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1

When to Start Antiretroviral Therapy  

MedlinePLUS

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

2

When to start antiretroviral therapy during tuberculosis treatment  

PubMed Central

Purpose of review Effective treatment exists for TB and for HIV but treating both diseases simultaneously presents several challenges. This review assessed the evidence for timing of antiretroviral therapy (ART) initiation in patents co-infected with TB. Recent findings Published evidence clearly demonstrates that TB HIV integration is essential for improved survival, but the question of when to start ART during TB treatment is more complex. Five randomised controlled trials assessed this question; four trials showed no difference in incidence rates of AIDS or death between TB patients initiating ART within 2 months compared to later during TB therapy, while one trial showed a significant survival gain with ART initiation within 2 weeks of TB therapy start. All five studies found improved AIDS-free survival with earlier ART initiation in TB patients with low CD4+ T-cell counts, except among patients with TB meningitis. The survival benefit was however, accompanied by increased immune reconstitution inflammatory syndrome events. Summary The trial data support the World Health Organisation recommendations on when to start ART in TB-HIV co-infected patients including earlier ART initiation in severely immune-compromised patients. However, several challenges remain in integrating TB and HIV treatment in public health care services. Additional research on timing of ART is needed for patients with drug-resistant and extra-pulmonary TB, notably TB meningitis. PMID:23188213

Naidoo, Kogieleum; Baxter, Cheryl; Abdool Karim, Salim S.

2013-01-01

3

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

PubMed Central

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

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

2012-01-01

4

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

PubMed Central

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

2013-01-01

5

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

PubMed Central

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

2013-01-01

6

Predictors of virologic response in persons who start antiretroviral therapy during recent HIV infection  

PubMed Central

Objective Despite evidence supporting antiretroviral therapy (ART) in recent HIV infection, little is known about factors that are associated with successful ART. We assessed demographic, virologic, and immunologic parameters to identify predictors of virologic response. Design A 24-week observational study of ART on persons enrolled within 6 months of their estimated date of infection (EDI) evaluated baseline demographics and the collection of blood and gut specimens. Methods Flow cytometry analyses of blood and gut lymphocytes allowed characterization of CD4+ and CD8+ T cells at study entry and end. Additional assessments included soluble CD14 (sCD14), lipopolysaccharide, CD4+ T-cell counts, and HIV RNA levels. Results Twenty nine participants initiated ART, and 17 achieved undetectable HIV RNA by study end. A longer time from EDI to ART, older age, higher sCD14, lower proportions of central memory CD4+ T cells, and higher proportions of activated CD8+ T cells were associated with detectable viremia. Multivariable logistic regression found only older age and elevated sCD14 were independently associated with persistent viremia. Additionally, we observed that ART in recent infection did not result in discernible recovery of CD4+ T cells in the gut. Conclusion In persons who started ART within 3–33 weeks from EDI, age and microbial translocation were associated with detectable HIV RNA. As observed in other cohorts, ART in recent infection did not improve proportions of total CD4+ T cells in gut-associated lymphoid tissue (GALT). This lends support to further evaluate the use of more potent ART or regimens that protect the GALT in recent HIV infection. PMID:24401640

Karris, Maile Y.; Kao, Yu-ting; Patel, Derek; Dawson, Matthew; Woods, Steven P.; Vaida, Florin; Spina, Celsa; Richman, Douglas; Little, Susan; Smith, Davey M.

2014-01-01

7

Treatment modification in HIV-Infected individuals starting antiretroviral therapy between 2011 and 2014  

PubMed Central

Introduction While antiretroviral therapy (ART) has increased the survival of HIV patients and turned HIV infection into a chronic condition, treatment modifications and poor adherence might limit this therapeutic success. Methods Patients from the Austrian HIV Cohort Study, who started their first ART after Rilpivirine became available in February 2011, were analyzed for factors associated with treatment modification which could be either a change of drugs or a stop of the regimen. A drug was considered as stopped when the regimen was interrupted for more than eight days. Drugs of particular interest were Darunavir (DRV), Atazanavir (ATV), Raltegravir (RAL), Rilpivirine (RPV) and Efavirenz (EFV). RPV and EFV were analyzed only when taken as single tablet regimen. Other drugs were summarized as “other.” Proportional hazards regression methods were used to identify predictors of discontinuation and Kaplan–Meier estimates were used to calculate probabilities of discontinuation. Patients who died were censored at the date of death. Results 965 patients started ART, 282 with DRV, 161 with ATV, 96 with RAL, 108 with RPV and 118 with EFV. Median time for taking initial ART is 11.6 months. 322 (33.4%) patients modified their initial ART. The overall probability of modification at one year was 28.7%, at two years 40.0% and at three years 49.8%. In a multivariable proportional hazards regression analysis, AIDS diagnosis at baseline and injecting drug use (IDU) of men compared with men who have sex with men (MSM) have a higher risk of switch/stop. Compared with DRV, RPV showed a much lower and ATV and particularly “other” a higher risk for discontinuation (Table 1). Availability of more effective/convenient treatment (28.9%) was the main reason for discontinuation, especially in the group “other” (43.5%), RAL (34.6%) and DRV (31.6%). Non-specified patient or physician wish to modify therapy was revealed in 17.4% and 9.3% respectively. EFV was modified in 52.8% due to central nervous system toxicity and ATV in 27.8% for gastrointestinal toxicity including hyperbilirubinemia. Conclusion Rates of modification and interruption were still high in recent years, particularly in the first year of ART. The decreased rate of modification found in patients treated with Rilpivirine may be attributed to selection of patients according to guidelines. PMID:25397512

Rappold, Michaela; Rieger, Armin; Steuer, Andrea; Geit, Maria; Sarcletti, Mario; Haas, Bernhard; Taylor, Ninon; Kanatschnig, Manfred; Leierer, Gisela; Ledergerber, Bruno; Zangerle, Robert

2014-01-01

8

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

PubMed Central

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

2014-01-01

9

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

Technology Transfer Automated Retrieval System (TEKTRAN)

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

10

Clinical impact and cost-effectiveness of antiretroviral therapy in India: starting criteria and second-line therapy  

PubMed Central

Background India has more than 5.7 million people infected with human immunodeficiency virus (HIV). In 2004, the Indian government began providing antiretroviral therapy (ART), and there are now an estimated 56 500 people receiving ART. Objective To project the life expectancy, cost, and cost-effectiveness associated with different strategies for using ART in India, to inform treatment programs. Methods We utilized an HIV disease simulation model, incorporating data on natural history, treatment efficacy, and costs of care from India. Input parameters for the simulated cohort included mean age 32.6 years and mean CD4 count 318 cells/?l (SD 291 cells/?l). We examined different criteria for starting and stopping ART with a first-line regimen of stavudine/lamivudine/nevirapine, and the impact of a second-line protease-inhibitor-based regimen. Cost-effectiveness in US dollars per year of life saved (US$/YLS) was compared incrementally among alternative starting, sequencing, and stopping criteria. Results Discounted (undiscounted) mean survival ranged from 34.5 (37.5) months with no ART to 64.7 (73.6) months with one line of therapy initiated at CD4 < 350 cells/?l, to 88.9 (106.5) months with two lines of therapy initiated at CD4 < 350 cells/?l. Lifetime medical costs ranged from US$530 (no ART) to US$5430 (two ART regimens) per person. With one line of therapy, the incremental cost-effectiveness ratios ranged from US$430/YLS to US$550/YLS as the CD4 starting criterion was increased from CD4 < 250 cells/?l to < 350 cells/?l. Use of two lines of therapy had an incremental cost-effectiveness ratio of US$1880/YLS compared with the use of first-line therapy alone. Results were sensitive to the costs of second-line therapy and criteria for stopping therapy. Conclusions In India, antiretroviral therapy will lead to major survival benefits and is cost-effective by World Health Organization criteria. The availability of second-line regimens will further increase survival, but their cost-effectiveness depends on their relative cost compared with first-line regimens. PMID:17620747

Freedberg, Kenneth A.; Kumarasamy, Nagalingeswaran; Losina, Elena; Cecelia, Anitha J.; Scott, Callie A.; Divi, Nomita; Flanigan, Timothy P.; Lu, Zhigang; Weinstein, Milton C.; Wang, Bingxia; Ganesh, Aylur K.; Bender, Melissa A.; Mayer, Kenneth H.; Walensky, Rochelle P.

2008-01-01

11

When to start antiretroviral therapy: the need for an evidence base during early HIV infection  

PubMed Central

Background Strategies for use of antiretroviral therapy (ART) have traditionally focused on providing treatment to persons who stand to benefit immediately from initiating the therapy. There is global consensus that any HIV+ person with CD4 counts less than 350 cells/?l should initiate ART. However, it remains controversial whether ART is indicated in asymptomatic HIV-infected persons with CD4 counts above 350 cells/?l, or whether it is more advisable to defer initiation until the CD4 count has dropped to 350 cells/?l. The question of when the best time is to initiate ART during early HIV infection has always been vigorously debated. The lack of an evidence base from randomized trials, in conjunction with varying degrees of therapeutic aggressiveness and optimism tempered by the risks of drug resistance and side effects, has resulted in divided expert opinion and inconsistencies among treatment guidelines. Discussion On the basis of recent data showing that early ART initiation reduces heterosexual HIV transmission, some countries are considering adopting a strategy of universal treatment of all HIV+ persons irrespective of their CD4 count and whether ART is of benefit to the individual or not, in order to reduce onward HIV transmission. Since ART has been found to be associated with both short-term and long-term toxicity, defining the benefit:risk ratio is the critical missing link in the discussion on earlier use of ART. For early ART initiation to be justified, this ratio must favor benefit over risk. An unfavorable ratio would argue against using early ART. Summary There is currently no evidence from randomized controlled trials to suggest that a strategy of initiating ART when the CD4 count is above 350 cells/?l (versus deferring initiation to around 350 cells/?l) results in benefit to the HIV+ person and data from observational studies are inconsistent. Large, clinical endpoint-driven randomized studies to determine the individual health benefits versus risks of earlier ART initiation are sorely needed. The counter-argument to this debate topic can be freely accessed here: http://www.biomedcentral.com/1741-7015/11/147. PMID:23767777

2013-01-01

12

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

PubMed

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

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

2014-01-01

13

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

Microsoft Academic Search

As Antiretroviral Therapy (ART) is scaled up in low- and middle-income countries, it is important to understand Quality of\\u000a Life (QOL) correlates including disease severity and person characteristics and to determine the extent of between-country\\u000a differences among those with HIV. QOL and medical data were collected from 1,563 of the 1,571 participants at entry into a\\u000a randomized clinical trial of

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

14

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

PubMed Central

Objective Clinical and immunological data about HIV in older adults from low and middle income countries is scarce. We aimed to describe differences between younger and older adults with HIV starting antiretroviral therapy in two low–income African countries. Methods Setting: HIV clinics in Uganda and Zimbabwe. Design: Secondary exploratory cross-sectional analysis of the DART randomized controlled trial. Outcome Measures: Clinical and laboratory characteristics were compared between adults aged 18-49 years (younger) and ? 50 years (older), using two exploratory multivariable logistic regression models, one with HIV viral load (measured in a subset pre-ART) and one without. Results A total of 3316 eligible participants enrolled in DART were available for analysis; 219 (7%) were ? 50 years and 1160 (35%) were male. Across the two adjusted regression models, older adults had significantly higher systolic blood pressure, lower creatinine clearance and were consistently less likely to be females compared to younger adults with HIV. Paradoxically, the models separately suggested that older adults had statistically significant (but not clinically important) higher CD4+ cell counts and higher plasma HIV–1 viral copies at initiation. Crude associations between older age and higher baseline hemoglobin, body mass index, diastolic blood pressure and lower WHO clinical stage were not sustained in the adjusted analysis. Conclusions Our study found clinical and immunological differences between younger and older adults, in a cohort of Africans starting antiretroviral therapy. Further investigations should explore how these differences could be used to ensure equity in service delivery and affect outcomes of antiretroviral therapy. PMID:24098434

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

2013-01-01

15

Comparing costs and effectiveness of different starting points for highly active antiretroviral therapy in HIV-positive patients. Evidence from the ICONA cohort.  

PubMed

We evaluated the costs and effectiveness of starting highly active antiretroviral therapy (HAART) at different points during the course of HIV infection, defined on the basis of CD4 T-lymphocytes counts. The study considered 3,250 HAART-naive patients of the Italian Cohort Naive Antiretrovirals (ICONA), enrolled and followed between 1997 and 2002. In correspondence to the thresholds of 500, 350, and 200 CD4 cells/mm(3), we selected immediate and deferred groups accounting for lead-time bias. The effects of immediate vs. deferred treatment on AIDS-free survival and direct health costs were estimated stratifying on the propensity score of immediate HAART initiation. The incremental cost-effectiveness ratio (ICER) and the cost-effectiveness acceptability curve were also obtained. Although immediate HAART initiation did not affect incidence AIDS and death at high CD4 levels, starting HAART with 200-349 CD4 cells/mm(3) rather than deferring it below 200 CD4 cells/mm(3), proved to be cost-effective. PMID:16404620

Merito, Monica; Pezzotti, Patrizio

2006-03-01

16

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

PubMed

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

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

2013-10-01

17

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

PubMed Central

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

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

18

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

PubMed Central

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

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

2014-01-01

19

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

PubMed Central

Background In HIV-infected persons, good adherence to antiretroviral therapy (ART) is essential for successful treatment outcomes. Patients’ worries before starting ART may affect their ART adherence and treatment outcomes. Methods Between 2004 and 2009, HIV-infected individuals in a prospective cohort study in rural Uganda were assessed for ART eligibility. A counsellor explained the ART eligibility criteria, adherence and side effects, and recorded the patients’ worries related to ART. Every quarter, patients who initiated ART had clinical, immunological (CD4 cell counts) and virological (viral loads) assessments, and data were collected on ART adherence using patients’ self-reports and pill counts. We describe the patients’ worries and examine their association with ART adherence, and immunological and virological outcomes. Results We assessed 421 patients, 271 (64%) were females, 318 (76%) were aged 30 years and above and 315 (75%) were eligible for ART. 277 (66%) reported any worry, and the proportions were similar by sex, age group and ART eligibility status. The baseline median CD4 counts and viral loads were similar among patients with any worry and those with no worry. The commonest worries were: fear of HIV serostatus disclosure; among 69 (16%) participants, lack of food when appetite improved after starting ART; 50 (12%), concurrent use of other medications; 33 (8%), adherence to ART; 28 (7%) and problems concerning condom use; 27 (6%). After 24 months or more on ART, patients who reported any worry had made more scheduled ART refill visits than patients who reported no worry (p<0.01), but the annual CD4 cell increases were similar (p=0.12). After one year on ART, patients who reported any worry had greater virological suppression than patients who reported no worry (p<0.05). Conclusions Despite the lack of significant associations of worries with unfavourable ART outcomes, physicians and counsellors should assist patients in overcoming their worries that can cause stress and discomfort. Food supplements may be desirable for some patients initiating ART. PMID:23651541

2013-01-01

20

When to Start Antiretroviral Therapy in Children Aged 2–5 Years: A Collaborative Causal Modelling Analysis of Cohort Studies from Southern Africa  

PubMed Central

Background There is limited evidence on the optimal timing of antiretroviral therapy (ART) initiation in children 2–5 y of age. We conducted a causal modelling analysis using the International Epidemiologic Databases to Evaluate AIDS–Southern Africa (IeDEA-SA) collaborative dataset to determine the difference in mortality when starting ART in children aged 2–5 y immediately (irrespective of CD4 criteria), as recommended in the World Health Organization (WHO) 2013 guidelines, compared to deferring to lower CD4 thresholds, for example, the WHO 2010 recommended threshold of CD4 count <750 cells/mm3 or CD4 percentage (CD4%) <25%. Methods and Findings ART-naďve children enrolling in HIV care at IeDEA-SA sites who were between 24 and 59 mo of age at first visit and with ?1 visit prior to ART initiation and ?1 follow-up visit were included. We estimated mortality for ART initiation at different CD4 thresholds for up to 3 y using g-computation, adjusting for measured time-dependent confounding of CD4 percent, CD4 count, and weight-for-age z-score. Confidence intervals were constructed using bootstrapping. The median (first; third quartile) age at first visit of 2,934 children (51% male) included in the analysis was 3.3 y (2.6; 4.1), with a median (first; third quartile) CD4 count of 592 cells/mm3 (356; 895) and median (first; third quartile) CD4% of 16% (10%; 23%). The estimated cumulative mortality after 3 y for ART initiation at different CD4 thresholds ranged from 3.4% (95% CI: 2.1–6.5) (no ART) to 2.1% (95% CI: 1.3%–3.5%) (ART irrespective of CD4 value). Estimated mortality was overall higher when initiating ART at lower CD4 values or not at all. There was no mortality difference between starting ART immediately, irrespective of CD4 value, and ART initiation at the WHO 2010 recommended threshold of CD4 count <750 cells/mm3 or CD4% <25%, with mortality estimates of 2.1% (95% CI: 1.3%–3.5%) and 2.2% (95% CI: 1.4%–3.5%) after 3 y, respectively. The analysis was limited by loss to follow-up and the unavailability of WHO staging data. Conclusions The results indicate no mortality difference for up to 3 y between ART initiation irrespective of CD4 value and ART initiation at a threshold of CD4 count <750 cells/mm3 or CD4% <25%, but there are overall higher point estimates for mortality when ART is initiated at lower CD4 values. Please see later in the article for the Editors' Summary PMID:24260029

Schomaker, Michael; Egger, Matthias; Ndirangu, James; Phiri, Sam; Moultrie, Harry; Technau, Karl; Cox, Vivian; Giddy, Janet; Chimbetete, Cleophas; Wood, Robin; Gsponer, Thomas; Bolton Moore, Carolyn; Rabie, Helena; Eley, Brian; Muhe, Lulu; Penazzato, Martina; Essajee, Shaffiq; Keiser, Olivia; Davies, Mary-Ann

2013-01-01

21

Initiation of antiretroviral therapy  

PubMed Central

With the widespread availability of antiretroviral therapy, there is a dramatic decline in HIV related morbidity and mortality in both developed and developing countries. Further, the current antiretroviral drug combinations are safer and the availability of newer monitoring assays and guidelines has vastly improved the patient management. The clinician needs to evaluate several key issues prior to institution of antiretroviral regimen including the correct stage of starting the treatment and the kind of regimen to initiate. In addition to various disease related factors, it is also critical to assess the patient's general condition including nutritional status, presence of co-morbidities and mental preparedness prior to starting the therapy. The patients need to develop an overall understanding of the treatment and its benefits and the importance of lifelong adherence to the drugs. The presence of special situations like pediatric age, older patients, pregnancy, lactation and presence of opportunistic infections also require modification of the therapy. This review briefly summarizes issues relevant to the clinician prior to the initiation of antiretroviral therapy. PMID:24958979

Pandhi, Deepika; Ailawadi, Pallavi

2014-01-01

22

Antiretroviral neurotoxicity  

PubMed Central

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

Robertson, Kevin; Liner, Jeff

2013-01-01

23

[Antiretroviral therapy].  

PubMed

Antiretroviral therapy to treat HIV, as we know it today, is nothing less than a huge success story in modern medical history. What used to be an almost certain death-sentence was transformed into a very manageable chronic disease by means of highly efficient und mostly well tolerated drugs. Today, HIV-infected patients treated according to international recommendations have a very good chance to outgo the negative effects of HIV-1 and are therefore able to reach an almost normal life expectancy. Furthermore, patients successfully treated with antiretroviral drugs are no longer infectious, which is an essential aspect of global strategies to overcome the pandemic. Nevertheless, due to the complexity of HIV, physicians treating patients with antiretroviral therapy require profound knowledge of aspects such as viral resistance mechanisms and immune reconstitution, as well as drug-toxicity und drug-drug-interactions. Many other aspects such as long-term side-effects of antiretroviral drugs are still unknown. Strict adherence to treatment is of utmost importance. PMID:25093310

von Braun, Amrei; Furrer, Hansjakob; Battegay, Manuel; Calmy, Alexandra; Cavassini, Matthias; Vernazza, Pietro; Bernasconi, Enos; Weber, Rainer; Günthard, Huldrych F

2014-08-01

24

Antiretroviral therapy associated mastopathy.  

PubMed

Reports about bilateral breast enlargement in patients on antiretroviral therapy are rare. It forms a constituent of the human immunodeficiency virus lipodystrophy syndrome. Often clinical suspicion followed by appropriate imaging evaluation is confirmative.A case of antiretroviral therapy associated mastopathy is therefore presented here so that increased awareness would obviate the need of mastectomy in such cases. We also emphasise the role of adequate counselling in this scenario in alleviating patients' anxiety. PMID:23024714

Sankaye, Smita; Kachewar, Sushil

2012-01-01

25

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

PubMed

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

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

2012-12-01

26

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

PubMed Central

Purpose of review The purpose of the study was to review recent evidence on the use of antiretrovirals during pregnancy and breastfeeding in low-income and middle-income settings. Recent findings Access to antiretroviral prophylaxis strategies for HIV-infected pregnant women has increased globally, but two-thirds of women in need still do not receive even the simplest regimen for the prevention of mother-to-child transmission of HIV, and most pregnant women in need of antiretroviral treatment do not receive it. The use of combination antiretroviral treatment in pregnancy in low-resource settings is safe and effective, and increasing evidence supports starting ongoing antiretroviral treatment at a CD4 cell count below 350/?l in pregnant women. The use of appropriate short-course antiretroviral prophylactic regimens is effective for prevention of mother-to-child transmission of HIV in women with higher CD4 cell counts. New data on the use of antiretroviral prophylaxis to prevent transmission through breastfeeding demonstrate that both maternal antiretroviral treatment and extended infant prophylaxis are effective. Summary Antiretroviral use in pregnancy can benefit mothers in need of treatment and reduce the risk of mother-to-child transmission. Emerging evidence of the effectiveness of antiretroviral prophylaxis in preventing transmission through breastfeeding is encouraging and likely to influence practice in the future. PMID:20046147

McIntyre, James

2010-01-01

27

Antiretroviral therapy 2000.  

PubMed

As we enter the new millennium, there have been dramatic improvements in the care of patients with HIV infection. These have prolonged life and decreased morbidity and mortality. There are fourteen currently available antiretrovirals approved in the United States for the treatment of this infection. The medications, including their pharmacokinetic properties, side effects, and dosing are reviewed. In addition, the current approach to the use of these medicines is discussed. PMID:11059817

Samuel, R; Suh, B

2000-10-01

28

Intrapartum Exposure to Nevirapine and Subsequent Maternal Responses to Nevirapine-Based Antiretroviral Therapy  

Microsoft Academic Search

background A single intrapartum dose of nevirapine for the prevention of mother-to-child trans- mission of human immunodeficiency virus (HIV) leads to the selection of resistance mutations. Whether there are clinically significant consequences in mothers who are subsequently treated with a nevirapine-containing regimen is unknown. methods We randomly assigned 1844 women in Thailand who received zidovudine during the third trimester of

Gonzague Jourdain; Nicole Ngo-Giang-Huong; Sophie Le Coeur; Chureeratana Bowonwatanuwong; Pacharee Kantipong; Pranee Leechanachai; Surabhon Ariyadej; Prattana Leenasirimakul; Scott Hammer; Marc Lallemant

2004-01-01

29

The Start of Head Start  

ERIC Educational Resources Information Center

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

Neugebauer, Roger

2010-01-01

30

Start Young!  

ERIC Educational Resources Information Center

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,…

Rubin, Penni

2002-01-01

31

Starting motor  

Microsoft Academic Search

This patent describes a starting motor having a housing, planetary reduction gears including an internal gear in the housing. The improvement consists of an elastic member having a first annular portion mounted in engagement with a fixed annular member of the housing and a plurality of protruding axially extending elastic portions providing a corrugated surface pressed into engagement with an

T. Tanaka; I Hamano

1989-01-01

32

Pilot programme for the rapid initiation of antiretroviral therapy in pregnancy in Cape Town, South Africa  

Microsoft Academic Search

Initiation of antiretroviral therapy (ART) in pregnancy is an important intervention to prevent the mother-to-child transmission (MTCT) of HIV and to promote maternal health. Early initiation of ART is particularly important to achieve viral suppression rapidly before delivery. However, current approaches to start ART in pregnancy may be problematic in many settings, with referrals between antenatal care (ANC) and ART

Landon Myer; Rose Zulliger; Samantha Black; David Pienaar; Linda-Gail Bekker

2012-01-01

33

Getting Started  

NSDL National Science Digital Library

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

Krasny, Marianne E.; Schneider, Rebecca L.; Morreale, Steven J.

2001-01-01

34

Start Young!  

NSDL National Science Digital Library

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

Rubin, Penni

2006-01-01

35

Starting motor  

SciTech Connect

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

Tanaka, T.; Hamano, I

1989-05-23

36

Antiretroviral Pharmacology in Mucosal Tissues  

PubMed Central

Strategies to prevent HIV infection using pre-exposure prophylaxis (PrEP) are required to curtail the HIV pandemic. The mucosal tissues of the genital and rectal tracts play a critical role in HIV acquisition, but antiretroviral (ARV) disposition and correlates of efficacy within these tissues are not well understood. Pre-clinical and clinical strategies to describe ARV pharmacokinetic-pharmacodynamic relationships (PK/PD) within mucosal tissues are currently being investigated. In this review, we summarize the physiochemical and biologic factors influencing ARV tissue exposure. Further, we discuss the necessary steps to generate relevant PK/PD data and the challenges associated with this process. Finally, we suggest how pre-clinical and clinical data might be practically translated into optimal PrEP dosing strategies for clinical trials testing using mathematical modeling and simulation. PMID:23764642

Thompson, Corbin G.; Cohen, Myron S.; Kashuba, Angela D.M.

2014-01-01

37

Use of Third Line Antiretroviral Therapy in Latin America  

PubMed Central

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-naďve 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

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

38

AIDS-related lymphoma: resolution with antiretroviral therapy alone.  

PubMed

Patients with HIV are at increased risk of malignancy, particularly lymphoma, which is the most common malignancy leading to death. With the advent of highly active antiretroviral therapy (HAART), patients live longer but have a longer duration of antigenic stimulation, increasing the prevalence of AIDS-related lymphoma (ARL) in the population living with HIV. Highly active antiretroviral therapy plays a direct role in preserving the immune system, helping to decrease the incidence of ARL. We present a case of a female patient with HIV (CD4 count of 576 cells/mm3) diagnosed with a stage Ill-B non-Hodgkin lymphoma in 2009 while off HAART. She was subsequently started on HAART, leading to full resolution of her lymphoma without any chemotherapeutic intervention. She was last seen in the clinic in December 2013 without any evidence of recurrence of her lymphoma. To our knowledge, this is the first case report of a stage III-B non-Hodgkin

Hallit, Rabih Riad; Afridi, Muhammad; Sison, Raymund; Szabela, Maria Elaine Y; Bajaj, Nikki; Alchaa, Roula; Hallit, Souheil; Awkar, Nelly; Boghossian, Jack; Slim, Jihad

2014-01-01

39

AIDS-related lymphoma: resolution with antiretroviral therapy alone.  

PubMed

Patients with HIV are at increased risk of malignancy, particularly lymphoma, which is the most common malignancy leading to death. With the advent of highly active antiretroviral therapy (HAART), patients live longer but have a longer duration of antigenic stimulation, increasing the prevalence of AIDS-related lymphoma (ARL) in the population living with HIV. Highly active antiretroviral therapy plays a direct role in preserving the immune system, helping to decrease the incidence of ARL. We present a case of a female patient with HIV (CD4 count of 576 cells/mm3) diagnosed with a stage Ill-B non-Hodgkin lymphoma in 2009 while off HAART. She was subsequently started on HAART, leading to full resolution of her lymphoma without any chemotherapeutic intervention. She was last seen in the clinic in December 2013 without any evidence of recurrence of her lymphoma. To our knowledge, this is the first case report of a stage III-B non-Hodgkin

Hallit, Rabih Riad; Afridi, Muhammad; Sison, Raymund; Szabela, Maria Elaine Y; Bajaj, Nikki; Alchaa, Roula; Hallit, Souheil; Awkar, Nelly; Boghossian, Jack; Slim, Jihad

2014-01-01

40

Anxiety and Depression Symptoms as Risk Factors for Non-adherence to Antiretroviral Therapy in Brazil  

Microsoft Academic Search

Depression and anxiety are common among HIV-infected people and rank among the strongest predictors of non-adherence to antiretroviral\\u000a therapy (ART). This longitudinal study aimed to assess whether symptoms of anxiety and depression are predictors of non-adherence\\u000a 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

Lorenza Nogueira Campos; Mark Drew Crosland Guimarăes; Robert H. Remien

2010-01-01

41

Brief report Tuberculosis following initiation of antiretroviral therapy  

E-print Network

1 Brief report Tuberculosis following initiation of antiretroviral therapy in low-income and high-income countries Running title: Tuberculosis on antiretroviral therapy The ART-LINC Collaboration words, 1 table, 1 figure, 13 references Key words: tuberculosis; antiretroviral therapy; HIV/AIDS; low

Paris-Sud XI, Université de

42

KNOWLEDGE AQUIRED THROUGH INDEPENDENT RESEARCH Five Classes of Antiretroviral Drugs  

E-print Network

Signaling Pathways of the Cell Effects of Antiretroviral Drugs in the Human Body Function of the Human of antiretroviral drug classes are generally most effective in treating early stage HIV? ENGAGEMENT DISCUSSIONRESEARCH KNOWLEDGE AQUIRED THROUGH INDEPENDENT RESEARCH Five Classes of Antiretroviral Drugs

Auerbach, Scott M.

43

Preferred antiretroviral drugs for the next decade of scale up  

PubMed Central

Global commitments aim to provide antiretroviral therapy (ART) to 15 million people living with HIV by 2015, and recent studies have demonstrated the potential for widespread ART to prevent HIV transmission. Increasingly, countries are adapting their national guidelines to start ART earlier, for both clinical and preventive benefits. To maximize the benefits of ART in resource-limited settings, six key principles need to guide ART choice: simplicity, tolerability and safety, durability, universal applicability, affordability and heat stability. Currently available drugs, combined with those in late-stage clinical development, hold great promise to simplify treatment in the short term. Over the longer term, newer technologies, such as long-acting formulations and nanotechnology, could radically alter the treatment paradigm. This commentary reviews recommendations made in an expert consultation on treatment scale up in resource-limited settings. PMID:23010379

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

2012-01-01

44

Pathogenesis and prevention of immune reconstitution disease during antiretroviral therapy  

PubMed Central

The risks of unmasking and paradoxical forms of immune reconstitution disease in HIV-infected patients starting antiretroviral therapy (ART) are fuelled by a combination of the late presentation of patients with advanced immunodeficiency, the associated high rates of opportunistic infections (OIs) and the need for rapid initiation of ART to minimize overall mortality risk. We review the risk factors and our current knowledge of the immunopathogenesis of immune reconstitution disease, leading to a discussion of strategies for prevention. Initiation of ART at higher CD4 counts, use of OI-preventive therapies prior to ART eligibility, intensified screening for OIs prior to ART initiation and optimum therapy for OIs are all needed. In addition, use of a range of pharmacological agents with immunosuppressive and immunomodulatory activity is being explored. PMID:21504399

Lawn, Stephen D; Meintjes, Graeme

2011-01-01

45

Progress in antiretroviral drug delivery using nanotechnology  

PubMed Central

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

Mallipeddi, Rama; Rohan, Lisa Cencia

2010-01-01

46

[Metabolic side effects of antiretroviral therapy].  

PubMed

Antiretroviral therapy for HIV-I-infections is accompanied with the occurrence of several metabolic side effects. An often encountered complication of antiretroviral therapy is the adipose redistribution syndrome characterised by an altered distribution of body fat, and linked with protease inhibitor (PI) and nucleoside-reverse-transcriptase inhibitors (NRTIs). Some NRTIs have lactate acidosis as a side effect in rare cases (0.1%), which is accompanied by a high mortality. The far less serious side effect hyperlactaemia is more frequently observed; this is a symptomatic elevation of the lactate level without acidosis. Insulin resistance is not only ascribed to therapy-induced lipoatrophy and visceral fat accumulation, it is also directly related to the use of some PIs and NRTIs. PIs and abacavir and to a lesser extend didanosine result in a high risk of cardiovascular disease. Moreover, the prevalence of traditional cardiovascular risk factors in HIV-infected subjects is higher than that in HIV-seronegative subjects. Clinically relevant interactions exist between PIs and statins. Pravastatin seems to be accompanied with the lowest chance of interaction and is therefore recommended as cholesterol-lowering therapy. The metabolic side effects are outweighed by the favourable effect of the antiretroviral agents. Counteraction of these side effects may therefore not be at the expense of the antiretroviral therapy. PMID:18590059

van der Valk, M; Reiss, P

2008-05-31

47

Antiretroviral therapy for prevention of HIV transmission: implications for Europe.  

PubMed

The aim of this review is to summarise the evidence on the population-level effect of antiretroviral therapy (ART) in preventing HIV infections, and to discuss potential implications in the European context of recommending starting ART when the CD4 count is above 350 cells/mm3. The ability of ART to reduce the risk of HIV transmission has been reported in observational studies and in a randomised controlled trial (HPTN 052), in which ART initiation reduced HIV transmission by 96% within serodiscordant couples. As yet, there is no direct evidence for such an effect among men having sex with men or people who inject drugs. HPTN 052 led international organisations to develop recommendations with a higher CD4 threshold for ART initiation. However, there remains a lack of strong evidence of clinical benefit for HIV-positive individuals starting ART with CD4 count above 350 cells/mm3. The main goal of ART provision should be to increase ART coverage for all those in need, based on the current guidelines, and the offer of ART to those who wish to reduce infectivity; increased HIV testing is therefore a key requirement. Other proven prevention means such as condom use and harm reduction for people who inject drugs remain critical. PMID:24308982

Cambiano, V; O'Connor, J; Phillips, A N; Rodger, A; Lodwick, R; Pharris, A; Lampe, F; Nakagawa, F; Smith, C; van de Laar, M J

2013-01-01

48

Drug Interactions with New and Investigational Antiretrovirals  

PubMed Central

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

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

2010-01-01

49

Bones, Fractures, Antiretroviral Therapy and HIV.  

PubMed

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

Battalora, Linda A; Young, Benjamin; Overton, Edgar T

2014-02-01

50

The Promise of Antiretrovirals for HIV Prevention  

PubMed Central

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

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

2013-01-01

51

Bones, Fractures, Antiretroviral Therapy and HIV  

PubMed Central

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

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

2014-01-01

52

Approved Antiretroviral Drugs Used for Pediatric Treatment of HIV Infection  

MedlinePLUS

... Radiation-Emitting Products Vaccines, Blood & Biologics Animal & ... drugs for pediatric treatment of HIV infection Approved generic formulations of antiretroviral drugs used in the treatment of ...

53

Antiretroviral Drugs Used in the Treatment of HIV Infection  

MedlinePLUS

... Radiation-Emitting Products Vaccines, Blood & Biologics Animal & ... drugs for pediatric treatment of HIV infection Approved generic formulations of antiretroviral drugs used in the treatment of ...

54

Impact of drug classes and treatment availability on the rate of antiretroviral treatment change in the TREAT Asia HIV Observational Database (TAHOD)  

Microsoft Academic Search

BACKGROUND: It is critical to understand the pattern of antiretroviral treatment (ART) prescription in different regions of the world as ART procurement needs to be anticipated. We aimed at exploring rates and predictors of ART combination changes in clinical practice in Treat Asia HIV Observational Database (TAHOD). METHODS: Rates of ART changes were examined in patients who started first line

Preeyaporn Srasuebkul; Alexandra Calmy; Jialun Zhou; Nagalingeswaran Kumarasamy; Matthew Law; Poh Lim

2007-01-01

55

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

PubMed

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

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

2014-01-01

56

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

PubMed

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

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

2014-01-01

57

WHO guidelines for antiretroviral therapy in serodiscordant couples in sub-Saharan Africa: how many fit?  

PubMed

To evaluate the implication of WHO guidelines for serodiscordant couples, we interviewed HIV-infected adults on their partner's serostatus. We found that 12% with more than 500 CD4+ cells/?l should be recommended antiretroviral treatment (ART) because their partner was seronegative; 24% could be recommended not to start ART because their partner was seropositive; and 64% could not be given any recommendation regarding ART early initiation because they had either no stable partnership (30%) or were in a stable partnership with a partner whose status they were not aware of (34%). PMID:24804862

Kouamé, Gérard; Danel, Christine; Moh, Raoul; Badjé, Anani; Jean, Kevin; N'takpe, Jean-Baptiste; Gabillard, Delphine; Le Carrou, Jérome; du Loű, Annabel Desgrées; Deschamps, Nina; Eholie, Serge; Anglaret, Xavier

2014-06-19

58

Modeling Antiretroviral Drug Responses for HIV-1 infected Patients Using Differential Equation Models  

PubMed Central

Summary We review mathematical modeling and related statistical issues of HIV dynamics primarily in response to antiretroviral drug therapy in this article. We start from a basic model of virus infection and then review a number of more advanced models with considering, e.g., pharmacokinetic factors, adherence and drug resistance. Specifically, we illustrate how mathematical models can be developed and parameterized to understand effects of long-term treatment and different treatment strategies on disease progression. In addition, we discuss a variety of parameter estimation methods for differential equation models that are applicable to either within- or between-host viral dynamics. PMID:23603208

Xiao, Yanni; Miao, Hongyu; Tang, Sanyi; Wu, Hulin

2014-01-01

59

Switching antiretroviral therapy to minimize metabolic complications  

PubMed Central

Advances in HIV therapy have made living with HIV for decades a reality for many patients. However, antiretroviral therapy has been associated with multiple long-term complications, including dyslipidemia, fat redistribution, insulin resistance and increased cardiovascular risk. As newer agents with improved metabolic profiles have become available, there is growing interest in the safety and efficacy of switching ART as a strategy to reduce long-term complications. This article reviews recently published data on switching ART to minimize the contributions of specific agents to these complications. PMID:22171239

Lake, Jordan E; Currier, Judith S

2011-01-01

60

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

Microsoft Academic Search

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

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

2006-01-01

61

Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection  

E-print Network

Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection Developed by the HHS Panel on Antiretroviral Therapy and Medical Management of HIV-Infected Children--A Working Group on Antiretroviral Therapy and Medical Management of HIV-Infected Children. Guidelines for the Use of Antiretroviral

Levin, Judith G.

62

Factors associated with timely initiation of antiretroviral therapy in two HIV clinics in Lilongwe, Malawi.  

PubMed

The World Health Organization (WHO) estimates that only 30% of eligible, HIV-infected individuals start antiretroviral therapy (ART). This study seeks to explore the geographic and individual factors associated with starting ART on time. This retrospective study includes 15,734 HIV-positive adults initiating ART at two HIV clinics in Lilongwe, Malawi. The outcome was starting ART within two weeks of meeting ART eligibility as defined by the Malawi ART guidelines. Euclidean distance from patient neighbourhood to their clinic was calculated using Google Earth. Logistic regression models assessed factors influencing starting ART on time. Of 15,734 adults initiating ART, 8178 were from Lighthouse (LH) and 7556 were from Martin Preuss Center (MPC). Combined, 68.7% started treatment on time. Patients who were eligible for ART based on a CD4 cell count <250 cells/mm(3) versus WHO stage were less likely to begin ART on time at both LH (odds ratio [OR] 0.16; 95% CI 0.13-0.19) and MPC (OR 0.24; 95% CI 0.21-0.28). Likelihood of starting on time decreased with each kilometer further from clinic location among LH patients (OR 0.97; 95% CI 0.94-0.99); distance was not significant at MPC. In conclusion, predictors differed by clinic. Distance to clinic and type of eligibility for ART significantly influence starting ART on time. PMID:23467293

Johnson, D C; Feldacker, C; Tweya, H; Phiri, S; Hosseinipour, M C

2013-01-01

63

Antiretroviral drugs: Critical issues and recent advances  

PubMed Central

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

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

2012-01-01

64

Smart Start News, 1999.  

ERIC Educational Resources Information Center

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

Harris, Monica, Ed.

1999-01-01

65

Current Perspectives on HIV-1 Antiretroviral Drug Resistance  

PubMed Central

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

Iyidogan, Pinar; Anderson, Karen S.

2014-01-01

66

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

PubMed Central

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

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

2014-01-01

67

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

PubMed

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

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

2012-02-01

68

Complications of HIV Disease and Antiretroviral Therapy  

PubMed Central

There is growing interest in the pathogenesis, treatment, and prevention of long-term complications of HIV disease and its therapies. Specifically, studies focused on cardiovascular, renal, bone, and fat abnormalities were prominent at the 17th Conference on Retroviruses and Opportunistic Infections. Although enthusiasm about the effectiveness of current antiretroviral therapy remains strong, collectively, the ongoing work in the area of HIV disease and treatment complications appears to reflect concerns that these clinical problems will continue to remain important and possibly increase over time in the current therapeutic era. This year’s conference also highlighted important data on prevention and optimal treatment of common coinfections that occur in HIV-infected individuals, including tuberculosis, influenza, and viral hepatitis. PMID:20516525

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

2011-01-01

69

Starting a Small Business  

NSDL National Science Digital Library

This is the first of several lessons on starting a small business. This class is intended for adults entrepreneurs who may be thinking of starting a business. This lesson gives economic information on small businesses. It also provides information to help the student determine whether they are ready to be a business owner and whether their particular business could succeed. QUESTION: If you were to start a small business or home occupation, what would it be? Create a document giving a brief description of a potential business idea. (You will not be required to share the information with class members.) LESSON: Please read the following articles. 1. Go to the ...

Duke, Sonya

2008-10-07

70

Continuous antiretroviral therapy decreases bone mineral density  

PubMed Central

Objectives To assess the effects of antiretroviral therapy (ART) on bone mineral density (BMD) Design Randomized comparison of continuous ART (viral suppression group; VS) with intermittent ART (drug conservation group; DC) Setting Outpatient clinics in the United States, Australia, and Spain. Participants Participants in the Strategies for Management of Antiretroviral Therapy Body Composition substudy. Main outcome measures Annual hip and spine BMD by dual-energy radiographic absorptiometry (DXA) and spine BMD by quantitative computed tomography (qCT). Methods Comparisons were by intention-to-treat analysis, using longitudinal models for change in BMD. Risk factors for BMD loss were evaluated. Results The 214 participants (median 44 years, 19% female participants, 73% on ART; median T-scores ?0.5 total hip, ?0.7 spine DXA, ?0.9 spine qCT; 98 randomized to VS and 116 to DC) were followed for a mean 2.4 years. With continuous ART, BMD declined per year by 0.8% (hip), 0.4% (spine DXA), and 2.4% (spine qCT). BMD declined significantly less with intermittent ART. Estimated DC minus VS group differences in mean BMD change through follow-up were 1.4% [hip; 95% confidence interval (CI) 0.6–2.3; P=0.002], 1.3% (spine DXA; 95% CI 0.1–2.4, P=0.03), and 3.0% (spine qCT; 95% CI 0.8–5.2, P=0.007). No consistent drug-specific association with BMD decline was found. In the parent study, 10 of 2753 participants in the VS group and two of 2720 in the DC group reported serious fractures (hazard ratio 4.9; 95% CI 1.1–22.5; P=0.04). Conclusion Continuous ART is associated with decline in BMD and possibly more fractures relative to intermittent, CD4 cell count-guided ART. PMID:19531929

Grund, Birgit; Peng, Grace; Gibert, Cynthia L.; Hoy, Jennifer F.; Isaksson, Rachel L.; Shlay, Judith C.; Martinez, Esteban; Reiss, Peter; Visnegarwala, Fehmida; Carr, Andrew D.

2009-01-01

71

Microneedle delivery for improved efficacy of antiretroviral and antibiotic drugs  

E-print Network

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

Stauber, Zachary Jason

2012-01-01

72

Starting an Investment Club  

E-print Network

the treasurer and one other member are given these E-161 8-02 STARTING AN INVESTMENT CLUB Jason Johnson, Bill Thompson and Wade Polk* * Assistant Professor and Extension Economist?Management, Assistant Professor and Extension Economist, and Extension Program...

Johnson, Jason; Thompson, Bill; Polk, Wade

2002-08-12

73

Antiretroviral therapy-associated serious and life-threatening toxicities  

Microsoft Academic Search

In the late 1980s and early 1990s, when HIV\\/AIDS had become the leading cause of death in 25- to 44-year-old persons in the\\u000a United States, it was acceptable to prescribe newer antiretroviral therapy such as zidovudine, which has significant bone\\u000a marrow toxicities but can potentially improve patient survival. Although current antiretroviral therapy is not likely to eradicate\\u000a HIV-1 infection, the

Alice K. Pau

2003-01-01

74

Five Year Outcomes of the China National Free Antiretroviral Treatment Program  

PubMed Central

Background China's National Free Antiretroviral Treatment Program began in 2002 and, by August 2008, included over 52,000 patients. Objective To report five year outcomes on adult mortality and immunological treatment failure rates and risk factors. Design Open cohort analysis of prospectively collected observational database. Patients All patients in national treatment database from June 2002-August 2008. Patients excluded if not started on triple therapy or had missing treatment regimen information. Intervention Antiretroviral therapy per Chinese national treatment guidelines. Measurements Mortality rate and immunologic treatment failure rate using World Health Organization criteria. Results Of 52,191 total patients, 48,785 were included. Median age was 38 years, 58% were male, 53% were infected through plasma/blood, and median baseline CD4 cell count was 118/?L. Mortality was greatest during the first three months of treatment (22.6/100 person-years) but declined to a steady rate of 4-5/100 person-years after six months and maintained over the subsequent 4˝ years. Baseline CD4 cell count <50/?L (adjusted hazard ratio [HR] 3.3, 95% confidence interval [CI] 2.9-3.8, compared to ?200/?L) and having 4-5 baseline symptom categories (adjusted HR 3.4, 95% CI 2.9-4.0, compared to no baseline symptoms) were the strongest mortality risk factors. Treatment failure was determined among 31,070 with ?1 follow-up CD4 cell count. Overall, 25% (12.0/100 person-years) failed treatment with the cumulative treatment failure rate increasing to 50% at five years. Limitation Immunologic treatment failure does not necessarily correlate well with virologic treatment failure. Conclusions The National Free Antiretroviral Treatment Program reduced mortality among adult AIDS patients in China to rates comparable to other low or middle-income countries. A cumulative immunological treatment failure rate of 50% after five years, with limited availability of second-line regimens, is of great concern. PMID:19687476

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

2009-01-01

75

The Survival Benefits of Antiretroviral Therapy in South Africa  

PubMed Central

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

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

2014-01-01

76

Engine starting and stopping  

NASA Astrophysics Data System (ADS)

Different starter systems for jet engines are discussed: electric, cartridge, iso-propyl-nitrate, air, gas turbine, and hydraulic. The fuel system, ignition system, air flow control system, and actual starting mechanism of an air starter motor system are considered. The variation of engine parameters throughout a typical starting sequence are described, with reference to examples for an RB211-535 engine. Physical constraints on engine starting are considered: rotating stall, light up, the window between hang and stall, hang, compressor stall, and the effects of ambient conditions. The following are also discussed: contractual and airworthiness requirements; windmilling; inflight relighting; afterburning light up; combustion stability; and broken shafts. Graphics illustrating the above are presented.

Curnock, Barry

77

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

PubMed

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-naďve 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 naďve 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?antiretroviral-naďve 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. PMID:24740443

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

2014-07-01

78

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

NASA Astrophysics Data System (ADS)

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

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

2013-10-01

79

Getting started information)  

E-print Network

Contents: Getting started (General information) 2 Customer Care 6 Health & Safety 7 Fire Safety as information that we are legally obliged to give (e.g. Health & Safety, fire evacuation procedures etc & twin). Lafrowda has 730 rooms in flats of up to 12 people. Each has a kitchen/diner/lounge area

Mumby, Peter J.

80

Start a Rock Collection  

NSDL National Science Digital Library

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

History, American M.

2012-06-26

81

Starting Material Silicon substrate  

E-print Network

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

Healy, Kevin Edward

82

Home Start Evaluation Study.  

ERIC Educational Resources Information Center

Case studies of eight Home Start programs are given as the third section of an evaluation study. Communities involved are Binghamton, New York; Franklin, North Carolina; Cleveland, Ohio; Harrogate, Tennessee; Houston, Texas; Weslaco, Texas; Millville, Utah; Parkersburg, West Virginia. Although each study varies in format, each describes in detail…

High/Scope Educational Research Foundation, Ypsilanti, MI.

83

PAINTING CHECKLIST GETTING STARTED  

E-print Network

PAINTING CHECKLIST GETTING STARTED o Choose your colour scheme o Test colours using sample pots o Measure the area to be painted · Choose paint finish, matt, semi-gloss, gloss etc · Type of paint to use, water-based etc · State of repair of current surface · Painting over oil-based/gloss paint or wallpaper

Peters, Richard

84

StartMe  

NSDL National Science Digital Library

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

85

Home Start Evaluation Study.  

ERIC Educational Resources Information Center

Case studies of seven Home Start programs are given as the third section of an evaluation study. Communities involved are Huntsville, Alabama; Fairbanks, Alaska; Fort Defiance, Arizona; Dardanelle, Arkansas; Wichita, Kansas; Gloucester, Massachusetts; and Reno, Nevada. Although each study varies in format, each describes in detail the degree and…

High/Scope Educational Research Foundation, Ypsilanti, MI.

86

Conceptualizing Antiretroviral Adherence in Beijing, China  

PubMed Central

International health experts agree that China is on the verge of an AIDS crisis. In response, the Chinese government initiated the “Four Frees and One Care” policy in 2003 to decrease economic barriers and increase access to antiretroviral therapies for people with HIV. However, long-term treatment success requires not only access, but high rates of medication adherence. This qualitative interview study with 29 persons receiving HIV care at Beijing’s Ditan Hospital identified barriers to and facilitators of medication adherence. The interviews were guided by an a priori conceptual model of adherence with four components: access, knowledge about medications, motivation, and proximal cues to action. Barriers to adherence were related to stigma and fear of discrimination; the medications themselves (including side effects and complicated dosing regimens); and other economic issues (i.e., costs of transportation, lab tests, and hospitalizations). Facilitators included participants’ strong will to live, use of electronic reminders, and family support. These results support the conceptual model and suggest that successful interventions must minimize stigma as it negatively affects all components of the model for adherence. PMID:18576162

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

2012-01-01

87

Antiretroviral procurement and supply chain management.  

PubMed

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

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

2014-01-01

88

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

PubMed Central

Background For antiretroviral therapy (ART) naive human immunodeficiency virus (HIV) infected adults suffering from tuberculosis (TB), there is uncertainty about the optimal time to initiate highly active antiretroviral therapy (HAART) after starting antituberculosis treatment (ATT), in order to minimize mortality, HIV disease progression, and adverse events. Methods In a randomized, open label trial at All India Institute of Medical Sciences, New Delhi, India, eligible HIV positive individuals with a diagnosis of TB were randomly assigned to receive HAART after 2-4 or 8-12?weeks of starting ATT, and were followed for 12?months after HAART initiation. Participants received directly observed therapy short course (DOTS) for TB, and an antiretroviral regimen comprising stavudine or zidovudine, lamivudine, and efavirenz. Primary end points were death from any cause, and progression of HIV disease marked by failure of ART. Findings A total of 150 patients with HIV and TB were initiated on HAART: 88 received it after 2-4?weeks (early ART) and 62 after 8-12?weeks (delayed ART) of starting ATT. There was no significant difference in mortality between the groups after the introduction of HAART. However, incidence of ART failure was 31% in delayed versus 16% in early ART arm (p?=?0.045). Kaplan Meier disease progression free survival at 12?months was 79% for early versus 64% for the delayed ART arm (p?=?0.05). Rates of adverse events were similar. Interpretation Early initiation of HAART for patients with HIV and TB significantly decreases incidence of HIV disease progression and has good tolerability. Trial registration CTRI/2011/12/002260 PMID:22846195

2012-01-01

89

Getting Started with Android  

Microsoft Academic Search

\\u000a Android is hot, and many people are developing Android applications (apps for short). Perhaps you would also like to develop\\u000a apps, but are unsure about how to get started. Although you could study Google’s online Android Developer’s Guide (http:\\/\\/developer.android.com\\/guide\\/index.html) to acquire the needed knowledge, you might be overwhelmed by the vast amount\\u000a of information that this guide presents. In contrast,

Dave Smith; Jeff Friesen

90

HIV Infection, Antiretroviral Therapy and Cardiovascular Risk  

PubMed Central

In the last 15 years, highly active antiretroviral therapy (HAART) has determined a dramatic reduction of both morbidity and mortality in human immunodeficiency virus (HIV)-infected subjects, transforming this infection in a chronic and manageable disease. Patients surviving with HIV in the developed world, in larger number men, are becoming aged. As it would be expected for a population of comparable age, many HIV-infected individuals report a family history of cardiovascular disease, a small proportion have already experienced a cardiovascular event and an increasing proportion has diabetes mellitus. Smoking rate is very high while an increasing proportion of HIV-infected individuals have dyslipidaemia. Studies suggest that these traditional risk factors could play an important role in the development of cardiovascular disease in these patients as they do in the general population. Thus, whilst the predicted 10-year cardiovascular disease risk remains relatively low at present, it will likely increase in relation to the progressive aging of this patient population. Thus, the long-term follow-up of HIV infected patients has to include co-morbidity management such as cardiovascular disease prevention and treatment. Two intriguing aspects related to the cardiovascular risk in patients with HIV infection are the matter of current investigation: 1) while these subjects share many cardiovascular risk factors with the general population, HIV infection itself increases cardiovascular risk; 2) some HAART regimens too influence atherosclerotic profile, partly due to lipid changes. Although the mechanisms involved in the development of cardiovascular complications in HIV-infected patients remain to be fully elucidated, treatment guidelines recommending interventions to prevent cardiovascular disease in these individuals are already available; however, their application is still limited. PMID:21776340

de Gaetano Donati, Katleen; Cauda, Roberto; Iacoviello, Licia

2010-01-01

91

Perceived adverse effects of antiretroviral therapy.  

PubMed

Adverse effects from antiretroviral therapy (ARV) for HIV are associated with medication nonadherence. The purposes of this study were to explore group differences in the reporting of adverse effects, identify individual adverse effects that are linked to nonadherence, and to explore the role of coping in the relationship between adverse effects and adherence. Cross-sectional interviews of 2,765 HIV-positive adults on ARV therapies in four U.S. cities were performed using a computerized assessment of self-reported adverse effects, coping self-efficacy, and adherence. There were no gender differences in the rate or severity of adverse effects reported. Latino respondents reported more adverse effects than either White or African Americans. Those taking a protease inhibitor (PI) reported a higher rate and greater severity of adverse effects. Older participants reported fewer adverse effects despite being more likely to be on a regimen containing a PI. Respondents with less than 90% adherence reported greater numbers and severity of adverse effects overall. In multivariate analyses, nausea, skin problems, vomiting, and memory adverse effects were independently related to less than 90% adherence over the prior three days. Coping moderated the relationship between nausea and adherence such that individuals who reported lower coping self-efficacy and experienced nausea were at increased risk for nonadherence, regardless of the length of time on the current ARV regimen. Women and men are similar in their overall reports of adverse effects, and Latinos report more adverse effects to ARVs than White or African American patients. Specific adverse effects (skin problems, memory problems, vomiting, and nausea) are more likely than others to be associated with missing ARV medications. Increasing adaptive coping self-efficacy among patients experiencing nausea may be a particularly effective strategy in increasing medication adherence. PMID:15793937

Johnson, Mallory O; Charlebois, Edwin; Morin, Stephen F; Catz, Sheryl L; Goldstein, Rise B; Remien, Robert H; Rotheram-Borus, Mary Jane; Mickalian, Joanne D; Kittel, Lauren; Samimy-Muzaffar, Farishta; Lightfoot, Marguerita A; Gore-Felton, Cheryl; Chesney, A

2005-02-01

92

Factors influencing global antiretroviral procurement prices  

PubMed Central

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

2009-01-01

93

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

PubMed

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

Mowatt, L

2013-01-01

94

Impact of African herbal medicines on antiretroviral metabolism.  

PubMed

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

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

2005-01-01

95

Comparative manufacture and cell-based delivery of antiretroviral nanoformulations  

PubMed Central

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

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

96

StartUpNation  

NSDL National Science Digital Library

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

97

Antiretroviral treatment reverses HIV-associated anemia in rural Tanzania  

PubMed Central

Background HIV-associated anemia is common and associated with poor prognosis. However, its response to antiretroviral treatment (ART) in rural Africa is poorly understood. Methods HIV-infected adults (?15 years) who enrolled in HIV care at Haydom Lutheran Hospital in northern Tanzania were included in the study. The effect of ART (zidovudine/stavudine + lamivudine + efavirenz/nevirapine) on HIV-associated anemia was studied in a subset of patients who were anemic at the time they started ART and had a follow-up hemoglobin measurement 12 months later. Pregnant women were excluded from the study, as were women who had given birth within the past 6 weeks. Anemia was defined as hemoglobin <12 g/dL in women and <13 g/dL in men. We applied paired sample T-tests to compare hemoglobin levels before and one year after ART initiation, and logistic regression models to identify predictors of persistent anemia. Results At enrollment, mean hemoglobin was 10.3 g/dL, and 649 of 838 patients (77.4%) were anemic. Of the anemic patients, 254 (39.1%) had microcytosis and hypochromia. Among 102 patients who were anemic at ART initiation and had a follow-up hemoglobin measurement after 12 months, the mean hemoglobin increased by 2.5 g/dL (P < 0.001); however, 39 patients (38.2%) were still anemic after 12 months of ART. Independent predictors of persistent anemia were mean cell volume in the lower quartile (<76.0 fL; Odds Ratio [OR] 4.34; 95% confidence interval [CI] 1.22-15.5) and a zidovudine-containing initial regimen (OR 2.91; 95% CI 1.03-8.19). Conclusions Most patients had anemia at enrollment, of whom nearly 40% had microcytosis and hypochromia suggestive of iron deficiency. The mean hemoglobin increased significantly in patients who received ART, but one third were still anemic 12 months after ART initiation indicating that additional interventions to treat HIV-associated anemia in rural Africa might be warranted, particularly in patients with microcytosis and those treated with zidovudine. PMID:21745396

2011-01-01

98

Minnesota: Early Head Start Initiatiive  

ERIC Educational Resources Information Center

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…

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

2012-01-01

99

Susceptibility of the human retrovirus XMRV to antiretroviral inhibitors  

Microsoft Academic Search

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

Robert A Smith; Geoffrey S Gottlieb; A Dusty Miller

2010-01-01

100

RESEARCH ARTICLE Open Access Prevalence, genetic diversity and antiretroviral  

E-print Network

-associated mutations among untreated HIV-1-infected pregnant women in Gabon, central Africa MĂ©lanie Caron1 , Sonia to antiretroviral drugs, Untreated pregnant women, Gabon, Central Africa Background Human immunodeficiency virus,3 and Mirdad Kazanji1,4* Abstract Background: In Africa, the wide genetic diversity of HIV has resulted

Paris-Sud XI, Université de

101

Common mental health problems and antiretroviral therapy adherence  

Microsoft Academic Search

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

Adriaan Nel; Ashraf Kagee

2011-01-01

102

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

E-print Network

and mail it with your check* or credit card information to: WSU Tri-Cities Business LINKS 2710 Crimson WayStart Smart: Steps to Starting a Business Workshop Registration The Start Smart workshop will cover: · How much money will you need to start and run the business until it is profitable? · What are your

Collins, Gary S.

103

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

PubMed Central

Background The provision of highly active antiretroviral therapy (HAART) in resource-limited settings follows a public health approach, which is characterised by a limited number of regimens and the standardisation of clinical and laboratory monitoring. In industrialized countries doctors prescribe from the full range of available antiretroviral drugs, supported by resistance testing and frequent laboratory monitoring. We compared virologic response, changes to first-line regimens, and mortality in HIV-infected patients starting HAART in South Africa and Switzerland. Methods and Findings We analysed data from the Swiss HIV Cohort Study and two HAART programmes in townships of Cape Town, South Africa. We included treatment-naďve patients aged 16 y or older who had started treatment with at least three drugs since 2001, and excluded intravenous drug users. Data from a total of 2,348 patients from South Africa and 1,016 patients from the Swiss HIV Cohort Study were analysed. Median baseline CD4+ T cell counts were 80 cells/?l in South Africa and 204 cells/?l in Switzerland. In South Africa, patients started with one of four first-line regimens, which was subsequently changed in 514 patients (22%). In Switzerland, 36 first-line regimens were used initially, and these were changed in 539 patients (53%). In most patients HIV-1 RNA was suppressed to 500 copies/ml or less within one year: 96% (95% confidence interval [CI] 95%–97%) in South Africa and 96% (94%–97%) in Switzerland, and 26% (22%–29%) and 27% (24%–31%), respectively, developed viral rebound within two years. Mortality was higher in South Africa than in Switzerland during the first months of HAART: adjusted hazard ratios were 5.90 (95% CI 1.81–19.2) during months 1–3 and 1.77 (0.90–3.50) during months 4–24. Conclusions Compared to the highly individualised approach in Switzerland, programmatic HAART in South Africa resulted in similar virologic outcomes, with relatively few changes to initial regimens. Further innovation and resources are required in South Africa to both achieve more timely access to HAART and improve the prognosis of patients who start HAART with advanced disease. PMID:18613745

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

2008-01-01

104

Pharmacokinetic and pharmacodynamic drug interactions between antiretrovirals and oral contraceptives.  

PubMed

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 on antiretrovirals and hormonal contraception. PMID:25331712

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

2015-01-01

105

Changes to antiretroviral drug regimens during integrated TB-HIV treatment: Results of the SAPiT trial  

PubMed Central

Background Frequency of drug changes in combination antiretroviral therapy among patients starting both tuberculosis (TB) and human immunodeficiency virus (HIV) therapy, as a result of treatment-limiting toxicity or virological failure, is not well established. Methods Patients in the Starting Antiretroviral Therapy at Three Points in Tuberculosis (SAPiT) trial were randomized to initiate antiretroviral therapy either early or late during TB treatment or after completion of TB treatment. Drug changes due to toxicity (defined as due to grade 3 or 4 adverse events) or virological failure (defined as viral load > 1000 copies/ml on two occasions, taken at least 4 weeks apart) were assessed in these patients. Results A total of 501 TB-HIV co-infected patients were followed for a mean of 16.0 (95% confidence interval (CI): 15.5 to 16.6) months after antiretroviral therapy (ART) initiation. The standard first-line ARVs used, were efavirenz, lamivudine and didanosine. Individual drug switches for toxicity occurred in 14 patients (incidence rate: 2.1 per 100 person-years; 95% (CI): 1.1 to 3.5), and complete regimen changes due to virological failure in 25 patients (incidence rate: 3.7 per 100 person-years; CI: 2.4 to 5.5). The most common treatment limiting toxicities were neuropsychiatric effects (n=4; 0.8%), elevated transaminase levels and hyperlactatemia (n= 3; 0.6%), and peripheral neuropathy (n=2; 0.4%). Complete regimen change due to treatment failure was more common in patients with CD4+ cell count <50cells/mm3 (p<0.001) at ART initiation and body mass index greater than 25 kg/m2 (p=0.01) at entry into the study. Conclusion Both drug switches and complete regimen change were uncommon in patients co-treated for TB-HIV with the chosen regimen. Patients with severe immunosuppression need to be monitored carefully, as they were most at risk for treatment failure requiring regimen change. PMID:24176943

Naidoo, Anushka; Naidoo, Kogieleum; Yende-Zuma, Nonhlanhla; Gengiah, Tanuja N; Padayatchi, Nesri; Gray, Andrew L.; Bamber, Sheila; Nair, Gonasagrie; Karim, Salim S Abdool

2013-01-01

106

Maryland Early Head Start Initiative  

ERIC Educational Resources Information Center

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…

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

2012-01-01

107

Antiretroviral effect of lovastatin on HIV1-infected individuals without highly active antiretroviral therapy (The LIVE study): a phase-II randomized clinical trial  

Microsoft Academic Search

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

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

2009-01-01

108

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

Microsoft Academic Search

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

Benjamin L. Allen

2008-01-01

109

Bridging the gap between antiretroviral access and adherence in Mexico.  

PubMed

The goal in this article is to examine social problems associated with highly active antiretroviral therapy (HAART) adherence in Mexico and the related challenges for Mexican persons living with HIV/AIDS (PLWHAs). The study was conducted from the perspective of infected and affected individuals. The authors completed 64 in-depth interviews with heterosexual male and female PLWHAs, as well as with some key individuals from their social network. Following the principles of grounded theory, they carried out inductive analysis to create codes and organize central themes. The authors identified problems related to accessing HAART and found that conditions for implementing recommendations made in the international literature to improve adherence are poor. The findings highlight the importance of social factors, such as health care system irregularities, ineffective physician-patient communication, and availability of family and other sources of social support such as self-help groups for PLWHAs' access and adherence to antiretroviral therapy in Mexico. PMID:17478643

Campero, Lourdes; Herrera, Cristina; Kendall, Tamil; Caballero, Marta

2007-05-01

110

Dangerous medicines: Unproven AIDS cures and counterfeit antiretroviral drugs  

PubMed Central

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

Amon, Joseph J

2008-01-01

111

Cold-start vs. warm-start miss ratios  

Microsoft Academic Search

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

Malcolm C. Easton; Ronald Fagin

1978-01-01

112

Emergence of HIV1 Drug Resistance During Antiretroviral Treatment  

Microsoft Academic Search

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

Libin Rong; Zhilan Feng; Alan S. Perelson

2007-01-01

113

Factors associated with suboptimal adherence to antiretroviral therapy in Asia  

PubMed Central

Introduction Adherence to antiretroviral therapy (ART) plays an important role in treatment outcomes. It is crucial to identify factors influencing adherence in order to optimize treatment responses. The aim of this study was to assess the rates of, and factors associated with, suboptimal adherence (SubAdh) in the first 24 months of ART in an Asian HIV cohort. Methods As part of a prospective resistance monitoring study, the TREAT Asia Studies to Evaluate Resistance Monitoring Study (TASER-M) collected patients’ adherence based on the World Health Organization-validated Adherence Visual Analogue Scale. SubAdh was defined in two ways: (i) <100% and (ii) <95%. Follow-up time started from ART initiation and was censored at 24 months, loss to follow-up, death, treatment switch, or treatment cessation for >14 days. Time was divided into four intervals: 0–6, 6–12, 12–18 and 18–24 months. Factors associated with SubAdh were analysed using generalized estimating equations. Results Out of 1316 patients, 32% ever reported <100% adherence and 17% ever reported <95%. Defining the outcome as SubAdh <100%, the rates of SubAdh for the four time intervals were 26%, 17%, 12% and 10%. Sites with an average of >2 assessments per patient per year had an odds ratio (OR)=0.7 (95% confidence interval (CI) (0.55 to 0.90), p=0.006), compared to sites with ?2 assessments per patient per year. Compared to heterosexual exposure, SubAdh was higher in injecting drug users (IDUs) (OR=1.92, 95% CI (1.23 to 3.00), p=0.004) and lower in homosexual exposure (OR=0.52, 95% CI (0.38 to 0.71), p<0.001). Patients taking a nucleoside transcriptase inhibitor and protease inhibitor (NRTI+PI) combination were less likely to report adherence <100% (OR=0.36, 95% CI (0.20 to 0.67), p=0.001) compared to patients taking an NRTI and non-nucleoside transcriptase inhibitor (NRTI+NNRTI) combination. SubAdh decreased with increasing time on ART (all p<0.001). Similar associations were found with adherence <95% as the outcome. Conclusions We found that SubAdh, defined as either <100% and <95%, was associated with mode of HIV exposure, ART regimen, time on ART and frequency of adherence measurement. The more frequently sites assessed patients, the lower the SubAdh, possibly reflecting site resourcing for patient counselling. Although social desirability bias could not be excluded, a greater emphasis on more frequent adherence counselling immediately following ART initiation and through the first six months may be valuable in promoting treatment and programme retention. PMID:24836775

Jiamsakul, Awachana; Kumarasamy, Nagalingeswaran; Ditangco, Rossana; Li, Patrick CK; Phanuphak, Praphan; Sirisanthana, Thira; Sungkanuparph, Somnuek; Kantipong, Pacharee; Lee, Christopher KC; Mustafa, Mahiran; Merati, Tuti; Kamarulzaman, Adeeba; Singtoroj, Thida; Law, Matthew

2014-01-01

114

Approved Generic Formulations of Antiretroviral Drugs Used in the Treatment of HIV Infection  

MedlinePLUS

... Radiation-Emitting Products Vaccines, Blood & Biologics Animal & ... drugs for pediatric treatment of HIV infection Approved generic formulations of antiretroviral drugs used in the treatment of ...

115

Antiretroviral therapy initiation in an Australian cohort: implications for increased use of antiretroviral therapy.  

PubMed

Human immunodeficiency virus (HIV) management is entering a "universal test and treat" phase, although the benefits from this approach in developed world scenarios are uncertain. We analyzed 79 combination anti-retroviral therapy (cART)-naďve HIV-positive individuals who were intensively prospectively followed from 2004 to 2013. We studied HIV-related illnesses, potential HIV transmissions, impact on sexual behavior, and factors impeding earlier cART initiation. Sixty-eight (86 %) subjects commenced cART at a mean of 6.0 years after diagnosis: 71 % with a CD4 T-cell count <350 cells/?l. A significant minority of subjects (29 %) resisted initiation of cART despite physician recommendation for a mean of 18 months. Only one HIV-related illness occurred in a patient who had not previously recorded a CD4 T-cell count <500 cell/?l, totaling 195 person-years of observation. A 40 % increase in sexually transmitted infections (STIs) occurred after commencing cART. We detected six HIV transmissions in our cohort, all of which were before initiating cART and 5 of them had a prior CD4 T-cell count <500 cells/?l. Illnesses related to cART deferral were rare and most HIV transmissions we detected occurred in people with a prior CD4 T-cell count <500 cells/?l. Our study raises concerns about increasing STI rates after cART initiation. Focusing resources on cART initiation among patients with CD4 T-cell counts <500 cells/?l and enhancing safe sexual practices should remain a priority. PMID:25139203

Stratov, I; Kent, S J

2015-02-01

116

START Background Report START, September 2013 1 BACKGROUND REPORT  

E-print Network

-Shabaab, terrorism in Kenya, and extended attacks involving hostages in barricade situations. AL-SHABAAB Since: Global Terrorism Database #12;START Background Report © START, September 2013 2 Bombing/ Explosion 38/ Infrastructure Attack 2.37% Hijacking 0.36% Al-Shabaab Attack Types, 2007-2012 (n=548) Source: Global Terrorism

Hill, Wendell T.

117

A Start-up company to start your career  

E-print Network

-up company? · Tremendous job insecurity ­ Funding may disappear in an instant ­ Technology, or marketing, may · Technology push · Market pull · Direction and focus of company almost always changes · Must meet needsA Start-up company to start your career Professional Development Seminar March 6, 2013 #12;What

118

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

PubMed

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. PMID:24352130

Jordan, Mr; Obeng-Aduasare, Y; Sheehan, H; Hong, Sy; Terrin, N; Duong, Dv; Trung, Nv; Wanke, C; Kinh, Nv; Tang, Am

2013-12-18

119

Maine: Early Head Start Initiatives  

ERIC Educational Resources Information Center

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

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

2012-01-01

120

Research Services START UP FUNDS  

E-print Network

/compliance/chreb/ Conjoint Faculties Research Ethics Board New website: www.ucalgary.ca/research/ethics/cfreb Animal Care-up spending (prior to any recruitment of research participants or the acquisition of animals) and timeResearch Services START UP FUNDS www.ucalgary.ca/research START UP FUNDS From time to time some

de Leon, Alex R.

121

Kansas: Early Head Start Initiative  

ERIC Educational Resources Information Center

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…

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

2012-01-01

122

Nebraska: Early Head Start Initiative  

ERIC Educational Resources Information Center

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…

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

2012-01-01

123

Antiretroviral Treatment Outcomes amongst Older Adults in a Large Multicentre Cohort in South Africa  

PubMed Central

Introduction Increasing numbers of patients are starting antiretroviral treatment (ART) at advanced age or reaching advanced age while on ART. We compared baseline characteristics and ART outcomes of older adults (aged ?55 years) vs. younger adults (aged 25–54 years) in routine care settings in South Africa. Methods A multicentre cohort study of ART-naďve adults starting ART at 89 public sector facilities was conducted. Mortality, loss to follow-up (LTFU), immunological and virological outcomes until five years of ART were compared using competing-risks regression, generalised estimating equations and mixed-effects models. Results 4065 older adults and 86,006 younger adults were included. There were more men amongst older adults; 44.7% vs. 33.4%; RR?=?1.34 (95% CI: 1.29–1.39). Mortality after starting ART was substantially higher amongst older adults, adjusted sub-hazard ratio (asHR)?=?1.44 over 5 years (95% CI: 1.26–1.64), particularly for the period 7–60 months of treatment, asHR?=?1.73 (95% CI: 1.44–2.10). LTFU was lower in older adults, asHR?=?0.87 (95% CI: 0.78–0.97). Achievement of virological suppression was greater in older adults, adjusted odds ratio?=?1.42 (95% CI: 1.23–1.64). The probabilities of viral rebound and confirmed virological failure were both lower in older adults, adjusted hazard ratios?=?0.69 (95% CI: 0.56–0.85) and 0.64 (95% CI: 0.47–0.89), respectively. The rate of CD4 cell recovery (amongst patients with continuous viral suppression) was 25 cells/6 months of ART (95% CI: 17.3–33.2) lower in older adults. Conclusions Although older adults had better virological outcomes and reduced LTFU, their higher mortality and slower immunological recovery warrant consideration of age-specific ART initiation criteria and management strategies. PMID:24949879

Fatti, Geoffrey; Mothibi, Eula; Meintjes, Graeme; Grimwood, Ashraf

2014-01-01

124

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

PubMed Central

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

Gutierrez, Félix; Padilla, Sergio; Masiá, Mar; Iribarren, José A.; Moreno, Santiago; Viciana, Pompeyo; Muńoz, 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

125

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

Microsoft Academic Search

Sub-Saharan Africa contains over 60% of the world's HIV infections and Zambia is among the most severely affected countries in the region. As antiretroviral programs have been rapidly expanding, the long-term success of these programs depends on a good understanding of the behavioral determinants of acceptance and adherence to antiretroviral therapy (ART). The study used qualitative methods to gain local

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

2009-01-01

126

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

Microsoft Academic Search

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

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

2010-01-01

127

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

ERIC Educational Resources Information Center

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

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

2009-01-01

128

Lessons learned during down referral of antiretroviral treatment in Tete, Mozambique  

Microsoft Academic Search

As sub-Saharan African countries continue to scale up antiretroviral treatment, there has been an increasing emphasis on moving provision of services from hospital level to the primary health care clinic level. Delivery of antiretroviral treatment at the clinic level increases the number of entry points to care, while the greater proximity of services encourages retention in care. In Tete City,

Tom Decroo; Isabella Panunzi; Carla das Dores; Fernando Maldonado; Marc Biot; Nathan Ford; Kathryn Chu

2009-01-01

129

Mother-to-child HIV transmission despite antiretroviral therapy in the ANRS French Perinatal Cohort  

E-print Network

therapy. Design: The French Perinatal Cohort (EPF), a multicenter prospective cohort of HIV infectedTITLE Mother-to-child HIV transmission despite antiretroviral therapy in the ANRS French Perinatal status as dependant variable, were conducted among 5271 mothers who received antiretroviral therapy

Boyer, Edmond

130

Factors associated with non-adherence to antiretroviral therapy in the SUN study  

Microsoft Academic Search

Background. Adherence of 95% or greater to highly active combination antiretroviral therapy is generally considered necessary to achieve optimal virologic suppression in HIV-infected patients. Understanding factors associated with poor adherence is essential to improve patient compliance, maximize virologic suppression, and reduce morbidity and mortality.Methods. We evaluated baseline data from 528 patients taking antiretrovirals, enrolled from March 2004 to June 2006,

Melanie Kyser; Kate Buchacz; Timothy J. Bush; Lois J. Conley; John Hammer; Keith Henry; Erna M. Kojic; Joel Milam; E. Turner Overton; Kathy C. Wood; John T. Brooks

2011-01-01

131

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

PubMed Central

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-naďve (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

2014-01-01

132

Medication Possession Ratio Predicts Antiretroviral Regimens Persistence in Peru  

PubMed Central

Objectives In developing nations, the use of operational parameters (OPs) in the prediction of clinical care represents a missed opportunity to enhance the care process. We modeled the impact of multiple measurements of antiretroviral treatment (ART) adherence on antiretroviral treatment outcomes in Peru. Design And Methods Retrospective cohort study including ART naďve, non-pregnant, adults initiating therapy at Hospital Nacional Cayetano Heredia, Lima-Peru (2006-2010). Three OPs were defined: 1) Medication possession ratio (MPR): days with antiretrovirals dispensed/days on first-line therapy; 2) Laboratory monitory constancy (LMC): proportion of 6 months intervals with ?1 viral load or CD4 reported; 3) Clinic visit constancy (CVC): proportion of 6 months intervals with ?1 clinic visit. Three multi-variable Cox proportional hazard (PH) models (one per OP) were fit for (1) time of first-line ART persistence and (2) time to second-line virologic failure. All models were adjusted for socio-demographic, clinical and laboratory variables. Results 856 patients were included in first-line persistence analyses, median age was 35.6 years [29.4-42.9] and most were male (624; 73%). In multivariable PH models, MPR (per 10% increase HR=0.66; 95%CI=0.61-0.71) and LMC (per 10% increase 0.83; 0.71-0.96) were associated with prolonged time on first-line therapies. Among 79 individuals included in time to second-line virologic failure analyses, MPR was the only OP independently associated with prolonged time to second-line virologic failure (per 10% increase 0.88; 0.77-0.99). Conclusions The capture and utilization of program level parameters such as MPR can provide valuable insight into patient-level treatment outcomes. PMID:24098475

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

2013-01-01

133

Nanoformulated Antiretroviral Drug Combinations Extend Drug Release and Antiretroviral Responses in HIV1Infected Macrophages: Implications for NeuroAIDS Therapeutics  

Microsoft Academic Search

We posit that improvements in pharmacokinetics and biodistributions of antiretroviral therapies (ART) for human immunodeficiency\\u000a virus type one-infected people can be achieved through nanoformulationed drug delivery systems. To this end, we manufactured\\u000a nanoparticles of atazanavir, efavirenz, and ritonavir (termed nanoART) and treated human monocyte-derived macrophages (MDM)\\u000a in combination therapies to assess antiretroviral responses. This resulted in improved drug uptake, release,

Ari S. Nowacek; JoEllyn McMillan; Reagan Miller; Alec Anderson; Barrett Rabinow; Howard E. Gendelman

2010-01-01

134

Metabolic and hepatobiliary side effects of antiretroviral therapy (ART).  

PubMed

Although antiretroviral therapy (ART) for human immunodeficiency virus (HIV) has been in use since 1987, the initiation of highly active ART has produced an increase in adverse drug reactions. This is a new challenge as many of the adverse drug reactions attributable to ART may be indistinguishable from non-drug-related illnesses. The emergency physician must be aware of the potential complications of ART as affected patients may present with nonspecific symptoms. The focus of this article is the metabolic and hepatobiliary adverse effects of ART. PMID:20413022

Lugassy, Daniel M; Farmer, Brenna M; Nelson, Lewis S

2010-05-01

135

Closing the Gap Antiretroviral Therapy for the Developing World  

NSDL National Science Digital Library

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

Pals-Rylaarsdam, Robin

2003-01-01

136

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

PubMed

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

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

2015-02-01

137

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

PubMed Central

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

2011-01-01

138

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

PubMed Central

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

2013-01-01

139

STARTing Again: What Happens After START I Expires?  

SciTech Connect

The Strategic Arms Reduction Treaty (START I), a seminal arms control agreement that substantially reduced the levels of deployed strategic nuclear arms in the United States and Russia, will expire in December 2009. At this time, it is unclear what—if anything—will replace it. While the treaty remains relevant, more than a simple extension is appropriate. Instead the authors advocate for a successor regime that builds on the START I legacy but does not rely on the traditional tools of arms control. This paper examines the strategic context in which a successor regime would be developed and proposes several recommendations for future action.

Mladineo, Stephen V.; Durbin, Karyn R.; Eastman, Christina M.

2007-08-01

140

An antimalarial extract from neem leaves is antiretroviral.  

PubMed

An acetone-water neem leaf extract with antimalarial activity was evaluated in vitro at 5 microg/ml for inhibition of adhesion of malaria parasite-infected erythrocytes and cancer cells to endothelial cells, and at 10 microg/ml for protection of lymphocytes against invasion by HIV. The extract was also evaluated in 10 patients with HIV/AIDS at 1000 mg daily for 30 d. The mean binding of infected erythrocytes and cancer cells per endothelial cell was 15 and 11 respectively in the absence of the extract, and 0 and 2 respectively in with the extract. In the absence and presence of the extract, 0% and 75%, respectively, of lymphocytes were protected. In the treated patients, haemoglobin concentration, mean CD4+ cell count and erythrocyte sedimentation rate, which were initially 9.8 g/dl, 126 cells/microl and 90 mm/h respectively, improved to 12.1 g/dl, 241 cells/microl and 49 mm/h. Mean bodyweight and platelet count, initially 57 kg and 328 x 10(3)/mm3 respectively, increased to 60 kg and 359 x 10(3)/mm3. No adverse effects were observed during the study. The extract showed antiretroviral activity with a mechanism of action that may involve inhibition of cytoadhesion. The results may help in the development of novel antiretroviral and antimalarial drugs. PMID:15138081

Udeinya, I J; Mbah, A U; Chijioke, C P; Shu, E N

2004-07-01

141

Drug-Drug Interactions: Antiretroviral Drugs and Recreational Drugs.  

PubMed

With the advances in antiretroviral (ARV) therapy, patients with Human Immunodeficiency Virus (HIV) infection are living longer, however, some patients encounter co- morbidities which sometimes require treatment. Therefore, during the treatment with ARV drugs these patients could take people take several recreational drugs (e.g. amphetamines, hallucinogenes, opiates, or alcohol) with a possible development of drug-drug interactions (DDIs). In particular, Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs/NtRTIs) are mainly excreted through the kidney and are not substrate of the cytochrome P450 or P-glycoprotein, therefore the DDIs during this treatment are minimal. In contrast, the other ARV drugs (i.e. non-nucleoside reverse-transcriptase inhibitors, Protease inhibitors, Integrase inhibitors, chemokine receptor 5 antagonists and HIV-fusion inhibitors) are an important class of antiretroviral medications that are frequent components of HAART regimens but shown several DDIs related to interaction with the cytochrome P450 or P-glycoprotein. In this paper we will review data concerning the possibility of DDI in HIV patients treated with ARV and taking recreational drugs. PMID:25429704

Staltari, Orietta; Leporini, Christian; Caroleo, Benedetto; Russo, Emilio; Siniscalchi, Antonio; De Sarro, Giovambattista; Gallelli, Luca

2014-11-26

142

Antiretroviral therapy in macrophages: implication for HIV eradication  

PubMed Central

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

Gavegnano, Christina; Schinazi, Raymond F

2010-01-01

143

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

PubMed

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. PMID:25542874

Camacho, Ángela; Rivero, Antonio

2014-11-01

144

Starting treatment according to guidelines evaluation: a multicentre audit of HIV patients in the UK.  

PubMed

The aim of this audit was to assess whether HIV patients are being started on antiretroviral therapy (ART) according to British and European guidelines. Data were collected from the Survey of Prevalent HIV Infections Diagnosed (SOPHID) return for 2010 at five major HIV management centres in the UK. Data from this 3873 patient cohort revealed 52 patients who should have been receiving ART according to the guidelines but were not. Of these, 23 patients elected not to start ART despite clinical advice to the contrary. Information required to assist in the decision for earlier ART initiation (CD4 count 350–500 cells/mL) was missing for some patients. Clinicians must pay attention to the regular assessment of patients with a CD4 count of 351–500 cells/mL so that all those who may benefit from earlier treatment are identified. Future research should investigate patient barriers to initiating therapy following recommendation by a clinician. PMID:24400349

Reeves, I; Premchand, N; Schwenk, A; Brennan-Benson, P; Cumming, S; Lee, V; Whitehead, T

2013-03-01

145

Reducing deaths from tuberculosis in antiretroviral treatment programmes in sub-Saharan Africa  

PubMed Central

Mortality rates are high in antiretroviral therapy (ART) programmes in sub-Saharan Africa, especially during the first few months of treatment. Tuberculosis (TB) has been identified as a major underlying cause. Under routine programme conditions, between 5% and 40% of adult patients enrolling in ART services have a baseline diagnosis of TB. There is also a high TB incidence during the first few months of ART (much of which is prevalent disease missed by baseline screening) and long-term rates remain several-fold higher than background. We identify three groups of patients entering ART programmes for which different interventions are required to reduce TB-related deaths. First, diagnostic screening is needed in patients who have undiagnosed active TB so that timely anti-tuberculosis treatment can be started. This may be greatly facilitated by new diagnostic assays such as the Xpert MTB/RIF assay. Second, patients with a diagnosis of active TB need optimised case management, which includes early initiation of ART (with timing now defined by randomised controlled trials), trimethoprim-sulphamethoxazole prophylaxis and treatment of co-morbidity. Third, all remaining patients who are TB-free at enrolment have high ongoing risk of developing TB and require optimised immune recovery (with ART ideally started early in the course of HIV infection), isoniazid preventive therapy and infection control to reduce infection risk. Further specific measures are needed to address multi-drug resistant TB (MDR-TB). Finally, scale-up of all these interventions requires nationally and locally tailored models of care that are patient-centred and provide integrated health care delivery for TB, HIV and other co-morbidities. PMID:22695302

Lawn, Stephen D.; Harries, Anthony D.; Meintjes, Graeme; Getahun, Haileyesus; Havlir, Diane V.; Wood, Robin

2013-01-01

146

Virological failure and drug resistance during first line anti-retroviral treatment in Indonesia.  

PubMed

The virological response and development of drug resistance during first-line anti-retroviral treatment (ART) were studied in Indonesia where the majority of patients infected with HIV have a history of injecting drug use, which is often linked with lower treatment adherence and development of drug-resistance. As many as 575 patients starting ART between September 2007 and March 2010 in Hasan Sadikin Hospital Bandung were followed prospectively. Clinical and laboratory monitoring was performed every 6 months. Plasma samples with HIV-RNA ? 400 copies/ml were examined for drug resistance mutations. Most patients were male (72.3%), 59.7% had a history of injecting drug use, and the median CD4+ cells count before start of ART was 35 cells/mm(3) (IQR 10-104). From 438 HIV patients with HIV-RNA measurements, 40 (9.1%) subjects had HIV-RNA ? 400 copies/ml after 24 weeks (median follow-up 16 (IQR 8-25) months). Of these failing patients 16 (47%) subjects had drug resistance mutations, predominantly M184V (35.3%), Y181C (23.5%), K103N (11.7%), and TAMs (11.7%). A history of treatment discontinuation ? 1 month, reported by 5.3% (23) of patients, was strongly associated with virological failure (adjusted OR 12.64, 95% CI 4.51-35.41); and a history of injecting drug use was not (OR 0.75, 95% CI 0.38-1.46). This is the largest and most systematic evaluation of virological response to first line ART in Indonesia. Patients in this cohort responded well to first line ART, with low rates of virological failure and drug resistance. A history of injecting drug use should not be a reason to withhold ART in this setting. PMID:23722251

Fibriani, Azzania; Wisaksana, Rudi; Indrati, Agnes; Hartantri, Yovita; van de Vijver, David; Schutten, Martin; Alisjahbana, Bachti; Sudjana, Primal; Boucher, Charles A B; van Crevel, Reinout; van der Ven, Andre

2013-08-01

147

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

PubMed Central

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

2014-01-01

148

How much do antiretroviral drugs penetrate into the central nervous system?  

PubMed Central

The central nervous system can act as a compartment in which HIV can replicate independently from plasma, and also as a sanctuary in which, under suboptimal drug pressure, HIV antiretroviral genetic variants can occur. Continuous replication of HIV in brain can contribute to neurocognitive impairment. Therefore, reaching adequate concentrations of antiretrovirals in the central nervous system might be essential in providing neuroprotection and improving neurocognition. Antiretrovirals have a restricted entry into the brain, due to several factors: the unique structure of the blood-brain barrier, and the existence of efficient efflux mechanisms. However, there is a high variability of antiretrovirals in reaching therapeutic drug concentrations in cerebrospinal fluid, that depend on the characteristics of the antiretrovirals (molecular weight, lipophilicity, protein binding) and on their capacity to be substrate for efflux transporters. The review aims to discuss the main mechanisms that interfere with antiretroviral penetration into central nervous system, and to summarize the current data concerning the penetrability of different antiretrovirals into the cerebrospinal fluid. Abbreviations: ART = antiretroviral treatment; ARV = antiretrovirals; NRTI = nucleos(t)idic reverse-transcriptase inhibitors; NNRTI = non-nucleosidic reverse transcriptase inhibitors; INNRT = integrase inhibitors; CNS = central nervous system; BBB = blood-brain barrier; CMT = carrier-mediated transport; AET = active efflux transports; PGP = P-glycoprotein; MRP = multidrug resistance-associated proteins; SLC = solute carriers; OATP = organic anion transporting polypeptide; OAT = organic anion transporters; OCT = organic cation transporters; EFV = Efavirenz; IDV = Indinavir; ZDV = Zidovudine; d4T = Stavudine; ABC = Abacavir; ddI = Didanosine; 3TC = Lamivudine; TDF = Tenofovir; NVP = Nevirapine; PI = Protease inhibitors; APV = Amprenavir; NFV = Nelfinavir; SQV = Saquinavir; ATV = Ataznavir; TPV = Tipranavir; DRV = Darunavir; T20 = Enfuvirtide; RGV = Raltegravir PMID:22514580

Ene, L; Duiculescu, D; Ruta, SM

2011-01-01

149

START-UP ACCIDENT ANALYSIS  

Microsoft Academic Search

S>Analog computer studies are made of two main areas of interest during ; a start-up accident; the ability of drivedown circuitry to shut down the reactor ; before reaching the power range, and the self shut-down characteristics of the ; reactor if the accident progresses into the power range. The results indicate ; that period drivedown circuitry would have to

MacNaughton

1958-01-01

150

Math Club Starting in Kindergarten  

ERIC Educational Resources Information Center

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…

Perry, Ann M.

2011-01-01

151

Head Start Center Design Guide.  

ERIC Educational Resources Information Center

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

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

152

Start Where Your Students Are  

ERIC Educational Resources Information Center

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…

Jackson, Robyn R.

2010-01-01

153

Entrepreneur Training Program. Getting Started.  

ERIC Educational Resources Information Center

This student workbook on starting a small business is part of the entrepreneur training program at Ocean County (New Jersey) Vocational-Technical Schools. The workbook consists of 16 units containing goals and objectives, study questions, exercises, sample materials, and information sheets. Unit topics are as follows: being a small business owner;…

De Maria, Richard

154

Head Start Dental Health Curriculum.  

ERIC Educational Resources Information Center

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

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

155

Ethical Imperative For Head Start  

ERIC Educational Resources Information Center

A Head Start Program should foster an ethically valid situation. Such a situation would encourage the physical, mental, social, emotional and ethical growth and development of the four-year-old with due concern for his needs, interests and special potentialities. (Author)

Pratt, Grace K.

1972-01-01

156

MAKING WAVES, DENVER HEAD START.  

ERIC Educational Resources Information Center

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…

Denver Opportunity, CO.

157

Antiretroviral bioanalysis methods of tissues and body biofluids  

PubMed Central

Research in the many areas of HIV treatment, eradication and prevention has necessitated measurement of antiretroviral (ARV) concentrations in nontraditional specimen types. To determine the knowledgebase of critical details for accurate bioanalysis, a review of the literature was performed and summarized. Bioanalytical assays for 31 ARVs, including metabolites, were identified in 205 publications measuring various tissues and biofluids. 18 and 30% of tissue or biofluid methods, respectively, analyzed more than one specimen type; 35–37% of the tissue or biofluid methods quantitated more than one ARV. 20 and 76% of tissue or biofluid methods, respectively, were used for the analysis of human specimens. HPLC methods with UV detection predominated, but chronologically MS detection began to surpass. 40% of the assays provided complete intra- and inter-assay validation data, but only 9% of publications provided any stability data with even less for the prevalent ARV in treatments. PMID:23394701

DiFrancesco, Robin; Maduke, Getrude; Patel, Rutva; Taylor, Charlene R; Morse, Gene D

2013-01-01

158

Head Start Impact Study: First Year Findings  

ERIC Educational Resources Information Center

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

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

2005-01-01

159

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

PubMed Central

Background Drug-related toxicity has been one of the main causes of antiretroviral treatment discontinuation. However, its determinants are not fully understood. Aim of this study was to investigate predictors of first-line antiretroviral therapy discontinuation due to adverse events and their evolution in recent years. Methods Patients starting first-line antiretroviral therapy were retrospectively selected. Primary end-point was the time to discontinuation of therapy due to adverse events, estimating incidence, fitting Kaplan-Meier and multivariable Cox regression models upon clinical/demographic/chemical baseline patients’ markers. Results 1,096 patients were included: 302 discontinuations for adverse events were observed over 1,861 person years of follow-up between 1988 and 2010, corresponding to an incidence (95% CI) of 0.16 (0.14-0.18). By Kaplan-Meier estimation, the probabilities (95% CI) of being free from an adverse event at 90 days, 180 days, one year, two years, and five years were 0.88 (0.86-0.90), 0.85 (0.83-0.87), 0.79 (0.76-0.81), 0.70 (0.67-0.74), 0.55 (0.50-0.61), respectively. The most represented adverse events were gastrointestinal symptoms (28.5%), hematological (13.2%) or metabolic (lipid and glucose metabolism, lipodystrophy) (11.3%) toxicities and hypersensitivity reactions (9.3%). Factors associated with an increased hazard of adverse events were: older age, CDC stage C, female gender, homo/bisexual risk group (vs. heterosexual), HBsAg-positivity. Among drugs, zidovudine, stavudine, zalcitabine, didanosine, full-dose ritonavir, indinavir but also efavirenz (actually recommended for first-line regimens) were associated to an increased hazard of toxicity. Moreover, patients infected by HIV genotype F1 showed a trend for a higher risk of adverse events. Conclusions After starting antiretroviral therapy, the probability of remaining free from adverse events seems to decrease over time. Among drugs associated with increased toxicity, only one is currently recommended for first-line regimens but with improved drug formulation. Older age, CDC stage, MSM risk factor and gender are also associated with an increased hazard of toxicity and should be considered when designing a first-line regimen. PMID:23145925

2012-01-01

160

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

PubMed

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

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

2014-06-01

161

Novel antiretroviral drugs and renal function monitoring of HIV patients.  

PubMed

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. PMID:25102336

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

162

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

PubMed

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-naďve 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. PMID:25542869

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

2014-11-01

163

Economics of antiretroviral treatment vs. circumcision for HIV prevention  

PubMed Central

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/?L. 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. PMID:23223563

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

2012-01-01

164

Decentralization of HIV care in Cameroon: Increased access to antiretroviral treatment and associated persistent barriers  

Microsoft Academic Search

ContextThe national antiretroviral treatment (ART) program in Cameroon has reached one of the highest rate of coverage in Western and Central Africa (58% of the estimated eligible HIV-infected population in June 2008).

Sandrine Loubiere; Sylvie Boyer; Camélia Protopopescu; Cécile Renée Bonono; Séverin-Cécile Abega; Bruno Spire; Jean-Paul Moatti

2009-01-01

165

A Mathematical Model of Antiretroviral Therapy Evaluation for HIV Type 1  

NASA Astrophysics Data System (ADS)

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.

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

2009-09-01

166

Five-year trends in antiretroviral usage and drug costs in HIV-infected children in Thailand  

PubMed Central

Background As antiretroviral treatment (ART) programmes mature, data on drug utilization and costs are needed to assess durability of treatments and inform programme planning. Methods Children initiating ART were followed in an observational cohort in Thailand. Treatment histories from 1999–2009 were reviewed. Treatment changes were categorized as: drug substitution (within class), switch across drug class (non-nucleoside reverse-transcriptase inhibitors (NNRTIs) and protease-inhibitor (PI), and to salvage therapy (dual PI or PI and NNRTI). Antiretroviral drug costs were calculated in six-month cycles (US$ 2009 prices). Predictors of high drug cost including characteristics at start of ART (baseline), initial regimen, treatment change and duration on ART were assessed using mixed-effects regression models. Results 507 children initiated ART with a median 54 (IQR, 36–72) months of follow-up. Fifty-two percent had a drug substitution, 21% switched across class and 2% to salvage therapy. When allowing for drug substitution, 78% remained on their initial regimen. Mean drug cost increased from $251 to $428 per child per year in the first and fifth year of therapy, respectively. PI-based and salvage regimens accounted for 16% and 2% of treatments prescribed and 33% and 5% of total costs, respectively. Predictors of high cost include: baseline age ?8 years, non nevirapine-based initial regimen; switch across drug class and to salvage regimen (p<0.005). Conclusion At 5 years, 21% of children switched across drug class and 2% received salvage therapy. The mean drug cost increased by 70%. Access to affordable second and third-line drugs is essential for the sustainability of treatment programmes. PMID:23945253

Collins, I; Cairns, J; Le Coeur, S; Pagdi, K; Ngampiyaskul, C; Layangool, P; Borkird, T; Na-Rajsima, S; Wanchaitanawong, V; Jourdain, G; Lallemant, M

2013-01-01

167

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

PubMed Central

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

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

2013-01-01

168

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

PubMed Central

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

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

2014-01-01

169

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

PubMed Central

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

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

2014-01-01

170

Interruptions of antiretroviral therapy in human immunodeficiency virus infection: are they detrimental to neurocognitive functioning?  

Microsoft Academic Search

Because interruptions of antiretroviral treatment may entail clinical risks for human immunodeficiency virus (HIV)-infected\\u000a individuals, we investigated their impact on neurocognitive functioning. Cross-sectional study was carried out, comparing\\u000a HIV-infected persons who had interrupted antiretroviral therapy in the past (interruption group, IG) with persons who had\\u000a never discontinued therapy (noninterruption group, NIG). Interruption was defined as the discontinuation of highly active

Jose A. Muńoz-Moreno; Carmina R. Fumaz; Anna Prats; Maria J. Ferrer; Eugčnia Negredo; Núria Pérez-Álvarez; José Moltó; Guadalupe Gómez; Maite Garolera; Bonaventura Clotet

2010-01-01

171

30 CFR 75.1913 - Starting aids.  

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

2014-07-01

172

30 CFR 75.1913 - Starting aids.  

Code of Federal Regulations, 2012 CFR

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

2012-07-01

173

30 CFR 75.1913 - Starting aids.  

Code of Federal Regulations, 2013 CFR

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

2013-07-01

174

30 CFR 75.1913 - Starting aids.  

Code of Federal Regulations, 2011 CFR

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

2011-07-01

175

30 CFR 75.1913 - Starting aids.  

Code of Federal Regulations, 2010 CFR

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

2010-07-01

176

Drug Abuse Prevention Starts with Parents  

MedlinePLUS

... Abuse Prevention Starts with Parents Ages & Stages Listen Drug Abuse Prevention Starts with Parents Article Body Drugs, including ... for a time when drugs may be offered. Drug abuse prevention starts with parents learning how to talk ...

177

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

PubMed

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

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

2015-02-01

178

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

PubMed Central

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

Rathbun, R. Chris; Liedtke, Michelle D.

2011-01-01

179

Integration of Antiretroviral Therapy Services into Antenatal Care Increases Treatment Initiation during Pregnancy: A Cohort Study  

PubMed Central

Objectives Initiation of antiretroviral therapy (ART) during pregnancy is critical to promote maternal health and prevent mother-to-child HIV transmission (PMTCT). The separation of services for antenatal care (ANC) and ART may hinder antenatal ART initiation. We evaluated ART initiation during pregnancy under different service delivery models in Cape Town, South Africa. Methods A retrospective cohort study was conducted using routinely collected clinic data. Three models for ART initiation in pregnancy were evaluated ART ‘integrated’ into ANC, ART located ‘proximal’ to ANC, and ART located some distance away from ANC (‘distal’). Kaplan-Meier methods and Poisson regression were used to examine the association between service delivery model and antenatal ART initiation. Results Among 14 617 women seeking antenatal care in the three services, 30% were HIV-infected and 17% were eligible for ART based on CD4 cell count <200 cells/µL. A higher proportion of women started ART antenatally in the integrated model compared to the proximal or distal models (55% vs 38% vs 45%, respectively, global p?=?0.003). After adjusting for age and gestation at first ANC visit, women who at the integrated service were significantly more likely to initiate ART antenatally (rate ratio 1.33; 95% confidence interval: 1.09–1.64) compared to women attending the distal model; there was no difference between the proximal and distal models in antenatal ART initiation however (p?=?0.704). Conclusions Integration of ART initiation into ANC is associated with higher levels of ART initiation in pregnancy. This and other forms of service integration may represent a valuable intervention to enhance PMTCT and maternal health. PMID:23696814

Stinson, Kathryn; Jennings, Karen; Myer, Landon

2013-01-01

180

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

PubMed Central

Objectives We investigated whether there are differences in the effects on microbial translocation (MT) and enterocyte damage by different antiretroviral therapy (ART) regimens after 1.5 years and whether antibiotic use has impact on MT. In a randomized clinical trial (NCT01445223) on first line ART, patients started either lopinavir/r (LPV/r) (n?=?34) or efavirenz (EFV) containing ART (n?=?37). Lipopolysaccharide (LPS), sCD14, anti-flagellin antibodies and intestinal fatty acid binding protein (I-FABP) levels were determined in plasma at baseline (BL) and week 72 (w72). Results The levels of LPS and sCD14 were reduced from BL to w72 (157.5 pg/ml vs. 140.0 pg/ml, p?=?0.0003; 3.13 ug/ml vs. 2.85 ug/ml, p?=?0.005, respectively). The levels of anti-flagellin antibodies had decreased at w72 (0.35 vs 0.31 [OD]; p<0.0004), although significantly only in the LPV/r arm. I-FABP levels increased at w72 (2.26 ng/ml vs 3.13 ng/ml; p<0.0001), although significantly in EFV treated patients only. Patients given antibiotics at BL had lower sCD14 levels at w72 as revealed by ANCOVA compared to those who did not receive (??=??0.47 µg/ml; p?=?0.015). Conclusions Markers of MT and enterocyte damage are elevated in untreated HIV-1 infected patients. Long-term ART reduces the levels, except for I-FABP which role as a marker of MT is questionable in ART-experienced patients. Why the enterocyte damage seems to persist remains to be established. Also antibiotic usage may influence the kinetics of the markers of MT. Trial Registration ClinicalTrials.gov NCT01445223 PMID:23383047

Vesterbacka, Jan; Nowak, Piotr; Barqasho, Babilonia; Abdurahman, Samir; Nyström, Jessica; Nilsson, Staffan; Funaoka, Hiroyuki; Kanda, Tatsuo; Andersson, Lars-Magnus; Gisslčn, Magnus; Sönnerborg, Anders

2013-01-01

181

Tuberculosis Immune Reconstitution Inflammatory Syndrome in Children Initiating Antiretroviral Therapy for HIV Infection  

PubMed Central

Background People with HIV initiating combination antiretroviral therapy are at risk for tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS). While this syndrome has been well researched in adults, little is known about the incidence, case fatality, underlying immunopathology and treatment approaches in children. Methods Major databases were searched for articles related to TB-IRIS in children. Data were abstracted using standardized forms. Results Thirteen studies were identified: 6 retrospective and 2 prospective cohort studies, 1 cross-sectional study, 3 case reports and 1 case series. In total, 303 cases of TB-IRIS were described, of which 270 were unmasking TB-IRIS, 12 paradoxical TB-IRIS and 21 were not classifiable due to lack of key information. None of the cohort studies had investigation of TB-IRIS as its primary aim. Nine studies were from Africa, 3 from Asia and 1 from Latin America. Age at cART initiation (reported by 12 studies) ranged from 1 month to 16 years. Median time from start of cART to IRIS diagnosis (reported by 8 studies) ranged from 8 days to 16 weeks. Few deaths attributable to TB-IRIS were recorded. Treatment was only discussed in 2 case studies, both of which reported children receiving corticosteroids. No studies evaluated risk factors for, or immunopathogenesis of, pediatric TB-IRIS. Conclusions There is a paucity of information available on TB-IRIS in children. Future research assessing incidence, risk factors, case fatality and optimal treatment or prevention strategies of TB-IRIS is needed. PMID:24736441

Link-Gelles, Ruth; Moultrie, Harry; Sawry, Shobna; Murdoch, David; Van Rie, Annelies

2014-01-01

182

Predictors of mortality in patients initiating antiretroviral therapy in Durban, South Africa  

PubMed Central

Objective To identify predictors of mortality in patients initiating antiretroviral therapy (ART) in Durban, South Africa. Design We conducted a retrospective cohort study analysing data on patients who presented to McCord Hospital, Durban, and started ART between 1 January 1999 and 29 February 2004. We performed univariate and multivariate analysis and constructed Kaplan-Meier curves to assess predictors. Results Three hundred and nine patients were included. Forty-nine (16%) had died by the conclusion of the study. In univariate analysis, the strongest predictors of mortality were a CD4 cell count <50/?l (hazard ratio (HR) 3.70, 95% confidence interval (CI) 1.96 ? 7.14), a haemoglobin concentration ?8 g/dl (HR 1.23, 95% CI 1.08 ? 1.40), a history of oral candidiasis (HR 3.17, 95% CI 1.70 ? 5.87) and a history of cryptococcal meningitis (HR 2.76, 95% CI 1.80 ? 19.2). A CD4 cell count <50/?l (HR 3.08, 95% CI 1.54 ? 5.88) and a history of oral candidiasis (HR 2.58, 95% CI 1.37 ? 4.88) remained significant in multivariate analysis. A history of tuberculosis was not a significant predictor of mortality. Conclusions Simple clinical and laboratory data independently predict mortality and allow for risk stratification in patients initiating ART in South Africa. Interventions enabling patients to be identified before they develop these clinical markers and earlier initiation of ART will help to ensure maximum benefits of therapy. PMID:18350223

Ojikutu, Bisola O; Zheng, Hui; Walensky, Rochelle P; Lu, Zhigang; Losina, Elena; Giddy, Janet; Freedberg, Kenneth A

2008-01-01

183

Effect of Persistency of First-Line HIV Antiretroviral Therapy on Clinical Outcomes  

PubMed Central

Abstract Persistency is the time from initiation to discontinuation of therapy. Previous research has described factors that affect the persistency of initial antiretroviral therapy (ART); however, the impact of persistency on clinical outcomes is unknown. A retrospective study was conducted of treatment-naive HIV patients initiating ART between January 1, 2000 and December 31, 2010 at an academic medical center. Descriptive statistics and Cox proportional hazards regression models with persistency as a time?varying covariate were fit for (1) immunologic failure (subsequent CD4 lower than initial CD4); (2) development of an opportunistic infection (OI) or malignancy; and (3) mortality. Analyses were repeated with an interaction term of persistency (per 180 days) and time (before and after 1 year of ART). Among 879 patients who started ART, the mean age was 38 years (±10) and most patients were racial/ethnic minority (59%), males (80%), and with baseline CD4 <200 cells/mm3 (52%). There were 100 deaths, 94 OIs/malignancy, and 183 immunologic failures; the mean persistency=723 days. In multivariable modeling, increased persistency decreased the overall and long-term hazard for immunologic failure (0.84 per 180 additional days; 0.70–1.00; 0.045). Increased persistency exhibited a potential trend toward decreased hazard for the occurrence of OI/malignancy (0.91; 0.80–1.03; 0.124) overall and after 1 year. Persistency exhibited a trend toward less risk of mortality in the first year of ART (0.42; 0.17–1.06; 0.067). In this study of the relationship between initial ART persistency and clinical outcomes, increased persistency was associated with a decreased hazard for the development of immunologic failure, a trend toward a decreased hazard for OI/malignancy, and a trend toward a decreased risk of first year mortality. Given these findings, the relationship between persistency and clinical outcomes merits further study. PMID:23151191

Westfall, Andrew O.; Mugavero, Michael; Nevin, Christa R.; Correll, Todd; Duggal, Amit; Guyer, William; Saag, Michael S.; Juday, Timothy

2013-01-01

184

Starting a High School newspaper  

NSDL National Science Digital Library

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

Dart, Greg

2007-10-19

185

Rapid starting methanol reactor system  

DOEpatents

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

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

1984-01-01

186

Start: Statler Hotel (star) Finish: Upson Hall  

E-print Network

Start: Statler Hotel (star) Finish: Upson Hall Duration: 1.30h Main route: Red arrows that start from Statler Hotel and end at Upson Hall 2nd route: Orange dashed line that starts from Statler Hotel and meets read line at McGraw Tower #12;3rd route: Red arrow backwards, starting from Statler Hotel 4th

Keinan, Alon

187

The Home Start Demonstration Program: An Overview.  

ERIC Educational Resources Information Center

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

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

188

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

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+??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 HBV or HCV was associated only to the development of mild liver toxicity, while the occurrence of moderate or severe hepatoxicity was correlated to a baseline CD4+ count?>?250/mm3. No statistically significant effect of the coinfections was observed on the efficacy of antiretroviral therapy. PMID:24708626

2014-01-01

189

Namibian prisoners describe barriers to HIV antiretroviral therapy adherence.  

PubMed

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

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

2014-01-01

190

Experiences of participating in an antiretroviral treatment adherence club.  

PubMed

In an effort to streamline the management of large numbers of patients receiving antiretroviral therapy (ART) in South Africa, adherence clubs were introduced in some districts in the Western Cape since 2008. Adherence clubs are group clinic visits of approximately 30 ART users who receive group adherence counselling and obtain a supply of medication. We sought to document the experiences of patients attending adherence clubs and health care workers (HCW's) at clinics where clubs were operating. Participants were six ART adherence club members and seven HCW's, which included HIV nurses, medical doctors, pharmacists and counsellors. Data in the form of one-on-one interviews were collected at the Infectious Diseases Clinic of a large district hospital in a peri-urban area in the Western Cape region of South Africa. The interviews covered ART users' experiences of the clubs, advantages and challenges that arose in the context of the club-based method of providing treatment, and the concerns faced by ART users and HCW's with regard to the clubs. The data were analysed using thematic analysis. There were clear benefits to the introduction of adherence clubs, most importantly the reduced amount of time ART users needed to spend at the clinic. Yet, various problems also emerged, the most important one being the logistical problems associated with the timely and correct delivery of drugs. These benefits and disadvantages are discussed in the context of providing ART services to large numbers of patients in post-apartheid South Africa. PMID:25168720

Dudhia, Raashika; Kagee, Ashraf

2014-08-28

191

HIV-1 dynamics at different time scales under antiretroviral therapy.  

PubMed

We exploit a model that considers three compartments: blood plasma (BP), lymphoid tissue-interstitial spaces (LT-IS), and follicular dendritic cells (FDC), for the HIV-1 dynamics under the application of highly active antiretroviral therapy (HAART) which allowed us to unravel distinct viral dynamics occurring in short- (2 days), middle- (21 days), and long-term (183 days) time scales. The different time scales are determined by the viral clearance rate, the ratio of productively infected CD4(+) T cells to chronically infected cells, and the dissociation rate of HIV-1 complexes from FDC. This generates a scenario in which, after an initial transient stage, the viral BP dynamics decouples and becomes governed by the lymphoid tissue (LT) dynamics; in a later stage, a new decoupling occurs in which the LT-IS dynamics is slaved to that of the FDC dynamics. We observed an initial increase in the viremia after HAART in a patient who did not receive protease inhibitors (PI). By means of the above-mentioned model we were able to highlight the relevant parameters which need to be estimated at three different time scales after HAART. PMID:16005903

García, José A; Soto-Ramírez, Luis E; Cocho, Germinal; Govezensky, Tzipe; José, Marco V

2006-01-01

192

Development of HIV Reservoir Targeted Long Acting Nanoformulated Antiretroviral Therapies  

PubMed Central

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

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

2014-01-01

193

Novel drug delivery approaches on antiviral and antiretroviral agents  

PubMed Central

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

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

2012-01-01

194

Interleukin-7 promotes HIV persistence during antiretroviral therapy  

PubMed Central

HIV persists in latently infected memory CD4+ T cells during antiretroviral therapy (ART). When administered to HIV-infected subjects receiving suppressive ART, interleukin-7 (IL-7) increases the number of CD4+ T cells by promoting their survival and proliferation. However, little is known about the impact of IL-7 on HIV persistence during ART. By isolating large numbers of CD4+ T cells from HIV-infected subjects, we demonstrate that IL-7 enhances viral production in productively infected cells but does not disrupt viral latency in latently infected cells. When administered to virally suppressed subjects, IL-7 led to the rapid proliferation of memory CD4+ T cells, which resulted in a 70% increase in the absolute number of circulating CD4+ T cells harboring integrated HIV DNA 4 weeks after therapy. The genetic diversity of the viral reservoir increased transiently in the majority of the subjects studied before returning to baseline values. Altogether, our results indicate that IL-7 promotes the mechanisms of HIV persistence during ART by enhancing residual levels of viral production and inducing proliferation of latently infected cells, and suggest that IL-7 does not represent a suitable candidate therapeutic strategy for HIV eradication. This trial was registered at www.clinicaltrials.gov as #NCT00099671 (AIDS Clinical Trials Group protocol 5214). PMID:23589672

Vandergeeten, Claire; Fromentin, Rémi; DaFonseca, Sandrina; Lawani, Mariam B.; Sereti, Irini; Lederman, Michael M.; Ramgopal, Moti; Routy, Jean-Pierre; Sékaly, Rafick-Pierre

2013-01-01

195

Lamivudine-PEGylated chitosan: a novel effective nanosized antiretroviral agent.  

PubMed

Due to the fact that a definite treatment for AIDS disease has not been discovered so far, antiretroviral drugs are relatively significant in controlling the disease. In this study, Lamivudine- which is an old and effective anti-AIDS drug- was connected to PEGylated chitosan nanoparticle in order to produce a new and greater version of Lamivudine. First, physicochemical studies such as HNMR, FTIR spectroscopy and CHN analysis were performed to ensure the proper synthesis. Following that, Lamivudine-PEGylated Chitosan (LPC) drug was evaluated in terms of its inhibitory capability in producing HIV virions and its cytotoxicity in different doses. HIV virions were created by transfection of psPAX2, PmzNL4-3 and pMD2.G plasmids into HEK293T cell line. Also, assessment of the P24 amounts of cell supernatant was performed using ELISA method. Among the different doses of LPC drug (0.1, 1, 10 and 100?M), it was found that 0.1?M was the most effective and least toxic dose compared to Lamivudine in the same dose. Results of this study indicate that LPC drug has the ability to inhibit HIV virus replication in a more significant way in comparison to the old drug. Besides, the drug has a low cytotoxicity and is effective with a lower dose. PMID:23808639

Aghasadeghi, Mohammad R; Heidari, Hossein; Sadat, Seyed M; Irani, Shiva; Amini, Safieh; Siadat, Seyed D; Fazlhashemy, Mohammad E; Zabihollahi, Rezvan; Atyabi, Seyed M; Momen, Seyed B; Khosraavy, Mohammad S; Davari, Mehdi; Darvish Mohammadi, Tahmineh; Doroudian, Mohammad; Ardestani, Mehdi S

2013-06-01

196

Antiretroviral potential of human tripartite motif-5 and related proteins.  

PubMed

TRIM5alpha is a potent inhibitor of infection by diverse retroviruses and is encoded by one of a large family of TRIM genes. We found that several TRIM motifs among a panel of selected human TRIM proteins (TRIM1, 5, 6, 18, 19, 21 22, 34) could inhibit infection when artificially targeted to an incoming HIV-1 capsid. Conversely, when ectopically expressed as authentic full-length proteins, most lacked activity against a panel of retroviruses. The exceptions were TRIM1, TRIM5 and TRIM34 proteins. Weak but specific inhibition of HIV-2/SIV(MAC) and EIAV by TRIM34 was noted, and human TRIM5alpha modestly, but specifically, inhibited an HIV-1 strain carrying a mutation in the cyclophilin binding loop (G89V). Restriction activity observed in ectopic expression assays was sometimes not detectable in corresponding RNAi-based knockdown experiments. However, endogenous owl monkey TRIMCyp potently inhibited an SIV(AGM) strain. Overall, sporadic examples of intrinsic antiretroviral activity exist in this panel of TRIM proteins. PMID:16828831

Zhang, Fengwen; Hatziioannou, Theodora; Perez-Caballero, David; Derse, David; Bieniasz, Paul D

2006-09-30

197

Antiretroviral treatment induced catatonia in 16-year-old boy  

PubMed Central

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.

Lingeswaran, Anand

2014-01-01

198

Temporal Trends in the Characteristics of Children at Antiretroviral Therapy Initiation in Southern Africa: The IeDEA-SA Collaboration  

PubMed Central

Background Since 2005, increasing numbers of children have started antiretroviral therapy (ART) in sub-Saharan Africa and, in recent years, WHO and country treatment guidelines have recommended ART initiation for all infants and very young children, and at higher CD4 thresholds for older children. We examined temporal changes in patient and regimen characteristics at ART start using data from 12 cohorts in 4 countries participating in the IeDEA-SA collaboration. Methodology/Principal Findings Data from 30,300 ART-naďve children aged <16 years at ART initiation who started therapy between 2005 and 2010 were analysed. We examined changes in median values for continuous variables using the Cuzick's test for trend over time. We also examined changes in the proportions of patients with particular disease severity characteristics (expressed as a binary variable e.g. WHO Stage III/IV vs I/II) using logistic regression. Between 2005 and 2010 the number of children starting ART each year increased and median age declined from 63 months (2006) to 56 months (2010). Both the proportion of children <1 year and ?10 years of age increased from 12 to 19% and 18 to 22% respectively. Children had less severe disease at ART initiation in later years with significant declines in the percentage with severe immunosuppression (81 to 63%), WHO Stage III/IV disease (75 to 62%), severe anemia (12 to 7%) and weight-for-age z-scorestart of therapy. However, even in 2010, a substantial number of infants and children started ART with advanced disease. These results highlight the importance of efforts to improve access to HIV diagnostic testing and ART in children. PMID:24363808

Davies, Mary-Ann; Phiri, Sam; Wood, Robin; Wellington, Maureen; Cox, Vivian; Bolton-Moore, Carolyn; Timmerman, Venessa; Moultrie, Harry; Ndirangu, James; Rabie, Helena; Technau, Karl; Giddy, Janet; Maxwell, Nicola; Boulle, Andrew; Keiser, Olivia; Egger, Matthias; Eley, Brian

2013-01-01

199

Impact of antiretroviral therapy on growth, body composition and metabolism in pediatric HIV patients.  

PubMed

Highly active antiretroviral therapy improves survival and growth in children with HIV infection. However, its use can be associated with adverse changes in body composition and metabolism. Bone mineral density can be adversely affected in HIV-positive children due to nutritional compromise or certain antiretrovirals. HIV-associated lipodystrophy, consisting of redistribution of adipose tissue, insulin resistance, and dyslipidemia, has also been described in children. Pediatric HIV patients may be at greater risk for these problems because of their longer potential lifetime exposure to these agents and because childhood is normally a period of rapid growth and tissue accretion. Healthcare providers for children with HIV infection must be aware of the potential complications associated with HIV antiretrovirals so that their antiviral efficacy can be balanced against their risk for side effects. In this review, we discuss the alterations in childhood growth and body composition that occur in HIV-infected children, and describe the impact of antiretroviral therapy on these outcomes. The problem of HIV-associated lipodystrophy syndrome in children is also discussed. Children with HIV should have their growth and body composition systematically monitored. Antiretroviral regimens should be tailored to optimize adherence and viral suppression while minimizing the potential for adverse side effects. PMID:20481647

Kim, Roy J; Rutstein, Richard M

2010-06-01

200

High incidence of intermittent care in HIV-1-infected patients in Curaçao before and after starting cART.  

PubMed

Retention in care is one of the major challenges to scaling up and maximizing the effectiveness of combination antiretroviral therapy (cART). High attrition rates have been reported in the Caribbean region, varying from 6% to 23%. We studied the incidence of and risk factors for intermittent care in a cohort of adult HIV-1-positive patients, who entered into care in Curaçao between January 2005 and July 2009. A total of 214 therapy-naďve HIV-1-infected patients aged 15 years or older, entered HIV care between January 2005 and July 2009. Intermittent care was defined as at least one period of 365 days or longer in which there was no HIV care contact in Curaçao. Cox regression models were used to identify characteristics associated with time to intermittent care. In all, 203 (95%) patients could be classified as having intermittent or continuous care. The incidence of intermittent care before starting cART was 25.4 per 100 person years observation (PYO), whilst it was 6.1 per 100 PYO after starting cART. Being born outside Curaçao was associated with intermittent care before and after starting cART. Time from diagnosis to entry into care was an independent predictor for intermittent care before starting cART. Younger age was independently associated with intermittent care after starting cART. Half of the patients returned to care after intermitting care. Upon returning to care, median CD4 count was 264 cells/mm(3) (IQR, 189-401) for those who intermitted care before starting cART, and 146 cells/mm(3) (IQR, 73-436) in those who intermitted care after starting cART. In conclusion, the incidence of intermitting care is high in Curaçao, especially before starting cART, and intermitting care before starting cART is an independent predictor for starting cART late. PMID:23428308

Hermanides, H S; Holman, R; Gras, L; Winkel, C N; Gerstenbluth, I; de Wolf, F; Duits, A J

2013-01-01

201

When should AIDS-free HIV-1 infected persons initiate antiretroviral therapy? Collaborative analysis of HIV cohort studies  

E-print Network

1 When should AIDS-free HIV-1 infected persons initiate antiretroviral therapy? Collaborative antiretroviral therapy (cART) should be initiated is a central, unresolved issue in the care of HIV-1 infected-1 infected individuals since its introduction in 1996.1,2 Short-term randomized controlled trials

202

Antiretroviral therapy in pregnant women with advanced HIV disease and pregnancy outcomes in Abidjan, Cte d'Ivoire  

E-print Network

in women receiving highly active antiretroviral treatment (HAART) in Africa are not well described. Methods1 Antiretroviral therapy in pregnant women with advanced HIV disease and pregnancy outcomes Sidaction and is now a fellow of the European and Developing Clinical Trial Partnership (EDCTP). Renaud

Paris-Sud XI, Université de

203

Illicit drug use, alcohol use and nicotine dependence as predictors of antiretroviral adherence in a sample of HIV positive smokers  

Microsoft Academic Search

Objective. Predictors of non-adherence to antiretroviral medications in a population of low-income, multiethnic, HIV-positive smokers were investigated. ^ Methods. A secondary analysis was conducted using baseline data collected from 326 patients currently prescribed antiretrovirals enrolled in a randomized clinical trial assessing smoking outcomes. Variables evaluated included demographics, stress, depression, nicotine dependence, illicit drug use and alcohol use. ^ Results. The

Rachel M Marks

2010-01-01

204

The HIV Antiretroviral Drug Efavirenz has LSD-Like Properties  

PubMed Central

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

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

2013-01-01

205

The HIV antiretroviral drug efavirenz has LSD-like properties.  

PubMed

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

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

206

Alaska Head Start. Annual Report for 1998.  

ERIC Educational Resources Information Center

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…

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

207

Alaska Head Start Annual Program Report, 1999.  

ERIC Educational Resources Information Center

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

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

208

Head Start Health Coordinators' Task Force Report.  

ERIC Educational Resources Information Center

The Head Start Health Coordinator's Task Force (HCTF) was charged to study and make recommendations to strengthen Head Start's health component, which is a vital part of the child development program. Since its inception in 1965, Head Start has served over 12 million economically disadvantaged children. Through the health component, children have…

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

209

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

PubMed Central

Introduction Patients who are lost to follow-up (LTFU) while on antiretroviral therapy (ART) pose challenges to the long-term success of ART programs. We describe the extent to which patients considered LTFU are misclassified as true disengagement from care when they are still alive on ART and explain reasons for ART discontinuation using our active tracing program to further improve ART retention programs and policies. Methods We identified adult ART patients who missed clinic appointment by more than 3 weeks between January 2006 and December 2010, assuming that such patients would miss their doses of antiretroviral drugs. Patients considered LTFU who consented during ART registration were traced by phone or home visits; true ART status after tracing was documented. Reasons for ART discontinuation were also recorded for those who stopped ART. Results Of the 4,560 suspected LTFU cases, 1,384 (30%) could not be traced. Of the 3,176 successfully traced patients, 952 (30%) were dead and 2,224 (70%) were alive, of which 2,183 (99.5%) started ART according to phone-based self-reports or physical verification during in-person interviews. Of those who started ART, 957 (44%) stopped ART and 1,226 (56%) reported still taking ART at the time of interview by sourcing drugs from another clinic, using alternative ART sources or making brief ART interruptions. Among 940 cases with reasons for ART discontinuations, failure to remember (17%), too weak/sick (12%), travel (46%), and lack of transport to the clinic (16%) were frequently cited; reasons differed by gender. Conclusion The LTFU category comprises sizeable proportions of patients still taking ART that may potentially bias retention estimates and misdirect resources at the clinic and national levels if not properly accounted for. Clinics should consider further decentralization efforts, increasing drug allocations for frequent travels, and improving communication on patient transfers between clinics to increase retention and adherence. PMID:24086627

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

2013-01-01

210

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

PubMed Central

Background In many HIV programmes in Africa, patients are assessed clinically and prepared for antiretroviral treatment over a period of 4–12 weeks. Mortality rates following initiation of ART are very high largely because patients present late with advanced disease. The rates of mortality and retention during the pre-treatment period are not well understood. We conducted an observational study to determine these rates. Methods HIV-infected subjects presenting at The AIDS Support Clinic in Jinja, SE Uganda, were assessed for antiretroviral therapy (ART). Eligible subjects were given information and counselling in 3 visits done over 4–6 weeks in preparation for treatment. Those who did not complete screening were followed-up at home. Survival analysis was done using poisson regression. Results 4321 HIV-infected subjects were screened of whom 2483 were eligible for ART on clinical or immunological grounds. Of these, 637 (26%) did not complete screening and did not start ART. Male sex and low CD4 count were associated independently with not completing screening. At follow-up at a median 351 days, 181 (28%) had died, 189 (30%) reported that they were on ART with a different provider, 158 (25%) were alive but said they were not on ART and 109 (17%) were lost to follow-up. Death rates (95% CI) per 100 person-years were 34 (22, 55) (n.18) within one month and 37 (29, 48) (n.33) within 3 months. 70/158 (44%) subjects seen at follow-up said they had not started ART because they could not afford transport. Conclusion About a quarter of subjects eligible for ART did not complete screening and pre-treatment mortality was very high even though patients in this setting were well informed. For many families, the high cost of transport is a major barrier preventing access to ART. PMID:19671185

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

2009-01-01

211

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

PubMed Central

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

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

2015-01-01

212

Prospective Cohort Study of the Impact of Antiretroviral Therapy on Employment Outcomes Among HIV Clients in Uganda  

PubMed Central

Abstract This study evaluates the impact of antiretroviral treatment (ART) on employment-related outcomes using prospective, longitudinal analysis. Starting in January 2008, 602 treatment-naďve clients in one rural clinic and in one clinic in the capital Kampala were interviewed about their medical history, and psychosocial and socioeconomic adjustment at baseline and at months 6 and 12. Half of the sample was eligible to receive ART, while the other half was also in HIV care, but not yet eligible for ART, therefore providing a comparison group that is similar to the treatment group in that its members are HIV-positive and have made the decision to enroll in HIV care. We found improvements in general health, reduction in the incidence of pain and health interfering with work, as well as improvements in work-related self-efficacy for both groups over time, but significantly more so for the group receiving ART treatment. At baseline, less than half of the people in the ART group worked, but after 6 months more than three quarters of them were working, surpassing the fraction of people working in the control group after 1 year. Another key finding of the study was the importance of mental health as a key mediator for employment-related outcomes. These data indicate that ART clients experience greater improvements compared to pre-ART clients, and not only with regard to general health, but also in restoring confidence in their ability to work, as well as actual work status. PMID:24320014

Glick, Peter; Kityo, Cissy; Mugyeni, Peter; Wagner, Glenn

2013-01-01

213

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

PubMed Central

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

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

2010-01-01

214

Prospective Predictors of Unprotected Anal Intercourse among HIV-Seropositive Men Who Have Sex with Men Initiating Antiretroviral Therapy  

PubMed Central

Contemporary HIV prevention efforts are increasingly focused on those already living with HIV/AIDS (i.e., “prevention with positives”). Key to these initiatives is research identifying the most risky behavioral targets. Using a longitudinal design, we examined socio-demographic and psychosocial factors that prospectively predicted unprotected anal intercourse (UAI) in a sample of 134 HIV-seropositive men who have sex with men (MSM) initiating, changing, or re-starting an antiretroviral therapy (ARV) regimen as part of a behavioral intervention study. Computer-based questionnaires were given at baseline and 6 months. In a sequential logistic regression, baseline measures of UAI (Step 1), socio-demographic factors such as Latino ethnicity (Step 2), and psychosocial factors such as crystal methamphetamine use, greater life stress, and lower trait anxiety (Step 3) were predictors of UAI at 6 months. Problem drinking was not a significant predictor. Prevention efforts among MSM living with HIV/AIDS might focus on multiple psychosocial targets, like decreasing their crystal methamphetamine use and teaching coping skills to deal with life stress. PMID:23640652

Pantalone, David W.; Huh, David; Nelson, Kimberly M.; Pearson, Cynthia R.; Simoni, Jane M.

2013-01-01

215

Characterization of peripheral and mucosal immune responses in rhesus macaques on long-term tenofovir and emtricitabine combination antiretroviral therapy  

PubMed Central

Background The goal of antiretroviral therapy (ART) is to suppress virus replication to limit immune system damage. Some have proposed combining ART with immune therapies to boost antiviral immunity. For this to be successful, ART must not impair physiological immune function. Methods We studied the impact of ART (tenofovir and emtricitabine) on systemic and mucosal immunity in uninfected and SIV-infected Chinese rhesus macaques. Subcutaneous ART was initiated 2 weeks after tonsillar inoculation with SIVmac239. Results There was no evidence of immune dysregulation as a result of ART in either infected or uninfected animals. Early virus-induced alterations in circulating immune cell populations (decreased central memory T cells and myeloid dendritic cells) were detected, but normalized shortly after ART initiation. ART-treated animals showed marginal SIV-specific T cell responses during treatment, which increased after ART discontinuation. Elevated expression of CXCL10 in oral, rectal and blood samples and APOBEC3G mRNA in oral and rectal tissues was observed during acute infection and was down-regulated after starting ART. ART did not impact the ability of the animals to respond to tonsillar application of polyICLC with increased CXCL10 expression in oral fluids and CD80 expression on blood myeloid dendritic cells. Conclusion Early initiation of ART prevented virus induced damage and did not impede mucosal or systemic immune functions. PMID:22820802

Jasny, E.; Geer, S.; Frank, I.; Vagenas, P.; Aravantinou, M.; Salazar, A.M.; Lifson, J.D.; Piatak, M; Gettie, A.; Blanchard, J.; Robbiani, M.

2012-01-01

216

Effect of home-based interventions on virologic outcomes in adults receiving antiretroviral therapy in Africa: a meta-analysis  

PubMed Central

Background The success of adherence to combination antiretroviral therapy (ART) in sub-Saharan Africa is hampered by factors that are unique to this setting. Home based interventions have been identified as possible strategies for decentralizing ART care and improving access and adherence to ART. There is need for evidence at individual- or community-level of the benefits of home-based interventions in improving HIV suppression in African patients receiving ART. Methods We conducted a systematic review and meta-analysis of the literature to assess the effect of home-based interventions on virologic outcomes in adults receiving ART in Africa. Results A total of 260 publications were identified by the search strategy, 249 were excluded on initial screening and 11 on full review, leaving 5 publications for analysis. The overall OR of virologic suppression at 12 months after starting ART of home-based interventions to standard of care was 1.13 (95% CI: 0.51–2.52). Conclusions There was insufficient data to know whether there is a difference in HIV suppression at 12 months in the home-based arm compared with the standard of care arm in adults receiving ART in Africa. Given the few trials conducted from Africa, there is need for further research that measures the effects of home-based models on HIV suppression in African populations. PMID:24606968

2014-01-01

217

Biomechanical analysis of backstroke swimming starts.  

PubMed

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

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

2011-07-01

218

Elimination of HIV in South Africa through Expanded Access to Antiretroviral Therapy: A Model Comparison Study  

PubMed Central

Background Expanded access to antiretroviral therapy (ART) using universal test and treat (UTT) has been suggested as a strategy to eliminate HIV in South Africa within 7 y based on an influential mathematical modeling study. However, the underlying deterministic model was criticized widely, and other modeling studies did not always confirm the study's finding. The objective of our study is to better understand the implications of different model structures and assumptions, so as to arrive at the best possible predictions of the long-term impact of UTT and the possibility of elimination of HIV. Methods and Findings We developed nine structurally different mathematical models of the South African HIV epidemic in a stepwise approach of increasing complexity and realism. The simplest model resembles the initial deterministic model, while the most comprehensive model is the stochastic microsimulation model STDSIM, which includes sexual networks and HIV stages with different degrees of infectiousness. We defined UTT as annual screening and immediate ART for all HIV-infected adults, starting at 13% in January 2012 and scaled up to 90% coverage by January 2019. All models predict elimination, yet those that capture more processes underlying the HIV transmission dynamics predict elimination at a later point in time, after 20 to 25 y. Importantly, the most comprehensive model predicts that the current strategy of ART at CD4 count ?350 cells/µl will also lead to elimination, albeit 10 y later compared to UTT. Still, UTT remains cost-effective, as many additional life-years would be saved. The study's major limitations are that elimination was defined as incidence below 1/1,000 person-years rather than 0% prevalence, and drug resistance was not modeled. Conclusions Our results confirm previous predictions that the HIV epidemic in South Africa can be eliminated through universal testing and immediate treatment at 90% coverage. However, more realistic models show that elimination is likely to occur at a much later point in time than the initial model suggested. Also, UTT is a cost-effective intervention, but less cost-effective than previously predicted because the current South African ART treatment policy alone could already drive HIV into elimination. Please see later in the article for the Editors' Summary PMID:24167449

Hontelez, Jan A. C.; Lurie, Mark N.; Bärnighausen, Till; Bakker, Roel; Baltussen, Rob; Tanser, Frank; Hallett, Timothy B.; Newell, Marie-Louise; de Vlas, Sake J.

2013-01-01

219

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

PubMed Central

Background This article presents part of the findings from a larger study that sought to assess the role that gender relations play in influencing equity regarding access and adherence to antiretroviral therapy (ART). Review of the literature has indicated that, in Southern and Eastern Africa, fewer men than women have been accessing ART, and the former start using ART late, after HIV has already been allowed to advance. The main causes for this gender gap have not yet been fully explained. Objective To explore how masculinity norms limit men's access to ART in Dar es Salaam. Design This article is based on a qualitative study that involved the use of focus group discussions (FGDs). The study employed a stratified purposive sampling technique to recruit respondents. The study also employed a thematic analysis approach. Results Overall, the study's findings revealed that men's hesitation to visit the care and treatment clinics signifies the superiority norm of masculinity that requires men to avoid displaying weakness. Since men are the heads of families and have higher social status, they reported feeling embarrassed at having to visit the care and treatment clinics. Specifically, male respondents indicated that going to a care and treatment clinic may raise suspicion about their status of living with HIV, which in turn may compromise their leadership position and cause family instability. Because of this tendency towards ‘hiding’, the few men who register at the public care and treatment clinics do so late, when HIV-related signs and symptoms are already far advanced. Conclusion This study suggests that the superiority norm of masculinity affects men's access to ART. Societal expectations of a ‘real man’ to be fearless, resilient, and emotionally stable are in direct conflict with expectations of the treatment programme that one has to demonstrate health-promoting behaviour, such as promptness in attending the care and treatment clinic, agreeing to take HIV tests, and disclosing one's status of living with HIV to at least one's spouse or partner. Hence, there is a need for HIV control agencies to design community-based programmes that will stimulate dialogue on the deconstruction of masculinity notions. PMID:24152373

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

2013-01-01

220

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

PubMed Central

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

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

2015-01-01

221

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

PubMed Central

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

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

2014-01-01

222

Transmitted antiretroviral drug resistance in treatment naďve HIV-infected persons in London in 2011 to 2013  

PubMed Central

Introduction Previously published UK data on HIV transmitted drug resistance (TDR) shows that it ranges between 3 and 9.4% [1,2]. However, there are no recent data from populations where HIV transmission rates are increasing. The aim of this study was to assess the prevalence of TDR in untreated HIV-infected individuals attending three HIV specialist clinics under the HIV Directorate, Chelsea and Westminster Hospital and based throughout London – the Kobler Clinic, 56 Dean Street and West London Centre for Sexual Health. Methods We included all patients with a HIV diagnosis, no history of antiretroviral therapy (ART) intake, attending one of the three clinics (Kobler (K), 56 Dean Street (DS) and West London (WL)), between 2011 and 2013 who started antiretrovirals. Reverse transcriptase (RT) and protease region sequencing was performed using Vircotype virtual phenotype resistance analysis. Drug resistance mutations were identified according to Stanford University HIV Drug Resistance Database (http://hivdb.stanford.edu/). Results Among 1705 HIV-1-infected patients enrolled in the study, 1252 were males (919 were MSM), 107 were females and 346 had no gender recorded. Ethnicity was 51.1% white British/Irish/other, 6.1% African, 2.1% Caribbean, 2.8% Asian, 1.3% Indian/Pakistani/Bangladeshi, 4.2%, other, 3.2% not stated, and 29.2% unknown. 547 were from K (84.3% males, 48.3% MSM), 826 were from DS (84.3% males, 71.9% MSM), and 109 from WL (87.2% males, 56.0% MSM), 223 from other sites not specified. 77.5% (1321 of 1705) of patients had baseline viral resistance testing performed. Prevalence of primary resistance in those with a baseline viral resistance test was 13.5% overall: 19.3% in K, 14.9% in DS, and 14.7% in WL. The most common mutations detected were: NRTI: 184V, 215F, 41L; NNRTI 103N, 179D, 90I; PI 90M, 46I, and 82A. Among patients who tested with TDR, 79.1% had one single mutation, 18.7% and 2.2% exhibited dual or triple class-resistant viruses, respectively. Conclusions This study across a large HIV Medicine Directorate reported an overall TDR prevalence which is higher than that previously published and with significant rates of NNRTI resistance at baseline. PMID:25397492

McFaul, Katie; Lim, Charlotte; Jones, Rachael; Asboe, David; Pozniak, Anton; Sonecha, Sonali; Boffito, Marta; Nwokolo, Nneka

2014-01-01

223

Host and viral determinants of Mx2 antiretroviral activity.  

PubMed

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

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

2014-07-01

224

Host and Viral Determinants of Mx2 Antiretroviral Activity  

PubMed Central

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

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

2014-01-01

225

Prevalence and predictors of anaemia in patients with HIV infection at the initiation of combined antiretroviral therapy in Xinjiang, China.  

PubMed

Summary We retrospectively analysed routinely collected baseline data of 2252 patients with HIV infection registered in the National Free Antiretroviral Treatment Program in Xinjiang province, China, from 2006 to 2011 to estimate the prevalence and predictors of anaemia at the initiation of combined antiretroviral therapy. Anaemia was diagnosed using the criteria set forth by the World Health Organisation, and univariate and multivariate logistic regression analyses were performed to determine its predictors. The prevalences of mild, moderate, and severe anaemia at the initiation of combined antiretroviral therapy were 19.2%, 17.1%, and 2.6%, respectively. Overall, 38.9% of the patients were anaemic at the initiation of combined antiretroviral therapy. The multivariate logistic regression analysis indicated that Uyghur ethnicity, female gender, lower CD4 count, lower body mass index value, self-reported tuberculosis infection, and oral candidiasis were associated with a higher prevalence of anaemia, whereas higher serum alanine aminotransferase level was associated with a lower prevalence of anaemia. The results suggest that the overall prevalence of anaemia at the initiation of combined antiretroviral therapy in patients with HIV infection is high in Xinjiang, China, but severe anaemia is uncommon. Patients in China should be routinely checked for anaemia prior to combined antiretroviral therapy initiation, and healthcare providers should carefully select the appropriate first-line combined antiretroviral therapy regimens for anaemic patients. PMID:24810220

Mijiti, Peierdun; Yuexin, Zhang; Min, Liu; Wubuli, Maimaitili; Kejun, Pan; Upur, Halmurat

2015-03-01

226

Factors Which Affect Adherence to Antiretroviral Medications in a Cohort of HIV-Positive VA Patients  

Microsoft Academic Search

We performed a one-year retrospective outpatient chart review of 161 HIV-positive patients at the Charleston, South Carolina VA Medical Center (VAMC). The primary endpoint of this study was to investigate whether specific antiretroviral medications were associated with an increased rate of adherence. As a secondary objective, we sought to determine the relationship between adherence, viral suppression, and common confounders in

Merideth Radney

227

Adherence to Antiretroviral Therapy for Pediatric HIV Infection: Review of the Literature and Recommendations for Research  

Microsoft Academic Search

This review described and compared empirical investigations of adherence to pediatric antiretroviral therapy (ART) and predictors\\/correlates of adherence with regard to methodology and outcome. Thirteen empirical studies of children's adherence to ART, conducted between the years 1981 and 2002 were identified. Investigations varied by age of participant, drug therapy regimen, method of adherence assessment, and by the reporting of predictors\\/correlates

Ric G. Steele; Dennis Grauer

2003-01-01

228

Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal  

E-print Network

Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission--A Working: Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission

Levin, Judith G.

229

Role of Viral Replication, Antiretroviral Therapy, and Immunodeficiency in HIV- Associated Atherosclerosis  

PubMed Central

Objective HIV-seropositive patients are at higher risk for atherosclerosis than HIV-seronegative persons. This has been variably attributed to antiretroviral drug toxicity, immunodeficiency, and/or HIV-associated inflammation. To evaluate the contributions of these factors to HIV-associated atherosclerosis, we assessed carotid artery intima-media thickness (IMT) in a diverse cohort of HIV-seronegative and seropositive adults, including a unique group of HIV-infected patients who were untreated, had undetectable viral loads and had preserved CD4+ T cell counts (HIV controllers). Methods and Results Carotid IMT was measured in 494 subjects, including 33 HIV controllers and 93 HIV-seronegative controls. HIV controllers had higher IMT than seronegative controls even after adjustment for traditional risk factors (p=0.003). IMT in controllers was similar to antiretroviral-untreated patients with detectable viremia. Across all subjects, IMT was strongly associated with the presence of HIV disease rather than viral load or CD4+ T cell count. C-reactive protein was higher in HIV controllers than HIV-seronegative persons. Antiretroviral drug exposure was also associated with higher IMT. Conclusions Increased atherosclerosis with HIV infection can occur in the absence of antiretroviral therapy, detectable viremia, or overt immunodeficiency. Chronic inflammation—which is higher in controllers than in HIV-uninfected persons—may account for early atherosclerosis in these patients. PMID:19390417

Hsue, Priscilla Y.; Hunt, Peter W.; Schnell, Amanda; Kalapus, S. Craig; Hoh, Rebecca; Ganz, Peter; Martin, Jeffrey N.; Deeks, Steven G.

2009-01-01

230

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

Microsoft Academic Search

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

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

2004-01-01

231

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

Microsoft Academic Search

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

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

2000-01-01

232

Cerebrospinal fluid signs of neuronal damage after antiretroviral treatment interruption in HIV1 infection  

Microsoft Academic Search

BACKGROUND: The neurofilament is a major structural component of myelinated axons. Increased cerebrospinal fluid (CSF) concentrations of the light chain of the neurofilament protein (NFL) can serve as a sensitive indicator of central nervous system (CNS) injury. To assess whether interrupting antiretroviral treatment of HIV infection might have a deleterious effect on the CNS, we measured NFL levels in HIV-infected

Magnus Gisslén; Lars Rosengren; Lars Hagberg; Steven G Deeks; Richard W Price

2005-01-01

233

Human Immunodeficiency Virus Type 1 Cloning Vectors for Antiretroviral Resistance Testing  

Microsoft Academic Search

Better detection of minority human immunodeficiency virus type 1 (HIV-1) populations containing gene mutations may improve the usefulness of antiretroviral resistance testing for clinical management. Molecular cloning of HIV-1 PCR products which might improve minority detection can be slow and difficult, and commercially available recombinant virus assays test drug susceptibility of virus pools. We describe novel plasmids and simple methods

JAVIER MARTINEZ-PICADO; LORRAINE SUTTON; MARIA PIA DE PASQUALE; ANU V. SAVARA; RICHARD T. D'AQUILA

1999-01-01

234

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

Microsoft Academic Search

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

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

1997-01-01

235

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

E-print Network

of HIV-1 to lay dormant in so called "reservoir cells". In this scenario, a subset of infected cellsUncertainty quantification for a model of HIV-1 patient response to antiretroviral therapy and H.T. Banks1, Abstract-- We consider a model for in-host HIV-1 infection dynamics developed

236

Nanotechnology applications for improved delivery of antiretroviral drugs to the brain  

Microsoft Academic Search

Human immunodeficiency virus (HIV) can gain access to the central nervous system during the early course of primary infection. Once in the brain compartment the virus actively replicates to form an independent viral reservoir, resulting in debilitating neurological complications, latent infection and drug resistance. Current antiretroviral drugs (ARVs) often fail to effectively reduce the HIV viral load in the brain.

Ho Lun Wong; Niladri Chattopadhyay; Xiao Yu Wu; Reina Bendayan

2010-01-01

237

The Roles of HIV-1 Proteins and Antiretroviral Drug Therapy in HIV-1-Associated Endothelial Dysfunction  

PubMed Central

Since the emergence of highly active antiretroviral therapy (HAART), human immunodeficiency virus-1 (HIV-1)-infected patients have demonstrated dramatic decreases in viral burden and opportunistic infections, and an overall increase in life expectancy. Despite these positive HAART-associated outcomes, it has become increasingly clear that HIV-1 patients have an enhanced risk of developing cardiovascular disease over time. Clinical studies are instrumental in our understanding of vascular dysfunction in the context of HIV-1 infection. However, most clinical studies often do not distinguish whether HIV-1 proteins, HAART, or a combination of these 2 factors cause cardiovascular complications. This review seeks to address the roles of both HIV-1 proteins and antiretroviral drugs in the development of endothelial dysfunction because endothelial dysfunction is the hallmark initial step of many cardiovascular diseases. We analyze recent in vitro and in vivo studies examining endothelial toxicity in response to HIV-1 proteins or in response to the various classes of antiretroviral drugs. Furthermore, we discuss the multiple mechanisms by which HIV-1 proteins and HAART injure the vascular endothelium in HIV-1 patients. By understanding the molecular mechanisms of HIV-1 protein- and antiretroviral-induced cardiovascular disease, we may ultimately improve the quality of life of HIV-1 patients through better drug design and the discovery of new pharmacological targets. PMID:18525451

Kline, Erik R.; Sutliff, Roy L.

2008-01-01

238

Postnatal Cytomegalovirus Exposure in Infants of Antiretroviral-Treated and Untreated HIV-Infected Mothers  

PubMed Central

HIV-1 and CMV are important pathogens transmitted via breastfeeding. Furthermore, perinatal CMV transmission may impact growth and disease progression in HIV-exposed infants. Although maternal antiretroviral therapy reduces milk HIV-1 RNA load and postnatal transmission, its impact on milk CMV load is unclear. We examined the relationship between milk CMV and HIV-1 load (4–6 weeks postpartum) and the impact of antiretroviral treatment in 69 HIV-infected, lactating Malawian women and assessed the relationship between milk CMV load and postnatal growth in HIV-exposed, breastfed infants through six months of age. Despite an association between milk HIV-1 RNA and CMV DNA load (0.39 log10 rise CMV load per log10 rise HIV-1 RNA load, 95% CI 0.13–0.66), milk CMV load was similar in antiretroviral-treated and untreated women. Higher milk CMV load was associated with lower length-for-age (?0.53, 95% CI: ?0.96, ?0.10) and weight-for-age (?0.40, 95% CI: ?0.67, ?0.13) Z-score at six months in exposed, uninfected infants. As the impact of maternal antiretroviral therapy on the magnitude of postnatal CMV exposure may be limited, our findings of an inverse relationship between infant growth and milk CMV load highlight the importance of defining the role of perinatal CMV exposure on growth faltering of HIV-exposed infants. PMID:24723745

Meyer, Sarah A.; Westreich, Daniel J.; Patel, Emily; Ehlinger, Elizabeth P.; Kalilani, Linda; Lovingood, Rachel V.; Denny, Thomas N.; Swamy, Geeta K.; Permar, Sallie R.

2014-01-01

239

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

ERIC Educational Resources Information Center

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,…

Delbene, Roxana

2012-01-01

240

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

PubMed Central

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

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

2011-01-01

241

Adherence and non-adherence to antiretroviral therapy from a capability theory perspective  

Microsoft Academic Search

It is widely recognized in the medical research literature that a rigorous adherence to antiretroviral therapies is needed in order to effectively achieve the virological, immunological and clinical benefits of these treatments. Nevertheless, these kinds of medications are characterized by particularly complex and heavy dosing regimens that increase the chances of non-compliance with the treatment. Several studies have attempted to

Gianfranco Giuntoli

242

Viral Decay Kinetics in the Highly Active Antiretroviral Therapy-Treated Rhesus Macaque Model of AIDS  

Microsoft Academic Search

To prevent progression to AIDS, persons infected with human immunodeficiency virus type 1 (HIV-1) must remain on highly active antiretroviral therapy (HAART) indefinitely since this modality does not eradicate the virus. The mechanisms involved in viral persistence during HAART are poorly understood, but an animal model of HAART could help elucidate these mechanisms and enable studies of HIV-1 eradication strategies.

Jesse D. Deere; Joanne Higgins; Elda Cannavo; Andradi Villalobos; Lourdes Adamson; Emilie Fromentin; Raymond F. Schinazi; Paul A. Luciw; Thomas W. North

2010-01-01

243

In Vivo Antiretroviral Activity of Stampidine in Chronically Feline Immunodeficiency Virus-Infected Cats  

PubMed Central

Here we report the antiretroviral activity of the experimental nucleoside reverse transcriptase inhibitor (NRTI) compound stampidine in cats chronically infected with feline immunodeficiency virus (FIV). Notably, a single oral bolus dose of 50 or 100 mg of stampidine per kg resulted in a transient ?1-log decrease in the FIV load of circulating peripheral blood mononuclear cells in five of six FIV-infected cats and no side effects. A 4-week stampidine treatment course with twice-daily administration of hard gelatin capsules containing 25 to 100 mg of stampidine per kg was also very well tolerated by cats at cumulative dose levels as high as 8.4 g/kg and exhibited a dose-dependent antiretroviral effect. One of three cats treated at the 25-mg/kg dose level, three of three cats treated at the 50-mg/kg dose level, and three of three cats treated at the 100-mg/kg dose level (but none of three control cats treated with placebo pills) showed a therapeutic response, as evidenced by a ?1-log reduction in the FIV load in peripheral blood mononuclear cells within 2 weeks. The previously documented in vitro and in vivo antiretroviral activity of stampidine against primary clinical human immunodeficiency virus type 1 isolates with genotypic and/or phenotypic NRTI resistance, together with its favorable animal toxicity profile, pharmacokinetics, and in vivo antiretroviral activity in FIV-infected cats, warrants further development of this promising new NRTI compound. PMID:12654652

Uckun, Fatih M.; Chen, Chun-Lin; Samuel, Peter; Pendergrass, Sharon; Venkatachalam, T. K.; Waurzyniak, Barbara; Qazi, Sanjive

2003-01-01

244

Adherence to antiretroviral treatment among pregnant and postpartum HIV-infected women  

Microsoft Academic Search

Among women with HIV infection, pregnancy is a time when maintenance of maternal health and reduction of vertical HIV transmission are primary concerns. Few studies have examined adherence to Antiretroviral Treatment (ART) during pregnancy and in the postpartum period when the demands of childcare may significantly interfere with women's self-care behaviors. This study examined ART use and adherence in HIV-infected

C. A. Mellins; C. Chu; K. Malee; S. Allison; R. Smith; L. Harris; A. Higgins; C. Zorrilla; S. Landesman; L. Serchuck; P. Larussa

2008-01-01

245

Improving adherence to highly active anti-retroviral therapy in Africa: the DREAM programme in Mozambique  

Microsoft Academic Search

Ensuring high levels of adherence to highly active anti-retroviral therapy (HAART) is a pri- ority in treating people living with AIDS. This study reports the rates of adherence of patients served by DREAM (Drug Resource Enhance- ment against AIDS and Malnutrition) in the city of Matola, Mozambique. DREAM, an innovative programme tailored for Africa, was implemented by the Community of

M. C. Marazzi; M. Bartolo; L. Emberti Gialloreti; P. Germano; G. Guidotti; G. Liotta; M. Magnano; San Lio; S. Mancinelli; M. A. Modolo; P. Narciso; C. F. Perno; P. Scarcella; G. Tintisona; L. Palombi

2006-01-01

246

Using motivational interviewing to promote adherence to antiretroviral medications: A randomized controlled study  

Microsoft Academic Search

The primary aim of this study was to test an intervention to support antiretroviral medication adherence among primarily low-income men and women with HIV. The study was a randomized controlled trial (Get Busy Living) with participants assigned to treatment (Motivational Interviewing [MI]) and control groups. Participants were recruited from an HIV\\/AIDS clinic in Atlanta, Georgia, US. Of those referred to

C. Diiorio; F. McCarty; K. Resnicow; M. McDonnell Holstad; J. Soet; K. Yeager; S. M. Sharma; D. E. Morisky; B. Lundberg

2008-01-01

247

Challenges in PMTCT antiretroviral adherence in northern KwaZulu-Natal, South Africa  

Microsoft Academic Search

Background. Women living with HIV in sub-Saharan Africa face significant challenges in accessing HIV care and adhering to antiretroviral therapy. Most reports have focused on issues relating to long-term adherence such as those surrounding stigma and disclosure, hunger, cultural factors, lack of accurate health information, lack of social support, medication side effects and overcrowded health systems. Information related to the

S. Mepham; Z. Zondi; A. Mbuyazi; N. Mkhwanazi; M. L. Newell

2011-01-01

248

Emergence of Minor Drug-Resistant HIV-1 Variants after Triple Antiretroviral Prophylaxis for Prevention of Vertical HIV-1 Transmission  

PubMed Central

Background WHO-guidelines for prevention of mother-to-child transmission of HIV-1 in resource-limited settings recommend complex maternal antiretroviral prophylaxis comprising antenatal zidovudine (AZT), nevirapine single-dose (NVP-SD) at labor onset and AZT/lamivudine (3TC) during labor and one week postpartum. Data on resistance development selected by this regimen is not available. We therefore analyzed the emergence of minor drug-resistant HIV-1 variants in Tanzanian women following complex prophylaxis. Method 1395 pregnant women were tested for HIV-1 at Kyela District Hospital, Tanzania. 87/202 HIV-positive women started complex prophylaxis. Blood samples were collected before start of prophylaxis, at birth and 1–2, 4–6 and 12–16 weeks postpartum. Allele-specific real-time PCR assays specific for HIV-1 subtypes A, C and D were developed and applied on samples of mothers and their vertically infected infants to quantify key resistance mutations of AZT (K70R/T215Y/T215F), NVP (K103N/Y181C) and 3TC (M184V) at detection limits of <1%. Results 50/87 HIV-infected women having started complex prophylaxis were eligible for the study. All women took AZT with a median duration of 53 days (IQR 39–64); all women ingested NVP-SD, 86% took 3TC. HIV-1 resistance mutations were detected in 20/50 (40%) women, of which 70% displayed minority species. Variants with AZT-resistance mutations were found in 11/50 (22%), NVP-resistant variants in 9/50 (18%) and 3TC-resistant variants in 4/50 women (8%). Three women harbored resistant HIV-1 against more than one drug. 49/50 infants, including the seven vertically HIV-infected were breastfed, 3/7 infants exhibited drug-resistant virus. Conclusion Complex prophylaxis resulted in lower levels of NVP-selected resistance as compared to NVP-SD, but AZT-resistant HIV-1 emerged in a substantial proportion of women. Starting AZT in pregnancy week 14 instead of 28 as recommended by the current WHO-guidelines may further increase the frequency of AZT-resistance mutations. Given its impact on HIV-transmission rate and drug-resistance development, HAART for all HIV-positive pregnant women should be considered. PMID:22384138

Hauser, Andrea; Sewangi, Julius; Mbezi, Paulina; Dugange, Festo; Lau, Inga; Ziske, Judith; Theuring, Stefanie; Kuecherer, Claudia; Harms, Gundel; Kunz, Andrea

2012-01-01

249

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

PubMed Central

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

2013-01-01

250

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

PubMed Central

Introduction In other disease areas, generic drugs are normally used after patent expiry. Patents on zidovudine, lamivudine, nevirapine and efavirenz have already expired. Patents will expire for abacavir in late 2014, lopinavir/r in 2016, and tenofovir, darunavir and atazanavir in 2017. However, patents on single-tablet regimens do not expire until after 2026. Methods The number of people taking each antiretroviral in the UK was estimated from 23,655 individuals in the UK CHIC cohort (2012 database). Costs of patented drugs were taken from the British National Formulary database, assuming a 30% discount. Costs of generic antiretrovirals were estimated using an 80% discount from patented prices, or actual costs where available. Two options were analysed: 1 – all patients use single-tablet regimens and patented versions of drugs; prices remain stable over time; 2 – all people switch from patented to generic drugs when available, after patent expiry (dates shown above). Results There were an estimated 67,000 people taking antiretrovirals in the UK in 2014, estimated to rise by 8% per year until 2018 (in line with previous rises). The most widely used antiretrovirals in the CHIC cohort were tenofovir (TDF) (75%), emtricitabine (FTC) (69%), efavirenz (EFV) (39%), lamivudine (3TC) (23%), abacavir (ABC) (18%), darunavir (DRV) (21%) and atazanavir (ATV) (16%). The predicted annual UK cost of generic ABC/3TC/EFV (three generic tablets once daily) was Ł1018 per person-year. Costs of patented single-tablet regimens ranged from Ł5000 to Ł7500 per person-year. Assuming continued use of patented antiretrovirals in the UK, the predicted total national costs of antiretroviral treatment were predicted to rise from Ł425 million in 2014 to Ł459 m in 2015, Ł495 m in 2016, Ł536 m in 2017 and Ł578 m in 2018. With a 100% switch to generics, total predicted costs were Ł337 m in 2014, Ł364 m in 2015, Ł382 m in 2016, Ł144 m in 2017 and Ł169 m in 2018. The total predicted saving over five years from a switch to generics was Ł1.1 billion. Conclusions Systematic switching from patented to generic antiretrovirals could potentially save approximately Ł1.1 billion in the UK over the next five years, compared with continued use of patented versions: this money could be spent on urgently needed HIV prevention programmes. Similar savings are feasible for other European countries, given parallel patent expiry dates. More detailed economic evaluation is required to show when patented single-tablet regimens provide value for money, compared to bioequivalent generic versions of 3–4 pills once daily. PMID:25394006

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

2014-01-01

251

Start-up of decentralized MBRs  

Microsoft Academic Search

This paper aims to be a quick reference guide to start-up decentralized membrane bioreactors (MBRs). The first part of this study focuses on the impact of different operational parameters on the start-up of decentralized MBRs, which can be easily reproduced in the field. Whereas wastewater is not an option to start-up decentralized MBRs, domestic activated sludge has shown to handle

J. A. Gil; E. Dorgeloh; J. B. van Lier; J. H. J. M. van der Graaf; D. Prats

252

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

PubMed Central

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

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

2014-01-01

253

Using Music with Head Start Children.  

ERIC Educational Resources Information Center

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…

Griffin, Louise

254

When Do Start-Ups Make Sense?  

ERIC Educational Resources Information Center

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…

Langemeyer, Clement J.

2005-01-01

255

NPRM: Head Start Program Performance Standards.  

ERIC Educational Resources Information Center

This document contains the Notice of Proposed Rulemaking (NPRM) on Head Start Program Performance Standards, appearing in the April 22, 1996 "Federal Register." The Administration for Children, Youth, and Families issued this notice to implement the statutory provisions for establishing program performance standards for early Head Start grantees…

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

256

Ignition system for starting a diesel engine  

SciTech Connect

In an auxiliary ignition system for starting a diesel engine having a plurality of plasma spark plugs installed in corresponding combustion chambers facing fuel injection valves, starting time is reduced by applying high ignition energy to the plugs following predetermined time intervals after fuel injection to the corresponding engine cylinders.

Ishikawa, Y.; Eudo, H.; Imai, I.; Sone, M.

1984-05-01

257

Application of SMES Unit in Black Start  

NASA Astrophysics Data System (ADS)

Blackout of large area is a serious threat to modern power system, so power system restoration which is called Black Start is a critical task for reducing economic losses and social unrest caused by blackout. Traditiona black start sometimes may suffer from inflexible black start units and overvoltage and serious oscillation. As a power storage unit, SMES has the ability of fast exchanging active and reactive power with power grid in all four quadrants, so it is proposed as a new solution to improve the black start process in this paper. Comparing to traditional black start, some unique advantages of SMES for black start are presented. Also SMES model and related control strategy are introduced in detail. A simulation model is established based on PSCAD/EMTDC to investigate the validity and flexibility of SMES in black start. Simulation results show that SMES unit can bring thermal generators online, and it has better performance on overvoltage restraint and amping oscillation than traditional black start. Also, the performance of nonlinear PID-controlled SMES is better than that of PID-controlled SMES.

Yang, Jun; Liu, Wenqing; Liu, Pei

258

Head Start Impact Study. Final Report  

ERIC Educational Resources Information Center

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…

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

259

Protease inhibitor plasma concentrations in HIV antiretroviral therapy.  

PubMed

Since the introduction of the HIV protease inhibitors in 1995, considerable progress has been made in the treatment of HIV-infected patients. However, treatment has not been without problems. Studies have demonstrated associations between protease inhibitor concentrations and efficacy and in some cases toxicity. As considerable inter-individual and intra-individual variations of protease inhibitor concentrations have been observed, it has been questioned to what extent this has clinical implications with regard to efficacy and toxicity. As a consequence the use of protease inhibitor concentration measurements to optimise HIV antiretroviral therapy (therapeutic drug monitoring--TDM) has been suggested. The objectives of this study, initiated in 2000, were: to establish a method for the simultaneous measurement of the available protease inhibitors; to explore the pharmacokinetics of the protease inhibitors in clinically relevant situations and in this context; to consider the applicability of TDM in protease inhibitor therapy. The presented studies and review demonstrate: 1) that it is feasible to measure protease inhibitor plasma concentrations in a clinical setting with precision and accuracy, and that protease inhibitor concentrations are very stable during different circumstances ex vivo; 2) that protease inhibitor plasma concentrations display limited long-term intra-individual variation but considerable inter-individual variation; 3) that protease inhibitor plasma concentrations display considerable intra-individual variations between morning and evening and in the case of drug-drug interactions; 4) that protease inhibitor drug-drug interactions can be unpredictable and adverse but also that protease inhibitor drug-drug interactions can be exploited to increase protease inhibitor concentrations or decrease protease inhibitor dose; 5) that increases in protease inhibitor plasma concentrations can enhance efficacy but also that decreases can reduce toxicity; 6) that the concentration-efficacy associations which have been established by others can be confirmed in clinical trials but that concentration-toxicity associations are more difficult to establish and confirm. The experiences with protease inhibitor therapy and the understanding of protease inhibitor pharmacokinetics have resulted in new treatment principles and the development of new and better protease inhibitors. Most patients achieve concentrations several folds higher than the minimum effective concentration with the regimens that are used currently (2007). As a result TDM in protease inhibitor therapy has become less relevant in HIV-infected patients receiving their first protease inhibitor. In protease inhibitor experienced patients, harbouring HIV with varying degrees of resistance/reduced susceptibility to protease inhibitors, the combination of TDM and genotypic resistance testing, seems to be a promising tool, but prospective studies are needed. In some patients with certain conditions or in certain circumstances known to be associated with considerable inter-individual or intra-individual variation of protease inhibitor concentrations (drug-drug interactions, gastrointestinal disease, pregnancy or children) TDM might also be of benefit. However, no studies have investigated these patients specifically in randomised TDM trials. PMID:19232158

Justesen, Ulrik Stenz

2008-11-01

260

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

PubMed Central

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

2012-01-01

261

The role of baseline HIV-1 RNA, drug resistance, and regimen type as determinants of response to first-line antiretroviral therapy.  

PubMed

The factors influencing virological response to first-line combined antiretroviral therapy (cART) in an Italian cohort of HIV-1-infected patients were examined. Eligible patients were those enrolled in a national prospective observational cohort (Antiretroviral Resistance Cohort Analysis), starting first-line cART between 2001 and 2011 and who had at least one follow-up of HIV-1 RNA. The primary endpoint was virological success, defined as the first viral load <50? copies/ml. Time to events were analyzed by Kaplan-Meier analysis and Cox proportional hazard model. One thousand three hundred five patients met the study inclusion criteria. In a multivariable model adjusting for transmission mode, presence of transmitted drug resistance, baseline CD4(+) cell count, viral subtype, and type of NRTI backbone employed, independent predictors of virological success were higher baseline viral load (?500,000 vs. <100,000 HR 0.52; P?100,000? copies/ml, virologic success was only associated with the use of integrase inhibitors in the first cART regimen. Independent predictors of immunological success were baseline CD4(+) cell count and wGSS <3. High baseline HIV-1 RNA, predicted activity of the first-line regimen based on genotypic resistance testing, gender, and use of new agents were found to predict time to achieve virological success. The type of initial nucleoside analog backbone was not found to predict virological response. PMID:25042976

Di Biagio, Antonio; Rusconi, Stefano; Marzocchetti, Angela; Signori, Alessio; Schiavetti, Irene; Bruzzone, Bianca; Monno, Laura; Punzi, Grazia; Colao, Maria Grazia; Penco, Giovanni; Zazzi, Maurizio; De Luca, Andrea

2014-10-01

262

Durability of first antiretroviral treatment in HIV chronically infected patients: why change and what are the outcomes?  

PubMed Central

Introduction First antiretroviral therapy (ART) is often switched to simpler, more potent or better tolerated regimens [1, 2]. Although discontinuation rates are frequently studied, the durability of regimens is rarely approached. Materials and Methods Retrospective study with the following objectives: analyze first ART schemes and their durability in naive patients with chronic HIV-1 and 2 infections, evaluate factors influencing ART change, second-line ART and consequent virologic and immunologic responses. Patients had follow-ups in a Central University Hospital, started ART between January 2007 and December 2012 and changed first regimens. Clinical data was obtained from medical records and analyzed using the Statistical Package for the Social Sciences (version 20). Results Of the 652 naive patients who started ART, 164 changed regimens. The majority had HIV-1 infection (n=158). The mean age was 43.9 years (standard deviation±14.3), with a male predominance of 57.9%. Regimens with efavirenz were the most common amongst HIV-1 patients (50%) followed by lopinavir/r (22%). In HIV-2 patients, lopinavir/r (n=3) regimens were most prevalent. First ART regimens had a mean duration of 12.1 months. There was no difference between NNRTI (59.8%) and protease inhibitor (40.2%) schemes regarding durability. Adverse reactions were the major cause of ART switching (55.5%) followed by therapy resistance (12.1%). Age was inversely related to durability (p=0.007 Mann-Whitney, Phi coefficient ?0.161) and associated with the appearance of adverse reactions (p=0.04, Chi-square). Younger patients had a reduced risk of adverse reactions by 27%. Adverse reactions increased the risk of inferior durability by 40%. Psychiatric symptoms (28.4%) were the most prevalent, all attributed to efavirenz. The year of ART initiation was associated with different durability rates (p=0.005, Mann-Whitney). Patients started on ART before the year 2010 reduced the probability of inferior ART duration by 25.8%. After second-line ART regimens, TCD4+ counts>500 cell/µL were increased by 38% and favourable virologic outcome achieved in 84%. Conclusions Adverse reactions were the main cause for ART switching, supporting a cautious approach when initiating regimens, particularly in older patients. All ART naive patients who changed initial therapy had favourable immunological and virologic responses. PMID:25397541

Moniz, Patricia; Alçada, Filipa; Peres, Susana; Borges, Fernando; Baptista, Teresa; Claudia Miranda, Ana; Antunes, Isabel; Aldir, Isabel; Ventura, Fernando; Nina, Jaime; Mansinho, Kamal

2014-01-01

263

Start 2: Thinking one move ahead  

SciTech Connect

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.

Gaines, L.L.

1991-11-01

264

Start 2: Thinking one move ahead  

SciTech Connect

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.

Gaines, L.L.

1991-11-01

265

[Impact of antiretroviral therapy on the magnitude of the HIV/AIDS epidemic in Brazil: various scenarios].  

PubMed

We applied the back-calculation method to estimate the magnitude of the HIV epidemic in Brazil, using the EM and EMS algorithms. Under certain assumptions regarding the behavior of infected patients towards combined antiretroviral therapy, we discuss five different scenarios applied to the Brazilian epidemic. Our objective was to illustrate the impact of combined antiretroviral treatment on the incubation period and thus on estimates of the size of the HIV-infected population, based on reported AIDS cases. PMID:12764469

Barbosa, Maria Tereza S; Struchiner, Claudio J

2003-01-01

266

An Antiretroviral\\/Zinc Combination Gel Provides 24 Hours of Complete Protection against Vaginal SHIV Infection in Macaques  

Microsoft Academic Search

BackgroundRepeated use, coitus-independent microbicide gels that do not contain antiretroviral agents also used as first line HIV therapy are urgently needed to curb HIV spread. Current formulations require high doses (millimolar range) of antiretroviral drugs and typically only provide short-term protection in macaques. We used the macaque model to test the efficacy of a novel combination microbicide gel containing zinc

Jessica Kenney; Meropi Aravantinou; Rachel Singer; Mayla Hsu; Aixa Rodriguez; Larisa Kizima; Ciby J. Abraham; Radhika Menon; Samantha Seidor; Anne Chudolij; Agegnehu Gettie; James Blanchard; Jeffrey D. Lifson; Michael Piatak; Jose A. Fernández-Romero; Thomas M. Zydowsky; Melissa Robbiani; Zandrea Ambrose

2011-01-01

267

Cost-effectiveness of Newer Antiretroviral Drugs in Treatment-Experienced Patients with Multi-drug Resistant HIV Disease  

PubMed Central

Objective Newer antiretroviral drugs provide substantial benefits but are expensive. We determined the cost-effectiveness of using antiretroviral drugs in combination for patients with multi-drug resistant HIV disease. Design We built a cohort state-transition model representing treatment-experienced patients with low CD4 counts, high viral load levels, and multi-drug resistant virus. We estimated the effectiveness of newer drugs (those approved in 2005 or later) from published randomized trials. We estimated other parameters from a randomized trial and from the literature. The model had a lifetime time horizon and used the perspective of an ideal insurer in the United States. The interventions were combination antiretroviral therapy, consisting of two newer drugs and one conventional drug, compared to three conventional drugs. Outcome measures were life-years, quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness. Results Substituting newer antiretroviral drugs increased expected survival by 3.9 years in advanced HIV disease. The incremental cost-effectiveness ratio of newer, compared to conventional, antiretroviral drugs was $75,556/QALY gained. Sensitivity analyses showed that substituting only one newer antiretroviral drug cost $54,559 to $68,732/QALY, depending on assumptions about efficacy. Substituting three newer drugs cost $105,956 to $117,477/QALY. Cost-effectiveness ratios were higher if conventional drugs were not discontinued. Conclusions In treatment-experienced patients with advanced HIV disease, use of newer antiretroviral agents can be cost effective, given a cost-effectiveness threshold in the range of $50,000 to $75,000 per QALY gained. Newer antiretroviral agents should be used in carefully selected patients for whom less expensive options are clearly inferior. PMID:24129369

Bayoumi, Ahmed M.; Barnett, Paul G.; Joyce, Vilija R.; Griffin, Susan C.; Sun, Huiying; Bansback, Nick J.; Holodniy, Mark; Sanders, Gillian; Brown, Sheldon T.; Kyriakides, Tassos C.; Angus, Brian; Cameron, D. William; Anis, Aslam H.; Sculpher, Mark; Owens, Douglas K.

2014-01-01

268

Prices of second-line antiretroviral treatment for middle-income countries inside versus outside sub-Saharan Africa  

PubMed Central

Introduction Antiretrovirals are available at low prices in sub-Saharan Africa, but these prices may not be consistently available for middle-income countries in other regions with large HIV epidemics. Over 30% of HIV infected people live in countries outside sub-Saharan Africa. Several key antiretrovirals are still on patent, with generic production restricted. We assessed price variations for key antiretroviral drugs inside versus outside sub-Saharan Africa. Methods HIV drug prices used in national programmes (2010–2014) were extracted from the WHO Global Price Reporting Mechanism database for all reporting middle-income countries as classified by the World Bank. Treatment costs (branded and generic) were compared for countries inside sub-Saharan Africa versus those outside. Five key second-line antiretrovirals were analysed: abacavir, atazanavir, darunavir, lopinavir/ritonavir, raltegravir. Results Prices of branded antiretrovirals were significantly higher outside sub-Saharan Africa (p<0.001, adjusted for year of purchase) (see Table 1). For example, the median (interquartile range) price of darunavir from Janssen was $732 (IQR $732-806) per person-year in sub-Saharan Africa versus $4689 (IQR $4075-5717) in non-African middle-income countries, an increase of 541%. However, when supplied by generic companies, most antiretrovirals were similarly priced between countries in sub-Saharan Africa and other regions. Conclusions Pharmaceutical companies are selling antiretrovirals to non-African middle-income countries at prices 74–541% higher than African countries with similar gross national incomes. However, generic companies are selling most of these drugs at similar prices across regions. Mechanisms to ensure fair pricing for patented antiretrovirals across both African and non-African middle-income countries need to be improved, to ensure sustainable treatment access. PMID:25394108

Simmons, Bryony; Hill, Andrew; Ford, Nathan; Ruxrungtham, Kiat; Ananworanich, Jintanat

2014-01-01

269

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

PubMed Central

Background HIV-infected patients starting antiretroviral treatment (ART) experience deep and early disorders in fat and bone metabolism, leading to concomitant changes in fat mass and bone mineral density. Methods We conducted a prospective study in treatment-naive HIV-infected patients randomized to receive two nucleoside reverse transcriptase inhibitors in combination with either a protease inhibitor (PI) or a non-nucleosidic reverse transcriptase inhibitor (NNRTI), to evaluate early changes in body composition, bone mineral density and metabolic markers as differentially induced by antiretroviral therapies. We measured changes in markers of carbohydrate, of fat and bone metabolism, and, using dual-emission X-ray absorptiometry (DXA), body composition and bone mineral density (BMD). Complete data on changes between baseline and after 21 months treatment were available for 35 patients (16 in the PI group and 19 in the NNRTI group). Results A significant gain in BMI and in total and lower limb fat mass was recorded only in patients receiving PI. A loss of lumbar BMD was observed in both groups, being higher with PI. Plasma markers of bone metabolism (alkaline phosphatase, osteocalcin, collagen crosslaps) and levels of parathormone and of 1,25diOH-vitamin D3 significantly increased in both groups, concomitant with a decline in 25OH-vitamin D3. Lipids and glucose levels increased in both groups but rise in triglyceride was more pronounced with PI. A correlation between loss of BMD and gain of fat mass is observed in patients starting PI. Conclusions We evidenced an early effect of ART on lipid and bone metabolisms. PI lead to a significant gain in fat mass correlated with a sharp drop in BMD but active bone remodelling is evident with all antiretroviral treatments, associated with low vitamin D levels and hyperparathyroidism. In parallel, signs of metabolic restoration are evident. However, early increases in lean and fat mass, triglycerides, waist circumference and leptin are much more pronounced with PI. PMID:23809140

2013-01-01

270

Immunologic status and virologic outcomes in repeat pregnancies to HIV-positive women not on antiretroviral therapy at conception: a case for lifelong antiretroviral therapy?  

PubMed

During their second pregnancy with diagnosed HIV (n = 1177), two-fifths of women in the UK/Ireland not on antiretroviral therapy (ART) at conception had an immunological indication for treatment (CD4(+) <350 cells/?l), of whom nearly half had CD4(+) at least 350 cells/?l in their previous pregnancy. Those initiating ART during pregnancy had a 4.3-fold increased odds of detectable viral load at delivery compared with those conceiving on treatment, suggesting that continuation of ART after pregnancy may be beneficial for many women. PMID:24685820

French, Clare E; Thorne, Claire; Tariq, Shema; Cortina-Borja, Mario; Tookey, Pat A

2014-06-01

271

QuickStart Guide LabVIEW QuickStart Guide  

E-print Network

QuickStart Guide LabVIEW QuickStart Guide February 1999 Edition Part Number 321527C-01 #12 rights reserved. #12;© National Instruments Corporation iii LabVIEW QuickStart Guide Contents Chapter 1 Introduction to LabVIEW What Is LabVIEW

Wedeward, Kevin

272

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

ERIC Educational Resources Information Center

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…

North Carolina Central Univ., Durham.

273

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

PubMed

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

Salo, Aki; Bezodis, Ian

2004-01-01

274

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

ERIC Educational Resources Information Center

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…

Rose, Lea Williams; Cheney, Nancy

2005-01-01

275

CD4 trajectory adjusting for dropout among HIV-positive patients receiving combination antiretroviral therapy in an East African HIV care centre  

PubMed Central

Objective Estimates of CD4 response to antiretroviral therapy (ART) obtained by averaging data from patients in care, overestimate population CD4 response and treatment program effectiveness because they do not consider data from patients who are deceased or not in care. We use mathematical methods to assess and adjust for this bias based on patient characteristics. Design We examined data from 25,261 HIV-positive patients from the East Africa IeDEA Consortium. Methods We used inverse probability of censoring weighting (IPCW) to represent patients not in care by patients in care with similar characteristics. We address two questions: What would the median CD4 be “had everyone starting ART remained on observation?” and “were everyone starting ART maintained on treatment?” Results Routine CD4 count estimates were higher than adjusted estimates even under the best-case scenario of maintaining all patients on treatment. Two years after starting ART, differences between estimates diverged from 30 cells/µL, assuming similar mortality and treatment access among dropouts as patients in care, to over 100 cells/µL assuming 20% lower survival and 50% lower treatment access among dropouts. When considering only patients in care, the proportion of patients with CD4 above 350 cells/µL was 50% adjusted to below 30% when accounting for patients not in care. One-year mortality diverged 6–14% from the naďve estimates depending on assumptions about access to care among lost patients. Conclusions Ignoring mortality and loss to care results in over-estimation of ART response for patients starting treatment and exaggerates the efficacy of treatment programs administering it. PMID:25131801

Kiragga, Agnes N; Lok, Judith J; Musick, Beverly S; Bosch, Ronald J; Mwangi, Ann; Wools-Kaloustian, Kara K; Yiannoutsos, Constantin T

2014-01-01

276

Predictors of delayed antiretroviral therapy initiation, mortality, and loss to followup in HIV infected patients eligible for HIV treatment: data from an HIV cohort study in India.  

PubMed

Studies from Sub-Saharan Africa have shown that a substantial number of HIV patients eligible for antiretroviral therapy (ART) do not start treatment. However, data from other low- or middle-income countries are scarce. In this study, we describe the outcomes of 4105 HIV patients who became ART eligible from January 2007 to November 2011 in an HIV cohort study in India. After three years of ART eligibility, 78.4% started ART, 9.3% died before ART initiation, and 10.3% were lost to followup. Diagnosis of tuberculosis, being homeless, lower CD4 count, longer duration of pre-ART care, belonging to a disadvantaged community, being widowed, and not living near a town were associated with delayed ART initiation. Diagnosis of tuberculosis, being homeless, lower CD4 count, shorter duration of pre-ART care, belonging to a disadvantaged community, illiteracy, and age >45 years were associated with mortality. Being homeless, being single, not living near a town, having a CD4 count <150 cells/?L, and shorter duration of pre-ART care were associated with loss to followup. These results highlight the need to improve the timely initiation of ART in HIV programmes in India, especially in ART eligible patients with tuberculosis, low CD4 counts, living in rural areas, or having a low socioeconomic status. PMID:24288689

Alvarez-Uria, Gerardo; Pakam, Raghavakalyan; Midde, Manoranjan; Naik, Praveen Kumar

2013-01-01

277

The physics of tokamak start-upa)  

NASA Astrophysics Data System (ADS)

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

Mueller, D.

2013-05-01

278

START USING THE NEW ONLINE METER  

E-print Network

START USING THE NEW ONLINE METER REQUEST FORM TOOL CAS login Logging in with your Princeton Net and convenient way for departments to send outgoing metered mail with Mail Services! The new Online Meter Request

Singh, Jaswinder Pal

279

The Physics of Tokamak Start-up  

SciTech Connect

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

D. Mueller

2012-11-13

280

34 CFR 200.16 - Starting points.  

Code of Federal Regulations, 2010 CFR

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

2010-07-01

281

34 CFR 200.16 - Starting points.  

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

2014-07-01

282

34 CFR 200.16 - Starting points.  

Code of Federal Regulations, 2012 CFR

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

2012-07-01

283

34 CFR 200.16 - Starting points.  

Code of Federal Regulations, 2011 CFR

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

2011-07-01

284

34 CFR 200.16 - Starting points.  

Code of Federal Regulations, 2013 CFR

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

2013-07-01

285

A New Start from Ground Zero?  

NASA Astrophysics Data System (ADS)

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.

Luisi, Pier Luigi

2015-01-01

286

Assisted workouts: starting my own workout program.  

PubMed

As an undergraduate student with cerebral palsy, I found it difficult to achieve my goal of starting a regular exercise program at my school, the University of Central Florida. However, when I started a program called Assisted Workouts in spring 2003. the struggle proved to be well worth it. The program is not only beneficial to me, but it has also opened the door for other students who, because of disability or injury, need assistance in using gym equipment. PMID:14717581

Cousminer, Douglas

2003-01-01

287

Clinical presentation and outcome of Tuberculosis in Human Immunodeficiency Virus infected children on anti-retroviral therapy  

PubMed Central

Background The tuberculosis (TB) and human immunodeficiency virus (HIV) epidemics are poorly controlled in sub-Saharan Africa, where highly active antiretroviral treatment (HAART) has become more freely available. Little is known about the clinical presentation and outcome of TB in HIV-infected children on HAART. Methods We performed a comprehensive file review of all children who commenced HAART at Tygerberg Children's Hospital from January 2003 through December 2005. Results Data from 290 children were analyzed; 137 TB episodes were recorded in 136 children; 116 episodes occurred before and 21 after HAART initiation; 10 episodes were probably related to immune reconstitution inflammatory syndrome (IRIS). The number of TB cases per 100 patient years were 53.3 during the 9 months prior to HAART initiation, and 6.4 during post HAART follow-up [odds ratio (OR) 16.6; 95% confidence interval (CI) 12.5–22.4]. A positive outcome was achieved in 97/137 (71%) episodes, 6 (4%) cases experienced no improvement, 16 (12%) died and the outcome could not be established in 18 (13%). Mortality was less in children on HAART (1/21; 4.8%) compared to those not on HAART (15/116; 12.9%). Conclusion We recorded an extremely high incidence of TB among HIV-infected children, especially prior to HAART initiation. Starting HAART at an earlier stage is likely to reduce morbidity and mortality related to TB, particularly in TB-endemic areas. Management frequently deviated from standard guidelines, but outcomes in general were good. PMID:18186944

Walters, Elisabetta; Cotton, Mark F; Rabie, Helena; Schaaf, H Simon; Walters, Lourens O; Marais, Ben J

2008-01-01

288

"It's all the time in my mind": facilitators of adherence to antiretroviral therapy in a Tanzanian setting.  

PubMed

Although HIV positive patients' adherence to antiretroviral therapy (ART) is relatively high in African nations, as compared with industrialized nations, few studies have explored why. In the research presented here we aimed to understand the dynamics of good adherence to ART among patients receiving free ART and HIV-related services from a clinic in Arusha, Tanzania. We conducted individual semi-structured interviews with 6 health care providers and 36 patients at a health care center in Arusha in 2006. Interviews were conducted in Swahili using interview guides informed by social cognitive theory. All interviews were audio-recorded, transcribed in Kiswahili, translated into English and coded for themes and patterns with ATLAS.ti. Of the 36 patients interviewed (mean time on ART 9.8 months; range 1-23 months), 32 reported perfect adherence in the previous month. Self-reported adherence was high despite economic hardship, depression, low rates of HIV disclosure and high perceived HIV-associated stigma. Five factors emerged to explain excellent adherence in the face of such barriers. First, all respondents experienced substantial improvements in their health after starting ART; this supported their confidence in the medication and motivated them to adhere. Second, their perceived need to be able to meet their family responsibilities motivated respondents to stay healthy. Third, respondents developed specific strategies to remember to take pills, particularly routinizing pill-taking by linking it with daily activities or events. Fourth, material and emotional support received from others facilitated adherence. Finally, respondents trusted the advice and instructions of their health care providers, who regularly emphasized adherence. The facilitating factors identified were consistent with the constructs of social cognitive theory and highlighted the importance of interventions that address multiple levels of influence on adherence. PMID:19328609

Watt, Melissa H; Maman, Suzanne; Earp, Jo Anne; Eng, Eugenia; Setel, Philip W; Golin, Carol E; Jacobson, Mark

2009-05-01

289

Mean CD4 cell count changes in patients failing a first-line antiretroviral therapy in resource-limited settings  

PubMed Central

Background Changes in CD4 cell counts are poorly documented in individuals with low or moderate-level viremia while on antiretroviral treatment (ART) in resource-limited settings. We assessed the impact of on-going HIV-RNA replication on CD4 cell count slopes in patients treated with a first-line combination ART. Method Naďve patients on a first-line ART regimen with at least two measures of HIV-RNA available after ART initiation were included in the study. The relationships between mean CD4 cell count change and HIV-RNA at 6 and 12?months after ART initiation (M6 and M12) were assessed by linear mixed models adjusted for gender, age, clinical stage and year of starting ART. Results 3,338 patients were included (14 cohorts, 64% female) and the group had the following characteristics: a median follow-up time of 1.6?years, a median age of 34?years, and a median CD4 cell count at ART initiation of 107 cells/?L. All patients with suppressed HIV-RNA at M12 had a continuous increase in CD4 cell count up to 18?months after treatment initiation. By contrast, any degree of HIV-RNA replication both at M6 and M12 was associated with a flat or a decreasing CD4 cell count slope. Multivariable analysis using HIV-RNA thresholds of 10,000 and 5,000 copies confirmed the significant effect of HIV-RNA on CD4 cell counts both at M6 and M12. Conclusion In routinely monitored patients on an NNRTI-based first-line ART, on-going low-level HIV-RNA replication was associated with a poor immune outcome in patients who had detectable levels of the virus after one year of ART. PMID:22742573

2012-01-01

290

Genetic Diversity of Simian Immunodeficiency Virus Encoding HIV-1 Reverse Transcriptase Persists in Macaques despite Antiretroviral Therapy ?  

PubMed Central

The impact of antiretroviral therapy (ART) on the genetics of simian immunodeficiency virus (SIV) or human immunodeficiency virus (HIV) populations has been incompletely characterized. We analyzed SIV genetic variation before, during, and after ART in a macaque model. Six pigtail macaques were infected with an SIV/HIV chimeric virus, RT-SHIVmne, in which SIV reverse transcriptase (RT) was replaced by HIV-1 RT. Three animals received a short course of efavirenz (EFV) monotherapy before combination ART was started. All macaques received 20 weeks of tenofovir, emtricitabine, and EFV. Plasma virus populations were analyzed by single-genome sequencing. Population diversity was measured by average pairwise difference, and changes in viral genetics were assessed by phylogenetic and panmixia analyses. After 20 weeks of ART, viral diversity was not different from pretherapy viral diversity despite more than 10,000-fold declines in viremia, indicating that, within this range, there is no relationship between diversity and plasma viremia. In two animals with consistent SIV RNA suppression to <15 copies/ml during ART, there was no evidence of viral evolution. In contrast, in the four macaques with viremias >15 copies/ml during therapy, there was divergence between pre- and during-ART virus populations. Drug resistance mutations emerged in two of these four animals, resulting in virologic failure in the animal with the highest level of pretherapy viremia. Taken together, these findings indicate that viral diversity does not decrease with suppressive ART, that ongoing replication occurs with viremias >15 copies/ml, and that in this macaque model of ART drug resistance likely emerges as a result of incomplete suppression and preexisting drug resistance mutations. PMID:21084490

Kearney, Mary; Spindler, Jon; Shao, Wei; Maldarelli, Frank; Palmer, Sarah; Hu, Shiu-Lok; Lifson, Jeffrey D.; KewalRamani, Vineet N.; Mellors, John W.; Coffin, John M.; Ambrose, Zandrea

2011-01-01

291

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

PubMed Central

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

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

292

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

PubMed Central

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

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

293

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

PubMed Central

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

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

2010-01-01

294

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

PubMed Central

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

Shahapur, Praveen R.; Bidri, Rajendra C.

2014-01-01

295

Mitochondrial DNA variation and changes in adiponectin and endothelial function in HIV-infected adults after antiretroviral therapy initiation.  

PubMed

Studies in persons of European descent have suggested that mitochondrial DNA (mtDNA) haplogroups influence antiretroviral therapy (ART) toxicity. We explored associations between mtDNA variants and changes in endothelial function and biomarkers among non-Hispanic white, ART-naive subjects starting ART. A5152s was a substudy of A5142, a randomized trial of initial class-sparing ART regimens that included efavirenz or lopinavir/ritonavir with nucleoside reverse transcriptase inhibitors (NRTIs), or both without NRTIs. Brachial artery flow-mediated dilation (FMD) and cardiovascular biomarker assessments were performed at baseline and at weeks 4 and 24. Ten haplogroup-defining mtDNA polymorphisms were determined. FMD and biomarker changes from baseline to week 24 by mtDNA variant were assessed using Wilcoxon rank-sum tests. Thirty-nine non-Hispanic white participants had DNA and 24-week data. The nonsynonymous m.10398A>G mtDNA polymorphism (N=8) was associated with higher median baseline adiponectin (5.0 vs. 4.2 ?g/ml; p=0.003), greater absolute (-1.9 vs. -0.2 ?g/ml) and relative (-33% vs. -3%) adiponectin decreases (p<0.001 for both), and lower week 24 brachial artery FMD (3.6% vs. 5.4%; p=0.04). Individual mtDNA haplogroups, including haplogroups H (N=13) and U (N=6), were not associated with adiponectin or FMD changes. In this small pilot study, adiponectin and brachial artery FMD on ART differed in non-Hispanic whites with a nonsynonymous mtDNA variant associated with several human diseases. These preliminary findings support the hypothesis that mtDNA variation influences metabolic ART effects. Validation studies in larger populations and in different racial/ethnic groups that include m.10398G carriers are needed. PMID:23944767

Hulgan, Todd; Stein, James H; Cotter, Bruno R; Murdock, Deborah G; Ritchie, Marylyn D; Dube, Michael P; Gerschenson, Mariana; Haas, David W; Torriani, Francesca J

2013-10-01

296

Adverse drug reactions to antiretroviral therapy during the early art period at a tertiary hospital in Ghana  

PubMed Central

Introduction Antiretroviral therapy (ART) has reduced HIV morbidity and mortality worldwide but has many adverse effects. These adverse drug reactions (ADRs) lead to discontinuations, disease progression or treatment failure. We explored the types and risk factors for ADRs in a cohort starting ART in a teaching hospital in Accra, Ghana where the main regimens used were a combination of nucleotide and non nucleotide reverse transcriptase inhibitors. Methods A Cross-sectional retrospective study was conducted reviewing data of 2042 patients initiated on HAART from 2003 to 2007. Univariate analysis was done for the dependent and independent variables. Stepwise logistic regression procedures were used to model the effect of gender on the development of ADRs controlling for other variables like age, marital status, weight at baseline and CD4 at baseline. Results The period prevalence of ADRs was 9.4%. The two most common adverse reactions were anaemia and diarrhoea. Female sex was a statistically significant independent predictor of an adverse drug reaction (AOR: 1.66, p = 0.01, CI: 1.16-2.36). CD4 counts 250 cells/mm3 or more was significantly associated with the occurrence of an ADR. The occurrence of anaemia in females was statistically significant compared to males. Conclusion Adverse drug reactions were less common than expected, anaemia was the commonest ADR. Female sex and high CD4 counts >250mm3 were predictors of ADRs whereas females were significantly more likely to develop anaemia than males. Recommendations were made for interventions to prevent and also mitigate the high levels of anaemia especially among women in the ART scale up. PMID:25368714

Lartey, Margaret; Asante-Quashie, Abena; Essel, Ama; Kenu, Ernest; Ganu, Vincent; Neequaye, Alfred

2014-01-01

297

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

PubMed

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. PMID:24720398

Chabrol, Fanny

2014-08-01

298

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

PubMed Central

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

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

2014-01-01

299

In vitro assessment of the adverse effects of antiretroviral drugs on the human male gamete.  

PubMed

This study was designed to investigate the in vitro effects of didanosine, zidovudine, saquinavir and indinavir, commonly used in highly active antiretroviral therapy, on human sperm fertility parameters. Thirty semen samples from healthy men were collected and prepared by gradient density method. Aliquots of 90% fractions with >80% motile spermatozoa were incubated for 1, 3, and 6h with different concentrations of the antiretroviral drugs (20, 40, and 80 ?g/ml). Sperm motility was evaluated by computer assisted sperm analysis system. Sperm mitochondrial potential was evaluated using 3,3'-dihexyloxacarbocyanine iodide (DIOC(6)) and the acrosome reaction was examined using pisum sativum agglutinin method. A dose-dependent decrease in sperm motility was observed with saquinavir. Saquinavir also induced a significant time and dose-dependent decrease in mitochondrial potential and an increase in spontaneous acrosome reaction. These findings indicate that, in vitro, higher doses of saquinavir have adverse effects on sperm motility, mitochondrial potential and acrosome reaction. PMID:21130153

Ahmad, G; Moinard, N; Jouanolou, V; Daudin, M; Gandia, P; Bujan, L

2011-03-01

300

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

PubMed Central

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

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

2006-01-01

301

The importance of the vaginal delivery route for antiretrovirals in HIV prevention  

PubMed Central

The HIV/AIDS pandemic continues to be a global health priority, with high rates of new HIV-1 infections persisting in young women. One HIV prevention strategy is topical pre-exposure prophylactics or microbicides, which are applied vaginally or rectally to protect the user from HIV and possibly other sexually transmitted infections. Vaginal microbicide delivery will be the focus of this review. Multiple nonspecific and specific antiretroviral microbicide products have been clinically evaluated, and many are in preclinical development. The events of HIV mucosal transmission and dynamics of the cervicovaginal environment should be considered for successful vaginal microbicide delivery. Beyond conventional vaginal formulations, intravaginal rings, tablets and films are employed as platforms in the hope to increase the likelihood of microbicide use. Furthermore, combining multiple antiretrovirals within a given formulation, combining a microbicide product with a vaginal device and integrating novel drug-delivery strategies within a microbicide product are approaches to successful vaginal-microbicide delivery. PMID:22468220

Ferguson, Lindsay M; Rohan, Lisa Cencia

2012-01-01

302

HIV-1 drug resistance mutations among antiretroviral-naive HIV-1-infected patients in Asia: results from the TREAT Asia Studies to Evaluate Resistance-Monitoring Study.  

PubMed

Of 682 antiretroviral-naďve patients initiating antiretroviral therapy in a prospective, multicenter human immunodeficiency virus type 1 (HIV-1) drug resistance monitoring study involving 8 sites in Hong Kong, Malaysia, and Thailand, the prevalence of patients with ?1 drug resistance mutation was 13.8%. Primary HIV drug resistance is emerging after rapid scaling-up of antiretroviral therapy use in Asia. PMID:21460324

Sungkanuparph, Somnuek; Oyomopito, Rebecca; Sirivichayakul, Sunee; Sirisanthana, Thira; Li, Patrick C K; Kantipong, Pacharee; Lee, Christopher K C; Kamarulzaman, Adeeba; Messerschmidt, Liesl; Law, Matthew G; Phanuphak, Praphan

2011-04-15

303

Development of a one-step immunochromatographic strip test for the rapid detection of nevirapine (NVP), a commonly used antiretroviral drug for the treatment of HIV\\/AIDS  

Microsoft Academic Search

Currently, high-performance liquid chromatographic (HPLC) methods are mainly used to measure antiretroviral plasma concentrations in HIV-infected patients. Although the utility of routine therapeutic drug monitoring (TDM) as an additional tool to optimize long-term antiretroviral therapy is unclear, if TDM is to be widely used, the availability of simple, cheap and reliable methods for the measurement of antiretroviral drug levels are

M. Pattarawarapan; S. Nangola; T. R. Cressey; C. Tayapiwatana

2007-01-01

304

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

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

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

305

Early Mortality and AIDS Progression Despite High Initial Antiretroviral Therapy Adherence and Virologic Suppression in Botswana  

Microsoft Academic Search

BackgroundAdverse outcomes occurring early after antiretroviral therapy (ART) initiation are common in sub-Saharan Africa, despite reports of high levels of ART adherence in this setting. We sought to determine the relationship between very early ART adherence and early adverse outcomes in HIV-infected adults in Botswana.MethodsThis prospective cohort study of 402 ART-naďve, HIV-infected adults initiating ART at a public HIV clinic

Katherine T. Steele; Andrew P. Steenhoff; Craig W. Newcomb; Tumelo Rantleru; Rudo Nthobatsang; Gloria Lesetedi; Scarlett L. Bellamy; Jean B. Nachega; Robert Gross; Gregory P. Bisson

2011-01-01

306

Multiple Measures Reveal Antiretroviral Adherence Successes and Challenges in HIV-Infected Ugandan Children  

Microsoft Academic Search

BackgroundAdherence to HIV antiretroviral therapy (ART) among children in developing settings is poorly understood.Methodology\\/Principal FindingsTo understand the level, distribution, and correlates of ART adherence behavior, we prospectively determined monthly ART adherence through multiple measures and six-monthly HIV RNA levels among 121 Ugandan children aged 2–10 years for one year. Median adherence levels were 100% by three-day recall, 97.4% by 30-day

Jessica E. Haberer; Julius Kiwanuka; Denis Nansera; Kathleen Ragland; Claude Mellins; David R. Bangsberg

2012-01-01

307

Improvements in virological control among women conceiving on combination antiretroviral therapy in Western Europe.  

PubMed

Among 396 HIV-infected women conceiving on combination antiretroviral therapy and enrolled in the European Collaborative Study in 2000-2011, the proportion with virological failure (>200 copies/ml after ?24 weeks of treatment) declined substantially from 34% in 2000-2001 to 3% in 2010-2011. In adjusted analyses, younger women and those with at least two children were at increased risk of virological failure, highlighting the importance of close monitoring and adherence support. PMID:23736151

Bailey, Heather; Townsend, Claire L; Cortina-Borja, Mario; Thorne, Claire

2013-09-10

308

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

PubMed

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

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

2013-04-01

309

Immune-recovery uveitis in patients with cytomegalovirus retinitis taking highly active antiretroviral therapy  

Microsoft Academic Search

PURPOSE: To investigate the clinical features associated with immune recovery in human immunodeficiency virus (HIV)–infected patients with cytomegalovirus retinitis who are taking highly active antiretroviral therapy.METHODS: Sixteen patients were evaluated prospectively at the National Eye Institute, Bethesda, Maryland. Evaluation included a medical history and a complete ophthalmologic examination. The examination included best-corrected visual acuity score measured by means of logarithmic

Michael R Robinson; George Reed; Karl G Csaky; Michael A Polis; Scott M Whitcup

2000-01-01

310

Short communication: intermediate prevalence of HIV type 1 primary antiretroviral resistance in Ceará State, Northeast Brazil.  

PubMed

Brazil is a large developing country where almost all FDA-licensed antiretrovirals are made available to more than 200,000 individuals under antiretroviral treatment. General primary HIV-1 resistance in Brazil is assumed to be low, but data are scarce, especially in the Northeast region. To evaluate the prevalence of primary HIV-1 antiretroviral resistance in the state of Ceará, Brazil, a cross-sectional prospective study of antiretroviral-naive HIV-1-infected individuals was performed between May 2008 and May 2009. Genomic sequences of reverse transcriptase and protease regions of the pol gene of HIV-1 using PCR products were obtained. Mutations related to resistance to NRTI, NNRTI, and PI were evaluated according to the WHO mutation list for primary resistance surveillance, which excludes common polymorphisms. Seventy-four individuals were evaluated (50% male) with a median age 30 years; 55.4% were men who have sex with men. Median CD4(+) T lymphocyte counts were 418 and 960 cells/mm(3) and the median viral loads were 4.41 and 4.46 log(10) RNA copies/ml for individuals older and younger that 18 years, respectively. Twenty-seven percent of patients were symptomatic. Five patients (6.8%) were recently infected, as detected by the BED test. The mutations 41L, 67N, 215D, 219Q, 101E, and 103N in the RT and 32I, 46I, 54V, 82T, and 90M, in the PR were identified in 9.5% of samples, more frequently in HIV subtype B (85.1%). A significant level of primary HIV resistance was detected in urban Northeast Brazil, a region geographically distant from the more highly populated and wealthier areas of Southeast Brazil, and this emphasizes the need for monitoring resistance in the studied area. PMID:20929346

Arruda, Erico; Simőes, Leda; Sucupira, Cecília; Medeiros, Melissa; Arruda, Eurico; Diaz, Ricardo S; Lima, Aldo

2011-02-01

311

In utero exposure to antiretroviral therapy: feasibility of long-term follow-up  

Microsoft Academic Search

Most uninfected children born to diagnosed HIV-infected women in the United Kingdom (UK) are exposed to antiretroviral therapy (ART) in utero and neonatally, and concerns exist about potential adverse effects of such exposure. We explored the feasibility of using national clinic-based follow-up to investigate the association between ART exposure and adverse health events occurring after the neonatal period. Active surveillance

Claire Hankin; Hermione Lyall; Barbara Willey; Catherine Peckham; Janet Masters; Pat Tookey

2009-01-01

312

Enhancing adherence to combination antiretroviral therapy in non-adherent HIV-positive men  

Microsoft Academic Search

This paper describes a preliminary study aimed at testing the efficacy of a brief medication counselling and behavioural intervention in improving adherence to combination antiretroviral medication therapy and prophylactic treatment among non-adherent men living with HIV. Twenty-one non-adherent HIV-positive men obtaining primary care clinical services at a Veterans Affairs Medical Center were recruited by health care providers. Intervention participants were

S. McPherson-Baker; R. M. Malow; F. Penedo; D. L. Jones; N. Schneiderman; N. G. Klimas

2000-01-01

313

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

Microsoft Academic Search

BackgroundFood insecurity is emerging as an important barrier to antiretroviral (ARV) adherence in sub-Saharan Africa and elsewhere, but little is known about the mechanisms through which food insecurity leads to ARV non-adherence and treatment interruptions.MethodologyWe conducted in-depth, open-ended interviews with 47 individuals (30 women, 17 men) living with HIV\\/AIDS recruited from AIDS treatment programs in Mbarara and Kampala, Uganda to

Sheri D. Weiser; David M. Tuller; Edward A. Frongillo; Jude Senkungu; Nozmu Mukiibi; David R. Bangsberg

2010-01-01

314

Methamphetamine use and neuropsychiatric factors are associated with antiretroviral non-adherence  

Microsoft Academic Search

The present study assesses the impact of methamphetamine (METH) on antiretroviral therapy (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 non-adherence. We examined HIV+ persons with DSM-IV-diagnosed lifetime history of METH abuse\\/dependence (HIV+ \\/METH+

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

2012-01-01

315

Quality of life and social support among patients receiving antiretroviral therapy in Western Uganda  

Microsoft Academic Search

Quality of life (QOL) among patients with HIV\\/AIDS has been shown to improve once treatment with antiretroviral therapy (ART) has been initiated. We conducted a cross-sectional study in Western Uganda to examine the factors associated with QOL among patients who had received ART for the duration of at least six months.We interviewed 330 patients attending the HIV\\/AIDS clinic at two

Francis Bajunirwe; Daniel J. Tisch; Charles H. King; Eric J. Arts; Sara M. Debanne; Ajay K. Sethi

2009-01-01

316

Identifying self-perceived HIV-related stigma in a population accessing antiretroviral therapy  

Microsoft Academic Search

This study identifies factors associated with self-perceived HIV-related stigma (stigma) among a cohort of individuals accessing antiretroviral therapy in British Columbia, Canada. Data were drawn from the Longitudinal Investigations into Supportive and Ancillary Health Services study, which collects social, clinical, and quality of life (QoL) information through an interviewer-administered survey. Clinical variables (i.e., CD4 count) were obtained through linkages with

Despina Tzemis; Jamie I. Forrest; Cathy M. Puskas; Wendy Zhang; Treena R. Orchard; Alexis K. Palmer; Colin W. McInnes; Kimberly A. Fernades; Julio S. G. Montaner; Robert S. Hogg

2012-01-01

317

Impact of metabolic complications on antiretroviral treatment adherence: Clinical and public health implications  

Microsoft Academic Search

Antiretroviral therapy (ART) is an effective strategy for preventing disease progression of HIV infection, particularly when\\u000a patients adhere closely to the treatment regimen. However, ART medications can cause side effects, including metabolic complications\\u000a that can impact patients’ adherence levels. Selected chronic complications associated with ART include lipodystrophy, hyperlipidemia,\\u000a insulin resistance and diabetes, peripheral neuropathy, and bone disorders such as osteopenia\\/osteoporosis.

Jean B. Nachega; Maria Paola Trotta; Mark Nelson; Adriana Ammassari

2009-01-01

318

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

PubMed Central

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

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

319

Inadequacies in antiretroviral therapy use among Aboriginal and other Canadian populations  

Microsoft Academic Search

We undertook this study to provide a profile of Aboriginal people initiating antiretroviral therapy and their response to treatment. Aboriginal peoples were identified through self-report. Baseline socio-demographics and risk factors were compared between Aboriginal and non-Aboriginal participants as were baseline factors associated with two consecutive plasma viral load measures below 500 copies\\/ml using contingency table analysis. Multivariate survival analysis of

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

2006-01-01

320

Decision Maker Priorities for Providing Antiretroviral Therapy in HIV-Infected South Africans: A Qualitative Assessment  

PubMed Central

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 HIV antiretroviral program decision making. 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 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

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

2012-01-01

321

Affective Correlates of Stimulant Use and Adherence to Antiretroviral Therapy Among HIV-positive Methamphetamine Users  

Microsoft Academic Search

The use of stimulants has important implications for HIV prevention and care. However, few investigations have examined psychological\\u000a correlates of substance use and adherence to anti-retroviral therapy (ART) among HIV-positive stimulant users. This cross-sectional\\u000a investigation examined affective correlates of stimulant use and ART adherence among HIV-positive methamphetamine users. In\\u000a total, 122 HIV-positive men who have sex with men or transgendered

Adam W. Carrico; Mallory O. Johnson; Grant N. Colfax; Judith Tedlie Moskowitz

2010-01-01

322

Adherence to anti-retroviral therapy among HIV patients in Bangalore, India  

Microsoft Academic Search

INTRODUCTION: Human Immunodeficiency Virus (HIV) has an estimated prevalence of 0.9% in India (5.2 million). Anti-retroviral drugs (ARV) are the treatments of choice and non-adherence is an important factor in treatment failure and development of resistance, as well as being a powerful predictor of survival. This study assesses adherence to ARV in HIV positive patients in Bangalore, India, a country

Mary B Cauldbeck; Catherine O'Connor; Mortimer B O'Connor; Jean A Saunders; Bhimasena Rao; V G Mallesh; Nagendrappa Kotehalappa Praveen Kumar; Gurushanthappa Mamtha; Claire McGoldrick; Robert BS Laing; Kadappa Shivappa Satish

2009-01-01

323

Numerical modelling of the perturbation of HIV1 during combination anti-retroviral therapy  

Microsoft Academic Search

A competitive, chaos-free, implicit, finite-difference method is developed and used for a novel deterministic model for the perturbation of HIV by combination antiretroviral therapy. The compartmental model monitors the interaction between HIV and CD4+ T cells, its principal target and site of replication in vivo, in the presence of reverse transcription inhibitors and protease inhibitors. The model exhibits two steady

A. B. Gumel; T. D. Loewen; P. N. Shivakumar; B. M. Sahai; P. Yu; M. L. Garba

2001-01-01

324

Effectiveness of Multidrug Antiretroviral Regimens to Prevent Mother-to-Child Transmission of HIV-1 in  

E-print Network

2008 in a reference hospital in Cameroon. HIV-positive pregnant women with CD4 #350 cells/mm3 received-to-Child Transmission of HIV-1 in Routine Public Health Services in Cameroon. PLoS ONE 5(4): e10411. doi:10.1371/journalEffectiveness of Multidrug Antiretroviral Regimens to Prevent Mother-to-Child Transmission of HIV-1

Paris-Sud XI, Université de

325

Transgenic mouse models of mitochondrial toxicity associated with HIV/AIDS and antiretrovirals.  

PubMed

Since the discovery of HIV-1 and the explosion of interest in antiretroviral therapy, there has been an increasing demand for animal models to determine the underlying mechanisms of HIV/AIDS disease progression. Additionally, the advent of nucleoside reverse transcriptase inhibitors (NRTI) and the associated side effects necessitated an approach to explore NRTI toxic mechanisms in vivo. Determining the pathophysiological effects of antiretroviral drugs (such as NRTIs) on animals became an important part of understanding the risks associated with current therapeutic approaches where mitochondrial toxicity is important. Transgenic mouse models (TG) in HIV/AIDS research are valuable tools to investigate the pathophysiology of HIV-1 infection and the effects of the antiretrovirals used to treat the infection. TGs enable investigators to control these variables experimentally. This chapter summarizes data from TG models that help unravel the individual and combined effects of HIV-1 infection and NRTI therapy on mouse physiology. Emphasis is placed on cardiac mitochondrial toxicity of NRTIs used in HIV/AIDS. PMID:20045731

Koczor, Christopher; Kohler, James; Lewis, William

2010-08-01

326

Morbidity in older HIV-infected patients: impact of long-term antiretroviral use.  

PubMed

The introduction of HAART has represented a major advance in the care of people with HIV. By markedly increasing life expectancy, HAART has significantly changed the pattern of HIV infection in developed countries, the "graying" of the HIV-infected population being a powerful testament to its success. However, this has presented physicians with new challenges relating to the care of older patients with HIV, many of whom exhibit a "frailty syndrome" associated with increased comorbidity and chronic low-grade inflammation in a process which has recently been termed "inflammaging". This paper reviews the pattern of morbidity seen in older HIV-infected patients and examines the effects, both beneficial and deleterious, of antiretroviral therapy. The efficacy and tolerability of antiretroviral therapy is of particular importance in older patients, given the likelihood that increased frailty may magnify the consequences both of suboptimal viral suppression and of toxicity, and in view of the complications that may arise from the presence of comorbidities and resultant polypharmacy. The challenge is to maximize antiviral efficacy and minimize toxicity, while taking into account the often complex web of comorbidities that may be present in these patients. This challenge is being met through the refinement of existing antiretroviral therapy regimens, the development of new agents, and a growing focus on a more holistic approach to care, which acknowledges the importance of the overall "health picture" and of good communication and cooperation between treating physicians and patients. PMID:24759453

Guaraldi, Giovanni; Prakash, Manyu; Moecklinghoff, Christiane; Stellbrink, Hans-Jürgen

2014-01-01

327

Antiretroviral treatment, management challenges and outcomes in perinatally HIV-infected adolescents  

PubMed Central

Three decades into the HIV/AIDS epidemic there is a growing cohort of perinatally HIV-infected adolescents globally. Their survival into adolescence and beyond represent one of the major successes in the battle against the disease that has claimed the lives of millions of children. This population is diverse and there are unique issues related to antiretroviral treatment and management. Drawing from the literature and experience, this paper discusses several broad areas related to antiretroviral management, including: 1) diverse presentation of HIV, (2) use of combination antiretroviral therapy including in the setting of co-morbidities and rapid growth and development, (3) challenges of cART, including nonadherence, resistance, and management of the highly treatment-experienced adolescent patient, (4) additional unique concerns and management issues related to PHIV-infected adolescents, including the consequences of longterm inflammation, risk of transmission, and transitions to adult care. In each section, the experience in both resource-rich and limited settings are discussed with the aim of highlighting the differences and importantly the similarities, to share lessons learnt and provide insight into the multi-faceted approaches that may be needed to address the challenges faced by this unique and resilient population. PMID:23782477

Agwu, Allison L; Fairlie, Lee

2013-01-01

328

Sexual risk behavior among people living with HIV and AIDS on antiretroviral therapy at the regional hospital of Sokodé, Togo  

PubMed Central

Background Several studies on the sexual risk behaviors in sub-Saharan Africa have reported that the initiation of antiretroviral therapy leads to safer sexual behaviors. There is however a persistence of risky sexual behavior which is evidenced by a high prevalence of sexually transmitted infections among people living with HIV and AIDS (PLWHA). We sought to determine the factors associated with risky sex among PLWHA on antiretroviral therapy in Togo. Methods An analytical cross-sectional survey was conducted from May to July 2013 at regional hospital of Sokodé, Togo, and targeted 291 PLWHA on antiretroviral therapy for at least three months. Results From May to July 2013, 291 PLWHA on antiretroviral treatment were surveyed. The mean age of PLWHA was 37.3 years and the sex ratio (male/female) was 0.4. Overall, 217 (74.6%) PLWHA were sexually active since initiation of antiretroviral treatment, of which, 74 (34.6%) had risky sexual relations. In multivariate analysis, the factors associated with risky sex were: the duration of antiretroviral treatment (1 to 3 years: aOR?=?27.08; p?=?0.003; more than 3 years: aOR?=?10.87; p?=?0.028), adherence of antiretroviral therapy (aOR?=?2.56; p?=?0.014), alcohol consumption before sex (aOR?=?3.59; p?=?0.013) and level of education (primary school: aOR?=?0.34 p?=?0.011; secondary school: aOR?=?0.23 p?=?0.003; high school: aOR?=?0.10; p?=?0.006). Conclusion There was a high prevalence of unsafe sex among PLWHA receiving ART at the hospital of Sokodé. Factors associated with sexual risk behaviors were: low education level, non-adherence to ART, alcohol consumption before sex and the duration of ART. It is important to strengthen the implementation of secondary prevention strategies among this population group. PMID:24952380

2014-01-01

329

Self-starting of passive mode locking  

NASA Astrophysics Data System (ADS)

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

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

2006-11-01

330

Alcohol cold starting - A theoretical study  

NASA Technical Reports Server (NTRS)

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.

Browning, L. H.

1983-01-01

331

Timing of antiretroviral therapy and regimen for HIV-infected patients with tuberculosis: the effect of revised HIV guidelines in Malawi  

PubMed Central

Background In July 2011, the Malawi national HIV program implemented the integrated antiretroviral therapy (ART) and prevention of mother-to-child transmission (PMTCT) guidelines. Among the principle goals of the guidelines were increasing ART uptake among TB/HIV co-infected patients and treating TB/HIV patients with a different drug regimen. We, therefore, assessed the effects of the new guidelines on ART uptake, the factors associated with ART uptake and the frequency of ARV-related adverse events in TB/HIV co-infected patients. Methods This was an observational cohort study using routine program data. All ART-naďve adult TB/HIV co-infected patients starting TB treatment over the six months preceding and following implementation of 2011 integrated ART/PMTCT guidelines were included. Results A total of 685 adult TB/HIV co-infected patients were registered in the study; 377 (55%) before and 308 (45%) after the implementation of the new guidelines. ART uptake increased from 70% (240/308) before implementation of the new guidelines to 78% (262/377) after the inception of the new guidelines (P=0.013). The proportion of TB patients initiating ART within two weeks of starting TB treatment increased from 30% before implementation of the new guidelines to 46% after implementation of the new guidelines (p <0.001). The median time from the start of TB treatment to ART initiation dropped from 16 days (IQR 14-31) before the new guidelines to 14 days (IQR 9-20; p?=?0.004) after implementing the new guidelines. Factors associated with ART uptake were enrolment in HIV care before starting TB treatment and being a retreatment TB patient. The overall frequency of ARV-related adverse events was higher in patients on d4T/3TC/NVP (35%) than those on TDF/3TC/EFV (25%) but not significantly different (P=0.052). Conclusion Implementation of the 2011 Malawi Integrated ART/PMTCT guidelines was associated with an overall increase in ART uptake among TB/HIV patients and with an increase in the number of patients initiating ART within two weeks of starting their TB treatment. However, the reduction in time between initiating TB treatment and starting ART was small suggesting that further measures must be implemented to facilitate ART uptake. Early enrolment in HIV care provides opportunities for timely ART initiation among TB patients. PMID:24555530

2014-01-01

332

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

PubMed Central

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

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

2007-01-01

333

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

PubMed

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

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

2014-07-30

334

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

PubMed Central

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

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

2010-01-01

335

Start-Up Success: Collection Development  

ERIC Educational Resources Information Center

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

Awe, Susan C.

2010-01-01

336

START THE CONVERSATION: HOW TO DISCUSS  

E-print Network

on research from the National Institute on Alcohol Abuse and Alcoholism, College Parents of America, MothersSTART THE CONVERSATION: HOW TO DISCUSS ALCOHOL WITH YOUR STUDENT #12;2 Why Now by the Center for Health Education & Wellness 1800 Volunteer Blvd., Suite 201 Knoxville, TN 37996-3104 865

Wang, Xiaorui "Ray"

337

How to Start Intergenerational Programs in Communities.  

ERIC Educational Resources Information Center

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

2002

338

Starting New Schools: Lessons for Success.  

ERIC Educational Resources Information Center

Arguments for beginning new schools as a robust alternative to the incremental improvement of existing schools are presented in this paper. The educational improvement approach of starting new schools or programs, rather than making incremental improvements or generating comprehensive change in existing schools, is advocated. Two major types of…

Jennings, Wayne B.

339

CRITICAL THINKING GETTING STARTED Other Handouts  

E-print Network

CRITICAL THINKING ­ GETTING STARTED Other Handouts: Analysing an Essay Question Improve Your Reading of Academic Texts What is critical thinking? Frequently asked questions by first year university students are: Why is critical thinking emphasised at university? How does it differ from the thinking I

340

Arcjet power supply and start circuit  

NASA Technical Reports Server (NTRS)

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.

Gruber, Robert P. (inventor)

1988-01-01

341

Reference Manual 7.1 Quick Start  

E-print Network

Chapter 7 Reference Manual 7.1 Quick Start This section provides a minimum of information about with the master spawning the slave processes, and without graphics. 7.1.1 Obtaining the software PHAML can, and defaults for your computer system. Instructions for modifying it can be found within the file. Now create

342

Advanced Research Computing Before We Start  

E-print Network

Advanced Research Computing Before We Start · Sign in · Copy files from the MIC directory Computing March 4, 2014 #12;Advanced Research Computing Outline · Background · The Intel Xeon Phi · Native Mode · Offloading ­ Automatic ­ Directives ­ Multiple MICs · MPI #12;Advanced Research Computing 4

Crawford, T. Daniel

343

Evaluation of Hawaii's Healthy Start Program  

Microsoft Academic Search

Hawaii's Healthy Start Program (HSP) is designed to prevent child abuse and neglect and to promote child health and development in newborns of families at risk for poor child outcomes. The program operates statewide in Hawaii and has inspired national and international adaptations, including Healthy Families America. This article describes HSP, its ongoing evaluation study, and evaluation findings at the

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

1999-01-01

344

Getting-Started Strategies and Cooperative Learning.  

ERIC Educational Resources Information Center

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

Myers, John J.; And Others

1991-01-01

345

Getting Started Advanced Search for Funding Opportunities  

E-print Network

Getting Started Advanced Search for Funding Opportunities For Assistance Delete Criteria to Update Search Funding ­ Finding Additional Sources Saving and Printing SPIN Search Results Past funding opportunities can be searched in InfoEd to: · find opportunities that were added prior to your account set

Duchowski, Andrew T.

346

Philadelphia's Independence Starts Here: Disability Arts Festival  

ERIC Educational Resources Information Center

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

Smith, Mimi Kenney

2008-01-01

347

Analysis of False Starts in Spontaneous Speech.  

ERIC Educational Resources Information Center

A primary difference between spontaneous speech and read speech concerns the use of false starts, where a speaker interrupts the flow of speech to restart his or her utterance. A study examined the acoustic aspects of such restarts in a widely-used speech database, examining approximately 1000 utterances, about 10% of which contained a restart.…

O'Shaughnessy, Douglas

348

GETTING STARTED IN MATH AND THE SCIENCES  

E-print Network

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

Myers, Lawrence C.

349

TRIP START TIME DISTRIBUTION Metro 1996  

E-print Network

APPENDIX B TRIP START TIME DISTRIBUTION #12;Metro 1996 0% 2% 4% 6% 8% 10% 12% 14% 430 530 630 730 hour window NHB HBO HBS HBW B.6 #12;Metro 1996 0% 2% 4% 6% 8% 10% 12% 14% 430 530 630 730 830 930 1030

Toronto, University of

350

Desert Gardening 101: Steps to Starting a  

E-print Network

Desert Gardening 101: Steps to Starting a Vegetable Garden Tuesday, September 27, 2011 9:00 ­ 10 Alliance Permaculture Design Course just recently. She is keenly interested in food forests, native food garden in the Southwest desert. Also, Evan from Sunizona Family Farms will offer samples of their organic

Hall, Sharon J.

351

Self-starting circuit for switching regulators  

NASA Technical Reports Server (NTRS)

Schematic is provided on a self-starting circuit for a switching regulator which uses a logic circuit to sense a change in output voltage and provides a correction signal for dc power sources. With this device, the total power consumed by the logic circuitry is held to a minimum, and the circuit receives the optimum regulated supply power.

Schraut, E. H.; Sohl, G.

1969-01-01

352

Health Coaching Available Starting November 20th  

E-print Network

Health Coaching Available Starting November 20th ! If you've completed your health survey and printed your report, which explains what you are doing well and what you can do better, health coaches are now available. . Our health coaches can work with you to help you take your health to the next level

Marsh, David

353

Developing a Head Start Training Plan.  

ERIC Educational Resources Information Center

This handbook outlines 10 steps in developing a training plan for Head Start. The introduction defines training and lists the benefits of a training plan. The bulk of the handbook consists of a detailed description of the 10 steps for development of a training plan, including each step's purpose, directions to accompany work sheets, and questions…

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

354

Verifying the INF and START treaties  

SciTech Connect

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.

Ifft, Edward [School of Foreign Service, Georgetown University, Washington, DC 20057 (United States)

2014-05-09

355

Verifying the INF and START treaties  

NASA Astrophysics Data System (ADS)

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.

Ifft, Edward

2014-05-01

356

Helping technology start-ups expand their  

E-print Network

a new online application, `Travel Time', which will revolutionise the way in which people search for any geographic location online. The challenge iGeolise is a start-up company that has created an innovative online platform which allows people to filter searches for geographic location by time rather than

Zharkova, Valentina V.

357

Innovations in Detroit Head Start. [Videotape].  

ERIC Educational Resources Information Center

The Reggio Emilia approach to early childhood teaching is based on curriculum and teaching practices developed in the preschools of Reggio Emilia, Italy. This video highlights an ongoing Detroit, Michigan Head Start staff development project, inspired by the Reggio Emilia approach. The staff development program was launched in consultation with…

Merrill-Palmer Inst., Detroit, MI.

358

Head Start Emergent Literacy Project. Training Manual.  

ERIC Educational Resources Information Center

This training manual was designed to provide information and support to Head Start teachers, staff, and parents in the area of emergent literacy. The first section, "What is Emergent Literacy and Why Should We Do It?" addresses the concept of emergent literacy, identifying six key elements: (1) learning to read and write begins very early in life;…

Nelson, Carol J.; And Others

359

Getting Started With Poly3D  

E-print Network

planar, polygonal-shaped elements of displacement discontinuity. Polygonal elements may have any number, of a fracture or fault surface as long as displacement discontinuity (joint aperature or fault slip) is con. This will make it easier for you to adapt Poly3D to your own problems. CHAPTER 2: Getting Started With Poly3D

Cooke, Michele

360

Getting started with Python Dr. Mark Lee  

E-print Network

Getting started with Python Dr. Mark Lee School of Computer Science University of Birmingham B15 2TT m.g.lee@cs.bham.ac.uk Introduction Python a very clear syntax and is an ideal first programming language. It's also very powerful ­ Python

Lee, Mark

361

Comprehensive Evaluation of Hawaii's Healthy Start Program.  

ERIC Educational Resources Information Center

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

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

362

Evaluation of Hawaii's Healthy Start Program.  

ERIC Educational Resources Information Center

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…

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

363

TOMORROW'S HEALTHCARE STARTS HERE THE MEDICAL COLLEGE  

E-print Network

TOMORROW'S HEALTHCARE STARTS HERE #12;THE MEDICAL COLLEGE OF WISCONSIN IS MORE THAN A MEDICAL SCHOOL. IT'S WHERE THE FUTURE OF HEALTHCARE BEGINS. It's where strategies are launched to ensure families have access to quality healthcare. It's where a passion for patient care drives innovative medical

364

The Start of a Tech Revolution  

ERIC Educational Resources Information Center

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

Dyrli, Kurt O.

2009-01-01

365

Super Start-the-School-Year Ideas.  

ERIC Educational Resources Information Center

Presents interactive activities and games designed to help teachers get to know new students quickly and help the students become comfortable with each other and their surroundings as the school year starts. The article addresses how to explore the new environment, handle concerns and conflicts, and work in cooperative groups. (SM)

Goldish, Meish

1991-01-01

366

SP100 start-up control strategy  

Microsoft Academic Search

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

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

1991-01-01

367

Self-starting, free piston Stirling engine  

Microsoft Academic Search

A free piston, Stirling engine is provided with seals which permit a limited range of friction-free displacer piston movement for allowing a starting perturbation of displacer piston position. The seal is a sealing ring resiliently mounted to one of two slidably engaged members of the Stirling engine with a limited freedom of movement relative to that member and sealingly slidable

Beale

1977-01-01

368

iBuyNU History -Quick Start IBuyNUHistoryQuickStart  

E-print Network

iBuyNU History - Quick Start iBuyNU Purchasing IBuyNUHistoryQuickStart Last Updated 10/16/2014 lks for and track submitted carts, purchase orders and invoices using history. History menu (side banner) 1. Click the History menu icon in the side banner. 2. Click Search Documents. (The History menu search page appears.) 3

Shull, Kenneth R.

369

Canterbury Bright Start Scholarships Page 1 of 2 CANTERBURY BRIGHT START SCHOLARSHIPS  

E-print Network

Canterbury Bright Start Scholarships Page 1 of 2 CANTERBURY BRIGHT START SCHOLARSHIPS CANTERBURY Education Millennial Trust was established in 2001 to offer scholarships to students from the Canterbury acknowledges the generosity of The Canterbury Community Trust in funding the scholarships. 2. NAME The award

Hickman, Mark

370

Head Start to Full Start: A Progression of Gains in Fulfilling Children's Preschool Needs.  

ERIC Educational Resources Information Center

This paper examines literature on early intervention programs for disadvantaged and culturally diverse children from the 1960s to the present. The focus is on Project Head Start and its history, follow-through support programs in the primary grades, and current research on emergent literacy. The background of Project Head Start is provided, and…

Sandel, Lenore

371

Predictors of adherence to antiretroviral therapy among people living with HIV\\/AIDS in resource-limited setting of southwest ethiopia  

Microsoft Academic Search

BACKGROUND: Good adherence to antiretroviral therapy is necessary to achieve the best virological response, lower the risk that drug resistance will develop, and reduce morbidity and mortality. Little is known about the rate and predictors of adherence in Ethiopia. Therefore this study determines the magnitude and predictors of adherence to antiretroviral therapy among people living with HIV\\/AIDS in Southwest Ethiopia.

Ayele Tiyou; Tefera Belachew; Fisehaye Alemseged; Sibhatu Biadgilign

2010-01-01

372

Economic Outcomes of Patients Receiving Antiretroviral Therapy for HIV\\/AIDS in South Africa Are Sustained through Three Years on Treatment  

Microsoft Academic Search

BackgroundAlthough the medical outcomes of antiretroviral therapy (ART) for HIV\\/AIDS are well described, less is known about how ART affects patients' economic activities and quality of life, especially after the first year on ART. We assessed symptom prevalence, general health, ability to perform normal activities, and employment status among adult antiretroviral therapy patients in South Africa over three full years

Sydney Rosen; Bruce Larson; Alana Brennan; Lawrence Long; Matthew Fox; Constance Mongwenyana; Mpefe Ketlhapile; Ian Sanne; Andrew Yates

2010-01-01

373

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

Microsoft Academic Search

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

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

2004-01-01

374

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

PubMed Central

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

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

2014-01-01

375

Pre-antiretroviral therapy serum selenium concentrations predict WHO stages 3, 4 or death but not virologic failure post-antiretroviral therapy.  

PubMed

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

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

2014-11-01

376

A Guide for Providing Social Services in Head Start.  

ERIC Educational Resources Information Center

The social services component of Head Start links family, Head Start, and the community. This document addresses components of Head Start, providing Head Start staff who have social services responsibility with a guide to the provision of services to families. The chapters in the guide are: (1) "Overview of Head Start," including its origins,…

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

377

Head Start Impact Study: First Year Findings. Executive Summary  

ERIC Educational Resources Information Center

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

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

2005-01-01

378

Chest Computed Tomography Findings in HIV-Infected Individuals in the Era of Antiretroviral Therapy  

PubMed Central

Background Chest radiographic abnormalities were common in HIV-infected individuals in the pre-combination antiretroviral therapy era, but findings may differ now due to a changing spectrum of pulmonary complications. Methods Cross-sectional study of radiographic abnormalities in an HIV-infected outpatient population during the antiretroviral therapy era. Demographics, chest computed tomography, and pulmonary function tests were obtained in HIV-infected volunteers without acute respiratory illness from the University of Pittsburgh HIV/AIDS clinic. Overall prevalence of radiographic abnormalities and potential risk factors for having any abnormality, nodules, or emphysema were evaluated using univariate and multivariable analyses. Results A majority of the 121 participants (55.4%) had a radiographic abnormality with the most common being emphysema (26.4%), nodules (17.4%), and bronchiectasis (10.7%). In multivariate models, age (odds ratio [OR] per year ?=?1.07, 95% confidence interval [CI] 1.04–1.14, p<0.001), pneumonia history (OR ?=?3.60, 95% CI ?=?1.27–10.20, p?=?0.016), and having ever smoked (OR ?=?3.66, p?=?0.013, 95% CI ?=?1.31–10.12) were significant predictors of having any radiographic abnormality. Use of antiretroviral therapy, CD4 cell count, and HIV viral load were not associated with presence of abnormalities. Individuals with radiographic emphysema were more likely to have airway obstruction on pulmonary function tests. Only 85.8% participants with nodules had follow-up imaging resulting in 52.4% having stable nodules, 23.8% resolution of their nodules, 4.8% development of a new nodule, and 4.8% primary lung cancer. Conclusions Radiographic abnormalities remain common in HIV-infected individuals with emphysema, nodules, and bronchiectasis being the most common. Age, smoking, and pneumonia were associated with radiographic abnormalities, but HIV-associated factors did not seem to predict risk. PMID:25409510

Clausen, Emily; Wittman, Catherine; Gingo, Matthew; Fernainy, Khaled; Fuhrman, Carl; Kessinger, Cathy; Weinman, Renee; McMahon, Deborah; Leader, Joseph; Morris, Alison

2014-01-01

379

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

PubMed Central

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

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

2013-01-01

380

Prevalence and determinants of transmitted antiretroviral drug resistance in HIV-1 infection.  

PubMed

Transmission of drug-resistant HIV-1 variants from antiretroviral treatment-experienced persons has been documented to occur through multiple routes, including sexual intercourse, intravenous drug use and vertically from mother to child. Newly infected persons with transmitted drug resistance (TDR) also act as a source for the onward transmission of resistant variants. Rates of virological suppression and behavioural patterns of treated populations and the relative fitness of drug-resistant variants are important determinants of the prevalence of TDR. Current estimates indicate that the prevalence is highest in regions and populations with long-established use of antiretroviral therapy. Limited data suggest that the incidence of TDR is rising in developing countries where access to therapy is increasing. There are methodological variations between studies, however, including those relative to the selection of the study population and the resistance interpretation system, which can skew prevalence estimates. TDR has important implications for the successful management of antiretroviral therapy. Routine resistance testing of drug-naive persons has been widely adopted in affluent countries and shown to effectively guide the selection of first-line regimens. Genotypic resistance tests offer a practical approach for detecting TDR. However, routine methods can only detect resistant mutants within the dominant quasi-species and fail to detect low-frequency resistant variants, which may become important once selective drug pressure is introduced. More sensitive testing methods are being evaluated but remain research tools at present. In addition, factors such as superinfection and possible differences in resistance patterns between plasma and cellular reservoirs and between anatomical compartments should be considered when evaluating TDR. PMID:17449483

Booth, Clare L; Geretti, Anna Maria

2007-06-01

381

Patient satisfaction with task shifting of antiretroviral services in Ethiopia: implications for universal health coverage.  

PubMed

Formalized task shifting structures have been used to rapidly scale up antiretroviral service delivery to underserved populations in several countries, and may be a promising mechanism for accomplishing universal health coverage. However, studies evaluating the quality of service delivery through task shifting have largely ignored the patient perspective, focusing on health outcomes and acceptability to health care providers and regulatory bodies, despite studies worldwide that have shown the significance of patient satisfaction as an indicator of quality. This study aimed to measure patient satisfaction with task shifting of antiretroviral services in hospitals and health centres in four regions of Ethiopia. This cross-sectional study used data collected from a time-motion study of patient services paired with 665 patient exit interviews in a stratified random sample of antiretroviral therapy clinics in 21 hospitals and 40 health centres in 2012. Data were analyzed using f-tests across provider types, and multivariate logistic regression to identify determinants of patient satisfaction. Most (528 of 665) patients were satisfied or somewhat satisfied with the services received, but patients who received services from nurses and health officers were significantly more likely to report satisfaction than those who received services from doctors [odds ratio (OR) 0.26, P < 0.01]. Investments in the health facility were associated with higher satisfaction (OR 1.07, P < 0.01), while costs to patients of over 120 birr were associated with lower satisfaction (OR 0.14, P < 0.05). This study showed high levels of patient satisfaction with task shifting in Ethiopia. The evidence generated by this study complements previous biomedical and health care provider/regulatory acceptability studies to support the inclusion of task shifting as a mechanism for scaling-up health services to achieve universal health coverage, particularly for underserved areas facing severe health worker shortages. PMID:25274640

Asfaw, Elias; Dominis, Sarah; Palen, John G H; Wong, Wendy; Bekele, Abebe; Kebede, Amha; Johns, Benjamin

2014-09-01

382

[Cryptococcal neuromeningitidis in HIV-infected patients in Bangui, in the era of antiretroviral treatment].  

PubMed

The cryptococcal neuromeningitis is the most common fungal meningitis infections in the course of HIV/AIDS. This is the number two of opportunist infection of the central nervous system. The authors post the outcomes of a retrospective study conducted related to 122 cases of cryptococcal neuromeningitis observed over for four years ago, in Bangui in the Central African Republic, this at time when antiretroviral treatment has been avaible, corresponding to a prevalence of 6.5%. These infections very aften occur more in female folk, and to patients whose average age is 35 years old, ranging from 18 to 69 years old. The clinical symptoms often found had been headache (98,3.%), fever (95.0%), the impairing of the overall condition of the patient (86.7%) and neck stiffness (85.9%). It makes sense to notice that comorbidity case alowgwith tuberculosis, intestinal candidiasis, bacterial pneumonia and Kaposi's diseases were found out. The screening of the cerebrospinal fluid showed a sound cell count and even low count in 12.2% of cases. Direct examination of cerebrospinal fluid with India ink helps in diagnosis of 97.5% of cases, and the culture carried out from 74 patients was in any case positive. This culture allowed the diagnosis of three patients whose examination along side with India ink has been negative. The CD4 cell count was less than 100/mm(3) in 97.7% of cases. The rate of the fatality cases has been 66.4%, it has been badly impacted by a CD4 count <50/mm(3) and the lack of antiretroviral therapy. Despite the establishment of a national antiretroviral treatment program to do influence the frequency of opportunistic infections whose cryptococcal neuromeningitis, this condition is still present although it is declining. The clinical variability of this disease requires early diagnosis to avoid delayed treatment corollary of a very high mortality as we have observed. PMID:24570116

Gbangba-Ngai, E; Fikouma, V; Mossoro-Kpinde, C D; Tekpa, G; Ouavene, J O; Yangba Mongba, D S A; Mbelesso, P

2014-05-01

383

Starting apparatus for internal combustion engines  

DOEpatents

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.

Dyches, Gregory M. (Barnwell, SC); Dudar, Aed M. (Augusta, GA)

1997-01-01

384

Adherence to highly active antiretroviral therapy and its correlates among HIV infected pediatric patients in Ethiopia  

PubMed Central

Background The introduction of combination antiretroviral therapy (ART) has resulted in striking reductions in HIV-related mortality. Despite increased availability of ART, children remain a neglected population. This may be due to concerns that failure to adhere appears to be related to continued viral replication, treatment failure and the emergence of drug-resistant strains of HIV. This study determines the rates and factors associated with adherence to Antiretroviral (ARV) Drug therapy in HIV-infected children who were receiving Highly Active Antiretroviral Therapy (HAART) in Addis Ababa, Ethiopia in 2008. Methods A cross-sectional study was conducted in five hospitals in Addis Ababa from February 18 – April 28, 2008. The study population entailed parents/caretaker and index children who were following ART in the health facilities. A structured questionnaire was used for data collection. Results A total of 390 children respondents were included in the study with a response rate of 91%. The majority, equaling 205 (52.6%) of the children, were greater than 9 years of age. Fifty five percent of the children were girls. A total of 339 children (86.9%) as reported by caregivers were adherent to antiretroviral drugs for the past 7 days before the interview. Numerous variables were found to be significantly associated with adherence: children whose parents did not pay a fee for treatment [OR = 0.39 (95%CI: 0.16, 0.92)], children who had ever received any nutritional support from the clinic [OR = 0.34 (95%CI: 0.14, 0.79)] were less likely to adhere. Whereas children who took co-trimoxazole medication/syrup besides ARVs [OR = 3.65 (95%CI: 1.24, 10.74)], children who did not know their sero-status [OR = 2.53 (95%CI: 1.24, 5.19)] and children who were not aware of their caregiver's health problem [OR = 2.45 (95%CI: 1.25, 4.81)] were more likely to adhere than their counterparts. Conclusion Adherence to HAART in children in Addis Ababa was higher than other similar setups. However, there are still significant numbers of children who are non-adherent to HAART. PMID:19061515

Biadgilign, Sibhatu; Deribew, Amare; Amberbir, Alemayehu; Deribe, Kebede

2008-01-01

385

Dermatological aspects of medicine: highly active antiretroviral therapy and the treatment of human immunodeficiency virus.  

PubMed

This is the sixth in a series of CPD articles aimed at reviewing the recent general medical literature relating to topics that may be of interest to dermatologists. In this issue the new classes of anti-retroviral drugs will be described in the context of the replication cycle of human immunodeficiency virus (HIV). The regimens of drug treatments and the more common side-effects including HIV-lipodystrophy syndrome will be discussed along with the recommendations for testing of people for HIV from new guidelines. PMID:19758384

Finucane, K A; Archer, C B

2010-01-01

386

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

PubMed

The objective of this study was to examine the spectrum of human immunodeficiency virus (HIV) brain pathology and its clinical correlates in the antiretroviral era. We carried out a cross-sectional survey, analyzing prospective clinical and neuropathological data collected by the National NeuroAIDS Tissue Consortium (NNTC), comprising 589 brain samples from individuals with advanced HIV disease collected from 1999 onwards. We assessed gender, ethnicity/race, mode of transmission, age, year of death, nadir CD4, plasma viral load, last antiretroviral regimen, presence of parenchymal HIV brain pathology, HIV-associated neurocognitive disorder, and major depressive disorder. We compared cohort demographic variables with Centers for Disease Control and Prevention US HIV/AIDS statistics and examined associations of parenchymal HIV brain pathology with demographic, clinical, and HIV disease factors. With regard to Centers for Disease Control and Prevention US data, the NNTC was similar in age distribution, but had fewer females and African Americans and more Hispanics and men who have sex with men. Only 22% of the brains examined were neuropathologically normal. Opportunistic infections occurred in 1% to 5% of the cohort. Parenchymal HIV brain pathology was observed in 17.5% of the cohort and was associated with nadir CD4 and plasma viral load. Brains without parenchymal HIV brain pathology often had other noninfectious findings or minimal nondiagnostic abnormalities that were associated with HIV-associated neurocognitive disorder. Clinically, 60% of the cohort reported a lifetime episode of major depressive disorder and 88% had a HIV-associated neurocognitive disorder. No pathological finding correlated with major depressive disorder. Both antiretroviral treatment regimen and elevated plasma HIV viral load were associated with presence of parenchymal HIV brain pathology; however, multivariate analyses suggest a stronger association with plasma viral load. The frequency of HIV brain pathology was lower than previous pre-antiretroviral reports, and was predicted by lower nadir CD4 and higher plasma viral load. Noninfectious pathologies and minimal changes correlated with HIV-associated neurocognitive disorder, suggesting a shift in pathogenesis from florid HIV replication to other, diverse mechanisms. PMID:20175693

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

2009-09-01

387

Autonomous Regulation and Locus of Control as Predictors of Antiretroviral Medication Adherence  

PubMed Central

The purpose of the current study was to examine the interrelationships between Autonomous Regulation (AR) and locus of control (LOC) and their prediction of Antiretroviral Therapy (ART) adherence among 189 HIV+ patients. Path analyses revealed that neither AR nor LOC directly predicted adherence although AR was indirectly related when mediated by self-efficacy. AR was positively related to internal and doctors LOC, but not related to chance or others LOC. Overall, results support Self Determination Theory’s conceptualization of AR and indicate that AR may be a more robust predictor of medication adherence than LOC variables. PMID:19383658

Lynam, Ian; Catley, Delwyn; Goggin, Kathy; Rabinowitz, Joshua L.; Gerkovich, Mary M.; Williams, Karen; Wright, Julie

2009-01-01

388

Factors Associated with Suboptimal Antiretroviral Therapy Adherence to Dose, Schedule, and Dietary Instructions  

Microsoft Academic Search

The purpose of this study was to assess the degree of suboptimal antiretroviral therapy adherence to dose, schedule, and dietary\\u000a instructions and to examine the effects of extra-personal, intra-personal, and inter-personal factors on suboptimal adherence\\u000a across the three types of instructions. Self-report and clinical data were collected from 193 sexually infected Swedish patients\\u000a receiving ART. Effects of extra-personal, intra-personal, and

Lena Nilsson Schönnesson; Mark L. Williams; Michael W. Ross; Göran Bratt; Blair Keel

2007-01-01

389

Antidepressant Treatment and Adherence to Combination Antiretroviral Therapy among Patients with AIDS and Diagnosed Depression  

Microsoft Academic Search

Background  The prevalence of depression is elevated among HIV-infected individuals and there is evidence that depression exerts a negative\\u000a impact on HIV medication adherence.\\u000a \\u000a \\u000a \\u000a Methods  Merged HIV\\/AIDS surveillance data and Medicaid claims data from January 1996 to December 1998 were used to identify AIDS-infected\\u000a patients with diagnosed depression, and filled prescriptions were used to identify their antidepressant use, and highly active\\u000a antiretroviral

James Walkup; Wenhui Wei; Usha Sambamoorthi; Stephen Crystal

2008-01-01

390

Immune reconstitution inflammatory syndrome after highly active antiretroviral therapy: a review.  

PubMed

The use of highly active antiretroviral therapy (HAART) in the management of human immunodeficiency virus (HIV) restores immune responses against pathogens and has greatly decreased mortality. However, in about 25% to 35% of patients receiving HAART, the reconstituted immune system leads to a pathological inflammatory response, commonly known as immune reconstitution inflammatory syndrome (IRIS), which causes substantial short-term morbidity or even mortality. Although we have gleaned some knowledge on IRIS in the past few years, a number of unanswered questions remain. In this review, we discuss the definition, diagnostic criteria, pathogenesis, risk factors, clinical spectrum including oral manifestations, and management of IRIS. PMID:19758406

Tsang, C S P; Samaranayake, L P

2010-04-01

391

Computation of Cold-Start Miss Ratios  

Microsoft Academic Search

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

Malcolm C. Easton

1978-01-01

392

Automatic control system of burner starting units  

Microsoft Academic Search

In developing and introducing all-purpose automatic control systems (ACS) for generating units as thermal power stations (ThPS), assembly of the automatic control set of burner starting units for the steam generators is one of the most difficult. The urgency of development of this kind of assembly is due to increased nonuniformity of the load demands from ThPs and the increased

E. I. Astashkin; F. G. Zhirnov; M. Ya. Khesin

1975-01-01

393

Starting Science, Books One, Two and Three  

Microsoft Academic Search

Book One: 122 pp, price Ł7.50 ISBN 0 19 914235 1Book Two: 122 pp, price Ł7.50 ISBN 0 19 914241 6Book Three: 106 pp, price Ł7.50 ISBN 0 19 914374 9 Starting Science Book One This highly successful book, first published in 1985, has been so popular that it has had to be reprinted every year since! Although the new

Jim Jardine

1996-01-01

394

Getting Started with Actionscript 3.0  

Microsoft Academic Search

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

Steve Webster; Todd Yard

395

New START, Eyjafjallajökull, and Nuclear Winter  

NASA Astrophysics Data System (ADS)

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

Robock, Alan

2010-11-01

396

Alternative starting materials for industrial processes.  

PubMed

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. PMID:11607260

Mitchell, J W

1992-02-01

397

40 CFR 86.1236-85 - Engine starting and restarting.  

Code of Federal Regulations, 2010 CFR

...shall begin when the engine starts. (2) The...necessary to keep the engine running. (3) If the manufacturer's operating instructions in the owner's...do not specify a warm engine starting procedure...until it starts. (4) If the...

2010-07-01

398

40 CFR 86.136-90 - Engine starting and restarting.  

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

2014-07-01

399

Effects of HIV infection and antiretroviral therapy with ritonavir on induction of osteoclast-like cells in postmenopausal women  

Microsoft Academic Search

Summary  Ritonavir (RTV) is a commonly used antiretroviral associated with bone loss. We show that peripheral blood mononuclear cells\\u000a (PBMCs) from human immunodeficiency virus (HIV)-positive women on RTV are more likely to differentiate into osteoclast-like\\u000a cells when cultured with their own sera than PBMCs and sera from HIV? women or HIV+ on other antiretrovirals.\\u000a \\u000a \\u000a \\u000a \\u000a Introduction  RTV increases differentiation of human adherent PBMCs

M. T. Yin; R. Modarresi; E. Shane; F. Santiago; D. C. Ferris; D. J. McMahon; C. A. Zhang; S. Cremers; J. Laurence

2011-01-01

400

Biomarkers From Late Pregnancy to 6 Weeks Postpartum in HIV-Infected Women Who Continue Versus Discontinue Antiretroviral Therapy After Delivery  

PubMed Central

Background Women who use antiretroviral therapy (ART) solely for the prevention of mother-to-child transmission of HIV discontinue postpartum. We hypothesized that women discontinuing ART by 6 weeks postpartum (“discontinuers”) would have elevated postpartum inflammatory biomarker levels relative to women remaining on ART postpartum (“continuers”). Methods Data from HIV-infected pregnant women enrolled in the International Maternal Pediatric Adolescent AIDS Clinical Trials Group P1025 with CD4 counts >350 cells per cubic millimeter before initiating ART or first pregnancy CD4 counts >400 cells per cubic millimeter after starting ART and with available stored plasma samples at >20 weeks of gestation, delivery, and 6 weeks postpartum were analyzed. Plasma samples were tested for highly sensitive C-reactive protein, D-dimer, and interleukin-6. We used longitudinal linear spline regression to model biomarkers over time. Results Data from 128 women (65 continuers and 63 discontinuers) were analyzed. All biomarkers increased from late pregnancy to delivery, then decreased postpartum (slopes different from 0, P < 0.001). Continuers had a steeper decrease in log D-dimer between delivery and 6 weeks postpartum than discontinuers (P = 0.002). Conclusions In contrast to results from treatment interruption studies in adults, both ART continuers and ART discontinuers had significant decreases in the levels of D-dimer, highly sensitive C-reactive protein, or interleukin-6 postpartum. Continuation was associated with a more rapid decline in D-dimer levels compared with discontinuation. PMID:23714738

Hoffman, Risa M.; Leister, Erin; Kacanek, Deborah; Shapiro, David E.; Read, Jennifer S.; Bryson, Yvonne; Currier, Judith S.

2013-01-01

401

Higher CD27+CD8+ T Cells Percentages during Suppressive Antiretroviral Therapy Predict Greater Subsequent CD4+ T Cell Recovery in Treated HIV Infection  

PubMed Central

HIV-mediated immune dysfunction may influence CD4+ T cell recovery during suppressive antiretroviral therapy (ART). We analyzed cellular biomarkers of immunological inflammation, maturation, and senescence in HIV-infected subjects on early suppressive ART. We performed longitudinal analyses of peripheral immunological biomarkers of subjects on suppressive ART (n?=?24) from early treatment (median 6.4 months, interquartile range [IQR] 4.8–13.9 months) to 1–2 years of follow-up (median 19.8 months, IQR 18.3–24.6 months). We performed multivariate regression to determine which biomarkers were associated with and/or predictive of CD4+ T cell recovery. After adjusting for the pre-ART CD4+ T cell count, age, proximal CD4+ T cell count, and length of ART medication, the percentage of CD27+CD8+ T cells remained significantly associated with the CD4+ T cell recovery rate (??=?0.092 cells/ul/month, P?=?0.028). In HIV-infected subjects starting suppressive ART, patients with the highest percentage of CD8+ T cells expressing CD27 had the greatest rate of CD4+ T cell recovery. PMID:24391889

Seu, Lillian; Ortiz, Gabriel M.; Epling, Lorrie; Sinclair, Elizabeth; Swainson, Louise A.; Bajpai, Urmila D.; Huang, Yong; Deeks, Steven G.; Hunt, Peter W.; Martin, Jeffrey N.; McCune, Joseph M.

2013-01-01

402

The Impact of Antiretroviral Therapy on Mortality in HIV Positive People during Tuberculosis Treatment: A Systematic Review and Meta-Analysis  

PubMed Central

Objective To quantify the impact of antiretroviral therapy (ART) on mortality in HIV-positive people during tuberculosis (TB) treatment. Design We conducted a systematic literature review and meta-analysis. Studies published from 1996 through February 15, 2013, were identified by searching electronic resources (Pubmed and Embase) and conference books, manual searches of references, and expert consultation. Pooled estimates for the outcome of interest were acquired using random effects meta-analysis. Subjects The study population included individuals receiving ART before or during TB treatment. Main Outcome Measures Main outcome measures were: (i) TB-case fatality ratio (CFR), defined as the proportion of individuals dying during TB treatment and, if mortality in HIV-positive people not on ART was also reported, (ii) the relative risk of death during TB treatment by ART status. Results Twenty-one studies were included in the systematic review. Random effects pooled meta-analysis estimated the CFR between 8% and 14% (pooled estimate 11%). Among HIV-positive TB cases, those receiving ART had a reduction in mortality during TB treatment of between 44% and 71% (RR?=?0.42, 95%CI: 0.29–0.56). Conclusion Starting ART before or during TB therapy reduces the risk of death during TB treatment by around three-fifths in clinical settings. National programmes should continue to expand coverage of ART for HIV positive in order to control the dual epidemic. PMID:25391135

Odone, Anna; Amadasi, Silvia; White, Richard G.; Cohen, Theodore; Grant, Alison D.; Houben, Rein M. G. J.

2014-01-01

403

Risk of HIV transmission from patients on antiretroviral therapy: A position statement from the Public Health Agency of Sweden and the Swedish Reference Group for Antiviral Therapy  

PubMed Central

The modern medical treatment of HIV with antiretroviral therapy (ART) has drastically reduced the morbidity and mortality in patients infected with this virus. ART has also been shown to reduce the transmission risk from individual patients as well as the spread of the infection at the population level. This position statement from the Public Health Agency of Sweden and the Swedish Reference Group for Antiviral Therapy is based on a workshop organized in the fall of 2012. It summarizes the latest research and knowledge on the risk of HIV transmission from patients on ART, with a focus on the risk of sexual transmission. The risk of transmission via shared injection equipment among intravenous drug users is also examined, as is the risk of mother-to-child transmission. Based on current knowledge, the risk of transmission through vaginal or anal intercourse involving the use of a condom has been judged to be minimal, provided that the person infected with HIV fulfils the criteria for effective ART. This probably also applies to unprotected intercourse, provided that no other sexually transmitted infections are present, although it is not currently possible to fully support this conclusion with direct scientific evidence. ART is judged to markedly reduce the risk of blood-borne transmission between people who share injection equipment. Finally, the risk of transmission from mother to child is very low, provided that ART is started well in advance of delivery. PMID:25073537

Berglund, Torsten; Gisslén, Magnus; Gröön, Peter; Sönnerborg, Anders; Tegnell, Anders; Alexandersson, Anders; Berggren, Ingela; Blaxhult, Anders; Brytting, Maria; Carlander, Christina; Carlson, Johan; Flamholc, Leo; Follin, Per; Haggar, Axana; Hansdotter, Frida; Josephson, Filip; Karlström, Olle; Liljeros, Fredrik; Navér, Lars; Pettersson, Karin; Johansson, Veronica Svedhem; Svennerholm, Bo; Tunbäck, Petra; Widgren, Katarina

2014-01-01

404

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

...Parent participation and transition of children into Head Start and from Head Start to...HUMAN SERVICES THE ADMINISTRATION FOR CHILDREN, YOUTH AND FAMILIES, HEAD START PROGRAM...PERFORMANCE STANDARDS ON SERVICES FOR CHILDREN WITH DISABILITIES Parent...

2014-10-01

405

Failure of daily tenofovir to prevent HIV transmission or the establishment of a significant viral reservoir despite continued antiretroviral therapy  

PubMed Central

Introduction Truvada is licenced for HIV-1 prevention in the USA and is available in the private sector. Tenofovir performed as well as Truvada in the PARTNERS PrEP study and is used as HIV pre-exposure prophylaxis (PreP) in some settings. The clinical efficacy of Tenofovir for PrEP outside a clinical trial is unknown. Antiretroviral therapy (ART) at acute HIV-1 infection (AHI) limits the size of the reservoir, optimizing the chance of maintaining viral control off therapy. As such ART at acute HIV infection is proposed to offer a functional cure in a minority of subjects. We present two cases where Tenofovir PrEP failed to prevent HIV acquisition and failed to limit viral reservoir. Materials and Methods Two individuals receiving tenofovir monotherapy for Hepatitis B monoinfection were diagnosed with AHI as defined by a negative HIV antibody test within three months of a positive HIV test following unsafe sex with casual male partners. In-depth histories were taken. Viral genotypes and Tenofovir drug levels were measured from samples taken as close to HIV seroconversion as possible and subsequent samples were analyzed for proviral Total HIV-1 DNA by qPCR. Results Patient A had received tenofovir for the preceding six years and always maintained an undetectable Hepatitis B viral load with no concerns about adherence. Two weeks preceding the positive HIV antibody test, he experienced mild symptoms (fever, pharyngitis) of HIV seroconversion. HIV status was confirmed by a repeat fourth generation HIV antibody test and by Western Blot and an HIV viral load was undetectable. Tenofovir trough level at HIV diagnosis was within normal limits. The regimen was intensified to Eviplera and a total HIV-1 DNA was 1381 copies/million CD4 T cells. Patient B received four regimens for hepatitis B treatment before starting tenofovir monotherapy in 2011 and subsequently maintained an undetectable hepatitis B viral load. After three years of tenofovir monotherapy he developed a severe symptomatic seroconversion illness and tested HIV antibody positive. The baseline HIV viral load was 103,306 copies/mL. The regimen was intensified and total HIV-1 DNA was 2746 copies/million CD4 T cells. Conclusions Further investigation into the efficacy of tenofovir for PrEP outside a clinical trial is required. ART at AHI does not always lead to a low viral reservoir. To explore the possibility of replication incompetent virus, viral outgrowth assays are underway. PMID:25397477

Davies, Olubanke; Alexander, Hannah; Robinson, Nicola; Pace, Matthew; Brady, Michael; Frater, John; Fox, Julie

2014-01-01

406

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

PubMed Central

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

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

2014-01-01

407

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

PubMed Central

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

Yoganathan, Katie; Brown, David; Yoganathan, Kathir

2012-01-01

408

CLEFT PALATE IN HIV-EXPOSED NEWBORNS OF MOTHERS ON HIGHLY ACTIVE ANTIRETROVIRAL THERAPY  

PubMed Central

Aims Cleft lip/palate, though rare, is the commonest head and neck congenital malformation. Both genetic and environmental factors have been implicated in the aetiopathogenesis but the role of in-utero exposure to human immunodeficiency virus (HIV) and highly active antiretroviral therapy (HAART) is still being investigated. This short communication reports the occurrence of cleft palate in three newborns exposed in-utero to HIV and HAART. Material and methods This is a case series of HIV-exposed newborns observed to have cleft palate among a larger cohort of HIV-exposed and unexposed newborns in a study evaluating the effect of HIV infection and HAART on newborn hearing. The Risk Ratio (RR) was calculated to detect a potential association between in-utero exposure to Efavirenz containing ART and cleft palate. Results Three HIV-exposed newborns with cleft palate were identified during hearing screening performed on 126 HIV-exposed and 121 HIV unexposed newborns. Two had exposure to tenofovir+lamivudine+efavirenz (TDF+3TC+EFV) while the third had exposure to zidovudine+lamivudine+nevirapine (ZDV+3TC+NVP) during the first trimester. There was no statistically significant association between presence of cleft palate and exposure to an EFV containing HAART regimen (p=0.07, RR=10.95 [0.94-126.84]). Conclusions This communication highlights the possible aetiologic role of HAART in cleft palate, the need for further prospective follow-up studies and establishment of antiretroviral pregnancy, birth and neonatal registries.

James, Ayotunde; Oluwatosin, Babatunde; Njideka, Georgina; Babafemi; Benjamin, Onyekwere George; Olufemi, David; Leo, Robert; Folorunso, Isaac; Phylis; Olusina, Olusegun

2014-01-01

409

Polymeric Nanoparticles Containing Combination Antiretroviral Drugs for HIV Type 1 Treatment  

PubMed Central

Abstract The use of combination antiretroviral nanoparticles (cART NPs) was investigated as a novel treatment approach for the inhibition of HIV-1 replication. We developed nanoparticles of biodegradable polymer, poly-(dl-lactide-co-glycolic acid; PLGA) containing efavirenz (EFV) and boosted lopinavir (lopinavir/ritonavir; LPV/r) by a high-pressure homogenization method. The method resulted in >79% drug entrapment efficiency for each of the three drugs. The average size of cART NPs was 138.3±55.4?nm as measured by dynamic light scanning, confirmed by scanning electron microscopy (SEM) with an average surface charge of ?13.7±4.5. Lissamine-rhodamine-labeled fluorescent PLGA NPs exhibited efficient uptake in nonimmune (HeLa cells) and immune (H9 T cells) cells as measured by confocal microscopy. Cells treated with cART NPs resulted in minimal loss of cell viability over 28 days. Subcellular fractionation studies demonstrated that HIV-1-infected H9 monocytic cells treated with cART NPs contained significantly (p<0.05) higher nuclear, cytoskeleton, and membrane antiretroviral drug levels compared to cells treated with drug solutions alone. Finally, cART NPs efficiently inhibited HIV-1 infection and transduction. The IC50 for each of the three drugs in the cART NPs was <31?nM. These experiments demonstrate the efficacy of a novel PLGA NPs formulation for the delivery of cART to inhibit HIV-1 replication. PMID:23289671

Shibata, Annemarie; McMullen, Emily; Pham, Alex; Belshan, Michael; Sanford, Bridget; Zhou, You; Goede, Michael; Date, Abjijit A.

2013-01-01

410

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

PubMed Central

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

Wilson, Eleanor M.P.; Sereti, Irini

2013-01-01

411

Effectiveness and Safety of Concurrent Use of First-Line Antiretroviral and Antituberculous Drugs in Rwanda  

PubMed Central

Background. Overlapping toxicity between drugs used for HIV and TB could complicate the management of HIV/TB coinfected patients, particularly those carrying multiple opportunistic infections. This study aimed to evaluate the clinical outcomes and adverse drug events in HIV patients managed with first-line antiretroviral and first-line anti-TB drugs. Methods. This is a retrospective study utilizing medical dossiers from single-HIV infected and HIV/TB coinfected patients already initiated on ART. Predictors of outcomes included changes in CD4 cells/mm3, body weight, physical improvement, death rate, and adverse drug reactions. Results. Records from 60 HIV patients and 60 HIV/TB patients aged between 20 and 58 years showed that all clinical indicators of effectiveness were better in single-HIV infected than in HIV/TB coinfected patients: higher CD4 cell counts, better physical improvement, and low prevalence of adverse drug events. The most frequently prescribed regimen was TDF/3TC/EFV+RHZE. The mortality rate was 20% in HIV/TB patients compared to 8.3% in the single-HIV group. Conclusion. Treatment regimens applied are efficient in controlling the progression of the infection. However, attention should be paid to adjust dosing when combining nonnucleoside antiretrovirals (EFV and NVR) with anti-TB drugs to minimize the risk of death by drug intoxication. PMID:24624142

Kadima, Justin Ntokamunda; Mukanyangezi, Marie Françoise; Uwizeye, Claude Bernard

2014-01-01

412

Pharmacotoxicology of monocyte-macrophage nanoformulated antiretroviral drug uptake and carriage  

PubMed Central

Limitations inherent to antiretroviral therapy (ART) in its pharmacokinetic properties remain despite over 15 years of broad use. Our laboratory has pioneered a means to improve ART delivery through monocyte-macrophage carriage of nanoformulated drug-encapsulated particles (nanoART). To this end, our prior works sought to optimize nanoART size, structure, and physical properties for cell uptake and antiretroviral activities. To test the functional consequences of indinavir, ritonavir, and efavirenz formulations we investigated relationships between human monocyte and macrophage cytotoxicities and nanoART dose, size, surfactant, and preparation. Wet-milled particles were significantly more cytotoxic to monocytes-macrophages than those prepared by homogenization; with concurrent induction of tumor necrosis factor-alpha. Interestingly, pure suspensions of indinavir and ritonavir at 0.5mM, and efavirenz at 0.1mM and 0.5mM also proved cytotoxic. Individual surfactants and formulated fluconazole neither affected cell function or viability. Although nanoART did not alter brain tight junction proteins ZO-2 and occludin, 0.5mM ritonavir formulations did alter brain transendothelial electric resistance. These results underscore the importance of evaluating the physicochemical and functional properties of nanoART before human evaluations. PMID:21175298

Bressani, Rafael F.; Nowacek, Ari S.; Singh, Sangya; Balkundi, Shantanu; Rabinow, Barrett; McMillan, JoEllyn; Gendelman, Howard E.; Kanmogne, Georgette D.

2013-01-01

413

The financial and service implications of splitting fixed-dose antiretroviral drugs - a case study.  

PubMed

In 2010/2011, regional commissioners withdrew payment for the fixed-dose combination Combivir, forcing a switch to component drugs. This was deemed clinically acceptable and annual savings of Ł44?k expected. We estimated the true costs of switching and examined patient outcomes. Information for 46 patients using Combivir was extracted from case notes for each clinical contact in the 12 months pre- and post-switch (clinician seen, tests, antiretrovirals). Post-switch care costs Ł93/patient more annually versus pre-switch (95% CI Ł424 to Ł609), yielding Ł4278/year more post-switch for all patients. Drug and pathology costs were more expensive post-switch and extra clinical visits required. None of these results were statistically significant. Forty-two per cent of patients switched directly or in the subsequent year to an alternative fixed-dose combination rather than generics. Costs in this group were significantly higher post-switch driven by drug cost. Six patients (13%) reported problems with the switch including confusion around dosing and new side effects. As less-expensive generic antiretroviral drugs become available, it may appear cheaper to switch from fixed-dose combinations to component drugs. However, the additional clinical costs involved may outweigh the initial cost savings of the drugs and switching may cause confusion for some patients, risking loss of adherence. PMID:24700200

Taylor, R; Carlin, E; Sadique, Z; Ahmed, I; Adams, Ej

2015-02-01

414

Vulnerability and non-adherence to antiretroviral therapy among HIV patients, Minas Gerais State, Brazil.  

PubMed

The aim of the present study was to describe vulnerability profiles and to verify their association with non-adherence to antiretroviral therapy (ART) among 295 HIV-patients receiving their first prescription in two public-referral centers in Minas Gerais States, Brazil. The cumulative incidence of non-adherence was 36.9%. Three pure vulnerability profiles (lower, medium and higher) were identified based on the Grade of Membership method (GoM). Pure type patients of the "higher vulnerability" profile had, when compared to the overall sample, an increased probability of being younger, not understanding the need of ART, having a personal reason to be HIV-tested, not disclosing their HIV status, having more than one (non-regular) sexual partner, reporting use of alcohol, tobacco and illicit drugs, and having sex among men. Non-adherence to ART was statistically associated (p < 0.001) with this profile. Also, the heterogeneity of the sample was found to be high, since over 40% were mixed type. The implications are that health staff should be trained to develop strategies for incorporating risk-reduction interventions, bearing in mind the three dimensions of vulnerability and the diversity of those patients initiating antiretroviral therapy. PMID:19009140

Bonolo, Palmira de Fátima; Machado, Carla Jorge; César, Cibele Comini; Ceccato, Maria das Graças Braga; Guimarăes, Mark Drew Crosland

2008-11-01

415

Human Breast Milk and Antiretrovirals Dramatically Reduce Oral HIV-1 Transmission in BLT Humanized Mice  

PubMed Central

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

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

2012-01-01

416

Understanding and mitigating HIV-related resource-based stigma in the era of antiretroviral therapy.  

PubMed

The perception in low-resource settings that investment of resources in people living with HIV (PLHIV) is wasted because AIDS is both an incurable and deadly disease is known as resource-based stigma. In this paper, we draw on in-depth interviews (IDI), focus group discussions (FGD), and key informant interviews (KII) with 77 HIV-positive microfinance participants and nongovernmental organization leaders to examine resource-based stigma in the context of increased access to antiretroviral therapy (ART) at an individual, household, and community level in Côte d'Ivoire. The purpose of this exploratory paper is to examine: (1) resource-based stigmatization in the era of ART and (2) the relationship among microfinance, a poverty-reduction intervention, and HIV stigmatization. The frequency with which resource-based stigma was discussed by respondents suggests that it is an important component of HIV-related stigma in this setting. It affected PLHIV's access to material as well as social resources, leading to economic discrimination and social devaluation. Participation in village savings and loans groups, however, mitigated resource-based HIV stigma, suggesting that in the era of increased access to antiretroviral therapy, economic programs should be considered as one possible HIV stigma-reduction intervention. PMID:23394104

Holmes, Kathleen; Winskell, Kate

2013-01-01

417

Mortality Associated With Discordant Responses to Antiretroviral Therapy in Resource-Constrained Settings  

PubMed Central

Objectives We assessed mortality associated with immunologic and virologic patterns of response at 6 months of highly active antiretroviral therapy (HAART) in HIV-infected individuals from resource-limited countries in Africa and South America. Methods Patients who initiated HAART between 1996 and 2007, were aged 16 years or older, and had at least one measurement (HIV-1 RNA plasma viral load or CD4 cell count) at 6 months of therapy (3 to 9 month window) were included. Therapy response was categorized as complete, discordant (virologic- or immunologic-only), and absent. Associations between 6-month response to therapy and all-cause mortality were assessed by Cox proportional hazards regression. Robust standard errors were calculated to account for intra-site correlation. Results A total of 7,160 patients, corresponding to 15,107 person-years, was analyzed. In multivariable analysis adjusted for age at HAART initiation, baseline clinical stage and CD4 cell count, year of HAART initiation, clinic, occurrence of an AIDS defining condition within the first 6 months of treatment, discordant and absent responses were associated with increased risk of death. Conclusions Similar to reports from high-income countries, discordant immunologic and virologic responses were associated with intermediate risk of death compared with complete and no response in this large cohort of HIV-1 patients from resource-limited countries. Our results support a recommendation for wider availability of plasma viral load testing to monitor antiretroviral therapy in these settings. PMID:20035163

2009-01-01

418

Potential implication of residual viremia in patients on effective antiretroviral therapy.  

PubMed

Abstract The current antiretroviral therapy (ART) has suppressed viremia to below the limit of detection of clinical viral load assays; however, it cannot eliminate viremia completely in the body even after prolonged treatment. Plasma HIV-1 loads persist at extremely low levels below the clinical detection limit. This low-level viremia (termed "residual viremia") cannot be abolished in most patients, even after the addition of a new class of drug, i.e., viral integrase inhibitor, to the combined antiretroviral regimens. Neither the cellular source nor the clinical significance of this residual viremia in patients on ART remains fully clear at present. Since residual plasma viruses generally do not evolve with time in the presence of effective ART, one prediction is that these viruses are persistently released at low levels from one or more stable but yet unknown HIV-1 reservoirs in the body during therapy. This review attempts to emphasize the source of residual viremia as another important reservoir (namely, "active reservoir") distinct from the well-known latent HIV-1 reservoir in the body, and why its elimination should be a priority in the effort for HIV-1 eradication. PMID:25428885

Sahu, Gautam K

2015-01-01

419

High virologic response rate after second-line boosted protease inhibitor-based antiretroviral therapy regimens in children from a resource limited setting  

PubMed Central

Background Limited data exist for the efficacy of second-line antiretroviral therapy among children in resource limited settings. We assessed the virologic response to protease inhibitor-based ART after failing first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens. Methods A retrospective chart review was conducted at 8 Thai sites of children who switched to PI –based regimens due to failure of NNRTI –based regimens. Primary endpoints were HIV RNA?starting PI-based regimens of 9.1?years for age, 10% for CD4%, and 4.8 log10 copies/ml for HIV RNA were included; 104 (41%) received a single ritonavir-boosted PI (sbPI) with 2 NRTIs and 137 (59%) received double-boosted PI (dbPI) with/without NRTIs based on physician discretion. SbPI children had higher baseline CD4 (17% vs. 6%, p?antiretroviral drugs is needed. PMID:22709957

2012-01-01

420

Utility of routine viral load, CD4 cell count, and clinical monitoring among adults with HIV receiving antiretroviral therapy in Uganda: randomised trial  

PubMed Central

Objective To evaluate the use of routine laboratory monitoring in terms of clinical outcomes among patients receiving antiretroviral therapy (ART) in Uganda. Design Randomised clinical trial Setting A home based ART programme in rural Uganda. Participants All participants were people with HIV who were members of the AIDS Support Organisation. Participants had CD4 cell counts <250 cells × 106/L or World Health Organization stage 3 or 4 disease. Interventions Participants were randomised to one of three different monitoring arms: a viral load arm (clinical monitoring, quarterly CD4 counts, and viral load measurements), CD4 arm (clinical monitoring and CD4 counts), or clinical arm (clinical monitoring alone). Main outcome measures Serious morbidity (newly diagnosed AIDS defining illness) and mortality. Results 1094 participants started ART; median CD4 count at baseline was 129 cells × 106/L. Median follow-up was three years. In total, 126 participants died (12%), 148 (14%) experienced new AIDS defining illnesses, and 61(6%) experienced virological failure, defined as two consecutive viral loads >500 copies/mL occurring more than three months after the start of ART. After adjustment for age, sex, baseline CD4 count, viral load, and body mass index, the rate of new AIDS defining events or death was higher in the clinical arm than the viral load arm (adjusted hazard ratio 1.83, P=0.002) or the CD4 arm (1.49, P=0.032). There was no significant difference between the CD4 arm and the viral load arm (1.23, P=0.31). Conclusion In patients receiving ART for HIV infection in Uganda, routine laboratory monitoring is associated with improved health and survival compared with clinical monitoring alone. Trial registration Clinical Trials NCT00119093. PMID:22074711

2011-01-01

421

Has the Rate of CD4 Cell Count Decline before Initiation of Antiretroviral Therapy Changed over the Course of the Dutch HIV Epidemic among MSM?  

PubMed Central

Introduction Studies suggest that the HIV-1 epidemic in the Netherlands may have become more virulent, leading to faster disease progression if untreated. Analysis of CD4 cell count decline before antiretroviral therapy (ART) initiation, a surrogate marker for disease progression, may be hampered by informative censoring as ART initiation is more likely with a steeper CD4 cell count decline. Methods Development of CD4 cell count from 9 to 48 months after seroconversion was analyzed using a mixed-effects model and 2 models that jointly modeled CD4 cell counts and time to censoring event (start ART, <100 CD4 cells/mm3, or AIDS) among therapy-naďve MSM HIV-1 seroconverters in the Netherlands. These models make different assumptions about the censoring process. Results All 3 models estimated lower median CD4 cell counts 9 months after seroconversion in later calendar years (623, 582, and 541 cells/mm3 for 1984–1995 [n?=?111], 1996–2002 [n?=?139], and 2003–2007 seroconverters [n?=?356], respectively, shared-parameter model). Only the 2 joint-models found a trend for a steeper decline of CD4 cell counts with seroconversion in later calendar years (overall p-values 0.002 and 0.06 for the pattern-mixture and the shared-parameter model, respectively). In the shared-parameter model the median decline from 9 to 48 months was 276 cellsmm3 for 1984–1995 seroconverters and 308 cells/mm3 for 2003–2007 seroconverters (difference in slope, p?=?0.045). Conclusion Mixed-effects models underestimate the CD4 cell decline prior to starting ART. Joint-models suggest that CD4 cell count declines more rapidly in patients infected between 2003 and 2007 compared to patients infected before 1996. PMID:23724048

Gras, Luuk; Geskus, Ronald B.; Jurriaans, Suzanne; Bakker, Margreet; van Sighem, Ard; Bezemer, Daniela; Fraser, Christophe; Prins, Jan M.; Berkhout, Ben

2013-01-01

422

Measuring adherence to antiretroviral treatment in resource-poor settings: The feasibility of collecting routine data for key indicators  

Microsoft Academic Search

BACKGROUND: An East African survey showed that among the few health facilities that measured adherence to antiretroviral therapy, practices and definitions varied widely. We evaluated the feasibility of collecting routine data to standardize adherence measurement using a draft set of indicators. METHODS: Targeting 20 facilities each in Ethiopia, Kenya, Rwanda, and Uganda, in each facility we interviewed up to 30

John C Chalker; Tenaw Andualem; Lillian N Gitau; Joseph Ntaganira; Celestino Obua; Hailu Tadeg; Paul Waako; Dennis Ross-Degnan

2010-01-01

423

Tobacco use and its determinants in HIV-infected patients on antiretroviral therapy in West African countries  

E-print Network

tobacco and cannabis consumption. Regular smokers were defined as present smokers who smoked >1 cigarette cigarette smoking and tuberculosis in HIV- infected patients, a major public health issue in this part Antiretroviral therapy (HAART), the pattern of AIDS-defining and non-AIDS defining disease conditions has evolved

Paris-Sud XI, Université de

424

Use of traditional medicine by HIV-infected individuals in South Africa in the era of antiretroviral therapy  

Microsoft Academic Search

As antiretroviral therapy (ART) becomes more available in African countries, the potential for interaction with traditional medicines becomes more important. We carried out a cross-sectional survey among individuals with moderate or advanced HIV disease attending a workplace clinic providing ART in South Africa to determine prevalence of traditional medicine use, source, recommended products and costs. Among 44 clinic attendees (100%

Dale A. Babb; Lindiwe Pemba; Pule Seatlanyane; Salome Charalambous; Gavin J. Churchyard; Alison D. Grant

2007-01-01

425

Genetic Characterization of Rebounding Human Immunodeficiency Virus Type 1 in Plasma during Multiple Interruptions of Highly Active Antiretroviral Therapy  

Microsoft Academic Search

Various strategies of interrupting highly active antiretroviral therapy (HAART) are being investigated for the treatment of human immunodeficiency virus (HIV) infection. Interruptions of greater than 2 weeks frequently result in rebound of plasma HIV RNA. In order to discern changes in the viral population that might occur during cycles of treatment interruption, we evaluated the homology of HIV-1 envelope gene

Mark Dybul; Marybeth Daucher; Mark A. Jensen; Claire W. Hallahan; Tae-Wook Chun; Michael Belson; Bertha Hidalgo; David C. Nickle; Christian Yoder; Julia A. Metcalf; Richard T. Davey; Linda Ehler; Diane Kress-Rock; Elizabeth Nies-Kraske; Shuying Liu; James I. Mullins; Anthony S. Fauci

2003-01-01

426

Generic and low dose antiretroviral therapy in adults and children: implication for scaling up treatment in resource limited settings  

Microsoft Academic Search

Although access to antiretroviral therapy (ART) for the treatment of HIV has increased during the last decade, many patients are still in need of treatment. With limited funds to provide ART to millions of patients worldwide, there is a need for alternative ways to scale up ART in resource limited settings. This review provides an overview of pharmacokinetic, safety and

Reshmie Ramautarsing; Jintanat Ananworanich

2010-01-01

427

Self-reported adherence to antiretroviral medications among participants in HIV clinical trials: The AACTG Adherence Instruments  

Microsoft Academic Search

This paper describes the AACTG Adherence Instruments, which are comprised of two self-report questionnaires for use in clinical trials conducted by the Adult AIDS Clinical Trials Group (AACTG). The questionnaires were administered to 75 patients at ten AACTG sites in the USA. All patients were taking combination antiretroviral therapy (ART), including at least one protease inhibitor. Eleven per cent of

M. A. Chesney; J. R. Ickovics; D. B. Chambers; A. L. Gifford; J. Neidig; B. Zwickl; A. W. Wu

2000-01-01

428

Non-AIDS defining deaths and immunodeficiency in the era of combination antiretroviral therapy. CASCADE, 1996-2006.  

E-print Network

1 Title: Non-AIDS defining deaths and immunodeficiency in the era of combination antiretroviral therapy. CASCADE, 1996-2006. (102 characters) Running head: Non-AIDS causes of death and immunodeficiency Epidemiologia, Rome, Italy. inserm-00388946,version1-10Jan2012 Author manuscript, published in "AIDS 2009

Paris-Sud XI, Université de

429

Factors influencing adherence to anti-retroviral treatment in children with human immunodeficiency virus in South India – a qualitative study  

Microsoft Academic Search

The aim of the study was to gain a deeper understanding of the factors that influence adherence to Anti-Retroviral Treatment (ART) in a paediatric population in South India. Semi-structured interviews, guided by a questionnaire based on literature review, were undertaken with 14 primary caregivers of children with Human Immunodeficiency Virus (HIV) on ART focussing on the factors influencing adherence and

Karthikeyan Paranthaman; Nagalingeswaran Kumarasamy; Devaleenol Bella; Premila Webster

2009-01-01

430

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

Technology Transfer Automated Retrieval System (TEKTRAN)

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

431

Leading articles HIV protease inhibitors: antiretroviral agents with anti-inflammatory, anti-angiogenic and anti-tumour activity  

Microsoft Academic Search

Despite mild toxicity and adverse effects, human immuno- deficiency virus (HIV) protease inhibitors (PIs), used in combination with reverse transcriptase nucleoside inhibitors (NRTIs), have turned AIDS into a chronic, manageable disease. Such combination therapy, known as highly active antiretroviral therapy (HAART), efficiently suppresses HIV replication leading to immune restoration in HIV-infected patients. HIV PIs act by blocking the HIV aspartyl

Paolo Monini; Cecilia Sgadari; Giovanni Barillari; Barbara Ensoli

432

The other genome: a systematic review of studies of mitochondrial DNA haplogroups and outcomes of HIV infection and antiretroviral therapy.  

PubMed

Mitochondrial toxicity is implicated in some treatment-limiting antiretroviral therapy complications, and reports of mitochondrial dysfunction in untreated HIV infection suggest antiretroviral therapy independent effects of HIV. Several studies have explored associations between mtDNA haplogroups (patterns of mtDNA polymorphisms) and outcomes of HIV infection and/or antiretroviral therapy, but findings have been inconsistent. We systematically reviewed published studies examining mtDNA haplogroups in HIV-infected persons to summarize reported outcome associations, and to highlight potential future research directions. We identified 21 articles published from 2005-2013. Multiple different phenotypes were studied; most were antiretroviral therapy associated metabolic outcomes (e.g. lipodystrophy, insulin resistance, and dyslipidemia). Haplogroup H was associated with the most outcomes, including AIDS progression, CD4 T-cell recovery, cirrhosis (in hepatitis C coinfection), and metabolic outcomes. This review is the first to focus on the emerging area of mtDNA haplogroups in HIV, and summarizes the published literature on associations between mtDNA haplogroups and clinical outcomes in populations of European and African descent. Several reported associations require replication and ideally biological verification before definitive conclusions can be drawn, but research in this area has the potential to explain outcome disparities and impact clinical management of patients. PMID:24322381

Hart, Anna B; Samuels, David C; Hulgan, Todd

2013-01-01

433

High-Performance Liquid Chromatography Methods to Simultaneous Determination of AntiRetroviral Drugs in Biological Matrices  

Microsoft Academic Search

Acquired immune deficiency syndrome or acquired immunodeficiency syndrome (AIDS or Aids) is symptoms and infections resulting from the damage to the human immune system. The purpose of this paper is to review the literature for high performance liquid chromatography methods to simultaneous determination of anti-retroviral drugs in biological matrices covering the articles mainly from 2001 to 2009. The biological matrix

Cafer Saka

2009-01-01

434

Treatment Effect and Drug-Resistant Mutations in Chinese AIDS Patients Switching to Second-Line Antiretroviral Therapy  

PubMed Central

This study aimed to investigate treatment effect, drug resistance changes, and their influencing factors in Chinese AIDS patients after switching to second-line antiretroviral therapy, and thus provide important information for the scale-up of second-line antiretroviral treatment in China. In Weishi county of Henan province, where second-line antiretroviral therapy was introduced early in China, 195 AIDS patients were enrolled, of which 127 patients met the switching criterion and 68 patients volunteered to switch drugs without meeting the switching criterion. CD4 cell count, viral load and in-house PCR genotyping for drug resistance were measured for all 195 subjects before drug switch, as well as 6 and 12 months after drug switch. Extensive secondary mutations to the protease inhibitor were observed, which suggested that long-term drug resistance surveillance is necessary for patients switching to second-line antiretroviral therapy. Multidrug resistance and cross-resistance were extensive in Chinese patients that experienced first-line treatment failure. Patients need timely CD4 count, viral load, and drug resistance monitoring in order to switch to second-line therapy under conditions of relatively good immunity and low viral duplication levels. PMID:25330204

Shang, Mingquan; Yang, Weiwei; Chen, Junli; Wang, Zhe

2014-01-01

435

Head Start Goes to School: 1995-96 Evaluation Report.  

ERIC Educational Resources Information Center

The Arizona Head Start--Public School Transition Project is 1 of 31 demonstration projects designed to test whether advances by Head Start children could be maintained by continuing Head Start-type services into kindergarten through the third grade, and to identify, develop, and implement transition practices to bridge the gap between Head Start

Mulholland, Lori; Shaw, Kathleen; Heffernon, Rick; Stafford, Mary E.

436

Beyond the Blueprint: Directions for Research on Head Start's Families.  

ERIC Educational Resources Information Center

Although public acceptance of Head Start is high, public understanding of what the program does remains limited. Studies of Head Start to date have been insufficient in quantity and scope. In November 1994, the Roundtable on Head Start Research began a series of discussions of new directions for Head Start research. The roundtable looked at…

Phillips, Deborah A., Ed.; Cabrera, Natasha J., Ed.

437

Impact on life expectancy of HIV-1 positive individuals of CD4+ cell count and viral load response to antiretroviral therapy  

PubMed Central

Objective: The objective of this study is to estimate life expectancies of HIV-positive patients conditional on response to antiretroviral therapy (ART). Methods: Patients aged more than 20 years who started ART during 2000–2010 (excluding IDU) in HIV clinics contributing to the UK CHIC Study were followed for mortality until 2012. We determined the latest CD4+ cell count and viral load before ART and in each of years 1–5 of ART. For each duration of ART, life tables based on estimated mortality rates by sex, age, latest CD4+ cell count and viral suppression (HIV-1 RNA <400?copies/ml), were used to estimate expected age at death for ages 20–85 years. Results: Of 21?388 patients who started ART, 961 (4.5%) died during 110?697 person-years. At start of ART, expected age at death [95% confidence interval (CI)] of 35-year-old men with CD4+ cell count less than 200, 200–349, at least 350?cells/?l was 71 (68–73), 78 (74–82) and 77 (72–81) years, respectively, compared with 78 years for men in the general UK population. Thirty-five-year-old men who increased their CD4+ cell count in the first year of ART from less than 200 to 200–349 or at least 350?cells/?l and achieved viral suppression gained 7 and 10 years, respectively. After 5 years on ART, expected age at death of 35-year-old men varied from 54 (48–61) (CD4+ cell count <200?cells/?l and no viral suppression) to 80 (76–83) years (CD4+ cell count ?350?cells/?l and viral suppression). Conclusion: Successfully treated HIV-positive individuals have a normal life expectancy. Patients who started ART with a low CD4+ cell count significantly improve their life expectancy if they have a good CD4+ cell count response and undetectable viral load. PMID:24556869

May, Margaret T.; Gompels, Mark; Delpech, Valerie; Porter, Kholoud; Orkin, Chloe; Kegg, Stephen; Hay, Phillip; Johnson, Margaret; Palfreeman, Adrian; Gilson, Richard; Chadwick, David; Martin, Fabiola; Hill, Teresa; Walsh, John; Post, Frank; Fisher, Martin; Ainsworth, Jonathan; Jose, Sophie; Leen, Clifford; Nelson, Mark; Anderson, Jane; Sabin, Caroline

2014-01-01