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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. When to Start Antiretroviral Therapy

    MedlinePlus

    ... away. What conditions increase the need to start ART? HIV-infected people with the following conditions should ... consider starting ART immediately. Once a person starts ART, why is medication adherence important? ART is a ...

  3. Predicting virological decay in patients starting combination antiretroviral therapy

    PubMed Central

    2016-01-01

    Objective: Model trajectories of viral load measurements from time of starting combination antiretroviral therapy (cART), and use the model to predict whether patients will achieve suppressed viral load (≤200 copies/ml) within 6-months of starting cART. Design: Prospective cohort study including HIV-positive adults (UK Collaborative HIV Cohort Study). Methods: Eligible patients were antiretroviral naive and started cART after 1997. Random effects models were used to estimate viral load trends. Patients were randomly selected to form a validation dataset with those remaining used to fit the model. We evaluated predictions of suppression using indices of diagnostic test performance. Results: Of 9562 eligible patients 6435 were used to fit the model and 3127 for validation. Mean log10 viral load trajectories declined rapidly during the first 2 weeks post-cART, moderately between 2 weeks and 3 months, and more slowly thereafter. Higher pretreatment viral load predicted steeper declines, whereas older age, white ethnicity, and boosted protease inhibitor/non-nucleoside reverse transcriptase inhibitors based cART-regimen predicted a steeper decline from 3 months onwards. Specificity of predictions and the diagnostic odds ratio substantially improved when predictions were based on viral load measurements up to the 4-month visit compared with the 2 or 3-month visits. Diagnostic performance improved when suppression was defined by two consecutive suppressed viral loads compared with one. Conclusions: Viral load measurements can be used to predict if a patient will be suppressed by 6-month post-cART. Graphical presentations of this information could help clinicians decide the optimum time to switch treatment regimen during the first months of cART. PMID:27124894

  4. When to Start Antiretroviral Therapy in Resource-limited Settings

    PubMed Central

    Walensky, Rochelle P.; Wolf, Lindsey L.; Wood, Robin; Fofana, Mariam O.; Freedberg, Kenneth A.; Martinson, Neil A.; Paltiel, A. David; Anglaret, Xavier; Weinstein, Milton C.; Losina, Elena

    2011-01-01

    Background Results of international clinical trials assessing when to initiate antiretroviral therapy (ART) will not be available for several years. Objective To inform HIV treatment decisions over the short- and long-term regarding the optimal CD4 threshold at which to initiate ART in South Africa, while awaiting “when to start” trial results. Design Cost-effectiveness analysis using a computer simulation model of HIV disease. Data Sources Published data from randomized trials and observational cohorts in South Africa. Target Population HIV-infected patients in South Africa. Time Horizon Five-year and lifetime. Perspective Modified societal. Interventions No treatment, initiate ART at CD4<250/μl, and initiate ART at CD4<350/μl. Outcome Measures Morbidity, mortality, life expectancy, medical costs, and cost-effectiveness. Results of Base-Case Analysis If 10-100% of HIV-infected patients are diagnosed and linked to care, initiating ART at CD4<350/μl would reduce severe opportunistic diseases by 22,000-221,000 and deaths by 25,000-253,000 during the next 5 years, compared to initiating ART at CD4<250/μl; cost increases would range from $142 million (10%) to $1.4 billion (100%). Either ART strategy increased long-term survival by at least 7.9 years, with a mean per person life expectancy of 3.8 years for no ART and 12.5 years for ART at <350/μl. Compared to initiating ART at <250/μl, initiating ART at <350/μl had an incremental cost-effectiveness ratio of $1,200/year of life saved. Results of Sensitivity Analysis Initiating ART at CD4<350/μl remained cost-effective over the next 5 years even if the probability that the trial would demonstrate superiority to earlier therapy is as low as 17%. Limitations This model does not consider the possible benefits of ART initiation at CD4>350/μl nor reduced HIV transmission. Conclusions Earlier ART initiation in South Africa will likely reduce morbidity and mortality, improve long-term survival, and be very cost

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

    PubMed

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

    2015-04-01

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

  6. [Clinical management of acute and chronic human immunodeficiency virus infection before starting antiretroviral treatment].

    PubMed

    Miró, José M; Manzardo, Christian; Zamora, Laura; Pumarola, Tomas; Herreras, Zoe; Gallart, Teresa; Gatell, José M

    2011-12-01

    The evaluation of new cases of HIV infection is relatively common in Spain, where several thousands of patients with new infections are diagnosed each year. Eighty per cent of them have a chronic HIV infection at the first clinical evaluation, which is symptomatic (late presenters) in up to 30% of patients. The initial evaluation of HIV infection is not only directed at determining the clinical, virological (plasma HIV RNA viral load, resistance test and viral tropism) and immunological (CD4+ T-cell cell count) situation of the patients, but must also address the study of their co-infections (hepatitis, tuberculosis) and comorbidities (cardiovascular, hepatic, renal and bone) and the risk of HIV transmission. This is needed in order to decide, whether or not to start antiretroviral treatment, and with which combined antiretroviral treatment to start with, the prophylaxis of opportunistic infections, and the treatment of coinfections and comorbidities. The past and current medical history, the physical examination and laboratory tests will help us decide if the patient is to receive therapeutic intervention. The level of CD4+ T-cell lymphocytes is the best marker to suggest when to start combined antiretroviral treatment, indicating whether or not to start prophylaxis against opportunistic infections (if patients have a CD4+ T-cell count below 200 cells/mm(3)), and in advanced patients should make us suspect the presence of active opportunistic diseases in symptomatic cases. The management of patients with HIV infection must also include appropriate health education on the modes of transmission and prevention of HIV infection, and also to explain its natural history and how it can be modified with proper antiretroviral treatment, as well as to promote a healthy life. No less important is the psychological support, as these patients must learn to live with a chronic infection, which managed properly can ensure a very good long-term prognosis and quality of life.

  7. Cause-Specific Mortality in HIV-Positive Patients Who Survived Ten Years after Starting Antiretroviral Therapy

    PubMed Central

    May, Margaret T.; Vehreschild, Janne; Obel, Niels; Gill, Michael John; Crane, Heidi; Boesecke, Christoph; Samji, Hasina; Grabar, Sophie; Cazanave, Charles; Cavassini, Matthias; Shepherd, Leah; d’Arminio Monforte, Antonella; Smit, Colette; Saag, Michael; Lampe, Fiona; Hernando, Vicky; Montero, Marta; Zangerle, Robert; Justice, Amy C.; Sterling, Timothy; Miro, Jose; Ingle, Suzanne; Sterne, Jonathan A. C.

    2016-01-01

    Objectives To estimate mortality rates and prognostic factors in HIV-positive patients who started combination antiretroviral therapy between 1996–1999 and survived for more than ten years. Methods We used data from 18 European and North American HIV cohort studies contributing to the Antiretroviral Therapy Cohort Collaboration. We followed up patients from ten years after start of combination antiretroviral therapy. We estimated overall and cause-specific mortality rate ratios for age, sex, transmission through injection drug use, AIDS, CD4 count and HIV-1 RNA. Results During 50,593 person years 656/13,011 (5%) patients died. Older age, male sex, injecting drug use transmission, AIDS, and low CD4 count and detectable viral replication ten years after starting combination antiretroviral therapy were associated with higher subsequent mortality. CD4 count at ART start did not predict mortality in models adjusted for patient characteristics ten years after start of antiretroviral therapy. The most frequent causes of death (among 340 classified) were non-AIDS cancer, AIDS, cardiovascular, and liver-related disease. Older age was strongly associated with cardiovascular mortality, injecting drug use transmission with non-AIDS infection and liver-related mortality, and low CD4 and detectable viral replication ten years after starting antiretroviral therapy with AIDS mortality. Five-year mortality risk was <5% in 60% of all patients, and in 30% of those aged over 60 years. Conclusions Viral replication, lower CD4 count, prior AIDS, and transmission via injecting drug use continue to predict higher all-cause and AIDS-related mortality in patients treated with combination antiretroviral therapy for over a decade. Deaths from AIDS and non-AIDS infection are less frequent than deaths from other non-AIDS causes. PMID:27525413

  8. 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/μl 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

  9. Immunodeficiency in children starting antiretroviral therapy in low-, middle- and high-income countries

    PubMed Central

    Koller, Manuel; Patel, Kunjal; Chi, Benjamin H.; Wools-Kaloustian, Kara; Dicko, Fatoumata; Chokephaibulkit, Kulkanya; Chimbetete, Cleophas; Avila, Dorita; Hazra, Rohan; Ayaya, Samual; Leroy, Valeriane; Trong, Huu Khanh; Egger, Matthias; Davies, Mary-Ann

    2014-01-01

    Background The CD4 cell count or percent (CD4%) at the start of combination antiretroviral therapy (cART) are important prognostic factors in children starting therapy and an important indicator of program performance. We describe trends and determinants of CD4 measures at cART initiation in children from low-, middle- and high-income countries. Methods We included children aged <16 years from clinics participating in a collaborative study spanning sub-Saharan Africa, Asia, Latin America and the United States of America (USA). Missing CD4 values at cART start were estimated through multiple imputation. Severe immunodeficiency was defined according to World Health Organization criteria. Analyses used generalized additive mixed models adjusted for age, country and calendar year. Results 34,706 children from nine low-income, six lower middle-income, four upper middle-income countries and one high-income country (United States of America, USA) were included; 20,624 children (59%) had severe immunodeficiency. In low-income countries the estimated prevalence of children starting cART with severe immunodeficiency declined from 76% in 2004 to 63% in 2010. Corresponding figures for lower middle-income countries were from 77% to 66% and for upper middle-income countries from 75% to 58%. In the USA, the percentage decreased from 42% to 19% during the period 1996 to 2006. In low- and middle-income countries infants and children aged 12-15 years had the highest prevalence of severe immunodeficiency at cART initiation. Conclusions Despite progress in most low- and middle-income countries, many children continue to start cART with severe immunodeficiency. Early diagnosis and treatment of HIV-infected children to prevent morbidity and mortality associated with immunodeficiency must remain a global public health priority. PMID:25501345

  10. Who starts antiretroviral therapy in Durban, South Africa?… not everyone who should

    PubMed Central

    Bassett, Ingrid V.; Regan, Susan; Chetty, Senica; Giddy, Janet; Uhler, Lauren M.; Holst, Helga; Ross, Douglas; Katz, Jeffrey N.; Walensky, Rochelle P.; Freedberg, Kenneth A.; Losina, Elena

    2012-01-01

    Objective To evaluate rates of antiretroviral therapy (ART) initiation within 12 months of a new HIV diagnosis in Durban, South Africa. Design Prospective observational cohort. Methods Adults (≥18 years) were enrolled before HIV testing at two outpatient clinics into the South African Test, Identify and Link cohort. Both sites offer comprehensive HIV care. HIV test results, CD4 cell counts, dates of ART initiation and dates of death were collected from medical records and 12-month patient/family interviews were conducted. ART eligibility was defined as a CD4 cell count less than 200 cells/μl within 90 days of HIV diagnosis. The primary endpoint was ART initiation within 12 months for ART-eligible subjects. Results From November 2006 to October 2008, 1474 newly diagnosed HIV-infected outpatients were enrolled, 1012 (69%) of whom underwent CD4 cell count testing within 90 days. The median CD4 cell count was 159 cells/μl (interquartile range 65–299). Of those who underwent CD4 cell count testing, 538 (53%) were ART-eligible. Only 210 (39%) eligible enrollees were known to have initiated ART within 12 months. Among ART-eligible subjects, there were 108 known deaths; 82% occurred before ART initiation or with unknown ART initiation status. Men [rate ratio (RR) 1.3, 95% confidence interval (CI) 1.1–1.5] and subjects without an HIV-infected family member/friend (RR 1.3, 95% CI 1.1–1.7) were more likely not to start ART. Conclusion Less than half of ART-eligible subjects started ART within 12 months. Substantial attrition and mortality follow HIV diagnosis before ART initiation in Durban, South Africa. Major efforts directed towards earlier HIV diagnosis, effective linkage to care and timely ART initiation are urgently needed. PMID:20023438

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

    PubMed Central

    Abdissa, Alemseged; Kæstel, Pernille; Tesfaye, Markos; Yilma, Daniel; Girma, Tsinuel; Wells, Jonathan C K; Ritz, Christian; Mølgaard, Christian; Michaelsen, Kim F; Zerfu, Dilnesaw; Brage, Søren; Andersen, Åse B; Friis, Henrik

    2014-01-01

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

  12. START or SMART? Timing of Antiretroviral Therapy Initiation and Cardiovascular Risk for People With Human Immunodeficiency Virus Infection

    PubMed Central

    Siedner, Mark J.

    2016-01-01

    The Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection (START) study has reinforced the benefits of early initiation of antiretroviral therapy (ART). However, a notable secondary finding from that study was that immediate initiation of ART did not prevent cardiovascular disease (CVD) events (0.17 vs 0.20 events/1000 person-years, P = .65). This result appears to contradict a body of evidence, most notably from the Strategies for Management of Antiretroviral Therapy (SMART) study, which reported a 70% increased hazard of cardiovascular events for those deferring or interrupting treatment. Thus, an important unresolved question is whether the timing of ART impacts CVD risk. In this review, published data on relationships between timing of ART and CVD risk are reviewed. The data support a role for ART in mitigating CVD risk at lower CD4 counts, but data also suggests that, among those initiating therapy early, ART alone appears to suboptimally mitigate CVD risk. Additional interventions to address CVD risk among human immunodeficiency virus-infected populations are likely to be needed. PMID:26989755

  13. START or SMART? Timing of Antiretroviral Therapy Initiation and Cardiovascular Risk for People With Human Immunodeficiency Virus Infection.

    PubMed

    Siedner, Mark J

    2016-01-01

    The Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection (START) study has reinforced the benefits of early initiation of antiretroviral therapy (ART). However, a notable secondary finding from that study was that immediate initiation of ART did not prevent cardiovascular disease (CVD) events (0.17 vs 0.20 events/1000 person-years, P = .65). This result appears to contradict a body of evidence, most notably from the Strategies for Management of Antiretroviral Therapy (SMART) study, which reported a 70% increased hazard of cardiovascular events for those deferring or interrupting treatment. Thus, an important unresolved question is whether the timing of ART impacts CVD risk. In this review, published data on relationships between timing of ART and CVD risk are reviewed. The data support a role for ART in mitigating CVD risk at lower CD4 counts, but data also suggests that, among those initiating therapy early, ART alone appears to suboptimally mitigate CVD risk. Additional interventions to address CVD risk among human immunodeficiency virus-infected populations are likely to be needed. PMID:26989755

  14. 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

  15. Drug-Resistant Tuberculosis among HIV-Infected Patients Starting Antiretroviral Therapy in Durban, South Africa

    PubMed Central

    Hom, Jeffrey K.; Wang, Bingxia; Chetty, Senica; Giddy, Janet; Mazibuko, Matilda; Allen, Jenny; Walensky, Rochelle P.; Losina, Elena; Freedberg, Kenneth A.; Bassett, Ingrid V.

    2012-01-01

    Objective To estimate the prevalence of drug-resistant tuberculosis (TB) and describe the resistance patterns in patients commencing antiretroviral therapy (ART) in an HIV clinic in Durban, South Africa. Design Cross-sectional cohort study. Methods Consecutive HIV-infected adults (≥18y/o) initiating HIV care were enrolled from May 2007–May 2008, regardless of signs or symptoms of active TB. Prior TB history and current TB treatment status were self-reported. Subjects expectorated sputum for culture (MGIT liquid and 7H11 solid medium). Positive cultures were tested for susceptibility to first- and second-line anti-tuberculous drugs. The prevalence of drug-resistant TB, stratified by prior TB history and current TB treatment status, was assessed. Results 1,035 subjects had complete culture results. Median CD4 count was 92/µl (IQR 42–150/µl). 267 subjects (26%) reported a prior history of TB and 210 (20%) were receiving TB treatment at enrollment; 191 (18%) subjects had positive sputum cultures, among whom the estimated prevalence of resistance to any antituberculous drug was 7.4% (95% CI 4.0–12.4). Among those with prior TB, the prevalence of resistance was 15.4% (95% CI 5.9–30.5) compared to 5.2% (95% CI 2.1–8.9) among those with no prior TB. 5.1% (95% CI 2.4–9.5) had rifampin or rifampin plus INH resistance. Conclusions The prevalence of TB resistance to at least one drug was 7.4% among adults with positive TB cultures initiating ART in Durban, South Africa, with 5.1% having rifampin or rifampin plus INH resistance. Improved tools for diagnosing TB and drug resistance are urgently needed in areas of high HIV/TB prevalence. PMID:22912845

  16. Outcomes among HIV-1 Infected Individuals First Starting Antiretroviral Therapy with Concurrent Active TB or Other AIDS-Defining Disease

    PubMed Central

    Périssé, André R. S.; Smeaton, Laura; Chen, Yun; La Rosa, Alberto; Walawander, Ann; Nair, Apsara; Grinsztejn, Beatriz; Santos, Breno; Kanyama, Cecilia; Hakim, James; Nyirenda, Mulinda; Kumarasamy, Nagalingeswaran; Lalloo, Umesh G.; Flanigan, Timothy; Campbell, Thomas B.; Hughes, Michael D.

    2013-01-01

    Background Tuberculosis (TB) is common among HIV-infected individuals in many resource-limited countries and has been associated with poor survival. We evaluated morbidity and mortality among individuals first starting antiretroviral therapy (ART) with concurrent active TB or other AIDS-defining disease using data from the “Prospective Evaluation of Antiretrovirals in Resource-Limited Settings” (PEARLS) study. Methods Participants were categorized retrospectively into three groups according to presence of active confirmed or presumptive disease at ART initiation: those with pulmonary and/or extrapulmonary TB (“TB” group), those with other non-TB AIDS-defining disease (“other disease”), or those without concurrent TB or other AIDS-defining disease (“no disease”). Primary outcome was time to the first of virologic failure, HIV disease progression or death. Since the groups differed in characteristics, proportional hazard models were used to compare the hazard of the primary outcome among study groups, adjusting for age, sex, country, screening CD4 count, baseline viral load and ART regimen. Results 31 of 102 participants (30%) in the “TB” group, 11 of 56 (20%) in the “other disease” group, and 287 of 1413 (20%) in the “no disease” group experienced a primary outcome event (p = 0.042). This difference reflected higher mortality in the TB group: 15 (15%), 0 (0%) and 41 (3%) participants died, respectively (p<0.001). The adjusted hazard ratio comparing the “TB” and “no disease” groups was 1.39 (95% confidence interval: 0.93–2.10; p = 0.11) for the primary outcome and 3.41 (1.72–6.75; p<0.001) for death. Conclusions Active TB at ART initiation was associated with increased risk of mortality in HIV-1 infected patients. PMID:24391801

  17. 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/μL 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/ μL (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

  18. Acute hypophosphataemia and hypokalaemia in a patient starting antiretroviral therapy in Zambia-a new context for refeeding syndrome?

    PubMed

    Nyirenda, Christopher; Zulu, Isaac; Kabagambe, Edmond K; Bagchi, Shashwatee; Potter, Dara; Bosire, Claire; Krishnasami, Zipporah; Heimburger, Douglas C

    2009-01-01

    High mortality rates have been reported in the first 90 days of antiretroviral therapy in Zambia and other low-income countries. We report a case of acute hypophosphataemia and hypokalaemia in the first week of antiretroviral therapy in a patient with extreme AIDS wasting. Given its occurrence in an extremely wasted patient, it may be physiologically similar to refeeding syndrome but other causes could be relevant as well. Acute hypophosphataemia may contribute to early antiretroviral therapy associated mortality in low-income countries.

  19. The initial feasibility of a computer-based motivational intervention for adherence for youth newly recommended to start antiretroviral treatment.

    PubMed

    Outlaw, Angulique Y; Naar-King, Sylvie; Tanney, Mary; Belzer, Marvin E; Aagenes, Anna; Parsons, Jeffrey T; Merlo, Lisa J

    2014-01-01

    Young people represent the largest number of new HIV infections, thus youth living with HIV (YLH) are likely to be the largest group to initiate antiretroviral treatment (ART). Adherence patterns for behaviorally infected YLH are not adequate to effectively manage the disease; therefore, novel interventions are needed to improve medication adherence. The purpose of the current study, which will precede a randomized controlled trial, was to assess the initial feasibility of an individually tailored computer-based two-session interactive motivational interviewing (MI) intervention for YLH newly recommended to start ART. Intervention development occurred in collaboration with three youth advisory groups. Ten youth (ages 18-24) were recruited to participate in this study. Participants completed the intervention online. Intervention components focused on medication adherence (rating perceived importance and confidence, and goal setting). Retention was 100% for both intervention sessions. All participants (n=10) felt medication adherence was important, but 80% felt confident they could manage their adherence to HIV medications. Ninety percent of participants set the goal of taking their HIV medications exactly as prescribed and reported success achieving this goal at follow-up. Additionally, participants were satisfied with the quality of the sessions and the amount of assistance they received for managing their adherence to HIV medications (90% participants for Session 1; 89% for Session 2). Per exit interview responses, participants felt that the intervention made them think more about their health and was a motivator for them to take better care of their health. In conclusion, the intervention was feasible for YLH enrolled in the study.

  20. The initial feasibility of a computer-based motivational intervention for adherence for youth newly recommended to start antiretroviral treatment.

    PubMed

    Outlaw, Angulique Y; Naar-King, Sylvie; Tanney, Mary; Belzer, Marvin E; Aagenes, Anna; Parsons, Jeffrey T; Merlo, Lisa J

    2014-01-01

    Young people represent the largest number of new HIV infections, thus youth living with HIV (YLH) are likely to be the largest group to initiate antiretroviral treatment (ART). Adherence patterns for behaviorally infected YLH are not adequate to effectively manage the disease; therefore, novel interventions are needed to improve medication adherence. The purpose of the current study, which will precede a randomized controlled trial, was to assess the initial feasibility of an individually tailored computer-based two-session interactive motivational interviewing (MI) intervention for YLH newly recommended to start ART. Intervention development occurred in collaboration with three youth advisory groups. Ten youth (ages 18-24) were recruited to participate in this study. Participants completed the intervention online. Intervention components focused on medication adherence (rating perceived importance and confidence, and goal setting). Retention was 100% for both intervention sessions. All participants (n=10) felt medication adherence was important, but 80% felt confident they could manage their adherence to HIV medications. Ninety percent of participants set the goal of taking their HIV medications exactly as prescribed and reported success achieving this goal at follow-up. Additionally, participants were satisfied with the quality of the sessions and the amount of assistance they received for managing their adherence to HIV medications (90% participants for Session 1; 89% for Session 2). Per exit interview responses, participants felt that the intervention made them think more about their health and was a motivator for them to take better care of their health. In conclusion, the intervention was feasible for YLH enrolled in the study. PMID:23869650

  1. 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

  2. Quality of life among individuals with HIV starting antiretroviral therapy in diverse resource-limited areas of the world.

    PubMed

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

    2012-02-01

    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

  3. 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.

  4. Predicting Patterns of Long-Term CD4 Reconstitution in HIV-Infected Children Starting Antiretroviral Therapy in Sub-Saharan Africa: A Cohort-Based Modelling Study

    PubMed Central

    Musiime, Victor; Prendergast, Andrew; Nathoo, Kusum; Kekitiinwa, Addy; Nahirya Ntege, Patricia; Gibb, Diana M.; Thiebaut, Rodolphe; Walker, A. Sarah; Klein, Nigel; Callard, Robin

    2013-01-01

    Background Long-term immune reconstitution on antiretroviral therapy (ART) has important implications for HIV-infected children, who increasingly survive into adulthood. Children's response to ART differs from adults', and better descriptive and predictive models of reconstitution are needed to guide policy and direct research. We present statistical models characterising, qualitatively and quantitatively, patterns of long-term CD4 recovery. Methods and Findings CD4 counts every 12 wk over a median (interquartile range) of 4.0 (3.7, 4.4) y in 1,206 HIV-infected children, aged 0.4–17.6 y, starting ART in the Antiretroviral Research for Watoto trial (ISRCTN 24791884) were analysed in an exploratory analysis supplementary to the trial's pre-specified outcomes. Most (n = 914; 76%) children's CD4 counts rose quickly on ART to a constant age-corrected level. Using nonlinear mixed-effects models, higher long-term CD4 counts were predicted for children starting ART younger, and with higher CD4 counts (p<0.001). These results suggest that current World Health Organization–recommended CD4 thresholds for starting ART in children ≥5 y will result in lower CD4 counts in older children when they become adults, such that vertically infected children who remain ART-naïve beyond 10 y of age are unlikely ever to normalise CD4 count, regardless of CD4 count at ART initiation. CD4 profiles with four qualitatively distinct reconstitution patterns were seen in the remaining 292 (24%) children. Study limitations included incomplete viral load data, and that the uncertainty in allocating children to distinct reconstitution groups was not modelled. Conclusions Although younger ART-naïve children are at high risk of disease progression, they have good potential for achieving high CD4 counts on ART in later life provided ART is initiated following current World Health Organization (WHO), Paediatric European Network for Treatment of AIDS, or US Centers for Disease Control and

  5. Role of low-frequency HIV-1 variants in failure of nevirapine-containing antiviral therapy in women previously exposed to single-dose nevirapine

    PubMed Central

    Boltz, Valerie F.; Zheng, Yu; Lockman, Shahin; Hong, Feiyu; Halvas, Elias K.; McIntyre, James; Currier, Judith S.; Chibowa, Margret C.; Kanyama, Cecelia; Nair, Apsara; Owino-Ong'or, Willis; Hughes, Michael; Coffin, John M.; Mellors, John W.

    2011-01-01

    In the OCTANE/A5208 study of initial antiretroviral therapy (ART) in women exposed to single-dose nevirapine (sdNVP) ≥6 mo earlier, the primary endpoint (virological failure or death) was significantly more frequent in the NVP-containing treatment arm than in the lopinavir/ritonavir-containing treatment arm. Detection of NVP resistance in plasma virus at study entry by standard population genotype was strongly associated with the primary endpoint in the NVP arm, but two-thirds of endpoints occurred in women without NVP resistance. We hypothesized that low-frequency NVP-resistant mutants, missed by population genotype, explained excess failure in the NVP treatment arm. Plasma samples from 232 participants were analyzed by allele-specific PCR at study entry to quantify NVP-resistant mutants down to 0.1% for 103N and 190A and to 0.3% for 181C. Of 201 women without NVP resistance by population genotype, 70 (35%) had NVP-resistant mutants detected by allele-specific PCR. Among these 70 women, primary endpoints occurred in 12 (32%) of 38 women in the NVP arm vs. 3 (9%) of 32 in the lopinavir/ritonavir-containing arm (hazard ratio = 3.84). The occurrence of a primary endpoint in the NVP arm was significantly associated with the presence of K103N or Y181C NVP-resistant mutations at frequencies >1%. The risk for a study endpoint associated with NVP-resistant mutant levels did not decrease with time. Therefore, among women with prior exposure to sdNVP, low-frequency NVP-resistant mutants were associated with increased risk for failure of NVP-containing ART. The implications for choosing initial ART for sdNVP-exposed women are discussed. PMID:21576473

  6. Mortality According to CD4 Count at Start of Combination Antiretroviral Therapy Among HIV-infected Patients Followed for up to 15 Years After Start of Treatment: Collaborative Cohort Study

    PubMed Central

    May, Margaret T.; Vehreschild, Jorg-Janne; Trickey, Adam; Obel, Niels; Reiss, Peter; Bonnet, Fabrice; Mary-Krause, Murielle; Samji, Hasina; Cavassini, Matthias; Gill, Michael John; Shepherd, Leah C.; Crane, Heidi M.; d'Arminio Monforte, Antonella; Burkholder, Greer A.; Johnson, Margaret M.; Sobrino-Vegas, Paz; Domingo, Pere; Zangerle, Robert; Justice, Amy C.; Sterling, Timothy R.; Miró, José M.; Sterne, Jonathan A. C.

    2016-01-01

    Background. CD4 count at start of combination antiretroviral therapy (ART) is strongly associated with short-term survival, but its association with longer-term survival is less well characterized. Methods. We estimated mortality rates (MRs) by time since start of ART (<0.5, 0.5–0.9, 1–2.9, 3–4.9, 5–9.9, and ≥10 years) among patients from 18 European and North American cohorts who started ART during 1996–2001. Piecewise exponential models stratified by cohort were used to estimate crude and adjusted (for sex, age, transmission risk, period of starting ART [1996–1997, 1998–1999, 2000–2001], and AIDS and human immunodeficiency virus type 1 RNA at baseline) mortality rate ratios (MRRs) by CD4 count at start of ART (0–49, 50–99, 100–199, 200–349, 350–499, ≥500 cells/µL) overall and separately according to time since start of ART. Results. A total of 6344 of 37 496 patients died during 359 219 years of follow-up. The MR per 1000 person-years was 32.8 (95% confidence interval [CI], 30.2–35.5) during the first 6 months, declining to 16.0 (95% CI, 15.4–16.8) during 5–9.9 years and 14.2 (95% CI, 13.3–15.1) after 10 years’ duration of ART. During the first year of ART, there was a strong inverse association of CD4 count at start of ART with mortality. This diminished over the next 4 years. The adjusted MRR per CD4 group was 0.97 (95% CI, .94–1.00; P = .054) and 1.02 (95% CI, .98–1.07; P = .32) among patients followed for 5–9.9 and ≥10 years, respectively. Conclusions. After surviving 5 years of ART, the mortality of patients who started ART with low baseline CD4 count converged with mortality of patients with intermediate and high baseline CD4 counts. PMID:27025828

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

    PubMed Central

    2013-01-01

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

  8. The effect of polymorphisms in candidate genes on the long-term risk of lipodystrophy and dyslipidemia in HIV-infected white patients starting antiretroviral therapy.

    PubMed

    Marzocchetti, Angela; Schwarz, Jessica; Di Giambenedetto, Simona; Colafigli, Manuela; Bracciale, Laura; Fabbiani, Massimilliano; Fantoni, Massimo; Trecarichi, Enrico; Cauda, Roberto; De Luca, Andrea

    2011-12-01

    We investigated whether polymorphisms in human candidate genes could be associated with a different risk of developing lipodystrophy and dyslipidemia in HIV-infected patients starting combination antiretroviral therapy (cART). Genomic DNA samples from white HIV-1-infected patients were analyzed for seven polymorphisms located in the MDR1, TNF-α, APM1, APOE, and LPL genes. Lipid data were retrospectively collected beginning with the initiation of cART. Lipodystrophy was assessed cross-sectionally and then prospectively. The association with lipodystrophy and National Cholesterol Evaluation Program Adult Treatment Panel III-defined lipid thresholds was analyzed using survival analysis and logistic regression. One-hundred and seventy-four patients were genotyped. In 151 patients assessed for lipodystrophy, MDR1 3435 T homozygosis was associated with a higher hazard (adjusted hazard ratio, aHR, versus CT 0.25; p=0.02) and tumor necrosis factor (TNF)-α 308 G homozygosis with a lower hazard (vs. AA aHR 2.14; p=0.04) of developing trunk fat accumulation after adjusting for gender and initial cART type. The TNF 238 GG genotype was associated with a higher risk of developing low HDL-cholesterol levels (adjusted odd ratio, aOR, 5.91; p=0.01) while patients carrying the LPL S477X mutation were at lower risk of reaching high non-HDL-cholesterol levels (aOR 0.39; p=0.05). The APOEe3/3 genotype patients were at lower risk (aOR 0.26, p=0.015), whereas the adiponectin 276 GT carriers were at higher risk of developing hypertriglyceremia (vs. GG aOR 3.10; p=0.04). Knowledge of the effect of genetic determinants on dyslipidemia and lipodystrophy may prompt the investigation of potential pathogenetic mechanisms and might eventually be used for guiding individualized treatment decisions.

  9. Daily co-trimoxazole prophylaxis in severely immunosuppressed HIV-infected adults in Africa started on combination antiretroviral therapy: an observational analysis of the DART cohort

    PubMed Central

    Walker, AS; Ford, D; Gilks, CF; Munderi, P; Ssali, F; Reid, A; Katabira, E; Grosskurth, H; Mugyenyi, P; Hakim, J; Darbyshire, JH; Gibb, DM; Babiker, AG

    2010-01-01

    Summary Background Co-trimoxazole prophylaxis can reduce mortality from untreated HIV infection in Africa; whether benefits occur alongside combination antiretroviral therapy (ART) is unclear. We estimated the effect of prophylaxis after ART initiation in adults. Methods Participants in our observational analysis were from the DART randomised trial of management strategies in HIV-infected, symptomatic, previously untreated African adults starting triple-drug ART with CD4 counts lower than 200 cells per μL. Co-trimoxazole prophylaxis was not routinely used or randomly allocated, but was variably prescribed by clinicians. We estimated effects on clinical outcomes, CD4 cell count, and body-mass index (BMI) using marginal structural models to adjust for time-dependent confounding by indication. DART was registered, number ISRCTN13968779. Findings 3179 participants contributed 14 214 years of follow-up (8128 [57%] person-years on co-trimoxazole). Time-dependent predictors of co-trimoxazole use were current CD4 cell count, haemoglobin concentration, BMI, and previous WHO stage 3 or 4 events on ART. Present prophylaxis significantly reduced mortality (odds ratio 0·65, 95% CI 0·50–0·85; p=0·001). Mortality risk reduction on ART was substantial to 12 weeks (0·41, 0·27–0·65), sustained from 12–72 weeks (0·56, 0·37–0·86), but not evident subsequently (0·96, 0·63–1·45; heterogeneity p=0·02). Variation in mortality reduction was not accounted for by time on co-trimoxazole or current CD4 cell count. Prophylaxis reduced frequency of malaria (0·74, 0·63–0·88; p=0·0005), an effect that was maintained with time, but we observed no effect on new WHO stage 4 events (0·86, 0·69–1·07; p=0·17), CD4 cell count (difference vs non-users, −3 cells per μL [−12 to 6]; p=0·50), or BMI (difference vs non-users, −0·04 kg/m2 [−0·20 to 0·13); p=0·68]. Interpretation Our results reinforce WHO guidelines and provide strong motivation for provision

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

    PubMed

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

    2012-05-01

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

  11. First-line antiretroviral therapy durability in a 10-year cohort of naïve adults started on treatment in Uganda

    PubMed Central

    Castelnuovo, Barbara; Kiragga, Agnes; Mubiru, Frank; Kambugu, Andrew; Kamya, Moses; Reynolds, Steven J

    2016-01-01

    Introduction The majority of studies from resource-limited settings only report short-term virological outcomes of patients on antiretroviral treatment (ART). We aim to describe the long-term durability of first-line ART and identify factors associated with long-term virological outcomes. Methods At the Infectious Diseases Institute in Kampala, Uganda, 559 adult patients starting ART in 2004 were enrolled into a research cohort and monitored with viral load (VL) testing every six months for 10 years. We report the proportion and cumulative probability of 1) achieving virologic suppression (at least one VL <400 copies/ml); 2) experiencing virologic failure in patients who achieved suppression (two consecutive VLs >1000 copies/ml or one VL >5000, for those without a subsequent one); 3) treatment failure (not attaining virologic suppression or experiencing virologic failure). We used Cox regression methods to determine the characteristics associated with treatment failure. We included gender, baseline age, WHO stage, body mass index, CD4 count, propensity score for initial ART regimen, VL, time-dependent CD4 count and adherence. Results Of the 559 patients enrolled, 472 (84.8%) had at least one VL (67 died, 13 were lost to follow-up, 4 transferred, 2 had no VL available); 73.6% started on d4T/3TC/nevirapine and 26.4% on AZT/3TC/efavirenz. Patients in the two groups had similar characteristics, except for the higher proportion of patients in WHO Stage 3/4 and higher VL in the efavirenz-based group. Four hundred thirty-nine (93%) patients achieved virologic suppression with a cumulative probability of 0.94 (confidence interval (CI): 0.92–0.96); 74/439 (16.9%) experienced virologic failure with a cumulative probability of 0.18 (CI: 0.15–0.22). In the multivariate analysis, initial d4T/3TC/nevirapine regimen (hazard ratio (HR): 3.02; CI: 3.02 (1.66–5.44, p<0.001)) and baseline VL ≥5 log10 copies/ml (HR: 2.29; CI: 1.29–4.04) were associated with treatment

  12. Antiretroviral drugs.

    PubMed

    De Clercq, Erik

    2010-10-01

    In October 2010, it will be exactly 25 years ago that the first antiretroviral drug, AZT (zidovudine, 3'-azido-2',3'-dideoxythymidine), was described. It was the first of 25 antiretroviral drugs that in the past 25 years have been formally licensed for clinical use. These antiretroviral drugs fall into seven categories [nucleoside reverse transcriptase inhibitors (NRTIs), nucleotide reverse transcriptase inhibitors (NtRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), fusion inhibitors (FIs), co-receptor inhibitors (CRIs) and integrase inhibitors (INIs). The INIs (i.e. raltegravir) represent the most recent advance in the search for effective and selective anti-HIV agents. Combination of several anti-HIV drugs [often referred to as highly active antiretroviral therapy (HAART)] has drastically altered AIDS from an almost uniformly fatal disease to a chronic manageable one.

  13. Efficacy and durability of nevirapine in antiretroviral drug näive patients.

    PubMed

    Lange, Joep M A

    2003-09-01

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

  14. Minimal impact of an iron-fortified lipid-based nutrient supplement on Hb and iron status: a randomised controlled trial in malnourished HIV-positive African adults starting antiretroviral therapy.

    PubMed

    James, Philip; Friis, Henrik; Woodd, Susannah; Rehman, Andrea M; PrayGod, George; Kelly, Paul; Koethe, John R; Filteau, Suzanne

    2015-08-14

    Anaemia, redistribution of Fe, malnutrition and heightened systemic inflammation during HIV infection confer an increased risk of morbidity and mortality in HIV patients. We analysed information on Fe status and inflammation from a randomised, double blind, controlled phase-III clinical trial in Lusaka, Zambia and Mwanza, Tanzania. Malnourished patients (n 1815) were recruited at referral to antiretroviral therapy (ART) into a two-stage nutritional rehabilitation programme, randomised to receive a lipid-based nutrient supplement with or without added micronutrients. Fe was included in the intervention arm during the second stage, given from 2 to 6 weeks post-ART. Hb, serum C-reactive protein (CRP), serum ferritin and soluble transferrin receptor (sTfR) were measured at recruitment and 6 weeks post-ART. Multivariable linear regression models were used to assess the impact of the intervention, and the effect of reducing inflammation from recruitment to week 6 on Hb and Fe status. There was no effect of the intervention on Hb, serum ferritin, sTfR or serum CRP. A one-log decrease of serum CRP from recruitment to week 6 was associated with a 1.81 g/l increase in Hb (95% CI 0.85, 2.76; P< 0.001), and a 0.11 log decrease in serum ferritin (95% CI - 0.22, 0.03; P= 0.012) from recruitment to week 6. There was no association between the change in serum CRP and the change in sTfR over the same time period (P= 0.78). In malnourished, HIV-infected adults receiving dietary Fe, a reduction in inflammation in the early ART treatment period appears to be a precondition for recovery from anaemia.

  15. The Majority of the Pre-Antiretroviral Population Who Were Lost to Follow-Up Stopped Their Care in Freetown, Sierra Leone: A 12-Month Prospective Cohort Study Starting with HIV Diagnosis

    PubMed Central

    Kelly, J. Daniel; Schlough, Gabriel Warren; Conteh, Sulaiman; Barrie, M. Bailor; Kargbo, Brima; Giordano, Thomas P.

    2016-01-01

    Background The heterogeneity of the pre-antiretroviral (pre-ART) population calls for more granular depictions of the cascade of HIV care. Methods We studied a prospective cohort of persons newly diagnosed with HIV infection from a single center in Freetown, Sierra Leone, over a 12-month period and then traced those persons who were lost to follow-up (LTFU) during pre-ART care (before ART initiation). ART eligibility was based on a CD4 cell count result of ≤ 350 mm/cells and/or WHO clinical stage 3 or 4. Persons who attended an appointment in the final three months were considered to be retained in care. Adherence to ART was measured using pharmacy refill dates. “Effective HIV care” was defined as completion of the cascade of care at 12-months regardless of whether patients are on ART. Tracing outcomes were obtained for those who were LTFU during pre-ART care. Results 408 persons newly diagnosed with HIV infection were screened, 338 were enrolled, and 255 persons were staged for ART. ART-ineligible persons had higher retention rates than ART-eligible persons (59.6% vs 41.8%, p = 0.03). 77 (22.8%) of 338 persons received effective HIV care. Most attrition (61.9%) occurred with persons during pre-ART care. 123 of 138 persons (89.1%) who were LTFU prior to ART initiation were found, and 91 of those 123 (74.0%) were alive. Of the 74 persons who were alive and described their engagement in care, 40 (54.1%) stopped care. Nearly half (42.5%) of those 40 stopped after assessment of ART-eligibility but before ART initiation. The main limitation of this study was the lack of tracing outcomes for those lost during ART care. Conclusions The majority of the pre-ART LTFU population stopped their care, particularly after ART-eligibility but before ART initiation. Interventions to hasten ART initiation and retain this at-risk group may have significant downstream impact on effective HIV care. PMID:26901765

  16. Antiretrovirals for developing world.

    PubMed

    Adler, M W

    1998-01-24

    The most recent UNAIDS figures indicate that approximately 30 million people are infected with HIV worldwide, 5.8 million of whom were newly infected during 1997. At the 10th International Conference on AIDS and Sexually Transmitted Diseases in Africa, the President and Secretary of Health of France called upon developed countries to establish a Therapeutic Assistance Fund to make antiretrovirals available to people with HIV/AIDS in sub-Saharan Africa. While the annual per capita health budget in most African countries is less than US$10, triple antiretroviral therapy against AIDS in the developed world costs $12,000-14,000 per patient per year. Calculations based upon a lower per patient cost of $7000, and treating all 1.4 million African AIDS cases, would cost US$10 billion per year for drugs alone, more than 30 times the amount currently spent annually by international donors for AIDS programs in the entire developing world. Basic infrastructural requirements would have to be met were antiretrovirals made widely available, ranging from HIV screening and counseling to the provision of clean water with which to consume the required 20-30 tablets per day. High program costs will challenge long-term sustainability. Universal access to care and treatment for HIV infection and AIDS is not a reality in the developed world, let alone feasible in developing countries. Given the competing health care priorities in developing countries, the high costs of antiretroviral agents, poor infrastructure, and inability to sustain such a program, the French initiative is ill-advised and foolish public health practice.

  17. The START Study to evaluate the effectiveness of a combination intervention package to enhance antiretroviral therapy uptake and retention during TB treatment among TB/HIV patients in Lesotho: rationale and design of a mixed-methods, cluster-randomized trial

    PubMed Central

    Howard, Andrea A.; Hirsch-Moverman, Yael; Frederix, Koen; Daftary, Amrita; Saito, Suzue; Gross, Tal; Wu, Yingfeng; Maama, Llang Bridget

    2016-01-01

    Background Initiating antiretroviral therapy (ART) early during tuberculosis (TB) treatment increases survival; however, implementation is suboptimal. Implementation science studies are needed to identify interventions to address this evidence-to-program gap. Objective The Start TB Patients on ART and Retain on Treatment (START) Study is a mixed-methods, cluster-randomized trial aimed at evaluating the effectiveness, cost-effectiveness, and acceptability of a combination intervention package (CIP) to improve early ART initiation, retention, and TB treatment success among TB/HIV patients in Berea District, Lesotho. Design Twelve health facilities were randomized to receive the CIP or standard of care after stratification by facility type (hospital or health center). The CIP includes nurse training and mentorship, using a clinical algorithm; transport reimbursement and health education by village health workers (VHW) for patients and treatment supporters; and adherence support using text messaging and VHW. Routine data were abstracted for all newly registered TB/HIV patients; anticipated sample size was 1,200 individuals. A measurement cohort of TB/HIV patients initiating ART was recruited; the target enrollment was 384 individuals, each to be followed for the duration of TB treatment (6–9 months). Inclusion criteria were HIV-infected; on TB treatment; initiated ART within 2 months of TB treatment initiation; age ≥18; English- or Sesotho-speaking; and capable of informed consent. The exclusion criterion was multidrug-resistant TB. Three groups of key informants were recruited from intervention clinics: early ART initiators; non/late ART initiators; and health care workers. Primary outcomes include ART initiation, retention, and TB treatment success. Secondary outcomes include time to ART initiation, adherence, change in CD4+ count, sputum smear conversion, cost-effectiveness, and acceptability. Follow-up and data abstraction are complete. Discussion The START

  18. 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…

  19. 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,…

  20. Individualization of antiretroviral therapy

    PubMed Central

    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

  1. Antiretroviral Therapy for HIV Infection: When to Initiate Therapy, Which Regimen to Use, and How to Monitor Patients on Therapy.

    PubMed

    Johnson, Steven C

    Antiretroviral therapy is recommended for all patients with HIV infection. The benefit of immediate antiretroviral therapy was confirmed by results from the START (Strategic Timing of Antiretroviral Treatment) trial, which showed a 57% reduction in risk for the composite end point of AIDS-related events, serious non-AIDS-related events, or death from any cause with immediate treatment in antiretroviral therapy-naive participants with CD4+ cell counts above 500/µL. Other changes in HIV care include the widespread adoption of integrase strand transfer inhibitor-based regimens. Considerations regarding when to initiate antiretroviral therapy, which initial regimens to use, and appropriate monitoring of individuals taking antiretroviral therapy are discussed. This article summarizes an IAS-USA continuing education webinar presented by Steven C. Johnson, MD, in July 2015.

  2. 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!”

  3. Supervision, monitoring and evaluation of nationwide scale-up of antiretroviral therapy in Malawi.

    PubMed Central

    Libamba, Edwin; Makombe, Simon; Mhango, Eustice; de Ascurra Teck, Olga; Limbambala, Eddie; Schouten, Erik J.; Harries, Anthony D.

    2006-01-01

    OBJECTIVE: To describe the supervision, monitoring and evaluation strategies used to assess the delivery of antiretroviral therapy during nationwide scale-up of treatment in Malawi. METHODS: In the first quarter of 2005, the HIV Unit of the Ministry of Health and its partners (the Lighthouse Clinic; Médecins Sans Frontières-Belgium, Thyolo district; and WHO's Country Office) undertook structured supervision and monitoring of all public sector health facilities in Malawi delivering antiretroviral therapy. FINDINGS: Data monitoring showed that by the end of 2004, there were 13,183 patients (5274 (40%) male, 12 527 (95%) adults) who had ever started antiretroviral therapy. Of patients who had ever started, 82% (10 761/13,183) were alive and taking antiretrovirals; 8% (1026/13,183) were dead; 8% (1039/13,183) had been lost to follow up; <1% (106/13,183) had stopped treatment; and 2% (251/13,183) had transferred to another facility. Of those alive and on antiretrovirals, 98% (7098/7258) were ambulatory; 85% (6174/7258) were fit to work; 10% (456/4687) had significant side effects; and, based on pill counts, 96% (6824/7114) had taken their treatment correctly. Mistakes in the registration and monitoring of patients were identified and corrected. Drug stocks were checked, and one potential drug stock-out was averted. As a result of the supervisory visits, by the end of March 2005 recruitment of patients to facilities scheduled to start delivering antiretroviral therapy had increased. CONCLUSION: This report demonstrates the importance of early supervision for sites that are starting to deliver antiretroviral therapy, and it shows the value of combining data collection with supervision. Making regular supervisory and monitoring visits to delivery sites are essential for tracking the national scale-up of delivery of antiretrovirals. PMID:16628306

  4. Antiretroviral restriction factors in mice.

    PubMed

    Nair, Smita; Rein, Alan

    2014-11-26

    One of the most exciting areas in contemporary retrovirus research is the discovery of "restriction factors". These are cellular proteins that act after virus entry to inhibit infection by or replication of retroviruses (and other viruses and intracellular pathogens). We briefly discuss here three antiretroviral restriction factors in mice: Fv1, APOBEC3, and tetherin, touching on both biological and molecular aspects of these restriction systems.

  5. Impact of earlier combination antiretroviral therapy on outcomes in children

    PubMed Central

    Cotton, Mark F.; Rabie, Helena

    2015-01-01

    Purpose of review Early initiation of combination antiretroviral therapy (ART) in infants below 12 weeks of age reduces morbidity and mortality. A recent report of transient HIV remission in a child beginning ART from the second day of life has focused attention on very early therapy in the first days of life. Recent findings In the randomized children with HIV, early antiretroviral limited ART beginning at a median of 7.4 weeks of age lowered mortality and disease progression significantly compared with deferred ART beginning at a median of 21 weeks on study. In high-burden settings, infants initiating ART appear sicker than in children with HIV early antiretroviral and start at a later age. Many could be diagnosed on the first day of life. There are still programmatic obstacles to early diagnosis and initiation of ART in high-burden settings. There is growing but insufficient information on ART dosages in newborn infants. Summary There is now increased focus on initiating ART as postexposure prophylaxis in newborn infants at high risk of vertical transmission in the hope of limiting morbidity and dissemination of the virus. PMID:25389804

  6. [Ergotism due to simultaneous use of ergot alkaloids and high activity antiretroviral therapy].

    PubMed

    Cifuentes M, Daniel; Blanco L, Sergio; Ramírez F, Camila

    2016-06-01

    High activity antiretroviral therapy may exacerbate the activity of ergot alkaloids due to an inhibition of cytochrome P450. We report a 57 years old female with AIDS treated with lamivudine, zidovudine, atazanavir, ritonavir and cotrimoxazole presenting with ischemic signs in the four limbs. There was acrocyanosis and weak radial and ulnar pulses. A family member referred that the patient used ergot alkaloids for headaches. An ergotism due to the simultaneous use of ergot alkaloids and antiretroviral therapy was suspected. The latter was discontinued and intravenous nitroglycerin, nifedipine and pentoxifyline were started with good results. PMID:27598502

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

    PubMed

    Scott, C; Brand, A; Natha, M

    2012-05-01

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

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

    PubMed Central

    2012-01-01

    Background Identification of the determinants of access to investigational drugs is important to promote equity and scientific validity in clinical research. We aimed to analyze factors associated with the use of experimental antiretrovirals in Italy. Methods We studied participants in the Italian Cohort of Antiretroviral-Naive Patients (ICoNA). All patients 18 years or older who had started cART (≥ 3 drugs including at least two NRTI) after their enrolment and during 1997-2007 were included in this analysis. We performed a random effect logistic regression analysis to take into account clustering observations within clinical units. The outcome variable was the use of an experimental antiretroviral, defined as an antiretroviral started before commercial availability, in any episode of therapy initiation/change. Use of an experimental antiretroviral obtained through a clinical trial or an expanded access program (EAP) was also analyzed separately. Results A total of 9,441 episodes of therapy initiation/change were analyzed in 3,752 patients. 392 episodes (360 patients) involved an experimental antiretroviral. In multivariable analysis, factors associated with the overall use of experimental antiretrovirals were: number of experienced drugs (≥ 8 drugs versus "naive": adjusted odds ratio [AOR] = 3.71) or failed antiretrovirals(3-4 drugs and ≥ 5 drugs versus 0-2 drugs: AOR = 1.42 and 2.38 respectively); calendar year (AOR = 0.80 per year) and plasma HIV-RNA copies/ml at therapy change (≥ 4 log versus < 2 log: AOR = 1.55). The probability of taking an experimental antiretroviral through a trial was significantly lower for patients suffering from liver co-morbidity(AOR = 0.65) and for those who experienced 3-4 drugs (vs naive) (AOR = 0.55), while it increased for multi-treated patients(AOR = 2.60). The probability to start an experimental antiretroviral trough an EAP progressively increased with the increasing number of experienced and of failed drugs and also

  9. New Antiretroviral Treatment for HIV.

    PubMed

    Badowski, Melissa E; Pérez, Sarah E; Biagi, Mark; Littler, John A

    2016-09-01

    The Joint United Nations Programme on HIV/AIDS (UNAIDS) has set the global goal of ending the AIDS world epidemic by 2030. In order to end this epidemic they have established a 90-90-90 goal to be achieved by 2020, which may be problematic, especially in low- and middle-income countries. This goal includes 90% of individuals with HIV globally being diagnosed, on treatment, and virologically suppressed. Based on global estimates from 2014-2015, approximately 36.9 million individuals are living with HIV. Of those, 53% have been diagnosed with HIV, 41% are on antiretroviral therapy (ART), and 32% have viral suppression with <1000 copies/ml. Comprehensive approaches are needed to improve the number of people living with HIV (PLWH) who are diagnosed, linked, and engaged in care. Once PLWH are retained in care, treatment is key to both HIV prevention and transmission. The development and advancement of new ART is necessary to assist in reaching these goals by improving safety profiles, decreasing pill burden, improving quality of life and life expectancy, and creating new mechanisms to overcome resistance. The focus of this review is to highlight and review data for antiretroviral agents recently added to the market as well as discuss agents in various stages of development (new formulations and mechanisms of action). PMID:27539455

  10. 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

  11. 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.

  12. 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

  13. Combination Antiretroviral Use and Preterm Birth

    PubMed Central

    Watts, D. Heather; Williams, Paige L.; Kacanek, Deborah; Griner, Raymond; Rich, Kenneth; Hazra, Rohan; Mofenson, Lynne M.; Mendez, Hermann A.

    2013-01-01

    Background. Use of antiretroviral drugs (ARVs) during pregnancy has been associated with higher risk of preterm birth. Methods. The Pediatric HIV/AIDS Cohort Study network's Surveillance Monitoring for ART Toxicities study is a US-based cohort of human immunodeficiency virus (HIV)–exposed uninfected children. We evaluated maternal ARV use during pregnancy and the risk of any type of preterm birth (ie, birth before 37 completed weeks of gestation), the risk of spontaneous preterm birth (ie, preterm birth that occurred after preterm labor or membrane rupture, without other complications), and the risk of small for gestational age (SGA; ie, a birth weight of <10th percentile for gestational age). Multivariable logistic regression models were used to evaluate the association of ARVs and timing of exposure, while adjusting for maternal characteristics. Results. Among 1869 singleton births, 18.6% were preterm, 10.2% were spontaneous preterm, and 7.3% were SGA. A total of 89% used 3-drug combination ARV regimens during pregnancy. In adjusted models, the odds of preterm birth and spontaneous preterm birth were significantly greater among mothers who used protease inhibitors during the first trimester (adjusted odds ratios, 1.55 and 1.59, respectively) but not among mothers who used nonnucleoside reverse-transcriptase inhibitor or triple-nucleoside regimens during the first trimester. Combination ARV exposure starting later in pregnancy was not associated with increased risk. No associations were observed between SGA and exposure to combination ARV regimens. Conclusions. Protease inhibitor use early in pregnancy may be associated with increased risk for prematurity. PMID:23204173

  14. Long-Term Control of Human Immunodeficiency Virus-1 Replication Despite Extensive Resistance to Current Antiretroviral Regimens: Clonal Analysis of Resistance Mutations in Proviral Deoxyribonucleic Acid

    PubMed Central

    Stella-Ascariz, Natalia; Montejano, Rocio; Martin-Vicente, María; Mingorance, Jesús; Pérez-Valero, Ignacio; Bernardino, José I.; Arribas, Jose R.

    2016-01-01

    Archived resistance mutations compromise antiretroviral treatment. We have investigated 3 selected aviremic patients who had extensive historical resistance to their current regimen. All 3 patients underwent unstructured treatment interruptions associated to the re-emergence of wild-type virus before starting their current suppressive regimes. Almost all historical resistance mutations detected in plasma were found in circulating proviral deoxyribonucleic acid. None of the clones analyzed was fully resistant to the current antiretroviral regimen. PMID:27006965

  15. Intellectual property rights, market competition and access to affordable antiretrovirals.

    PubMed

    Pascual, Fernando

    2014-01-01

    The number of patients receiving antiretroviral therapy (ART) has increased from around half a million in 2003 to almost 10 million in only 10 years, and will continue to increase in the coming years. Over 16 million more are eligible to start ART according to the last World Health Organization (WHO) guidelines. The demand is also switching from the less expensive antiretrovirals (ARVs) that allowed such scale-up to newer more expensive ones with fewer side effects or those that can be used by people who have developed resistance to first-line treatment. However, patents on these new drugs can delay robust generic competition and, consequently, price reduction made possible by economies of scale. Various ways to address this issue have been envisaged or implemented, including the use of the flexibilities available under the Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS), systematic widespread voluntary licensing, of which the Medicines Patent Pool (MPP) is an example, and the application of different prices in different countries, called tiered pricing. This paper helps explain the impact of patents on market competition for ARVs and analyses various approaches available today to minimize this impact.

  16. Intellectual property rights, market competition and access to affordable antiretrovirals.

    PubMed

    Pascual, Fernando

    2014-01-01

    The number of patients receiving antiretroviral therapy (ART) has increased from around half a million in 2003 to almost 10 million in only 10 years, and will continue to increase in the coming years. Over 16 million more are eligible to start ART according to the last World Health Organization (WHO) guidelines. The demand is also switching from the less expensive antiretrovirals (ARVs) that allowed such scale-up to newer more expensive ones with fewer side effects or those that can be used by people who have developed resistance to first-line treatment. However, patents on these new drugs can delay robust generic competition and, consequently, price reduction made possible by economies of scale. Various ways to address this issue have been envisaged or implemented, including the use of the flexibilities available under the Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS), systematic widespread voluntary licensing, of which the Medicines Patent Pool (MPP) is an example, and the application of different prices in different countries, called tiered pricing. This paper helps explain the impact of patents on market competition for ARVs and analyses various approaches available today to minimize this impact. PMID:25309984

  17. HIV-1 antiretroviral drug therapy.

    PubMed

    Arts, Eric J; Hazuda, Daria J

    2012-04-01

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

  18. Antiretroviral Therapy in the Clinic▿

    PubMed Central

    Tsibris, Athe M. N.; Hirsch, Martin S.

    2010-01-01

    Antiretroviral therapy in the developed world has resulted in substantial reductions in HIV-associated morbidity and mortality, changing an HIV diagnosis from a likely death sentence into a manageable chronic infection (F. J. Palella, Jr., K. M. Delaney, A. C. Moorman, M. O. Loveless, J. Fuhrer, G. A. Satten, D. J. Aschman, and S. D. Holmberg, N. Engl. J. Med. 338:853-860, 1998). Several million years of life have been saved by effective anti-HIV treatment, although these successes should not obscure the magnitude of the ongoing worldwide HIV epidemic (R. P. Walensky, A. D. Paltiel, E. Losina, L. M. Mercincavage, B. R. Schackman, P. E. Sax, M. C. Weinstein, and K. A. Freedberg, J. Infect. Dis. 194:11-19, 2006). Readers of the Journal of Virology are doubtless aware of the fundamental advances in retrovirology that have made possible the development of potent inhibitors of HIV replication. In this review, we focus on the issues surrounding how these drugs and drug regimens are actually used in clinical settings. Their proper use requires detailed knowledge of the natural history of HIV infection, the pharmacology of the individual drugs, the complexities of drug-drug interactions, and the use of sophisticated molecular tests for monitoring of viral load, immunologic response, and drug resistance. PMID:20181709

  19. 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…

  20. Head Start Facilities Manual.

    ERIC Educational Resources Information Center

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

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

  1. Non-Antiretroviral Microbicides for HIV Prevention

    PubMed Central

    Scott, Yanille; Dezzutti, Charlene S.

    2016-01-01

    Non-antiretroviral microbicide candidates were previously explored as a female-controlled method of preventing sexual transmission of HIV. These products contained non-HIV specific active compounds that were ultimately found to disrupt the vaginal epithelium, cause increased immune activation in the female genital tract, disturb vaginal flora, and/or cause other irritation that precluded their use as vaginal microbicides. Due to the failure of these first-generation candidates, there was a shift in focus to developing HIV pre-exposure prophylaxis and microbicides containing small-molecule antiretrovirals. Even with the limited success of the antiretroviral-based microbicides in clinical evaluations and no commercially available products, there has been significant progress in microbicide research. The lessons learned from previous trials have given rise to more rigorous preclinical evaluation that aims to be better at predicting microbicide efficacy and safety and to novel formulation and delivery technologies. These advances have resulted in renewed interest in developing non-antiretroviral-based microbicides, such as broadly neutralizing antibodies (for example, VRC01) and anti-viral proteins (for example, Griffithsin), as options for persons not wanting to use antiretroviral drugs, and for their potential to prevent multiple sexually transmitted infections. PMID:27438574

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

    PubMed

    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.

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

    PubMed

    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

  4. 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

  5. Starting School in August

    ERIC Educational Resources Information Center

    Chmelynski, Carol

    2006-01-01

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

  6. CROI 2016: Advances in Antiretroviral Therapy.

    PubMed

    Taylor, Barbara S; Olender, Susan A; Tieu, Hong-Van; Wilkin, Timothy J

    2016-01-01

    The 2016 Conference on Retroviruses and Opportunistic Infections highlighted exciting advances in antiretroviral therapy, including important data on investigational antiretroviral drugs and clinical trials. Clinical trials demonstrated benefits from a long-acting injectable coformulation given as maintenance therapy, examined intravenous and subcutaneous administration of a monoclonal antibody directed at the CD4 binding site of HIV-1, and provided novel data on tenofovir alafenamide. Several studies focused on the role of HIV drug resistance, including the significance of minority variants, transmitted drug resistance, use of resistance testing, and drug class-related resistance. Novel data on the HIV care continuum in low- and middle-income settings concentrated on differentiated HIV care delivery models and outcomes. Data on progress toward reaching World Health Organization 90-90-90 targets as well as outcomes related to expedited initiation of HIV treatment and adherence strategies were presented. Results from a trial in Malawi showed reduced rates of mother-to-child transmission among HIV-infected women who initiated antiretroviral therapy prior to pregnancy, and several studies highlighted the effect of antiretroviral therapy in pediatric populations. A special session was dedicated to the findings of studies of Ebola virus disease and treatment during the outbreak in West Africa. PMID:27398863

  7. Progress in antiretroviral drug delivery using nanotechnology.

    PubMed

    Mallipeddi, Rama; Rohan, Lisa Cencia

    2010-08-09

    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.

  8. 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

  9. Pharmacokinetics of Antiretrovirals in Mucosal Tissue

    PubMed Central

    Cottrell, M.L.; Srinivas, N.; Kashuba, A.D.M.

    2015-01-01

    Introduction In the absence of an HIV vaccine or cure, antiretroviral (ARV) based prevention strategies are being investigated to reduce HIV incidence. These prevention strategies depend on achieving effective drug concentrations at the site HIV exposure which is most commonly the mucosal tissues of the lower gastrointestinal tract and the female genital tract. Areas covered This article collates all known data regarding drug exposure in these vulnerable mucosal tissues, and reviews important mechanisms of ARV drug distribution. Research papers and abstracts describing antiretroviral pharmacokinetics in the female genital tract and lower gastrointestinal mucosal tissues available in MEDLINE® or presented at scientific conferences prior to December 2014 are reviewed in detail. Important influences on ARV mucosal tissue distribution, including protein binding, active drug transport, and endogenous hormones, are also reviewed. Expert opinion ARVs exhibit highly variable pharmacokinetics in mucosal tissues. In general, antiretroviral exposure is higher in the lower gastrointestinal tract compared to the female genital tract, but concentrations required for protective efficacy are largely unknown. The expected site of HIV exposure represents an important consideration when designing and optimizing antiretroviral based prevention strategies. PMID:25797064

  10. Starting an aphasia center?

    PubMed

    Elman, Roberta J

    2011-08-01

    Starting an aphasia center can be an enormous challenge. This article provides initial issues to review and consider when deciding whether starting a new organization is right for you. Determining the need for the program in your community, the best size and possible affiliation for the organization, and available resources, as well as developing a business plan, marketing the program, and building awareness in the community, are some of the factors that are discussed. Specific examples related to starting the Aphasia Center of California are provided.

  11. Antiretroviral Therapies in Women after Single-Dose Nevirapine Exposure

    PubMed Central

    Lockman, S.; Hughes, M.D.; McIntyre, J.; Zheng, Y.; Chipato, T.; Conradie, F.; Sawe, F.; Asmelash, A.; Hosseinipour, M.C.; Mohapi, L.; Stringer, E.; Mngqibisa, R.; Siika, A.; Atwine, D.; Hakim, J.; Shaffer, D.; Kanyama, C.; Wools-Kaloustian, K.; Salata, R.A.; Hogg, E.; Alston-Smith, B.; Walawander, A.; Purcelle-Smith, E.; Eshleman, S.; Rooney, J.; Rahim, S.; Mellors, J.W.; Schooley, R.T.; Currier, J.S.

    2010-01-01

    BACKGROUND Peripartum administration of single-dose nevirapine reduces mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) but selects for nevirapine-resistant virus. METHODS In seven African countries, women infected with HIV-1 whose CD4+ T-cell counts were below 200 per cubic millimeter and who either had or had not taken single-dose nevirapine at least 6 months before enrollment were randomly assigned to receive antiretroviral therapy with tenofovir–emtricitabine plus nevirapine or tenofovir-emtricitabine plus lopinavir boosted by a low dose of ritonavir. The primary end point was the time to confirmed virologic failure or death. RESULTS A total of 241 women who had been exposed to single-dose nevirapine began the study treatments (121 received nevirapine and 120 received ritonavir-boosted lopinavir). Significantly more women in the nevirapine group reached the primary end point than in the ritonavir-boosted lopinavir group (26% vs. 8%) (adjusted P = 0.001). Virologic failure occurred in 37 (28 in the nevirapine group and 9 in the ritonavir-boosted lopinavir group), and 5 died without prior virologic failure (4 in the nevirapine group and 1 in the ritonavir-boosted lopinavir group). The group differences appeared to decrease as the interval between single-dose nevirapine exposure and the start of antiretroviral therapy increased. Retrospective bulk sequencing of baseline plasma samples showed nevirapine resistance in 33 of 239 women tested (14%). Among 500 women without prior exposure to single-dose nevirapine, 34 of 249 in the nevirapine group (14%) and 36 of 251 in the ritonavir-boosted lopinavir group (14%) had virologic failure or died. CONCLUSIONS In women with prior exposure to peripartum single-dose nevirapine (but not in those without prior exposure), ritonavir-boosted lopinavir plus tenofovir–emtricitabine was superior to nevirapine plus tenofovir–emtricitabine for initial antiretroviral therapy. (Funded by the National

  12. Drug Interactions with New and Investigational Antiretrovirals

    PubMed Central

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

    2010-01-01

    More than 20 individual and fixed-dose combinations of antiretrovirals are approved for the treatment of human immunodeficiency virus (HIV) infection. However, owing to the ongoing limitations of drug resistance and adverse effects, new treatment options are still required. A number of promising new agents in existing or new drug classes are in development or have recently been approved by the US FDA. Since these agents will be used in combination with other new and existing antiretrovirals, understanding the potential for drug interactions between these compounds is critical to their appropriate use. This article summarizes the drug interaction potential of new and investigational protease inhibitors (darunavir), non-nucleoside reverse transcriptase inhibitors (etravirine and rilpivirine), chemokine receptor antagonists (maraviroc, vicriviroc and INCB 9471), integrase inhibitors (raltegravir and elvitegravir) and maturation inhibitors (bevirimat). PMID:19492868

  13. Individualization of antiretroviral therapy - Pharmacogenomic aspect

    PubMed Central

    Dalal, Bhavik; Shankarkumar, Aruna; Ghosh, K.

    2015-01-01

    Combination therapy with three drug regimens for human immunodeficiency virus (HIV) infection significantly suppresses the viral replication. However, this therapeutic impact is restricted by adverse drug events and response in terms of short and long term efficacy. There are multiple factors involved in different responses to antiretrovirals (ARVs) such as age, body weight, disease status, diet and heredity. Pharmacogenomics deals with individual genetic make-up and its role in drug efficacy and toxicity. In depth genetic research has provided evidence to predict the risk of developing certain toxicities for which personalized screening and surveillance protocols may be developed to prevent side effects. Here we describe the use of pharmacogenomics for optimal use of HAART (highly active antiretroviral therapy). PMID:26831415

  14. Challenges in initiating antiretroviral therapy in 2010.

    PubMed

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

    2010-08-01

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

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

    PubMed Central

    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

  16. 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.

  17. Global challenges in the development and delivery of paediatric antiretrovirals.

    PubMed

    Bowen, Asha; Palasanthiran, Pamela; Sohn, Annette H

    2008-06-01

    By the end of 2006, compared with 28% coverage for adults, only 15% of children with HIV that needed antiretroviral treatment were receiving it. Major challenges in delivering treatment include the lack of paediatric antiretrovirals that can be dosed in small children and limited studies examining safety and efficacy for existing antiretroviral formulations. The high costs of treatment have been reduced through the use of generic, fixed-dose combination drugs. Evidence-based strategies for managing resistance and the scale-up of pharmacological trials for children in low- and middle-income countries are crucial to the success and future development of paediatric antiretrovirals.

  18. 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

  19. Starting in School

    ERIC Educational Resources Information Center

    Albertine, Susan

    2012-01-01

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

  20. TARCOG Home Start Program.

    ERIC Educational Resources Information Center

    Top of Alabama Regional Council of Governments, Huntsville. Human Resources Program.

    This report describes the Top of Alabama Regional Council of Governments (TARCOG) Home Start Program. Five aspects of the program are presented. (1) The nutrition component is aimed at helping parents make the best use of food resources through good planning, buying, and cooking. (2) The health program involves provision of medical and dental…

  1. “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

  2. 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/μl (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

  3. Adherence to HIV/AIDS antiretroviral therapy among drug users: A qualitative study in Iran

    PubMed Central

    Hosseini, Zahra; Eftkhar, Hasan; Nedjat, Saharnaz; Ebadi, Abbas; Abbasian, Ladan; Zamani, Fereshte; Aghamollaei, Teamur; Shojaeizade, Davood

    2016-01-01

    Background: The introduction of antiretroviral therapy has caused a remarkable decrease in the occurrence of diseases and mortality among HIV-positive patients, while this success has not been achieved among injection addicts due to a low adherence to antiretroviral medicine. This study aims at clarifying the important factors affecting adherence to treatment in addicts suffering from HIV. Materials and Methods: In this qualitative research, data were gathered through in-depth interviews and field notes, and were interpreted through content analysis in the form of constant comparison. The participants were 16 drug addicts living with HIV/AIDS. Most of them had records of imprisonment and were receiving Highly Active Antiretroviral Therapy (HAART) drug treatments in the AIDS center of Imam Khomeini Hospital complex, affiliated to Tehran University of Medical Sciences. Sampling was started in a purposive method and was continued until data were saturated. Results: Four main categories including psychological reactions, contradictory beliefs, perceived support, and individual and environmental barriers were extracted from the data, each having some sub-categories. Conclusions: The obtained results indicated that adherence to the treatment of HIV is not constant and mono-dimensional, but is a function of different factors. Hence, an individual having feeble adherence in a specific time and under specific circumstances may show desirable adherence under a different circumstance. Thus, treatment of addicts living with HIV/AIDS requires physical, psychological, and social attention along with drug treatments. PMID:26985220

  4. Timing of antiretroviral therapy and TB treatment outcomes in patients with TB-HIV in Myanmar

    PubMed Central

    Shewade, H. D.; Kyaw, N. T. T.; Oo, M. M.; Aung, T. K.; Aung, S. T.; Oo, H. N.; Win, T.; Harries, A. D.

    2016-01-01

    Setting: Integrated HIV Care programme, Mandalay, Myanmar. Objectives: To determine time to starting antiretroviral treatment (ART) in relation to anti-tuberculosis treatment (ATT) and its association with TB treatment outcomes in patients co-infected with tuberculosis (TB) and the human immunodeficiency virus (HIV) enrolled from 2011 to 2014. Design: Retrospective cohort study. Results: Of 1708 TB-HIV patients, 1565 (92%) started ATT first and 143 (8%) started ART first. Treatment outcomes were missing for 226 patients and were thus not included. In those starting ATT first, the median time to starting ART was 8.6 weeks. ART was initiated after 8 weeks in 830 (53%) patients. Unsuccessful outcome was found in 7%, with anaemia being an independent predictor. In patients starting ART first, the median time to starting ATT was 21.6 weeks. ATT was initiated within 3 months in 56 (39%) patients. Unsuccessful outcome was found in 12%, and in 20% of those starting ATT within 3 months. Patients with CD4 count <100/mm3 had a four times higher risk of an unsuccessful outcome. Conclusions: Timing of ART in relation to ATT was not an independent risk factor for unsuccessful outcome. Extensive screening for TB with rapid and sensitive diagnostic tests in HIV-infected persons and close monitoring of anaemia and immunosuppression are recommended to further improve TB treatment outcomes among patients with TB-HIV. PMID:27358804

  5. Clinical implications of resistance to antiretroviral drugs.

    PubMed

    Vella, S

    1997-06-01

    New virological concepts are emerging and results from trials using potent combinations have demonstrated that drug resistance in AIDS therapy can be delayed, if not completely overcome, by appropriate treatment strategies. The definition and measures of resistance are explained, including the general mechanisms of resistance. Resistance patterns with nucleoside analogues, non-nucleoside reverse transcriptase inhibitors, and protease inhibitors are examined, followed by a discussion of the clinical implications. It is suggested that, based on HIV-1 replication in vivo, early and aggressive antiretroviral therapy is needed to minimize the negative consequences of its replication. Recommended clinical guidelines for avoiding drug resistance are listed. PMID:11364354

  6. Identification of Interferon-Stimulated Genes with Antiretroviral Activity.

    PubMed

    Kane, Melissa; Zang, Trinity M; Rihn, Suzannah J; Zhang, Fengwen; Kueck, Tonya; Alim, Mudathir; Schoggins, John; Rice, Charles M; Wilson, Sam J; Bieniasz, Paul D

    2016-09-14

    Interferons (IFNs) exert their anti-viral effects by inducing the expression of hundreds of IFN-stimulated genes (ISGs). The activity of known ISGs is insufficient to account for the antiretroviral effects of IFN, suggesting that ISGs with antiretroviral activity are yet to be described. We constructed an arrayed library of ISGs from rhesus macaques and tested the ability of hundreds of individual macaque and human ISGs to inhibit early and late replication steps for 11 members of the retroviridae from various host species. These screens uncovered numerous ISGs with antiretroviral activity at both the early and late stages of virus replication. Detailed analyses of two antiretroviral ISGs indicate that indoleamine 2,3-dioxygenase 1 (IDO1) can inhibit retroviral replication by metabolite depletion while tripartite motif-56 (TRIM56) accentuates ISG induction by IFNα and inhibits the expression of late HIV-1 genes. Overall, these studies reveal numerous host proteins that mediate the antiretroviral activity of IFNs. PMID:27631702

  7. Identification of Interferon-Stimulated Genes with Antiretroviral Activity.

    PubMed

    Kane, Melissa; Zang, Trinity M; Rihn, Suzannah J; Zhang, Fengwen; Kueck, Tonya; Alim, Mudathir; Schoggins, John; Rice, Charles M; Wilson, Sam J; Bieniasz, Paul D

    2016-09-14

    Interferons (IFNs) exert their anti-viral effects by inducing the expression of hundreds of IFN-stimulated genes (ISGs). The activity of known ISGs is insufficient to account for the antiretroviral effects of IFN, suggesting that ISGs with antiretroviral activity are yet to be described. We constructed an arrayed library of ISGs from rhesus macaques and tested the ability of hundreds of individual macaque and human ISGs to inhibit early and late replication steps for 11 members of the retroviridae from various host species. These screens uncovered numerous ISGs with antiretroviral activity at both the early and late stages of virus replication. Detailed analyses of two antiretroviral ISGs indicate that indoleamine 2,3-dioxygenase 1 (IDO1) can inhibit retroviral replication by metabolite depletion while tripartite motif-56 (TRIM56) accentuates ISG induction by IFNα and inhibits the expression of late HIV-1 genes. Overall, these studies reveal numerous host proteins that mediate the antiretroviral activity of IFNs.

  8. 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.

  9. Drug Interactions and Antiretroviral Drug Monitoring

    PubMed Central

    Foy, Matthew; Sperati, C. John; Lucas, Gregory M.

    2014-01-01

    Due to the improved longevity afforded by combination antiretroviral therapy (cART), HIV-infected individuals are developing several non-AIDS related comorbid conditions. Consequently, medical management of the HIV-infected population is increasingly complex, with a growing list of potential drug-drug interactions (DDIs). This article reviews some of the most relevant and emerging potential interactions between antiretroviral medications and other agents. The most common DDIs are those involving protease inhibitors or non-nucleoside reverse transcriptase inhibitors which alter the cytochrome P450 enzyme system and/or drug transporters such as p-glycoprotein. Of note are the new agents for the treatment of chronic hepatitis C virus infection. These new classes of drugs and others drugs which are increasingly used in this patient population represent a significant challenge with regard to achieving the goals of effective HIV suppression and minimization of drug-related toxicities. Awareness of DDIs and a multidisciplinary approach are imperative in reaching these goals. PMID:24950731

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

    PubMed Central

    2010-01-01

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

  11. Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults

    PubMed Central

    Günthard, Huldrych F.; Saag, Michael S.; Benson, Constance A.; del Rio, Carlos; Eron, Joseph J.; Gallant, Joel E.; Hoy, Jennifer F.; Mugavero, Michael J.; Sax, Paul E.; Thompson, Melanie A.; Gandhi, Rajesh T.; Landovitz, Raphael J.; Smith, Davey M.; Jacobsen, Donna M.; Volberding, Paul A.

    2016-01-01

    IMPORTANCE New data and therapeutic options warrant updated recommendations for the use of antiretroviral drugs (ARVs) to treat or to prevent HIV infection in adults. OBJECTIVE To provide updated recommendations for the use of antiretroviral therapy in adults (aged ≥18 years) with established HIV infection, including when to start treatment, initial regimens, and changing regimens, along with recommendations for using ARVs for preventing HIV among those at risk, including preexposure and postexposure prophylaxis. EVIDENCE REVIEW A panel of experts in HIV research and patient care convened by the International Antiviral Society-USA reviewed data published in peer-reviewed journals, presented by regulatory agencies, or presented as conference abstracts at peer-reviewed scientific conferences since the 2014 report, for new data or evidence that would change previous recommendations or their ratings. Comprehensive literature searches were conducted in the PubMed and EMBASE databases through April 2016. Recommendations were by consensus, and each recommendation was rated by strength and quality of the evidence. FINDINGS Newer data support the widely accepted recommendation that antiretroviral therapy should be started in all individuals with HIV infection with detectable viremia regardless of CD4 cell count. Recommended optimal initial regimens for most patients are 2 nucleoside reverse transcriptase inhibitors (NRTIs) plus an integrase strand transfer inhibitor (InSTI). Other effective regimens include nonnucleoside reverse transcriptase inhibitors or boosted protease inhibitors with 2 NRTIs. Recommendations for special populations and in the settings of opportunistic infections and concomitant conditions are provided. Reasons for switching therapy include convenience, tolerability, simplification, anticipation of potential new drug interactions, pregnancy or plans for pregnancy, elimination of food restrictions, virologic failure, or drug toxicities. Laboratory

  12. 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…

  13. 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…

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

    PubMed Central

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

    2014-01-01

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

  15. 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

  16. 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.

  17. 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

  18. Managing antiretroviral-associated liver disease.

    PubMed

    Dieterich, Douglas

    2003-09-01

    The use of all potent drugs is associated with toxicities and antiretroviral (ARV) drugs are no exception. Antiretroviral therapy-associated hepatic toxicity is of increasing concern in the management of patients with HIV/AIDS. Liver toxicity has been reported in some HIV-infected patients being treated with drugs from all of these classes of ARV drugs: protease inhibitors (PIs), nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). Although the majority of cases involve asymptomatic elevations of liver enzymes (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]), severe, and, in a minority of cases, life threatening, liver disease has been reported in patients treated with ARV drugs. The exact causes of elevated plasma levels of AST and ALT are complex and, in many cases, obscure. The combination of viral hepatic disease, drugs that act adversely directly on the liver and drugs that act on other systems of the body which in turn, adversely affect the liver, can result in hepatic toxicity. Such toxicity may be inappropriately attributed solely to the direct effect of a drug. Knowledge of the possible causes of liver toxicity, and ways to avoid it, should reduce the risk of developing hepatotoxicity. The physician's task is to prevent the development of liver toxicity, e.g., by choosing appropriate therapeutic regimens and by careful management of the patient. This involves frequent monitoring of the patient, both clinically and by utilizing liver function tests on a regular basis. If signs and symptoms of liver disease do develop, prompt and expert management is essential. This review discusses the influence of a number of factors on hepatic toxicity including viral hepatitis, insulin resistance and the specific ARV drugs used in the treatment of patients with HIV/AIDS.

  19. 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

  20. High frequency of antiretroviral drug resistance among HIV-infected adults receiving first-line highly active antiretroviral therapy in N'Djamena, Chad.

    PubMed

    Koyalta, Donato; Charpentier, Charlotte; Beassamda, Jatibi; Rey, Elisabeth; Si-Mohamed, Ali; Djemadji-Oudjeil, Noël; Bélec, Laurent

    2009-07-01

    Antiretroviral drug resistance was evaluated in 88 adults infected with human immunodeficiency virus, most with subtype CRF11_cpx, who had received a first-line antiretroviral regimen for 6 months, in N'Djamena, Chad. A total of 47 patients (53%) had detectable viral load at month 6, and 56 (64%) had at least 1 antiretroviral resistance mutation observed.

  1. 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…

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

    PubMed Central

    Taylor, S.; Pereira, A.

    2001-01-01

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

  3. Timing of Antiretroviral Therapy for HIV-1 Infection and Tuberculosis

    PubMed Central

    Havlir, D. V.; Kendall, M. A.; Ive, P.; Kumwenda, J.; Swindells, S.; Qasba, S. S.; Luetkemeyer, A. F.; Hogg, E.; Rooney, J.; Wu, X.; Hosseinipour, M. C.; Lalloo, U.; Veloso, V. G.; Some, F. F.; Kumarasamy, N.; Padayatchi, N.; Santos, B. R.; Reid, S.; Hakim, J.; Mohapi, L.; Mugyenyi, P.; Sanchez, J.; Lama, J. R.; Pape, J. W.; Sattler, F. R.; Asmelash, A.; Moko, E.; Sawe, F.; Andersen, J.; Sanne, I.

    2012-01-01

    Background Antiretroviral therapy (ART) is indicated during tuberculosis (TB) treatment of patients infected with HIV-1, but the urgency to start ART at TB diagnosis for patients of varying levels of immune compromise is not known. Methods We conducted an open label, randomized study comparing immediate (within 2 weeks of TB treatment initiation) to early (8–12 weeks) ART among HIV-1 infected patients with CD4+ lymphocytes < 250/mm3 and suspected TB. The primary study endpoint was proportion of patients who survived without an AIDS-defining illness at 48 weeks. Results 809 patients with median baseline CD4+ lymphocytes of 77 cells/mm3 and HIV-1 RNA of 5.43 log10 copies/mL were enrolled. In the immediate arm, 12.9% of patients experienced an AIDS-defining illness or death by 48 weeks compared to 16.1% in the early arm (p=0.45; 95% confidence interval (CI) for difference: −1.8%, 8.1%). In patients with screening CD4+ lymphocytes <50 cells/mm3, 15.5% of patients on the immediate arm vs. 26.6% on early ART experienced an AIDS defining illness or death (p=0.02; difference CI: 1.5%, 20.5%). TB immune reconstitution inflammatory syndrome (IRIS) was more common with immediate ART (11% vs. 5%: p=0.002). Viral suppression at 48 weeks was 74% and did not differ between arms (p=0.38). Conclusion Overall, immediate ART did not reduce AIDS-defining illnesses and death compared to early ART. For persons with CD4+ lymphocytes < 50 cells/mm3, immediate ART had 42% less AIDS defining illnesses and death compared to early ART. (ClinicalTrial.gov number NCT00108862.) PMID:22010914

  4. 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

  5. HIV, antiretroviral treatment, hypertension, and stroke in Malawian adults

    PubMed Central

    Corbett, Elizabeth L.; Connor, Myles D.; Mzinganjira, Henry; Kampondeni, Sam; Choko, Augustine; Hopkins, Mark; Emsley, Hedley C.A.; Bryer, Alan; Faragher, Brian; Heyderman, Robert S.; Allain, Theresa J.; Solomon, Tom

    2016-01-01

    Objective: To investigate HIV, its treatment, and hypertension as stroke risk factors in Malawian adults. Methods: We performed a case-control study of 222 adults with acute stroke, confirmed by MRI in 86%, and 503 population controls, frequency-matched for age, sex, and place of residence, using Global Positioning System for random selection. Multivariate logistic regression models were used for case-control comparisons. Results: HIV infection (population attributable fraction [PAF] 15%) and hypertension (PAF 46%) were strongly linked to stroke. HIV was the predominant risk factor for young stroke (≤45 years), with a prevalence of 67% and an adjusted odds ratio (aOR) (95% confidence interval) of 5.57 (2.43–12.8) (PAF 42%). There was an increased risk of a stroke in patients with untreated HIV infection (aOR 4.48 [2.44–8.24], p < 0.001), but the highest risk was in the first 6 months after starting antiretroviral therapy (ART) (aOR 15.6 [4.21–46.6], p < 0.001); this group had a lower median CD4+ T-lymphocyte count (92 vs 375 cells/mm3, p = 0.004). In older participants (HIV prevalence 17%), HIV was associated with stroke, but with a lower PAF than hypertension (5% vs 68%). There was no interaction between HIV and hypertension on stroke risk. Conclusions: In a population with high HIV prevalence, where stroke incidence is increasing, we have shown that HIV is an important risk factor. Early ART use in immunosuppressed patients poses an additional and potentially treatable stroke risk. Immune reconstitution inflammatory syndrome may be contributing to the disease mechanisms. PMID:26683649

  6. Antiretroviral Therapy for the Prevention of HIV-1 Transmission.

    PubMed

    Cohen, Myron S; Chen, Ying Q; McCauley, Marybeth; Gamble, Theresa; Hosseinipour, Mina C; Kumarasamy, Nagalingeswaran; Hakim, James G; Kumwenda, Johnstone; Grinsztejn, Beatriz; Pilotto, Jose H S; Godbole, Sheela V; Chariyalertsak, Suwat; Santos, Breno R; Mayer, Kenneth H; Hoffman, Irving F; Eshleman, Susan H; Piwowar-Manning, Estelle; Cottle, Leslie; Zhang, Xinyi C; Makhema, Joseph; Mills, Lisa A; Panchia, Ravindre; Faesen, Sharlaa; Eron, Joseph; Gallant, Joel; Havlir, Diane; Swindells, Susan; Elharrar, Vanessa; Burns, David; Taha, Taha E; Nielsen-Saines, Karin; Celentano, David D; Essex, Max; Hudelson, Sarah E; Redd, Andrew D; Fleming, Thomas R

    2016-09-01

    Background An interim analysis of data from the HIV Prevention Trials Network (HPTN) 052 trial showed that antiretroviral therapy (ART) prevented more than 96% of genetically linked infections caused by human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples. ART was then offered to all patients with HIV-1 infection (index participants). The study included more than 5 years of follow-up to assess the durability of such therapy for the prevention of HIV-1 transmission. Methods We randomly assigned 1763 index participants to receive either early or delayed ART. In the early-ART group, 886 participants started therapy at enrollment (CD4+ count, 350 to 550 cells per cubic millimeter). In the delayed-ART group, 877 participants started therapy after two consecutive CD4+ counts fell below 250 cells per cubic millimeter or if an illness indicative of the acquired immunodeficiency syndrome (i.e., an AIDS-defining illness) developed. The primary study end point was the diagnosis of genetically linked HIV-1 infection in the previously HIV-1-negative partner in an intention-to-treat analysis. Results Index participants were followed for 10,031 person-years; partners were followed for 8509 person-years. Among partners, 78 HIV-1 infections were observed during the trial (annual incidence, 0.9%; 95% confidence interval [CI], 0.7 to 1.1). Viral-linkage status was determined for 72 (92%) of the partner infections. Of these infections, 46 were linked (3 in the early-ART group and 43 in the delayed-ART group; incidence, 0.5%; 95% CI, 0.4 to 0.7) and 26 were unlinked (14 in the early-ART group and 12 in the delayed-ART group; incidence, 0.3%; 95% CI, 0.2 to 0.4). Early ART was associated with a 93% lower risk of linked partner infection than was delayed ART (hazard ratio, 0.07; 95% CI, 0.02 to 0.22). No linked infections were observed when HIV-1 infection was stably suppressed by ART in the index participant. Conclusions The early initiation of ART led to a sustained

  7. [Recommendations for initial antiretroviral treatment in HIV-infected children. Update 2003].

    PubMed

    2004-03-01

    Highly active antiretroviral therapy in HIV-infected children has been associated with a dramatic decrease in progression to AIDS and HIV-related deaths, and infected children currently have an excellent quality of life. Antiretroviral drugs cannot eradicate the virus, although they can achieve a situation of latent infection. However, chronic use of these drugs has multiple adverse effects, the most important of which are metabolic complications. The large number of drugs required and patient characteristics such as age, tolerance to drugs, adherence, and social problems make unifying the criteria for initial therapy in HIV-infected children difficult. A balance should be sought between not delaying the start of treatment, to avoid immunologic deterioration, and minimizing the long-term adverse effects of the therapy. The present treatment recommendations are adapted from international guidelines and are based on a literature review and on our own experience. Our group previously published recommendations on the treatment of HIV-infected children and the aim of the present article is to provide an update.

  8. 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.

  9. Antiretroviral procurement and supply chain management.

    PubMed

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

    2014-01-01

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

  10. Antiretroviral procurement and supply chain management.

    PubMed

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

    2014-01-01

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

  11. Pharmacokinetics and drug-drug interactions of antiretrovirals: an update.

    PubMed

    Dickinson, Laura; Khoo, Saye; Back, David

    2010-01-01

    Current antiretroviral treatment has allowed HIV infection to become a chronic manageable condition with many HIV patients living longer. However, available antiretrovirals are not without limitations, for example the development of resistance and adverse effects. Consequently, new drugs in existing and novel classes are urgently required to provide viable treatment options to patients with few remaining choices. Darunavir, etravirine, maraviroc and raltegravir have been recently approved for treatment-experienced patients and other agents such as rilpivirine, vicriviroc and elvitegravir are currently under phase III study. Clinical studies are necessary to optimise potential treatment combinations and to manage drug-drug interactions to help avoid toxicity or therapy failure. This review aims to summarise the pharmacokinetics and key drug-drug interaction studies for newly available antiretrovirals and those in development. Further information regarding drug-drug interactions of well established antiretrovirals and those recently approved are readily available online at sites such as http://www.hiv-druginteractions.org, http://www.clinicaloptions.com/hiv, http://hivinsite.ucsf.edu. 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.

  12. 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…

  13. Nebraska: Early Head Start Initiative

    ERIC Educational Resources Information Center

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

    2012-01-01

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

  14. 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

  15. Adherence to Antiretroviral Therapy and Virologic Failure

    PubMed Central

    Bezabhe, Woldesellassie M.; Chalmers, Leanne; Bereznicki, Luke R.; Peterson, Gregory M.

    2016-01-01

    Abstract The often cited need to achieve ≥95% (nearly perfect) adherence to antiretroviral therapy (ART) for successful virologic outcomes in HIV may present a barrier to initiation of therapy in the early stages of HIV. This meta-analysis synthesized 43 studies (27,905 participants) performed across >26 countries, to determine the relationship between cut-off point for optimal adherence to ART and virologic outcomes. Meta-analysis was performed using a random-effect model to calculate pooled odds ratios with corresponding 95% confidence intervals. The mean rate of patients reporting optimal adherence was 63.4%. Compared with suboptimal adherence, optimal adherence was associated with a lower risk of virologic failure (0.34; 95% CI: 0.26–0.44). There were no significant differences in the pooled odds ratios among different optimal adherence thresholds (≥98–100%, ≥95%, ≥80–90%). Study design (randomized controlled trial vs observational study) (regression coefficient 0.74, 95% CI: 0.04–1.43, P < 0.05) and study region (developing vs developed countries; regression coefficient 0.56, 95% CI: 0.01–1.12, P < 0.05) remained as independent predictors of between-study heterogeneity, with more patients with optimal adherence from developing countries or randomized controlled trials experiencing virologic failure. The threshold for optimal adherence to achieve better virologic outcomes appears to be wider than the commonly used cut-off point (≥95% adherence). The cut-off point for optimal adherence could be redefined to a slightly lower level to encourage the prescribing ART at an early stage of HIV infection. PMID:27082595

  16. Anxiety and depression symptoms as risk factors for non-adherence to antiretroviral therapy in Brazil.

    PubMed

    Campos, Lorenza Nogueira; Guimarães, Mark Drew Crosland; Remien, Robert H

    2010-04-01

    Depression and anxiety are common among HIV-infected people and rank among the strongest predictors of non-adherence to antiretroviral therapy (ART). This longitudinal study aimed to assess whether symptoms of anxiety and depression are predictors of non-adherence among patients initiating ART at two public referral centers (n = 293) in Belo Horizonte, Brazil. Prevalence of severe anxiety and depression symptoms before starting ART was 12.6% and 5.8%, respectively. Severe anxiety was a predictor of non-adherence to ART during follow-up period (RH = 1.87; 95% CI = 1.14-3.06) adjusted for low education, unemployment, alcohol use in the last month and symptoms of AIDS; while a history of injection drug use had borderline statistical significance with non-adherence. These findings suggest that using a brief screening procedure to assess anxiety and depression symptoms before initiating ART help identify individuals for interventions to improve adherence and quality of life.

  17. The (political) economics of antiretroviral treatment in developing countries.

    PubMed

    Nattrass, Nicoli J

    2008-12-01

    Despite unprecedented international mobilisation to support universal provision of highly active antiretroviral therapy (HAART), national governments continue to play the key role in determining access to treatment. Whereas some AIDS-affected countries have performed as well as or better than expected given their level of development, institutional characteristics and demographic challenges (e.g. Thailand and Brazil), others (notably South Africa) have not. This article argues that the 'economics' of antiretroviral drug delivery is at heart a political-economy of access to treatment. It depends on commitment on the part of national governments to negotiate with pharmaceutical companies over patented antiretroviral drug prices, on their policy towards compulsory licensing, and on the approach they adopt to delivering HAART. Civil society has an important role to play in encouraging governments to become, and remain, committed to taking action to ensure sustainable and widespread access to HAART.

  18. [Allergic hypersensitivity to antiretroviral drugs: etravirine, raltegravir and darunavir].

    PubMed

    Sánchez-Olivas, Manuel Anastacio; Valencia-Zavala, Martha Patricia; Vega-Robledo, Gloria Bertha; Sánchez-Olivas, Jesús Alberto; Velázquez-Sámano, Guillermo; Sepúlveda-Velázquez, Guadalupe

    2015-01-01

    All antiretroviral drugs can have both short-term and long-term adverse events. The risk of specific side effects varies from drug to drug, from drug class to drug class, and from patient to patient. A better understanding of the adverse effects of antiretroviral agents is of interest not only for HIV specialists, but also for other physicians who care allergy reactions in HIV-positive patients. Each antiretroviral medication is associated with its own specific adverse effects or may cause problems only in particular circumstances. In this article some adverse allergic effects of HAART therapy in the treatment of HIV from a patient are reviewed. Our aim is to gain a working knowledge of these adverse effects, promoting the early recognition and reversal of potentially serious adverse effects, and reducing the potential for adverse drug interactions.

  19. [CLINICAL AND PHARMACOECONOMIC RESULTS OF THE USAGE OF VARIOUS HIV REVERSE TRANSCRIPTASE INHIBITORS IN THE SCHEMES OF ANTIRETROVIRAL THERAPY OF PATIENT RECEIVING THERAPY FOR THE CHRONIC HEPATITIS C VIRUS].

    PubMed

    Moshkovich, G F; Minaeva, S V; Varlova, L W; Goryaeva, M P; Gulyaeva, S S; Tichonova, E V

    2016-01-01

    Efficacy, safety, and economical aspects of treatment with abacavir, zidovudine, stavudine, and phosphazide in the schemes of antiretroviral therapy of the HIV-infected patients receiving therapy for hepatitis C virus were tested. Clinical, immunological, and virologic efficacy of treatment and dynamics of hemoglobin, thrombocytes, and alanine aminotransferase as markers of common adverse events recorded at the start of the antiviral therapy of chronic hepatitis C and after 4, 8, 12, 24, 48 weeks of the treatment were evaluated. The usage of these drugs in the schemes of antiretroviral therapy exhibited efficacy, high tolerability and safety for all HIV reverse transcriptase inhibitors.

  20. [CLINICAL AND PHARMACOECONOMIC RESULTS OF THE USAGE OF VARIOUS HIV REVERSE TRANSCRIPTASE INHIBITORS IN THE SCHEMES OF ANTIRETROVIRAL THERAPY OF PATIENT RECEIVING THERAPY FOR THE CHRONIC HEPATITIS C VIRUS].

    PubMed

    Moshkovich, G F; Minaeva, S V; Varlova, L W; Goryaeva, M P; Gulyaeva, S S; Tichonova, E V

    2016-01-01

    Efficacy, safety, and economical aspects of treatment with abacavir, zidovudine, stavudine, and phosphazide in the schemes of antiretroviral therapy of the HIV-infected patients receiving therapy for hepatitis C virus were tested. Clinical, immunological, and virologic efficacy of treatment and dynamics of hemoglobin, thrombocytes, and alanine aminotransferase as markers of common adverse events recorded at the start of the antiviral therapy of chronic hepatitis C and after 4, 8, 12, 24, 48 weeks of the treatment were evaluated. The usage of these drugs in the schemes of antiretroviral therapy exhibited efficacy, high tolerability and safety for all HIV reverse transcriptase inhibitors. PMID:27145599

  1. 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.

  2. 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/μL. 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/μL for a minimum of three months. Despite HAART, patients with a CD4 count < 50 cells/μL 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

  3. 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/μL. 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/μL for a minimum of three months. Despite HAART, patients with a CD4 count < 50 cells/μL 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.

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

    PubMed Central

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

    2013-01-01

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

  5. Long-Term Outcomes on Antiretroviral Therapy in a Large Scale-Up Program in Nigeria

    PubMed Central

    Meloni, Seema T.; Chang, Charlotte A.; Eisen, Geoffrey; Jolayemi, Toyin; Banigbe, Bolanle; Okonkwo, Prosper I.; Kanki, Phyllis J.

    2016-01-01

    Background While there has been a rapid global scale-up of antiretroviral therapy programs over the past decade, there are limited data on long-term outcomes from large cohorts in resource-constrained settings. Our objective in this evaluation was to measure multiple outcomes during first-line antiretroviral therapy in a large treatment program in Nigeria. Methods We conducted a retrospective multi-site program evaluation of adult patients (age ≥15 years) initiating antiretroviral therapy between June 2004 and February 2012 in Nigeria. The baseline characteristics of patients were described and longitudinal analyses using primary endpoints of immunologic recovery, virologic rebound, treatment failure and long-term adherence patterns were conducted. Results Of 70,002 patients, 65.2% were female and median age was 35 (IQR: 29–41) years; 54.7% were started on a zidovudine-containing and 40% on a tenofovir-containing first-line regimen. Median CD4+ cell counts for the cohort started at 149 cells/mm3 (IQR: 78–220) and increased over duration of ART. Of the 70,002 patients, 1.8% were reported as having died, 30.1% were lost to follow-up, and 0.1% withdrew from treatment. Overall, of those patients retained and with viral load data, 85.4% achieved viral suppression, with 69.3% achieving suppression by month 6. Of 30,792 patients evaluated for virologic failure, 24.4% met criteria for failure and of 45,130 evaluated for immunologic failure, 34.0% met criteria for immunologic failure, with immunologic criteria poorly predicting virologic failure. In adjusted analyses, older age, ART regimen, lower CD4+ cell count, higher viral load, and inadequate adherence were all predictors of virologic failure. Predictors of immunologic failure differed slightly, with age no longer predictive, but female sex as protective; additionally, higher baseline CD4+ cell count was also predictive of failure. Evaluation of long-term adherence patterns revealed that the majority of patients

  6. Novel oral anticoagulants and HIV: dabigatran use with antiretrovirals.

    PubMed

    Perram, Jacinta; Joseph, Joanne; Holloway, Cameron

    2015-01-01

    Compatibility of novel oral anticoagulants in patients with HIV taking combined antiretroviral therapy has not been established, with no published reports of successful concurrent use. We present a case where chronic anticoagulation was indicated in a patient with treated HIV and non-valvular atrial fibrillation who refused warfarin therapy. The patient tolerated the combination, with dabigatran blood levels within the expected range at a standard dosing regimen, without evidence of bleeding or other adverse outcomes. While further research is needed to establish the role of novel oral anticoagulants in patients taking antiretrovirals, this case suggests that dabigatran may be a viable option for selected patients.

  7. 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

  8. 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

  9. Accountability Starts with the Superintendent

    ERIC Educational Resources Information Center

    Ricketts, Kenneth E.

    1973-01-01

    Describes how Lawndale District, near Los Angeles, developed a system of accountability starting with the superintendent. Describes the subgoals and objectives developed by the superintendent in cooperation with the Board of Trustees and members of the community. (JF)

  10. Montessori Head Start Implementation Brief.

    ERIC Educational Resources Information Center

    Clifford, Alcillia; Kahn, David

    1995-01-01

    Discusses the use of the Montessori method in Head Start programs, focusing on educational environment, teacher training, parent involvement, and funding. Outlines the phased implementation of a Montessori program and provides a list of Montessori publications and organizations. (MDM)

  11. Generic antiretroviral drugs and HIV care: An economic review.

    PubMed

    Yazdanpanah, Y; Schwarzinger, M

    2016-03-01

    The cost of HIV care in European countries is high. Direct medical costs, in France, have been estimated at 500,000 Euros per patient's lifetime (20,000 Euros/year/patient). Overall, 73% of these costs are related to antiretroviral treatments. In the current financial crisis context, some European countries are beginning to make economic decisions on the drugs to be used. These approaches are likely to become more frequent. It is obviously essential to prescribe the most effective, appropriate, best tolerated, and easy-to-use antiretroviral treatments to patients. However, while taking the above into consideration, and if various treatment options or combinations are available, cost should also be considered in the treatment choice. One may thus reflect on the use of generic antiretroviral agents as they have just been launched in France. We aimed to review the cost and cost-effectiveness of generic antiretroviral drugs and to review treatment strategies other than generic drugs that could help reduce HIV-related costs. HIV clinicians should consider treatment costs to avoid any future coercive measures. PMID:26905394

  12. 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

  13. Clinical Pharmacokinetics of Antiretroviral Drugs in Older Persons

    PubMed Central

    Schoen, John C.; Erlandson, Kristine Mace

    2013-01-01

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

  14. Pharmacogenetics as a tool to tailor antiretroviral therapy: A review.

    PubMed

    Aceti, Antonio; Gianserra, Laura; Lambiase, Lara; Pennica, Alfredo; Teti, Elisabetta

    2015-08-12

    Highly active antiretroviral therapy (HAART) has substantially changed human immunodeficiency virus (HIV) infection from an inexorably fatal condition into a chronic disease with a longer life expectancy. This means that HIV patients should receive antiretroviral drugs lifelong, and the problems concerning with a chronic treatment (tolerability, side effects, adherence to treatment) have now become dominant. In this context, strategies for the treatment personalization have taken a central role in optimizing the therapeutic response and prevention of adverse drug reactions. In this setting, the study of pharmacogenetics features could be a very useful tool in clinical practice; moreover, nowadays the study of genetic profiles allows optimizations in the therapeutic management of People Living With HIV (PLWH) through the use of test introduced into clinical practice and approved by international guidelines for the adverse effects prevention such as the genetic test HLA-B*5701 to detect hypersensitivity to Abacavir. For other tests further studies are needed: CYP2B6 516 G > T testing may be able to identify patients at higher risk of Central Nervous System side effects following standard dosing of Efavirenz, UGT1A1*28 testing before initiation of antiretroviral therapy containing Atazanavir may aid in identifying individuals at risk of hyperbilirubinaemia. Pharmacogenetics represents a ​​research area with great growth potential which may be useful to guide the rational use of antiretrovirals. PMID:26279982

  15. Generic antiretroviral drugs and HIV care: An economic review.

    PubMed

    Yazdanpanah, Y; Schwarzinger, M

    2016-03-01

    The cost of HIV care in European countries is high. Direct medical costs, in France, have been estimated at 500,000 Euros per patient's lifetime (20,000 Euros/year/patient). Overall, 73% of these costs are related to antiretroviral treatments. In the current financial crisis context, some European countries are beginning to make economic decisions on the drugs to be used. These approaches are likely to become more frequent. It is obviously essential to prescribe the most effective, appropriate, best tolerated, and easy-to-use antiretroviral treatments to patients. However, while taking the above into consideration, and if various treatment options or combinations are available, cost should also be considered in the treatment choice. One may thus reflect on the use of generic antiretroviral agents as they have just been launched in France. We aimed to review the cost and cost-effectiveness of generic antiretroviral drugs and to review treatment strategies other than generic drugs that could help reduce HIV-related costs. HIV clinicians should consider treatment costs to avoid any future coercive measures.

  16. Pharmacogenetics as a tool to tailor antiretroviral therapy: A review

    PubMed Central

    Aceti, Antonio; Gianserra, Laura; Lambiase, Lara; Pennica, Alfredo; Teti, Elisabetta

    2015-01-01

    Highly active antiretroviral therapy (HAART) has substantially changed human immunodeficiency virus (HIV) infection from an inexorably fatal condition into a chronic disease with a longer life expectancy. This means that HIV patients should receive antiretroviral drugs lifelong, and the problems concerning with a chronic treatment (tolerability, side effects, adherence to treatment) have now become dominant. In this context, strategies for the treatment personalization have taken a central role in optimizing the therapeutic response and prevention of adverse drug reactions. In this setting, the study of pharmacogenetics features could be a very useful tool in clinical practice; moreover, nowadays the study of genetic profiles allows optimizations in the therapeutic management of People Living With HIV (PLWH) through the use of test introduced into clinical practice and approved by international guidelines for the adverse effects prevention such as the genetic test HLA-B*5701 to detect hypersensitivity to Abacavir. For other tests further studies are needed: CYP2B6 516 G > T testing may be able to identify patients at higher risk of Central Nervous System side effects following standard dosing of Efavirenz, UGT1A1*28 testing before initiation of antiretroviral therapy containing Atazanavir may aid in identifying individuals at risk of hyperbilirubinaemia. Pharmacogenetics represents a ​​research area with great growth potential which may be useful to guide the rational use of antiretrovirals. PMID:26279982

  17. Cost-effectiveness analysis of using antiretroviral drug resistance testing.

    PubMed

    Lauria, Francesco Nicola; Angeletti, Claudio

    2003-01-01

    Human immunodeficiency virus (HIV)-infected patients failing highly active antiretroviral therapy (HAART) have a substantially lower chance of clinical success than naive patients given their first antiretroviral therapy. This suggests that HAART failure is a determinant for an increase in the cost of treatment. A review of the literature regarding cost and impact of antiretroviral drug-resistance testing was performed. Examination of existing methods to execute a cost-effectiveness analysis on the use of these tests in clinical practice was also undertaken. The cost of treatment failure in HIV-infected patients has been quantified in several retrospective studies. The cost of care for patients with virological suppression was significantly lower than those with a single virological failure. Moreover, the latter group had lower costs than patients with multiple failures. The result of the cost-effective analysis based on a specific model application using genotypic resistance assays to guide the choice of a subsequent therapy in HIV disease, is cost-effective under a wide range of assumptions regarding effectiveness and costs. The available studies on the cost-effective evaluation of genotypic tests are limited, and the respective studies supply important indications on cost-effective evaluations. Despite its demonstrated benefits, antiretroviral drug resistance testing presents features and limitations that also restrict the cost-effectiveness analysis. PMID:15000585

  18. 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

  19. Pharmacokinetic and pharmacodynamic drug interactions between antiretrovirals and oral contraceptives.

    PubMed

    Tittle, Victoria; Bull, Lauren; Boffito, Marta; Nwokolo, Nneka

    2015-01-01

    More than 50 % of women living with HIV in low- and middle-income countries are of reproductive age, but there are limitations to the administration of oral contraception for HIV-infected women receiving antiretroviral therapy due to drug-drug interactions caused by metabolism via the cytochrome P450 isoenzymes and glucuronidation. However, with the development of newer antiretrovirals that use alternative metabolic pathways, options for contraception in HIV-positive women are increasing. This paper aims to review the literature on the pharmacokinetics and pharmacodynamics of oral hormonal contraceptives when given with antiretroviral agents, including those currently used in developed countries, older ones that might still be used in salvage regimens, or those used in resource-limited settings, as well as newer drugs. Nucleos(t)ide reverse transcriptase inhibitors (NRTIs), the usual backbone to most combined antiretroviral treatments (cARTs) are characterised by a low potential for drug-drug interactions with oral contraceptives. On the other hand non-NRTIs (NNRTIs) and protease inhibitors (PIs) may interact with oral contraceptives. Of the NNRTIs, efavirenz and nevirapine have been demonstrated to cause drug-drug interactions; however, etravirine and rilpivirine appear safe to use without dose adjustment. PIs boosted with ritonavir are not recommended to be used with oral contraceptives, with the exception of boosted atazanavir which should be used with doses of at least 35 µg of estrogen. Maraviroc, an entry inhibitor, is safe for co-administration with oral contraceptives, as are the integrase inhibitors (INIs) raltegravir and dolutegravir. However, the INI elvitegravir, which is given in combination with cobicistat, requires a dose of estrogen of at least 30 µg. Despite the growing evidence in this field, data are still lacking in terms of large cohort studies, randomised trials and correlations to real clinical outcomes, such as pregnancy rates, in women

  20. Antiretroviral therapy reduces neurodegeneration in human immunodeficiency virus infection

    PubMed Central

    Bryant, Alex K.; Ellis, Ronald J.; Umlauf, Anya; Gouaux, Ben; Soontornniyomkij, Virawudh; Letendre, Scott L.; Achim, Cristian L.; Masliah, Eliezer; Grant, Igor; Moore, David J.

    2015-01-01

    Objective To determine the effect of virally-suppressive antiretroviral therapy on cortical neurodegeneration and associated neurocognitive impairment. Design Retrospective, postmortem observational study. Methods Clinical neuropsychological and postmortem neuropathology data were analyzed in 90 human immunodeficiency virus-infected volunteers from the general community who had never undergone antiretroviral therapy (n=7, “naïve”) or who had undergone antiretroviral therapy and whose plasma viral load was detectable (n = 64 “unsuppressed”) or undetectable (n = 19, “suppressed”) at the last clinical visit prior to death. Subjects were predominately male (74/90, 82%) with a mean age of 44.7 years (SD 9.8). Cortical neurodegeneration was quantified by measuring microtubule-associated protein (MAP2) and synaptophysin (SYP) density in midfrontal cortex tissue sections. Results The suppressed group had higher SYP density than the naïve group (p = 0.007) and higher MAP2 density than the unsuppressed group (p = 0.04). The suppressed group had lower odds of human immunodeficiency virus-associated neurocognitive disorders than naïve (OR 0.07, p = 0.03). Higher SYP was associated with lower likelihood of human immunodeficiency virus-associated neurocognitive disorders in univariable (OR 0.8, p=0.03) and multivariable models after controlling for antiretroviral treatment and brain human immunodeficiency virus p24 protein levels (OR 0.72, p=0.01). Conclusions We conclude that virally suppressive antiretroviral treatment protects against cortical neurodegeneration. Further, we find evidence supporting the causal chain from treatment-mediated peripheral and central nervous system viral load suppression to reduced neurodegeneration and improved neurocognitive outcomes. PMID:25686681

  1. 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…

  2. MAKING WAVES, DENVER HEAD START.

    ERIC Educational Resources Information Center

    Denver Opportunity, CO.

    THIS DOCUMENT PROVIDES A DESCRIPTIVE SURVEY OF PROJECT HEAD START ACTIVITIES IN DENVER, COLORADO. THE PRIMARY EDUCATIONAL OBJECTIVES OF THE PROGRAM ARE CITED AS (1) CONCEPT DEVELOPMENT THROUGH EXPERIENCES IN AN ENLARGED ENVIRONMENT, (2) SELF-CONCEPT DEVELOPMENT THROUGH SUCCESSFUL INTERACTION WITH TEACHERS AND WITH PEERS, AND (3) THE DEVELOPMENT OF…

  3. Start Where Your Students Are

    ERIC Educational Resources Information Center

    Jackson, Robyn R.

    2010-01-01

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

  4. Head Start Dental Health Curriculum.

    ERIC Educational Resources Information Center

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

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

  5. Math Club Starting in Kindergarten

    ERIC Educational Resources Information Center

    Perry, Ann M.

    2011-01-01

    Starting a math club as early as kindergarten and having a range of grade levels in attendance can be successful. With the help of the older students, the varied age groups are entertained and excited about attending math club. The purpose of the club is to enrich the classroom mathematics curriculum with hands-on activities and to have members…

  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. 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

  8. Discordant Treatment Responses to Combination Antiretroviral Therapy in Rwanda: A Prospective Cohort Study

    PubMed Central

    Kayigamba, Felix R.; Franke, Molly F.; Bakker, Mirjam I.; Rodriguez, Carly A.; Bagiruwigize, Emmanuel; Wit, Ferdinand WNM; Rich, Michael L.; Schim van der Loeff, Maarten F.

    2016-01-01

    Introduction Some antiretroviral therapy naïve patients starting combination antiretroviral therapy (cART) experience a limited CD4 count rise despite virological suppression, or vice versa. We assessed the prevalence and determinants of discordant treatment responses in a Rwandan cohort. Methods A discordant immunological cART response was defined as an increase of <100 CD4 cells/mm3 at 12 months compared to baseline despite virological suppression (viral load [VL] <40 copies/mL). A discordant virological cART response was defined as detectable VL at 12 months with an increase in CD4 count ≥100 cells/mm3. The prevalence of, and independent predictors for these two types of discordant responses were analysed in two cohorts nested in a 12-month prospective study of cART-naïve HIV patients treated at nine rural health facilities in two regions in Rwanda. Results Among 382 patients with an undetectable VL at 12 months, 112 (29%) had a CD4 rise of <100 cells/mm3. Age ≥35 years and longer travel to the clinic were independent determinants of an immunological discordant response, but sex, baseline CD4 count, body mass index and WHO HIV clinical stage were not. Among 326 patients with a CD4 rise of ≥100 cells/mm3, 56 (17%) had a detectable viral load at 12 months. Male sex was associated with a virological discordant treatment response (P = 0.05), but age, baseline CD4 count, BMI, WHO HIV clinical stage, and travel time to the clinic were not. Conclusions Discordant treatment responses were common in cART-naïve HIV patients in Rwanda. Small CD4 increases could be misinterpreted as a (virological) treatment failure and lead to unnecessary treatment changes. PMID:27438000

  9. Impact of HIV type 1 genetic subtype on the outcome of antiretroviral therapy.

    PubMed

    Atlas, Ann; Granath, Fredrik; Lindström, Anna; Lidman, Knut; Lindbäck, Stefan; Alaeus, Annette

    2005-03-01

    The objective of this study was to investigate the short-term virological outcome of antiretroviral combination therapy (ART) in relation to infection with different HIV-1 genetic subtypes. Antiretroviral drug-naive patients in Sweden were prospectively enrolled and followed for 6 months when starting ART in the period from January 1998 to January 2002. Plasma-HIV-1 RNA levels, CD4 counts, and type of ART regimen were recorded. The HIV-1 subtype was determined by direct sequencing of regions of the env or pol genes. Data from 172 patients who harbored subtypes A, B, C, D, G, and CRF01_AE were analyzed (32 A, 44 B, 34 C, 18 D, 5 G, and 19 CRF01_AE). Of all patients 84% had undetectable plasma HIV-1 RNA levels after 6 months of ART. Patients infected with CRF01_AE more often had undetectable HIV-1 RNA plasma levels than patients infected with subtypes A or D. However, the possibility that this difference is due to ethnicity cannot be ruled out. Of patients of African origin, 77% had undetectable viral load after 6 months of treatment, while the corresponding figures for Caucasians and Asians were 91% and 100%, respectively. Thus, we have found an overall good short-term virological outcome after the initiation of ART in a cohort of ARV-naive patients of diverse ethnic background infected with different HIV-1 genetic subtypes. In univariate analysis ethnicity, but not genetic subtype, correlated with virological response. However, the impact of ethnicity was moderate. Patients of African origin, who had the poorest outcome, showed a 77% virological response rate.

  10. EXPANDING ANTIRETROVIRAL OPTIONS IN RESOURCE-LIMITED SETTINGS – A COSTEFFECTIVENESS ANALYSIS

    PubMed Central

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

    2009-01-01

    Background Current World Health Organization (WHO) guidelines for treatment of HIV in resource-limited settings call for two antiretroviral regimens. The effectiveness and cost-effectiveness of increasing the number of antiretroviral regimens is unknown. Methods Using a simulation model, we compared the survival and costs of current WHO regimens with two 3-regimen strategies: an initial regimen of three nucleoside reverse transcriptase inhibitors followed by the WHO regimens; and the WHO regimens followed by a regimen with a second-generation boosted protease inhibitor (2bPI). We evaluated monitoring with CD4 counts only and with both CD4 counts and viral load. We used cost and effectiveness data from Cape Town, and tested all assumptions in sensitivity analyses. Results Over the lifetime of the cohort, 25.6% of individuals failed both WHO regimens by virologic criteria. However, when patients were monitored using CD4 counts alone, only 6.5% were prescribed additional HAART, due to missed and delayed detection of failure. The life expectancy gain for individuals who took a 2bPI was 6.7–8.9 months, depending on the monitoring strategy. When CD4 alone was available, adding a regimen with a 2bPI was associated with an incremental cost-effectiveness ratio of $2,581 per year-of-life gained, and when viral load was available, the ratio was $6,519 per year-of-life gained. Strategies with triple-NRTI regimens in initial therapy were dominated. Results were sensitive to the price of 2bPIs. Conclusions About 1 in 4 individuals who start HAART in sub-Saharan Africa will fail currently recommended regimens. At current prices, adding a regimen with a 2bPI is cost-effective for South Africa and other middle-income countries by WHO standards. PMID:19448557

  11. 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

  12. Growth response to antiretroviral treatment in HIV-infected children: A cohort study from Lilongwe, Malawi

    PubMed Central

    Weigel, Ralf; Phiri, Sam; Chiputula, Fred; Gumulira, Joe; Brinkhof, Martin; Gsponer, Thomas; Tweya, Hannock; Egger, Matthias; Keiser, Olivia

    2013-01-01

    Summary Objective Malnutrition is common in HIV-infected children in Africa and an indication for antiretroviral treatment (ART). We examined anthropometric status and response to ART in children treated at a large public-sector clinic in Malawi. Methods All children aged <15 years who started ART between January 2001 and December 2006 were included and followed until March 2008. Weight and height were measured at regular intervals from 1 year before to 2 years after the start of ART. Sex- and age-standardized z-scores were calculated for weight-for-age (WAZ) and height-for-age (HAZ). Predictors of growth were identified in multivariable mixed-effect models. Results A total of 497 children started ART and were followed for 972 person-years. Median age (inter-quartile range; IQR) was 8 years (4 to 11 years). Most children were underweight (52% of children), stunted (69%), in advanced clinical stages (94% in WHO stages 3 or 4) and had severe immunodeficiency (77%). After starting ART median (IQR) WAZ and HAZ increased from −2.1 (−2.7 to −1.3) and −2.6 (−3.6 to −1.8) to −1.4 (−2.1 to −0.8) and −1.8 (−2.4 to −1.1) at 24 months, respectively (p<0.001). In multivariable models, baseline WAZ and HAZ scores were the most important determinants of growth trajectories on ART. Conclusions Despite a sustained growth response to ART among children remaining on therapy, normal values were not reached. Interventions leading to earlier HIV diagnosis and initiation of treatment could improve growth response. PMID:20561308

  13. HBV Lamivudine Resistance among Hepatitis B and HIV Co-infected Patients Starting Lamivudine, Stavudine and Nevirapine in Kenya

    PubMed Central

    Nina Kim, H.; Scott, John; Cent, Anne; Cook, Linda; Ashley Morrow, Rhoda; Richardson, Barbra; Tapia, Kenneth; Jerome, Keith R.; Lule, Godfrey; John-Stewart, Grace; Chung, Michael H.

    2011-01-01

    Widespread use of lamivudine in antiretroviral therapy may lead to hepatitis B virus resistance in HIV-HBV co-infected patients from endemic settings where tenofovir is not readily available. We evaluated 389 Kenyan HIV-infected adults before and for 18 months after starting highly-active antiretroviral therapy with stavudine, lamivudine and nevirapine. Twenty-seven (6.9%) were HBsAg(+) and anti-HBs negative: 24 were HBeAg-negative, 18 had HBV DNA ≤10,000 IU/ml. Sustained HBV suppression to <100 IU/ml occurred in 89% of 19 evaluable patients. Resistance occurred in only 2 subjects, both with high baseline HBV DNA levels. Lamivudine resistance can emerge in the setting of incomplete HBV suppression but was infrequently observed among HIV-HBV co-infected patients with low baseline HBV DNA levels. PMID:21914062

  14. Did Universal Access to ARVT in Mexico Impact Suboptimal Antiretroviral Prescriptions?

    PubMed Central

    Caro-Vega, Yanink; Sierra-Madero, Juan; Colchero, M. Arantxa; Crabtree-Ramírez, Brenda; Bautista-Arredondo, Sergio

    2013-01-01

    Background. Universal access to antiretroviral therapy (ARVT) started in Mexico in 2001; no evaluation of the features of ARVT prescriptions over time has been conducted. The aim of the study is to document trends in the quality of ARVT-prescription before and after universal access. Methods. We describe ARVT prescriptions before and after 2001 in three health facilities from the following subsystems: the Mexican Social Security (IMSS), the Ministry of Health (SSA), and National Institutes of Health (INS). Combinations of drugs and reasons for change were classified according to current Mexican guidelines and state-of-the-art therapy. Comparisons were made using χ2 tests. Results. Before 2001, 29% of patients starting ARVT received HAART; after 2001 it increased to 90%. The proportion of adequate prescriptions decreased within the two periods of study in all facilities (P value < 0.01). The INS and SSA were more likely to be prescribed adequately (P value < 0.01) compared to IMSS. The distribution of reasons for change was not significantly different during this time for all facilities (P value > 0.05). Conclusions. Universal ARVT access in Mexico was associated with changes in ARVT-prescription patterns over time. Health providers' performance improved, but not homogeneously. Training of personnel and guidelines updating is essential to improve prescription. PMID:24396592

  15. Identification of beneficiaries of free anti-retroviral drugs in Malawi: a community consensus process.

    PubMed

    Muula, A S; Maseko, F C

    2007-05-01

    Malawi is a southeastern Africa country that has been heavily affected by the AIDS pandemic. It is estimated that about 170,000 people were in need of highly active antiretroviral therapy (HAART) for the treatment of AIDS in 2006. At the end of 2006, at least 55,000 people in Malawi were on HAART treatment, mostly through the free public sector program. At the time the program was being initiated, an ethical question needed to be answered in respect to who would be targeted for free treatment in an environment where medications, human and other resources were not enough to cater for all who were clinically eligible to be on treatment. In this paper we report on a qualitative study that was carried out to obtain public perceptions and input as to which criteria ought to have been applied to identify persons or groups of persons to be targeted in the free HAART program. In general, there was no agreement as to who should be prioritised for HAART, whether treatment should be free to user or whether cost-sharing should be introduced. While it may have been relatively straightforward in obtaining consensus and agreement among medical practitioners on the clinical criteria for HART in Malawi, deciding on the social criteria was complex. The decision to start the nationwide HAART program was started with the understanding that virtually every social group could be justified as worth of free HAART.

  16. Did Universal Access to ARVT in Mexico Impact Suboptimal Antiretroviral Prescriptions?

    PubMed

    Caro-Vega, Yanink; Volkow, Patricia; Sierra-Madero, Juan; Colchero, M Arantxa; Crabtree-Ramírez, Brenda; Bautista-Arredondo, Sergio

    2013-01-01

    Background. Universal access to antiretroviral therapy (ARVT) started in Mexico in 2001; no evaluation of the features of ARVT prescriptions over time has been conducted. The aim of the study is to document trends in the quality of ARVT-prescription before and after universal access. Methods. We describe ARVT prescriptions before and after 2001 in three health facilities from the following subsystems: the Mexican Social Security (IMSS), the Ministry of Health (SSA), and National Institutes of Health (INS). Combinations of drugs and reasons for change were classified according to current Mexican guidelines and state-of-the-art therapy. Comparisons were made using χ (2) tests. Results. Before 2001, 29% of patients starting ARVT received HAART; after 2001 it increased to 90%. The proportion of adequate prescriptions decreased within the two periods of study in all facilities (P value < 0.01). The INS and SSA were more likely to be prescribed adequately (P value < 0.01) compared to IMSS. The distribution of reasons for change was not significantly different during this time for all facilities (P value > 0.05). Conclusions. Universal ARVT access in Mexico was associated with changes in ARVT-prescription patterns over time. Health providers' performance improved, but not homogeneously. Training of personnel and guidelines updating is essential to improve prescription.

  17. 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

  18. 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.

  19. 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…

  20. 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.

  1. Dangerous medicines: Unproven AIDS cures and counterfeit antiretroviral drugs

    PubMed Central

    Amon, Joseph J

    2008-01-01

    Background Increasing access to antiretroviral therapy (ART) is a critical goal endorsed by the United Nations and all of its member states. At the same time, anecdotal accounts suggest that the promotion of unproven AIDS 'cures' and remedies are widespread, and in the case of The Gambia, Iran and South Africa, have been promoted by governments directly. Although a range of legislative and regulatory measures have been adopted by some governments, and technical assistance has been provided by international agencies to address counterfeit medicines generally, the threat of counterfeit antiretroviral drugs is not being addressed. Discussion Countries, charged with fulfilling the right to health and committed to expanding access to ART must explicitly recognize their obligation to combat unproven AIDS treatments and ensure the availability of a safe and efficacious drugs supply. International donors must help support and coordinate these efforts. PMID:18304316

  2. [SSRI AND BONE METABOLISM IN HIV + PATIENTS WITH ANTIRETROVIRAL THERAPY].

    PubMed

    Mazzoglio y Nabar, Martín J; Muñiz, Milagros María; Mejías Delamano, Alexis A; Muñoz, Santiago; Magrath Guimet, Nahuel

    2015-01-01

    We report a series of 9 male HIV + patients, average age of 41.2 years, viral load negative (<50 copies RNA/ml), treated with antiretroviral (nucleoside and non-nucleoside inhibitors of reverse transcriptase) without systemic infections, the CNS diseases or marker or corticoidoterapia in progress. Were evaluated and supported by their infectologists interconsultation during the period October 2008-October 2013 by depressive syndrome. Psychotherapeutic and psychiatric treatment was initiated with SSRIs and clonazepam; Neuroimaging control and biochemical laboratory studies at baseline and 2 months of treatment were conducted. In the course of psychopharmacological treatment not suffer fractures due to falls and alterations were detected in bone metabolism markers and images. He studied with endocrinology and interdisciplinary medical clinic, decided to withdraw the SSRIs with normalization of biochemical values and psychotherapeutic treatment was continued. We will raise the associations between the use of SSRIs, disturbances of bone metabolism with clinical correlation and possible drug interactions between antidepressants and antiretroviral. PMID:26650557

  3. 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.

  4. Viral dynamics model with CTL immune response incorporating antiretroviral therapy.

    PubMed

    Wang, Yan; Zhou, Yicang; Brauer, Fred; Heffernan, Jane M

    2013-10-01

    We present two HIV models that include the CTL immune response, antiretroviral therapy and a full logistic growth term for uninfected CD4+ T-cells. The difference between the two models lies in the inclusion or omission of a loss term in the free virus equation. We obtain critical conditions for the existence of one, two or three steady states, and analyze the stability of these steady states. Through numerical simulation we find substantial differences in the reproduction numbers and the behaviour at the infected steady state between the two models, for certain parameter sets. We explore the effect of varying the combination drug efficacy on model behaviour, and the possibility of reconstituting the CTL immune response through antiretroviral therapy. Furthermore, we employ Latin hypercube sampling to investigate the existence of multiple infected equilibria. PMID:22930342

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

    PubMed

    Lo, Bernard; Padian, Nancy; Barnes, Mark

    2007-06-19

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

  6. Pharmacokinetics and pharmacodynamics of antiretrovirals in the central nervous system.

    PubMed

    Calcagno, Andrea; Di Perri, Giovanni; Bonora, Stefano

    2014-10-01

    HIV-positive patients may be effectively treated with highly active antiretroviral therapy and such a strategy is associated with striking immune recovery and viral load reduction to very low levels. Despite undeniable results, the central nervous system (CNS) is commonly affected during the course of HIV infection, with neurocognitive disorders being as prevalent as 20-50 % of treated subjects. This review discusses the pathophysiology of CNS infection by HIV and the barriers to efficacious control of such a mechanism, including the available data on compartmental drug penetration and on pharmacokinetic/pharmacodynamic relationships. In the reviewed articles, a high variability in drug transfer to the CNS is highlighted with several mechanisms as well as methodological issues potentially influencing the observed results. Nevirapine and zidovudine showed the highest cerebrospinal fluid (CSF) to plasma ratios, although target concentrations are currently unknown for the CNS. The use of the composite CSF concentration effectiveness score has been associated with better virological outcomes (lower HIV RNA) but has been inconsistently associated with neurocognitive outcomes. These findings support the CNS effectiveness of commonly used highly antiretroviral therapies. The use of antiretroviral drugs with increased CSF penetration and/or effectiveness in treating or preventing neurocognitive disorders however needs to be assessed in well-designed prospective studies.

  7. Care of Patients With HIV Infection: Antiretroviral Drug Regimens.

    PubMed

    Bolduc, Philip; Roder, Navid; Colgate, Emily; Cheeseman, Sarah H

    2016-04-01

    The advent of combination antiretroviral drug regimens has transformed HIV infection from a fatal illness into a manageable chronic condition. All patients with HIV infection should be considered for antiretroviral therapy, regardless of CD4 count or HIV viral load, for individual benefit and to prevent HIV transmission. Antiretroviral drugs affect HIV in several ways: entry inhibitors block HIV entry into CD4 T cells; nucleotide and nucleoside reverse transcriptase inhibitors prevent reverse transcription from RNA to DNA via chain-terminating proteins; nonnucleoside reverse transcriptase inhibitors prevent reverse transcription through enzymatic inhibition; integrase strand transfer inhibitors block integration of viral DNA into cellular DNA; protease inhibitors block maturation and production of the virus. Current guidelines recommend six combination regimens for initial therapy. Five are based on tenofovir and emtricitabine; the other uses abacavir and lamivudine. Five include integrase strand transfer inhibitors. HIV specialists should assist with treating patients with complicated HIV infection, including patients with treatment-resistant HIV infection, coinfection with hepatitis B or C virus, pregnancy, childhood infections, severe opportunistic infections, complex drug interactions, significant drug toxicity, or comorbidities. Family physicians can treat most patients with HIV infection effectively by choosing appropriate treatment regimens, monitoring patients closely, and retaining patients in care. PMID:27092564

  8. Simplification Strategies to Reduce Antiretroviral Drug Exposure: Progress and Prospects

    PubMed Central

    McKinnon, John E.; Mellors, John W.; Swindells, Susan

    2009-01-01

    Current US guidelines for initial therapy of HIV-1 infection recommend daily, life-long treatment with a combination of three antiretroviral drugs consisting of two nucleoside analog reverse transcriptase (RT) inhibitors and a nonnucleoside RT inhibitor or a protease inhibitor. Although this approach has been successful in reducing morbidity and mortality from HIV-1 infection, concerns remain about adverse events from chronic drug exposure, the requirement for daily medication adherence, the risk of HIV-1 drug resistance, and high treatment costs. The availability of antiretrovirals that are co-formulated and dosed once-daily have reduced pill burden and have simplified dosing schedules, but have not lowered drug exposure or cost. These limitations have stimulated research into drug-sparing strategies including intermittent therapy and simplified maintenance regimens. Randomized clinical trials have shown greater mortality with intermittent therapy compared with continuous therapy leading to rejection of this strategy. Pilot studies of simplified maintenance therapy with a ritonavir-boosted protease inhibitor alone have shown more promise, although concerns remain. This article reviews progress in simplification of antiretroviral therapy, recent clinical trial results, and prospects for the future. PMID:19320232

  9. 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

  10. Treatment of HIV in the CNS: effects of antiretroviral therapy and the promise of non-antiretroviral therapeutics.

    PubMed

    Peluso, Michael J; Spudich, Serena

    2014-09-01

    The growing recognition of the burden of neurologic disease associated with HIV infection in the last decade has led to renewed efforts to characterize the pathophysiology of the virus within the central nervous system (CNS). The concept of the AIDS-dementia complex is now better understood as a spectrum of HIV-associated neurocognitive disorders (HAND), which range from asymptomatic disease to severe impairment. Recent work has shown that even optimally treated patients can experience not only persistent HAND, but also the development of new neurologic abnormalities despite viral suppression. This has thrown into question what the impact of antiretroviral therapy has been on the incidence and prevalence of neurocognitive dysfunction. In this context, the last few years have seen a concentrated effort to identify the effects that antiretroviral therapy has on the neurologic manifestations of HIV and to develop therapeutic modalities that might specifically alter the trajectory of HIV within the CNS.

  11. Rapid starting methanol reactor system

    DOEpatents

    Chludzinski, Paul J.; Dantowitz, Philip; McElroy, James F.

    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. Correlates of non-adherence to antiretroviral therapy in a cohort of HIV-positive drug users receiving antiretroviral therapy in Hanoi, Vietnam.

    PubMed

    Jordan, M R; Obeng-Aduasare, Y; Sheehan, H; Hong, S Y; Terrin, N; Duong, D V; Trung, N V; Wanke, C; Kinh, N V; Tang, A M

    2014-08-01

    The HIV epidemic in Vietnam is concentrated, with high prevalence estimates among injection drug users and commercial sex workers. Socio-demographics, substance use and clinical correlates of antiretroviral therapy non-adherence were studied in 100 HIV-1 infected drug users receiving antiretroviral therapy for at least 6 months in Hanoi, Vietnam. All study participants were men with a mean age of 29.9 ± 4.9 years. The median duration on antiretroviral therapy was 16.2 ± 12.7 months; 83% reported 'very good' or 'perfect' adherence in the past 30 days on a subjective one-item Likert scale at time of study enrollment; 48% of participants reported drug use within the previous 6 months, with 22% reporting current drug use. Injection drug use with or without non-injection drug use in the past 6 months (95% C.I. 2.19, 1.30-3.69) and years on antiretroviral therapy (95% C.I. 1.43, 1.14-1.78) were correlated with suboptimal adherence. These findings support Vietnam's ongoing scale-up of harm reduction programmes for injection drug users and their integration with antiretroviral therapy delivery. Moreover, results highlight the need to identify and implement new ways to support high levels of antiretroviral therapy adherence as duration on antiretroviral therapy increases.

  13. 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.

  14. Antiretroviral treatment regardless of CD4 count: the universal answer to a contextual question.

    PubMed

    Eholié, Serge P; Badje, Anani; Kouame, Gérard M; N'takpe, Jean-Baptiste; Moh, Raoul; Danel, Christine; Anglaret, Xavier

    2016-01-01

    After a period where it was recommended to start antiretroviral therapy (ART) early, the CD4 threshold for treating asymptomatic adults dropped to 200/mm(3) at the beginning of the 2000s. This was mostly due to a great prudence with regards to drug toxicity. The ART-start CD4 threshold in most international guidelines was then raised to 350/mm(3) in 2006-2009 and to 500/mm(3) in 2009-2013. Between 2012 and 2015, international guidelines went the last step further and recommended treating all HIV-infected adults regardless of their CD4 count. This ultimate step was justified by the results of three randomized controlled trials, HPTN 052, Temprano ANRS 12136 and START. These three trials assessed the benefits and risks of starting ART immediately upon inclusion ("early ART") versus deferring ART until the current starting criteria were met ("deferred ART"). Taken together, they recruited 8427 HIV-infected adults in 37 countries. The primary outcome was severe morbidity, a composite outcome that included all-cause deaths, AIDS diseases, and non-AIDS cancers in the three trials. The trial results were mutually consistent and reinforcing. The overall risk of severe morbidity was significantly 44-57 % lower in patients randomized to early ART as compared to deferred ART. Early ART also decreased the risk of AIDS, tuberculosis, invasive bacterial diseases and Kaposi's sarcoma considered separately. The incidence of severe morbidity was 3.2 and 3.5 times as high in HPTN052 and Temprano as in START, respectively. This difference is mostly due to the geographical context of morbidity. The evidence is now strong that initiating ART at high CD4 counts entails individual benefits worldwide, and that this is all the more true in low resource contexts where tuberculosis and other bacterial diseases are highly prevalent. These benefits in addition to population benefits consisting of preventing HIV transmission demonstrated in HPTN052, justify the recommendation that HIV

  15. Antiretroviral treatment regardless of CD4 count: the universal answer to a contextual question.

    PubMed

    Eholié, Serge P; Badje, Anani; Kouame, Gérard M; N'takpe, Jean-Baptiste; Moh, Raoul; Danel, Christine; Anglaret, Xavier

    2016-01-01

    After a period where it was recommended to start antiretroviral therapy (ART) early, the CD4 threshold for treating asymptomatic adults dropped to 200/mm(3) at the beginning of the 2000s. This was mostly due to a great prudence with regards to drug toxicity. The ART-start CD4 threshold in most international guidelines was then raised to 350/mm(3) in 2006-2009 and to 500/mm(3) in 2009-2013. Between 2012 and 2015, international guidelines went the last step further and recommended treating all HIV-infected adults regardless of their CD4 count. This ultimate step was justified by the results of three randomized controlled trials, HPTN 052, Temprano ANRS 12136 and START. These three trials assessed the benefits and risks of starting ART immediately upon inclusion ("early ART") versus deferring ART until the current starting criteria were met ("deferred ART"). Taken together, they recruited 8427 HIV-infected adults in 37 countries. The primary outcome was severe morbidity, a composite outcome that included all-cause deaths, AIDS diseases, and non-AIDS cancers in the three trials. The trial results were mutually consistent and reinforcing. The overall risk of severe morbidity was significantly 44-57 % lower in patients randomized to early ART as compared to deferred ART. Early ART also decreased the risk of AIDS, tuberculosis, invasive bacterial diseases and Kaposi's sarcoma considered separately. The incidence of severe morbidity was 3.2 and 3.5 times as high in HPTN052 and Temprano as in START, respectively. This difference is mostly due to the geographical context of morbidity. The evidence is now strong that initiating ART at high CD4 counts entails individual benefits worldwide, and that this is all the more true in low resource contexts where tuberculosis and other bacterial diseases are highly prevalent. These benefits in addition to population benefits consisting of preventing HIV transmission demonstrated in HPTN052, justify the recommendation that HIV

  16. Loss to Care and Death Before Antiretroviral Therapy in Durban, South Africa

    PubMed Central

    Bassett, Ingrid V.; Wang, Bingxia; Chetty, Senica; Mazibuko, Matilda; Bearnot, Benjamin; Giddy, Janet; Lu, Zhigang; Losina, Elena; Walensky, Rochelle P.; Freedberg, Kenneth A.

    2009-01-01

    Objective To examine the loss to care and mortality rates before starting antiretroviral therapy (ART) among ART eligible HIV-infected patients in Durban, South Africa. Design Retrospective cohort study. Methods We reviewed data from ART eligible adults (≥18 years) at an urban HIV clinic that charges a monthly fee from July to December 2006. ART eligibility was based on CD4 count ≤200 cells per microliter or clinical criteria and a psychosocial assessment. Patients who did not start ART and were lost within 3 months were phoned. Correlates of loss to care were evaluated using logistic regression. Results During the study period, 501 patients registered for ART training. Mean time from initial CD4 count to first ART training was 3.6 months (interquartile range 2.3−3.9 months). Four hundred eight patients (81.4%) were in care and on ART at 3-month follow-up, and 11 (2.2%) were in care but had not initiated ART. Eighty-two ART eligible patients (16.4%) were lost before ART initiation. Of these, 28 (34.1%) had died; two thirds of deaths occurred before or within 2 months after the first ART training. Despite multiple attempts, 32 patients (39%) were unreachable by phone. Lower baseline CD4 counts (≤100 cells/μL) and unemployment were independently associated with being lost. Conclusions Loss to care and death occur frequently before starting ART at an HIV clinic in Durban, South Africa. This delay from CD4 count to ART training, even among those with the lowest CD4 counts, highlights the need for interventions that improve linkage to care and prioritize ART initiation for those with low baseline CD4 counts. PMID:19504725

  17. Cardiac Effects of Antiretroviral-Naïve versus Antiretroviral-Exposed HIV Infection in Children

    PubMed Central

    Grobbee, Diederick E.; Burgner, David; Kurniati, Nia

    2016-01-01

    Background Cardiac involvement in HIV infected children has been frequently reported, but whether this is due to HIV infection itself or to antiretroviral treatment (ART) is unknown. Methods This cross sectional study involved 114 vertically-acquired HIV-infected (56 ART-naive, 58 ART-exposed) and 51 healthy children in Jakarta, Indonesia. Echocardiography was performed to measure dimensions of the left ventricle (LV) and systolic functions. We applied general linear modeling to evaluate the associations between HIV infection/treatment status and cardiac parameters with further adjustment for potential confounders or explanatory variables. Findings are presented as (adjusted) mean differences between each of the two HIV groups and healthy children, with 95% confidence intervals and p values. Results Compared to healthy children, ART-naïve HIV-infected children did not show significant differences in age-and-height adjusted cardiac dimensions apart from larger LV internal diameter (difference 2.0 mm, 95%CI 0.2 to 3.7), whereas ART exposed HIV infection showed thicker LV posterior walls (difference = 1.1 mm, 95%CI 0.5 to 1.6), larger LV internal diameter (difference = 1.7 mm, 95%CI 0.2 to 3.2) and higher LV mass (difference = 14.0 g, 7.4 to 20.5). With respect to systolic function, reduced LV ejection fraction was seen in both ART-naïve HIV infected (adjusted difference = -6.7%, -11.4 to -2.0) and, to a lesser extent, in ART-exposed HIV infected children (difference = -4.5%, -8.5 to -0.4). Inflammation level seemed to be involved in most associations in ART-exposed HIV-infected, but few, if any, for decreased function in the ART-naive ones, whereas lower hemoglobin appeared to partially mediate chamber dilation in both groups and reduced function, mainly in ART-exposed children. Conclusions ART-naive HIV infected children have a substantial decrease in cardiac systolic function, whereas the ART-exposed have thicker ventricular walls with larger internal diameter

  18. 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.

  19. Ingredients: where pet food starts.

    PubMed

    Thompson, Angele

    2008-08-01

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

  20. 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...

  1. 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...

  2. 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...

  3. 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...

  4. 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...

  5. Clinical Outcome of HIV-Infected Patients with Sustained Virologic Response to Antiretroviral Therapy: Long-Term Follow-Up of a Multicenter Cohort

    PubMed Central

    Gutierrez, Félix; Padilla, Sergio; Masiá, Mar; Iribarren, José A.; Moreno, Santiago; Viciana, Pompeyo; Muñoz, Leopoldo; Sirvent, José L. Gómez; Vidal, Francesc; López-Aldeguer, José; Blanco, José R.; Leal, Manuel; Rodríguez-Arenas, María Angeles; Hoyos, Santiago Perez

    2006-01-01

    Background Limited information exists on long-term prognosis of patients with sustained virologic response to antiretroviral therapy. We aimed to assess predictors of unfavorable clinical outcome in patients who maintain viral suppression with HAART. Methods Using data collected from ten clinic-based cohorts in Spain, we selected all antiretroviral-naive adults who initiated HAART and maintained plasma HIV-1 RNA levels <500 copies/mL throughout follow-up. Factors associated with disease progression were determined by Cox proportional-hazards models. Results Of 2,613 patients who started HAART, 757 fulfilled the inclusion criteria. 61% of them initiated a protease inhibitor-based HAART regimen, 29.7% a nonnucleoside reverse-transcriptase inhibitor-based regimen, and 7.8% a triple-nucleoside regimen. During 2,556 person-years of follow-up, 22 (2.9%) patients died (mortality rate 0.86 per 100 person-years), and 40 (5.3%) died or developed a new AIDS-defining event. The most common causes of death were neoplasias and liver failure. Mortality was independently associated with a CD4-T cell response <50 cells/L after 12 months of HAART (adjusted hazard ratio [AHR], 4.26 [95% confidence interval {CI}, 1.68–10.83]; P = .002), and age at initiation of HAART (AHR, 1.06 per year; 95% CI, 1.02–1.09; P = .001). Initial antiretroviral regimen chosen was not associated with different risk of clinical progression. Conclusions Patients with sustained virologic response on HAART have a low mortality rate over time. Long-term outcome of these patients is driven by immunologic response at the end of the first year of therapy and age at the time of HAART initiation, but not by the initial antiretroviral regimen selected. PMID:17183720

  6. 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.

  7. Guillain Barre syndrome in an HIV-1-infected patient after the beginning of combined antiretroviral therapy: an immune reconstitution inflammatory syndrome?

    PubMed

    Fantauzzi, Alessandra; Digiulio, Maria Anna; Cavallari, Eugenio Nelson; d'Ettorre, Gabriella; Vullo, Vincenzo; Mezzaroma, Ivano

    2014-01-01

    HIV-1-associated Guillan-Barre syndrome (hGBS) is an ascendant progressive polyradiculoneuropathy described throughout the course of the viral disease, mainly associated with the acute retroviral syndrome. HGBS is occasionally described in severely immunocompromised subjects in the context of the immune reconstitution inflammatory syndrome. The case described occurred soon after the start of a combined antiretroviral treatment in an HIV-1 infected patient with ulcerative colitis in the absence of severe immunosuppression. This manifestation may be interpreted as an uncommon appearance of an immune reconstitution syndrome in the presence of a predisposing autoimmune pathology.

  8. 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…

  9. [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

  10. Does antiretroviral therapy initiation increase sexual risk taking in Kenyan female sex workers? A retrospective case–control study

    PubMed Central

    Mawji, Elysha; Wachihi, Charles; Chege, Duncan; Thottingal, Paul; Kariri, Anthony; Plummer, Francis; Ball, T Blake; Jaoko, Walter; Ngugi, Elizabeth; Kimani, Joshua; Gelmon, Lawrence; Nagelkerke, Nico; Kaul, Rupert

    2012-01-01

    Objectives Although antiretroviral therapy (ART) prolongs life and reduces infectiousness, in some contexts, it has been associated with increased sexual risk taking. Design Retrospective case–control study. Setting Nairobi-based dedicated female sex worker (FSW) clinic. Participants HIV-infected FSWs before and after ART initiation (n=62); HIV-infected and -uninfected control FSWs not starting ART during the same follow-up period (n=40). Intervention Initiation of ART. Primary outcome measures Self-reported condom use, client numbers and sexually transmitted infection incidence over the study period (before and after ART initiation in cases). Results Sexual risk-taking behaviour with casual clients did not increase after ART initiation; condom use increased and sexually transmitted infection incidence decreased in both cases and controls, likely due to successful cohort-wide HIV prevention efforts. Conclusions ART provision was not associated with increases in unsafe sex in this FSW population. PMID:22466157

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

    PubMed Central

    Bennett, Sara; Chanfreau, Catherine

    2005-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  13. 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

  14. Antiretroviral Therapy for Prevention of Human Immunodeficiency Virus Infection.

    PubMed

    Kalapila, Aley G; Marrazzo, Jeanne

    2016-07-01

    Human immunodeficiency virus (HIV) infection is considered a chronic medical condition. Several new drugs are available, including fixed-dose combination tablets, that have greatly simplified combination antiretroviral therapy (ART) regimens to treat HIV, while increasing the life-expectancy of infected individuals. In the last decade, multiple well-regarded studies have established the benefits of using ART in high-risk, HIV-negative persons to prevent HIV acquisition. The primary care provider must not only understand commonly encountered issues pertaining to ART, such as toxicities and drug interactions, but also needs to be aware of using ART for HIV prevention. PMID:27235622

  15. Combination antiretroviral studies for patients with primary biliary cirrhosis

    PubMed Central

    Lytvyak, Ellina; Montano-Loza, Aldo J; Mason, Andrew L

    2016-01-01

    Following the characterization of a human betaretrovirus in patients with primary biliary cirrhosis (PBC), pilot studies using antiretroviral therapy have been conducted as proof of principal to establish a link of virus with disease and with the eventual aim to find better adjunct therapies for patients unresponsive to ursodeoxycholic acid. In the first open label pilot study, the reverse transcriptase inhibitor lamivudine had little demonstrable biochemical or histological effect after 1 year. Whereas, lamivudine in combination with zidovudine was associated with a significant reduction in alkaline phosphatase as well as improvement in necroinflammatory score, cholangitis and ductopenia over a 12 mo period. A double blind, multi-center randomized controlled trial using lamivudine with zidovudine for 6 mo confirmed a significant reduction in alkaline phosphatase, ALT and AST in patients on antiviral therapy. However, none of the patients achieved the stringent endpoint criteria for normalization of alkaline phosphatase. Furthermore, some patients developed biochemical rebound consistent with drug resistance. A major fault of these studies has been the inability to measure the viral load in peripheral blood and therefore, provide a direct correlation between improvement of hepatic biochemistry and reduction in viral load. Nevertheless, viral mutants to lamivudine with zidovudine were later characterized in the NOD.c3c4 mouse model of PBC that has been used to test other antiretroviral regimens to betaretrovirus. The combination of tenofovir and emtricitabine reverse transcriptase inhibitors and the HIV protease inhibitor, lopinavir were found to abrogate cholangitis in the NOD.c3c4 mouse model and the same regimen normalized the liver tests in a PBC patient with HIV and human betaretrovirus infection. This combination antiretroviral therapy has now been used in a double blind randomized controlled crossover study for patients with PBC followed by an open label

  16. Anxiety and depression symptoms as risk factors for non-adherence to antiretroviral therapy in Brazil

    PubMed Central

    Campos, Lorenza Nogueira; Guimarães, Mark Drew Crosland; Remien, Robert H.

    2009-01-01

    Depression and anxiety are common among HIV-infected people and rank among the strongest predictors of non-adherence to antiretroviral therapy (ART). This longitudinal study aimed to assess whether symptoms of anxiety and depression are predictors of non-adherence among patients initiating ART at two public referral centers (n=293) in Belo Horizonte, Brazil. Prevalence of severe anxiety and depression symptoms before starting ART was 12.6% and 5.8%, respectively. Severe anxiety was a predictor of non-adherence to ART during follow-up period (RH=1.87; 95% CI=1.14–3.06) adjusted for low education, unemployment, alcohol use in the last month and symptoms of AIDS; while a history of injection drug use had borderline statistical significance with non-adherence. These findings suggest that using a brief screening procedure to assess anxiety and depression symptoms before initiating ART help identify individuals for interventions to improve adherence and quality of life. PMID:18648925

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

    PubMed Central

    2011-01-01

    Background Rhodococcus equi (R.equi) is an acid fast, GRAM + coccobacillus, which is widespread in the soil and causes pulmonary and extrapulmonary infections in immunocompromised people. In the context of HIV infection, R.equi infection (rhodococcosis) is regarded as an opportunistic disease, and its outcome is influenced by highly active antiretroviral therapy (HAART). Case presentation We report two cases of HIV-related rhodococcosis that disseminated despite suppressive HAART and anti-rhodococcal treatment; in both cases there was no immunological recovery, with CD4+ cells count below 200/μL. In the first case, pulmonary rhodococcosis presented 6 months after initiation of HAART, and was followed by an extracerebral intracranial and a cerebral rhodococcal abscess 1 and 8 months, respectively, after onset of pulmonary infection. The second case was characterized by a protracted course with spread of infection to various organs, including subcutaneous tissue, skin, colon and other intra-abdominal tissues, and central nervous system; the spread started 4 years after clinical resolution of a first pulmonary manifestation and progressed over a period of 2 years. Conclusions Our report highlights the importance of an effective immune recovery, despite fully suppressive HAART, along with anti-rhodococcal therapy, in order to clear rhodococcal infection. PMID:22168333

  18. Rapid HIV Viral Load Suppression in those Initiating Antiretroviral Therapy at First Visit after HIV Diagnosis.

    PubMed

    Hoenigl, Martin; Chaillon, Antoine; Moore, David J; Morris, Sheldon R; Mehta, Sanjay R; Gianella, Sara; Amico, K Rivet; Little, Susan J

    2016-01-01

    Expert guidelines for antiretroviral therapy (ART) now recommend ART as soon as possible in all HIV infected persons to reduce the risk of disease progression and prevent transmission. The goal of this observational study was to evaluate the impact of very early ART initiation and regimen type on time to viral suppression. We evaluated time to viral suppression among 86 persons with newly-diagnosed HIV infection who initiated ART within 30 days of diagnosis. A total of 36 (42%) had acute, 27 (31%) early, and 23 (27%) had established HIV infection. The median time from an offer of immediate ART to starting ART was 8 days. A total of 56/86 (65%) initiated an integrase inhibitor-based regimen and 30/86 (35%) a protease inhibitor-based regimen. The time to viral suppression was significantly shorter in those receiving an integrase inhibitor- versus a protease inhibitor-based regimen (p = 0.022). Twenty-two (26%) initiated ART at their HIV care intake visit and 79% of these participants achieved viral suppression at week 12, 82% at week 24 and 88% at week 48. ART initiated at the intake visit led to rapid and reliable viral suppression in acute, early and chronic HIV infection, in particular when integrase inhibitor-based regimens were used. PMID:27597312

  19. Rapid HIV Viral Load Suppression in those Initiating Antiretroviral Therapy at First Visit after HIV Diagnosis

    PubMed Central

    Hoenigl, Martin; Chaillon, Antoine; Moore, David J.; Morris, Sheldon R.; Mehta, Sanjay R.; Gianella, Sara; Amico, K. Rivet; Little, Susan J.

    2016-01-01

    Expert guidelines for antiretroviral therapy (ART) now recommend ART as soon as possible in all HIV infected persons to reduce the risk of disease progression and prevent transmission. The goal of this observational study was to evaluate the impact of very early ART initiation and regimen type on time to viral suppression. We evaluated time to viral suppression among 86 persons with newly-diagnosed HIV infection who initiated ART within 30 days of diagnosis. A total of 36 (42%) had acute, 27 (31%) early, and 23 (27%) had established HIV infection. The median time from an offer of immediate ART to starting ART was 8 days. A total of 56/86 (65%) initiated an integrase inhibitor-based regimen and 30/86 (35%) a protease inhibitor-based regimen. The time to viral suppression was significantly shorter in those receiving an integrase inhibitor- versus a protease inhibitor-based regimen (p = 0.022). Twenty-two (26%) initiated ART at their HIV care intake visit and 79% of these participants achieved viral suppression at week 12, 82% at week 24 and 88% at week 48. ART initiated at the intake visit led to rapid and reliable viral suppression in acute, early and chronic HIV infection, in particular when integrase inhibitor-based regimens were used. PMID:27597312

  20. Non-communicable diseases in antiretroviral therapy recipients in Kagera Tanzania: a cross-sectional study

    PubMed Central

    Magafu, Mgaywa Gilbert Mjungu Damas; Moji, Kazuhiko; Igumbor, Ehimario Uche; Magafu, Naoko Shimizu; Mwandri, Michael; Mwita, Julius Chacha; Habte, Dereje; Rwegerera, Godfrey Mutashambara; Hashizume, Masahiro

    2013-01-01

    Introduction The aim of this study was to describe the extent of self-reported non-communicable diseases (NCDs) among highly active antiretroviral therapy (HAART) recipients in Kagera region in Tanzania and their effect on health-related quality of life (HRQOL). This study was conducted 2 years after HAART administration was started in Kagera region. Methods The SF-36 questionnaire was used to collect the HRQOL data of 329 HAART recipients. Questions on the NCDs, socio-demographic characteristics and treatment information were validated and added to the SF-36. Bivariate analyses involving socio-demographic characteristics and SF-36 scores of the recipients were performed. Multiple logistic regression was employed to compute adjusted odds ratios for different explanatory variables on physical functioning and mental health scores. Results Respondents who reported having 1 or more NCDs were 57.8% of all the respondents. Arthritis was the commonest NCD (57.8%). Respondents with the NCDs were more likely to have HRQOL scores below the mean of the general Tanzanian population. The population attributable fraction (PAF) for the NCDs on physical functioning was 0.28 and on mental health was 0.22. Conclusion Self-reported NCDs were prevalent among the HAART recipients in Kagera region. They accounted for 28% of the physical functioning scores and 22% of the mental health scores that were below the mean of the general Tanzanian population. Therefore, the integration of NCD care is important in the management of HIV/AIDS. PMID:24711874

  1. Delayed HIV detection among infants exposed to postnatal antiretroviral prophylaxis during breastfeeding

    PubMed Central

    King, Caroline C.; Kourtis, Athena P.; Persaud, Deborah; Nelson, Julie A.E.; Ziemniak, Carrie; Hudgens, Michael G.; Tegha, Gerald; Chasela, Charles S.; Jamieson, Denise J.; van der Horst, Charles M.

    2015-01-01

    Objective The objective of this study is to determine whether detection of HIV infection was delayed in infants exposed to antiretroviral prophylaxis to prevent HIV transmission during breastfeeding. Design The Breastfeeding, Antiretrovirals and Nutrition (BAN) study was a randomized trial of 2369 mother–infant pairs conducted from 2004 to 2010. In addition to an intrapartum regimen, all mother–infant pairs were randomly assigned to three antiretroviral intervention arms during 28 weeks of breastfeeding: no further antiretroviral prophylaxis (control arm); infant-daily nevirapine (nevirapine arm); and maternal zidovudine, lamivudine and either nevirapine, nelfinavir or lopinavir-ritonavir (maternal arm). After breastfeeding cessation counselling and stopping the antiretroviral interventions by 28 weeks, 28 infant HIV infections occurred. Methods To determine whether these infections occurred during the breastfeeding and antiretroviral intervention phase but had delayed detection on the antiretroviral arms, we performed ultrasensitive (droplet digital PCR) HIV testing on infants with stored peripheral blood mononuclear cell (PBMC) specimens at 24 weeks (n = 9). Results Of the nine infants, all three on the infant nevirapine arm had detectable HIV DNA at 24 weeks, compared with two of four on the maternal antiretroviral arm and one of two on the control arm. For infants with detectable HIV at 24 weeks, the median delay in detection between the ultrasensitive and standard assays was 18.3 weeks for the nevirapine arm, 15.4 weeks for the maternal arm and 9.4 weeks for the control arm. Conclusion The prolonged inability to detect HIV with standard assays in the context of postnatal antiretroviral prophylaxis suggests that early antiretrovirals may restrict HIV replication sufficiently to lead to missed diagnosis among infected infants. Therefore, repeat virologic testing is warranted beyond the WHO-recommended point of testing at 6 weeks after breastfeeding cessation

  2. A pilot study of health beliefs and attitudes concerning measures of antiretroviral adherence among prisoners receiving directly observed antiretroviral therapy.

    PubMed

    White, Becky L; Wohl, David A; Hays, Ron D; Golin, Carol E; Liu, Honghu; Kiziah, C Nichole; Simpson, Gregory; Kaplan, Andrew H

    2006-06-01

    High level adherence to antiretroviral therapy (ART) is required to achieve and maintain suppression of HIV replication. Although directly observed therapy (DOT) has been suggested as an intervention to improve adherence, there is a paucity of data describing the attitudes and beliefs regarding DOT for ART among HIV-infected individuals. This study was designed to evaluate the acceptability and psychometric properties of a survey instrument for use in assessing barriers and facilitators of adherence to ART DOT in prison. From July 1, 1999 to April 1, 2000, we piloted an interviewer-administered questionnaire to assess health beliefs and attitudes regarding HIV treatment among 65 HIV-infected prison inmates receiving one or more of their antiretrovirals via directly observed therapy (DOT). The first 24 participants were administered the questionnaire to determine the feasibility of surveying prisoners in a correctional setting. There were no adherence data collected on these participants. The remaining 41 participants had their adherence measured in addition to receiving the questionnaire. Thirty-one were included in the final analysis because 10 did not complete the study. Multiple antiretroviral adherence measures (electronic device medication monitoring [eDEM] caps, medication administration records [MARs], and pill counts) were assessed among a subset of the participants (n = 31) and correlated to the instrument response items. The median internal consistency reliability coefficient for the multi-item scales was 0.79. The strongest correlation between inmates' beliefs and their adherence was between "positive beliefs about protease inhibitors" and the MAR adherence measure (r = 0.72; p < 0.001). This study provides preliminary support for the psychometric properties of the survey in this correctional setting. PMID:16789854

  3. Antiretroviral drug resistance among antiretroviral-naïve and treatment experienced patients infected with HIV in Iran.

    PubMed

    Baesi, Kazem; Ravanshad, Mehrdad; Ghanbarisafari, Maryam; Saberfar, Esmaeil; Seyedalinaghi, Seyedahmad; Volk, Jonathan E

    2014-07-01

    Resistance to antiretroviral therapy (ART) threatens the success of programs to reduce HIV morbidity and mortality, particularly in countries with few treatment options. In the present study, genotype and phenotype data from ART-naïve and experienced hospitalized patients infected with HIV in Tehran, Iran were used to assess the prevalence and types of transmitted (TDR) and acquired drug resistance (ADR) mutations. All 30 participants naïve to ART and 62 of 70 (88.6%) participants receiving ART had detectable viral loads. Among participants receiving ART with sequencing data available (n = 62), 36 (58.1%) had at least one drug resistance mutation; the most common mutations were K103N (21.0%), M184V (19.4%), and the thymidine analogue mutations. Seven (11.3%), 27 (43.5%), and two (3.2%) of these participants had resistance to one, two, and three drug classes, respectively. High-level resistance to efavirenz (EFV) was more common among participants on EFV-based regimens than high-level lopinavir/ritonivar (LPV/r) resistance among those on LPV/r-based regimens (55.3% vs. 6.7%, P < 0.0001). Two (6.7%) antiretroviral-naïve participants had K103N mutations. These findings document an alarmingly high frequency of multiple HIV drug class resistance in Iran, confirm the presence of TDR, and highlight the need for systematic viral load monitoring and drug resistance testing, including at diagnosis. Expanded access to new antiretroviral medications from additional drug classes is needed.

  4. Interactions between alcohol and the antiretroviral medications ritonavir or efavirenz

    PubMed Central

    McCance-Katz, Elinore F.; Gruber, Valerie A.; Beatty, George; Lum, Paula J.; Rainey, Petrie M.

    2013-01-01

    Objective Alcohol abuse occurs frequently in those with HIV infection. Alcohol has been linked to poor response to HIV treatment and more rapid progression of HIV. One possible contributor to such observations is drug interactions between alcohol and antiretroviral medications (ARV). This study examined drug interactions between antiretroviral therapies (ART) containing either efavirenz or ritonavir with alcohol. Methods HIV-infected individuals not currently receiving ART participated in a randomized, double-blind, placebo-controlled, study in which alcohol (or placebo) was administered and followed by blood sampling for pharmacokinetics, subjective, cardiovascular, and neuropsychological responses obtained at pre-determined times. ART was then initiated and alcohol (or placebo) sessions were repeated after at least two weeks of observed ART. Results Blood alcohol concentrations (BAC) were lower following ART in a pattern consistent with decreased bioavailability. No effect of alcohol on ritonavir or efavirenz pharmacokinetics was observed. A pharmacodynamic interaction between alcohol and efavirenz was observed as evidenced by no change in intoxication or drowsiness before and after efavirenz ART despite lower BAC. Conclusions These results show the effectiveness of implementing ART and its role in diminution of BAC which could be associated with decreased risk of physiological toxicities related to alcohol consumption relative to those with untreated HIV infection. A potential pharmacodynamic interaction between alcohol and efavirenz was observed as demonstrated by a lack of decline in ratings of intoxication and drowsiness despite decreased BAC. Alcohol consumption did not alter the pharmacokinetics of ritonavir or efavirenz. PMID:23666322

  5. Photosensitization is required for antiretroviral activity of hypericin

    NASA Astrophysics Data System (ADS)

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

    1991-06-01

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

  6. [Positioning of lopinavir/ritonavir in antiretroviral treatment schemes].

    PubMed

    Camacho, Ángela; Rivero, Antonio

    2014-11-01

    Lopinavir/ritonavir (LPV/r) was approved for use in the treatment of human immunodeficiency virus (HIV) infection in 2001 and is the protease inhibitor that has been most widely studied in clinical trials. Despite the time interval since its approval, all the evidence accumulated in the last 14 years indicates that LPV/r continues to occupy an important position among antiretroviral drugs. Firstly, LPV/r plus 2 nucleoside/nucleotide analogs is still considered a good option for initial antiretroviral therapy (ART). Secondly, numerous studies have evaluated the efficacy and safety of new initial ART strategies based on LPV/r in dual therapy. The results obtained suggest that LPV/r plus lamivudine (3TC) or raltegravir can be as effective in initial ART as standard triple therapy and justify their consideration as alternative regimens in this scenario. Thirdly, LPV/r is a pioneer drug, as well as being the agent with the largest amount of evidence from clinical trials on simplification to monotherapy (LPV/r) or dual therapy (LPV/r + 3TC). Lastly, LPV/r is highly useful is special situations. It has a low risk of liver toxicity in patients with chronic liver disease, its use is preferred in the treatment of patients with HIV-2, and it is safe and effective in preventing vertical HIV transmission.

  7. A Systematic Review Comparing Antiretroviral Adherence Descriptive and Intervention Studies

    PubMed Central

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

    2009-01-01

    We examined the extent to which studies aimed at testing interventions to improve antiretroviral adherence have targeted the facilitators of and barriers known to affect adherence. Of the 88 reports reviewed, 41 were reports of descriptive studies conducted with U.S. HIV-positive women and 47 were reports of intervention studies conducted with U.S. HIV-positive persons. We extracted from the descriptive studies all findings addressing any factor linked to antiretroviral adherence and from the intervention studies, information on the nature of the intervention, the adherence problem targeted, the persons targeted for the intervention, and the intervention outcomes desired. We discerned congruence between the prominence of substance abuse as a factor identified in the descriptive studies as a barrier to adherence and its prominence as the problem most addressed in those reports of intervention studies that specified the problems targeted for intervention. We also discerned congruence between the prominence of family and provider support as factors identified in the descriptive studies as facilitators of adherence and the presence of social support as an intervention component and outcome variable. Less discernible in the reports of intervention studies was specific attention to other factors prominent in the descriptive studies, which may be due to the complex nature of the problem, individualistic and rationalist slant of interventions, or simply the ways interventions were presented. Our review raises issues about niche standardization and intervention tailoring, targeting, and fidelity. PMID:20024751

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

    PubMed

    Mayer, Kenneth H

    2014-07-01

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

  9. Implications of patent pools on innovation regarding antiretrovirals.

    PubMed

    Noehrenberg, Eric

    2010-01-19

    Patent pools have been promoted as an innovative means of promoting the production of fixed-dose combination antiretroviral medicines (ARVs), which can be particularly appropriate for resource-poor settings. An important question, however, is what are the implications of patent pools on innovation for creating new and improved antiretrovirals. Indeed, given the continuing mutation of HIV and growing resistance to existing treatments, continued innovation in ARV development is vital for addressing these challenges. Would patent pools be a hindrance or rather a stimulus for further innovation? This question is particularly relevant in light of UNITAID's initiative to create a patent pool for ARV development, focusing on pediatric formulations and new combinations, by the end of 2009. In this article, the author argues that a voluntary and well-designed patent pool, involving both innovative and generic manufacturers, focused on developing fixed-dose combinations for resource-poor markets with the greatest need, could actually stimulate increased innovation to meet these needs. Indeed, by bringing together the major ARV producers worldwide to collaborate on developing products which will meet the needs of the poorest, an ARV patent pool could create significant public health benefits. UNITAID has taken the lead in designing and implementing such a pool and UNITAID's experience will have important lessons for policy-makers in the future.

  10. Effects of Co-Trimoxazole on Microbial Translocation in HIV-1-Infected Patients Initiating Antiretroviral Therapy.

    PubMed

    Vesterbacka, Jan; Barqasho, Babilonia; Häggblom, Amanda; Nowak, Piotr

    2015-08-01

    Microbial translocation (MT) contributes to immune activation during HIV-1 infection, and persists after initiation of antiretroviral therapy (ART). We investigated whether levels of MT markers are influenced by the use of co-trimoxazole (TMP-SMX) in HIV-1 patients. Plasma samples were obtained from HIV-1-infected patients initiating ART with (n=13) or without (n=13) TMP-SMX prophylaxis. Markers of MT [lipopolysaccharide-binding protein (LBP), lipopolysaccharide (LPS), soluble CD14 (sCD14), and intestinal fatty acid binding protein (I-FABP)] were assessed at baseline (BL), at 1 month, and at 1 year by the Limulus Amebocyte Lysate Assay or ELISA. BL levels of LBP were elevated in both categories of patients; they were highest in patients starting ART and TMP-SMX (median, μg/ml: 36.7 vs. 4.3, respectively, p=0.001) and correlated inversely with CD4(+) T cell counts (ρ=-0.65; p=0.005). Patients receiving ART and TMP-SMX had a significant reduction in LBP between BL and 1 year (median, μg/ml: 36.7 vs. 11.1; p=0.003). In contrast, levels of LPS at BL were lower in patients starting ART and TMP-SMX compared to those without TMP-SMX (median, pg/ml: 221 vs. 303 respectively; p=0.002) and did not change at 1 year. The increased BL levels of sCD14 had declined in both groups at 1 year. No difference in I-FABP levels was found between BL and 1 year. Concomitant use of ART and TMP-SMX reduces microbial translocation markers LBP and sCD14, probably due to its impact on the gut microbiota. Effective ART for 1 year does not restore gut-blood barrier dysfunction. PMID:26059763

  11. Impact of three empirical tuberculosis treatment strategies for people initiating antiretroviral therapy

    PubMed Central

    Van Rie, Annelies; Westreich, Daniel; Sanne, Ian

    2016-01-01

    Background Early mortality in people initiating antiretroviral treatment (ART) in Africa remains high. Empiric TB treatment strategies aim to reduce early mortality by initiating TB treatment in individuals without clinical suspicion of TB who are at high-risk of death from undiagnosed TB. Methods Using data from 16,913 individuals starting ART under programmatic conditions, we simulated the impact of three empiric treatment strategies on mortality and incident TB: two randomized clinical trials (REMEMBER and PrOMPT) and a pragmatic approach. The main analysis assumed that 50% of early deaths and 100% of incident TB is averted in those eligible and ignored outcomes in those lost to follow up. Results The increase in individuals eligible for TB treatment under empirical TB treatment strategies ranged from 4.4% to 31.4% as compared to those started on clinical or mycobacteriological grounds. The proportion of deaths averted by empiric treatment strategies ranged from 5.5% to 25.4%. The proportion of incident TB cases averted ranged from 10.9% to 57.3%. The proportion receiving any TB treatment during the first six months of ART increased from the observed 24.0% to an estimated 27.5%, 40.4% and 51.3% under the PrOMPT, REMEMBER and pragmatic approach, respectively. Conclusion The impact of empiric TB treatment strategies depends greatly on the eligibility criteria chosen. The additional strain placed on TB treatment facilities and the relatively limited impact of some empirical TB strategies raise the question whether the benefits will outweigh the risks at population level. PMID:25299868

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

    PubMed

    Chileshe, Muatale; Bond, Virginia Anne

    2010-01-01

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

  13. 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

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

    PubMed Central

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

    2012-01-01

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

  15. 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

  16. HIV Drug Resistance Among Children Initiating First-Line Antiretroviral Treatment in Uganda

    PubMed Central

    Sigaloff, Kim Catherina Eve; Boender, Tamara Sonia; Kaudha, Elizabeth; Kayiwa, Joshua; Musiime, Victor; Mukuye, Andrew; Kiconco, Mary; Nankya, Immaculate; Nakatudde-Katumba, Llilian; Calis, Job C.J.; Rinke de Wit, Tobias F.; Mugyenyi, Peter N.

    2016-01-01

    Abstract Background: There are limited data on primary human immunodeficiency virus drug resistance (HIVDR) in pediatric populations. This study aimed to assess the prevalence of primary HIVDR and associated risk factors among children initiating first-line antiretroviral therapy (ART) in Uganda. Methods: At three Ugandan clinics, children (age <12 years) requiring ART were recruited between January 2010 and August 2011. Before starting ART, blood was collected for viral load and pol gene sequencing. Drug resistance mutations were determined using the 2010 International AIDS Society–USA mutation list. Risk factors for HIVDR were assessed with multivariate regression analysis. Results: Three hundred nineteen HIV-infected children with a median age of 4.9 years were enrolled. Sequencing was successful in 279 children (87.5%). HIVDR was present in 10% of all children and 15.2% of children <3 years. Nucleoside reverse transcriptase inhibitors (NRTIs), non-NRTI (NNRTI), and dual-class resistance was present in 5.7%, 7.5%, and 3.2%, respectively. HIVDR occurred in 35.7% of prevention of mother-to-child transmission (PMTCT)–exposed children, 15.6% in children with unknown PMTCT history, and 7.7% among antiretroviral-naive children. History of PMTCT exposure [adjusted odds ratio (AOR): 2.6, 95% CI: 1.3–5.1] or unknown PMTCT status (AOR: 3.8, 95% CI: 1.1–13.5), low CD4 (AOR: 2.2, 95% CI: 1.3–3.6), current breastfeeding (AOR: 7.4, 95% CI: 2.6–21), and current maternal ART use (AOR: 6.4, 95% CI: 3.4–11.9) emerged as risk factors for primary HIVDR in multivariate analysis. Conclusion: Pretreatment HIVDR is high, especially in children with PMTCT exposure. Protease inhibitor (PI)–based regimens are advocated by the World Health Organization, but availability in children is limited. Children with (unknown) PMTCT exposure, low CD4 count, current breastfeeding, or maternal ART need to be prioritized to receive PI-based regimens. PMID:26723018

  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. Alaska Head Start Annual Program Report, 1999.

    ERIC Educational Resources Information Center

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

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

  19. Alaska Head Start. Annual Report for 1998.

    ERIC Educational Resources Information Center

    Alaska State Dept. of Community and Regional Affairs, Juneau.

    This annual report details the accomplishments of the Alaska Head Start Program for fiscal year 1998. The report begins with a graphic presentation of the locations of Alaska Head Start programs and a table delineating the administrative and program partners of Head Start, its service population, eligibility requirements, funding sources, service…

  20. Monitoring of HAART regime antiretrovirals in serum of acquired immunodeficiency syndrome patients by micellar liquid chromatography.

    PubMed

    Casas-Breva, I; Peris-Vicente, J; Rambla-Alegre, M; Carda-Broch, S; Esteve-Romero, J

    2012-09-21

    A methodology based on micellar liquid chromatography to monitor five antiretroviral drugs (lamivudine, stavudine, tenofovir, zidovudine and efavirenz) was proposed. Antiretrovirals were studied in sets of three, corresponding to each highly active antiretroviral therapy (HAART) regime, prescribed to acquired immunodeficiency syndrome (AIDS)-infected patients. Four aqueous micellar mobile phases buffered at pH 7 were optimized to separate these compounds, using sodium dodecyl sulfate as the tensioactive, and 1-propanol or 1-pentanol as the organic modifier. The composition of each mobile phase was optimized for each antiretroviral. The common separation conditions were: C18 apolar column (125 × 4.6 mm, 5 μm particle size), UV detection set at 214 nm, and mobile phase running at 1 mL min(-1) without controlling the temperature. The finally suggested method was validated for five analysed antiretroviral drugs following the US Food and Drug Administration guidelines in terms of: linearity between 0.5 and 50 ppm (r(2) > 0.9995), sensitivity (LOD lower than 0.25 ppm), intra- and inter-day precision (<7.1 and <5.2%, respectively) and accuracy (recovery 88.5-105.3% and 93.5-101.3%, respectively), as well as robustness (<6.5%). The proposed method was used to monitor the level of antiretrovirals in the serum of AIDS patients. The suggested methodology was found to be useful in the routine analysis of antiretrovirals in serum samples.

  1. 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/μl 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

  2. Biomechanical analysis of backstroke swimming starts.

    PubMed

    de Jesus, K; de Jesus, K; Figueiredo, P; Gonçalves, P; Pereira, S; Vilas-Boas, J P; Fernandes, R J

    2011-07-01

    The relationships between the start time and kinematic, kinetic and electromyographic data were examined in order to establish the common features of an effective backstroke swimming start. Complementarily, different starting positions were analysed to identify the parameters that account for the fastest backstroke start time under different constraints. 6 high-level swimmers performed 4×15 m maximal trials of each start variants with different feet position: parallel and entirely submerged (BSFI) and above water surface (BSFE), being monitored with synchronized dual-media image, underwater platform plus handgrip with a load cell, and eletromyographic signal of RECTUS FEMORIS and GASTROCNEMIUS MEDIALIS. Mean and SD values of start time for BSFI and BSFE were 2.03 ± 0.19 and 2.14 ± 0.36 s, respectively. In both starts, high associations (r > =0.75, p < 0.001) were observed between start time and centre of mass resultant average velocity at glide phase and horizontal impulse at take-off for BSFI, and centre of mass horizontal position at the start signal for BSFE. It was concluded that the greater impulse during the take-off and its transformation into a fast underwater movement are determinant to decrease the start time at BSFI. Regarding BSFE, a greater centre of mass pool-wall approximation might imply a flatter take-off angle, compromising underwater velocity and starting performance. PMID:21563041

  3. Managed Problem Solving for Antiretroviral Therapy Adherence: A Randomized Trial

    PubMed Central

    Gross, Robert; Bellamy, Scarlett L.; Chapman, Jennifer; Han, Xiaoyan; O’Duor, Jacqueline; Palmer, Steven C.; Houts, Peter S.; Coyne, James C.; Strom, Brian L.

    2015-01-01

    Background Adherence to antiretroviral therapy is critical to successful treatment of HIV. Few interventions have been demonstrated to improve both adherence and virological outcomes. We sought to determine whether an intervention derived from problem solving theory, Managed Problem Solving (MAPS), would improve antiretroviral outcomes. Methods We conducted a randomized investigator blind trial of MAPS compared with usual care in HIV-1 infected individuals at three HIV clinics in Philadelphia, PA. Eligible patients had plasma HIV-1 viral loads >1000 copies/ml and were initiating or changing therapy. MAPS consists of four in-person and 12 telephone-based meetings with a trained interventionist, then monthly follow-up calls for a year. Primary outcome was medication adherence measured using electronic monitors, summarized as fraction of doses taken quarterly over one year. Secondary outcome was undetectable HIV viral load over one year. We assessed 218 for eligibility, with 190 eligible and 180 enrolled, 91 randomized to MAPS and 89 to usual care. 56 participants were lost to follow-up: 33 in MAPS and 23 in usual care. Results In primary intention-to-treat analyses, the odds of being in a higher adherence category was 1.78 (95% CI:1.07–2.96) times greater for MAPS than usual care. In secondary analyses, the odds of an undetectable viral load was 1.48 (95% CI: 0.94–2.31) times greater for MAPS than usual care. In as-treated analyses, the effect of MAPS was stronger for both outcomes. There was neither a difference by prior treatment status nor change in effect over time. Conclusions MAPS is an effective antiretroviral adherence intervention over the first year with a new regimen. It was equally effective at improving adherence in treatment experienced and naïve patients and did not lose effect over time. Implementation of MAPS should be strongly considered where resources are available. Trial Registration ClinicalTrials.gov, NCT00130273 PMID:23358784

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

    PubMed

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

    2007-01-01

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

  5. Could antiretroviral neurotoxicity play a role in the pathogenesis of cognitive impairment in treated HIV disease?.

    PubMed

    Underwood, Jonathan; Robertson, Kevin R; Winston, Alan

    2015-01-28

    Whilst effective antiretroviral therapy is protective against the more severe forms of HIV-associated brain disease, there remains a large burden of clinically symptomatic cognitive impairment in the modern era. Although several potential pathogenic mechanisms have been proposed, the underlying pathology remains elusive. In this review, we summarize the evidence describing neuronal toxicity of antiretroviral agents themselves in both preclinical and clinical situations, as well as the potential pathological mechanisms underlying this toxicity. We also consider the implications for future practice and clinical research in which case determining optimal antiretroviral combinations that effectively suppress HIV replication whilst minimizing neurotoxic effects on the central nervous system may become paramount.

  6. The Association of Adherence to Antiretroviral Therapy with Healthcare Utilization and Costs for Medical Care

    PubMed Central

    Gardner, Edward M.; Maravi, Moises E.; Rietmeijer, Cornelis; Davidson, Arthur J.; Burman, William J.

    2009-01-01

    Background The association between antiretroviral adherence, healthcare utilization and medical costs has not been well studied. Objective To examine the relationship of adherence to antiretroviral medications to healthcare utilization and healthcare costs. Methods A retrospective cohort study was conducted using data from 325 previously antiretroviral medication-naive HIV-infected individuals initiating first antiretroviral therapy from 1997 through 2003. The setting was an inner-city safety net hospital and HIV clinic in the US. Adherence was assessed using pharmacy refill data. The average wholesale price was used for prescription costs. Healthcare utilization data and medical costs were obtained from the hospital billing database, and differences according to quartile of adherence were compared using analysis of variance (ANOVA). Multivariate logistic regression was used to assess predictors of higher annual medical costs. Sensitivity analyses were used to examine alternative antiretroviral pricing schemes. The perspective was that of the healthcare provider, and costs were in year 2005 values. Results In 325 patients followed for a mean (± SD) 3.2 (1.9) years, better adherence was associated with lower healthcare utilization but higher total medical costs. Annual non-antiretroviral medical costs were $US7612 in the highest adherence quartile versus $US10 190 in the lowest adherence quartile. However, antiretroviral costs were significantly higher in the highest adherence quartile ($US17 513 vs $US8690), and therefore the total annual medical costs were also significantly higher in the highest versus lowest adherence quartile ($US25 125 vs $US18 880). In multivariate analysis, for every 10% increase in adherence, the odds of having annual medical costs in the highest versus lowest quartile increased by 87% (odds ratio 1.87; 95% CI 1.45, 2.40). In sensitivity analyses, very low antiretroviral prices (as seen in resource-limited settings) inverted this

  7. Literacy, education and adherence to antiretroviral therapy in The Gambia.

    PubMed

    Hegazi, A; Bailey, R L; Ahadzie, B; Alabi, A; Peterson, K

    2010-11-01

    We examined the relationship of patients' literacy and education to antiretroviral therapy (ART) adherence in an urban treatment centre in The Gambia. Information on education and literacy systematically collected before ART initiation was compared against selected adherence outcomes. Formally educated patients were significantly more likely to achieve virological suppression at both six and 12 months (87% vs. 67%, OR=3.13, P=0.03; 88% vs. 63%, OR=4.49, P=0.007, respectively). Literate patients had similar benefit at 12 months (OR=3.39 P=0.03), with improved virological outcomes associated with degree of literacy (P=0.003). A trend towards similar results was seen at 6 months for Koranically educated patients; however, this was no longer apparent at 12 months. No significant correlation was seen between socio-demographic characteristics and missed appointments. Our study suggests that literacy, formal education and possibly Koranic education may impact favourably on adherence to ART.

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

    PubMed

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

    2015-01-01

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

  9. Pharmacokinetic, Pharmacogenetic, and Other Factors Influencing CNS Penetration of Antiretrovirals

    PubMed Central

    Babalola, Chinedum Peace; Morse, Gene D.; Taiwo, Babafemi

    2016-01-01

    Neurological complications associated with the human immunodeficiency virus (HIV) are a matter of great concern. While antiretroviral (ARV) drugs are the cornerstone of HIV treatment and typically produce neurological benefit, some ARV drugs have limited CNS penetration while others have been associated with neurotoxicity. CNS penetration is a function of several factors including sieving role of blood-brain and blood-CSF barriers and activity of innate drug transporters. Other factors are related to pharmacokinetics and pharmacogenetics of the specific ARV agent or mediated by drug interactions, local inflammation, and blood flow. In this review, we provide an overview of the various factors influencing CNS penetration of ARV drugs with an emphasis on those commonly used in sub-Saharan Africa. We also summarize some key associations between ARV drug penetration, CNS efficacy, and neurotoxicity. PMID:27777797

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

    PubMed

    Furuoka, Fumitaka; 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

  11. 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

  12. What Time is it? Adherence to Antiretroviral Therapy in Ethiopia

    PubMed Central

    Tiruneh, Yordanos M.; Wilson, Ira B.

    2016-01-01

    This study assessed adherence to antiretroviral therapy (ART) among people living with HIV/AIDS in Ethiopia and explored the sociocultural context in which they relate to their regimen requirements. Data were collected through semi-structured in-depth interviews with 105 patients on ART and observations held at the study clinic. We analyzed data using both qualitative and quantitative methods. Our findings indicate that study participants are highly adherent to dose but less adherent to dose schedule. Strict dose time instructions were reported as stressful and unrealistic. The discrepancy between adherence to dose and dose schedule could be explained by time perception, difficulty with the strictness of medication regimens, or beliefs about dose timing adherence. Care providers should acknowledge the complexities of medication practices and engage in shared decision-making to incorporate patients’ perspectives and identify effective interventions. PMID:26873491

  13. African Mitochondrial DNA Subhaplogroups and Peripheral Neuropathy during Antiretroviral Therapy

    PubMed Central

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

    2010-01-01

    Susceptibility to peripheral neuropathy during antiretroviral therapy with nucleoside reverse transcriptase inhibitors (NRTIs) was previously associated with a European mitochondrial DNA (mtDNA) haplogroup among non-Hispanic white persons. To determine if NRTI-associated peripheral neuropathy was related to mtDNA variation in non-Hispanic black persons, we sequenced mtDNA of participants from AIDS Clinical Trials Group study 384. Of 156 non-Hispanic blacks with genomic data, 51 (33%) developed peripheral neuropathy. In a multivariate model, African mtDNA subhaplogroup L1c was an independent predictor of peripheral neuropathy (OR=3.7, 95% CI 1.1-12.0). An African mtDNA subhaplogroup is for the first time implicated in susceptibility to NRTI-associated toxicity. PMID:20402593

  14. Antiretroviral Therapy Initiation Following Policy Changes: Observations From China

    PubMed Central

    Li, Li; Ji, Guoping; Lin, Chunqing; Liang, Li-Jung; Lan, Chiao-Wen

    2016-01-01

    China’s HIV/AIDS treatment policies have been evolving over the preceding decade. This study describes patterns of antiretroviral therapy (ART) initiation for a sample of people living with HIV/AIDS (PLHIV) in rural Anhui, China, where most PLHIV were infected via paid plasma donation during the 1990s. A total of 481 PLHIV who were receiving ART were included in our analyses. Times between HIV diagnosis and the initiation of ART were examined relative to the time points when major ART-related policies changed in China. More than half (53%) of PLHIV who had been diagnosed by 2003 received ART within 6 months, whereas 93% of PLHIV who had been diagnosed in 2010 or later received ART within 6 months. The study results provide additional support that the “Four Frees and One Care” policy in 2003 and the relaxation of ART eligibility in 2010 have facilitated the initiation of treatment for PLHIV in China. PMID:27217427

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

    PubMed

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

    2011-01-01

    Since 2004, Georgia achieved universal access to free antiretroviral therapy (ART). A retrospective cohort study was conducted to evaluate the outcomes of Georgia's ART program. The study included adult patients enrolled in the ART program from 2004 through 2009. Of 752 patients, 76% were men, 60% were injection drug users (IDU), 59% had a history of an AIDS-defining illness, and 53% were coinfected with hepatitis C. The median baseline CD4 cell count was 141 cells/mm(3). During followup, 152 (20%) patients died, with the majority of deaths occurring within 12 months of ART initiation. Mortality was associated with advanced immunodeficiency or the presence of incurable disease at baseline. Among patients remaining on treatment, the median CD4 gain was 216 cell/mm(3) and 86% of patients had viral load <400 copies/ml at the last clinical visit. The Georgia ART program has been successful in treating injection drug users infected with HIV.

  16. Fanconi Syndrome and Antiretrovirals: It Is Never Too Late.

    PubMed

    Luni, Faraz Khan; Khan, Abdur Rahman; Prashar, Rohini; Vetteth, Sandeep; Duggan, Joan M

    2016-01-01

    Antiretroviral medications such as tenofovir have been associated with Fanconi syndrome (FS) usually identified within the first 1-29 months after exposure to the medication. We present a case of life-threatening FS which developed in a 37-year-old woman with HIV after 8 years of asymptomatic tenofovir use. The patient was diagnosed with HIV in 1996 at 20 years of age, hepatitis C 10 years later, and Staphylococcus aureus sepsis with secondary osteomyelitis of the spine 3 years before admission for FS. She developed nausea, vomiting, diarrhea, and generalized weakness over a 2-week time period and presented to the hospital. In the emergency department, her serum potassium was 1.5 mEq/L, bicarbonate was 12 mEq/L, chloride was 111 mEq/L, phosphorus was 1.8 mg/dL, and creatinine was 1.95 mg/dL (baseline, 1.4). Arterial blood gas revealed a non-anion gap (hyperchloremic) metabolic acidosis. Type 2 renal tubular acidosis induced by antiretroviral therapy (ART) was suspected and the ART was discontinued with resolution of the renal abnormalities within 7 days. A non-tenofovir-containing ART regimen consisting of lamivudine/abacavir and efavirenz was begun, and over the next 8 months, the patient was without recurrence of the FS. This case report demonstrates the acute development of FS after prolonged exposure to tenofovir without exposure to additional nephrotoxins such as nonsteroidal medications or aminoglycosides. Tenofovir can cause FS at any time and should be considered in any patient presenting with renal tubular acidosis type 2 while on tenofovir regardless of the duration of drug exposure.

  17. Cohort Profile: Antiretroviral Therapy Cohort Collaboration (ART-CC)

    PubMed Central

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

    2014-01-01

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

  18. What's new for antiretroviral treatment in women with HIV.

    PubMed

    Andany, Nisha; Walmsley, Sharon L

    2016-01-01

    Currently, women represent 52% of persons infected with HIV worldwide and 23% of those in the United States. Combination antiretroviral therapy (cART) has resulted in remarkable reductions in HIV-associated morbidity and mortality, and has dramatically improved life expectancy. Treatment guidelines do not differ for HIV-infected men and non-pregnant women. However, clinical trials of antiretroviral agents have limited female enrolment, and results from these predominantly male studies are extrapolated to the female population. Furthermore, many of these studies do not report gender subgroup analyses, and those that do are underpowered to detect differences between men and women, limiting the ability to assess if results are equally applicable to both sexes. Women may have differential responses to and adverse events from cART. A limited number of female-only clinical trials have demonstrated that female recruitment and retention in these studies is feasible. Therefore, urgent attention is required to improve the body of knowledge regarding clinical efficacy, safety and tolerability of cART in women. In particular, women living with HIV are faced with various sexual and reproductive health concerns that may influence choice of cART. These include potential interactions with hormonal contraception, safety in pregnancy, and the impact of the transition through menopause and development of age-related comorbidities. Finally, the ongoing advances in biomedical HIV prevention, particularly pre-exposure prophylaxis (PrEP), provide an enormous opportunity to enhance HIV prevention in high-risk women, in efforts to further reduce global burden of the pandemic. PMID:27482438

  19. Novel antiretroviral drugs and renal function monitoring of HIV patients.

    PubMed

    Maggi, Paolo; Montinaro, Vincenzo; Mussini, Cristina; Di Biagio, Antonio; Bellagamba, Rita; Bonfanti, Paolo; Calza, Leonardo; Cherubini, Chiara; Corsi, Paola; Gargiulo, Miriam; Montella, Francesco; Rusconi, Stefano

    2014-01-01

    Chronic kidney disease is a major comorbidity in patients affected by HIV infection. In addition, the introduction of new antiretroviral agents that interact with creatinine transporters is raising some concerns. In this review we analyze the currently available data about three new antiretroviral drugs and one new pharmacokinetic enhancer. Three of them (rilpivirine, cobicistat, dolutegravir) have shown some interactions with renal function, while tenofovir alafenamide fumarate reduces the plasmatic concentration of the parent drug. The future use of tenofovir alafenamide seems to be encouraging in order to reduce the renal interaction of tenofovir. Rilpivirine, cobicistat, and dolutegravir reduce the tubular secretion of creatinine, inducing a decrease of estimated glomerular filtration rate according to creatinine. Rilpivirine and dolutegravir block the uptake of creatinine from the blood, inhibiting organic cation transporter 2, and cobicistat interacts with the efflux inhibiting multidrug and toxin extrusion protein 1. This effect can then be considered a "reset" of the estimated glomerular filtration rate according to creatinine. However, clinicians should carefully monitor renal function in order to identify possible alterations suggestive of a true renal functional impairment. Owing to the interference of these drugs with creatinine secretion, an alternative way of estimation of glomerular filtration rate would be desirable. However, at the moment, other methods of direct glomerular filtration rate measurement have a high impact on the patient, are not readily available, or are not reliable in HIV patients. Consequently, use of classic formulas to estimate glomerular filtration rate is still recommended. Also, tubular function needs to be carefully monitored with simple tests such as proteinuria, phosphatemia, urinary excretion of phosphate, normoglycemic glycosuria, and excretion of uric acid.

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed

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

    2014-06-01

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

  2. Platelet count kinetics following interruption of antiretroviral treatment

    PubMed Central

    Zetterberg, Eva; Neuhaus, Jacqueline; Baker, Jason V.; Somboonwit, Charurut; Llibre, Josep M.; Palfreeman, Adrian; Chini, Maria; Lundgren, Jens D.

    2014-01-01

    Objectives To investigate the mechanisms of platelet kinetics in the Strategies for Management of Antiretroviral Therapy (SMART) study that demonstrated excess mortality with CD4 guided episodic antiretroviral therapy (ART) drug conservation compared with continuous treatment viral suppression. Follow-up analyses of stored plasma samples demonstrated increased activation of both inflammatory and coagulation pathways after stopping ART. Design SMART patients from sites that determined platelets routinely. Methods Platelet counts were retrospectively collected from 2206 patients from visits at study entry, and during follow-up. D-dimer levels were measured at study entry, month 1, and 2. Results Platelet levels decreased in the drug conservation group following randomization, but remained stable in the viral suppression group [median (IQR) decline from study entry to month 4: −24 000/µl (−54 000 to 4000) vs. 3000 (−22 000 to 24 000), respectively, P < 0.0001)] and the rate of developing thrombocytopenia (<100 000/µl) was significantly higher in the drug conservation vs. the viral suppression arm (unadjusted drug conservation/viral suppression [HR (95%CI) = 1.8 (1.2–2.7)]. The decline in platelet count among drug conservation participants on fully suppressive ART correlated with the rise in D-dimer from study entry to either month 1 or 2 (r = −0.41; P = 0.02). Among drug conservation participants who resumed ART 74% recovered to their study entry platelet levels. Conclusion Interrupting ART increases the risk of thrombocytopenia, but reinitiation of ART typically reverses it. Factors contributing to declines in platelets after interrupting ART may include activation of coagulation pathways or HIV-1 replication itself. The contribution of platelets in HIV-related procoagulant activity requires further study. PMID:23018440

  3. Economics of antiretroviral treatment vs. circumcision for HIV prevention.

    PubMed

    Bärnighausen, Till; Bloom, David E; Humair, Salal

    2012-12-26

    The HIV Prevention Trials Network (HPTN) 052 study, which showed the effectiveness of antiretroviral treatment in reducing HIV transmission, has been hailed as a "game changer" in the fight against HIV, prompting calls for scaling up treatment as prevention (TasP). However, it is unclear how TasP can be financed, given flat-lining support for global HIV programs. We assess whether TasP is indeed a game changer or if comparable benefits are obtainable at similar or lower cost by increasing coverage of medical male circumcision (MMC) and antiretroviral treatment (ART) at CD4 <350/μL. We develop a new mathematical model and apply it to South Africa, finding that high ART coverage combined with high MMC coverage provides approximately the same HIV incidence reduction as TasP, for $5 billion less over 2009-2020. MMC outperforms ART significantly in cost per infection averted ($1,096 vs. $6,790) and performs comparably in cost per death averted ($5,198 vs. $5,604). TasP is substantially less cost effective at $8,375 per infection and $7,739 per death averted. The prevention benefits of HIV treatment are largely reaped with high ART coverage. The most cost-effective HIV prevention strategy is to expand MMC coverage and then scale up ART, but the most cost-effective HIV-mortality reduction strategy is to scale up MMC and ART jointly. TasP is cost effective by commonly used absolute benchmarks but it is far less cost effective than MMC and ART. Given South Africa's current annual ART spending, the $5 billion in savings offered by MMC and ART over TasP in the next decade, for similar health benefits, challenges the widely hailed status of TasP as a game changer.

  4. [Lopinavir/ritonavir in new initial antiretroviral treatment strategies].

    PubMed

    Rolón, María José; Figueroa, María Inés; Sued, Omar; Cahn, Pedro

    2014-11-01

    According to evidence from randomized controlled trials and epidemiological data, the antiretroviral treatment (ART) of choice has consisted of the combination of 2 nucleoside analog reverse-transcriptase inhibitors (NRTI) plus 1 non-nucleoside analog reverse-transcriptase inhibitor (NNRTI) or a protease inhibitor (PI) for more than 17 years. There are several unresolved issues, notably the toxocity associated with NRTI, especially thymidine analogs, and the possibility of cross resistance, which may affect subsequent treatment. The development of new antiretroviral drugs with simpler dosing regimens and lower toxicity has led to evaluation of innovative strategies such as dual therapy for initial ART in treatment-naive, with the aim of preventing long-term toxicity and increasing treatment adherence. Despite encouraging results, some combinations have proven unsatisfactory. The strategies with favorable results to date consist of twice-daily lopinavir/ritonavir (LPV/r)-based regimens, those in the PROGRESS (LPV/r + raltegravir) and GARDEL (LPV/r + lamivudine) trials, and the combination of darunavir and raltegravir (NEAT 001 trial), although the latter observed a higher tendency (statistically nonsignificant) to virological failure in the dual combination arm. These trials were based on the use of NRTI-sparing regimens consisting of 2-3 fully- active agents for highly-active ART in treatment-naïve HIV-positive patients. Recent studies provide evidence supporting the use of NRTI-sparing regimens in HIV-infected patients with failure to an initial NNRTI-based ART regimen. The present review will discuss only LPV/r-based innovative strategies in initial ART regimens.

  5. 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 PKCε independent, and alcohol-induced painful neuropathy, PKCε 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 PKCε 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

  6. 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.

  7. 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…

  8. 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.

  9. 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.

  10. Risk Factors for Incident Diabetes in a Cohort Taking First-Line Nonnucleoside Reverse Transcriptase Inhibitor-Based Antiretroviral Therapy.

    PubMed

    Karamchand, Sumanth; Leisegang, Rory; Schomaker, Michael; Maartens, Gary; Walters, Lourens; Hislop, Michael; Dave, Joel A; Levitt, Naomi S; Cohen, Karen

    2016-03-01

    Efavirenz is the preferred nonnucleoside reverse transcriptase inhibitor (NNRTI) in first-line antiretroviral therapy (ART) regimens in low- and middle-income countries, where the prevalence of diabetes is increasing. Randomized control trials have shown mild increases in plasma glucose in participants in the efavirenz arms, but no association has been reported with overt diabetes. We explored the association between efavirenz exposure and incident diabetes in a large Southern African cohort commencing NNRTI-based first-line ART. Our cohort included HIV-infected adults starting NNRTI-based ART in a private sector HIV disease management program from January 2002 to December 2011. Incident diabetes was identified by the initiation of diabetes treatment. Patients with prevalent diabetes were excluded. We included 56,298 patients with 113,297 patient-years of follow-up (PYFU) on first-line ART. The crude incidence of diabetes was 13.24 per 1000 PYFU. Treatment with efavirenz rather than nevirapine was associated with increased risk of developing diabetes (hazard ratio 1.27 (95% confidence interval (CI): 1.10-1.46)) in a multivariate analysis adjusting for age, sex, body mass index, baseline CD4 count, viral load, NRTI backbone, and exposure to other diabetogenic medicines. Zidovudine and stavudine exposure were also associated with an increased risk of developing diabetes. We found that treatment with efavirenz, as well as stavudine and zidovudine, increased the risk of incident diabetes. Interventions to detect and prevent diabetes should be implemented in ART programs, and use of antiretrovirals with lower risk of metabolic complications should be encouraged. PMID:26945366

  11. Risk Factors for Incident Diabetes in a Cohort Taking First-Line Nonnucleoside Reverse Transcriptase Inhibitor-Based Antiretroviral Therapy

    PubMed Central

    Karamchand, Sumanth; Leisegang, Rory; Schomaker, Michael; Maartens, Gary; Walters, Lourens; Hislop, Michael; Dave, Joel A.; Levitt, Naomi S.; Cohen, Karen

    2016-01-01

    Abstract Efavirenz is the preferred nonnucleoside reverse transcriptase inhibitor (NNRTI) in first-line antiretroviral therapy (ART) regimens in low- and middle-income countries, where the prevalence of diabetes is increasing. Randomized control trials have shown mild increases in plasma glucose in participants in the efavirenz arms, but no association has been reported with overt diabetes. We explored the association between efavirenz exposure and incident diabetes in a large Southern African cohort commencing NNRTI-based first-line ART. Our cohort included HIV-infected adults starting NNRTI-based ART in a private sector HIV disease management program from January 2002 to December 2011. Incident diabetes was identified by the initiation of diabetes treatment. Patients with prevalent diabetes were excluded. We included 56,298 patients with 113,297 patient-years of follow-up (PYFU) on first-line ART. The crude incidence of diabetes was 13.24 per 1000 PYFU. Treatment with efavirenz rather than nevirapine was associated with increased risk of developing diabetes (hazard ratio 1.27 (95% confidence interval (CI): 1.10–1.46)) in a multivariate analysis adjusting for age, sex, body mass index, baseline CD4 count, viral load, NRTI backbone, and exposure to other diabetogenic medicines. Zidovudine and stavudine exposure were also associated with an increased risk of developing diabetes. We found that treatment with efavirenz, as well as stavudine and zidovudine, increased the risk of incident diabetes. Interventions to detect and prevent diabetes should be implemented in ART programs, and use of antiretrovirals with lower risk of metabolic complications should be encouraged. PMID:26945366

  12. The incidence and spectrum of AIDS-defining illnesses in persons treated with antiretroviral drugs.

    PubMed

    Forrest, D M; Seminari, E; Hogg, R S; Yip, B; Raboud, J; Lawson, L; Phillips, P; Schechter, M T; O'Shaughnessy, M V; Montaner, J S

    1998-12-01

    The incidence and spectrum of primary AIDS-defining illnesses in human immunodeficiency virus-positive patients receiving antiretroviral drugs may have changed since the introduction of newer antiretroviral agents. We performed a retrospective analysis of patients enrolled in the British Columbia Drug Treatment Program who were ever prescribed antiretroviral drugs between 1 January 1994 and 31 December 1996. Rates were calculated on a 6-month basis. There were 344 AIDS cases diagnosed among 2,533 participants between 1994 and 1996. The incidence of primary AIDS diseases decreased from 1994 to 1996, with a sharp decline in 1995 and 1996. There was no statistically significant change in the incidence of primary AIDS diagnoses relative to one another, and Pneumocystis carinii pneumonia and Kaposi's sarcoma remain the most common AIDS index diagnoses. In patients receiving antiretroviral therapy in the modern era, the incidence of AIDS-defining illnesses has decreased substantially, but the spectrum of AIDS-defining illnesses remains unchanged.

  13. A Mathematical Model of Antiretroviral Therapy Evaluation for HIV Type 1

    NASA Astrophysics Data System (ADS)

    Raimundo, Silvia Martorano; Venturino, Ezio; Mo Yang, Hyun

    2009-09-01

    Treating HIV-infected patients with a combination of several antiretroviral drugs can lead to emergence of the drug-resistant strain. This work proposes a mathematical model to evaluate the emergence of HIV-1 drug resistant during antiretroviral therapy. The model assumes that all susceptible individuals who can be infected by the wildtype strain (sensible to the treatment) or by drug-resistant virus receive antiretroviral therapy. Patients on treatment regimen can evolve to a state of success or failure and for the individuals in therapeutic fail the therapeutic schema is changed. The analysis of system is performed. The existence and stability of the steady states are considered. We address an analytical expression for the reproductive number in a community where antiretroviral therapy are widely used to treat HIV and where both drug sensitive and drug resistant strains are co-circulating.

  14. The Impact of Non-Antiretroviral Polypharmacy on the Continuity of Antiretroviral Therapy (ART) Among HIV Patients.

    PubMed

    Krentz, Hartmut B; Gill, M John

    2016-01-01

    Improved survival achieved by many patients with HIV/AIDS has complicated their medical care as increasing numbers of co-morbidities leads to polypharmacy, increased pill burdens, and greater risks of drug-drug interactions potentially compromising antiretroviral treatment (ART). We examined the impact of non-antiretroviral polypharmacy on ART for all adults followed at the Southern Alberta Clinic, Calgary, Canada. Polypharmacy was defined as ≥5 daily medications. We compared the impact of polypharmacy on continuous (i.e., remaining on same ART for ≥6 months) vs. non-continuous (i.e., discontinuing or switching ART) ART dosing frequency, number of ART pills, number of non-ART medications, and age. Of 1190 (89.5%) patients on ART, 95% were on three-drug regimens, 63.9% on QD ART, and 62% ≥3 ART pills daily; 32.2% were experiencing polypharmacy. Polypharmacy was associated with lower CD4, AIDS, >180 months living with HIV, higher numbers of ART pills, and older age (all p < 0.01); 32.1% stopped or switched ART. Polypharmacy increased the risk for non-continuous ART (36.8% vs. 30.0%; p < 0.01). Non-continuous ART increased with daily ART pill count but not increased age. Non-adherence and adverse effects accounted for the majority of non-continuous ART. We found a strong association between polypharmacy and non-continuous ART, potentially leading to effective ART being compromised. Collaborative approaches are needed to anticipate the negative impacts of polypharmacy.

  15. Adherence to Antiretroviral Therapy During and After Pregnancy: Cohort Study on Women Receiving Care in Malawi's Option B+ Program

    PubMed Central

    Haas, Andreas D.; Msukwa, Malango T.; Egger, Matthias; Tenthani, Lyson; Tweya, Hannock; Jahn, Andreas; Gadabu, Oliver J.; Tal, Kali; Salazar-Vizcaya, Luisa; Estill, Janne; Spoerri, Adrian; Phiri, Nozgechi; Chimbwandira, Frank; van Oosterhout, Joep J.; Keiser, Olivia

    2016-01-01

    Background. Adherence to antiretroviral therapy (ART) is crucial to preventing mother-to-child transmission of human immunodeficiency virus (HIV) and ensuring the long-term effectiveness of ART, yet data are sparse from African routine care programs on maternal adherence to triple ART. Methods. We analyzed data from women who started ART at 13 large health facilities in Malawi between September 2011 and October 2013. We defined adherence as the percentage of days “covered” by pharmacy claims. Adherence of ≥90% was deemed adequate. We calculated inverse probability of censoring weights to adjust adherence estimates for informative censoring. We used descriptive statistics, survival analysis, and pooled logistic regression to compare adherence between pregnant and breastfeeding women eligible for ART under Option B+, and nonpregnant and nonbreastfeeding women who started ART with low CD4 cell counts or World Health Organization clinical stage 3/4 disease. Results. Adherence was adequate for 73% of the women during pregnancy, for 66% in the first 3 months post partum, and for about 75% during months 4–21 post partum. About 70% of women who started ART during pregnancy and breastfeeding adhered adequately during the first 2 years of ART, but only about 30% of them had maintained adequate adherence at every visit. Risk factors for inadequate adherence included starting ART with an Option B+ indication, at a younger age, or at a district hospital or health center. Conclusions. One-third of women retained in the Option B+ program adhered inadequately during pregnancy and breastfeeding, especially soon after delivery. Effective interventions to improve adherence among women in this program should be implemented. PMID:27461920

  16. CD4+ T cell counts in initiation of antiretroviral therapy in HIV infected asymptomatic individuals; controversies and inconsistencies.

    PubMed

    Maina, E K; Bonney, E Y; Bukusi, E A; Sedegah, M; Lartey, M; Ampofo, W K

    2015-12-01

    The primary goal when devising strategies to define the start of therapy in HIV infected individuals is to avoid HIV disease progression and toxicity from antiretroviral therapy (ART). Intermediate goals includes, avoiding resistance by suppressing HIV replication, reducing transmission, limiting spread and diversity of HIV within the body and protecting the immune system from harm. The question of how early or late to start ART and achieve both primary and intermediate goals has dominated HIV research. The distinction between early and late treatment of HIV infection is currently a matter of CD4+ T cells count, a marker of immune status, rather than on viral load, a marker of virus replication. Discussions about respective benefits of early or delayed therapy, as well as the best CD4+ T cell threshold during the course of HIV infection at which ART is initiated remains inconclusive. Guidelines issued by various agencies, provide different initiation recommendations. This can be confusing for clinicians and policy-makers when determining the best time to initiate therapy. Optimizing ART initiation strategies are clearly complex and must be balanced between individual and broader public health needs. This review assesses available data that contributes to the debate on optimal time to initiate therapy in HIV-infected asymptomatic individuals. We also review reports on CD4+ T cell threshold to guide initiation of ART and finally discuss arguments for and against early or late initiation of ART.

  17. Act local, think global: how the Malawi experience of scaling up antiretroviral treatment has informed global policy.

    PubMed

    Harries, Anthony D; Ford, Nathan; Jahn, Andreas; Schouten, Erik J; Libamba, Edwin; Chimbwandira, Frank; Maher, Dermot

    2016-01-01

    The scale-up of antiretroviral therapy (ART) in Malawi was based on a public health approach adapted to its resource-poor setting, with principles and practices borrowed from the successful tuberculosis control framework. From 2004 to 2015, the number of new patients started on ART increased from about 3000 to over 820,000. Despite being a small country, Malawi has made a significant contribution to the 15 million people globally on ART and has also contributed policy and service delivery innovations that have supported international guidelines and scale up in other countries. The first set of global guidelines for scaling up ART released by the World Health Organization (WHO) in 2002 focused on providing clinical guidance. In Malawi, the ART guidelines adopted from the outset a more operational and programmatic approach with recommendations on health systems and services that were needed to deliver HIV treatment to affected populations. Seven years after the start of national scale-up, Malawi launched a new strategy offering all HIV-infected pregnant women lifelong ART regardless of the CD4-cell count, named Option B+. This strategy was subsequently incorporated into a WHO programmatic guide in 2012 and WHO ART guidelines in 2013, and has since then been adopted by the majority of countries worldwide. In conclusion, the Malawi experience of ART scale-up has become a blueprint for a public health response to HIV and has informed international efforts to end the AIDS epidemic by 2030. PMID:27600800

  18. Act local, think global: how the Malawi experience of scaling up antiretroviral treatment has informed global policy.

    PubMed

    Harries, Anthony D; Ford, Nathan; Jahn, Andreas; Schouten, Erik J; Libamba, Edwin; Chimbwandira, Frank; Maher, Dermot

    2016-01-01

    The scale-up of antiretroviral therapy (ART) in Malawi was based on a public health approach adapted to its resource-poor setting, with principles and practices borrowed from the successful tuberculosis control framework. From 2004 to 2015, the number of new patients started on ART increased from about 3000 to over 820,000. Despite being a small country, Malawi has made a significant contribution to the 15 million people globally on ART and has also contributed policy and service delivery innovations that have supported international guidelines and scale up in other countries. The first set of global guidelines for scaling up ART released by the World Health Organization (WHO) in 2002 focused on providing clinical guidance. In Malawi, the ART guidelines adopted from the outset a more operational and programmatic approach with recommendations on health systems and services that were needed to deliver HIV treatment to affected populations. Seven years after the start of national scale-up, Malawi launched a new strategy offering all HIV-infected pregnant women lifelong ART regardless of the CD4-cell count, named Option B+. This strategy was subsequently incorporated into a WHO programmatic guide in 2012 and WHO ART guidelines in 2013, and has since then been adopted by the majority of countries worldwide. In conclusion, the Malawi experience of ART scale-up has become a blueprint for a public health response to HIV and has informed international efforts to end the AIDS epidemic by 2030.

  19. CD4+ T cell counts in initiation of antiretroviral therapy in HIV infected asymptomatic individuals; controversies and inconsistencies.

    PubMed

    Maina, E K; Bonney, E Y; Bukusi, E A; Sedegah, M; Lartey, M; Ampofo, W K

    2015-12-01

    The primary goal when devising strategies to define the start of therapy in HIV infected individuals is to avoid HIV disease progression and toxicity from antiretroviral therapy (ART). Intermediate goals includes, avoiding resistance by suppressing HIV replication, reducing transmission, limiting spread and diversity of HIV within the body and protecting the immune system from harm. The question of how early or late to start ART and achieve both primary and intermediate goals has dominated HIV research. The distinction between early and late treatment of HIV infection is currently a matter of CD4+ T cells count, a marker of immune status, rather than on viral load, a marker of virus replication. Discussions about respective benefits of early or delayed therapy, as well as the best CD4+ T cell threshold during the course of HIV infection at which ART is initiated remains inconclusive. Guidelines issued by various agencies, provide different initiation recommendations. This can be confusing for clinicians and policy-makers when determining the best time to initiate therapy. Optimizing ART initiation strategies are clearly complex and must be balanced between individual and broader public health needs. This review assesses available data that contributes to the debate on optimal time to initiate therapy in HIV-infected asymptomatic individuals. We also review reports on CD4+ T cell threshold to guide initiation of ART and finally discuss arguments for and against early or late initiation of ART. PMID:26475399

  20. 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

  1. Self-reported adherence to antiretroviral therapy in HIV+ population from Bata, Equatorial Guinea.

    PubMed

    Salmanton-García, Jon; Herrador, Zaida; Ruiz-Seco, Pilar; Nzang-Esono, Jesús; Bendomo, Veronica; Bashmakovic, Emma; Nseng-Nchama, Gloria; Benito, Agustín; Aparicio, Pilar

    2016-01-01

    The human immunodeficiency virus (HIV) and the acquired immune deficiency syndrome (AIDS) represent a serious public health problem in Equatorial Guinea, with a prevalence of 6.2% among adults. the high-activity antiretroviral treatment (HAART) coverage data is 10 points below the overall estimate for Sub-Saharan Africa, and only 61% patients continue with HAART 12 months after it started. This study aims to assess HAART adherence and related factors in Litoral Province of Equatorial Guinea. In this cross-sectional study, socio-demographic and clinical data were collected at Regional Hospital of Bata, during June-July 2014. Adherence to treatment was assessed by using the Spanish version of CEAT-VIH. Bivariate and linear regression analyses were employed to assess HAART adherence-related factors. We interviewed 50 men (35.5%) and 91 women (64.5%), with a mean age of 47.7 ± 8.9 and 36.2 ± 11.2, respectively (p < .001). Overall, 55% patients had low or insufficient adherence. CEAT-VIH score varied by ethnic group (p = .005). There was a positive correlation between CEAT-VIH score and current CD4 T-cells count (p = .013). The Cronbach's α value was 0.52. To our knowledge, this is the first study to assess HAART adherence in Equatorial Guinea. Internal reliability for CEAT-VIH was low, nonetheless the positive correlation between the CEAT-VIH score and the immunological status of patients add value to our findings. Our results serve as baseline for future research and will also assist stakeholders in planning and undertaking contextual and evidence-based policy initiatives.

  2. 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

  3. Patient attrition from the HIV antiretroviral therapy program at two hospitals in Haiti

    PubMed Central

    Puttkammer, Nancy H.; Zeliadt, Steven B.; Baseman, Janet G.; Destiné, Rodney; Domerçant, Jean Wysler; Coq, Nancy Rachel Labbé; Raphael, Nernst Atwood; Sherr, Kenneth; Tegger, Mary; Yuhas, Krista; Barnhart, Scott

    2016-01-01

    Objective To identify factors associated with antiretroviral therapy (ART) attrition among patients initiating therapy in 2005–2011 at two large, public-sector department-level hospitals, and to inform interventions to improve ART retention. Methods This retrospective cohort study used data from the iSanté electronic medical record (EMR) system. The study characterized ART attrition levels and explored the patient demographic, clinical, temporal, and service utilization factors associated with ART attrition, using time-to-event analysis methods. Results Among the 2 023 patients in the study, ART attrition on average was 17.0 per 100 person-years (95% confidence interval (CI): 15.8–18.3). In adjusted analyses, risk of ART attrition was up to 89% higher for patients living in distant communes compared to patients living in the same commune as the hospital (hazard ratio: 1.89, 95%CI: 1.54–2.33; P < 0.001). Hospital site, earlier year of ART start, spending less time enrolled in HIV care prior to ART initiation, receiving a non-standard ART regimen, lacking counseling prior to ART initiation, and having a higher body mass index were also associated with attrition risk. Conclusions The findings suggest quality improvement interventions at the two hospitals, including: enhanced retention support and transportation subsidies for patients accessing care from remote areas; counseling for all patients prior to ART initiation; timely outreach to patients who miss ART pick-ups; “bridging services” for patients transferring care to alternative facilities; routine screening for anticipated interruptions in future ART pick-ups; and medical case review for patients placed on non-standard ART regimens. The findings are also relevant for policymaking on decentralization of ART services in Haiti. PMID:25563149

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

    PubMed Central

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

    2015-01-01

    Objective To estimate the prognostic value of T-cell subsets in Zambian patients initiating antiretroviral therapy (ART), and to assess the impact of a nutritional intervention on T-cell subsets. Methods This was a sub-study of a randomised clinical trial of a nutritional intervention for malnourished adults initiating ART. Participants in a randomised controlled trial (NUSTART trial) were enrolled between April and December 2012. Participants received lipid-based nutritional supplement either with or without additional vitamins and minerals. Immunophenotyping was undertaken at baseline and, in survivors, after 12 weeks of ART to characterize T-cell subsets using the markers CD3, CD4, CD8, CD45RA, CCR7, CD28, CD57, CD31, α4β7, Ki67, CD25 and HLA-DR. Univariate and multivariate survival analysis was performed, and responses to treatment were analysed using the Wicoxon rank-sum test. Results Among 181 adults, 36 (20%) died by 12 weeks after starting ART. In univariate analysis, patients who died had fewer proliferating, more naïve and fewer gut homing CD4+ T-cells compared to survivors; and more senescent and fewer proliferating CD8+ T-cells. In a multivariate Cox regression model high naïve CD4+, low proliferating CD4+, high senescent CD8+ and low proliferating CD8+ subsets were independently associated with increased risk of death. Recent CD4+ thymic emigrants increased less between recruitment and 12 weeks of ART in the intervention group compared to the control group. Conclusions Specific CD4+ T-cell subsets are of considerable prognostic significance for patients initiating ART in Zambia, but only thymic output responded to this nutritional intervention. PMID:26083409

  5. Using Music with Head Start Children.

    ERIC Educational Resources Information Center

    Griffin, Louise

    This pamphlet describes the function of music in Head Start programs. Suggestions are made to help children sense motion and develop their self-concepts and motor coordination skills through rhythmic songs and activities. The construction and use of rhythm instruments are suggested as a means of involving mothers in Head Start programs. Certain…

  6. 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…

  7. 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…

  8. Administration for Children and Families: Head Start

    ERIC Educational Resources Information Center

    US Department of Health and Human Services, 2010

    2010-01-01

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

  9. Delivering Sure Start in Rural Communities

    ERIC Educational Resources Information Center

    Willan, Jenny

    2007-01-01

    This paper explores and questions some of the evidence used to support early childhood interventions in the UK, and reports on discussions with three rural Mini Sure Start project leaders in Devon. Sure Start funding in the UK has been repeatedly increased to provide more centres for 0-3-year-olds and their parents. It is increasingly linked to…

  10. 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…

  11. The Texas Head Start Metro Models.

    ERIC Educational Resources Information Center

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

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

  12. Head Start's Broken Promise. On the Issues

    ERIC Educational Resources Information Center

    Besharov, Douglas J.

    2005-01-01

    In this short essay, Douglas J. Besharov argues that Congress should mandate an honest assessment of Head Start's strengths and weaknesses to enable the program to more effectively enhance early childhood education. He discusses evidence of Head Start's limited effectiveness and proposes that it begin operating based on research.

  13. 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…

  14. 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…

  15. Historical Perspectives on Project Head Start.

    ERIC Educational Resources Information Center

    Slaughter, Diana T.

    Historical changes in the emphasis and focus of Project Head Start from 1965 to the present are briefly reviewed in this paper. Head Start was conceived of as primary prevention designed to enable children from lower income families to obtain educational prerequisites to formal schooling. The early years of the project were also characterized by…

  16. The biomechanical structure of swim start performance.

    PubMed

    Fischer, Sebastian; Kibele, Armin

    2016-11-01

    The aim of this study was to analyse the significance of various biomechanical parameters in swim start performance for the grab and track start techniques. To do so, structural equation models were analysed, incorporating measurements for the take-off phase, flight phase and entry phase. Forty-six elite German swimmers (18 female and 28 male; age: 20.1 ± 4.2 yrs; PB (100 m Freestyle): 53.6 ± 2.9 s) participated in the study. Their swim start performance was examined within a 25-m sprint test. Structural equation modelling was conducted in separate models for the block time, flight time and water time and in a combined model for swim start time. Our main finding was that swim start time is predominantly related to water time and determined to a lesser extent by block time and flight time. We conclude that more emphasis should be given to the water immersion behaviour and the gliding phase when analysing swim start performance. Furthermore, significant differences were found between the grab start and track techniques as regards the biomechanical parameters representing the take-off phase and water phase. PMID:27239685

  17. 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.

  18. 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.

  19. Physics of Tokamak Plasma Start-up

    NASA Astrophysics Data System (ADS)

    Mueller, Dennis

    2012-10-01

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

  20. 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.

  1. 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

  2. METHADONE MAINTENANCE THERAPY PROMOTES INITIATION OF ANTIRETROVIRAL THERAPY AMONG INJECTION DRUG USERS

    PubMed Central

    Uhlmann, Sasha; Milloy, M-J; Kerr, Thomas; Zhang, Ruth; Guillemi, Silvia; Marsh, David; Hogg, Robert S.; Montaner, Julio S. G.; Wood, Evan

    2010-01-01

    Aims Despite proven benefits of antiretroviral therapy (ART), many HIV-infected injection drug users (IDU) do not access treatment even in settings with free health care. We examined whether methadone maintenance therapy (MMT) increased initiation and adherence to ART among an IDU population with free health care. Design We prospectively examined a cohort of opioid-using antiretroviral-naïve HIV-infected IDU and investigated factors associated with initiation of antiretroviral therapy as well as subsequent adherence. Factors independently associated with time to first initiation of antiretroviral therapy were modelled using Cox proportional hazards regression. Findings Between May 1996 and April 2008, 231 antiretroviral-naïve HIV-infected opioid using IDU were enrolled, among whom 152 (65.8%) initiated ART, for an incidence density of 30.5 (95% confidence interval [CI]: 25.9–35.6) per 100 person-years. After adjustment for time-updated clinical characteristics and other potential confounders, use of MMT was independently associated with more rapid uptake of antiretroviral therapy (relative hazard = 1.62 [95% CI: 1.15–2.28]; p = 0.006). Those prescribed methadone also had higher rates of ART adherence after first antiretroviral initiation (odds ratio = 1.49 [95% CI: 1.07–2.08]; p = 0.019). Conclusion These results demonstrate that MMT contributes to more rapid initiation and subsequent adherence to ART among opioid-using HIV-infected IDU. Addressing international barriers to the use and availability of methadone may dramatically increase uptake of HIV treatment among this population. PMID:20331553

  3. Protocol for a Randomized Controlled Trial Evaluating Mobile Text Messaging to Promote Retention and Adherence to Antiretroviral Therapy for People Living With HIV in Burkina Faso

    PubMed Central

    Ouedraogo, Denis; Artavia-Mora, Luis; Bedi, Arjun; Thiombiano, Boundia Alexandre

    2016-01-01

    Background Retention in care and adherence to antiretroviral therapy (ART) among people living with human immunodeficiency virus (PLHIV) is a critical challenge in many African countries including Burkina Faso. Delivering text messaging (short message service, SMS) interventions through mobile phones may help facilitate health service delivery and improve patient health. Despite this potential, no evaluations have been delivered for national scale settings to demonstrate the impact of mobile health (mHealth) for PLHIV. Objectives This study aims to test the impact of SMS text messaging reminders for PLHIV in Burkina Faso, who are under ART. The evaluation identifies whether patients who receive SMS text messages are more likely to (1) retain in care (measured as a dichotomous variable), (2) adhere to antiretroviral regimens (measured as the number of doses missed in the past 7 days), and (3) experience slower disease progression (measured with T-lymphocytes cells). The second objective is to assess its effects on the frequency of health center visits, physical and psychosocial health, nutrition and whether the type of message (text vs image) and frequency (weekly vs semiweekly) have differential impacts including the possibility of message fatigue over time. Methods This 24-month, wide-scale intervention implements a randomized controlled trial (RCT) to evaluate the impact of four variants of a mHealth intervention versus a control group. Our sample comprises adult patients (>15 years of age) undergoing antiretroviral therapy with access to mobile phone services. Multivariate regression analysis will be used to analyze the effect of the intervention on the study population. Data collection is done at baseline and three follow-up waves 6, 12, and 24 months after the intervention starts. Results The targeted 3800 patients were recruited between February 2015 and May 2015. But political uncertainty delayed the launch of the intervention until October 2015. Data

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

    ERIC Educational Resources Information Center

    National Head Start Association, Alexandria, VA.

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

  5. 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…

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

    ERIC Educational Resources Information Center

    Ryan, Joel; Allen, Ben

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

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

    ERIC Educational Resources Information Center

    North Carolina Central Univ., Durham.

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

  8. Failure to Restore the Vγ2-Jγ1.2 Repertoire in HIV-infected Men Receiving Highly Active Antiretroviral Therapy (HAART)

    PubMed Central

    Hebbeler, Andrew M.; Propp, Nadia; Cairo, Cristiana; Li, Haishan; Cummings, Jean Saville; Jacobson, Lisa P.; Margolick, Joseph B.; Pauza, C. David

    2008-01-01

    Gammadelta (γδ) T cells expressing the Vγ2-Jγ1.2Vδ2 (Vγ9-JPVδ2, alternate nomenclature) T cell receptor (TCR) constitute the major peripheral blood population of γδ T cells in adult humans and are specifically depleted during human immunodeficiency virus (HIV) disease. Vγ2-Jγ1.2Vδ2 T cells provide a convenient model for assessing the impact of antiretroviral therapy on cell populations that are not susceptible to direct infection because they do not express CD4 and depletion occurs by indirect mechanisms. We obtained longitudinal PBMC samples from 16 HIV-infected individuals who were enrolled in the Multicenter AIDS Cohort Study (MACS) and starting highly active antiretroviral therapy (HAART). Vγ2-Jγ1.2Vδ2 T cells were depleted in these individuals as a result of HIV infection. Despite evidence for clinical benefits of HAART, the Vγ2-Jγ1.2Vδ2 T cell repertoire did not recover after HAART initiation irrespective of treatment duration. These studies highlight important defects among cell subsets lost due to indirect effects of HIV. PMID:18606571

  9. Antiretroviral resistance mutations in human immunodeficiency virus type 1 infected patients enrolled in genotype testing at the Central Public Health Laboratory, São Paulo, Brazil: preliminary results.

    PubMed

    Rodrigues, Rosangela; Vazquez, Carla Maria Pasquareli; Colares, Jeova Keny; Custodio, Renata Marconi; Bonásser Filho, Francisco; Souza, Lenice do Rosário; Gianna, Maria Clara; Marques, Cristiano Corrêa de Azevedo; Brígido, Luís Fernando de Macedo

    2005-02-01

    Antiretroviral resistance mutations (ARM) are one of the major obstacles for pharmacological human immunodeficiency virus (HIV) suppression. Plasma HIV-1 RNA from 306 patients on antiretroviral therapy with virological failure was analyzed, most of them (60%) exposed to three or more regimens, and 28% of them have started therapy before 1997. The most common regimens in use at the time of genotype testing were AZT/3TC/nelfinavir, 3TC/D4T/nelfinavir and AZT/3TC/efavirenz. The majority of ARM occurred at protease (PR) gene at residue L90 (41%) and V82 (25%); at reverse transcriptase (RT) gene, mutations at residue M184 (V/I) were observed in 64%. One or more thymidine analogue mutations were detected in 73%. The number of ARM at PR gene increased from a mean of four mutations per patient who showed virological failure at the first ARV regimens to six mutations per patient exposed to six or more regimens; similar trend in RT was also observed. No differences in ARM at principal codon to the three drug classes for HIV-1 clades B or F were observed, but some polymorphisms in secondary codons showed significant differences. Strategies to improve the cost effectiveness of drug therapy and to optimize the sequencing and the rescue therapy are the major health priorities.

  10. Favorable therapeutic response with an antiretroviral salvage regimen in an HIV-1-positive subject infected with a CRF11-cpx virus.

    PubMed

    Tau, Pamela; Mancon, Alessandro; Mileto, Davide; Di Nardo Stuppino, Silvia; Bottani, Giulia; Gismondo, Maria Rita; Galli, Massimo; Micheli, Valeria; Rusconi, Stefano

    2014-05-01

    HIV drug resistance still represents a crucial problem in antiretroviral therapy. We report a case of a naive patient, harboring a CRF11-cpx virus, which showed drug resistance mutations in the reverse transcriptase. A drug resistance genotyping test was performed for the pol (protease, reverse transcriptase, and integrase) and V3 regions. The initial clinical parameter results showed a 4 log level of HIV-RNA (12,090 cp/ml) and a very low CD4(+) cell count (35 cells/μl). We designed an initial highly active antiretroviral therapy (HAART) regimen including lamivudine (3TC)+abacavir (ABC)+booster ritonavir (DRV/r). The virus was highly resistant to all nucleoside and nucleotide reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) except for ABC, tenofovir (TDF), and efavirenz (EFV) and was susceptible to all protease inhibitors (PIs) and integrase inhibitors (INIs). A salvage regimen including raltegravir (RAL)+DRV/r was started. Ten months later, the immunovirological status shows CD4(+) 142/μl and HIV-RNA <37 cp/ml. Our results demonstrate the effectiveness of a treatment combination that includes RAL+DRV/r in a patient infected with a complex X4-tropic CRF11-cpx virus.

  11. [Antiretroviral therapy in human immunodeficiency virus infection: an update].

    PubMed

    Chaix, F; Goujard, C

    2009-06-01

    Since the onset of the human immunodeficiency virus (HIV) epidemic, the care of infected patients improved dramatically. Whereas the disease was almost always fatal, the development of new drugs and new therapeutic strategies now allow a prolonged survival. However, the complexity of patient care is increasing and physicians face new clinical events and treatment toxicities. Recent molecules and follow-up according to the recent French recommendations will be presented here. The objectives of the treatment is to decrease mortality and morbidity of the HIV infection, by restoring near normal CD4+ T cell counts and qualitative T CD4+ responses, associated with a sustained reduction in viral replication. This objective must be reached by minimizing toxicity of antiretroviral drugs. Newly developed drugs that are better-tolerated and new therapeutic classes should improve outcome at all stages of HIV infection. Whereas viral eradication remains unrealistic and protective vaccines will not be soon available, direct consequences of long term HIV infection and issues related to an ageing HIV infected population raise up new research topics. Prevention of new infections, improvement in the precocity of care by a better-targeted screening and assessment of therapy before an established immune deficiency appear as the main priorities for the coming years. PMID:19237230

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

    PubMed Central

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

    2009-01-01

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

  13. Oropharyngeal Candidiasis in the Era of Antiretroviral Therapy

    PubMed Central

    Thompson, George R.; Patel, Payal K.; Kirkpatrick, William R.; Westbrook, Steven D.; Berg, Deborah; Erlandsen, Josh; Redding, Spencer W.; Patterson, Thomas F.

    2009-01-01

    Oropharyngeal candidiasis (OPC) remains a common problem in the HIV-infected population despite the availability of antiretroviral therapy (ART). Although Candida albicans is the most frequently implicated pathogen, other Candida spp. may also cause infection. The emergence of antifungal resistance within these causative yeasts, especially in patients with recurrent oropharyngeal infection or with long-term use of antifungal therapies, requires a working knowledge of alternative antifungal agents. Identification of the infecting organism and antifungal susceptibility testing enhances the ability of clinicians to prescribe appropriate antifungal therapy. Characterization of the responsible mechanisms has improved our understanding of the development of antifungal resistance and could enhance the management of these infections. Immune reconstitution has been shown to reduce rates of oropharyngeal candidiasis but few studies have evaluated the current impact of ART on the epidemiology of oropharyngeal candidiasis and antifungal resistance in these patients. Preliminary results from an ongoing clinical study showed that in patients with advanced AIDS oral yeast colonization was extensive, occurring in 81.1% of the 122 patients studied and symptomatic infection occurred in a third. In addition, resistant yeasts were still common occurring in 25.3% of patients colonized with yeasts or with symptomatic infection. Thus, oropharyngeal candidasis remains a significant infection in advanced AIDS even with ART. Current knowledge of the epidemiology, pathogenesis, clinical presentation, treatment, and mechanisms of antifungal resistance observed in oropharyngeal candidiasis are important in managing patients with this infection and are the focus of this review. PMID:20156694

  14. Development of HIV reservoir targeted long acting nanoformulated antiretroviral therapies.

    PubMed

    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.

  15. 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

  16. 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

  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.

  18. Genital HSV Shedding among Kenyan Women Initiating Antiretroviral Therapy

    PubMed Central

    Manguro, Griffins O.; Masese, Linnet N.; Deya, Ruth W.; Magaret, Amalia; Wald, Anna; McClelland, R. Scott; Graham, Susan M.

    2016-01-01

    Objectives Genital ulcer disease (GUD) prevalence increases in the first month of antiretroviral treatment (ART), followed by a return to baseline prevalence by month 3. Since most GUD is caused by herpes simplex virus type 2 (HSV-2), we hypothesized that genital HSV detection would follow a similar pattern after treatment initiation. Methods We conducted a prospective cohort study of 122 HSV-2 and HIV-1 co-infected women with advanced HIV disease who initiated ART and were followed closely with collection of genital swab specimens for the first three months of treatment. Results At baseline, the HSV detection rate was 32%, without significant increase in genital HSV detection noted during the first month or the third month of ART. HIV-1 shedding declined during this period; no association was also noted between HSV and HIV-1 shedding during this period. Conclusion Because other studies have reported increased HSV detection in women initiating ART and we have previously reported an increase in GUD during early ART, it may be prudent to counsel HIV-1 infected women initiating ART that HSV shedding in the genital tract may continue after ART initiation. PMID:27683204

  19. 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

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

    PubMed

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

    2014-01-01

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

  1. Common mental health problems and antiretroviral therapy adherence.

    PubMed

    Nel, Adriaan; Kagee, Ashraf

    2011-11-01

    This paper reviews the literature on various mental health problems and their impact on adherence to antiretroviral therapy (ART). Depression, anxiety disorders, and disorders related to substance abuse were identified as key role-players influencing adherence. The severity of symptoms related to these disorders was found to be inversely related to ART adherence, with the possible exception of post-traumatic stress disorder (PTSD). PTSD was found to have both positive and negative implications for adherence, with severity of symptoms ranging from health-protective concern to disabling distress. Possible solutions aimed at addressing the adverse effects of mental health problems on adherence are discussed. Routine screening in ART settings is suggested in settings where follow-up of positive screen scores are possible, along with the necessary interventions to resolve the disorder of concern. Suggested interventions include utilising psychotherapeutic treatment, both in isolation and in conjunction with medication, to address mental health problems. Furthermore, finding effective ways of marshalling social support is recommended for ensuring optimal adherence, and possibly mitigating the adverse effects of mental health problems. Further research is needed to find feasible ways of identifying, assessing and treating patients with mental health problems in resource-constrained settings where HIV prevalence is highest.

  2. Real-time adherence monitoring for HIV antiretroviral therapy.

    PubMed

    Haberer, Jessica E; Kahane, Josh; Kigozi, Isaac; Emenyonu, Nneka; Hunt, Peter; Martin, Jeffrey; Bangsberg, David R

    2010-12-01

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

  3. Antiretroviral Therapy and Central Nervous System HIV-1 Infection

    PubMed Central

    Price, Richard W.; Spudich, Serena

    2008-01-01

    Central nervous system (CNS) HIV-1 infection begins during primary viremia and continues throughout the course of untreated systemic infection. While frequently accompanied by local inflammatory reactions detectable in cerebrospinal fluid (CSF), CNS HIV-1 infection is not usually clinically apparent. In a minority of patients, CNS HIV-1 infection evolves late in the course of systemic infection into encephalitis, which compromises brain function and presents clinically as AIDS dementia complex (ADC). Combination highly active antiretroviral therapy (HAART) has had a major impact on all aspects of HIV-1 CNS infection and disease. In those with asymptomatic infection, HAART usually effectively suppresses CSF HIV-1 and markedly reduces the incidence of symptomatic ADC. In those presenting with ADC, HAART characteristically prevents neurological progression and leads to variable, and at times substantial, recovery. Treatment has similarly reduced CNS opportunistic infections. With better control of these severe disorders, attention has turned to the possible consequences of chronic silent infection, and the issue of whether indolent, low-grade brain injury might require earlier treatment intervention. PMID:18447615

  4. Drug Abuse Prevention Starts with Parents

    MedlinePlus

    ... Stages Listen Español Text Size Email Print Share Drug Abuse Prevention Starts with Parents Page Content Article ... Learn the facts about the harmful effects of drugs. Talk with your child about the negative effects ...

  5. The physics of tokamak start-up

    SciTech Connect

    Mueller, D.

    2013-05-15

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

  6. Doctors' Group Backs Later School Start Times

    MedlinePlus

    ... School Start Times New policy aims to tackle sleep deprivation among teens To use the sharing features on ... June 16, 2016 (HealthDay News) -- To help ease sleep deprivation among teens, the American Medical Association recommends that ...

  7. The physics of tokamak start-upa)

    NASA Astrophysics Data System (ADS)

    Mueller, D.

    2013-05-01

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

  8. Start small and build toward business intelligence.

    PubMed

    Kirby, Sean; Robertson, Brian

    2009-01-01

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

  9. 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.

  10. Progress Against Heart Deaths Starting to Wane

    MedlinePlus

    ... Against Heart Deaths Starting to Wane, Report Warns Obesity, diabetes epidemics may be to blame, doctors say To ... It is likely that the dual epidemics of obesity and diabetes, which began around 1985, are the major contributors ...

  11. Factors associated with antiretroviral treatment uptake and adherence: a review. Perspectives from Australia, Canada, and the United Kingdom.

    PubMed

    Bolsewicz, K; Debattista, J; Vallely, A; Whittaker, A; Fitzgerald, L

    2015-01-01

    International focus on reducing onward HIV transmission emphasizes the need for routine HIV testing and early uptake of antiretroviral treatment (ART). Strategic targets have been set for 2020 to achieve the goal of 90% of people infected with HIV diagnosed, 90% of identified cases on treatment, and 90% of persons on treatment virally suppressed (90-90-90). It is vital to understand the complexity of factors influencing a person's treatment decisions over time and the context which may enable better adherence. In this paper we present findings from the review of published and gray literature (2003-2013) on the documented factors associated with treatment initiation and adherence in the general adult population of Australia, Canada, and the UK. A framework developed by Begley, McLaws, Ross, and Gold [2008. Cognitive and behavioural correlates of non-adherence to HIV anti-retroviral therapy: Theoretical and practical insight for clinical psychology and health psychology. Clinical Psychologist, 12(1), 9-17] in Australia was adapted to summarize the findings. A systematic database search using keywords and a set of inclusion criteria yielded 17 studies (Australia = 6; Canada = 8; UK = 3). In addition 11 reports were included in the review. We found that a person's abilities and motivations (intrapersonal factors, reported in 7 studies) to start and continue ART are influenced by a host of interconnected factors spanning relationship (interpersonal, 3 studies) and broader structural (extrapersonal, 15 studies) factors that are situated within social determinants of health. People therefore evaluate various costs and benefits of starting and staying on treatment, in which biomedical concerns play an important yet often subsidiary role. In this review the economic barriers to care were found to be significant and under-reported, highlighting the persistent health inequities in terms of access to services. Our understanding of the context around people's use of

  12. Factors associated with antiretroviral treatment uptake and adherence: a review. Perspectives from Australia, Canada, and the United Kingdom.

    PubMed

    Bolsewicz, K; Debattista, J; Vallely, A; Whittaker, A; Fitzgerald, L

    2015-01-01

    International focus on reducing onward HIV transmission emphasizes the need for routine HIV testing and early uptake of antiretroviral treatment (ART). Strategic targets have been set for 2020 to achieve the goal of 90% of people infected with HIV diagnosed, 90% of identified cases on treatment, and 90% of persons on treatment virally suppressed (90-90-90). It is vital to understand the complexity of factors influencing a person's treatment decisions over time and the context which may enable better adherence. In this paper we present findings from the review of published and gray literature (2003-2013) on the documented factors associated with treatment initiation and adherence in the general adult population of Australia, Canada, and the UK. A framework developed by Begley, McLaws, Ross, and Gold [2008. Cognitive and behavioural correlates of non-adherence to HIV anti-retroviral therapy: Theoretical and practical insight for clinical psychology and health psychology. Clinical Psychologist, 12(1), 9-17] in Australia was adapted to summarize the findings. A systematic database search using keywords and a set of inclusion criteria yielded 17 studies (Australia = 6; Canada = 8; UK = 3). In addition 11 reports were included in the review. We found that a person's abilities and motivations (intrapersonal factors, reported in 7 studies) to start and continue ART are influenced by a host of interconnected factors spanning relationship (interpersonal, 3 studies) and broader structural (extrapersonal, 15 studies) factors that are situated within social determinants of health. People therefore evaluate various costs and benefits of starting and staying on treatment, in which biomedical concerns play an important yet often subsidiary role. In this review the economic barriers to care were found to be significant and under-reported, highlighting the persistent health inequities in terms of access to services. Our understanding of the context around people's use of

  13. 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

  14. A New Start from Ground Zero?

    NASA Astrophysics Data System (ADS)

    Luisi, Pier Luigi

    2014-12-01

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

  15. Preference for starting and finishing behavior patterns.

    PubMed Central

    Shimp, C P; Sabulsky, S L; Childers, L J

    1989-01-01

    Pigeon's key pecking was reinforced with food in two experiments in which the correspondence between preference for starting one of two reinforced behavior patterns and the likelihood of finishing it subsequently was examined. Reinforcers were scheduled according to concurrent schedules for two classes of interresponse times, modified such that reinforcers followed a center-key peck terminating either a shorter interresponse time started by a left-key peck or a longer interresponse time started by a right-key peck. In Experiment 1, the times when reinforcers potentially were available were not discriminated, whereas in Experiment 2 they were. Absolute reinforced pattern durations were varied. The relative frequency of starting a particular pattern was highly correlated with relative frequency of that completed pattern in both experiments. Other relations between starting and finishing a pattern depended on whether reinforced interresponse times were discriminated. For instance, preference for starting a pattern sometimes correlated negatively with the likelihood of subsequently completing it. The present experiments are described as capturing part of the ordinary language meaning of "intention," according to which an organism's behavior at one moment sets the occasion for an observer to say that the organism "intends" in the future to engage in one behavior rather than another. PMID:2584918

  16. The impact of HBV or HCV infection in a cohort of HIV-infected pregnant women receiving a nevirapine-based antiretroviral regimen in Malawi

    PubMed Central

    2014-01-01

    Background Coinfection with the hepatitis viruses is common in the HIV population in sub-Saharan Africa. The aim of this study was to assess, in a cohort of HIV-infected pregnant women receiving antiretroviral drugs (ARVs), the prevalence of HBV and HCV infections and to determine the impact of these infections on the occurrence of liver toxicity and on the viro-immunological response. Methods Women were screened for HBsAg and HCV-RNA before starting, at week 25 of gestational age, an antiretroviral regimen consisting of lamivudine and nevirapine plus either stavudine or zidovudine. Women with CD4+ < 350/mm3 continued ARVs indefinitely, while the other women interrupted treatment 6 months postpartum (end of breastfeeding period). Both groups were followed for 2 years after delivery. Liver function was monitored by alanine aminotransferase (ALT) measurement. The Cox proportional hazards model was used to identify factors associated with the emergence of liver toxicity. Results A total of 28 women out of the 309 enrolled in the study (9.1%) were coinfected with HBV (n. 27), or HCV (n. 1). During follow-up 125 women (40.4%) developed a grade ≥ 1 ALT elevation, 28 (9.1%) a grade ≥ 2 and 6 (1.9%) an elevation defining grade 3 toxicity. In a multivariate model including age, baseline CD4+ count and hemoglobin level, the presence of either HBV or HCV infection was significantly associated with the development of an ALT increase of any grade (P = 0.035). Moderate or severe liver laboratory toxicity (grade ≥ 2) was more frequent among women with baseline CD4+ > 250/mm3 (P = 0.030). In HBV-infected women a baseline HBV-DNA level above 10,000 IU/ml was significantly associated to the development of liver toxicity of grade ≥ 1 (P = 0.040). Coinfections had no impact on the immunological and virological response to antiretroviral drugs up to 2 years after delivery. Conclusions In this cohort of nevirapine-treated women the presence of

  17. Elevated CD8 T-cell counts and virological failure in HIV-infected patients after combination antiretroviral therapy.

    PubMed

    Ku, Nam Su; Jiamsakul, Awachana; Ng, Oon Tek; Yunihastuti, Evy; Cuong, Do Duy; Lee, Man Po; Sim, Benedict Lim Heng; Phanuphak, Praphan; Wong, Wing-Wai; Kamarulzaman, Adeeba; Zhang, Fujie; Pujari, Sanjay; Chaiwarith, Romanee; Oka, Shinichi; Mustafa, Mahiran; Kumarasamy, Nagalingeswaran; Van Nguyen, Kinh; Ditangco, Rossana; Kiertiburanakul, Sasisopin; Merati, Tuti Parwati; Durier, Nicolas; Choi, Jun Yong

    2016-08-01

    Elevated CD8 counts with combination antiretroviral therapy (cART) initiation may be an early warning indicator for future treatment failure. Thus, we investigated whether elevated CD8 counts were associated with virological failure (VF) in the first 4 years of cART in Asian HIV-infected patients in a multicenter regional cohort.We included patients from the TREAT Asia HIV Observational Database (TAHOD). Patients were included in the analysis if they started cART between 1996 and 2013 with at least one CD8 measurement within 6 months prior to cART initiation and at least one CD8 and viral load (VL) measurement beyond 6 months after starting cART. We defined VF as VL ≥400 copies/mL after 6 months on cART. Elevated CD8 was defined as CD8 ≥1200 cells/μL. Time to VF was modeled using Cox regression analysis, stratified by site.In total, 2475 patients from 19 sites were included in this analysis, of whom 665 (27%) experienced VF in the first 4 years of cART. The overall rate of VF was 12.95 per 100 person-years. In the multivariate model, the most recent elevated CD8 was significantly associated with a greater hazard of VF (HR = 1.35, 95% CI 1.14-1.61; P = 0.001). However, the sensitivity analysis showed that time-lagged CD8 measured at least 6 months prior to our virological endpoint was not statistically significant (P = 0.420).This study indicates that the relationship between the most recent CD8 count and VF was possibly due to the CD8 cells reacting to the increase in VL rather than causing the VL increase itself. However, CD8 levels may be a useful indicator for VF in HIV-infected patients after starting cART.

  18. 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

  19. Antiretroviral Resistance among HIV Type 1-Infected Women First Exposed to Antiretrovirals during Pregnancy: Plasma versus PBMCs

    PubMed Central

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

    2008-01-01

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

  20. Adherence to antiretrovirals in people coinfected with the human immunodeficiency virus and tuberculosis1

    PubMed Central

    Lemos, Larissa de Araújo; Fiuza, Maria Luciana Teles; Reis, Renata Karina; Ferrer, André Carvalho; Gir, Elucir; Galvão, Marli Teresinha Gimeniz

    2016-01-01

    Objective: assess the adherence levels to antiretroviral therapy in people coinfected with HIV/tuberculosis and correlate these levels with the sociodemographic and clinical variables of the study population. Method: cross-sectional study involving 74 male and female adults coinfected with HIV/tuberculosis. For the data collection, a sociodemographic and clinical assessment form and the Antiretroviral Treatment Adherence Assessment Questionnaire were used. For the data analysis, the software STATA version 11 was used, through descriptive statistics, Fisher's chi-square exact test and the probability test. Results: men were predominant (79.7%), between 30 and 39 years of age (35.1%), low income (75.7%) and pulmonary tuberculosis (71.6%). Adherence to antiretroviral therapy was inappropriate in 78.1% of the men; 61.0% of single people; 47.0% unemployed and 76.5% among people gaining less than one minimum wage. A significant difference was observed between compliance and length of use of antiretrovirals (p=0.018), sexual orientation (p=0.024) and number of children (p=0.029). Conclusion: the coinfected patients presented inappropriate adherence to the antiretrovirals, a fact that negatively affects the health conditions of the people living with HIV/tuberculosis coinfection. A statistically significant correlation was found between the levels of adherence and some sociodemographic and clinical characteristics. PMID:27192416

  1. Fate of the antiretroviral drug tenofovir in agricultural soil.

    PubMed

    Al-Rajab, Abdul Jabbar; Sabourin, Lyne; Chapman, Ralph; Lapen, David R; Topp, Edward

    2010-10-15

    Tenofovir (9-(R)-(2-phosphonylmethoxypropyl)-adenine) is an antiretroviral drug widely used for the treatment of human immunodeficiency virus (HIV-1) and Hepatitis B virus (HBV) infections. Tenofovir is extensively and rapidly excreted unchanged in the urine. In the expectation that tenofovir could potentially reach agricultural lands through the application of municipal biosolids or wastewater, and in the absence of any environmental fate data, we evaluated its persistence in selected agricultural soils. Less than 10% of [adenine-8-(14)C]-tenofovir added to soils varying widely in texture (sand, loam, clay loam) was mineralized in a 2-month incubation under laboratory conditions. Tenofovir was less readily extractable from clay soils than from a loam or a sandy loam soil. Radioactive residues of tenofovir were removed from the soil extractable fraction with DT(50)s ranging from 24±2 to 67+22days (first order kinetic model) or 44+9 to 127+55days (zero order model). No extractable transformation products were detectable by HPLC. Tenofovir mineralization in the loam soil increased with temperature (range 4°C to 30°C), and did not occur in autoclaved soil, suggesting a microbial basis. Mineralization rates increased with soil moisture content, ranging from air-dried to saturated. In summary, tenofovir was relatively persistent in soils, there were no extractable transformation products detected, and the response of [adenine-8-(14)C]-tenofovir mineralization to soil temperature and heat sterilization indicated that the molecule was biodegraded by aerobic microorganisms. Sorption isotherms with dewatered biosolids suggested that tenofovir residues could potentially partition into the particulate fraction during sewage treatment. PMID:20800877

  2. Cellular Responses and Tissue Depots for Nanoformulated Antiretroviral Therapy

    PubMed Central

    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

  3. Alcohol use disorders and antiretroviral therapy among prisoners in Argentina

    PubMed Central

    Alpert, Michael; Wickersham, Jeffrey A.; Vázquez, Mariana; Altice, Frederick L.

    2013-01-01

    Purpose While Argentina has significantly improved access to HIV care and antiretroviral therapy (ART) for both the general population and prisoners, the prevalence of alcohol use disorders (AUDs) among HIV-infected prisoners and their relationship to accessing ART in Argentina is currently unknown. This study aims to characterize the substance abuse patterns of HIV-infected prisoners in Argentina and to assess the independent correlates of receipt of pre-incarceration ART. Design/methodology/approach An anonymous, cross-sectional survey of 100 HIV-infected federal prisoners was conducted in the Buenos Aires municipality from July–December 2010. AUDs were assessed using the AUDIT scale. Findings A majority (63 per cent) of participants met criteria for AUDs, 45 per cent of subjects were diagnosed with HIV in prison and one-quarter had initiated ART during the current incarceration. In addition, over one-third (35 per cent) of participants did not receive ART during the pre-incarceration period despite receiving it upon incarceration. This correlated significantly with the presence of having an AUD (AOR 0.20, 95 per cent CI 0.06–0.74, p = 0.016). Practical implications AUDs are prevalent among HIV-infected prisoners in Argentina and are significantly related to negative secondary HIV prevention and treatment outcomes. While Argentina has provided an exemplary model of HIV-related health care reform within its prisons, future efforts to provide screening and treatment for AUDs are needed to improve the health of the nation’s incarcerated population. Originality/value This paper is the first to describe pre-incarceration drug and alcohol use disorders and issues related to access to ART among prisoners in Argentina. PMID:24772187

  4. The HIV Antiretroviral Drug Efavirenz has LSD-Like Properties

    PubMed Central

    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

    2013-01-01

    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-HT2A receptors. In rodents, interaction with the 5-HT2A receptor, a primary site of action of lysergic acid diethylamine (LSD), appears to dominate efavirenz's behavioral profile. Both LSD and efavirenz reduce ambulation in a novel open-field environment. Efavirenz occasions drug-lever responding in rats discriminating LSD from saline, and this effect is abolished by selective blockade of the 5-HT2A receptor. Similar to LSD, efavirenz induces head-twitch responses in wild-type, but not in 5-HT2A-knockout, mice. Despite having GABAA-potentiating effects (like benzodiazepines and barbiturates), and interactions with dopamine transporter, serotonin transporter, and vesicular monoamine transporter 2 (like cocaine and methamphetamine), efavirenz fails to maintain responding in rats that self-administer cocaine, and it fails to produce a conditioned place preference. Although its molecular pharmacology is multifarious, efavirenz's prevailing behavioral effect in rodents is consistent with LSD-like activity mediated via the 5-HT2A receptor. This finding correlates, in part, with the subjective experiences in humans who abuse efavirenz and with specific dose-dependent adverse neuropsychiatric events, such as hallucinations and night terrors, reported by HIV patients taking it as a medication. PMID:23702798

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

    PubMed Central

    Tiliscan, Cătălin; Aramă, Victoria; Mihăilescu, Raluca; Munteanu, Daniela Ioana; Streinu-Cercel, Adrian; Ion, Daniela Adriana; Rădulescu, Mihaela Andreea; Popescu, Cristina; Lobodan, Alina Elena; Negru, Anca Ruxandra; Aramă, Ştefan 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

  6. 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.

  7. Adverse drug reactions associated with antiretroviral therapy in South Africa.

    PubMed

    Birbal, Sumeshni; Dheda, Mukesh; Ojewole, Elizabeth; Oosthuizen, Frasia

    2016-09-01

    South Africa has one of the highest prevalences of HIV and AIDS in the world. HIV/AIDS patients face countless challenges, one of which is the risk of adverse drug reactions (ADRs). This study aimed to describe the ADRs reported in South Africa with reference to the type of ADRs, antiretrovirals (ARVs) implicated, seriousness of the ADRs and patient demographics associated with specific ADRs. A retrospective quantitative study was carried out using ADR reports submitted to the National Department of Health (NDoH) from 1 January 2010 to 31 December 2014. A descriptive and inferential analysis was carried out to determine the strength of the relationships between different variables. A total of 2 489 reports were analysed. This study found evidence of ADRs among patients on regimens based on stavudine (n = 1 256, 50.46%), efavirenz (n = 572, 22.98%), zidovudine (n = 209, 8.40%), tenofovir (n = 203, 8.16%) and nevirapine (n = 153, 6.15%). The 10 most common ADRs reported with the use of ARVs were peripheral neuropathy (n = 472, 19%), lipodystrophy (n = 471, 18.9%), serious skin reactions (n = 266, 10.7%), gynaecomastia (n = 219, 8.8%), renal failure (n = 140, 5.6%), dizziness (n = 133, 5.3%), hyperlactatemia (n = 118, 4.7%), psychosis/hallucinations (n = 47, 1.9%), sleep disturbances (n = 44, 1.8%) and vomiting (n = 44, 1.8%). Female patients were more likely to experience peripheral neuropathy, lipodystrophy, skin rash, anaemia and hyperlactatemia, while male patients were more prone to experience gynaecomastia and peripheral neuropathy. In addition, patients aged 30-44 years reported the most ADRs. Most reactions resulted from the use of stavudine, efavirenz, zidovudine, nevirapine and tenofovir in the population groups identified in this study. PMID:27681148

  8. 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

  9. Relatively High Prevalence of Drug Resistance Among Antiretroviral-Naive Patients from Henan, Central China

    PubMed Central

    Li, Lingnuo; Sun, Binlian; Zeng, Haiyan; Sun, Zhiwu; Sun, Guoqing

    2014-01-01

    Abstract To elucidate the prevalence of HIV-1 subtypes and transmitted drug resistance in Henan, central China, HIV-1-positive blood samples from 187 antiretroviral-naive patients were collected in our study from August 2009 to November 2010. Subtype B′ (92.0%, 172 of 187) remains the predominant HIV-1 subtype in Henan province and was prevalent in all risk populations and geographic regions. Of 98 pol sequences 67 (68.4%) harbored drug resistance mutations, and only 14 (14.3%, 14 of 98) sequences have mutations associated with significantly reduced phenotypic susceptibility to antiretroviral drugs. The unexpectedly high percentage of drug resistance in Henan province is mainly due to the prevalence of minor mutations in the protease and integrase regions, especially A71T/V and L68V/I/IM/LV. In all, we detected a relatively high prevalence of drug resistance with unique mutation distributions among antiretroviral-naive patients from Henan province. PMID:23800338

  10. Antiretroviral Therapy for HIV-2 Infection: Recommendations for Management in Low-Resource Settings

    PubMed Central

    Peterson, Kevin; Jallow, Sabelle; Rowland-Jones, Sarah L.; de Silva, Thushan I.

    2011-01-01

    HIV-2 contributes approximately a third to the prevalence of HIV in West Africa and is present in significant amounts in several low-income countries outside of West Africa with historical ties to Portugal. It complicates HIV diagnosis, requiring more expensive and technically demanding testing algorithms. Natural polymorphisms and patterns in the development of resistance to antiretrovirals are reviewed, along with their implications for antiretroviral therapy. Nonnucleoside reverse transcriptase inhibitors, crucial in standard first-line regimens for HIV-1 in many low-income settings, have no effect on HIV-2. Nucleoside analogues alone are not sufficiently potent enough to achieve durable virologic control. Some protease inhibitors, in particular those without ritonavir boosting, are not sufficiently effective against HIV-2. Following review of the available evidence and taking the structure and challenges of antiretroviral care in West Africa into consideration, the authors make recommendations and highlight the needs of special populations. PMID:21490779

  11. Regression of both oral mucocele and parotid swellings, following antiretroviral therapy.

    PubMed

    Syebele, Kabunda

    2010-01-01

    HIV-salivary gland associated disease is a well accepted concept in the HIV-related literature. Parotid swellings, especially in its cystic benign lymphoepithelial form, have been largely reported. Oral mucoceles (ranulas) were also associated with HIV in some publications. The exact nature of this link between mucoceles and HIV is still to be clarified. The mainstream treatment of most of parotid pathologies and oral mucoceles remains surgical approach. Strong evidences do, however, exist about lymphopithelial lesions of parotid glands that have been successfully treated with antiretroviral drugs. We present a case of intraoral mucocele, coexisting with bilateral parotid gland lymphoepithelial lesions, on a 2-year-old HIV-positive patient. Both parotid gland swellings and the sublingual mucocele have completely regressed following antiretroviral therapy. No surgical intervention was required. Conversely to benign lymphoepithelial lesions of parotid glands, the regression of oral mucocele on HIV-positive patient, following antiretroviral drugs therapy appears to be a rare phenomenon.

  12. 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.

  13. 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-κB 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.

  14. Self-Efficacy and Depression as Mediators of the Relationship between Pain and Antiretroviral Adherence

    PubMed Central

    Berg, Karina M.; Cooperman, Nina A.; Newville, Howard; Arnsten, Julia H.

    2009-01-01

    The goals of this study were to examine the association between pain and antiretroviral adherence, and to estimate the mediating effect of adherence self-efficacy and depression symptom severity. Surveys using audio computer-assisted self-interview were conducted among 70 HIV-infected current and former drug users enrolled in a methadone program. We assessed antiretroviral adherence and adherence self-efficacy using questions from the Adult Clinical Trials Group survey. We considered participants adherent if they reported taking at least 95% of prescribed antiretrovirals over the past seven days. We assessed depression symptom severity using the depression subscale of the Brief Symptom Inventory. Participants reported pain of any duration in response to a question from the Brief Pain Inventory. Participants reporting pain were 87% less likely to be classified as adherent compared to those without pain [ORunadj = 0.13 (95%CI 0.03–0.52)]. When we examined adherence self-efficacy as a mediator of the relationship between pain and adherence, criteria for partial mediation were met. Adjusting for self-efficacy, the beta coefficient for pain decreased by 23% but the independent relationship between pain and antiretroviral adherence was maintained. Mediation criteria were not met when we examined the mediating effect of depression symptom severity on the relationship between pain and adherence. Adjusting for depression symptom severity, the beta coefficient for pain decreased by 9% and the relationship between pain and antiretroviral adherence remained significant. Our results indicate that neither adherence self-efficacy nor depression symptom severity fully mediated the relationship between pain and adherence. HIV providers should recognize the potential impact of pain on antiretroviral adherence among current and former drug users. PMID:19229695

  15. Ability to Work and Employment Rates in Human Immunodeficiency Virus (HIV)-1-Infected Individuals Receiving Combination Antiretroviral Therapy: The Swiss HIV Cohort Study.

    PubMed

    Elzi, Luigia; Conen, Anna; Patzen, Annalea; Fehr, Jan; Cavassini, Matthias; Calmy, Alexandra; Schmid, Patrick; Bernasconi, Enos; Furrer, Hansjakob; Battegay, Manuel

    2016-01-01

    Background.  Limited data exist on human immunodeficiency virus (HIV)-infected individuals' ability to work after receiving combination antiretroviral therapy (cART). We aimed to investigate predictors of regaining full ability to work at 1 year after starting cART. Methods.  Antiretroviral-naive HIV-infected individuals <60 years who started cART from January 1998 through December 2012 within the framework of the Swiss HIV Cohort Study were analyzed. Inability to work was defined as a medical judgment of the patient's ability to work as 0%. Results.  Of 5800 subjects, 4382 (75.6%) were fully able to work, 471 (8.1%) able to work part time, and 947 (16.3%) were unable to work at baseline. Of the 947 patients unable to work, 439 (46.3%) were able to work either full time or part time at 1 year of treatment. Predictors of recovering full ability to work were non-white ethnicity (odds ratio [OR], 2.06; 95% confidence interval [CI], 1.20-3.54), higher education (OR, 4.03; 95% CI, 2.47-7.48), and achieving HIV-ribonucleic acid <50 copies/mL (OR, 1.83; 95% CI, 1.20-2.80). Older age (OR, 0.55; 95% CI, .42-.72, per 10 years older) and psychiatric disorders (OR, 0.24; 95% CI, .13-.47) were associated with lower odds of ability to work. Recovering full ability to work at 1 year increased from 24.0% in 1998-2001 to 41.2% in 2009-2012, but the employment rates did not increase. Conclusions.  Regaining full ability to work depends primarily on achieving viral suppression, absence of psychiatric comorbidity, and favorable psychosocial factors. The discrepancy between patients' ability to work and employment rates indicates barriers to reintegration of persons infected with HIV. PMID:26955645

  16. Elevated Plasma Viral Loads in Romidepsin-Treated Simian Immunodeficiency Virus-Infected Rhesus Macaques on Suppressive Combination Antiretroviral Therapy.

    PubMed

    Del Prete, Gregory Q; Oswald, Kelli; Lara, Abigail; Shoemaker, Rebecca; Smedley, Jeremy; Macallister, Rhonda; Coalter, Vicky; Wiles, Adam; Wiles, Rodney; Li, Yuan; Fast, Randy; Kiser, Rebecca; Lu, Bing; Zheng, Jim; Alvord, W Gregory; Trubey, Charles M; Piatak, Michael; Deleage, Claire; Keele, Brandon F; Estes, Jacob D; Hesselgesser, Joseph; Geleziunas, Romas; Lifson, Jeffrey D

    2016-03-01

    Replication-competent human immunodeficiency virus (HIV) persists in infected people despite suppressive combination antiretroviral therapy (cART), and it represents a major obstacle to HIV functional cure or eradication. We have developed a model of cART-mediated viral suppression in simian human immunodeficiency virus (SIV) mac239-infected Indian rhesus macaques and evaluated the impact of the histone deacetylase inhibitor (HDACi) romidepsin (RMD) on viremia in vivo. Eight macaques virologically suppressed to clinically relevant levels (<30 viral RNA copies/ml of plasma), using a three-class five-drug cART regimen, received multiple intravenous infusions of either RMD (n = 5) or saline (n = 3) starting 31 to 54 weeks after cART initiation. In vivo RMD treatment resulted in significant transient increases in acetylated histone levels in CD4(+) T cells. RMD-treated animals demonstrated plasma viral load measurements for each 2-week treatment cycle that were significantly higher than those in saline control-treated animals during periods of treatment, suggestive of RMD-induced viral reactivation. However, plasma virus rebound was indistinguishable between RMD-treated and control-treated animals for a subset of animals released from cART. These findings suggest that HDACi drugs, such as RMD, can reactivate residual virus in the presence of suppressive antiviral therapy and may be a valuable component of a comprehensive HIV functional cure/eradication strategy. PMID:26711758

  17. Elevated Plasma Viral Loads in Romidepsin-Treated Simian Immunodeficiency Virus-Infected Rhesus Macaques on Suppressive Combination Antiretroviral Therapy

    PubMed Central

    Del Prete, Gregory Q.; Oswald, Kelli; Lara, Abigail; Shoemaker, Rebecca; Smedley, Jeremy; Macallister, Rhonda; Coalter, Vicky; Wiles, Adam; Wiles, Rodney; Li, Yuan; Fast, Randy; Kiser, Rebecca; Lu, Bing; Zheng, Jim; Alvord, W. Gregory; Trubey, Charles M.; Piatak, Michael; Deleage, Claire; Keele, Brandon F.; Estes, Jacob D.; Hesselgesser, Joseph; Geleziunas, Romas

    2015-01-01

    Replication-competent human immunodeficiency virus (HIV) persists in infected people despite suppressive combination antiretroviral therapy (cART), and it represents a major obstacle to HIV functional cure or eradication. We have developed a model of cART-mediated viral suppression in simian human immunodeficiency virus (SIV) mac239-infected Indian rhesus macaques and evaluated the impact of the histone deacetylase inhibitor (HDACi) romidepsin (RMD) on viremia in vivo. Eight macaques virologically suppressed to clinically relevant levels (<30 viral RNA copies/ml of plasma), using a three-class five-drug cART regimen, received multiple intravenous infusions of either RMD (n = 5) or saline (n = 3) starting 31 to 54 weeks after cART initiation. In vivo RMD treatment resulted in significant transient increases in acetylated histone levels in CD4+ T cells. RMD-treated animals demonstrated plasma viral load measurements for each 2-week treatment cycle that were significantly higher than those in saline control-treated animals during periods of treatment, suggestive of RMD-induced viral reactivation. However, plasma virus rebound was indistinguishable between RMD-treated and control-treated animals for a subset of animals released from cART. These findings suggest that HDACi drugs, such as RMD, can reactivate residual virus in the presence of suppressive antiviral therapy and may be a valuable component of a comprehensive HIV functional cure/eradication strategy. PMID:26711758

  18. Elevated Plasma Viral Loads in Romidepsin-Treated Simian Immunodeficiency Virus-Infected Rhesus Macaques on Suppressive Combination Antiretroviral Therapy.

    PubMed

    Del Prete, Gregory Q; Oswald, Kelli; Lara, Abigail; Shoemaker, Rebecca; Smedley, Jeremy; Macallister, Rhonda; Coalter, Vicky; Wiles, Adam; Wiles, Rodney; Li, Yuan; Fast, Randy; Kiser, Rebecca; Lu, Bing; Zheng, Jim; Alvord, W Gregory; Trubey, Charles M; Piatak, Michael; Deleage, Claire; Keele, Brandon F; Estes, Jacob D; Hesselgesser, Joseph; Geleziunas, Romas; Lifson, Jeffrey D

    2015-12-28

    Replication-competent human immunodeficiency virus (HIV) persists in infected people despite suppressive combination antiretroviral therapy (cART), and it represents a major obstacle to HIV functional cure or eradication. We have developed a model of cART-mediated viral suppression in simian human immunodeficiency virus (SIV) mac239-infected Indian rhesus macaques and evaluated the impact of the histone deacetylase inhibitor (HDACi) romidepsin (RMD) on viremia in vivo. Eight macaques virologically suppressed to clinically relevant levels (<30 viral RNA copies/ml of plasma), using a three-class five-drug cART regimen, received multiple intravenous infusions of either RMD (n = 5) or saline (n = 3) starting 31 to 54 weeks after cART initiation. In vivo RMD treatment resulted in significant transient increases in acetylated histone levels in CD4(+) T cells. RMD-treated animals demonstrated plasma viral load measurements for each 2-week treatment cycle that were significantly higher than those in saline control-treated animals during periods of treatment, suggestive of RMD-induced viral reactivation. However, plasma virus rebound was indistinguishable between RMD-treated and control-treated animals for a subset of animals released from cART. These findings suggest that HDACi drugs, such as RMD, can reactivate residual virus in the presence of suppressive antiviral therapy and may be a valuable component of a comprehensive HIV functional cure/eradication strategy.

  19. Is early antiretroviral therapy initiation useful in HIV(+) adults without co-infections?

    PubMed

    Chauriye, Verónica; Monsalve, Ximena

    2015-12-02

    HIV infection is a worldwide epidemic. Antiretroviral therapy has dramatically changed the outcome of the disease but there is still controversy about the best time to initiate it, especially in patients with CD4 counts over 350 cells/µL. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified two systematic reviews including four pertinent randomized controlled trials overall. We concluded early initiation of antiretroviral therapy probably reduces mortality, risk of opportunistic infections and tuberculosis, but increases the risk of important adverse effects.

  20. Antiretroviral concentrations in small hair samples as a feasible marker of adherence in rural Kenya.

    PubMed

    Hickey, Matthew D; Salmen, Charles R; Tessler, Robert A; Omollo, Dan; Bacchetti, Peter; Magerenge, Richard; Mattah, Brian; Salmen, Marcus R; Zoughbie, Daniel; Fiorella, Kathryn J; Geng, Elvin; Njoroge, Betty; Jin, Chengshi; Huang, Yong; Bukusi, Elizabeth A; Cohen, Craig R; Gandhi, Monica

    2014-07-01

    Antiretroviral hair levels objectively quantify drug exposure over time and predict virologic responses. We assessed the acceptability and feasibility of collecting small hair samples in a rural Kenyan cohort. Ninety-five percentage of participants (354/373) donated hair. Although median self-reported adherence was 100% (interquartile range, 96%-100%), a wide range of hair concentrations likely indicates overestimation of self-reported adherence and the advantages of a pharmacologic adherence measure. Higher nevirapine hair concentrations observed in women and older adults require further study to unravel behavioral versus pharmacokinetic contributors. In resource-limited settings, hair antiretroviral levels may serve as a low-cost quantitative biomarker of adherence.

  1. Response to antiretroviral therapy in occult hepatitis B and HIV co-infection in West Africa.

    PubMed

    Chadwick, David; Stanley, Alastair; Sarfo, Stephen; Appiah, Lambert; Ankcorn, Michael; Foster, Geraldine; Schwab, Uli; Phillips, Richard; Geretti, Anna M

    2013-01-01

    This study evaluated the outcome of first-line antiretroviral therapy among 35 Ghanaians with occult HBV/HIV co-infection, comparing them over 2 years to 120 patients with HBsAg+ HBV/HIV co-infection and 230 patients without HBV co-infection. Increases in CD4 cell count and BMI were similar, whereas elevations of hepatic transaminases were more frequent in both the occult HBV and HBsAg+ patients. Occult HBV/HIV co-infection appears not to impact adversely on response to antiretroviral therapy in Ghana. PMID:22874516

  2. Is early antiretroviral therapy initiation useful in HIV(+) adults without co-infections?

    PubMed

    Chauriye, Verónica; Monsalve, Ximena

    2015-01-01

    HIV infection is a worldwide epidemic. Antiretroviral therapy has dramatically changed the outcome of the disease but there is still controversy about the best time to initiate it, especially in patients with CD4 counts over 350 cells/µL. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified two systematic reviews including four pertinent randomized controlled trials overall. We concluded early initiation of antiretroviral therapy probably reduces mortality, risk of opportunistic infections and tuberculosis, but increases the risk of important adverse effects. PMID:26639366

  3. Can antiretroviral therapy be used to prevent sexual transmission of human immunodeficiency virus type 1?

    PubMed

    Hosseinipour, Mina; Cohen, Myron S; Vernazza, Pietro L; Kashuba, Angela D M

    2002-05-15

    Approximately 5 million people annually are newly infected with human immunodeficiency virus (HIV). Although education, behavior modification, and promotion of condom use are effective transmission-prevention measures, the severity of the pandemic demands that all possible prevention strategies be explored. Antiretroviral therapy has the potential to decrease sexual transmission of HIV type 1 by reducing levels of HIV RNA and thus decreasing the risk that infected persons will transmit the disease or by its use as preexposure or postexposure prophylaxis. In this article, we explore the rationale for using antiretroviral therapy to prevent sexual transmission of HIV, as well as the limitations of this approach. PMID:11981736

  4. 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

  5. 34 CFR 200.16 - Starting points.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 34 Education 1 2012-07-01 2012-07-01 false Starting points. 200.16 Section 200.16 Education Regulations of the Offices of the Department of Education OFFICE OF ELEMENTARY AND SECONDARY EDUCATION, DEPARTMENT OF EDUCATION TITLE I-IMPROVING THE ACADEMIC ACHIEVEMENT OF THE DISADVANTAGED Improving...

  6. How to Start Intergenerational Programs in Communities.

    ERIC Educational Resources Information Center

    2002

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

  7. 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…

  8. Starting Salary Outcomes of Cooperative Education Graduates.

    ERIC Educational Resources Information Center

    Gardner, Philip D.; And Others

    1992-01-01

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

  9. 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…

  10. How To Start a Child Care Center.

    ERIC Educational Resources Information Center

    Benner, Phylis M., Comp.; Hollestelle, Kay, Comp.

    This paper is addressed to those who want to start their own child care center, and provides guidelines for doing so. It identifies the first things to be considered--planning and conducting a community needs assessment to analyze the competition in the area and make the decision of opening a day care center, and gathering information from a…

  11. Promoting Reading and Writing in Head Start.

    ERIC Educational Resources Information Center

    Dodge, Diane Trister

    1997-01-01

    Notes Head Start's obligation to promote literacy skills; presents pertinent strategies: (1) encourage families to talk with and read to children; (2) read to children every day; (3) create a print-rich environment; and (4) infuse reading and writing activities throughout the curriculum. Discusses importance of focusing on language and literacy…

  12. 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)

  13. Effects of sled towing on sprint starts.

    PubMed

    Cottle, Casey A; Carlson, Lara A; Lawrence, Michael A

    2014-05-01

    Sled towing is a popular method of sprint training. Researchers have struggled to identify a loading scheme that is most appropriate to improve sprint performance in the acceleration phase. The purpose of this study was to determine if loads of 10% body weight (BWT) or 20% BWT produced significantly greater propulsive ground reaction force (GRF) impulse, peak propulsive GRF, or a greater propulsive rate of force development (RFD) than an unweighted sprint start. Seventeen healthy court and field athletes (10 men, 7 women; 20.9 ± 1.1 years) completed 5 starts of each condition (unweighted, 10% BWT, 20% BWT). Participants began each start in an upright staggered stance. Propulsive GRF impulse was greater in the 20% BWT condition than the unweighted condition in both limbs and greater in the 20% BWT condition than the 10% BWT condition in the front leg only, and vertical GRF impulse was greater in the 20% BWT than the unweighted condition. In summary, our results suggest that a 10% BWT load is not sufficient to increase propulsive GRF impulse. A loading scheme of 20% BWT is sufficient to increase propulsive GRF impulse. Coaches seeking to improve sprint starts may observe improvements using a load of 20% BWT during training while towing a sled.

  14. 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.

  15. 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…

  16. Comprehensive Evaluation of Hawaii's Healthy Start Program.

    ERIC Educational Resources Information Center

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

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

  17. Evaluation of Hawaii's Healthy Start Program.

    ERIC Educational Resources Information Center

    Duggan, Anne K.; McFarlane, Elizabeth C.; Windham, Amy M.; Rohde, Charles A.; Salkever, David S.; Fuddy, Loretta; Rosenberg, Leon A.; Buchbinder, Sharon B.; Sia, Calvin C. J.

    1999-01-01

    Describes Hawaii's Healthy Start Program (HST), its ongoing evaluation study, and evaluation findings at the end of two of a planned three years of family-program participation and follow-up. HST uses home visitors to help prevent abusive and neglectful parenting. Found significant differences in program implementation among the three…

  18. How to Start a Day Care Center.

    ERIC Educational Resources Information Center

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

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

  19. Verifying the INF and START treaties

    NASA Astrophysics Data System (ADS)

    Ifft, Edward

    2014-05-01

    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.

  20. Head Start and Private/Public Partnerships.

    ERIC Educational Resources Information Center

    Holmes, Maggie

    1994-01-01

    Describes educational partnerships between Head Start programs and the Whirlpool Corporation, Johnson and Johnson, the Girl Scouts, Palmolive Corporation, and Children's World Learning Centers. Also provides advice and specific strategies for educators seeking to initiate partnerships with public and private organizations. (MDM)

  1. Start the New Year in the Spring.

    ERIC Educational Resources Information Center

    Curtis, Vernon B.; Smith, Steven H.

    1994-01-01

    Most schools need to review and revise disciplinary rules each year, but good administrator never publishes list of rules that have not been endorsed by "significant others" on staff or in community. By starting process in April or May, instead of August, the principal has several months to secure the necessary endorsements and involve parents.…

  2. An Alternative Starting Point for Fraction Instruction

    ERIC Educational Resources Information Center

    Cortina, José Luis; Višnovská, Jana; Zúñiga, Claudia

    2015-01-01

    We analyze the results of a study conducted for the purpose of assessing the viability of an alternative starting point for teaching fractions. The alternative is based on Freudenthal's insights about fraction as comparison. It involves portraying the entities that unit fractions quantify as always being apart from the reference unit, instead of…

  3. 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.

  4. Getting-Started Strategies and Cooperative Learning.

    ERIC Educational Resources Information Center

    Myers, John J.; And Others

    1991-01-01

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

  5. 34 CFR 200.16 - Starting points.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 34 Education 1 2011-07-01 2011-07-01 false Starting points. 200.16 Section 200.16 Education Regulations of the Offices of the Department of Education OFFICE OF ELEMENTARY AND SECONDARY EDUCATION, DEPARTMENT OF EDUCATION TITLE I-IMPROVING THE ACADEMIC ACHIEVEMENT OF THE DISADVANTAGED Improving...

  6. Starting a Business in the Permian Basin.

    ERIC Educational Resources Information Center

    Harrison, Danny

    The business and economic development center of Midland College provides assistance to small businesses. Written for use by future and current small business owners and entrepreneurs living in a 17-county area of the Permian Basin of Texas, this guidebook describes the procedures for developing a business plan and for successfully starting and…

  7. 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…

  8. 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…

  9. A climate change simulation starting from 1935

    NASA Astrophysics Data System (ADS)

    Cubasch, U.; Hegerl, G. C.; Hellbach, A.; Höck, H.; Mikolajewicz, U.; Santer, B. D.; Voss, R.

    1995-03-01

    Due to restrictions in the available computing resources and a lack of suitable observational data, transient climate change experiments with global coupled ocean-atmosphere models have been started from an initial state at equilibrium with the present day forcing. The historical development of greenhouse gas forcing from the onset of industrialization until the present has therefore been neglected. Studies with simplified models have shown that this “cold start” error leads to a serious underestimation of the anthropogenic global warming. In the present study, a 150-year integration has been carried out with a global coupled ocean-atmosphere model starting from the greenhouse gas concentration observed in 1935, i.e., at an early time of industrialization. The model was forced with observed greenhouse gas concentrations up to 1985, and with the equivalent C02 concentrations stipulated in Scenario A (“Business as Usual”) of the Intergovernmental Panel on Climate Change from 1985 to 2085. The early starting date alleviates some of the cold start problems. The global mean near surface temperature change in 2085 is about 0.3 K (ca. 10%) higher in the early industrialization experiment than in an integration with the same model and identical Scenario A greenhouse gas forcing, but with a start date in 1985. Comparisons between the experiments with early and late start dates show considerable differences in the amplitude of the regional climate change patterns, particularly for sea level. The early industrialization experiment can be used to obtain a first estimate of the detection time for a greenhouse-gas-induced near-surface temperature signal. Detection time estimates are obtained using globally and zonally averaged data from the experiment and a long control run, as well as principal component time series describing the evolution of the dominant signal and noise modes. The latter approach yields the earliest detection time (in the decade 1990 2000) for the

  10. Multi-dose Romidepsin Reactivates Replication Competent SIV in Post-antiretroviral Rhesus Macaque Controllers

    PubMed Central

    Policicchio, Benjamin B.; Xu, Cuiling; Brocca-Cofano, Egidio; Raehtz, Kevin D.; He, Tianyu; Ma, Dongzhu; Li, Hui; Haret-Richter, George S.; Dunsmore, Tammy; Trichel, Anita; Mellors, John W.; Hahn, Beatrice H.; Shaw, George M.; Ribeiro, Ruy M.; Pandrea, Ivona; Apetrei, Cristian

    2016-01-01

    Viruses that persist despite seemingly effective antiretroviral treatment (ART) and can reinitiate infection if treatment is stopped preclude definitive treatment of HIV-1 infected individuals, requiring lifelong ART. Among strategies proposed for targeting these viral reservoirs, the premise of the “shock and kill” strategy is to induce expression of latent proviruses [for example with histone deacetylase inhibitors (HDACis)] resulting in elimination of the affected cells through viral cytolysis or immune clearance mechanisms. Yet, ex vivo studies reported that HDACis have variable efficacy for reactivating latent proviruses, and hinder immune functions. We developed a nonhuman primate model of post-treatment control of SIV through early and prolonged administration of ART and performed in vivo reactivation experiments in controller RMs, evaluating the ability of the HDACi romidepsin (RMD) to reactivate SIV and the impact of RMD treatment on SIV-specific T cell responses. Ten RMs were IV-infected with a SIVsmmFTq transmitted-founder infectious molecular clone. Four RMs received conventional ART for >9 months, starting from 65 days post-infection. SIVsmmFTq plasma viremia was robustly controlled to <10 SIV RNA copies/mL with ART, without viral blips. At ART cessation, initial rebound viremia to ~106 copies/mL was followed by a decline to < 10 copies/mL, suggesting effective immune control. Three post-treatment controller RMs received three doses of RMD every 35–50 days, followed by in vivo experimental depletion of CD8+ cells using monoclonal antibody M-T807R1. RMD was well-tolerated and resulted in a rapid and massive surge in T cell activation, as well as significant virus rebounds (~104 copies/ml) peaking at 5–12 days post-treatment. CD8+ cell depletion resulted in a more robust viral rebound (107 copies/ml) that was controlled upon CD8+ T cell recovery. Our results show that RMD can reactivate SIV in vivo in the setting of post-ART viral control

  11. Multi-dose Romidepsin Reactivates Replication Competent SIV in Post-antiretroviral Rhesus Macaque Controllers.

    PubMed

    Policicchio, Benjamin B; Xu, Cuiling; Brocca-Cofano, Egidio; Raehtz, Kevin D; He, Tianyu; Ma, Dongzhu; Li, Hui; Sivanandham, Ranjit; Haret-Richter, George S; Dunsmore, Tammy; Trichel, Anita; Mellors, John W; Hahn, Beatrice H; Shaw, George M; Ribeiro, Ruy M; Pandrea, Ivona; Apetrei, Cristian

    2016-09-01

    Viruses that persist despite seemingly effective antiretroviral treatment (ART) and can reinitiate infection if treatment is stopped preclude definitive treatment of HIV-1 infected individuals, requiring lifelong ART. Among strategies proposed for targeting these viral reservoirs, the premise of the "shock and kill" strategy is to induce expression of latent proviruses [for example with histone deacetylase inhibitors (HDACis)] resulting in elimination of the affected cells through viral cytolysis or immune clearance mechanisms. Yet, ex vivo studies reported that HDACis have variable efficacy for reactivating latent proviruses, and hinder immune functions. We developed a nonhuman primate model of post-treatment control of SIV through early and prolonged administration of ART and performed in vivo reactivation experiments in controller RMs, evaluating the ability of the HDACi romidepsin (RMD) to reactivate SIV and the impact of RMD treatment on SIV-specific T cell responses. Ten RMs were IV-infected with a SIVsmmFTq transmitted-founder infectious molecular clone. Four RMs received conventional ART for >9 months, starting from 65 days post-infection. SIVsmmFTq plasma viremia was robustly controlled to <10 SIV RNA copies/mL with ART, without viral blips. At ART cessation, initial rebound viremia to ~106 copies/mL was followed by a decline to < 10 copies/mL, suggesting effective immune control. Three post-treatment controller RMs received three doses of RMD every 35-50 days, followed by in vivo experimental depletion of CD8+ cells using monoclonal antibody M-T807R1. RMD was well-tolerated and resulted in a rapid and massive surge in T cell activation, as well as significant virus rebounds (~104 copies/ml) peaking at 5-12 days post-treatment. CD8+ cell depletion resulted in a more robust viral rebound (107 copies/ml) that was controlled upon CD8+ T cell recovery. Our results show that RMD can reactivate SIV in vivo in the setting of post-ART viral control. Comparison of

  12. Cerebrospinal fluid HIV infection and pleocytosis: Relation to systemic infection and antiretroviral treatment

    PubMed Central

    Spudich, Serena S; Nilsson, Annelie C; Lollo, Nicole D; Liegler, Teri J; Petropoulos, Christos J; Deeks, Steven G; Paxinos, Ellen E; Price, Richard W

    2005-01-01

    Background Central nervous system (CNS) exposure to HIV is a universal facet of systemic infection. Because of its proximity to and shared barriers with the brain, cerebrospinal fluid (CSF) provides a useful window into and model of human CNS HIV infection. Methods Prospective study of the relationships of CSF to plasma HIV RNA, and the effects of: 1) progression of systemic infection, 2) CSF white blood cell (WBC) count, 3) antiretroviral therapy (ART), and 4) neurological performance. One hundred HIV-infected subjects were cross-sectionally studied, and 28 were followed longitudinally after initiating or changing ART. Results In cross-sectional analysis, HIV RNA levels were lower in CSF than plasma (median difference 1.30 log10 copies/mL). CSF HIV viral loads (VLs) correlated strongly with plasma VLs and CSF WBC counts. Higher CSF WBC counts associated with smaller differences between plasma and CSF HIV VL. CSF VL did not correlate with blood CD4 count, but CD4 counts <50 cells/μL associated with a low prevalence of CSF pleocytosis and large differences between plasma and CSF VL. CSF HIV RNA correlated neither with the severity of the AIDS dementia complex (ADC) nor abnormal quantitative neurological performance, although these measures were associated with depression of CD4 counts. In subjects starting ART, those with lower CD4 counts had slower initial viral decay in CSF than in plasma. In all subjects, including five with persistent plasma viremia and four with new-onset ADC, CSF HIV eventually approached or reached the limit of viral detection and CSF pleocytosis resolved. Conclusion CSF HIV infection is common across the spectrum of infection and is directly related to CSF pleocytosis, though whether the latter is a response to or a contributing cause of CSF infection remains uncertain. Slowing in the rate of CSF response to ART compared to plasma as CD4 counts decline indicates a changing character of CSF infection with systemic immunological progression

  13. Multi-dose Romidepsin Reactivates Replication Competent SIV in Post-antiretroviral Rhesus Macaque Controllers.

    PubMed

    Policicchio, Benjamin B; Xu, Cuiling; Brocca-Cofano, Egidio; Raehtz, Kevin D; He, Tianyu; Ma, Dongzhu; Li, Hui; Sivanandham, Ranjit; Haret-Richter, George S; Dunsmore, Tammy; Trichel, Anita; Mellors, John W; Hahn, Beatrice H; Shaw, George M; Ribeiro, Ruy M; Pandrea, Ivona; Apetrei, Cristian

    2016-09-01

    Viruses that persist despite seemingly effective antiretroviral treatment (ART) and can reinitiate infection if treatment is stopped preclude definitive treatment of HIV-1 infected individuals, requiring lifelong ART. Among strategies proposed for targeting these viral reservoirs, the premise of the "shock and kill" strategy is to induce expression of latent proviruses [for example with histone deacetylase inhibitors (HDACis)] resulting in elimination of the affected cells through viral cytolysis or immune clearance mechanisms. Yet, ex vivo studies reported that HDACis have variable efficacy for reactivating latent proviruses, and hinder immune functions. We developed a nonhuman primate model of post-treatment control of SIV through early and prolonged administration of ART and performed in vivo reactivation experiments in controller RMs, evaluating the ability of the HDACi romidepsin (RMD) to reactivate SIV and the impact of RMD treatment on SIV-specific T cell responses. Ten RMs were IV-infected with a SIVsmmFTq transmitted-founder infectious molecular clone. Four RMs received conventional ART for >9 months, starting from 65 days post-infection. SIVsmmFTq plasma viremia was robustly controlled to <10 SIV RNA copies/mL with ART, without viral blips. At ART cessation, initial rebound viremia to ~106 copies/mL was followed by a decline to < 10 copies/mL, suggesting effective immune control. Three post-treatment controller RMs received three doses of RMD every 35-50 days, followed by in vivo experimental depletion of CD8+ cells using monoclonal antibody M-T807R1. RMD was well-tolerated and resulted in a rapid and massive surge in T cell activation, as well as significant virus rebounds (~104 copies/ml) peaking at 5-12 days post-treatment. CD8+ cell depletion resulted in a more robust viral rebound (107 copies/ml) that was controlled upon CD8+ T cell recovery. Our results show that RMD can reactivate SIV in vivo in the setting of post-ART viral control. Comparison of

  14. 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

  15. 78 FR 2038 - Notice of Availability of Proposed New Starts and Small Starts Policy Guidance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-09

    ... Investment Projects published elsewhere in this issue of the Federal Register. Specifically, this proposed... capital investment projects each time the agency makes significant changes to the process and criteria... announcing the availability of proposed policy guidance to sponsors of New Starts and Small Starts...

  16. 77 FR 3838 - Notice of Availability of Proposed New Starts/Small Starts Policy Guidance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-25

    ... the Notice of Proposed Rulemaking for Major Capital Investment Projects by describing the detailed measures proposed for evaluation of projects seeking New Starts and Small Starts funding and the way these measures would be used in project ratings if adopted. The proposed regulations and appendix are intended...

  17. Special Analysis of Migrant Education Even Start Data. Even Start Information System.

    ERIC Educational Resources Information Center

    Tao, Fumiyo; Arriola, Christine

    This report analyzes data submitted by 11 of 14 state Migrant Education Even Start (MEES) projects operating in 1994-95. These projects provide migrant families with an integrated program of early childhood education, adult education, and parenting education. The data were drawn from the Even Start Information System (ESIS), which collected…

  18. National Evaluation of the Even Start Family Literacy Program: Report on Migrant Even Start Projects.

    ERIC Educational Resources Information Center

    Levin, Marjorie; Gamse, Beth; Swartz, Janet; Tao, Fumiyo; Tarr, Hope

    In fall 1994, 14 state Migrant Education Programs were receiving direct federal grants to administer Migrant Even Start projects. These projects provide migrant families with an integrated program of early childhood education, adult education, and parenting education. As part of the national evaluation of the Even Start Family Literacy Program,…

  19. Health outcomes among HIV-positive Latinos initiating antiretroviral therapy in North America versus Central and South America

    PubMed Central

    Cesar, Carina; Koethe, John R; Giganti, Mark J; Rebeiro, Peter; Althoff, Keri N; Napravnik, Sonia; Mayor, Angel; Grinsztejn, Beatriz; Wolff, Marcelo; Padgett, Denis; Sierra-Madero, Juan; Gotuzzo, Eduardo; Sterling, Timothy R; Willig, James; Levison, Julie; Kitahata, Mari; Rodriguez-Barradas, Maria C; Moore, Richard D; McGowan, Catherine; Shepherd, Bryan E; Cahn, Pedro

    2016-01-01

    Introduction Latinos living with HIV in the Americas share a common ethnic and cultural heritage. In North America, Latinos have a relatively high rate of new HIV infections but lower rates of engagement at all stages of the care continuum, whereas in Latin America antiretroviral therapy (ART) services continue to expand to meet treatment needs. In this analysis, we compare HIV treatment outcomes between Latinos receiving ART in North America versus Latin America. Methods HIV-positive adults initiating ART at Caribbean, Central and South America Network for HIV (CCASAnet) sites were compared to Latino patients (based on country of origin or ethnic identity) starting treatment at North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) sites in the United States and Canada between 2000 and 2011. Cox proportional hazards models compared mortality, treatment interruption, antiretroviral regimen change, virologic failure and loss to follow-up between cohorts. Results The study included 8400 CCASAnet and 2786 NA-ACCORD patients initiating ART. CCASAnet patients were younger (median 35 vs. 37 years), more likely to be female (27% vs. 20%) and had lower nadir CD4 count (median 148 vs. 195 cells/µL, p<0.001 for all). In multivariable analyses, CCASAnet patients had a higher risk of mortality after ART initiation (adjusted hazard ratio (AHR) 1.61; 95% confidence interval (CI): 1.32 to 1.96), particularly during the first year, but a lower hazard of treatment interruption (AHR: 0.46; 95% CI: 0.42 to 0.50), change to second-line ART (AHR: 0.56; 95% CI: 0.51 to 0.62) and virologic failure (AHR: 0.52; 95% CI: 0.48 to 0.57). Conclusions HIV-positive Latinos initiating ART in Latin America have greater continuity of treatment but are at higher risk of death than Latinos in North America. Factors underlying these differences, such as HIV testing, linkage and access to care, warrant further investigation. PMID:26996992

  20. Antiretroviral Regimens in Pregnancy and Breast-Feeding in Botswana

    PubMed Central

    Shapiro, R.L.; Hughes, M.D.; Ogwu, A.; Kitch, D.; Lockman, S.; Moffat, C.; Makhema, J.; Moyo, S.; Thior, I.; McIntosh, K.; van Widenfelt, E.; Leidner, J.; Powis, K.; Asmelash, A.; Tumbare, E.; Zwerski, S.; Sharma, U.; Handelsman, E.; Mburu, K.; Jayeoba, O.; Moko, E.; Souda, S.; Lubega, E.; Akhtar, M.; Wester, C.; Tuomola, R.; Snowden, W.; Martinez-Tristani, M.; Mazhani, L.; Essex, M.

    2010-01-01

    BACKGROUND The most effective highly active antiretroviral therapy (HAART) to prevent mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) in pregnancy and its efficacy during breast-feeding are unknown. METHODS We randomly assigned 560 HIV-1–infected pregnant women (CD4+ count, ≥200 cells per cubic millimeter) to receive coformulated abacavir, zidovudine, and lamivudine (the nucleoside reverse-transcriptase inhibitor [NRTI] group) or lopinavir–ritonavir plus zidovudine-lamivudine (the protease-inhibitor group) from 26 to 34 weeks’ gestation through planned weaning by 6 months post partum. A total of 170 women with CD4+ counts of less than 200 cells per cubic millimeter received nevirapine plus zidovudine–lamivudine (the observational group). Infants received single-dose nevirapine and 4 weeks of zidovudine. RESULTS The rate of virologic suppression to less than 400 copies per milliliter was high and did not differ significantly among the three groups at delivery (96% in the NRTI group, 93% in the protease-inhibitor group, and 94% in the observational group) or throughout the breast-feeding period (92% in the NRTI group, 93% in the protease-inhibitor group, and 95% in the observational group). By 6 months of age, 8 of 709 live-born infants (1.1%) were infected (95% confidence interval [CI], 0.5 to 2.2): 6 were infected in utero (4 in the NRTI group, 1 in the protease-inhibitor group, and 1 in the observational group), and 2 were infected during the breast-feeding period (in the NRTI group). Treatment-limiting adverse events occurred in 2% of women in the NRTI group, 2% of women in the protease-inhibitor group, and 11% of women in the observational group. CONCLUSIONS All regimens of HAART from pregnancy through 6 months post partum resulted in high rates of virologic suppression, with an overall rate of mother-to-child transmission of 1.1%. (ClinicalTrials.gov number, NCT00270296.) PMID:20554983

  1. 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

  2. Financing equitable access to antiretroviral treatment in South Africa

    PubMed Central

    2010-01-01

    Background While South Africa spends approximately 7.4% of GDP on healthcare, only 43% of these funds are spent in the public system, which is tasked with the provision of care to the majority of the population including a large proportion of those in need of antiretroviral treatment (ART). South Africa is currently debating the introduction of a National Health Insurance (NHI) system. Because such a universal health system could mean increased public healthcare funding and improved access to human resources, it could improve the sustainability of ART provision. This paper considers the minimum resources that would be required to achieve the proposed universal health system and contrasts these with the costs of scaled up access to ART between 2010 and 2020. Methods The costs of ART and universal coverage (UC) are assessed through multiplying unit costs, utilization and estimates of the population in need during each year of the planning cycle. Costs are from the provider’s perspective reflected in real 2007 prices. Results The annual costs of providing ART increase from US$1 billion in 2010 to US$3.6 billion in 2020. If increases in funding to public healthcare only keep pace with projected real GDP growth, then close to 30% of these resources would be required for ART by 2020. However, an increase in the public healthcare resource envelope from 3.2% to 5%-6% of GDP would be sufficient to finance both ART and other services under a universal system (if based on a largely public sector model) and the annual costs of ART would not exceed 15% of the universal health system budget. Conclusions Responding to the HIV-epidemic is one of the many challenges currently facing South Africa. Whether this response becomes a “resource for democracy” or whether it undermines social cohesiveness within poor communities and between rich and poor communities will be partially determined by the steps that are taken during the next ten years. While the introduction of a

  3. Predictors of Antiretroviral Treatment Failure in an Urban HIV Clinic

    PubMed Central

    Robbins, Gregory K.; Daniels, Brock; Zheng, Hui; Chueh, Henry; Meigs, James B.; Freedberg, Kenneth A.

    2008-01-01

    Background Predictors of antiretroviral treatment (ART) failure are not well characterized for heterogeneous clinic populations. Methods A retrospective analysis was conducted of HIV-infected patients followed in an urban HIV clinic with an HIV RNA measurement ≤400 copies/mL on ART between January 1, 2003, and December 31, 2004. The primary endpoint was treatment failure, defined as virologic failure (≥1 HIV RNA measurement >400 copies/mL), unsanctioned stopping of ART, or loss to follow-up. Prior ART adherence and other baseline patient characteristics, determined at the time of the first suppressed HIV RNA load on or after January 1, 2003, were extracted from the electronic health record (EHR). Predictors of failure were assessed using proportional hazards modeling. Results Of 829 patients in the clinic, 614 had at least 1 HIV RNA measurement ≤400 copies/mL during the study period. Of these, 167 (27.2%) experienced treatment failure. Baseline characteristics associated with treatment failure in the multivariate model were: poor adherence (hazard ratio [HR] = 3.44; 95% confidence interval [CI]: 2.34 to 5.05), absolute neutrophil count <1000/mm3 (HR = 2.90, 95% CI: 1.26 to 6.69), not suppressed on January 1, 2003 (HR = 2.69, 95% CI: 1.78 to 4.07) or <12 months of suppression (HR = 1.64, 95% CI: 1.10 to 2.45), CD4 count <200 cells/mm3 (HR = 1.90, 95% CI: 1.31 to 2.76), nucleoside-only regimen (HR = 1.75, 95% CI: 1.08 to 2.82), prior virologic failure (HR = 1.70, 95% CI: 1.22 to 2.39) and ≥1 missed visit in the prior year (HR = 1.56, 95% CI: 1.13 to 2.16). Conclusions More than one quarter of patients in a heterogeneous clinic population had treatment failure over a 2-year period. Prior ART adherence and other EHR data readily identify patient characteristics that could trigger specific interventions to improve ART outcomes. PMID:17106280

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

    PubMed Central

    2013-01-01

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

  5. Simian immunodeficiency virus (SIV) infection of infant rhesus macaques as a model to test antiretroviral drug prophylaxis and therapy: oral 3'-azido-3'-deoxythymidine prevents SIV infection.

    PubMed

    Van Rompay, K K; Marthas, M L; Ramos, R A; Mandell, C P; McGowan, E K; Joye, S M; Pedersen, N C

    1992-11-01

    The prophylactic and therapeutic properties of 3'-azido-3'-deoxythymidine (AZT) against simian immunodeficiency virus (SIV) infection were tested in four 3-month-old rhesus macaques. The infant monkeys were inoculated intravenously with a low dose (1 to 10 100% animal infectious doses) of uncloned SIVmac. The monkeys were treated orally with 50 mg of AZT per kg of body weight every 8 h; two animals were started on treatment 2 h prior to virus inoculation, and two animals were started on treatment 6 weeks later. All four animals were treated for a period of 6 to 10 weeks. Outward signs of AZT toxicity were absent, but a mild macrocytic anemia occurred soon after therapy was started and resolved shortly after it was discontinued. The two infants that were begun on AZT treatment 2 h prior to virus inoculation never became infected, as demonstrated by the inability to detect cell-free or cell-associated virus in the blood, proviral DNA in peripheral blood mononuclear cells, or anti-SIV antibodies. AZT administration over a 10-week period had no detectable effect on the course of disease in the two animals that were begun on treatment after the infection had been established. In addition to demonstrating the prophylactic effect of AZT against low-dose SIV exposure, the study demonstrated the ease with which infant rhesus macaques can be used for antiretroviral drug testing. PMID:1489181

  6. 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

  7. Success with antiretroviral treatment for children in Kigali, Rwanda: Experience with health center/nurse-based care

    PubMed Central

    van Griensven, Johan; De Naeyer, Ludwig; Uwera, Jeanine; Asiimwe, Anita; Gazille, Claire; Reid, Tony

    2008-01-01

    Background Although a number of studies have shown good results in treating children with antiretroviral drugs (ARVs) in hospital settings, there is limited published information on results in pediatric programs that are nurse-centered and based in health centers, in particular on the psychosocial aspects of care. Methods Program treatment and outcome data were reported from two government-run health centers that were supported by Médecins Sans Frontières (MSF) in Kigali, Rwanda between October 2003 and June 2007. Interviews were held with health center staff and MSF program records were reviewed to describe the organization of the program. Important aspects included adequate training and supervision of nurses to manage ARV treatment. The program also emphasized family-centered care addressing the psychosocial needs of both caregivers and children to encourage early diagnosis, good adherence and follow-up. Results A total of 315 children (< 15 years) were started on ARVs, at a median age of 7.2 years (range: 0.7–14.9). Sixty percent were in WHO clinical stage I/II, with a median CD4% of 14%. Eighty-nine percent (n = 281) started a stavudine-containing regimen, mainly using the adult fixed-dose combination. The median follow-up time after ARV initiation was 2 years (interquartile range 1.2–2.6). Eighty-four percent (n = 265) of children were still on treatment in the program. Thirty (9.5%) were transferred out, eight (2.6%) died and 12 (3.8%) were lost to follow-up. An important feature of the study was that viral loads were done at a median time period of 18 months after starting ARVs and were available for 87% of the children. Of the 174 samples, VL was < 400 copies/ml in 82.8% (n = 144). Two children were started on second-line ARVs. Treatment was changed due to toxicity for 26 children (8.3%), mainly related to nevirapine. Conclusion This report suggests that providing ARVs to children in a health center/nurse-based program is both feasible and very

  8. Start currents in an overmoded gyrotron

    NASA Astrophysics Data System (ADS)

    Yeddulla, M.; Nusinovich, G. S.; Antonsen, T. M.

    2003-11-01

    High-power long-pulse millimeter-wave gyrotrons operate in high-order modes. The spectral density of these modes is very high. Therefore, self-excitation conditions can be fulfilled for several modes simultaneously. Correspondingly, in order to determine which mode will be excited first in such a device, the starting currents of competing modes should be calculated much more accurately than in gyrotrons with a rarer spectrum. In the present paper, an existing linear theory is generalized to take into account effects of magnetic field tapering, cavity profile, finite beam thickness, velocity spread and axially dependent beam coupling to the fields of competing modes. Starting currents are calculated for the operating and the most dangerous competing mode in a 140 GHz gyrotron, which is under development at Communication and Power Industries. Calculations show that the radial position of the electron beam plays a critical role in deciding which mode dominates the mode competition.

  9. Starting apparatus for internal combustion engines

    DOEpatents

    Dyches, Gregory M.; Dudar, Aed M.

    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.

  10. 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.

  11. Initiating Antiretroviral Therapy for HIV at a Patient’s First Clinic Visit: The RapIT Randomized Controlled Trial

    PubMed Central

    Rosen, Sydney; Maskew, Mhairi; Fox, Matthew P.; Nyoni, Cynthia; Mongwenyana, Constance; Sanne, Ian; Sauls, Celeste; Long, Lawrence

    2016-01-01

    Background High rates of patient attrition from care between HIV testing and antiretroviral therapy (ART) initiation have been documented in sub-Saharan Africa, contributing to persistently low CD4 cell counts at treatment initiation. One reason for this is that starting ART in many countries is a lengthy and burdensome process, imposing long waits and multiple clinic visits on patients. We estimated the effect on uptake of ART and viral suppression of an accelerated initiation algorithm that allowed treatment-eligible patients to be dispensed their first supply of antiretroviral medications on the day of their first HIV-related clinic visit. Methods and Findings RapIT (Rapid Initiation of Treatment) was an unblinded randomized controlled trial of single-visit ART initiation in two public sector clinics in South Africa, a primary health clinic (PHC) and a hospital-based HIV clinic. Adult (≥18 y old), non-pregnant patients receiving a positive HIV test or first treatment-eligible CD4 count were randomized to standard or rapid initiation. Patients in the rapid-initiation arm of the study (“rapid arm”) received a point-of-care (POC) CD4 count if needed; those who were ART-eligible received a POC tuberculosis (TB) test if symptomatic, POC blood tests, physical exam, education, counseling, and antiretroviral (ARV) dispensing. Patients in the standard-initiation arm of the study (“standard arm”) followed standard clinic procedures (three to five additional clinic visits over 2–4 wk prior to ARV dispensing). Follow up was by record review only. The primary outcome was viral suppression, defined as initiated, retained in care, and suppressed (≤400 copies/ml) within 10 mo of study enrollment. Secondary outcomes included initiation of ART ≤90 d of study enrollment, retention in care, time to ART initiation, patient-level predictors of primary outcomes, prevalence of TB symptoms, and the feasibility and acceptability of the intervention. A survival analysis

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

    PubMed Central

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

    2011-01-01

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

  13. Antiretroviral therapy for prevention of HIV transmission in HIV-discordant couples.

    PubMed

    Anglemyer, Andrew; Horvath, Tara; Rutherford, George

    2013-10-16

    CLINICAL QUESTION Does treating the HIV-infected partner in a serodiscordant couple reduce the risk of HIV transmission to the uninfected partner? BOTTOM LINE Compared with serodiscordant couples without treatment, couples in which the infected partner is treated with antiretroviral therapy have a lower risk of HIV transmission.

  14. [Severe or life-threatening interactions between antiretrovirals and non-HIV drugs].

    PubMed

    Manzardo, Christian; Tuset, Montserrat; Miró, Jose M; Gatell, Jose M

    2015-01-01

    Highly active antiretroviral therapy has helped to improved control of the HIV infection, and has led to a progressively older population with the infection having a life expectancy quite similar to that of the general population. On the other hand, it is also known that HIV infection, even in patients with undetectable viral loads and good immunity, carries an increased cardiovascular risk, as well as an increased incidence of certain cancers. Therefore, the majority of HIV-infected patients receive several drugs (either prescribed by the physician or self-administered) combined with antiretrovirals. This article reviews the interactions between antiretrovirals and other drugs that can cause significant damage to patients, or even be life-threatening and of whom clinicians, especially those not directly treating HIV-infected patients, should be aware. A review is also presented on the implications of interactions between antiretrovirals and other drugs in special situations, such as the co-administration with cytostatics, immunesuppressants used in solid organ transplantation, or patients receiving new treatments for hepatitisC. Generally, combinations with two nucleos(t)ide reverse transcriptase inhibitors and raltegravir (or in the near future, dolutegravir) are those with less potential for clinically significant interactions. PMID:24913990

  15. 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,…

  16. Metabolic alterations in HIV-infected pregnant women: moving to metabolic tailoring of antiretroviral drugs.

    PubMed

    Guaraldi, Giovanni; Stentarelli, Chiara; Da Silva, Anarita Domingues; Luzi, Kety; Neri, Isabella; Cellini, Monica; Petrella, Elisabetta; Garlassi, Elisa; Menozzi, Marianna; Facchinetti, Fabio; Mussini, Cristina

    2014-01-01

    The most striking effect of increased survival and improved quality of life in HIV-infected women undergoing antiretroviral therapy is the feasibility of motherhood-desire satisfaction. However, such advantages are often associated with drug-related metabolic toxicities, particularly relevant in the pregnancy context. Recent guidelines provide recommendations and trends for the use of antiretroviral therapy in pregnant women, but current literature falls short of providing specific insights on the need for metabolic monitoring and treatment in HIV-infected pregnant women. In this review we provide specific insight into the state-of-the-art of: detection, evaluation, and management of metabolic alterations in this special population. Pregnancy is in fact a metabolic transition process, potentially associated with specific diseases in the mother, in the newborn, and in the adulthood of the child. We will not simply discuss antiretroviral therapy metabolic toxicities, but rather their interaction with the physiological metabolic changes occurring during pregnancy. Close monitoring is needed to diagnose metabolic alterations that can lead to adverse outcomes in the mother, in the newborn, and potentially in adulthood. Lifestyle interventions and an appropriate metabolic tailoring of antiretroviral therapy drugs need to be considered in the prevention and treatment of metabolic alteration during pregnancy.

  17. 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…

  18. 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.

  19. Osteoporosis and multiple fractures in an antiretroviral-naive, HIV-positive child.

    PubMed

    Soler Palacin, P; Torrent, A; Rossich, R; Moraga, F A; Yeste, D; Carreño, J C; Encabo, G; Figueras, C

    2007-08-01

    As a result of the increased incidence of osteopenia and osteoporosis in HIV-infected patients, numerous publications have suggested that there may be a link between bone metabolism alterations and HIV infection. The early bone loss seen in these patients was initially attributed to the use of highly active antiretroviral treatment (HAART) that included protease inhibitors. Recent studies, however, have suggested that it may be a direct consequence of the viral infection on bone metabolism, persistent activation of pro-inflammatory cytokines (TNFa), or altered vitamin D metabolism secondary to the virus, combined with subsequent factors (e.g., antiretroviral treatment) that aggravate the bone demineralization. We present an antiretroviral-naive 6-year-old girl with vertically transmitted HIV infection who presented with severe osteoporosis and multiple pathological fractures of the vertebrae, ribs, and upper and lower limbs. The child was treated with HAART, appropriate nutritional support for her age, physiotherapy and rehabilitation, calcium and vitamin D supplements, and alendronate therapy. After 6 weeks of treatment, the intense pain and muscle atrophy had disappeared and she was able to walk unassisted. At 6 months, bone mass had increased by 72%. The interest of this case lies in the presence of severe osteoporosis and multiple pathological fractures in an HIVinfected naive child. To date, this condition has only been described in patients treated with antiretrovirals. Moreover, this is the first reported HIV-positive pediatric patient treated with bisphosphonates, which proved to be highly successful.

  20. 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

  1. 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…

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

    PubMed Central

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

    2012-01-01

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

  3. Benefits and Risks of Antiretroviral Therapy for Perinatal HIV Prevention.

    PubMed

    Fowler, Mary G; Qin, Min; Fiscus, Susan A; Currier, Judith S; Flynn, Patricia M; Chipato, Tsungai; McIntyre, James; Gnanashanmugam, Devasena; Siberry, George K; Coletti, Anne S; Taha, Taha E; Klingman, Karin L; Martinson, Francis E; Owor, Maxensia; Violari, Avy; Moodley, Dhayendre; Theron, Gerhard B; Bhosale, Ramesh; Bobat, Raziya; Chi, Benjamin H; Strehlau, Renate; Mlay, Pendo; Loftis, Amy J; Browning, Renee; Fenton, Terence; Purdue, Lynette; Basar, Michael; Shapiro, David E; Mofenson, Lynne M

    2016-11-01

    Background Randomized-trial data on the risks and benefits of antiretroviral therapy (ART) as compared with zidovudine and single-dose nevirapine to prevent transmission of the human immunodeficiency virus (HIV) in HIV-infected pregnant women with high CD4 counts are lacking. Methods We randomly assigned HIV-infected women at 14 or more weeks of gestation with CD4 counts of at least 350 cells per cubic millimeter to zidovudine and single-dose nevirapine plus a 1-to-2-week postpartum "tail" of tenofovir and emtricitabine (zidovudine alone); zidovudine, lamivudine, and lopinavir-ritonavir (zidovudine-based ART); or tenofovir, emtricitabine, and lopinavir-ritonavir (tenofovir-based ART). The primary outcomes were HIV transmission at 1 week of age in the infant and maternal and infant safety. Results The median CD4 count was 530 cells per cubic millimeter among 3490 primarily black African HIV-infected women enrolled at a median of 26 weeks of gestation (interquartile range, 21 to 30). The rate of transmission was significantly lower with ART than with zidovudine alone (0.5% in the combined ART groups vs. 1.8%; difference, -1.3 percentage points; repeated confidence interval, -2.1 to -0.4). However, the rate of maternal grade 2 to 4 adverse events was significantly higher with zidovudine-based ART than with zidovudine alone (21.1% vs. 17.3%, P=0.008), and the rate of grade 2 to 4 abnormal blood chemical values was higher with tenofovir-based ART than with zidovudine alone (2.9% vs. 0.8%, P=0.03). Adverse events did not differ significantly between the ART groups (P>0.99). A birth weight of less than 2500 g was more frequent with zidovudine-based ART than with zidovudine alone (23.0% vs. 12.0%, P<0.001) and was more frequent with tenofovir-based ART than with zidovudine alone (16.9% vs. 8.9%, P=0.004); preterm delivery before 37 weeks was more frequent with zidovudine-based ART than with zidovudine alone (20.5% vs. 13.1%, P<0.001). Tenofovir-based ART was associated

  4. 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... policy guidance on the New and Small Starts capital project review and evaluation process and criteria...) published by FTA in June 2010, which sought public comment on the New Starts and Small Starts...

  5. 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

  6. 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

  7. Getting started in academic cardiothoracic surgery.

    PubMed

    Verrier, E D

    2000-04-01

    Preparing to begin a career in academic cardiothoracic surgery requires forethought and desire. Success mandates honesty, discipline, opportunity, and support. This article will attempt to review some fundamental concepts important in starting such an academic career. The thoughts are somewhat personal and not meant to be inclusive. The article will briefly discuss the following issues: choosing the first job, transitions, effective time management, developing clinical confidence, the continued need for mentorship, developing educational value, developing a philosophy of academic growth, intellectual and emotional honesty, myths, mental and physical health, and keys to success. PMID:10727955

  8. Biomechanical analysis of different starting strategies utilized during cross-country skiing starts.

    PubMed

    Wiltmann, Victor Wennemar; Holmberg, Hans-Christer; Pelttari, Pasi; Mikkola, Jussi; Häkkinen, Keijo; Ohtonen, Olli; Linnamo, Vesa

    2016-11-01

    The present study was designed to analyse and compare the kinetics and kinematics associated with three different starting strategies during classic cross-country ski racing. Inside a ski tunnel, 12 elite male skiers performed three sets of three 38 m starts. Each set included one start using: double poling only (DP), diagonal stride only (DIA) and freely chosen (FREE) (i.e. where subjects used the strategy or combination of strategies they felt was fastest) in random order. The first 18 m was performed on a series of force plates that measured horizontal and vertical forces followed by 20 m of a standard snow track. Additionally, cycle characteristics and joint angles were measured. DIA and FREE were faster over 38 m than DP (P < .01). Net horizontal impulse (taking into account both positive and negative impulses) 5-10 m after the start was lower during DP than during DIA and FREE (both P < .05). All subjects skied faster when using only DIA for the entire 38 m. Furthermore, the sum duration and frequency of propulsive contacts over the first 18 m was less in DP than DIA and FREE (P < .01). In conclusion, differences between the starting strategies examined was especially pronounced during the initial cycles. Transition from DIA to DP during the start also slowed the skiers, but optimal timing for such a transition was not elucidated.

  9. API consensus guidelines for use of antiretroviral therapy in adults (API-ART guidelines). Endorsed by the AIDS Society of India.

    PubMed

    Gupta, S B; Pujari, S N; Joshi, S R; Patel, A K

    2006-01-01

    With rational use of antiretroviral therapy (ART), human immunodeficiency virus (HIV) infection has been transformed into a chronic manageable illness like diabetes and hypertension. These guidelines provide information on state of art, evidence based approach for use of ART in Indian context. When to initiate ART? Antiretroviral therapy is indicated for all symptomatic HIV infected persons regardless of CD4 counts and plasma viral load (PVL) levels. In asymptomatic patients, ART should be offered when the CD4 counts < 200/mm3 and should be considered in patients with CD4 counts between 200-250/mm3. Therapy is not recommended for patients with CD4 count more than 350/ mm3. Involvement of patient in all treatment decisions and assessing readiness is critical before initiating ART. What to start with? A non-nucleoside reverse transcriptase inhibitor (NNRTI) based regimen is recommended for antiretroviral naïve patients. The choice between nevirapine and efavirenz is based on differences in adverse events profiles; cost and availability of convenient fixed dose combinations and need for concomitant use of rifampicin. A backbone of 2-nucleoside reverse transcriptase inhibitors (NRTIs) is combined with the NNRTI. Various combinations and ART strategies not to be used in clinical practice has been enlisted. How to follow up? Recommendations have been made for baseline evaluation and monitoring of patients on ART. These include guidelines on laboratory and clinical evaluation. A plasma viral load at 6 months after initiation of first-line ART is strongly recommended. Yearly estimation of lipid profile has been recommended. How to identify and manage ART failure? The guidelines recognize the issue of identifying ART failure late if only CD4 counts are used for monitoring. In the absence of resistance testing various second-line regimens have been enlisted. A boosted protease inhibitor based regimen is recommended in this situation to be combined with 2-NRTIs. Special

  10. API consensus guidelines for use of antiretroviral therapy in adults (API-ART guidelines). Endorsed by the AIDS Society of India.

    PubMed

    Gupta, S B; Pujari, S N; Joshi, S R; Patel, A K

    2006-01-01

    With rational use of antiretroviral therapy (ART), human immunodeficiency virus (HIV) infection has been transformed into a chronic manageable illness like diabetes and hypertension. These guidelines provide information on state of art, evidence based approach for use of ART in Indian context. When to initiate ART? Antiretroviral therapy is indicated for all symptomatic HIV infected persons regardless of CD4 counts and plasma viral load (PVL) levels. In asymptomatic patients, ART should be offered when the CD4 counts < 200/mm3 and should be considered in patients with CD4 counts between 200-250/mm3. Therapy is not recommended for patients with CD4 count more than 350/ mm3. Involvement of patient in all treatment decisions and assessing readiness is critical before initiating ART. What to start with? A non-nucleoside reverse transcriptase inhibitor (NNRTI) based regimen is recommended for antiretroviral naïve patients. The choice between nevirapine and efavirenz is based on differences in adverse events profiles; cost and availability of convenient fixed dose combinations and need for concomitant use of rifampicin. A backbone of 2-nucleoside reverse transcriptase inhibitors (NRTIs) is combined with the NNRTI. Various combinations and ART strategies not to be used in clinical practice has been enlisted. How to follow up? Recommendations have been made for baseline evaluation and monitoring of patients on ART. These include guidelines on laboratory and clinical evaluation. A plasma viral load at 6 months after initiation of first-line ART is strongly recommended. Yearly estimation of lipid profile has been recommended. How to identify and manage ART failure? The guidelines recognize the issue of identifying ART failure late if only CD4 counts are used for monitoring. In the absence of resistance testing various second-line regimens have been enlisted. A boosted protease inhibitor based regimen is recommended in this situation to be combined with 2-NRTIs. Special

  11. 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.

  12. The GlueX Start Counter

    NASA Astrophysics Data System (ADS)

    Llodra, Anthony; Pooser, Eric; GlueX Collaboration

    2015-04-01

    The GlueX experiment, which is online as of October of 2014, will study meson photo production with unprecedented precision. This experiment will use the coherent bremsstrahlung technique to produce a 9 GeV linearly polarized photon beam incident on a liquid H2 target kept at a few degrees Kelvin. A Start Counter detector has been fabricated to identify the accelerator electron beam buckets, approximately 2 nanoseconds apart, and to provide accurate timing information. This detector is designed to operate at photon intensities of up to 108 γ/s in the coherent peak and provide a timing resolution of less than 350 picoseconds so as to provide successful identification of the electron beam buckets. It consists of a cylindrical array of 30 scintillators with pointed ends that bend towards the beam at the downstream end. The EJ-200 scintillator is best suited for the Start Counter due to its fast decay time on the order of 2 nanoseconds and long attenuation length. Silicon Photo Multiplier (SiPM) detectors have been selected as the readout system and are to be placed as close as possible, less than 300 micron, to the upstream end of each scintillator. The methods/details of the assembly and the optimization of the surface quality of scintillator paddles are discussed. This work was supported in part by DoE Contracts DE-FG02-99ER41065 and DE-AC05-06OR23177.

  13. Antiretroviral Resistance After First-Line Antiretroviral Therapy Failure in Diverse HIV-1 Subtypes in the SECOND-LINE Study.

    PubMed

    Lam, Edward P; Moore, Cecilia L; Gotuzzo, Eduardo; Nwizu, Chidi; Kamarulzaman, Adeeba; Chetchotisakd, Ploenchan; van Wyk, Jean; Teppler, Hedy; Kumarasamy, Nagalingeswaran; Molina, Jean-Michel; Emery, Sean; Cooper, David A; Boyd, Mark A

    2016-09-01

    We investigate mutations and correlates according to HIV-1 subtype after virological failure (VF) of standard first-line antiretroviral therapy (ART) (non-nucleoside/nucleotide reverse transcriptase inhibitor [NNRTI] +2 nucleoside/nucleotide reverse transcriptase inhibitor [N(t)RTI]). SECOND-LINE study participants were assessed at baseline for HIV-1 subtype, demographics, HIV-1 history, ART exposure, viral load (VL), CD4(+) count, and genotypic ART resistance. We used backward stepwise multivariate regression (MVR) to assess associations between baseline variables and presence of ≥3 N(t)RTI mutations, ≥1 NNRTI mutation, ≥3 thymidine analog-N(t)RTI [ta-N(t)RTI] mutations (TAMs), the K65/K70 mutation, and predicted etravirine (ETV)/rilpivirine (RPV) activity. The inclusion p-value for MVR was p < .2. The exclusion p-value from stepwise elimination was p > .05. Of 541 participants, 491 (91%) had successfully characterized baseline viral isolates. Subtype distribution: B (n = 123, 25%), C (n = 202, 41%), CRF01_AE (n = 109, 22%), G (n = 25, 5%), and CRF02_AG (n = 27, 5%). Baseline CD4(+) 200-394 cells/mm(3) were associated with <3 N(t)RTI mutations (OR = 0.47; 95% CI 0.29-0.77; p = .003), absence of the K65/K70 mutation (OR = 0.43; 95% CI 0.26-0.73; p = .002), and higher ETV sensitivity (OR = 0.52; 95% CI 0.35-0.78; p = .002). Recent tenofovir (TDF) use was associated with K65/K70 mutations (OR = 8.91; 95% CI 5.00-15.85; p < .001). Subtype CRF01_AE was associated with ≥3 N(t)RTI mutations (OR = 2.34; 95% CI 1.31-4.17; p = .004) and higher RPV resistance (OR = 2.13; 95% CI 1.30-3.49; p = .003), and subtype C was associated with <3 TAMs (OR = 0.45; 95% CI 0.21-0.99; p = .015). Subtypes CRF01_AE (OR = 2.46; 95% CI 1.26-4.78; p = .008) and G (OR = 4.77; 95% CI 1.44-15.76; p = .01) were associated with K65/K70 mutations. Higher VL at confirmed first-line VF was

  14. Elevated CD8 T-cell counts and virological failure in HIV-infected patients after combination antiretroviral therapy

    PubMed Central

    Ku, Nam Su; Jiamsakul, Awachana; Ng, Oon Tek; Yunihastuti, Evy; Cuong, Do Duy; Lee, Man Po; Sim, Benedict Lim Heng; Phanuphak, Praphan; Wong, Wing-Wai; Kamarulzaman, Adeeba; Zhang, Fujie; Pujari, Sanjay; Chaiwarith, Romanee; Oka, Shinichi; Mustafa, Mahiran; Kumarasamy, Nagalingeswaran; Van Nguyen, Kinh; Ditangco, Rossana; Kiertiburanakul, Sasisopin; Merati, Tuti Parwati; Durier, Nicolas; Choi, Jun Yong

    2016-01-01

    Abstract Elevated CD8 counts with combination antiretroviral therapy (cART) initiation may be an early warning indicator for future treatment failure. Thus, we investigated whether elevated CD8 counts were associated with virological failure (VF) in the first 4 years of cART in Asian HIV-infected patients in a multicenter regional cohort. We included patients from the TREAT Asia HIV Observational Database (TAHOD). Patients were included in the analysis if they started cART between 1996 and 2013 with at least one CD8 measurement within 6 months prior to cART initiation and at least one CD8 and viral load (VL) measurement beyond 6 months after starting cART. We defined VF as VL ≥400 copies/mL after 6 months on cART. Elevated CD8 was defined as CD8 ≥1200 cells/μL. Time to VF was modeled using Cox regression analysis, stratified by site. In total, 2475 patients from 19 sites were included in this analysis, of whom 665 (27%) experienced VF in the first 4 years of cART. The overall rate of VF was 12.95 per 100 person-years. In the multivariate model, the most recent elevated CD8 was significantly associated with a greater hazard of VF (HR = 1.35, 95% CI 1.14–1.61; P = 0.001). However, the sensitivity analysis showed that time-lagged CD8 measured at least 6 months prior to our virological endpoint was not statistically significant (P = 0.420). This study indicates that the relationship between the most recent CD8 count and VF was possibly due to the CD8 cells reacting to the increase in VL rather than causing the VL increase itself. However, CD8 levels may be a useful indicator for VF in HIV-infected patients after starting cART. PMID:27512885

  15. Elevated CD8 T-cell counts and virological failure in HIV-infected patients after combination antiretroviral therapy.

    PubMed

    Ku, Nam Su; Jiamsakul, Awachana; Ng, Oon Tek; Yunihastuti, Evy; Cuong, Do Duy; Lee, Man Po; Sim, Benedict Lim Heng; Phanuphak, Praphan; Wong, Wing-Wai; Kamarulzaman, Adeeba; Zhang, Fujie; Pujari, Sanjay; Chaiwarith, Romanee; Oka, Shinichi; Mustafa, Mahiran; Kumarasamy, Nagalingeswaran; Van Nguyen, Kinh; Ditangco, Rossana; Kiertiburanakul, Sasisopin; Merati, Tuti Parwati; Durier, Nicolas; Choi, Jun Yong

    2016-08-01

    Elevated CD8 counts with combination antiretroviral therapy (cART) initiation may be an early warning indicator for future treatment failure. Thus, we investigated whether elevated CD8 counts were associated with virological failure (VF) in the first 4 years of cART in Asian HIV-infected patients in a multicenter regional cohort.We included patients from the TREAT Asia HIV Observational Database (TAHOD). Patients were included in the analysis if they started cART between 1996 and 2013 with at least one CD8 measurement within 6 months prior to cART initiation and at least one CD8 and viral load (VL) measurement beyond 6 months after starting cART. We defined VF as VL ≥400 copies/mL after 6 months on cART. Elevated CD8 was defined as CD8 ≥1200 cells/μL. Time to VF was modeled using Cox regression analysis, stratified by site.In total, 2475 patients from 19 sites were included in this analysis, of whom 665 (27%) experienced VF in the first 4 years of cART. The overall rate of VF was 12.95 per 100 person-years. In the multivariate model, the most recent elevated CD8 was significantly associated with a greater hazard of VF (HR = 1.35, 95% CI 1.14-1.61; P = 0.001). However, the sensitivity analysis showed that time-lagged CD8 measured at least 6 months prior to our virological endpoint was not statistically significant (P = 0.420).This study indicates that the relationship between the most recent CD8 count and VF was possibly due to the CD8 cells reacting to the increase in VL rather than causing the VL increase itself. However, CD8 levels may be a useful indicator for VF in HIV-infected patients after starting cART. PMID:27512885

  16. Intensive Tuberculosis Screening for HIV-Infected Patients Starting ART in Durban, South Africa

    PubMed Central

    Bassett, Ingrid V.; Wang, Bingxia; Chetty, Senica; Giddy, Janet; Losina, Elena; Mazibuko, Matilda; Bearnot, Benjamin; Allen, Jenny; Tech, B; Walensky, Rochelle P.; Freedberg, Kenneth A.

    2011-01-01

    Background The World Health Organization (WHO) recommends cough as the trigger for tuberculosis (TB) screening in HIV-infected patients, with acid fast bacillus (AFB) smear as the initial diagnostic test. Our objective was to assess the yield and cost of a more intensive TB screening in HIV-infected patients starting antiretroviral therapy (ART) in Durban, South Africa. Methods We prospectively enrolled adults, regardless of TB signs/symptoms, undergoing pre-ART training from May ‘07–May ‘08. Following symptom screen, patients expectorated sputum for AFB smear, TB polymerase chain reaction (PCR), and mycobacterial culture. Sensitivity and specificity of different symptoms and tests, alone and in combination, were compared to a gold standard of 6-week TB culture results. Program costs included personnel, materials and cultures. Results Of 1,035 subjects, 487 (59%) were female; median CD4 count was 100/μl. Two-hundred and ten (20%) were receiving TB treatment and were excluded. Of the remaining 825 subjects, 158 (19%) had positive sputum cultures, of whom 14 (9%) had a positive AFB smear and 82 (52%) reported cough. The combination of cough, other symptoms, AFB smear, and chest x-ray had 93% (CI 88–97%) sensitivity and 15% (CI 13–18%) specificity. The incremental cost of intensive screening including culture was $360/additional TB case identified. Conclusions Nearly 20% of patients starting ART in Durban, South Africa had undiagnosed, culture-positive pulmonary TB. Despite WHO recommendations, neither cough nor AFB smear were adequately sensitive for screening. TB sputum cultures should be performed before ART initiation, regardless of symptoms, in areas of high HIV/TB prevalence. PMID:20735240

  17. Prevalence and Outcomes of Hepatitis B Coinfection and Associated Liver Disease Among Antiretroviral Therapy-Naive Individuals in a Rural Tanzanian Human Immunodeficiency Virus Cohort

    PubMed Central

    Ramírez-Mena, Adrià; Glass, Tracy R.; Winter, Annja; Kimera, Namvua; Ntamatungiro, Alex; Hatz, Christoph; Tanner, Marcel; Battegay, Manuel; Furrer, Hansjakob; Wandeler, Gilles; Letang, Emilio

    2016-01-01

    Background. We evaluated the prevalence of chronic hepatitis B virus (HBV) infection and liver fibrosis/cirrhosis in human immunodeficiency virus (HIV)-infected individuals enrolled in a rural Tanzanian prospective cohort and assessed hepatic fibrosis progression 12–24 months after antiretroviral treatment (ART) initiation. Methods. All ART-naive HIV-infected adults ≥15-year-old enrolled in the Kilombero and Ulanga Antiretroviral Cohort who started ART between 2005 and 2015 were included. Pre-ART factors associated with significant liver fibrosis (aspartate aminotransferase-to-platelet ratio index [APRI] >1.5) and cirrhosis (APRI > 2.0) were identified using logistic regression. Results. Of 3097 individuals screened, 227 (7.3%; 95% CI, 6.4–8.2) were hepatitis B surface antigen (HBsAg) positive. Before ART initiation, 9.1% individuals had significant liver fibrosis and 5.3% had cirrhosis. Human immunodeficiency virus/HBV-coinfected individuals were more likely to have an APRI score indicating significant fibrosis (14.2% vs 8.7%, P = .03) and cirrhosis (9.2% vs 4.9%, P = .03) than HBV-uninfected patients. CD4 cell count <200 cell/μL and alcohol consumption were independently associated with pre-ART APRI score, indicating significant fibrosis and cirrhosis in multivariable analyses. Among individuals with elevated APRI measurements pre- and 12–24 months post-ART initiation, 53 of 57 (93.0%) of HIV-monoinfected and 4 of 5 (80.0%) of HIV/HBV-coinfected had a regression to APRI < 1.5. Conclusions. Hepatic fibrosis and cirrhosis were common in our cohort, especially among HIV/HBV-coinfected individuals. The APRI improved in most patients. Pre-ART HBsAg screening and early onset of tenofovir-based ART for HIV/HBV-coinfection should be prioritized in sub-Saharan Africa.

  18. Hepatic steatosis in HIV-HCV coinfected patients receiving antiretroviral therapy is associated with HCV-related factors but not antiretrovirals

    PubMed Central

    2012-01-01

    Background In HIV and hepatitis C virus (HCV) coinfected patients, the role of antiretroviral therapy (ART) on hepatic steatosis (HS) remains controversial. Methods HIV/HCV coinfected patients receiving ART and previously untreated for HCV who underwent a liver biopsy were included. Cumulative duration of exposure to each antiretroviral was recorded up to liver biopsy date. Logistic regression analyses evaluated factors associated with steatosis and its severity. Results 184 patients were included: median age 41years, 84% male, 89% Caucasian, 61% with a past history of intravenous drug use. HCV genotypes were 1 (55%), 2 (6%), 3 (26%), and 4 (13%). Median HCV-RNA was 6.18 log10 IU/ml. HIV-RNA was undetectable (<400 copies/ml) in 67% of patients. Median CD4 count was 321/mm3. All patients had been exposed to nucleoside reverse transcriptase inhibitors (median cumulative exposure 56months); 126 received protease inhibitors (23months), and 79 non-nucleoside reverse transcriptase inhibitors (16months). HS was observed in 102 patients (55%): 41% grade 1; 5% grade 2, and 9% grade 3. In multivariate analysis, HCV genotype 3 and HCV viral load were moderately associated with mild steatosis but strongly with grade 2-3 steatosis. After adjustment for the period of biopsy, no association was detected between HS and exposure to any antiretroviral class or drug, or duration of ART globally or comparing genotype 3 to others. Conclusions Among our ART-treated HIV-HCV cohort predominantly infected with genotype 1, 55% of patients had HS which was associated with HCV-related factors, but not ART class or duration of exposure. PMID:22490728

  19. Novel Codon Insert in HIV Type 1 Clade B Reverse Transcriptase Associated with Low-Level Viremia During Antiretroviral Therapy

    PubMed Central

    Gianella, Sara; Vazquez, Homero; Ignacio, Caroline; Zweig, Adam C.; Richman, Douglas D.; Smith, Davey M.

    2014-01-01

    Abstract We investigated the pol genotype in two phylogenetically and epidemiologically linked partners, who were both experiencing persistent low-level viremia during antiretroviral therapy. In one partner we identified a new residue insertion between codon 248 and 249 of the HIV-1 RNA reverse transcriptase (RT) coding region (HXB2 numbering). We then investigated the potential impact of identified mutations in RT and antiretroviral binding affinity using a novel computational approach. PMID:24020934

  20. CD4 responses in the setting or suboptimal virological responses to antiretroviral therapy: features, outcomes, and associated factors.

    PubMed

    Collazos, Julio; Asensi, Víctor; Cartón, José Antonio

    2009-07-01

    The factors associated with discordant viroimmunological responses following antiretroviral therapy are unclear. We studied 1380 patients who initiated a protease inhibitor (PI)-based antiretroviral regimen and who fulfilled the criteria for inclusion. Of them, 255 (18.5%) had CD4 increases > or =100 cells/microl after 1 year of therapy despite detectable viral load (immunological responders); they were compared with 669 patients (48.5%) who had CD4 increases <100 cells/microl regardless of their final viral load (immunological nonresponders). Immunological responders had higher rates of sexual acquisition of HIV (p = 0.03), lower rates of clinical progression (p = 0.02), higher probabilities of being naive to antiretroviral therapy (p = 0.006) or to PI if antiretroviral experienced (p = 0.03), higher rates of receiving only nucleoside reverse transcriptase inhibitors in addition to the PI (p = 0.04), and lower baseline CD4 counts (p = 0.007) and higher viral loads (p = 0.009), as compared with nonresponders. Multivariate analysis revealed that sexual transmission of HIV (homosexual p = 0.004, heterosexual p = 0.03), no prior PI experience (p = 0.005), absence of clinical progression (p = 0.02), and lower baseline CD4 counts (p = 0.03) were independently associated with immunological response. However, these factors differed according to the patients' prior antiretroviral status, as higher baseline viral load was also associated with immunological response in antiretroviral-experienced patients (p = 0.02), whereas baseline CD4 count (p = 0.007) was the only predictive parameter in antiretroviral-naive patients. We conclude that immunological responses despite suboptimal viral suppression are common. Prior PI experience, HIV transmission category, baseline CD4 counts, and clinical progression were independently predictive of this condition, although the associated factors were different depending on the patient's prior antiretroviral history.

  1. Method and apparatus for starting supersonic compressors

    SciTech Connect

    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.

  2. Getting started in medical education scholarship.

    PubMed

    Cook, David A

    2010-01-01

    Education scholarship and research are critically important in extending our ability to teach and assess effectively. Those considering a scholarly project in medical education should consider the following tips, learned from personal experience and supported by literature: 1) get some training, 2) find a mentor, 3) ask important questions, 4) start small and grow, 5) aim high, 6) don't wait for the perfect study, 7) plan for adequate time and other resources, 8) attend to ethical issues, 9) network with others in the field, and 10) recognize that this is hard work. By following these steps and planning ahead, scholars will be better poised to make meaningful contributions to the art and science of medical education.

  3. The UK sugar tax - a healthy start?

    PubMed

    Jones, C M

    2016-07-22

    The unexpected announcement by the UK Chancellor of the Exchequer of a levy on sugar sweetened beverages (SSBs) on the 16 March 2016, should be welcomed by all health professionals. This population based, structural intervention sends a strong message that there is no place for carbonated drinks, neither sugared nor sugar-free, in a healthy diet and the proposed levy has the potential to contribute to both general and dental health. The sugar content of drinks exempt from the proposed sugar levy will still cause tooth decay. Improving the proposed tax could involve a change to a scaled volumetric tax of added sugar with a lower exemption threshold. External influences such as the Common Agricultural Policy and the Transatlantic Trade and Investment Partnership may negate the benefits of the sugar levy unless it is improved. However, the proposed UK sugar tax should be considered as a start in improving the nation's diet.

  4. Move signals the 'start of new era'.

    PubMed

    Baillie, Jonathan

    2012-10-01

    Thirty-one years after its establishment in a small office in Wigan, independent life safety equipment manufacturer, C-TEC, has moved into a new 75,000 ft2 factory, 'the size of three football pitches', marking the start of what founder and MD, Andrew Foster, dubs 'the next phase in our exciting development'. The past year has also seen the firm busy on the new product front, with the launch of a 'revolutionary' new range of touchscreen-controlled analogue addressable fire alarms panels which the company claims will put it 'way ahead of the competition', and, in response to demand from nursing and care home operator customers, the introduction of a range of components designed to facilitate dementia care as an extension to its well-established Quantec addressable call system. HEJ editor, Jonathan Baillie, reports.

  5. Choosing Wisely? Let's Start with Working Wisely.

    PubMed

    Kurdyak, Paul; Wiesenfeld, Lesley; Sockalingam, Sanjeev

    2016-01-01

    There is an increasing emphasis on quality and, relatedly, cost-effectiveness as it relates to the delivery of health care. Choosing Wisely is an initiative adopted by numerous specialties with the goal of starting a dialogue about efficient use of health care resources. People need to be able to access care to have an opportunity to choose wisely. There is a considerable amount of evidence that access to care is poor for specialty mental health care, particularly access to psychiatrists. Consequently, we suggest that psychiatrists and the broader mental health system need to consider working wisely, and in our paper outline key issues (for example, implementation of wait times and objective measures of need in a centralized referral management system; incorporation of performance indicators with longitudinal monitoring for continuous quality improvement) that need to be addressed to develop a mental health system that would allow people to access care to choose wisely. PMID:27582450

  6. Re-starting an Arnoldi iteration

    SciTech Connect

    Lehoucq, R.B.

    1996-12-31

    The Arnoldi iteration is an efficient procedure for approximating a subset of the eigensystem of a large sparse n x n matrix A. The iteration produces a partial orthogonal reduction of A into an upper Hessenberg matrix H{sub m} of order m. The eigenvalues of this small matrix H{sub m} are used to approximate a subset of the eigenvalues of the large matrix A. The eigenvalues of H{sub m} improve as estimates to those of A as m increases. Unfortunately, so does the cost and storage of the reduction. The idea of re-starting the Arnoldi iteration is motivated by the prohibitive cost associated with building a large factorization.

  7. The UK sugar tax - a healthy start?

    PubMed

    Jones, C M

    2016-07-22

    The unexpected announcement by the UK Chancellor of the Exchequer of a levy on sugar sweetened beverages (SSBs) on the 16 March 2016, should be welcomed by all health professionals. This population based, structural intervention sends a strong message that there is no place for carbonated drinks, neither sugared nor sugar-free, in a healthy diet and the proposed levy has the potential to contribute to both general and dental health. The sugar content of drinks exempt from the proposed sugar levy will still cause tooth decay. Improving the proposed tax could involve a change to a scaled volumetric tax of added sugar with a lower exemption threshold. External influences such as the Common Agricultural Policy and the Transatlantic Trade and Investment Partnership may negate the benefits of the sugar levy unless it is improved. However, the proposed UK sugar tax should be considered as a start in improving the nation's diet. PMID:27444594

  8. Mortality and virologic outcomes following access to antiretroviral therapy among a cohort of HIV-infected women who received single-dose nevirapine in Lusaka, Zambia

    PubMed Central

    Kuhn, Louise; Semrau, Katherine; Ramachandran, Shobana; Sinkala, Moses; Scott, Nancy; Kasonde, Prisca; Mwiya, Mwiya; Kankasa, Chipepo; Decker, Don; Thea, Donald M.; Aldrovandi, Grace M.

    2009-01-01

    Objectives Single-dose nevirapine (SDNVP) for prevention of mother-to-child HIV transmission selects mutations conferring resistance to non-nucleoside reverse transcriptase inhibitor (NNRTI)-based therapy. We investigated mortality and virologic and clinical outcomes following introduction of antiretroviral treatment (ART) among a cohort of women given SDNVP. Methods When ART programs were introduced in 2004 in Lusaka, Zambia, we were completing a trial of infant feeding which involved following HIV-infected women who received SDNVP between 2001 and 2005. Women still in follow-up or who could be contacted were evaluated for eligibility for ART (CD4 count <200 or <350 and WHO stage ≥ 3) and started on NNRTI-based therapy if eligible. We compared mortality in the cohort of women before and after ART access, and examined, among women initiating ART, whether virologic response was better allowing a longer time to elapse between SDNVP and treatment initiation. Results In the cohort of 872 women, mortality more than halved after ART became available (relative hazard [RH] = 0.46 95% CI: 0.23–0.91 p=0.03). Of 161 SDNVP-exposed women followed on NNRTI-based ART, 70.8% suppressed (viral load <400 copies/ml). Only 3/8 (37.5%) women SDNVP-exposed <6 months of starting therapy suppressed compared to 13/22 (59.1%) who started 6–12 months, 44/61 (72.1 %) 12–24 months, and 54/70 (77.1%) >24 months post-exposure (chi-square trend p=0.01). Conclusions Most SDNVP-exposed women respond well to NNRTI-based therapy but there was an attenuation of therapy efficacy that persisted to 12 months after exposure. Women should be screened for ART eligibility during pregnancy and started on effective regimens before delivery. PMID:19506483

  9. 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...

  10. 46 CFR 112.50-7 - Compressed air starting.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 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...

  11. Head Start Celebrates 20th Anniversary and America's Future.

    ERIC Educational Resources Information Center

    Flores, Alfredo; And Others

    1985-01-01

    Articles in this serial publication highlight the past, present, and possible future of Project Head Start and celebrate the project's 20th birthday. "Head Start: Today and Yesterday" (Alfred Flores) emphasizes the goals of Head Start. "Why Head Start Is a Winner" (Mary Tom Riley and Jamie Tucker) reports the results of longitudinal studies of the…

  12. Impact of HIV-1 Subtype and Antiretroviral Therapy on Protease and Reverse Transcriptase Genotype: Results of a Global Collaboration

    PubMed Central

    2005-01-01

    Background The genetic differences among HIV-1 subtypes may be critical to clinical management and drug resistance surveillance as antiretroviral treatment is expanded to regions of the world where diverse non-subtype-B viruses predominate. Methods and Findings To assess the impact of HIV-1 subtype and antiretroviral treatment on the distribution of mutations in protease and reverse transcriptase, a binomial response model using subtype and treatment as explanatory variables was used to analyze a large compiled dataset of non-subtype-B HIV-1 sequences. Non-subtype-B sequences from 3,686 persons with well characterized antiretroviral treatment histories were analyzed in comparison to subtype B sequences from 4,769 persons. The non-subtype-B sequences included 461 with subtype A, 1,185 with C, 331 with D, 245 with F, 293 with G, 513 with CRF01_AE, and 618 with CRF02_AG. Each of the 55 known subtype B drug-resistance mutations occurred in at least one non-B isolate, and 44 (80%) of these mutations were significantly associated with antiretroviral treatment in at least one non-B subtype. Conversely, of 67 mutations found to be associated with antiretroviral therapy in at least one non-B subtype, 61 were also associated with antiretroviral therapy in subtype B isolates. Conclusion Global surveillance and genotypic assessment of drug resistance should focus primarily on the known subtype B drug-resistance mutations. PMID:15839752

  13. Population-level associations between antiretroviral therapy scale-up and all-cause mortality in South Africa.

    PubMed

    Larson, Elysia; Bendavid, Eran; Tuoane-Nkhasi, Maletela; Mbengashe, Thobile; Goldman, Thurma; Wilson, Melinda; Klausner, Jeffrey D

    2014-08-01

    Our aim was to describe the association between increasing access to antiretroviral therapy and all-cause mortality in South Africa from 2005 to 2009. We undertook a longitudinal, population-level study, using antiretroviral monitoring data reported by PEPFAR implementing partners and province-level and national all-cause mortality records from Statistics South Africa (provider of official South African government statistics) to analyse the association between antiretroviral therapy and mortality. Using mixed effects models with a random intercept for province, we estimated the contemporaneous and lagging association between antiretroviral therapy and all-cause mortality in South Africa. We also conducted subgroup analyses and estimated the number of deaths averted. For each 100 HIV-infected individuals on antiretroviral therapy reported by PEPFAR implementing partners in South African treatment programmes, there was an associated 2.9 fewer deaths that year (95% CI: 1.5, 4.2) and 6.3 fewer deaths the following year (95% CI: 4.6, 8.0). The associated decrease in mortality the year after treatment reporting was seen in both adults and children, and men and women. Treatment provided from 2005 to 2008 was associated with 28,305 deaths averted from 2006 to 2009. The scale-up of antiretroviral therapy in South Africa was associated with a significant reduction in national all-cause mortality.

  14. 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

  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. A Pilot Study of Raltegravir Plus Combination Antiretroviral Therapy in Early Human Immunodeficiency Virus Infection: Challenges and Lessons Learned.

    PubMed

    Collier, Ann C; Chun, Tae-Wook; Maenza, Janine; Coombs, Robert W; Tapia, Kenneth; Chang, Ming; Stevens, Claire E; Justement, J Shawn; Murray, Danielle; Stekler, Joanne D; Mullins, James I; Holte, Sarah E

    2016-01-01

    Availability of integrase strand transfer inhibitors created interest in determining whether their use would decrease persistently infected cell numbers. This study hypothesized that adding raltegravir (RAL) to standard antiretroviral therapy (ART) would decrease human immunodeficiency virus (HIV)-infected CD4(+) T cells more than standard combination ART. This was a pilot, randomized study comparing open-label standard triple ART to standard triple ART plus RAL over 96 weeks in ART-naive adults with early HIV infection. The primary objective was to compare quantity and trajectory of HIV DNA. Eighty-two persons were referred. A diverse set of reasons precluded the enrollment of all but 10. Those who enrolled and completed the study had an estimated median duration of HIV infection of 74 days at ART start. The groups had similar baseline characteristics. The RAL group had more rapid first phase plasma HIV RNA decay (0.67 log10 copies/mL/day) than with combination ART (0.34 log10copies/mL/day), p = 0.037. Second phase HIV RNA decay, residual viremia, cell-associated RNA, HIV DNA, CD4(+) T-cells with replication-competent virus, and 2LTR circle levels did not differ between groups. Among those with entry plasma HIV RNA levels above the median, 2LTR circles were significantly lower over time than in those with lower entry HIV RNA levels (p = 0.02). Our results suggest homogeneity of responses in cell-associated RNA, HIV DNA, CD4(+) T-cells with replication-competent virus, and 2LTR circles with early HIV in both ART groups. The kinetics of 2LTR DNA did not reflect the kinetics of plasma HIV RNA decline following ART initiation.

  17. Survival of people on antiretroviral treatment in Zambia: a retrospective cohort analysis of HIV clients on ART

    PubMed Central

    Amanzi, Patrick; Michelo, Charles; Simoonga, Christopher; Dambe, Rosalia; Chongwe, Gershom

    2016-01-01

    Introduction Provision of free anti-retroviral therapy in Zambia started in June 2004. There were only 15,000 people on treatment as at December that year, mainly due to lack of access. This number rose to 580,000 people as at December 2013. The general objective of this study was to determine survival of people on ART and to examine associated predictors for survival. Methods The study included ART patients enrolled between the year 2002 and 2013 (n=10,395) in 285 health facilities in Zambia. Patient files were analyzed retrospectively. The study used Kaplan Meier and Cox-proportional hazard models to describe the relationship between lost to follow up and age, sex, baseline CD4 cell count and weight. Results Results showed that lost to follow up accounted for 90% of the clients that had dropped out, while 10% was to deaths. Low baseline CD4 count (p-value 0.001, HR 0.9994, (95% CI 0.9993, 0.9996) at initiation was associated with lost to follow up together with weight at initiation (p-value 0.031, HR 0.9987 at 95% CI (0.9975, 0.9998)) of ART. Conclusion This study has demonstrated that lost to follow up is a substantial contributing factor to drop outs among HIV patients on treatment. Strengthening of community treatment supporters especially immediate family members in emphasizing to the client the need to continue treatment is necessary. The health facility could do more in emphasizing the importance of treatment especially in the initial stages. Further, in order to reduce opportunistic infections and probable deaths during treatment, cotrimoxazole prophylaxis should be maintained so as to raise the CD4 levels. Improved nutritional assessment and counseling to boost the nutritional status of the clients throughout should be encouraged. PMID:27642482

  18. 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

  19. Antiretroviral drug expenditure, pricing and judicial demand: an analysis of federal procurement data in Brazil from 2004–2011

    PubMed Central

    2014-01-01

    Background Previous studies have described expenditures for antiretroviral (ARV) medicines in Brazil through 2005. While prior studies examined overall expenditures, they have not have analyzed drug procurement data in order to describe the role of court litigation on access and pricing. Methods ARV drug procurement from private sector sources for the years 2004–2011 was obtained through the general procurement database of the Brazilian Federal Government (SIASG). Procurement was measured in Defined Daily Doses (DDD) per 1000 persons-under-treatment per day. Expenditures and price per DDD were calculated and expressed in U.S. Dollars. Justifications for ARV purchases were examined in order to determine the relationship between health litigation and incorporation into Brazil’s national treatment guidelines. Results Drug procurement of ARVs from private sources underwent marked expansion in 2005, peaked in 2009, and stabilized to 2008 levels by 2011. Expenditures followed procurement curves. Medications which were procured for the first time after 2007 cost more than medicines which were introduced before 2007. Judicial actions initially resulted in purchases of newer medications for a select number of patients in Brazil but ultimately expanded availability to a larger population through incorporation into the national treatment guidelines. Conclusions Drug procurement and expenditures for ARVs in Brazil varied between 2004–2011. The procurement of some drugs from the private sector ceased after public manufacturers started producing them locally. Judicial demand has resulted in the incorporation of newer drugs into the national treatment guidelines. In order for the AIDS treatment program to remain sustainable, efforts should be pursued to reduce prices through generic drugs, price negotiation and other public health flexibilities such as compulsory licensing. PMID:24735589

  20. 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

  1. Monitoring and Switching of First-line Antiretroviral Therapy in sub-Saharan Africa: Collaborative Analysis of Adult Treatment Cohorts

    PubMed Central

    Haas, Andreas D.; Keiser, Olivia; Balestre, Eric; Brown, Steve; Bissagnene, Emmanuel; Chimbetete, Cleophas; Dabis, François; Davies, Mary-Ann; Hoffmann, Christopher J.; Oyaro, Patrick; Parkes-Ratanshi, Rosalind; Reynolds, Steven J.; Sikazwe, Izukanji; Wools-Kaloustian, Kara; Zannou, Djimon Marcel; Wandeler, Gilles; Egger, Matthias

    2015-01-01

    Background HIV-1 viral load (VL) testing is recommended to monitor antiretroviral therapy (ART) but not universally available. We examined monitoring of first-line and switching to second-line ART in sub-Saharan Africa, 2004–2013. Methods Adult HIV-1 infected patients starting combination ART in 16 countries were included. Switching was defined as a change from a non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based regimen to a protease inhibitor (PI)-based regimen, with a change of ≥1 NRTI. Virological and immunological failures were defined per World Health Organization criteria. We calculated cumulative probabilities of switching and hazard ratios with 95% confidence intervals (CI) comparing routine VL monitoring, targeted VL monitoring, CD4 cell monitoring and clinical monitoring, adjusted for programme and individual characteristics. Findings Of 297,825 eligible patients, 10,352 patients (3·5%) switched during 782,412 person-years of follow-up. Compared to CD4 monitoring hazard ratios for switching were 3·15 (95% CI 2·92–3·40) for routine VL, 1·21 (1·13–1·30) for targeted VL and 0·49 (0·43–0·56) for clinical monitoring. Overall 58.0% of patients with confirmed virological and 19·3% of patients with confirmed immunological failure switched within 2 years. Among patients who switched the percentage with evidence of treatment failure based on a single CD4 or VL measurement ranged from 32·1% with clinical to 84.3% with targeted VL monitoring. Median CD4 counts at switching were 215 cells/µl under routine VL monitoring but lower with other monitoring (114–133 cells/µl). Interpretation Overall few patients switched to second-line ART and switching occurred late in the absence of routine viral load monitoring. Switching was more common and occurred earlier with targeted or routine viral load testing. PMID:26423252

  2. A Pilot Study of Raltegravir Plus Combination Antiretroviral Therapy in Early Human Immunodeficiency Virus Infection: Challenges and Lessons Learned.

    PubMed

    Collier, Ann C; Chun, Tae-Wook; Maenza, Janine; Coombs, Robert W; Tapia, Kenneth; Chang, Ming; Stevens, Claire E; Justement, J Shawn; Murray, Danielle; Stekler, Joanne D; Mullins, James I; Holte, Sarah E

    2016-01-01

    Availability of integrase strand transfer inhibitors created interest in determining whether their use would decrease persistently infected cell numbers. This study hypothesized that adding raltegravir (RAL) to standard antiretroviral therapy (ART) would decrease human immunodeficiency virus (HIV)-infected CD4(+) T cells more than standard combination ART. This was a pilot, randomized study comparing open-label standard triple ART to standard triple ART plus RAL over 96 weeks in ART-naive adults with early HIV infection. The primary objective was to compare quantity and trajectory of HIV DNA. Eighty-two persons were referred. A diverse set of reasons precluded the enrollment of all but 10. Those who enrolled and completed the study had an estimated median duration of HIV infection of 74 days at ART start. The groups had similar baseline characteristics. The RAL group had more rapid first phase plasma HIV RNA decay (0.67 log10 copies/mL/day) than with combination ART (0.34 log10copies/mL/day), p = 0.037. Second phase HIV RNA decay, residual viremia, cell-associated RNA, HIV DNA, CD4(+) T-cells with replication-competent virus, and 2LTR circle levels did not differ between groups. Among those with entry plasma HIV RNA levels above the median, 2LTR circles were significantly lower over time than in those with lower entry HIV RNA levels (p = 0.02). Our results suggest homogeneity of responses in cell-associated RNA, HIV DNA, CD4(+) T-cells with replication-competent virus, and 2LTR circles with early HIV in both ART groups. The kinetics of 2LTR DNA did not reflect the kinetics of plasma HIV RNA decline following ART initiation. PMID:26862469

  3. Reliability of reporting of HIV status and antiretroviral therapy usage during verbal autopsies: a large prospective study in rural Malawi

    PubMed Central

    Mclean, Estelle M.; Chihana, Menard; Mzembe, Themba; Koole, Olivier; Kachiwanda, Lackson; Glynn, Judith R.; Zaba, Basia; Nyirenda, Moffat; Crampin, Amelia C.

    2016-01-01

    Objective Verbal autopsies (VAs) are interviews with a relative or friend of the deceased; VAs are a technique used in surveillance sites in many countries with incomplete death certification. The goal of this study was to assess the accuracy and validity of data on HIV status and antiretroviral therapy (ART) usage reported in VAs and their influence on physician attribution of cause of death. Design This was a prospective cohort study. Methods The Karonga Health and Demographic Surveillance Site monitors demographic events in a population in a rural area of northern Malawi; a VA is attempted on all deaths reported. VAs are reviewed by clinicians, who, with additional HIV test information collected pre-mortem, assign a cause of death. We linked HIV/ART information reported by respondents during adult VAs to database information on HIV testing and ART use and analysed agreement using chi-square and kappa statistics. We used multivariable logistic regression to analyse factors associated with agreement. Results From 2003 to 2014, out of a total of 1,952 VAs, 80% of respondents reported the HIV status of the deceased. In 2013–2014, this figure was 99%. Of those with an HIV status known to the study, there was 89% agreement on HIV status between the VA and pre-mortem data, higher for HIV-negative people (92%) than HIV-positive people (83%). There was 84% agreement on whether the deceased had started ART, and 72% of ART initiation dates matched within 1 year. Conclusions In this population, HIV/ART information was often disclosed during a VA and matched well with other data sources. Reported HIV/ART status appears to be a reliable source of information to help classification of cause of death. PMID:27293122

  4. A Study of Compliance to Antiretroviral Therapy among HIV Infected Patients at a Tertiary Care Hospital in North Karnataka

    PubMed Central

    Hasabi, Ishwar Siddappa; Kachapur, Chandrashekar; Kaulgud, Ram Suresh

    2016-01-01

    Introduction Compliance to Antiretroviral Therapy (ART) is a primary determinant of treatment success of HIV-AIDS. Many studies have shown inadequate compliance to ART in the Indian population. Aim To assess the compliance to ART among HIV infected patients, to explore the factors affecting compliance and impact of compliance on CD4 count. Materials and Methods A cross-sectional study was conducted with 200 adult patients attending ART center, KIMS, Hubli. The patients were randomly selected and compliance to ART over preceding 3 months was assessed. Reasons for non- compliance were assessed among those with inadequate compliance. Results Mean age of the study population was 40.07±9.99 years. The sex ratio was 1.02:1 (M:F). Majority of patients were in WHO stage 1 with treatment, with CD4 count above 500/μl. Pulmonary tuberculosis was the most common opportunistic infection. Most of the patients were on long term ART, more than 5 years {81 (40.5%)}. Most of the patients were on ZLN regimen {97 (48.5%)}. Compliance over the preceding 3 months was 94.84± 14.93% for ART and 88.97±23.75% for opportunistic infection prophylaxis. There was no significant difference in compliance in relation to age group, sex, educational status, residence, religion, habits, HIV status of spouse or child, the regimen of ART and frequency of dosing. The compliance was better among those on long term treatment, i.e., those on treatment for more than 5 years compared to those who started ART in last 1 year (p=0.06). The most common reasons given by patients for non-compliance were going away from home, busy with other work and simply forgot. Better compliance was associated with higher CD4 count. Conclusion Compliance to ART was inadequate in the studied population, which is a major obstacle to success of ART. PMID:27437267

  5. 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

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

    PubMed Central

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

    2011-01-01

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

  7. Antiretroviral regimen and suboptimal medication adherence are associated with low-level human immunodeficiency virus viremia.

    PubMed

    Konstantopoulos, Christina; Ribaudo, Heather; Ragland, Kathleen; Bangsberg, David R; Li, Jonathan Z

    2015-01-01

    Episodes of human immunodeficiency virus low-level viremia (LLV) are common in the clinical setting, but its association with antiretroviral therapy (ART) regimen and adherence remains unclear. Antiretroviral therapy adherence was evaluated in participants of the Research on Access to Care in the Homeless cohort by unannounced pill counts. Factors associated with increased risk of LLV include treatment with a protease inhibitor (PI)-based regimen (ritonavir-boosted PI vs nonnucleoside reverse-transcriptase inhibitor: adjusted hazard ratio [HR], 3.1; P = .01) and lower ART adherence over the past 3 months (HR, 1.1 per 5% decreased adherence, adjusted; P = .050). Patients with LLV may benefit from ART adherence counseling and potentially regimen modification. PMID:25884007

  8. Choosing Initial Antiretroviral Therapy: Current Recommendations for Initial Therapy and Newer or Investigational Agents.

    PubMed

    Gulick, Roy M

    2015-01-01

    There is general consistency among US and European guidelines regarding the initiation of antiretroviral therapy for HIV-infected individuals. Recent and ongoing trials comparing regimens may lead to reevaluation of initial treatment choices. The choice of antiretroviral regimen will also likely be affected by development, evaluation, and availability of newer drugs. This article reviews currently recommended regimens and characteristics of selected current investigational drugs, including the nucleotide analogue reverse transcriptase inhibitor tenofovir alafenamide, the nonnucleoside reverse transcriptase inhibitor doravirine, the integrase strand transfer inhibitor cabotegravir, the HIV entry inhibitor BMS-663068, and the HIV maturation inhibitor BMS-955176. This article summarizes a presentation by Roy M. Gulick, MD, MPH, at the IAS-USA continuing education program, Improving the Management of HIV Disease, held in New York, New York, in March 2015 and September 2015. PMID:26713502

  9. Displacement and HIV: Factors Influencing Antiretroviral Therapy Use by Ethnic Shan Migrants in Northern Thailand.

    PubMed

    Murray, Jordan K; DiStefano, Anthony S; Yang, Joshua S; Wood, Michele M

    2016-01-01

    Migrant populations face increased HIV vulnerabilities, including limited access to antiretroviral therapy. Civil conflict in Myanmar has displaced thousands of people from the minority Shan ethnic group into northern Thailand, where they bear a disproportionate HIV burden. To identify barriers and facilitators of antiretroviral therapy use in this population, we conducted a rapid ethnographic assessment and case study with a clinical sample of Shan migrants receiving treatment for HIV in a district hospital in Chiang Mai, Thailand, Thai nurses providing their care, and health care administrators (n = 23). Barriers included fears of arrest and deportation, communication difficulties, perceived social marginalization, limited HIV knowledge, and lack of finances. Facilitating factors included hospital-based migrant registration services and community outreach efforts involving support group mobilization, referral practices, and radio broadcasts. These findings provided a contextualized account to inform policies, community interventions, and nursing practice to increase treatment access for minority migrant groups. PMID:27188762

  10. Biomedicine, public health, and citizenship in the advent of antiretrovirals in Botswana.

    PubMed

    Chabrol, Fanny

    2014-08-01

    Often celebrated as a model of development in Africa, Botswana nonetheless endured a severe HIV epidemic. This article describes the singularity of the Botswana experience in facing AIDS and creating the widest possible access to antiretroviral medications for its citizens. Through exploration of different sets of actors and the construction of their ethics of treatment, it is possible to examine how free and universal access was created within the national antiretroviral program. This article underscores the importance of the site and the local dynamics in the advent of an ethics of access to treatment for Botswana citizens. At the intersection of national citizenship, pharmaceutical philanthropy, and biomedical collaborations, Botswana is an exemplary case (one of the first and unique in its kind) of global health programs for access to drugs in which patients' rights are tied to science and pharmaceutical development. As such it also bears some limitations and concerns over its sustainability.

  11. HIV/AIDS and Infertility: Emerging Problems in the Era of Highly Active Antiretrovirals

    PubMed Central

    Kushnir, Vitaly A.; Lewis, William

    2011-01-01

    Objective To review the effects of HIV/AIDS, associated co-morbid conditions, and side effects of antiretroviral treatment on fertility. Design A Pubmed computer search was performed to identify relevant articles. Setting Research institution. Intervention(s) None. Result(s) Biological alterations in reproductive physiology may account for sub-fertility in patients infected with HIV. Psychosocial factors in patients with HIV infection may affect reproductive desires and outcomes. Antiretroviral medications may have direct toxicity on gametes and embryos. Available evidence indicates that fertility treatments can be a safe option for HIV-discordant couples; although, potential risk of viral transmission cannot be completely eliminated. Conclusion(s) Reproductive desires are increasingly becoming prominent in the healthcare of young HIV-infected patients. Additional data is needed to address the effect of HIV and its treatments on fertility and reproductive outcomes. PMID:21722892

  12. HIV cell-to-cell transmission: effects on pathogenesis and antiretroviral therapy

    PubMed Central

    Agosto, Luis M.; Uchil, Pradeep D.; Mothes, Walther

    2015-01-01

    The human immunodeficiency virus (HIV) spreads more efficiently in vitro when infected cells directly contact uninfected cells to form virological synapses. A hallmark of virological synapses is that viruses can be transmitted at a higher multiplicity of infection (MOI) that, in vitro, results in a higher number of proviruses. Whether HIV also spreads by cell-cell contact in vivo is a matter of debate. Here we discuss recent data that suggest that contact-mediated transmission largely manifests itself in vivo as CD4+ T cell depletion. The assault of a cell by a large number of incoming particles is likely efficiently sensed by the innate cellular surveillance to trigger cell death. The large number of particles transferred across virological synapses has also been implicated in reduced efficacy of antiretroviral therapies. Thus, antiretroviral therapies must remain effective against the high MOI observed during cell-to-cell transmission to inhibit both viral replication and the pathogenesis associated with HIV infection. PMID:25766144

  13. Given Resource Constraints, It Would Be Unethical To Divert Antiretroviral Drugs From Treatment To Prevention

    PubMed Central

    Macklin, Ruth; Cowan, Ethan

    2013-01-01

    Striking advances in HIV prevention have set the stage for renewed debate on setting priorities in the fight against HIV/AIDS. Two new prevention strategies preexposure prophylaxis and treatment as prevention—use antiretroviral drugs for prevention of HIV/AIDS in addition to treating patients. The potential for success of these new prevention strategies sets up an ethical dilemma: where resources are limited and supplies of lifesaving antiretroviral medications are insufficient to treat those currently living with HIV, how should these resources be divided between treatment and prevention? This article explores several ethical principles used in formulating public health policy. Assuming that limited resources are available for spending on drugs, we conclude that it would be unethical to watch patients with treatable AIDS worsen and die, even with supportive care, so that medications for treatment can be diverted for prevention. PMID:22778343

  14. Nanosilver based anionic linear globular dendrimer with a special significant antiretroviral activity.

    PubMed

    Ardestani, Mehdi Shafiee; Fordoei, Alireza Salehi; Abdoli, Asghar; Ahangari Cohan, Reza; Bahramali, Golnaz; Sadat, Seyed Mehdi; Siadat, Seyed Davar; Moloudian, Hamid; Nassiri Koopaei, Nasser; Bolhasani, Azam; Rahimi, Pooneh; Hekmat, Soheila; Davari, Mehdi; Aghasadeghi, Mohammad Reza

    2015-05-01

    HIV is commonly caused to a very complicated disease which has not any recognized vaccine, so designing and development of novel antiretroviral agents with specific application of nanomedicine is a globally interested research subject worldwide. In the current study, a novel structure of silver complexes with anionic linear globular dendrimer was synthesized, characterized and then assessed against HIV replication pathway in vitro as well. The results showed a very good yield of synthesis (up to 70%) for the nano-complex as well as a very potent significant (P < 0.05) antiretroviral activity with non-severe toxic effects in comparison with the Nevirapine as standard drug in positive control group. According to the present data, silver anionic linear globular dendrimers complex may have a promising future to inhibit replication of HIV viruse in clinical practice.

  15. Lung cancer in HIV-infected patients in the combination antiretroviral treatment era

    PubMed Central

    Moltó, José; Sirera, Guillem; Clotet, Bonaventura

    2015-01-01

    The advent of combination antiretroviral treatment (cART) has been followed by a decrease in HIV-associated morbidity and mortality, but also by an apparent increase in the incidence of non-AIDS-defining cancers (NADCs). The risk of lung cancer is substantially higher in HIV-infected patients than in the general population, in part due to aging and tobacco use, and it is the most frequent NADC. The management of lung cancer in HIV-infected patients has some peculiarities that need to be taken into account. This review focuses on the epidemiology, risk factors, and clinical management of lung cancer in HIV-infected patients. In addition, screening tools and future perspectives are also discussed. Keywords Lung cancer; non-AIDS-defining cancers (NADCs); HIV infection; antiretroviral treatment PMID:26798577

  16. 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

  17. Nanosilver based anionic linear globular dendrimer with a special significant antiretroviral activity.

    PubMed

    Ardestani, Mehdi Shafiee; Fordoei, Alireza Salehi; Abdoli, Asghar; Ahangari Cohan, Reza; Bahramali, Golnaz; Sadat, Seyed Mehdi; Siadat, Seyed Davar; Moloudian, Hamid; Nassiri Koopaei, Nasser; Bolhasani, Azam; Rahimi, Pooneh; Hekmat, Soheila; Davari, Mehdi; Aghasadeghi, Mohammad Reza

    2015-05-01

    HIV is commonly caused to a very complicated disease which has not any recognized vaccine, so designing and development of novel antiretroviral agents with specific application of nanomedicine is a globally interested research subject worldwide. In the current study, a novel structure of silver complexes with anionic linear globular dendrimer was synthesized, characterized and then assessed against HIV replication pathway in vitro as well. The results showed a very good yield of synthesis (up to 70%) for the nano-complex as well as a very potent significant (P < 0.05) antiretroviral activity with non-severe toxic effects in comparison with the Nevirapine as standard drug in positive control group. According to the present data, silver anionic linear globular dendrimers complex may have a promising future to inhibit replication of HIV viruse in clinical practice. PMID:25893388

  18. 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

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

    PubMed

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

    2015-01-01

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

  20. Interruption of antiretroviral therapy is associated with increased plasma cystatin C

    PubMed Central

    Mocroft, A; Wyatt, C; Szczech, L; Neuhaus, J; El-Sadr, W; Tracy, R; Kuller, L; Shlipak, M; Angus, B; Klinker, H; Ross, M

    2009-01-01

    Background Cystatin C has been proposed as an alternative marker of renal function. We sought to determine if participants randomized to episodic use of antiretroviral therapy guided by CD4+ count (drug conservation; DC) had altered cystatin C levels compared to those randomised to continuous antiretroviral therapy (viral suppression; VS) in the Strategies for Management of Antiretroviral Therapy Trial, and to identify factors associated with increased cystatin C. Methods Cystatin C was measured in plasma collected at randomization, 1, 2, 4, 8 and 12 months after randomization in a random sample of 249 and 250 participants in the DC and VS groups respectively. Logistic regression was used to model the odds of ≥ 0.15 mg/dl increase in cystatin C (1 standard deviation [SD]) in the first month after randomisation, adjusting for demographic and clinical characteristics. Results At randomisation, mean (SD) cystatin C level was 0.99 (0.26 mg/dl) and 1.01 (0.28 mg/dl) in the DC and VS arms respectively (p=0.29). In the first month after randomisation, 21.8% and 10.6% had ≥0.15 mg/dl increase in cystatin C in the DC and VS arm respectively (p=0.0008). The difference in cystatin C between the treatment arms was maintained through 1 year after randomisation. After adjustment, participants in the VS arm had significantly reduced odds of ≥0.15 mg/dl increase in cystatin C in the first month (OR 0.42; 95% CI 0.23–0.74, p=0.0023). Conclusions These results demonstrate that interruption of antiretroviral therapy is associated with an increase in cystatin C, which may reflect worsened renal function. PMID:19050388

  1. Antiretroviral therapy CNS penetration and HIV-1–associated CNS disease

    PubMed Central

    Winston, A.; Walsh, J.; Post, F.; Porter, K.; Gazzard, B.; Fisher, M.; Leen, C.; Pillay, D.; Hill, T.; Johnson, M.; Gilson, R.; Anderson, J.; Easterbrook, P.; Bansi, L.; Orkin, C.; Ainsworth, J.; Palfreeman, A.; Gompels, M.; Phillips, A.N.; Sabin, C.A.

    2011-01-01

    Objective: The impact of different antiretroviral agents on the risk of developing or surviving CNS disease remains unknown. The aim of this study was to investigate whether using antiretroviral regimens with higher CNS penetration effectiveness (CPE) scores was associated with reduced incidence of CNS disease and improved survival in the UK Collaborative HIV Cohort (CHIC) Study. Methods: Adults without previous CNS disease, who commenced combination antiretroviral therapy (cART) between 1996 and 2008, were included (n = 22,356). Initial and most recent cART CPE scores were calculated. CNS diseases were HIV encephalopathy (HIVe), progressive multifocal leukoencephalopathy (PML), cerebral toxoplasmosis (TOXO), and cryptococcal meningitis (CRYPTO). Incidence rates and overall survival were stratified by CPE score. A multivariable Poisson regression model was used to identify independent associations. Results: The median (interquartile range) CPE score for initial cART regimen increased from 7 (5–8) in 1996–1997 to 9 (8–10) in 2000–2001 and subsequently declined to 6 (7–8) in 2006–2008. Differences in gender, HIV acquisition risk group, and ethnicity existed between CPE score strata. A total of 251 subjects were diagnosed with a CNS disease (HIVe 80; TOXO 59; CRYPTO 56; PML 54). CNS diseases occurred more frequently in subjects prescribed regimens with CPE scores ≤4, and less frequently in those with scores ≥10; however, these differences were nonsignificant. Initial and most recent cART CPE scores ≤4 were independently associated with increased risk of death. Conclusion: Clinical status at time of commencing cART influences antiretroviral selection and CPE score. This information should be considered when utilizing CPE scores for retrospective analyses. PMID:21339496

  2. Decision maker priorities for providing antiretroviral therapy in HIV-infected South Africans: a qualitative assessment.

    PubMed

    Kimmel, April D; Daniels, Norman; Betancourt, Theresa S; Wood, Robin; Prosser, Lisa A

    2012-01-01

    In resource-limited settings, successful HIV treatment scale-up has been tempered by reports of funding shortfalls. We aimed to determine the priorities, including ethical considerations, of decision makers for HIV antiretroviral programs. We conducted qualitative interviews with 12 decision makers, identified using purposive sampling. Respondents engaged in one-on-one, semi-structured interviews. We developed an interview guide to direct questions about key priorities and motivations for decision making about HIV antiretroviral programs. We evaluated textual data from the interviews to identify themes. Among 12 respondents, 10 (83%) lived and worked in South Africa. Respondents came from Western Cape, Gauteng, and KwaZulu-Natal provinces and worked primarily in urban settings. The respondents supported prioritizing individual patients based on treatment adherence, pregnancy status to prevent maternal-to-child HIV transmission and/or orphans, and severity of illness. However, priorities based on severity of illness varied, with first-come/first-serve, prioritization of the most severely ill, and prioritization of the least severely ill discussed. Respondents opposed prioritizing based on patient socioeconomic characteristics. Other priorities included the number of persons receiving treatment; how treated patients are distributed in the population (e.g., urban/rural); and treatment policy (e.g., number of antiretroviral regimens). Motivations included humanitarian concerns; personal responsibility for individual patients; and clinical outcomes (e.g., patient-level morbidity/mortality, saving lives) and/or social outcomes (e.g., restoring patients as functional family members). Decision makers have a wide range of priorities for antiretroviral provision in South Africa, and the motivations underlying these priorities suggest at times conflicting ethical considerations for providing HIV treatment when resources are limited. PMID:22304657

  3. Low incidence of abacavir hypersensitivity reaction among African children initiating antiretroviral therapy.

    PubMed

    Nahirya-Ntege, Patricia; Musiime, Victor; Naidoo, Bethany; Bakeera-Kitaka, Sabrina; Nathoo, Kusum; Munderi, Paula; Mugyenyi, Peter; Kekitiinwa, Adeodata; Bwakura-Dangarembizi, Mutsa F; Crawley, Jane

    2011-06-01

    Hypersensitivity reactions are reported in approximately 5% of adults receiving abacavir, but there are few published data in children. Among 1150 African children receiving antiretroviral therapy in a randomized trial, suspected hypersensitivity reactions to abacavir were rare (0.3%; 95% CI, 0.01-0.9). Patients were managed successfully through the provision of clear guidelines and education of clinical staff, children, and their caregivers.

  4. Bacillary angiomatosis: A rare finding in the setting of antiretroviral drugs.

    PubMed

    Madua, M C

    2015-10-01

    An HIV-positive 39-year-old man presented with generalised nodular lesions. He was apyrexial and normotensive, with a normal respiratory rate. The rest of the examination was normal. He had been on antiretroviral therapy for >4 years; most importantly, he was on a second-line regimen (lopinavir/ritonavir (Aluvia) based). The appearance of the lesions, together with the history, led to the following possible diagnoses: bacillary angiomatosis, cutaneous cryptococcosis, nodular Kaposi sarcoma or cutaneous histoplasmosis.

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

    PubMed Central

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

    2015-01-01

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

  6. Risk of Cardiovascular Events Among Patients Initiating Efavirenz-Containing Versus Efavirenz-Free Antiretroviral Regimens

    PubMed Central

    Rosenblatt, Lisa; Farr, Amanda M.; Johnston, Stephen S.; Nkhoma, Ella T.

    2016-01-01

    Background. Efavirenz (EFV), an antiretroviral medication used to treat human immunodeficiency virus (HIV) infection, can increase lipid levels. Because hyperlipidemia is associated with increased risk for cardiovascular (CV) events, this study compared the risk of CV events in patients initiating EFV-containing vs EFV-free antiretroviral regimens. Methods. Antiretroviral-naive HIV-positive (HIV+) patients ages 18–64 were selected from commercial and Medicaid insurance claims databases. Patients with ≥1 claim for antiretroviral medications between January 1, 2007 and December 31, 2013 were classified into 2 cohorts: EFV-containing or EFV-free regimens. Patients were required to have 6 months of continuous enrollment before initiation, with no evidence of a CV event during this time. Patients were observed from initiation until the occurrence of a CV event, disenrollment, or study end. Cardiovascular events were identified through diagnosis or procedure codes for myocardial infarction, stroke, percutaneous coronary intervention, or coronary artery bypass graft. We calculated unadjusted incidence rates (IRs) and fit propensity-score-weighted Cox proportional hazards models. Results. There were 22 212 patients (11 978 EFV-containing and 10 234 EFV-free) identified in the commercial database and 7400 patients identified (2943 EFV-containing and 4457 EFV-free) in the Medicaid database. Cardiovascular events were rare (commercial IR = 396 per 100 000 person-years; Medicaid IR = 973 per 100 000 person-years). In propensity-score-weighted models, hazards of CV events were significantly lower for EFV-containing regimens in the commercial database (hazard ratio [HR] = 0.68; 95% confidence interval [CI], .49–.93) No significant difference was found in the Medicaid database (HR = 0.83; 95% CI, .58–1.19). Conclusions. This analysis found no evidence of increased risk of CV events among HIV+ patients initiating EFV-containing regimens. PMID:27186585

  7. Extended Deterrence, Nuclear Proliferation, and START III

    SciTech Connect

    Speed, R.D.

    2000-06-20

    Early in the Cold War, the United States adopted a policy of ''extended nuclear deterrence'' to protect its allies by threatening a nuclear strike against any state that attacks these allies. This threat can (in principle) be used to try to deter an enemy attack using conventional weapons or one using nuclear, chemical, or biological weapons. The credibility of a nuclear threat has long been subject to debate and is dependent on many complex geopolitical factors, not the least of which is the military capabilities of the opposing sides. The ending of the Cold War has led to a significant decrease in the number of strategic nuclear weapons deployed by the United States and Russia. START II, which was recently ratified by the Russian Duma, will (if implemented) reduce the number deployed strategic nuclear weapons on each side to 3500, compared to a level of over 11,000 at the end of the Cold War in 1991. The tentative limit established by Presidents Clinton and Yeltsin for START III would reduce the strategic force level to 2000-2500. However, the Russians (along with a number of arms control advocates) now argue that the level should be reduced even further--to 1500 warheads or less. The conventional view is that ''deep cuts'' in nuclear weapons are necessary to discourage nuclear proliferation. Thus, as part of the bargain to get the non-nuclear states to agree to the renewal of the Nuclear Non-Proliferation Treaty, the United States pledged to work towards greater reductions in strategic forces. Without movement in the direction of deep cuts, it is thought by many analysts that some countries may decide to build their own nuclear weapons. Indeed, this was part of the rationale India used to justify its own nuclear weapons program. However, there is also some concern that deep cuts (to 1500 or lower) in the U.S. strategic nuclear arsenal could have the opposite effect. The fear is that such cuts might undermine extended deterrence and cause a crisis in confidence

  8. CD4+ guided antiretroviral treatment interruption in HIV infection: a meta-analysis.

    PubMed

    Seminari, Elena; De Silvestri, Annalisa; Boschi, Andrea; Tinelli, Carmine

    2008-01-01

    The aim of this meta-analysis study was to evaluate the relative risk of death or AIDS-defining events associated to CD4+ guided treatment interruption in patients with chronic HIV infection. A search was conducted using PubMed and Cochrane Library; key words for PubMed were: "antiretroviral therapy and interrupt*" in the full papers from January 1, 2000 up to and including December 31, 2007. To limit the publication bias, clinical trials performed on the topic of the meta-analysis were searched also on http://www.clinicaltrial.gov. Inclusion criteria of studies were: starting a CD4+ guided interruption of HAART in HIV chronically infected patients with CD4+ cell count > 350 cells/mm3, age > 13 years old, and absence of concomitant use of immunomodulatory drugs. Using a conservative approach, to be included in the meta-analysis, studies had to have a follow up period > 100 person years to minimize the bias of a too short observation time. The studies were classified into two categories: randomized clinical trial (one arm stops therapy and other arms continues HAART) and cohort studies. For each study measures of effect (hazard ratio or incidence rate ratio) were reported, when available, uncorrected and corrected for potential confounders. Publication bias was assessed graphically through funnel plot. Pooled relative risk and pooled risk difference were calculated by use of a random effects model following the DerSimonian-Laird method. Observational studies were considered separately and the incidence of primary endpoint was evaluated in each study and the cumulative incidence was calculated. Of the 555 full papers found, all abstracts were screened and 58 full text articles for potential inclusion were retrieved and 18 were retained (seven randomized clinical trials and 11 observational studies). In randomized clinical trials, the meta-analysis showed that the pooled relative risk of AIDS-defining event or mortality was 2.50 (95% CI: 1.87-3.34; p < 0.001); the

  9. 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…

  10. Early Head Start Research: Pathways to Quality and Full Implementation in Early Head Start Programs.

    ERIC Educational Resources Information Center

    Kisker, Ellen Eliason; Paulsell, Diane; Love, John M.; Raikes, Helen

    As part of a multi-faceted effort, the National Early Head Start Research and Evaluation project examined the nature and extent of implementation in key program areas and the quality of crucial child development services in 17 research programs funded early in the initiative. Implementation data were collected through three rounds of site visits,…

  11. A Comparison of Written Compositions of Head-Start Pupils with Non-Head-Start Pupils.

    ERIC Educational Resources Information Center

    Houston, David Ree

    This study--a follow-up to one conducted by Giles in 1965-- compared the written compositions of fourth grade pupils who had been in Project Head Start in the summer of 1965 with those of comparable pupils not in the program to determine possible differences in their written language development. Seventy Negro students were divided by sex and…

  12. National Head Start Association Position Paper: Why Conservatives Should Support Head Start.

    ERIC Educational Resources Information Center

    Allen, Ben; Greene, Sarah; McGrady, Michael; Boel, Bridget; Ryan, Joel; Whitehead, Diane; Smith, Angela; Kane, Elizabeth; Qualls, Brocklin; Wahid, Kahree

    Head Start is a comprehensive federal preschool program, serving children prenatal through age 5 and their families with the overall goal of increasing the school readiness of young children in low-income families. Noting that the program has typically garnered strong support from political liberals and moderates, this position paper of the…

  13. Enhancing Health in the Head Start Workplace. Training Guides for the Head Start Learning Community.

    ERIC Educational Resources Information Center

    Bowman (James) Associates, San Francisco, CA.

    This training guide is intended to increase the understanding and skills of Head Start managers and directors to: (1) identify the ways in which employee health affects the organization's effectiveness; (2) design training programs that encourage employees to improve their own health; (3) understand how the organization contributes to the overall…

  14. A single centre cohort experience with a new once daily antiretroviral drug

    PubMed Central

    Stebbing, J; Bower, M; Holmes, P; Gazzard, B; Nelson, M

    2006-01-01

    Background Atazanavir, an azadipeptide protease inhibitor (PI) with once daily dosing, a lack of insulin resistance, lipid increase, and gastrointestinal toxicities, is approved in combination with other antiretrovirals for the treatment of patients infected with HIV. Unboosted atazanavir is also used in highly active antiretroviral therapy (HAART) naive patients. Methods The study prospectively followed up an established cohort of patients who received atazanavir, and for whom one year of follow up data were available. Results It was found that use of atazanavir in intent to treat and on treatment analyses, maintained and led to virological suppression and increases in CD4 count in both PI naive and experienced patients. Virological failure occurred in 7% of patients and the main toxicity was hyperbilirubinaemia, which led to treatment withdrawal in 2%. Its efficacy and safety profile was similar to that seen in previous randomised studies investigating its use. Conclusions These data should provide reassurance for clinicians wishing to introduce a new antiretroviral into an established cohort. PMID:16679474

  15. Antiretroviral adherence interventions: a review of current literature and ongoing studies.

    PubMed

    Simoni, Jane M; Frick, Pamela A; Pantalone, David W; Turner, Barbara J

    2003-01-01

    Adherence has proven to be Achilles' heel of antiretroviral therapy. To achieve the nearly perfect adherence apparently necessary for optimal effects, individuals often require assistance. In this review, we examine antiretroviral therapy adherence intervention studies and reviews published through January 2003 as well as abstracts of ongoing National Institutes of Health-funded research projects aimed at enhancing antiretroviral therapy adherence. The 21 published studies we located utilized 4 intervention strategies: cognitive-behavioral, behavioral, directly observed therapy, and affective. Most of these were pilot or feasibility studies. However, the 4 randomized controlled trials conducted with adequate methologic rigor suggest some promising yet preliminary effects of a pharmacist-led individualized intervention, a cognitive-behavioral educational intervention based on self-efficacy theory, and cue-dose training when combined with monetary reinforcement. The 39 ongoing federally funded studies offer superior methodologic sophistication and include some innovative strategies, such as the use of handheld devices, two-way pagers, and alarmed medication vials, along with enhancement of social and emotional support.

  16. The spectrum of kidney disease in patients with AIDS in the era of antiretroviral therapy

    PubMed Central

    Wyatt, Christina M.; Morgello, Susan; Katz-Malamed, Rebecca; Wei, Catherine; Klotman, Mary E.; Klotman, Paul E.; D’Agati, Vivette D.

    2009-01-01

    With prolonged survival and aging of the HIV-infected population in the era of antiretroviral therapy, biopsy series have found a broad spectrum of HIV-related and co-morbid kidney disease in these patients. Our study describes the variety of renal pathology found in a prospective cohort of antiretroviral-experienced patients (the Manhattan HIV Brain Bank) who had consented to postmortem organ donation. Nearly one-third of 89 kidney tissue donors had chronic kidney disease, and evidence of some renal pathology was found in 75. The most common diagnoses were arterionephrosclerosis, HIV-associated nephropathy and glomerulonephritis. Other diagnoses included pyelonephritis, interstitial nephritis, diabetic nephropathy, fungal infection and amyloidosis. Excluding 2 instances of acute tubular necrosis, slightly over one-third of the cases would have been predicted using current diagnostic criteria for chronic kidney disease. Based on semi-quantitative analysis of stored specimens, pre-mortem microalbuminuria testing could have identified an additional 12 cases. Future studies are needed to evaluate the cost-effectiveness of more sensitive methods for defining chronic kidney disease, in order to identify HIV-infected patients with early kidney disease who may benefit from antiretroviral therapy and other interventions known to delay disease progression and prevent complications. PMID:19052538

  17. Neuropathic and neurocongnitive complications of antiretroviral therapy among HIV-infected patients.

    PubMed

    Suvada, Jose

    2013-09-01

    The neurologic events related to antiretroviral therapy (ART) in HIV-infected ART-naive patients are relatively common. Side effects of ART and complications of HIV infection may overlap significantly. Establishing etiology of neurologic (neuropathy and neuropathic pain, changes in cognition, dementia, and myelopathy) and psychiatric (neurocognitive disorders, depression, anxiety, substance abuse and dependence, and others) complications can present a significant challenge. It has long been documented that neurologic and psychological side effects can occur with many of the agents used to treat HIV infection. Particularly, efavirenz from the non-nucleoside reverse transcriptase inhibitor (NNRTI) has been associated with neurologic and psychological complaints that may be difficult to differentiate from pre-existing mental illness, substance abuse, and HIV-related neuropsychiatric symptoms. Peripheral neuropathy (PN) of at least 6 different types is a well-known adverse effect of treatment with nucleoside reverse transcriptase inhibitors (NRTIs) in HIV-infected patients. Lack of dealing with early stages of neurologic and psychological side effects of HIV infection and Highly Active Anti-retroviral Therapy (HAART) are observed in daily practice. The purpose of this article is to identify the neurologic, neuropsychiatric and psychiatric complications related to HIV and anti-retroviral therapy, to discuss current knowledge about these disorders, and to suggest strategies for their diagnosis and management.

  18. Methods Development for Blood Borne Macrophage Carriage of Nanoformulated Antiretroviral Drugs

    PubMed Central

    Roy, Upal; Martinez-Skinner, Andrea; McMillan, JoEllyn; Gendelman, Howard E.

    2010-01-01

    Nanoformulated drugs can improve pharmacodynamics and bioavailability while serving also to reduce drug toxicities for antiretroviral (ART) medicines. To this end, our laboratory has applied the principles of nanomedicine to simplify ART regimens and as such reduce toxicities while improving compliance and drug pharmacokinetics. Simple and reliable methods for manufacturing nanoformulated ART (nanoART) are shown. Particles of pure drug are encapsulated by a thin layer of surfactant lipid coating and produced by fractionating larger drug crystals into smaller ones by either wet milling or high-pressure homogenization. In an alternative method free drug is suspended in a droplet of a polymer. Herein, drug is dissolved within a polymer then agitated by ultrasonication until individual nanosized droplets are formed. Dynamic light scattering and microscopic examination characterize the physical properties of the particles (particle size, charge and shape). Their biologic properties (cell uptake and retention, cytotoxicity and antiretroviral efficacy) are determined with human monocyte-derived macrophages (MDM). MDM are derived from human peripheral blood monocytes isolated from leukopacks using centrifugal elutriation for purification. Such blood-borne macrophages may be used as cellular transporters for nanoART distribution to human immunodeficiency virus (HIV) infected organs. We posit that the repackaging of clinically available antiretroviral medications into nanoparticles for HIV-1 treatments may improve compliance and positively affect disease outcomes. PMID:21178968

  19. 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

  20. 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

  1. Advance Care Planning and HIV Infection in the Era of Antiretroviral Therapy: A Review.

    PubMed

    Sangarlangkarn, Aroonsiri; Merlin, Jessica S; Tucker, Rodney O; Kelley, Amy S

    In the era of antiretroviral therapy, HIV infection has become a chronic illness with associated multimorbidity, and practitioners are faced with an emerging population of HIV-infected patients with evolving needs for advance care planning (ACP), defined as communication between individuals and their proxies to plan for future health care decisions. This article provides a review of original research studies on ACP in HIV-infected adults in the era of antiretroviral therapy (1996-present) from PubMed, EMBASE, and PsycINFO. Eleven studies conducted between 1996 and 2015 met the selection criteria, with study sizes ranging from 9 to 2864 participants. Most studies consisted of white men in outpatient settings and had poorly defined definitions of ACP. Prevalence of ACP was variable (36%-54% had end-of-life communication, 8%-47% had advance directives). Lack of ACP was most commonly associated with low income, followed by lower severity of illness, low education level, black or Hispanic race, female sex, younger age, injection drug use, and social isolation. Practitioners reported limited time or energy and inadequate preparation or training as barriers to ACP. Existing literature on ACP in the era of antiretroviral therapy is limited, but shows that ACP prevalence in HIV-infected individuals is variable depending on socioeconomic factors, severity of illness, and practitioner resources and training. More research is needed to increase ACP among HIV-infected individuals. PMID:27398771

  2. Nondisclosure of HIV Status in a Clinical Trial Setting: Antiretroviral Drug Screening Can Help Distinguish Between Newly Diagnosed and Previously Diagnosed HIV Infection

    PubMed Central

    Marzinke, Mark A.; Clarke, William; Wang, Lei; Cummings, Vanessa; Liu, Ting-Yuan; Piwowar-Manning, Estelle; Breaud, Autumn; Griffith, Sam; Buchbinder, Susan; Shoptaw, Steven; del Rio, Carlos; Magnus, Manya; Mannheimer, Sharon; Fields, Sheldon D.; Mayer, Kenneth H.; Wheeler, Darrell P.; Koblin, Beryl A.; Eshleman, Susan H.; Fogel, Jessica M.

    2014-01-01

    In The HIV Prevention Trials Network 061 study, 155 human immunodeficiency virus (HIV)–infected men reported no prior HIV diagnosis; 83 of those men had HIV RNA levels of <1000 copies/mL at enrollment. Antiretroviral drug testing revealed that 65 of the 83 (78.3%) men were on antiretroviral treatment. Antiretroviral drug testing can help distinguish between newly diagnosed and previously diagnosed HIV infection. PMID:24092804

  3. The effect of entrainment on starting vortices

    NASA Astrophysics Data System (ADS)

    Rosi, Giuseppe; Rival, David

    2015-11-01

    Recent work shows that vortex detachment behind accelerating plates coincides with when streamlines enclosing the starting vortex (SV) form a full saddle. In the case of a linearly accelerating plate, it can be shown that vorticity-containing mass, and thus the SV's development scale with only dimensionless towed distance, while the SV's circulation scales with the acceleration rate. This results in shear-layer instabilities whose structure is Reynold-number independent, but whose strength scale with Reynolds number. It is hypothesized that the increased strength of the instabilities promotes entrainment, which causes the formation of the full saddle and thereby detachment to occur at an earlier dimensionless towed distance. To test this hypothesis, a circular plate is linearly accelerated from rest to pinch-off with chord-based Reynolds numbers of 103, 104, and 105 at the midpoint of the motion. Planar PIV data is acquired, from which FTLE and enstrophy fields are calculated. Vortex detachment is identified from the dynamics of the FTLE saddles, while the enstrophy fields are used to calculate both the vorticity-containing mass entering from the shear layer and the mass entrained from the quiescent surroundings.

  4. 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.

  5. 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

  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.

  7. Kyrgyzstan starts up its first refinery

    SciTech Connect

    McLeod, G.

    1997-05-05

    The Central Asian republic of Kyrgyzstan started up its first oil refinery in October 1996. The 10,000 b/d plant is designed to produce gasoline, diesel, and mazut (heavy fuel oil) from local Kyrgyz crude. Before construction of the Jalalabad refinery, all finished petroleum products were imported from neighboring countries. Kyrgyzstan`s demand for finished products is about 40,000 b/d. The new refinery was designed and constructed by Petrofac of Tyler, Texas, on behalf of Kyrgoil Corp., Calgary. Kyrgoil is a partner with the Kyrgyz state oil company, Kyrgyzsneft, in a venture called Kyrzgyz Petroleum Co. (KPC). KPC has undertaken restoration and continued development of the oil fields in Kyrgyzstan`s Fergana basin, in addition to the refinery project. The company also has marketing rights for finished products within Kyrgyzstan. The refinery comprises: a hydroskimming (atmospheric distillation) section, diesel steam stripping, gasoline blending, and utilities and off-sites, including steam generation, power generation, tank farm, truck and rail tank-car loading and unloading facilities, crude inlet pipeline, high-voltage power line, substation, air compression, laboratory, and maintenance facilities.

  8. Rehabilitation starts in the intensive care unit.

    PubMed

    Rozeboom, Nathan; Parenteau, Kathy; Carratturo, Daniel

    2012-01-01

    Each year between 10 000 and 12 000 spinal cord injuries occur in the United States. Once injured, many of these patients will receive a portion of their care in an intensive care unit (ICU), where their treatment will begin. Harborview Medical Center in Seattle, Washington, provides comprehensive care to approximately 60 to 70 cervical spinal cord injuries each year. Because of many factors such as hemodynamic instability, pulmonary complications, and risk of infection, patients with cervical spinal cord injuries can spend up to 2 or more weeks in the ICU before they transfer to a rehabilitation unit. To achieve optimal outcomes, it is imperative that members of the interdisciplinary team work together in a consistent, goal-oriented, collaborative manner. This team includes physicians, nurses, respiratory therapists, physical and occupational therapists, speech pathologists, dieticians, and rehabilitation psychologists. An individual plan is developed for each patient and rehabilitation starts in the ICU as soon as the patient is medically stable. This article will highlight the management strategies used in the neuroscience ICU at Harborview Medical Center and will include a case study as an example of the typical experience for our patients with high cervical cord injury.

  9. [Indications for starting kidney replacement therapy].

    PubMed

    Tornero Molina, F; Remón Rodríguez, C

    2008-01-01

    In view of the lack of scientific evidence to support the initiation of KRT from a specific filtration rate, certain conclusions can be drawn whose application in clinical practice may be useful. The recommendations we could make are: - Scheduled initiation of KRT is associated with a better patient prognosis (Strength of Recommendation B). - KRT should be planned in advance so that the patient can freely choose the technique for KRT (Strength of Recommendation B). - If the patient starts HD with a permanent vascular access, his/her course will be better (Strength of Recommendation B). - When the patient has any clinical indication for initiating KRT, this should not be postponed (Strength of Recommendation A). - Glomerular filtration rate is the best way to assess kidney function (Strength of Recommendation B). - Patients with a glomerular filtration rate less than 15 ml/min and any symptom associated with uremia not correctable by conventional treatment should be assessed for the initiation of KRT (Strength of Recommendation C). - Patients with a glomerular filtration rate less than 6-8 ml/min should initiate KRT even if they are minimally symptomatic (Strength of Recommendation C). - Patients with more comorbidities or more extreme ages (children, elderly, diabetics, heart disease patients,...) could benefit from the initiation of KRT before other types of patients (Strength of Recommendation C). - Some patients with associated comorbid conditions could even benefit from the initiation of KRT with glomerular filtration rates above 15 ml/min (Strength of Recommendation C). PMID:19018746

  10. 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

  11. Economic savings versus health losses: The cost-effectiveness of generic antiretroviral therapy in the United States

    PubMed Central

    Walensky, Rochelle P.; Sax, Paul E.; Nakamura, Yoriko M.; Weinstein, Milton C.; Pei, Pamela P.; Freedberg, Kenneth A.; Paltiel, A. David; Schackman, Bruce R.

    2013-01-01

    Background US HIV treatment guidelines recommend branded once-daily, one-pill efavirenz/emtricitabine/tenofovir as preferred first-line antiretroviral treatment (ART). With the anticipated approval of generic efavirenz in 2012 in the US, the cost of a once-daily, three-pill alternative (generic efavirenz, generic lamivudine, tenofovir) will decrease, but adherence and virologic suppression may be reduced. Objectives To assess the clinical impact, costs, and cost-effectiveness of the generic-based three-pill regimen compared to the branded, co-formulated regimen. To project the potential national savings in the first year of a switch to generic-based ART. Design Mathematical simulation of HIV disease. Data Sources Published data from US clinical trials and observational cohorts. Target Population HIV-infected patients eligible to start on or switch to an efavirenz-based generic ART regimen. Time Horizon Lifetime, One-year Perspective US health system Interventions No ART (for comparison), Three-pill Generic ART, and Branded ART Outcome Measures Quality-adjusted life expectancy, costs, and incremental cost-effectiveness ratios (ICER, $/quality-adjusted life expectancy [QALY]). Results of Base-Case Analysis Compared to No ART, Generic ART has an ICER of $21,100/QALY. Compared to Generic ART, Branded ART increases lifetime costs by $42,500, and per-person survival gains by 0.37 QALYs, for an ICER of $114,800/QALY. Estimated first-year savings, if all eligible US patients start on or switch to Generic ART, are $920 million. Results of Sensitivity Analysis Most plausible assumptions about Generic ART efficacy and costs lead to Branded ART ICERs >$100,000/QALY. Limitations The efficacy and price reduction associated with generics are unknown; estimates are intended to be conservative. Conclusions Compared to a slightly less effective generic-based regimen, the cost-effectiveness of first-line Branded ART exceeds $100,000/QALY. Generic-based ART in the US could yield

  12. Shift mechanism for engine starting apparatus

    SciTech Connect

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

    1986-04-01

    This patent describes a shift lever mechanism for translating axial movement of the plunger of a starter solenoid into axial movement of a pinion of an engine starting apparatus. This apparatus consists of, a starter solenoid having an axially shiftable plunger and a coil winding, a spring opposing pull-in movement of the plunger and a solenoid switch operated to a closed condition when the plunger is completely pulled-in, a shift lever actuator carried by the plunger for axial movement therewith. The actuator has a pair of spaced surfaces, a pivotally mounted shift lever one end of which is adapted to be coupled to the pinion. The opposite end of the shift lever has a pair of opposed shift lever surfaces that respectively engage the surfaces on the actuator. The actuator surfaces and the shift lever surfaces are substantially engaged when the shift lever is in an at rest postion. The surfaces on the shift lever are at different radial distances from the pivot point of the shift lever and are arranged relative to the surfaces on the actuator such that when the solenoid plunger pulls-in the surface on the shift lever that is at the greater radial distance from the pivot point is moved by a surface of the actuator and the other surface on the shift lever becomes separated by a predetermined amount from its cooperating surface on the actuator. The amount of separation is sufficient to allow the solenoid switch to be actuated to an open condition when the solenoid coil winding is deenergized and the spring shifts and plunger to reengage the separated surfaces.

  13. Life's Starting Materials Found in Dusty Disk

    NASA Technical Reports Server (NTRS)

    2005-01-01

    [figure removed for brevity, see original site] Full Image of Graph

    This graph, or spectrum, from NASA's Spitzer Space Telescope tells astronomers that some of the most basic ingredients of DNA and protein are concentrated in a dusty planet-forming disk circling a young sun-like star called IRS 46. These data also indicate that the ingredients -- molecular gases called acetylene and hydrogen cyanide -- are located in the star's terrestrial planet zone, the region where scientists believe Earth-like planets would be most likely to form.

    The data were acquired by Spitzer's infrared spectrograph, which split light from the star's disk into distinct features characteristic of a particular chemical. The features, seen here as bumps and squiggles, are like bar codes used in supermarkets to identify different products. In this case, the products are the two DNA and protein precursors, acetylene and hydrogen cyanide, as well as carbon dioxide gas. All three gases are termed 'organic' because they contain the element carbon.

    The shapes of the features in this spectrum helped pinpoint the location of the gases in the star's disk. A feature's shape reflects the temperature of the gas. By comparison with model spectra, astronomers were able to deduce that the gases are present in regions where the temperature ranges from approximately the boiling point of water on Earth (212 degrees Fahrenheit), to nearly a thousand degrees Fahrenheit. Such hot temperatures place the gases in the star's terrestrial planet zone, which is sometimes referred to as the 'Goldilocks' zone because it is just right for Earths.

    Acetylene and hydrogen cyanide are some of life's most basic starting materials. If you mix them together in a test tube with water, and give them some kind of surface on which to be concentrated and react, you'll get a slew of organic compounds, including many of the 20 essential amino acids and one of the four chemical units, called bases, that make up

  14. Starting up microbial enhanced oil recovery.

    PubMed

    Siegert, Michael; Sitte, Jana; Galushko, Alexander; Krüger, Martin

    2014-01-01

    This chapter gives the reader a practical introduction into microbial enhanced oil recovery (MEOR) including the microbial production of natural gas from oil. Decision makers who consider the use of one of these technologies are provided with the required scientific background as well as with practical advice for upgrading an existing laboratory in order to conduct microbiological experiments. We believe that the conversion of residual oil into natural gas (methane) and the in situ production of biosurfactants are the most promising approaches for MEOR and therefore focus on these topics. Moreover, we give an introduction to the microbiology of oilfields and demonstrate that in situ microorganisms as well as injected cultures can help displace unrecoverable oil in place (OIP). After an initial research phase, the enhanced oil recovery (EOR) manager must decide whether MEOR would be economical. MEOR generally improves oil production but the increment may not justify the investment. Therefore, we provide a brief economical assessment at the end of this chapter. We describe the necessary state-of-the-art scientific equipment to guide EOR managers towards an appropriate MEOR strategy. Because it is inevitable to characterize the microbial community of an oilfield that should be treated using MEOR techniques, we describe three complementary start-up approaches. These are: (i) culturing methods, (ii) the characterization of microbial communities and possible bio-geochemical pathways by using molecular biology methods, and (iii) interfacial tension measurements. In conclusion, we hope that this chapter will facilitate a decision on whether to launch MEOR activities. We also provide an update on relevant literature for experienced MEOR researchers and oilfield operators. Microbiologists will learn about basic principles of interface physics needed to study the impact of microorganisms living on oil droplets. Last but not least, students and technicians trying to understand

  15. Arginine requirement of starting broiler chicks.

    PubMed

    Cuca, M; Jensen, L S

    1990-08-01

    Three experiments were conducted to estimate the arginine requirement of male broiler chicks from 0 to 3 wk of age. The experiments were conducted in battery brooders with wires floors, and the birds received water and feed ad libitum. In the first experiment, chicks were fed a diet based on corn, soybean meal, casein, and corn-gluten meal containing 3,200 kcal ME per kg and either 20 or 23% crude protein. Regression analysis indicated an arginine requirement of 1.22% for maximum growth rate and feed efficiency with the 20% protein diet. For chicks fed the 23% protein diet, neither growth rate nor feed efficiency was significantly different among the diets containing arginine ranging from 1.13 to 1.43%. In the second experiment, a basal diet was used containing 17.5% casein and 22.5% protein with arginine ranging from 1.03 to 1.43%. An arginine requirement of 1.18% for maximum body weight gain was estimated by regression analysis, but no significant response to arginine above the basal level was observed for feed efficiency. Performance of chicks fed the basal diet was somewhat reduced because of a difficulty with adherence of feed to the beaks. In a third experiment, three basal diets containing 21, 22, or 23% protein were formulated from practical ingredients without use of casein. The requirement for maximum growth rate and feed efficiency was estimated to be 1.24 to 1.28% for the three diets. The results of these investigations indicate that the arginine requirement for starting chicks suggested by the National Research Council in 1984 of 1.44% in diets containing 3,200 kcal ME per kg is too high for practical diets. The data presented here support an arginine requirement of 1.25%. PMID:2235851

  16. Incidence of virological failure and major regimen change of initial combination antiretroviral therapy in the Latin America and the Caribbean: an observational cohort study

    PubMed Central

    Cesar, Carina; Jenkins, Cathy A.; Shepherd, Bryan E.; Padgett, Denis; Mejía, Fernando; Ribeiro, Sayonara Rocha; Cortes, Claudia P.; Pape, Jean W.; Madero, Juan Sierra; Fink, Valeria; Sued, Omar; McGowan, Catherine; Cahn, Pedro

    2015-01-01

    Background Access to combination antiretroviral therapy (cART) is expanding in Latin America and the Caribbean (LAC). There is little information in this region regarding incidence of and factors associated with regimen failure and regimen change. Methods Antiretroviral-naïve adults starting cART from 2000-2014 at sites in seven countries throughout LAC were included. Cumulative incidence of virologic failure and major regimen change were estimated with death considered a competing event. Findings 14,027 cART initiators (60% male, median age 37 years, median CD4 156 cells/mm3, median HIV-RNA 5·0 log10 copies/mL, and 28% with clinical AIDS) were followed for a median of 3·9 years. 1,719 patients presented virologic failure and 1,955 had a major regimen change. Excluding GHESKIO-Haiti (which did not regularly measure HIV-RNA), cumulative incidence of virologic failure was 7·8%, 19·2%, and 25·8% at one, three, and five years after cART initiation, respectively; cumulative incidence of major regimen change was 5·9%, 12·7%, and 18·2%. Incidence of major regimen change at GHESKIO-Haiti at five years was 10·7%. Virologic failure was associated with younger age (adjusted hazard ratio[aHR]=2·03 for 20 vs. 40 years; 95% confidence interval[CI] 1·68-2·44), infection through injection-drug use (IDU) (aHR=1·60; 95%CI 1·02-2·52), initiation in earlier calendar years (aHR=1·28 for 2002 vs. 2006; 95%CI 1·13-1·46), and starting with a boosted protease inhibitor (aHR=1·17 vs. non-nucleoside reverse transcriptase inhibitor; 95%CI 1·00-1·64). Interpretation Incidence of virologic failure was generally lower than in North America/Europe. Our results suggest the need to design strategies to reduce failure and major regimen change among younger patients and those with a history of IDU. Funding US National Institutes of Health: U01 AI069923. PMID:26520929

  17. 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

  18. Pakistan/USAID to start CSM project.

    PubMed

    1984-01-01

    Pakistan, with the assistance of funds for the US Agency for International Development (USAID), is about to start its novel approach to contraceptive social marketing (CSM). This new effort suggests a marked policy shift on the part of the Pakistan government toward intensifying its family planning activities. The program will be government-operated and supported by AID over the next 5 years with $20 million, more than double the cost of similar CSM projects elswhere. Distribution of a condom on a pilot project basis is expected to begin by December 1984. Sales of a low-dose oral contraceptive (OC) could begin in test market areas by mid-1985, with national launching of both products tentatively scheduled for January 1986. The Pakistan/USAID agreement represents the 1st time since the formation of India's Nirodh project in the late 1960s that a CSM program is being established without the involvement of either an international social marketing contractor or a country's family planning association. The Pakistan CSM program will be managed by a policy board composed of representatives from the government's Ministries of Planning, Health and Education; a resident advisor from USAID; and a local company responsible for product marketing and distribution. The approach has received a skeptical response among international social marketing experts about the program's chances for success. Their doubts extend to 2 other aspects of the proposed design: an official of the Ministry of Planning's Population and Welfare Division expects the CSM program to generate sufficient revenues to cover all operating costs following the 5-year subsidy period, while also providing attractive profit margins for the marketing/distribution company; and the government prohibits mass media advertising of contraceptives. According to AID, the issue of mass media contraceptive advertising has not yet been resolved, and a national survey will be conducted to determine what communication needs are

  19. 40 CFR 1065.930 - Engine starting, restarting, and shutdown.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... otherwise, start, restart, and shut down the test engine for field testing as follows: (a) Start or restart... continue testing. (d) Shut down and restart the engine according to the manufacturer's specifications,...

  20. 40 CFR 1065.930 - Engine starting, restarting, and shutdown.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... otherwise, start, restart, and shut down the test engine for field testing as follows: (a) Start or restart... continue testing. (d) Shut down and restart the engine according to the manufacturer's specifications,...