mental illness, substance abuse), patient-enabling factors (e.g., social support, reminder strategies, medication characteristics, transportation, housing, insurance), and healthcare environment factors (e.g., pharmacy services, clinic experiences, provider characteristics). Evidence-based recommendations for improving retention and adherence include (1) systematic monitoring of clinic attendance and ART adherence; (2) use of peer or paraprofessional navigators to re-engage patients in care and help them remain in care; (3) optimization of ART regimens and pharmaceutical supply chain management systems; (4) provision of reminder devices and tools; (5) general education and counseling; (6) engagement of peer, family, and community support groups; (7) case management; and (8) targeting patients with substance abuse and mental illness. Further research is needed on effective monitoring strategies and interventions that focus on improving retention and adherence, with specific attention to the healthcare environment. PMID:25792300

  13. In vitro-in vivo Pharmacokinetic correlation model for quality assurance of antiretroviral drugs

    PubMed Central

    Restrepo Valencia, Piedad

    2015-01-01

    Introduction: The in vitro-in vivo pharmacokinetic correlation models (IVIVC) are a fundamental part of the drug discovery and development process. The ability to accurately predict the in vivo pharmacokinetic profile of a drug based on in vitro observations can have several applications during a successful development process. Objective: To develop a comprehensive model to predict the in vivo absorption of antiretroviral drugs based on permeability studies, in vitro and in vivo solubility and demonstrate its correlation with the pharmacokinetic profile in humans. Methods: Analytical tools to test the biopharmaceutical properties of stavudine, lamivudine y zidovudine were developed. The kinetics of dissolution, permeability in caco-2 cells and pharmacokinetics of absorption in rabbits and healthy volunteers were evaluated. Results: The cumulative areas under the curve (AUC) obtained in the permeability study with Caco-2 cells, the dissolution study and the pharmacokinetics in rabbits correlated with the cumulative AUC values in humans. These results demonstrated a direct relation between in vitro data and absorption, both in humans and in the in vivo model. Conclusions: The analytical methods and procedures applied to the development of an IVIVC model showed a strong correlation among themselves. These IVIVC models are proposed as alternative and cost/effective methods to evaluate the biopharmaceutical properties that determine the bioavailability of a drug and their application includes the development process, quality assurance, bioequivalence studies and pharmacosurveillance. PMID:26600625

  14. Pneumococcal vaccination among HIV-infected adult patients in the era of combination antiretroviral therapy

    PubMed Central

    Lee, Kuan-Yeh; Tsai, Mao-Song; Kuo, Kuang-Che; Tsai, Jen-Chih; Sun, Hsin-Yun; Cheng, Aristine C; Chang, Sui-Yuan; Lee, Chen-Hsiang; Hung, Chien-Ching

    2014-01-01

    HIV-infected patients remain at higher risk for pneumococcal disease than the general population despite immune reconstitution and suppression of HIV replication with combination antiretroviral therapy. Vaccination with 23-valent pneumococcal polysaccharide vaccine (PPV23) composed of T-cell-independent antigens has been recommended to reduce the risk of pneumococcal disease in HIV-infected adults. However, given the heterogeneity of study design, execution and subjects enrolled, studies examining serological responses to PPV23 yielded conflicting results and observational studies of clinical effectiveness only provided moderate evidence to support the routine use of PPV23 in HIV-infected adults. Pneumococcal conjugate vaccine (PCV), with conjugation of the capsular polysaccharide to a protein carrier, is more immunogenic than PPV23 and has been demonstrated to protect against pneumococcal disease in HIV-infected children and recurrent invasive pneumococcal disease in HIV-infected adolescents and adults. Guidelines have recently been revised to recommend that HIV-infected patients aged 19 y or older receive one dose of 13-valent pneumococcal conjugate vaccine (PCV13) followed by a booster vaccination with PPV23. In this paper, we review the studies using different vaccination strategies to improve immunogenicity among HIV-infected adult patients. PMID:25483681

  15. Antiretroviral medication support practices among partners of men who have sex with men: a qualitative study.

    PubMed

    Wrubel, Judith; Stumbo, Scott; Johnson, Mallory O

    2008-11-01

    The aim of this qualitative study is to describe the practical support for antiretroviral therapy (ART) adherence offered by partners of men with HIV. Twenty couples in which at least one partner was HIV positive and on ART were interviewed separately about their involvement in their partners' ART adherence. The interview elicited narratives of specific recent events around taking medication, as well as accounts of what the participants usually did to support their partners' adherence. Three members of the qualitative team coded and verified the interviews for adherence support practices. Partners offered a wide range of kinds of practical support. Reminding included (1) regular reminding that was habitually offered, (2) situational reminding adapted to changing circumstances, and (3) intensive reminding, either regular (i.e., nagging) or situational. Instrumental helping involved monitoring medication adherence, bringing or setting out medications at the dose time, organizing the pills, and requesting and/or picking up refills. Coaching involved situational problem-solving and shaping behavior by reinforcing incremental gains and offering affirmations. Findings demonstrate a range of support practices for ART adherence, often tailored to partners' styles or to the changing process of adherence. By examining narratives of support transactions as they occurred, the study discriminated among the different dimensions, forms, sources and contexts of social support. These distinctions, often neglected in social support research, have implications for HIV care and research. PMID:19025479

  16. Service delivery interventions to improve adolescents’ linkage, retention and adherence to antiretroviral therapy and HIV care*

    PubMed Central

    MacPherson, Peter; Munthali, Chigomezgo; Ferguson, Jane; Armstrong, Alice; Kranzer, Katharina; Ferrand, Rashida A.; Ross, David A.

    2015-01-01

    OBJECTIVES Adolescents living with HIV face substantial difficulties in accessing HIV care services and have worse treatment outcomes than other age groups. The objective of this review was to evaluate the effectiveness of service delivery interventions to improve adolescents’ linkage from HIV diagnosis to antiretroviral therapy (ART) initiation, retention in HIV care and adherence to ART. METHODS We systematically searched the Medline, SCOPUS and Web of Sciences databases and conference abstracts from the International AIDS Conference and International Conference on AIDS and STIs in Africa (ICASA). Studies published in English between 1st January 2001 and 9th June 2014 were included. Two authors independently evaluated reports for eligibility, extracted data and assessed methodological quality using the Cochrane risk of bias tool and Newcastle–Ottawa Scale. RESULTS Eleven studies from nine countries were eligible for review. Three studies were randomised controlled trials. Interventions assessed included individual and group counselling and education; peer support; directly observed therapy; financial incentives; and interventions to improve the adolescent-friendliness of clinics. Most studies were of low to moderate methodological quality. CONCLUSIONS This review identified limited evidence on the effectiveness of service delivery interventions to support adolescents’ linkage from HIV diagnosis to ART initiation, retention on ART and adherence to ART. Although recommendations are qualified because of the small numbers of studies and limited methodological quality, offering individual and group education and counselling, financial incentives, increasing clinic accessibility and provision of specific adolescent-tailored services appear promising interventions and warrant further investigation. PMID:25877007

  17. Adherence to antiretroviral therapy in a context of universal access, in Rio de Janeiro, Brazil.

    PubMed

    Remien, R H; Bastos, F I; Jnr, V Terto; Raxach, J C; Pinto, R M; Parker, R G; Berkman, A; Hacker, M A

    2007-07-01

    Adherence is integral to improving and maintaining the health and quality of life of people living with HIV. Two-hundred HIV-positive adults recruited from teaching hospitals and non-governmental organizations (NGOs) in Rio de Janeiro City were assessed on socio-demographic factors, adherence to antiretroviral therapy (ART) and psychosocial factors hypothesized to be associated with ART. Predictors of non-adherence were analyzed using bivariate and multivariate analyses. Self-reported medication adherence was high (82% had adherence >90%). Non-adherence was associated with personal factors (i.e. sexual orientation, self-efficacy), physical factors (i.e. loss of appetite) and interpersonal factors (i.e. doctor-patient relationship). Adherence in Brazil is as good, if not better, than that seen in the US and western Europe, which is noteworthy since the sample was derived predominantly from public healthcare settings. It is possible that the connection to NGOs in Rio de Janeiro City played a helpful role in achieving high levels of adherence in this sample of people living with HIV and AIDS. Recommendations, based on study findings, include enhancing and sustaining supportive services for NGOs, promoting patient self-efficacy and behavioral skills for adherence, increasing social network support and having healthcare providers directly address patients' medication beliefs, attitudes and experience with side effects. PMID:17573593

  18. Adherence to antiretroviral therapy in a context of universal access, in Rio de Janeiro, Brazil

    PubMed Central

    REMIEN, R. H.; BASTOS, F. I.; TERTO, V.; RAXACH, J. C.; PINTO, R. M.; PARKER, R. G.; BERKMAN, A.; HACKER, M. A.

    2012-01-01

    Adherence is integral to improving and maintaining the health and quality of life of people living with HIV. Two-hundred HIV-positive adults recruited from teaching hospitals and non-governmental organizations (NGOs) in Rio de Janeiro City were assessed on socio-demographic factors, adherence to antiretroviral therapy (ART) and psychosocial factors hypothesized to be associated with ART. Predictors of non-adherence were analyzed using bivariate and multivariate analyses. Self-reported medication adherence was high (82% had adherence > 90%). Non-adherence was associated with personal factors (i.e. sexual orientation, self-efficacy), physical factors (i.e. loss of appetite) and interpersonal factors (i.e. doctor-patient relationship). Adherence in Brazil is as good, if not better, than that seen in the US and western Europe, which is noteworthy since the sample was derived predominantly from public healthcare settings. It is possible that the connection to NGOs in Rio de Janeiro City played a helpful role in achieving high levels of adherence in this sample of people living with HIV and AIDS. Recommendations, based on study findings, include enhancing and sustaining supportive services for NGOs, promoting patient self-efficacy and behavioral skills for adherence, increasing social network support and having healthcare providers directly address patients’ medication beliefs, attitudes and experience with side effects. PMID:17573593

  19. Risk factors for intestinal parasitosis among antiretroviral-treated HIV/AIDS patients in Ethiopia.

    PubMed

    Mahmud, Mahmud Abdulkader; Bezabih, Afework Mulugeta; Gebru, Rezene Berhe

    2014-10-01

    Summary A cross-sectional survey was conducted to determine the risk factors associated with intestinal parasitosis in HIV/AIDS patients receiving antiretroviral therapy (ART). Socio-demographic information was collected and faecal samples were analysed from 384 randomly selected patients on ART. Data on CD4+ T-cell counts and World Health Organization clinical staging were obtained from the medical records at the hospital. The overall prevalence of intestinal parasitosis was 56% (95% confidence interval [CI]: 51% to 61%). No opportunistic intestinal parasites or Schistosoma haematobium eggs were detected. Unavailability of latrine and lack of hand washing with soap were associated with Entamoeba histolytica/dispar (adjusted odds ratio [AOR], 2.75; 95% CI: 1.77 to 4.27 and AOR, 2.67; 95% CI: 1.60 to 4.44, respectively) and Giardia lamblia (AOR, 2.08; 95% CI: 1.08 to 3.99 and AOR, 2.46; 95% CI: 1.06 to 5.75, respectively) infections. Intestinal parasitosis was significantly associated with low CD4 cell count (p?=?0.002). In contrast, intestinal parasitic infections were not associated (p?>?0.05) with the World Health Organization disease staging. In summary, poor personal hygiene and sanitation practice contributed to the high prevalence of intestinal parasitosis. Routine diagnosis for intestinal parasitic infections should be performed in patients attending ART clinics in this setting. PMID:24554001

  20. Viraemia and HIV-1 drug resistance mutations among patients receiving antiretroviral treatment in Mozambique.

    PubMed

    Maldonado, F; Biot, M; Roman, F; Masquelier, C; Anapenge, M; Bastos, R; Chuquela, H C; Arendt, V; Schmit, J C; Zachariah, R

    2009-06-01

    This study was conducted among individuals taking first-line antiretroviral treatment (ART) for at least 12 months under programme conditions in Maputo, Mozambique in order to report on the level of detectable viraemia and the proportion and types of drug resistance mutations among those with detectable viral loads. HIV-1 RNA viral load levels (lower detection limit <50 copies/ml) were measured, and resistance mutations were sequenced. One hundred and forty-nine consecutive patients (69% females, median age 36 years) were included after a mean follow-up time of 23 months. One hundred and seven (72%; 95% CI 64-79) had undetectable viral load, while in 42 (28%, 95% CI 21-36) viral load was detectable (range 50-58884 copies/ml). From 15 patients with viral load >1000 copies/ml, 12 viruses were sequenced: eight were C subtypes and four were circulating recombinant forms (CRF08). Eight (5%; 95% CI 2-9) patients with detectable viral load had one or more major resistance mutations. Nucleoside reverse transcriptase inhibitor (NRTI) and non-NRTI mutations were observed. There were no major mutations for resistance to protease inhibitors. In Maputo, the level of detectable viraemia is reassuringly low. While embarking on ART scale-up, wider surveillance is warranted to monitor programme quality and limit the development of drug resistance, which remains a major potential challenge for the future of ART in Africa. PMID:18804251

  1. Access to generic antiretrovirals: inequality, intellectual property law, and international trade agreements.

    PubMed

    Castro, Arachu; Westerhaus, Michael

    2007-01-01

    The governments of numerous low- and middle-income countries are currently instituting rules that strengthen changes in domestic intellectual property legislation, often made to conform to the mandates of "free" trade agreements signed with the United States. These measures frequently include intellectual property provisions that extend beyond the patent law standards agreed upon in recent World Trade Organization negotiations, which promised to balance the exigencies of public health and patent holders. In this paper, we analyze the concern that this augmentation of patent law standards will curtail access to essential medicines, particularly as they relate to the AIDS pandemic. We critically examine the potential threats posed by trade agreements vis-à-vis efforts to provide universal access to antiretroviral medications and contend that the conditioning of economic development upon the strengthening of intellectual property law demands careful attention when public health is at stake. Finally, we examine advocacy successes in challenging patent law and conclude that greater advocacy and policy strategies are needed to ensure the protection of global health in trade negotiations. PMID:17308722

  2. Nevirapine-Based Antiretroviral Therapy Impacts Artesunate and Dihydroartemisinin Disposition in HIV-Infected Nigerian Adults

    PubMed Central

    Fehintola, Fatai A.; Scarsi, Kimberly K.; Ma, Qing; Parikh, Sunil; Morse, Gene D.; Taiwo, Babafemi; Akinola, Ibrahim Tope; Adewole, Isaac F.; Lindegardh, Niklas; Phakderaj, Aphiradee; Ojengbede, Oladosu; Murphy, Robert L.; Akinyinka, Olusegun O.; Aweeka, Francesca T.

    2012-01-01

    Background. Nevirapine- (NVP-) based antiretroviral therapy (ART) and artesunate-amodiaquine are frequently coprescribed in areas of HIV and malaria endemicity. We explored the impact of this practice on artesunate and dihydroartemisinin pharmacokinetics. Methods. We conducted a parallel-group pharmacokinetic comparison between HIV-infected patients receiving NVP-based ART (n = 10) and ART-naive controls (n = 11). Artesunate-amodiaquine 200/600?mg was given daily for three days. Measurement of drug concentrations occurred between 0 and 96 hours after the final dose. Pharmacokinetic parameters were determined using noncompartmental analysis. Results. Comparing the NVP group to controls, clearance of artesunate was reduced 50% (1950 versus 2995 L/h; P = 0.03), resulting in a 45% increase in the AUC0-96 (105 versus 69?ug?hr/L; P = 0.02). The half-life of dihydroartemisinin was shorter in the NVP group (1.6 versuss 3.2?h; P = 0.004), but other dihydroartemisinin pharmacokinetic parameters were unchanged. A lower conversion of artesunate to dihydroartemisinin was observed in the NVP group (dihydroartemisinin: artesunate AUC0-96 = 5.6 versuss 8.5 in NVP and control groups, respectively, P = 0.008). Conclusion. Although NVP-containing ART impacted some pharmacokinetic parameters of artesunate and dihydroartemisinin, overall exposure was similar or better in the NVP group. PMID:22500218

  3. Antiretroviral Therapy in Prevention of HIV and TB: Update on Current Research Efforts

    PubMed Central

    Granich, Reuben; Gupta, Somya; Sutha, Amitabh B; Smyth, Caoimhe; Hoos, David; Vitoria, Marco; Simao, Mariangela; Hankins, Catherine; Schwartlander, Bernard; Ridzon, Renee; Bazin, Brigitte; Williams, Brian; Lo, Ying-Ru; McClure, Craig; Montaner, Julio; Hirnschall, Gottfried

    2011-01-01

    There is considerable scientific evidence supporting the use of antiretroviral therapy (ART) in prevention of human immunodeficiency virus (HIV) and tuberculosis (TB) infections. The complex nature of the HIV and TB prevention responses, resource constraints, remaining questions about cost and feasibility, and the need to use a solid evidence base to make policy decisions, and the implementation challenges to translating trial data to operational settings require a well-organised and coordinated response to research in this area. To this end, we aimed to catalogue the ongoing and planned research activities that evaluate the impact of ART plus other interventions on HIV- and/or TB-related morbidity, mortality, risk behaviour, HIV incidence and transmission. Using a limited search methodology, 50 projects were identified examining ART as prevention, representing 5 regions and 52 countries with a global distribution. There are 24 randomised controlled clinical trials with at least 12 large randomised individual or community cluster trials in resource-constrained settings that are in the planning or early implementation stages. There is considerable heterogeneity between studies in terms of methodology, interventions and geographical location. While the identified studies will undoubtedly advance our understanding of the efficacy and effectiveness of ART for prevention, some key questions may remain unanswered or only partially answered. The large number and wide variety of research projects emphasise the importance of this research issue and clearly demonstrate the potential for synergies, partnerships and coordination across funding agencies. PMID:21999779

  4. The impact of HIV treatment-related stigma on uptake of antiretroviral therapy.

    PubMed

    Cama, Elena; Brener, Loren; Slavin, Sean; de Wit, John

    2015-01-01

    HIV-related stigma has been linked to avoidance of health care services and suboptimal adherence to antiretroviral therapy (ART). However, less is known about concerns of stigma related specifically to the taking of ART in uptake of treatment. This study examines experiences of HIV treatment-related stigma and assesses if these experiences are associated with ART uptake, independent of general HIV-related stigma. People living with HIV (PLHIV; n = 697) were targeted to complete an online questionnaire measuring perceived HIV- and treatment-related stigma, social support, self-esteem, resilience, psychological distress, health satisfaction and quality of life. Findings suggest that experiences of general and treatment-related stigma were common, and that participants appear to experience greater stigma related to taking HIV treatment than general stigma associated with HIV. Neither general nor treatment-related stigma uniquely impacted HIV treatment uptake. Instead, treatment uptake was associated with being older (adjusted OR 1.05; 95% CIs: 1.03, 1.08), greater duration of HIV infection (adjusted OR 1.07; 95% CIs: 1.03-1.11) and having greater health satisfaction (adjusted OR 1.28; 95% CIs: 1.03, 1.59). Findings highlight that concerns around taking HIV treatment can be an added source of stigma for PLHIV, however other factors may be greater contributors to the likelihood of taking HIV treatment. PMID:25564893

  5. Clinical, immunological, and virological outcomes of pediatric antiretroviral therapy in central China

    PubMed Central

    2014-01-01

    Background Antiretroviral therapy (ART) reduces HIV-related mortality and morbidity substantially in children. The clinical characteristics, immunological and virological outcomes were evaluated in HIV-infected children receiving ART. Methods Twenty-six HIV-1-infected children receiving ART in Hubei province, China, were enrolled retrospectively in this study. During the period of ART, plasma viral load, lymphocyte phenotype of CD4 and CD8 cells and clinical events were assessed. Results The median duration of ART was 41 months (18–72.3 months). In children showing clinical improvement, high viral suppression rate below log10 (2.7) copies/ml by the third months of ART was observed. The median CD4 cell counts reached to 820.5/?l by 12 months and the median ratio of CD4/CD8 increased to 0.6 by 21 months. The counts of peripheral white blood cells and red blood cells decreased in the first 12 months, while Hb concentration, MCV and MCH increased (P < 0.001). Conclusions Despite the limited small sample size, ART is an effective strategy for inhibiting HIV replication and reconstructing the immunological response in children with AIDS. PMID:24994004

  6. Antiretroviral treatment in HIV-1 infected pediatric patients: focus on efavirenz

    PubMed Central

    Larru, Beatriz; Eby, Jessica; Lowenthal, Elizabeth D

    2015-01-01

    Efavirenz is a non-nucleoside reverse transcriptase inhibitor (NNRTI), used for the treatment of human immunodeficiency virus (HIV)-1 infection. Approved by the US Food and Drug Administration in 1998, its indication was recently extended to include children as young as 3 months of age. The World Health Organization and many national guidelines consider efavirenz to be the preferred NNRTI for first-line treatment of children over the age of 3 years. Clinical outcomes of patients on three-drug antiretroviral regimens which include efavirenz are as good as or better than those for patients on all other currently approved HIV medications. Efavirenz is dosed once daily and has pediatric-friendly formulations. It is usually well tolerated, with central nervous system side effects being of greatest concern. Efavirenz increases the risk of neural tube defects in nonhuman primates and therefore its use during the first trimester of pregnancy is limited in some settings. With minimal interactions with antituberculous drugs, efavirenz is preferred for use among patients with HIV/tuberculosis coinfection. Efavirenz can be rendered inactive by a single point mutation in the reverse transcriptase enzyme. Newer NNRTI drugs such as etravirine, not yet approved for use in children under the age of 6 years, may maintain their activity following development of efavirenz resistance. This review highlights key points from the existing literature regarding the use of efavirenz in children and suggests directions for future investigation. PMID:25937791

  7. Antiretroviral Therapy Use, Medication Adherence, and Viral Suppression Among PLWHA with Panic Symptoms.

    PubMed

    Sam, Tanyka Suzanne; Hutton, Heidi E; Lau, Bryan; McCaul, Mary E; Keruly, Jeanne; Moore, Richard; Chander, Geetanjali

    2015-11-01

    Panic symptoms are prevalent among PLWHAs, yet few studies have examined their relationship with HIV outcomes. Using data from an observational cohort study in Baltimore, MD, we examined the association between panic symptoms and antiretroviral therapy (ART) use, medication adherence, and viral suppression. Data were analyzed using generalized estimating equations and adjusted for age, sex, race/ethnicity, cocaine and/or heroin use, clinic enrollment time, alcohol use, and depressive symptoms. Between June 2010 and September 2012, 1195 individuals participated in 2080 audio computer assisted interviews; 9.9 % (n = 118) of individuals endorsed current panic symptoms. In multivariate analysis, panic symptoms were associated with decreased ART use (IRR 0.94; p = 0.05). Panic symptoms were neither associated with medication adherence nor viral suppression. These findings were independent of depressive symptoms and substance use. Panic symptoms are under-recognized in primary care settings and present an important barrier to ART use. Further studies investigating the reasons for this association are needed. PMID:25903506

  8. Interactions between natural health products and antiretroviral drugs: pharmacokinetic and pharmacodynamic effects.

    PubMed

    Lee, Lawrence S; Andrade, Adriana S A; Flexner, Charles

    2006-10-15

    Concurrent use of natural health products (NHPs) with antiretroviral drugs (ARVs) is widespread among human immunodeficiency virus-infected patients. This article reviews the clinical pharmacokinetic and pharmacodynamic interactions between NHPs and ARVs. Many NHPs are complex mixtures and are likely to contain organic compounds that may induce and/or inhibit drug metabolizing enzymes and drug transporters. Although the weight of evidence for the effects of certain NHPs varies and many studies of these products lack scientific rigor, it has been observed that St. John's wort clearly induces cytochrome P450 3A4 and P-glycoprotein and reduces protease inhibitor and nonnucleoside reverse-transcriptase inhibitor concentrations, thereby increasing the likelihood of therapeutic failure. Limited clinical research suggests that intake of garlic and vitamin C results in reductions in ARV concentrations. The intake of milk thistle, Echinacea species, and goldenseal inhibits cytochrome P450 enzymes in vitro and may increase ARV concentrations, but by clinically unimportant amounts. Intake of fish oil reduces ARV-induced hypertriglyceridemia without significantly affecting lopinavir concentrations. Before recommending the use of NHPs as adjuncts to ARV use, studies should first exclude significant pharmacokinetic interactions and ensure that ARV efficacy is maintained. PMID:16983620

  9. Adult combination antiretroviral therapy in sub-Saharan Africa: lessons from Botswana and future challenges

    PubMed Central

    Wester, C William; Bussmann, Hermann; Koethe, John; Moffat, Claire; Vermund, Sten; Essex, Max; Marlink, Richard G

    2009-01-01

    Numerous national public initiatives offering first-line combination antiretroviral therapy (cART) for HIV infection have commenced in sub-Saharan Africa since 2002. Presently, 2.1 million of an estimated seven million Africans in need of cART are receiving treatment. Analyses from the region report favorable clinical/treatment outcomes and impressive declines in AIDS-related mortality among HIV-1-infected adults and children receiving cART. While immunologic recovery, virologic suppression and cART adherence rates are on par with resource-rich settings, loss to follow-up and high mortality rates, especially within the first 6 months of treatment, remain a significant problem. Over the next decade, cART coverage rates are expected to improve across the region, with attendant increases in healthcare utilization for HIV- and non-HIV-related complications and the need for expanded laboratory and clinical services. Planned and in-progress trials will evaluate the use of cART to prevent primary HIV-1 infection with so-called ‘test and treat’ expansions of coverage and treatment. Education and training programs as well as patient-retention strategies will need to be strengthened as national cART programs are expanded and more people require lifelong monitoring and care. PMID:20161344

  10. In what ways do communities support optimal antiretroviral treatment in Zimbabwe?

    PubMed

    Scott, K; Campbell, C; Madanhire, C; Skovdal, M; Nyamukapa, C; Gregson, S

    2014-12-01

    Little research has been conducted on how pre-existing indigenous community resources, especially social networks, affect the success of externally imposed HIV interventions. Antiretroviral treatment (ART), an externally initiated biomedical intervention, is being rolled out across sub-Saharan Africa. Understanding the ways in which community networks are working to facilitate optimal ART access and adherence will enable policymakers to better engage with and bolster these pre-existing resources. We conducted 67 interviews and eight focus group discussions with 127 people from three key population groups in Manicaland, eastern Zimbabwe: healthcare workers, adults on ART and carers of children on ART. We also observed over 100 h of HIV treatment sites at local clinics and hospitals. Our research sought to determine how indigenous resources were enabling people to achieve optimal ART access and adherence. We analysed data transcripts using thematic network technique, coding references to supportive community networks that enable local people to achieve ART access and adherence. People on ART or carers of children on ART in Zimbabwe report drawing support from a variety of social networks that enable them to overcome many obstacles to adherence. Key support networks include: HIV groups; food and income support networks; home-based care, church and women's groups; family networks; and relationships with healthcare providers. More attention to the community context in which HIV initiatives occur will help ensure that interventions work with and benefit from pre-existing social capital. PMID:23503291

  11. Highly active antiretroviral therapy reduces pulmonary IL-8 in HIV-positive women smokers.

    PubMed

    Taylor, Gregory H; Williams, Adrienne A; Garzino-Demo, Alfredo

    2016-03-01

    Increased levels of the proinflammatory cytokine IL-8 are detected in the sputum of patients with chronic obstructive pulmonary disease (COPD) and during the pathological pulmonary manifestations of HIV infection : To explore a potential interrelationship between smoking, highly active antiretroviral therapy (HAART) and HIV immune status, we collected sputum samples, along with complete pulmonary function tests from groups of HIV-infected women smokers who were either on or off HAART. Analysis of the patient's sputum for cell count along with quantitative measures of IL-8 was performed and correlated with concurrent assessment of pulmonary function test (PFT). We found that HIV-positive smokers had decreased measurements on PFT of the diffusing capacity of the lung for carbon monoxide (DLCO) compared to standard reference values that did not differ with HAART usage. HAART, when controlled for CD4, showed a suppressive effect on the levels of pro inflammatory cytokine IL-8 in sputum. We conclude that in the era of HAART, HIV along with concurrent tobacco smoking is associated with declines in PFT in HIV-infected women. The use of HAART in patients appears to mitigate the increases in IL-8 levels in relation to immune status based on CD4 count. PMID:26656889

  12. Diabetes and Hypertension among Patients Receiving Antiretroviral Treatment Since 1998 in Senegal: Prevalence and Associated Factors

    PubMed Central

    Diouf, Assane; Cournil, Amandine; Ba-Fall, Khadidiatou; Ngom-Guèye, Ndèye Fatou; Eymard-Duvernay, Sabrina; Ndiaye, Ibrahima; Batista, Gilbert; Guèye, Papa Mandoumbé; Bâ, Pape Samba; Taverne, Bernard; Delaporte, Eric; Sow, Papa Salif

    2012-01-01

    Cardiovascular risk factors in people on antiretroviral treatment (ART) are poorly documented in resource-constrained settings. A cross-sectional study was conducted in 2009 to assess prevalence of diabetes and hypertension in a sample of 242 HIV-infected patients who had initiated ART between 1998 and 2002 in Dakar, Senegal (ANRS 1215 observational cohort). World Health Organization (WHO) criteria were applied to diagnose diabetes and hypertension. Multiple logistic regressions were used to identify factors associated with diabetes and hypertension. Patients had a median age of 46 years and had received ART for a median duration of about 9 years. 14.5% had diabetes and 28.1% had hypertension. Long duration of ART (?119 months), older age, higher body mass index (BMI), and higher levels of total cholesterol were associated with higher risks of diabetes. Older age, higher BMI at ART initiation, and higher levels of triglycerides were associated with higher risk of hypertension. This study shows that diabetes and hypertension were frequent in these Senegalese HIV patients on ART. It confirms the association between duration of ART and diabetes and highlights the need to implement programs for prevention of cardiovascular risk factors in HIV patients from resource-constrained settings. PMID:24052880

  13. Neurologic Complications of HIV-1 Infection and Its Treatment in the Era of Antiretroviral Therapy

    PubMed Central

    Kranick, Sarah M.; Nath, Avindra

    2012-01-01

    Purpose of Review: Neurologic complications of HIV infection are unfortunately common, even in the era of effective antiretroviral treatment (ART). The consulting neurologist is often asked to distinguish among neurologic deterioration due to opportunistic infection (OI), immune reconstitution, or the effect of the virus itself, and to comment on the role of immunomodulatory agents in patients with HIV infection. Additionally, as successful virologic control has extended the life span of patients with HIV infection, neurologists are called upon to manage long-term complications, such as neurocognitive disorders and peripheral neuropathy. Recent Findings: Despite the use of ART, significant numbers of patients continue to be affected by HIV-associated neurocognitive disorders, although with milder forms compared to the pre-ART era. Regimens of ART have been ranked according to CNS penetration and are being studied with regard to neuropsychological outcomes. Nucleoside analogs with the greatest potential for peripheral neurotoxicity are no longer considered first-line agents for HIV treatment. Efavirenz, a non-nucleoside reverse transcriptase inhibitor, has the greatest frequency of neurologic side effects among newer ART regimens. The spectrum of clinical manifestations of immune reconstitution inflammatory syndrome (IRIS) continues to grow, including IRIS without underlying OI. A greater understanding of pathophysiology and risk factors has shown that while HIV should be treated early to prevent severe immunocompromise, delayed initiation of ART may be helpful while treating OIs. Summary: This article reviews the neurologic complications of HIV infection, or its treatment, most commonly encountered by neurologists. PMID:23221843

  14. The impact of antiretroviral therapy on population-level virulence evolution of HIV-1.

    PubMed

    Roberts, Hannah E; Goulder, Philip J R; McLean, Angela R

    2015-12-01

    In HIV-infected patients, an individual's set point viral load (SPVL) strongly predicts disease progression. Some think that SPVL is evolving, indicating that the virulence of the virus may be changing, but the data are not consistent. In addition, the widespread use of antiretroviral therapy (ART) has the potential to drive virulence evolution. We develop a simple deterministic model designed to answer the following questions: what are the expected patterns of virulence change in the initial decades of an epidemic? Could administration of ART drive changes in virulence evolution and, what is the potential size and direction of this effect? We find that even without ART we would not expect monotonic changes in average virulence. Transient decreases in virulence following the peak of an epidemic are not necessarily indicative of eventual evolution to avirulence. In the short term, we would expect widespread ART to cause limited downward pressure on virulence. In the long term, the direction of the effect is determined by a threshold condition, which we define. We conclude that, given the surpassing benefits of ART to the individual and in reducing onward transmission, virulence evolution considerations need have little bearing on how we treat. PMID:26609066

  15. Production of antiretroviral drugs in middle- and low-income countries.

    PubMed

    Pinheiro, Eloan dos Santos; Brüning, Karin; Macedo, M Fernanda; Siani, Antonio C

    2014-01-01

    This review outlines the main issues concerning the production of antiretroviral (ARV) drugs in middle- and low-income countries and the relevant political, legal and technical requirements for supporting such production. The requirements for efficient local production, including the manufacture of generic and branded products and public demand, have been considered from economic, market and socio-political perspectives. A steady and consistent government policy is crucial to success. Additional crucial factors in establishing local production are adequate infrastructure, qualified human resources in technical and managerial areas, and production-distribution logistics systems. The creation or strengthening of a national drug regulatory agency is a basic requirement. Production of ARVs relies on the structure of the international market for active pharmaceutical ingredients (APIs), which are highly monopolized for inclusion in branded or patented drugs, or are concentrated in a few Asian generic companies. Countries seeking to begin local production must develop strategies to overcome the various barriers. For instance, sub-Saharan African countries may benefit from developing multilateral health agreements with neighbouring countries. Such agreements are recommended and should be complemented by technology transfers, especially for the manufacture of APIs. Achieving a production level that is sustainable in the long term is crucial to maintaining patients' access to ARVs. PMID:25310755

  16. Prevalence of Pulmonary Tuberculosis Among HIV Positive Patients Attending Antiretroviral Therapy Clinic

    PubMed Central

    Giri, Purushottam A; Deshpande, Jayant D; Phalke, Deepak B

    2013-01-01

    Background: Tuberculosis (TB) is the most common serious opportunistic infection in HIV positive patients and is the manifestation of AIDS in more than 50% of cases in developing countries. TB can occur at any time during the course of HIV infection. Aim: To describe the socio-demographic profile and prevalence of pulmonary tuberculosis (HIV/TB co-infection) among HIV positive patients been attended at the antiretroviral therapy clinic (ART) clinic at tertiary care teaching hospital of western Maharashtra, India. Materials and Methods: A cross-sectional study was carried out at the ART clinic of Pravara Rural Hospital, Loni, from June 2011 to May 2012. A total of 1012 HIV positive patients, who attended ART clinic, receiving ART treatment during the study period, were included in the analysis. The statistical analysis was performed using SPSS software (Version 17.0). Results: This study showed 1012/172 (17%) prevalence of pulmonary tuberculosis among HIV positive patients, of which 87 (50.58%) were males and 85 (48.42%) were females. Low CD4 count (< 50/?l) had statistically significant association with HIV/TB co-infection as compared to HIV infection only (P < 0.0001). Conclusion: The study showed that 17% of HIV infected persons had tuberculosis co-infection. More strategic preventive measures that enhance body immunity among HIV patients are highly needed as early as possible before they develop active tuberculosis. PMID:23923111

  17. Determinants of Antiretroviral Therapy Adherence among Women in Southern Malawi: Healthcare Providers' Perspectives

    PubMed Central

    Modeste, Naomi N.; Lee, Jerry W.; Gleason, Peter C.; Maynard-Tucker, Gisele

    2014-01-01

    Background. The purpose of this study was to explore healthcare providers' perspectives on antiretroviral (ART) adherence in two ART clinics in southern Malawi. Nonadherence to ART is a significant hindrance to the success of HIV/AIDS treatment. Methods. A one-on-one semistructured interview was conducted with eight healthcare providers in two ART clinics in rural and urban southern Malawi. The interviews were focused on factors facilitating or hindering ART adherence and strategies to improve adherence. Interviews were audio-recorded, transcribed, and content-analyzed with the use of the constant comparison approach. Results. Of the eight participants, 63% were between the ages of 20 and 30 years and 37% were HIV counselors. Factors facilitating adherence include patients' belief and knowledge, HIV/AIDS education, and a supportive network. Barriers to adherence include discrimination, nondisclosure of HIV status, food insecurity, medication side effects, religion, misinformation, and staff and drug shortages. Strategies to improve adherence were identified by participants to include nutritional/food supplementation for malnourished or undernourished patients and patient counseling. Conclusions. There is a need for collaborative efforts between healthcare providers, patients, and faith-based organizations to identify and address hindrances and facilitators to patients' adherence. Further research is needed to develop strategies addressing religion, staff, and drug shortages. PMID:25610641

  18. Drug–drug interactions between anti-retroviral therapies and drugs of abuse in HIV systems

    PubMed Central

    Rao, PSS; Earla, Ravindra; Kumar, Anil

    2015-01-01

    Introduction Substance abuse is a common problem among HIV-infected individuals. Importantly, addictions as well as moderate use of alcohol, smoking, or other illicit drugs have been identified as major reasons for non-adherence to antiretroviral therapy (ART) among HIV patients. The literature also suggests a decrease in the response to ART among HIV patients who use these substances, leading to failure to achieve optimal virological response and increased disease progression. Areas covered This review discusses the challenges with adherence to ART as well as observed drug interactions and known toxicities with major drugs of abuse, such as alcohol, smoking, methamphetamine, cocaine, marijuana, and opioids. The lack of adherence and drug interactions potentially lead to decreased efficacy of ART drugs and increased ART, and drugs of abuse-mediated toxicity. As CYP is the common pathway in metabolizing both ART and drugs of abuse, we discuss the possible involvement of CYP pathways in such drug interactions. Expert opinion We acknowledge that further studies focusing on common metabolic pathways involving CYP and advance research in this area would help to potentially develop novel/alternate interventions and drug dose/regimen adjustments to improve medication outcomes in HIV patients who consume drugs of abuse. PMID:25539046

  19. Initiation, Adherence, and Retention in a Randomized Controlled Trial of Directly Administered Antiretroviral Therapy

    PubMed Central

    Maru, Duncan Smith-Rohrberg; Bruce, R. Douglas; Walton, Mary; Mezger, Jo Anne; Springer, Sandra A.; Shield, David

    2009-01-01

    Directly administered antiretroviral therapy (DAART) can improve health outcomes among HIV-infected drug users. An understanding of the utilization of DAART—initiation, adherence, and retention—is critical to successful program design. Here, we use the Behavioral Model to assess the enabling, predisposing, and need factors impacting adherence in our randomized, controlled trial of DAART versus self-administered therapy (SAT) among 141 HIV-infected drug users. Of 88 participants randomized to DAART, 74 (84%) initiated treatment, and 51 (69%) of those who initiated were retained in the program throughout the entire six-month period. Mean adherence to directly observed visits was 73%, and the mean overall composite adherence score was 77%. These results were seen despite the finding that 75% of participants indicated that they would prefer to take their own medications. Major causes of DAART discontinuation included hospitalization, incarceration, and entry into drug-treatment programs. The presence of depression and the lack of willingness to travel greater than four blocks to receive DAART predicted time-to-discontinuation. PMID:18085432

  20. Attitudes to directly observed antiretroviral treatment in a workplace HIV care programme in South Africa

    PubMed Central

    Page?Shipp, Liesl S; Charalambous, Salome; Roux, Surita; Dias, Belinda; Sefuti, Clement; Churchyard, Gavin J; Grant, Alison D

    2007-01-01

    Objective To investigate attitudes to directly observed antiretroviral therapy (DOT ART) among HIV infected adults attending a workplace HIV care programme in South Africa. Methods Clients attending workplace HIV clinics in two regions were interviewed using a semi?structured questionnaire. Results 100 individuals (99% male, mean age 40.2?years) participated, 61% were already taking ART by self administration. 71% had previous tuberculosis (TB) with the majority having received DOT for TB. 65% of individuals indicated that they would not like to receive ART by DOT—the main reason given was a desire to take responsibility for their own treatment. This contrasted with 79% who thought TB treatment by DOT a good idea. On questioning about disclosure, 70% reported disclosure to their sexual partners and 21% to fellow workers. 78% of individuals indicated willingness to support someone else taking ART. Conclusion ART by DOT was not an immediately popular concept with our patients, primarily because of a desire to retain responsibility for their own treatment. More work is needed to understand what key elements of treatment support are needed to promote adherence. PMID:17567686

  1. Modified directly observed therapy for antiretroviral therapy: a primer from the field.

    PubMed

    Goggin, Kathy; Liston, Robin J; Mitty, Jennifer Adelson

    2007-01-01

    Modified directly observed therapy (mDOT), in which a portion of total doses of a medication regime is ingested under supervision, has demonstrated efficacy as an intervention to assist patients in maintaining adherence to complicated antiretroviral therapy (ART). Although findings are favorable, existing efficacy studies fail to provide sufficient detail to guide others who wish to implement mDOT interventions. The aim of this article is to provide a primer for practitioners and researchers who wish to implement mDOT interventions. Drawing on the experience of 10 federally funded research projects, we provide guidance on critical questions for program implementation, including: who should be targeted, length/duration/content/location/tapering of sessions, staffing, incentives, and approaches to data collection. In addition, guidance on staff training and minimum requirements for mDOT interventions is offered along with real-world examples of mDOT interventions. mDOT is feasible and easily adapted to many settings and target populations. Interventions should match the specific needs of the target population and setting and be flexible in terms of design and delivery. mDOT should be considered among the spectrum of adherence interventions. PMID:17639650

  2. Small magnetite antiretroviral therapeutic nanoparticle probes for MRI of drug biodistribution

    PubMed Central

    Guo, Dongwei; Li, Tianyuzi; McMillan, JoEllyn; Sajja, Balasrinivasa R; Puligujja, Pavan; Boska, Michael D; Gendelman, Howard E; Liu, Xin-Ming

    2013-01-01

    Aim Drug toxicities, compliance and penetrance into viral reservoirs have diminished the efficacy of long-term antiretroviral therapy (ART) for treatment of HIV infection. Cell-targeted nanoformulated ART was developed to improve disease outcomes. However, rapid noninvasive determination of drug biodistribution is unrealized. To this end, small magnetite ART (SMART) nanoparticles can provide assessments of ART biodistribution by MRI. Materials & methods Poly(lactic-co-glycolic acid), 1,2-distearoyl-sn-glycero-3-phosphocholine- and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-(methoxy-PEG 2000)-encased particles were synthesized with atazanavir (ATV) and magnetite. Uptake and retention of ATV and magnetite administered at 3:1 ratios (weight/weight) were determined in human monocyte-derived macrophages and mice. Results SMART particles were taken up and retained in macrophages. In mice, following parenteral SMART injection, magnetite and drug biodistribution paralleled one another with MRI signal intensity greatest in the liver and spleen at 24 h. Significantly, ATV and magnetite levels correlated. Conclusion SMART can permit rapid assessment of drug tissue concentrations in viral reservoirs. PMID:23905578

  3. Human Immunodeficiency Virus-Associated Diarrhea: Still an Issue in the Era of Antiretroviral Therapy.

    PubMed

    Dikman, Andrew E; Schonfeld, Emily; Srisarajivakul, Nalinee C; Poles, Michael A

    2015-08-01

    Over half of patients with human immunodeficiency virus (HIV) experience diarrhea that contributes negatively to quality of life and adherence to antiretroviral therapy (ART). Opportunistic infectious agents that cause diarrhea in patients with HIV span the array of protozoa, fungi, viruses, and bacteria. With global use of ART, the incidence of diarrhea because of opportunistic infections has decreased; however, the incidence of noninfectious diarrhea has increased. The etiology of noninfectious diarrhea in patients with HIV is multifactorial and includes ART-associated diarrhea and gastrointestinal damage related to HIV infection (i.e., HIV enteropathy). A basic algorithm for the diagnosis of diarrhea in patients with HIV includes physical examination, a review of medical history, assessment of HIV viral load and CD4+ T cell count, stool microbiologic assessment, and endoscopic evaluation, if needed. For patients with negative diagnostic results, the diagnosis of noninfectious diarrhea may be considered. Pharmacologic options for the treatment of noninfectious diarrhea are primarily supportive; however, the use of many unapproved agents is based on unstudied and anecdotal information. In addition, these agents can be associated with treatment-limiting adverse events (AEs), such as drug-drug interactions with ART regimens, abuse liability, and additional gastrointestinal AEs. Currently, crofelemer, an antisecretory agent, is the only therapy approved in the USA for the symptomatic relief of noninfectious diarrhea in patients with HIV on ART. PMID:25772777

  4. Attitudes of serodiscordant couples towards antiretroviral-based HIV prevention strategies in Kenya: a qualitative study.

    PubMed

    Fowler, Nikola; Arkell, Paul; Abouyannis, Michael; James, Catherine; Roberts, Lesley

    2015-01-01

    This qualitative study aims to gain in-depth information about the attitudes of HIV-serodiscordant couples towards two new methods of HIV prevention; Pre-Exposure Prophylaxis and Treatment as Prevention, both of which have been recently recommended by the World Health Organisation. Semi-structured interviews were conducted with 38 individuals in a serodiscordant relationship in Western Kenya. Topic guides were used to elicit information on perceived benefits, concerns, and preferences towards Treatment as Prevention and Pre-Exposure Prophylaxis. Data evaluation and thematic generation were developed using framework analysis. Results suggest that the majority of participants, irrespective of gender and HIV status, found Treatment as Prevention the more acceptable strategy. Key factors influencing this decision were HIV-negative participants' limited motivation to take prophylactic antiretrovirals and the likely health improvements Treatment as Prevention offers HIV-positive partners. However, issues were raised concerning the likelihood of low concurrent condom use and poor medication adherence when using these preventative approaches. It was concluded that the adoption of Treatment as Prevention as a method of HIV control in Kenya is likely to be more readily accepted by serodiscordant couples than Pre-exposure Prophylaxis. However, future implementation of either strategy would require measures to address the possibility of risk compensation and poor adherence. PMID:25375792

  5. Prescription medication misuse among HIV-infected individuals taking antiretroviral therapy.

    PubMed

    Newville, Howard; Roley, Jason; Sorensen, James L

    2015-01-01

    HIV has become a highly treatable disease due to advances in antiretroviral therapy (ART). Additionally, HIV-infected individuals often take opiates, barbiturates, and benzodiazepines to treat co-occurring conditions, including pain and symptoms of HIV. We sought to examine prescription medication misuse by surveying 295 HIV-infected patients receiving ART. Participants answered questions about their demographics, alcohol and other drug use, psychiatric diagnoses, ART adherence and side effects, and quality of life. Eleven percent of our sample acknowledged prescription medication misuse. In regression analysis, prescription medication misusers were more likely to report any drinking to intoxication (OR=4.31, 95% CI: 1.35-13.76, p=0.013), reported greater severity of ART side effects (OR=1.05, 95% CI: 1.01-1.10, p=0.041), and demonstrated poorer cognitive functioning (OR=0.97, 95% CI: 0.94-0.99, p=0.048) compared to those who did not misuse prescription medications. Special care should be taken by medical providers before prescribing medications that may be abused or diverted. Patients should also be screened for aberrant use, even if not prescribed. ART side effects, cognitive deficits, and alcohol abuse may serve as risk factors or indicators of prescription medication misuse, and should be monitored. PMID:25245428

  6. In vitro assessment of antiretroviral drugs demonstrates potential for ototoxicity.

    PubMed

    Thein, Pru; Kalinec, Gilda M; Park, Channy; Kalinec, Federico

    2014-04-01

    Several studies have reported an increased incidence of auditory dysfunction among HIV/AIDS patients. We used auditory HEI-OC1 cells in cell viability, flow cytometry and caspases 3/7-activation studies to investigate the potential ototoxicity of fourteen HIV antiretroviral agents: Abacavir, AZT, Delavirdine, Didenosine, Efavirenz, Emtricitabine, Indinavir, Lamivudine, Nefinavir, Nevirapine, Tenofovir, Ritonavir, Stavudine and Zalcitabine, as well as combinations of these agents as used in the common anti-HIV cocktails Atripla™, Combivir™, Epzicom™, Trizivir™, and Truvada™. Our results suggested that most of the single assayed anti-HIV drugs are toxic for HEI-OC1 auditory cells. The cocktails, on the other hand, decreased auditory cells' viability with high significance, with the following severity gradient: Epzicom ? Trizivir > Atripla ? Combivir > Truvada. Interestingly, our results suggest that Trizivir- and Epzicom-induced cell death would be mediated by a caspase-independent mechanism. l-Carnitine, a natural micronutrient known to protect HEI-OC1 cells against some ototoxic drugs as well as to decrease neuropathies associated with anti-HIV treatments, increased viability of cells treated with Lamivudine and Tenofovir as well as with the cocktail Atripla, but had only minor effects on cells treated with other drugs and drug combinations. Altogether, these results suggest that some frequently used anti-HIV agents could have deleterious effects on patients' hearing, and provide arguments in favor of additional studies aimed at elucidating the potential ototoxicity of current as well as future anti-HIV drugs. PMID:24487230

  7. HIV-1 Antiretroviral Drug Resistance in Pregnant Women in Jamaica A Preliminary Report

    PubMed Central

    Amarakoon, II; Ramkissoon, A; Pierre, R; Eyzaguirre, LM; Carr, JK; Blattner, WA; Roye, ME

    2014-01-01

    ABSTRACT This preliminary report sought to provide insight into the genetic diversity of human immunodeficiency virus drug resistance (HIVDR) in Jamaica. This was done by investigating the genetic diversity associated with drug resistance in pregnant women living with HIV attending antenatal clinics in Kingston, Jamaica. Blood samples were collected and viral RNA were extracted and analysed. The protease and reverse transcriptase (Pro-RT) genes were amplified using the nested polymerase chain reaction (PCR) method. Polymerase chain reaction amplicons were obtained for nine (56%) of 16 patients, of which five (55%) were antiretroviral (ARV) drug naïve and four (45%) were treatment experienced. Three minor protease inhibitor resistant-conferring mutations (A71AT, A71V, A71T) and five mutations conferring high to low-level resistance (K219EK, T69S, K103S, G190A and K103N) were detected in the RT region. More than 50% of the resistance mutations found were detected in ARV drug naïve individuals, implying that viruses are being transmitted with the ARV resistance. These preliminary results will inform the health practitioners of the level of drug resistance that is being transmitted as well as strengthen the need to initiate a national baseline survey on HIVDR in Jamaica. PMID:25803373

  8. High levels of Zinc-?-2-Glycoprotein among Omani AIDS patients on combined antiretroviral therapy

    PubMed Central

    Hasson, Sidgi Syed Anwer; Al-Balushi, Mohammed Saeed; Al Yahmadi, Muzna Hamed; Al-Busaidi, Juma Zaid; Said, Elias Antony; Othman, Mohammed Shafeeq; Sallam, Talal Abdullah; Idris, Mohammed Ahmad; Al-Jabri, Ali Abdullah

    2014-01-01

    Objective To investigate the levels of zinc-?-2-glycoprotein (ZAG) among Omani AIDS patients receiving combined antiretroviral therapy (cART). Methods A total of 80 Omani AIDS patients (45 males and 35 females), average age of 36 years, who were receiving cART at the Sultan Qaboos University Hospital (SQUH), Muscat, Oman, were tested for the levels of ZAG. In addition, 80 healthy blood donors (46 males and 34 females), average age of 26 years, attending the SQUH Blood Bank, were tested in parallel as a control group. Measurement of the ZAG levels was performed using a competitive enzyme-linked immunosorbent assay and in accordance with the manufacturer's instructions. Results The ZAG levels were found to be significantly higher among AIDS patients compared to the healthy individuals (P=0.033). A total of 56 (70%) of the AIDS patients were found to have higher levels of ZAG and 16 (20%) AIDS patients were found to have high ZAG levels, which are significantly (P>0.031) associated with weight loss. Conclusions ZAG levels are high among Omani AIDS patients on cART and this necessitates the measurement of ZAG on routine basis, as it is associated with weight loss. PMID:25183329

  9. HIV persistence in the setting of antiretroviral therapy: when, where and how does HIV hide?

    PubMed Central

    Kulpa, Deanna A.; Chomont, Nicolas

    2015-01-01

    Advances in the treatment of HIV infection have dramatically reduced the death rate from AIDS and improved the quality of life of many HIV-infected individuals. However, the possible long-term toxicity associated with antiretroviral therapy (ART), stigma and cost, all contribute to the necessity of finding a cure for HIV infection. In infected individuals taking ART, HIV persists in a small number of cells that can survive for the lifetime of the infected person. These persistently infected cells, usually referred as the ‘reservoirs for HIV infection’, are the main barriers to a cure. The diversity of the tissues and cellular types in which HIV persists, as well as the multiplicity of the molecular mechanisms contributing to HIV persistence, complicate the efforts to develop a safe, effective, and globally accessible cure for HIV. In this review, we summarise recent data that contribute to our understanding of HIV persistence during ART by addressing three questions pertaining to the HIV reservoir: (1) when is the reservoir established; (2) where is the reservoir maintained; and (3) how does the reservoir persist? PMID:26448966

  10. Highly active antiretroviral therapy potently suppresses HIV infection in humanized Rag2-/-gammac-/- mice.

    PubMed

    Sango, Kaori; Joseph, Aviva; Patel, Mahesh; Osiecki, Kristin; Dutta, Monica; Goldstein, Harris

    2010-07-01

    Humanized Rag2(-/-)gamma(c)(-/-) mice (Hu-DKO mice) become populated with functional human T cells, B cells, and dendritic cells following transplantation with human hematopoietic stem cells (HSC) and represent an improved model for studying HIV infection in vivo. In the current study we demonstrated that intrasplenic inoculation of hu-DKO mice with HIV-1 initiated a higher level of HIV infection than intravenous or intraperitoneal inoculation, associated with a reciprocal decrease in peripheral CD4(+) T cells and increase in peripheral CD8(+) T cells. HIV infection by intrasplenic injection increased serum levels of human IgG and IgM including human IgM and IgG specific for HIV-1 gp120. There was a significant inverse correlation between the level of HIV-1 infection and the extent of CD4(+) T cell depletion. Highly active antiretroviral therapy (HAART) initiated 1 week after HIV-1 inoculation markedly suppressed HIV-1 infection and prevented CD4(+) T cell depletion. Taken together, these findings demonstrate that intrasplenic injection of hu-DKO mice with HIV is a more efficient route of HIV infection than intravenous or intraperitoneal injection and generates increased infection associated with an increased anti-HIV humoral response. This animal model can serve as a valuable in vivo model to study the efficacy of anti-HIV therapies. PMID:20624075

  11. Differences in antiretroviral scale up in three South African provinces: the role of implementation management

    PubMed Central

    2010-01-01

    Background South Africa’s antiretroviral programme is governed by defined national plans, establishing treatment targets and providing funding through ring-fenced conditional grants. However, in terms of the country’s quasi-federal constitution, provincial governments bear the main responsibility for provision of health care, and have a certain amount of autonomy and therefore choice in the way their HIV/AIDS programmes are implemented. Methods The paper is a comparative case study of the early management of ART scale up in three South African provincial governments – Western Cape, Gauteng and Free State – focusing on both operational and strategic dimensions. Drawing on surveys of models of ART care and analyses of the policy process conducted in the three provinces between 2005 and 2007, as well as a considerable body of grey and indexed literature on ART scale up in South Africa, it draws links between implementation processes and variations in provincial ART coverage (low, medium and high) achieved in the three provinces. Results While they adopted similar chronic disease care approaches, the provinces differed with respect to political and managerial leadership of the programme, programme design, the balance between central standardisation and local flexibility, the effectiveness of monitoring and evaluation systems, and the nature and extent of external support and programme partnerships. Conclusions This case study points to the importance of sub-national programme processes and the influence of factors other than financing or human resource capacity, in understanding intervention scale up. PMID:20594370

  12. Effects of Hormonal Contraception on Anti-Retroviral Drug Metabolism, Pharmacokinetics and Pharmacodynamics

    PubMed Central

    Thurman, Andrea Ries; Anderson, Sharon; Doncel, Gustavo F

    2014-01-01

    Among women, human immunodeficiency virus type 1 (HIV-1) infection is most prevalent in those of reproductive age. These women are also at risk of unintended or mistimed pregnancies. Hormonal contraceptives (HCs) are one of the most commonly used methods of family planning world-wide. Therefore concurrent use of HC among women on anti-retroviral medications (ARVs) is increasingly common. ARVs are being investigated and have been approved for pre-exposure prophylaxis (PrEP), and therefore drug-drug interactions must also be considered in HIV-1 negative women who want to prevent both unintended pregnancy and HIV-1 infection. This article will review four main interactions: (1) the effect of HCs on ARV pharmacokinetics (PK) and pharmacodynamics (PD) during therapy, (2) the effect of ARVs on HC PK and PD, (3) the role of drug transporters on drug-drug interactions and (4) ongoing research into the effect of HCs on pre-exposure prophylaxis PK and PD. PMID:24521428

  13. A Second Look at the Association between Gender and Mortality on Antiretroviral Therapy

    PubMed Central

    Koenig, Serena P.; Bornstein, Alexandra; Severe, Karine; Fox, Elizabeth; Dévieux, Jessy G.; Severe, Patrice; Joseph, Patrice; Marcelin, Adias; Bright, Dgndy Alexandre; Pham, Ngoc; Cremieux, Pierre; Pape, Jean William

    2015-01-01

    Objective We assessed the association between gender and mortality on antiretroviral therapy (ART) using identical models with and without sex-specific categories for weight and hemoglobin. Design Cohort study of adult patients on ART. Setting GHESKIO Clinic in Port-au-Prince, Haiti. Participants 4,717 ART-naïve adult patients consecutively enrolled on ART at GHESKIO from 2003 to 2008. Main Outcome Measure Mortality on ART; multivariable analyses were conducted with and without sex-specific categories for weight and hemoglobin. Results In Haiti, male gender was associated with mortality (OR 1.61; 95% CI: 1.30–2.00) in multivariable analyses with hemoglobin and weight included as control variables, but not when sex-specific interactions with hemoglobin and weight were used. Conclusions If sex-specific categories are omitted, multivariable analyses indicate a higher risk of mortality for males vs. females of the same weight and hemoglobin. However, because males have higher normal values for weight and hemoglobin, the males in this comparison would generally have poorer health status than the females. This may explain why gender differences in mortality are sometimes observed after controlling for differences in baseline variables when gender-specific interactions with weight and hemoglobin are omitted. PMID:26562018

  14. A Qualitative Study of Patient Motivation to Adhere to Combination Antiretroviral Therapy in South Africa

    PubMed Central

    Gray, Debra; Gengiah, Santhanalakshmi; Kunene, Pinky; Gengiah, Tanuja N.; Naidoo, Kogieleum; Grant, Alison D.

    2015-01-01

    Abstract Taken as prescribed, that is, with high adherence, combination antiretroviral therapy (ART) has changed HIV infection and disease from being a sure predictor of death to a manageable chronic illness. Adherence, however, is difficult to achieve and maintain. The CAPRISA 058 study was conducted between 2007 and 2009 to test the efficacy of individualized motivational counselling to enhance ART adherence in South Africa. As part of the overall trial, a qualitative sub-study was conducted, including 30 individual interviews and four focus group discussions with patients in the first 9 months of ART initiation. Data were inductively analyzed, using thematic analysis, to identify themes central to ART adherence in this context. Four themes emerged that characterize the participants' experiences and high motivation to adhere to ART. Participants in this study were highly motivated to adhere, as they acknowledged that ART was ‘life-giving’, in the face of a large amount of morbidity and mortality. They were further supported by techniques of routine remembering, and highlighted the importance of good social support and access to supportive healthcare workers, to their continued success in negotiating their treatment. Participants in the current study told us that their adherence motivation is enhanced by free accessible care, approachable and supportive healthcare workers, broad social acceptance of ART, and past first-hand experiences with AIDS-related co-morbidity and mortality. Programs that include specific attention to these aspects of care will likely be successful in the long term. PMID:25692575

  15. Infectious diarrhoea in antiretroviral therapy-naïve HIV/AIDS patients in Kenya

    PubMed Central

    Wanyiri, Jane W.; Kanyi, Henry; Maina, Samuel; Wang, David E.; Ngugi, Paul; O'Connor, Roberta; Kamau, Timothy; Waithera, Tabitha; Kimani, Gachuhi; Wamae, Claire N.; Mwamburi, Mkaya; Ward, Honorine D.

    2013-01-01

    Background Diarrhoea is a significant cause of morbidity and mortality in immunocompromised patients. The objectives of this study were to investigate the aetiological agents, risk factors and clinical features associated with diarrhoea in HIV/AIDS patients in Kenya. Methods Sociodemographic, epidemiological and clinical data were obtained for 164 HIV/AIDS patients (70 with and 94 without diarrhoea) recruited from Kenyatta National Hospital, Kenya. Stool samples were examined for enteric pathogens by microscopy and bacteriology. Results Intestinal protozoa and fungi were identified in 70% of patients, more frequently in those with diarrhoea (p<0.001). Helminths were detected in 25.6% of patients overall, and bacterial pathogens were identified in 51% of patients with diarrhoea. Polyparasitism was more common in patients with diarrhoea than those without (p<0.0001). Higher CD4+ T-cell count (OR = 0.995, 95% CI 0.992–0.998) and water treatment (OR = 0.231, 95% CI 0.126–0.830) were associated with a lower risk of diarrhoea, while close contact with cows (OR = 3.200, 95% CI 1.26–8.13) or pigs (OR = 11.176, 95% CI 3.76–43.56) were associated with a higher risk of diarrhoea. Conclusions Multiple enteric pathogens that are causative agents of diarrhoea were isolated from stools of antiretroviral therapy-naïve HIV/AIDS patients, indicating a need for surveillance, treatment and promotion of hygienic practices. PMID:24026463

  16. Health-related Quality of Life Assessment after Antiretroviral Therapy: A Review of the Literature

    PubMed Central

    Gakhar, Harleen; Kamali, Amanda

    2015-01-01

    Antiretroviral (ARV) treatment for HIV infection has resulted in significant improvement in immunologic and virologic parameters, as well as a reduction in AIDS-defining illnesses and death. Over 25 medications are approved for use, usually in combination regimens of three or four ARVs. Several ARVs are now available as combinatorial products, which have been associated with better adherence. However, while ARV therapy has prolonged life, ARVs also pose a challenge for quality of life as they can cause significant side effects in addition to the potential for drug toxicity and interaction. Given the many complications, side effects and symptoms of HIV/AIDS in addition to associated medical and psychiatric co-morbidities, the need to understand and assess how these interactions may affect health-related quality of life (HRQOL) has grown. Numerous instruments (some validated, others not) are available and have been applied to understanding how ARV treatment affects HRQOL in those with HIV infection, both in clinical trials and clinical practice. In general, ARV treatment improves HRQOL, but this is dependent on the population being studied, the HRQOL instrument being used and the timeframe during which HRQOL has been studied. This article provides a review of the literature on quality of-life assessment as it relates to ARV treatment in developed countries and briefly reviews the HRQOL instruments used, how they have been applied to ARV utilization, and where future research should be applied in HRQOL assessment and HIV infection. PMID:23591907

  17. HIV Drug Resistance-Associated Mutations in Antiretroviral Naïve HIV-1-Infected Latin American Children

    PubMed Central

    Soto-Ramirez, Luis E.; Rodriguez-Diaz, Roberto; Harris, D. Robert; Hazra, Rohan

    2010-01-01

    Our goal was to describe the presence of HIV drug resistance among HIV-1-infected, antiretroviral (ARV) naïve children and adolescents in Latin America and to examine resistance in these children in relation to drug exposure in the mother. Genotyping was performed on plasma samples obtained at baseline from HIV-1-infected participants in a prospective cohort study in Brazil, Argentina, and Mexico (NISDI Pediatric Study). Of 713 HIV-infected children enrolled, 69 were ARV naïve and eligible for the analysis. At enrollment, mean age was 7.3 years; 81.2% were infected with HIV perinatally. Drug resistance mutations (DRMs) were detected in 6 (8.7%; 95% confidence interval 3.1–18.2%) ARV-naïve subjects; none of the mothers of these 6 received ARVs during their pregnancies and none of the children received ARV prophylaxis. Reverse transcriptase mutations K70R and K70E were detected in 3 and 2 subjects, respectively; protease mutation I50?V was detected in 1 subject. Three of the 6 children with DRMs initiated ARV therapy during followup, with a good response in 2. The overall rate of primary drug resistance in this pediatric HIV-infected population was low, and no subjects had more than 1 DRM. Mutations associated with resistance to nucleoside reverse transcriptase inhibitors were the most prevalent. PMID:22331986

  18. Dyslipidemia in a Cohort of HIV-infected Latin American Children Receiving Highly Active Antiretroviral Therapy*

    PubMed Central

    Brewinski, Margaret; Megazzini, Karen; Freimanis Hance, Laura; Cruz, Miguel Cashat; Pavia-Ruz, Noris; Della Negra, Marinella; Ferreira, Flavia Gomes Faleiro; Marques, Heloisa

    2011-01-01

    In order to describe the prevalence of hypercholesterolemia and hypertriglyceridemia in a cohort of HIV-infected children and adolescents in Latin America and to determine associations with highly active antiretroviral therapy (HAART), we performed this cross-sectional analysis within the NICHD International Site Development Initiative pediatric cohort study. Eligible children had to be at least 2 years of age and be on HAART. Among the 477 eligible HIV-infected youth, 98 (20.5%) had hypercholesterolemia and 140 (29.4%) had hypertriglyceridemia. In multivariable analyses, children receiving protease inhibitor (PI)-containing HAART were at increased risk for hypercholesterolemia [adjusted odds ratio (AOR)?=?2.7, 95% confidence interval (CI) 1.3–5.6] and hypertriglyceridemia (AOR?=?3.5, 95% CI 1.9–6.4) compared with children receiving non-nucleoside reverse transcriptase inhibitor (NNRTI)-containing HAART. In conclusion, HIV-infected youth receiving PI-containing HAART in this Latin American cohort were at increased risk for hypercholesterolemia and hypertriglyceridemia compared with those receiving NNRTI-containing HAART. PMID:20889625

  19. Factors impacting the provision of antiretroviral therapy to people living with HIV: the view from Haiti.

    PubMed

    Rouzier, Vanessa; Farmer, Paul E; Pape, Jean W; Jerome, Jean-Gregory; Van Onacker, Joelle Deas; Morose, Willy; Joseph, Patrice; Leandre, Fernet; Severe, Patrice; Barry, Donna; Deschamps, Marie-Marcelle; Koenig, Serena P

    2014-01-01

    Haiti is the poorest country in the Western Hemisphere and has the highest number of people living with HIV in the Caribbean, the region most impacted by HIV outside of Africa. Despite continuous political, socioeconomic and natural catastrophes, Haiti has mounted a very successful response to the HIV epidemic. Prevention and treatment strategies implemented by the government in collaboration with non-governmental organizations have been instrumental in decreasing the national HIV prevalence from a high of 6.2% in 1993 to 2.2% in 2012. We describe the history and epidemiology of HIV in Haiti and the expansion of antiretroviral therapy (ART) over the past decade, with the achievement of universal access to ART for patients meeting the 2010 World Health Organization guidelines. We also describe effective models of care, successes and challenges of international funding, and current challenges in the provision of ART. We are optimistic that the goal of providing ART for all in need remains in reach. PMID:25310257

  20. Use of antiretroviral therapies among HIV-infected men who have sex with men: a household-based sample of 4 major American cities.

    PubMed Central

    Stall, R; Pollack, L; Mills, T C; Martin, J N; Osmond, D; Paul, J; Binson, D; Coates, T J; Catania, J A

    2001-01-01

    OBJECTIVES: This study sought to determine the prevalence and determinants of use of recommended antiretroviral regimens among urban seropositive men who have sex with men (MSM). METHODS: A probability telephone sample of MSM was taken within regions of Chicago, Los Angeles, New York, and San Francisco. Analysis focused on use of antiretroviral therapies. RESULTS: Although the majority of seropositive MSM with CD4 counts below 500 per microliter were using recommended antiretroviral regimens, 26% of seropositive MSM were not receiving such care. Men who were younger, who reported a sexual orientation other than homosexual, who had a more recent interview date, who were at middle levels of affiliation with the gay community, and who reported higher levels of perceived exclusivity on the part of the gay community were less likely to be using recommended antiretroviral regimens. CONCLUSIONS: Although current efforts to make antiretroviral therapies available to HIV-seropositive MSM are reasonably effective, additional efforts are needed for MSM characterized by relative youth and lower social support. PMID:11344885

  1. Managing potential drug-drug interactions between gastric acid-reducing agents and antiretroviral therapy: experience from a large HIV-positive cohort.

    PubMed

    Lewis, J M; Stott, K E; Monnery, D; Seden, K; Beeching, N J; Chaponda, M; Khoo, S; Beadsworth, Mbj

    2016-02-01

    Drug-drug interactions between antiretroviral therapy and other drugs are well described. Gastric acid-reducing agents are one such class. However, few data exist regarding the frequency of and indications for prescription, nor risk assessment in the setting of an HIV cohort receiving antiretroviral therapy. To assess prevalence of prescription of gastric acid-reducing agents and drug-drug interaction within a UK HIV cohort, we reviewed patient records for the whole cohort, assessing demographic data, frequency and reason for prescription of gastric acid-reducing therapy. Furthermore, we noted potential drug-drug interaction and whether risk had been documented and mitigated. Of 701 patients on antiretroviral therapy, 67 (9.6%) were prescribed gastric acid-reducing therapy. Of these, the majority (59/67 [88.1%]) were prescribed proton pump inhibitors. We identified four potential drug-drug interactions, which were appropriately managed by temporally separating the administration of gastric acid-reducing agent and antiretroviral therapy, and all four of these patients remained virally suppressed. Gastric acid-reducing therapy, in particular proton pump inhibitor therapy, appears common in patients prescribed antiretroviral therapy. Whilst there remains a paucity of published data, our findings are comparable to those in other European cohorts. Pharmacovigilance of drug-drug interactions in HIV-positive patients is vital. Education of patients and staff, and accurate data-gathering tools, will enhance patient safety. PMID:25721922

  2. Pushed or Pulled? Exploring the Factors Underpinning Graduate Start-Ups and Non-Start-Ups

    ERIC Educational Resources Information Center

    Nabi, G.; Walmsley, A.; Holden, R.

    2015-01-01

    The study explores the nature and mixture of push--pull factors in the journey from higher education into graduate entrepreneurship. Using longitudinal data from 15 graduates of a British university, it compares graduates who started their own business with graduates that did not. Importantly, both groups had initially indicated a strong desire to…

  3. Head Start Teaching Center: Evaluation of a New Approach to Head Start Staff Development.

    ERIC Educational Resources Information Center

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

    1997-01-01

    Briefly describes the national Head Start Teaching Center model, the implementation of this model in the New England region, the outcome evaluation plan, and results from the first year of training. Finds that training significantly increased trainees' knowledge, skills, and expertise. (EV)

  4. Implications of Brain Development Research for Even Start Family Literacy Programs. Look at Even Start.

    ERIC Educational Resources Information Center

    Logue, Mary Ellin

    Even Start is a federally funded program addressing the literacy needs of children and parents by offering parenting education, early childhood education, parent and child together time, and adult education. Noting that recent research on brain development and learning prompts a reexamination of beliefs and practices related to child rearing,…

  5. SOHO, an early start, a long lifetime

    NASA Astrophysics Data System (ADS)

    1996-01-01

    SOHO currently cruises through space towards its station near the so-called first Lagrange point 1.5 million km towards the Sun where it will be in uninterrupted daylight and where the gravitational pull of the Sun and the Earth are balanced. The spacecraft is now expected to arrive at its station on 14 March 1996, two weeks earlier than originally planned. Coincidentally, this is the tenth anniversary of another space milestone, the encounter of ESA's Giotto probe with Comet Halley! An optimised orbit-shaping manoeuvre on 4 January, further refined SOHO's trajectory. Enough fuel remains on board to maintain SOHO's position in space for at least twenty instead of the planned six years. All systems of the 1850 kg spacecraft designed and built by European industry have been checked after launch and are in excellent shape. Their nominal performance has allowed an early and uninterrupted start of the commissioning of the scientific payload. SOHO's 12 scientific instruments* are currently being tested. Scientists are studying the first images and calibrating their instruments for the scheduled start of operations in late March. The craft's particle detectors investigating "in situ" the solar wind streaming around SOHO at its vantage point near Lagrange point 1, have been operational for some time and SOHO's first image of the Sun was taken on 19 December 1995. "All those who have worked tirelessly on the SOHO payload, spacecraft and ground-segment are to be congratulated on their excellent work and for having developed the most remarkable tool to help us understand the Sun and its environment, the heliosphere" said Roger Bonnet, ESA's Director of Science. According to present plans one month of early science is scheduled to begin around end of March and scientists hope to present their initial findings to the wide public by early May. SOHO is a project of international cooperation between ESA and NASA. The mission is led and coordinated by ESA who also procured the spacecraft; NASA provided the launch and operates the satellite. The European scientists who designed nine of the observatory's instruments and their US colleagues who built a further three are all present at Goddard Space Flight Center, where they jointly plan the optimum scientific use of the satellite. The spacecraft is part of the international Solar-Terrestrial Science Programme, the next member of which is Cluster, a flotilla of four spacecraft that will study how the Sun affects Earth and surrounding space. Cluster is scheduled for launch in May 1996 on the first Ariane 5 rocket. It will be the second mission belonging to the first "Cornerstone" of ESA's long- term scientific programme "Horizon 2000".

  6. Spreading continents kick-started plate tectonics.

    PubMed

    Rey, Patrice F; Coltice, Nicolas; Flament, Nicolas

    2014-09-18

    Stresses acting on cold, thick and negatively buoyant oceanic lithosphere are thought to be crucial to the initiation of subduction and the operation of plate tectonics, which characterizes the present-day geodynamics of the Earth. Because the Earth's interior was hotter in the Archaean eon, the oceanic crust may have been thicker, thereby making the oceanic lithosphere more buoyant than at present, and whether subduction and plate tectonics occurred during this time is ambiguous, both in the geological record and in geodynamic models. Here we show that because the oceanic crust was thick and buoyant, early continents may have produced intra-lithospheric gravitational stresses large enough to drive their gravitational spreading, to initiate subduction at their margins and to trigger episodes of subduction. Our model predicts the co-occurrence of deep to progressively shallower mafic volcanics and arc magmatism within continents in a self-consistent geodynamic framework, explaining the enigmatic multimodal volcanism and tectonic record of Archaean cratons. Moreover, our model predicts a petrological stratification and tectonic structure of the sub-continental lithospheric mantle, two predictions that are consistent with xenolith and seismic studies, respectively, and consistent with the existence of a mid-lithospheric seismic discontinuity. The slow gravitational collapse of early continents could have kick-started transient episodes of plate tectonics until, as the Earth's interior cooled and oceanic lithosphere became heavier, plate tectonics became self-sustaining. PMID:25230662

  7. A Head Start to a Healthy Heart

    NASA Technical Reports Server (NTRS)

    2002-01-01

    Cambridge Heart, Inc., has licensed the only U.S. Food and Drug Administration-cleared tool to identify those at risk for sudden cardiac death (SCD). The Microvolt T-Wave Alternans Test(TM) was invented by Dr. Richard J. Cohen, a professor at the Harvard-Massachusetts Institute of Technology (MIT) Division of Health Sciences and Technology, with developmental support and funding from NASA's Johnson Space Center and the National Space Biomedical Research Institute (NSBRI) in Houston, Texas. In 1993, MIT licensed the technology to Cambridge Heart, Inc., a start-up company that Dr. Cohen helped to establish. Cambridge Heart's non-invasive technology measures T-wave alternans, a change from one heartbeat to the next that is too minute to be detected by a standard electrocardiogram. Cardiac patients with such a change in heartbeat regulation are faced with a much greater risk of ventricular arrhythmia and SCD than those without it. The company's ability to measure electrical alternans on a microvolt level has been clinically proven to be just as accurate as - and in some studies, more accurate than - more costly and somewhat risky, invasive procedures, such as electrophysiological testing.

  8. Martensite start temperature as a weldability index

    SciTech Connect

    Olson, D.L.; Liu, S.; Wang, W.; Pieters, R.R.G.M.; Ibarra, S.

    1996-12-31

    Traditionally, welding experts have used carbon equivalent type expressions, which include chemical composition and cooling rates, to determine the susceptibility of a steel and its weldment to hydrogen damage. Experimental diagrams that map cracking versus non-cracking behavior as a function of hydrogen and carbon equivalent have also been proposed for practical applications. More recently, however, there is a growing concern that the hydrogen distribution across the weldment is non-uniform. Depending on the hardenability of the heat affected zone (base metal) and the weld metal, the two regions may undergo austenite decomposition, more specifically, martensite transformation at different times. As a result of the earlier or later transformation of the weld metal (compared with the heat affected zone), hydrogen may accumulate in the weld metal or in the heat affected zone. Selective distribution of hydrogen will lead to decreased or increased hydrogen damage susceptibility of the welded joint. By investigating the martensite start temperature of the weld metal and of the base metal, together with the amount of hydrogen pickup, the hydrogen outgassing behavior and distribution across the weldment can be modeled.

  9. 40 CFR 1065.525 - Engine starting, restarting, and shutdown.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...of the following methods: (1) Start the engine as recommended in the...using a production starter motor or air-start system and either an adequately charged...supply, or a suitable compressed air source. (2) Use the...

  10. 45 CFR 1311.1 - Head Start Fellows Program Purpose.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...Continued) OFFICE OF HUMAN DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH...SERVICES THE ADMINISTRATION FOR CHILDREN, YOUTH AND FAMILIES, HEAD START...to Head Start and to other child development and family services...

  11. 45 CFR 1311.1 - Head Start Fellows Program Purpose.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...Continued) OFFICE OF HUMAN DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH...SERVICES THE ADMINISTRATION FOR CHILDREN, YOUTH AND FAMILIES, HEAD START...to Head Start and to other child development and family services...

  12. 45 CFR 1311.1 - Head Start Fellows Program Purpose.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ...Continued) OFFICE OF HUMAN DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH...SERVICES THE ADMINISTRATION FOR CHILDREN, YOUTH AND FAMILIES, HEAD START...to Head Start and to other child development and family services...

  13. 45 CFR 1311.1 - Head Start Fellows Program Purpose.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ...Continued) OFFICE OF HUMAN DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH...SERVICES THE ADMINISTRATION FOR CHILDREN, YOUTH AND FAMILIES, HEAD START...to Head Start and to other child development and family services...

  14. 45 CFR 1311.1 - Head Start Fellows Program Purpose.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ...Continued) OFFICE OF HUMAN DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH...SERVICES THE ADMINISTRATION FOR CHILDREN, YOUTH AND FAMILIES, HEAD START...to Head Start and to other child development and family services...

  15. Start-up manufacturing firms: operations for survival 

    E-print Network

    Liu, Kuangyi

    2009-11-25

    Start-up firms play an important role in the economy. Statistics show that a large percent of start-up firms fail after few years of establishment. Raising capital, which is crucial to success, is one of the difficulties ...

  16. 7 CFR 1430.205 - Selection of starting month.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...LOANS, PURCHASES, AND OTHER OPERATIONS DAIRY PRODUCTS Milk Income Loss Contract Program...Selection of starting month. (a) A dairy operation that enters into a...business day preceding the weekend. A dairy operation cannot select as the start...

  17. 40 CFR 86.1236-85 - Engine starting and restarting.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Evaporative Emission Test Procedures for New Gasoline-Fueled, Natural Gas-Fueled, Liquefied Petroleum Gas-Fueled and Methanol-Fueled Heavy-Duty Vehicles § 86.1236-85 Engine starting and restarting. (a) Starting. (1) The...

  18. 46 CFR 112.50-5 - Electric starting.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...HOMELAND SECURITY (CONTINUED) ELECTRICAL ENGINEERING EMERGENCY LIGHTING AND POWER SYSTEMS Emergency Diesel and Gas Turbine Engine Driven Generator Sets § 112.50-5 Electric starting. An electric starting system must have...

  19. 46 CFR 112.50-3 - Hydraulic starting.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...HOMELAND SECURITY (CONTINUED) ELECTRICAL ENGINEERING EMERGENCY LIGHTING AND POWER SYSTEMS Emergency Diesel and Gas Turbine Engine Driven Generator Sets § 112.50-3 Hydraulic starting. A hydraulic starting system must meet the...

  20. 46 CFR 112.50-3 - Hydraulic starting.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ...HOMELAND SECURITY (CONTINUED) ELECTRICAL ENGINEERING EMERGENCY LIGHTING AND POWER SYSTEMS Emergency Diesel and Gas Turbine Engine Driven Generator Sets § 112.50-3 Hydraulic starting. A hydraulic starting system must meet the...