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Sample records for starting nevirapine-containing antiretroviral

  1. When to start antiretroviral therapy.

    PubMed

    Rhame, Frank S

    2011-02-01

    Antiretrovirals perform superbly in combating HIV infection. But when to initiate therapy in asymptomatic, nonpregnant, hepatitis-free, HIV-infected persons is not securely established. Of two completed randomized trials using modern therapy, a Haitian trial demonstrated a benefit to initiating therapy between 200 and 350 CD4 cells/mm(3) as compared with less than 200 CD4 cells/mm(3) and an international trial demonstrated a benefit to starting at greater than 350 CD4 cells/mm(3) as compared with less than 250 CD4 cells/mm(3). Many observational cohorts support initiating treatment at less than 350 CD4 cells/mm(3). Of these, three large studies supported initiation at less than 350 cells/mm(3), less than 450 CD4 cells/mm(3), and less than 500 CD4 cells/mm(3), respectively, but only the last supported starting at higher counts. Such studies are not probative, given the problem of confounding. No conventional antiretroviral regimen is free of long-term adverse effects, especially over decades of use. All are expensive and require expensive monitoring. When resources are restricted, initiation of antiretrovirals for persons with high CD4 count diverts treatment from more needy persons. Pathophysiological considerations favor universal treatment because antiretrovirals mitigate systemic inflammation, which aggravates atherosclerosis. There are suggestions that HIV hastens the natural decline of cognitive, renal, and pulmonary function as well as bone mineral loss; the mechanism(s) are uncertain, as is the ability of antiretrovirals to counteract the probable acceleration. The four major guideline panels, although all have issued updates in the past year, are not consistent in recommendations for treatment of HIV-infected persons with counts greater than 350 CD4 cells/mm(3). PMID:21308456

  2. When to Start Antiretroviral Therapy

    MedlinePlus

    ... Recent (Early) HIV Infection Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal ... HIV-Infected Pregnant Women Who Have Never Received Antiretroviral Drugs (Antiretroviral Naive)

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

    PubMed

    Rodrguez, Mnica; Flores, Pal; Ahumada, Vctor; Vzquez-Vzquez, Lorena; Alvarado-de la Barrera, Claudia; Reyes-Tern, Gustavo

    2012-01-01

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

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

    PubMed

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

    2011-12-01

    The evaluation of new cases of HIV infection is relatively common in Spain, where several thousands of patients with new infections are diagnosed each year. Eighty per cent of them have a chronic HIV infection at the first clinical evaluation, which is symptomatic (late presenters) in up to 30% of patients. The initial evaluation of HIV infection is not only directed at determining the clinical, virological (plasma HIV RNA viral load, resistance test and viral tropism) and immunological (CD4+ T-cell cell count) situation of the patients, but must also address the study of their co-infections (hepatitis, tuberculosis) and comorbidities (cardiovascular, hepatic, renal and bone) and the risk of HIV transmission. This is needed in order to decide, whether or not to start antiretroviral treatment, and with which combined antiretroviral treatment to start with, the prophylaxis of opportunistic infections, and the treatment of coinfections and comorbidities. The past and current medical history, the physical examination and laboratory tests will help us decide if the patient is to receive therapeutic intervention. The level of CD4+ T-cell lymphocytes is the best marker to suggest when to start combined antiretroviral treatment, indicating whether or not to start prophylaxis against opportunistic infections (if patients have a CD4+ T-cell count below 200 cells/mm(3)), and in advanced patients should make us suspect the presence of active opportunistic diseases in symptomatic cases. The management of patients with HIV infection must also include appropriate health education on the modes of transmission and prevention of HIV infection, and also to explain its natural history and how it can be modified with proper antiretroviral treatment, as well as to promote a healthy life. No less important is the psychological support, as these patients must learn to live with a chronic infection, which managed properly can ensure a very good long-term prognosis and quality of life. PMID:22078726

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

    PubMed Central

    2013-01-01

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

  6. Optimum time to start antiretroviral therapy during HIV-associated opportunistic infections

    PubMed Central

    Lawn, Stephen D.; Török, M. Estée; Wood, Robin

    2013-01-01

    Purpose of review We review recently published literature concerning the optimum time to start antiretroviral therapy (ART) in patients with HIV-associated opportunistic infections (OIs). Recent findings In addition to data from observational studies, results from six randomised controlled clinical trials were available by July 2010. The collective findings of these trials were that patients with CD4 cell counts <200 cells/μL who start ART within the first two weeks of treatment for OIs including Pneumocystis jirovecii pneumonia, serious bacterial infections or pulmonary tuberculosis have lower mortality when compared to patients starting ART at later time-points. Moreover, patients with pulmonary tuberculosis and CD4 counts of 200-500 cells/μL who started ART during TB treatment had improved survival compared to those who deferred ART until after the end of treatment. In contrast, in two separate studies, immediate ART conferred no survival benefit in patients with TB meningitis and was associated with substantially higher mortality risk in patients with cryptococcal meningitis. Summary Initiation of ART during the first 2 weeks of treatment for serious opportunistic infections has been shown to be associated with improved survival with the exception of patients with tuberculous meningitis and cryptococcal meningitis. Further clinical trials are ongoing. PMID:21150593

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

    2013-01-01

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

  10. Earlier versus Later Start of Antiretroviral Therapy in HIV-Infected Adults with Tuberculosis

    PubMed Central

    Blanc, François-Xavier; Sok, Thim; Laureillard, Didier; Borand, Laurence; Rekacewicz, Claire; Nerrienet, Eric; Madec, Yoann; Marcy, Olivier; Chan, Sarin; Prak, Narom; Kim, Chindamony; Lak, Khemarin Kim; Hak, Chanroeurn; Dim, Bunnet; Sin, Chhun Im; Sun, Sath; Guillard, Bertrand; Sar, Borann; Vong, Sirenda; Fernandez, Marcelo; Fox, Lawrence; Delfraissy, Jean-François; Goldfeld, Anne E.

    2016-01-01

    Background Tuberculosis remains an important cause of death among patients infected with the human immunodeficiency virus (HIV). Robust data are lacking with regard to the timing for the initiation of antiretroviral therapy (ART) in relation to the start of antituberculosis therapy. Methods We tested the hypothesis that the timing of ART initiation would significantly affect mortality among adults not previously exposed to antiretroviral drugs who had newly diagnosed tuberculosis and CD4+ T-cell counts of 200 per cubic millimeter or lower. After beginning the standard, 6-month treatment for tuberculosis, patients were randomly assigned to either earlier treatment (2 weeks after beginning tuberculosis treatment) or later treatment (8 weeks after) with stavudine, lamivudine, and efavirenz. The primary end point was survival. Results A total of 661 patients were enrolled and were followed for a median of 25 months. The median CD4+ T-cell count was 25 per cubic millimeter, and the median viral load was 5.64 log10 copies per milliliter. The risk of death was significantly reduced in the group that received ART earlier, with 59 deaths among 332 patients (18%), as compared with 90 deaths among 329 patients (27%) in the later-ART group (hazard ratio, 0.62; 95% confidence interval [CI]; 0.44 to 0.86; P = 0.006). The risk of tuberculosis-associated immune reconstitution inflammatory syndrome was significantly increased in the earlier-ART group (hazard ratio, 2.51; 95% CI, 1.78 to 3.59; P<0.001). Irrespective of the study group, the median gain in the CD4+ T-cell count was 114 per cubic millimeter, and the viral load was undetectable at week 50 in 96.5% of the patients. Conclusions Initiating ART 2 weeks after the start of tuberculosis treatment significantly improved survival among HIV-infected adults with CD4+ T-cell counts of 200 per cubic millimeter or lower. (Funded by the French National Agency for Research on AIDS and Viral Hepatitis and the National Institutes of Health; CAMELIA ClinicalTrials.gov number, NCT01300481.) PMID:22010913

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

    PubMed Central

    Siedner, Mark J.

    2016-01-01

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

  12. Lipoprotein Changes in HIV-Infected Antiretroviral-Naïve Individuals after Starting Antiretroviral Therapy: ACTG Study A5152s Stein: Lipoprotein Changes on Antiretroviral Therapy

    PubMed Central

    Stein, James H.; Komarow, Lauren; Cotter, Bruno R.; Currier, Judith S.; Dubé, Michael P.; Fichtenbaum, Carl J.; Gerschenson, Mariana; Mitchell, Carol K.C.; Murphy, Robert L.; Squires, Kathleen; Parker, Robert A.; Torriani, Francesca J.

    2008-01-01

    Background Dyslipidemia is a frequent complication of antiretroviral therapy (ART) for patients with human immunodeficiency virus infection (HIV). The effects of ART on lipoproteins are less well-understood, and have not been investigated in a prospective study where assignment to ART is randomized. Objective To evaluate the effects of three class-sparing ART regimens on lipids and lipoproteins. Methods This was a substudy of a prospective, multicenter study treatment-naïve HIV-infected individuals randomly assigned to receive a regimen of nucleoside reverse transcriptase inhibitors (NRTIs) + the non-nucleoside reverse transcriptase inhibitor efavirenz, NRTIs + the protease inhibitor lopinavir/ritonavir, or a NRTI-sparing regimen of efavirenz + lopinavir/ritonavir. Lipoproteins were measured by nuclear magnetic resonance spectroscopy. Results Among the 82 participants, total and small low-density lipoprotein concentrations increased (median, interquartile range) by 152 (-49 - +407, p<0.01) and 130 (-98 - +417, p<0.01) nmol/L, respectively, especially in the arms containing lopinavir/ritonavir (pKW<0.04). Very low-density lipoproteins also increased (p<0.01), with a larger increase in the arms that contained lopinavir/ritonavir (p=0.022). High-density lipoproteins increased by 6.0 nmol/L (2.8 - 10.4, p<0.01), but differences between arms were not significant (pKW=0.069). Changes were not related to changes in markers of insulin/glucose metabolism. Conclusions Total and small low-density lipoprotein concentrations increased, especially in the arms containing lopinavir/ritonavir, as did increases in total very low-density lipoproteins. Adverse changes were especially prominent in the arm with efavirenz + lopinavir/ritonavir. PMID:19956354

  13. Lipoprotein Changes in HIV-Infected Antiretroviral-Naïve Individuals after Starting Antiretroviral Therapy: ACTG Study A5152s Stein: Lipoprotein Changes on Antiretroviral Therapy.

    PubMed

    Stein, James H; Komarow, Lauren; Cotter, Bruno R; Currier, Judith S; Dubé, Michael P; Fichtenbaum, Carl J; Gerschenson, Mariana; Mitchell, Carol K C; Murphy, Robert L; Squires, Kathleen; Parker, Robert A; Torriani, Francesca J

    2008-12-01

    BACKGROUND: Dyslipidemia is a frequent complication of antiretroviral therapy (ART) for patients with human immunodeficiency virus infection (HIV). The effects of ART on lipoproteins are less well-understood, and have not been investigated in a prospective study where assignment to ART is randomized. OBJECTIVE: To evaluate the effects of three class-sparing ART regimens on lipids and lipoproteins. METHODS: This was a substudy of a prospective, multicenter study treatment-naïve HIV-infected individuals randomly assigned to receive a regimen of nucleoside reverse transcriptase inhibitors (NRTIs) + the non-nucleoside reverse transcriptase inhibitor efavirenz, NRTIs + the protease inhibitor lopinavir/ritonavir, or a NRTI-sparing regimen of efavirenz + lopinavir/ritonavir. Lipoproteins were measured by nuclear magnetic resonance spectroscopy. RESULTS: Among the 82 participants, total and small low-density lipoprotein concentrations increased (median, interquartile range) by 152 (-49 - +407, p<0.01) and 130 (-98 - +417, p<0.01) nmol/L, respectively, especially in the arms containing lopinavir/ritonavir (p(KW)<0.04). Very low-density lipoproteins also increased (p<0.01), with a larger increase in the arms that contained lopinavir/ritonavir (p=0.022). High-density lipoproteins increased by 6.0 nmol/L (2.8 - 10.4, p<0.01), but differences between arms were not significant (p(KW)=0.069). Changes were not related to changes in markers of insulin/glucose metabolism. CONCLUSIONS: Total and small low-density lipoprotein concentrations increased, especially in the arms containing lopinavir/ritonavir, as did increases in total very low-density lipoproteins. Adverse changes were especially prominent in the arm with efavirenz + lopinavir/ritonavir. PMID:19956354

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

    PubMed Central

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

    2015-01-01

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

  15. Antiretroviral Treatment-Associated Tuberculosis in a Prospective Cohort of HIV-Infected Patients Starting ART

    PubMed Central

    Worodria, William; Massinga-Loembe, Marguerite; Mayanja-Kizza, Harriet; Namaganda, Jane; Kambugu, Andrew; Manabe, Yukari C.; Kestens, Luc; Colebunders, Robert

    2011-01-01

    Commencement of antiretroviral treatment (ART) in severely immunosuppressed HIV-infected persons is associated with unmasking of subclinical disease. The subset of patients that are diagnosed with tuberculosis (TB) disease while on ART have been classified as ART-associated TB. Few studies have reported the incidence of ART-associated TB and unmasking TB-IRIS according to the International Network for the Study of HIV-Associated IRIS (INSHI) consensus definition. To determine the incidence and predictors of ART-associated TB, we screened 219 patients commencing ART at the Infectious Diseases Clinic in Kampala, Uganda for TB by symptoms, sputum microscopy, and chest X-rays and followed them for one year. Fourteen (6.4%) patients were diagnosed with TB during followup. Eight (3.8%) patients had ART-associated TB (incidence rate of 4.3 per 100 person years); of these, three patients fulfilled INSHI criteria for unmasking TB-associated IRIS (incidence rate of 1.6 per 100 person years). A body mass index of less than 18.5 kg/m2 BMI (HR 5.85 95% CI 1.24–27.46, P = .025) and a C-reactive protein greater than 5 mg/L (HR 8.23 95% CI 1.36–38.33, P = .020) were risk factors for ART-associated TB at multivariate analysis. In conclusion, with systematic TB screening (including culture and chest X-ray), the incidence of ART-associated TB is relatively low in settings with high HIV and TB prevalence. PMID:21197091

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

    2013-01-01

    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/μl should initiate ART. However, it remains controversial whether ART is indicated in asymptomatic HIV-infected persons with CD4 counts above 350 cells/μl, or whether it is more advisable to defer initiation until the CD4 count has dropped to 350 cells/μl. 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/μl (versus deferring initiation to around 350 cells/μl) results in benefit to the HIV+ person and data from observational studies are inconsistent. Large, clinical endpoint-driven randomized studies to determine the individual health benefits versus risks of earlier ART initiation are sorely needed. The counter-argument to this debate topic can be freely accessed here: http://www.biomedcentral.com/1741-7015/11/147. PMID:23767777

  19. Mortality of HIV-infected patients starting potent antiretroviral therapy: comparison with the general population in nine industrialized countries

    PubMed Central

    2009-01-01

    Background Mortality in HIV-infected patients has declined substantially with combination antiretroviral therapy (ART), but it is unclear whether it has reached that of the general population. We compared mortality in patients starting ART in nine countries of Europe and North America with the corresponding general population, taking into account their response to ART. Methods Eligible patients were enrolled in prospective cohort studies participating in the ART Cohort Collaboration. We calculated the ratio of observed to expected deaths from all causes [standardized mortality ratio (SMR)], measuring time from 6 months after starting ART, according to risk group, clinical stage at the start of ART and CD4 cell count and viral load at 6 months. Expected numbers of deaths were obtained from age-, sex- and country-specific mortality rates. Results Among 29 935 eligible patients, 1134 deaths were recorded in 131 510 person-years of follow-up. The median age was 37 years, 8162 (27%) patients were females, 4400 (15%) were injecting drug users (IDUs) and 6738 (23%) had AIDS when starting ART. At 6 months, 23 539 patients (79%) had viral load measurements ≤500 copies/ml. The lowest SMR, 1.05 [95% confidence interval (CI) 0.82–1.35] was found for men who have sex with men (MSM) who started ART free of AIDS, reached a CD4 cell count of ≥350 cells/μL and suppressed viral replication to ≤500 copies/ml by the sixth month. In contrast, the SMR was 73.7 (95% CI 46.4–116.9) in IDUs who failed to suppress viral replication and had CD4 cell counts <50 cells/μL at 6 months. The percentage of patients with SMRs <2 was 46% for MSM, 42% for heterosexually infected patients and 0% for patients with a history of injection drug use. Corresponding percentages for SMRs >10 were 4, 14 and 47%. Conclusions In industrialized countries, the mortality experience of HIV-infected patients who start ART and survive the first 6 months continues to be higher than in the general population, but for many patients excess mortality is moderate and comparable with patients having other chronic conditions. Much of the excess mortality might be prevented by earlier diagnosis of HIV followed by timely initiation of ART. PMID:19820106

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

    PubMed Central

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

    2014-01-01

    Objective: Few data describe antiretroviral treatment (ART)-related adverse events when treatment is initiated at CD4+ cell counts more than 350 cells/μl. 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/μl. 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/μl, 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/μl [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/μl 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/μl. Whilst evidence from randomized controlled trials is awaited, the timing of ART initiation in terms of benefits and risks of ART remains an important question. PMID:24583670

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

    PubMed

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

    2014-01-01

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

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

    PubMed Central

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

    2010-01-01

    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. PMID:20485497

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

    PubMed

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

    2015-04-01

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

  4. Toxicity-related antiretroviral drug treatment modifications in individuals starting therapy: A cohort analysis of time patterns, sex, and other risk factors

    PubMed Central

    Mihanović, Marta Perović; Haque, Najm S.; Rutherford, George W.; Zekan, Šime; Begovac, Josip

    2013-01-01

    Background Modifications to combination antiretroviral drug therapy (CART) regimens can occur for a number of reasons, including adverse drug effects. We investigated the frequency of and reasons for antiretroviral drug modifications (ADM) during the first 3 years after initiation of CART, in a closed cohort of CART-naïve adult patients who started treatment in the period 1998–2007 in Croatia. Material/Methods We calculated differential toxicity rates by the Poisson method. In multivariable analysis, we used a discrete-time regression model for repeated events for the outcome of modification due to drug toxicity. Results Of 321 patients who started CART, median age was 40 years, 19% were women, baseline CD4 was <200 cells/mm3 in 71%, and viral load was ≥100 000 copies/mL in 69%. Overall, 220 (68.5%) patients had an ADM; 124 (56%) of these had ≥1 ADM for toxicity reasons. Only 12.7% of individuals starting CART in the period 1998–2002 and 39.4% in the period 2003–2007 remained on the same regimen after 3 years. The following toxicities caused ADM most often: lipoatrophy (22%), gastrointestinal symptoms (20%), and neuropathy (18%). Only 5% of drug changes were due to virologic failure. Female sex (hazard ratio [HR], 2.42 95%; confidence intervals, 1.39–4.24) and older age (HR, 1.42 per every 10 years) were associated with toxicity-related ADM in the first 3 months of a particular CART regimen, but after 3 months of CART they were not. Conclusions Less toxic and better-tolerated HIV treatment options should be available and used more frequently in Croatia. PMID:23787803

  5. Retention and attrition during the preparation phase and after start of antiretroviral treatment in Thyolo, Malawi, and Kibera, Kenya: implications for programmes?

    PubMed

    Zachariah, R; Tayler-Smith, K; Manzi, M; Massaquoi, M; Mwagomba, B; van Griensven, J; van Engelgem, I; Arnould, L; Schouten, E J; Chimbwandira, F M; Harries, A D

    2011-08-01

    Among adults eligible for antiretroviral therapy (ART) in Thyolo (rural Malawi) and Kibera (Nairobi, Kenya), this study (a) reports on retention and attrition during the preparation phase and after starting ART and (b) identifies risk factors associated with attrition. 'Retention' implies being alive and on follow-up, whilst 'attrition' implies loss to follow-up, death or stopping treatment (if on ART). There were 11,309 ART-eligible patients from Malawi and 3633 from Kenya, of whom 8421 (74%) and 2792 (77%), respectively, went through the preparation phase and started ART. In Malawi, 2649 patients (23%) were lost to attrition in the preparation phase and 2189 (26%) after starting ART. Similarly, in Kenya 546 patients (15%) were lost to attrition in the ART preparation phase and 647 (23%) while on ART. Overall programme attrition was 43% (4838/11,309) for Malawi and 33% (1193/3633) for Kenya. Restricting cohort evaluation to 'on ART' (as is usually done) underestimates overall programme attrition by 38% in Malawi and 36% in Kenya. Risk factors associated with attrition in the preparation phase included male sex, age <35 years, advanced HIV/AIDS disease and increasing malnutrition. Considerable attrition occurs during the preparation phase of ART, and programme evaluations confined to on-treatment analysis significantly underestimate attrition. This has important operational implications, which are discussed here. PMID:21724219

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  11. Impact of nutritional supplementation on immune response, body mass index and bioelectrical impedance in HIV-positive patients starting antiretroviral therapy

    PubMed Central

    2013-01-01

    Background Challenges to HIV care in resource limited settings (RLS) include malnutrition. Limited evidence supports the benefit of nutritional supplementation when starting antiretroviral therapy (ART) in RLS. Methods Randomized controlled pilot study. HIV-positive ART-naive adults with self-reported weight loss were randomized to receive ART plus FutureLife porridge® nutritional supplement (NS) (388 kcal/day) or ART alone (Controls) for 6 months. Patients returned for monthly assessments and blood was drawn at enrolment and 6 months on ART. Differences in body composition, biochemical and laboratory parameters were estimated at 6 months on treatment. Results Of the 36 randomized patients, 26 completed the 6 month follow-up (11 NS vs 15 Controls). At enrolment, groups were similar in terms of age, gender, body mass index (BMI) and bioelectrical impedance. NS patients had a lower median CD4 count (60 cells/mm3 [IQR 12–105 vs 107 cells/mm3 [IQR 63–165]; p = 0.149) and hemoglobin (10.3 g/dL [IQR 9.0-11.3] vs 13.1 g/dL [IQR 11.1-14.7]; p = 0.001). At 6 months, NS patients increased their median CD4 count by 151 cells/mm3 [IQR 120–174) vs 77 cells/mm3 [IQR 33–145] in the Controls. NS patients had higher mean percentage change in body weight (12.7% vs 4.9%; p = 0.047), BMI (7.8% vs 5.5%; p = 0.007), absolute CD4 count (83.0% vs 46.4%, p = 0.002) and hemoglobin (9.5% vs 1.0%; p = 0.026). Patients in the NS arm had a higher mean percentage fat-free mass (16.7% vs −3.5%, p = 0.036), total body water (13.0% vs −1.9%, p = 0.026), intracellular water (16.1% vs −4.1%, p = 0.010) and basal metabolic rate (5.3% vs −0.2%, p = 0.014) compared to Controls. Patients in the NS arm also showed an improvement in physical activity at 6 months post-ART initiation compared to Controls (p = 0.037). Conclusion Preliminary results are encouraging and suggest that NS taken concurrently with ART can promote weight gain, improve immune response and improve physical activity in HIV-positive patients that present at ART initiation with weight loss. PMID:23919622

  12. Antiretroviral drugs.

    PubMed

    De Clercq, Erik

    2010-10-01

    In October 2010, it will be exactly 25 years ago that the first antiretroviral drug, AZT (zidovudine, 3'-azido-2',3'-dideoxythymidine), was described. It was the first of 25 antiretroviral drugs that in the past 25 years have been formally licensed for clinical use. These antiretroviral drugs fall into seven categories [nucleoside reverse transcriptase inhibitors (NRTIs), nucleotide reverse transcriptase inhibitors (NtRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), fusion inhibitors (FIs), co-receptor inhibitors (CRIs) and integrase inhibitors (INIs). The INIs (i.e. raltegravir) represent the most recent advance in the search for effective and selective anti-HIV agents. Combination of several anti-HIV drugs [often referred to as highly active antiretroviral therapy (HAART)] has drastically altered AIDS from an almost uniformly fatal disease to a chronic manageable one. PMID:20471318

  13. Delayed-type hypersensitivity skin test reactivity and survival in HIV-infected patients in Uganda: should anergy be a criterion to start antiretroviral therapy in low-income countries?

    PubMed

    Jones-López, Edward C; Okwera, Alphonse; Mayanja-Kizza, Harriet; Ellner, Jerrold J; Mugerwa, Roy D; Whalen, Christopher C

    2006-01-01

    Access to antiretroviral (ARV) drugs is improving in sub-Saharan Africa but still constrained by several clinical and logistical obstacles. There is a need to develop affordable markers to guide initiation of treatment. We present a prospective cohort study of 779 patients participating in a TB prophylaxis trial. We performed separate analyses for anergic and nonanergic subjects. Prognostic factors for anergic and nonanergic subjects differed between groups. Individuals with anergy and constitutional symptoms were at the highest risk of death. Incident tuberculosis and CD4 < 200 cells/muL at enrollment were the strongest risk factors for death. HIV disease is associated with substantial morbidity and mortality in this population. The burden caused by tuberculosis is particularly high. Anergy is a strong and independent predictor of death. World Health Organization criteria to start ARV may be strengthened with the addition of DTH testing, an inexpensive and readily available tool in sub-Saharan Africa. PMID:16407361

  14. Antiretroviral therapy: current drugs.

    PubMed

    Pau, Alice K; George, Jomy M

    2014-09-01

    The rapid advances in drug discovery and the development of antiretroviral therapy is unprecedented in the history of modern medicine. The administration of chronic combination antiretroviral therapy targeting different stages of the human immunodeficiency virus' replicative life cycle allows for durable and maximal suppression of plasma viremia. This suppression has resulted in dramatic improvement of patient survival. This article reviews the history of antiretroviral drug development and discusses the clinical pharmacology, efficacy, and toxicities of the antiretroviral agents most commonly used in clinical practice to date. PMID:25151562

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

    PubMed

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

    2015-08-14

    Anaemia, redistribution of Fe, malnutrition and heightened systemic inflammation during HIV infection confer an increased risk of morbidity and mortality in HIV patients. We analysed information on Fe status and inflammation from a randomised, double blind, controlled phase-III clinical trial in Lusaka, Zambia and Mwanza, Tanzania. Malnourished patients (n 1815) were recruited at referral to antiretroviral therapy (ART) into a two-stage nutritional rehabilitation programme, randomised to receive a lipid-based nutrient supplement with or without added micronutrients. Fe was included in the intervention arm during the second stage, given from 2 to 6 weeks post-ART. Hb, serum C-reactive protein (CRP), serum ferritin and soluble transferrin receptor (sTfR) were measured at recruitment and 6 weeks post-ART. Multivariable linear regression models were used to assess the impact of the intervention, and the effect of reducing inflammation from recruitment to week 6 on Hb and Fe status. There was no effect of the intervention on Hb, serum ferritin, sTfR or serum CRP. A one-log decrease of serum CRP from recruitment to week 6 was associated with a 1.81 g/l increase in Hb (95% CI 0.85, 2.76; P< 0.001), and a 0.11 log decrease in serum ferritin (95% CI - 0.22, 0.03; P= 0.012) from recruitment to week 6. There was no association between the change in serum CRP and the change in sTfR over the same time period (P= 0.78). In malnourished, HIV-infected adults receiving dietary Fe, a reduction in inflammation in the early ART treatment period appears to be a precondition for recovery from anaemia. PMID:26179616

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

    PubMed Central

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

    2016-01-01

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

  17. Unresolved antiretroviral treatment management issues in HIV-infected children.

    PubMed

    Heidari, Shirin; Mofenson, Lynne M; Hobbs, Charlotte V; Cotton, Mark F; Marlink, Richard; Katabira, Elly

    2012-02-01

    Antiretroviral therapy in children has expanded dramatically in low-income and middle-income countries. The World Health Organization revised its pediatric HIV guidelines to recommend initiation of antiretroviral therapy in all HIV-infected children younger than 2 years, regardless of CD4 count or clinical stage. The number of children starting life-long antiretroviral therapy should therefore expand dramatically over time. The early initiation of antiretroviral therapy has indisputable benefits for children, but there is a paucity of definitive information on the potential adverse effects. In this review, a comprehensive literature search was conducted to provide an overview of our knowledge about the complications of treating pediatric HIV. Antiretroviral therapy in children, as in adults, is associated with enhanced survival, reduction in opportunistic infections, improved growth and neurocognitive function, and better quality of life. Despite antiretroviral therapy, HIV-infected children may continue to lag behind their uninfected peers in growth and development. In addition, epidemic concurrent conditions, such as tuberculosis, malaria, and malnutrition, can combine with HIV to yield more rapid disease progression and poor treatment outcomes. Additional studies are required to evaluate the long-term effects of antiretroviral therapy in HIV-infected infants, children, and adolescents, particularly in resource-limited countries where concomitant infections and conditions may enhance the risk of adverse effects. There is an urgent need to evaluate drug-drug interactions in children to determine optimal treatment regimens for both HIV and coinfections. PMID:22138766

  18. Pharmacogenetics of antiretrovirals.

    PubMed

    Tozzi, Valerio

    2010-01-01

    The introduction of highly active antiretroviral therapy (HAART) as standard of care has changed the natural history of HIV infection into a manageable chronic disease requiring long-term antiretroviral (ARV) treatment. However, response to HAART is often limited by the occurrence of toxicity or by the emergence of drug resistance. Antiretroviral treatment is characterized by differing rates of adverse events and responses. Genetic variations between human beings account for a relevant proportion of this variability. A relevant number of associations between human genetic variants and predisposition to adverse events have been described and for some antiretroviral drugs a clear and casual genotype-phenotype correlation has already been established. The strong association between abacavir hypersensitivity reaction and HLA-B*5701 has been demonstrated in both observational and blinded randomized clinical trials in racially diverse populations and represents the best example of the clinical utility of pharmacogenetic screening in HIV medicine. Genotyping for HLA-B*5701 before prescribing an abacavir containing regimen has been introduced into routine clinical practice as the standard of care for all patients. Other well-established associations include CYP2B6 alleles and efavirenz central nervous system side effects, UGT1A1 alleles and atazanavir-associated hyperbilirubinemia and HLA class II allele HLA-DRB*0101 and nevirapine-associated hypersensitivity. Despite genetic associations having been described for peripheral neuropathy, lipodystrophy, hyperlipidaemia, pancreatitis and renal proximal tubulopathy, numerous barriers exist to the successful introduction of widespread genetic testing to the clinic. Future prospects point in the direction of individualization of antiretroviral therapy through insights from host genetics. The present paper is aimed to provide a comprehensive review of the published literature and to summarize the state of research in this area. This article forms part of a special issue of Antiviral Research marking the 25th anniversary of antiretroviral drug discovery and development, Vol 85, issue 1, 2010. PMID:19744523

  19. Antiretroviral therapy in primary HIV infection.

    PubMed

    Powderly, William G

    2013-05-01

    Evaluation of: SPARTAC Trial Investigators, Fidler S, Porter K et al. Short-course antiretroviral therapy in primary HIV infection. N. Engl. J. Med. 368, 207-217 (2013). The timing of antiretroviral therapy (ART) in patients who present with primary HIV infection is uncertain. This paper compared three strategies: ART for 48 weeks; ART for 12 weeks; or no therapy in 366 patients with primary HIV infection. They showed that 48 weeks of ART significantly reduced the risk of needing definitive therapy (after a median follow-up of 4.2 years). However, the median delay in needing to start definitive therapy (61 weeks) is not significantly greater than the amount of treatment given (48 weeks) to achieve this result, suggesting that the clinical benefit of immediate ART in primary HIV infection is not yet clear. PMID:24236621

  20. 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.

    PubMed

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

    2006-05-01

    Sustained virological suppression requires adherence to >95% of doses of therapy. Overall there is paucity of data on adherence interventions among women and post-intervention outcomes. In this pilot study, we evaluated a novel strategy of weekly delivery of medications (Directly Delivered Therapy: DDT) for six months using an outreach worker (ORW), among ARV naïve indigent women starting HAART and compared the 'during intervention' and 'post-intervention' outcomes to the health care team (a nurse educator, a case worker, a pharmacist and social worker/drug addictions counsellor) based approach termed Adherence Coordination Services (ACS) and the Standard of Care (SoC) historical referent group. The baseline characteristics of the three groups were comparable. The proportion of women who achieved sustained virologic suppression in 4-8 month period for DDT; ACS and SoC groups were 86% (18/21); 54% (6/11); and 36% (8/22) (P<0.004); and in the 10-14 month period were 80% (12/15); 54% (6/11) and 45%(10/22) (P=0.036 for DDT vs. SoC). Retention rate in the DDT was 87%, and 92% of 307 ORW visits were kept, and post-intervention satisfaction was high. Short-term weekly delivery of medications using a community based liaison is a feasible, acceptable and a cost-effective strategy for improving both short-term and perhaps long-term adherence among women initiating their first HAART regimen. PMID:16809110

  1. Resolution of recalcitrant hand warts in an HIV-infected patient treated with potent antiretroviral therapy.

    PubMed

    Spach, D H; Colven, R

    1999-05-01

    Human papilloma virus (HPV)-related cutaneous manifestations occur with increased frequency and severity among HIV-infected persons. In this report, we describe an HIV-infected man with persistent, severe cutaneous hand warts that did not respond to multiple therapies, including liquid nitrogen cryotherapy, topical dinitrochlorobenzene, topical podophyllin, and intralesional interferon-alfa injections. Approximately 1 year after starting a potent protease inhibitor-containing antiretroviral regimen, the patient's recalcitrant cutaneous warts markedly diminished in size, even though the patient did not receive any specific therapy for the warts after starting aggressive antiretroviral therapy. The patient continued on a potent protease inhibitor-containing antiretroviral regimen and, approximately 2 years later, the warts completely resolved. Our patient's dramatic clinical improvement of cutaneous HPV infection that followed protease inhibitor-containing antiretroviral therapy provides a clear-cut example that protease inhibitor-containing combination antiretroviral therapy can produce significant clinical benefit. PMID:10321624

  2. Pharmacogenomics of antiretrovirals.

    PubMed

    Roca, Bernardino

    2008-06-01

    HIV infection is a serious but treatable disease, yet current treatment is limited by development of resistance and high rates of adverse drug reactions. Antiretroviral therapy is especially suitable for pharmacogenomic investigation as both drug exposure and treatment response can be reliably measured. Increasing knowledge about genes implicated in pharmacokinetics, mode of action, efficacy, and toxicity of drugs has already provided relevant results for clinical practice, for example: The strong association of the abacavir hypersensitivity reaction with HLA-B*5701 permits testing patients for the allele, and if present avoiding the drug and therefore preventing the reaction. Persons with the allele CYP2B6*6 present higher efavirenz "area under the curve" and have increased risk of neuropsychological toxicity. Additional gene variants are being discovered that influence the action of antiretroviral drugs. And, moreover, it is expected that larger-scale comprehensive genome approaches will profoundly improve the landscape of knowledge of HIV therapy in the future. The present article shows some recent patents related to the treatment of viral infections. PMID:18673126

  3. The Start of Head Start

    ERIC Educational Resources Information Center

    Neugebauer, Roger

    2010-01-01

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

  4. The Start of Head Start

    ERIC Educational Resources Information Center

    Neugebauer, Roger

    2010-01-01

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

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

    PubMed Central

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

    2006-01-01

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

  6. Start Young!

    ERIC Educational Resources Information Center

    Rubin, Penni

    2002-01-01

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

  7. Start Young!

    ERIC Educational Resources Information Center

    Rubin, Penni

    2002-01-01

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

  8. Antiretroviral therapy: Shifting sands.

    PubMed

    Sashindran, V K; Chauhan, Rajeev

    2016-01-01

    HIV/AIDS has been an extremely difficult pandemic to control. However, with the advent of antiretroviral therapy (ART), HIV has now been transformed into a chronic illness in patients who have continued treatment access and excellent long-term adherence. Existing indications for ART initiation in asymptomatic patients were based on CD4 levels; however, recent evidence has broken the shackles of CD4 levels. Early initiation of ART in HIV patients irrespective of CD4 counts can have profound positive impact on morbidity and mortality. Early initiation of ART has been found not only beneficial for patients but also to community as it reduces the risk of transmission. There have been few financial concerns about providing ART to all HIV-positive people but various studies have proven that early initiation of ART not only proves to be cost-effective but also contributes to economic and social growth of community. A novel multidisciplinary approach with early initiation and availability of ART at its heart can turn the tide in our favor in future. Effective preexposure prophylaxis and postexposure prophylaxis can also lower transmission risk of HIV in community. New understanding of HIV pathogenesis is opening new vistas to cure and prevention. Various promising candidate vaccines and drugs are undergoing aggressive clinical trials, raising optimism for an ever-elusive cure for HIV. This review describes various facets of tectonic shift in management of HIV. PMID:26900224

  9. Press Start

    NASA Astrophysics Data System (ADS)

    Harteveld, Casper

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

  10. Neuropsychiatric complications of antiretroviral therapy.

    PubMed

    Cespedes, Michelle S; Aberg, Judith A

    2006-01-01

    Neuropsychiatric adverse effects related to potent antiretroviral therapy are among the complications that can lead to poor adherence, treatment interruptions, or change of antiretroviral therapy regimens. For a historical perspective, we review early literature and case reports with CNS adverse effects attributed to antiretrovirals. The variability of the cerebrospinal fluid penetration of individual antiretrovirals may contribute to their potential for behavioural and psychiatric manifestations. The majority of neuropsychiatric complications related to potent antiretroviral therapy have been associated with the use of the efavirenz. Updates on the risk of neuropsychiatric manifestations with efavirenz use in patients with a history of psychiatric disorders or substance abuse are reviewed. We include a critical review of recently published data on the long-term CNS adverse effects with efavirenz. Special attention is given to the results of recent investigations on the relationship between the pharmacogenomics of genes responsible for efavirenz metabolism and the plasma concentration of efavirenz. It is important to note that there is no established direct correlation of efavirenz concentrations and symptoms. It is not recommended for practitioners to adjust efavirenz doses in order to prevent or alleviate CNS adverse effects. Patients may be placed at risk for virological failure and resistance if they receive suboptimal doses of efavirenz. The aim of this article is to give a concise review and an update on recent literature concerning neuropsychiatric effects of antiretroviral use in HIV-infected patients. Our intent is to present practitioners with data that can be used in a practical way to both educate and improve outcomes in the HIV-infected patient population. PMID:16970510

  11. Starting motor

    SciTech Connect

    Tanaka, T.; Hamano, I

    1989-05-23

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

  12. Recommendations in pediatric antiretroviral therapy.

    PubMed

    Ikeda, Takehisa; Ch'ng, Tong Wei; Oleske, James M

    2007-02-01

    The pathogenesis of HIV infection and the general principles of therapy are the same for HIV-infected adults, adolescents, children and infants. However, antiretroviral treatment of HIV infection in pediatrics requires the consideration of a number of factors specific to its population, including differences in drug pharmacokinetics and the use of virologic and immunologic markers, as well as age-related adherence issues. This review summarizes the text of the Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection, which was updated in October 2006. The guidelines are the work of the Working Group on Antiretroviral Therapy and Medical Management of HIV-Infected Children, a group of the Office of AIDS Research Advisory Council of the National Institutes of Health, which reviews new data on an ongoing basis and provides regular updates to the guidelines. As these guidelines were developed for the US, they may not be applicable in other countries. This summary does not attempt to place the Working Group guidelines in the context of international guidelines, nor does it attempt to detail the use of antiretroviral medication in the prevention of perinatal transmission of HIV, such as addressing the use of zidovudine versus single-dose nevirapine. PMID:17257086

  13. Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection

    PubMed Central

    2015-01-01

    BACKGROUND Data from randomized trials are lacking on the benefits and risks of initiating antiretroviral therapy in patients with asymptomatic human immunodeficiency virus (HIV) infection who have a CD4+ count of more than 350 cells per cubic millimeter. METHODS We randomly assigned HIV-positive adults who had a CD4+ count of more than 500 cells per cubic millimeter to start antiretroviral therapy immediately (immediate-initiation group) or to defer it until the CD4+ count decreased to 350 cells per cubic millimeter or until the development of the acquired immunodeficiency syndrome (AIDS) or another condition that dictated the use of antiretroviral therapy (deferred-initiation group). The primary composite end point was any serious AIDS-related event, serious non–AIDS-related event, or death from any cause. RESULTS A total of 4685 patients were followed for a mean of 3.0 years. At study entry, the median HIV viral load was 12,759 copies per milliliter, and the median CD4+ count was 651 cells per cubic millimeter. On May 15, 2015, on the basis of an interim analysis, the data and safety monitoring board determined that the study question had been answered and recommended that patients in the deferred-initiation group be offered antiretroviral therapy. The primary end point occurred in 42 patients in the immediate-initiation group (1.8%; 0.60 events per 100 person-years), as compared with 96 patients in the deferred-initiation group (4.1%; 1.38 events per 100 person-years), for a hazard ratio of 0.43 (95% confidence interval [CI], 0.30 to 0.62; P<0.001). Hazard ratios for serious AIDS-related and serious non–AIDS-related events were 0.28 (95% CI, 0.15 to 0.50; P<0.001) and 0.61 (95% CI, 0.38 to 0.97; P = 0.04), respectively. More than two thirds of the primary end points (68%) occurred in patients with a CD4+ count of more than 500 cells per cubic millimeter. The risks of a grade 4 event were similar in the two groups, as were the risks of unscheduled hospital admissions. CONCLUSIONS The initiation of antiretroviral therapy in HIV-positive adults with a CD4+ count of more than 500 cells per cubic millimeter provided net benefits over starting such therapy in patients after the CD4+ count had declined to 350 cells per cubic millimeter. (Funded by the National Institute of Allergy and Infectious Diseases and others; START ClinicalTrials.gov number, NCT00867048.) PMID:26192873

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

    PubMed

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

    1999-03-01

    The field of antiretroviral therapy is evolving at a very rapid pace. At this time, the initiation and optimization of antiretroviral therapy is based on serial plasma viral load determinations which aim to suppress viral replication to as low as possible for as long as possible, thus preventing disease progression. Currently available antiretrovirals require combination therapy with at least three agents to achieve this goal. Increasing availability of newer and more potent antiretroviral regimens will continue to enhance and simplify the number of therapeutic options available in the not too distant future. PMID:10337460

  15. Macrophage endocytic trafficking of antiretroviral nanoparticles

    PubMed Central

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

    2011-01-01

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

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

    PubMed

    Jesson, J; Leroy, V

    2015-05-01

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

  17. Modeling AIDS survival after initiation of antiretroviral treatment by Weibull models with changepoints

    PubMed Central

    2009-01-01

    Background Mortality of HIV-infected patients initiating antiretroviral therapy in the developing world is very high immediately after the start of ART therapy and drops sharply thereafter. It is necessary to use models of survival time that reflect this change. Methods In this endeavor, parametric models with changepoints such as Weibull models can be useful in order to explicitly model the underlying failure process, even in the case where abrupt changes in the mortality rate are present. Estimation of the temporal location of possible mortality changepoints has important implications on the effective management of these patients. We briefly describe these models and apply them to the case of estimating survival among HIV-infected patients who are initiating antiretroviral therapy in a care and treatment programme in sub-Saharan Africa. Results As a first reported data-driven estimate of the existence and location of early mortality changepoints after antiretroviral therapy initiation, we show that there is an early change in risk of death at three months, followed by an intermediate risk period lasting up to 10 months after therapy. Conclusion By explicitly modelling the underlying abrupt changes in mortality risk after initiation of antiretroviral therapy we are able to estimate their number and location in a rigorous, data-driven manner. The existence of a high early risk of death after initiation of antiretroviral therapy and the determination of its duration has direct implications for the optimal management of patients initiating therapy in this setting. PMID:19558677

  18. Med-psych drug-drug interactions update. Antiretrovirals, part III: antiretrovirals and drugs of abuse.

    PubMed

    Wynn, Gary H; Cozza, Kelly L; Zapor, Michael J; Wortmann, Glenn W; Armstrong, Scott C

    2005-01-01

    The third in a series reviewing the HIV/AIDS antiretroviral drugs, this report summarizes the interactions between antiretrovirals and common drugs of abuse. In an overview format for primary care physicians and psychiatrists, the metabolism and drug interactions in the context of antiretroviral therapy are presented for the following drugs of abuse: alcohol, benzodiazepines, cocaine, GHB (liquid X), ketamine (special K), LSD (acid), MDMA (Ecstasy), opiates, PCP (angel dust), and THC (marijuana). PMID:15765827

  19. The Starting Early Starting Smart Story.

    ERIC Educational Resources Information Center

    Casey Family Programs, Seattle, WA.

    Starting Early Starting Smart (SESS) is an early childhood public/private initiative designed to identify new, empirical knowledge about the effectiveness of integrating substance abuse prevention, addictions treatment, and mental health services with primary health care and childcare service settings (e.g., Head Start, day care, preschool) to…

  20. [Antiretroviral therapy: useful from prevention to HIV treatment].

    PubMed

    Tshikung, Olivier Nawej; Calmy, Alexandra

    2016-01-13

    In 2015, the publication of important studies allowed the development of new guidelines, notably by WHO and the European AIDS ClinicalSociety (EACS), for HIV preventive treatment (pre-exposure prophylaxis), as well as for the start of antiretroviral treatment. The START and TEMPRANO studies have extended the treatment to all HIV-infected patients, irrespective of the level of immunosuppression and therefore the CD4 count. In addition, innovative screening methods, such as self-tests, are now available in all French pharmacies since 15 September 2015. The latest developments in 2015 concerning the prevention, screening, and treatment of HIV are discussed in this article and will certainly have an impact on the care of patients in Switzerland. PMID:26946715

  1. Use of Third Line Antiretroviral Therapy in Latin America

    PubMed Central

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

    2014-01-01

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

  2. New Antiretroviral Therapies for Pediatric HIV Infection

    PubMed Central

    Morris, Jennifer L.; Kraus, Donna M.

    2005-01-01

    Human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome affect millions of children worldwide. The development of antiretroviral therapy has significantly improved the morbidity and mortality of pediatric patients infected with HIV. Currently, 4 classes of antiretroviral agents exist: nucleoside / nucleotide reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, and entry inhibitors. A total of 21 single-entity antiretroviral agents and 4 co-formulated antiretroviral products hold Food and Drug Administration (FDA) approval for treatment of HIV-1 infection. However, not all of these agents are indicated for use in patients less than 18 years of age. Since the year 2000, 7 new antiretroviral agents (atazanavir, emtricitabine, enfuvirtide, fosamprenavir, lopinavir/ritonavir, tenofovir, and tipranavir) have been approved by the FDA for use in adult patients as part of combination therapy for the treatment of HIV-1 infection. Although only 3 of these newer agents (emtricitabine, enfuvirtide, and lopinavir/ritonavir) are currently FDA approved for use in pediatric patients, pediatric clinical studies of the other 4 new agents are currently underway. The purpose of this article is to review these 7 new antiretroviral agents and describe their roles in the treatment of pediatric HIV infection. For each drug, the following information will be addressed: FDA-approved indication and age groups, clinical efficacy, pharmacokinetics, adverse drug reactions, clinically relevant drug interactions, pediatric and adult dosing, dosage forms, administration, and place in the treatment of pediatric HIV infection. PMID:23118639

  3. Combination Antiretroviral Use and Preterm Birth

    PubMed Central

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

    2013-01-01

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

  4. Accelerated Suppression of Primary Epstein-Barr Virus Infection in HIV-Infected Infants Initiating Lopinavir/Ritonavir-Based Versus Nevirapine-Based Combination Antiretroviral Therapy

    PubMed Central

    Slyker, Jennifer A.; Casper, Corey; Tapia, Kenneth; Richardson, Barbra; Bunts, Lisa; Huang, Meei-Li; Wamalwa, Dalton; Benki-Nugent, Sarah; John-Stewart, Grace

    2014-01-01

    We compared primary Epstein-Barr virus (EBV) infection and suppression between Kenyan human immunodeficiency virus–infected infants starting nevirapine-based vs lopinavir/ritonavir-based antiretroviral regimens. Although the rate of EBV infection was similar between groups, infants receiving lopinavir/ritonavir suppressed EBV more rapidly. Our findings suggest that specific antiretrovirals may potentially impact the risk of future EBV-associated malignancies. PMID:24550373

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  7. HIV-1 Antiretroviral Drug Therapy

    PubMed Central

    Arts, Eric J.; Hazuda, Daria J.

    2012-01-01

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

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

    PubMed

    Pascual, Fernando

    2014-01-01

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

  9. [Companion Diagnostics for Selecting Antiretroviral Drugs against HIV-1].

    PubMed

    Fukutake, Katsuyuki

    2015-11-01

    Currently, the treatment of human immunodeficiency virus involves combination therapy, as antiretroviral therapy(ART). The treatment has improved steadily since the advent of potent combination therapy in 1996. New drugs that offer new mechanisms of action, improvements in potency and activity even against multidrug-resistant viruses, dosing convenience, and tolerability have been approved. Among ART with useful drugs, there are two important examinations before starting the treatment using the two kinds of drug. CCR5 co-receptor antagonists, maraviroc, prevent HIV entry into target cells by binding to CCR5 receptors. Genotypic assays have been developed that can determine or predict the co-receptor tropism(i.e., CCR5, CXCR4, or both) of the patient's dominant virus population. The assay for HIV-1 co-receptor usage should be performed whenever the use of a CCR5 antagonist is being considered. One of the nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), abacavir, is an important agent to develop recommended regimens for antiretroviral therapy. Serious and sometimes fatal hypersensitivity reactions have been associated with abacavir-containing products, ZIAGEN, Epzicom, and Triumeq. Patients who carry the HLA-B*5701 allele are at high-risk of a hypersensitivity reaction to abacavir. Prior to initiating therapy with abacavir, performing a screening test for the HLA-B*5701 allele is recommended. [Review]. PMID:26995879

  10. The clinical implications of antiretroviral pharmacogenomics.

    PubMed

    Fox, Julie; Boffito, Marta; Winston, Alan

    2006-06-01

    Heterogeneity exists in the effectiveness and toxic effects of antiretroviral agents between individuals and populations. Although patient-related clinical variables such as age, sex and ethnic origin have been associated with drug response, inherited predispositions may have a significant effect on treatment outcome. The role of host and pathogen pharmacogenomics is gaining increasing interest in the field of both antiretrovirals in development, such as the chemokine (C-C motif) receptor 5 (CCR5) inhibitors, and in established therapies where toxicity and efficacy may be predicted. Despite numerous studies available in the literature, the interpretation of the relationship between genetic polymorphisms and clinical outcomes is often posed with many confounding variables, making clinical interpretations of these results difficult. This review summarizes the key findings in the growing knowledge between human genetics and response to antiretroviral drugs and how these findings may be effectively applied in a clinical context. PMID:16753006

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

  13. CD4 Cell Count: Declining Value for Antiretroviral Therapy Eligibility.

    PubMed

    Ying, Roger; Granich, Reuben M; Gupta, Somya; Williams, Brian G

    2016-04-15

    Antiretroviral therapy (ART) policy for people living with human immunodeficiency virus (HIV) has historically been based on clinical indications, such as opportunistic infections and CD4 cell counts. Studies suggest that CD4 counts early in HIV infection do not predict relevant public health outcomes such as disease progression, mortality, and HIV transmission in people living with HIV. CD4 counts also vary widely within individuals and among populations, leading to imprecise measurements and arbitrary ART initiation. To capture the clinical and preventive benefits of treatment, the global HIV response now focuses on increasing HIV diagnosis and ART coverage. CD4 counts for ART initiation were necessary when medications were expensive and had severe side effects, and when the impact of early ART initiation was unclear. However, current evidence suggests that although CD4 counts may still play a role in guiding clinical care to start prophylaxis for opportunistic infections, CD4 counts should cease to be required for ART initiation. PMID:26826372

  14. Antiretroviral (HIV-1) activity of azulene derivatives.

    PubMed

    Peet, Julia; Selyutina, Anastasia; Bredihhin, Aleksei

    2016-04-15

    The antiretroviral activity of azulene derivatives was detected for the first time. A series of eighteen diversely substituted azulenes was synthesized and tested in vitro using HIV-1 based virus-like particles (VLPs) and infectious HIV-1 virus in U2OS and TZM-bl cell lines. Among the compounds tested, the 2-hydroxyazulenes demonstrated the most significant activity by inhibiting HIV-1 replication with IC50 of 2-10 and 8-20μM for the VLPs and the infectious virus, respectively. These results indicate that azulene derivatives may be potentially useful candidates for the development of antiretroviral agents. PMID:26964674

  15. Project Head Start.

    ERIC Educational Resources Information Center

    Valentine, Jeanette; And Others

    1980-01-01

    This article, excerpted from the epilogue to the book "Project Head Start" edited by E. Zigler and J. Valentine, provides a brief overview of the impetus, goals, problems, and accomplishments of Head Start. (DB)

  16. Head Start Automation Manual.

    ERIC Educational Resources Information Center

    Maryland Univ., College Park. Univ. Coll.

    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,…

  17. The Head Start Debates

    ERIC Educational Resources Information Center

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

    2004-01-01

    The future of Head Start depends on how well people learn from and apply the lessons from its past. That's why everyone involved in early education needs this timely, forward-thinking book from the leader of Head Start. The first book to capture the Head Start debates in all their complexity and diversity, this landmark volume brings together the…

  18. Progress in antiretroviral drug delivery using nanotechnology

    PubMed Central

    Mallipeddi, Rama; Rohan, Lisa Cencia

    2010-01-01

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

  19. Update on opportunistic infections in the era of effective antiretroviral therapy.

    PubMed

    Zanoni, Brian C; Gandhi, Rajesh T

    2014-09-01

    Despite enormous improvements in effectiveness of treatment for HIV infection, opportunistic infections continue to occur in those who have not yet been diagnosed with HIV and in those who are not receiving antiretroviral therapy. This review focuses on tuberculosis and cryptococcal infections, the most common opportunistic infections (OIs) in patients living with human immunodeficiency virus infection around the world, as well as on new developments in progressive multifocal leukoencephalopathy and pneumocystis pneumonia. In the sections on these conditions, updates on diagnosis, treatment, and complications, as well as information on when to start antiretroviral therapy is provided. The article concludes with a discussion of new data on 2 vaccine-preventable OIs, human papillomavirus and varicella-zoster virus. PMID:25151568

  20. Start with Science

    ERIC Educational Resources Information Center

    Erickson, Susan

    2012-01-01

    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…

  1. Starting School in August

    ERIC Educational Resources Information Center

    Chmelynski, Carol

    2006-01-01

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

  2. Smart Start News, 1999.

    ERIC Educational Resources Information Center

    Harris, Monica, Ed.

    1999-01-01

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

  3. Aboriginal Head Start.

    ERIC Educational Resources Information Center

    Dunning, Paula

    2000-01-01

    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)

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

    PubMed

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

    2013-01-01

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

  5. Interventions to improve adherence to antiretroviral therapy.

    PubMed

    Tuldr, Albert; Wu, Albert W

    2002-12-15

    Recent research has shown that very high levels of adherence are required to obtain the maximum benefit of highly active antiretroviral therapy (HAART). This situation justifies the importance of developing efficient strategies to improve adherence to drugs against HIV. A comprehensive range of factors are the targets of the most effective interventions to improve adherence, including cognitive, behavioral, emotional, and social aspects. The authors describe three theoretical models that can help identify barriers and guide interventions. Most of the interventions are complex and may include more convenient care, provision of information, counseling, reminders, reinforcement, self-monitoring, family therapy, or additional supervision or attention. The authors suggest aspects that should be included in interventions to promote adherence based on a review of the literature and clinical experience. Limited evidence suggests that interventions to enhance adherence to antiretroviral therapy in people with HIV are most likely to be successful when they are comprehensive, longitudinal, and tailored to the person. PMID:12562041

  6. The clinical pharmacology of antiretrovirals in development.

    PubMed

    Winston, Alan; Mallon, Patrick Wg; Boffito, Marta

    2006-06-01

    Drugs in development for the management of HIV type 1 (HIV-1) infection include agents in existing classes and agents of novel classes. Of existing classes, new protease inhibitors, nucleoside reverse transcriptase inhibitors and non-nucleoside reverse transcriptase inhibitors are in development. Novel therapeutic approaches include the development of chemokine receptor (CCR)5 antagonists, integrase inhibitors and maturation inhibitors. CCR5 antagonists are thought to inhibit HIV-1 entry into host cells by occupying a specific site on the CCR5 receptor, preventing attachment of the HIV-1 envelope protein gp120. Integrase inhibitors are small synthetically prepared molecules that block RNA/DNA interactions and modify protein or enzyme synthesis. Data on the pharmacokinetics and pharmacodynamics of these new antiretroviral agents continue to generate interest. This review reports the known data on the pharmacokinetics of experimental antiretrovirals, and describe the main drug-drug interactions studied so far. PMID:16863445

  7. Individualization of antiretroviral therapy - Pharmacogenomic aspect.

    PubMed

    Dalal, Bhavik; Shankarkumar, Aruna; Ghosh, K

    2015-12-01

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

  8. Drug Interactions with New and Investigational Antiretrovirals

    PubMed Central

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

    2010-01-01

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

  9. Individualization of antiretroviral therapy - Pharmacogenomic aspect

    PubMed Central

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

    2015-01-01

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

  10. Challenges in initiating antiretroviral therapy in 2010.

    PubMed

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

    2010-08-01

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

  11. Timing of antiretroviral therapy: an immunological perspective.

    PubMed

    Imami, Nesrina; Hardy, Gareth

    2003-02-01

    The success of an effective antiretroviral therapy regimen depends upon its effects on the viral load, the CD4 T-cell count and the ability to preserve and/or restore useful HIV-1-specific immune responses. Many new problems that limit the effectiveness of current treatment are arising during comparison of the differing positions taken in the British and American guidelines. A further difficulty is that many patients present for the first time in the clinic with AIDS-related illness and profound immunosuppression. Pitfalls such as a failure to eradicate the virus, the induction of side effects and a lack of regeneration of HIV-1-specific responses require frequent updates of the guidelines and reviews of the timing of initiation of effective antiretroviral therapy and of strategies for optimising the long-term success of antiretroviral therapy. Treatment guidelines encompass the choice of initial and subsequent regimens, treatment successes and failures, the timing of treatment and, finally, lay down the foundations for promising immune-based therapies and future drug regimens. PMID:12840710

  12. The discovery and development of antiretroviral agents.

    PubMed

    Lange, Joep M A; Ananworanich, Jintanat

    2014-01-01

    Since the discovery of HIV as the causative agent of AIDS in 1983/1984, remarkable progress has been made in finding antiretroviral drugs (ARVs) that are effective against it. A major breakthrough occurred in 1996 when it was found that triple drug therapy (HAART) could durably suppress viral replication to minimal levels. It was then widely felt, however, that HAART was too expensive and complex for low- and middle-income countries, and so, with the exception of a few of these countries, such as Brazil, a massive scale-up did not begin until the WHO launched its '3 by 5' initiative and sizeable funding mechanisms, such as the Global Fund to Fight AIDS, TB and Malaria and the US President's Emergency Plan for AIDS Relief (PEPFAR), came into existence. A pivotal enabler of the scale-up was a steady lowering of drug prices through entry of generic antiretrovirals, competition between generic manufacturers and the making of volume commitments. The WHO Prequalification of Medicines Programme and the Expedited Review Provision of the US Food and Drug Administration have been important for the assurance of quality standards. Antiretroviral drug development by research-based pharmaceutical companies continues, with several important innovative products, such as long-acting agents, in the pipeline. PMID:25310317

  13. Starting an aphasia center?

    PubMed

    Elman, Roberta J

    2011-08-01

    Starting an aphasia center can be an enormous challenge. This article provides initial issues to review and consider when deciding whether starting a new organization is right for you. Determining the need for the program in your community, the best size and possible affiliation for the organization, and available resources, as well as developing a business plan, marketing the program, and building awareness in the community, are some of the factors that are discussed. Specific examples related to starting the Aphasia Center of California are provided. PMID:21968562

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  16. How Do I Start?

    MedlinePlus

    ... in Reviewed April 16, 2014 Select a Language: Fact Sheet 201 How Do I Start? DID YOU JUST ... tests, opportunistic infections, and living with HIV. This Fact Sheet was sponsored by the US Food and Drug ...

  17. Starting treatment in pediatric HIV infection: try to clarify a gray area.

    PubMed

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

    2015-05-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  20. Short- and long-term immunological and virological outcome in HIV-infected infants according to the age at antiretroviral treatment initiation.

    PubMed

    Goetghebuer, Tessa; Le Chenadec, Jerome; Haelterman, Edwige; Galli, Luisa; Dollfus, Catherine; Thorne, Claire; Judd, Ali; Keiser, Olivia; Ramos, Jose Tomas; Levy, Jack; Warszawski, Josiane

    2012-03-01

    The clinical benefit of antiretroviral therapy in infants is established. In this cohort collaboration, we compare immunological and virological response to treatment started before or after 3 months of age. Early initiation provides a better short-term response, although evolution after 12 months of age is similar in both groups. PMID:22198788

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

    PubMed Central

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

    2013-01-01

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

  2. Magnitude and Predictors of Anti-Retroviral Treatment (ART) Failure in Private Health Facilities in Addis Ababa, Ethiopia

    PubMed Central

    Teshome Yimer, Yesunesh; Yalew, Alemayehu Worku

    2015-01-01

    Background The public health approach to antiretroviral treatment management encourages the public private partnership in resource limited countries like Ethiopia. As a result, some private health facilities are accredited to provide antiretroviral treatment free services. Evidence on magnitude and predictors of treatment failure are crucial for timely actions. However, there are few studies in this regard. Objective To assess the magnitude and predictors of ART failure in private health facilities in Addis Ababa, Ethiopia. Methods The study followed retrospective cohort design, with 525 adult antiretroviral treatment clients who started the treatment since October 2009 and have at least six months follow up until December 31, 2013. Kaplan Meier survival analysis and Cox proportional hazard model were used for analysis. Results Treatment failure, using the three WHO antiretroviral treatment failure criteria, was 19.8%. The immunologic, clinical, and virologic failures were 15%, 6.3% and 1.3% respectively. The mean and median survival times in months were 41.17 with 95% Confidence Interval (CI) [39.69, 42.64] and 49.00, 95% CI [47.71, 50.29] respectively. The multivariate cox regression analysis showed years since HIV diagnosis (Adjusted Hazard Ratio (AHR)=13.87 with 95% CI [6.65, 28.92]), disclosure (AHR=0.59, 95% CI [0.36, 0.96]), WHO stage at start (AHR=1.84, 95% CI [1.16, 2.93]), weight at baseline (AHR=0.58, 95% CI [0.38, 0.89]), and functionality status at last visit (AHR=2.57, 95% CI [1.59, 4.15]) were independent predictors of treatment failure. Conclusion The study showed that the treatment failure is high among the study subjects. The predictors for antiretroviral treatment failure were years since HIV diagnosis, weight at start, WHO stage at start, status at last visit and disclosure. Recommendations Facilities need to monitor antiretroviral treatment clients to avoid disease progression and drug resistance. PMID:25946065

  3. Switching antiretroviral therapy to minimize metabolic complications

    PubMed Central

    Lake, Jordan E; Currier, Judith S

    2011-01-01

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

  4. TARCOG Home Start Program.

    ERIC Educational Resources Information Center

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

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

  5. Starting A Program.

    ERIC Educational Resources Information Center

    Costello, Phillip M.

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

  6. Mapping Sure Start Scotland.

    ERIC Educational Resources Information Center

    Cunningham-Burley, Sarah; Jamieson, Lynn; Morton, Sarah; Adam, Rachel; McFarlane, Vivienne

    Sure Start Scotland is part of a broader action program for children from birth to age three and their families with the objectives of improving children's social and emotional development, health, and ability to learn, as well as strengthening families and communities. This summary report details a "mapping" project to identify services for young…

  7. Nutrition and Head Start.

    ERIC Educational Resources Information Center

    Wardle, Francis; Winegarner, Nola

    1992-01-01

    A Head Start center assessed and improved its nutrition program. The process involved understanding the program's flaws; developing strategies for change that emphasized mental health and education and impacted all components of the curriculum; and fostering positive staff attitudes toward nutrition. (SM)

  8. "New Start at 45."

    ERIC Educational Resources Information Center

    Greenstein, Pearl

    1989-01-01

    New Start at 45, operated by Fujitsu Ltd. in Japan, is a management development course for 45-year-old adults in management or supervisory positions. Two components are a 6-week liberal arts curriculum and a 2-week, intensive course in either international management, sales management, or subsidiaries management. Benefits include increased…

  9. Starting Trees from Cuttings.

    ERIC Educational Resources Information Center

    Kramer, David C.

    1983-01-01

    Describes a procedure for starting tree cuttings from woody plants, explaining "lag time," recommending materials, and giving step-by-step instructions for rooting and planting. Points out species which are likely candidates for cuttings and provides tips for teachers for developing a unit. (JM)

  10. Starting in School

    ERIC Educational Resources Information Center

    Albertine, Susan

    2012-01-01

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

  11. The long-term outcomes of antiretroviral treatment initiated with mono or dual nucleoside reverse transcriptase inhibitors in HIV-1-infected children: an Asian observational study

    PubMed Central

    Wittawatmongkol, Orasri; Mohamed, Thahira J; Le, Thoa PK; Ung, Vibol; Maleesatharn, Alan; Hansudewechakul, Rawiwan; Nguyen, Lam V; Kumarasamy, Nagalingeswaran; Lumbiganon, Pagakrong; Sudjaritruk, Tavitiya; Bunupuradah, Torsak; Yusoff, Nik KN; Kurniati, Nia; Fong, Moy S.; Nallusamy, Revathy; Kariminia, Azar; Sohn, Annette H.; Chokephaibulkit, Kulkanya

    2016-01-01

    After a median of 115.9 months of follow-up, 90% of 206 HIV-1-infected children in a cohort in Asia who initiated antiretroviral treatment (ART) with mono or dual nucleoside reverse transcriptase inhibitors were alive and had comparable immunological and virological outcomes as compared to the 1,915 children who had started with highly active antiretroviral regimens. However, these children had higher rates of treatment-related adverse events, opportunistic infections, and cumulative mortality, and were more likely to require protease inhibitor-containing regimens or other more novel ART-based regimens.

  12. Drug Interactions and Antiretroviral Drug Monitoring

    PubMed Central

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

    2014-01-01

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

  13. Antiretroviral drugs: Critical issues and recent advances

    PubMed Central

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

    2012-01-01

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

  14. Antiretroviral drugs: critical issues and recent advances.

    PubMed

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

    2012-05-01

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

  15. Opportunistic infections and immune reconstitution inflammatory syndrome in HIV-1-infected adults in the combined antiretroviral therapy era: a comprehensive review.

    PubMed

    Manzardo, Christian; Guardo, Alberto C; Letang, Emilio; Plana, Montserrat; Gatell, Jose M; Miro, Jose M

    2015-06-01

    Despite the availability of effective combined antiretroviral treatment, many patients still present with advanced HIV infection, often accompanied by an AIDS-defining disease. A subgroup of patients starting antiretroviral treatment under these clinical conditions may experience paradoxical worsening of their disease as a result of an exaggerated immune response towards an active (but also subclinical) infectious agent, despite an appropriate virological and immunological response to the treatment. This clinical condition, known as immune reconstitution inflammatory syndrome, may cause significant morbidity and even mortality if it is not promptly recognized and treated. This review updates current knowledge about the incidence, diagnostic criteria, risk factors, clinical manifestations, and management of opportunistic infections and immune reconstitution inflammatory syndrome in the combined antiretroviral treatment era. PMID:25860288

  16. Evaluating Ourselves in Head Start.

    ERIC Educational Resources Information Center

    Nomland, Ella Kube; And Others

    This Head Start evaluation system was developed at the request of the California Head Start Directors Association. There was a broad-based input in all phases of its development, from Head Start directors, Head Start staff from all components, and Head Start parents. It was extensively field tested in one of the major California Head Start…

  17. Antiretroviral treatment literacy among HIV voluntary counseling and testing clients in Moshi, Tanzania, 2003 to 2005.

    PubMed

    Landman, Keren Z; Thielman, Nathan M; Mgonja, Anna; Shao, Humphrey J; Itemba, Dafrosa K; Ndosi, Evelyn M; Tribble, Alison C; Shao, John F; Bartlett, John A; Crump, John A

    2007-03-01

    Antiretroviral treatment literacy leads to greater HIV testing and treatment and antiretroviral treatment adherence. Among northern Tanzanian subjects, antiretroviral treatment awareness was only 17%. Factors associated with low antiretroviral treatment literacy included having exchanged money or gifts for sex, living in rural areas, having more than 2 children, and having a primary education only. Previous HIV testing was protective against low antiretroviral treatment literacy. These results support refocusing HIV education efforts and increasing synergy between HIV prevention and treatment programs. PMID:17329501

  18. Enceladus: Starting Hydrothermal Activity

    NASA Technical Reports Server (NTRS)

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

    2011-01-01

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

  19. Current Perspectives on HIV-1 Antiretroviral Drug Resistance

    PubMed Central

    Iyidogan, Pinar; Anderson, Karen S.

    2014-01-01

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

  20. Adding value to antiretroviral proficiency testing

    PubMed Central

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

    2015-01-01

    Background Clinical trial specimens tested for antiretroviral (ARV) concentrations often require compliance with Clinical Laboratory Improvement Act and/or the Food and Drug Administration bioanalytical guidance. Experimental The Clinical Pharmacology Quality Assurance Program (CPQA) designed 8 proficiency testing (PT) rounds over 4 years to assess precision, specificity and stability. Results Ten laboratories provided blinded proficiency data to support continued acceptable precision of ARV methods. Specificity samples identified little bias for individual methods; hemolyzed (87%) and lipemic (86%) results were ≤10% of their control results. Stability was established for ARVs in plasma at −70°C for 2.5–3.6 years. Conclusion PT provided by the CPQA assured continued acceptability of individual laboratory assay performances for precision and specificity, and obtained ARV stability during long term storage. PMID:25413704

  1. Complications of HIV Disease and Antiretroviral Therapy

    PubMed Central

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

    2011-01-01

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

  2. Antiretrovirals inhibit arginase in human microglia.

    PubMed

    Lisi, Lucia; Laudati, Emilia; Miscioscia, Teresa F; Dello Russo, Cinzia; Topai, Alessandra; Navarra, Pierluigi

    2016-01-01

    Preliminary evidence in an animal model, that is, primary cultures of rat microglia cells, suggested that some antiretroviral drugs (ARVs), namely darunavir, atazanavir, efavirenz, and nevirapine, increase NO production through a mechanism involving the inhibition of arginase (ARG) activity. This study was conceived to investigate the effects of ARVs on ARG activity in a human experimental model. We compared CHME-5 human microglial immortalized cells under basal conditions with cells exposed to either IL-4, a mix of inflammatory cytokines, or both stimuli given together. We also tested the effects of ARVs on CHME-5 cell lysates after exposure to the above stimuli. Moreover, the interaction between the ARVs and ARG was investigated via computational chemistry. We found that ARVs consistently inhibit ARG activity both in intact and lysed cells. In docking studies, darunavir and atazanavir showed similar scores compared with both l-arginine and the ARG antagonist nor-NOHA. Efavirenz and nevirapine, which are less potent in inhibiting ARG in the biochemical assay, also had lower scores. In conclusion, the present findings in a human model support the notion that ARG pathway can present a new, additional molecular target for different ARVs in HIV treatments. We found that antiretroviral drugs (ARVs) consistently inhibit arginase (ARG)-I activity both in intact and lysed cells. In docking studies, darunavir (DRV) and atazanavir (ATV) showed similar scores compared to both l-arginine and the ARG antagonist, Nω-hydroxy-nor-arginine (nor-NOHA). Efavirenz (EFV) and nevirapine (NVP), which are less potent in inhibiting ARG in the biochemical assay, also had lower scores. In conclusion, the present findings in a human model support the notion that ARG pathway can be envisioned as an additional and new molecular target of different ARVs in HIV treatments. PMID:26466119

  3. Increasing antiretroviral drug access for children with HIV infection.

    PubMed

    Havens, Peter L; Gibb, Diana M

    2007-04-01

    Although there have been great gains in the prevention of pediatric HIV infection and provision of antiretroviral therapy for children with HIV infection in resource-rich countries, many barriers remain to scaling up HIV prevention and treatment for children in resource-limited areas of the world. Appropriate testing technologies need to be made more widely available to identify HIV infection in infants. Training of practitioners in the skills required to care for children with HIV infection is required to increase the number of children receiving antiretroviral therapy. Lack of availability of appropriate antiretroviral drug formulations that are easily usable and inexpensive is a major impediment to optimal care for children with HIV. The time and energy spent trying to develop liquid antiretroviral formulations might be better used in the manufacture of smaller pill sizes or crushable tablets, which are easier to dispense, transport, store, and administer to children. PMID:17403860

  4. Minnesota: Early Head Start Initiatiive

    ERIC Educational Resources Information Center

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

    2012-01-01

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

  5. Missouri: Early Head Start Initiative

    ERIC Educational Resources Information Center

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

    2012-01-01

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

  6. Adherence to HIV antiretrovirals among persons with serious mental illness.

    PubMed

    Wagner, Glenn J; Kanouse, David E; Koegel, Paul; Sullivan, Greer

    2003-04-01

    Despite the absence of empirical evidence, serious mental illness is assumed to be a high risk factor for nonadherence to HIV antiretroviral regimens. To assess antiretroviral adherence among persons with serious mental illness, we conducted a study in which adherence was observed over a 2-week period with electronic monitoring bottle caps and self-report. Forty-seven participants enrolled, with all but two (96%) completing the study. Psychiatric diagnoses included bipolar depression (n = 24), schizophrenia (n = 12), schizoaffective disorder (n = 5), and major depression with psychotic features (n = 6). Mean adherence (proportion of prescribed doses taken) was 66% (standard deviation [SD] = 34), as measured by electronic monitoring; 40% demonstrated at least 90% adherence, but 31% had less than 50% adherence. Self-reported adherence to psychotropics was moderately correlated with self-reported (r = 0.45, p < 0.05) and electronically monitored (r = 0.39, p < 0.05) antiretroviral adherence. Viral load (log(10)) was negatively correlated with electronically monitored (r = -0.28, p < 0.10) and self-reported (r = -0.39, p < 0.05) antiretroviral adherence, after controlling for the length of time on treatment. These findings suggest that many patients with serious mental illness are able to adhere very well to antiretroviral regimens, yet a substantial proportion of our sample displayed poor adherence, indicating the need for research to further assess the factors that influence adherence to antiretrovirals in this population. PMID:12737641

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  9. Starting physiology: bioelectrogenesis.

    PubMed

    Baptista, Vander

    2015-12-01

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

  10. Manual for Head Start Administrators. Volume I: Head Start Requirements.

    ERIC Educational Resources Information Center

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

    Head Start Administrators must be fully knowledgeable of all applicable Federal requirements and skilled in applying these requirements in the daily operation of their program, whether starting a new program or striving to maintain a high quality program. This manual provides Head Start administrators with a compilation of the program requirements…

  11. Long-term outcome of patients after a single interruption of antiretroviral therapy: a cohort study

    PubMed Central

    2012-01-01

    Background To describe the long term outcome of patients who interrupted highly active antiretroviral therapy (HAART) once, identify the variables associated with earlier need to re-start HAART, and the response when therapy was resumed. A retrospective observational cohort of 66 adult patients with HIV-1 infection who interrupted HAART with a CD4+cell count ≥350 cells/μL and undetectable viral load (VL) was performed. The pre-established CD4+ cell count for restarting therapy was 300cells/μL. Cox regression was used to analyse the variables associated with earlier HAART reinitiation. Results The median follow-up was 209 weeks (range, 64–395). Rates of HIV-related or possible HIV-related events were 0.37 (one case of acute retroviral syndrome) and 1.49 per 100 patient-years, respectively. Two patients died after re-starting therapy and having reached undetectable VL. Three patients suffered a sexually transmitted disease while off therapy. Fifty patients (76%) resumed therapy after a median of 97 weeks (range, 17–267). Age, a nadir of CD4+ <250 cells/μL, and a mean VL during interruption of >10,000 copies/ml were independent predictors for earlier re-start. The intention-to-treat success rate of the first HAART resumed regimen was 85.4%. There were no differences by regimen used, nor between regimens that were the same as or different from the one that had been interrupted. Conclusions Our data suggest highly active antiretroviral therapy may be interrupted in selected patients because in these patients, when the HAART is restarted, the viral and clinical response may be achieved. PMID:23095460

  12. Antiretroviral procurement and supply chain management.

    PubMed

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

    2014-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2013-10-01

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

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

    PubMed

    2004-03-01

    Highly active antiretroviral therapy in HIV-infected children has been associated with a dramatic decrease in progression to AIDS and HIV-related deaths, and infected children currently have an excellent quality of life. Antiretroviral drugs cannot eradicate the virus, although they can achieve a situation of latent infection. However, chronic use of these drugs has multiple adverse effects, the most important of which are metabolic complications. The large number of drugs required and patient characteristics such as age, tolerance to drugs, adherence, and social problems make unifying the criteria for initial therapy in HIV-infected children difficult. A balance should be sought between not delaying the start of treatment, to avoid immunologic deterioration, and minimizing the long-term adverse effects of the therapy. The present treatment recommendations are adapted from international guidelines and are based on a literature review and on our own experience. Our group previously published recommendations on the treatment of HIV-infected children and the aim of the present article is to provide an update. PMID:14987518

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

    PubMed

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

    2015-06-01

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

  16. Maryland Early Head Start Initiative

    ERIC Educational Resources Information Center

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

    2012-01-01

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

  17. Nearly Full Employment Recovery Among South African HIV Patients On Antiretroviral Therapy: Evidence From A Large Population Cohort

    PubMed Central

    Bor, Jacob; Tanser, Frank; Newell, Marie-Louise; Bärnighausen, Till

    2013-01-01

    Antiretroviral therapy for HIV may have important economic benefits for patients and their households. We quantified the impact of HIV treatment on employment status among HIV patients in rural South Africa who were enrolled in a public-sector HIV treatment program supported by the U.S. President’s Emergency Plan for AIDS Relief. We linked clinical data from more than 2000 patients in the treatment program with ten years of longitudinal socioeconomic data from a complete community-based population cohort of over 30,000 adults residing in the clinical catchment area. We estimated the employment effects of HIV treatment in fixed effects regressions. Four years after the initiation of antiretroviral therapy, employment among HIV patients had recovered to about 90 percent of baseline rates observed in the same patients three to five years before they started treatment. Many patients initiated treatment early enough that they were able to avoid any loss of employment due to HIV. These results represent the first estimates of employment recovery among HIV patients in a general population, relative to the employment levels that these patients had prior to job-threatening illness and the decision to seek care. We find large economic benefits to HIV treatment. For some patients, further gains could be obtained from initiating antiretroviral therapy earlier, prior to HIV-related job loss. PMID:22778335

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

    MedlinePlus

    ... AIDS HIV/AIDS Treatment Approved generic formulations of antiretroviral drugs used in the treatment of HIV infection Share ... in HIV/AIDS Treatment HIV/AIDS Related Therapies Antiretroviral drugs used in the treatment of HIV infection Approved ...

  19. Factors influencing global antiretroviral procurement prices

    PubMed Central

    2009-01-01

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

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

    PubMed

    Nattrass, Nicoli J

    2008-12-01

    Despite unprecedented international mobilisation to support universal provision of highly active antiretroviral therapy (HAART), national governments continue to play the key role in determining access to treatment. Whereas some AIDS-affected countries have performed as well as or better than expected given their level of development, institutional characteristics and demographic challenges (e.g. Thailand and Brazil), others (notably South Africa) have not. This article argues that the 'economics' of antiretroviral drug delivery is at heart a political-economy of access to treatment. It depends on commitment on the part of national governments to negotiate with pharmaceutical companies over patented antiretroviral drug prices, on their policy towards compulsory licensing, and on the approach they adopt to delivering HAART. Civil society has an important role to play in encouraging governments to become, and remain, committed to taking action to ensure sustainable and widespread access to HAART. PMID:18964022

  1. Pharmacokinetics and therapeutic drug monitoring of antiretrovirals in pregnant women

    PubMed Central

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

    2008-01-01

    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. PMID:18537960

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

    PubMed

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

    2015-09-15

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

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed

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

    2011-01-01

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

  5. Antiretroviral Therapy as HIV Prevention: Status and Prospects

    PubMed Central

    Venkatesh, Kartik K.

    2010-01-01

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

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

    PubMed

    Mowatt, L

    2013-01-01

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

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

    PubMed

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

    2013-01-01

    The 2013 World Health Organization's (WHO) Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection provide more than 50 new recommendations across the continuum of HIV care, including recommendations on HIV testing, using antiretroviral drugs for prevention, linking individuals to HIV care and treatment services, initiating and maintaining antiretroviral therapy (ART) and monitoring treatment. Guidance is provided across all age groups and populations of adults, pregnant and breastfeeding women, adolescents and key populations. The guidelines are based on a public health approach to expanding the use of ARV drugs for HIV treatment and prevention, with a particular focus on resource-limited settings. The most important new clinical recommendations include: treating adults, adolescents and older children earlier - starting ART in all individuals with a CD4 cell count of 500 cells/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

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

    PubMed Central

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

    2014-01-01

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

  9. Successful antiretroviral therapy by using unusual antiretroviral combinations in heavily pre-treated patients: two case reports.

    PubMed

    Taramasso, Lucia; Dentone, Chiara; Alessandrini, Anna; Bruzzone, Bianca; Icardi, Giancarlo; Garraffo, Rodolphe; De Macina, Ilaria; Viscoli, Claudio; Di Biagio, Antonio

    2015-10-01

    In the context of HIV-infected patients with several past antiretroviral therapies and multiple failures, it is possible to be faced with viruses resistant to all drug classes. We report on two HIV-1 infected patients in which the historical genotype showed mutations against all the major drug classes and in which viral suppression has been obtained by non-conventional antiretroviral therapy regimens, including the combination of darunavir at high dosage (800 mg bid), dolutegravir (50 mg bid) and a third agent, i.e. enfuvirtide in the first case and etravirine in the second one. PMID:25332227

  10. Head Start Nutrition Education Curriculum.

    ERIC Educational Resources Information Center

    Montclair State Coll., Upper Montclair, NJ.

    This multidisciplinary preschool nutrition education curriculum was written for use in the instruction of 3- to 5-year-olds in the National Head Start program. Introductory notes on cooking experiences for Head Start children and suggested menus for young children are followed by nine units. The curriculum incorporates a variety of teaching…

  11. Head Start Program Performance Standards.

    ERIC Educational Resources Information Center

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

    This manual presents the Project Head Start program goals and performance standards in the areas of education, health and nutrition services, social services, and parent involvement. A short discussion of general Head Start goals, performance standard development, implementation, and enforcement is included. Each performance standard is…

  12. Maine: Early Head Start Initiatives

    ERIC Educational Resources Information Center

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

    2012-01-01

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

  13. Head Start Embraces Language Diversity

    ERIC Educational Resources Information Center

    David, Judy, Comp.

    2005-01-01

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

  14. Nebraska: Early Head Start Initiative

    ERIC Educational Resources Information Center

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

    2012-01-01

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

  15. Kansas: Early Head Start Initiative

    ERIC Educational Resources Information Center

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

    2012-01-01

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

  16. Clinically Relevant Pharmacokinetic Herb-drug Interactions in Antiretroviral Therapy.

    PubMed

    Fasinu, Pius S; Gurley, Bill J; Walker, Larry A

    2015-01-01

    For healthcare professionals, the volume of literature available on herb-drug interactions often makes it difficult to separate experimental/potential interactions from those deemed clinically relevant. There is a need for concise and conclusive information to guide pharmacotherapy in HIV/AIDS. In this review, the bases for potential interaction of medicinal herbs with specific antiretroviral drugs are presented, and several botanicals are discussed for which clinically relevant interactions in humans are established. Such studies have provided, in most cases, sufficient ground to warrant the avoidance of concurrent administration of antiretroviral (ARVs) drugs with St John's wort (Hypericum perforatum), black pepper (Piper species) and grapefruit juice. Other botanicals that require caution in the use with antiretrovirals include African potato (Hypoxis hemerocallidea), ginkgo (Ginkgo biloba), ginseng (Panax species), garlic (Allium sativum), goldenseal (Hydrastis canadensis) and kava kava (Piper methysticum). The knowledge of clinically significant herb-drug interaction will be important in order to avoid herb-induced risk of sub-therapeutic exposure to ARVs (which can lead to viral resistance) or the precipitation of toxicity (which may lead to poor compliance and/or discontinuation of antiretroviral therapy). PMID:26526838

  17. Neurological and psychiatric adverse effects of antiretroviral drugs.

    PubMed

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

    2014-02-01

    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

  18. Clinical Pharmacokinetics of Antiretroviral Drugs in Older Persons

    PubMed Central

    Schoen, John C.; Erlandson, Kristine Mace

    2013-01-01

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

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

    PubMed

    Yazdanpanah, Y; Schwarzinger, M

    2016-03-01

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

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

    PubMed Central

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

    2015-01-01

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

  1. Improved antiretroviral refill adherence in HIV-focused community pharmacies

    PubMed Central

    Cocohoba, Jennifer M.; Murphy, Patricia; Pietrandoni, Glen; Guglielmo, B. Joseph

    2015-01-01

    Objective To determine differences in patient characteristics, antiretroviral therapy (ART) regimen characteristics, and regimen refill adherence for HIV-focused pharmacy (HIV-P) versus traditional pharmacy (TP) users. Design Retrospective cohort study Setting California Walgreens pharmacies, May 2007 – August 2009 Participants HIV-positive (HIV+) patients with greater than 30 days of antiretroviral prescription claims. Main outcome measures Modified medication possession ratio (mMPR) to calculate regimen refill adherence, and dichotomous measure of optimal adherence ≥ 95%. Results 4254 HIV-P and 11679 TP users were included. Compared to TP users, HIV-P users traveled farther to pharmacies (5.03 vs. 1.26 miles), filled more chronic disease medications (35% vs. 30%), and received more fixed-dose combination tablets (92% vs. 83%); all p < 0.01. Median mMPR was higher for HIV-P users (90% vs. 77%, p < 0.0001). After adjustment for age, gender, insurance, medication use, and distance from pharmacy, use of HIV-P (OR= 2.18, 95% CI 1.88–2.52) and use of fixed-dose combination antiretroviral tablets (OR=2.43, 95% CI 1.83–3.22) were factors most strongly associated with having ≥ 95% regimen refill adherence. Conclusion For HIV+ patients struggling with antiretroviral adherence, clinicians could consider minimizing pill burden with combination tablets and referral to an HIV-focused pharmacy. PMID:23023860

  2. Comparison of the effectiveness of initial combined antiretroviral therapy with nelfinavir or efavirenz at a university-based outpatient service in Brazil.

    PubMed

    Vanni, T; Morejón, K M; Santana, R C; Melo, L de; Ferrão, S B R L; Amorim, A P; Gaspar, G G; Ponzi, C C; Golin, N A; Custódio, F L; Marangoni, A T D; Campos, C P; Fonseca, B A L

    2007-07-01

    Since there are some concerns about the effectiveness of highly active antiretroviral therapy in developing countries, we compared the initial combination antiretroviral therapy with zidovudine and lamivudine plus either nelfinavir or efavirenz at a university-based outpatient service in Brazil. This was a retrospective comparative cohort study carried out in a tertiary level hospital. A total of 194 patients receiving either nelfinavir or efavirenz were identified through our electronic database search, but only 126 patients met the inclusion criteria. Patients were included if they were older than 18 years old, naive for antiretroviral therapy, and had at least 1 follow-up visit after starting the antiretroviral regimen. Fifty-one of the included patients were receiving a nelfinavir-based regimen and 75 an efavirenz-based regimen as outpatients. Antiretroviral therapy was prescribed to all patients according to current guidelines. By intention-to-treat (missing/switch = failure), after a 12-month period, 65% of the patients in the efavirenz group reached a viral load <400 copies/mL compared to 41% of the patients in the nelfinavir group (P = 0.01). The mean CD4 cell count increase after a 12-month period was also greater in the efavirenz group (195 x 10(6) cells/L) than in the nelfinavir group (119 x 10(6) cells/L; P = 0.002). The efavirenz-based regimen was superior compared to the nelfinavir-based regimen. The low response rate in the nelfinavir group might be partially explained by the difficulty of using a regimen requiring a higher patient compliance (12 vs 3 pills a day) in a developing country. PMID:17653450

  3. The START III bargaining space

    SciTech Connect

    Karas, T.H.

    1998-08-01

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

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

    PubMed

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

    2015-01-01

    More than 50 % of women living with HIV in low- and middle-income countries are of reproductive age, but there are limitations to the administration of oral contraception for HIV-infected women receiving antiretroviral therapy due to drug-drug interactions caused by metabolism via the cytochrome P450 isoenzymes and glucuronidation. However, with the development of newer antiretrovirals that use alternative metabolic pathways, options for contraception in HIV-positive women are increasing. This paper aims to review the literature on the pharmacokinetics and pharmacodynamics of oral hormonal contraceptives when given with antiretroviral agents, including those currently used in developed countries, older ones that might still be used in salvage regimens, or those used in resource-limited settings, as well as newer drugs. Nucleos(t)ide reverse transcriptase inhibitors (NRTIs), the usual backbone to most combined antiretroviral treatments (cARTs) are characterised by a low potential for drug-drug interactions with oral contraceptives. On the other hand non-NRTIs (NNRTIs) and protease inhibitors (PIs) may interact with oral contraceptives. Of the NNRTIs, efavirenz and nevirapine have been demonstrated to cause drug-drug interactions; however, etravirine and rilpivirine appear safe to use without dose adjustment. PIs boosted with ritonavir are not recommended to be used with oral contraceptives, with the exception of boosted atazanavir which should be used with doses of at least 35 µg of estrogen. Maraviroc, an entry inhibitor, is safe for co-administration with oral contraceptives, as are the integrase inhibitors (INIs) raltegravir and dolutegravir. However, the INI elvitegravir, which is given in combination with cobicistat, requires a dose of estrogen of at least 30 µg. Despite the growing evidence in this field, data are still lacking in terms of large cohort studies, randomised trials and correlations to real clinical outcomes, such as pregnancy rates, in women on antiretrovirals and hormonal contraception. PMID:25331712

  5. Antiretroviral therapy reduces neurodegeneration in human immunodeficiency virus infection

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

    2012-01-01

    Background The extent to which the prognosis for AIDS and death of patients initiating highly active antiretroviral therapy (HAART) continues to be affected by their characteristics at the time of initiation (baseline) is unclear. Methods We analyzed data on 20,379 treatment-naive HIV-1–infected adults who started HAART in 1 of 12 cohort studies in Europe and North America (61,798 person-years of follow-up, 1844 AIDS events, and 1005 deaths). Results Although baseline CD4 cell count became less prognostic with time, individuals with a baseline CD4 count <25 cells/µL had persistently higher progression rates than individuals with a baseline CD4 count >350 cells/µL (hazard ratio for AIDS = 2.3, 95% confidence interval [CI]: 1.0 to 2.3; mortality hazard ratio = 2.5, 95% CI: 1.2 to 5.5, 4 to 6 years after starting HAART). Rates of AIDS were persistently higher in individuals who had experienced an AIDS event before starting HAART. Individuals with presumed transmission by means of injection drug use experienced substantially higher rates of AIDS and death than other individuals throughout follow-up (AIDS hazard ratio = 1.6, 95% CI: 0.8 to 3.0; mortality hazard ratio = 3.5, 95% CI: 2.2 to 5.5, 4 to 6 years after starting HAART). Conclusions Compared with other patient groups, injection drug users and patients with advanced immunodeficiency at baseline experience substantially increased rates of AIDS and death up to 6 years after starting HAART. PMID:18043315

  7. Psychiatric Advance Directives: Getting Started

    MedlinePlus

    ... Getting Started State by State Info FAQs Educational Webcasts Links Current Research In the News Legal Issues ... How to write a Psychiatric Advance Directive?" View webcast (15:04) What are Psychiatric Advance Directives? View ...

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

    PubMed

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

    2015-07-01

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

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

    PubMed Central

    2011-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

    Attaran, A; Gillespie-White, L

    2001-10-17

    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

  12. Cotrimoxazole prophylaxis and antiretroviral therapy: an observational cohort study in China

    PubMed Central

    Cheng, Wei; Wu, Yasong; Wen, Yi; Ma, Ye; Zhao, Decai; Dou, Zhihui; Zhang, Weiwei; Bulterys, Marc

    2015-01-01

    Abstract Objective To assess if cotrimoxazole prophylaxis administered early during antiretroviral therapy (ART) reduces mortality in Chinese adults who are infected with human immunodeficiency virus (HIV). Methods We did a retrospective observational cohort study using data from the Chinese national free antiretroviral database. Patients older than 14 years who started ART between 1 January 2010 and 31 December 2012 and had baseline CD4+ T-lymphocyte (CD4+ cell) count less than 200cells/L were followed until death, loss to follow-up or 31 December 2013. Hazard ratios (HRs) for several variables were calculated using multivariate analyses. Findings The analysis involved 23?816 HIV-infected patients, 2706 of whom died during the follow-up. Mortality in patients who did and did not start cotrimoxazole during the first 6months of ART was 5.3 and 7.0 per 100personyears, respectively. Cotrimoxazole was associated with a 37% reduction in mortality (hazard ratio, HR: 0.63; 95% confidence interval, CI: 0.560.70). Cotrimoxazole in addition to ART reduced mortality significantly over follow-up lasting 6months (HR: 0.65; 95%CI: 0.590.73), 12months (HR: 0.58; 95%CI: 0.490.70), 18months (HR: 0.49; 95%CI: 0.380.63) and 24months (HR: 0.66; 95%CI: 0.480.90). The mortality reduction was evident in patients with baseline CD4+ cell counts less than 50cells/L (HR: 0.60; 95%CI: 0.540.67), 5099cells/L (HR: 0.66; 95%CI: 0.560.78) and 100199cells/L (HR: 0.78; 95%CI: 0.620.98). Conclusion Cotrimoxazole prophylaxis started early during ART reduced mortality and should be offered to HIV-infected patients in low- and middle-income countries. PMID:25838611

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

    PubMed Central

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

    2013-01-01

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

  14. Impulsively started incompressible turbulent jet

    SciTech Connect

    Witze, P O

    1980-10-01

    Hot-film anemometer measurements are presented for the centerline velocity of a suddenly started jet of air. The tip penetration of the jet is shown to be proportional to the square-root of time. A theoretical model is developed that assumes the transient jet can be characterized as a spherical vortex interacting with a steady-state jet. The model demonstrates that the ratio of nozzle radius to jet velocity defines a time constant that uniquely characterizes the behavior and similarity of impulsively started incompressible turbulent jets.

  15. Secondary mania in patients with HIV infection: are antiretrovirals protective?

    PubMed

    Mijch, A M; Judd, F K; Lyketsos, C G; Ellen, S; Cockram, A

    1999-01-01

    A case-control study of 19 patients with HIV-associated mania and 57 HIV-seropositive control patients matched by CD4 cell count, age, and year of treatment was undertaken to investigate associations with risk factors for human immunodeficiency virus (HIV) infection, treatment, and disease. There was no significant difference between groups for HIV exposure category, baseline health status, or drugs other than antiretrovirals. Zidovudine therapy provided a significant protective effect against the development of mania, whether administered at or prior to diagnosis of mania. In a 3-year follow-up study, incident AIDS dementia was significantly more common in patients with mania, despite no apparent difference in survival between cases and controls. These findings strengthen the evidence of an etiological association of HIV neuropathology with AIDS mania by demonstrating a protective effect of an antiretroviral agent able to penetrate the central nervous system. PMID:10570761

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

    NASA Astrophysics Data System (ADS)

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

    2007-02-01

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

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

    PubMed Central

    Amon, Joseph J

    2008-01-01

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

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

    PubMed

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

    2013-10-01

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

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

    PubMed Central

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

    2014-01-01

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

  20. Can Urine Lamivudine Be Used to Monitor Antiretroviral Treatment Adherence?

    PubMed Central

    Kumar, Agibothu K. Hemanth; Ramachandran, Geetha; Kumar, Periyaiyah; Kumaraswami, Vasanthapuram; Swaminathan, Soumya

    2006-01-01

    Patient adherence to treatment is an important factor in the effectiveness of antiretroviral regimens. Adherence to treatment could be monitored by estimation of antiretroviral drugs in biological fluids. We aimed to obtain information on the quantity and duration of excretion of lamivudine in urine following oral administration of a single dose of 300 mg and to assess its suitability for adherence monitoring purposes. Spot urine samples were collected before dosing and at 4, 8, 12, 24, 28, 32, 48, 72, and 96 hours post dosing from 10 healthy subjects, and lamivudine was estimated by high-pressure liquid chromatography (HPLC). Lamivudine values were expressed as a ratio of urine creatinine. About 91% of the ingested drug was excreted by 24 hours, and the concentration thereafter in urine was very negligible. A lamivudine value of 0.035 mg/mg creatinine or less at 48 hours is suggestive of a missed dose in the last 24 hours. The study findings showed that estimation of urine lamivudine in spot specimens could be useful in monitoring patient adherence to antiretroviral treatment. However, this needs to be confirmed on a larger sample size and among patients on once-daily and twice-daily treatment regimens. PMID:17415333

  1. Can Urine Lamivudine Be Used to Monitor Antiretroviral Treatment Adherence?

    PubMed Central

    2006-01-01

    Patient adherence to treatment is an important factor in the effectiveness of antiretroviral regimens. Adherence to treatment could be monitored by estimation of antiretroviral drugs in biological fluids. We aimed to obtain information on the quantity and duration of excretion of lamivudine in urine following oral administration of a single dose of 300 mg and to assess its suitability for adherence monitoring purposes. Spot urine samples were collected before dosing and at 4, 8, 12, 24, 28, 32, 48, 72, and 96 hours post dosing from 10 healthy subjects, and lamivudine was estimated by high-pressure liquid chromatography (HPLC). Lamivudine values were expressed as a ratio of urine creatinine. About 91% of the ingested drug was excreted by 24 hours, and the concentration thereafter in urine was very negligible. A lamivudine value of 0.035 mg/mg creatinine or less at 48 hours is suggestive of a missed dose in the last 24 hours. The study findings showed that estimation of urine lamivudine in spot specimens could be useful in monitoring patient adherence to antiretroviral treatment. However, this needs to be confirmed on a larger sample size and among patients on once-daily and twice-daily treatment regimens.

  2. Antiretrovirals and safer conception for HIV-serodiscordant couples

    PubMed Central

    Matthews, Lynn T.; Smit, Jennifer A.; Cu-Uvin, Susan; Cohan, Deborah

    2013-01-01

    Purpose of review Many men and women living with HIV and their uninfected partners attempt to conceive children. HIV-prevention science can be applied to reduce sexual transmission risk while respecting couples’ reproductive goals. Here we discuss antiretrovirals as prevention in the context of safer conception for HIV-serodiscordant couples. Recent findings Antiretroviral therapy (ART) for the infected partner and pre-exposure prophylaxis (PrEP) for the uninfected partner reduce the risk of heterosexual HIV transmission. Several demonstration projects suggest the feasibility and acceptability of antiretroviral (ARV)s as periconception HIV-prevention for HIV-serodiscordant couples. The application of ARVs to periconception risk reduction may be limited by adherence. Summary For male-infected (M+F−) couples who cannot access sperm processing and female-infected (F+M−) couples unwilling to carry out insemination without intercourse, ART for the infected partner, PrEP for the uninfected partner, combined with treatment for sexually transmitted infections, sex limited to peak fertility, and medical male circumcision (for F+M couples) provide excellent, well tolerated options for reducing the risk of periconception HIV sexual transmission. PMID:23032734

  3. Adverse effects of antiretroviral therapy for HIV infection.

    PubMed

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

    2004-01-20

    Long-term remission of HIV-1 disease can be readily achieved by combinations of antiretroviral agents. The suppression of plasma viral loads to less than the limit of quantification of the most sensitive commercially available assays (i.e., less than 50 copies/mL) and the coincident improvement in CD4 T cell counts is associated with resolution of established opportunistic infections and a decrease in the risk of new opportunistic infections. However, prolonged treatment with combination regimens can be difficult to sustain because of problems with adherence and toxic effects. All antiretroviral drugs can have both short-term and long-term adverse events. The risk of specific side effects varies from drug to drug, from drug class to drug class, and from patient to patient. A better understanding of the adverse effects of antiretroviral agents is of interest not only for HIV specialists as they try to optimize therapy, but also for other physicians who care for HIV-positive patients. PMID:14734438

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

    PubMed

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

    2016-04-01

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

  5. HANDBOOK FOR PROJECT HEAD START.

    ERIC Educational Resources Information Center

    GRAHAM, JORY

    THIS BOOKLET WAS DESIGNED TO MEET SOME IMMEDIATE NEEDS FOR THE FIRST SUMMER SESSION OF PROJECT HEAD START. IT CONTAINS SOME OF THE MOST WORKABLE AND PROMISING TEACHING METHODS IN THE ENTIRE FIELD OF COMPENSATORY EDUCATIONS, METHODS THAT HAVE BEEN USED IN PRIVATELY SPONSORED CENTERS AND HAVE PROVED VALUABLE IN COPING WITH PROBLEMS ENCOUNTERED IN…

  6. Head Start Dental Health Curriculum.

    ERIC Educational Resources Information Center

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

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

  7. Rigor Made Easy: Getting Started

    ERIC Educational Resources Information Center

    Blackburn, Barbara R.

    2012-01-01

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

  8. Volunteer Grandparents in Head Start.

    ERIC Educational Resources Information Center

    Riley, Mary Tom; Blume, Libby Balter

    Intended for participants in the volunteer grandparents program, this manual briefly defines Head Start program purposes, goals, and recipients and describes training guidelines for volunteer grandparents and staff training coordinators. Training for the volunteer grandparent project is outlined in terms of volunteer service, personal

  9. Starting with the Business Basics.

    ERIC Educational Resources Information Center

    Hoffman, Carl

    1999-01-01

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

  10. Employment Obtaining and Business Starting

    ERIC Educational Resources Information Center

    Lan, Jian

    2009-01-01

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

  11. Head Start Center Design Guide.

    ERIC Educational Resources Information Center

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

    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…

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

    PubMed Central

    Renner, Lorna A; Dicko, Fatoumata; Kouéta, Fla; Malateste, Karen; Gueye, Ramatoulaye D; Aka, Edmond; Eboua, Tanoh K; Azondékon, Alain; Okomo, Uduok; Touré, Pety; Ekouévi, Didier; Leroy, Valeriane

    2013-01-01

    Introduction There is a risk of anaemia among HIV-infected children on antiretroviral therapy (ART) containing zidovudine (ZDV) recommended in first-line regimens in the WHO guidelines. We estimated the risk of severe anaemia after initiation of a ZDV-containing regimen in HIV-infected children included in the IeDEA West African database. Methods Standardized collection of data from HIV-infected children (positive PCR<18 months or positive serology ≥18 months) followed up in HIV programmes was included in the regional IeDEA West Africa collaboration. Ten clinical centres from seven countries contributed (Benin, Burkina Faso, Côte d'Ivoire, Gambia, Ghana, Mali and Senegal) to this collection. Inclusion criteria were age <16 years and starting ART. We explored the data quality of haemoglobin documentation over time and the incidence and predictors of severe anaemia (Hb<7g/dL) per 100 child-years of follow-up over the duration of first-line antiretroviral therapy. Results As of December 2009, among the 2933 children included in the collaboration, 45% were girls, median age was five years; median CD4 cell percentage was 13%; median weight-for-age z-score was −2.7; and 1772 (60.4%) had a first-line ZDV-containing regimen. At baseline, 70% of the children with a first-line ZDV-containing regimen had a haemoglobin measure available versus 76% in those not on ZDV (p≤0.01): the prevalence of severe anaemia was 3.0% (n=38) in the ZDV group versus 10.2% (n=89) in those without (p<0. 01). Over the first-line follow-up, 58.9% of the children had ≥1 measure of haemoglobin available in those exposed to ZDV versus 60.4% of those not (p=0.45). Severe anaemia occurred in 92 children with an incidence of 2.47 per 100 child-years of follow-up in those on a ZDV-containing regimen versus 4.25 in those not (p≤0.01). Adjusted for age at ART initiation and first-line regimen, a weight-for-age z-score ≤−3 was a strong predictor associated with a 5.59 times risk of severe anaemia (p<0.01). Conclusions Severe anaemia is frequent at baseline and guides the first-line ART prescription, but its incidence seems rare among children on ART. Severe malnutrition at baseline is a strong predictor for development of severe anaemia, and interventions to address this should form an integral component of clinical care. PMID:24047928

  13. Nanoformulated Antiretroviral Combinations Extend Drug Release and Antiretroviral Responses in HIV-1 Infected Macrophages: Implications for NeuroAIDS Therapeutics

    PubMed Central

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

    2012-01-01

    We posit that improvements in pharmacokinetics and biodistributions of antiretroviral therapies (ART) for human immunodeficiency virus-type one infected people can be achieved through developments in nanoformulations. To this end, we manufactured nanoparticles of atazanavir, efavirenz, and ritonavir (termed nanoART) and treated human monocyte-derived macrophages (MDM) in combination therapies. This resulted in improved drug uptake, release and antiretroviral efficacy over monotherapy. MDM rapidly, within minutes, ingested nanoART combinations, at equal or similar rates, as individual formulations. Combination nanoART ingested by MDM facilitated drug release from 15 to > 20 days. These findings are noteworthy as a nanoART cell-mediated drug delivery provides a means to deliver therapeutics to viral sanctuaries, such as the central nervous system during progressive human immunodeficiency virus-type one infection. The work brings us yet another step closer to realizing the utility of nanoART for virus-infected people. PMID:20237859

  14. Renal impairment in a rural African antiretroviral programme

    PubMed Central

    2009-01-01

    Background There is little knowledge regarding the prevalence and nature of renal impairment in African populations initiating antiretroviral treatment, nor evidence to inform the most cost effective methods of screening for renal impairment. With the increasing availability of the potentially nephrotixic drug, tenofovir, such information is important for the planning of antiretroviral programmes Methods (i) Retrospective review of the prevalence and risk factors for impaired renal function in 2189 individuals initiating antiretroviral treatment in a rural African setting between 2004 and 2007 (ii) A prospective study of 149 consecutive patients initiating antiretrovirals to assess the utility of urine analysis for the detection of impaired renal function. Severe renal and moderately impaired renal function were defined as an estimated GFR of ? 30 mls/min/1.73 m2 and 3060 mls/min/1.73 m2 respectively. Logistic regression was used to determine odds ratio (OR) of significantly impaired renal function (combining severe and moderate impairment). Co-variates for analysis were age, sex and CD4 count at initiation. Results (i) There was a low prevalence of severe renal impairment (29/2189, 1.3% 95% C.I. 0.81.8) whereas moderate renal impairment was more frequent (287/2189, 13.1% 95% C.I. 11.614.5) with many patients having advanced immunosuppression at treatment initiation (median CD4 120 cells/?l). In multivariable logistic regression age over 40 (aOR 4.65, 95% C.I. 3.546.1), male gender (aOR 1.89, 95% C.I. 1.392.56) and CD4<100 cells/ul (aOR 1.4, 95% C.I. 1.071.82) were associated with risk of significant renal impairment (ii) In 149 consecutive patients, urine analysis had poor sensitivity and specificity for detecting impaired renal function. Conclusion In this rural African setting, significant renal impairment is uncommon in patients initiating antiretrovirals. Urine analysis alone may be inadequate for identification of those with impaired renal function where resources for biochemistry are limited. PMID:19715590

  15. School start times for adolescents.

    PubMed

    2014-09-01

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

  16. Head Start Oral Health Assessment.

    PubMed

    Reed, Rebecca; York, Jill; Dady, Nadege; Chaviano-Moran, Rosa; Jiang, Shuying; Holtzman, Joseph

    2016-05-01

    Purpose A Head Start program located in Paterson, New Jersey considered establishing a school-based dental clinic to address unmet oral health needs such as access to care and the need for restorative treatment. The purpose of this study was to establish the oral health status of Head Start children, their treatment needs, and parents' interest and willingness to utilize a school-based dental clinic. Description School-based dental care has been used to address access to care issues, particularly among children who live in underserved areas. A 21 item survey was used to correlate the results of an oral exam performed on the Head Start children and the parents' preferences, beliefs and access patterns. Fisher's exact test and Chi squared test were used to study the association among variable with significance levels set at 0.05. Assessment The oral exam revealed a high caries rate amongst all of the children. Parental responses indicated strong support for the establishment of a school-based clinic and identified the need for further parental education. Having a regular source of care was found to be unrelated to treatment needs. Conclusion Further education of the parents regarding the child's oral health is critical to the success and viability of this school-based clinic. PMID:27017227

  17. Pregnancy is associated with elevation of liver enzymes in HIV-positive women on antiretroviral therapy

    PubMed Central

    HUNTINGTON, Susie; THORNE, Claire; NEWELL, Marie-Louise; ANDERSON, Jane; TAYLOR, Graham P; PILLAY, Deenan; HILL, Teresa; TOOKEY, Pat A; SABIN, Caroline

    2015-01-01

    Objective To assess whether pregnancy is associated with an increased risk of liver enzyme elevation (LEE) and severe LEE in HIV-positive women on antiretroviral therapy (ART). Design Two observational studies; the UK Collaborative HIV Cohort (UK CHIC) study and the UK and Ireland National Study of HIV in Pregnancy and Childhood (NSHPC). Methods Combined data from UK CHIC and NSHPC were used to identify factors associated with LEE (grade 1-4) and severe LEE (grade 3-4). Women starting ART in 2000-2012 were included irrespective of pregnancy status. Cox proportional hazards were used to assess fixed and time-dependent covariates including pregnancy status, CD4 count, drug regimen and hepatitis B/C (HBV/HCV) co-infection. Results One-quarter (25.7%, 982/3815) of women were pregnant during follow-up; 14.2% (n=541) when starting ART. The rate of LEE was 14.5/100 person-years (PY) in and 6.0/100 PY outside of pregnancy. The rate of severe LEE was 3.9/100 PY in and 0.6/100 PY outside of pregnancy. The risk of LEE and severe LEE was increased during pregnancy (LEE: aHR 1.66 [1.31-2.09]; severe LEE: aHR 3.57 [2.30-5.54]), including in secondary analyses excluding 541 women pregnant when starting ART. Other factors associated with LEE and severe LEE included lower CD4 count (<250 cells/mm3), HBV/HCV co-infection and calendar year. Conclusions Although few women developed severe LEE, this study provides further evidence that pregnancy is associated with increased risk of LEE and severe LEE, reinforcing the need for regular monitoring of liver biomarkers during pregnancy. PMID:25710412

  18. Sex Differences in HIV Outcomes in the Highly Active Antiretroviral Therapy Era: A Systematic Review

    PubMed Central

    Melekhin, Vlada V.; Sterling, Timothy R.

    2014-01-01

    Abstract 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

  19. PENTA 2009 guidelines for the use of antiretroviral therapy in paediatric HIV-1 infection.

    PubMed

    Welch, Steve; Sharland, Mike; Lyall, E G Hermione; Tudor-Williams, Gareth; Niehues, Tim; Wintergerst, Uwe; Bunupuradah, Torsak; Hainaut, Marc; Della Negra, Marinella; Pena, Maria José Mellado; Amador, José Tomas Ramos; Gattinara, Guido Castelli; Compagnucci, Alexandra; Faye, Albert; Giaquinto, Carlo; Gibb, Diana M; Gandhi, Kate; Forcat, Silvia; Buckberry, Karen; Harper, Lynda; Königs, Christoph; Patel, Deepak; Bastiaans, Diane

    2009-11-01

    PENTA Guidelines aim to provide practical recommendations for treating children with HIV infection in Europe. Changes to guidance since 2004 have been informed by new evidence and by expectations of better outcomes following the ongoing success of antiretroviral therapy (ART). Participation in PENTA trials of simplifying treatment is encouraged. The main changes are in the following sections: 'When to start ART': Treatment is recommended for all infants, and at higher CD4 cell counts and percentages in older children, in line with changes to adult guidelines. The number of age bands has been reduced to simplify and harmonize with other paediatric guidelines. Greater emphasis is placed on CD4 cell count in children over 5 years, and guidance is provided where CD4% and CD4 criteria differ. 'What to start with': A three-drug regimen of two nucleoside reverse transcriptase inhibitors (NRTIs) with either a nonnucleoside reverse transcriptase inhibitor (NNRTI) or a boosted protease inhibitor (PI) remains the first choice combination. Lamivudine and abacavir are the NRTI backbone of choice for most children, based on long-term follow-up in the PENTA 5 trial. Stavudine is no longer recommended. Whether to start with an NNRTI or PI remains unclear, but PENPACT 1 trial results in 2009 may help to inform this. All PIs should be ritonavir boosted. Recommendations on use of resistance testing, therapeutic drug monitoring and HLA testing draw from data in adults and from European paediatric cohort studies. Recently updated US and WHO paediatric guidelines provide more detailed review of the evidence base. Differences between guidelines are highlighted and explained. PMID:19878352

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

    PubMed Central

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

    2016-01-01

    Background Cardiac involvement in HIV infected children has been frequently reported, but whether this is due to HIV infection itself or to antiretroviral treatment (ART) is unknown. Methods This cross sectional study involved 114 vertically-acquired HIV-infected (56 ART-naive, 58 ART-exposed) and 51 healthy children in Jakarta, Indonesia. Echocardiography was performed to measure dimensions of the left ventricle (LV) and systolic functions. We applied general linear modeling to evaluate the associations between HIV infection/treatment status and cardiac parameters with further adjustment for potential confounders or explanatory variables. Findings are presented as (adjusted) mean differences between each of the two HIV groups and healthy children, with 95% confidence intervals and p values. Results Compared to healthy children, ART-naïve HIV-infected children did not show significant differences in age-and-height adjusted cardiac dimensions apart from larger LV internal diameter (difference 2.0 mm, 95%CI 0.2 to 3.7), whereas ART exposed HIV infection showed thicker LV posterior walls (difference = 1.1 mm, 95%CI 0.5 to 1.6), larger LV internal diameter (difference = 1.7 mm, 95%CI 0.2 to 3.2) and higher LV mass (difference = 14.0 g, 7.4 to 20.5). With respect to systolic function, reduced LV ejection fraction was seen in both ART-naïve HIV infected (adjusted difference = -6.7%, -11.4 to -2.0) and, to a lesser extent, in ART-exposed HIV infected children (difference = -4.5%, -8.5 to -0.4). Inflammation level seemed to be involved in most associations in ART-exposed HIV-infected, but few, if any, for decreased function in the ART-naive ones, whereas lower hemoglobin appeared to partially mediate chamber dilation in both groups and reduced function, mainly in ART-exposed children. Conclusions ART-naive HIV infected children have a substantial decrease in cardiac systolic function, whereas the ART-exposed have thicker ventricular walls with larger internal diameter and higher mass, but less functional impairment. PMID:26789522

  1. Starting apparatus for internal combustion engines

    SciTech Connect

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

    1995-01-01

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

  2. Head Start Impact Study: First Year Findings

    ERIC Educational Resources Information Center

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

    2005-01-01

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

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

    PubMed Central

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

    2006-01-01

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

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

    PubMed

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

    2014-01-01

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

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

    PubMed Central

    Broder, Samuel

    2010-01-01

    In the last 25 years, HIV-1, the retrovirus responsible for the Acquired Immunodeficiency Syndrome (AIDS), has gone from being an “inherently untreatable” infectious agent to one eminently susceptible to a range of approved therapies. During a five-year period, starting in the mid-1980s, my group at the National Cancer Institute played a role in the discovery and development of the first generation of antiretroviral agents, starting in 1985 with Retrovir® (zidovudine, AZT) in a collaboration with scientists at the Burroughs-Wellcome Company (now GlaxoSmithKline). We focused on AZT and related congeners in the dideoxynucleoside family of nucleoside reverse transcriptase inhibitors (NRTIs), taking them from the laboratory to the clinic in response to the pandemic of AIDS, then a terrifying and lethal disease. These drugs proved, above all else, that HIV-1 infection is treatable, and such proof provided momentum for new therapies from many sources, directed at a range of viral targets, at a pace that has rarely if ever been matched in modern drug development. Antiretroviral therapy has brought about a substantial decrease in the death rate due to HIV-1 infection, changing it from a rapidly lethal disease into a chronic manageable condition, compatible with very long survival. This has special implications within the classic boundaries of public health around the world, but at the same time in certain regions may also affect a cycle of economic and civil instability in which HIV-1/AIDS is both cause and consequence. Many challenges remain, including 1.) the life-long duration of therapy; 2.) the ultimate role of pre-exposure prophylaxis (PrEP); 3.) the cardiometabolic side effects or other toxicities of long-term therapy; 4.) the emergence of drug-resistance and viral genetic diversity (non-B subtypes); 5.) the specter of new cross-species transmissions from established retroviral reservoirs in apes and Old World monkeys; and 6.) the continued pace of new HIV-1 infections in many parts of the world. All of these factors make refining current therapies and developing new therapeutic paradigms essential priorities, topics covered in articles within this special issue of Antiviral Research. Fortunately, there are exciting new insights into the biology of HIV-1, its interaction with cellular resistance factors, and novel points of attack for future therapies. Moreover, it is a short journey from basic research to public health benefit around the world. The current science will lead to new therapeutic strategies with far-reaching implications in the HIV-1/AIDS pandemic. This article forms part of a special issue of Antiviral Research marking the 25th anniversary of antiretroviral drug discovery and development, Vol 85, issue 1, 2010. PMID:20018391

  6. Practical ethics. A fresh start?

    PubMed

    Palmer, Isaac; Neufelder, Daniel

    2007-06-01

    You are a newly hired CEO and need to hire a chief operating officer. You really wanted to hire a previous employee, Joe, a COO whose abilities put him ahead of the competition. He was a star performer who has a gift for working with physicians--something that needs special attention at your hospital. Now you've learned he's had several public scenes while drinking in restaurants. He's told you those were isolated incidents, due to personal problems that are over. He'd like to move and make a fresh start. What do you do? PMID:17703546

  7. Starting pitch for carbon fibers

    SciTech Connect

    Uemura, S.; Takashima, H.; Kato, O.; Harakawa, M.

    1986-04-01

    This patent describes a starting pitch for producing carbon fiber. This pitch essentially consists of a mixture of (a) 100 parts by weight of a petroleum pitch and (b) 5 to 500 parts by weight of a methanol-insoluble and benzene-soluble component contained in a heavy oil obtained in a fluid catalytic cracking of petroleum. The heavy oil has a boiling range not lower than 200/sup 0/C. The component has been obtained by treating the heavy oil with methanol and benzene so as to remove methanol soluble and benzene insoluble fractions therefrom while retaining therein methanol-insoluble and benzene-soluble fractions.

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

    ERIC Educational Resources Information Center

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

    2009-01-01

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

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

    PubMed Central

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

    2012-01-01

    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. PMID:22872107

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

    PubMed Central

    Bennett, Sara; Chanfreau, Catherine

    2005-01-01

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

  11. Timing of antiretroviral therapy initiation after diagnosis of recent human immunodeficiency virus infection and CD4(+) T-cell recovery.

    PubMed

    Ding, Y; Duan, S; Wu, Z; Ye, R; Yang, Y; Yao, S; Wang, J; Xiang, L; Jiang, Y; Lu, L; Jia, M; Detels, R; He, N

    2016-03-01

    We retrospectively examined the timing of antiretroviral therapy (ART) initiation and CD4(+) T-cell recovery over 36months among recent human immunodeficiency virus (HIV) infections using BED (HIV-1 subtypes B, E and D) immunoglobulin G capture enzyme immunoassay (BED-CEIA). Regardless of baseline CD4(+) counts, individuals (n=393) who initiated ART >2months after diagnosis had significantly decreased probability and rate of achieving CD4(+) counts ?900cells/?L or ?600cells/?L than those individuals (n=135) who started ART earlier (?2months). But the mean CD4(+) counts in two groups converged after 30months of treatment. Early ART initiation leads to accelerated CD4(+) recovery, but does not offer a long-term advantage in CD4(+) counts. PMID:26627338

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

    PubMed

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

    2015-04-01

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

  13. Rapid starting methanol reactor system

    DOEpatents

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

    1984-01-01

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

  14. Starting a nursing consultation practice.

    PubMed

    Schulmeister, L

    1999-03-01

    Because the clinical nurse specialist (CNS) role has been changed or eliminated in many hospital organizations, many CNSs in career transition are considering establishing collaborative or independent nursing consultation practices. Opportunities for consultants exist in diverse practice settings and specialties. Before starting a consultation practice, the CNS should carefully examine goals, identify resources, and begin contacting potential referral sources. He or she must also decide what form of business organization to establish and write a business plan to solidify ideas and prepare for the unexpected. Most CNS consultants rely on personal savings to cover initial business and personal expenses, and many continue working as a CNS until the consultation practice is established. Fees can be set based on community standards, what the market will bear, desired projected income, or a third-party payor's fee schedule. The consultation practice can be marketed by word of mouth, inexpensive advertising techniques such as distributing flyers and business cards, direct mall, and media advertising. In today's healthcare marketplace, opportunities abound for the CNS risk-taker interested in starting a nursing consultation practice. PMID:10382408

  15. The Effect of Antiretrovirals on Plasmodium falciparum Liver Stages

    PubMed Central

    Hobbs, Charlotte V.; De La Vega, Patricia; Penzak, Scott R.; Van Vliet, Jillian; Krzych, Urszula; Sinnis, Photini; Borkowsky, William; Duffy, Patrick E.

    2014-01-01

    HIV and malaria overlap geographically, but the full impact of different antiretrovirals (ARVs) on malaria remains poorly understood. We examined the antimalarial activity of the HIV protease inhibitors (PI) lopinavir and saquinavir and the non-nucleoside reverse transcriptase inhibitor (NNRTIs) nevirapine on Plasmodium falciparum liver stages. Our results demonstrate that the HIV PI lopinavir inhibits liver stage parasites at clinically relevant concentrations, that is, at drug levels achieved in HIV-infected patients on standard dosing regimens. Because drugs that inhibit liver stages target parasites when they are present in lower numbers, these results might have implications for eradication efforts. PMID:23907270

  16. Helping the urban poor stay with antiretroviral HIV drug therapy.

    PubMed Central

    Bamberger, J D; Unick, J; Klein, P; Fraser, M; Chesney, M; Katz, M H

    2000-01-01

    Recent studies have documented dramatic decreases in opportunistic infections, hospitalizations, and mortality among HIV-infected persons, owing primarily to the advent of highly active antiretroviral medications. Unfortunately, not all segments of the population living with HIV benefit equally from treatment. In San Francisco, only about 30% of the HIV-infected urban poor take combination highly active antiretroviral medications, as compared with 88% of HIV-infected gay men. Practitioners who care for the urban poor are reluctant to prescribe these medications, fearing inadequate or inconsistent adherence to the complicated medical regimen. Persons typically must take 2 to 15 pills at a time, 2 to 3 times a day. Some of the medications require refrigeration, which may not be available to the homeless poor. Most homeless persons do not have food available to them on a consistent schedule. Therefore, they may have difficulty adhering to instructions to take medications only on an empty stomach or with food. Lack of a safe place to store medications may be an issue for some. In addition, many urban poor live with drug, alcohol, or mental health problems, which can interfere with taking medications as prescribed. Inconsistent adherence to medication regimens has serious consequences. Patients do not benefit fully from treatments, and they will become resistant to the medications in their regimen as well as to other medications in the same classes as those in their regimen. Development of resistance has implications for the broader public health, because inadvertent transmission of multidrug-resistant strains of HIV has been demonstrated. Concern that the urban poor will not adhere to highly active antiretroviral medication regimens has led to debate on the role of clinicians and public health officials in determining who can comply with these regimens. Rather than define the characteristics that would predict adherence to these regimens, the San Francisco Department of Public Health created a program to support adherence among those who may have the greatest difficulty complying with complicated highly active antiretroviral medication regimens. The program, dubbed the Action Point Adherence Project, was conceived through a community planning process in preparation for a city-wide summit on HIV/AIDS that took place in January 1998. Action Point is funded by the city and the county of San Francisco. Now in its 10th month, the program continues to show promising evidence of improving clients' biological and social indicators. PMID:10800416

  17. Enfuvirtide: a new class of antiretroviral therapy for HIV infection.

    PubMed

    Leao, J C; Frezzini, C; Porter, S

    2004-11-01

    Enfuvirtide is the first of a new class of antiretroviral agents recently approved for the treatment of human immunodeficiency virus (HIV)-1 infection. Present available data suggest that enfuvirtide may be a promising agent for the control of HIV infection in patients who have previously received reverse transcriptase inhibitor and protease inhibitor regimens and who are either intolerant to such drugs and/or who have gone into virological failure. Perhaps the greater limitation to the clinical use of enfuvirtide is the cost, limiting its use in the developing world. PMID:15533206

  18. Preventing antiretroviral anarchy in sub-Saharan Africa.

    PubMed

    Harries, A D; Nyangulu, D S; Hargreaves, N J; Kaluwa, O; Salaniponi, F M

    2001-08-01

    Combination antiretroviral therapy has dramatically improved the survival of patients living with HIV and AIDS in industrialised countries of the world. Despite this enormous benefit, there are some major problems and obstacles to be overcome.(1) Treatment of HIV-infection is likely to be lifelong.(2) Unfortunately, many HIV-infected individuals cannot tolerate the toxic effects of the drugs, or have difficulty complying with treatment which involves large numbers of pills and complicated dosing schedules. Poor adherence to treatment leads to the emergence of drug-resistant viral strains that need new combinations of drugs or new drugs altogether. PMID:11502341

  19. Combination antiretroviral studies for patients with primary biliary cirrhosis.

    PubMed

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

    2016-01-01

    Following the characterization of a human betaretrovirus in patients with primary biliary cirrhosis (PBC), pilot studies using antiretroviral therapy have been conducted as proof of principal to establish a link of virus with disease and with the eventual aim to find better adjunct therapies for patients unresponsive to ursodeoxycholic acid. In the first open label pilot study, the reverse transcriptase inhibitor lamivudine had little demonstrable biochemical or histological effect after 1 year. Whereas, lamivudine in combination with zidovudine was associated with a significant reduction in alkaline phosphatase as well as improvement in necroinflammatory score, cholangitis and ductopenia over a 12 mo period. A double blind, multi-center randomized controlled trial using lamivudine with zidovudine for 6 mo confirmed a significant reduction in alkaline phosphatase, ALT and AST in patients on antiviral therapy. However, none of the patients achieved the stringent endpoint criteria for normalization of alkaline phosphatase. Furthermore, some patients developed biochemical rebound consistent with drug resistance. A major fault of these studies has been the inability to measure the viral load in peripheral blood and therefore, provide a direct correlation between improvement of hepatic biochemistry and reduction in viral load. Nevertheless, viral mutants to lamivudine with zidovudine were later characterized in the NOD.c3c4 mouse model of PBC that has been used to test other antiretroviral regimens to betaretrovirus. The combination of tenofovir and emtricitabine reverse transcriptase inhibitors and the HIV protease inhibitor, lopinavir were found to abrogate cholangitis in the NOD.c3c4 mouse model and the same regimen normalized the liver tests in a PBC patient with HIV and human betaretrovirus infection. This combination antiretroviral therapy has now been used in a double blind randomized controlled crossover study for patients with PBC followed by an open label extension study. Only a third of the PBC patients were able to tolerate the lopinavir but those maintained on tenofovir, emtricitabine and lopinavir experienced sustained and clinically meaningful reduction in hepatic biochemistry. While we await the histological and virological evaluation, it is clear that better tolerated regimens of antiretroviral treatment will be required in future clinical trials. PMID:26755881

  20. Combination antiretroviral studies for patients with primary biliary cirrhosis

    PubMed Central

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

    2016-01-01

    Following the characterization of a human betaretrovirus in patients with primary biliary cirrhosis (PBC), pilot studies using antiretroviral therapy have been conducted as proof of principal to establish a link of virus with disease and with the eventual aim to find better adjunct therapies for patients unresponsive to ursodeoxycholic acid. In the first open label pilot study, the reverse transcriptase inhibitor lamivudine had little demonstrable biochemical or histological effect after 1 year. Whereas, lamivudine in combination with zidovudine was associated with a significant reduction in alkaline phosphatase as well as improvement in necroinflammatory score, cholangitis and ductopenia over a 12 mo period. A double blind, multi-center randomized controlled trial using lamivudine with zidovudine for 6 mo confirmed a significant reduction in alkaline phosphatase, ALT and AST in patients on antiviral therapy. However, none of the patients achieved the stringent endpoint criteria for normalization of alkaline phosphatase. Furthermore, some patients developed biochemical rebound consistent with drug resistance. A major fault of these studies has been the inability to measure the viral load in peripheral blood and therefore, provide a direct correlation between improvement of hepatic biochemistry and reduction in viral load. Nevertheless, viral mutants to lamivudine with zidovudine were later characterized in the NOD.c3c4 mouse model of PBC that has been used to test other antiretroviral regimens to betaretrovirus. The combination of tenofovir and emtricitabine reverse transcriptase inhibitors and the HIV protease inhibitor, lopinavir were found to abrogate cholangitis in the NOD.c3c4 mouse model and the same regimen normalized the liver tests in a PBC patient with HIV and human betaretrovirus infection. This combination antiretroviral therapy has now been used in a double blind randomized controlled crossover study for patients with PBC followed by an open label extension study. Only a third of the PBC patients were able to tolerate the lopinavir but those maintained on tenofovir, emtricitabine and lopinavir experienced sustained and clinically meaningful reduction in hepatic biochemistry. While we await the histological and virological evaluation, it is clear that better tolerated regimens of antiretroviral treatment will be required in future clinical trials. PMID:26755881

  1. Effect of Antiretroviral Therapy on HIV Reservoirs in Elite Controllers

    PubMed Central

    Chun, Tae-Wook; Shawn Justement, J.; Murray, Danielle; Kim, Connie J.; Blazkova, Jana; Hallahan, Claire W.; Benko, Erika; Costiniuk, Cecilia T.; Kandel, Gabor; Ostrowski, Mario; Kaul, Rupert; Moir, Susan; Casazza, Joseph P.; Koup, Richard A.; Kovacs, Colin; Fauci, Anthony S.

    2013-01-01

    Elite controllers suppress human immunodeficiency virus (HIV) viremia to below the limit of detection in the absence of antiretroviral therapy (ART). However, precise frequencies of CD4+ T cells carrying replication-competent HIV and/or the dynamics of the infectious viral reservoirs in response to initiation and discontinuation of ART in elite controllers are unknown. We show that the size of the pool of CD4+ T cells harboring infectious HIV diminished significantly after initiation of ART and rebounded to baseline upon cessation of therapy. Our data provide compelling evidence that persistent viral replication occurs in untreated elite controllers even in the absence of detectable plasma viremia. PMID:23847057

  2. Utilizing a new class of antiretrovirals: role of fusion inhibitors in HIV disease management.

    PubMed

    Murphy, Robert L

    2003-12-01

    HIV-infected patients who stand to benefit most from the availability of new antiretrovirals are those who have the fewest treatment options. Clinical trials have shown that in antiretroviral-experienced patients requiring a regimen change, including an antiretroviral drug from a previously unused class, is associated with greater treatment response. In clinical trials of the entry inhibitor enfuvirtide, triple-class-experienced patients treated with enfuvirtide plus an optimized background regimen of 3 to 5 active antiretrovirals consistently showed virologic and immunologic responses superior to those of the patients who received optimized background treatment alone, regardless of the number of active antiretroviral drugs included in the optimized background treatment. Adverse events have not been observed to be considerably greater among enfuvirtide-treated patients than among those receiving optimized background treatment alone. Injection site reactions of mostly mild to moderate severity were the most common adverse events in the enfuvirtide group, with few resulting in discontinuation. PMID:19960652

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  5. Postexposure prophylactic effect of hepatitis B virus (HBV)-active antiretroviral therapy against HBV infection.

    PubMed

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

    2015-02-01

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

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

    PubMed Central

    2011-01-01

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

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

    PubMed Central

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

    2009-01-01

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

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

    PubMed

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

    2006-06-01

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

  9. Geneva summit: a fresh start

    SciTech Connect

    Reagan, R.

    1985-01-01

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

  10. 30 CFR 75.1913 - Starting aids.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

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

  11. 30 CFR 75.1913 - Starting aids.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

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

  12. 30 CFR 75.1913 - Starting aids.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

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

  13. 30 CFR 75.1913 - Starting aids.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

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

  14. 30 CFR 75.1913 - Starting aids.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

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

  15. Sclerosing cholangitis by cytomegalovirus in highly active antiretroviral therapy era.

    PubMed

    Hidalgo-Tenorio, Carmen; Blasco-Morente, Gonzalo

    2013-10-01

    Sclerosing cholangitis (SC) due to cytomegalovirus (CMV) is very rare. It has been described mainly in immunocompromised patients. Currently, in HIV infected patients it is exceptional. The most of cases belong to pre-highly active antiretroviral therapy (pre-HAART) and those cases were in stage AIDS with less than 100 CD4/ microl. The most frequently involved pathogen in pre-HAART period was Cryptosporidium parvum (30-57 %) and CMV (10-30 %); in late HAART period this information are unaware. CMV has been implicated as a possible etiological agent in primary SC partly because of the ability to cause liver damage and its relationship with smooth muscle antibodies. The most effective treatment for SC was the combination of antiretroviral therapy and endoscopic retrograde cholangiopancreatography with sphincterotomy and stent placement.Following, we present the first case of late HAART period which describes a SC extrahepatic without papillary stenosis with CMV as the only cause and clinical presentation of HIV infection in a woman with 177 CD4/microl. PMID:24467502

  16. [AIDS treatment in Africa: the risk of antiretroviral resistance].

    PubMed

    Hamers, R L; Schuurman, R; van Vugt, M; Derdelinckx, I; Rinke de Wit, T F

    2007-12-01

    --In recent years, implementation of antiretroviral therapy in developing countries with a high prevalence of HIV-1 has been recognised as a public health priority. Consequently, the availability ofantiretroviral combination therapy for people with HIV is increasing rapidly in sub-Saharan Africa. --HIV treatment programmes are implemented according to the standardised, simplified public health guidelines developed by the World Health Organization (WHO). --However, the implementation of treatment programmes in Africa is hindered by several factors, including the lack of adequate immunological and virological laboratory monitoring, insufficient support for adherence to therapy, vulnerable health care systems and the use of suboptimal drug combinations. --These suboptimal treatment conditions increase the risk that resistant virus strains will emerge that are less susceptible to standard first-line combination therapy, thus threatening the long-term success of the treatment programmes. --The WHO has initiated HIVResNet, an international expert advisory board that has developed a global strategy for surveillance and prevention of antiretroviral drug resistance. --The Dutch initiative known as 'PharmAccess African studies to evaluate resistance' (PASER) is contributing to this strategy by creating a surveillance network in sub-Saharan Africa. PMID:18179083

  17. Antiretroviral medication: an emerging category of prescription drug misuse

    PubMed Central

    Davis, Glen P.; Surratt, Hilary L.; Levin, Frances R.; Blanco, Carlos

    2013-01-01

    Background and Objectives Prescription drug abuse has been a focus of public health concern over the past two decades with many studies addressing patterns of narcotic analgesic abuse and diversion. Most research in this domain has centered on controlled substances with known abuse liability. However, the scientific literature has been virtually silent regarding other prescribed medications with previously undocumented addictive potential, such as antiretroviral medications (ARV) for treatment of HIV. Methods This paper reviews the available evidence that suggests a growing problem of ARV diversion and abuse and explores the reasons for the misuse of these medications based on the theoretical neuropsychiatric effects of ARVs and the drug-drug interactions between ARVs and other drugs of abuse. Results Review of media reports and qualitative studies suggest that ARV medications are an emerging drug of abuse. Claims about the psychoactive effects of these antiretroviral drugs are supported by scientific case reports. Conclusions and Scientific Significance This article reviews the evidence to date of an emerging problem of diversion and misuse of ARV medications for recreational purposes. Implications of ARV misuse and diversion are discussed with suggestions for future research and intervention. PMID:24102874

  18. Barriers to antiretroviral therapy adherence in rural Mozambique

    PubMed Central

    2011-01-01

    Background HIV is treated as a chronic disease, but high lost-to-follow-up rates and poor adherence to medication result in higher mortality, morbidity, and viral mutation. Within 18 clinical sites in rural Zambzia Province, Mozambique, patient adherence to antiretroviral therapy has been sub-optimal. Methods To better understand barriers to adherence, we conducted 18 community and clinic focus groups in six rural districts. We interviewed 76 women and 88 men, of whom 124 were community participants (CP; 60 women, 64 men) and 40 were health care workers (HCW; 16 women, 24 men) who provide care for those living with HIV. Results While there was some consensus, both CP and HCW provided complementary insights. CP focus groups noted a lack of confidentiality and poor treatment by hospital staff (42% CP vs. 0% HCW), doubt as to the benefits of antiretroviral therapy (75% CP vs. 0% HCW), and sharing medications with family members (66% CP vs. 0%HCW). Men expressed a greater concern about poor treatment by HCW than women (83% men vs. 0% women). Health care workers blamed patient preference for traditional medicine (42% CP vs. 100% HCW) and the side effects of medication for poor adherence (8% CP vs. 83% CHW). Conclusions Perspectives of CP and HCW likely reflect differing sociocultural and educational backgrounds. Health care workers must understand community perspectives on causes of suboptimal adherence as a first step toward effective intervention. PMID:21846344

  19. Photosensitization is required for antiretroviral activity of hypericin

    NASA Astrophysics Data System (ADS)

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

    1991-06-01

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

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

    PubMed

    Camacho, Ángela; Rivero, Antonio

    2014-11-01

    Lopinavir/ritonavir (LPV/r) was approved for use in the treatment of human immunodeficiency virus (HIV) infection in 2001 and is the protease inhibitor that has been most widely studied in clinical trials. Despite the time interval since its approval, all the evidence accumulated in the last 14 years indicates that LPV/r continues to occupy an important position among antiretroviral drugs. Firstly, LPV/r plus 2 nucleoside/nucleotide analogs is still considered a good option for initial antiretroviral therapy (ART). Secondly, numerous studies have evaluated the efficacy and safety of new initial ART strategies based on LPV/r in dual therapy. The results obtained suggest that LPV/r plus lamivudine (3TC) or raltegravir can be as effective in initial ART as standard triple therapy and justify their consideration as alternative regimens in this scenario. Thirdly, LPV/r is a pioneer drug, as well as being the agent with the largest amount of evidence from clinical trials on simplification to monotherapy (LPV/r) or dual therapy (LPV/r + 3TC). Lastly, LPV/r is highly useful is special situations. It has a low risk of liver toxicity in patients with chronic liver disease, its use is preferred in the treatment of patients with HIV-2, and it is safe and effective in preventing vertical HIV transmission. PMID:25542874

  1. Effect of antiretroviral drugs on the quality of semen.

    PubMed

    Lambert-Niclot, Sidonie; Poirot, Catherine; Tubiana, Roland; Houssaini, Allal; Souli, Cathia; Dominguez, Stphanie; Schubert, Benoit; Prades, Marie; Bonmarchand, Manuela; Calvez, Vincent; Flandre, Philippe; Peytavin, Gilles; Marcelin, Anne-Genevive

    2011-08-01

    The aim of this cross-sectional study was to determine which antiretroviral drugs (ARVs) are associated with changes in the characteristics of semen and the impact of these ARVs according to their score penetration into the male genital compartment. Data from 144 men infected with HIV-1 enrolled in an Assisted Reproductive Technology program were analyzed retrospectively. A seminal penetration score of ARV was based on the available literature. The nonparametric Kruskal-Wallis test and chi-square test were used. There was no difference on sperm parameters between NRTI, NNRTI, or PI regimen. In patients receiving NRTIs or PIs no differences were observed between antiretrovirals of these classes. However, in patients receiving NNRTIs, nevirapine (n?=?22) was associated with a higher percentage of progressively motile spermatozoa (P?

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

    PubMed Central

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

    2014-01-01

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

  3. Challenges, successes and patterns of enrolment in the INSIGHT Strategic Timing of AntiRetroviral Treatment trial

    PubMed Central

    Grarup, J; Rappoport, C; Engen, NW; Carey, C; Hudson, F; Denning, E; Sharma, S; Florence, E; Vjecha, MJ

    2015-01-01

    Objectives To describe the challenges, successes and patterns of enrolment in the Strategic Timing of AntiRetroviral Treatment (START) study. Methods START is a collaboration of many partners with central coordination provided by the protocol team, the statistical and data management centre (SDMC), INSIGHT network leadership, international coordinating centres and site coordinating centres. The SDMC prepared reports on study accrual, baseline characteristics and site performance that allowed monitoring of enrolment and data quality and helped ensure the successful enrolment of this large international trial. We describe the pattern of enrolment and challenges faced during the enrolment period of the trial. Results An initial pilot phase began in April 2009 and established feasibility of accrual at 101 sites. In August 2010, funding approval for an expanded definitive phase led to the successful accrual of 4688 participants from 215 sites in 35 countries by December 2013. Challenges to accrual included regulatory delays (e.g., national/local ethics approval, drug importation approval) and logistical obstacles (e.g., execution of contracts with pharmaceutical companies, set up of a central drug repository, translation of participant materials). The personal engagement of investigators, strong central study coordination, and frequent and transparent communication with site investigators, community members and participants were key contributing factors to this success. Conclusions Accrual into START was completed in a timely fashion despite multiple challenges. This success was due to the efforts of site investigators committed to maintaining study equipoise, transparent and responsive study coordination, and community involvement in problem-solving. PMID:25711319

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

    PubMed

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

    2012-09-21

    A methodology based on micellar liquid chromatography to monitor five antiretroviral drugs (lamivudine, stavudine, tenofovir, zidovudine and efavirenz) was proposed. Antiretrovirals were studied in sets of three, corresponding to each highly active antiretroviral therapy (HAART) regime, prescribed to acquired immunodeficiency syndrome (AIDS)-infected patients. Four aqueous micellar mobile phases buffered at pH 7 were optimized to separate these compounds, using sodium dodecyl sulfate as the tensioactive, and 1-propanol or 1-pentanol as the organic modifier. The composition of each mobile phase was optimized for each antiretroviral. The common separation conditions were: C18 apolar column (125 × 4.6 mm, 5 μm particle size), UV detection set at 214 nm, and mobile phase running at 1 mL min(-1) without controlling the temperature. The finally suggested method was validated for five analysed antiretroviral drugs following the US Food and Drug Administration guidelines in terms of: linearity between 0.5 and 50 ppm (r(2) > 0.9995), sensitivity (LOD lower than 0.25 ppm), intra- and inter-day precision (<7.1 and <5.2%, respectively) and accuracy (recovery 88.5-105.3% and 93.5-101.3%, respectively), as well as robustness (<6.5%). The proposed method was used to monitor the level of antiretrovirals in the serum of AIDS patients. The suggested methodology was found to be useful in the routine analysis of antiretrovirals in serum samples. PMID:22858583

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2007-01-01

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

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

    PubMed Central

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

    2014-01-01

    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. PMID:24932169

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

    PubMed Central

    Hoque, Mohammad Zahirul

    2015-01-01

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

  9. Early Combination Antiretroviral Therapy Limits HIV-1 Persistence in Children.

    PubMed

    Luzuriaga, Katherine

    2016-01-14

    Globally, 240,000 infants are newly infected with HIV-1 each year and 3.2 million children are living with the infection. Combination antiretroviral therapy (cART) has reduced HIV-1-related disease and mortality in children but is not curative owing to the early generation of a latent reservoir of long-lived memory CD4(+) T cells bearing replication-competent HIV-1 provirus integrated into cellular DNA. This review focuses on recent advances in our understanding of the establishment of HIV-1 persistence in children and how early initiation of cART in the setting of the developing infant immune system limits the formation of the long-lived latent CD4(+) cell reservoir that remains a barrier to remission or cure. PMID:26768239

  10. Behcet's disease with HIV infection: response to antiretroviral therapy.

    PubMed

    Mahajan, Vikram K; Sharma, Nand Lal; Sharma, Vikas C; Sharma, Ramesh Chander; Sarin, Sandip

    2005-01-01

    The differential diagnosis of oral ulcerations in a patient with AIDS/HIV infection is often challenging to the clinician. While old diseases have appeared in a new garb, many new ones are also being recognized. The association of Behetaet's disease and AIDS/HIV infection has been recently recognized. We present an HIV-positive patient having oro-genital aphthosis conforming to the diagnostic criteria for Behetaet's disease. Erythema nodosum, periphlebitis, erythematous papulopustular lesions, half and half nails, ocular congestion, raised ESR and dimorphic anemia were some other features present. He had low CD4+/CD8+ counts. He had no other HIV-related disease. He responded well to triple anti-retroviral treatment alone. The possible pathomechanism of the occurrence of both diseases is also discussed. PMID:16394440

  11. Management of antiretroviral therapy in neonates, children, and adolescents.

    PubMed

    Neely, Michael; Kovacs, Andrea

    2004-06-01

    There have been tremendous advances in the prevention of maternal-to-child transmission of HIV and treatment of HIV-infected children and adolescents. Although multiple classes of anti-HIV drugs are available that can control viral replication and stabilize immune function when used in combination, patients and their providers must also manage complex and frequently toxic regimens. This article updates our original report that summarizes official National Institutes of Health guidelines for the prevention of perinatal HIV infection and the management of pediatric and adolescent HIV infection and provides the most current updates on indications for therapy, recommended first-line therapy, criteria for changing therapy, salvage therapy, novel management strategies, and a comprehensive summary of available antiretroviral agents. PMID:16091229

  12. Antiretroviral bioanalysis methods of tissues and body biofluids

    PubMed Central

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

    2013-01-01

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

  13. The role of HIV serostatus disclosure in antiretroviral medication adherence.

    PubMed

    Stirratt, Michael J; Remien, Robert H; Smith, Anna; Copeland, Olivia Q; Dolezal, Curtis; Krieger, Daniel

    2006-09-01

    This study examined the relationship between HIV serostatus disclosure and adherence to antiretroviral therapy (ART). The study was conducted with 215 HIV-seropositive patients who demonstrated poor adherence (<80%) and who were in serodiscordant relationships. Participants completed self-report measures regarding HIV serostatus disclosure and reasons for missing ART doses, as well as electronic monitoring of ART adherence (MEMS caps). Overall, 19% of the sample reported missing medication doses in the last two months due to concerns regarding serostatus disclosure. Participants who reported greater serostatus disclosure to others demonstrated higher rates of adherence, and this relationship remained after controlling for other explanatory variables. The relationship between disclosure and adherence was not mediated by practical support for adherence from others. Interventions to improve ART adherence should address the role of serostatus disclosure by providing patients with skills to maintain adherence in contexts of non-disclosure and to make informed choices regarding selective disclosure. PMID:16721505

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

    PubMed Central

    Khoza-Shangase, Katijah

    2011-01-01

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

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

    PubMed

    Ferrari, Luiz F; Levine, Jon D

    2010-09-01

    A major dose-limiting side effect of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) chemotherapies, such as the nucleoside reverse transcriptase inhibitors (NRTIs), is a small-fiber painful peripheral neuropathy, mediated by its mitochondrial toxicity. Co-morbid conditions may also contribute to this dose-limiting effect of HIV/AIDS treatment. Alcohol abuse, which alone also produces painful neuropathy, is one of the most important co-morbid risk factors for peripheral neuropathy in patients with HIV/AIDS. Despite the prevalence of this problem and its serious impact on the quality of life and continued therapy in HIV/AIDS patients, the mechanisms by which alcohol abuse exacerbates highly active antiretroviral therapy (HAART)-induced neuropathic pain has not been demonstrated. In this study, performed in rats, we investigated the cellular mechanism by which consumed alcohol impacts antiretroviral-induced neuropathic pain. NRTI 2',3'-dideoxycytidine (ddC; 50 mg/kg) neuropathy was mitochondrial-dependent and PKCε-independent, and alcohol-induced painful neuropathy was PKCε-dependent and mitochondrial-independent. At low doses, ddC (5 mg/kg) and alcohol (6.5% ethanol diet for 1 week), which alone do not affect nociception, together produce profound mechanical hyperalgesia. This hyperalgesia is mitochondrial-dependent but PKCε-independent. These experiments, which provide the first model for studying the impact of co-morbidity in painful neuropathy, support the clinical impression that alcohol consumption enhances HIV/AIDS therapy neuropathy, and provide evidence for a role of mitochondrial mechanisms underlying this interaction. PMID:20726883

  16. Mediators of antiretroviral adherence: a multisite international study.

    PubMed

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

    2013-01-01

    The purpose of this study was to investigate the effects of stressful life events (SLE) on medication adherence (3 days, 30 days) as mediated by sense of coherence (SOC), self-compassion (SCS), and engagement with the healthcare 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 US. Statistical tests to explore the effects of stressful life events on antiretroviral medication adherence included descriptive statistics, multivariate analysis of variance, analysis of variance 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 days and 30 days) indicated these combined variables were related to adherence whether 3 days or 30 days to different degrees at the various sites. SLE, SCS, SOC, and eHCP were significant predictors of adherence past 3 days for the United States (p = < 0.001), Canada (p = 0.006), and Namibia (p = 0.019). The combined independent variables were significant predictors of adherence past 30 days only in the United States 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. PMID:22774796

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

    PubMed

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

    2016-01-01

    Antiretroviral medications such as tenofovir have been associated with Fanconi syndrome (FS) usually identified within the first 1-29 months after exposure to the medication. We present a case of life-threatening FS which developed in a 37-year-old woman with HIV after 8 years of asymptomatic tenofovir use. The patient was diagnosed with HIV in 1996 at 20 years of age, hepatitis C 10 years later, and Staphylococcus aureus sepsis with secondary osteomyelitis of the spine 3 years before admission for FS. She developed nausea, vomiting, diarrhea, and generalized weakness over a 2-week time period and presented to the hospital. In the emergency department, her serum potassium was 1.5 mEq/L, bicarbonate was 12 mEq/L, chloride was 111 mEq/L, phosphorus was 1.8 mg/dL, and creatinine was 1.95 mg/dL (baseline, 1.4). Arterial blood gas revealed a non-anion gap (hyperchloremic) metabolic acidosis. Type 2 renal tubular acidosis induced by antiretroviral therapy (ART) was suspected and the ART was discontinued with resolution of the renal abnormalities within 7 days. A non-tenofovir-containing ART regimen consisting of lamivudine/abacavir and efavirenz was begun, and over the next 8 months, the patient was without recurrence of the FS. This case report demonstrates the acute development of FS after prolonged exposure to tenofovir without exposure to additional nephrotoxins such as nonsteroidal medications or aminoglycosides. Tenofovir can cause FS at any time and should be considered in any patient presenting with renal tubular acidosis type 2 while on tenofovir regardless of the duration of drug exposure. PMID:24914503

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

    PubMed

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

    2014-06-01

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

  19. Platelet count kinetics following interruption of antiretroviral treatment

    PubMed Central

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

    2014-01-01

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

  20. Emergence of HIV-1 drug resistance during antiretroviral treatment.

    PubMed

    Rong, Libin; Feng, Zhilan; Perelson, Alan S

    2007-08-01

    Treating HIV-infected patients with a combination of several antiretroviral drugs usually contributes to a substantial decline 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 virus variants, which subsequently results in incomplete viral suppression and a greater risk of disease progression. In this paper, we use a simple mathematical model to study the mechanism of the emergence of drug resistance during therapy. The model includes two viral strains: wild-type and drug-resistant. The wild-type strain can mutate and become drug-resistant during the process of reverse transcription. The reproductive ratio [Symbol: see text](0) for each strain is obtained and stability results of the steady states are given. We show that drug-resistant virus is more likely to arise when, in the presence of antiretroviral treatment, the reproductive ratios of both strains are close. The wild-type virus can be suppressed even when the reproductive ratio of this strain is greater than 1. A pharmacokinetic model including blood and cell compartments is employed to estimate the drug efficacies of both the wild-type and the drug-resistant strains. We investigate how time-varying drug efficacy (due to the drug dosing schedule and suboptimal adherence) affects the antiviral response, particularly the emergence of drug resistance. Simulation results suggest that perfect adherence to regimen protocol will well suppress the viral load of the wild-type strain while drug-resistant variants develop slowly. However, intermediate levels of adherence may result in the dominance of the drug-resistant virus several months after the initiation of therapy. When more doses of drugs are missed, the failure of suppression of the wild-type virus will be observed, accompanied by a relatively slow increase in the drug-resistant viral load. PMID:17450401

  1. Engine management during NTRE start up

    NASA Technical Reports Server (NTRS)

    Bulman, Mel; Saltzman, Dave

    1993-01-01

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

  2. Alaska Head Start Annual Program Report, 1999.

    ERIC Educational Resources Information Center

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

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

  3. Alaska Head Start. Annual Report for 1998.

    ERIC Educational Resources Information Center

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

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

  4. Drug Abuse Prevention Starts with Parents

    MedlinePlus

    ... other kind of drug. That is why grade school is a good time to start talking about the dangers of drug use. Prepare ... about difficult topics. Then, the programs offered by school, sports, and other groups can support what you have started. Prevention Starts With Parents As a parent, you have a ...

  5. Head Start Health Coordinators' Task Force Report.

    ERIC Educational Resources Information Center

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

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

  6. JumpStart III Final Report.

    ERIC Educational Resources Information Center

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

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

  7. Antiretroviral therapy for HIV-infected people in Papua New Guinea: challenges and opportunities.

    PubMed

    McBride, W J; Bradford, D

    2004-01-01

    Antiretroviral treatment services for Papua New Guineans infected with HIV (human immunodeficiency virus) have been severely limited because of the expense and difficulty in gaining access to antiretroviral drugs and the tests that are required to monitor the response of patients to them. Because some Papua New Guineans are beginning to seek out these services in Australia, clinicians are being challenged to manage the condition properly across an international border. Several case histories presented here highlight such difficulties. Progress is being made to reduce drug prices and simplify tablet-taking regimens, which has made the use of antiretroviral therapy more feasible. We briefly discuss infrastructure requirements for the more widespread provision of antiretroviral treatment services within Papua New Guinea. PMID:16496512

  8. ROLE OF PLACENTAL ATP-BINDING CASSETTE (ABC) TRANSPORTERS IN ANTIRETROVIRAL THERAPY DURING PREGNANCY

    PubMed Central

    Gulati, Abhishek; Gerk, Phillip M.

    2010-01-01

    Highly Active Anti-Retroviral Therapy (HAART) is used to treat HIV-infected patients and involves administration of multiple antiretroviral drugs acting at different steps of the HIV life cycle. In treating HIV-infected pregnant patients, the aim of therapy is not only to treat the mother but also to prevent the transmission of the virus to the fetus. Among the antiretroviral drugs used, there are differences in the extent of transfer of these drugs across the placenta; HIV protease inhibitors are particularly poorly transferred. Activities of ABC transporters expressed in the human placenta as well as differences in plasma protein binding may account for the poor transplacental transfer of certain drugs. This review discusses factors affecting the extent of placental transfer of antiretroviral drugs during pregnancy. These issues may also apply to drugs in other therapeutic categories. PMID:19067393

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

    NASA Astrophysics Data System (ADS)

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

    2009-09-01

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

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

    PubMed Central

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

    2014-01-01

    Objective: To assess factors at the start of antiretroviral therapy (ART) associated with long-term virological response in children. Design: Multicentre national cohort. Methods: Factors associated with viral load below 400 copies/ml by 12 months and virologic failure among children starting 3/4-drug ART in the UK/Irish Collaborative HIV Paediatric Study were assessed using Poisson models. Results: Nine hundred and ninety-seven children started ART at a median age of 7.7 years (inter-quartile range 2.9–11.7), 251 (25%) below 3 years: 411 (41%) with efavirenz and two nucleoside reverse transcriptase inhibitors (EFV + 2NRTIs), 264 (26%) with nevirapine and two NRTIs (NVP + 2NRTIs), 119 (12%; 106 NVP, 13 EFV) with non-nucleoside reverse transcriptase inhibitor and three NRTIs (NNRTI + 3NRTIs), and 203 (20%) with boosted protease inhibitor-based regimens. Median follow-up after ART initiation was 5.7 (3.0–8.8) years. Viral load was less than 400 copies/ml by 12 months in 92% [95% confidence interval (CI) 91–94%] of the children. Time to suppression was similar across regimens (P = 0.10), but faster over calendar time, with older age and lower baseline viral load. Three hundred and thirty-nine (34%) children experienced virological failure. Although progression to failure varied by regimen (P < 0.001) and was fastest for NVP + 2NRTIs regimens, risk after 2 years on therapy was similar for EFV + 2NRTIs and NVP + 2NRTIs, and lowest for NNRTI + 3NRTIs regimens (P-interaction = 0.03). Older age, earlier calendar periods and maternal ART exposure were associated with increased failure risk. Early treatment discontinuation for toxicity occurred more frequently for NVP-based regimens, but 5-year cumulative incidence was similar: 6.1% (95% CI 3.9–8.9%) NVP, 8.3% (95% CI 5.6–11.6) EFV, and 9.8% (95% CI 5.7–15.3%) protease inhibitor-based regimens (P = 0.48). Conclusion: Viral load suppression by 12 months was high with all regimens. NVP + 3NRTIs regimens were particularly efficacious in the longer term and may be a good alternative to protease inhibitor-based ART in young children. PMID:25389551

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

    PubMed

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

    2016-03-01

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

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

    PubMed Central

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

    2016-01-01

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

  13. Congenital Anomalies and in utero Antiretroviral Exposure in HIV-exposed Uninfected Infants

    PubMed Central

    Williams, Paige L.; Crain, Marilyn; Yildirim, Cenk; Hazra, Rohan; Van Dyke, Russell B.; Rich, Kenneth; Read, Jennifer S.; Stuard, Emma; Rathore, Mobeen; Mendez, Hermann A.; Watts, D. Heather

    2014-01-01

    Importance Most studies examining the association of prenatal antiretroviral exposures with congenital anomalies (CAs) in children born to HIV-infected women have been reassuring, but some suggest increased risk with specific antiretrovirals. Objectives To evaluate associations of in utero antiretroviral exposures with CAs in HIV-exposed uninfected children. Design prospective cohort study, the Pediatric HIV/AIDS Cohort Study (PHACS) Surveillance Monitoring of ART Toxicities (SMARTT) study. Setting 22 US medical centers Participants 2580 HIV-exposed, uninfected children enrolled in SMARTT between 2007–2012. Exposures First trimester exposure to any antiretroviral and to specific antiretroviral medications. Main Outcome The primary endpoint was a CA, based on clinician review of infant physical examinations according to the Antiretroviral Pregnancy Registry modification of the Metropolitan Atlanta Congenital Defects Program. Rates of CAs were estimated overall and by birth year. Logistic regression models were used to evaluate associations of CAs with first trimester antiretroviral exposures, adjusting for demographic and maternal characteristics. Results CAs occurred in 175 of 2580 children, yielding a prevalence of 6.78% (95% CI: 5.85–7.82%); there were 242 confirmed major CAs (72 musculoskeletal, 55 cardiovascular). The prevalence of CAs increased significantly in successive birth cohorts (3.8% for children born <2002 up to 8.3% for 2008–2010). In adjusted models, there was no association of first trimester exposures to any antiretroviral, to combination antiretroviral regimens, or to any drug class with CAs. No individual antiretroviral in the reverse transcriptase inhibitor drug classes was associated with increased risk of CAs. Among protease inhibitors, higher odds of CAs were observed for atazanavir (adjusted odds ratio (aOR)=1.93, 95% confidence interval (CI):1.23,3.03) and for ritonavir used as a booster (aOR=1.52, 95%CI: 1.08,2.14). With first trimester atazanavir, risks were highest for skin and musculoskeletal CAs (aORs=5.24 and 2.55, respectively). Conclusions and Relevance Few individual antiretrovirals and no drug classes were associated with increased risk of CAs after adjustment for calendar year and maternal characteristics. While the overall risk remained low, there was a relative increase in successive years and with atazanavir exposure. Given the low absolute CA risk, the benefits of recommended ARV use during pregnancy still outweigh such risks, although further studies are warranted. PMID:25383770

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

    PubMed

    Krentz, Hartmut B; Gill, M John

    2016-01-01

    Improved survival achieved by many patients with HIV/AIDS has complicated their medical care as increasing numbers of co-morbidities leads to polypharmacy, increased pill burdens, and greater risks of drug-drug interactions potentially compromising antiretroviral treatment (ART). We examined the impact of non-antiretroviral polypharmacy on ART for all adults followed at the Southern Alberta Clinic, Calgary, Canada. Polypharmacy was defined as ≥5 daily medications. We compared the impact of polypharmacy on continuous (i.e., remaining on same ART for ≥6 months) vs. non-continuous (i.e., discontinuing or switching ART) ART dosing frequency, number of ART pills, number of non-ART medications, and age. Of 1190 (89.5%) patients on ART, 95% were on three-drug regimens, 63.9% on QD ART, and 62% ≥3 ART pills daily; 32.2% were experiencing polypharmacy. Polypharmacy was associated with lower CD4, AIDS, >180 months living with HIV, higher numbers of ART pills, and older age (all p < 0.01); 32.1% stopped or switched ART. Polypharmacy increased the risk for non-continuous ART (36.8% vs. 30.0%; p < 0.01). Non-continuous ART increased with daily ART pill count but not increased age. Non-adherence and adverse effects accounted for the majority of non-continuous ART. We found a strong association between polypharmacy and non-continuous ART, potentially leading to effective ART being compromised. Collaborative approaches are needed to anticipate the negative impacts of polypharmacy. PMID:26544766

  15. Correlates of antiretroviral and antidepressant adherence among depressed HIV-infected patients.

    PubMed

    Bottonari, Kathryn A; Tripathi, Shanti P; Fortney, John C; Curran, Geoff; Rimland, David; Rodriguez-Barradas, Maria; Gifford, Allen L; Pyne, Jeffrey M

    2012-05-01

    Although crucial for efficacy of pharmacotherapy, adherence to prescribed medication regimens for both antiretrovirals and antidepressants is often suboptimal. As many depressed HIV-infected individuals are prescribed both antiretrovirals and antidepressants, it is important to know whether correlates of nonadherence are similar or different across type of regimen. The HIV Translating Initiatives for Depression into Effective Solutions (HI-TIDES) study was a single-blinded, longitudinal, randomized controlled effectiveness trial comparing collaborative care to usual depression care at three Veterans Affairs HIV clinics. The current investigation utilized self-report baseline interview and chart-abstracted data. Participants were 225 depressed HIV-infected patients who were prescribed an antidepressant (n=146), an antiretroviral (n=192), or both (n=113). Treatment adherence over the last 4 days was dichotomized as "less than 90% adherence" or "90% or greater adherence." After identifying potential correlates of nonadherence, we used a seemingly unrelated regression (SUR) bivariate probit model, in which the probability of adherence to HIV medications and the probability of adherence to antidepressant medications are modeled jointly. Results indicated that 75.5% (n=146) of those prescribed antiretrovirals reported 90%-plus adherence to their antiretroviral prescription and 76.7% (n=112) of those prescribed antidepressants reported 90%-plus adherence to their antidepressant prescription, while 67% of those prescribed both (n=113) reported more than 90% adherence to both regimens. SUR results indicated that education, age, and HIV symptom severity were significant correlates of antiretroviral medication adherence while gender and generalized anxiety disorder diagnosis were significant correlates of adherence to antidepressant medications. In addition, antiretroviral adherence did not predict antidepressant adherence (β=1.62, p=0.17), however, antidepressant adherence did predict antiretroviral adherence (β=2.30, p<0.05). PMID:22536930

  16. Biomechanical analysis of backstroke swimming starts.

    PubMed

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

    2011-07-01

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

  17. Clinical management of dyslipidaemia associated with combination antiretroviral therapy in HIV-infected patients.

    PubMed

    Calza, Leonardo; Colangeli, Vincenzo; Manfredi, Roberto; Bon, Isabella; Re, Maria Carla; Viale, Pierluigi

    2016-06-01

    The introduction of potent combination antiretroviral therapy (cART) has had a remarkable impact on the natural history of HIV infection, leading to a dramatic decline in the mortality rate and a considerable increase in the life expectancy of HIV-positive people. However, cART use is frequently associated with several metabolic complications, mostly represented by lipid metabolism alterations, which are reported very frequently among persons treated with antiretroviral agents. In particular, hyperlipidaemia occurs in up to 70%-80% of HIV-positive subjects receiving cART and is mainly associated with specific antiretroviral drugs belonging to three classes of antiretroviral agents: NRTIs, NNRTIs and PIs. The potential long-term consequences of cART-associated dyslipidaemia are not completely understood, but an increased risk of premature coronary heart disease has been reported in HIV-infected patients on cART, so prompt correction of lipid metabolism abnormalities is mandatory in this population. Dietary changes, regular aerobic exercise and switching to a different antiretroviral regimen associated with a more favourable metabolic profile are the first steps in clinical management, but lipid-lowering therapy with fibrates or statins is often required. In this case, the choice of hypolipidaemic drugs should take into account the potential pharmacokinetic interactions with many antiretroviral agents. PMID:26846208

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

    PubMed

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

    2015-02-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2010-01-01

    Background Food insecurity is emerging as an important barrier to antiretroviral (ARV) adherence in sub-Saharan Africa and elsewhere, but little is known about the mechanisms through which food insecurity leads to ARV non-adherence and treatment interruptions. Methodology We conducted in-depth, open-ended interviews with 47 individuals (30 women, 17 men) living with HIV/AIDS recruited from AIDS treatment programs in Mbarara and Kampala, Uganda to understand how food insecurity interferes with ARV therapy regimens. Interviews were transcribed, coded for key themes, and analyzed using grounded theory. Findings Food insecurity was common and an important barrier to accessing medical care and ARV adherence. Five mechanisms emerged for how food insecurity can contribute to ARV non-adherence and treatment interruptions or to postponing ARV initiation: 1) ARVs increased appetite and led to intolerable hunger in the absence of food; 2) Side effects of ARVs were exacerbated in the absence of food; 3) Participants believed they should skip doses or not start on ARVs at all if they could not afford the added nutritional burden; 4) Competing demands between costs of food and medical expenses led people either to default from treatment, or to give up food and wages to get medications; 5) While working for food for long days in the fields, participants sometimes forgot medication doses. Despite these obstacles, many participants still reported high ARV adherence and exceptional motivation to continue therapy. Conclusions While reports from sub-Saharan Africa show excellent adherence to ARVs, concerns remain that these successes are not sustainable in the presence of widespread poverty and food insecurity. We provide further evidence on how food insecurity can compromise sustained ARV therapy in a resource-limited setting. Addressing food insecurity as part of emerging ARV treatment programs is critical for their long-term success. PMID:20442769

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

    PubMed

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

    2016-05-01

    The human immunodeficiency virus (HIV) and the acquired immune deficiency syndrome (AIDS) represent a serious public health problem in Equatorial Guinea, with a prevalence of 6.2% among adults. the high-activity antiretroviral treatment (HAART) coverage data is 10 points below the overall estimate for Sub-Saharan Africa, and only 61% patients continue with HAART 12 months after it started. This study aims to assess HAART adherence and related factors in Litoral Province of Equatorial Guinea. In this cross-sectional study, socio-demographic and clinical data were collected at Regional Hospital of Bata, during June-July 2014. Adherence to treatment was assessed by using the Spanish version of CEAT-VIH. Bivariate and linear regression analyses were employed to assess HAART adherence-related factors. We interviewed 50 men (35.5%) and 91 women (64.5%), with a mean age of 47.7 ± 8.9 and 36.2 ± 11.2, respectively (p < .001). Overall, 55% patients had low or insufficient adherence. CEAT-VIH score varied by ethnic group (p = .005). There was a positive correlation between CEAT-VIH score and current CD4 T-cells count (p = .013). The Cronbach's α value was 0.52. To our knowledge, this is the first study to assess HAART adherence in Equatorial Guinea. Internal reliability for CEAT-VIH was low, nonetheless the positive correlation between the CEAT-VIH score and the immunological status of patients add value to our findings. Our results serve as baseline for future research and will also assist stakeholders in planning and undertaking contextual and evidence-based policy initiatives. PMID:26698540

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  6. [Acquired immunodeficiency syndrome-associated progressive multifocal leukoencephalopathy treated with highly active anti-retroviral therapy].

    PubMed

    Shimizu, Y; Ota, K; Takeuchi, M; Iwata, M; Yogo, Y

    2000-08-01

    We reported a patient with acquired immunodeficiency syndrome (AIDS)-associated progressive multifocal leukoencephalopathy (AIDS-PML), whose condition improved after highly active anti-retroviral therapy (HAART). A 70-year-old man was admitted to our hospital because of worsening left hemiplegia and disturbance of consciousness. During the past 30 years, he frequently traveled to the United States and southeast Asia. On neurological examination, he was somnolent and left hemiplegia with severe rigospasticity was present. The deep tendon reflexes showed hyper-reflexes with extensor plantar responses. Laboratory studies showed pancytopenia and positive HIV-1 antibodies. The CD4 cell count was 38/mm3 and his HIV viral RNA load in the blood was 9,500 copies/ml. T2-weighted magnetic resonance imaging (MRI) of the brain revealed asymmetrical high intensity white matter lesions in the right fronto-parietal, and left frontal regions and in the cerebellar hemisphere. The cerebrospinal fluid (CSF) protein elevated to 91 mg/dl with a normal cell count. The diagnosis of PML was confirmed by the detection of JC virus DNA in the CSF using a nested polymerase chain reaction assay. Three weeks after starting HAART with zidovudine, lamivudine, and indinavir, he was able to respond to simple commands. Two months later, the HIV viral RNA load decreased to less than 400 copies/mm3, and no JC virus DNA was detected in the CSF, with an increase of the CD4 cell count to 285/mm3 in the blood. A follow-up MRI of the brain showed a reduction in the cerebellar and cerebral white matter lesions. The recovering immune function by decreasing of the HIV load after HAART might suppress JC virus replication. It was suggested that HAART would become a beneficial treatment for patients with AIDS-PML. PMID:11218704

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

    Rathbun, R. Chris; Liedtke, Michelle D.

    2011-01-01

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

  9. Microcomputer controlled soft start of motor

    NASA Astrophysics Data System (ADS)

    Gao, Miao; Wang, Yanpeng; Li, Shian

    2005-12-01

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

  10. Antiretroviral Treatment and Sexual Risk Behavior in South Africa.

    PubMed

    Risher, Kathryn; Rehle, Thomas; Simbayi, Leickness; Shisana, Olive; Celentano, David D

    2016-04-01

    The sexual behavior of individuals living with HIV determines the onward transmission of HIV. With the understanding that antiretroviral therapy (ART) prevents transmission of HIV, the sexual behaviors of the individuals not on ART with unsuppressed viral loads becomes of the greatest importance in elucidating transmission. We assessed the association between being on ART and sexual risk behavior among those living with HIV in a nationally representative population-based cross-sectional survey of households in South Africa that was conducted in 2012. Of 2237 adults (aged 15-49) who tested HIV-seropositive, 667 (29.8 %) had detectable antiretroviral drugs in their blood specimens. Among males, 77.7 % of those on ART reported having had sex in the past year contrasted with 88.4 % of those not on ART (p = 0.001); among females, 72.2 % of those on ART reported having had sex in the past year while 80.3 % of those not on ART did (p < 0.001). For males and females, the odds of reporting consistent condom use and condom use at last sex were statistically significantly higher for individuals on ART compared to those not on ART (males: consistent condom use aOR 2.8, 95 % CI 1.6-4.9, condom use at last sex aOR 2.6, 95 % CI 1.5-4.6; females: consistent condom use aOR 2.3, 95 % CI 1.7-3.1, condom use at last sex aOR 2.3, 95 % CI 1.7-3.1), while there were no statistically significant differences in odds of reporting multiple sexual partners in the past year. In this nationally representative population-based survey of South African adults, we found evidence of less risky sexual risk behavior among people living with HIV on ART compared to those not on ART. PMID:26194426

  11. 76 FR 37174 - Capital Investment Program-New Starts and Small Starts Program Funds

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-24

    ... Federal Transit Administration Capital Investment Program--New Starts and Small Starts Program Funds... Transportation's (DOT) Federal Transit Administration (FTA) announces the apportionment of the FY 2011 Capital... appropriated for the Capital Investments Grant Account, which includes the New Starts and Small Starts...

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

    ERIC Educational Resources Information Center

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

    2009-01-01

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

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

    ERIC Educational Resources Information Center

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

    2009-01-01

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

  14. Start II, red ink, and Boris Yeltsin

    SciTech Connect

    Arbatov, A.

    1993-04-01

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

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

    PubMed Central

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

    2015-01-01

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

  16. Persistence of genotypic resistance to nelfinavir among women exposed to prophylactic antiretroviral therapy during pregnancy.

    PubMed

    Kakehasi, Fabiana M; Tupinambás, Unaí; Cleto, Silvia; Aleixo, Agdemir; Lin, Elisa; Melo, Victor H; Aguiar, Regina A L P; Pinto, Jorge A

    2007-12-01

    We assessed the development of drug resistance in women exposed to antiretroviral therapy (ART) for prevention of mother-to-child transmission (PMTCT) after 24 weeks postpartum in a prospective cohort of HIV-1-infected women. HIV-1-infected women, who received prophylactic ART during pregnancy, had genotypic resistance testing performed at the start (T1) of and 24 weeks after ART interruption (T2). The women had CD4 counts >250 cells/ml and no AIDS defining conditions. Of the 30 eligible women, the median age was 27 years [25-75% interquartile range (IQR): 21-32] and the median gestational age of ART initiation was 22 weeks (IQR: 19-27): 19 (63.3%) received zidovudine (ZDV) plus lamivudine (3TC) plus nelfinavir (NFV). At entry, most women (96.7%) were asymptomatic (CDC93 A1/A2), with a median CD4 count of 446 (IQR: 353-686) and median viral load (VL) of 8560 copies/ml (IQR: 3,252-19,515). No HIV-1 vertical transmission was observed. HIV subtype B was the most prevalent (70%). The development of new mutations associated with ART resistance was analyzed at T2. NFV resistance was observed in 4 out of 17 (23.5%) patients exposed to this drug: two major mutations D30N (1/17) and L90M (1/17) and minor mutations (N88S, 2/17). Mutations on positions 44, 69, and 118 (1/28) were present on reverse transcriptase (RT) analysis. No new nonnucleoside reverse transcriptase inhibitor (NNRTI)-associated mutation was observed. In this cohort, ART regimens were very efficient at blocking HIV vertical transmission. However, the high rate of NFV-resistant mutations observed in the postpartum period indicates the need for discussion of ART choices during pregnancy and the potential impact on future therapeutic options for these women. Women previously exposed to ART for PMTCT who will start HIV treatment should have genotypic resistance testing performed. PMID:18160009

  17. Novel drug delivery approaches on antiviral and antiretroviral agents

    PubMed Central

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

    2012-01-01

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

  18. The Impact of Antiretroviral Therapy on Lung Immunology.

    PubMed

    Cribbs, Sushma K; Fontenot, Andrew P

    2016-04-01

    Despite the introduction of antiretroviral therapy (ART), human immunodeficiency virus-1 (HIV) continues to cause a major impact worldwide. HIV-induced lung disease continues to represent a significant source of morbidity and mortality, although the spectrum of pulmonary diseases has changed. HIV significantly affects the lung, causing acute and chronic cellular changes in the alveolar space. The impact of ART on lung immunology still needs to be fully elucidated. Similar to the periphery, ART affects HIV viral load and reconstitutes CD4(+) T cells in the lung. ART has been associated with significant decreases in bronchoalveolar lavage lymphocytes and increases in B-cell numbers and functionality, resulting in improved immune responses to vaccinations. There are substantial clinical implications of these ART-induced alterations, including the emergence of immune reconstitution inflammatory syndrome and the increased incidences of noninfectious lung diseases, such as lung cancer and chronic obstructive lung disease. There continues to be many unanswered questions regarding the effects of ART on lung health and, in particular, the immune system. Growing knowledge in this area will hopefully diminish the incidence of these noninfectious lung diseases and further improve the health of individuals living with HIV. PMID:26974295

  19. Interleukin-7 promotes HIV persistence during antiretroviral therapy.

    PubMed

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

    2013-05-23

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

  20. Interleukin-7 promotes HIV persistence during antiretroviral therapy

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2015-01-01

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

  3. Antiretroviral Therapy Outcomes in Patients with Severe Mental Illness.

    PubMed

    Karstaedt, Alan S; Kooverjee, Sadhna; Singh, Lucille; Jeenah, Yasmien; Jonsson, Gregory

    2015-01-01

    A retrospective cohort analysis was performed to describe outcomes and retention in care on antiretroviral therapy (ART) of 53 patients with severe mental illness (SMI). Diagnoses were psychosis secondary to HIV (24 patients), psychosis not otherwise specified (12), mania with or without psychosis (9), depression with psychotic features (4), and schizophrenia and bipolar mood disorder (2 each). The median baseline CD4 count was 66/mm(3) and viral load was 5.4 log10 copies/mL. Thirteen (25%) patients were lost to follow-up (10 within 6 months), 3 were transferred out, and 3 died. By week 96, 29 (85%) of 34 (64%) patients still in care had a viral load <400 copies/mL and 26 (76%) a viral load <25 copies/mL. Median CD4 count increased to 307/mm(3). Twenty-seven of 34 patients discontinued antipsychotic medication. Patients with SMI and advanced HIV infection responded well to ART. The first 6 months was important for retention in care. PMID:26173943

  4. Modifying Antiretroviral Therapy in Virologically Suppressed HIV-1-Infected Patients.

    PubMed

    Collins, Sean E; Grant, Philip M; Shafer, Robert W

    2016-01-01

    HIV-1-infected patients with suppressed plasma viral loads often require changes to their antiretroviral (ARV) therapy to manage drug toxicity and intolerance, to improve adherence, and to avoid drug interactions. In patients who have never experienced virologic failure while receiving ARV therapy and who have no evidence of drug resistance, switching to any of the acceptable US Department of Health and Human Services first-line therapies is expected to maintain virologic suppression. However, in virologically suppressed patients with a history of virologic failure or drug resistance, it can be more challenging to change therapy while still maintaining virologic suppression. In these patients, it may be difficult to know whether the discontinuation of one of the ARVs in a suppressive regimen constitutes the removal of a key regimen component that will not be adequately supplanted by one or more substituted ARVs. In this article, we review many of the clinical scenarios requiring ARV therapy modification in patients with stable virologic suppression and outline the strategies for modifying therapy while maintaining long-term virologic suppression. PMID:26677129

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

    PubMed Central

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

    2011-01-01

    Since 2004, Georgia achieved universal access to free antiretroviral therapy (ART). A retrospective cohort study was conducted to evaluate the outcomes of Georgia's ART program. The study included adult patients enrolled in the ART program from 2004 through 2009. Of 752 patients, 76% were men, 60% were injection drug users (IDU), 59% had a history of an AIDS-defining illness, and 53% were coinfected with hepatitis C. The median baseline CD4 cell count was 141 cells/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. PMID:21490781

  6. The first decade of antiretroviral therapy in Africa

    PubMed Central

    2011-01-01

    The past decade has seen remarkable progress in increasing access to antiretroviral therapy in resource-limited settings. Early concerns about the cost and complexity of treatment were overcome thanks to the efforts of a global coalition of health providers, activists, academics, and people living with HIV/AIDS, who argued that every effort must be made to ensure access to essential care when millions of lives depended on it. The high cost of treatment was reduced through advocacy to promote access to generic drugs; care provision was simplified through a public health approach to treatment provision; the lack of human resources was overcome through task-shifting to support the provision of care by non-physicians; and access was expanded through the development of models of care that could work at the primary care level. The challenge for the next decade is to further increase access to treatment and support sustained care for those on treatment, while at the same time ensuring that the package of care is continuously improved such that all patients can benefit from the latest improvements in drug development, clinical science, and public health. PMID:21958478

  7. Support required for antiretroviral uptake in developing countries.

    PubMed

    Gold, Julian

    2002-08-01

    It is evident from the current global debate on improving care and treatment for people living with HIV that antiretroviral therapy will become increasingly available in resource-poor countries. As this happens, there is an imperative to determine which factors will promote optimal use of these complex therapies to minimise the potentially serious consequences of poor adherence and the development of a worse epidemic of multidrug-resistant HIV (MDRHIV). In parallel with the process of allocating funds to purchase drugs, there needs to be a pro-active scaling up of healthcare worker training and infrastructure support systems and development of continuity of care from healthcare services into the community. The engagement of healthcare workers in the HIV epidemic has been largely ignored in favour of a focus on prevention which, understandably, works through the non-government sector as the vehicle for implementation. This upscaling and recruitment of healthcare workers needs involvement not only from our more eminent clinicians as spokespeople but also from experienced field workers, who will be caring for the majority of patients as they become ill. This article identifies the multidimensional approach necessary to implement a broad initiative for care and treatment and discusses the possible strategies and consequences of each factor. PMID:12442167

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

    PubMed

    Lingeswaran, Anand

    2014-01-01

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

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

    PubMed

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

    2014-01-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2014-05-01

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

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

    PubMed

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

    2015-01-01

    International focus on reducing onward HIV transmission emphasizes the need for routine HIV testing and early uptake of antiretroviral treatment (ART). Strategic targets have been set for 2020 to achieve the goal of 90% of people infected with HIV diagnosed, 90% of identified cases on treatment, and 90% of persons on treatment virally suppressed (90-90-90). It is vital to understand the complexity of factors influencing a person's treatment decisions over time and the context which may enable better adherence. In this paper we present findings from the review of published and gray literature (2003-2013) on the documented factors associated with treatment initiation and adherence in the general adult population of Australia, Canada, and the UK. A framework developed by Begley, McLaws, Ross, and Gold [2008. Cognitive and behavioural correlates of non-adherence to HIV anti-retroviral therapy: Theoretical and practical insight for clinical psychology and health psychology. Clinical Psychologist, 12(1), 9-17] in Australia was adapted to summarize the findings. A systematic database search using keywords and a set of inclusion criteria yielded 17 studies (Australia = 6; Canada = 8; UK = 3). In addition 11 reports were included in the review. We found that a person's abilities and motivations (intrapersonal factors, reported in 7 studies) to start and continue ART are influenced by a host of interconnected factors spanning relationship (interpersonal, 3 studies) and broader structural (extrapersonal, 15 studies) factors that are situated within social determinants of health. People therefore evaluate various costs and benefits of starting and staying on treatment, in which biomedical concerns play an important yet often subsidiary role. In this review the economic barriers to care were found to be significant and under-reported, highlighting the persistent health inequities in terms of access to services. Our understanding of the context around people's use of ART remains poor. Qualitative social research within HIV-positive communities is urgently needed to capture people's lived experiences and may address some of this deficit in understanding. PMID:26641139

  13. Historical Perspectives on Project Head Start.

    ERIC Educational Resources Information Center

    Slaughter, Diana T.

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

  14. Start-up analysis for marketing strategy.

    PubMed

    Griffith, M J; Baloff, N

    1984-01-01

    The complex start-up effect on utilization of health care services is too often overlooked or underestimated by marketing planners, leading to a range of negative consequences for both the users of services and the provider organization. Start-up analysis allows accurate estimation of these utilization effects for coordinated strategic planning among marketing finance, and operations. PMID:10269085

  15. Administration for Children and Families: Head Start

    ERIC Educational Resources Information Center

    US Department of Health and Human Services, 2010

    2010-01-01

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

  16. Report of First National Home Start Conference.

    ERIC Educational Resources Information Center

    Kapfer, Sherry

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

  17. Head Start. What Works Clearinghouse Intervention Report

    ERIC Educational Resources Information Center

    What Works Clearinghouse, 2015

    2015-01-01

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

  18. Head Start Impact Study. Technical Report

    ERIC Educational Resources Information Center

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

    2010-01-01

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

  19. National Head Start Bulletin, 1993-1995.

    ERIC Educational Resources Information Center

    National Head Start Bulletin, 1995

    1995-01-01

    This document consists of the 15 issues of the "National Head Start Bulletin" published during the three-year period 1993-1995. The bulletin is devoted to subjects of concern to Head Start teachers and administrators; each issue focuses on one topic. A main article and several smaller articles discuss various aspects of the topic for that issue.…

  20. Head Start--Twenty Years Later.

    ERIC Educational Resources Information Center

    Heller, Dinah

    1985-01-01

    In addition to its basic function, the Head Start program provides access to health care, nutrition, and social services. Its services are comprehensive, parents and community are involved, and staff development is an integral feature. New York State's allocations of federal funds for handicapped children are based on Head Start's annual reports.…

  1. The Phenomenon of Business Start-Ups.

    ERIC Educational Resources Information Center

    Melis, Africa

    1990-01-01

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

  2. Head Start Impact Study. Final Report

    ERIC Educational Resources Information Center

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

    2010-01-01

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

  3. Using Music with Head Start Children.

    ERIC Educational Resources Information Center

    Griffin, Louise

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

  4. Assisted Workouts: Starting My Own Workout Program

    ERIC Educational Resources Information Center

    Cousminer, Douglas

    2003-01-01

    As an undergraduate student with cerebral palsy, I found it difficult to achieve my goal of starting a regular exercise program at my school, the University of Central Florida. However, when I started a program called Assisted Workouts in spring 2003. the struggle proved to be well worth it. The program is not only beneficial to me, but it has…

  5. When Do Start-Ups Make Sense?

    ERIC Educational Resources Information Center

    Langemeyer, Clement J.

    2005-01-01

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

  6. [Treatment of opportunistic infections in adolescent and adult patients infected with the human immunodeficiency virus during the era of highly active antiretroviral therapy. AIDS Study Group (GESIDA) and National AIDS Plan Expert Committee].

    PubMed

    2008-01-01

    Despite the huge advance that highly active antiretroviral therapy has represented for the prognosis of infection by human immunodeficiency virus (HIV), opportunistic infections continue to be a cause of morbidity and mortality in HIV-infected patients. This is often the case because of severe immunodepression, poor adherence to antiretroviral therapy, failure of therapy, or the fact that patients are unaware of their HIV-positive status and debut with an opportunistic infection. This article updates the guidelines on treatment of acute episodes of various opportunistic infections in HIV-infected patients, including infections due to parasites, fungi, viruses, mycobacteria, and bacteria. This edition has a new chapter on imported parasite infections as well as additional information on endemic mycoses in the chapter on fungal infections, taking into account the growing number of immigrants in our setting. Lastly, the chapter on the immune reconstitution syndrome has also been updated, providing relevant data on a phenomenon that has clinical and diagnostic repercussions in patients who start antiretroviral therapy while they are severely immunodepressed (English version available at http://www.gesida.seimc.org). PMID:18588819

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

    PubMed Central

    2014-01-01

    Background Coinfection with the hepatitis viruses is common in the HIV population in sub-Saharan Africa. The aim of this study was to assess, in a cohort of HIV-infected pregnant women receiving antiretroviral drugs (ARVs), the prevalence of HBV and HCV infections and to determine the impact of these infections on the occurrence of liver toxicity and on the viro-immunological response. Methods Women were screened for HBsAg and HCV-RNA before starting, at week 25 of gestational age, an antiretroviral regimen consisting of lamivudine and nevirapine plus either stavudine or zidovudine. Women with CD4+ < 350/mm3 continued ARVs indefinitely, while the other women interrupted treatment 6 months postpartum (end of breastfeeding period). Both groups were followed for 2 years after delivery. Liver function was monitored by alanine aminotransferase (ALT) measurement. The Cox proportional hazards model was used to identify factors associated with the emergence of liver toxicity. Results A total of 28 women out of the 309 enrolled in the study (9.1%) were coinfected with HBV (n. 27), or HCV (n. 1). During follow-up 125 women (40.4%) developed a grade ≥ 1 ALT elevation, 28 (9.1%) a grade ≥ 2 and 6 (1.9%) an elevation defining grade 3 toxicity. In a multivariate model including age, baseline CD4+ count and hemoglobin level, the presence of either HBV or HCV infection was significantly associated with the development of an ALT increase of any grade (P = 0.035). Moderate or severe liver laboratory toxicity (grade ≥ 2) was more frequent among women with baseline CD4+ > 250/mm3 (P = 0.030). In HBV-infected women a baseline HBV-DNA level above 10,000 IU/ml was significantly associated to the development of liver toxicity of grade ≥ 1 (P = 0.040). Coinfections had no impact on the immunological and virological response to antiretroviral drugs up to 2 years after delivery. Conclusions In this cohort of nevirapine-treated women the presence of HBV or HCV was associated only to the development of mild liver toxicity, while the occurrence of moderate or severe hepatoxicity was correlated to a baseline CD4+ count > 250/mm3. No statistically significant effect of the coinfections was observed on the efficacy of antiretroviral therapy. PMID:24708626

  8. START Analysis for ESAS Capability Needs Prioritization

    NASA Technical Reports Server (NTRS)

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

    2006-01-01

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

  9. Transmission risk behaviour at enrolment in participants in the INSIGHT Strategic Timing of AntiRetroviral Treatment trial

    PubMed Central

    Rodger, Alison J; Lampe, Fiona C; Grulich, Andrew E; Fisher, Martin; Friedland, Gerald; Phanuphak, Nittaya; Bogner, Johannes R.; Pereira, Luiz Carlos; Rietmeijer, Cornelis; Burman, Bill; Phillips, Andrew

    2014-01-01

    Background A proportion of HIV-positive people have condomless sex. Antiretroviral treatment (ART) reduces infectiousness, but a substantial proportion of HIV-diagnosed people are not yet on ART. We describe baseline self-reported risk behaviours in ART-naïve START trial participants. Methods All START participants completed a risk behaviour questionnaire. Data were collected on sociodemographics, lifestyle factors, health and wellbeing status, and clinical status. Recent sexual behaviour and HIV transmission beliefs in the context of ART were also assessed. The primary interest was in condomless sex with serodifferent partners (CLS-D). Results 4601 of 4685 HIV-positive participants (98%) completed the questionnaire (2559 men who have sex with men [MSM]; 803 heterosexual men; 1239 women). Region of recruitment was Europe/Israel 33%, South America/Mexico 25%; Africa 22%; other 21%. Median age was 36 years (IQR 29, 44). 45% reported white ethnicity and 31% black ethnicity. 2% had HIV viral load <50 copies/mL. 17% (767/4601) reported CLS-D; 20% of MSM compared to 10% in heterosexual men and 14% in women. MSM were also more likely to report multiple CLS-D partners. Possible risk limitation measures in MSM included seropositioning. CLS-D was more commonly reported by participants from South America/Mexico compared to Europe. Knowledge of ART impact on transmission risk was low. Discussion A substantial minority recruited to the START study reported CLS-D at baseline. CLS-D reporting was higher in MSM than heterosexuals and varied significantly according to region of recruitment. A substantial proportion of MSM reporting CLS-D appear to take transmission risk limitation measures. PMID:25711325

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

    PubMed

    Sanne, Ian; van der Horst, Charles

    2004-09-01

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

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

    PubMed Central

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

    2015-01-01

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

  12. Start 2: Thinking one move ahead

    SciTech Connect

    Gaines, L.L.

    1991-11-01

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

  13. Start 2: Thinking one move ahead

    SciTech Connect

    Gaines, L.L.

    1991-11-01

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

  14. Healthy start program participation: the consumers' perspective.

    PubMed

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

    2011-01-01

    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

  15. Soft start of submersible pumped oil wells

    SciTech Connect

    Neely, A.B.; Patterson, M.M.

    1982-01-01

    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 5 to 8 times running current. Such surges can damage the motor and cause line voltage irregularities. Also, stopping can result in significant amperage and voltage spikes. Therefore, most operators are reluctant to start and stop a submersible pumping installation more often than 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 6 silicon-controlled rectifiers was tested. The current surge on start was limited to ca 2.5 times full-load amperage. The time required to bring the motor to full speed was increased from ca 0.25 sec to 1.3 sec. The well was cycling on-off ca 6 times per day. The unit was start-stopped ca 900 times during the test.

  16. Soft start of submersible pumped oil wells

    SciTech Connect

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

    1984-04-01

    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.

  17. Soft start of submersible pumped oil wells

    SciTech Connect

    Neely, A.B.; Patterson, M.M.

    1982-09-01

    Cyclic operation of submersible pumping is considered undesirable because of the start-stop characteristics of the installation. ''Across-theline'' 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 November 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.

  18. Starting Circuit For Erasable Programmable Logic Device

    NASA Technical Reports Server (NTRS)

    Cole, Steven W.

    1990-01-01

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

  19. Physicists: A Start-Ups's Secret Weapon

    NASA Astrophysics Data System (ADS)

    Smoliar, Laura

    2001-03-01

    High-tech start-ups have been a magnet for engineers, MBAs, and money. However, the vital and rewarding role of physicists in these ventures is often overlooked. This talk will focus on the essential contributions physicists make and the various positions physicists hold "behind the scenes" in high-tech start-ups. As the high-tech economy continues to heat up, especially in telecommunications, the opportunities for physicists continue to expand. This is truely a time for physicists to make their mark in the start-up world.

  20. Head Start: The Nation's Pride, A Nation's Challenge. Recommendations for Head Start in the 1990s.

    ERIC Educational Resources Information Center

    Lombardi, Joan

    1990-01-01

    Based on the May 1990 report of Head Start's Silver Ribbon Panel, this article provides background information on the panel, summarizes Head Start's successes and challenges, outlines the commendations, and discusses implications of the panel's report. (BG)

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

    PubMed Central

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

    2013-01-01

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

  2. Cellular Responses and Tissue Depots for Nanoformulated Antiretroviral Therapy

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2013-11-01

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

  4. Contagiousness under antiretroviral therapy and stigmatization toward people with HIV.

    PubMed

    Drewes, Jochen; Kleiber, Dieter

    2014-01-01

    Perceived contagiousness is a major dimension underlying HIV-related stigmatization. Antiretroviral therapy (ART) can diminish contagiousness by reducing viral load levels in HIV-infected individuals. To test the assumption that reductions in contagiousness can lead to a decrease in stigmatizing reactions, we conducted an experimental online study. A sample of 752 participants (50.9% female) read a short vignette depicting an HIV-positive individual with either a high or a low viral load and were either given or not given information about the association between viral load and contagiousness. Subsequently, participants were asked to rate their willingness to stigmatize this individual by responding to two measures of social and physical distance. Differences between the low and the high viral load information groups and the combined no-information groups (forming a quasi-control group) were analyzed using analysis of covariance (ANCOVA), controlling for gender and baseline perceptions of contagiousness. The covariates, perceived contagiousness at baseline and gender, were associated with social and physical distancing, but the viral load/information factor was only significant in physical distancing. Planned contrast analyses confirmed that physical distancing in the informed group was lower in the low viral load condition compared to the high viral load condition and to the control group. We thus found evidence for the significant role of perceived contagiousness in the HIV-related stigma and were able to experimentally demonstrate the potential of ART to reduce HIV-related stigmatization by lowering viral load and contagiousness, when these changes are accompanied by a decreased perception of contagiousness. PMID:24779483

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

    Syebele, Kabunda

    2010-01-01

    HIV-salivary gland associated disease is a well accepted concept in the HIV-related literature. Parotid swellings, especially in its cystic benign lymphoepithelial form, have been largely reported. Oral mucoceles (ranulas) were also associated with HIV in some publications. The exact nature of this link between mucoceles and HIV is still to be clarified. The mainstream treatment of most of parotid pathologies and oral mucoceles remains surgical approach. Strong evidences do, however, exist about lymphopithelial lesions of parotid glands that have been successfully treated with antiretroviral drugs. We present a case of intraoral mucocele, coexisting with bilateral parotid gland lymphoepithelial lesions, on a 2-year-old HIV-positive patient. Both parotid gland swellings and the sublingual mucocele have completely regressed following antiretroviral therapy. No surgical intervention was required. Conversely to benign lymphoepithelial lesions of parotid glands, the regression of oral mucocele on HIV-positive patient, following antiretroviral drugs therapy appears to be a rare phenomenon. PMID:19879006

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

    ERIC Educational Resources Information Center

    Ryan, Joel; Allen, Ben

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

  9. A Review of Head Start Research Since 1970. Head Start Evaluation, Synthesis and Utilization Project.

    ERIC Educational Resources Information Center

    Hubbell, Ruth

    This review attempts to summarize the major findings concerning the impact of Head Start that have been reported in the literature published since 1970, and to communicate these results to policymakers, researchers, Head Start program staff, and others. The review constitutes an update of "A Review of Head Start Research since 1969 and an…

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

    ERIC Educational Resources Information Center

    Rose, Lea Williams; Cheney, Nancy

    2005-01-01

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

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

    ERIC Educational Resources Information Center

    Gopalan, Pritha

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

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

    PubMed

    Salo, Aki; Bezodis, Ian

    2004-01-01

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

  13. Development of cryptococcal immune reconstitution inflammatory syndrome 41 months after the initiation of antiretroviral therapy in an AIDS patient.

    PubMed

    Hashimoto, Hideki; Hatakeyama, Shuji; Yotsuyanagi, Hiroshi

    2015-01-01

    Cryptococcal meningitis is one of the most lethal fungal infections in patients with acquired immune deficiency syndrome (AIDS). The incidence of and mortality from cryptococcal meningitis have markedly decreased since the introduction of combination antiretroviral therapy (cART). However, despite its benefits, the initiation of cART results in immune reconstitution inflammatory syndrome (IRIS) in some patients. Although IRIS is occasionally difficult to distinguish from relapse or treatment failure, the distinction is important because IRIS requires a different treatment. Here, we present the case of a patient with AIDS who developed symptoms of cryptococcal IRIS 41 months after starting cART. To the best of our knowledge, the time between cART initiation and the onset of cryptococcal IRIS in this patient is the longest that has been reported in the literature. PMID:26425133

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

    PubMed Central

    2014-01-01

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

  15. The Physics of Tokamak Start-up

    SciTech Connect

    D. Mueller

    2012-11-13

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

  16. Start small and build toward business intelligence.

    PubMed

    Kirby, Sean; Robertson, Brian

    2009-01-01

    To use business intelligence effectively, healthcare organizations should start small, align organizationally, and leverage success. Organizations should determine which measures they need and how to present them. Organizations should reinvest savings to continually improve. PMID:19161037

  17. The physics of tokamak start-up

    SciTech Connect

    Mueller, D.

    2013-05-15

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

  18. 34 CFR 200.16 - Starting points.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ..., DEPARTMENT OF EDUCATION TITLE I-IMPROVING THE ACADEMIC ACHIEVEMENT OF THE DISADVANTAGED Improving Basic... proficient level of academic achievement. (b) Each starting point must be based, at a minimum, on the...

  19. A new start from ground zero?

    PubMed

    Luisi, Pier Luigi

    2014-12-01

    It is pointed out that one of the main reasons of lack of real conceptual progress in the field may lie in the fact that questions concerning the biogenesis of macromolecules have never been asked or addressed in a proper way. We should start again research on the origin of life starting from "ground zero" and focusing on the prebiotic synthesis of ordered sequences of proteins and nucleic acids. PMID:25618540

  20. A New Start from Ground Zero?

    NASA Astrophysics Data System (ADS)

    Luisi, Pier Luigi

    2014-12-01

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

  1. Urgent-start peritoneal dialysis: nursing aspects.

    PubMed

    Groenhoff, Cheryl; Delgado, Edna; McClernon, Marilyn; Davis, Alicia; Malone, Latasha; Majirsky, Janet; Guest, Steven

    2014-01-01

    Urgent-start peritoneal dialysis (PD) refers to the initiation of dialysis soon after a PD catheter placement and is a treatment option available to the late-referred patient with advanced kidney disease. This article reviews nursing aspects of urgent-start PD and can serve as a guide for this evolving clinical pathway that can provide renal replacement therapy for a critical segment of the population with Stage 5 chronic kidney disease who require renal replacement therapy. PMID:25244889

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

    PubMed

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

    2015-11-01

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

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

    PubMed

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

    2014-01-01

    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

  4. [Central nervous system infections in HIV patients in the era of high activity antiretroviral treatment].

    PubMed

    Rivas González, P; Fernández Guerrero, M L

    2005-06-01

    Although the incidence of most central nervous system infections in HIV+ patients has decreased after the introduction of the modern antiretroviral treatments, they are still a major cause of morbidity and mortality. New technologies in molecular biology and neuroradiology establish the diagnosis in many cases and have decreased the need for cerebral biopsy. Prognosis has improved substantially after the introduction of high activity antiretroviral treatment; more active treatments are needed, however, for infections as PML or citomegalovirus encephalitis because of their still unacceptably high mortality. PMID:15970136

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

    2014-01-01

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

  9. Prospective predictors of unprotected anal intercourse among HIV-seropositive men who have sex with men initiating antiretroviral therapy.

    PubMed

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

    2014-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2011-01-01

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

  12. Long-Term Effectiveness of Antiretroviral Therapy in China: An Observational Cohort Study from 2003-2014.

    PubMed

    Huang, Peng; Tan, Jingguang; Ma, Wenzhe; Zheng, Hui; Lu, Yan; Wang, Ning; Peng, Zhihang; Yu, Rongbin

    2015-08-01

    In order to assess the effectiveness of the Chinese government's expanded access program, a cohort study on all adult HIV patients in Shenzhen was conducted from December 2003 to February 2014 to estimate the effects of antiretroviral therapy (ART) on mortality, tuberculosis and CD4 cell counts. Marginal structural regression models adjusted for baseline and time-varying covariates. Of the 6897 patients enrolled and followed up for a maximum of 178 months, 44.92% received ART. Among patients who commenced receiving ART during the study, there were 98 deaths and 59 new tuberculosis diagnoses, while there were 410 deaths and 201 new tuberculosis diagnoses among those without ART. ART was associated with both lower mortality (hazard ratio [HR] = 0.18; 95% confidence interval [CI] = 0.11-0.27) and the presence of tuberculosis (HR = 0.27; 95% CI = 0.19-0.37). Each month of ART was associated with an average increase in CD4 cell count of 6.52 cells/µL (95% CI = 6.08-7.12 cells/µL). In conclusions, the effectiveness of ART provided by China government health services is the same as that in higher-income countries. Accounting to higher mortality rates from the delay of starting ART, faster expansion and timely imitation of ART are urgent. PMID:26213959

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

    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

    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. PMID:23144991

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

    TOXLINE Toxicology Bibliographic Information

    Tenthani L; Cataldo F; Chan AK; Bedell R; Martiniuk AL; van Lettow M

    2012-01-01

    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.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

    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.

    2014-01-01

    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

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

    PubMed

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

    2015-07-01

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

  20. HLA B∗5701 status, disease progression, and response to antiretroviral therapy

    PubMed Central

    2013-01-01

    Objective: In addition to hypersensitivity reactions to abacavir, HLA B∗5701 has been associated with slow or nonprogression of HIV infection. We explored the effect of HLA B∗5701 on CD4+ cell count and viral load in untreated patients and on responses to nonabacavir-containing combination antiretroviral therapy (cART) in a large UK-based cohort. Design: Analysis of a cohort of HIV-infected adults. Methods: In untreated patients, CD4+ cell count and viral load at study entry were compared in HLAB∗5701-positive and HLAB∗5701-negative individuals and linear regression tested for an interaction effect of viral load and HLA B∗5701 on CD4+ cell count. In patients starting a nonabacavir cART regimen, Cox proportional hazards models compared virological responses to cART among HLA B∗5701-negative, HLA B∗5701-positive, and those not tested. Six-month and 12-month changes in CD4+ cell count were used as outcomes in linear regression to compare immunological response to cART in these groups. Results: ART-naive HLA B∗5701-positive individuals had higher CD4+ cell count (P <0.0001) and lower viral load (P <0.0001) at study entry than negatives; however, HLA B∗5701 status was not found to effect the association between viral load and CD4+ cell count (interaction P value = 0.09). HLA B∗5701-positive patients were more likely to achieve viral suppression than negative patients on a nonabacavir regimen [hazard ratio = 1.29, 95% confidence interval, CI (1.15–1.54)] and less likely to experience viral rebound [hazard ratio = 0.61, 95% CI (0.37–0.99)]. Conclusion: Better virological but not immunological responses to cART were seen in HLA B∗5701-positive patients on nonabacavir regimens. This study provides further evidence of the potentially beneficial effect of HLA B∗5701 on HIV progression. PMID:23921616

  1. Financing equitable access to antiretroviral treatment in South Africa

    PubMed Central

    2010-01-01

    Background While South Africa spends approximately 7.4% of GDP on healthcare, only 43% of these funds are spent in the public system, which is tasked with the provision of care to the majority of the population including a large proportion of those in need of antiretroviral treatment (ART). South Africa is currently debating the introduction of a National Health Insurance (NHI) system. Because such a universal health system could mean increased public healthcare funding and improved access to human resources, it could improve the sustainability of ART provision. This paper considers the minimum resources that would be required to achieve the proposed universal health system and contrasts these with the costs of scaled up access to ART between 2010 and 2020. Methods The costs of ART and universal coverage (UC) are assessed through multiplying unit costs, utilization and estimates of the population in need during each year of the planning cycle. Costs are from the provider’s perspective reflected in real 2007 prices. Results The annual costs of providing ART increase from US$1 billion in 2010 to US$3.6 billion in 2020. If increases in funding to public healthcare only keep pace with projected real GDP growth, then close to 30% of these resources would be required for ART by 2020. However, an increase in the public healthcare resource envelope from 3.2% to 5%-6% of GDP would be sufficient to finance both ART and other services under a universal system (if based on a largely public sector model) and the annual costs of ART would not exceed 15% of the universal health system budget. Conclusions Responding to the HIV-epidemic is one of the many challenges currently facing South Africa. Whether this response becomes a “resource for democracy” or whether it undermines social cohesiveness within poor communities and between rich and poor communities will be partially determined by the steps that are taken during the next ten years. While the introduction of a universal system will be complex, it could generate a health system responsive to the needs of all South Africans. PMID:20594368

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2010-01-01

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

  4. Timing of Antiretroviral Therapy after Diagnosis of Cryptococcal Meningitis

    PubMed Central

    Boulware, David R.; Meya, David B.; Muzoora, Conrad; Rolfes, Melissa A.; Huppler Hullsiek, Katherine; Musubire, Abdu; Taseera, Kabanda; Nabeta, Henry W.; Schutz, Charlotte; Williams, Darlisha A.; Rajasingham, Radha; Rhein, Joshua; Thienemann, Friedrich; Lo, Melanie W.; Nielsen, Kirsten; Bergemann, Tracy L.; Kambugu, Andrew; Manabe, Yukari C.; Janoff, Edward N.; Bohjanen, Paul R.; Meintjes, Graeme

    2014-01-01

    Background Cryptococcal meningitis accounts for 20 to 25% of acquired immunodeficiency syndrome–related deaths in Africa. Antiretroviral therapy (ART) is essential for survival; however, the question of when ART should be initiated after diagnosis of cryptococcal meningitis remains unanswered. Methods We assessed survival at 26 weeks among 177 human immunodeficiency virus–infected adults in Uganda and South Africa who had cryptococcal meningitis and had not previously received ART. We randomly assigned study participants to undergo either earlier ART initiation (1 to 2 weeks after diagnosis) or deferred ART initiation (5 weeks after diagnosis). Participants received amphotericin B (0.7 to 1.0 mg per kilogram of body weight per day) and fluconazole (800 mg per day) for 14 days, followed by consolidation therapy with fluconazole. Results The 26-week mortality with earlier ART initiation was significantly higher than with deferred ART initiation (45% [40 of 88 patients] vs. 30% [27 of 89 patients]; hazard ratio for death, 1.73; 95% confidence interval [CI], 1.06 to 2.82; P = 0.03). The excess deaths associated with earlier ART initiation occurred 2 to 5 weeks after diagnosis (P = 0.007 for the comparison between groups); mortality was similar in the two groups thereafter. Among patients with few white cells in their cerebrospinal fluid (<5 per cubic millimeter) at randomization, mortality was particularly elevated with earlier ART as compared with deferred ART (hazard ratio, 3.87; 95% CI, 1.41 to 10.58; P = 0.008). The incidence of recognized cryptococcal immune reconstitution inflammatory syndrome did not differ significantly between the earlier-ART group and the deferred-ART group (20% and 13%, respectively; P = 0.32). All other clinical, immunologic, virologic, and microbiologic outcomes, as well as adverse events, were similar between the groups. Conclusions Deferring ART for 5 weeks after the diagnosis of cryptococcal meningitis was associated with significantly improved survival, as compared with initiating ART at 1 to 2 weeks, especially among patients with a paucity of white cells in cerebrospinal fluid. (Funded by the National Institute of Allergy and Infectious Diseases and others; COAT ClinicalTrials.gov number, NCT01075152.) PMID:24963568

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

    PubMed Central

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

    2014-01-01

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

  6. Neurocognitive Function in HIV Infected Patients on Antiretroviral Therapy

    PubMed Central

    Winston, Alan; Arenas-Pinto, Alejandro; Stöhr, Wolfgang; Fisher, Martin; Orkin, Chloe M.; Aderogba, Kazeem; De Burgh-Thomas, Andrew; O'Farrell, Nigel; Lacey, Charles JN.; Leen, Clifford; Dunn, David; Paton, Nicholas I.

    2013-01-01

    Objective To describe factors associated with neurocognitive (NC) function in HIV-positive patients on stable combination antiretroviral therapy. Design We undertook a cross-sectional analysis assessing NC data obtained at baseline in patients entering the Protease-Inhibitor-Monotherapy-Versus-Ongoing-Triple therapy (PIVOT) trial. Main outcome measure NC testing comprised of 5 domains. Raw results were z-transformed using standard and demographically adjusted normative datasets (ND). Global z-scores (NPZ-5) were derived from averaging the 5 domains and percentage of subjects with test scores >1 standard deviation (SD) below population means in at least two domains (abnormal Frascati score) calculated. Patient characteristics associated with NC results were assessed using multivariable linear regression. Results Of the 587 patients in PIVOT, 557 had full NC results and were included. 77% were male, 68% Caucasian and 28% of Black ethnicity. Mean (SD) baseline and nadir CD4+ lymphocyte counts were 553(217) and 177(117) cells/µL, respectively, and HIV RNA was <50 copies/mL in all. Median (IQR) NPZ-5 score was −0.5 (−1.2/−0) overall, and −0.3 (−0.7/0.1) and −1.4 (−2/−0.8) in subjects of Caucasian and Black ethnicity, respectively. Abnormal Frascati scores using the standard-ND were observed in 51%, 38%, and 81%, respectively, of subjects overall, Caucasian and Black ethnicity (p<0.001), but in 62% and 69% of Caucasian and Black subjects using demographically adjusted-ND (p = 0.20). In the multivariate analysis, only Black ethnicity was associated with poorer NPZ-5 scores (P<0.001). Conclusions In this large group of HIV-infected subjects with viral load suppression, ethnicity but not HIV-disease factors is closely associated with NC results. The prevalence of abnormal results is highly dependent on control datasets utilised. Trial registry ClinicalTrials.gov, NCT01230580 PMID:23646111

  7. Nanoformulated antiretroviral drug combinations extend drug release and antiretroviral responses in HIV-1-infected macrophages: implications for neuroAIDS therapeutics.

    PubMed

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

    2010-12-01

    We posit that improvements in pharmacokinetics and biodistributions of antiretroviral therapies (ART) for human immunodeficiency virus type one-infected people can be achieved through nanoformulationed drug delivery systems. To this end, we manufactured nanoparticles of atazanavir, efavirenz, and ritonavir (termed nanoART) and treated human monocyte-derived macrophages (MDM) in combination therapies to assess antiretroviral responses. This resulted in improved drug uptake, release, and antiretroviral efficacy over monotherapy. MDM rapidly, within minutes, ingested nanoART combinations, at equal or similar rates, as individual formulations. Combination nanoART ingested by MDM facilitated individual drug release from 15 to >20 days. These findings are noteworthy as a nanoART cell-mediated drug delivery provides a means to deliver therapeutics to viral sanctuaries, such as the central nervous system during progressive human immunodeficiency virus type one infection. The work brings us yet another step closer to realizing the utility of nanoART for virus-infected people. PMID:20237859

  8. Early virological failure and the development of antiretroviral drug resistance mutations in HIV-infected Ugandan children

    PubMed Central

    Ruel, Theodore D.; Kamya, Moses R.; Li, Pelin; Pasutti, William; Charlebois, Edwin D.; Liegler, Teri; Dorsey, Grant; Rosenthal, Philip J.; Havlir, Diane V.; Wong, Joseph K.; Achan, Jane

    2011-01-01

    Background Without virologic testing, HIV-infected African children starting antiretroviral (ARV)-therapy are at risk for undetected virological failure and the development of ARV-resistance. We sought to determine the prevalence of early virologic failure (EVF), to characterize the evolution of ARV-resistance mutations, and to predict the impact on second-line therapy. Methods The prevalence of EVF (HIV-RNA >400 copies/mL on sequential visits after 6 months of therapy) was identified among 120 HIV-infected Ugandan children starting ARV-therapy. ARV-mutations were identified by population sequencing of HIV-1 pol in sequential archived specimens. Composite discrete genotypic susceptibility scores (dGSS) were determined for second-line ARV-regimens. Results EVF occurred in 16 (13%) children and persisted throughout a median (IQR) 938 (760-1066) days of follow-up. M184V and non-nucleoside-reverse-transcriptase-inhibitor-associated mutations emerged within 6 months of EVF; thymidine-analog-mutations arose after 12 months. Worse dGSS scores correlated with increasing duration of failure (Spearman R = −0.47, p=0.001). Only 1 child met World Health Organization CD4 criteria for ARV-failure at the time of EVF or during the follow-up period. Conclusions A significant portion of HIV-infected African children experience EVF that would be undetected using CD4/clinical monitoring and resulted in the accumulation of ARV-mutations that could compromise second line therapy options. PMID:21099693

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

    PubMed Central

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

    2016-01-01

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

  10. Transmitted drug resistance to rilpivirine among antiretroviral-naïve patients living with HIV from northern Poland

    PubMed Central

    Parczewski, Miłosz; Urbańska, Anna; Maciejewska, Katarzyna; Witak-Jȩdra, Magdalena; Leszczyszyn-Pynka, Magdalena

    2014-01-01

    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. PMID:24746180

  11. HIV research trials versus standard clinics for antiretroviral-naïve patients: the outcomes differ but do the patients?

    PubMed

    Williams, A J; Wallis, E; Orkin, C

    2016-06-01

    Exclusion criteria for HIV treatment-naïve drug trials can be stringent and selection bias exists, making it difficult to extrapolate results into the 'real world' clinical situation. We aim to compare the demographics, virological outcomes and psychosocial complexity in adult HIV-infected treatment-naïve patients from our cohort initiating combination antiretroviral therapy (cART) in research trials versus standard clinics. In our unit from 2006 to 2011, 1202 standard clinic and 69 research trial patients initiated cART; every eighth standard clinics patient was included to create a standard clinics:research trials patient ratio of 2:1. Notes were retrospectively reviewed for patient demographics, attendance rates and virological outcomes. Data from 221 antiretroviral-naïve patients starting cART were analysed: 152 standard clinic patients and 69 from research trials. In the research trials group, there was an overrepresentation of men (p = 0.041), men who have sex with men (p < 0.001), patients of white ethnicity (p = 0.01), employed patients (p = 0.01) and patients using excessive alcohol (p = 0.02). There was equal representation of drug use, depression and referral to psychology, psychiatry and social work in both groups. The research trials group at baseline had significantly higher CD4 counts (p < 0.001), lower viral loads (p = 0.01) and more patients achieved undetectable viral loads at three (p < 0.001), six (p < 0.001) and 24 months (p = 0.033). There is a prevailing common preconception that participants in clinical trials are uncomplicated, unlike their 'real-life' counterparts. We demonstrated important similarities in psychosocial complexity as well as differences in demographics and virological outcomes in trial and non-trial patients. Clinicians need to be aware of these discrepancies to ensure the facilitation of a heterogeneous population participating in research trials. PMID:25999167

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

    PubMed Central

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

    1992-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  14. Alcohol cold starting - A theoretical study

    NASA Technical Reports Server (NTRS)

    Browning, L. H.

    1983-01-01

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

  15. Kansas refinery starts up coke gasification unit

    SciTech Connect

    Rhodes, A.K.

    1996-08-05

    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.

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2011-01-01

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

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

    ERIC Educational Resources Information Center

    Delbene, Roxana

    2012-01-01

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

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

    PubMed

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

    2015-11-01

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

  20. Cancellers - Exploring the Possibility of Receptor Decoy Traps As a Superior Anti-Retroviral Strategy.

    PubMed

    Jeremiah, Sundararaj Stanley; Ohba, Kenji; Yamamoto, Naoki

    2016-01-01

    The global Human Immunodeficiency Virus (HIV) pandemic is still spreading due to the lack of ideal anti-retroviral measures and their availability. Till date, all attempts to produce an efficient vaccine have ended with unsatisfactory results. The highly active anti-retroviral therapy (HAART) is the only effective weapon currently available and is widely being used for curtailing the HIV pandemic. However, the HAART is also expected to fail in the near future due to the emergence and dissemination of antiviral resistance. This review sheds light on the reasons for the failure of the conventional anti-viral measures against HIV and the novel anti-retroviral strategies currently being developed. The various principles to be considered for the success of a novel anti-retroviral strategy are elaborately emphasized and an innovative concept is proposed on these lines. The proposed concept intends to use receptor decoy traps (RDT) called cancellers which are erythrocytes expressing the HIV entry receptors on their surface. If successfully developed, the cancellers would be capable of active targeting of the free HIV particles leading to the trapping of the viruses within the canceller, resulting in the neutralization of infectivity of the trapped virus. The possible ways of translating this concept into reality and the probable hurdles that can be encountered in the process are subsequently discussed. Also, the scope of cancellers in therapeutic and/or preventive strategies against HIV infection is envisaged upon their successful development. PMID:25882216

  1. Adherence to directly observed antiretroviral therapy among human immunodeficiency virus-infected prison inmates.

    PubMed

    Wohl, David A; Stephenson, Becky L; Golin, Carol E; Kiziah, C Nichole; Rosen, David; Ngo, Bich; Liu, Honghu; Kaplan, Andrew H

    2003-06-15

    Directly observed therapy (DOT) for human immunodeficiency virus (HIV) infection is commonly used in correctional settings; however, the efficacy of DOT for treating HIV infection has not been determined. We prospectively assessed adherence to antiretroviral therapy regimens among 31 HIV-infected prison inmates who were receiving >or=1 antiretrovirals via DOT. Adherence was measured by self-report, pill count, electronic monitoring caps, and, for DOT only, medication administration records. Overall, median adherence was 90%, as measured by pill count; 86%, by electronic monitoring caps; and 100%, by self-report. Adherence, as measured by electronic monitoring caps, was >90% in 32% of the subjects. In 91% of cases, adherence, as measured by medication administration records, was greater than that recorded by electronic monitoring caps for the same medications administered by DOT. Objective methods of measurement revealed that adherence to antiretroviral regimens administered wholly or in part by DOT was antiretroviral therapy. PMID:12802758

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

    ERIC Educational Resources Information Center

    Roberts, Kathleen Johnston

    2005-01-01

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

  3. New Insights into HIV-1 Persistence in Sanctuary Sites During Antiretroviral Therapy.

    PubMed

    Poveda, Eva; Tabernilla, Andrés

    2016-01-01

    Current combinations of antiretroviral drugs for the treatment of HIV infection can successfully achieve and maintain long-term suppression of HIV-1 replication in plasma. Still, none of these therapies is capable of eradicating the virus from the long-lived cellular reservoir that represents the major barrier to HIV cure. PMID:27028272

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

    PubMed Central

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

    2009-01-01

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

  5. Can highly active antiretroviral therapy reduce the spread of HIV?: A study in a township of South Africa

    PubMed Central

    Auvert, Bertran; Males, Sylvia; Puren, Adrian; Taljaard, Dirk; Caraël, Michel; Williams, Brian

    2004-01-01

    SUMMARY Background Calls have been made for the large-scale delivery of highly active antiretroviral therapy (HAART) to people infected with HIV in developing countries. If this is to be done, estimates of the number of people who currently require HAART in high HIV-prevalence areas of sub-Saharan Africa are needed and the impact of the widespread use of HAART on transmission and hence the spread of HIV must be assessed. Objectives To estimate the proportion of people who would be eligible for combination antiretroviral (ARV) therapy and hence to evaluate the potential impact of providing HAART on the spread of HIV-1 under the WHO guideline, in a South African township with a high prevalence of HIV-1. Design A community-based, cross-sectional study in a township near Johannesburg, South Africa of a random sample of approximately 1,000 men and women aged 15 to 49 years. Materials and methods Background characteristics and sexual behaviour were recorded by questionnaire. Participants were tested for HIV-1 and their CD4+ cell counts and plasma HIV-1 RNA loads were measured. The proportion of people whose CD4+ cell count was less than 200 cells/mm3 and would be eligible to receive HAART under the WHO guideline was estimated. The potential impact of antiretroviral drugs on the spread of HIV-1 in this setting was determined firstly by estimating among the partnerships engaged in by HIV-1 positive individuals the proportion of spousal and non-spousal partnerships eligible to receive HAART, and secondly by calculating the potential impact of HAART on the annual risk of HIV-1 transmission due to sexual contacts of HIV-1 infected persons. The results were compared with those obtained when using the USDHHS guideline. Results The overall prevalence of HIV-1 infection was 21.8% (19.2% – 24.6%), and of these people 9.5% (6.1% – 14.9%), or 2.1% (1.3% – 3.3%) of all 15 to 49 year olds, would be eligible for HAART (ranges are 95% confidence limits). In each of the next three years 6.3% (4.6% – 8.4%) of those currently infected with HIV-1 will need to start HAART. Among the partnerships where individuals were HIV-1 positive only a small proportion of spousal partnerships (7.6%; 3.4% – 15.6%) and non-spousal partnerships (5.7%; 3.0% – 10.2%) involve a partner with a CD4+ cell count below 200 cells/mm3 and would benefit from the reduction of transmission due to the V 20 decrease in plasma HIV-1 RNA load under HAART. Estimates of the impact of HAART on the annual risk of HIV-1 transmission show that this risk would be reduced by 11.9% (7.1% – 17.0%). When using USDHHS guideline the fraction of HIV-1 positive eligible for HAART reached 56.3% (49.1% – 63.2%) and the impact of HAART on the annual risk of HIV-1 transmission reached 71.8% (64.5% – 77.5%). Conclusion The population impact of HAART on reducing sexual transmission of HIV-1 is likely to be small under the WHO guideline and reducing the spread of HIV-1 will depend on further strengthening conventional prevention efforts. A much higher impact of HAART is to be expected if USDHHS guideline is to be used. PMID:15097305

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

    PubMed Central

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

    2016-01-01

    Background High rates of patient attrition from care between HIV testing and antiretroviral therapy (ART) initiation have been documented in sub-Saharan Africa, contributing to persistently low CD4 cell counts at treatment initiation. One reason for this is that starting ART in many countries is a lengthy and burdensome process, imposing long waits and multiple clinic visits on patients. We estimated the effect on uptake of ART and viral suppression of an accelerated initiation algorithm that allowed treatment-eligible patients to be dispensed their first supply of antiretroviral medications on the day of their first HIV-related clinic visit. Methods and Findings RapIT (Rapid Initiation of Treatment) was an unblinded randomized controlled trial of single-visit ART initiation in two public sector clinics in South Africa, a primary health clinic (PHC) and a hospital-based HIV clinic. Adult (≥18 y old), non-pregnant patients receiving a positive HIV test or first treatment-eligible CD4 count were randomized to standard or rapid initiation. Patients in the rapid-initiation arm of the study (“rapid arm”) received a point-of-care (POC) CD4 count if needed; those who were ART-eligible received a POC tuberculosis (TB) test if symptomatic, POC blood tests, physical exam, education, counseling, and antiretroviral (ARV) dispensing. Patients in the standard-initiation arm of the study (“standard arm”) followed standard clinic procedures (three to five additional clinic visits over 2–4 wk prior to ARV dispensing). Follow up was by record review only. The primary outcome was viral suppression, defined as initiated, retained in care, and suppressed (≤400 copies/ml) within 10 mo of study enrollment. Secondary outcomes included initiation of ART ≤90 d of study enrollment, retention in care, time to ART initiation, patient-level predictors of primary outcomes, prevalence of TB symptoms, and the feasibility and acceptability of the intervention. A survival analysis was conducted comparing attrition from care after ART initiation between the groups among those who initiated within 90 d. Three hundred and seventy-seven patients were enrolled in the study between May 8, 2013 and August 29, 2014 (median CD4 count 210 cells/mm3). In the rapid arm, 119/187 patients (64%) initiated treatment and were virally suppressed at 10 mo, compared to 96/190 (51%) in the standard arm (relative risk [RR] 1.26 [1.05–1.50]). In the rapid arm 182/187 (97%) initiated ART ≤90 d, compared to 136/190 (72%) in the standard arm (RR 1.36, 95% confidence interval [CI], 1.24–1.49). Among 318 patients who did initiate ART within 90 d, the hazard of attrition within the first 10 mo did not differ between the treatment arms (hazard ratio [HR] 1.06; 95% CI 0.61–1.84). The study was limited by the small number of sites and small sample size, and the generalizability of the results to other settings and to non-research conditions is uncertain. Conclusions Offering single-visit ART initiation to adult patients in South Africa increased uptake of ART by 36% and viral suppression by 26%. This intervention should be considered for adoption in the public sector in Africa. Trial Registration ClinicalTrials.gov NCT01710397, and South African National Clinical Trials Register DOH-27-0213-4177. PMID:27163694

  7. Sexual risk behaviors among HIV-patients receiving antiretroviral therapy in Southern Thailand: roles of antiretroviral adherence and serostatus disclosure.

    PubMed

    Thanawuth, Nattasiri; Rojpibulstit, Malee

    2016-05-01

    The objective of this study was to examine the extent of unprotected sex among patients already established in HIV-medical care and their associated factors. Sexually active patients who were receiving antiretroviral therapy (ART) from five public hospitals in Trang province, Southern Thailand, were interviewed. Of 279 studied patients, 37.3% had unprotected sex in the prior 3 months and 27.2% did not disclose their serostatus to sexual partners. The median duration interquartile range (IQR) of using ART was 47 (27-60) months and 26.7% were non-adherent to ART (i.e., taking less than 95% of the prescribed doses). More than one-third had the perception that ART use would protect against HIV transmission even with unprotected sex. About 36.6% reported that they were unaware of their current CD4 counts and nearly one-third did not receive any safe sex counseling at each medical follow-up. After adjustment for potential confounders, non-adherence to ART and HIV-nondisclosure were strongly associated with an increase in the risk of unprotected sex with the adjusted odds ratio (aOR) of 5.03 (95% CI 2.68-9.44) and 3.89 (95% CI 1.57-9.61), respectively. In contrast, the risk for engaging in unprotected sex was less likely among patients having a negative-serostatus partner (aOR = 0.30; 95% CI 0.12-0.75), a longer duration of the use of ART (aOR = 0.98; 95%CI 0.97-0.99) and an unawareness of their current CD4 levels (aOR = 0.54; 95% CI 0.30-0.99). To maximize the benefits from ART, there should be a bigger emphasis on the "positive prevention" program and more efforts are needed to target the population at risk for unprotected sex. Strategies to encourage adherence to ART and for disclosure of serostatus are also required. PMID:26666292

  8. School Start Time and Teen Sleep.

    ERIC Educational Resources Information Center

    Wahlstrom, Kyla L.

    2000-01-01

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

  9. Start Your Own Business. Interim Guide.

    ERIC Educational Resources Information Center

    Manitoba Dept. of Education and Training, Winnipeg.

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

  10. Starting New Schools: Lessons for Success.

    ERIC Educational Resources Information Center

    Jennings, Wayne B.

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

  11. Innovations in Detroit Head Start. [Videotape].

    ERIC Educational Resources Information Center

    Merrill-Palmer Inst., Detroit, MI.

    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…

  12. Addressing Tooth Decay in Head Start Children

    ERIC Educational Resources Information Center

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

    2012-01-01

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

  13. Verifying the INF and START treaties

    NASA Astrophysics Data System (ADS)

    Ifft, Edward

    2014-05-01

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

  14. You Can Start Your Own School!

    ERIC Educational Resources Information Center

    Adams, Caralee

    2007-01-01

    Many teachers, fueled by their passion, classroom experience, and entrepreneurial verve, decide to start their own schools. With the needs of children driving their every decision, teachers can create successful schools where students thrive. In this article, teachers who established their own schools--from public charters to private…

  15. Verifying the INF and START treaties

    SciTech Connect

    Ifft, Edward

    2014-05-09

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

  16. Head Start: A Child Development Program.

    ERIC Educational Resources Information Center

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

    This booklet discusses the origins and components of Head Start, a federal project launched in 1965 to help break the cycle of poverty by providing preschool children of low-income families with a comprehensive program to meet their emotional, social, health, nutritional, and psychological needs. The description of the program notes that in fiscal…

  17. MATC Project Get Started: Phase II Report.

    ERIC Educational Resources Information Center

    Milwaukee Area Technical Coll., WI.

    Milwaukee Area Technical College's (MATC) Project Get Started assesses mothers on welfare, analyzes their child care needs, makes recommendations, and engages 75% of the women in an appropriate job activity for at least 10 hours per week. Mothers attend an orientation that furnishes information on the project and on "W-2," the state's new welfare…

  18. Basic Education Through Head Start Programs

    ERIC Educational Resources Information Center

    Wilson, LaVisa Cam

    1977-01-01

    Reports results of a study which surveyed adult education opportunities presently being provided or facilitated by Head Start programs in Alabama and examined the types of adult education programs, patterns of participation in adult basic education General Educational Development (ABE/GED) programs, and the effect of class location on GED…

  19. Getting a Good Start in School.

    ERIC Educational Resources Information Center

    Copple, Carol, Ed.

    In 1990, the National Education Goals were established by the President and the 50 state governors. Goal 1 states that by the year 2000, all children in America will start school ready to learn. This booklet is a condensed version of an earlier document intended to further amplify the dimensions of early learning and development used by the…

  20. Project Great Start Biennial Evaluation Report.

    ERIC Educational Resources Information Center

    Rudy, Dennis W.

    Project Great Start is designed to provide non-, limited-, and near-native English proficient students with improved, intensified, and increased learning opportunities for accelerated English acquisition and significant academic achievement. It focuses on three groups: students, parents, and school staff. Students and parents benefit from separate…

  1. Head Start Fathers' Involvement with Their Children

    ERIC Educational Resources Information Center

    Gorvine, Benjamin J.

    2010-01-01

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

  2. Arcjet power supply and start circuit

    NASA Technical Reports Server (NTRS)

    Gruber, Robert P. (Inventor)

    1988-01-01

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

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

    ERIC Educational Resources Information Center

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

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

  4. 75 FR 57704 - Head Start Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-22

    ... reliable assessment of the quality of preschool classrooms. The CLASS: Pre-K also has been used extensively... children's development and learning. The CLASS: Pre-K looks at three dimensions of quality in preschool... quality across all Head Start programs. Participation in high-quality early childhood care and...

  5. 76 FR 14841 - Head Start Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-18

    ... population of 1,000 or less individuals and the following conditions apply: There is no other preschool... community is in a location which, by reason of remoteness, does not permit reasonable access to preschool... Start Centers'' before the House Education and Labor Committee on May 18, 2010, which is available...

  6. Self-starting circuit for switching regulators

    NASA Technical Reports Server (NTRS)

    Schraut, E. H.; Sohl, G.

    1969-01-01

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

  7. How To Start a Child Care Center.

    ERIC Educational Resources Information Center

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

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

  8. The Head Start-Kiwanis Connection.

    ERIC Educational Resources Information Center

    NHSA Journal, 1993

    1993-01-01

    Highlights the efforts of 11 Kiwanis groups across the country who have formed partnerships with Head Start centers. Sponsored activities described include (1) reading and literacy programs; (2) building and maintenance projects for centers and playgrounds; (3) a health fair; (4) a family sports event; and (5) donations of time, labor, books,…

  9. Head Start and Private/Public Partnerships.

    ERIC Educational Resources Information Center

    Holmes, Maggie

    1994-01-01

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

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

    ERIC Educational Resources Information Center

    Smith, Mimi Kenney

    2008-01-01

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

  11. Start-Up Success: Collection Development

    ERIC Educational Resources Information Center

    Awe, Susan C.

    2010-01-01

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

  12. Analysis of False Starts in Spontaneous Speech.

    ERIC Educational Resources Information Center

    O'Shaughnessy, Douglas

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

  13. Getting-Started Strategies and Cooperative Learning.

    ERIC Educational Resources Information Center

    Myers, John J.; And Others

    1991-01-01

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

  14. The Start of a Tech Revolution

    ERIC Educational Resources Information Center

    Dyrli, Kurt O.

    2009-01-01

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

  15. Start-Up Success: Collection Development

    ERIC Educational Resources Information Center

    Awe, Susan C.

    2010-01-01

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

  16. Adolescent Sleep Needs and School Starting Times.

    ERIC Educational Resources Information Center

    Wahlstrom, Kyla L., Ed.

    A key task for schools is to ensure that the conditions in which learning is to take place address the biological needs of the learners. This book examines sleep needs of adolescents and discusses the implications of these needs for school starting times. This book is a collection of five articles that appeared in a special section of the Phi…

  17. An Alternative Starting Point for Fraction Instruction

    ERIC Educational Resources Information Center

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

    2015-01-01

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

  18. How to Start a Free University.

    ERIC Educational Resources Information Center

    Marsello, Greg

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

  19. How to Start Intergenerational Programs in Communities.

    ERIC Educational Resources Information Center

    2002

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

  20. The Start of a Tech Revolution

    ERIC Educational Resources Information Center

    Dyrli, Kurt O.

    2009-01-01

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

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

    ERIC Educational Resources Information Center

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

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

  2. Access to antiretroviral therapy among HIV/AIDS patients in Chiang Mai province, Thailand

    PubMed Central

    Himakalasa, Woraluck; Grisurapong, Siriwan; Phuangsaichai, Sasipen

    2013-01-01

    The objective of this study is to investigate the access to antiretroviral treatment among human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) patients in Chiang Mai province, Thailand. Access to antiretroviral treatment is defined in terms of availability, affordability, and acceptability. The data for the study were collected during the period of April 1, 2012–May 31, 2012 from a sample of 380 HIV/AIDS patients in eight hospitals who had received antiretroviral treatment for more than 6 months at the time of data collection. The results of the study show that for most patients, the average traveling time to access health care was acceptable, but the nearly half day waiting time caused them to be absent from their work. In particular, it took longer for patients in the rural and lower income groups to access the treatment than the other groups. Their travel times and food costs relating to the treatment were found to be relatively high and therefore these patients had a higher tendency to borrow or seek financial assistance from their relatives. However, due to improvements in the access to treatment, most patients were satisfied with the services they received. The results imply that policy should be implemented to raise the potential of subdistrict hospitals where access to antiretroviral treatment is available, with participating HIV/AIDS patients acting as volunteers in providing services and other forms of health promotion to new patients. Privacy issues could be reduced if the antiretroviral treatment was isolated from other health services. Additionally, efforts to educate HIV/AIDS patients and society at large should be made. PMID:23986652

  3. Taking the START II debate to Moscow

    SciTech Connect

    1996-10-01

    The author explains why the START II Treaty should be ratified and implemented. When the START I reductions are completed, the United States, and Russia will each have about 6,000 strategic nuclear warheads. Additionally, there are thousands of nuclear warheads in our tactical forces, with thousands more in secure storage areas. And there are thousands of kilograms of weapons-grade uranium and plutonium in storage, with nuclear reactors making still more. This huge infrastructure requires a considerable expense to maintain, and it requires stringent safety and security measures. The security features are particularly important since a handful of rogue nations are trying to get their hands on our nuclear weapons or the plutonium which would allow them to make their own. Additionally, terrorist groups are seeking to obtain nuclear weapons or assorted radioactive material. Therefore, it is in the supreme interest of Russia and the United States, the two great nuclear powers, to lead the world in controlling these terrible weapons and the deadly plutonium from which they are made. Key to this control is making the dramatic reductions in the deadly legacy of the Cold War-the nuclear infrastructure: warheads, missiles, weapons-grade uranium and plutonium, launch facilities, and manufacturing facilities. We initiated reductions in 1991 with the START I treaty, which reduces nuclear warheads by half-Russia and the United States are both well ahead of schedule in making the reductions called for in START I. We followed that in 1994 with the Trilateral Agreement to transfer nuclear weapons from Ukraine to Russia. Today, Ukraine and Kazakhstan are nuclear-weapons free. The next major step is START II, which will result in another reduction in nuclear warheads by half. Both Russia and the United States have far too many nuclear weapons and we can both improve our security and our safety by making dramatic reductions.

  4. The Effects of Head Start Health Services: Executive Summary of the Head Start Health Evaluation.

    ERIC Educational Resources Information Center

    Fosburg, Linda B.; And Others

    This report summarizes findings of an evaluation of Head Start health services. Chapter one presents an overview of the background of the evaluation project. Chapter two highlights findings for the major evaluation questions. These questions focus specifically on children's health status prior to entry into Head Start, health services subsequently

  5. Head Start Program Performance Standards. OCD-HS Head Start Policy Manual.

    ERIC Educational Resources Information Center

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

    A list of Project Head Start Performance Standards is presented. It is the latest phase of an ongoing effort to provide comprehensive developmental services to children from low-income families. This issuance attempts to set forth those basic standards in operational terms as part of the Head Start Improvement and Innovation effort. (CK)

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

    ERIC Educational Resources Information Center

    Tao, Fumiyo; Arriola, Christine

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

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

    ERIC Educational Resources Information Center

    ZERO TO THREE, 2007

    2007-01-01

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

  8. Starting apparatus for internal combustion engines

    DOEpatents

    Dyches, Gregory M.; Dudar, Aed M.

    1997-01-01

    An internal combustion engine starting apparatus uses a signal from a curt sensor to determine when the engine is energized and the starter motor should be de-energized. One embodiment comprises a transmitter, receiver, computer processing unit, current sensor and relays to energize a starter motor and subsequently de-energize the same when the engine is running. Another embodiment comprises a switch, current transducer, low-pass filter, gain/comparator, relay and a plurality of switches to energize and de-energize a starter motor. Both embodiments contain an indicator lamp or speaker which alerts an operator as to whether a successful engine start has been achieved. Both embodiments also contain circuitry to protect the starter and to de-energize the engine.

  9. Verifying START: From satellites to suspect sites

    SciTech Connect

    Lockwood, D. )

    1990-10-01

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

  10. New procedure speeds cold start, protects turbine

    SciTech Connect

    Mallard, R.E.; Jordan, C.A.

    1995-09-01

    System dispatch from today`s power plants must consider availability of purchase power (buy and sell), fuel prices, and unit availability and efficiency. To gain the best combination of these factors, steam units must be capable of quick removal and return to service. However, unit startups are expensive, time consuming nd operationally demanding. For example, excessive thermal stresses can be catastrophic to a unit. With those factors in mind, Jacksonville Electric Authority (JEA) developed the ``valve open start`` procedure described here.

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

    PubMed

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

    2015-01-01

    The swimming start is typically broken into three sub-phases; on-block, flight, and underwater phases. While overall start performance is highly important to elite swimming, the contribution of each phase and important technical components within each phase, particularly with the new kick-start technique, has not been established. The aim of this study was to identify technical factors associated with overall start performance, with a particular focus on the underwater phase. A number of parameters were calculated from 52 starts performed by elite freestyle and butterfly swimmers. These parameters were split into above-water and underwater groupings, before factor analysis was used to reduce parameter numbers for multiple regression. For the above-water phases, 81% of variance in start performance was accounted for by take-off horizontal velocity. For the underwater water phase, 96% of variance was accounted for with time underwater in descent, time underwater in ascent and time to 10 m. Therefore, developing greater take-off horizontal velocity and focussing on the underwater phase by finding the ideal trajectory will lead to improved start performance. PMID:25555171

  12. CD4+ T cell recovery during suppression of HIV replication: an international comparison of the immunological efficacy of antiretroviral therapy in North America, Asia and Africa

    PubMed Central

    Geng, Elvin H; Neilands, Torsten B; Thièbaut, Rodolphe; Bosco Bwana, Mwebesa; Nash, Denis; Moore, Richard D; Wood, Robin; Marcel Zannou, Djimon; Althoff, Keri N; Lian Lim, Poh; Nachega, Jean B; Easterbrook, Philippa J; Kambugu, Andrew; Little, Francesca; Nakigozi, Gertrude; Nakanjako, Damalie; Kiggundu, Valerian; Chung Ki Li, Patrick; Bangsberg, David R; Fox, Matthew P; Prozesky, Hans W; Hunt, Peter W; Davies, Mary-Ann; Reynolds, Steven J; Egger, Matthias; Yiannoutsos, Constantin T; Vittinghoff, Eric V; Deeks, Steven G; Martin, Jeffrey N

    2015-01-01

    Background: Even among HIV-infected patients who fully suppress plasma HIV RNA replication on antiretroviral therapy, genetic (e.g. CCL3L1 copy number), viral (e.g. tropism) and environmental (e.g. chronic exposure to microbial antigens) factors influence CD4 recovery. These factors differ markedly around the world and therefore the expected CD4 recovery during HIV RNA suppression may differ globally. Methods: We evaluated HIV-infected adults from North America, West Africa, East Africa, Southern Africa and Asia starting non-nucleoside reverse transcriptase inhibitor-based regimens containing efavirenz or nevirapine, who achieved at least one HIV RNA level <500/µl in the first year of therapy and observed CD4 changes during HIV RNA suppression. We used a piecewise linear regression to estimate the influence of region of residence on CD4 recovery, adjusting for socio-demographic and clinical characteristics. We observed 28 217 patients from 105 cohorts over 37 825 person-years. Results: After adjustment, patients from East Africa showed diminished CD4 recovery as compared with other regions. Three years after antiretroviral therapy initiation, the mean CD4 count for a prototypical patient with a pre-therapy CD4 count of 150/µl was 529/µl [95% confidence interval (CI): 517–541] in North America, 494/µl (95% CI: 429–559) in West Africa, 515/µl (95% CI: 508–522) in Southern Africa, 503/µl (95% CI: 478–528) in Asia and 437/µl (95% CI: 425–449) in East Africa. Conclusions: CD4 recovery during HIV RNA suppression is diminished in East Africa as compared with other regions of the world, and observed differences are large enough to potentially influence clinical outcomes. Epidemiological analyses on a global scale can identify macroscopic effects unobservable at the clinical, national or individual regional level. PMID:25859596

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

    PubMed Central

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

    2015-01-01

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

  14. Combination Antiretroviral Treatment for Women Previously Treated Only in Pregnancy: Week 24 Results of AIDS Clinical Trials Group Protocol A5227

    PubMed Central

    Vogler, Mary A; Smeaton, Laura M; Wright, Rodney L; Cardoso, Sandra Wagner; Sanchez, Jorge; Infante, Rosa; Moran, Laura E; Godfrey, Catherine; Demeter, Lisa M; Johnson, Victoria A

    2014-01-01

    Background Women with HIV and prior exposure to combination antiretroviral therapy (cART) solely for prevention of Mother to Child Transmission (pMTCT) need to know whether they can later be treated successfully with a commonly used regimen of efavirenz (EFV) and co-formulated emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF) Methods Non-pregnant women with plasma HIV-1 RNA of ≥ 500 copies/mL, previously cART- exposed for pMTCT only, were eligible if they were off ART for ≥ 24 weeks prior to entry, were without evidence of drug resistance on standard genotyping, and were ready to start EFV plus FTC/TDF. The primary endpoint was virologic response (defined as plasma HIV RNA <400 copies/mL) at 24 weeks. Results 54 women were enrolled between 10/07 and 12/09; 52/54 completed 24 weeks of follow- up. Median baseline CD4+ T-cell count was 265/mm3 and baseline plasma HIV-1 RNA was 4.6 log10 copies/mL. Median prior cART duration was 14 weeks, and median time elapsed from the last pMTCT dose to entry was 22 months. Virologic response at 24 weeks was observed in 42/52 women or 81% (exact 95% CI: 68%–90%). There were no differences in response by country, by number or class of prior pMTCT exposures. While confirmed virologic failure occurred in 8 women, no virologic failures were observed in women reporting perfect early adherence. Conclusions In this first prospective clinical trial studying combination antiretroviral re- treatment in women with a history of pregnancy-limited cART, the observed virologic response to TDF/FTC and EFV at 24 weeks was 81%. Virologic failures occurred and correlated with self-reported non-adherence. PMID:24759064

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

    PubMed Central

    2012-01-01

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

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

    ERIC Educational Resources Information Center

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

    2005-01-01

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

  17. A Guide for Providing Social Services in Head Start.

    ERIC Educational Resources Information Center

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

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

  18. Effect of Antiretroviral Therapy on HIV-mediated Impairment of the Neutrophil Antimycobacterial Response

    PubMed Central

    Bangani, Nonzwakazi; Goliath, Rene; Kampmann, Beate; Wilkinson, Katalin A.; Wilkinson, Robert J.; Martineau, Adrian R.

    2015-01-01

    Rationale: Experimental and epidemiological evidence suggests that neutrophils are important in the host response to tuberculosis. HIV infection, which increases the risk of tuberculosis, adversely affects neutrophil function. Objectives: To determine the impact of HIV and antiretroviral therapy on neutrophil antimycobacterial activity. Methods: We performed a cross-sectional comparison of neutrophil functions in 20 antiretroviral-naive HIV-infected and 20 HIV-uninfected individuals using luminescence-, flow cytometry–, and ELISA-based assays. We then conducted a prospective study in the HIV-infected individuals investigating these parameters during the first 6 months of antiretroviral therapy. Surface markers of neutrophil activation were investigated in a separate cohort using flow cytometry. Measurements and Main Results: HIV infection impaired control of Mycobacterium tuberculosis by neutrophils (mean ratio of mycobacterial luminescence in neutrophil samples vs. serum controls at 1 hour in HIV-infected participants, 0.88 ± 0.13 vs. HIV-uninfected participants, 0.76 ± 0.14; P = 0.01; at 24 hours, 0.82 ± 0.13 vs. 0.71 ± 0.13; P = 0.01). The extent of impairment correlated with log[HIV viral load]. Neutrophil cell death after 24 hours’ incubation with M. tuberculosis was higher in the HIV-infected cohort (85.3 ± 11.8% vs. 57.9 ± 22.4% necrotic cells; P < 0.0001). Neutrophils from HIV-infected participants demonstrated significantly more CD62L-negative cells (median, 23.0 vs. 8.5%; P = 0.008) and CD16-negative cells (3.2 vs. 1.3%, P = 0.03). Antiretroviral therapy restored mycobacterial restriction and pattern of neutrophil death toward levels seen in HIV-uninfected persons. Conclusions: Neutrophils in antiretroviral-naive HIV-infected persons are hyperactivated, eliminate M. tuberculosis less effectively than in HIV-uninfected individuals, and progress rapidly to necrotic cell death. These factors are ameliorated by antiretroviral therapy. PMID:26368270

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  3. 76 FR 50813 - Major Capital Investment Projects; Guidance on News Starts/Small Starts Policies and Procedures

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-16

    ... Federal Transit Administration Major Capital Investment Projects; Guidance on News Starts/Small Starts... policy guidance on the New and Small Starts capital project review and evaluation process and criteria...) published by FTA in June 2010, which sought public comment on the New Starts and Small Starts...

  4. Limiting SLCMs - a better way to START

    SciTech Connect

    Rubin, J.P.

    1989-04-01

    For nearly six years of US-Soviet negotiations on strategic arms, the United States has managed to avoid facing up to the arms control challenge posed by sea-launched cruise missiles (SLCMs). Later in 1989, US and Soviet negotiators are scheduled to resume work on a largely complete START treaty requiring deep reductions in US and Soviet strategic arms. SLCMs seem certain to be the most contentious of the remaining treaty issues. To be sure, until the all-important question of SDI and the ABM Treaty is resolved, the entire negotiation will remain deadlocked. But given the technical, budgetary and legal obstacles SDI faces in the United States, the Soviet willingness to accept less-than-absolute limits on the program, and the stated views of key advisers to President Bush, there are grounds for cautious optimism. Along with its decision on SDI the Bush administration's approach to SLCMs can be viewed as an important indicator of President Bush's interest in completing an early START treaty. A negotiating stance that continues the ill-advised US refusal to establish genuine arms control limitations on SLCMs would suggest that President Bush is unwilling or unable to make the kind of tough political decisions necessary to achieve this historic treaty. On the other hand, if US negotiators are authorized at the appropriate time to explore with the Soviet side some of the new arms control schemes for SLCMs developed over the past several years, not only could START be completed relatively quickly, but the treaty would better serve US security interests.

  5. Alternative starting materials for industrial processes.

    PubMed Central

    Mitchell, J W

    1992-01-01

    In the manufacture of chemical feedstocks and subsequent processing into derivatives and materials, the U.S. chemical industry sets the current standard of excellence for technological competitiveness. This world-class leadership is attributed to the innovation and advancement of chemical engineering process technology. Whether this status is sustained over the next decade depends strongly on meeting increasingly demanding challenges stimulated by growing concerns about the safe production and use of chemicals without harmful impacts on the environment. To comply with stringent environmental regulations while remaining economically competitive, industry must exploit alternative benign starting materials and develop environmentally neutral industrial processes. Opportunities are described for development of environmentally compatible alternatives and substitutes for some of the most abundantly produced, potentially hazardous industrial chemicals now labeled as "high-priority toxic chemicals." For several other uniquely important commodity chemicals where no economically competitive, environmentally satisfactory, nontoxic alternative starting material exists, we advocate the development of new dynamic processes for the on-demand generation of toxic chemicals. In this general concept, which obviates mass storage and transportation of chemicals, toxic raw materials are produced in real time, where possible, from less-hazardous starting materials and then chemically transformed immediately into the final product. As a selected example for semiconductor technology, recent progress is reviewed for the on-demand production of arsine in turnkey electrochemical generators. Innovation of on-demand chemical generators and alternative processes provide rich areas for environmentally responsive chemical engineering processing research and development for next-generation technology. Images PMID:11607260

  6. Turbojet-engine Starting and Acceleration

    NASA Technical Reports Server (NTRS)

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

    1956-01-01

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

  7. Getting Started in Research with Undergraduates

    NASA Astrophysics Data System (ADS)

    Schuh, Merlyn D.; Karukstis, Kerry K.

    2004-03-01

    The Council on Undergraduate Research (CUR) is a leading advocate and promoter of high-quality collaborative undergraduate student-faculty research. This article outlines the activities and programs of CUR and briefly describes services available to CUR members. Two of CUR's "How to…" booklets are described that relate to starting a research career and mentoring of undergraduate students. The article highlights forthcoming conferences and institutes sponsored by CUR and notes new features of the CUR Quarterly that are of special interest to faculty who supervise undergraduate researchers. Readers are directed to the CUR Web site for additional information.

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

    PubMed Central

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

    2015-01-01

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

  9. Short message service (SMS) reminders and real-time adherence monitoring improve antiretroviral therapy adherence in rural Uganda

    PubMed Central

    Haberer, Jessica E.; Musiimenta, Angella; Atukunda, Esther C.; Musinguzi, Nicholas; Wyatt, Monique A.; Ware, Norma C.; Bangsberg, David R.

    2016-01-01

    Objective: To explore the effects of four types of short message service (SMS) plus real-time adherence monitoring on antiretroviral therapy (ART) adherence: daily reminders, weekly reminders, reminders triggered after a late or missed dose (delivered to patients), and notifications triggered by sustained adherence lapses (delivered to patient-nominated social supporters). Design: Pilot randomized controlled trial. Methods: Sixty-three individuals initiating ART received a real-time adherence monitor and were randomized (1 : 1 : 1): (1) Scheduled SMS reminders (daily for 1 month, weekly for 2 months), then SMS reminders triggered by a late or missed dose (no monitoring signal within 2 h of expected dosing); SMS notifications to social supporters for sustained adherence lapses (no monitoring signal for >48 h) added after 3 months. (2) Triggered SMS reminders starting at enrolment; SMS notifications to social supporters added after 3 months. (3) Control: No SMS. HIV RNA was determined at 9 months. Percentage adherence and adherence lapses were compared by linear generalized estimating equations and Poisson regression, respectively. Results: Median age was 31 years, 65% were women, and median enrolment CD4+ cell count was 322 cells/μl 97% took once daily tenofovir/emtricitabine/efavirenz. Compared to control, adherence was 11.1% higher (P = 0.04) and more than 48-h lapses were less frequent (IRR 0.6, P = 0.02) in the scheduled SMS arm. Adherence and more than 48-h lapses were similar in the triggered SMS arm and control. No differences in HIV RNA were seen. Conclusion: Scheduled SMS reminders improved ART in the context of real-time monitoring. Larger studies are needed to determine the impact of triggered reminders and role of social supporters in improving adherence. PMID:26760452

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

    PubMed Central

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

    2009-01-01

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

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

    PubMed Central

    2014-01-01

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

  12. Five-year follow-up of children with perinatal HIV-1 infection receiving early highly active antiretroviral therapy

    PubMed Central

    2009-01-01

    Background Early highly active antiretroviral therapy (HAART), started within the first months of age, has been proven to be the optimal strategy to prevent immunological and clinical deterioration in perinatally HIV-infected children. Nevertheless, data about long-term follow-up of early treated children are lacking. Methods We report data from 40 perinatally HIV-infected-children receiving early HAART, with a median follow-up period of 5.96 years (interquartile range [IQR]:4.21–7.62). Children were enrolled at birth in the Italian Register for HIV Infection in Children. Comparison with 91 infected children born in the same period, followed-up from birth, and receiving deferred treatment was also provided. Results Nineteen children (47.5%) were still receiving their first HAART regimen at last follow-up. In the remaining children the first regimen was discontinued, after a median period of 3.77 years (IQR: 1.71–5.71) because of viral failure (8 cases), liver toxicity (1 case), structured therapy interruption (3 cases), or simplification/switch to a PI-sparing regimen (9 cases). Thirty-nine (97.5%) children showed CD4+ T-lymphocyte values>25%, and undetectable viral load was reached in 31 (77.5%) children at last visit. Early treated children displayed significantly lower viral load than not-early treated children, until 6 years of age, and higher median CD4+ T-lymphocyte percentages until 4 years of age. Twenty-seven (29.7%) not-early treated vs. 0/40 early treated children were in clinical category C at last follow-up (P < 0.0001). Conclusion Our findings suggest that clinical, virologic and immunological advantages from early-HAART are long-lasting. Recommendations indicating the long-term management of early treated children are needed. PMID:19709432

  13. Treatment with Antiretroviral Therapy is Not Associated with Increased Sexual Risk Behaviour in Kenyan Female Sex Workers

    PubMed Central

    McClelland, R. Scott; Graham, Susan M.; Richardson, Barbra A.; Peshu, Norbert; Masese, Linnet N.; Wanje, George H.; Mandaliya, Kishorchandra N.; Kurth, Ann E.; Jaoko, Walter; Ndinya-Achola, J. O.

    2010-01-01

    Objective The objective of this study was to test the hypothesis that sexual risk behaviour would increase following initiation of antiretroviral therapy (ART) in Kenyan female sex workers (FSWs). Design Prospective cohort study. Setting FSW cohort in Mombasa, Kenya, 1993-2008. Subjects 898 women contributed HIV-1-seropositive follow-up visits, of whom 129 initiated ART. Intervention Beginning in March 2004, ART was provided to women qualifying for treatment according to Kenyan National Guidelines. Participants received sexual risk reduction education and free condoms at every visit. Main Outcome Measures Main outcome measures included unprotected intercourse, abstinence, 100% condom use, number of sexual partners, and frequency of sex. Outcomes were evaluated at monthly follow-up visits using a one week recall interval. Results Compared to non-ART-exposed follow-up, visits following ART initiation were not associated with an increase in unprotected sex (adjusted odds ratio [AOR] 0.86, 95% confidence interval [CI] 0.62-1.19, P=0.4). There was a non-significant decrease in abstinence (AOR 0.81, 95% CI 0.65-1.01, P=0.07), which was offset by a substantial increase in 100% condom use (AOR 1.54, 95% CI 1.07-2.20, P=0.02). Numbers of sex partners and frequency of sex were similar before versus after starting ART. A trend for decreased sexually transmitted infections following ART initiation provides additional support for the validity of the self-reported behavioural outcomes (AOR 0.67, 95% CI 0.44-1.02, P=0.06). Conclusions In the setting of ongoing risk reduction education and provision of free condoms, initiation of ART was not associated with increased sexual risk behaviour in this cohort of Kenyan FSWs. PMID:20179576

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  16. AIDS and non-AIDS related mortality in the Asia Pacific region in the era of combination antiretroviral treatment

    PubMed Central

    Falster, Kathleen; Choi, Jun Yong; Donovan, Basil; Duncombe, Chris; Mulhall, Brian; Sowden, David; Zhou, Jialun; Law, Matthew G.

    2010-01-01

    Introduction Although studies have shown reductions in mortality from AIDS after the introduction of combination antiretroviral treatment (cART), little is known about cause-specific mortality in low income settings in the cART era. We explored predictors of AIDS and non-AIDS mortality and compared cause-specific mortality across high and low income settings in the Asia Pacific region. Methods We followed patients in the Asia Pacific HIV Observational Database from the date they started cART (or cohort enrolment if cART initiation was identified retrospectively), until the date of death or last follow-up visit. Competing risks methods were used to estimate the cumulative incidence, and to investigate predictors, of AIDS and non-AIDS mortality. Results Of 4252 patients, 215 died; 89 from AIDS, 97 from non-AIDS causes and 29 from unknown causes. Age >50 years (hazard ratio (HR), 4.29; 95%CI, 2.10-8.79) and CD4 counts ≤100 cells/μL (HR, 8.59; 95%CI, 5.66-13.03) were associated with an increased risk of non-AIDS mortality. Risk factors for AIDS mortality included CD4 counts ≤100 cells/μL (HR, 34.97; 95%CI, 18.01-67.90) and HIV RNA ≥10,001 (HR 4.21; 95%CI 2.07-8.55). There was some indication of a lower risk of non-AIDS mortality in Asian high, and possibly low, income countries compared to Australia. Conclusions Immune deficiency is associated with an increased risk of AIDS and non-AIDS mortality. Older age predicts non-AIDS mortality in the cART era. Less conclusive was the association between country-income level and cause-specific mortality because of the relatively high proportion of unknown causes of death in low income settings. PMID:19752715

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2009-05-01

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

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed Central

    Chang, Bei-Hung; Sommers, Elizabeth

    2011-01-01

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

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

    PubMed Central

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

    2011-01-01

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

  2. Metabolic syndrome before and after initiation of antiretroviral therapy in treatment-naïve HIV-infected individuals

    PubMed Central

    Krishnan, S; Schouten, JT; Atkinson, B; Brown, T; Wohl, D; McComsey, GA; Glesby, MJ; Shikuma, C; Haubrich, R; Tebas, P; Campbell, TB; Jacobson, DL

    2012-01-01

    Background Metabolic syndrome (MetS) is a cluster of risk factors for cardiovascular disease and diabetes, many of which are associated with HIV and antiretroviral therapy (ART). We examined prevalence and incidence of MetS, and risk factors for MetS in ART-naïve HIV-infected individuals starting ART. Methods MetS, defined by the Adult Treatment Panel III criteria, was assessed at and after ART initiation in HIV-infected individuals who enrolled in selected AIDS Clinical Trials Group (ACTG) trials and were followed long-term after these trials as part of the ACTG Longitudinal Linked Randomized Trials cohort. Cox proportional hazards models were used to examine risk factors of incident MetS. Adjusted hazard ratios (aHR) and 95% confidence intervals (CI) are reported. Results At ART initiation, the prevalence of MetS was 20%. After ART initiation, the incidence of MetS was 8.5 per 100 person-years. After adjusting for demographics and body mass index, the risk of MetS was decreased for CD4+ T-cell counts>50 cells/mm3 (aHR = 0.62, 95% CI=0.43 to 0.90 for CD4>500), and the risk was increased for HIV-1 RNA >400 copies/mL (aHR=1.55 (95% CI=1.25 to 1.92) and use of a protease-inhibitor (PI) based regimen (relative to no PI use, aHR=1.25 (95% CI=1.04 to 1.51) for any PI use). Conclusion In HIV-infected individuals on ART, virologic suppression and maintenance of high CD4+ T-cell counts may be potentially modifiable factors that can reduce the risk of MetS. The effect of MetS on the risk of cardiovascular disease and diabetes needs to be evaluated. PMID:22828718

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

    PubMed

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

    2016-01-01

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

  4. Expansion of HIV care and treatment in Yunnan Province, China: treatment outcomes with scale up of combination antiretroviral therapy.

    PubMed

    Chen, Juemin; Yu, Bo; Wang, Yungshen; Tang, Michele; Hu, Yanhong; Cai, Thomas; Zhang, Fujie; von Zinkernagel, Deborah; Harwell, Joseph I; Huang, Zhihuan Jennifer

    2014-01-01

    Effective health care models to scale up combination antiretroviral therapy (ART) are needed in rural southwestern China. We aimed to evaluate the ART treatment outcomes and their associations with patients' demographic characteristics and pre-treatment clinical features in a scaled-up provincial ART program serving eight heavily HIV-affected prefectures in Yunnan Province. We abstracted information from a computerized database for adults initiating ART between July 2007 and September 2008. Survival functions of mortality and treatment failure were calculated by age group, gender, transmission mode, and baseline CD4 count. Multivariable Cox regression analyses were conducted to find independent associations of various demographic and baseline clinical features with outcome variables. Of the 1967 patients in the mortality analysis, there were 110 deaths, of which 16 were coded as accidents or suicides. Adjusted hazard ratios (AHR) associated with mortality were greater for patients with baseline CD4 counts <100 cells/µl vs. patients with CD4 counts ≥200 cells/µl, for male vs. female, for single vs. married, and for those acquired HIV through injection drug use (IDU) vs. other modes of transmission. Successful treatment was 81.3% at six months after treatment started. Immunologic treatment failure was associated with baseline CD4 counts but not with demographic characteristics. Overall loss to follow-up rate was 2.1%. Collaboration between clinics and community networks are distinctive features of Yunnan's model for scaling up ART across a diverse, poor, and rural population. This study finds that the strategy can succeed even if 40% of the patients have a history of IDU. PMID:24116389

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

    PubMed Central

    Moltó, José; Sirera, Guillem; Clotet, Bonaventura

    2015-01-01

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

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

    PubMed

    Chabrol, Fanny

    2014-08-01

    Often celebrated as a model of development in Africa, Botswana nonetheless endured a severe HIV epidemic. This article describes the singularity of the Botswana experience in facing AIDS and creating the widest possible access to antiretroviral medications for its citizens. Through exploration of different sets of actors and the construction of their ethics of treatment, it is possible to examine how free and universal access was created within the national antiretroviral program. This article underscores the importance of the site and the local dynamics in the advent of an ethics of access to treatment for Botswana citizens. At the intersection of national citizenship, pharmaceutical philanthropy, and biomedical collaborations, Botswana is an exemplary case (one of the first and unique in its kind) of global health programs for access to drugs in which patients' rights are tied to science and pharmaceutical development. As such it also bears some limitations and concerns over its sustainability. PMID:24720398

  7. Commentary: Early antiretroviral therapy for HIV infection in sub-Saharan Africa, a challenging new step.

    PubMed

    Laurent, Christian

    2010-12-01

    Recent changes in guidelines (World Health Organization (WHO), USA, and likely Europe soon) all move towards earlier initiation of antiretroviral therapy in asymptomatic patients infected with human immunodeficiency virus (HIV). Sonia Menon appropriately questions the feasibility and consequences at both individual and community levels of the early initiation of antiretroviral therapy in sub-Saharan Africa as likely effects will be both positive and negative. Local context should drive the uptake process in every country. Money, national and international, will be essential for the successful implementation of the new WHO recommendation. Leaders at both levels must take their responsibilities and mobilize the necessary resources, for example, doubling those for the Global Fund to Fight AIDS, Tuberculosis and Malaria from $10 billion to $20 billion USD for 2011-2013. PMID:21119647

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

    PubMed Central

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

    2006-01-01

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

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

    PubMed

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

    2014-07-01

    Antiretroviral hair levels objectively quantify drug exposure over time and predict virologic responses. We assessed the acceptability and feasibility of collecting small hair samples in a rural Kenyan cohort. Ninety-five percentage of participants (354/373) donated hair. Although median self-reported adherence was 100% (interquartile range, 96%-100%), a wide range of hair concentrations likely indicates overestimation of self-reported adherence and the advantages of a pharmacologic adherence measure. Higher nevirapine hair concentrations observed in women and older adults require further study to unravel behavioral versus pharmacokinetic contributors. In resource-limited settings, hair antiretroviral levels may serve as a low-cost quantitative biomarker of adherence. PMID:24694932

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

    PubMed

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

    2015-08-01

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

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

    PubMed Central

    2010-01-01

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

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

    PubMed

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

    2015-05-01

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

  13. The occurrence of anti-retroviral compounds used for HIV treatment in South African surface water.

    PubMed

    Wood, Timothy Paul; Duvenage, Cornelia S J; Rohwer, Egmont

    2015-04-01

    The study and quantification of personal care products, such as pharmaceuticals, in surface water has become popular in recent years; yet very little description of these compounds' presence in South African surface water exists in the literature. Antiretrovirals (ARVs), used to treat human immunodeficiency virus (HIV) are rarely considered within this field. A new method for the simultaneous quantification of 12 antiretroviral compounds in surface water using the standard addition method is described. Water samples were concentrated by a generic automated solid phase extraction method and analysed by ultra-high pressure liquid chromatography tandem mass spectrometry (UHPLC-MS/MS). Substantial matrix effect was encountered in the samples with an average method detection limit of 90.4 ng/L. This is the first reported countrywide survey of South African surface water for the quantification of these compounds with average concentrations ranging between 26.5 and 430 ng/L. PMID:25681819

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

    PubMed Central

    Ferguson, Lindsay M; Rohan, Lisa Cencia

    2012-01-01

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

  15. Antiretroviral Therapy in Relation to Birth Outcomes among HIV-infected Women: A Cohort Study.

    PubMed

    Li, Nan; Sando, Mary Mwanyika; Spiegelman, Donna; Hertzmark, Ellen; Liu, Enju; Sando, David; Machumi, Lameck; Chalamilla, Guerino; Fawzi, Wafaie

    2016-04-01

    Although the beneficial effects of antiretroviral (ARV) therapy for preventing mother-to-child transmission are indisputable, studies in developed and developing countries have reported conflicting findings on the association between ARV exposure and adverse birth outcomes. We conducted a prospective observational study at 10 human immunodeficiency virus (HIV) care and treatment centers in Dar es Salaam, Tanzania. Multivariate log-binomial regression was used to investigate the associations between ARV use and adverse birth outcomes among HIV-negative HIV-exposed infants. Our findings demonstrate an increased risk of adverse birth outcomes associated with the use of highly active antiretroviral therapy during pregnancy. Further studies are needed to investigate the underlying mechanisms and identify the safest ARV regimens for use during pregnancy. PMID:26265780

  16. "Doing the Best We Can": Providing Care in a Malawian Antiretroviral Clinic.

    PubMed

    Rosenthal, Anat

    2016-01-01

    Following a national policy shift toward universal access to antiretroviral therapy (ART) in Malawi, hospitals and clinics around the country made major changes to enable the provision of ART. In this already resource-limited environment, the provision of ART brought new health care delivery challenges to bear on both patients and health care professionals. The substance and form of these local interventions are affected by a multilayered global context. Drawing on fieldwork in an antiretroviral clinic in rural Malawi, this article discusses the daily implications of providing and receiving care in the context of a massive global shift in health policy, and argues that in order to fully understand the process of service rollout in all its complexity, care should be explored not only from the patients' perspective but also from that of local and international health care professionals and policymakers. PMID:26258466

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

    PubMed Central

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

    2009-01-01

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

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

    PubMed

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

    2013-04-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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