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1

When to start antiretroviral therapy.  

PubMed

The question of when to initiate antiretroviral therapy has been a central controversy in HIV management for more than 15 years, yet there are limited data from randomized controlled trials addressing it. A major obstacle to performing such a study is the need for large numbers of asymptomatic, antiretroviral therapy-naive individuals observed over many years beginning from when their CD4+ cell counts are above 500/mm3. Observational cohort studies with substantial person-years of follow-up have informed this debate in the absence of randomized trials. Emerging evidence regarding the damage caused by untreated HIV infection-related inflammation and immune activation at all stages of disease, and the benefits of modern antiretroviral therapy in preventing both AIDS- and non-AIDS-related morbidity and mortality has supported a return to starting treatment early. The NA-ACCORD (North American AIDS Cohort Collaboration on Research and Design) study compared long-term outcomes of immediate versus deferred therapy at 2 CD4+ cell count thresholds. Results showed a 94% increased risk of all-cause mortality when antiretroviral therapy was deferred at CD4+ cell counts greater than 500/mm3. This article summarizes presentations made by Mari M. Kitahata, MD, MPH, at the International AIDS Society-USA continuing medical education programs held in November 2009 in New York City and May 2010 in San Francisco. The original presentations are available as Webcasts at www.iasusa.org. PMID:20921578

Kitahata, Mari M

2010-01-01

2

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 ...

3

When to start antiretroviral therapy: as soon as possible  

PubMed Central

Background The debate regarding ‘When to Startantiretroviral therapy has raged since the introduction of zidovudine in 1987. Based on the entry criteria for the original Burroughs Wellcome 002 study, the field has been anchored to CD4 cell counts as the prime metric to indicate treatment initiation for asymptomatic individuals infected with Human Immunodeficiency Virus. The pendulum has swung back and forth based mostly on the relative efficacy, toxicity and convenience of available regimens. Discussion In today’s world, several factors have converged that compel us to initiate therapy as soon as possible: 1) The biology of viral replication (1 to 10 billion viruses per day) strongly suggests that we should be starting early. 2) Resultant inflammation from unchecked replication is associated with earlier onset of multiple co-morbid conditions. 3) The medications available today are more efficacious and less toxic than years past. 4) Clinical trials have demonstrated benefits for all but the highest CD4 strata (>500 cells/?l). 5) Some cohort studies have demonstrated the clear benefit of antiretroviral therapy at any CD4 count and no cohort studies have demonstrated that early therapy is more detrimental than late therapy at the population level. 6) In addition to the demonstrated and inferred benefits to the individual patient, we now have evidence of a Public Health benefit from earlier intervention: treatment is prevention. Summary From a practical, common sense perspective we are talking about life-long therapy. Whether we start at a CD4 count of 732 cells/?l or 493 cells/?l, the patient will be on therapy for over 40 to 50 years. There does not seem to be much benefit in waiting and there likely is significant long-term harm. Do not wait. Treat early. The counter-argument to this debate topic can be freely accessed here: http://www.biomedcentral.com/1741-7015/11/148.

2013-01-01

4

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.

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

2013-01-01

5

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.

Rodriguez, Monica; Flores, Paul; Ahumada, Victor; Vazquez-Vazquez, Lorena; Alvarado-de la Barrera, Claudia; Reyes-Teran, Gustavo

2012-01-01

6

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

PubMed Central

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

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

2012-01-01

7

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

Microsoft Academic Search

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

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

2009-01-01

8

Life Expectancies of South African Adults Starting Antiretroviral Treatment: Collaborative Analysis of Cohort Studies  

PubMed Central

Background Few estimates exist of the life expectancy of HIV-positive adults receiving antiretroviral treatment (ART) in low- and middle-income countries. We aimed to estimate the life expectancy of patients starting ART in South Africa and compare it with that of HIV-negative adults. Methods and Findings Data were collected from six South African ART cohorts. Analysis was restricted to 37,740 HIV-positive adults starting ART for the first time. Estimates of mortality were obtained by linking patient records to the national population register. Relative survival models were used to estimate the excess mortality attributable to HIV by age, for different baseline CD4 categories and different durations. Non-HIV mortality was estimated using a South African demographic model. The average life expectancy of men starting ART varied between 27.6 y (95% CI: 25.2–30.2) at age 20 y and 10.1 y (95% CI: 9.3–10.8) at age 60 y, while estimates for women at the same ages were substantially higher, at 36.8 y (95% CI: 34.0–39.7) and 14.4 y (95% CI: 13.3–15.3), respectively. The life expectancy of a 20-y-old woman was 43.1 y (95% CI: 40.1–46.0) if her baseline CD4 count was ?200 cells/µl, compared to 29.5 y (95% CI: 26.2–33.0) if her baseline CD4 count was <50 cells/µl. Life expectancies of patients with baseline CD4 counts ?200 cells/µl were between 70% and 86% of those in HIV-negative adults of the same age and sex, and life expectancies were increased by 15%–20% in patients who had survived 2 y after starting ART. However, the analysis was limited by a lack of mortality data at longer durations. Conclusions South African HIV-positive adults can have a near-normal life expectancy, provided that they start ART before their CD4 count drops below 200 cells/µl. These findings demonstrate that the near-normal life expectancies of HIV-positive individuals receiving ART in high-income countries can apply to low- and middle-income countries as well. Please see later in the article for the Editors' Summary

Johnson, Leigh F.; Mossong, Joel; Dorrington, Rob E.; Schomaker, Michael; Hoffmann, Christopher J.; Keiser, Olivia; Fox, Matthew P.; Wood, Robin; Prozesky, Hans; Giddy, Janet; Garone, Daniela Belen; Cornell, Morna; Egger, Matthias; Boulle, Andrew

2013-01-01

9

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

PubMed Central

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

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

2012-01-01

10

Immunologic risk factors for early mortality after starting antiretroviral therapy in HIV-infected Zambian children.  

PubMed

To explore immunologic risk factors for death within 90 days of highly active antiretroviral therapy (HAART) initiation, CD4(+) and CD8(+) T cell subsets were measured by flow cytometry and characterized by logistic regression in 149 Zambian children between 9 months and 10 years of age enrolled in a prospective, observational study of the impact of HAART on measles immunity. Of 21 children who died during follow-up, 17 (81%) had known dates of death and 16 (76%) died within 90 days of initiating HAART. Young age and low weight-for-age z-scores were associated with increased risks of mortality within 90 days of starting HAART, whereas CD4(+) T cell percentage was not associated with mortality. After adjusting for these factors, each 10% increase in CD8(+) effector T cells increased the odds of overall mortality [OR=1.43 (95% CI: 1.08, 1.90)] and was marginally associated with early mortality [OR=1.29 (95% CI: 0.97, 1.72)]. Conversely, each 10% increase in CD4(+) central memory T cells decreased the odds of overall [OR=0.06 (95% CI: 0.01, 0.59)] and early mortality [OR=0.09 (95% CI: 0.01, 0.97)]. Logistic regression prediction models demonstrated areas under the receiver-operator characteristic curves of ?85% for early and overall mortality, with bootstrapped sensitivities of 82-85% upon validation, supporting the predictive accuracy of the models. CD4(+) and CD8(+) T cell subsets may be more accurate predictors of early mortality than CD4(+) T cell percentages and could be used to identify children who would benefit from more frequent clinical monitoring after initiating HAART. PMID:23025633

Rainwater-Lovett, Kaitlin; Nkamba, Hope C; Mubiana-Mbewe, Mwangelwa; Moore, Carolyn Bolton; Moss, William J

2013-03-01

11

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.

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

12

Immunologic Risk Factors for Early Mortality After Starting Antiretroviral Therapy in HIV-Infected Zambian Children  

PubMed Central

Abstract To explore immunologic risk factors for death within 90 days of highly active antiretroviral therapy (HAART) initiation, CD4+ and CD8+ T cell subsets were measured by flow cytometry and characterized by logistic regression in 149 Zambian children between 9 months and 10 years of age enrolled in a prospective, observational study of the impact of HAART on measles immunity. Of 21 children who died during follow-up, 17 (81%) had known dates of death and 16 (76%) died within 90 days of initiating HAART. Young age and low weight-for-age z-scores were associated with increased risks of mortality within 90 days of starting HAART, whereas CD4+ T cell percentage was not associated with mortality. After adjusting for these factors, each 10% increase in CD8+ effector T cells increased the odds of overall mortality [OR=1.43 (95% CI: 1.08, 1.90)] and was marginally associated with early mortality [OR=1.29 (95% CI: 0.97, 1.72)]. Conversely, each 10% increase in CD4+ central memory T cells decreased the odds of overall [OR=0.06 (95% CI: 0.01, 0.59)] and early mortality [OR=0.09 (95% CI: 0.01, 0.97)]. Logistic regression prediction models demonstrated areas under the receiver-operator characteristic curves of ?85% for early and overall mortality, with bootstrapped sensitivities of 82–85% upon validation, supporting the predictive accuracy of the models. CD4+ and CD8+ T cell subsets may be more accurate predictors of early mortality than CD4+ T cell percentages and could be used to identify children who would benefit from more frequent clinical monitoring after initiating HAART.

Rainwater-Lovett, Kaitlin; Nkamba, Hope C.; Mubiana-Mbewe, Mwangelwa; Moore, Carolyn Bolton

2013-01-01

13

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.

2014-01-01

14

Factors Influencing Retention in Care after Starting Antiretroviral Therapy in a Rural South African Programme  

Microsoft Academic Search

IntroductionThe prognosis of patients with HIV in Africa has improved with the widespread use of antiretroviral therapy (ART) but these successes are threatened by low rates of long-term retention in care. There are limited data on predictors of retention in care, particularly from rural sites.MethodsProspective cohort analysis of outcome measures in adults from a rural HIV care programme in Madwaleni,

Tom H. Boyles; Lynne S. Wilkinson; Rory Leisegang; Gary Maartens; Robert J. Wilkinson

2011-01-01

15

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

PubMed Central

Background Mortality in HIV-infected patients who have access to highly active antiretroviral therapy (ART) has declined in sub-Saharan Africa, but it is unclear how mortality compares to the non-HIV–infected population. We compared mortality rates observed in HIV-1–infected patients starting ART with non-HIV–related background mortality in four countries in sub-Saharan Africa. Methods and Findings Patients enrolled in antiretroviral treatment programmes in Côte d'Ivoire, Malawi, South Africa, and Zimbabwe were included. We calculated excess mortality rates and standardised mortality ratios (SMRs) with 95% confidence intervals (CIs). Expected numbers of deaths were obtained using estimates of age-, sex-, and country-specific, HIV-unrelated, mortality rates from the Global Burden of Disease project. Among 13,249 eligible patients 1,177 deaths were recorded during 14,695 person-years of follow-up. The median age was 34 y, 8,831 (67%) patients were female, and 10,811 of 12,720 patients (85%) with information on clinical stage had advanced disease when starting ART. The excess mortality rate was 17.5 (95% CI 14.5–21.1) per 100 person-years SMR in patients who started ART with a CD4 cell count of less than 25 cells/µl and World Health Organization (WHO) stage III/IV, compared to 1.00 (0.55–1.81) per 100 person-years in patients who started with 200 cells/µl or above with WHO stage I/II. The corresponding SMRs were 47.1 (39.1–56.6) and 3.44 (1.91–6.17). Among patients who started ART with 200 cells/µl or above in WHO stage I/II and survived the first year of ART, the excess mortality rate was 0.27 (0.08–0.94) per 100 person-years and the SMR was 1.14 (0.47–2.77). Conclusions Mortality of HIV-infected patients treated with combination ART in sub-Saharan Africa continues to be higher than in the general population, but for some patients excess mortality is moderate and reaches that of the general population in the second year of ART. Much of the excess mortality might be prevented by timely initiation of ART. Please see later in the article for Editors' Summary

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

2009-01-01

16

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

PubMed Central

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

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

2012-01-01

17

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

Microsoft Academic Search

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

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

2004-01-01

18

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

PubMed Central

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

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

2013-01-01

19

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.

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

20

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.

2013-01-01

21

DEPRESSION AND SEXUAL RISKBEHAVIOR AMONG CLIENTS ABOUT TO START HIV ANTIRETROVIRAL THERAPY IN UGANDA  

PubMed Central

Objective We investigated depression in relationship to sexual risk behavior with primary partners among HIVclients in Uganda. Methods Baseline data were analyzed from a cohort of clients starting ART. The Patient Health Questionnaire (PHQ-9) was used to classify depressive severity (none, minor and major depression) and symptom type (cognitive and somatic). Condom use was assessed over the past 6 months and during the last episode of sexual intercourse. Results 386 participants had a primary sex partner, with whom 41.6% always used condoms during sex over the past 6 months, and 62.4% during last sex. Use of a condom during last sex was associated with having no depression and lower PHQ-9 total and cognitive and somatic subscale scores in bivariate analyses; most of these relationships were marginally significant for sex over the past 6 months. Controlling for demographics, HIV disclosure and partner HIV status, only minor depression was associated with unprotected sex. Conclusion Depressive symptoms, even if not a clinical disorder, warrant early detection and treatment for promoting HIV prevention among HIV-affected couples.

Musisi, Seggane; Wagner, Glenn J.; Ghosh-Dastidar, Bonnie; Nakasujja, Noeline; Dickens, Akena; Okello, Elialilia

2013-01-01

22

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

PubMed Central

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

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

2014-01-01

23

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

24

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

PubMed Central

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

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

2010-01-01

25

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

26

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

PubMed Central

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

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

2013-01-01

27

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

28

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

PubMed

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

Gold, R S; Ridge, D T

2001-12-01

29

Are there benefits to starting antiretroviral therapy during primary HIV infection? Conclusions from the Seattle Primary Infection Cohort vary by control group.  

PubMed

It is controversial whether starting combination antiretroviral therapy (cART) during primary HIV infection (PHI) is beneficial. Subjects in this observational cohort began cART <30 days (group 1: acute treatment, n = 40), 31-180 days (group 2: early treatment, n = 82) or >180 days (group 3: delayed treatment, n = 35) after HIV infection, and were compared with 27 historical and 60 contemporary controls. Time to HIV-related diagnoses did not differ for group 1 (adjusted hazard ratio [aHR] 1.44, P = 0.3) or group 2 (aHR 1.17, P = 0.5) compared with contemporary controls, but it was delayed for both treated groups (aHR 0.38 for group 1, P = 0.01; and aHR 0.28 for group 2, P < 0.0001) compared with historical controls. Although rates of HIV-related diagnoses were similar in acutely treated subjects and contemporary controls, results were confounded by associations between higher CD4 counts, lower HIV RNA levels and delayed disease progression as reasons for deferring treatment. Randomized trials are needed to address benefits of cART during PHI. PMID:22581875

Stekler, J D; Wellman, R; Holte, S; Maenza, J; Stevens, C E; Corey, L; Collier, A C

2012-03-01

30

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

PubMed Central

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

2014-01-01

31

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

PubMed

We investigated whether polymorphisms in human candidate genes could be associated with a different risk of developing lipodystrophy and dyslipidemia in HIV-infected patients starting combination antiretroviral therapy (cART). Genomic DNA samples from white HIV-1-infected patients were analyzed for seven polymorphisms located in the MDR1, TNF-?, APM1, APOE, and LPL genes. Lipid data were retrospectively collected beginning with the initiation of cART. Lipodystrophy was assessed cross-sectionally and then prospectively. The association with lipodystrophy and National Cholesterol Evaluation Program Adult Treatment Panel III-defined lipid thresholds was analyzed using survival analysis and logistic regression. One-hundred and seventy-four patients were genotyped. In 151 patients assessed for lipodystrophy, MDR1 3435 T homozygosis was associated with a higher hazard (adjusted hazard ratio, aHR, versus CT 0.25; p=0.02) and tumor necrosis factor (TNF)-? 308 G homozygosis with a lower hazard (vs. AA aHR 2.14; p=0.04) of developing trunk fat accumulation after adjusting for gender and initial cART type. The TNF 238 GG genotype was associated with a higher risk of developing low HDL-cholesterol levels (adjusted odd ratio, aOR, 5.91; p=0.01) while patients carrying the LPL S477X mutation were at lower risk of reaching high non-HDL-cholesterol levels (aOR 0.39; p=0.05). The APOEe3/3 genotype patients were at lower risk (aOR 0.26, p=0.015), whereas the adiponectin 276 GT carriers were at higher risk of developing hypertriglyceremia (vs. GG aOR 3.10; p=0.04). Knowledge of the effect of genetic determinants on dyslipidemia and lipodystrophy may prompt the investigation of potential pathogenetic mechanisms and might eventually be used for guiding individualized treatment decisions. PMID:21595566

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

2011-12-01

32

When to start antiretroviral therapy  

Microsoft Academic Search

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

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

2006-01-01

33

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

PubMed Central

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

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

2012-01-01

34

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

PubMed

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

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

2012-05-01

35

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-naïve 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

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

36

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

Microsoft Academic Search

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

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

2008-01-01

37

Short Communication: Factors Influencing Time to CD4+ T Cell Counts >200 Cells/mm3 in HIV-Infected Individuals with CD4+ T Cell <50 Cells/mm3 at the Time of Starting Combination Antiretroviral Therapy  

PubMed Central

Abstract We evaluated factors influencing time to CD4+ T cell counts >200 cells/mm3 in HIV-infected individuals with CD4+ T cell <50 cells/mm3 starting combination antiretroviral therapy (cART). We included a total of 29 patients on successful cART for more than 1 year. In a logistic regression model, higher pre-cART CD4+ T cell counts were significantly associated with shorter time to CD4+ T cell counts >200cells/mm3 in HIV-infected individuals with baseline CD4+ T cell <50 cells/mm3. In survival analysis, patients having higher pre-cART CD4+ T cell counts, especially 40–49 cells/mm3, were at significantly higher risk of achieving CD4+ T cell counts >200 cells/mm3.

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

2012-01-01

38

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.

Pandhi, Deepika; Ailawadi, Pallavi

2014-01-01

39

Antiretroviral neurotoxicity.  

PubMed

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

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

2012-10-01

40

Home-based versus clinic-based care for patients starting antiretroviral therapy with low CD4+ cell counts: findings from a cluster-randomized trial  

PubMed Central

Objectives: African health services have shortages of clinical staff. We showed previously, in a cluster-randomized trial, that a home-based strategy using trained lay-workers is as effective as a clinic-based strategy. It is not known whether home-based care is suitable for patients with advanced HIV disease. Methods: The trial was conducted in Jinja, Uganda. One thousand, four hundred and fifty-three adults initiating ART between February 2005 and January 2009 were randomized to receive either home-based care or routine clinic-based care, and followed up for about 3 years. Trained lay workers, supervised by clinical staff based in a clinic, delivered the home-based care. In this sub-analysis, we compared survival between the two strategies for those who presented with CD4+ cell count less than 50 cells/?l and those who presented with higher CD4+ cell counts. We used Kaplan–Meier methods and Poisson regression. Results: Four hundred and forty four of 1453 (31%) participants had baseline CD4+ cell count less than 50?cells/?l. Overall, 110 (25%) deaths occurred among participants with baseline CD4+ cell count less than 50?cells/?l and 87 (9%) in those with higher CD4+ cell count. Among participants with CD4+ cell count less than 50?cells/?l, mortality rates were similar for the home and facility-based arms; adjusted mortality rate ratio 0.80 [95% confidence interval (CI) 0.53–1.18] compared with 1.22 (95% CI 0.78–1.89) for those who presented with higher CD4+ cell count. Conclusion: HIV home-based care, with lay workers playing a major role in the delivery of care including providing monthly adherence support, leads to similar survival rates as clinic-based care even among patients who present with very low CD4+ cell count. This emphasises the critical role of adherence to antiretroviral therapy.

Woodd, Susannah L.; Grosskurth, Heiner; Levin, Jonathan; Amuron, Barbara; Namara, Geoffrey; Birunghi, Josephine; Coutinho, Alex; Jaffar, Shabbar

2014-01-01

41

Lack of short-term increase in serum mediators of fibrogenesis and in non-invasive markers of liver fibrosis in HIV/hepatitis C virus-coinfected patients starting maraviroc-based antiretroviral therapy.  

PubMed

The aim of this study was to analyze serum changes in mediators of fibrogenesis and in non-invasive markers of liver fibrosis among HIV/HCV-coinfected patients starting maraviroc (MVC)-based antiretroviral therapy. Patients included in this prospective pilot study met the following criteria: (1) HIV-infection, (2) detectable serum HCV-RNA, and ((3) started MVC. Transforming growth factor-?1 (TGF-beta1), matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) were measured in serum samples at baseline and 6 months after starting MVC. AST-to-platelet ratio index (APRI) was assessed at the same time points. Twenty-four patients were analyzed. Median (IQR) serum levels at baseline and after 6 months on MVC of TGF-beta1 were 27,295 (20,562-36,844) and 33,753 (18,973-46,130) pg/mL (p=0.116), of MMP-2 were 216 (186-274) and 241 (194-306) ng/mL (p=0.247), and of TIMP-1 were 237 (170-284) and 216 (171-271) ng/mL (p=0.415). APRI levels were 0.99 (0.53-3.46) at baseline and 0.83 (0.48-2.34) at 6 months (p=0.16). Serum mediators of liver fibrogenesis and fibrosis do not change significantly in HIV/HCV-coinfected patients in the short-term after starting MVC. As TGF-beta1 levels have been shown to increase over time in HCV infection and liver fibrosis worsens rapidly in HIV/HCV coinfection, these parameters seem to evolve in a different way in MVC-treated patients. PMID:22258426

Macías, J; Viloria, M M; Rivero, A; de los Santos, I; Márquez, M; Portilla, J; Di Lello, F; Camacho, A; Sanz-Sanz, J; Ojeda, G; Mata, R; Gómez-Mateos, J; Pineda, J A

2012-08-01

42

Advances in antiretroviral therapy.  

PubMed

The 18th Conference on Retroviruses and Opportunistic Infections maintained its tradition of being the preeminent forum for detailing the state-of the-art in antiretroviral therapy. There were important presentations on investigational antiretroviral drugs, clinical trials in treatment-experienced patients, and new antiretroviral strategies. Relevant data on resistance to antiretroviral drugs and pharmacokinetic interactions were discussed. There were extensive presentations on antiretroviral therapy in resource-limited settings, including large-scale clinical trials, scale-up of antiretroviral therapy, adherence, retention in care, and treatment outcomes for children and adults. Prevention of mother-to-child transmission continued to be an important part of the conference. PMID:21868824

Taylor, Barbara; Olender, Susan; Wilkin, Timothy J; Hammer, Scott M

2011-01-01

43

Antiretroviral Treatment 2010: Progress and Controversies  

PubMed Central

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

Gulick, Roy M.

2011-01-01

44

Safety and tolerability of depot medroxyprogesterone acetate among HIV-infected women on antiretroviral therapy: ACTG A5093  

PubMed Central

Background Concomitant use of antiretrovirals (ARV) and hormonal contraceptives may change the metabolism of each and the resulting safety profiles. We evaluated the safety and tolerability of depot medroxyprogesterone acetate (DMPA) among women on ARV. Study Design HIV-infected women on selected ARV regimens or no ARV were administered DMPA 150 mg intramuscularly and evaluated for 12 weeks for adverse events, changes in CD4+ count and HIV RNA levels, and ovulation. Results Seventy evaluable subjects were included, 16 on nucleoside only or no ARV, 21 on nelfinavir-containing regimens, 17 on efavirenz-containing regimens, and 16 on nevirapine-containing regimens. Nine grade 3 or 4 adverse events occurred in 7 subjects; none were judged related to DMPA. The most common findings possibly related to DMPA were abnormal vaginal bleeding (9, 12.7%), headache (3, 4.2%), abdominal pain, mood changes, insomnia, anorexia, and fatigue, each occurring in 2 (2.9%) subjects. No significant changes in CD4+ count or HIV RNA levels occurred with DMPA. No evidence of ovulation was detected, and no pregnancies occurred. Conclusions The clinical profile associated with DMPA administration in HIV-infected women, most on ARV, appears similar to that seen in HIV-uninfected women. DMPA prevented ovulation and did not affect CD4+ counts or HIV RNA levels. In concert with previously published DMPA/ARV interaction data, these data suggest that DMPA can be used safely by HIV-infected women on the ARV studied.

Watts, D Heather; Park, Jeong-Gun; Cohn, Susan E; Yu, Song; Hitti, Jane; Stek, Alice; Clax, Pamela A.; Muderspach, Laila; Lertora, Juan JL

2008-01-01

45

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

PubMed Central

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

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

2014-01-01

46

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

Microsoft Academic Search

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

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

2006-01-01

47

New antiretroviral agents  

Microsoft Academic Search

Despite advances in HIV treatment and the availability of 22 approved antiretroviral drugs, newer compounds are needed that\\u000a are better tolerated, less toxic, more convenient, or have improved activity against drug-resistant viruses. In addition to\\u000a newer agents in development in traditional antiretroviral classes (reverse transcriptase inhibitors, protease inhibitors),\\u000a a number of compounds in newer mechanistic classes also are under development,

Lawrence Siegel; Roy M. Gulick

2007-01-01

48

Pharmacogenetics of antiretroviral therapy.  

PubMed

Introduction: Human genetic testing is rapidly entering into most medical disciplines, mainly as a way to predict hereditary conditions including predisposition to cancers or degenerative diseases. Another area of interest for human genomics is to ascertain the therapeutic effect and prevent potential toxicities and/or drug-drug interactions of medication. Areas covered: Several human genotypes have been associated with differences in the metabolism and transport of antiretroviral agents that ultimately affect drug exposure. The accelerated discovery of new gene mutations and polymorphisms that influence the effects of antiretroviral drugs provides a unique opportunity for a personalized medicine approach in the management of lifelong HIV therapy. Expert opinion: Integration of human genomic screening into HIV clinical management will be cost-effective, maximizing the benefit of drugs with the lowest risk of side effects for a given patient. PMID:24941049

Barreiro, Pablo; Fernández-Montero, José Vicente; de Mendoza, Carmen; Labarga, Pablo; Soriano, Vincent

2014-08-01

49

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

50

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

51

Variable Impact on Mortality of AIDS-Defining Events Diagnosed during Combination Antiretroviral Therapy: Not All AIDS-Defining Conditions Are Created Equal Antiretroviral Therapy Cohort Collaboration (ART-CC)  

Microsoft Academic Search

Background. The extent to which mortality differs following individual acquired immunodeficiency syndrome (AIDS)-defining events (ADEs) has not been assessed among patients initiating combination antiretroviral therapy. Methods. We analyzed data from 31,620 patients with no prior ADEs who started combination antiretroviral therapy. Cox proportional hazards models were used to estimate mortality hazard ratios for each ADE that occurred in >50 patients,

A. Mocroft; J. A. C. Sterne; M. Egger; M. May; S. Grabar; H. Furrer; C. Sabin; G. Fatkenheuer; A. Justice; P. Reiss; A. d. A. Monforte; J. Gill; R. Hogg; F. Bonnet; M. Kitahata; S. Staszewski; J. Casabona; R. Harris; M. Saag

2009-01-01

52

Good response to lopinavir/ritonavir-containing antiretroviral regimens in antiretroviral-naive HIV-2-infected patients.  

PubMed

In 29 antiretroviral-naive HIV-2-infected patients starting lopinavir/ritonavir-containing regimen, the median CD4 cell count change from baseline (142 cells/microl) was +71 cells/microl at week 24 and +132 cells/microl at week 96. Seventeen (59%) patients had a CD4 cell count increase of at least 50 cells/microl and undetectable HIV-2 RNA at week 24 and were considered as responders to treatment. This sustained elevation of CD4 cell count in the first 2 years of combination antiretroviral therapy shows the potential for lopinavir/ritonavir regimens as first-line therapy in HIV-2 infection. PMID:19349850

Bénard, Antoine; Damond, Florence; Campa, Pauline; Peytavin, Gilles; Descamps, Diane; Lascoux-Combes, Caroline; Taieb, Audrey; Simon, François; Autran, Brigitte; Brun-Vézinet, Françoise; Chêne, Geneviève; Matheron, Sophie

2009-06-01

53

Individualization of antiretroviral therapy  

PubMed Central

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

Pavlos, Rebecca; Phillips, Elizabeth J

2012-01-01

54

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

PubMed Central

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

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

2006-01-01

55

Newer antiretroviral agents and how to use them  

Microsoft Academic Search

Several relatively new antiretroviral drugs have been approved or are under investigation. These include nucleoside and nonnucleoside\\u000a reverse transcriptase inhibitors, protease and integrase strand transfer inhibitors, CCR5 antagonists, and an entirely new\\u000a class of maturation inhibitors. Although most of these drugs were developed for patients with drug-resistant HIV-1, some have\\u000a demonstrated a potential role for those starting treatment for the

Holly H. Kim; Eric S. Daar

2009-01-01

56

Variable impact on mortality of AIDS-defining events diagnosed during combination antiretroviral therapy: not all AIDS-defining conditions are created equal  

Microsoft Academic Search

BACKGROUND: The extent to which mortality differs following individual acquired immunodeficiency syndrome (AIDS)-defining events (ADEs) has not been assessed among patients initiating combination antiretroviral therapy. METHODS: We analyzed data from 31,620 patients with no prior ADEs who started combination antiretroviral therapy. Cox proportional hazards models were used to estimate mortality hazard ratios for each ADE that occurred in >50 patients,

A. Mocroft; J. A. Sterne; M. Egger; M. May; S. Grabar; H. Furrer; C. Sabin; G. Fatkenheuer; A. Justice; P. Reiss; A. d' Arminio Monforte; J. Gill; R. Hogg; F. Bonnet; M. Kitahata; S. Staszewski; J. Casabona; R. Harris; M. Saag; P. P. Koopmans; R. van Crevel; R. de Groot; M. Keuter; F. Post; A. J. A. M. van der Ven; A. Warris

2009-01-01

57

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

58

Adverse effects of antiretroviral therapy  

Microsoft Academic Search

HAART will need to be indefinite for clinical benefits to be preserved. Second, the severity of the HIV epidemic led to accelerated licensing of many antiretroviral agents, often with very little known about long-term safety. Third, the sustained benefits of HAART have led to far greater numbers of HIV-1-infected patients receiving at least three drugs for greater periods of time.

Andrew Carr; David A Cooper

2000-01-01

59

HIV-1 superinfection with a triple-class drug-resistant strain in a patient successfully controlled with antiretroviral treatment.  

PubMed

We report a case of HIV-1 superinfection (HSI) with a clade B, triple-class resistant virus in a patient successfully controlling viremia with continuous combination antiretroviral therapy started 8 years earlier during primary HIV infection. The course of HIV infection prior to HSI was monitored in both the source partner and recipient (8 and 11 years, respectively) and 4 years following HSI. This case report demonstrates re-infection with HIV-1 despite effective combination antiretroviral therapy. PMID:24911350

Castro, Erika; Zhao, Hong; Cavassini, Matthias; Mullins, James I; Pantaleo, Giuseppe; Bart, Pierre-Alexandre

2014-07-31

60

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

PubMed

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

Kotzé, J E; McDonald, T

2010-06-01

61

Nucleoside-sparing antiretroviral regimens.  

PubMed

Nucleoside reverse transcriptase inhibitors (NRTIs) were the first drugs approved for use as antiretroviral therapy in patients infected with HIV. Despite the introduction of other classes of antiretroviral drugs, they remain an important component of combination regimens as recommended by many treatment guidelines. They also continue to be used in prevention of disease from mother to child, postexposure prophylaxis, and more recently for preexposure prophylaxis. Unfortunately, the toxicities associated with this class of drugs can limit their use. Although NRTI-sparing regimens are not currently recommended for first-line therapy there is an increasing amount of data supporting their use in both treatment-naive and in treatment-experienced patients. PMID:24880455

de la Torre, Pola; George, Jomy; Baxter, John D

2014-07-01

62

Combination antiretroviral therapy in population affected by conflict: outcomes from large cohort in northern Uganda  

PubMed Central

Objective To measure the clinical and immunological outcomes of HIV positive adult patients receiving combination antiretroviral therapy in conflict affected northern Uganda. Design Prospective cohort study. Setting Gulu District, northern Uganda. Participants 1625 adults (aged over 14 years) receiving combination antiretroviral therapy. Main outcome measures Primary outcome: all cause mortality. Secondary outcomes: impact of covariates (sex, age, CD4 count at start, adherence, tuberculosis at start, duration of treatment, and internally displaced person status) on mortality. Results Sixty nine (4.2%) patients died during follow-up. The mortality incidence rate was 3.48 (95% confidence interval 2.66 to 4.31) per 100 person years. Patients started treatment with a median CD4 count of 157 (interquartile range 90-220) cells/?l; most (1009; 63%) had World Health Organization stage 2 defined illness. Sixty two patients had pulmonary tuberculosis at the start of treatment. Of the 1521 patients with adherence data, 118 (7.8%) had adherence of less than 95% and 1403 (92.2%) had adherence of 95% or above. Conclusion Patients receiving combination antiretroviral therapy in conflict affected northern Uganda had a mortality comparable to that of patients in peaceful, low income settings and better adherence than patients in higher income settings. These favourable findings highlight the need to expand access to combination antiretroviral therapy in populations affected by armed conflict.

2009-01-01

63

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

Microsoft Academic Search

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

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

2006-01-01

64

Antiretroviral treatment in Georgia.  

PubMed

HIV infection is the major public health, social and economic problem in Georgia. The aim of this study is to evaluate effectiveness of ARV treatment system in Georgia. Study included 1052 people living with HIV/AIDS in Georgia registered at Infectious Disease, AIDS and Clinical Immunology Research Center since 2004. To ensure universal access to ARV therapy all HIV/AIDS individuals included in the study were investigated by special algorithm, all identified patients requiring ARV therapy were offered treatment and monitored during therapy on treatment effectiveness and side effects. Detection of HIV antibodies was performed by ELISA with further confirmation by Western Blot Assay. HIV-1 RNA in plasma was measured by quantitative Polymerase Chain Reaction. For determination of percentages and absolute count of T lymphocyte subpopulations single-platform immunophenotyping technique using the Becton-Dickinson FACSCalibur flow cytometer was applied. For resistance testing TRUGENE HIV-1 Genotyping Kit with the OpenGene DNA Sequencing System (Siemens) was used. Treatment was offered to 595 HIV/AIDS patients. 594 patients started treatment, 1 patient refused. Out of treated 594 HIV/AIDS patients 22 patients discontinued, 111 patients died and 461 patients are currently on ARV treatment. Out of treated patients 406 adults and 21 children are receiving first-line treatment, 31 adults and 2 children are on second-line treatment and 1 adult is receiving salvage regimen. Treatment failure was defined in 55 cases. Among them immunological failure was observed in 7 cases, clinical failure in 1 case and virologic failure in 47 cases. Prevalence of drug resistance among virologic failure cases accounted for 72% and inadequate adherence for 28% cases. Majority of death cases among ARV treated patients was due to non-AIDS related or incurable conditions, while deaths due to AIDS related conditions mainly were associated to the delayed referral of patients in already advanced stage of disease. It's worth to mention that highest number of death cases was due to liver failure in HIV/HCV and/or HBV co-infected patients. PMID:19124910

Tsertsvadze, T; Bolokadze, N; Sharvadze, L; Gabunia, P; Dvali, N

2008-12-01

65

Clinical pharmacological investigations of antiretroviral drugs  

Microsoft Academic Search

The major aim of all studies described in this thesis is to contribute to the optimisation of antiretroviral drug treatment in HIV-infected patients by the assessment and interpretation of pharmacokinetic characteristics of antiretroviral drugs. In the first chapter the current knowledge on the relationships between pharmacokinetics and treatment outcomes is summarised into practical guidelines for TDM. In subsequent chapters the

B. S. Kappelhoff

2005-01-01

66

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

PubMed Central

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

2012-01-01

67

Why Kids Start  

MedlinePLUS

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

68

Head Start Automation Manual.  

ERIC Educational Resources Information Center

The task for the National Data Management Project is to share technological capabilities with the Head Start Community in order to implement improved services for children and families involved in Head Start. Many Head Start programs have incorporated technology into their programs, including word processing, database management systems,…

Maryland Univ., College Park. Univ. Coll.

69

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.

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

2014-01-01

70

How does Antiretroviral Therapy Affect HIV Mutation?  

NSDL National Science Digital Library

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

Devin Iimoto (Whittier College;)

2005-06-11

71

Impact of Antiretroviral Therapy on Renal Function among HIV-Infected Tanzanian Adults: A Retrospective Cohort Study  

PubMed Central

Background Data regarding the outcomes of HIV-infected adults with baseline renal dysfunction who start antiretroviral therapy are conflicting. Methods We followed up a previously-published cohort of HIV-infected adult outpatients in northwest Tanzania who had high prevalence of renal dysfunction at the time of starting antiretroviral therapy (between November 2009 and February 2010). Patients had serum creatinine, proteinuria, microalbuminuria, and CD4+ T-cell count measured at the time of antiretroviral therapy initiation and at follow-up. We used the adjusted Cockroft-Gault equation to calculate estimated glomerular filtration rates (eGFRs). Results In this cohort of 171 adults who had taken antiretroviral therapy for a median of two years, the prevalence of renal dysfunction (eGFR <90 mL/min/1.73 m2) decreased from 131/171 (76.6%) at the time of ART initiation to 50/171 (29.2%) at the time of follow-up (p<0.001). Moderate dysfunction (eGFR<60 mL/min/1.73 m2) decreased from 21.1% at antiretroviral therapy initiation to 1.1% at follow-up (p<0.001), as did the prevalence of microalbuminuria (72% to 44%, p<0.001). Use of tenofovir was not associated with renal dysfunction at follow-up. Conclusion Mild and moderate renal dysfunction were common in this cohort of HIV-infected adults initiating antiretroviral therapy, and both significantly improved after a median follow-up time of 2 years. Our work supports the renal safety of antiretroviral therapy in African adults with mild-moderate renal dysfunction, suggesting that these regimens do not lead to renal damage in the majority of patients and that they may even improve renal function in patients with mild to moderate renal dysfunction.

Mpondo, Bonaventura C. T.; Kalluvya, Samuel E.; Peck, Robert N.; Kabangila, Rodrick; Kidenya, Benson R.; Ephraim, Lucheri; Fitzgerald, Daniel W.; Downs, Jennifer A.

2014-01-01

72

Unmasking cryptococcal meningitis immune reconstitution inflammatory syndrome in pregnancy induced by HIV antiretroviral therapy with postpartum paradoxical exacerbation  

PubMed Central

Cryptococcosis is the most common cause of meningitis in Africa due to the high burden of HIV. Immune reconstitution inflammatory syndrome (IRIS) is a frequent and deadly complication of cryptococcal meningitis. We report a fatal case of cryptococcal-IRIS in a pregnant woman that began after starting antiretroviral therapy (unmasking IRIS) and markedly worsened postpartum after delivery (paradoxical IRIS).

Kiggundu, Reuben; Rhein, Joshua; Meya, David B.; Boulware, David R.; Bahr, Nathan C.

2014-01-01

73

"Risk factors associated with virologic failure in HIV-infected patients receiving antiretroviral therapy at a public hospital in Peru"  

PubMed Central

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

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

2013-01-01

74

Unmasking cryptococcal meningitis immune reconstitution inflammatory syndrome in pregnancy induced by HIV antiretroviral therapy with postpartum paradoxical exacerbation.  

PubMed

Cryptococcosis is the most common cause of meningitis in Africa due to the high burden of HIV. Immune reconstitution inflammatory syndrome (IRIS) is a frequent and deadly complication of cryptococcal meningitis. We report a fatal case of cryptococcal-IRIS in a pregnant woman that began after starting antiretroviral therapy (unmasking IRIS) and markedly worsened postpartum after delivery (paradoxical IRIS). PMID:24944885

Kiggundu, Reuben; Rhein, Joshua; Meya, David B; Boulware, David R; Bahr, Nathan C

2014-07-01

75

Bacterial start site prediction  

Microsoft Academic Search

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

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

1999-01-01

76

Aboriginal Head Start.  

ERIC Educational Resources Information Center

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

Dunning, Paula

2000-01-01

77

Start with Science  

ERIC Educational Resources Information Center

The author has found over her 13 years of teaching that starting off the school year with a science investigation has been a great method to learn about her students, to engage them about science before the school year even starts, and to build a foundation for a year of engaging science experiences. This article describes four such activities…

Erickson, Susan

2012-01-01

78

Start at the End ...  

ERIC Educational Resources Information Center

Start at the end; that's the way to improve children's plans for investigations. Strange as it may seem, there are times when beginning at the beginning of an investigation is not the best way to start things off. To give children the opportunity to ask questions and plan what to do, sometimes it is best to get them first to consider others' data…

Goldsworthy, Anne

2005-01-01

79

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

PubMed Central

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

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

2010-01-01

80

Sustained antiretroviral treatment adherence in survivors of the pre-HAART era: attitudes and beliefs  

Microsoft Academic Search

The objective of this study was to assess adherence of HIV-1-infected patients who started treatment in the pre-HAART era and to determine variables associated with better adherence, including relevant attitudes and beliefs. This is a cross-sectional study enrolling patients who had received antiretroviral therapy for ?10 years. Adherence was evaluated through self-reporting and plasma drug concentrations. Treatment variables, attitudes and

C. R. Fumaz; J. A. Muñoz-Moreno; J. Moltó; M. J. Ferrer; R. López-Blázquez; E. Negredo; R. Paredes; G. Gómez; B. Clotet

2008-01-01

81

A feasibility study of immediate versus deferred antiretroviral therapy in children with HIV infection  

Microsoft Academic Search

OBJECTIVE: To evaluate the feasibility of a large immediate versus deferred antiretroviral therapy (ART) study in children. METHODS: We conducted an open-label pilot randomized clinical trial study in 43 Thai children with CD4 15 to 24% of starting generic AZT\\/3TC\\/NVP immediately (Arm 1) or deferring until CD4 < 15% or CDC C (Arm 2). Primary endpoints were recruitment rate, adherence

Jintanat Ananworanich; Pope Kosalaraksa; Umaporn Siangphoe; Chulapan Engchanil; Chitsanu Pancharoen; Pagakrong Lumbiganon; Jintana Intasan; Wichitra Apateerapong; Theshinee Chuenyam; Sasiwimol Ubolyam; Torsak Bunupuradah; Joep Lange; David A Cooper; Praphan Phanuphak

2008-01-01

82

Decay Kinetics of Human Immunodeficiency Virus-Specific Effector Cytotoxic T Lymphocytes after Combination Antiretroviral Therapy  

Microsoft Academic Search

Little is known of the changes in human immunodeficiency virus type 1 (HIV-1)-specific effector cytotoxic T lymphocytes (CTL) after potent antiretroviral therapy. Using HLA\\/peptide tetrameric complexes, we show that after starting treatment, there are early rapid fluctuations in the HIV-1-specific CTL response which last 1 to 2 weeks. These fluctuations are followed by an exponential decay (median half-life, 45 days)

G. S. OGG; X. JIN; S. BONHOEFFER; P. MOSS; M. A. NOWAK; S. MONARD; J. P. SEGAL; Y. CAO; S. L. ROWLAND-JONES; A. HURLEY; M. MARKOWITZ; D. D. HO; A. J. MCMICHAEL; D. F. NIXON

1999-01-01

83

HIV-1 antiretroviral drug therapy.  

PubMed

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

Arts, Eric J; Hazuda, Daria J

2012-04-01

84

Costs of Anti-Retroviral Treatment in Zambia.  

National Technical Information Service (NTIS)

This report analyzes the costs and resource requirements associated with the provision of antiretroviral (ARV) therapy in the public health sector in Zambia. It provides per-patient cost estimates for highly active anti-retroviral therapy (HAART), volunta...

G. Kombe O. Smith

2003-01-01

85

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

PubMed Central

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

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

2012-01-01

86

Preferred antiretroviral drugs for the next decade of scale up  

PubMed Central

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

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

2012-01-01

87

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.

Lawn, Stephen D; Meintjes, Graeme

2011-01-01

88

Psychiatric Advance Directives: Getting Started  

MedlinePLUS

... Home Getting Started National Resource Center on Psychiatric Advance Directives - Getting Started Getting Started Psychiatric advance directives (PADs) are relatively new legal instruments that may ...

89

[The potential nephrotoxicity of antiretroviral drugs].  

PubMed

 The intensive studies carried out in many scientific laboratories and the efforts of numerous pharmaceutical companies have led to the development of drugs which are able to effectively inhibit HIV proliferation. At present, a number of antiretroviral agents with different mechanisms of action are available. Unfortunately, long-term use of antiretroviral drugs, however, does not remain indifferent to the patient and can cause significant side effects. In the present work, the antiretroviral drugs with a nephrotoxicity potential most commonly used in clinical practice are described. In the review attention has also been focused on the nephropathy resulting from the HIV infection alone and the influence of genetic factors on the occurrence of pathological changes in the kidney. PMID:23001202

Marchewka, Zofia; Szyma?ska, Beata; P?onka, Joanna

2012-01-01

90

Monochromatic precursor starts  

NASA Astrophysics Data System (ADS)

Whistler precursors are discrete emissions that precede two-hop whistlers, starting shortly after the one-hop delay. More evidence is presented that the precursor and associated whistler propagate through the same duct, and observations of a new type of precursor are presented. This new precursor has a monochromatic precursor start (MPS) which may or may not trigger a riser. Although MPS's may be emissions entrained by power line radiation (PLR), phase analysis of the starting frequencies shows that they are not simply related to harmonics of the power line frequencies in the two conjugate regions (50 Hz in New Zealand, 60 Hz in Alaska). If the MPS is due to entrainment by PLR, then previous theories of precursor generation need not be discarded. Forward triggering of a precursor at a power line harmonic by a hybrid whistler may occur.

Rietveld, M. T.

1980-05-01

91

Starting in School  

ERIC Educational Resources Information Center

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

Albertine, Susan

2012-01-01

92

Is Head Start Dying?  

ERIC Educational Resources Information Center

Analysis of problems faced by Head Start and its present status includes a review of its transfer from O.E.O. to H.E.W., its extensions, the Westinghouse Report, and other studies and articles. Decline in public interest and support is noted. (KW)

Sherman, Ann; And Others

1971-01-01

93

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.

Mallipeddi, Rama; Rohan, Lisa Cencia

2010-01-01

94

Antiretroviral treatment of maternal HIV infection.  

PubMed Central

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

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

2004-01-01

95

Antiretroviral therapy for tuberculosis control in nine African countries  

PubMed Central

HIV has increased the incidence of tuberculosis (TB) by up to sevenfold in African countries, but antiretroviral therapy (ART) reduces the incidence of AIDS-related TB. We use a mathematical model to investigate the short-term and long-term impacts of ART on the incidence of TB, assuming that people are tested for HIV once a year, on average, and start ART at a fixed time after HIV seroconversion or at a fixed CD4+ cell count. We fit the model to trend data on HIV prevalence and TB incidence in nine countries in sub-Saharan Africa. If HIV-positive people start ART within 5 y of seroconversion, the incidence of AIDS-related TB in 2015 will be reduced by 48% (range: 37–55%). Long-term reductions depend sensitively on the delay to starting ART. If treatment is started 5, 2, or 1 y after HIV seroconversion, or as soon as people test positive, the incidence in 2050 will be reduced by 66% (range: 57–80%), 95% (range: 93–96%), 97.7% (range: 96.9–98.2%) and 98.4% (range: 97.8–98.9%), respectively. In the countries considered here, early ART could avert 0.71 ± 0.36 [95% confidence interval (CI)] million of 3.4 million cases of TB between 2010 and 2015 and 5.8 ± 2.9 (95% CI) million of 15 million cases between 2015 and 2050. As more countries provide ART at higher CD4+ cell counts, the impact on TB should be investigated to test the predictions of this model.

Williams, Brian G.; Granich, Reuben; De Cock, Kevin M.; Glaziou, Philippe; Sharma, Abhishek; Dye, Christopher

2010-01-01

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 âÂÂLean from the Expertsâ 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

Hepatoxicity of new antiretrovirals: a systematic review.  

PubMed

There has been a major paradigm shift in the management of HIV infected patients, with earlier initiation of antiretroviral treatment and lifelong exposure to drugs for which long-term safety issues must be faced by clinicians. Within the past 5 years, new drugs from both previously established and novel therapeutic classes have been released that tend to be safer and more efficient than their former combinations. Although hepatotoxicity was one of the most common side effects from initial antiretrovirals, phase II/III safety data regarding liver tolerance from more recent drugs are reassuring. However, data on the long-term exposure to these therapeutic options are needed, and a handful of case reports are emerging, reporting rare but potentially life-threatening adverse hepatic events in patients with hepatitis co-infection or taking other hepatotoxic drugs. PMID:23522569

Surgers, Laure; Lacombe, Karine

2013-04-01

98

Perceived burden in adherence of antiretroviral treatment in rural China  

Microsoft Academic Search

To determine the level of antiretroviral treatment adherence and explore the correlated factors of perceived burden of taking antiretroviral medications among people living with HIV (PLH) in a rural area of China. Data were collected from 66 PLH who were currently receiving antiretroviral treatment. Face-to-face interviews were conducted during August to October, 2009. Approximately 18.2% of participants failed to adhere

Li Li; Guoping Ji; Yingying Ding; Junru Tian; Alex Lee

2011-01-01

99

Perceived burden in adherence of antiretroviral treatment in rural China  

Microsoft Academic Search

To determine the level of antiretroviral treatment adherence and explore the correlated factors of perceived burden of taking antiretroviral medications among people living with HIV (PLH) in a rural area of China. Data were collected from 66 PLH who were currently receiving antiretroviral treatment. Face-to-face interviews were conducted during August to October, 2009. Approximately 18.2% of participants failed to adhere

Li Li; Guoping Ji; Yingying Ding; Junru Tian; Alex Lee

2012-01-01

100

Pediatric adherence to HIV antiretroviral therapy  

Microsoft Academic Search

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

Jessica Haberer; Claude Mellins

2009-01-01

101

Cardiovascular toxicity with highly active antiretroviral therapy  

Microsoft Academic Search

Highly active antiretroviral therapy (HAART) has dramatically improved the life expectancy of patients with human immunodeficiency\\u000a virus (HIV). Specific toxicities cited for HAART include elevations in serum levels of total cholesterol and triglycerides,\\u000a reduction in high-density lipoprotein cholesterol, alterations in the distribution of body fat, increases in insulin resistance,\\u000a and diabetes, which are major risk factors for cardiovascular disease (CVD).

Biykem Bozkurt

2004-01-01

102

HIV, Antiretroviral Therapies, and the Brain  

Microsoft Academic Search

While combination antiretroviral therapy (CART) has decreased the incidence of HIV-associated dementia, the severest form\\u000a of HIV-associated neurocognitive disorders (HAND), mild neurocognitive disorder and asymptomatic neurocognitive impairment\\u000a continue to persist, and there is evidence that neurocognitive deficits present even in acute HIV infection. Recent studies\\u000a demonstrate that CART regimens with higher central nervous system (CNS) penetration effectiveness ranks may improve

Kevin J. Liner; Michelle J. Ro; Kevin R. Robertson

2010-01-01

103

ACTG A5164: Early Antiretroviral Therapy Reduces AIDS Progression/Death in Individuals with Acute Opportunistic Infections: A Multicenter Randomized Strategy Trial.  

National Technical Information Service (NTIS)

This product consists of SAS 9 files containing data from a randomized strategy trial of Immediate (in 2 weeks of start OI treatment) vs. Deferred antiretroviral treatment (in 6 weeks) in HIV-infected adults with acute opportunistic infections, included i...

2009-01-01

104

Challenges in initiating antiretroviral therapy in 2010.  

PubMed

Many clinical trials have shown that initiating antiretroviral therapy (ART) at higher rather than lower CD4 T cell-positive counts results in survival benefit. Early treatment can help prevent end-organ damage associated with HIV replication and can decrease infectivity. The mainstay of treatment is either a non-nucleoside reverse transcriptase inhibitor or a ritonavir-boosted protease inhibitor in combination with two nucleoside reverse transcriptase inhibitors. While effective at combating HIV, ART can produce adverse alterations of lipid parameters, with some studies suggesting a relationship between some anti-retroviral agents and cardiovascular disease. As the HIV-positive population ages, issues such as hypertension and diabetes must be taken into account when initiating ART. Adhering to ART can be difficult; however, nonoptimal adherence to ART can result in the development of resistance; thus, drug characteristics and the patient's preparedness to begin therapy must be considered. Reducing the pill burden through the use of fixed-dose antiretroviral drug combinations can facilitate adherence. PMID:23365594

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

2010-08-01

105

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

106

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.

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

2014-01-01

107

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 LoÛ, Annabel Desgrées; Deschamps, Nina; Eholie, Serge; Anglaret, Xavier

2014-06-19

108

Outcomes of a remote, decentralized health center-based HIV/AIDS antiretroviral program in Zambia, 2003 to 2007.  

PubMed

A cross-sectional study of patients living with HIV/ AIDS treated during 2003 to 2007 in decentralized, rural health centers in Zambia was performed to measure virological outcomes after 12 months of antiretroviral therapy and identify factors associated with virological failure. Data from 228 patients who started antiretroviral therapy >12 months prior were analyzed. In all, 93% received stavudine + lamivudine + nevirapine regimens, and median antiretroviral therapy duration was 23.5 months (interquartile range 20-28). Of the 205 patients tested for viral load, 177 (86%) had viral load <1000 copies/mL. Probability of developing virological failure (viral load >1000 copies/mL) was 8.9% at 24 months and 19.6% at 32 months. Predictors for virological failure were <100% adherence, body mass index <18.5 kg/m(2), and women <40 years old. Of those with virological failure who underwent 3 to 6 months of intensive adherence counseling, 45% obtained virological success. In a remote, resource-limited setting in decentralized health centers, virological and immunological assessments of patients on antiretroviral therapy >12 months showed that positive health outcomes are achievable. PMID:19211930

Elema, Riekje; Mills, Clair; Yun, Oliver; Lokuge, Kamalini; Ssonko, Charles; Nyirongo, Nashiola; Mtonga, Velepi; Zulu, Henry; Tu, David; Verputten, Meggy; O'Brien, Daniel P

2009-01-01

109

Pharmacokinetics and drug–drug interactions of antiretrovirals: An update  

Microsoft Academic Search

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

Laura Dickinson; Saye Khoo; David Back

2010-01-01

110

PHEV Cold Start Emissions Management.  

National Technical Information Service (NTIS)

Plug-in hybrid electric vehicles (PHEV) operate predominantly as electric vehicles (EV) with intermittent assist from the engine. As a consequence, the engine can be subjected to multiple cold start events. These cold start events have a significant impac...

2013-01-01

111

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.

Lake, Jordan E; Currier, Judith S

2011-01-01

112

Sex differentials in the uptake of antiretroviral treatment in Zambia.  

PubMed

This study explores socio-structural factors that influence uptake of antiretroviral treatment (ART) in Zambia and assess differences between men and women. We conducted a case-control study nested in a community- and health facility-based survey, between September 2010 and February 2011. Cases were defined as HIV-positive individuals who, while eligible, never started ART and controls were HIV-positive individuals who were on ART. Cases and controls were matched by place of residence. We performed a conditional logistic regression analysis using a discrete logistic model stratified by sex. Overall, a significantly larger proportion of men (32.7%) than women (25.6%) did not uptake ART (Pearson ?(2) = 5.9135; p = 0.015). In the crude analysis, poor health status and low self-efficacy were common factors associated with non-uptake in both sexes. After adjusting for covariates, men were more likely than women to refuse ART even though men's self-rated health was lower than women's. In general, the adjusted analysis suggests that HIV status disclosure affects uptake in both sexes but women's uptake of ART is largely hampered by poverty-related factors while for men, side effects and social pressure, probably associated with masculinity, are more important barriers. Alarmingly men's health seems to deteriorate until they start treatment, in contrast to women. Understanding gender differences in uptake and attitudes to ART is a crucial component to providing effective and appropriate health care to both men and women living with HIV/AIDS in Zambia. PMID:24666201

Gari, S; Martin-Hilber, A; Malungo, J R S; Musheke, M; Merten, S

2014-10-01

113

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.

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

2012-01-01

114

Safety and tolerability of antiretrovirals during pregnancy.  

PubMed

Combination antiretroviral therapy (CART) dramatically decreases mother-to-child HIV-1 transmission (MTCT), but maternal adverse events are not infrequent. A review of 117 locally followed pregnancies revealed 7 grade ? 3 AEs possibly related to antiretrovirals, including 2 hematologic, 3 hepatic, and 2 obstetric cholestasis cases. A fetal demise was attributed to obstetric cholestasis, but no maternal deaths occurred. The drugs possibly associated with these AE were zidovudine, nelfinavir, lopinavir/ritonavir, and indinavir. AE or intolerability required discontinuation/substitution of nevirapine in 16% of the users, zidovudine in 10%, nelfinavir in 9%, lopinavir/ritonavir in 1%, but epivir and stavudine in none. In conclusion, nevirapine, zidovudine, and nelfinavir had the highest frequency of AE and/or the lowest tolerability during pregnancy. Although nevirapine and nelfinavir are infrequently used in pregnancy at present, zidovudine is included in most MTCT preventative regimens. Our data emphasize the need to revise the treatment recommendations for pregnant women to include safer and better-tolerated drugs. PMID:21603231

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

2011-01-01

115

Safety and Tolerability of Antiretrovirals during Pregnancy  

PubMed Central

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

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

2011-01-01

116

Emerging drug targets for antiretroviral therapy.  

PubMed

Current targets for antiretroviral therapy (ART) include the viral enzymes reverse transcriptase and protease. The use of a combination of inhibitors targeting these enzymes can reduce viral load for a prolonged period and delay disease progression. However, complications of ART, including the emergence of viruses resistant to current drugs, are driving the development of new antiretroviral agents targeting not only the reverse transcriptase and protease enzymes but novel targets as well. Indeed, enfuvirtide, an inhibitor targeting the viral envelope protein (Env) was recently approved for use in combination therapy in individuals not responding to current antiretroviral regimens. Emerging drug targets for ART include: (i) inhibitors that directly or indirectly target Env; (ii) the HIV enzyme integrase; and (iii) inhibitors of maturation that target the substrate of the protease enzyme. Env mediates entry of HIV into target cells via a multistep process that presents three distinct targets for inhibition by viral and cellular-specific agents. First, attachment of virions to the cell surface via nonspecific interactions and CD4 binding can be blocked by inhibitors that include cyanovirin-N, cyclotriazadisulfonamide analogues, PRO 2000, TNX 355 and PRO 542. In addition, BMS 806 can block CD4-induced conformational changes. Secondly, Env interactions with the co-receptor molecules can be targeted by CCR5 antagonists including SCH-D, maraviroc (UK 427857) and aplaviroc (GW 873140), and the CXCR4 antagonist AMD 070. Thirdly, fusion of viral and cellular membranes can be inhibited by peptides such as enfuvirtide and tifuvirtide (T 1249). The development of entry inhibitors has been rapid, with an increasing number entering clinical trials. Moreover, some entry inhibitors are also being evaluated as candidate microbicides to prevent mucosal transmission of HIV. The integrase enzyme facilitates the integration of viral DNA into the host cell genome. The uniqueness and specificity of this reaction makes integrase an attractive drug target. However, integrase inhibitors have been slow to reach clinical development, although recent contenders, including L 870810, show promise. Inhibitors that target viral maturation via a unique mode of action, such as PA 457, also have potential. In addition, recent advances in our understanding of cellular pathways involved in the life cycle of HIV have also identified novel targets that may have potential for future antiretroviral intervention, including interactions between the cellular proteins APOBEC3G and TSG101, and the viral proteins Vif and p6, respectively. In summary, a number of antiretroviral agents in development make HIV entry, integration and maturation emerging drug targets. A multifaceted approach to ART, using combinations of inhibitors that target different steps of the viral life cycle, has the best potential for long-term control of HIV infection. Furthermore, the development of microbicides targeting HIV holds promise for reducing HIV transmission events. PMID:16114975

Reeves, Jacqueline D; Piefer, Andrew J

2005-01-01

117

Antiretroviral Therapy-associated Serious and Life-threatening Toxicities.  

PubMed

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 United States, it was acceptable to prescribe newer antiretroviral therapy such as zidovudine, which has significant bone marrow toxicities but can potentially improve patient survival. Although current antiretroviral therapy is not likely to eradicate HIV-1 infection, the advances in the use of combination antiretroviral therapy (including protease inhibitors and non-nucleoside reverse transcriptase inhibitors) have dramatically improved the overall survival, immune status, and productivity of HIV-infected individuals in developed countries. Instead of prevention and treatment of HIV-associated complications, many of the patients" clinic visits are focused on finding strategies to manage and prevent antiretroviral therapy-associated complications. Because only a few HIV-infected persons fulfilling stringent inclusion criteria were included in premarketing clinical trials and because the US Food and Drug Administration"s (FDA) accelerated approval process for antiretroviral therapy requires only 24-week safety and efficacy data, newly emerging and previously unrecognized adverse effects of antiretroviral therapy continue to surface when these drugs are administered to a larger patient population for a longer duration. Unfortunately, some of these adverse effects can be unpredictable and serious, and, if not recognized early and managed aggressively, can lead to fatality. This article reviews four of the most serious, life-threatening toxicities associated with antiretroviral therapy. PMID:13678573

Pau, Alice K.

2003-10-01

118

Calculating the affordability of antiretrovirals in St Lucia.  

PubMed

The cost of antiretrovirals is borne by donors in many low- and middle-income countries, including St Lucia. Although donor involvement has facilitated access to antiretrovirals, donor engagement in HIV/AIDS has changed over the years. This paper assesses the affordability of antiretrovirals at the individual level if donors were no longer available to fund the cost of first and second-line antiretrovirals and a prospective third-line regimen. Various conceptions of affordability are reviewed using different assumptions of what is required to maintain a standard of living that would avoid individuals descending into poverty as a result of antiretroviral purchases. These concepts of affordability are operationalized using data from the Household Budgeting Survey conducted in St Lucia in 2005/2006. While there is a range of results for the affordability of first and second-line antiretrovirals depending on which standard of affordability is used, third-line antiretrovirals are unaffordable to more than 80% of the population across the four standards of affordability used - the national poverty line, 50% of median annual consumption, 10% of annual consumption and a proposed reasonable minimum standard. PMID:24756598

Reddock, J R; Grignon, M

2013-01-01

119

HLA-Bw4 homozygosity is associated with an impaired CD4 T cell recovery after initiation of antiretroviral therapy.  

PubMed

We assessed the influence of human leukocyte antigen (HLA) alleles HLA-Bw4 and HLA-Bw6 on CD4 T cell recovery after starting successful combination antiretroviral therapy in 265 individuals. The median gains in the CD4 T cell count after 4 years were 258 cells/microL for HLA-Bw4 homozygotes, 321 cells/microL for HLA-Bw4/Bw6 heterozygotes, and 363 cells/microL for HLA-Bw6 homozygotes (P = .01, compared with HLA-Bw4 homozygotes). HLA-Bw4 homozygosity appears to predict an impaired CD4 T cell recovery after initiation of combination antiretroviral therapy. PMID:18466093

Rauch, Andri; Nolan, David; Furrer, Hansjakob; McKinnon, Elizabeth; John, Mina; Mallal, Simon; Gaudieri, Silvana; Günthard, Huldrych F; Schmid, Patrick; Battegay, Manuel; Hirschel, Bernard; Telenti, Amalio; James, Ian

2008-06-15

120

The Cost-Effectiveness of Early Access to HIV Services and Starting cART in the UK 1996–2008  

Microsoft Academic Search

AimTo calculate use, cost and cost-effectiveness of people living with HIV (PLHIV) starting routine treatment and care before starting combination antiretroviral therapy (cART) and PLHIV starting first-line 2NRTIs+NNRTI or 2NRTIs+PIboosted, comparing PLHIV with CD4?200 cells\\/mm3 and CD4>200 cells\\/mm3. Few studies have calculated the use, cost and cost-effectiveness of routine treatment and care before starting cART and starting cART above and

Eduard J. Beck; Sundhiya Mandalia; Roshni Sangha; Peter Sharott; Mike Youle; Guy Baily; Ray Brettle; Mark Gompels; Margaret Johnson; Brendan McCarron; Ed Ong; Anton Pozniak; Achim Schwenk; Stephen Taylor; John Walsh; Ed Wilkins; Ian Williams; Brian Gazzard

2011-01-01

121

Antiretroviral-based HIV-1 Prevention: Antiretroviral Treatment and Pre-Exposure Prophylaxis  

PubMed Central

Antiretroviral-based HIV-1 prevention strategies – including antiretroviral treatment (ART) to reduce the infectiousness of HIV-1 infected persons and oral and topical pre-exposure prophylaxis (PrEP) for uninfected persons to prevent HIV-1 acquisition – are the most promising new approaches for decreasing HIV-1 spread. Observational studies among HIV-1 serodiscordant couples have associated ART initiation with a reduction in HIV-1 transmission risk of 80–92%, and a recent randomized trial demonstrated that earlier initiation of ART (i.e., at CD4 counts between 350 and 550 cells/mm3), in the context of virologic monitoring and adherence support, resulted in a 96% reduction in HIV-1 transmission. A number of ongoing and recently-completed clinical trials have assessed the efficacy of PrEP for HIV-1 prevention as peri-coitally administered or daily-administered 1% tenofovir gel and daily oral tenofovir and combination emtricitabine/tenofovir. Completed studies have demonstrated HIV-1 protection efficacies ranging from 39% to 75%. However, two trials in African women have shown no HIV-1 protection with PrEP; the reasons for lack of efficacy in those trials are being investigated. Adherence is likely key to efficacy of antiretrovirals for HIV-1 prevention, both as ART and PrEP. Critical unanswered questions for successful delivery of antiretroviral-based HIV-1 prevention include how to target ART and PrEP to realize maximum population benefits, whether HIV-1 infected persons at earlier stages of infection would accept ART to reduce their risk for transmitting HIV-1 and highest-risk HIV-1 negative persons would use PrEP, and whether high adherence could be sustained to achieve high effectiveness.

Celum, Connie; Baeten, Jared

2012-01-01

122

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

123

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.

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

2011-01-01

124

Rolling Out Antiretrovirals in Africa: There Are Still Challenges Ahead  

Microsoft Academic Search

only currently available as abstracts, and as a result, a critical analysis of the strengths and,weaknesses,of the various programs,is not,possible. There is no doubt that the availability of antiretroviral

R. Colebunders; A. Ronald; E. Katabira; M. Sande

2005-01-01

125

Early Antiretroviral Therapy and Mortality among HIV-Infected Infants  

PubMed Central

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

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

2010-01-01

126

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

127

Facilitating Compound Progression of Antiretroviral Agents via Modeling and Simulation  

Microsoft Academic Search

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

Jeffrey S. Barrett

2007-01-01

128

Internal Impedance of Starting Batteries.  

National Technical Information Service (NTIS)

Starting batteries of the lead accumulator type have an internal impedance which varies with, among other things, the load conditions, working temperature and measurement frequency. The impedance lies between 3 and 30 mohm with frequencies between 20 and ...

R. Andersson

1971-01-01

129

Head Start Dental Health Curriculum.  

National Technical Information Service (NTIS)

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

1997-01-01

130

Antiretroviral drug resistance among antiretroviral-naïve 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-naïve and experienced hospitalized patients infected with HIV in Tehran, Iran were used to assess the prevalence and types of transmitted (TDR) and acquired drug resistance (ADR) mutations. All 30 participants naïve to ART and 62 of 70 (88.6%) participants receiving ART had detectable viral loads. Among participants receiving ART with sequencing data available (n?=?62), 36 (58.1%) had at least one drug resistance mutation; the most common mutations were K103N (21.0%), M184V (19.4%), and the thymidine analogue mutations. Seven (11.3%), 27 (43.5%), and two (3.2%) of these participants had resistance to one, two, and three drug classes, respectively. High-level resistance to efavirenz (EFV) was more common among participants on EFV-based regimens than high-level lopinavir/ritonivar (LPV/r) resistance among those on LPV/r-based regimens (55.3% vs. 6.7%, P?antiretroviral-naïve participants had K103N mutations. These findings document an alarmingly high frequency of multiple HIV drug class resistance in Iran, confirm the presence of TDR, and highlight the need for systematic viral load monitoring and drug resistance testing, including at diagnosis. Expanded access to new antiretroviral medications from additional drug classes is needed. PMID:24740443

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

2014-07-01

131

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

NASA Astrophysics Data System (ADS)

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

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

2013-10-01

132

Patient-Reported Symptoms on the Antiretroviral Regimen Efavirenz/Emtricitabine/Tenofovir  

PubMed Central

Abstract Most patients (80–90%) newly diagnosed with HIV are started on the antiretroviral regimen efavirenz, emtricitabine, and tenofovir (EFV/FTC/TDF). Existing studies of patient tolerability, however, are limited. We compared symptom experiences of patients on EFV/FTC/TDF, and the subsequent impact on health-related quality of life, with those of patients on other combination antiretroviral therapy (cART). We conducted a cross-sectional analysis of the Veterans Aging Cohort Study from February 2008 to August 2009 to compare the symptom experiences of patients on EFV/FTC/TDF vs. other cART, unadjusted and then adjusted for treatment characteristics, and comorbid disease severity. We then assessed the association between EFV/FTC/TDF use and health-related quality of life. Among the 1,759 patients in our analytic sample, EFV/FTC/TDF use was associated with fewer symptoms than was other cART. The use of EFV/FTC/TDF was independently associated with health-related quality of life, and this association was at least partially explained by symptom burden.

Gordon, Kirsha; Rodriguez-Barradas, Maria C.; Justice, Amy C.

2012-01-01

133

Immune control of HIV-1 infection after therapy interruption: immediate versus deferred antiretroviral therapy  

PubMed Central

Background The optimal stage for initiating antiretroviral therapies in HIV-1 bearing patients is still a matter of debate. Methods We present computer simulations of HIV-1 infection aimed at identifying the pro et contra of immediate as compared to deferred Highly Active Antiretroviral Therapy (HAART). Results Our simulations highlight that a prompt specific CD8+ cytotoxic T lymphocytes response is detected when therapy is delayed. Compared to very early initiation of HAART, in deferred treated patients CD8+ T cells manage to mediate the decline of viremia in a shorter time and, at interruption of therapy, the virus experiences a stronger immune pressure. We also observe, however, that the immunological effects of the therapy fade with time in both therapeutic regimens. Thus, within one year from discontinuation, viral burden recovers to the value at which it would level off in the absence of therapy. In summary, simulations show that immediate therapy does not prolong the disease-free period and does not confer a survival benefit when compared to treatment started during the chronic infection phase. Conclusion Our conclusion is that, since there is no therapy to date that guarantees life-long protection, deferral of therapy should be preferred in order to minimize the risk of adverse effects, the occurrence of drug resistances and the costs of treatment.

2009-01-01

134

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

135

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

Microsoft Academic Search

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

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

2008-01-01

136

Levels of Human Immunodeficiency Virus Type 1Specific Cytotoxic T-Lymphocyte Effector and Memory Responses Decline after Suppression of Viremia with Highly Active Antiretroviral Therapy  

Microsoft Academic Search

Therapeutic suppression of human immunodeficiency virus type 1 (HIV-1) replication may help elucidate interactions between the host cellular immune responses and HIV-1 infection. We performed a detailed longitudinal evaluation of two subjects before and after the start of highly active antiretroviral therapy (HAART). Both subjects had evidence of in vivo-activated and memory cytotoxic T-lymphocyte precursor (CTLp) activity against multiple HIV-1

SPYROS A. KALAMS; PHILIP J. GOULDER; AMY K. SHEA; NORMAN G. JONES; ALICJA K. TROCHA; GRAHAM S. OGG; BRUCE D. WALKER

1999-01-01

137

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

Microsoft Academic Search

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

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

2010-01-01

138

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

PubMed Central

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

2012-01-01

139

Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection, August 11, 2011.  

National Technical Information Service (NTIS)

These guidelines address issues specific to the use of antiretroviral therapy (ART) for HIV-infected infants, children, and adolescents (through puberty). Included is information on the management of adverse events of antiretroviral (ARV) drugs in childre...

2011-01-01

140

Off to a Good Start.  

ERIC Educational Resources Information Center

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

Hoffman, Carl

1994-01-01

141

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.

142

Rigor Made Easy: Getting Started  

ERIC Educational Resources Information Center

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

Blackburn, Barbara R.

2012-01-01

143

Starting School: A Community Endeavor  

ERIC Educational Resources Information Center

Much of the current debate about children's transition to school focuses on children's readiness for school. Indeed, Boethel (2004, p. 17) describes transition as the "focal point of readiness." Typically, this focus extends to considering children's competencies--particularly their skills and abilities--at the time of starting school. This…

Dockett, Sue; Perry, Bob

2008-01-01

144

Whitepaper: Starting a New Program  

NSDL National Science Digital Library

This is a white paper on starting a geospatial educational program. The paper covers the growth of geospatial technology and introduces a model for creating a program in the field. Useful logic model templates are included to help educators going through the process. This paper would be a useful resource for educators and administrators creating a program from scratch at their institution.

Johnson, Ann B.; Lewis, Chris

2011-08-08

145

Cost-Effectiveness of Genotypic Antiretroviral Resistance Testing in HIV-Infected Patients with Treatment Failure  

Microsoft Academic Search

Background. Genotypic antiretroviral resistance testing (GRT) in HIV infection with drug resistant virus is recommended to optimize antiretroviral therapy, in particular in patients with virological failure. We estimated the clinical effect, cost and cost- effectiveness of using GRT as compared to expert opinion in patients with antiretroviral treatment failure. Methods. We developed a mathematical model of HIV disease to describe

Pedram Sendi; Huldrych F. Günthard; Mathew Simcock; Bruno Ledergerber; Jörg Schüpbach; Manuel Battegay

2007-01-01

146

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

147

Update on antiretroviral treatment during primary HIV infection.  

PubMed

Primary HIV-1 infection covers a period of around 12 weeks in which the virus disseminates from the initial site of infection into different tissues and organs. In this phase, viremia is very high and transmission of HIV is an important issue. Most guidelines recommend antiretroviral treatment in patients who are symptomatic, although the indication for treatment remains inconclusive in asymptomatic patients. In this article the authors review the main virological and immunological events during this early phase of infection, and discuss the arguments for and against antiretroviral treatment. Recommendations of different guidelines, the issue of the HIV transmission and transmission of resistance to antiretroviral drugs, as well as recently available information opening perspectives for functional cure in patients treated in very early steps of HIV infection are also discussed. PMID:24803105

Ambrosioni, Juan; Nicolas, David; Sued, Omar; Agüero, Fernando; Manzardo, Christian; Miro, Jose M

2014-07-01

148

Pharmacokinetics and therapeutic drug monitoring of antiretrovirals in pregnant women  

PubMed Central

Highly active antiretroviral therapy is recommended for HIV-infected pregnant women to prevent mother-to-child transmission. The specific physiological background induced by pregnancy leads to significant changes in maternal pharmacokinetics, suggesting potential variability in plasma concentrations of antiretrovirals during gestation. Therapeutic drug monitoring (TDM) of protease inhibitors (PIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs) is recommended in certain situations, including pregnancy, but its systematic use in HIV-infected pregnant women remains controversial. This review provides an update of the pharmacokinetic data available for PIs and NNRTIs in pregnant women and highlights the clinical interest of systematic TDM of certain antiretroviral drugs during pregnancy, including nevirapine, nelfinavir, saquinavir, indinavir and lopinavir.

Roustit, Matthieu; Jlaiel, Malik; Leclercq, Pascale; Stanke-Labesque, Francoise

2008-01-01

149

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

PubMed Central

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

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

2013-01-01

150

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

PubMed

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

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

2013-01-01

151

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

PubMed Central

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

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

2014-01-01

152

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.

2009-01-01

153

[Considerations in first line antiretroviral selection for adults].  

PubMed

One of the main factors that influence the success of antiretroviral therapy is adherence to treatment. However, there are other elements that physicians must be aware in order to obtain maximal therapeutic efficacy. A diverse range of antiretroviraldrugs have been approved for its use in HIV infected patients with HIV, but each one of them has its own particular indications and contraindications. The selection of antiretrovirals will depend on factors such as age, sex, co-morbidities, co-infections, virologic and immunological status of the patient. Intake schedules and possible interactions with other drugs are also essential points to considerate for a favorable outcome of treatment. PMID:24248168

Ceballos, M Elena

2013-10-01

154

Comparative manufacture and cell-based delivery of antiretroviral nanoformulations  

PubMed Central

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

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

2011-01-01

155

Whoonga and the abuse and diversion of antiretrovirals in soweto, South Africa.  

PubMed

Media reports have described recreational use of HIV antiretroviral medication in South Africa, but little has been written about this phenomenon in the scientific literature. We present original, qualitative data from eight semi-structured interviews that characterize recreational antiretroviral use in Soweto, South Africa. Participants reported that antiretrovirals, likely efavirenz, are crushed, mixed with illicit drugs (in a mixture known as whoonga), and smoked. They described medications being stolen from patients and expressed concern that antiretroviral abuse jeopardized the safety of both patients and users. Further studies are needed to understand the prevalence, patterns, and consequences of antiretroviral abuse and diversion. PMID:24370963

Rough, Kathryn; Dietrich, Janan; Essien, Thandekile; Grelotti, David J; Bansberg, David R; Gray, Glenda; Katz, Ingrid T

2014-07-01

156

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

157

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

PubMed

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

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

2013-07-01

158

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

PubMed Central

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

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

2013-01-01

159

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

PubMed Central

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

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

2008-01-01

160

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

161

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

162

Clinical Pharmacokinetics of Antiretroviral Drugs in Older Persons  

PubMed Central

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

Schoen, John C.; Erlandson, Kristine Mace

2013-01-01

163

Barriers to Antiretroviral Treatment in Ethiopia: A Qualitative Study  

Microsoft Academic Search

Objective: Ethiopia has made meaningful headway in improving access to HIV care and treatment but client attrition remains a daunting challenge. The objective of this study was to describe the major reasons of patient attrition from treatment at hospital and health center levels in Oromia region of Ethiopia. Methods: This qualitatively designed study was based on semistructured interview with antiretroviral

Taye T. Balcha; Anders Jeppsson; Abera Bekele

2011-01-01

164

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

165

Enhancing antiretroviral therapy for human immunodeficiency virus cognitive disorders  

Microsoft Academic Search

The benefits of combination antiretroviral therapy (ART) for HIV cognitive disorders vary substantially between indi- viduals. This study evaluated whether cerebrospinal fluid (CSF) drug penetration and CSF virological suppression in- fluence the extent of neuropsychological (NP) improvement during ART. Overall performance on a battery of NP tests administered at baseline and follow-up (median 15 weeks) was computed by using the

Scott L. Letendre; J. Allen McCutchan; Meredith E. Childers; Steven P. Woods; Deborah Lazzaretto; Robert K. Heaton; Igor Grant; Ronald J. Ellis

2004-01-01

166

Severe demyelinating leukoencephalopathy in AIDS patients on antiretroviral therapy  

Microsoft Academic Search

Objectives: To describe a severe form of demyelinating HIV-associated leukoence- phalopathy in AIDS patients failing highly active antiretroviral therapy (HAART), its relationship to clinical and neuroimaging findings, and suggest hypotheses regarding pathogenesis. Design and methods: AIDS patients who failed HAART and displayed severe leuko- encephalopathy were included. All cases had detailed neuromedical, neuro- psychological, neuroimaging and postmortem neuropathological examination. Immunocytochemical

T. Dianne Langford; Scott L. Letendre; Thomas D. Marcotte; Ronald J. Ellis; J. Allen Mccutchan; Igor Grant; Margaret E. Mallory; Lawrence A. Hansen; Sarah Archibald

167

Neurological and psychiatric adverse effects of antiretroviral drugs.  

PubMed

Antiretroviral drugs are associated with a variety of adverse effects on the central and peripheral nervous systems. The frequency and severity of neuropsychiatric adverse events is highly variable, with differences between the antiretroviral classes and amongst the individual drugs in each class. In the developing world, where the nucleoside reverse transcriptase inhibitor (NRTI) stavudine remains a commonly prescribed antiretroviral, peripheral neuropathy is an important complication of treatment. Importantly, this clinical entity is often difficult to distinguish from human immunodeficiency virus (HIV)-induced peripheral neuropathy. Several clinical trials have addressed the efficacy of various agents in the treatment of NRTI-induced neurotoxicity. NRTI-induced neurotoxicity is caused by inhibition of mitochondrial DNA polymerase. This mechanism is also responsible for the mitochondrial myopathy and lactic acidosis that occur with zidovudine. NRTIs, particularly zidovudine and abacavir, may also cause central nervous system (CNS) manifestations, including mania and psychosis. The non-nucleoside reverse transcriptase inhibitor (NNRTI) efavirenz is perhaps the antiretroviral most commonly associated with CNS toxicity, causing insomnia, irritability and vivid dreams. Recent studies have suggested that the risk of developing these adverse effects is increased in patients with various cytochrome P450 2B6 alleles. Protease inhibitors cause perioral paraesthesias and may indirectly increase the relative risk of stroke by promoting atherogenesis. HIV integrase inhibitors, C-C chemokine receptor type 5 (CCR5) inhibitors and fusion inhibitors rarely cause neuropsychiatric manifestations. PMID:24362768

Abers, Michael S; Shandera, Wayne X; Kass, Joseph S

2014-02-01

168

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

169

Factors Influencing Medication Adherence Beliefs and Self-Efficacy in Persons Naive to Antiretroviral Therapy: A Multicenter, Cross-Sectional Study  

Microsoft Academic Search

It is widely recognized that adherence to antiretroviral therapy is critical to long-term treatment success, yet rates of adherence to antiretroviral medications are frequently subtherapeutic. Beliefs about antiretroviral therapy and psychosocial characteristics of HIV-positive persons naive to therapy may influence early experience with antiretroviral medication adherence and therefore could be important when designing programs to improve adherence to antiretroviral therapy.

Nancy R. Reynolds; Marcia A. Testa; Linda G. Marc; Margaret A. Chesney; Judith L. Neidig; Scott R. Smith; Stefano Vella; Gregory K. Robbins

2004-01-01

170

How to Start Interventional Radiology  

PubMed Central

Interventional techniques aim to find safer and better ways to treat vascular diseases even in many instances, the interventional radiology solutions has been considered the only treatment option for the patients. Interventional radiologists are specialists who perform minimally invasive procedures instead of surgery or other treatments. These procedures apply various imaging and catheterization procedures in order to diagnose and treat diseases. In each country, interventional radiology practice establishment of varies according to local factors, but following a standard strategy seems better to set up this facility. According to above mentioned points, we decided to establish this specialty in our hospital since 2001 as the pioneer center in Iran. In this presentation we will discuss about our experience for start interventional radiology.

Ghanaati, Hossein; Firouznia, Kavous; Jalali, Amir Hossein; Shakiba, Madjid

2013-01-01

171

How to start interventional radiology.  

PubMed

Interventional techniques aim to find safer and better ways to treat vascular diseases even in many instances, the interventional radiology solutions has been considered the only treatment option for the patients. Interventional radiologists are specialists who perform minimally invasive procedures instead of surgery or other treatments. These procedures apply various imaging and catheterization procedures in order to diagnose and treat diseases. In each country, interventional radiology practice establishment of varies according to local factors, but following a standard strategy seems better to set up this facility. According to above mentioned points, we decided to establish this specialty in our hospital since 2001 as the pioneer center in Iran. In this presentation we will discuss about our experience for start interventional radiology. PMID:24693402

Ghanaati, Hossein; Firouznia, Kavous; Jalali, Amir Hossein; Shakiba, Madjid

2013-12-01

172

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

PubMed Central

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

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

2013-01-01

173

Do patents for antiretroviral drugs constrain access to AIDS treatment in Africa?  

PubMed

Public attention and debate recently have focused on access to treatment of acquired immunodeficiency syndrome (AIDS) in poor, severely affected countries, such as those in Africa. Whether patents on antiretroviral drugs in Africa are impeding access to lifesaving treatment for the 25 million Africans with human immunodeficiency virus infection is unknown. We studied the patent statuses of 15 antiretroviral drugs in 53 African countries. Using a survey method, we found that these antiretroviral drugs are patented in few African countries (median, 3; mode, 0) and that in countries where antiretroviral drug patents exist, generally only a small subset of antiretroviral drugs are patented (median and mode, 4). The observed scarcity of patents cannot be simply explained by a lack of patent laws because most African countries have offered patent protection for pharmaceuticals for many years. Furthermore, in this particular case, geographic patent coverage does not appear to correlate with antiretroviral treatment access in Africa, suggesting that patents and patent law are not a major barrier to treatment access in and of themselves. We conclude that a variety of de facto barriers are more responsible for impeding access to antiretroviral treatment, including but not limited to the poverty of African countries, the high cost of antiretroviral treatment, national regulatory requirements for medicines, tariffs and sales taxes, and, above all, a lack of sufficient international financial aid to fund antiretroviral treatment. We consider these findings in light of policies for enhancing antiretroviral treatment access in poor countries. PMID:11597292

Attaran, A; Gillespie-White, L

2001-10-17

174

Transmitted HIV Resistance to First-Line Antiretroviral Therapy in Lima, Peru  

PubMed Central

Abstract Transmission of drug-resistant HIV (TDR) has been associated with virologic failure of “first-line,” nonnucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral therapy (ART). A national ART program began in Peru in 2004. We evaluated the prevalence of TDR in individuals initiating ART and their virologic outcome during 2 years of ART. HIV-infected, ARV-naive subjects who met criteria to start ART in Lima, Peru were enrolled in a longitudinal observational study between July 2007 and February 2009. Blood plasma and cells obtained prior to ART initiation were assessed for antiretroviral (ARV) resistance by an oligonucleotide ligation assay (OLA) sensitive to 2% mutant at reverse transcriptase (RT) codons K103N, Y181C, G190A, and M184V and a subset by consensus sequencing. A total of 112 participants were enrolled; the mean CD4 was 134±89 cells/?l and the median plasma HIV RNA was 93,556 copies/ml (IQR 62,776–291,364). Drug resistance mutations conferring high-level resistance to ARV were rare, detected in one of 96 (1%) evaluable participants. This subject had the Y181C mutation detected in both plasma and peripheral blood mononuclear cells (PBMCs) at a concentration of 100% by OLA and consensus sequencing; nevertheless nevirapine-ART suppressed her viral replication. Consensus sequencing of 37 (19%) participants revealed multiple polymorphisms that occasionally have been associated with low-level reductions in ARV susceptibility. A low prevalence of TDR was detected among Peruvians initiating ART. Given the increasing availability of ART, continuing surveillance is needed to determine if TDR increases and the mutant codons associated with virologic failure.

Soria, Jaime; Bull, Marta; Mitchell, Caroline; La Rosa, Alberto; Dross, Sandra; Kraft, Kelli; Coombs, Robert; Ticona, Eduardo

2012-01-01

175

HIV-positive status disclosure among men and women receiving antiretroviral treatment in eastern Ethiopia.  

PubMed

Disclosure of HIV infection status is a difficult process that involves communication of information about a potentially stigmatizing and transmissible illness. Despite this it is important for preventing HIV infection and mitigating its impacts. This study aims to describe disclosure of HIV diagnosis and factors associated with it among a cohort of patients receiving antiretroviral treatment in eastern Ethiopia. A descriptive study was conducted among a random sample of patients that started antiretroviral treatment in three hospitals located in eastern Ethiopia. Unadjusted and adjusted logistic regression models were used to examine association and derive odds ratios (OR) as well as 95% confidence intervals. A total of 1540 study participants were included in the study, where 963 (62.5%) were females and 574 (37.3%) males. Most of the married participants have disclosed to their wife or husband (402, 66.3%), but the overall sample had much lower rates of disclosure to brothers or sisters (262, 17.0%), and relatives (259, 16.8%). A small number of patients (11.6%, 179) did not disclose their infection status at all and none of the patients (0, 0%) had disclosed to all of their family members. In the multivariate logistic regression analysis patients who were not married (OR 1.54; 95% CI 1.01-2.35) and illiterate (OR 1.81; 95% CI 1.03-3.20) had higher odds of nondisclosure. The findings of the study revealed a lower level of HIV disclosure status compared to similar settings. Therefore, more focus should be given to unmarried and illiterate persons during counseling sessions. PMID:23244574

Reda, Ayalu A; Biadgilign, Sibhatu; Deribe, Kebede; Deribew, Amare

2013-08-01

176

Improvement in vitamin D deficiency following antiretroviral regime change: Results from the MONET trial.  

PubMed

Low levels of vitamin D are reported in HIV-infected individuals. In HIV-negative people, low vitamin D levels have been associated with an increased risk of cardiovascular disease and cancer and with worse survival. The MONET trial recruited 256 European patients with HIV RNA <50 copies/ml at screening, while taking either NNRTI- or PI-based HAART. Patients were switched to DRV/r 800/100?mg once daily, either as monotherapy or with two NRTIs. In all, 221 patients were measured for 25-hydroxyvitamin D at a central laboratory before randomized treatment started and at week 96. Multiple regression was used to correlate vitamin D levels with gender, season, ethnic group, treatment group, and use of antiretrovirals. Overall, 80% of patients were male and 91% were white, with a mean age of 44 years. At screening, 170/221 (77%) patients had vitamin D deficiency (<50?nmol/liter). At the screening visit, lower vitamin D levels were significantly associated with calendar month (p?=?0.0067), black ethnicity (p?=?0.013), use of efavirenz (p?=?0.0062), and use of zidovudine (p?=?0.015). Mean vitamin D levels were lowest from January to April (mean?=?35.8?nmol/liter) and highest in September (mean?=?45.4?nmol/liter). Increases in vitamin D between screening and week 96 were significantly greater for patients who discontinued efavirenz or zidovudine before the MONET trial versus those who stopped other antiretrovirals. At screening, lower vitamin D levels were associated with season, race, and use of efavirenz and/or zidovudine. Switching from efavirenz and/or zidovudine to darunavir/ritonavir during the trial led to increases in vitamin D levels. Routine screening of HIV-positive patients for vitamin D should be considered and the optimal management further defined. PMID:20854196

Fox, Julie; Peters, Barry; Prakash, Manyu; Arribas, Jose; Hill, Andrew; Moecklinghoff, Christiane

2011-01-01

177

Long-Term CD4+ Cell Count in Response to Combination Antiretroviral Therapy  

PubMed Central

Objective There is a continuous debate on how to adequately evaluate long-term CD4+ cell count in response to combination antiretroviral therapy (ART) among human immunodeficiency virus (HIV)-infected individuals. Our study evaluated the long-term CD4+ cell count response (up to ten years) after initiation of ART and described the differences in the CD4+ cell count response stratified by pretreatment CD4+ cell count, and other socio-demographic, behavioral, and clinical factors. Methods The study population included patients starting ART in the clinical cohorts of Rio de Janeiro, Brazil, and Baltimore, United States. Inverse probability of censoring weighting was used to estimate mean annual CD4+ cell counts while adjusting for choice of initial ART regimen, ART discontinuation and losses-to-follow-up. Results From 1997 to 2011, 3116 individuals started ART; preferred initial regimen was NNRTI-based (63%). The median follow-up time was 5 years, 10% of the individuals had nine or more years of follow-up. Observed CD4+ cell counts increased throughout the ten years of follow-up. Weighted results, in contrast, increased up to year four and plateaued thereafter with 50% of the population reaching CD4+ cell counts of 449/?L or more. Out of all stratification variables considered, only individuals with pre-treatment CD4+ cell counts ?350/?L showed increasing CD4+ cell counts over time with 76% surpassing the CD4+ cell count >500/?L threshold at year ten. Conclusion The present study corroborates the growing body of knowledge advocating early start of ART by showing that only patients who start ART early fully recover to normal CD4+ cell counts.

Luz, Paula M.; Grinsztejn, Beatriz; Velasque, Luciane; Pacheco, Antonio G.; Veloso, Valdilea G.; Moore, Richard D.; Struchiner, Claudio J.

2014-01-01

178

Factors affecting timing of antiretroviral treatment initiation based on monitoring CD4 counts  

PubMed Central

Objective To evaluate factors affecting antiretroviral therapy (ART) start time when triggered by a CD4 count < 350 cells/?l while monitoring counts over time. Measurement frequency, requirement for confirmatory counts, and precision and accuracy of CD4 enumeration technology were considered. Methods Using a model of CD4 count trajectories among seroconverters in the Multicenter AIDS Cohort Study, sequences of counts were simulated for a large hypothetical population monitored for 5 years from seroconversion. Time of first count < 350 cells/?l was defined as ART start time. The simulation was adapted to evaluate the effect of the above factors on these times. ART initiation was considered “very late” among patients whose underlying trajectory declined below 200 cells/?l during the period simulated if no previous observed count was < 350 cells/?l. Results For 12-, 6-, 4- and 3-monthly measurements, median start time was 48, 36, 32 and 30 months after seroconversion and proportion of patients starting ART very late was 11.5%, 1.6%, 0.2% and 0.1%. For 6-monthly measurements, requiring confirmation increased the median to 49 months and proportion to 8.9%. Changes in standard deviation of short-term variability in counts of 25% and measurement bias for a novel technology of ± 10% changed median time by ± 6 months with modest change in the proportion very late (range 0.5% to 3.2%). Conclusion 6-monthly measurements appear adequate in achieving low rates of very late ART whereas confirmation affects rates adversely. Studies comparing new versus standard measurement technologies should focus on ruling out modest bias, particularly proximal to important thresholds for treatment management.

NOUBARY, Farzad; HUGHES, Michael D.

2012-01-01

179

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

PubMed Central

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

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

2013-01-01

180

Dangerous medicines: Unproven AIDS cures and counterfeit antiretroviral drugs  

PubMed Central

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

Amon, Joseph J

2008-01-01

181

Antiretroviral treatment French guidelines 2013: economics influencing science.  

PubMed

Guidelines for the preferred choice of initial combination antiretroviral therapy in those living with HIV are provided by several national and international committees. Following the recent presentation of the 2013 French guidelines on antiretroviral therapy, there has been a debate regarding whether and/or how economics should influence guideline decisions and to what extent this should counterbalance valid scientific evidence. We discuss here the reasons for the unique nature of some of the proposals made by the French guidelines panel. Indeed, some recommendations are debatable. In the new French guidelines, economic considerations significantly influence and, in some instances, take precedence over the scientific evidence, leading to guidelines that are significantly different from those of other national and international committees. PMID:24443513

Raffi, F; Reynes, J

2014-05-01

182

Real-Time Adherence Monitoring for HIV Antiretroviral Therapy  

Microsoft Academic Search

Current adherence assessments typically detect missed doses long after they occur. Real-time, wireless monitoring strategies\\u000a for antiretroviral therapy may provide novel opportunities to proactively prevent virologic rebound and treatment failure.\\u000a Wisepill, a wireless pill container that transmits a cellular signal when opened, was pilot tested in ten Ugandan individuals\\u000a for 6 months. Adherence levels measured by Wisepill, unannounced pill counts, and

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

2010-01-01

183

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

184

The impact of host pharmacogenetics on antiretroviral drug disposition  

Microsoft Academic Search

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

Andrew Owen

2006-01-01

185

Human Immunodeficiency Virus: Resistance to Antiretroviral Drugs in Developing Countries  

Microsoft Academic Search

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

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

186

Therapy naivete in the era of potent antiretroviral therapy  

Microsoft Academic Search

Antiretroviral therapy (ART) use was examined in a cohort of homosexual men infected with HIV-1 for long periods. Multivariate logistic regression models, stratified by clinical indication (below and above 500 CD4 cells\\/?l or prior AIDS), were used to determine predictors of ART naivete. Of the 673 men seen at visit 28 (10\\/97–4\\/98), 89 (13.2%) never used ART and 548 (81.4%)

L. P Jacobson; M. E Gore; S. A Strathdee; J. P Phair; S Riddler; R Detels; for the Multicenter AIDS Cohort Study

2001-01-01

187

Antiretroviral treatment strategies in resource-limited settings  

Microsoft Academic Search

To date, a minority of persons living with HIV worldwide has benefited from the advances in HIV therapeutics fueled by the\\u000a scientific community, policy-makers, advocates, and the pharmaceutical industry in the global North. A growing body of evidence\\u000a demonstrates that access to highly active antiretroviral therapy can be successfully scaled-up in less wealthy nations in\\u000a the South. High rates of

Anna K. Person; Habib O. Ramadhani; Nathan M. Thielman

2007-01-01

188

Patient-perceived barriers to antiretroviral adherence: Associations with race  

Microsoft Academic Search

New antiretroviral (ARV) regimens require strict adherence if optimal suppression of HIV is to be maintained. This study is a theory-based examination of racial differences in patient-perceived barriers and reported ARV adherence. Participants (N=149) completed the Patient Medication Adherence Questionnaire (PMAQ), measuring adherence and perceived barriers to adherence. Adherence was defined as a self-report of 100% adherence in the past

T. F. Ferguson; K. E. Stewart; E. Funkhouser; J. Tolson; A. O. Westfall; M. S. Saag

2002-01-01

189

Molecular evolution of the antiretroviral TRIM5 gene  

Microsoft Academic Search

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

Welkin E. Johnson; Sara L. Sawyer

2009-01-01

190

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.

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

191

Threshold virus dynamics with impulsive antiretroviral drug effects  

PubMed Central

The purposes of this paper are twofold: to develop a rigorous approach to analyze the threshold behaviors of nonlinear virus dynamics models with impulsive drug effects and to examine the feasibility of virus clearance following the Manuals of National AIDS Free Antiviral Treatment in China. An impulsive system of differential equations is developed to describe the within-host virus dynamics of both wild-type and drug-resistant strains when a combination of antiretroviral drugs is used to induce instantaneous drug effects at a sequence of dosing times equally spaced while drug concentrations decay exponentially after the dosing time. Threshold parameters are derived using the basic reproduction number of periodic epidemic models, and are used to depict virus clearance/persistence scenarios using the theory of asymptotic periodic systems and the persistence theory of discrete dynamical systems. Numerical simulations using model systems parametrized in terms of the antiretroviral therapy recommended in the aforementioned Manuals illustrate the theoretical threshold virus dynamics, and examine conditions under which the impulsive antiretroviral therapy leads to treatment success. In particular, our results show that only the drug-resistant strain can dominate (the first-line treatment program guided by the Manuals) or both strains may be rapidly eliminated (the second-line treatment program), thus the work indicates the importance of implementing the second-line treatment program as soon as possible.

Lou, Jie; Lou, Yijun; Wu, Jianhong

2013-01-01

192

Threshold virus dynamics with impulsive antiretroviral drug effects.  

PubMed

The purposes of this paper are twofold: to develop a rigorous approach to analyze the threshold behaviors of nonlinear virus dynamics models with impulsive drug effects and to examine the feasibility of virus clearance following the Manuals of National AIDS Free Antiviral Treatment in China. An impulsive system of differential equations is developed to describe the within-host virus dynamics of both wild-type and drug-resistant strains when a combination of antiretroviral drugs is used to induce instantaneous drug effects at a sequence of dosing times equally spaced while drug concentrations decay exponentially after the dosing time. Threshold parameters are derived using the basic reproduction number of periodic epidemic models, and are used to depict virus clearance/persistence scenarios using the theory of asymptotic periodic systems and the persistence theory of discrete dynamical systems. Numerical simulations using model systems parametrized in terms of the antiretroviral therapy recommended in the aforementioned Manuals illustrate the theoretical threshold virus dynamics, and examine conditions under which the impulsive antiretroviral therapy leads to treatment success. In particular, our results show that only the drug-resistant strain can dominate (the first-line treatment program guided by the Manuals) or both strains may be rapidly eliminated (the second-line treatment program), thus the work indicates the importance of implementing the second-line treatment program as soon as possible. PMID:21987085

Lou, Jie; Lou, Yijun; Wu, Jianhong

2012-10-01

193

The immune reconstitution inflammatory syndrome with tuberculosis: a common problem in Ethiopian HIV-infected patients beginning antiretroviral therapy.  

PubMed

The Immune Reconstitution Inflammatory Syndrome (IRIS) in Ethiopian HIV-infected patients coinfected with tuberculosis (TB) was studied. HIV-infected outpatients initiating antiretroviral therapy (ART) at an HIV clinic in northern Ethiopia from January 2007 through September 2008 were identified (n = 1977). Patients with TB-IRIS occurring within 6 months of starting ART (n = 143) were compared with a control group of patients with HIV who began ART but did not develop TB-IRIS (n = 277). ART was not interrupted in any patient. Eleven (8%) patients with TB-IRIS died. New or "unmasked" TB with accompanying IRIS occurred in 132 or 92% of the cases. Worsening or "paradoxical" TB (ie, already known to be present and treated) was accompanied by IRIS in 11 (8%) patients. There was no significant difference between "unmasked" and "paradoxical" cases with respect to presentation of disease and outcome. Only a low baseline CD4 count (mean: 102 cells/?L) and a past history of World Health Organization (WHO) Clinical Stage 3 or 4 were associated with TB-IRIS (P < .05). The clinical manifestations of TB-IRIS were diverse, requiring a high index of suspicion. For example, pleural disease occurred in 13 patients, TB lymphadenitis in 17, intracranial TB in 9 patients, and disseminated TB in 15 patients. The majority of patients (88%) responded to continuation of ART and TB therapy. Thus, TB-IRIS is common in Ethiopian patients beginning ART, occurring in 7% of patients initiating antiretroviral therapy. PMID:21521804

Ali, Kedir; Klotz, Stephen A

2012-01-01

194

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

PubMed Central

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

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

2013-01-01

195

30 CFR 57.10010 - Starting precautions.  

Code of Federal Regulations, 2013 CFR

...AND HEALTH SAFETY AND HEALTH STANDARDS-UNDERGROUND METAL AND NONMETAL MINES Aerial Tramways § 57.10010 Starting precautions. Where possible, aerial tramways shall not be started until the operator has ascertained that everyone is...

2013-07-01

196

30 CFR 56.10010 - Starting precautions.  

Code of Federal Regulations, 2013 CFR

...SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES Aerial Tramways § 56.10010 Starting precautions. Where possible, aerial tramways shall not be started until the operator has ascertained that everyone is...

2013-07-01

197

Patient Retention and Adherence to Antiretrovirals in a Large Antiretroviral Therapy Program in Nigeria: A Longitudinal Analysis for Risk Factors  

Microsoft Academic Search

BackgroundSubstantial resources and patient commitment are required to successfully scale-up antiretroviral therapy (ART) and provide appropriate HIV management in resource-limited settings. We used pharmacy refill records to evaluate risk factors for loss to follow-up (LTFU) and non-adherence to ART in a large treatment cohort in Nigeria.Methods and FindingsWe reviewed clinic records of adult patients initiating ART between March 2005 and

Man Charurat; Modupe Oyegunle; Renata Benjamin; Abdulrazaq Habib; Emeka Eze; Prince Ele; Iquo Ibanga; Samuel Ajayi; Maria Eng; Prosanta Mondal; Usman Gebi; Emilia Iwu; Mary-Ann Etiebet; Alash'le Abimiku; Patrick Dakum; John Farley; William Blattner; Landon Myer

2010-01-01

198

Phase Shifter Start/Stop Electronic Trimming.  

National Technical Information Service (NTIS)

The phase shifter start/stop electronic trimming circuit provides a means for electronically trimming phase shifters when stop/start two-axis steering is used. A time delay is incorporated into the start logic line of each phase shifter driver allowing th...

J. M. Loomis

1981-01-01

199

Shining Bright: Head Start Inclusion. [Videotape].  

ERIC Educational Resources Information Center

This video features teachers and parents commenting on the Manhattan-Ogden (Kansas) school district's successful collaboration with the local Head Start program to gradually include disabled children in the regular Head Start classroom. Teachers describe how disabled children had been segregated at the Head Start school and how, after attempts at…

Lindeman, David P.; Adams, Tracy

200

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

201

Structural Model of Head Start Classroom Quality.  

ERIC Educational Resources Information Center

Previous research has not statistically analyzed the teacher and classroom structural characteristics related to the quality of Head Start. This study developed, tested, and validated a model to identify the characteristics and beliefs of Head Start teachers and teacher aides and the classroom structural dimensions associated with Head Start

Abbott-Shim, Martha; Lambert, Richard; McCarty, Frances

202

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-naïve 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.

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

2014-01-01

203

Sex differences in HIV outcomes in the highly active antiretroviral therapy era: a systematic review.  

PubMed

To assess sex disparities in AIDS clinical and laboratory outcomes in the highly active antiretroviral therapy (HAART) era we conducted a systematic review of the published literature on mortality, disease progression, and laboratory outcomes among persons living with HIV and starting HAART. We performed systematic PubMed and targeted bibliographic searches of observational studies published between January, 1998, and November, 2013, that included persons starting HAART and reported analyses of mortality, progression to AIDS, or virologic or immunologic treatment outcomes by sex. Risk ratios (relative risks, odd ratios, and hazard ratios) and 95% confidence intervals were obtained. Sixty-five articles were included in this review. Thirty-nine studies were from North America and Europe and 26 were from Latin America, Asia, and Africa. Forty-four studies (68%) showed no statistically significant difference in risk of mortality, progression to AIDS, or virologic or immunologic treatment outcomes by sex. Decreased risk of death among females compared to males was observed in 24 of the 25 articles that included mortality analyses [pooled risk ratio 0.72 (95% confidence interval=0.69-0.75)], and decreased risk of death or AIDS was observed in 9 of the 13 articles that examined the composite outcome [pooled risk ratio=0.91 (0.84-0.98)]. There was no significant effect of sex on the risk of progression to AIDS [pooled risk ratio=1.15 (0.99-1.31)]. In this systematic review, females starting HAART appeared to have improved survival compared to males. However, this benefit was not associated with decreased progression to either AIDS or to differences in virologic or immunologic treatment outcomes. PMID:24401107

Castilho, Jessica L; Melekhin, Vlada V; Sterling, Timothy R

2014-05-01

204

Predictors of Tuberculosis in the? First Six Months after Initiation of Antiretroviral Therapy: a Case-Control Study  

PubMed Central

SUMMARY Setting Adult HIV clinic in Tanzania. Objective In Africa, 10% of HIV infected adults starting antiretroviral therapy (ART) die within the first year, and tuberculosis (TB) is the leading cause of death. In this study, we investigated the predictors of ART-associated TB. Design In this nested case-control study, adults starting ART were screened for TB according to the WHO protocol and those not diagnosed with TB were observed for six months. Patients diagnosed with tuberculosis were defined as cases, and controls were selected from among patients who did not develop tuberculosis using incidence density matching. Results Among the 2514 HIV positive adults in our cohort, 72 (3%) were diagnosed with TB during the first six months of ART. By multivariate analysis, baseline characteristics predictive of TB were cough, fever, and night sweats and 76% (55/72) of cases had at least one of these symptoms at the time of starting ART. Conclusion 75% of patients who developed TB during the first six months of ART had symptoms of TB at time of starting ART but the symptoms were sub-diagnostic. Improved TB diagnostics and/or better strategies for empirical anti-TB are needed for patients with symptoms of TB at ART initiation.

Peck, Robert N.; Luhanga, Andrew; Kalluvya, Samuel; Todd, Jim; Lugoba, Shibide; Fitzgerald, Daniel W.; Downs, Jennifer A.

2013-01-01

205

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.

Gutierrez, Felix; Padilla, Sergio; Masia, Mar; Iribarren, Jose A.; Moreno, Santiago; Viciana, Pompeyo; Munoz, Leopoldo; Sirvent, Jose L. Gomez; Vidal, Francesc; Lopez-Aldeguer, Jose; Blanco, Jose R.; Leal, Manuel; Rodriguez-Arenas, Maria Angeles; Hoyos, Santiago Perez

2006-01-01

206

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

PubMed

HIV-1-associated Guillan-Barre syndrome (hGBS) is an ascendant progressive polyradiculoneuropathy described throughout the course of the viral disease, mainly associated with the acute retroviral syndrome. HGBS is occasionally described in severely immunocompromised subjects in the context of the immune reconstitution inflammatory syndrome. The case described occurred soon after the start of a combined antiretroviral treatment in an HIV-1 infected patient with ulcerative colitis in the absence of severe immunosuppression. This manifestation may be interpreted as an uncommon appearance of an immune reconstitution syndrome in the presence of a predisposing autoimmune pathology. PMID:24531178

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

2014-01-01

207

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

Microsoft Academic Search

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

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

2003-01-01

208

Prescribing and using self-injectable antiretrovirals: How concordant are physician and patient perspectives?  

Microsoft Academic Search

BACKGROUND: The selection of agents for any treatment regimen is in part influenced by physician and patient attitudes. This study investigated attitudinal motivators and barriers to the use of self-injectable antiretroviral agents among physicians and patients and measured the degree of concordance between physician and patient perspectives. METHODS: Attitudes toward prescribing and usage of self-injectable antiretroviral therapy (SIAT) were assessed

Robert Horne; Colin Kovacs; Christine Katlama; Bonaventura Clotet; Carmina R Fumaz; Michael Youle; Ranjababu Kulasegaram; Martin Fisher; Calvin Cohen; Jihad Slim; Peter Shalit; Vanessa Cooper; Christos Tsoukas

2009-01-01

209

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

Microsoft Academic Search

BackgroundThe 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

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

2008-01-01

210

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

Microsoft Academic Search

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

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

2008-01-01

211

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

212

Two strategies to increase adherence to HIV antiretroviral medication: Life-Steps and medication monitoring  

Microsoft Academic Search

Advances in the medical treatment of HIV have made it clear that adherence to highly active antiretroviral treatment is a crucial feature for treatment success. The present paper had two goals: (1) to examine psychosocial predictors of adherence in persons receiving HIV antiretroviral therapy; (2) to compared two minimal-treatment interventions to increase HIV medication adherence in a subset of persons

Steven A. Safren; Michael W. Otto; Jonathan L. Worth; Elizabeth Salomon; William Johnson; Kenneth Mayer; Steven Boswell

2001-01-01

213

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

PubMed Central

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

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

2012-01-01

214

Decline in HIV infectivity following the introduction of highly active antiretroviral therapy  

Microsoft Academic Search

Objective: Little is known about the degree to which widespread use of antiretroviral therapy in a community reduces uninfected individuals' risk of acquiring HIV. We estimated the degree to which the probability of HIV infection from an infected partner (the infectivity) declined following the introduction of highly active antiretroviral therapy (HAART) in San Francisco. Design: Homosexual men from the San

Travis C. Porco; Jeffrey N. Martin; Kimberly A. Page-shafer; Amber Cheng; Edwin Charlebois; Robert M. Grant; Dennis H. Osmond

2004-01-01

215

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

216

Factors associated with self-reported adherence to antiretroviral therapy in a Tanzanian setting  

Microsoft Academic Search

This study aimed to determine the level of antiretroviral adherence and factors associated with adherence among patients receiving free antiretroviral therapy (ART) at one clinic in Tanzania. Adult patients were recruited into the cross-sectional study and completed a survey that included self-reported adherence over four days and over one month. Less than 95% adherence on either measure was considered “poor.”

Melissa H. Watt; Suzanne Maman; Carol E. Golin; Jo Anne Earp; Eugenia Eng; Shrikant I. Bangdiwala; Mark Jacobson

2010-01-01

217

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

Microsoft Academic Search

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

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

2007-01-01

218

Antiretroviral treatment adherence among HIV patients in KwaZulu-Natal, South Africa  

Microsoft Academic Search

BACKGROUND: Successful antiretroviral treatment is dependent on sustaining high rates of adherence. In the southern African context, only a handful of studies (both quantitative and qualitative) have looked at the determinants including a health behaviour theory of adherence to antiretroviral therapy. The aim of this study is to assess factors including the information, motivation and behavioural skills model (IMB) contributing

Karl Peltzer; Natalie Friend-du Preez; Shandir Ramlagan; Jane Anderson

2010-01-01

219

Assessment of an Antiretroviral Adherence Sensitivity Training Exercise in the Doctor Of Pharmacy Curriculum  

Microsoft Academic Search

The degree of HIV viral suppression is closely linked to the patient's ability to adhere to complex antiretroviral medication regimens. Unfortunately, numerous reports indicate that healthcare professionals have difficulty understanding the adherence problems that patients who are HIV- positive may encounter. The purpose of this project was to assess the value of performing an antiretroviral adherence sensitivity training exercise in

Douglas Slain; Diane Casdorph; Thomas Mclntire

2002-01-01

220

Adherence to Antiretroviral Therapy in an Urban, Free-Care HIV Clinic in Guatemala City, Guatemala  

Microsoft Academic Search

Background: Numerous studies have demonstrated that, in addition to inherent qualities of antiretroviral (ARV) medications, adherence is affected by demographic, socioeconomic, and psychological factors. There are limited data about factors affecting adherence to antiretroviral therapy (ART) among HIV-infected persons in urban Guatemalan HIV care centers. Methods: Participants were patients at an urban, free-care public clinic in Guatemala City and obtained

Jeffrey I. Campbell; Ana Lucía Ruano; Blanca Samayoa; Dina Lorena Estrado Muy; Eduardo Arathoon; Benjamin Young

2010-01-01

221

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

PubMed

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

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

2012-02-01

222

Does antiretroviral therapy increase or decrease the risk of cardiovascular disease?  

PubMed

Atherosclerosis is a complex inflammatory process that has been identified as an important problem in persons with HIV infection. Epidemiologic studies have linked certain antiretroviral medications (some nucleoside reverse transcriptase inhibitors and protease inhibitors) with a higher risk of coronary heart disease (CHD). Conversely, nonnucleoside reverse transcriptase inhibitors, entry inhibitors, and integrase inhibitors appear neutral. HIV infection is a chronic inflammatory process associated with endothelial dysfunction, atherogenic dyslipidemia, and a higher risk for CHD. Initiation of antiretroviral therapy in the short term appears to lower CHD risk, regardless of the specific agents used. However, adequately powered randomized trials of antiretroviral therapy with CHD as a primary end point are lacking. Thus, the evidence of whether antiretroviral therapy increases or decreases CHD risk in persons with HIV is perplexing. This article reviews the current controversy of the role of HIV and antiretroviral therapy in the development of cardiovascular disease. PMID:20425563

Fichtenbaum, Carl J

2010-05-01

223

Mediators of antiretroviral adherence: a multisite international study  

PubMed Central

The purpose of this study was to investigate the effects of stressful life events (SLE on medication adherence (3 day, 30 day) as mediated by sense of coherence (SOC), self-compassion (SCS), and engagement with the health care provider (eHCP) and whether this differed by international site. Data were obtained from a cross-sectional sample of 2082 HIV positive adults between September 2009 and January 2011 from sites in Canada, China, Namibia, Puerto Rico, Thailand and the U.S. Statistical tests to explore the effects of stressful life events on antiretroviral medication adherence included descriptive statistics, multivariate analysis of variance (MANOVA), analysis of variance (ANOVA) with Bonferroni post-hoc analysis, and path analysis. An examination by international site of the relationships between SLE, SCS, SOC and eHCP with adherence (3 day, 30 day) indicated these combined variables were related to adherence whether 3 day or 30 day to different degrees at the various sites. SLE, SCS, SOC, and eHCP were significant predictors of adherence past 3 days for the U.S (p= <.001), Canada (p= .006), and Namibia (p= .019). The combined independent variables were significant predictors of adherence past 30 days only in the U.S. and Canada. Engagement with the provider was a significant correlate for antiretroviral adherence in most, but not all, of these countries. Thus the importance of eHCP cannot be overstated. Nonetheless, our findings need to be accompanied by the caveat that research on variables of interest while enriched by a sample obtained from international sites, may not have the same relationships in each country. Mediators of antiretroviral adherence: a multisite international study

Corless, I. B.; Guarino, A.J.; Nicholas, P.K.; Tyer-Viola, L; Kirksey, K.; Brion, J.; Rose, Dawson; Eller, L.S.; Rivero-Mendez, M.; Kemppainen, J.; Nokes, K.; Sefcik, E.; Voss, J.; Wantland, D.; Johnson, M.O.; Phillips, C.J.; Webel, A.; Iipinge, S.; Portillo, C.; Wei-Ti-Chen; Maryland, M.; Hamilton, M. J; Reid, P.; Hickey, D.; Holzemer, W.L.

2012-01-01

224

Prevention of HIV-1 Infection with Early Antiretroviral Therapy  

PubMed Central

Background Antiretroviral therapy that reduces viral replication could limit the transmission of human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples. Methods In nine countries, we enrolled 1763 couples in which one partner was HIV-1–positive and the other was HIV-1–negative; 54% of the subjects were from Africa, and 50% of infected partners were men. HIV-1–infected subjects with CD4 counts between 350 and 550 cells per cubic millimeter were randomly assigned in a 1:1 ratio to receive antiretroviral therapy either immediately (early therapy) or after a decline in the CD4 count or the onset of HIV-1–related symptoms (delayed therapy). The primary prevention end point was linked HIV-1 transmission in HIV-1–negative partners. The primary clinical end point was the earliest occurrence of pulmonary tuberculosis, severe bacterial infection, a World Health Organization stage 4 event, or death. Results As of February 21, 2011, a total of 39 HIV-1 transmissions were observed (incidence rate, 1.2 per 100 person-years; 95% confidence interval [CI], 0.9 to 1.7); of these, 28 were virologically linked to the infected partner (incidence rate, 0.9 per 100 person-years, 95% CI, 0.6 to 1.3). Of the 28 linked transmissions, only 1 occurred in the early-therapy group (hazard ratio, 0.04; 95% CI, 0.01 to 0.27; P<0.001). Subjects receiving early therapy had fewer treatment end points (hazard ratio, 0.59; 95% CI, 0.40 to 0.88; P = 0.01). Conclusions The early initiation of antiretroviral therapy reduced rates of sexual transmission of HIV-1 and clinical events, indicating both personal and public health benefits from such therapy.

Cohen, Myron S.; Chen, Ying Q.; McCauley, Marybeth; Gamble, Theresa; Hosseinipour, Mina C.; Kumarasamy, Nagalingeswaran; Hakim, James G.; Kumwenda, Johnstone; Grinsztejn, Beatriz; Pilotto, Jose H.S.; Godbole, Sheela V.; Mehendale, Sanjay; Chariyalertsak, Suwat; Santos, Breno R.; Mayer, Kenneth H.; Hoffman, Irving F.; Eshleman, Susan H.; Piwowar-Manning, Estelle; Wang, Lei; Makhema, Joseph; Mills, Lisa A.; de Bruyn, Guy; Sanne, Ian; Eron, Joseph; Gallant, Joel; Havlir, Diane; Swindells, Susan; Ribaudo, Heather; Elharrar, Vanessa; Burns, David; Taha, Taha E.; Nielsen-Saines, Karin; Celentano, David; Essex, Max; Fleming, Thomas R.

2011-01-01

225

Antiretroviral adherence during pregnancy and postpartum in Latin America.  

PubMed

Adherence to antiretrovirals by pregnant women (and postpartum women if breastfeeding) is crucial to effectively decrease maternal viral load and decrease the risk of mother-to-child transmission of HIV. Our objectives were to describe self-reported adherence to antiretrovirals during the antepartum (after 22 weeks of pregnancy) and postpartum periods (6-12 weeks and 6 months), and identify predictors of adherence among HIV-infected women enrolled and followed in a prospective cohort study from June 2008 to June 2010 at multiple sites in Latin America. Adherence was evaluated using the number of missed and expected doses during the 3 days before the study visit. At the pre-delivery visit, 340 of 376 women (90%) reported perfect adherence. This rate significantly decreased by 6-12 weeks (171/214 [80%]) and 6 months postpartum (163/199 [82%], p<0.01). The odds for less than perfect adherence at the pre-delivery visit was significantly higher for pregnant women with current tobacco use (odds ratio [OR]=2.9, 95% confidence interval [CI]: 1.46-6.14; p=0.0029). At 6-12 weeks postpartum, the probability of non-perfect adherence increased by 6% for each 1 year increase in age (OR=1.06, 95% CI: 1.00-1.12, p=0.0497). At 6 months postpartum, the odds of nonperfect adherence was higher for those who were currently using alcohol (OR=3.04, 95% CI: 1.34-6.90; p=0.0079). Although a self-report measure of adherence based on only 3 days may lead to overestimation of actual adherence over time, women with perfect adherence had lower viral loads and higher CD4 counts. Adherence to antiretrovirals decreased significantly postpartum. Interventions should target women at high risk for lower adherence during pregnancy and postpartum, including tobacco and alcohol users. PMID:22663185

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

2012-08-01

226

Antiretroviral Adherence During Pregnancy and Postpartum in Latin America  

PubMed Central

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

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

2012-01-01

227

Approaches to rationing antiretroviral treatment: ethical and equity implications.  

PubMed Central

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

Bennett, Sara; Chanfreau, Catherine

2005-01-01

228

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

PubMed Central

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

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

2013-01-01

229

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

PubMed

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

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

2014-03-01

230

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

PubMed

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

Dunbar, Deanne

2011-06-01

231

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

232

Regulatory Considerations for Antiretroviral Prophylaxis to Prevent HIV Acquisition.  

PubMed

Antiretrovirals (ARVs) decrease the infectiousness of treated HIV-infected persons and can reduce the acquisition of HIV infection when taken by uninfected persons. Coformulated emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) is approved in the United States for the preexposure prophylaxis (PrEP) indication, changing the regulatory landscape for new prophylactic agents. We describe the challenge of conducting rigorous clinical end-point trials for prophylactic agents and point to alternatives that leverage new information about correlates of HIV risk and protection. PMID:25056397

Miller, V; Grant, R M

2014-08-01

233

Generic antiretroviral drugs in developing countries: friends or foes?  

PubMed

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

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

2014-02-20

234

Start II, red ink, and Boris Yeltsin  

SciTech Connect

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

Arbatov, A.

1993-04-01

235

START user manual version 2.1  

NASA Astrophysics Data System (ADS)

The Simulation Tool for Atmospheric Reentry Trajectories (START) version 2.1 is presented. The software is capable of doing six degrees of freedom reentry simulations, starting with a deorbit burn maneuver in orbit. After the atmospheric entry, the descent under a parachute can be simulated as well. Central bodies included are: Earth, the Moon, Mars and Titan. The program was equipped with a menu oriented user interface, giving full access to the input data. The manual is focused on how to use the software. Before discussing the capabilities of START, a short overview of START and some general remarks on the user interface are given.

Mooij, E.

1993-07-01

236

Adapting a Computer Curriculum to Head Start.  

ERIC Educational Resources Information Center

Describes the development and implementation of the Activating Children through Technology (ACTT) computer curriculum in Parents and Child Together (PACT) Head Start classrooms in Springfield, Illinois. (BB)

Hutinger, Patricia L.; And Others

1990-01-01

237

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.

2013-01-01

238

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

PubMed Central

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

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

2013-01-01

239

Structural barriers to timely initiation of antiretroviral treatment in Vietnam: findings from six outpatient clinics.  

PubMed

In Vietnam, premature mortality due to AIDS-related conditions is commonly associated with late initiation to antiretroviral therapy (ART). This study explores reasons for late ART initiation among people living with HIV (PLHIV) from the perspectives of health care providers and PLHIV. The study was undertaken in six clinics from five provinces in Vietnam. Baseline CD4 counts were collected from patient records and grouped into three categories: very late initiators (?100 cells/mm(3) CD4), late initiators (100-200 cells/mm(3)) and timely initiators (200-350 cells/mm(3)). Thirty in-depth interviews with patients who started ART and 15 focus group discussions with HIV service providers were conducted and thematic analysis of the content performed. Of 934 patients, 62% started ART very late and 11% initiated timely treatment. The proportion of patients for whom a CD4 count was obtained within six months of their HIV diagnosis ranged from 22% to 72%. The proportion of patients referred to ART clinics by voluntary testing and counselling centres ranged from 1% to 35%. Structural barriers to timely ART initiation were poor linkage between HIV testing and HIV care and treatment services, lack of patient confidentiality and a shortage of HIV/AIDS specialists. If Vietnam's treatment practice is to align with WHO recommendations then the connection between voluntary counselling and testing service and ART clinics must be improved. Expansion and decentralization of HIV/AIDS services to allow implementation at the community level increased task sharing between doctors and nurses to overcome limited human resources, and improved patient confidentiality are likely to increase timely access to HIV treatment services for more patients. PMID:23240013

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

2012-01-01

240

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

241

Effect of baseline renal function on tenofovir-containing antiretroviral therapy outcomes in zambia.  

PubMed

Background.?Although tenofovir disoproxil fumarate (TDF) use has increased as part of first-line antiretroviral therapy (ART) across sub-Saharan Africa, renal outcomes among patients receiving TDF remain poorly understood. We assessed changes in renal function and mortality in patients starting TDF- or non-TDF-containing ART in Lusaka, Zambia. Methods.?We included patients aged ?16 years who started ART from 2007 onward, with documented baseline weight and serum creatinine. Renal dysfunction was categorized as mild (estimated glomerular filtration rate [eGFR], 60-89 mL/min), moderate (30-59 mL/min), or severe (<30 mL/min) according to the chronic kidney disease-epidemiology (CKD-EPI) formula. Differences in eGFR during ART were analyzed using linear mixed-effect models. The odds of developing moderate or severe eGFR decrease and mortality were assessed using logistic and competing risk regression, respectively. Results.?We included 62 230 adults, of which 38 716 (62.2%) initiated a TDF-based regimen. The proportion with moderate or severe renal dysfunction at baseline was lower in the TDF than in the non-TDF group (1.9% vs 4.0%). Among patients with no or mild renal dysfunction, those receiving TDF were more likely to develop moderate (adjusted odds ratio, 3.11; 95% confidence interval, 2.52-3.87) or severe ( 2.43; 1.80-3.28) eGFR decrease, although the incidence in such episodes was low. Among patients with moderate or severe renal dysfunction at baseline, renal function improved independently of ART regimen, and mortality rates were similar in both treatment groups. Conclusions.?TDF use did not attenuate renal function recovery or increase the mortality rate in patients with renal dysfunction. Further studies are needed to determine the role of routine renal function monitoring before and during ART use in Africa. PMID:24585558

Mulenga, Lloyd; Musonda, Patrick; Mwango, Albert; Vinikoor, Michael J; Davies, Mary-Ann; Mweemba, Aggrey; Calmy, Alexandra; Stringer, Jeffrey S; Keiser, Olivia; Chi, Benjamin H; Wandeler, Gilles

2014-05-01

242

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.

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

2013-01-01

243

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

PubMed Central

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

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

2013-01-01

244

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-naïve 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

245

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

PubMed Central

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

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

2010-01-01

246

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

PubMed Central

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

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

2014-01-01

247

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

PubMed Central

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

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

2012-01-01

248

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

PubMed

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

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

2014-01-01

249

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

250

JobStart: The Road to Independence.  

ERIC Educational Resources Information Center

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

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

251

Getting Started: What's Your Fitness Level?  

MedlinePLUS

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

252

The Phenomenon of Business Start-Ups.  

ERIC Educational Resources Information Center

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

Melis, Africa

1990-01-01

253

Head Start Home-Based Resource Directory.  

ERIC Educational Resources Information Center

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

Trans-Management Systems, Inc.

254

Impact Of Transient Inrush On MOV Starting  

Microsoft Academic Search

This paper is the result of a recent NRC concern with the impact of transient inrush current on motor operated valve (MOV) starting. It provides the background for this issue, discusses the accuracy of measured current traces, presents the theory behind transient inrush, analyzes a set of VOTES test data, and discusses its impact on motor starting to determine whether

R. H. Buchert; C. E. Beck

1993-01-01

255

Head Start Impact Study. Technical Report  

ERIC Educational Resources Information Center

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

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

256

Design improvements in air turbine start systems  

NASA Astrophysics Data System (ADS)

The main engine air turbine start system, which typically consists of an air turbine staxter and starter control valve, is a key contributor to aircraft dispatch reliability. Evolving aircraft propulsion systems have resulted in more aggressive operational environments, thus providing the impetus to improve the design of the start systems to enhance their durability and aid in improving both dispatch reliability and system responsiveness.

Farnsworth, G. A.; Plevich, C. W.; Durnal, K.

1992-10-01

257

Head Start's Broken Promise. On the Issues  

ERIC Educational Resources Information Center

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

Besharov, Douglas J.

2005-01-01

258

Photosensitization is required for antiretroviral activity of hypericin  

NASA Astrophysics Data System (ADS)

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

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

1991-06-01

259

Antimalaria Action of Antiretroviral Drugs on Plasmodium berghei in Mice  

PubMed Central

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

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

2013-01-01

260

Antiretroviral chemoprophylaxis: state of evidence and the research agenda.  

PubMed

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

Mayer, Kenneth H

2014-07-01

261

Informed consent in an antiretroviral trial in Nigeria.  

PubMed

We examined the process of informed consent in an antiretroviral trial in Nigeria. A semi-structured questionnaire was administered to 88 out of 180 people enrolled in the trial. This covered all aspects of the information disclosed in the leaflet of the antiretroviral trial. We found that 75 (85 per cent) of the respondents knew that the purpose of the research was to test a new drug and 13 (14 per cent) believed that they were receiving free treatment for HIV. Participants understood certain aspects of the research, especially the benefits and duration. Their understanding of the trial's risks and their right to refuse to participate and to withdraw was low. Their level of understanding was significantly related to age but not to gender, marriage, education, religion, employment and occupation. Signed informed consent is not a guarantee that participants have understood the information given to them and therefore made a voluntary decision to participate. Researchers should make sure that the process of obtaining informed consent achieves the desired outcome. This is especially important in the developing world where access to health care is limited, potential participants are poor and literacy levels are low. PMID:18630217

Manafa, Ogenna; Lindegger, Graham; Ijsselmuiden, Carel

2007-01-01

262

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.

Gavegnano, Christina; Schinazi, Raymond F

2010-01-01

263

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

PubMed Central

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

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

2013-01-01

264

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

Ene, L; Duiculescu, D; Ruta, SM

2011-01-01

265

Soft start of submersible pumped oil wells  

SciTech Connect

Cyclic operation of submersible pumping is considered undesirable because of the start-stop characteristics of the installation. ''Across-the-line'' starting results in large current surges, typically five to eight times running current. Such surges can damage the motor and its cable and also cause line voltage irregularities. Also, stopping can result in significant amperage and voltage spikes. Because of this, most operators are very reluctant to start and stop a submersible pumping installation any more often than absolutely necessary. This creates design problems in sizing the pump. Reduced-voltage starting should minimize the severe strain imposed on the electrical system by an instantaneous start. A reduced-voltage solid-state starter using six silicon-controlled rectifiers was tested between Nov. 1981 and March 1982. The current surge on start was limited to about 2.5 times full-load amperage. The time required to bring the motor to full speed was increased from about 0.25 seconds to 1.3 seconds. The well was cycling on-off about six times per day. The unit was start-stopped about 900 times during the test. A prototype production model is available.

Neeley, A.B.; Patterson, M.M.

1984-04-01

266

Healthy start lessons learned on interconception care.  

PubMed

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

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

2008-01-01

267

Healthy start program participation: the consumers' perspective.  

PubMed

In 1991, the federal Maternal and Child Health Bureau developed the Healthy Start Initiative as a comprehensive community-based program to eliminate the high rates of poor pregnancy outcomes among women of color. To date, few studies of the programmatic outcomes of this Initiative have examined the views of Healthy Start consumers. To understand the benefits of Healthy Start from their consumers' perspective, the Pittsburgh Allegheny County Healthy Start project conducted a survey of 202 of their Healthy Start participants in 2003. The participants completing the survey reported benefits of participating in the program including stress reduction, receiving resources and referrals, and consistent social support of program staff. According to the project's annual statistics, Healthy Start has improved pregnancy outcomes among African American women participants in the Pittsburgh community. However, and according to these participants, the quality of staff and consumer connectedness, availability and consistency of material resources, and social support are as critical as more traditional health interventions to their satisfaction, motivation to participate, and willingness to refer others to the program. Women of color will often forego health services perceived as intimidating and/or culturally insensitive, but programs such as the Healthy Start Initiative offer a critical link that encourages participation and, as a result, improves maternal and child health status. PMID:21213185

Ley, Christine E; Copeland, Valire Carr; Flint, Cheryl Squire

2011-01-01

268

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

269

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

270

Physics of Tokamak Plasma Start-up  

NASA Astrophysics Data System (ADS)

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

Mueller, Dennis

2012-10-01

271

High Initial HIV/AIDS-Related Mortality and -Its Predictors among Patients on Antiretroviral Therapy in the Kagera Region of Tanzania: A Five-Year Retrospective Cohort Study  

PubMed Central

We examined mortality rates and its predictors from a five years retrospective cohort data of HIV/AIDs patients attending care and treatment clinic in Biharamulo Tanzania. Cox regression analysis was used to identify predictors of mortality. Of the 546 patient records retrieved, the mean age was 37 years with median CD4 count of 156 cells. The mortality rate was 4.32/100 person years at risk with males having three times higher mortality compared to females. Starting Antiretroviral treatment with advanced disease state, body weight below 45 kegs, WHO stage 4 disease, and CD4 cells below 50 were main predictors of mortality. Promoting early voluntary counselling and testing should be given a priority to facilitate timely start of treatment.

Mageda, Kihulya; Leyna, Germana Henry; Mmbaga, Elia John

2012-01-01

272

Cutaneous Adverse Reactions to Highly Antiretroviral Therapy in HIV-Positive Patients  

PubMed Central

Adverse drug reactions to highly antiretroviral therapy (HAART) are major obstacles in its success. Although overall mortality from HIV has dramatically declined owing to HAART, these antiretroviral regimens have been associated with a wide spectrum of severe cutaneous reactions. The severity of cutaneous adverse reactions varies greatly, and some may be difficult to manage. To optimize adherence and efficacy of antiretroviral treatment, clinicians must focus on preventing adverse effects whenever possible, and distinguish those that are self-limited from those that are potentially serious. This paper presents the case of a serious cutaneous adverse reaction to Atripla in a HIV-positive 50-year-old Caucasian woman.

Pistone, G.; Pistone, A.; Sorbello, D.; Viviano, E.; Bongiorno, M.R.

2014-01-01

273

A study on VSC-HVDC based black start compared with traditional black start  

Microsoft Academic Search

A good black-start scheme is important and necessary to resume power supply fast and efficiently after black out, and how to choose black-start power is the first thing to consider in the scheme. In this paper, the advantages of VSC-HVDC as black start power are analyzed with contrast to traditional black start power. The ability of VSC-HVDC to soft energize

Sheng Li; Mingxia Zhou; Zongqi Liu; Jianhua Zhang; Yinhui Li

2009-01-01

274

Starting a Community Orchard in North Dakota.  

National Technical Information Service (NTIS)

This publication is a guide to help North Dakotans start community orchards. We discuss the basics of establishing the orchard and selecting cultivars. We describe organizational structures, financial considerations, and highlight the activities of other ...

T. J. Kalb

2011-01-01

275

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

276

76 FR 70009 - Head Start Program  

Federal Register 2010, 2011, 2012, 2013

...Administration for Children and Families...AND HUMAN SERVICES Administration for Children and Families 45 CFR Part 1307 RIN 0970-AC44...Head Start (OHS), Administration for Children and Families (ACF), Department...

2011-11-09

277

The physics of tokamak start-up  

NASA Astrophysics Data System (ADS)

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

Mueller, D.

2013-05-01

278

34 CFR 200.16 - Starting points.  

Code of Federal Regulations, 2013 CFR

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

2013-07-01

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. 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. [Princeton Plasma Physics Laboratory, P.O. Box 451 Princeton, New Jersey 08543 (United States)] [Princeton Plasma Physics Laboratory, P.O. Box 451 Princeton, New Jersey 08543 (United States)

2013-05-15

280

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

ERIC Educational Resources Information Center

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

Gopalan, Pritha

281

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

PubMed Central

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

2012-01-01

282

Starting algorithms for some DIRK methods  

NASA Astrophysics Data System (ADS)

When differential equations are solved with implicit Runge-Kutta methods, the computational effort is dominated by the cost of solving the nonlinear systems. That is why it is important to have good starting values to begin the iterations. In this paper we construct starting algorithms for some DIRK methods. Numerical experiments have been carried out in order to compare the initializers studied in this paper with others used in the literature.

Higueras, Inmaculada; Roldán, Teo

2000-07-01

283

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

PubMed

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

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

2013-10-01

284

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.

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

2013-01-01

285

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

PubMed

Since 2004, Georgia achieved universal access to free antiretroviral therapy (ART). A retrospective cohort study was conducted to evaluate the outcomes of Georgia's ART program. The study included adult patients enrolled in the ART program from 2004 through 2009. Of 752 patients, 76% were men, 60% were injection drug users (IDU), 59% had a history of an AIDS-defining illness, and 53% were coinfected with hepatitis C. The median baseline CD4 cell count was 141?cells/mm(3). During followup, 152 (20%) patients died, with the majority of deaths occurring within 12 months of ART initiation. Mortality was associated with advanced immunodeficiency or the presence of incurable disease at baseline. Among patients remaining on treatment, the median CD4 gain was 216?cell/mm(3) and 86% of patients had viral load <400 copies/ml at the last clinical visit. The Georgia ART program has been successful in treating injection drug users infected with HIV. PMID:21490781

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

2011-01-01

286

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

PubMed Central

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

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

2011-01-01

287

Relationship of Prospective Memory to Neuropsychological Function and Antiretroviral Adherence  

PubMed Central

Prospective memory is defined as the ability to “remember to remember” something at a future time despite intervening distractions and may be particularly important in remembering to take prescribed medication among people infected with HIV. Ninety-seven HIV-positive participants in a clinical trial had their adherence measured by electronic pillcaps and were administered neuropsychological screening tests and the memory for intentions screening test (MIST). Factor analysis of the MIST and other neuropsychological measures identified four factors. Two were derived from MIST subscales and accounted for approximately 50% of the variance in cognitive functioning. Only one factor was significantly correlated with adherence, and this was a MIST factor. In this preliminary study, the MIST assessed a memory function that (a) could be distinguished from traditional retrospective recall and executive functioning and (b) was correlated with antiretroviral adherence.

Contardo, Christopher; Black, Anne C.; Beauvais, John; Dieckhaus, Kevin; Rosen, Marc I.

2009-01-01

288

Antiretroviral therapy in resource-poor countries: illusions and realities.  

PubMed

The prospects for antiretroviral therapy in resource-poor settings have changed recently and considerably with the availability of generic drugs, the drastic price reduction of brand-name drugs, and the simplification of treatment. However, such cost reductions, although allowing the implementation of large-scale donor programs, have yet to render treatment accessible and possible in the general population. Successfully providing HIV treatment in high-prevalence/high-caseload countries may require that we redefine the problem as a public health mass therapy program rather than a multiplication of clinical situations. The public health goal cannot simply be the reduction of morbidity and mortality for those treated but must be the reduction in morbidity and mortality for the many, that is, at a population level. PMID:15933242

Desvarieux, Moïse; Landman, Roland; Liautaud, Bernard; Girard, Pierre-Marie

2005-07-01

289

Antiretroviral Therapy-Associated Acute Motor and Sensory Axonal Neuropathy  

PubMed Central

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

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

2011-01-01

290

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

PubMed Central

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

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

2010-01-01

291

Changing predictors of mortality over time from cART start: implications for care  

PubMed Central

Objective To determine predictors of mortality and changes in those predictors over time on combination antiretroviral therapy (cART) in South Africa. Design A cohort study. Methods Using routine clinic data with up to 4 years follow-up after ART initiation and with death ascertainment from a national vital statistics register, we used proportional hazards modeling to assess baseline and time-updated predictors of mortality, and changes in strength of those predictors over time on cART. Furthermore, we compared CD4 count among individuals who died by duration on cART. Results 15,060 subjects (64% men, median CD4 count 127 cells/mm3) started antiretroviral therapy between January 2003 and January 2008. Over a median follow-up of 1.8 years, 2,658 subjects died. The baseline characteristics of WHO stage, haemoglobin, CD4 count, HIV RNA level, and symptoms were all associated with mortality during the first 12 months of cART but lost association thereafter. However time updated factors of CD4 count, body mass index, symptoms, anemia, and HIV RNA suppression remained strong predictors of death. Most recent CD4 count prior to death rose from 71 during the first 3 months of cART to 175 cells/mm3 after >3 years of cART. Conclusion Over 4 years of cART, risk of death declined and associations with mortality changed. An increase in CD4 count at death and changing associations with mortality may suggest a shift in causes of death, possibly from opportunistic infections to other infections and chronic illnesses.

Hoffmann, Christopher J; Fielding, Katherine L; Johnston, Victoria; Charalambous, Salome; Innes, Craig; Moore, Richard D; Chaisson, Richard E; Grant, Alison D; Churchyard, Gavin J

2013-01-01

292

Platelet count kinetics following interruption of antiretroviral treatment  

PubMed Central

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

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

2014-01-01

293

Methamphetamine use and neuropsychiatric factors are associated with antiretroviral nonadherence  

PubMed Central

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

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

2012-01-01

294

Highly active antiretroviral therapy: Does it Sound toxic?  

PubMed Central

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

Khoza-Shangase, Katijah

2011-01-01

295

IMPACT P1060: Antiretroviral Treatment for Children with No Peripartum Nevirapine Exposure.  

National Technical Information Service (NTIS)

Nevirapine-based antiretroviral therapy is the predominant (and often the only) regimen available for children in resource-limited settings. Nevirapine resistance after exposure to the drug for prevention of maternal-to-child human immunodeficiency virus ...

2012-01-01

296

Ocular Syphilis in HIV-Positive Patients Receiving Highly Active Antiretroviral Therapy  

Microsoft Academic Search

BackgroundFrom October 2001 to October 2002, we have observed a surprisingly high incidence of ocular syphilis in human immunodeficiency virus-positive (HIV+) patients receiving highly active antiretroviral therapy at our clinic.

Gayle P. Balba; Princy N. Kumar; Andrea N. James; Anurag Malani; Allan G. Palestine; James N. Welch; Joseph G. Timpone

2006-01-01

297

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

298

Predictors of suboptimal CD4 response among women achieving virologic suppression in a randomized antiretroviral treatment trial, Africa  

PubMed Central

Background A subset of HIV-1 infected patients starting highly active antiretroviral treatment (HAART) experience suboptimal CD4 response (SCR) despite virologic suppression. We studied the rate of and risk factors for SCR among women starting HAART in the ACTG A5208 study conducted in 7 African countries. 741 HAART-naive women with screening CD4 count <200 cells/?L were randomized to start HAART with Tenofovir/Emtricitabine plus either Nevirapine or Lopinavir/Ritonavir. Methods This analysis includes the 625 women who remained on-study through 48 weeks without experiencing protocol-defined virologic failure. We defined SCR as?starting HAART, 11% of women with virologic suppression through 48 weeks experienced SCR. These patients were also less likely to achieve CD4???350 cells/?L by 96 weeks. The underlying causes and long term clinical implications of SCR deserve further investigation. Trial registration Clinicaltrials.gov Identifier: NCT00089505

2014-01-01

299

Early mortality among adults accessing antiretroviral treatment programmes in sub-Saharan Africa  

Microsoft Academic Search

Two-thirds of the world's HIV-infected people live in sub-Saharan Africa, and more than 1.5 million of them die annually. As access to antiretroviral treatment has expanded within the region; early pessimism concerning the delivery of antiretroviral treatment using a large-scale public health approach has, at least in the short term, proved to be broadly unfounded. Immunological and virological responses to

Stephen D. Lawn; Anthony D. Harries; Xavier Anglaret; Landon Myer; Robin Wood

2008-01-01

300

A qualitative study of persons who are 100% adherent to antiretroviral therapy  

Microsoft Academic Search

This qualitative study examined the medication-taking behaviors and attitudes of participants determined to be 100% adherers to antiretroviral therapy from a NIH-funded study testing a 12-week telephone adherence intervention. Using open-ended questions, interviewers collected data on a sample of 13 informants, whose medication adherence to a randomly selected antiretroviral medication was 100%, based on a 30-day data collection using electronic

M. P. Lewis; A. Colbert; J. Erlen; M. Meyers

2006-01-01

301

Understanding the facilitators and barriers of antiretroviral adherence in Peru: A qualitative study  

Microsoft Academic Search

BACKGROUND: Antiretroviral scale-up is increasing in resource-constrained settings. To date, few studies have explored the barriers and facilitators of adherence to ART in these settings. Facilitators and barriers of antiretroviral adherence in Peru are not completely understood. METHODS: At two clinics that serve a large number of HIV-positive individuals in Lima, Peru, 31 in-depth interviews were carried out in 2006

Walter H Curioso; Deanna Kepka; Robinson Cabello; Patricia Segura; Ann E Kurth

2010-01-01

302

Acute liver failure associated with antiretroviral treatment for HIV: a report of six cases  

Microsoft Academic Search

Background\\/Aims: Severe hepatotoxicity is a rare but potentially fatal side effect of all antiretrovirals. We report a series of six human immunodeficiency virus (HIV)-infected patients admitted with acute liver failure (ALF) over a 25-month period, of whom five died. All had been treated with a range of antiretroviral therapy and only two had had acquired immune deficiency syndrome (AIDS) defining

Sarah J Clark; Sarah Creighton; Bernard Portmann; Christopher Taylor; Julia A Wendon; Matthew E Cramp

2002-01-01

303

Antiretrovirals Induce Endothelial Dysfunction via an Oxidant-Dependent Pathway and Promote Neointimal Hyperplasia  

PubMed Central

Human immunodeficiency virus-1 antiretroviral treatment is associated with an increased incidence of atherosclerosis. We hypothesized that antiretrovirals directly impair endothelial function after short-term exposure and that with chronic exposure, this dysfunction promotes a proliferative response, inducing neointimal hyperplasia, thus contributing to vascular lesion formation. To test this hypothesis, we treated mice with the nucleoside reverse transcriptase inhibitor azidothymidine (AZT), the protease inhibitor indinavir, or AZT + indinavir. Treatment with AZT or AZT + indinavir for 5 days impaired endothelium-dependent vessel relaxation. Though indinavir treatment alone did not alter vessel relaxation, it potentiated the impairment of endothelium-dependent relaxation induced by AZT. Coadministration of the antioxidant Mn (III) tetrakis (1-methyl-4-pyridyl) porphyrin attenuated antiretroviral-induced endothelial dysfunction, suggesting that oxidant production may have a causal role in the observed endothelial dysfunction. To test whether the antiretrovirals promote a proliferative response following endothelial dysfunction, we treated mice with antiretrovirals for 14 days and then induced a carotid endothelial injury. Two weeks later, we observed a dramatic increase in neointimal formation in all antiretroviral-treated animals, and the newly formed neointima was comprised mainly of proliferated smooth muscle cells. Although a functional endothelium surrounding the lesioned area and re-endothelialization across the area of injury is important in reducing proliferation in this model, we tested whether the neointimal hyperplasia was associated with endothelial dysfunction. Plasma levels of asymmetric dimethylarginine, a biomarker of endothelial dysfunction, increased after treatment with indinavir or AZT + indinavir. On the other hand, treatment with AZT or AZT + indinavir increased endothelial vascular cell adhesion molecule staining. We conclude that short-term treatment with antiretrovirals elicited a direct impairment in endothelial function, in part via an oxidant-dependent pathway. These antiretrovirals also exacerbated injury-induced vascular smooth muscle cell proliferation and neointimal hyperplasia, likely because of their inhibition of endothelial function.

Jiang, Bo; Khandelwal, Alok R.; Rogers, Lynette K.; Hebert, Valeria Y.; Kleinedler, James J.; Zavecz, James H.; Shi, Weibin; Orr, A. Wayne; Dugas, Tammy R.

2010-01-01

304

HIV antiretroviral therapy in resource-limited settings: Experiences from Haiti  

Microsoft Academic Search

An unprecedented international effort to expand high activity antiretroviral therapy (HAART) to resource-poor nations has\\u000a been launched. The World Health Organization (WHO) has created antiretroviral (ARV) treatment guidelines adapted to resource-poor\\u000a settings. The first-line regimen is two nucleoside reverse transcriptase inhibitors (NsRTIs) and one nonnucleoside reverse\\u000a transcriptase inhibitor (NNRTI). Therapy is initiated by clinical staging and CD4 T-cell counts when

Alysa Krain; Daniel W. Fitzgerald

2005-01-01

305

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

PubMed

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

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

2009-10-01

306

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

PubMed

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

Trezza, Christine R; Kashuba, Angela D M

2014-07-01

307

Survey of physician knowledge regarding antiretroviral medications in hospitalized HIV-infected patients  

PubMed Central

Background Antiretroviral prescribing errors are common among hospitalized patients. Inadequate medical knowledge is likely one of the factors leading to these errors. Our objective was to determine the proportion of hospital physicians with knowledge gaps about prescribing antiretroviral medications for hospitalized HIV-infected patients and to correlate knowledge with length and type of medical training and experience. Methods We conducted an electronic survey comprising of ten clinical scenarios based on antiretroviral-prescribing errors seen at two community teaching hospitals. It also contained demographic questions regarding length and type of medical training and antiretroviral prescribing experience. Three hundred and forty three physicians at both hospitals were asked to anonymously complete the survey between February 2007 and April 2007. Results One hundred and fifty-seven physicians (46%) completed at least one question. The mean percentage of correct responses was 33% for resident physicians, 37% for attending physicians, and 93% for Infectious Diseases or HIV (ID/HIV) specialist physicians. Higher scores were independently associated with ID/HIV specialty, number of outpatients seen per month and physician reported comfort level in managing HIV patients (P < .001). Conclusion Non-ID/HIV physicians had uniformly poor knowledge of common antiretroviral medication regimens. Involvement of ID/HIV specialists in the prescribing of antiretrovirals in hospitalized patients might mitigate prescribing errors stemming from knowledge deficits.

2009-01-01

308

The relationship between CAM use and adherence to antiretroviral therapies among persons living with HIV.  

PubMed

Objective: The use of complementary and alternative medicine (CAM) among people living with HIV and AIDS (PLWHA) may undermine other adaptive illness management behaviors, such as treatment adherence. The present study tests the hypothesis that CAM use is associated with intentional lapses in adherence (e.g., "medication vacations"), perhaps due to negative beliefs about antiretroviral therapy (ART). Method: Cross-sectional interviews with 116 PLWHA were completed using a computerized assessment of self-reported CAM use and ART adherence. Results: Almost half of participants used CAM to treat or manage HIV-related health concerns in the past month, and 78% had used CAM since being diagnosed with HIV. Seventy-one percent of participants endorsed at least one domain of intentional nonadherence since starting HIV treatment. As hypothesized, CAM users did not differ from nonusers on overall ART adherence. Contrary to hypotheses, CAM users were less likely to report taking medication vacations or having stopped taking HIV medications without their doctor's approval compared with nonusers. CAM intensity was also related to intentional nonadherence, such that patients who engaged in more CAM tended to report fewer skipped doses and fewer nonprescribed adjustments to their medication regimen in the past month. Conclusions: Findings suggest that PLWHA use CAM as an adjunct to ART and that CAM use does not undermine ART adherence. Needed now is longitudinal research to determine how a proactive, holistic approach to HIV care interacts with conventional HIV treatment over time, and whether CAM use impacts long-term quality of life and health outcomes. (PsycINFO Database Record (c) 2014 APA, all rights reserved). PMID:23957898

Littlewood, Rae A; Vanable, Peter A

2014-07-01

309

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

PubMed Central

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

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

2012-01-01

310

Effect of antiretroviral therapy on patients' economic well being: five-year follow-up  

PubMed Central

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

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

2014-01-01

311

Prevalence of Congenital Anomalies in Infants with in Utero Exposure to Antiretrovirals  

PubMed Central

Background While use of efficacious interventions, including antiretrovirals (ARVs), has reduced dramatically the rate of mother-to-child transmission (MTCT) of HIV, the safety of in utero ARV exposure remains of concern. Methods Data regarding 1112 infants enrolled in the International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT) protocol P1025 born between 2002 and 2007 were analyzed for this study. Congenital anomalies were classified based on the Metropolitan Atlanta Congenital Defects Program (MACDP) guidelines. Associations between congenital anomalies and timing of first in utero exposure to ARVs were evaluated by logistic regression analysis. Results 61 of the 1112 infants had congenital anomalies identified and confirmed, resulting in a prevalence of 5.49/100 live births (95%CI: 4.22–6.99). Among the 80 anomalies identified, the organ systems involved included: cardiovascular (n=33), musculoskeletal (n=15), renal (n=9), genitourinary (n=6), craniofacial (n=4), and central nervous system (n=2). First trimester exposure to efavirenz was associated with a significantly increased risk of congenital anomalies (OR 2.84, 95%CI: 1.13–7.16). No significant associations were observed between exposure to other individual ARVs or classes of ARVs started at any time during pregnancy and infant congenital anomalies. Conclusions The observed rate of congenital anomalies in this cohort is higher than previously reported for the general population, but is consistent with rates observed in other recent studies of children born to HIV-infected women. Cardiovascular anomalies occurred most frequently. With the exception of a known teratogen (efavirenz), no statistically significant associations between in utero exposure to ARVs and congenital anomalies were identified.

KNAPP, KATHERINE M.; BROGLY, SUSAN B.; MUENZ, DANIEL G.; SPIEGEL, HANS M.; CONWAY, DANIEL H.; SCOTT, GWENDOLYN B.; TALBOT, JEFFREY T.; SHAPIRO, DAVID E.; READ, JENNIFER S.

2011-01-01

312

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

PubMed Central

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

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

2010-01-01

313

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

PubMed Central

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

2011-01-01

314

CD4-guided structured treatment interruptions of antiretroviral therapy in HIV disease: Projecting beyond clinical trials  

PubMed Central

Background International trials have shown that CD4-guided structured treatment interruptions (STI) of antiretroviral therapy (ART) lead to worse outcomes than continuous treatment. We simulated continuous ART and STI strategies with higher CD4 interruption/reintroduction thresholds than those assessed in the trials. Methods We used the Cost-Effectiveness of Preventing AIDS Complications (CEPAC) Model to simulate cohorts of African adults with different CD4 counts at presentation (?200/?l, 201–350/?l, 351–500/?l). We varied ART initiation criteria (immediate, CD4<350/?l or severe opportunistic event, CD4<200/?l or severe opportunistic event), and ART interruption/reintroduction CD4 thresholds (e.g. 350/250/?l, 500/350/?l, 700/500/?l). First-line therapy was non-nucleoside reverse transcriptase inhibitor (NNRTI)-based and 2nd-line was protease inhibitor (PI)-based. Results STI generally led to a lower life expectancy than continuous ART, regardless of ART initiation criteria and interruption/reintroduction thresholds. Life expectancy increased with earlier ART initiation and higher interruption/reintroduction thresholds. STI reduced life expectancy by 48–69 months and by 11–30 months, compared to continuous ART when interruption/reintroduction thresholds were 350/250/?l and 500/350/?l, depending on ART initiation criteria. When patients interrupted/reintroduced ART at CD4 700/500/?l, life expectancies for STI ranged from 2 months lower to 1 month higher than continuous ART. Life expectancy for patients on STI increased with decreased risk of virologic resistance after ART interruptions. Conclusions STI with NNRTI-based regimens was almost always less effective than continuous treatment, regardless of interruption/reintroduction thresholds. The risks associated with STI decrease only if patients start ART earlier, interrupt/reintroduce treatment at very high CD4 thresholds (700/500/?l) and use first-line medications with higher resistance barriers, such as PIs.

Yazdanpanah, Yazdan; Wolf, Lindsey L.; Anglaret, Xavier; Gabillard, Delphine; Walensky, Rochelle P.; Moh, Raoul; Danel, Christine; Sloan, Caroline E.; Losina, Elena; Freedberg, Kenneth A.

2011-01-01

315

Starting Point: Teaching Entry Level Geoscience  

NSDL National Science Digital Library

The Starting Point collection consists of resources found within the Starting Point website to support teaching entry-level undergraduate geoscience of all types. The collection includes modules on instructional methods that make up the Starting Point site. Examples demonstrate ways of using these methods in geoscience courses and laboratories, and the websites referenced in the site that provide additional information and resources. The collection includes resources that span the needs of faculty and graduate students in designing, developing, and delivering entry-level undergraduate courses in the geosciences. It consists primarily of instructional materials and activities, annotations and materials supporting the use of instructional materials and activities, information on instructional methods and issues in teaching customized for geoscientists, primary sources, review articles, summaries and bibliographies pertaining to pedagogy, assessment, issues in teaching, course development and management, and learning science.

2003-09-02

316

How does a black hole horizon start?  

NASA Astrophysics Data System (ADS)

When a black hole is created by gravitational collapse, there is a region of spacetime before the collapse where there is no horizon. Before the matter can fall through the horizon and create a black hole, the horizon has to start and expand to meet the matter. The starting point or points is where the generators enter the horizon. This set is a lower-dimensional, connected subset of a spacelike surface. By way of examples we will discuss the early configuration of the horizon to the time that matter enters. )

Brill, Dieter

2010-02-01

317

Kansas refinery starts up coke gasification unit  

SciTech Connect

Texaco Refining and Marketing Inc. has started up a gasification unit at its El Dorado, Kan., refinery. The unit gasifies delayed coke and other refinery waste products. This is the first refinery to install a coke-fueled gasification unit for power generation. Start-up of the $80-million gasification-based power plant was completed in mid-June. The gasifier produces syngas which, along with natural gas, fuels a combustion turbine. The turbine produces virtually 100% of the refinery`s electricity needs and enough heat to generate 40% of its steam requirements.

Rhodes, A.K.

1996-08-05

318

A study on the black start capability of VSC-HVDC using soft-starting mode  

Microsoft Academic Search

A good black-start scheme is important and necessary to resume power supply fast and efficiently after black out, and how to choose black-start power is the first thing to consider in the scheme. In this paper, the advantages of VSC-HVDC as black start power are analyzed. The ability of VSC-HVDC to soft energize major power system equipment is proved through

Mingxia Zhou; Sheng Li; Jianhua Zhang; Zongqi Liu; Yinhui Li

2009-01-01

319

Determinants and causes of mortality in HIV-infected patients receiving antiretroviral therapy in Burkina Faso: a five-year retrospective cohort study.  

PubMed

In this study, we investigated the causes of death and the factors associated with mortality in a cohort of patients receiving highly active antiretroviral therapy (HAART) in Burkina Faso, an African country with limited resources. This retrospective cohort study included patients aged 15 years and older who started HAART for the first time between January 2003 and December 2008 in 14 health districts. We used survival analyses, including the Kaplan-Meier method, to examine potential predictors of death and two Cox proportional hazard models to estimate hazard ratios for death, first from baseline covariates and then from time-dependent covariates. A total of 6641 patients initiated HAART during this period; of these, 5608 were included in the analysis. By the end of the study period, 4310 of those patients were still receiving HAART, 690 had died, 207 had been transferred and 401 were lost to follow-up. The median duration of follow-up was 23.2 months [interquartile range (IQR): 12.4-36.9], and the overall incidence of mortality was 6 per 100 person-years. The clinical stage, CD4 count, body mass index (BMI), haemoglobin level, HAART regimen, gender, age, profession and year of initiation were the primary risk factors associated with death. In the multivariate analysis, BMI, clinical stage, treatment regimen and CD4 count remained significantly associated with death. The most frequent causes of death were wasting syndrome, tuberculosis and anaemia. This result highlights the already advanced stage of immunodeficiency among patients in Burkina Faso when they start HAART. Testing patients for HIV and starting antiretroviral therapy earlier are necessary to further reduce the mortality of patients living with HIV. This study provides a solid evidence base with which future evaluations of HAART in Burkina Faso can be compared. PMID:22148973

Kouanda, S; Meda, I B; Nikiema, L; Tiendrebeogo, S; Doulougou, B; Kaboré, I; Sanou, M J; Greenwell, F; Soudré, R; Sondo, B

2012-01-01

320

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

321

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.

322

Head Start Fathers' Involvement with Their Children  

ERIC Educational Resources Information Center

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

Gorvine, Benjamin J.

2010-01-01

323

Head Start Teachers' Use of Verbal Encouragement.  

ERIC Educational Resources Information Center

To assess teachers' statements that influence affective growth in children, two observation instruments were developed, and direct observations were made in seven suburban Head Start centers to compare the communications of 20 teachers to 21 handicapped and 21 nonhandicapped children. (SBH)

Harlan, Jean Durgin; Leyser, Yona

1980-01-01

324

New Start: Bibliographic Instruction for Nontraditional Students.  

ERIC Educational Resources Information Center

The New Start program at the University of Nebraska-Omaha was initiated in 1975 to focus on the needs and concerns of nontraditional students, i.e, individuals who are at least 25 years old and have been away from formal education for at least three years. Offered as an elective course for one hour of credit, the program includes reviews of basic…

Dickson, Laura K.; And Others

325

National Home Start Evaluation: Field Procedures Manual.  

ERIC Educational Resources Information Center

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

Nauta, Marrit J.

326

Synthetic crude starts flowing to markets  

Microsoft Academic Search

The first commercial production of synthetic crude from Athabasca tar sands was scheduled to begin by the middle of 1967. The project was completed in June and is undergoing test runs. As a result, manufactured crude oil will start flowing toward a Canadian refinery on Sept. 30, 1967, at the rate of 45,000 bpd. Athabasca tar sand deposits are particularly

1967-01-01

327

Can Students Predict Starting Salaries? Yes!  

ERIC Educational Resources Information Center

We use Dutch panel data in which students have been asked to state their expected starting salary and confront these with realisations four years later. Both level and structure of expectations and realisations are remarkably close: we barely find systematic under- or overestimation effects.

Webbink, Dinand; Hartog, Joop

2004-01-01

328

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

329

Addressing Tooth Decay in Head Start Children  

ERIC Educational Resources Information Center

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

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

2012-01-01

330

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

331

Structural Model of Head Start Classroom Quality.  

ERIC Educational Resources Information Center

Developed, tested, and validated a model of Head Start classroom quality incorporating characteristics and beliefs of teachers and aides and classroom structural dimensions. Found that teacher/aide education level directly affected inappropriate beliefs, which impacted inappropriate instructional activities, which influenced classroom quality.…

Abbott-Shim, Martha; Lambert, Richard; McCarty, Frances

2000-01-01

332

School Start Time and Teen Sleep.  

ERIC Educational Resources Information Center

Sleep studies have shown that teenagers' internal clocks are incompatible with most high schools' early hours. Research in two Minnesota districts indicates that later school starting times can benefit teens and everyone dealing with them. Student participation in sports and other afterschool activities remained high. (MLH)

Wahlstrom, Kyla L.

2000-01-01

333

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

334

Technology in a Head Start Parent Center.  

ERIC Educational Resources Information Center

Unless children and parents have training and access to computers and the power they offer, computers create a barrier for them as they navigate a society that depends on computers for information and occupational advancement. This paper describes a program developed by North Shore Head Start in Beverly, Massachusetts and CAST (Center for Applied…

Hughes, Bob; Coyne, Peggy; Waddell, Sandy

335

Teacher Research: Getting Started. Research to Practice.  

ERIC Educational Resources Information Center

Typically, teacher research is conducted because teachers want to have some questions answered. Starting effective teacher research begins by framing the question in a way that will yield the best research. Three important suggestions when framing teacher research questions are as follows: the question needs to be open ended enough to allow…

Bardine, Bryan

336

Electric arc heater is self starting  

NASA Technical Reports Server (NTRS)

Remote method initiates an electric arc over a large range of gaps between two water-cooled electrodes of an arc-heated wind tunnel without disassembling the arc unit. This type of starting system can be used on both three-phase ac arc heaters and dc arc heaters.

Brown, R. D.

1966-01-01

337

Mental Health Services in Head Start  

ERIC Educational Resources Information Center

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

Frey, Andy

2008-01-01

338

New Teacher Resource Book: Getting Started  

NSDL National Science Digital Library

This chapter of the Resource Book for the Beginning Physics Teacher provides four example activities that can be used on the first days of class to get students started taking an active role in their learning. These provide an introduction to a learning cycle approach to science.

Mader, Jan; Winn, Mary

2006-08-16

339

Apps for Assessment: A Starting Point  

Microsoft Academic Search

Many mobile applications, also known as apps, are excellent instruments for gathering qualitative and quantitative data. This article is a starting point for those interested in gathering assessment data using mobile tools and provides assessment app type overviews and examples. With relatively little effort, libraries can take advantage of mobile apps and gather compelling assessment data more easily than ever

Rachel Besara

2012-01-01

340

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

341

Starting with "I": Personal Essays by Teenagers.  

ERIC Educational Resources Information Center

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

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

342

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

343

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

PubMed

HIV drug resistance still represents a crucial problem in antiretroviral therapy. We report a case of a naive patient, harboring a CRF11-cpx virus, which showed drug resistance mutations in the reverse transcriptase. A drug resistance genotyping test was performed for the pol (protease, reverse transcriptase, and integrase) and V3 regions. The initial clinical parameter results showed a 4 log level of HIV-RNA (12,090 cp/ml) and a very low CD4(+) cell count (35 cells/?l). We designed an initial highly active antiretroviral therapy (HAART) regimen including lamivudine (3TC)+abacavir (ABC)+booster ritonavir (DRV/r). The virus was highly resistant to all nucleoside and nucleotide reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) except for ABC, tenofovir (TDF), and efavirenz (EFV) and was susceptible to all protease inhibitors (PIs) and integrase inhibitors (INIs). A salvage regimen including raltegravir (RAL)+DRV/r was started. Ten months later, the immunovirological status shows CD4(+) 142/?l and HIV-RNA <37 cp/ml. Our results demonstrate the effectiveness of a treatment combination that includes RAL+DRV/r in a patient infected with a complex X4-tropic CRF11-cpx virus. PMID:24279648

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

2014-05-01

344

Antiretroviral Treatment for Children with Peripartum Nevirapine Exposure  

PubMed Central

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

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

2010-01-01

345

Early changes in parathyroid hormone concentrations in HIV-infected patients initiating antiretroviral therapy with tenofovir.  

PubMed

Initiation of combined antiretroviral therapy (cART) is associated with bone loss, which may be more intense with regimens including tenofovir. The underlying mechanisms are not well understood. Cross-sectional data have linked tenofovir with higher parathyroid hormone (PTH) concentrations in patients with vitamin D deficiency. We performed a longitudinal study with a 48-week follow-up to evaluate sequential changes in PTH and 25-hydroxyvitamin D [25(OH)D] levels in patients starting cART with either tenofovir/emtricitabine or abacavir/lamivudine. Fifty-seven patients were included, 31 initiating tenofovir/emtricitabine and 26 initiating abacavir/lamivudine. Median PTH levels turned out to be significantly higher among tenofovir/emtricitabine users at week 4 (p=0.01), week 24 (p=0.008), and week 36 (p=0.02), and were above the upper limits of normal values (ULN) at weeks 24, 36, and 48 only in patients receiving tenofovir/emtricitabine. 25(OH)D, serum and urine calcium and phosphate, and renal-tubular maximum reabsorption of phosphate to the glomerular filtration rate (TmP/GFR) levels did not differ between the two treatment arms over the study period. Among tenofovir/emtricitabine users, median (interquartile range) PTH concentrations were significantly higher in patients with suboptimal 25(OH)D levels (<30 ?g/liter) at week 24 [63 (57.8-82.4) ng/liter vs. 54.3 (34.4-63.067.5) ng/liter, p=0.05] and week 48 [67.5 (59.6-86.0) ng/liter vs. 41.9 (37.3-68.8) ng/liter, p=0.03]. A multivariable logistic regression model showed that tenofovir/emtricitabine use was an independent predictor of high PTH levels (?53 ng/liter). Starting cART with tenofovir regimens is associated with an elevation in PTH plasma concentrations soon after introducing the drug. Suboptimal baseline 25(OH)D levels increase the risk of developing secondary hyperparathyroidism among tenofovir users. PMID:21639815

Masiá, Mar; Padilla, Sergio; Robledano, Catalina; López, Natividad; Ramos, José Manuel; Gutiérrez, Felix

2012-03-01

346

Reproductive Intentions and Outcomes among Women on Antiretroviral Therapy in Rural Uganda: A Prospective Cohort Study  

PubMed Central

Background Antiretroviral therapy (ART) may influence the biological, social and behavioral determinants of pregnancy in HIV-infected women. However, there are limited longitudinal data on the reproductive intentions and outcomes among women on ART in Africa. Methodology /Principal Findings Using a prospective cohort design, we analyzed trends in desire for children and predictors of pregnancy among a cohort of 733 HIV-infected women in rural Uganda who initiated ART between May 2003 and May 2004 and were followed up in their homes until June 2006. Women answered in-depth social and behavioral questionnaires administered every quarter in year 1 after initiating ART, and every 6 to 12 months thereafter. Use of family planning methods was assessed at 18 and 24 months after starting ART. We tested for non-constant pregnancy incidence by using a shape parameter test from the Weibull distribution. We modeled repeated measurements of all variables related to the women's desire for children over time using a generalized estimating equation (GEE) extension to the logistic regression model. Risk factors for pregnancy were examined using Cox proportional hazards model. 711 women eligible for the study were followed-up for a median time of 2.4 years after starting ART. During this time, less than 7% of women reported wanting more children at any time point yet 120 (16.9%) women experienced 140 pregnancies and pregnancy incidence increased from 3.46 per 100 women-years (WY) in the first quarter to 9.5 per 100 WY at 24 months (p<0.0001). This was paralleled by an increase in the proportion of women reporting sexual activity in the past 3 months, from 24.4% at baseline to 32.5% over 24 months of follow-up (p?=?0.001). Only 14% of women used permanent or semi-permanent family planning methods by their second year on ART. In the multivariate model, younger age (HR?=?2.71 per 10-year decrease, 95% CI: 2.95–3.78), having a BMI>18.5 (HR?=?1.09, CI: 1.01–1.18) and not having used condoms consistently in the last 3 months (HR?=?1.79, CI: 1.02–3.13) were independently associated with pregnancy. Conclusion/Significance Women on ART and their partners should be consistently counseled on the effects of ART in restoring fertility, and offered regularly free and comprehensive family planning services as part of their standard package of care.

Homsy, Jaco; Bunnell, Rebecca; Moore, David; King, Rachel; Malamba, Samuel; Nakityo, Rose; Glidden, David; Tappero, Jordan; Mermin, Jonathan

2009-01-01

347

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

PubMed Central

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

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

2010-01-01

348

Family-Centered Head Start for Infants and Toddlers: A Renewed Direction for Project Head Start.  

ERIC Educational Resources Information Center

Discusses calls for Head Start to expand its services for children from birth to three years and to devise standards for infants and toddlers. Recent policy decisions resulting in such expansion are discussed. The need for Head Start staff involved with infant and toddler care to be trained about infancy is considered in detail. (BG)

Pizzo, Peggy Daly

1990-01-01

349

The difference is in the start: impact of timing and start procedure on sprint running performance.  

PubMed

The difference is in the start: impact of timing and start procedure on sprint running performance. The purpose of this study was to compare different sprint start positions and to generate correction factors between popular timing triggering methods on 40-m/40-yd sprint time. Fourteen female athletes (17 ± 1 years), personal best 100 m: 13.26 (±0.68) seconds and 11 male athletes (20 ± 5 years), personal best 100 m: 11.58 (±0.74) seconds participated. They performed 2 series of 3 40-m sprints in randomized order: (a) start from the block, measured by means of Brower audio sensor (BAS) and Dartfish video timing (DVT), (b) 3-point start, measured by using hand release pod (HR) and DVT, and (c) standing start, triggered by both photocell across starting line (SFC), and foot release (FR) plus DVT. Video analysis was performed by 2 independent observers and averaged. Simultaneous measurements at national athletics competitions demonstrated that DVT and BAS were equivalent to Omega Timing within the limits of precision of video timing (±0.01 seconds). Hand and floor timer triggering showed small but significant biases compared with movement captured from video (0.02-0.04 seconds), presumably because of sensitivity of pressure thresholds. Coefficient of variation for test-retest timing using different starting positions ranged from 0.7 to 1.0%. Compared with block starts reacting to gunfire, HR, SFC, and FR starts yielded 0.17 ± 0.09, 0.27 ± 0.12, and 0.69 ± 0.11 second faster times, respectively, over 40 m (all p < 0.001) because of inclusion or exclusion of reaction time, plus momentum, and body position differences at trigger moment. Correction factors for the conversion of 40 m/40 yd and 40 yd/40 m were 0.92 and 1.08, respectively. The correction factors obtained from this study may facilitate more meaningful comparisons of published sprint performances. PMID:22233797

Haugen, Thomas A; Tønnessen, Espen; Seiler, Stephen K

2012-02-01

350

Verifying START: From satellites to suspect sites  

SciTech Connect

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

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

1990-10-01

351

Prospective antiretroviral treatment of asymptomatic, HIV-1 infected controllers.  

PubMed

The study of HIV-infected "controllers" who are able to maintain low levels of plasma HIV RNA in the absence of antiretroviral therapy (ART) may provide insights for HIV cure and vaccine strategies. Despite maintaining very low levels of plasma viremia, controllers have elevated immune activation and accelerated atherosclerosis. However, the degree to which low-level replication contributes to these phenomena is not known. Sixteen asymptomatic controllers were prospectively treated with ART for 24 weeks. Controllers had a statistically significant decrease in ultrasensitive plasma and rectal HIV RNA levels with ART. Markers of T cell activation/dysfunction in blood and gut mucosa also decreased substantially with ART. Similar reductions were observed in the subset of "elite" controllers with pre-ART plasma HIV RNA levels below conventional assays (<40 copies/mL). These data confirm that HIV replication persists in controllers and contributes to a chronic inflammatory state. ART should be considered for these individuals (ClinicalTrials.gov NCT01025427). PMID:24130489

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

2013-01-01

352

Long-acting injectable antiretrovirals for HIV treatment and prevention  

PubMed Central

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

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

2013-01-01

353

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

2014-08-01

354

Effective treatment of a highly active antiretroviral regimen through jejunostomy.  

PubMed

A 49-year-old woman voluntarily not receiving HIV treatment was admitted to the emergency department showing sepsis and peritonism. She required several surgical procedures for intestinal perforations. Finally, a proximal-terminal jejunostomy and a distal mucous jejunostomy were performed. At this time, her HIV viral load was 531?388 copies/ml and CD4 count was 193 cells/?l. Then, HAART was restarted with lopinavir/ritonavir 400/100 mg plus lamivudine 150 mg/12 hours, and etravirine 400 mg/24 hours. Each drug was dissolved in 20 ml of water and administered through the distal jejunostomy. In 2 months, her HIV viral load decreased in 3·9 log and CD4 count increased in 70 cells/?l. On day 250, an intestinal tract reconstruction was performed and short after highly active antiretroviral therapy (HAART) was restarted orally. Lopinavir/ritonavir, etravirine, and lamivudine administered through a jejunostomy resulted effective in decreasing HIV viral load and increasing CD4 lymphocyte count in a HIV patient who could not receive treatment orally. PMID:24075526

Florit-Sureda, Marta; Giner-Soriano, Maria; Antonio, Javier Mateu-de; Carmona-Yelo, Alexia

2014-06-01

355

Novel drug delivery approaches on antiviral and antiretroviral agents.  

PubMed

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

2012-07-01

356

Adherence to Antiretrovirals Among US Women During and After Pregnancy  

PubMed Central

Background Antiretrovirals (ARVs) are recommended for maternal health and to reduce HIV-1 mother-to-child transmission, but suboptimal adherence can counteract its benefits. Objectives To describe antepartum and postpartum adherence to ARV regimens and factors associated with adherence. Methods We assessed adherence rates among subjects enrolled in Pediatric AIDS Clinical Trials Group Protocol 1025 from August 2002 to July 2005 on tablet formulations with at least one self-report adherence assessment. Perfectly adherent subjects reported no missed doses 4 days before their study visit. Generalized estimating equations were used to compare antepartum with postpartum adherence rates and to identify factors associated with perfect adherence. Results Of 519 eligible subjects, 334/445 (75%) reported perfect adherence during pregnancy. This rate significantly decreased 6, 24, and 48 weeks postpartum [185/284 (65%), 76/118 (64%), and 42/64 (66%), respectively (P < 0.01)]. Pregnant subjects with perfect adherence had lower viral loads. The odds of perfect adherence were significantly higher for women who initiated ARVs during pregnancy (P < 0.01), did not have AIDS (P = 0.02), never missed prenatal vitamins (P < 0.01), never used marijuana (P = 0.05), or felt happy all or most of the time (P < 0.01). Conclusions Perfect adherence to ARVs was better antepartum, but overall rates were low. Interventions to improve adherence during pregnancy are needed.

Bardeguez, Arlene D.; Lindsey, Jane C.; Shannon, Maureen; Tuomala, Ruth E.; Cohn, Susan E.; Smith, Elizabeth; Stek, Alice; Buschur, Shelly; Cotter, Amanda; Bettica, Linda; Read, Jennifer S.

2009-01-01

357

Prevalence of Metabolic Syndrome Among Antiretroviral-Naive and Antiretroviral-Experienced HIV-1 Infected Thai Adults.  

PubMed

Abstract Metabolic syndrome (MS), a group of interrelated risk factors for cardiovascular diseases (CVD) and type 2 diabetes, has been increasingly reported among HIV-infected patients. Data on the prevalence and risk factors for MS among HIV-1 infected Thai adults are limited. The study collected cross-sectional data from 580 HIV-1 infected adults-46.2% were men and 71% were antiretroviral therapy (ART)-experienced. The majority (78.8%) of them used non-nucleoside reverse transcriptase inhibitor-based regimens. Data on lipid profiles, fasting blood glucose, CD4 count, HIV RNA, antiretroviral therapy (ART), anthropometry, food intake, and exercise were recorded. MS was defined using American Heart Association/National Heart Lung and Blood Institute criteria. Overall prevalence of MS was 22.2%; 15.9% in ART-naïve group vs. 24.9% in ART-experienced group, p?=?0.018. Significant risk factors for MS in multivariate analyses included age ?35 years (odds ratio, OR, 4.2, 95%CI 1.6-11.0, p?=?0.004), high cholesterol (OR 4.7, 95%CI 1.7-12.9, p?=?0.002), and living outside Bangkok (OR 4.2, 95%CI 1.6-10.8, p?=?0.003) in the ART-naïve group, and female gender (OR 1.7, 95%CI 1.0-2.8, p?=?0.05), lipodystrophy (OR 1.8, 95%CI 1.0-3.0, p?=?0.032), high cholesterol (OR 1.9, 95%CI 1.1-3.1, p?=?0.015), and food insecurity (OR 1.8, 95%CI 1.0-3.3, p?=?0.05) in the ART-experienced group. All variables, except for female gender in the ART-experienced group, remained significantly associated with MS in a model where lipodystrophy was excluded. We concluded that MS was common among HIV-1-infected Thai adults. As HIV-infected patients get older, early screening and intervention, such as ART modification to avoid lipodystrophy, may reduce MS and CVD-related morbidities and mortalities in long-term care. PMID:24914459

Jantarapakde, Jureeporn; Phanuphak, Nittaya; Chaturawit, Chintana; Pengnonyang, Supabhorn; Mathajittiphan, Pornpen; Takamtha, Piyaporn; Dungjun, Narunat; Pinyakorn, Suteeraporn; Pima, Warabhorn; Prasithsirikul, Wisit; Phanuphak, Praphan

2014-07-01

358

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

359

Kyrgyzstan starts up its first refinery  

Microsoft Academic Search

The Central Asian republic of Kyrgyzstan started up its first oil refinery in October 1996. The 10,000 b\\/d plant is designed to produce gasoline, diesel, and mazut (heavy fuel oil) from local Kyrgyz crude. Before construction of the Jalalabad refinery, all finished petroleum products were imported from neighboring countries. Kyrgyzstan`s demand for finished products is about 40,000 b\\/d. The new

1997-01-01

360

Start Young: Early Childhood Science Activities  

NSDL National Science Digital Library

You asked for it--now you've got it! In a focus group at a recent NSTA convention, teachers of prekindergarten through second grade clamored for help. They do want easy-to-do science activities they can use for everyday teaching. But they don't want to be forced to adapt material meant for older children. So here's the solution. Start Young! offers a wealth of simple educational activities designed to use right away with even the littlest scientists. The book includes a chapter of helpful background on the latest thinking about effective ways to introduce science in early childhood. But the bulk of the book is two dozen articles compiled from Science and Children, NSTA's award-winning journal for elementary school teachers. Among the topics: � Playful science activities for young children � The science and mathematics of building structures � Planning a Rock Day � What makes miniature sleds go, go, go � Figuring out how big is big and how big is small � Learning about birds, flight, ponds, and the environment � Creating science centers for all students Everyone who works with young children knows how eager they are to see, smell, hear, and touch the world around them. Encourage that natural curiosity while laying a foundation for a lifetime of learning about science. Start Young! is the age-appropriate resource to help you start them off right.

2006-01-01

361

A Fast-Starting Robotic Fish  

NASA Astrophysics Data System (ADS)

We have built a simple mechanical system to emulate the fast-start performance of fish. The system consisted of a thin metal beam covered by a urethane rubber fish body. The body form of the mechanical fish in this work was modeled from a pike species, which is the most successfully studied fast-start specialist species. The mechanical fish was held in curvature and hung in water by two restraining lines, which were simultaneously released by pneumatic cutting mechanisms. The potential energy in the beam was transferred into the fluid, thereby accelerating the fish, similar to a pike. We measured the resulting velocity and acceleration, as well as the efficiency of propulsion for the mechanical fish model and also ran a series of flow visualization tests to observe the resulting flow pattern. We also studied the influence of stiffness and geometry of the tail on the efficiency of propulsion and flow pattern. The hydrodynamic efficiency of the fish, calculated by the transfer of energy, was around 10%. Flow visualization of the mechanical fast-start wake was also analyzed, showing that the acceleration is associated with the fast movement of an intense vortex in a near-lateral direction.

Modarres-Sadeghi, Yahya; Watts, Matthew; Conte, Joe; Hover, Franz; Triantafyllou, Michael

2009-11-01

362

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

PubMed Central

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

2013-01-01

363

Implementing HIV-1 genotypic resistance testing in antiretroviral therapy programs in africa: needs, opportunities, and challenges.  

PubMed

Tremendous progress has been made with the scale-up of antiretroviral therapy in Africa, with an estimated seven million people now receiving antiretroviral therapy in the region. The long-term success of antiretroviral therapy programs depends on appropriate strategies to deal with potential threats, one of which is the emergence and spread of antiretroviral drug resistance. Whilst public health surveillance forms the mainstay of the World Health Organization approach to antiretroviral drug resistance, there is likely to be increasing demand for access to drug resistance testing as programs mature and as HIV clinical management becomes more complex. African-owned research initiatives have helped to develop affordable resistance testing appropriate for use in the region, and have developed delivery models for resistance testing at different levels of the public health system. Some upper-middle-income countries such as Botswana and South Africa have introduced drug resistance testing for selected patient groups to guide clinical management. The scale-up of resistance testing will require substantial expansion of clinical and laboratory capacity in the region, but the expertise and resources exist in Africa to support this. The long-term population health impact and cost-effectiveness of resistance testing in the region will also require further investigation. PMID:24322382

Lessells, Richard J; Avalos, Ava; de Oliveira, Tulio

2013-01-01

364

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

365

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

PubMed Central

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

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

2008-01-01

366

Response to antiretroviral therapy (ART): comparing women with previous use of zidovudine monotherapy (ZDVm) in pregnancy with ART na?ve 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-naïve (n?=?1937) and ZDVm-experienced (n?=?91) women had similar increases in CD4 count and a similar proportion achieving virological suppression; both groups had a low risk of AIDS. Conclusions In this setting, antenatal ZDVm exposure did not adversely impact on outcomes once ART was initiated for the woman’s health.

2014-01-01

367

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

Microsoft Academic Search

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

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

2006-01-01

368

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

Microsoft Academic Search

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

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

2008-01-01

369

Human Immunodeficiency Virus Replication and Genotypic Resistance in Blood and Lymph Nodes after a Year of Potent Antiretroviral Therapy  

Microsoft Academic Search

Potent antiretroviral therapy can reduce human immunodeficiency virus (HIV) in plasma to levels below the limit of detection for up to 2 years, but the extent to which viral replication is suppressed is unknown. To search for ongoing viral replication in 10 patients on combination antiretroviral therapy for up to 1 year, the emergence of genotypic drug resistance across different

HULDRYCH F. GUNTHARD; JOSEPH K. WONG; CAROLINE C. IGNACIO; JOHN C. GUATELLI; NANETTE L. RIGGS; DIANE V. HAVLIR; DOUGLAS D. RICHMAN

1998-01-01

370

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

National Technical Information Service (NTIS)

In order for Head Start programs to successfully include children with significant disabilities, staff must take steps to get ready. They must acquire special knowledge and skills to help children with disabilities and their families take full advantage o...

1997-01-01

371

K.CC Start-Stop Counting  

NSDL National Science Digital Library

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

372

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

PubMed Central

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

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

2013-01-01

373

40 CFR 1065.525 - Engine starting, restarting, and shutdown.  

Code of Federal Regulations, 2013 CFR

...methods: (1) Start the engine as recommended in the...production starter motor or air-start system and either...supply, or a suitable compressed air source. (2) Use the dynamometer to start the engine. To do this, motor...

2013-07-01

374

46 CFR 112.50-5 - Electric starting.  

Code of Federal Regulations, 2010 CFR

...SECURITY (CONTINUED) ELECTRICAL ENGINEERING EMERGENCY LIGHTING AND POWER SYSTEMS Emergency Diesel and Gas Turbine Engine Driven Generator Sets § 112.50-5 Electric starting. An electric starting system must have a starting...

2009-10-01

375

46 CFR 112.50-5 - Electric starting.  

Code of Federal Regulations, 2010 CFR

...SECURITY (CONTINUED) ELECTRICAL ENGINEERING EMERGENCY LIGHTING AND POWER SYSTEMS Emergency Diesel and Gas Turbine Engine Driven Generator Sets § 112.50-5 Electric starting. An electric starting system must have a starting...

2010-10-01

376

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

ERIC Educational Resources Information Center

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

Hart, Katherine; Schumacher, Rachel

2004-01-01

377

Kinetics and Determining Factors of the Virologic Response to Antiretrovirals during Pregnancy  

PubMed Central

HIV-infected pregnant women with undetectable plasma HIV RNA concentrations at delivery pose a minimal risk of vertical transmission. We studied the kinetics and the determinants of the virologic response to antiretroviral therapy in 117 consecutive pregnancies. Patients who initiated therapy during pregnancy had a VL decrease of 2 and 2.5 log10 after 4 and 24 weeks, respectively. Therapeutic drug monitoring (TDM) of the protease inhibitors administered in doses recommended for nonpregnant adults resulted in below-target concentrations in 29%, 35%, and 44% of 1st, 2nd, and 3rd trimester measurements, respectively, but low drug concentrations did not correlate with virologic failure. Demographic characteristics, antiretroviral experience prior to pregnancy, baseline VL, or use of specific antiretrovirals did not affect the virologic response. Adherence to ?95% of prescribed doses and utilization of psychosocial services were associated with undetectable plasma HIV RNA at delivery. In conclusion, the virologic responses of pregnant and nonpregnant adults share similar charactersitics.

Weinberg, Adriana; Harwood, Jeri E. F.; McFarland, Elizabeth J.; Pappas, Jennifer; Davies, Jill; Kinzie, Kay; Barr, Emily; Paul, Suzanne; Salbenblatt, Carol; Soda, Elizabeth; Vazquez, Anna; Peloquin, Charles A.; Levin, Myron J.

2009-01-01

378

Predictors of mortality among HIV infected children on anti-retroviral therapy in Mekelle Hospital, Northern Ethiopia: a retrospective cohort study  

PubMed Central

Background The introduction of antiretroviral therapy in 1996 improved the longevity and wellbeing of peoples living with HIV in the industrialized world including children. This survival benefit of antiretroviral therapy (ART) in reducing HIV related deaths has been well studied in the developed world. In resource-poor settings, where such treatment was started recently, there is inadequate information about impact of ART on the survival of patients especially in children. So, this study aims to investigate predictors of mortality of children on ART. Therefore, the objective of this study was to identify predictors of mortality among children on HAART. Methods A retrospective cohort study was conducted on 432 children who initiated antiretroviral therapy from June 2006 to June 2011 at pediatrics ART clinic in Mekelle Hospital, Northern-Ethiopia. Data were extracted from electronic and paper based medical records database and analyzed using Kaplan Meier survival and Cox proportional hazard model to identify independent predictors of children’s mortality on ART. Results The total time contributed by the study participants were 14,235 child-months with median follow up of 36 months. The mortality rate of this cohort was 1.40 deaths per 1000 child-months or 16.85 deaths per 1000 child-years. Age less than 18 months [ Adj.HR (95% CI) = (4.39(1.15-17.41)], CD4 percentage <10 [Adj.HR (95% CI) = 2.98(1.12-7.94)], WHO clinical stage (III&IV) [Adj.HR (95% CI) = 4.457(1.01-19.66)], chronic diarrhea[Adj.HR (95% CI) = 4.637(1.50-14.31)] and hemoglobin < 8 g/dl[Adj.HR (95% CI) = 3.77(1.29-10.98)] all at baseline were significantly and independently associated with survival of children on ART. Conclusions Mortality of children on ART was low and factors that affect mortality of children on ART were age less than 18 months, lower CD4 percentage, advanced WHO clinical stage (III&IV), presence of chronic diarrhea and lower hemoglobin level all at baseline. The high early mortality rate would support the value of an earlier treatment start before development of signs of immunodeficiency syndrome despite the method of HIV diagnosis and WHO stage.

2013-01-01

379

Antiretroviral monocyte efficacy score linked to cognitive impairment in HIV  

PubMed Central

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

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

2013-01-01

380

Fate of the antiretroviral drug tenofovir in agricultural soil.  

PubMed

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

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

2010-10-15

381

Stages of change for adherence to antiretroviral medications.  

PubMed

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

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

2013-10-01

382

Alcohol use disorders and antiretroviral therapy among prisoners in Argentina  

PubMed Central

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

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

2013-01-01

383

Antiretroviral Outcomes in South African Prisoners: A Retrospective Cohort Analysis  

PubMed Central

Background and Methods Little is known about antiretroviral therapy (ART) outcomes in prisoners in Africa. We conducted a retrospective review of outcomes of a large cohort of prisoners referred to a public sector, urban HIV clinic. The review included baseline characteristics, sequential CD4 cell counts and viral load results, complications and co-morbidities, mortality and loss to follow-up up to 96 weeks on ART. Findings 148 inmates (133 male) initiated on ART were included in the study. By week 96 on ART, 73% of all inmates enrolled in the study and 92% of those still accessing care had an undetectable viral load (<400copies/ml). The median CD4 cell count increased from 122 cells/mm3 at baseline to 356 cells/mm3 by 96 weeks. By study end, 96 (65%) inmates had ever received tuberculosis (TB) therapy with 63 (43%) receiving therapy during the study: 28% had a history of TB prior to ART initiation, 33% were on TB therapy at ART initiation and 22% developed TB whilst on ART. Nine (6%) inmates died, 7 in the second year on ART. Loss to follow-up (LTF) was common: 14 (9%) patients were LTF whilst still incarcerated, 11 (7%) were LTF post-release and 9 (6%) whose movements could not be traced. 16 (11%) inmates had inter-correctional facility transfers and 34 (23%) were released of whom only 23 (68%) returned to the ART clinic for ongoing follow-up. Conclusions Inmates responded well to ART, despite a high frequency of TB/HIV co-infection. Attention should be directed towards ensuring eligible prisoners access ART programs promptly and that inter-facility transfers and release procedures facilitate continuity of care. Institutional TB control measures should remain a priority.

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

2012-01-01

384

Anti-retroviral activity of TRIM5 alpha.  

PubMed

Human immunodeficiency virus type 1 (HIV-1) shows a very narrow host range limited to humans and chimpanzees. Experimentally, HIV-1 does not infect Old World monkeys, such as rhesus (Rh) and cynomolgus (CM) monkeys, and fails to replicate in activated CD4 positive T lymphocytes obtained from these monkeys. In contrast, simian immunodeficiency virus isolated from a macaque monkey (SIVmac) can replicate well in both Rh and CM. In 2004, tripartite motif 5 alpha (TRIM5 alpha) was identified as a host factor which plays an important role in the restricted host range of HIV-1. Rh and CM TRIM5 alpha restrict HIV-1 infection but not SIVmac, while in comparison, anti-viral activity of human TRIM5 alpha against those viruses is very weak. TRIM5 alpha consists of the RING, B-box 2, coiled-coil and SPRY (B30.2) domains. The RING domain is frequently found in E3 ubiquitin ligase and TRIM5 alpha is degraded via the ubiquitin-proteasome pathway during HIV-1 restriction. TRIM5 alpha recognises the multimerised capsid (viral core) of an incoming virus by its alpha-isoform specific SPRY domain and is believed to be involved in innate immunity to control retroviral infection. Differences in amino acid sequences in the SPRY domain of TRIM5 alpha of different monkey species were found to affect species-specific restriction of retrovirus infection, while differences in amino acid sequences in the viral capsid protein determine viral sensitivity to restriction. Accurate structural analysis of the binding surface between the viral capsid protein and TRIM5 alpha SPRY is thus required for the development of new antiretroviral drugs that enhance anti-HIV-1 activity of human TRIM5 alpha. PMID:20049904

Nakayama, Emi E; Shioda, Tatsuo

2010-03-01

385

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

386

Longitudinal lactate levels from routine point-of-care monitoring in adult Malawian antiretroviral therapy patients: associations with stavudine toxicities  

PubMed Central

Introduction Stavudine is still widely used in under-resourced settings such as Malawi due to its low price. It frequently causes peripheral neuropathy and lipodystrophy and increases the risk of lactic acidosis and other high lactate syndromes. Methods We studied the association of longitudinal lactate levels, obtained by routine, 3-monthly point-of-care monitoring, with peripheral neuropathy, lipodystrophy and high lactate syndromes in adult Malawians who were in the second year of stavudine containing antiretroviral therapy (ART). Results Point-of-care lactate measurements were feasible in a busy urban ART clinic. Of 1170 lactate levels collected from 253 patients over the course of one year, 487 (41.8%) were elevated (>2.2mg/dl), 58 (5.0%) were highly elevated (>3.5mg/dl). At least one elevated lactate level occurred in 210 (83.0%) of patients and sustained hyperlactatemia in 65 (26.4%). In random effects analyses lipodystrophy and peripheral neuropathy were associated with higher lactate levels. Only five patients developed high lactate syndromes (one lactic acidosis) of whom no preceding lactate measurements were available because events had started before enrolment. Lactate levels significantly decreased over time and no high lactate syndromes were observed after the 15th month on ART. Conclusion Lipodystrophy and peripheral neuropathy were associated with higher lactate levels. Lactate levels decreased over time, coinciding with absence of new high lactate syndromes after the 15th month on ART.

Chagoma, Newton; Mallewa, Jane; Kaunda, Symon; Njalale, Yasin; Kampira, Elizabeth; Mukaka, Mavuto; Heyderman, Robert S; van Oosterhout, Joep J

2013-01-01

387

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

PubMed Central

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

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

2011-01-01

388

Regional Anthropometry Changes in Antiretroviral-Na?ve Persons Initiating a Zidovudine-Containing Regimen in Mbarara, Uganda  

PubMed Central

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

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

2011-01-01

389

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

PubMed Central

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

2011-01-01

390

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

PubMed

People living with HIV who are taking antiretroviral therapy (ART) are increasingly involved in 'positive prevention' initiatives. These are generally oriented to promoting abstinence, 'being faithful' (partner reduction) and condom use (ABC). We conducted a longitudinal qualitative study with people living with HIV using ART, who were provided with adherence education and counselling support by a Ugandan non-governmental organisation, The AIDS Support Organisation (TASO). Forty people were selected sequentially as they started ART, stratified by sex, ART delivery mode (clinic- or home-based) and HIV progression stage (early or advanced) and interviewed at enrollment and at 3, 6, 18 and 30 months. At initiation of ART, participants agreed to follow TASO's positive-living recommendations. Initially poor health prevented sexual activity. As health improved, participants prioritised resuming economic production and support for their children. With further improvements, sexual desire resurfaced and people in relationships cemented these via sex. The findings highlight the limitations of HIV prevention based on medical care/personal counselling. As ART leads to health improvements, social norms, economic needs and sexual desires increasingly influence sexual behaviour. Positive prevention interventions need to seek to modify normative and economic influences on sexual behaviour, as well as to provide alternatives to condoms. PMID:21390948

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

2011-05-01

391

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.

2014-01-01

392

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.

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

393

Primary antiretroviral drug resistance among HIV type 1-infected individuals in Brazil.  

PubMed

Infection with drug-resistant human immunodeficiency virus type 1 (HIV-1) has been documented in all countries that have surveyed for it and may result in an unfavorable response to therapy. The prevalence and characteristics of individuals with transmitted resistance to antiretroviral drugs have been scarcely described in Brazil. We performed antiretroviral resistance testing prior to initiation of therapy in 400 subjects enrolled from 20 centers in 13 Brazilian cities between March and September 2007. Genotyping was conducted using PCR-amplified HIV pol products by automated sequencing, and genotype interpretation was done according to the IAS-USA consensus. Of 400 eligible participants, 387 (95.8%) were successfully tested. Seven percent of antiretroviral-naive patients carried viruses with one or more major mutation associated with drug resistance. The prevalence of these mutations was 1.0% for protease inhibitors, 4.4% for nonnucleoside reverse transcriptase inhibitors, and 1.3% for nucleoside reverse transcriptase inhibitors. The frequency of multidrug resistance among the resistant strains was 13.6%. Among subjects infected with drug-resistant virus, the majority were infected with subtype B viruses (91%). Subjects from the city of São Paulo had higher transmitted resistance mutations compared to the rest of the country. Reporting a partner taking antiretroviral medications was associated with a higher chance of harboring HIV variants with major drug resistance mutations [odds ratio = 2.57 (95% confidence interval, 1.07-6.16); p = 0.014]. Resistance testing in drug-naive individuals identified 7% of subjects with mutations associated with reduced susceptibility to antiretroviral drugs. Continued surveillance of drug-resistant HIV-1 in Brazil is warranted when guidelines for HIV prophylaxis and treatment are updated. Resistance testing among drug-naive patients prior to treatment initiation should be considered, mainly directed at subjects whose partners are already on antiretroviral therapy. PMID:19689190

Sprinz, Eduardo; Netto, Eduardo M; Patelli, Maria; Lima, J S; Lima, Maria Patelli J S; Furtado, Juvênao J D; da Eira, Margareth; Zajdenverg, Roberto; Madruga, José V; Lewi, David S; Machado, Alcyone A; Pedro, Rogério J; Soares, Marcelo A

2009-09-01

394

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

PubMed Central

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

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

2013-01-01

395

NOVEL DELIVERY SYSTEM ENHANCES EFFICACY OF ANTIRETROVIRAL THERAPY IN ANIMAL MODEL FOR HIV-1 ENCEPHALITIS (HIVE)  

PubMed Central

Most potent anti-retroviral drugs (e.g., HIV-1 protease inhibitors) poorly penetrate the blood-brain barrier. Brain distribution can be limited by the efflux transporter, P-glycoprotein (P-gp). The ability of a novel drug delivery system (block co-polymer P85) that inhibits P-gp, to increase the efficacy of anti-retroviral drugs in brain was examined using a severe combined immunodeficiency (SCID) mouse model of HIV-1 encephalitis (HIVE). SCID mice inoculated with HIV-1 infected human monocyte-derived macrophages (MDM) into the basal ganglia were treated with P85, anti-retroviral therapy (ART) [zidovudine, lamivudine and nelfinavir, (NEL)], or P85 and ART. Mice were sacrificed on days 7 and 14, and brains were evaluated for levels of viral infection. Anti-viral effects of NEL, P85 or their combination were evaluated in vitro using HIV-1 infected MDM and demonstrated anti-retroviral effects of P85 alone. In SCID mice injected with virus-infected MDM the combination of ART-P85 and ART alone showed a significant decrease of HIV-1 p24 expressing MDM (25% and 33% of controls, respectively) at day 7 while P85 alone group was not different from control. At day 14, all treatment groups showed a significant decrease in percentage of HIV-1 infected MDM as compared to control. P85 alone and combined ART-P85 groups showed the most significant reduction in percentage of HIV-1 p24 expressing MDM (8–22% of control) that were superior to the ART alone group (38% of control). Our findings indicate major anti-retroviral effects of P85 and enhanced in vivo efficacy of antiretroviral drugs when combined with P85 in a SCID mouse model of HIVE.

Spitzenberger, Timothy J.; Heilman, David; Diekmann, Casey; Batrakova, Elena; Kabanov, Alexander; Gendelman, Howard E.; Elmquist, William F.; Persidsky, Yuri

2011-01-01

396

Novel delivery system enhances efficacy of antiretroviral therapy in animal model for HIV-1 encephalitis.  

PubMed

Most potent antiretroviral drugs (e.g., HIV-1 protease inhibitors) poorly penetrate the blood-brain barrier. Brain distribution can be limited by the efflux transporter, P-glycoprotein (P-gp). The ability of a novel drug delivery system (block co-polymer P85) that inhibits P-gp, to increase the efficacy of antiretroviral drugs in brain was examined using a severe combined immunodeficiency (SCID) mouse model of HIV-1 encephalitis (HIVE). Severe combined immunodeficiency mice inoculated with HIV-1 infected human monocyte-derived macrophages (MDM) into the basal ganglia were treated with P85, antiretroviral therapy (ART) (zidovudine, lamivudine and nelfinavir (NEL)), or P85 and ART. Mice were killed on days 7 and 14, and brains were evaluated for levels of viral infection. Antiviral effects of NEL, P85, or their combination were evaluated in vitro using HIV-1 infected MDM and showed antiretroviral effects of P85 alone. In SCID mice injected with virus-infected MDM, the combination of ART-P85 and ART alone showed a significant decrease of HIV-1 p24 expressing MDM (25% and 33% of controls, respectively) at day 7 while P85 alone group was not different from control. At day 14, all treatment groups showed a significant decrease in percentage of HIV-1 infected MDM as compared with control. P85 alone and combined ART-P85 groups showed the most significant reduction in percentage of HIV-1 p24 expressing MDM (8% to 22% of control) that were superior to the ART alone group (38% of control). Our findings indicate major antiretroviral effects of P85 and enhanced in vivo efficacy of antiretroviral drugs when combined with P85 in a SCID mouse model of HIVE. PMID:17063148

Spitzenberger, Timothy J; Heilman, David; Diekmann, Casey; Batrakova, Elena V; Kabanov, Alexander V; Gendelman, Howard E; Elmquist, William F; Persidsky, Yuri

2007-05-01

397

Comparison of levels of antiretroviral drugs with efficacy in children with HIV infection  

Microsoft Academic Search

Objective  To determine the prevelance of low and high antiretroviral (ARV) plasma levels and to analyze correlation between ARV concentrations\\u000a and the appearance of therapeutic failure and toxicity.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  The authors present here a study evaluating antiretroviral plasma concentrations in HIV infected children on nonnucleoside\\u000a reverse transcriptase inhibitors and protease inhibitors based therapy. The authors carried out a multicentre, cross-sectional\\u000a study, including

Ana Pilar Nso; Beatriz Larru; Jose Ma Bellón; Ma José Mellado; Jose Tomás Ramos; Ma Isabel González; María Luisa Navarro; María Ángeles Muñoz-Fernández; María Isabel de José

2010-01-01

398

Genotypic prediction of resistant mutation in HIV-1 pol gene towards the antiretroviral drugs.  

PubMed

Mutation in HIV-1 pol gene confers the resistance to antiretroviral drugs. Three nucleotide sequences of HIV-1 pol gene products were selected and HIV BLAST was performed. Amino acid positions of 30 sequences were compared with HXB2 reference strain. Two sequences of protease show the major mutation with mutations sites of I54V and V82A and 8 sequences shown other mutations. One sequence of integrase with minor mutation of E157Q and 9 sequences with other mutations were inferred. This study is useful in making more accurate prediction of results with better combination Highly Active Antiretroviral Therapy (HAART) and important mutations. PMID:21441094

Kumar, Amit; Jadhav, Chandrakant

2011-01-01

399

Delayed onset renal failure in a patient on tenofovir based antiretroviral regimen.  

PubMed

Tenofovir is recommended as one of the first line agents in combination with other antiretroviral drugs for management of human immunodeficiency virus (HIV). It is known to cause renal failure after exposure for a median duration of 5 months. We report tenofovir induced adverse drug reaction in a 56-year-old female patient who was diagnosed to have HIV 1 infection since 10 years. The combination antiretroviral treatment included tenofovir, emtricitabine and ritonavir/lopinavir regimen since the last 6 years. She presented with recent onset renal failure and renal biopsy showed interstitial nephritis which could probably attributable to tenofovir. PMID:24741201

Krishna, M Murali; Subbalaxmi, M V S; Uppin, Megha; Radhika, S

2014-03-01

400

Delayed onset renal failure in a patient on tenofovir based antiretroviral regimen  

PubMed Central

Tenofovir is recommended as one of the first line agents in combination with other antiretroviral drugs for management of human immunodeficiency virus (HIV). It is known to cause renal failure after exposure for a median duration of 5 months. We report tenofovir induced adverse drug reaction in a 56-year-old female patient who was diagnosed to have HIV 1 infection since 10 years. The combination antiretroviral treatment included tenofovir, emtricitabine and ritonavir/lopinavir regimen since the last 6 years. She presented with recent onset renal failure and renal biopsy showed interstitial nephritis which could probably attributable to tenofovir.

Krishna, M. Murali; Subbalaxmi, M. V. S.; Uppin, Megha; Radhika, S.

2014-01-01

401

Depression associated with antiretroviral drug therapy in HIV: case report and overview.  

PubMed

Depression is the main psychiatric symptom in patients living with HIV. Genetic predisposition, stress from disease as well as the antiretroviral therapy itself are discussed as pathogenic factors. We report a 35-year-old HIV-positive man suffering from bipolar disorder who developed major depression shortly after commercing combination antiretroviral therapy (cART) on three occasions. The first two times the patient ceased therapy autonomously, and the depression disappeared completely. The close connection between cART and major depression in the present case supports the depression-inducing potential of cART. Additionally, we present an overview of literature. PMID:22807551

Kaestner, F; Anneken, K; Mostert, C; Reichelt, D; Rothermundt, M; Evers, S; Husstedt, I W

2012-06-01

402

Subacute hypersensitivity pneumonitis in an HIV infected patient receiving antiretroviral therapy  

PubMed Central

Abnormal pulmonary immune response to various antigens can lead to hypersensitivity pneumonitis. This disease has not previously been reported in HIV infected patients. This case report describes an HIV infected woman who developed subacute hypersensitivity pneumonitis in response to bird exposure. The disease manifested itself only after the patient experienced an improvement in her CD4 positive T lymphocyte count secondary to antiretroviral therapy. This case emphasises the need to consider non-HIV associated diseases in patients with HIV and suggests that diseases in which host immune response plays an essential role in pathogenesis may become more prevalent in HIV infected patients receiving effective antiretroviral therapy.??

Morris, A.; Nishimura, S.; Huang, L.

2000-01-01

403

Pyoderma gangrenosum successfully treated with antiretroviral therapy alone in a human immunodeficiency virus-infected individual.  

PubMed

We report a case of a 60-year-old man infected with human immunodeficiency virus (HIV) who was transferred to our hospital for management of multiple non-healing, painful ulcers on the lower extremities. The histological findings of the biopsy specimen were compatible with the diagnosis of pyoderma gangrenosum (PG). An association between HIV infection and the development of PG was considered after a thorough investigation. Antiretroviral therapy without the use of adjunctive immunosuppressive agents resulted in clinical improvement. Our case implies that antiretroviral therapy alone could heal PG in untreated HIV-infected patients. PMID:24767463

Sakamoto, Naoya; Yanagisawa, Naoki; Sekiya, Noritaka; Suganuma, Akihiko; Imamura, Akifumi; Ajisawa, Atsushi

2014-08-01

404

HIV Viremia and Incidence of Non-Hodgkin Lymphoma in Patients Successfully Treated With Antiretroviral Therapy.  

PubMed

Background.?The incidence of non-Hodgkin lymphoma (NHL) in human immunodeficiency virus (HIV)-infected patients remains high despite treatment with antiretroviral therapy (ART). Methods.?We evaluated NHL incidence in HIV-infected patients followed in the Centers for AIDS Research Network of Integrated Clinical Systems who started combination ART and achieved suppression of HIV. We estimated the hazard ratio for NHL by time-varying HIV viremia categories, accounting for time-varying CD4 cell count using marginal structural models. Results.?We observed 37 incident NHL diagnoses during 21 607 person-years of follow-up in 6036 patients (incidence rate, 171 per 100 000 person-years; 95% confidence interval [CI], 124-236). NHL incidence was high even among patients with nadir CD4 cell count >200 cells/µL (140 per 100 000 person-years [95% CI, 80-247]). Compared with ?50 copies/mL, hazard ratios (HRs) for NHL were higher among those with HIV viremia of 51-500 copies/mL (HR current = 1.66 [95% CI, .70-3.94]; HR 3-month lagged = 2.10 [95% CI, .84-5.22]; and HR 6-month lagged = 1.46 [95% CI, .60-3.60]) and >500 copies/mL (HR current = 2.39 [95% CI, .92-6.21]; HR 3-month lagged = 3.56 [95% CI, 1.21-10.49]; and HR 6-month lagged = 2.50 [95% CI, .91-6.84]). Current HIV RNA as a continuous variable was also associated with NHL (HR = 1.42 per log10 copies/mL [95% CI, 1.05-1.92]). Conclusions.?Our findings demonstrate a high incidence of NHL among HIV-infected patients on ART and suggest a role of HIV viremia in the pathogenesis of NHL. Earlier initiation of potent ART and maximal continuous suppression of HIV viremia may further reduce NHL risk. PMID:24523217

Achenbach, Chad J; Buchanan, Ashley L; Cole, Stephen R; Hou, Lifang; Mugavero, Michael J; Crane, Heidi M; Moore, Richard D; Haubrich, Richard H; Gopal, Satish; Eron, Joseph J; Hunt, Peter W; Rodriguez, Benigno; Mayer, Kenneth; Saag, Michael S; Kitahata, Mari M

2014-06-01

405

Long-Term Survival in HIV Positive Patients with up to 15 Years of Antiretroviral Therapy  

PubMed Central

Background Life expectancy has increased for newly diagnosed HIV patients since the inception of combination antiretroviral treatment (cART), but there remains a need to better understand the characteristics of long-term survival in HIV-positive patients. We examined long-term survival in HIV-positive patients receiving cART in the Australian HIV Observational Database (AHOD), to describe changes in mortality compared to the general population and to develop longer-term survival models. Methods Data were examined from 2,675 HIV-positive participants in AHOD who started cART. Standardised mortality ratios (SMR) were calculated by age, sex and calendar year across prognostic characteristics using Australian Bureau of Statistics national data as reference. SMRs were examined by years of duration of cART by CD4 and similarly by viral load. Survival was analysed using Cox-proportional hazards and parametric survival models. Results The overall SMR for all-cause mortality was 3.5 (95% CI: 3.0–4.0). SMRs by CD4 count were 8.6 (95% CI: 7.2–10.2) for CD4<350 cells/µl; 2.1 (95% CI: 1.5–2.9) for CD4?=?350–499 cells/µl; and 1.5 (95% CI: 1.1–2.0) for CD4?500 cells/µl. SMRs for patients with CD4 counts <350 cells/µL were much higher than for patients with higher CD4 counts across all durations of cART. SMRs for patients with viral loads greater than 400 copies/ml were much higher across all durations of cART. Multivariate models demonstrated improved survival associated with increased recent CD4, reduced recent viral load, younger patients, absence of HBVsAg-positive ever, year of HIV diagnosis and incidence of ADI. Parametric models showed a fairly constant mortality risk by year of cART up to 15 years of treatment. Conclusion Observed mortality remained fairly constant by duration of cART and was modelled accurately by accepted prognostic factors. These rates did not vary much by duration of treatment. Changes in mortality with age were similar to those in the Australian general population.

McManus, Hamish; O'Connor, Catherine C.; Boyd, Mark; Broom, Jennifer; Russell, Darren; Watson, Kerrie; Roth, Norman; Read, Phillip J.; Petoumenos, Kathy; Law, Matthew G.

2012-01-01

406

Involving expert patients in antiretroviral treatment provision in a tertiary referral hospital HIV clinic in Malawi  

PubMed Central

Background Current antiretroviral treatment (ART) models in Africa are labour intensive and require a high number of skilled staff. In the context of constraints in human resources for health, task shifting is considered a feasible alternative for ART service delivery. In 2006, Dignitas International in partnership with the Malawi Ministry of Health trained a cadre of expert patients at the HIV Clinic at a tertiary referral hospital in Zomba, Malawi. Expert patients were trained to assist with clinic tasks including measurement of vital signs, anthropometry and counseling. Methods A descriptive observational study using mixed methods was conducted two years after the start of program implementation. Semi-structured interviews were conducted with 20 patients, seven expert patients and six formal health care providers to explore perceptions towards the expert patients’ contributions in the clinic. Structured exit interviews with 81 patients, assessed whether essential ART information was conveyed during counseling sessions. Vital signs and anthropometry measurements performed by expert patients were repeated by a nurse to assess accuracy of measurements. Direct observations quantified the time spent with each patient. Results There were minor differences in measurement of patients’ weight, height and temperature between the expert patients and the nurse. The majority of patients exiting a counseling session reported, without prompting, at least three side effects of ART, correct actions to be taken on observing a side-effect, and correct consequences of non-adherence to ART. Expert patients carried out 368 hours of nurse tasks each month, saving two and a half full-time nurse equivalents per month. Formal health care workers and patients accept and value expert patients’ involvement in ART provision and care. Expert patients felt valued by patients for being a ‘role model’, or a ‘model of hope’, promoting positive living and adherence to ART. Conclusions Expert patients add value to the ART services at a tertiary referral HIV clinic in Malawi. Expert patients carry out shifted tasks acceptably, saving formal health staff time, and also act as ‘living testimonies’ of the benefits of ART and can be a means of achieving greater involvement of People Living with HIV in HIV treatment programs.

2012-01-01

407

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

PubMed Central

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

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

2013-01-01

408

Clinical Mentorship of Nurse Initiated Antiretroviral Therapy in Khayelitsha, South Africa: A Quality of Care Assessment  

PubMed Central

Introduction To combat the AIDS epidemic and increase HIV treatment access, the South African government implemented a nurse-based, doctor-supported model of care that decentralizes administration of antiretroviral treatment (ART) for HIV positive patients through nurse initiated and managed ART. Médecins Sans Frontières (MSF) implemented a mentorship programme to ensure successful task-shifting, subsequently assessing the quality of clinical care provided by nurses. Methods A before-after cross-sectional study was conducted on nurses completing the mentorship programme in Khayelitsha, South Africa, from February 2011-September 2012. Routine clinical data from 229 patient folders and 21 self-assessment questionnaires was collected to determine the number of patients initiated on ART by nurses; quality of ART management before-after mentorship; patient characteristics for doctor and nurse ART initiations; and nurse self-assessments after mentorship. Results Twenty one nurses were authorized by one nurse mentor with one part-time medical officer's support, resulting in nurses initiating 77% of ART eligible patients. Improvements in ART management were found for drawing required bloods (91% vs 99%, p?=?0.03), assessing adherence (50% vs 78%, p<0.001) and WHO staging (63% vs 91%, p<0.001). Nurse ART initiation indicators were successfully completed at 95–100% for 11 of 16 indicators: clinical presentation; patient weight; baseline blood work (CD4, creatinine, haemoglobin); STI screening; WHO stage, correlating medical history; medications prescribed appropriately; ART start date; and documented return date. Doctors initiated more patients with TB/HIV co-infection and WHO Stage 3 and 4 disease than nurses. Nurse confidence improved for managing HIV-infected children and pregnant women, blood result interpretation and long-term side effects. Conclusions Implementation of a clinical mentorship programme in Khayelitsha led to nurse initiation of a majority of eligible patients, enabling medical officers to manage complex cases. As mentorship can increase clinical confidence and enhance professional development, it should be considered essential for universal ART access in resource limited settings.

Green, Ann; de Azevedo, Virginia; Patten, Gabriela; Davies, Mary-Ann; Ibeto, Mary; Cox, Vivian

2014-01-01

409

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

PubMed Central

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

2011-01-01

410

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

PubMed Central

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

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

2011-01-01

411

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

Federal Register 2010, 2011, 2012, 2013

...DEPARTMENT OF TRANSPORTATION Federal Transit Administration Major Capital Investment Projects; Guidance on News Starts/Small Starts Policies and Procedures AGENCY: Federal Transit Administration (FTA), DOT. ACTION:...

2011-08-16

412

Transmitted drug resistance to rilpivirine among antiretroviral-na?ve patients living with HIV from northern Poland  

PubMed Central

Introduction Rilpivirine (RPV) is a second-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) that was recently approved for the treatment of antiretroviral-naïve individuals with HIV-1 viral load of <100,000 copies/ml. As transmission of the drug resistance mutations to this NNRTI may affect treatment outcomes, the frequency of primary, RPV-associated drug resistance mutations was assessed in this study. Methods For the study, 244 viral genome sequences from antiretroviral-naïve individuals were obtained by bulk sequencing. RPV-associated mutations were divided into RPV resistance mutations (K101E/P, E138A/G/K/Q/R, V179L, Y181C/I/V, Y188L, H221Y, F227C and M230I/L) according to the International AIDS Society-USA (IAS-USA) mutation list and variants potentially affecting RPV susceptibility (L100I, K101H/T, E138S, V179F/D/G/T, G190A/E/S, F227L and M230V) based on the in vitro and in vivo data. Results IAS-USA RPV drug resistance mutations were found in 5.3% sequences, with E138A and E138G being the most common (3.7 and 0.8%, respectively), followed by K101E (0.4%) and Y181C (0.4%), with no significant differences in the frequency between subtype B and non-B clades. Mutations potentially reducing RPV susceptibility were found in 2.5% of sequences, and they included V179D (1.6%) and G190A (0.8%), with equal distribution among non-B (n=2, 2.5%) and subtype B (n=4, 2.5%) clades. Clustering of RPV mutations was infrequent. Conclusions Prevalence of RPV-associated drug resistance mutations was low in the analysed sample and did not vary across the subtypes. The frequency of variants with potential influence on RPV susceptibility was similar among non-B variants if compared to B clades. Transmitted drug resistance to RPV is uncommon, which makes this a good option for the treatment of ARV-naïve patients; however, genotype resistance testing should remain compulsory before starting an RPV-based regimen.

Parczewski, Milosz; Urbanska, Anna; Maciejewska, Katarzyna; Witak-Jedra, Magdalena; Leszczyszyn-Pynka, Magdalena

2014-01-01

413

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

PubMed Central

Abstract As increasing numbers of persons are placed on potentially life-saving combination antiretroviral therapy (cART) in sub-Saharan Africa, it is imperative to identify the psychosocial and social factors that may influence antiretroviral (ARV) medication adherence. Using an 87 question survey, the following data were collected from patients on cART in Botswana: demographics, performance (Karnofsky) score, perceived stigma and level of HIV disclosure, attitudes and beliefs concerning HIV/AIDS, substance and/or drug use, depression, and pharmacy and healthcare provider-related factors. Overall adherence rates were determined by patient self-report, institutional adherence, and a