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Sample records for starting nevirapine-containing antiretroviral

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

    PubMed

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

    2015-12-01

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

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

    PubMed Central

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

    2014-01-01

    Objectives Artesunate plus amodiaquine is used for malaria treatment in regions with overlapping HIV endemicity. Co-administration of artesunate/amodiaquine with antiretroviral therapy (ART) may result in drugdrug interactions, but minimal data exist. This study evaluated the impact of nevirapine-based ART, containing a backbone of zidovudine and lamivudine, on the disposition of amodiaquine and its active metabolite, desethylamodiaquine (DEAQ). Methods This was an open-label, parallel-group pharmacokinetic comparison between HIV-infected, adult subjects receiving steady-state nevirapine-based ART (n?=?10) and ART-naive subjects (control group, n?=?11). All subjects received a loose formulation of artesunate/amodiaquine (200/600 mg) daily for 3 days, with serial pharmacokinetic sampling over 96 h following the final dose of artesunate/amodiaquine. Amodiaquine and DEAQ were quantified using a validated HPLC method with UV detection. Pharmacokinetic parameters were determined using standard non-compartmental methods. Results Exposures to both amodiaquine and DEAQ were significantly lower in the nevirapine-based ART group compared with the control group (amodiaquine AUC024 145 versus 204 ngh/mL, P?=?0.02; DEAQ AUC096 14?571 versus 21?648 ngh/mL, P?

  3. When to Start Antiretroviral Therapy

    MedlinePLUS

    ... last reviewed 2/24/2016) Key Points Antiretroviral therapy (ART) is the use of HIV medicines to treat ... HIV medicine? Treatment with HIV medicines (called antiretroviral therapy or ART for short) is recommended for everyone infected with ...

  4. When to start antiretroviral therapy: as soon as possible

    PubMed Central

    2013-01-01

    Background The debate regarding When to Start antiretroviral therapy has raged since the introduction of zidovudine in 1987. Based on the entry criteria for the original Burroughs Wellcome 002 study, the field has been anchored to CD4 cell counts as the prime metric to indicate treatment initiation for asymptomatic individuals infected with Human Immunodeficiency Virus. The pendulum has swung back and forth based mostly on the relative efficacy, toxicity and convenience of available regimens. Discussion In todays world, several factors have converged that compel us to initiate therapy as soon as possible: 1) The biology of viral replication (1 to 10 billion viruses per day) strongly suggests that we should be starting early. 2) Resultant inflammation from unchecked replication is associated with earlier onset of multiple co-morbid conditions. 3) The medications available today are more efficacious and less toxic than years past. 4) Clinical trials have demonstrated benefits for all but the highest CD4 strata (>500 cells/?l). 5) Some cohort studies have demonstrated the clear benefit of antiretroviral therapy at any CD4 count and no cohort studies have demonstrated that early therapy is more detrimental than late therapy at the population level. 6) In addition to the demonstrated and inferred benefits to the individual patient, we now have evidence of a Public Health benefit from earlier intervention: treatment is prevention. Summary From a practical, common sense perspective we are talking about life-long therapy. Whether we start at a CD4 count of 732 cells/?l or 493 cells/?l, the patient will be on therapy for over 40 to 50 years. There does not seem to be much benefit in waiting and there likely is significant long-term harm. Do not wait. Treat early. The counter-argument to this debate topic can be freely accessed here: http://www.biomedcentral.com/1741-7015/11/148. PMID:23767762

  5. 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

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

    PubMed

    Mir, Jos M; Manzardo, Christian; Zamora, Laura; Pumarola, Tomas; Herreras, Zoe; Gallart, Teresa; Gatell, Jos 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

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

    PubMed Central

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

    2012-01-01

    Objective To provide estimates of mortality among HIV-infected patients starting combination antiretroviral therapy. Methods We report on the death rates from 122?925 adult HIV-infected patients aged 15?years or older from East, Southern and West Africa, Asia Pacific and Latin America. We use two methods to adjust for biases in mortality estimation resulting from loss from follow-up, based on double-sampling methods applied to patient outreach (Kenya) and linkage with vital registries (South Africa), and apply these to mortality estimates in the other three regions. Age, gender and CD4 count at the initiation of therapy were the factors considered as predictors of mortality at 6, 12, 24 and >24?months after the start of treatment. Results Patient mortality was high during the first 6?months after therapy for all patient subgroups and exceeded 40 per 100 patient years among patients who started treatment at low CD4 count. This trend was seen regardless of region, demographic or disease-related risk factor. Mortality was under-reported by up to or exceeding 100% when comparing estimates obtained from passive monitoring of patient vital status. Conclusions Despite advances in antiretroviral treatment coverage many patients start treatment at very low CD4 counts and experience significant mortality during the first 6?months after treatment initiation. Active patient tracing and linkage with vital registries are critical in adjusting estimates of mortality, particularly in low- and middle-income settings. PMID:23172344

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

    PubMed Central

    2013-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  10. 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

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

    PubMed Central

    2014-01-01

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

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

    PubMed Central

    Siedner, Mark J.

    2016-01-01

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

  13. 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

  14. 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

  15. 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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2009-01-01

    Background Mortality in HIV-infected patients who have access to highly active antiretroviral therapy (ART) has declined in sub-Saharan Africa, but it is unclear how mortality compares to the non-HIVinfected population. We compared mortality rates observed in HIV-1infected patients starting ART with non-HIVrelated background mortality in four countries in sub-Saharan Africa. Methods and Findings Patients enrolled in antiretroviral treatment programmes in Cte d'Ivoire, Malawi, South Africa, and Zimbabwe were included. We calculated excess mortality rates and standardised mortality ratios (SMRs) with 95% confidence intervals (CIs). Expected numbers of deaths were obtained using estimates of age-, sex-, and country-specific, HIV-unrelated, mortality rates from the Global Burden of Disease project. Among 13,249 eligible patients 1,177 deaths were recorded during 14,695 person-years of follow-up. The median age was 34 y, 8,831 (67%) patients were female, and 10,811 of 12,720 patients (85%) with information on clinical stage had advanced disease when starting ART. The excess mortality rate was 17.5 (95% CI 14.521.1) per 100 person-years SMR in patients who started ART with a CD4 cell count of less than 25 cells/l and World Health Organization (WHO) stage III/IV, compared to 1.00 (0.551.81) per 100 person-years in patients who started with 200 cells/l or above with WHO stage I/II. The corresponding SMRs were 47.1 (39.156.6) and 3.44 (1.916.17). Among patients who started ART with 200 cells/l or above in WHO stage I/II and survived the first year of ART, the excess mortality rate was 0.27 (0.080.94) per 100 person-years and the SMR was 1.14 (0.472.77). Conclusions Mortality of HIV-infected patients treated with combination ART in sub-Saharan Africa continues to be higher than in the general population, but for some patients excess mortality is moderate and reaches that of the general population in the second year of ART. Much of the excess mortality might be prevented by timely initiation of ART. Please see later in the article for Editors' Summary PMID:19399157

  18. 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...

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

    PubMed Central

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

    2013-01-01

    Background Tuberculosis (TB) is common among HIV-infected individuals in many resource-limited countries and has been associated with poor survival. We evaluated morbidity and mortality among individuals first starting antiretroviral therapy (ART) with concurrent active TB or other AIDS-defining disease using data from the Prospective Evaluation of Antiretrovirals in Resource-Limited Settings (PEARLS) study. Methods Participants were categorized retrospectively into three groups according to presence of active confirmed or presumptive disease at ART initiation: those with pulmonary and/or extrapulmonary TB (TB group), those with other non-TB AIDS-defining disease (other disease), or those without concurrent TB or other AIDS-defining disease (no disease). Primary outcome was time to the first of virologic failure, HIV disease progression or death. Since the groups differed in characteristics, proportional hazard models were used to compare the hazard of the primary outcome among study groups, adjusting for age, sex, country, screening CD4 count, baseline viral load and ART regimen. Results 31 of 102 participants (30%) in the TB group, 11 of 56 (20%) in the other disease group, and 287 of 1413 (20%) in the no disease group experienced a primary outcome event (p?=?0.042). This difference reflected higher mortality in the TB group: 15 (15%), 0 (0%) and 41 (3%) participants died, respectively (p<0.001). The adjusted hazard ratio comparing the TB and no disease groups was 1.39 (95% confidence interval: 0.932.10; p?=?0.11) for the primary outcome and 3.41 (1.726.75; p<0.001) for death. Conclusions Active TB at ART initiation was associated with increased risk of mortality in HIV-1 infected patients. PMID:24391801

  20. 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

  1. 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

  2. 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

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

    PubMed Central

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

    2014-01-01

    Objective: Few data describe antiretroviral treatment (ART)-related adverse events when treatment is initiated at CD4+ cell counts more than 350?cells/?l. We compared rates of laboratory-defined adverse events (LDAEs) according to CD4+ cell count at ART initiation. Design: Analysis of on-going cohort study. Methods: ART-naive persons initiating ART from 2000 to 2010 were included. Chi-square, analysis of variance (ANOVA) and KruskalWallis tests compared characteristics among those starting ART with a CD4+ cell count of 350 or less, 351499 and at least 500?cells/?l. Time-updated Poisson regression compared rates of LDAE in the three CD4+ cell strata. Cox proportional hazard models compared risk of ART discontinuation. Results: Nine thousand, four hundred and six individuals were included: median age 37 years, 61% white, 80% men, median viral load 4.8?log copies/ml. Four hundred and forty-seven (4.9%) and 1099 (11.7%) started ART with a CD4+ cell count at least 500 and 351499?cells/?l, respectively. One thousand, two hundred and eighty-three (13.6%) patients experienced at least one LDAE. The rate of LDAE did not differ between those starting ART with a CD4+ cell count 351499 and less than 350?cells/?l [relative rate 0.90, 95% confidence interval (CI) 0.741.09)], but an increased risk of ART discontinuation was observed (hazard ratio 1.58, 95% CI 1.102.27). Those starting ART at CD4+ cell count at least 500?cells/?l had an increased rate of LDAE (relative rate 1.44, 95% CI 1.131.82) but were not more likely to discontinue ART (hazard ratio 1.15, 95% CI 0.642.09). Conclusion: This study demonstrates the need to consider ART-related toxicities when initiating therapy at CD4+ cell counts at least 500?cells/?l. Whilst evidence from randomized controlled trials is awaited, the timing of ART initiation in terms of benefits and risks of ART remains an important question. PMID:24583670

  4. 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

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

    PubMed

    Eholi, 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 Cte 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 Cte 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

  6. Differing spectrum of HIV-associated ophthalmic disease among patients starting antiretroviral therapy in India and South Africa

    PubMed Central

    Pathai, Sophia; Gilbert, Clare; Weiss, Helen A; McNally, Matthew; Lawn, Stephen D

    2011-01-01

    Differences in the prevalence and spectrum of HIV-associated ophthalmic disease in Africa and Asia are not well documented. We studied two comparable cohorts of patients initiating antiretroviral therapy in Mumbai, India, and Cape Town, South Africa. The prevalence of HIV-associated ophthalmic disease was higher in the Indian population (17.5%) than in the South African population (12.1%). This was largely because of vitreo-retinal opportunistic infections (11.4%vs. 2.6%, respectively), notably cytomegalovirus retinitis. This difference persisted after adjusting for confounding factors (adjusted odds ratio = 11.32, 95% confidence interval: 2.6748.13), confirming a marked geographical difference in the prevalence of HIV-associated retinal disease. PMID:21371217

  7. 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

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

    PubMed Central

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

    2014-01-01

    Purpose Young people with behaviorally acquired HIV (BHIV) are less likely than adults to initiate antiretroviral therapy (ART) despite meeting treatment criteria. We explored critical factors involved in healthcare providers decision-making regarding ART initiation for young people with BHIV (ages 1224). Methods Semi-structured interviews were conducted with 23 HIV providers from diverse training backgrounds caring for youth with BHIV at 4 adult clinics and 1 pediatric clinic in a high prevalence urban city. Interview domains probed clinical and non-clinical patient characteristics, the role of adherence, and provider attitudes working with youth to establish decision-making priorities for ART initiation. The constant comparative approach was used to develop grounded theory on providers decision-making on ART initiation. Results Clinical criteria, particularly the CD4 count, and the public health implications of HIV transmission determined the urgency for ART initiation. However, patient-related concerns regarding treatment readiness and adherence hampered the decision to initiate, especially at higher CD4 counts. Providers who acknowledged developmental characteristics of youth (e.g. evolving adult identity and self-efficacy around health management) appeared more cautious in assessing future ART adherence and responded with intensive clinical support. Extensive involvement of multidisciplinary teams was identified as an important strategy to retain youth in care, whereas strengthening youth-targeted approaches may be an unmet need in adult clinics. Conclusion Evaluation of providers awareness of the developmental features of youth and characteristics of youth-targeted approaches in clinics caring for youth with BHIV may inform interventions to increase youth engagement in care and subsequent decisions to successfully initiate ART. PMID:24794054

  9. 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

  10. 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

  11. 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

  12. 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) (388kcal/day) or ART alone (Controls) for 6months. Patients returned for monthly assessments and blood was drawn at enrolment and 6months on ART. Differences in body composition, biochemical and laboratory parameters were estimated at 6months on treatment. Results Of the 36 randomized patients, 26 completed the 6month 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 12105 vs 107 cells/mm3 [IQR 63165]; p?=?0.149) and hemoglobin (10.3g/dL [IQR 9.0-11.3] vs 13.1g/dL [IQR 11.1-14.7]; p?=?0.001). At 6months, NS patients increased their median CD4 count by 151 cells/mm3 [IQR 120174) vs 77 cells/mm3 [IQR 33145] 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 6months 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

  13. Pharmacogenetics of toxicity, plasma trough concentration and treatment outcome with nevirapine-containing regimen in anti-retroviral-nave HIV-infected adults: an exploratory study of the TRIANON ANRS 081 trial.

    PubMed

    Gozalo, Claire; Grard, Laurence; Loiseau, Pascale; Morand-Joubert, Laurence; Peytavin, Gilles; Molina, Jean-Michel; Dellamonica, Pierre; Becquemont, Laurent; Aboulker, Jean-Pierre; Launay, Odile; Verstuyft, Cline

    2011-12-01

    The aim of this exploratory study was to investigate in a homogeneous population of anti-retroviral nave HIV-1-infected adults, the relationships between genetic polymorphisms involved in nevirapine metabolism [CYP2B6 516G>T, 785A>G and 1459C>T; CYP3A5 6986A>G (CYP3A5*3)], transport (ABCB1 2677G>T/A and 3435C>T), and antigen recognition (HLA-DRB1*0101), and the hepatic and/or cutaneous toxicity occurring within the first 8 or 72 weeks of treatment, plasma trough concentrations (C(trough) ) at week 8 and immuno-virological response to nevirapine at week 24. Associations between genetic polymorphisms and toxicity, C(trough) and response to nevirapine were performed in a population of 72 HIV-1 positive and nevirapine-treated patients followed during 72 weeks, as part of the previous study called: ANRS081 'Trianon' trial. Among the 18 patients who developed toxicity events during the 72 weeks of the study, 12 patients exhibited early toxicity before week 8. No significant association could be evidenced between any of the analysed single nucleotide polymorphisms (SNPs) and nevirapine early or global toxicity, pharmacokinetics and immuno-virological responses even though a possible association between CYP2B6 516G>T and 1459C>T and the trough level of nevirapine was suggested. PMID:21824325

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

    PubMed

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

    2012-12-01

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

  16. 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

  17. 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

  18. AIDS and Non-AIDS Morbidity and Mortality Across the Spectrum of CD4 Cell Counts in HIV-Infected Adults Before Starting Antiretroviral Therapy in Cte dIvoire

    PubMed Central

    Minga, Albert; Gabillard, Delphine; Ouassa, Timothe; Messou, Eugene; Morris, Brandon; Traore, Moussa; Coulibaly, Ali; Freedberg, Kenneth A.; Lewden, Charlotte; Mnan, Herv; Abo, Yao; Dakoury-Dogbo, Nicole; Toure, Siaka; Seyler, Catherine

    2012-01-01

    Background.?In Western Europe, North America, and Australia, large cohort collaborations have been able to estimate the short-term CD4 cell countspecific risk of AIDS or death in untreated human immunodeficiency virus (HIV)infected adults with high CD4 cell counts. In subSaharan Africa, these CD4 cell countspecific estimates are scarce. Methods.?From 1996 through 2006, we followed up 2 research cohorts of HIV-infected adults in Cte dIvoire. This included follow-up off antiretroviral therapy (ART) across the entire spectrum of CD4 cell counts before the ART era, and only in patients with CD4 cell counts >200?cells/?L once ART became available. Data were censored at ART initiation. We modeled the CD4 cell count decrease using an adjusted linear mixed model. CD4 cell countspecific rates of events were obtained by dividing the number of first events occurring in a given CD4 cell count stratum by the time spent in that stratum. Results.?Eight hundred sixty patients were followed off ART over 2789 person-years (PY). In the ?650, 500649, 350499, 200349, 100199, 5099, and 049?cells/?L CD4 cell count strata, the rates of AIDS or death were 0.9, 1.7, 3.7, 10.4, 30.9, 60.8, and 99.9 events per 100 PY, respectively. In patients with CD4 cell counts ?200 CD4?cells/?L, the most frequent AIDS-defining disease was tuberculosis (decreasing from 4.0 to 0.6 events per 100 PY for 200349 and ?650 cells/?L, respectively), and the most frequent HIV non-AIDS severe diseases were visceral bacterial diseases (decreasing from 9.1 to 3.6 events per 100 PY). Conclusions.?Rates of AIDS or death, tuberculosis, and invasive bacterial diseases are substantial in patients with CD4 cell counts ?200 cells/?L. Tuberculosis and bacterial diseases should be the most important outcomes in future trials of early ART in subSaharan Africa. PMID:22173233

  19. [Characteristics of antiretroviral drugs].

    PubMed

    Ribera, Esteban; Tuset, Montse; Martn, Maite; del Cacho, Elena

    2011-05-01

    As of November 2010, a total of 22 antiretroviral agents are marketed in Spain. These agents are divided into 6 classes according to their mechanism of action: 1) nucleos(t)ide reverse transcriptase inhibitors (NRTI) (abacavir, didanosine, emtricitabine, stavudine, lamivudine, zidovudine, and tenofovir), 2) non-nucleoside reverse transcriptase inhibitors (NNRTI) (efavirenz, etravirine, and nevirapine), 3) protease inhibitors (PI) (atazanavir, darunavir, fosamprenavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, tipranavir), 4) entry inhibitors (enfuvirtide), 5) coreceptor CCR5 inhibitors (maraviroc), and 6) integrase inhibitors (raltegravir). All 22 agents are indicated for the treatment of HIV-1 infection in combination with other antiretroviral drugs. Most have also proven to be active against HIV-2 (except the NNRTIs, enfuvirtide, and maraviroc) and some are active against hepatitis B virus (lamivudine, emtricitabine, and tenofovir). The present article reviews the main characteristics of the different antiretroviral agents and classes, namely, commercial presentations, paediatric and adult dosages, dose adjustments in renal and hepatic insufficiency, pharmacokinetics and interactions, mechanism of action, treatment indications, resistance, adverse effects, and safety during pregnancy and breastfeeding. Some of the characteristics of antiretrovirals are class-specific and common to other agents of the same class, and others are individual and different from those of other drugs in the same class. Knowledge of these characteristics enables us to prepare efficacious therapeutic regimens according to the specific requirements of the patient (tolerability, simplicity, adaptability to lifestyle) and clinical setting (naive, simplification, rescue, resistance). PMID:21531048

  20. [Antiretroviral therapy and pregnancy].

    PubMed

    Wunder, D; Evison, J M

    2005-01-01

    Whereas the perinatal transmission rate with untreated HIV positive women is around 30%, the results of Pediatric AIDS Clinical Trials Group in 1994 showed a reduction by nearly 70% with Zidovudin chemoprophylaxis. The transmission rate can even be reduced to under 2%, if a cesarean section before onset of labour and before premature rupture of membranes is done in addition. An individualized, optimal antiretroviral combination therapy, ideally introduced in the second trimenon (in special cases even already in the first trimenon), is of great importance. As a further strategy of prevention of perinatal transmission, intravenous Zidovudin chemoprophylaxis should be given in addition to the mother during labour and to the newborn during the first six weeks of life. Besides very few exceptions, long-term data after intrauterine administration of antiretroviral therapy do not show any teratogen or other long term consequences to date. The situation in developing countries is very critical with still high transmission rates because of the lack of antiretroviral therapy due to logistical reasons and costs and the need of breastfeeding. For these reasons, more and more feasible short protocols are developed with at least fifty percent reduction of neonatal transmission rates. PMID:15702705

  1. Finishing START

    SciTech Connect

    Clausen, P.A. )

    1990-01-01

    This article examines START (Strategic arms reduction talks), a treaty for arms control being negotiated between the Soviet Union and United States. The author discusses the major provisions of START and analyzes the effect it would have on the military capabilities of both countries. Its implications for the U.S. strategic defense initiative, control for SLCMSs (sea-launched cruise missiles), and status of mobile ICBMs (inter-continental ballistic missiles) are addressed. An agenda for post-START nuclear arms control is proposed.

  2. 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…

  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. 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

  5. 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,

  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. 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

  8. 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!

  9. 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.

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. Beginning antiretroviral therapy for patients with HIV.

    PubMed

    Johnson, Jennifer A; Sax, Paul E

    2014-09-01

    In this article, we review the options for initial antiretroviral therapy, including the data from clinical trials to support these choices and the factors to consider in selection of a regimen to best fit each patient. PMID:25151564

  16. 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

  17. 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

  18. [Drug interactions with antiretroviral agents].

    PubMed

    Furlan, V; Taburet, A M

    2001-01-01

    Concomitant administration of three or more antiretroviral drugs is the standard treatment for HIV-infected patients. I.p. and NNRT are metabolized by cytochrome P450 and are inhibitors or inducers of CYP3A4. Therefore a number of drug-drug interactions are likely to occur. Ritonavir, a potent CYP3A4 inhibitor, is coadministered with saquinavir, indinavir and amprenavir to enhance their plasma concentrations and their virological efficacy. In contrast, nevirapine and efavirenz are CYP3A4 inducers, which warrant an increase in i.p. dosing. These properties lead to interactions with other drugs metabolized by CYP3A4 and a knowledge or the route of biotransformation is useful to avoid side-effects or decrease efficacy (as in the case of statine coadministration). Some important interactions can lead to contraindications such as coadministration of rifampicine, astemizole, ergot derivates or cizapride, as a large decrease or increase in concentration can lead to inefficacy or to major side-effects. Clinical trials and notification of side-effects are important to detect unpredictable interactions and to propose guidelines; such an example is therapeutic drug monitoring of methadone to avoid withdrawal syndrome when coadministered with ritonavir or nelfinavir. PMID:11475806

  19. 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

  20. Which factors hinder the decision of Polish HIV-positive patients to take up antiretroviral therapy?

    PubMed

    Rogowska-Szadkowska, D; Chlabicz, S; Oltarzewska, M A; Sawicka-Powierza, J

    2009-03-01

    The implementation of highly active antiretroviral therapy (HAART) in 1996 has significantly reduced mortality and morbidity for HIV-positive patients worldwide. However not all eligible persons start HAART. To identify reasons for therapy refusal by HIV-positive persons we performed a questionnaire study. The investigation was conducted among 321 HIV-positive individuals and focused on the decision to take up antiretroviral treatment. Out of 71 untreated patients, 34 (47.9%) admitted that in their case the therapy was not indicated, whereas 20 (28.3%) were afraid of potential side effects that might change their appearance, e.g. face lipoatrophy. Only the treated patients had been prepared to take up therapy, although 17 patients (6.0%) had not received any explanation of the therapy principles, aims or necessity to comply with medication regime. The therapy is generally not discussed with the patients for whom it is not currently indicated, which may contribute to the fixation of fears and prejudices. Doctors who treat HIV-positive patients should be aware of the prejudices and fears their patients have towards antiretroviral therapy in order to react properly and by means of the available antiretroviral drugs help prolong life and improve its quality. PMID:19280405

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

    PubMed Central

    Andreu-Crespo, ngels; Llibre, Josep M; Cardona-Peitx, Glria; Sala-Piol, 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

  2. 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

  3. 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

  4. 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)

  5. Nevada Head Start, 2002.

    ERIC Educational Resources Information Center

    Biagi, Kathy

    This pamphlet describes the current services of the Nevada Head Start program. Information is provided on program eligibility requirements, the number of children and families served during the 2001-2002 program year, the counties served by Head Start programs, health services provided, demographic characteristics of families served by Head Start,

  6. 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,…

  7. The Head Start Debates

    ERIC Educational Resources Information Center

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

    2004-01-01

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

  8. Head Start Reborn.

    ERIC Educational Resources Information Center

    Gleason, Sarah

    1993-01-01

    Responds to criticism of Head Start by outlining Head Start's goals and design; reviewing research studies of the program's effectiveness; discussing the cost of funding quality programs; and providing examples of expanded Head Start programs that serve infants, toddlers, and school age children, and examples of creative uses of supplementary

  9. 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

  10. Antiretroviral penetration into the CNS and incidence of AIDS-defining neurologic conditions

    PubMed Central

    Cain, Lauren E.; Justice, Amy; Tate, Janet; Logan, Roger; Sabin, Caroline; Winston, Alan; van Sighem, Ard; Miro, Jose M.; Podzamczer, Daniel; Olson, Ashley; Arribas, Jos Ramn; Moreno, Santiago; Meyer, Laurence; del Romero, Jorge; Dabis, Franois; Bucher, Heiner C.; Wandeler, Gilles; Vourli, Georgia; Skoutelis, Athanasios; Lanoy, Emilie; Gasnault, Jacques; Costagliola, Dominique; Hernn, Miguel A.

    2014-01-01

    Objective: The link between CNS penetration of antiretrovirals and AIDS-defining neurologic disorders remains largely unknown. Methods: HIV-infected, antiretroviral therapynaive individuals in the HIV-CAUSAL Collaboration who started an antiretroviral regimen were classified according to the CNS Penetration Effectiveness (CPE) score of their initial regimen into low (<8), medium (89), or high (>9) CPE score. We estimated intention-to-treat hazard ratios of 4 neuroAIDS conditions for baseline regimens with high and medium CPE scores compared with regimens with a low score. We used inverse probability weighting to adjust for potential bias due to infrequent follow-up. Results: A total of 61,938 individuals were followed for a median (interquartile range) of 37 (18, 70) months. During follow-up, there were 235 cases of HIV dementia, 169 cases of toxoplasmosis, 128 cases of cryptococcal meningitis, and 141 cases of progressive multifocal leukoencephalopathy. The hazard ratio (95% confidence interval) for initiating a combined antiretroviral therapy regimen with a high vs low CPE score was 1.74 (1.15, 2.65) for HIV dementia, 0.90 (0.50, 1.62) for toxoplasmosis, 1.13 (0.61, 2.11) for cryptococcal meningitis, and 1.32 (0.71, 2.47) for progressive multifocal leukoencephalopathy. The respective hazard ratios (95% confidence intervals) for a medium vs low CPE score were 1.01 (0.73, 1.39), 0.80 (0.56, 1.15), 1.08 (0.73, 1.62), and 1.08 (0.73, 1.58). Conclusions: We estimated that initiation of a combined antiretroviral therapy regimen with a high CPE score increases the risk of HIV dementia, but not of other neuroAIDS conditions. PMID:24907236

  11. 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

  12. 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…

  13. 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,

  14. 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

  15. 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

  16. 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

  17. Switch strategies in antiretroviral therapy regimens.

    PubMed

    Van den Eynde, Eva; Podzamczer, Daniel

    2014-09-01

    Despite great advances in antiretroviral therapy in the last decade, several limitations still remain such as adverse effects, lack of adherence and drug-drug interactions. Switching antiretroviral therapy in stable, virologically suppressed patients with the aim of improving tolerability and convenience is an expanding strategy in clinical practice. Several factors need to be taken into consideration when switching a suppressive regimen, such as previous virologic failure, genetic barrier of the new regimen, prior duration of virologic suppression and expected level of adherence. The most frequently used strategies include reductions in the number of pills, drugs or doses. Although switching strategies may be useful, not all the regimens used in clinical practice are based on data from randomized clinical trials and some may not be the best option for certain patients; therefore, therapy should be individualized taking into consideration available information as well as patient and drug characteristics. PMID:25075752

  18. [Progress in Antiretroviral Therapy and HAND].

    PubMed

    Matsui, Yusuke; Takaori-Kondo, Akifumi

    2015-07-01

    Today, over 20,000 people are thought to be infected with human immunodeficiency virus (HIV) in Japan. Antiretroviral therapy (ART) has substantially improved the prognosis of HIV-infected patients, but long-term medication generates new problems. This article overviews the progress of anti-HIV therapies and explains the concept of HIV-associated neurocognitive disorders (HAND) as a noted complication of HIV infection. PMID:26160822

  19. [Psychological variables and adherence to antiretroviral treatment].

    PubMed

    Gordillo Alvarez-Valds, M V; Gonzlez-Lahoz, J

    2000-01-01

    The aim of this study is to discuss the implications of a good adherence to antiretroviral therapy, the factors affecting adherence, and the different methods used today to evaluate it. As conclusion, the authors emphasize the convenience of an interdisciplinary collaboration between professionals in order to improve patient's adherence. The possibility to use a multifactorial approach to assess adherence, taking into account psychological variables, is also underlined. PMID:10730405

  20. 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

  1. Challenges in initiating antiretroviral therapy in 2010

    PubMed Central

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

    2010-01-01

    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 patients 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

  2. 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

  3. 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

  4. 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

  5. Global Challenges in the Development and Delivery of Paediatric Antiretrovirals

    PubMed Central

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

    2008-01-01

    By the end of 2006, compared with 28% coverage for adults, only 15% of children with HIV who needed antiretroviral treatment were receiving it. Major challenges in delivering treatment include the lack of paediatric antiretrovirals that can be dosed in small children and limited studies examining safety and efficacy for existing antiretroviral formulations. The high costs of treatment have been reduced through the use of generic, fixed-dose combination drugs. Evidence-based strategies for managing resistance and the scale-up of pharmacological trials for children in low- and middle-income countries are critical to the success and future development of paediatric antiretrovirals. PMID:18549980

  6. The VACS Index Predicts Mortality In A Young, Healthy HIV Population Starting Highly Active Antiretroviral Therapy

    PubMed Central

    Bebu, Ionut; Tate, Janet; Rimland, David; Mesner, Octavio; Macalino, Grace E.; Ganesan, Anuradha; Okulicz, Jason F.; Bavaro, Mary; Weintrob, Amy C.; Justice, Amy C.; Agan, Brian K.

    2014-01-01

    Background The Veterans Aging Cohort Study (VACS) Index is a weighted combination of age and eight clinical variables. It has been well correlated with all-cause mortality among HIV-infected patients. The U.S. Military HIV Natural History Study (NHS) cohort provides a different validation population profile, being younger and healthier. A significant portion of the US HIV population is similarly composed, so evaluation of the VACS Index in this population is of great interest. Methods NHS subjects have medical history and laboratory data collected at six month visits. We performed an external validation of the VACS Index in the NHS evaluating correlation, discrimination, and calibration for all-cause mortality following HAART initiation (HI). We then tested whether combining longitudinal VACS Index values at different time points improves prediction of mortality. Results The VACS Index at one year after HI was well correlated with all-cause mortality (Harrells c-statistic 0.78), provided good discrimination (log-rank p <0.05), and was marginally well calibrated using Brier score. Accounting for VACS Index at HI and 6 months after HI significantly improved a standard model including only the VACS Index at 1 year after HI (Net Reclassification Improvement=25.2%, 10.9-48.9% 95% CI). Conclusions The VACS Index was well correlated and provided good discrimination with respect to all-cause mortality among HAART initiating subjects in the NHS. Moderate overprediction of mortality in this young, healthy population suggests minor recalibration could improve fit among similar patients. Considering VACS Index at HI and 6 months improved outcome prediction and allowed earlier risk assessment. PMID:24226058

  7. 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

  8. 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): 1.367.19] and facility. Independent baseline predictors for HIVDR mutations at T2 were: CD4 count <250 cells/?l (AOR 2.80, 95% CI: 1.087.29) and viral load ?100,000 copies/ml (AOR 2.48, 95% CI: 1.006.14). 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

  9. “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

  10. Engine starting and stopping

    NASA Astrophysics Data System (ADS)

    Curnock, Barry

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

  11. "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…

  12. 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

  13. 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

  14. "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

  15. 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)

  16. Is Head Start Dying?

    ERIC Educational Resources Information Center

    Sherman, Ann; And Others

    1971-01-01

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

  17. Head Start Curriculum Guide.

    ERIC Educational Resources Information Center

    Smith, Clare Coe; And Others

    One of a series of guides for preschool teachers and aides, the book offers a Head Start curriculum guide to help achieve goals regarding social behavior, general attitudes, academic skills, health, and parent development. Information on curriculum is divided into areas of bloc time outline, classroom arrangement, building concepts (such as

  18. Smart Start Evaluation Plan.

    ERIC Educational Resources Information Center

    Bryant, Donna; Burchinal, Margaret; Buysse, Virginia; Kotch, Jonathan; Maxwell, Kelly; Neenan, Peter; Noblit, George; Orthner, Dennis; Peisner-Feinberg, Ellen; Telfair, Joseph

    Smart Start is North Carolina's partnership between state government and local leaders, service providers, and families to better serve children under 6 years of age and their families. This report describes the comprehensive plan to evaluate the state and local goals and objectives of the program, focusing on the components addressing the

  19. Home Start Curriculum Guide.

    ERIC Educational Resources Information Center

    Roggman, Lori; And Others

    This curriculum guide contains monthly work plans and weekly activity units for a Home Start Program. Emphasis is placed on the importance of the home, the family unit, and the education and development of young children by their own parents. Yearly goals include concern for the following: physical and dental health, nutrition, mental health and

  20. 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

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

    PubMed

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

    2013-01-01

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

  2. 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

  3. 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

  4. 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

  5. Comparison of Treatment Outcomes of New Smear-Positive Pulmonary Tuberculosis Patients by HIV and Antiretroviral Status in a TB/HIV Clinic, Malawi

    PubMed Central

    Tweya, Hannock; Feldacker, Caryl; Phiri, Sam; Ben-Smith, Anne; Fenner, Lukas; Jahn, Andreas; Kalulu, Mike; Weigel, Ralf; Kamba, Chancy; Banda, Rabecca; Egger, Matthias; Keiser, Olivia

    2013-01-01

    Background Smear-positive pulmonary TB is the most infectious form of TB. Previous studies on the effect of HIV and antiretroviral therapy on TB treatment outcomes among these highly infectious patients demonstrated conflicting results, reducing understanding of important issues. Methods All adult smear-positive pulmonary TB patients diagnosed between 2008 and 2010 in Malawis largest public, integrated TB/HIV clinic were included in the study to assess treatment outcomes by HIV and antiretroviral therapy status using logistic regression. Results Of 2,361 new smear-positive pulmonary TB patients, 86% had successful treatment outcome (were cured or completed treatment), 5% died, 6% were lost to follow-up, 1% failed treatment, and 2% transferred-out. Overall HIV prevalence was 56%. After adjusting for gender, age and TB registration year, treatment success was higher among HIV-negative than HIV-positive patients (adjusted odds ratio 1.49; 95% CI: 1.141.94). Of 1,275 HIV-infected pulmonary TB patients, 492 (38%) received antiretroviral therapy during the study. Pulmonary TB patients on antiretroviral therapy were more likely to have successful treatment outcomes than those not on ART (adjusted odds ratio : 1.83; 95% CI: 1.292.60). Conclusion HIV co-infection was associated with poor TB treatment outcomes. Despite high HIV prevalence and the integrated TB/HIV setting, only a minority of patients started antiretroviral therapy. Intensified patient education and provider training on the benefits of antiretroviral therapy could increase antiretroviral therapy uptake and improve TB treatment success among these most infectious patients. PMID:23457534

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

    PubMed Central

    2010-01-01

    In 2007 an estimated 33 million people were living with HIV; 67% resided in sub-Saharan Africa, with 35% in eight countries alone. In 2007, there were about 1.4 million HIV-positive tuberculosis cases. Globally, approximately 4 million people had been given highly active antiretroviral therapy (HAART) by the end of 2008, but in 2007, an estimated 6.7 million were still in need of HAART and 2.7 million more became infected with HIV. Although there has been unprecedented investment in confronting HIV/AIDS - the Joint United Nations Programme on HIV/AIDS estimates $13.8 billion was spent in 2008 - a key challenge is how to address the HIV/AIDS epidemic given limited and potentially shrinking resources. Economic disparities may further exacerbate human rights issues and widen the increasingly divergent approaches to HIV prevention, care and treatment. HIV transmission only occurs from people with HIV, and viral load is the single greatest risk factor for all modes of transmission. HAART can lower viral load to nearly undetectable levels. Prevention of mother to child transmission offers proof of the concept of HAART interrupting transmission, and observational studies and previous modelling work support using HAART for prevention. Although knowing one's HIV status is key for prevention efforts, it is not known with certainty when to start HAART. Building on previous modelling work, we used an HIV/AIDS epidemic of South African intensity to explore the impact of testing all adults annually and starting persons on HAART immediately after they are diagnosed as HIV positive. This theoretical strategy would reduce annual HIV incidence and mortality to less than one case per 1000 people within 10 years and it would reduce the prevalence of HIV to less than 1% within 50 years. To explore HAART as a prevention strategy, we recommend further discussions to explore human rights and ethical considerations, clarify research priorities and review feasibility and acceptability issues. PMID:20205768

  7. 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…

  8. 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

  9. Early versus deferred antiretroviral therapy for children older than 1 year infected with HIV (PREDICT): a multicentre, randomised, open-label trial

    PubMed Central

    Puthanakit, Thanyawee; Vonthanak, Saphonn; Ananworanich, Jintanat; Kosalaraksa, Pope; Hansudewechakul, Rawiwan; Vibol, Ung; Kerr, Stephen J.; Kanjanavanit, Suparat; Ngampiyaskul, Chaiwat; Wongsawat, Jurai; Luesomboon, Wicharn; Ngo-Giang-Huong, Nicole; Chettra, Kea; Cheunyam, Theshinee; Suwarnlerk, Tulathip; Ubolyam, Sasiwimol; Shearer, William T.; Paul, Robert; Mofenson, Lynne M.; Fox, Lawrence; Law, Matthew G.; Cooper, David A.; Phanuphak, Praphan; Vun, Mean Chhi; Ruxrungtham, Kiat

    2012-01-01

    Summary Background The optimum time to start antiretroviral therapy for children diagnosed with HIV infection after 1 year of age is unknown. We assessed whether antiretroviral therapy could be deferred until CD4 percentages declined to less than 15% without affecting AIDS-free survival. Methods In our multicentre, randomised, open-label trial at nine research sites in Thailand and Cambodia, we enrolled children aged 112 years who were infected with HIV and had CD4 percentages of 1524%. Participants were randomly assigned (1:1) by a minimisation scheme to start antiretroviral therapy at study entry (early treatment group) or antiretroviral therapy to start when CD4 percentages declined to less than 15% (deferred treatment group). The primary endpoint was AIDS-free survival (based on US Centers for Disease Control and Prevention category C events) at week 144, assessed with the Kaplan-Meier analysis and the log-rank approach. This study is registered with ClinicalTrials.gov, number NCT00234091. Findings Between March 28, 2006, and Sept 10, 2008, we enrolled 300 Thai and Cambodian children infected with HIV, with a median age of 64 years (IQR 3984). 150 children were randomly allocated early antiretroviral therapy (one participant was excluded from analyses after withdrawing before week 0) and 150 children were randomly allocated deferred antiretroviral therapy. Median baseline CD4 percentage was 19% (1622%). 69 children (46%) in the deferred treatment group started antiretroviral therapy during the study. AIDS-free survival at week 144 in the deferred treatment group was 987% (95% CI 947997; 148 of 150 patients) compared with 979% (937993; 146 of 149 patients) in the early treatment group (p=06). Interpretation AIDS-free survival in both treatment groups was high. This low event rate meant that our study was underpowered to detect differences between treatment start times and thus additional follow-up of study participants or future studies are needed to answer this clinical question. Funding US National Institutes of Health, Division of AIDS; National Institute of Allergy and Infectious Diseases; National Institute of Child Health and Human Development; and National Institute of Mental Health. PMID:23059199

  10. The Setpoint Study (ACTG A5217): Effect of Immediate Versus Deferred Antiretroviral Therapy on Virologic Set Point in Recently HIV-1Infected Individuals

    PubMed Central

    DeGruttola, Victor; Sun, Xin; Fiscus, Susan A.; Del Rio, Carlos; Hare, C. Bradley; Markowitz, Martin; Connick, Elizabeth; Macatangay, Bernard; Tashima, Karen T.; Kallungal, Beatrice; Camp, Rob; Morton, Tia; Daar, Eric S.; Little, Susan

    2012-01-01

    (See the editorial commentary by Tossonian and Conway, on pages 1012.) Background.?The benefits of antiretroviral therapy during early human immunodeficiency virus type 1 (HIV-1) infection remain unproved. Methods.?A5217 study team randomized patients within 6 months of HIV-1 seroconversion to receive either 36 weeks of antiretrovirals (immediate treatment [IT]) or no treatment (deferred treatment [DT]). Patients were to start or restart antiretroviral therapy if they met predefined criteria. The primary end point was a composite of requiring treatment or retreatment and the log10 HIV-1 RNA level at week 72 (both groups) and 36 (DT group). Results.?At the June 2009 Data Safety Monitoring Board (DSMB) review, 130 of 150 targeted participants had enrolled. Efficacy analysis included 79 individuals randomized ?72 weeks previously. For the primary end point, the IT group at week 72 had a better outcome than the DT group at week 72 (P = .005) and the DT group at week 36 (P = .002). The differences were primarily due to the higher rate of progression to needing treatment in the DT group (50%) versus the IT (10%) group. The DSMB recommended stopping the study because further follow-up was unlikely to change these findings. Conclusions.?Progression to meeting criteria for antiretroviral initiation in the DT group occurred more frequently than anticipated, limiting the ability to evaluate virologic set point. Antiretrovirals during early HIV-1 infection modestly delayed the need for subsequent treatment. Clinical Trials Registration.?NCT00090779. PMID:22180621

  11. 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.

  12. Experiencing antiretroviral adherence: helping healthcare staff better understand adherence to paediatric antiretrovirals

    PubMed Central

    2010-01-01

    Background Lack of adherence to antiretroviral medications is one of the key challenges for paediatric HIV care and treatment programmes. There are few hands-on opportunities for healthcare workers to gain awareness of the psychosocial and logistic challenges that caregivers face when administering daily antiretroviral therapy to children. This article describes an educational activity that allows healthcare workers to simulate this caregiver role. Methods Paediatric formulations of several antiretroviral medications were dispensed to a convenience sample of staff at the Baylor College of Medicine-Bristol-Myers Squibb Children's Clinical Center of Excellence in Mbabane, Swaziland. The amounts of the medications remaining were collected and measured one week later. Adherence rates were calculated. Following the exercise, a brief questionnaire was administered to all staff participants. Results The 27 clinic staff involved in the exercise had varying and low adherence rates over the week during which the exercise was conducted. Leading perceived barriers to adherence included: "family friends don't help me remember/tell me I shouldn't take it" and "forgot". Participants reported that the exercise was useful as it allowed them to better address the challenges faced by paediatric patients and caregivers. Conclusions Promoting good adherence practices among caregivers of children on antiretrovirals is challenging but essential in the treatment of paediatric HIV. Participants in this exercise achieved poor adherence rates, but identified with many of the barriers commonly reported by caregivers. Simulations such as this have the potential to promote awareness of paediatric ARV adherence issues among healthcare staff and ultimately improve adherence support and patient outcomes. PMID:21134284

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

    PubMed

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

    2015-10-23

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

  14. 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

  15. 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

  16. Pediatric Adherence to HIV Antiretroviral Therapy

    PubMed Central

    Mellins, Claude

    2010-01-01

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

  17. Taking Antiretroviral Therapy for HIV Infection

    PubMed Central

    Laws, M Barton; Wilson, Ira B; Bowser, Diana M; Kerr, Sarah E

    2000-01-01

    OBJECTIVE To describe how people with HIV understand and experience the problem of adhering to antiretroviral medication regimens. DESIGN We performed a qualitative study based on interviews with HIV-infected patients, including 46 clients of AIDS service organizations, who were sampled according to age, ethnicity, and injection drug use history, and a convenience sample of 15 patients. Interviews were conducted in English or Spanish and were audiotaped and transcribed. PARTICIPANTS Of 52 respondents who had prescriptions for antiretroviral therapy, 25 were randomly selected for in-depth analysis. Of these, 5 reported having an AIDS diagnosis, 15 reported symptoms they attributed to HIV, and 5 reported having no symptoms of HIV disease. MEASUREMENTS AND MAIN RESULTS Investigators prepared structured abstracts of interviews to extract adherence-related data. One investigator compared the abstracts with the original transcripts to confirm the interpretations, and used the abstracts to organize and classify the findings. Most subjects (84%) reported recent nonadherent behavior, including ceasing treatment, medication holidays, sleeping through doses, forgetting doses, skipping doses due to side effects, and following highly asymmetric schedules. Initially, most reported that they were not significantly nonadherent, and many did not consider their behavior nonadherent. Only a minority clearly understood the possible consequences of missing doses. Most said they had not discussed their nonadherence with their physicians. CONCLUSIONS Many people rationalize their difficulty in adhering to HIV treatment by deciding that the standard of adherence they can readily achieve is appropriate. Physicians should inquire about adherence-related behavior in specific detail, and ensure that patients understand the consequences of not meeting an appropriate standard. PMID:11119181

  18. 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

  19. 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

  20. 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

  1. Antiretroviral Drugs Used in the Treatment of HIV Infection

    MedlinePLUS

    ... Treatment Antiretroviral drugs used in the treatment of HIV infection Share Tweet Linkedin Pin it More sharing ... Email Print Drugs Used in the Treatment of HIV Infection Click on drug brand name for additional ...

  2. 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

  3. 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

  4. The Survival Benefits of Antiretroviral Therapy in South Africa

    PubMed Central

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

    2014-01-01

    Background.?We sought to quantify the survival benefits attributable to antiretroviral therapy (ART) in South Africa since 2004. Methods.?We used the Cost-Effectiveness of Preventing AIDS ComplicationsInternational model (CEPAC) to simulate 8 cohorts of human immunodeficiency virus (HIV)infected patients initiating ART each year during 20042011. Model inputs included cohort-specific mean CD4+ T-cell count at ART initiation (112178 cells/L), 24-week ART suppressive efficacy (78%), second-line ART availability (2.4% of ART recipients), and cohort-specific 36-month retention rate (55%71%). CEPAC simulated survival twice for each cohort, once with and once without ART. The sum of the products of per capita survival differences and the total numbers of persons initiating ART for each cohort yielded the total survival benefits. Results.?Lifetime per capita survival benefits ranged from 9.3 to 10.2 life-years across the 8 cohorts. Total estimated population lifetime survival benefit for all persons starting ART during 20042011 was 21.7 million life-years, of which 2.8 million life-years (12.7%) had been realized by December 2012. By 2030, benefits reached 17.9 million life-years under current policies, 21.7 million life-years with universal second-line ART, 23.3 million life-years with increased linkage to care of eligible untreated patients, and 28.0 million life-years with both linkage to care and universal second-line ART. Conclusions.?We found dramatic past and potential future survival benefits attributable to ART, justifying international support of ART rollout in South Africa. PMID:24307741

  5. 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.; Ndungu, 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-nave 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

  6. What to Start: Selecting a First HIV Regimen

    MedlinePLUS

    ... medicines to treat HIV infection is called antiretroviral therapy (ART). People on ART take a combination of HIV ... treat HIV infection. HIV treatment (also called antiretroviral therapy or ART) begins with choosing an HIV regimen. People on ...

  7. 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…

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

    ERIC Educational Resources Information Center

    Welshman, John

    2010-01-01

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

  9. New strategies for lowering the costs of antiretroviral treatment and care for people with HIV/AIDS in the United Kingdom

    PubMed Central

    Gazzard, Brian; Moecklinghoff, Christiane; Hill, Andrew

    2012-01-01

    In the UK, the annual cost of treatment and care for people with human immunodeficiency virus (HIV)/acquired immune deficiency virus (AIDS) rose by over 600% from 104 million in 1997 to 762 million in 2010; approximately two-thirds of the 762 million cost of treatment and care in 2010 was for the procurement of antiretrovirals and other related drugs. The number of people accessing care for HIV/AIDS rose from 22,000 in 2000 to 65,000 in 2009. Adoption of test and treat guidelines for treating all HIV-infected people with antiretrovirals would further increase the burden of costs. Given the current economic situation, there is now a new focus on strategies for treatment and care of people with HIV-1 infection which can maintain efficacy but at a lower cost. In this review, we propose three strategies which could potentially lower the costs of treatment and care, ie, stopping testing CD4 counts for patients with full HIV RNA suppression on antiretroviral treatment and recent CD4 counts above 350 cells/?L; more widespread use of generic antiretrovirals as replacements for patients currently taking patented versions; and use of darunavir-ritonavir monotherapy as a switch option for patients with full HIV RNA suppression on other antiretrovirals and no history of virological failure. However, it is important that high standards of clinical care are maintained despite cost-saving measures. Antiretrovirals with generic alternatives may have toxicity issues, eg, zidovudine and nevirapine. There could be ethical issues in starting patients on these drugs if they are currently tolerating other treatments. The use of darunavir-ritonavir monotherapy is not consistently recommended in international HIV treatment guidelines. PMID:22888265

  10. Antiretroviral procurement and supply chain management.

    PubMed

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

    2014-01-01

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

  11. 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…

  12. [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

  13. 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

  14. 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.

  15. Provision of antiretroviral therapy in South Africa: the nuts and bolts.

    PubMed

    Bekker, Linda-Gail; Venter, Francois; Cohen, Karen; Goemare, Eric; Van Cutsem, Gilles; Boulle, Andrew; Wood, Robin

    2014-01-01

    Public sector antiretroviral provision had a slow start in South Africa despite a raging epidemic and a World AIDS conference that shed significant public light on the disparities of therapy access globally. This was largely due to political prevarication in the midst of AIDS denialism. There has been an unprecedented expansion in the HIV treatment programme since 2008. As a result, South Africa now has the largest number of patients on antiretroviral drugs in the world, and South African life expectancy has increased by more than a decade. However, this has led to a number of fiscal, logistic and operational challenges that the country must face as the treatment programme continues to expand. Challenges include increasing detection within communities, linkage and retention in care, while strengthening operational support functions such as consistent drug supply, health staffing and infrastructure, diagnostic services, programme monitoring and sustainable financing. As a middle-income country, albeit with marked income inequality, and the heaviest HIV burden in the world, South Africa is a test case of whether a large-scale public health programme can boast of success in the face of numerous other health-system challenges. PMID:25310359

  16. [Antiretroviral treatment adherence and its association with TCD4+ lymphocyte subsets in children with HIV/AIDS].

    PubMed

    Balbaryski, Jeannette; Simonte, Karina; Urteneche, Ins; Candi, Marcela; Gaddi, Eduardo; Barboni, Graciela

    2013-01-01

    Human immunodeficiency virus infection causes a severe depletion of TCD4+ lymphocytes and a sustained immune activation state, hallmarks findings that led to numerical and phenotypic changes in the TCD4+ subsets. Highly active anti-retroviral therapy has substantially modified the course of HIV infection. Correct adherence to the treatment results in a decrease in viral load at undetectable levels and a significant increase in the number of peripheral T cell lymphocytes. In the present study association between changes in T cell subsets and treatment adherence was evaluated in 28 HIV (+) infected children, before and after 9 months on average, from starting anti-retroviral therapy. The group of 18 patients with good adherence, above 95%, showed a significant increase in CD4+CD45RA+CD62L+ naive cells percentual levels and a decrease in the CD4+CD45RA-CD62L+ central memory subset, between the two points of the follow-up period. Conversely, 10 children with failure in the adherence did not show significant differences in the percentual levels of both subsets. Improvement in the percentage of adherence among paediatric population, optimizing antiretroviral treatment, allows a quick and significant reduction of viral replication. This feature is associated with the progressive reconstitution of the immune system. PMID:23924530

  17. 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

  18. 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

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

    PubMed

    Snchez-Olivas, Manuel Anastacio; Valencia-Zavala, Martha Patricia; Vega-Robledo, Gloria Bertha; Snchez-Olivas, Jess Alberto; Velzquez-Smano, Guillermo; Seplveda-Velzquez, Guadalupe

    2015-01-01

    All antiretroviral drugs can have both short-term and long-term adverse events. The risk of specific side effects varies from drug to drug, from drug class to drug class, and from patient to patient. A better understanding of the adverse effects of antiretroviral agents is of interest not only for HIV specialists, but also for other physicians who care allergy reactions in HIV-positive patients. Each antiretroviral medication is associated with its own specific adverse effects or may cause problems only in particular circumstances. In this article some adverse allergic effects of HAART therapy in the treatment of HIV from a patient are reviewed. Our aim is to gain a working knowledge of these adverse effects, promoting the early recognition and reversal of potentially serious adverse effects, and reducing the potential for adverse drug interactions. PMID:25958378

  20. 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

  1. Starting Early Starting Smart: Summary of Early Findings.

    ERIC Educational Resources Information Center

    2001

    Starting Early Starting Smart (SESS) provides an integrated system of child-centered, family-focused, and community-based services targeted to at-risk children from birth to age seven at twelve sites across the country. To access families that are often not in the mainstream of service access and use, SESS programs partner with primary care

  2. 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

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

    PubMed

    Mowatt, L

    2013-01-01

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

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

    PubMed Central

    Hoen, Bruno; Bonnet, Fabrice; Delaugerre, Constance; Delobel, Pierre; Goujard, Ccile; LHnaff, 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 patients own sake and for promoting treatment as prevention. PMID:24942364

  5. 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

  6. Assessing teratogenicity of antiretroviral drugs: monitoring and analysis plan of the Antiretroviral Pregnancy Registry.

    PubMed

    Covington, Deborah L; Tilson, Hugh; Elder, Jenna; Doi, Peggy

    2004-08-01

    This paper describes the Antiretroviral Pregnancy Registry's (APR) monitoring and analysis plan. APR is overseen by a committee of experts in obstetrics, pediatrics, teratology, infectious diseases, epidemiology and biostatistics from academia, government and the pharmaceutical industry. APR uses a prospective exposure-registration cohort design. Clinicians voluntarily register pregnant women with prenatal exposures to any antiretroviral therapy and provide fetal/neonatal outcomes. A birth defect is any birth outcome > or = 20 weeks gestation with a structural or chromosomal abnormality as determined by a geneticist. The prevalence is calculated by dividing the number of defects by the total number of live births and is compared to the prevalence in the CDC's population-based surveillance system. Additionally, first trimester exposures, in which organogenesis occurs, are compared with second/third trimester exposures. Statistical inference is based on exact methods for binomial proportions. Overall, a cohort of 200 exposed newborns is required to detect a doubling of risk, with 80% power and a Type I error rate of 5%. APR uses the Rule of Three: immediate review occurs once three specific defects are reported for a specific exposure. The likelihood of finding three specific defects in a cohort of < or = 600 by chance alone is less than 5% for all but the most common defects. To enhance the assurance of prompt, responsible, and appropriate action in the event of a potential signal, APR employs the strategy of 'threshold'. The threshold for action is determined by the extent of certainty about the cases, driven by statistical considerations and tempered by the specifics of the cases. PMID:15317035

  7. 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…

  8. 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…

  9. 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…

  10. 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

  11. 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…

  12. 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

  13. Whoonga and the Abuse and Diversion of Antiretrovirals in Soweto, South Africa

    PubMed Central

    Rough, Kathryn; Dietrich, Janan; Essien, Thandekile; Grelotti, David J.; Bansberg, David R.; Gray, Glenda

    2014-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  15. 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

  16. 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

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

    PubMed

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

    2015-08-12

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

  18. Antiretroviral Treatment and Resistance Patterns in HIV-Infected Children.

    PubMed

    Adetokunboh, Olatunji; Atibioke, Oluyemi; Balogun, Tolulope; Oluwasanu, Mojisola

    2015-10-01

    Paediatric HIV-infected patients have higher risk of developing resistance to antiretroviral drugs, and from public health perspective, drug resistance remains a limiting factor for effective management of HIV infection in children. We reviewed the current evidences available on the antiretroviral treatment and resistance patterns in HIV-infected children. Prevalence of HIV drug resistance varied among the three main classes of antiretroviral drugs, namely nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors and protease inhibitors in both treatment nave and treatment-experienced children in different countries. Most of the patients with extensive triple-class drug-resistant mutations were found to be considerably exposed to the three main classes of antiretroviral agents. Identification of genetic factors linked with susceptibility to perinatal transmission of HIV may be key in understanding the development of resistance due to waning antiviral effectiveness. Children who were less likely to achieve viral re-suppression were more likely to have resistance mutations. Newer drugs such as etravirine can be used as alternatives in case of resistance to efavirenz while newly developed diagnostic method such as next-generation sequencing is a platform for improving quality of detections especially minor variant drug resistance mutations. PMID:26319052

  19. 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

  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. Clinically relevant drug-drug interactions between antiretrovirals and antifungals

    PubMed Central

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

    2015-01-01

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

  2. 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

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

    SciTech Connect

    Johnson, A.T.

    1992-01-01

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

  4. 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.

  5. 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 35g 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 30g. 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

  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. 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

  8. 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

  9. 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

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

    PubMed Central

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

    2013-01-01

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

  11. Behavioral and electrophysiological abnormalities in two rat models of antiretroviral drug-induced neuropathy.

    PubMed

    Garcia-Perez, Elizabeth; Sol, Rom; Sumalla, Mireia; Serra, Jordi

    2015-09-01

    Painful peripheral neuropathy due to the antiretroviral therapy used to treat HIV is one of the most prevalent side effects occurring in at least 30% of patients living with this infection. We have evaluated the electrophysiological and behavioral effects of d4T and ddC on peripheral large and small nerve fibers in male rats treated with d4T (Sprague-Dawley, 50 mg/kg, twice within 1 week), ddC (Wistar, 50 mg/kg, 3 times per week for 3 weeks), or vehicle. The effect of the interventions was assessed using behavioral measures of mechanical sensitivity, conventional nerve conduction studies, and microneurographic single nerve C-fiber recordings. To mimic as much as possible the human clinical condition, all treated animals were included in the study. No statistically significant differences were observed in behavioral parameters of mechanical sensitivity. Nerve conduction studies did not reveal any significant change in the ddC-treated group. In contrast, we observed electrophysiological evidence of significant demyelinating neuropathy 1 week after the start of d4T treatment. Additionally, spontaneous activity in mechanoinsensitive C-nociceptors was observed in both drug-treated groups. No relationship could be established between measures of spontaneous activity in C-nociceptors and the results of the behavioral tests. Our results show that both models of antiretroviral-induced neuropathy differ in their effects on peripheral nerves. However, both groups present abnormal spontaneous activity in mechanoinsensitive C-nociceptors that can be used as a model for pharmacological intervention. PMID:25932691

  12. Accuracy of WHO CD4 cell count criteria for virological failure of antiretroviral therapy

    PubMed Central

    Keiser, Olivia; MacPhail, Patrick; Boulle, Andrew; Wood, Robin; Schechter, Mauro; Dabis, Franois; Sprinz, Eduardo; Egger, Matthias

    2013-01-01

    Summary OBJECTIVES To examine the accuracy of the World Health Organization immunological criteria for virological failure of antiretroviral treatment. METHODS Analysis of 10 treatment programmes in Africa and South America that monitor both CD4 cell counts and HIV-1 viral load. Adult patients with at least two CD4 counts and viral load measurements between month 6 and 18 after starting a non-nucleoside reverse transcriptase inhibitor-based regimen were included. WHO immunological criteria include CD4 counts persistently <100 cells/?l, a fall below the baseline CD4 count, or a fall of >50% from the peak value. Virological failure was defined as two measurements ?10 0000 copies/ml (higher threshold) or ?500 copies/ml (lower threshold). Measures of accuracy with exact binomial 95% confidence intervals (CI) were calculated. RESULTS A total of 2009 patients were included. During 1856 person-years of follow up 63 patients met the immunological criteria and 35 patients (higher threshold) and 95 patients (lower threshold) met the virological criteria. Sensitivity [95% confidence interval (CI)] was 17.1% (6.633.6%) for the higher and 12.6% (6.721.0%) for the lower threshold. Corresponding results for specificity were 97.1% (96.397.8%) and 97.3% (96.598.0%), for positive predictive value 9.5% (3.619.6%) and 19.0% (10.230.9%) and for negative predictive value 98.5% (97.999.0%) and 95.7% (94.796.6%). CONCLUSIONS The positive predictive value of the WHO immunological criteria for virological failure of antiretroviral treatment in resource-limited settings is poor, but the negative predictive value is high. Immunological criteria are more appropriate for ruling out than for ruling in virological failure in resource-limited settings. PMID:19624478

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

    PubMed Central

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

    2015-01-01

    Background The optimal time to initiate antiretroviral therapy (ART) in human immunodeficiency virus (HIV)associated tuberculous meningitis is unknown. Methods We conducted a randomized, double-blind, placebo-controlled trial of immediate versus deferred ART in patients with HIV-associated tuberculous meningitis to determine whether immediate ART reduced the risk of death. Antiretroviral drugs (zidovudine, lamivudine, and efavirenz) were started either at study entry or 2 months after randomization. All patients were treated with standard antituberculosis treatment, adjunctive dexamethasone, and prophylactic co-trimoxazole and were followed up for 12 months. We conducted intention-to-treat, per-protocol, and prespecified subgroup analyses. Results A total of 253 patients were randomized, 127 in the immediate ART group and 126 in the deferred ART group; 76 and 70 patients died within 9 months in the immediate and deferred ART groups, respectively. Immediate ART was not significantly associated with 9-month mortality (hazard ratio [HR], 1.12; 95% confidence interval [CI], .811.55; P = .50) or the time to new AIDS events or death (HR, 1.16; 95% CI, .871.55; P = .31). The percentage of patients with severe (grade 3 or 4) adverse events was high in both arms (90% in the immediate ART group and 89% in the deferred ART group; P = .84), but there were significantly more grade 4 adverse events in the immediate ART arm (102 in the immediate ART group vs 87 in the deferred ART group; P = .04). Conclusions Immediate ART initiation does not improve outcome in patients presenting with HIV-associated tuberculous meningitis. There were significantly more grade 4 adverse events in the immediate ART arm, supporting delayed initiation of ART in HIV-associated tuberculous meningitis. Clinical Trials Registration ISRCTN63659091. PMID:21596680

  14. 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

  15. 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.

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

    PubMed Central

    Caro-Vega, Yanink; Sierra-Madero, Juan; Colchero, M. Arantxa; Crabtree-Ramrez, 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 ?2 tests. Results. Before 2001, 29% of patients starting ARVT received HAART; after 2001 it increased to 90%. The proportion of adequate prescriptions decreased within the two periods of study in all facilities (P value < 0.01). The INS and SSA were more likely to be prescribed adequately (P value < 0.01) compared to IMSS. The distribution of reasons for change was not significantly different during this time for all facilities (P value > 0.05). Conclusions. Universal ARVT access in Mexico was associated with changes in ARVT-prescription patterns over time. Health providers' performance improved, but not homogeneously. Training of personnel and guidelines updating is essential to improve prescription. PMID:24396592

  17. 76 FR 70009 - Head Start Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-09

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

  18. 75 FR 57704 - Head Start Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-22

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

  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. 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

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

    PubMed

    Mazzoglio y Nabar, Martn J; Muiz, Milagros Mara; Mejas Delamano, Alexis A; Muoz, Santiago; Magrath Guimet, Nahuel

    2015-01-01

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

  2. Cardiovascular risk assessment in antiretroviral-nave HIV patients.

    PubMed

    Maggi, Paolo; Quirino, Tiziana; Ricci, Elena; De Socio, Giuseppe Vittorio L; Gadaleta, Aurora; Ingrassia, Fabrizio; Perilli, Francesco; Lillo, Antonio; Bonfanti, Paolo

    2009-10-01

    Various studies have been conducted to evaluate the role of antiretroviral therapy in the onset of cardiovascular risk among HIV-1-infected patients, while fewer data are available regarding antiretroviral-nave patients. Our objective was to evaluate the cardiovascular risk among nave subjects examining traditional risk factors, immunovirologic parameters, assessing the Framingham risk score (FRS), and detecting the presence of subclinical carotid lesions by means of color Doppler ultrasonography. One hundred seventy-two antiretroviral-nave patients underwent color Doppler ultrasonography. An intima-media thickness (IMT) greater than 0.9 mm and/or atherosclerotic plaques were considered pathologic findings. Demographic, immunovirologic data, and risk factors for cardiovascular disease were collected. The 10-year probability of acute coronary events was assessed by the FRS. The statistical analysis was performed using t test and chi(2), Fisher's test, and conditional multiple logistic. Thirty-six patients (20.9%) had lesions at ultrasonographic investigation. The presence of lesions was significantly related to male gender (p = 0.005), age (p = 0.003), sedentary life (p = 0.05), Centers for Disease Control and Prevention (CDC) group C or CD4(+) less than 150 cells/mm(3), and viral load (VL) > 100,000 copies per milliliter (p = 0.04). The presence of subclinical carotid lesions showed a highly significant direct association with the estimated FRS (p < 0.002). The presence of subclinical atheromasic lesion results was also high among antiretroviral-nave patients. FRS is highly predictive of the lesions, but also an advanced stage of disease plays a significant role. Our data support the hypothesis that HIV infection per se is a risk factor for atherosclerosis. We recommend an ultrasonographic assessment both among patients with FRS 6% or more and among those in advanced stage of disease. PMID:19824809

  3. 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

  4. Even Start Questions and Answers.

    ERIC Educational Resources Information Center

    RMC Research Corp., Hampton, NH. Parent Involvement Center.

    This guide for school district administrators answers question about Even Start, a new, special family-centered compensatory education program funded under Chapter 1 of the Education Consolidation and Improvement Act of 1981 that combines adult literacy, parent education, and early childhood education. The following issues about program design are

  5. 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…

  6. Math Club Starting in Kindergarten

    ERIC Educational Resources Information Center

    Perry, Ann M.

    2011-01-01

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

  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. 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

  9. 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

  10. [The pharmacoeconomics of antiretroviral drugs and the role of adherence].

    PubMed

    Bargiacchi, Olivia; Brondolo, Roberta; Rizzo, Giovanni; Garavelli, Pietro Luigi

    2012-12-01

    In the past decade health care expenses have increased by 50% in Italy, a country whose population mostly consists of people aged over 50 years old, the main users of health care services. Pharmaceutical expenditure is the main issue: monoclonal antibodies, biological immunosuppressants, antitumorals and antiretrovirals are the most expensive drugs. The cost of HIV/AIDS has remained constant during the last four years. Despite the increase in pharmaceutical costs, which made the infection chronic, hospitalization costs have been reduced. With sustainable economic development as a chiefly long-term target, a clinical governance system is nonetheless needed which also takes account of the adherence to antiretroviral therapy: thus poor adherence leads to a reduction in efficacy and at the same time an increase in welfare and community costs. Recently in SSvD "Prevention and cure of HIV infection and related syndromes" of "Maggiore della Carit" University Hospital, Novara, adherence to antiretroviral therapy in 100 consecutive patients was evaluated. The results show that patients with high adherence to the treatment prescribed have a less expensive drug combination. Moreover, with better infection control and a higher immune recovery, they have less impact on social and health care costs. PMID:23299063

  11. 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

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

    PubMed Central

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

    2009-01-01

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

  13. 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

  14. Factors associated with suboptimal adherence to antiretroviral therapy in Asia

    PubMed Central

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

    2014-01-01

    Introduction Adherence to antiretroviral therapy (ART) plays an important role in treatment outcomes. It is crucial to identify factors influencing adherence in order to optimize treatment responses. The aim of this study was to assess the rates of, and factors associated with, suboptimal adherence (SubAdh) in the first 24 months of ART in an Asian HIV cohort. Methods As part of a prospective resistance monitoring study, the TREAT Asia Studies to Evaluate Resistance Monitoring Study (TASER-M) collected patients adherence based on the World Health Organization-validated Adherence Visual Analogue Scale. SubAdh was defined in two ways: (i) <100% and (ii) <95%. Follow-up time started from ART initiation and was censored at 24 months, loss to follow-up, death, treatment switch, or treatment cessation for >14 days. Time was divided into four intervals: 06, 612, 1218 and 1824 months. Factors associated with SubAdh were analysed using generalized estimating equations. Results Out of 1316 patients, 32% ever reported <100% adherence and 17% ever reported <95%. Defining the outcome as SubAdh <100%, the rates of SubAdh for the four time intervals were 26%, 17%, 12% and 10%. Sites with an average of >2 assessments per patient per year had an odds ratio (OR)=0.7 (95% confidence interval (CI) (0.55 to 0.90), p=0.006), compared to sites with ?2 assessments per patient per year. Compared to heterosexual exposure, SubAdh was higher in injecting drug users (IDUs) (OR=1.92, 95% CI (1.23 to 3.00), p=0.004) and lower in homosexual exposure (OR=0.52, 95% CI (0.38 to 0.71), p<0.001). Patients taking a nucleoside transcriptase inhibitor and protease inhibitor (NRTI+PI) combination were less likely to report adherence <100% (OR=0.36, 95% CI (0.20 to 0.67), p=0.001) compared to patients taking an NRTI and non-nucleoside transcriptase inhibitor (NRTI+NNRTI) combination. SubAdh decreased with increasing time on ART (all p<0.001). Similar associations were found with adherence <95% as the outcome. Conclusions We found that SubAdh, defined as either <100% and <95%, was associated with mode of HIV exposure, ART regimen, time on ART and frequency of adherence measurement. The more frequently sites assessed patients, the lower the SubAdh, possibly reflecting site resourcing for patient counselling. Although social desirability bias could not be excluded, a greater emphasis on more frequent adherence counselling immediately following ART initiation and through the first six months may be valuable in promoting treatment and programme retention. PMID:24836775

  15. 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

  16. 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

  17. Maternal or Infant Antiretroviral Drugs to Reduce HIV-1 Transmission

    PubMed Central

    Chasela, Charles S.; Hudgens, Michael G.; Jamieson, Denise J.; Kayira, Dumbani; Hosseinipour, Mina C.; Kourtis, Athena P.; Martinson, Francis; Tegha, Gerald; Knight, Rodney J.; Ahmed, Yusuf I.; Kamwendo, Deborah D.; Hoffman, Irving F.; Ellington, Sascha R.; Kacheche, Zebrone; Soko, Alice; Wiener, Jeffrey B.; Fiscus, Susan A.; Kazembe, Peter; Mofolo, Innocent A.; Chigwenembe, Maggie; Sichali, Dorothy S.; van der Horst, Charles M.

    2012-01-01

    Background We evaluated the efficacy of a maternal triple-drug antiretroviral regimen or infant nevirapine prophylaxis for 28 weeks during breast-feeding to reduce postnatal transmission of human immunodeficiency virus type 1 (HIV-1) in Malawi. Methods We randomly assigned 2369 HIV-1positive, breast-feeding mothers with a CD4+ lymphocyte count of at least 250 cells per cubic millimeter and their infants to receive a maternal antiretroviral regimen, infant nevirapine, or no extended postnatal antiretroviral regimen (control group). All mothers and infants received perinatal prophylaxis with single-dose nevirapine and 1 week of zidovudine plus lamivudine. We used the KaplanMeier method to estimate the cumulative risk of HIV-1 transmission or death by 28 weeks among infants who were HIV-1negative 2 weeks after birth. Rates were compared with the use of the log-rank test. Results Among motherinfant pairs, 5.0% of infants were HIV-1positive at 2 weeks of life. The estimated risk of HIV-1 transmission between 2 and 28 weeks was higher in the control group (5.7%) than in either the maternal-regimen group (2.9%, P = 0.009) or the infant-regimen group (1.7%, P<0.001). The estimated risk of infant HIV-1 infection or death between 2 and 28 weeks was 7.0% in the control group, 4.1% in the maternal-regimen group (P = 0.02), and 2.6% in the infant-regimen group (P<0.001). The proportion of women with neutropenia was higher among those receiving the antiretroviral regimen (6.2%) than among those in either the nevirapine group (2.6%) or the control group (2.3%). Among infants receiving nevirapine, 1.9% had a hypersensitivity reaction. Conclusions The use of either a maternal antiretroviral regimen or infant nevirapine for 28 weeks was effective in reducing HIV-1 transmission during breast-feeding. (ClinicalTrials.gov number, NCT00164736.) PMID:20554982

  18. Prevalence of oral candidiasis in HIV/AIDS children in highly active antiretroviral therapy era. A literature analysis.

    PubMed

    Gaitn-Cepeda, Luis Alberto; Snchez-Vargas, Octavio; Castillo, Nydia

    2015-08-01

    SummaryHighly active antiretroviral therapy has decreased the morbidity and mortality related to HIV infection, including oral opportunistic infections. This paper offers an analysis of the scientific literature on the epidemiological aspects of oral candidiasis in HIV-positive children in the combination antiretroviral therapy era. An electronic databases search was made covering the highly active antiretroviral therapy era (1998 onwards). The terms used were oral lesions, oral candidiasis and their combination with highly active antiretroviral therapy and HIV/AIDS children. The following data were collected from each paper: year and country in which the investigation was conducted, antiretroviral treatment, oral candidiasis prevalence and diagnostic parameters (clinical or microbiological). Prevalence of oral candidiasis varied from 2.9% in American HIV-positive children undergoing highly active antiretroviral therapy to 88% in Chilean HIV-positive children without antiretroviral therapy. With respect to geographical location and antiretroviral treatment, higher oral candidiasis prevalence in HIV-positive children on combination antiretroviral therapy/antiretroviral therapy was reported in African children (79.1%) followed by 45.9% reported in Hindu children. In HIV-positive Chilean children on no antiretroviral therapy, high oral candidiasis prevalence was reported (88%) followed by Nigerian children (80%). Oral candidiasis is still frequent in HIV-positive children in the highly active antiretroviral therapy era irrespective of geographical location, race and use of antiretroviral therapy. PMID:25156369

  19. 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

  20. High prevalence of HIV-1 drug resistance among patients on first-line antiretroviral treatment in Lom, Togo

    PubMed Central

    2011-01-01

    Background With widespread use of antiretroviral (ARV) drugs in Africa, one of the major potential challenges is the risk of emergence of ARV drug-resistant HIV strains. Our objective is to evaluate the virological failure and genotypic drug-resistance mutations in patients receiving first-line highly active antiretroviral therapy (HAART) in routine clinics that use the World Health Organization public health approach to monitor antiretroviral treatment (ART) in Togo. Methods Patients on HAART for one year (10-14 months) were enrolled between April and October 2008 at three sites in Lom, the capital city of Togo. Plasma viral load was measured with the NucliSENS EasyQ HIV-1 assay (Biomrieux, Lyon, France) and/or a Generic viral load assay (Biocentric, Bandol, France). Genotypic drug-resistance testing was performed with an inhouse assay on plasma samples from patients with viral loads of more than 1000 copies/ml. CD4 cell counts and demographic data were also obtained from medical records. Results A total of 188 patients receiving first-line antiretroviral treatment were enrolled, and 58 (30.8%) of them experienced virologic failure. Drug-resistance mutations were present in 46 patients, corresponding to 24.5% of all patients enrolled in the study. All 46 patients were resistant to non-nucleoside reverse-transcriptase inhibitors (NNRTIs): of these, 12 were resistant only to NNRTIs, 25 to NNRTIs and lamivudine/emtricitabine, and eight to all three drugs of their ARV regimes. Importantly, eight patients were already predicted to be resistant to etravirine, the new NNRTI, and three patients harboured the K65R mutation, inducing major resistance to tenofovir. Conclusions In Togo, efforts to provide access to ARV therapy for infected persons have increased since 2003, and scaling up of ART started in 2007. The high number of resistant strains observed in Togo shows clearly that the emergence of HIV drug resistance is of increasing concern in countries where ART is now widely used, and can compromise the long-term success of first- and second-line ART. PMID:21663632

  1. Treatment exhaustion of highly active antiretroviral therapy (HAART) among individuals infected with HIV in the United Kingdom: multicentre cohort study

    PubMed Central

    Sabin, Caroline A; Hill, Teresa; Lampe, Fiona; Matthias, Ryanne; Bhagani, Sanjay; Gilson, Richard; Youle, Mike S; Johnson, Margaret A; Fisher, Martin; Scullard, George; Easterbrook, Philippa; Gazzard, Brian; Phillips, Andrew N

    2005-01-01

    Objectives To investigate whether there is evidence that an increasing proportion of HIV infected patients is starting to experience increases in viral load and decreases in CD4 cell count that are consistent with exhaustion of available treatment options. Design Multicentre cohort study. Setting Six large HIV treatment centres in southeast England. Participants All individuals seen for care between 1 January 1996 and 31 December 2002. Main outcome measures Exposure to individual antiretroviral drugs and drug classes, CD4 count, plasma HIV RNA burden. Results Information is available on 16 593 individuals (13 378 (80.6%) male patients, 10 340 (62.3%) infected via homosexual or bisexual sex, 4426 (26.7%) infected via heterosexual sex, median age 34 years). Overall, 10 207 of the 16 593 patients (61.5%) have been exposed to any antiretroviral therapy. This proportion increased from 41.2% of patients under follow up at the end of 1996 to 71.3% of those under follow up in 2002. The median CD4 count and HIV RNA burden of patients under follow up in each year changed from 270 cells/mm3 and 4.34 log10 copies/ml in 1996 to 408 cells/mm3 and 1.89 log10 copies/ml, respectively, in 2002. By 2002, 3060 (38%) of patients who had ever been treated with antiretroviral therapy had experienced all three main classes. Of these, around one quarter had evidence of viral load failure with all these three classes. Patients with three class failure were more likely to have an HIV RNA burden > 2.7 log10 copies/ml and a CD4 count < 200 cells/mm3. Conclusions The proportion of individuals with HIV infection in the United Kingdom who have been treated has increased gradually over time. A substantial proportion of these patients seem to be in danger of exhausting their options for antiretroviral treatment. New drugs with low toxicity, which are not associated with cross resistance to existing drugs, are urgently needed for such patients. PMID:15749728

  2. Starting apparatus for internal combustion engines

    DOEpatents

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

    1995-01-01

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

  3. 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

  4. 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 Jos Mellado; Amador, Jos Tomas Ramos; Gattinara, Guido Castelli; Compagnucci, Alexandra; Faye, Albert; Giaquinto, Carlo; Gibb, Diana M; Gandhi, Kate; Forcat, Silvia; Buckberry, Karen; Harper, Lynda; Knigs, 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

  5. 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

  6. 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

  7. Cardiac Effects of Antiretroviral-Nave 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-nave 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-nave 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

  8. Retention in care under universal Antiretroviral Therapy for HIV Infected Pregnant and Breastfeeding Women (Option B+) in Malawi

    PubMed Central

    TWEYA, Hannock; JAHN, Andreas; van OOSTERHOUT, Joep J.; CHIMBWANDIRA, Frank; CHIRWA, Zengani; NGAMBI, Wingston; BAKALI, Alan; PHIRI, Sam; MYER, Landon; VALERI, Fabio; ZWAHLEN, Marcel; WANDELER, Gilles

    2014-01-01

    OBJECTIVE To explore the levels and determinants of loss to follow-up (LTF) under universal lifelong antiretroviral therapy (ART) for pregnant and breastfeeding women (Option B+) in Malawi. DESIGN, SETTING, and PARTICIPANTS We examined retention in care, beginning at date of ART initiation and up to six months, for women in the Option B+ program. We analysed nation-wide facility-level data on women who started ART at 540 facilities (n=21 939). The study included individual-level data on patients who started ART at 19 large facilities (n=11 534). RESULTS Of the women who started ART under Option B+ (n=21 939), 17% appeared to be LTF six months after start. Most losses occurred in the first 3 months of therapy. Option B+ patients who started therapy during pregnancy were five times more likely than women who started ART in WHO stage 3/4 or with a CD4 cell count ?350 cells/?l, to never return after their initial clinic visit (odds ratio 5.0, 95% CI 4.2-6.1). Option B+ patients who started therapy while breastfeeding were twice as likely to miss their first follow-up visit (odds ratio 2.2, 95% CI 1.8-2.8). LTF was highest in pregnant Option B+ patients who began ART at large clinics on the day they were diagnosed with HIV. LTF varied considerably between facilities, ranging from 0% to 58%. CONCLUSION Decreasing LTF will improve the effectiveness of the Option B+ approach. Tailored interventions, like community- or family-based PMTCT models could improve its effectiveness. PMID:24468999

  9. Getting started with electronic mail.

    PubMed Central

    Van Vuren, D D; Johnson, D E

    1985-01-01

    This paper gives suggestions to librarians on how to get started with electronic mail. It discusses the cost- and time-saving advantages of using electronic mail rather than TWX, United States mail, or telephones for communicating ILL requests and messages. For instance, preliminary cost data show that electronic mail is often half as expensive as TWX and costs no more than a 22 stamp. Key management concerns that must be considered when setting up electronic mail are discussed, including the need for subscribers to agree on one system. Also covered are the types of equipment that can be used with electronic mail, including print terminals. PMID:4027444

  10. 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

  11. 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

  12. 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

  13. 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

  14. Rapid starting methanol reactor system

    DOEpatents

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

    1984-01-01

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

  15. Antiretroviral Adherence During Pregnancy and Postpartum in Latin America

    PubMed Central

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

    2012-01-01

    Abstract Adherence to antiretrovirals by pregnant women (and postpartum women if breastfeeding) is crucial to effectively decrease maternal viral load and decrease the risk of mother-to-child transmission of HIV. Our objectives were to describe self-reported adherence to antiretrovirals during the antepartum (after 22 weeks of pregnancy) and postpartum periods (612 weeks and 6 months), and identify predictors of adherence among HIV-infected women enrolled and followed in a prospective cohort study from June 2008 to June 2010 at multiple sites in Latin America. Adherence was evaluated using the number of missed and expected doses during the 3 days before the study visit. At the pre-delivery visit, 340 of 376 women (90%) reported perfect adherence. This rate significantly decreased by 612 weeks (171/214 [80%]) and 6 months postpartum (163/199 [82%], p<0.01). The odds for less than perfect adherence at the pre-delivery visit was significantly higher for pregnant women with current tobacco use (odds ratio [OR]=2.9, 95% confidence interval [CI]: 1.466.14; p=0.0029). At 612 weeks postpartum, the probability of non-perfect adherence increased by 6% for each 1 year increase in age (OR=1.06, 95% CI: 1.001.12, p=0.0497). At 6 months postpartum, the odds of nonperfect adherence was higher for those who were currently using alcohol (OR=3.04, 95% CI: 1.346.90; p=0.0079). Although a self-report measure of adherence based on only 3 days may lead to overestimation of actual adherence over time, women with perfect adherence had lower viral loads and higher CD4 counts. Adherence to antiretrovirals decreased significantly postpartum. Interventions should target women at high risk for lower adherence during pregnancy and postpartum, including tobacco and alcohol users. PMID:22663185

  16. 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

  17. 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

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

    PubMed

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

    2015-10-01

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

  19. Response to antiretroviral therapy (ART): comparing women with previous use of zidovudine monotherapy (ZDVm) in pregnancy with ART nave 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-nave (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 womans health. PMID:24593018

  20. Epidemiology and Management of Antiretroviral-Associated Cardiovascular Disease

    PubMed Central

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

    2015-01-01

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

  1. 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

  2. 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

  3. 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

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

    PubMed

    Dunbar, Deanne

    2011-06-01

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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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/?L. In the first case, pulmonary rhodococcosis presented 6 months after initiation of HAART, and was followed by an extracerebral intracranial and a cerebral rhodococcal abscess 1 and 8 months, respectively, after onset of pulmonary infection. The second case was characterized by a protracted course with spread of infection to various organs, including subcutaneous tissue, skin, colon and other intra-abdominal tissues, and central nervous system; the spread started 4 years after clinical resolution of a first pulmonary manifestation and progressed over a period of 2 years. Conclusions Our report highlights the importance of an effective immune recovery, despite fully suppressive HAART, along with anti-rhodococcal therapy, in order to clear rhodococcal infection. PMID:22168333

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

    PubMed Central

    Campos, Lorenza Nogueira; Guimares, 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=1.143.06) 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

  12. Antiretroviral Therapy Adherence and Use of an Electronic Shared Medical Record Among People Living with HIV.

    PubMed

    Saberi, Parya; Catz, Sheryl L; Leyden, Wendy A; Stewart, Christine; Ralston, James D; Horberg, Michael A; Grothaus, Louis; Silverberg, Michael J

    2015-06-01

    Electronic shared medical records (SMR) are emerging healthcare technologies that allow patients to engage in their healthcare by communicating with providers, refilling prescriptions, scheduling appointments, and viewing portions of medical records. We conducted a pre-post cohort study of HIV-positive adults who used and did not use SMR in two integrated healthcare systems. We compared the difference in antiretroviral refill adherence between SMR users and age- and sex-frequency matched non-users from the 12-month period prior to SMR useto the 12-month period starting 6 months after initiation of SMR use. High adherence was maintained among SMR users (change = -0.11 %) but declined among non-users (change = -2.05 %; p = 0.003). Among SMR users, there was a steady improvement in adherence as monthly frequency of SMR use increased (p = 0.009). SMR use, particularly more frequent use, is associated with maintaining high adherence and non-use is associated with declines in adherence over time among patients with access to these online services. PMID:25572829

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

    PubMed Central

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

    2013-01-01

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

  14. Reduced Adherence to Antiretroviral Therapy among HIV-infected Tanzanians Seeking Cure from the Loliondo Healer

    PubMed Central

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

    2014-01-01

    The predictors for seeking alternative therapies for HIV-infection in sub-Saharan Africa are unknown. Among a prospective cohort of 442 HIV-infected patients in Moshi, Tanzania, 249 (56%) sought cure from a newly popularized religious healer in Loliondo (450 kilometers away), and their adherence to antiretrovirals (ARVs) dropped precipitously (OR=0.20, 95% CI, 0.090.44, p<0.001) following the visit. Compared to those not attending Loliondo, attendees were more likely to have been diagnosed with HIV more remotely (3.8 vs. 3.0 years prior, p<0.001), have taken ARVs longer (3.4 vs. 2.5 years, p<0.001), have higher median CD4+ lymphocyte counts (429 vs. 354 cells/mm3, p<0.001), be wealthier (wealth index 10.9 vs. 8.8, p = 0.034), and receive care at the private versus the public hospital (p=0.012). In multivariable logistic regression, only years since the start of ARVs remained significant (OR, 1.49, 95% CI, 1.231.80). Treatment fatigue may play a role in the lure of alternative healers. PMID:24525471

  15. How to Start Interventional Radiology

    PubMed Central

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

    2013-01-01

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

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. A Multicenter Study of Initiation of Antiretroviral Therapy and Transmitted Drug Resistance in Antiretroviral-Naive Adolescents and Young Adults With HIV in New York City

    PubMed Central

    Gagliardo, Christina; Brozovich, Ava; Birnbaum, Jeffrey; Radix, Anita; Foca, Marc; Nelson, John; Saiman, Lisa; Yin, Michael; Carras-Terzian, Elektra; West, Emily; Neu, Natalie

    2014-01-01

    Background.?In December 2009, the Department of Health and Human Services guidelines for initiation of antiretroviral therapy (ART) changed to include patients with CD4 counts between 350 and 500 cells/L. The aims of this study were to assess uptake of this recommendation in ART-naive youth with human immunodeficiency virus (HIV) and to describe the epidemiology of transmitted genotypic drug resistance mutations (DRMs) in this population. Methods.?A multicenter, retrospective cohort study of ART initiation in ART-naive youth was performed. Eligible subjects were 1325 years of age, were diagnosed with HIV within 1 year of presentation to care at the study sites, and presented to care from January 2007 to June 2011. Results.?Of 685 potential subjects identified, 331 (49%) fulfilled inclusion criteria. Mean CD4 count at presentation to care was 452 cells/L. Overall, 191 (58%) subjects started ART. The mean CD4 count at ART initiation was 261 cells/L before and 363 cells/L after the 2009 guideline change (P < .0001). Of 212 (64%) subjects with resistance testing available prior to ART initiation, 38 (18%) subjects had a major DRM and an increased proportion of resistance was seen in later study years. Conclusions.?Our study demonstrated an uptake in recently changed guideline recommendations to treat HIV-infected individuals at higher CD4 counts and reinforces the importance of performing resistance testing at entry into care, as 18% of our population had major DRMs prior to initiation of ART. PMID:24429431

  1. 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.

  2. [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

  3. 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

  4. 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?

  5. Practical and Conceptual Challenges in Measuring Antiretroviral Adherence

    PubMed Central

    Berg, Karina M.; Arnsten, Julia H.

    2010-01-01

    Accurate measurement of antiretroviral adherence is essential for targeting and rigorously evaluating interventions to improve adherence and prevent viral resistance. Across diseases, medication adherence is an individual, complex, and dynamic human behavior that presents unique measurement challenges. Measurement of medication adherence is further complicated by the diversity of available measures, which have different utility in clinical and research settings. Limited understanding of how to optimize existing adherence measures has hindered progress in adherence research in both HIV and other diseases. Though self-report is the most widely used adherence measure and the most promising for use in clinical care and resource limited settings, adherence researchers have yet to develop evidence-based standards for self-reported adherence. In addition, the use of objective measures, such as electronic drug monitoring or pill counts, is limited by poor understanding of the source and magnitude of error biasing these measures. To address these limitations, research is needed to evaluate methods of combining information from different measures. The goals of this review are to describe the state of the science of adherence measurement, to discuss the advantages and disadvantages of common adherence measurement methods, and to recommend directions for improving antiretroviral adherence measurement in research and clinical care. PMID:17133207

  6. 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

  7. Monitoring adherence to antiretroviral treatment in Brazil: an urgent challenge.

    PubMed

    Rocha, Gustavo Machado; Machado, Carla Jorge; Acurcio, Francisco de Assis; Guimares, Mark Drew Crosland

    2011-01-01

    The aim of this study was to describe the effect of non-adherence on the main laboratory outcomes, TCD4+ lymphocyte count and viral load, routinely used to monitor patients initiating treatment according to three different approaches to measure adherence to antiretroviral therapy. Among 288 participants, 22.9%, 31.9% and 74.3% were considered non-adherent, according to medical charts, self-report and pharmacy records, respectively. Depending on the adherence measures used, the average gain in TCD4+ lymphocyte count ranged from 142.4 to 195.4 cells/mm3 among adherent patients, and from 58.5 to 99.8 lymphocytes TCD4+/mm3 among those non-adherent. The average reduction on viral load ranged from 4.25 to 4.62 log copies/mL among the adherent patients, and from 1.99 to 4.07 log among those non-adherent. Monitoring antiretroviral adherence should be considered a priority in these public AIDS referral centers in order to identify patients at high risk of developing virologic failure. Early interventions are necessary in order to maintain the initial therapeutic regimens for longer periods. PMID:21503526

  8. Mortality after failure of antiretroviral therapy in sub-Saharan Africa

    PubMed Central

    Keiser, Olivia; Tweya, Hannock; Braitstein, Paula; Dabis, Franois; Mac Phail, Patrick; Boulle, Andrew; Nash, Denis; Wood, Robin; Lthi, Ruedi; Brinkhof, Martin WG; Schechter, Mauro; Egger, Matthias

    2010-01-01

    Summary Objective To assess the outcome of patients who experienced treatment failure with anti-retrovirals in sub-Saharan Africa. Methods Analysis of 11 ART programmes in sub-Saharan Africa. World Health Organization (WHO) criteria were used to define treatment failure. All ART-nave patients aged >16 years who started with a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen and had at least six months of follow-up were eligible. For each patient who switched to a second-line regimen, 10 matched patients who remained on a non-failing first-line regimen were selected. Time was measured from the time of switching, from the corresponding time in matched patients, or from the time of treatment failure in patients who remained on a failing regimen. Mortality was analyzed using Kaplan-Meier curves and random-effects Cox models. Results Of 16,591 adult patients starting ART, 382 patients (2.3%) switched to a second-line regimen. Another 323 patients (1.9%) did not switch despite developing immunological or virological failure. Cumulative mortality at one year was 4.2% (95% CI 2.2-7.8%) in patients who switched to a second-line regimen and 11.7% (7.3%-18.5%) in patients who remained on a failing first-line regimen, compared to 2.2% (1.6-3.0%) in patients on a non-failing first-line regimen (p<0.0001). Differences in mortality were not explained by nadir CD4 cell count, age or differential loss to follow-up. Conclusions Many patients who meet criteria for treatment failure do not switch to a second-line regimen and die. There is an urgent need to clarify the reasons why in sub-Saharan Africa many patients remain on failing first-line ART. PMID:20003034

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

    PubMed Central

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

    2010-01-01

    Background Although combination antiretroviral therapy (cART) initiated in the acute phase of HIV-1 infection may prevent expansion of the latent reservoir, its benefits remain controversial. In the current study, HIV-1 RNA transcription patterns in peripheral blood mononuclear cells (PBMC) were monitored during acute cART to assess the effect of early treatment on cellular viral reservoirs. Methodology/Principal Findings Acutely HIV-1 infected patients (n?=?24) were treated within 315 weeks after infection. Patients elected to cease treatment after ?1 year of therapy. HIV-1 DNA (vDNA), HIV-1 RNA species expressed both in latently and productively infected cells, unspliced (UsRNA), multiply spliced (MsRNA-tatrev; MsRNA-nef), and PBMC-associated extracellular virion RNA (vRex), expressed specifically by productively infected cells, were quantified in PBMC by patient matched real-time PCR prior, during and post cART. In a matched control-group of patients on successful cART started during chronic infection (n?=?15), UsRNA in PBMC and vDNA were measured cross-sectionally. In contrast to previous reports, PBMC-associated HIV-1 RNAs declined to predominantly undetectable levels on cART. After cART cessation, UsRNA, vRex, and MsRNA-tatrev rebounded to levels not significantly different to those at baseline (p>0.1). In contrast, MsRNA-nef remained significantly lower as compared to pretreatment (p?=?0.015). UsRNA expressed at the highest levels of all viral RNAs, was detectable on cART in 42% of patients with cART initiated during acute infection as opposed to 87% of patients on cART initiated during chronic infection (Fisher's exact test; p?=?0.008). Accordingly, UsRNA levels were 105fold lower in the acute as compared to the chronic group. Conclusion Early intervention resulted in profound depletion of PBMC expressing HIV-1 RNA. This is contrary to chronically infected patients who predominantly showed continuous UsRNA expression on cART. Thus, antiretroviral treatment initiated during the acute phase of infection prevented establishment or expansion of long-lived transcriptionally active viral cellular reservoirs in peripheral blood. PMID:20967271

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

    PubMed

    Dhamija, P; Bansal, D; Medhi, B

    2009-07-01

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

  11. 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

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

    PubMed

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

    2013-05-01

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

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

    PubMed

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

    2015-01-28

    Whilst effective antiretroviral therapy is protective against the more severe forms of HIV-associated brain disease, there remains a large burden of clinically symptomatic cognitive impairment in the modern era. Although several potential pathogenic mechanisms have been proposed, the underlying pathology remains elusive. In this review, we summarize the evidence describing neuronal toxicity of antiretroviral agents themselves in both preclinical and clinical situations, as well as the potential pathological mechanisms underlying this toxicity. We also consider the implications for future practice and clinical research in which case determining optimal antiretroviral combinations that effectively suppress HIV replication whilst minimizing neurotoxic effects on the central nervous system may become paramount. PMID:25426811

  14. 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

  15. 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

  16. 30 CFR 75.1913 - Starting aids.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... fuel starting aids shall be stored in metal enclosures that are used only for storage of starting aids. Such metal enclosures must be conspicuously marked, secured, and protected from damage. (c)...

  17. 30 CFR 57.10010 - Starting precautions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

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

  18. 30 CFR 56.10010 - Starting precautions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

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

  19. Long-Distance Caregiving -- Getting Started

    MedlinePLUS

    ... Distance Caregiving—Getting Started Heath and Aging Long-Distance Caregiving—Getting Started Who is a long-distance ... of your family member. Who is a long-distance caregiver? Anyone, anywhere, can be a long-distance ...

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

    PubMed

    do Lago, Regina Ferro; Costa, Nilson do Rosrio

    2010-11-01

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

  1. 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

  2. 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

  3. 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

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

    PubMed

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

    2011-01-01

    Guillain-Barr syndrome (GBS) has been reported in HIV-infected patients in association with the immune reconstitution syndrome whose symptoms can be mimicked by highly active antiretroviral therapy (HAART)-mediated mitochondrial toxicity. We report a case of a 17-year-old, HIV-infected patient on HAART with a normal CD4 count and undetectable viral load, presenting with acute lower extremity weakness associated with lactatemia. Electromyography/nerve conduction studies revealed absent sensory potentials and decreased compound muscle action potentials, consistent with a diagnosis of acute motor and sensory axonal neuropathy. Lactatemia resolved following cessation of HAART; however, neurological deficits minimally improved over several months in spite of immune modulatory therapy. This case highlights the potential association between HAART, mitochondrial toxicity and acute axonal neuropathies in HIV-infected patients, distinct from the immune reconstitution syndrome. PMID:21327178

  5. Antiretroviral bioanalysis methods of tissues and body biofluids.

    PubMed

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

    2013-02-01

    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

  6. 76 FR 37174 - Capital Investment Program-New Starts and Small Starts Program Funds

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-24

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

  7. 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.

  8. Antiretroviral Treatment Regimen Outcomes Among HIV-Infected Prisoners

    PubMed Central

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

    2008-01-01

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

  9. 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

  10. 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

  11. 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, Franois; Ftkenheuer, 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

  12. Antiretroviral Therapy Outcomes among Adolescents and Youth in Rural Zimbabwe

    PubMed Central

    Bygrave, Helen; Mtangirwa, Judith; Ncube, Kwenzakwenkosi; Ford, Nathan; Kranzer, Katharina; Munyaradzi, Dhodho

    2012-01-01

    Around 2 million adolescents and 3 million youth are estimated to be living with HIV worldwide. Antiretroviral outcomes for this group appear to be worse compared to adults. We report antiretroviral therapy outcomes from a rural setting in Zimbabwe among patients aged 1030 years who were initiated on ART between 2005 and 2008. The cohort was stratified into four age groups: 1015 (young adolescents) 15.119 years (adolescents), 19.124 years (young adults) and 24.129.9 years (older adults). Survival analysis was used to estimate rates of deaths and loss to follow-up stratified by age group. Endpoints were time from ART initiation to death or loss to follow-up. Follow-up of patients on continuous therapy was censored at date of transfer, or study end (31 December 2008). Sex-adjusted Cox proportional hazards models were used to estimate hazard ratios for different age groups. 898 patients were included in the analysis; median duration on ART was 468 days. The risk of death were highest in adults compared to young adolescents (aHR 2.25, 95%CI 1.174.35). Young adults and adolescents had a 23 times higher risk of loss to follow-up compared to young adolescents. When estimating the risk of attrition combining loss to follow-up and death, young adults had the highest risk (aHR 2.70, 95%CI 1.624.52). This study highlights the need for adapted adherence support and service delivery models for both adolescents and young adults. PMID:23285204

  13. 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

  14. 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

  15. 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…

  16. HBV influence on Response to Antiretroviral Therapy in Horizontally HIV-HBV Coinfected Patient during Early Childhood

    PubMed Central

    Niculescu, Irina; Cup?a, A.M.; Stoian, Andreea Cristina; Dumitrescu, FLorentina; Giubelan, L.I.; Alexandru, D.O.

    2013-01-01

    Background: There are few studies on pediatric HIV-HBV coinfection, so evidences about relationships between the two viruses are scarce. Objectives: influence of HBV infection on virological and immunological response to antiretroviral therapy (ART) in antiretroviral-nave horizontally HIV-HBV coinfected subjects during early childhood. Material and methods: observational study on 826 HIV+ subjects in evidence of Craiova Regional Centre (CRC); we analyzed the immunological and virological response at 6-12 months after starting first antiretroviral regimens compared in 2 groups: horizontally HIV-HBV coinfected subjects during early childhood (CoS) versus horizontally HIV infected subjects during early childhood without HBV infection (non-CoS). Results: Number of subjects: CoS-66 subjects, non-CoS-132 subjects. Demographic data: CoS-gender ratio F:M=0.886, the majority lived in rural area (57.58%), mean age on diagnosis-9.2884.607 years, non-CoS-gender ratio F:M=0.859, the majority lived in urban area (53.79%), mean age on diagnosis-10.7425.107 years. At baseline, HIV category was: CoS-A-1.52%, B-80.30%, C-18.18%, non-CoS-A-2.27%, B-70.45%, C-27.27% (p Chi2=0.332), the mean CD4+ cell count was: CoS-148.33148.10 cells/ml, non-CoS-163.17155.39 cells/ml (p Student=0.521) and the mean HIV viral load (HIV VL) was: CoS-5.060.80 lgcopies/ml (for 29 subjects), non-CoS-5.040.84 lgcopies/ml (for 61 subjects) (p Student=0.978). At the end of the studied period, the mean increase in CD4+ cell count was: CoS-177.068141.676 cells/ml, non-CoS-176.015191.751 cells/ml (p Student=0.969) and the mean decrease in HIV VL was: CoS-5.040.79 lgcopies/ml, non-COS-4.692.04 lgcopies/ml (p Student=0.911). Conclusions: The presence of HBV coinfection does not influence immunological or virological response to ART. PMID:24778861

  17. 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

  18. 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

  19. 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

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

    PubMed

    Ruz-Lpez, Patricia; Moreno-Coutio, Gabriela; Fernndez-Martnez, Ramn; Espinoza-Hernndez, Jessica; Rodrguez-Zulueta, Patricia; Reyes-Tern, Gustavo

    2015-09-01

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

  1. 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

  2. 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 20072012. 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: 5.857.82%); 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 20082010). 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

  3. 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

  4. Osteoarticular complications related to HIV infection and highly active antiretroviral therapy.

    PubMed

    Lima, Ana Lcia Lei Munhoz; Zumiotti, Arnaldo Valdir; Camanho, Gilberto Luis; Benegas, Eduardo; dos Santos, Alexandre Leme Godoy; D'Elia, Caio Oliveira; Oliveira, Priscila Rosalba Domingos

    2007-08-01

    With the significant increase in life expectancy for HIV-infected patients in the era of high potency antiretroviral therapy, major metabolic changes have been observed due to the prolonged period of the viral infection and the treatment itself. Osteoarticular changes resulting from these processes are mainly reported in long term HIV-infected patients receiving high potency antiretroviral therapy and include osteopenia/osteoporosis, osteonecrosis, carpal tunnel syndrome and adhesive capsulitis of the shoulder. PMID:17873999

  5. 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

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

    PubMed

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

    2015-12-01

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

  7. 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; Loureno, 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 (20002006 and 20072012) and CD4+ cell count at cART initiation (<500 versus ?500 cells/?l). We considered both baseline and longitudinal covariates. We fitted different multivariable models using cross-sectional and longitudinal statistical methods, depending on the outcome. Results Patients who initiated cART with a CD4+ cell count at least 500 cells/?l in 20072012 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

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

    PubMed Central

    Puttkammer, Nancy H.; Zeliadt, Steven B.; Baseman, Janet G.; Destin, Rodney; Domerant, Jean Wysler; Coq, Nancy Rachel Labb; 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 20052011 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 iSant 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): 15.818.3). 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: 1.542.33; 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

  9. 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

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

    PubMed Central

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

    2015-01-01

    Abstract Objective To propose two new indicators for monitoring access to antiretroviral treatment (ART) for human immunodeficiency virus (HIV); (i)the time from HIV seroconversion to ART initiation, and (ii)the time from ART eligibility to initiation, referred to as delay in ART initiation. To estimate values of these indicators in Cameroon. Methods We used linear regression to model the natural decline in CD4+ T-lymphocyte (CD4+ cell) numbers in HIV-infected individuals over time. The model was fitted using data from a cohort of 351 people in Cte dIvoire. We used the model to estimate the time from seroconversion to ART initiation and the delay in ART initiation in a representative sample of 4154 HIV-infected people who started ART in Cameroon between 2007 and 2010. Findings In Cameroon, the median CD4+ cell counts at ART initiation increased from 140 cells/?l (interquartile range, IQR: 66 to 210) in 20072009 to 163 cells/?l (IQR: 73 to 260) in 2010. The estimated average time from seroconversion to ART initiation decreased from 10.4years (95% confidence interval, CI: 10.3 to 10.5) to 9.8years (95% CI: 9.6 to 10.0). Delay in ART initiation increased from 3.4years (95% CI: 3.1 to 3.7) to 5.8years (95% CI: 5.6 to 6.2). Conclusion The estimated time to initiate ART and the delay in ART initiation indicate that progress in Cameroon is insufficient. These indicators should help monitor whether public health interventions to accelerate ART initiation are successful. PMID:26478609

  11. 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) nave 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 nave 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 nave 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

  12. The WHO public-health approach to antiretroviral treatment against HIV in resource-limited settings.

    PubMed

    Gilks, Charles F; Crowley, Siobhan; Ekpini, Ren; Gove, Sandy; Perriens, Jos; Souteyrand, Yves; Sutherland, Don; Vitoria, Marco; Guerma, Teguest; De Cock, Kevin

    2006-08-01

    WHO has proposed a public-health approach to antiretroviral therapy (ART) to enable scaling-up access to treatment for HIV-positive people in developing countries, recognising that the western model of specialist physician management and advanced laboratory monitoring is not feasible in resource-poor settings. In this approach, standardised simplified treatment protocols and decentralised service delivery enable treatment to be delivered to large numbers of HIV-positive adults and children through the public and private sector. Simplified tools and approaches to clinical decision-making, centred on the "four Ss"--when to: start drug treatment; substitute for toxicity; switch after treatment failure; and stop--enable lower level health-care workers to deliver care. Simple limited formularies have driven large-scale production of fixed-dose combinations for first-line treatment for adults and lowered prices, but to ensure access to ART in the poorest countries, the care and drugs should be given free at point of service delivery. Population-based surveillance for acquired and transmitted resistance is needed to address concerns that switching regimens on the basis of clinical criteria for failure alone could lead to widespread emergence of drug-resistant virus strains. The integrated management of adult or childhood illness (IMAI/IMCI) facilitates decentralised implementation that is integrated within existing health systems. Simplified operational guidelines, tools, and training materials enable clinical teams in primary-care and second-level facilities to deliver HIV prevention, HIV care, and ART, and to use a standardised patient-tracking system. PMID:16890837

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

    PubMed Central

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

    2012-01-01

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

  14. [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

  15. The public health approach to identify antiretroviral therapy failure: high-level nucleoside reverse transcriptase inhibitor resistance among Malawians failing first-line antiretroviral therapy

    PubMed Central

    Hosseinipour, Mina C.; van Oosterhout, Joep J.G.; Weigel, Ralf; Phiri, Sam; Kamwendo, Debbie; Parkin, Neil; Fiscus, Susan A.; Nelson, Julie A.E.; Eron, Joseph J.; Kumwenda, Johnstone

    2010-01-01

    Background Over 150 000 Malawians have started antiretroviral therapy (ART), in which first-line therapy is stavudine/lamivudine/nevirapine. We evaluated drug resistance patterns among patients failing first-line ART on the basis of clinical or immunological criteria in Lilongwe and Blantyre, Malawi. Methods Patients meeting the definition of ART failure (new or progressive stage 4 condition, CD4 cell count decline more than 30%, CD4 cell count less than that before treatment) from January 2006 to July 2007 were evaluated. Among those with HIV RNA of more than 1000 copies/ml, genotyping was performed. For complex genotype patterns, phenotyping was performed. Results Ninety-six confirmed ART failure patients were identified. Median (interquartile range) CD4 cell count, log10 HIV-1 RNA, and duration on ART were 68 cells/?l (23174), 4.72 copies/ml (4.265.16), and 36.5 months (26.649.8), respectively. Ninety-three percent of samples had nonnucleoside reverse transcriptase inhibitor mutations, and 81% had the M184V mutation. The most frequent pattern included M184V and nonnucleoside reverse transcriptase inhibitor mutations along with at least one thymidine analog mutation (56%). Twenty-three percent of patients acquired the K70E or K65R mutations associated with tenofovir resistance; 17% of the patients had pan-nucleoside resistance that corresponded to K65R or K70E and additional resistance mutations, most commonly the 151 complex. Emergence of the K65R and K70E mutations was associated with CD4 cell count of less than 100 cells/?l (odds ratio 6.1) and inversely with the use of zidovudine (odds ratio 0.18). Phenotypic susceptibility data indicated that the nucleoside reverse transcriptase inhibitor backbone with the highest activity for subsequent therapy was zidovudine/lamivudine/tenofovir, followed by lamivudine/tenofovir, and then abacavir/didanosine. Conclusion When clinical and CD4 cell count criteria are used to monitor first-line ART failure, extensive nucleoside reverse transcriptase inhibitor and nonnucleoside reverse transcriptase inhibitor resistance emerges, with most patients having resistance profiles that markedly compromise the activity of second-line ART. PMID:19417582

  16. 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.

  17. 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

  18. 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.

  19. Wireless "Jump" Starts for Partly Disabled Equipment

    NASA Technical Reports Server (NTRS)

    Castle, K. D.

    1986-01-01

    Equipment activated when normal remote starting does not work Beam from nearby station first carries raw energy and then subsystemactivating signals to equipment crippled by discharged storage batteries. Operators start up equipment without approaching it under hazardous conditions. Potential terrestrial applications for scheme include starting of robots on such remotely-controlled hazardous tasks as handling of explosives or retrieval or deposition of objects in hostile environments.

  20. 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

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

    PubMed Central

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

    2015-01-01

    Objective: The objective of this study is to assess the risk of viral rebound in postpartum women on suppressive combination antiretroviral therapy (cART). Methods: Using data from the UK Collaborative HIV Cohort (UK CHIC) study and the UK and Ireland National Study of HIV in Pregnancy and Childhood (NSHPC), women with HIV-RNA 50?copies/ml or less at delivery in 20062011, 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 KaplanMeier analysis; adjusted hazard ratios (aHRs) for the 03 and 312 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) 4.07.7] experienced viral rebound by 3 months, and 2.2% (1.43.0%) of their controls. The risk of viral rebound was higher in postpartum women than in controls during the first 3 months [aHR 2.63 (1.584.39)] but not during the 312 months postdelivery/pseudo-delivery. In postpartum women who started cART during pregnancy, 27% (2232%) experienced viral rebound by 3 months, and 3.0% (1.64.4%) 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 (3.5812.29); 312 months: aHR 4.05 (2.038.09)]. Conclusion: In women on suppressive cART, the risk of viral rebound is increased following delivery, especially in the first 3 months, which may be related to reduced adherence, indicating the need for additional adherence support for postpartum women. PMID:26544700

  2. 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

  3. 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

  4. Predictors of Adherence to Antiretroviral Therapy in Rural Zambia

    PubMed Central

    Carlucci, James G.; Kamanga, Aniset; Sheneberger, Robb; Shepherd, Bryan E.; Jenkins, Cathy A.; Spurrier, John; Vermund, Sten H.

    2009-01-01

    Background/Objective Antiretroviral therapy (ART) adherence levels of ?95% optimize outcomes and minimize HIV drug resistance. As such, identifying barriers to adherence is essential. We sought to assess travel to point-of-care for ART as a potential barrier to adherence in rural Zambia, within the context of patient demographics, perceived stigma, and selected clinical indices. Methods We studied 424 patients receiving ART from the Macha Mission Hospital (MMH). Interviews ascertained age, gender, education, perceived stigma, nearest rural health facility (RHF), and mode/cost/time of transport for each study participant. Motorcycle odometer and global positioning system way-points measured distance from the MMH to each of the RHFs, estimating patients home-to-MMH travel distances. Body mass index, World Health Organization HIV/AIDS stage, and pill counts were assessed from review of patients medical and pharmacy records. Results At least 95% adherence was documented for 83.7% of the patients in their first months of ART. Travel-related factors did not predict adherence. Adherence was higher for those on ART for a longer time (odds ratio = 1.04 per day; P = 0.002). Conclusions Patients in rural Zambia can achieve adherence rates compatible with good clinical outcomes despite long travel distances. The MMH was able to provide quality HIV/AIDS care by implementing programmatic features selecting for a highly adherent population in this resource-limited setting. PMID:18209678

  5. 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

  6. 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

  7. 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

  8. Barriers to Sustaining Antiretroviral Treatment in Kisesa, Tanzania

    PubMed Central

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

    2009-01-01

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

  9. Effective treatment of a highly active antiretroviral regimen through jejunostomy.

    PubMed

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

    2014-06-01

    A 49-year-old woman voluntarily not receiving HIV treatment was admitted to the emergency department showing sepsis and peritonism. She required several surgical procedures for intestinal perforations. Finally, a proximal-terminal jejunostomy and a distal mucous jejunostomy were performed. At this time, her HIV viral load was 531?388 copies/ml and CD4 count was 193 cells/?l. Then, HAART was restarted with lopinavir/ritonavir 400/100 mg plus lamivudine 150 mg/12 hours, and etravirine 400 mg/24 hours. Each drug was dissolved in 20 ml of water and administered through the distal jejunostomy. In 2 months, her HIV viral load decreased in 39 log and CD4 count increased in 70 cells/?l. On day 250, an intestinal tract reconstruction was performed and short after highly active antiretroviral therapy (HAART) was restarted orally. Lopinavir/ritonavir, etravirine, and lamivudine administered through a jejunostomy resulted effective in decreasing HIV viral load and increasing CD4 lymphocyte count in a HIV patient who could not receive treatment orally. PMID:24075526

  10. 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

  11. Development of HIV Reservoir Targeted Long Acting Nanoformulated Antiretroviral Therapies

    PubMed Central

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

    2014-01-01

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

  12. 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

  13. 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

  14. Structured antiretroviral treatment interruptions in chronically HIV-1-infected subjects

    PubMed Central

    Ortiz, Gabriel M.; Wellons, Melissa; Brancato, Jason; Vo, Ha T. T.; Zinn, Rebekah L.; Clarkson, Daniel E.; Van Loon, Katherine; Bonhoeffer, Sebastian; Miralles, G. Diego; Montefiori, David; Bartlett, John A.; Nixon, Douglas F.

    2001-01-01

    The risks and benefits of structured treatment interruption (STI) in HIV-1-infected subjects are not fully understood. A pilot study was performed to compare STI with continuous highly active antiretroviral therapy (HAART) in chronic HIV-1-infected subjects with HIV-1 plasma RNA levels (VL) <400 copies per ml and CD4+ T cells >400 per ?l. CD4+ T cells, VL, HIV-1-specific neutralizing antibodies, and IFN-?-producing HIV-1-specific CD8+ and CD4+ T cells were measured in all subjects. STIs of 1-month duration separated by 1 month of HAART, before a final 3-month STI, resulted in augmented CD8+ T cell responses in all eight STI subjects (P = 0.003), maintained while on HAART up to 22 weeks after STI, and augmented neutralization titers to autologous HIV-1 isolate in one of eight subjects. However, significant decline of CD4+ T cell count from pre-STI level, and VL rebound to pre-HAART baseline, occurred during STI (P = 0.001 and 0.34, respectively). CD4+ T cell counts were regained on return to HAART. Control subjects (n = 4) maintained VL <400 copies per ml and stable CD4+ T cell counts, and showed no enhancement of antiviral CD8+ T cell responses. Despite increases in antiviral immunity, no control of VL was observed. Future studies of STI should proceed with caution. PMID:11687611

  15. Antiretroviral Therapy in Zambia: Do Partners on ART Enhance Adherence?

    PubMed Central

    Jones, Deborah; Cook, Ryan; Spence, Andrew; Weiss, Stephen M.; Chitalu, Ndashi

    2016-01-01

    Background Adherence to antiretroviral therapy (ART) is essential to optimize HIV treatment outcomes. Among individuals on ART, targeted peer support has been found to support adherence. This study of Zambian heterosexual couples living with HIV examined whether partners would exert a positive influence on each other's adherence, and compared adherence between couples in which either one or both members were on ART. Methods Couples (n = 446 participants), in which either or both member were on ART were assessed at baseline, 6 and 12 months. Results Most participants (64%, n = 263) were on ART; overall, uptake of ART increased to 74% at 12 months. At baseline, 76% reported near perfect adherence; at 6 and 12 months, 66% and 70% were adherent, respectively. A regression analysis indicated that the decline in adherence did not differ between those couples in which one or both partners were on ART [F (2, 624) = 0.37, p = .692]. Pairwise comparison indicated that adherence primarily decreased between baseline and 6 months (t = 2.72, p = .007), and was stable 6 to 12 months. Conclusions This study of couples in Zambia found adherence was not enhanced by having a partner on ART, and that adherence declined over time. Partners on ART may not necessarily provide support for adherence to each other. Partners may represent an untapped resource for optimizing adherence; results highlight the need for provider guidance and structured adherence interventions targeting partner adherence support. PMID:25294856

  16. Factors associated with non-adherence to antiretroviral therapy in adults with AIDS in the first six months of treatment in Salvador, Bahia State, Brazil.

    PubMed

    Silva, Jos Adriano Ges; Dourado, Ins; Brito, Ana Maria de; Silva, Carlos Alberto Lima da

    2015-06-01

    The control of viral replication is essential in the highly active antiretroviral therapy (HAART), and adherence to therapy is instrumental for such control. Individual and external factors influence adhesion to the use of antiretroviral (ARV) drugs. This is a cross-sectional study to investigate factors associated with non-adherence to HAART in AIDS patients in Salvador, Bahia State, Brazil, with age ? 13 years and first prescription in 2009. Data was collected from patient charts and pharmacy records. From a total of 216 patients, 65.3% were males; mean age 37.8 9.5 years; single, 67.9%; heterosexual, 64%; more than 8 years of school education, 65.3%; alcohol users, 61.5%; non-smokers, 75,1% or non-illicit drug users, 93.7%. A proportion of 94% started ARV therapy with TCD4+ < 350 cells/mm3; 61.8% were symptomatic; and 68.4% had an adverse drug reaction. The prevalence of non-adherence was 25%. The variables associated were: longer time between HIV infection and AIDS (aOR = 3.9), adverse drug reaction (aOR = 2.4), under 34 years of age (aOR = 2.2), less than 8 years of school education (aOR = 2.2) and illicit drugs use (aOR = 2.6). A high-non-adherence rate is an important problem within the first six months of HAART. PMID:26200367

  17. Head Start Home-Based Resource Directory.

    ERIC Educational Resources Information Center

    Trans-Management Systems, Inc.

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

  18. Application of SMES Unit in Black Start

    NASA Astrophysics Data System (ADS)

    Yang, Jun; Liu, Wenqing; Liu, Pei

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

  19. 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…

  20. Trident SSBNS in START. Final report

    SciTech Connect

    Ackley, R.T.

    1990-04-30

    This report advocates not agreeing to ballistic missile warhead sublimits in START in order to place maximum reliance on the Trident/D-5 strategic weapon system. With reduced numbers in our post-START inventory, it is mandatory to emphasize our most survivable, capable, flexible and affordable systems for deterrence and defense.

  1. 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

  2. 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…

  3. 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,…

  4. 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.…

  5. 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.…

  6. 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…

  7. 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…

  8. JobStart: The Road to Independence.

    ERIC Educational Resources Information Center

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

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

  9. 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

  10. 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

    2015-12-01

    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

  11. 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).

  12. Comparison of Antiretroviral Regimens: Adverse Effects and Tolerability Failure that Cause Regimen Switching

    PubMed Central

    Jung, Hyejin; Kim, Sujeong; Lee, Jong Myung

    2015-01-01

    Background The efficacy of antiretroviral therapy (ART) has improved, and the adverse effects of antiretroviral drugs have been reduced. However, these adverse effects still significantly influence patient compliance, increasing the risk of tolerability failure. Therefore, we investigated the adverse effects and tolerability failure causing changes in the first ART regimen, and identified the regimens that were most vulnerable to switching. Materials and Methods We enrolled patients with human immunodeficiency virus (HIV) who commenced their first ART between January 1, 2011 and July 30, 2014. Patients who started their first ART regimen at the Kyungpook National University Hospital were included in the study if they were aged ?18 years and were followed-up for ?12 weeks. The primary dependent variable was the duration of treatment on the same ART regimen. We analyzed the maintenance rate of the first ART regimen based on the treatment duration between these groups using survival analysis and log rank test. The frequency of the adverse effects of ART regimens was analyzed by multiple response data analysis. Results During the investigation period, 137 patients were enrolled. Eighty-one patients were maintained on the initial treatment regimen (59.1%). In protease inhibitor (PI)-based regimen group, 54 patients were maintained on the initial treatment regimen (54/98, 55.1%). In non-nucleoside reverse transcriptase inhibitor (NNRTI)-and integrase inhibitor (II)-based regimen group, 15 (15/26, 57.7%) and 12 (12/13, 92.3%) patients were maintained on the initial treatment regimen, respectively. Adverse effects that induced ART switching included rash (16/35, 45.7%), gastrointestinal discomfort or pain (7/35, 20%), diarrhea (7/35, 20%), hyperbilirubinemia (6/35, 17.1%), headache or dizziness (3/35, 8.5%). Among the treatment regimens, the group receiving an II-based regimen showed the least switching. The group receiving PI-and NRTI-based regimens were most likely to switch due to adverse effects during the early treatment period. However, after about 18 months, switching was rarely observed in these groups. Among the PI drugs, darunavir/ritonavir showed fewer drug changes than atazanavir/ritonavir (P = 0.004, log rank test) and lopinavir/ritonavir (P = 0.010). Among the NNRTI drugs, rilpivirne produced less switching than efavirenz (P = 0.045). Conclusions Adverse effects to ART resulted in about a quarter of patients switching drugs during the early treatment period. II-based regimens were advantageous because they were less likely to induce switching within 18 months of treatment commencement. These findings indicated the importance of considering and monitoring the adverse effects of ART in order to improve adherence. PMID:26788406

  13. 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

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

    PubMed Central

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

    2008-01-01

    Abstract Resistance-associated mutations (RAMs) in plasma samples from HIV-1-infected women who received antiretroviral (ARV) prophylaxis during pregnancy was assessed and correlated with the detection of RAMs in peripheral blood mononuclear cells (PMBCs). The study population was composed of HIV-1-infected women enrolled in a prospective cohort study in Latin America and the Caribbean (NISDI Perinatal Study) as of March 1, 2005, who were diagnosed with HIV-1 infection during the current pregnancy, who received ARVs during pregnancy for prevention of mother-to-child transmission of HIV-1, and who were followed through at least the 612 week postpartum visit. Plasma samples collected at enrollment during pregnancy and at 612 weeks postpartum were assayed for RAMs. Plasma results were compared to previously described PBMC results from the same study population. Of 819 enrolled subjects, 197 met the eligibility criteria. Nucleic acid amplification was accomplished in 123 plasma samples at enrollment or 612 weeks postpartum, and RAMs were detected in 22 (17.9%; 95%CI: 11.725.9%). Previous analyses had demonstrated detection of RAMs in PBMCs in 19 (16.1%). There was high concordance between RAMs detected in plasma and PBMC samples, with only eight discordant pairs. The prevalence of RAMs among these pregnant, HIV-1-infected women is high (>15%). Rates of detection of RAMs in plasma and PBMC samples were similar. PMID:18507526

  15. 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

  16. 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.

  17. Start 2: Thinking one move ahead

    SciTech Connect

    Gaines, L.L.

    1991-11-01

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

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. 77 FR 3838 - Notice of Availability of Proposed New Starts/Small Starts Policy Guidance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-25

    ... Federal Transit Administration Notice of Availability of Proposed New Starts/Small Starts Policy Guidance AGENCY: Federal Transit Administration (FTA), DOT. ACTION: Notice of availability; request for comments. SUMMARY: This notice announces the availability of the Federal Transit Administration's (FTA)...

  3. 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)

  4. Cerebrospinal fluid neopterin decay characteristics after initiation of antiretroviral therapy

    PubMed Central

    2013-01-01

    Background Neopterin, a biomarker of macrophage activation, is elevated in the cerebrospinal fluid (CSF) of most HIV-infected individuals and decreases after initiation of antiretroviral therapy (ART). We studied decay characteristics of neopterin in CSF and blood after commencement of ART in HIV-infected subjects and estimated the set-point levels of CSF neopterin after ART-mediated viral suppression. Methods CSF and blood neopterin were longitudinally measured in 102 neurologically asymptomatic HIV-infected subjects who were treatment-nave or had been off ART for ? 6 months. We used a non-linear model to estimate neopterin decay in response to ART and a stable neopterin set-point attained after prolonged ART. Seven subjects with HIV-associated dementia (HAD) who initiated ART were studied for comparison. Results Non-HAD patients were followed for a median 84.7 months. Though CSF neopterin concentrations decreased rapidly after ART initiation, it was estimated that set-point levels would be below normal CSF neopterin levels (<5.8 nmol/L) in only 60/102 (59%) of these patients. Pre-ART CSF neopterin was the primary predictor of set-point (P <0.001). HAD subjects had higher baseline median CSF neopterin levels than non-HAD subjects (P <0.0001). Based on the non-HAD model, only 14% of HAD patients were predicted to reach normal levels. Conclusions After virologically suppressive ART, abnormal CSF neopterin levels persisted in 41% of non-HAD and the majority of HAD patients. ART is not fully effective in ameliorating macrophage activation in CNS as well as blood, especially in subjects with higher pre-ART levels of immune activation. PMID:23664008

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

    PubMed

    Martinez-Skinner, Andrea L; Aranga, 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

  6. Changes in metabolic syndrome status after initiation of antiretroviral therapy

    PubMed Central

    Krishnan, S; Schouten, JT; Atkinson, B; Brown, TT; Wohl, D; McComsey, GA; Glesby, MJ; Shikuma, C; Haubrich, R; Jacobson, DL

    2014-01-01

    Background Data on changes in metabolic syndrome (MetS) status in HIV-infected adults on antiretroviral therapy (ART) are limited. Method MetS was assessed at ART initiation and every 48 weeks on ART in ART-nave HIV-infected individuals from the AIDS Clinical Trials Group Longitudinal Linked Randomized Trials (ALLRT) cohort. MetS, defined using the ATP-III criteria, required at least three of: elevated fasting glucose, hypertension, elevated waist circumference, elevated triglycerides, low HDL cholesterol. Prevalence of MetS and the individual criteria were compared between ART initiation and during follow-up using McNemars test. Results At ART initiation, 450 (20%) ALLRT participants had MetS. After 96 weeks of ART, 37% of the 411 with MetS at ART initiation and with available data at this time-point did not meet the MetS criteria. Among these participants, there was a dramatic decline in the proportion with low HDL (95% versus 26%, p<0.0001). Among the 63% that continued to meet MetS criteria at week 96, the proportion with ?4 criteria was higher at week 96 compared to ART initiation (48% versus 40%, p=0.03); at week 96, the proportion with high triglycerides was greater (87% versus 69%, p<0.0001) as was the proportion with high glucose (59% versus 42%, p<0.0001). Conclusion One in five ART-nave subjects met criteria for MetS at ART initiation. While more than half of these individuals continued to have MetS after 96 weeks of ART, 37% with MetS at ART initiation no longer met criteria for MetS; this decrease was driven largely by increases in HDL cholesterol. PMID:25321179

  7. 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

  8. 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

  9. 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

  10. Antiretroviral therapy management and rationalisation of available resources.

    PubMed

    Cirioni, Oscar; Castelletti, Sefora; Ucciferri, Claudio; Falasca, Katia; Orsetti, Elena; Mazzocato, Susanna; Valeriani, Chiara; Di Campli, Francesco Maria; Barchiesi, Francesco; Vecchiet, Jacopo; Giacometti, Andrea

    2015-12-01

    The treatment of HIV disease has led to a new division of management costs by shifting most of the necessary resources from inpatient treatment to outpatient management. Among the initiatives aimed at rationalising the resources available, we compared efficacy, tolerability and pharmacoeconomic impact of different regimes of antiretroviral therapy (ART). The survey covered the first 50 patients, clinically stable and with good viro-immunological response, who switched in June 2012 from an ART based on the triple combination of tenofovir (TDF), emtricitabine (FTC) and a protease inhibitor boosted with ritonavir (PI/r) or a non-nucleoside reverse transcriptase inhibitor (NNRTI), to a treatment based on abacavir (ABC), lamivudine (3TC) and a PI/r or NNRTI. Of the 50 patients who operated the switch, 39 replaced a PI with nevirapine (NVP), for which the largest group of patients was treated with ABC + 3TC + NVP. On 31 May 2015, all patients completed the observation period of 96 weeks, with a mean observation period of 132 weeks and clinical-laboratory checks every four months. Laboratory analysis revealed an optimal maintenance of viral suppression and absolute and relative number of CD4 + lymphocytes and improving trend of creatinine, proteinuria, serum phosphate and bone alkaline phosphatase. There was a variable effect on lipids, with a drop in triglycerides associated with a modest increase in total cholesterol. Much of the HIV-positive population reporting to our hospitals (>50%) comprises individuals who have for years been in stable viraemic suppression, making a satisfactory immune recovery while in good overall clinical condition. This type of patient was the target of the present survey. At the end of 96 weeks of observation the new regimes were well tolerated and did not lead to viro-immunological or clinical deterioration. Pharmacoeconomic analysis showed better containment of the overall costs. No patient needed to be hospitalised during the observation period. PMID:26700083

  11. Adherence to antiretroviral therapy among HIV-infected methadone patients: effect of ongoing illicit drug use.

    PubMed

    Stein, M D; Rich, J D; Maksad, J; Chen, M H; Hu, P; Sobota, M; Clarke, J

    2000-05-01

    Methadone maintenance patients infected with human immunodeficiency virus (HIV) currently receiving antiretroviral therapy had HIV RNA testing and were surveyed regarding their adherence to their treatment regimens. Adherence was measured using self-report on four questions relating to medication use in the last day and last month and whether the patient took "drug holidays." Of the patients (N = 42), 52% were receiving two-drug antiretroviral therapy and 48% were receiving triple therapy that included a protease inhibitor. Persons on triple therapy reported higher rates of adherence on all measures and were more likely to have undetectable HIV RNA levels than persons on dual therapy (60% vs. 50%). Ongoing illicit drug injection was the only factor significantly associated (p < .05) with multiple measure nonadherence; however, it was not associated with undetectable HIV RNA level. Levels of nonadherence were comparable to estimates from other chronic diseases, but this finding has important implications for patients receiving highly active antiretroviral therapy. PMID:10852356

  12. Head Starts Impact is Contingent on Alternative Type of Care in Comparison Group

    PubMed Central

    Brooks-Gunn, Jeanne; Waldfogel, Jane

    2014-01-01

    Using data (n = 3,790 with 2,119 in the 3-year-old cohort and 1,671 in the 4-year-old cohort) from 353 Head Start centers in the Head Start Impact Study, the only large-scale randomized experiment in Head Start history, this paper examined the impact of Head Start on childrens cognitive and parent-reported social-behavioral outcomes through first grade contingent on the child care arrangements used by children who were randomly assigned to the control group (i.e., parental care, relative/non-relative care, another Head Start program, or other center-based care). A principal score matching approach was adopted to identify children assigned to Head Start who were similar to children in the control group with a specific care arrangement. Overall, the results showed that the effects of Head Start varied substantially contingent on the alternative child care arrangements. Compared to children in parental care and relative/non-relative care, Head Start participants generally had better cognitive and parent-reported behavioral development, with some benefits of Head Start persisting through first grade; in contrast, few differences were found between Head Start and other center-based care. The results have implications regarding the children for whom Head Start is most beneficial as well as how well Head Start compares to other center-based programs. PMID:25329552

  13. 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

  14. 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

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

    ERIC Educational Resources Information Center

    North Carolina Central Univ., Durham.

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

  16. 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

  17. Head Start Program Performance Measures. Second Progress Report. Head Start Research.

    ERIC Educational Resources Information Center

    Westat, Inc., Rockville, MD.

    In 1995, Head Start developed performance measures to promote accountability through the assessment of program quality and outcomes. This report is the Head Start program's second progress report on its self-assessment using the Program Performance Measures. The measures are grouped under the five objectives of Head Start: (1) enhance children's

  18. 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.

  19. What to Expect When Starting Cardiac Rehabilitation

    MedlinePLUS

    ... continue cardiac rehab depends on your situation. Health Assessment Before you start cardiac rehab, your rehab team ... steady or irregular). An EKG also shows the strength and timing of electrical signals as they pass ...

  20. Report Analysis: The Impact of Head Start

    ERIC Educational Resources Information Center

    Smith, Marshall S.; Bissell, Joan S.

    1970-01-01

    The Westinghouse-Ohio national evaluation of Head Start stated that the benefits that its participants received were of minimal long-term value. This conclusion was criticized by social scientists and statisticians. (CK)

  1. 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.

  2. The nurse practitioner's role in managing dyslipidemia and other cardiovascular risk factors in HIV-infected patients: impact of antiretroviral therapy.

    PubMed

    Willard, Suzanne

    2006-01-01

    The beneficial effects of antiretroviral therapy (ART) for the treatment of HIV disease have been accompanied by metabolic changes associated with an increased risk of cardiovascular disease. These changes, which include dyslipidemia, change in body fat distribution, and insulin resistance, resemble the symptoms of metabolic syndrome. Protease inhibitors, nucleoside analogue reverse transcriptase inhibitors, and nonnucleoside reverse transcriptase inhibitors have all been associated with dyslipidemia to varying degrees. In addition, patients on ART show an increased risk of myocardial infarction and other cardiovascular events. According to the recommendations of the National Cholesterol Education Program and the Adult AIDS Clinical Trial Group, health care providers should assess cardiovascular risk before starting ART and then continue to monitor lipid levels. Treatment of ART-associated dyslipidemia should follow the following sequence: therapeutic lifestyle changes, lipid-lowering drug therapy, and finally, modifying ART if necessary. By providing education, support, and follow-up care, nurse practitioners can help to implement these steps. PMID:16686080

  3. 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

  4. Antiretroviral adherence and use of alternative therapies among older HIV-infected adults.

    PubMed Central

    Wutoh, A. K.; Brown, C. M.; Kumoji, E. K.; Daftary, M. S.; Jones, T.; Barnes, N. A.; Powell, N. J.

    2001-01-01

    OBJECTIVE: To investigate adherence to antiretroviral therapy and use of alternative therapies among older human immunodeficiency virus (HIV)-infected adults, and to assess relationships between antiretroviral adherence and clinical outcomes. METHODS: One hundred older HIV-infected patients, aged 50 and over, treated at two large HIV clinics in Washington, DC, were enrolled. A cross-sectional methodology used structured interviews to investigate antiretroviral regimens, use of alternative therapies, and demographics. Medical records provided viral load and CD4 count within 3 months of interview. RESULTS: The mean self-reported adherence was 94%, and 55 patients reported 100% adherence to antiretroviral therapy. Correlation analysis showed a significant negative correlation between adherence and viral load (r = -312, p = 0.005). There was no significant difference in adherence based on race, gender, mode of transmission, or education. Twenty-one patients (21%) reported the use of an alternative therapy, with several patients using multiple alternative therapies. There was no significant difference in adherence score (p = 0.514) or viral load (p = 0.860) based upon use of alternative therapies. CONCLUSIONS: Older HIV-infected study patients reported high levels of adherence to antiretroviral regimens, and adherence was highly correlated with HIV viral load. Use of alternative therapies did not significantly impact adherence to antiretroviral agents or viral load. High adherence among this older population may be related to older patients' familiarity with medication usage, their increasing awareness of HIV as a disease that requires optimal adherence, and educational efforts promoted by the two clinics in which they are clients. PMID:11491273

  5. 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

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

    PubMed Central

    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

    2014-01-01

    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. 95% of participants (354/373) donated hair. Although median self-reported adherence was 100% (IQR 96100%), a wide range of hair concentrations likely indicates overestimation of self-reported adherence and the advantages of a pharmacologic adherence measure. Higher nevirapine (NVP) 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

  7. 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 nave 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

  8. 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

  9. 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

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

    PubMed Central

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

    2013-01-01

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

  11. 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

  12. Long-Term Effectiveness of Antiretroviral Therapy in China: An Observational Cohort Study from 20032014

    PubMed Central

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

    2015-01-01

    In order to assess the effectiveness of the Chinese governments 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] = 0.110.27) and the presence of tuberculosis (HR = 0.27; 95% CI = 0.190.37). Each month of ART was associated with an average increase in CD4 cell count of 6.52 cells/L (95% CI = 6.087.12 cells/L). 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. 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: 0.512.52). 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

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  17. 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

  18. Differences in Response to Antiretroviral Therapy by Sex and Hepatitis C Infection Status.

    PubMed

    Marcus, Julia L; Leyden, Wendy A; Chao, Chun R; Xu, Lanfang; Quesenberry, Charles P; Tien, Phyllis C; Klein, Daniel B; Towner, William J; Horberg, Michael A; Silverberg, Michael J

    2015-07-01

    Hepatitis C virus (HCV) co-infection and biological sex may each affect response to antiretroviral therapy (ART), yet no studies have examined HIV-associated outcomes by both HCV status and sex. We conducted a cohort study of HIV-infected adults initiating ART in Kaiser Permanente California during 1996-2011. We used piecewise linear regression to assess CD4 changes by sex and HCV status over 5 years. We used Cox regression to estimate hazard ratios (HR) by sex and HCV status for HIV RNA <500 copies/mL over 1 year, and for AIDS and death over the follow-up period. Among 12,865 subjects, there were 154 HIV/HCV-co-infected women, 1000 HIV/HCV-co-infected men, 1088 HIV-mono-infected women, and 10,623 HIV-mono-infected men. CD4 increases were slower in the first year for HIV/HCV-co-infected women (75 cells/?L) and men (70 cells/?L) compared with HIV-mono-infected women (145 cells/?L) and men (120 cells/?L; p<0.001). After 5 years, women had higher CD4 than men in both HIV-mono-infected (598 vs. 562 cells/?L, p=0.003) and HIV/HCV-co-infected individuals (567 vs. 509 cells/?L, p=0.003). Regardless of sex, HIV/HCV co-infection was associated with 40% higher mortality [95% confidence interval (CI): 1.2-1.6] compared with HIV mono-infection, but was not associated with AIDS (HR 1.1, 95% CI: 0.9-1.3) or achieving HIV RNA <500 copies/mL (HR 1.0, 95% CI: 0.9-1.1). HIV/HCV-co-infected men and women have slower CD4 recovery after starting ART and have increased mortality compared with HIV-mono-infected men and women. HCV should be aggressively treated in HIV/HCV-co-infected adults, regardless of sex. PMID:26061798

  19. 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

  20. 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-nave 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-nave, 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 Fishers 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 (2.7811.77), 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

  1. 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

  2. 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

  3. 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

  4. Impact of Antiretroviral Therapy on Opportunistic Infections of HIV-Infected Children in the TREAT Asia Pediatric HIV Observational Database

    PubMed Central

    Prasitsuebsai, Wasana; Kariminia, Azar; Puthanakit, Thanyawee; Lumbiganon, Pagakrong; Hansudewechakul, Rawiwan; Moy, Fong Siew; Law, Matthew; Kumarasamy, Nagalingeswaran; Razali, Kamarul; Sirisanthana, Virat; Sohn, Annette H.; Chokephaibulkit, Kulkanya

    2014-01-01

    Background There are limited data on opportunistic infections (OI) and factors associated with their occurrence after highly active antiretroviral therapy (HAART) in Asian children. The use of HAART in Asia started much later than in developed countries and therefore reported findings may not be fully applicable to the pediatric HIV epidemic in Asia. Methods Retrospective and prospectively collected data from the TREAT Asia Pediatric HIV Observational Database cohort study from March 1993 to March 2009 were analyzed. OIs were defined according to WHO clinical staging criteria, and incidence rates calculated. Factors associated with the incidence of severe OIs were analyzed using random effects Poisson regression modeling. Results Of 2280 children in the cohort, 1752 were ever reported to have received ART, of whom 1480 (84%) started on HAART. Before commencing any ART, OIs occurred at a rate of 89.5 per 100 person-years. The incidence rate was 28.8 infections per 100 person-years during mono- or dual-therapy, and 10.5 infections per 100 person-years during HAART. The most common OIs both before and after ART initiation were recurrent upper respiratory tract infections, persistent oral candidiasis, and pulmonary tuberculosis. The incidence rates of WHO clinical stage 3 or 4 OIs after HAART were highest among children <18 months of age and those with low weight-for-age z scores, CD4 cell percentage <15%, and WHO stage 3 at HAART initiation. Conclusions Despite dramatic declines in their incidence, OIs remained important causes of morbidity after HAART initiation in this regional cohort of HIV-infected children in Asia. PMID:24378942

  5. 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

  6. HIV type 1 subtype diversity and drug resistance among HIV type 1-infected Kenyan patients initiating antiretroviral therapy.

    PubMed

    Lihana, Raphael W; Khamadi, Samoel A; Lubano, Kizito; Lwembe, Raphael; Kiptoo, Michael K; Lagat, Nancy; Kinyua, Joyceline G; Okoth, Fredrick A; Songok, Elijah M; Makokha, Ernest P; Ichimura, Hiroshi

    2009-12-01

    The treatment of HIV-1 infection with antiretroviral drugs has greatly improved the survival of those who are infected. However, HIV-1 diversity and drug resistance are major challenges in patient management, especially in resource-poor countries. To evaluate HIV-1 genetic diversity and drug resistance-associated mutations among drug-naive patients in Kenya prior to antiretroviral therapy (ART), a genetic analysis of HIV-1 pol-RT and env-gp41 was performed on samples collected from 53 (18 males and 35 females) consenting patients between April and June 2005. The average age, baseline CD4(+) T cell counts, and viral loads were 38 (range, 24-62) years, 475 (range, 203-799) cells/mm(3), and 4.7 (range, 3.4-5.9) log(10) copies/ml, respectively. Phylogenetic analysis revealed that 40 samples (75.5%) were concordant subtypes for the two genes and 13 (24.5%) were discordant, suggesting possible recombination and/or dual infections. Prevalent subtypes included A1/A1(pol-RT/env-gp41), 31 (58.5%); D/D, 9 (16.9%); A1/C, 2 (3.8%); A1/D, 4 (7.5%); G/A1, 2 (3.8%); A1/A2, 1 (1.9%); C/A1, 2 (3.8%); D/A1, 1(1.9%); and D/A2, 1 (1.9%). Major reverse transcriptase inhibitor (RTI) resistance-associated mutations were found in four patients (7.5%). Of these patients, three had nucleoside RTI resistance mutations, such as M184V, K65R, D67N, K70R, and K219Q. Nonnucleoside RTI resistance-associated mutations K103N and Y181C were detected in three patients and one patient, respectively. Multiple drug resistance mutations were observed in this drug-naive population. With increasing numbers of patients that require treatment and the rapid upscaling of ART in Kenya, HIV-1 drug resistance testing is recommended before starting treatment in order to achieve better clinical outcomes. PMID:19954302

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

    PubMed Central

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

    2010-01-01

    Abstract As increasing numbers of persons are placed on potentially life-saving combination antiretroviral therapy (cART) in sub-Saharan Africa, it is imperative to identify the psychosocial and social factors that may influence antiretroviral (ARV) medication adherence. Using an 87 question survey, the following data were collected from patients on cART in Botswana: demographics, performance (Karnofsky) score, perceived stigma and level of HIV disclosure, attitudes and beliefs concerning HIV/AIDS, substance and/or drug use, depression, and pharmacy and healthcare provider-related factors. Overall adherence rates were determined by patient self-report, institutional adherence, and a culturally modified Morisky scale. Three hundred adult patients were recruited between April and May 2005. The overall cART adherence rate was 81.3% based on 4 day and 1 month patient recall and on clinic attendance for ARV medication refills during the previous 3 months. Adults receiving cART for 16 months were the least adherent (77%) followed by those receiving cART for greater than 12 months (79%). Alcohol use, depression, and nondisclosure of positive HIV status to their partner were predictive of poor adherence rates (p value <0.02). A significant proportion (81.3%) of cART-treated adults were adherent to their prescribed treatment, with rates superior to those reported in resource-rich settings. Adherence rates were poorest among those just starting cART, most likely due to the presence of ARV-related toxicity. Adherence was lower among those who have been treated for longer periods of time (greater than 1 year), suggesting complacency, which may become a significant problem, especially among these long-term cART-treated patients who return to improved physical and mental functioning and may be less motivated to adhere to their ARV medications. Healthcare providers should encourage HIV disclosure to at-risk partners and provide ongoing counseling and education to help patients recognize and overcome HIV-associated stigma, alcohol abuse, and depression. PMID:20518649

  8. 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.

  9. 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.

  10. 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

  11. Osmotic pump tablets for delivery of antiretrovirals to the vaginal mucosa

    PubMed Central

    Rastogi, Rachna; Teller, Ryan S.; Mesquita, Pedro M. M.; Herold, Betsy C.; Kiser, Patrick F.

    2013-01-01

    Vaginal pre-exposure prophylaxis has focused heavily on gel formulations. Low adherence linked with frequent dosing and short therapeutic duration has emerged as the major reason for inconsistent efficacy outcomes with gels in clinical trials. Osmotic pumps can achieve versatile drug release profiles however, have not been explored for vaginal delivery. In this report, we describe an osmotic pump tablet (OPT) that can deliver antiretrovirals for several days. We also describe configuring the OPT for pH sensitive delivery where the drug delivery system consistently delivers a antiretroviral at vaginal pH and then gives a burst release triggered by a coitally associated pH increase. We have investigated the vaginal OPT for multiple day delivery of a potent antiretroviral, IQP-0528 in a sheep model. To effectively register spatial drug distribution we also engineered a tool to precisely collect multiple vaginal fluid samples. In a 10-day duration post single application, high micromolar mucosal levels were obtained with peak concentration more than 6 logs higher than IQP-0528 EC50. Overall, our results show successful implementation of the osmotic pump technology for vaginal antiretroviral delivery. PMID:23973812

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed

    Manzardo, Christian; Tuset, Montserrat; Mir, 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

  14. Immunogenetics of CD4 lymphocyte count recovery during antiretroviral therapy: An AIDS Clinical Trials Group study.

    PubMed

    Haas, David W; Geraghty, Daniel E; Andersen, Janet; Mar, Jessica; Motsinger, Alison A; D'Aquila, Richard T; Unutmaz, Derya; Benson, Constance A; Ritchie, Marylyn D; Landay, Alan

    2006-10-15

    During antiretroviral therapy, CD4 lymphocyte count increases are modest in some patients despite virologic control. We explored whether polymorphisms in genes important for T cell expansion, survival, and apoptosis are associated with the magnitude of CD4 lymphocyte count recovery during antiretroviral therapy. We studied treatment-naive individuals who achieved sustained control of plasma viremia (<400 HIV-1 RNA copies/mL) for at least 48 weeks after initiation of antiretroviral therapy and compared genotypes among individuals who had an increase of either <200 or > or =200 CD4 cells/mm3 from baseline. A total of 137 single-nucleotide polymorphisms across 17 genes were characterized in 873 study participants. In multivariate analyses that controlled for clinical variables, polymorphisms in genes encoding tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), TNF- alpha , Bcl-2-interacting molecule (Bim), interleukin (IL)-15, and IL-15 receptor alpha chain (IL-15R alpha ) were associated with the magnitude of the increase in CD4 lymphocyte count, as were haplotypes in genes encoding interferon- alpha , IL-2, and IL-15R alpha (P < .05, for each). Multifactor dimensionality reduction identified a gene-gene interaction between IL-2/IL-15 receptor common beta chain and IL-2/IL-7/IL-15 receptor common gamma chain. Immune recovery during antiretroviral therapy is a complex phenotype that is influenced by multiple genetic variants. Future studies should validate these tentative associations and define underlying mechanisms. PMID:16991084

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

    ERIC Educational Resources Information Center

    Delbene, Roxana

    2012-01-01

    The medical literature reports that antiretrovirals (ARVs) are considered attitudinal objects (Dunbar-Jacob, 1995). Drawing on the pragmatics of emotion (Caffi & Janney, 1994), this study analyzes how patients' stances about their ARTs shape their emotional relationships with their treatments. The data, collected in a public hospital in Uruguay,

  16. 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

  17. Osmotic pump tablets for delivery of antiretrovirals to the vaginal mucosa.

    PubMed

    Rastogi, Rachna; Teller, Ryan S; Mesquita, Pedro M M; Herold, Betsy C; Kiser, Patrick F

    2013-10-01

    Vaginal pre-exposure prophylaxis has focused heavily on gel formulations. Low adherence linked with frequent dosing and short therapeutic duration has emerged as the major reason for inconsistent efficacy outcomes with gels in clinical trials. Osmotic pumps can achieve versatile drug release profiles however, have not been explored for vaginal delivery. In this report, we describe an osmotic pump tablet (OPT) that can deliver antiretrovirals for several days. We also describe configuring the OPT for pH sensitive delivery where the drug delivery system consistently delivers an antiretroviral at vaginal pH and then gives a burst release triggered by a coitally associated pH increase. We have investigated the vaginal OPT for multiple day delivery of a potent antiretroviral, IQP-0528 in a sheep model. To effectively register spatial drug distribution we also engineered a tool to precisely collect multiple vaginal fluid samples. In a 10-day duration post single application, high micromolar mucosal levels were obtained with peak concentration more than 6 logs higher than the EC50 of IQP-0528. Overall, our results show successful implementation of the osmotic pump technology for vaginal antiretroviral delivery. PMID:23973812

  18. Early antiretroviral treatment prevents the development of CNS abnormalities in SIV-infected rhesus monkeys

    PubMed Central

    Marcondes, Maria Cecilia G.; Flynn, Claudia; Huitron-Rezendiz, Salvador; Watry, Debbie D.; Zandonatti, Michelle; Fox, Howard S.

    2009-01-01

    Objective Neurocognitive disorders are devastating consequences of HIV infection. While antiretroviral regimens have been efficacious in both improving life expectancy and decreasing dementia, there has not been an effect on the overall prevalence of HIV-associated neurocognitive disorders. Whether early institution of treatment, or treatment with drugs that effectively penetrate the blood brain barrier, would help protect from such conditions is not known. Using the SIV/macaque model, we investigated the hypothesis that early introduction of antiretroviral treatment can protect the brain. Design and Methods Animals were inoculated with SIV, and upon resolution of the acute infection period divided into two groups and treated, or not, with combination antiretoviral therapy. Viral, immune, and physiological parameters were measured during the course of infection, followed by assessment of viral, immune, and molecular parameters in the brain. Results We observed that even with agents that show poor penetration into the CNS, early antiretroviral treatment prevented characteristic neurophysiological and locomotor alterations arising after infection, and resulted in a significant decrease in brain viral load. Although the number of infiltrating immune cells in the brain did not change with treatment, their phenotype did, favoring an enrichment of effector T cells. Early treatment also significantly lowered brain levels of IFN?, a cytokine that can lead to neurocognitive and behavioral alterations. Conclusion Early antiretroviral treatment prevents CNS dysfunction by decreasing brain viral load and IFN? levels, which can have a profound impact over the course of infection. PMID:19455015

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

    PubMed

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

    2014-01-01

    The most striking effect of increased survival and improved quality of life in HIV-infected women undergoing antiretroviral therapy is the feasibility of motherhood-desire satisfaction. However, such advantages are often associated with drug-related metabolic toxicities, particularly relevant in the pregnancy context. Recent guidelines provide recommendations and trends for the use of antiretroviral therapy in pregnant women, but current literature falls short of providing specific insights on the need for metabolic monitoring and treatment in HIV-infected pregnant women. In this review we provide specific insight into the state-of-the-art of: detection, evaluation, and management of metabolic alterations in this special population. Pregnancy is in fact a metabolic transition process, potentially associated with specific diseases in the mother, in the newborn, and in the adulthood of the child. We will not simply discuss antiretroviral therapy metabolic toxicities, but rather their interaction with the physiological metabolic changes occurring during pregnancy. Close monitoring is needed to diagnose metabolic alterations that can lead to adverse outcomes in the mother, in the newborn, and potentially in adulthood. Lifestyle interventions and an appropriate metabolic tailoring of antiretroviral therapy drugs need to be considered in the prevention and treatment of metabolic alteration during pregnancy. PMID:24584105

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

    PubMed Central

    2013-01-01

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

  2. 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

  3. Starting a Business in the Permian Basin.

    ERIC Educational Resources Information Center

    Harrison, Danny

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

  4. 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

  5. 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…

  6. 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.

  7. 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…

  8. 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.

  9. Teacher Research: Getting Started. Research to Practice.

    ERIC Educational Resources Information Center

    Bardine, Bryan

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

  10. 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

  11. 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.

  12. 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.

  13. 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

  14. 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…

  15. Head Start: How Research Changed Public Policy.

    ERIC Educational Resources Information Center

    Brown, Bernard

    1985-01-01

    Traces the history of longitudinal research on effects of Head Start since the 1960s and assesses its impact on government financial support and public policy. Findings of the Westinghouse Report and of the Consortium for Longitudinal Studies on early intervention programs are reported. (DT)

  16. 34 CFR 200.16 - Starting points.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 34 Education 1 2013-07-01 2013-07-01 false Starting points. 200.16 Section 200.16 Education Regulations of the Offices of the Department of Education OFFICE OF ELEMENTARY AND SECONDARY EDUCATION, DEPARTMENT OF EDUCATION TITLE I-IMPROVING THE ACADEMIC ACHIEVEMENT OF THE DISADVANTAGED Improving...

  17. 34 CFR 200.16 - Starting points.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 34 Education 1 2014-07-01 2014-07-01 false Starting points. 200.16 Section 200.16 Education Regulations of the Offices of the Department of Education OFFICE OF ELEMENTARY AND SECONDARY EDUCATION, DEPARTMENT OF EDUCATION TITLE I-IMPROVING THE ACADEMIC ACHIEVEMENT OF THE DISADVANTAGED Improving...

  18. 34 CFR 200.16 - Starting points.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

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

  19. 34 CFR 200.16 - Starting points.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

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

  20. 34 CFR 200.16 - Starting points.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false Starting points. 200.16 Section 200.16 Education Regulations of the Offices of the Department of Education OFFICE OF ELEMENTARY AND SECONDARY EDUCATION, DEPARTMENT OF EDUCATION TITLE I-IMPROVING THE ACADEMIC ACHIEVEMENT OF THE DISADVANTAGED Improving...

  1. 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…

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

    ERIC Educational Resources Information Center

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

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

  3. Evaluation of Hawaii's Healthy Start Program.

    ERIC Educational Resources Information Center

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

    1999-01-01

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

  4. 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

  5. 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

  6. 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…

  7. Addressing Tooth Decay in Head Start Children

    ERIC Educational Resources Information Center

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

    2012-01-01

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

  8. 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…

  9. The Canada NewStart Program.

    ERIC Educational Resources Information Center

    Sloan, E. P.

    This speech described the development and current status of the Canada NewStart Program, in which specially created corporations have been conducting action research on disadvantaged groups (largely Indians and Metis) in remote areas of Alberta, Saskatchewan, and Manitoba, and for undereducated persons in economically depressed areas of Prince

  10. 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)

  11. Sure Start: A Guide for Trailblazers.

    ERIC Educational Resources Information Center

    Department for Education and Employment, London (England).

    Based on the evidence that early intervention and support can reduce family breakdown, strengthen children's school readiness, and benefit society in the long term, the Sure Start program in England is designed to offer support enabling parents to strengthen their relationship with their children and to access more fully local community services.

  12. 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

  13. 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…

  14. Mental Health Services in Head Start

    ERIC Educational Resources Information Center

    Frey, Andy

    2008-01-01

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

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

    PubMed Central

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

    2011-01-01

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

  17. Antiretroviral blood levels in HIV/HCV-coinfected patients with cirrhosis after liver transplant: a report of three cases.

    PubMed

    Righi, E; Londero, A; Pea, F; Bonora, S; Nasta, P; Della Siega, P; Delle Foglie, P; Villa, G; Giglio, O; Dal Zoppo, S; Baccarani, U; Bassetti, M

    2015-02-01

    Since the introduction of combined antiretroviral therapy, human immunodeficiency virus (HIV) infection is no longer a contraindication for solid organ transplantation. In HIV/hepatitis C virus (HCV)-coinfected patients undergoing liver transplantation, HCV-related cirrhosis, drug-drug interactions, and calcineurin inhibitors-related toxicity affect clinical outcomes. Therapeutic drug monitoring can be useful to assess antiretroviral over- or underexposure in this cohort. We report the clinical characteristics along with antiretroviral trough levels of maraviroc, darunavir, and etravirine in 3 HIV/HCV-coinfected liver transplant recipients who developed post-transplant liver cirrhosis. PMID:25620392

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

    ERIC Educational Resources Information Center

    Education Development Center, Inc., Newton, MA.

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

  19. 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

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

    ERIC Educational Resources Information Center

    ZERO TO THREE, 2007

    2007-01-01

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

  1. 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.

  2. 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.

  3. The GlueX Start Counter

    NASA Astrophysics Data System (ADS)

    Pooser, Eric; GlueX Collaboration

    2015-03-01

    The GlueX experiment will study meson photoproduction with unprecedented precision. This experiment will use the coherent bremsstrahlung technique to produce a 9 GeV linearly polarized photon beam incident on a liquid H2 target. A Start Counter detector has been fabricated to identify the accelerator electron beam buckets, approximately 2 ns apart, and to provide accurate timing information which is used in the level-1 trigger of the experiment. This detector is designed to operate at photon intensities of up to 108 ? / s in the coherent peak and provide a timing resolution < 350 ps so as to provide successful identification of the electron beam buckets to within 99 % accuracy. Furthermore, the Start Counter detector will provide excellent solid angle coverage, ~ 90 % of 4 ? hermeticity , and a high degree of segmentation for background rejection. It consists of a cylindrical array of 30 scintillators with pointed ends that bend towards the beam at the downstream end. Silicon PhotoMultiplier (SiPM) detectors have been selected as the readout system. The physical properties of the Start Counter have been studied extensively. The results of theses studies are discussed. This material is based upon work supported by the U.S. Department of Energy, Office of Science, and Office of Nuclear Physics under Contracts DE-AC05-06OR23177 & DE-FG02-99ER41065.

  4. The GlueX Start Counter

    NASA Astrophysics Data System (ADS)

    Pooser, Eric; GlueX Collaboration

    2015-04-01

    The GlueX experiment will study meson photoproduction with unprecedented precision. This experiment will use the coherent bremsstrahlung technique to produce a 9 GeV linearly polarized photon beam incident on a liquid H2 target. A Start Counter detector has been fabricated to identify the accelerator electron beam buckets, approximately 2 ns apart, and to provide accurate timing information which is used in the level-1 trigger of the experiment. This detector is designed to operate at photon intensities of up to 108 ? / s in the coherent peak and provide a timing resolution < 350ps so as to provide successful identification of the electron beam buckets to within 99 % accuracy. Furthermore, the Start Counter detector will provide excellent solid angle coverage, ~ 90 % of 4 ? hermeticity , and a high degree of segmentation for background rejection. It consists of a cylindrical array of 30 scintillators with pointed ends that bend towards the beam at the downstream end. Silicon PhotoMultiplier (SiPM) detectors have been selected as the readout system. The physical properties of the Start Counter have been studied extensively. The results of theses studies are discussed. This material is based upon work supported by the U.S. Department of Energy, Office of Science, Office of Nuclear Physics under Contracts DE-AC05-06OR23177 & DE-FG02-99ER41065.

  5. A Fast-Starting Robotic Fish

    NASA Astrophysics Data System (ADS)

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

    2009-11-01

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

  6. 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

  7. 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

  8. 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; Thibaut, 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/l 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/l was 529/l [95% confidence interval (CI): 517541] in North America, 494/l (95% CI: 429559) in West Africa, 515/l (95% CI: 508522) in Southern Africa, 503/l (95% CI: 478528) in Asia and 437/l (95% CI: 425449) 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

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

    PubMed Central

    De Salvador-Guillout, 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 (2.5423.2)]. Conclusions Our findings suggest an association between initiation of an INSTI-containing regimen and CD4/CD8 ratio normalization at one year in nave 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

  10. 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

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

    PubMed

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

    2014-10-01

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

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

    PubMed Central

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

    2014-01-01

    Introduction First antiretroviral therapy (ART) is often switched to simpler, more potent or better tolerated regimens [1, 2]. Although discontinuation rates are frequently studied, the durability of regimens is rarely approached. Materials and Methods Retrospective study with the following objectives: analyze first ART schemes and their durability in naive patients with chronic HIV-1 and 2 infections, evaluate factors influencing ART change, second-line ART and consequent virologic and immunologic responses. Patients had follow-ups in a Central University Hospital, started ART between January 2007 and December 2012 and changed first regimens. Clinical data was obtained from medical records and analyzed using the Statistical Package for the Social Sciences (version 20). Results Of the 652 naive patients who started ART, 164 changed regimens. The majority had HIV-1 infection (n=158). The mean age was 43.9 years (standard deviation14.3), with a male predominance of 57.9%. Regimens with efavirenz were the most common amongst HIV-1 patients (50%) followed by lopinavir/r (22%). In HIV-2 patients, lopinavir/r (n=3) regimens were most prevalent. First ART regimens had a mean duration of 12.1 months. There was no difference between NNRTI (59.8%) and protease inhibitor (40.2%) schemes regarding durability. Adverse reactions were the major cause of ART switching (55.5%) followed by therapy resistance (12.1%). Age was inversely related to durability (p=0.007 Mann-Whitney, Phi coefficient ?0.161) and associated with the appearance of adverse reactions (p=0.04, Chi-square). Younger patients had a reduced risk of adverse reactions by 27%. Adverse reactions increased the risk of inferior durability by 40%. Psychiatric symptoms (28.4%) were the most prevalent, all attributed to efavirenz. The year of ART initiation was associated with different durability rates (p=0.005, Mann-Whitney). Patients started on ART before the year 2010 reduced the probability of inferior ART duration by 25.8%. After second-line ART regimens, TCD4+ counts>500 cell/L were increased by 38% and favourable virologic outcome achieved in 84%. Conclusions Adverse reactions were the main cause for ART switching, supporting a cautious approach when initiating regimens, particularly in older patients. All ART naive patients who changed initial therapy had favourable immunological and virologic responses. PMID:25397541

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

    PubMed Central

    2012-01-01

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

  14. 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

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

    PubMed

    Collazos, Julio; Asensi, Vctor; Cartn, Jos Antonio

    2009-07-01

    The factors associated with discordant viroimmunological responses following antiretroviral therapy are unclear. We studied 1380 patients who initiated a protease inhibitor (PI)-based antiretroviral regimen and who fulfilled the criteria for inclusion. Of them, 255 (18.5%) had CD4 increases > or =100 cells/microl after 1 year of therapy despite detectable viral load (immunological responders); they were compared with 669 patients (48.5%) who had CD4 increases <100 cells/microl regardless of their final viral load (immunological nonresponders). Immunological responders had higher rates of sexual acquisition of HIV (p = 0.03), lower rates of clinical progression (p = 0.02), higher probabilities of being naive to antiretroviral therapy (p = 0.006) or to PI if antiretroviral experienced (p = 0.03), higher rates of receiving only nucleoside reverse transcriptase inhibitors in addition to the PI (p = 0.04), and lower baseline CD4 counts (p = 0.007) and higher viral loads (p = 0.009), as compared with nonresponders. Multivariate analysis revealed that sexual transmission of HIV (homosexual p = 0.004, heterosexual p = 0.03), no prior PI experience (p = 0.005), absence of clinical progression (p = 0.02), and lower baseline CD4 counts (p = 0.03) were independently associated with immunological response. However, these factors differed according to the patients' prior antiretroviral status, as higher baseline viral load was also associated with immunological response in antiretroviral-experienced patients (p = 0.02), whereas baseline CD4 count (p = 0.007) was the only predictive parameter in antiretroviral-naive patients. We conclude that immunological responses despite suboptimal viral suppression are common. Prior PI experience, HIV transmission category, baseline CD4 counts, and clinical progression were independently predictive of this condition, although the associated factors were different depending on the patient's prior antiretroviral history. PMID:19621987

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

    PubMed Central

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

    2014-01-01

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

  17. 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

  18. 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

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

    PubMed Central

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

    2014-01-01

    Objective Estimates of CD4 response to antiretroviral therapy (ART) obtained by averaging data from patients in care, overestimate population CD4 response and treatment program effectiveness because they do not consider data from patients who are deceased or not in care. We use mathematical methods to assess and adjust for this bias based on patient characteristics. Design We examined data from 25,261 HIV-positive patients from the East Africa IeDEA Consortium. Methods We used inverse probability of censoring weighting (IPCW) to represent patients not in care by patients in care with similar characteristics. We address two questions: What would the median CD4 be had everyone starting ART remained on observation? and were everyone starting ART maintained on treatment? Results Routine CD4 count estimates were higher than adjusted estimates even under the best-case scenario of maintaining all patients on treatment. Two years after starting ART, differences between estimates diverged from 30 cells/L, assuming similar mortality and treatment access among dropouts as patients in care, to over 100 cells/L assuming 20% lower survival and 50% lower treatment access among dropouts. When considering only patients in care, the proportion of patients with CD4 above 350 cells/L was 50% adjusted to below 30% when accounting for patients not in care. One-year mortality diverged 614% from the nave estimates depending on assumptions about access to care among lost patients. Conclusions Ignoring mortality and loss to care results in over-estimation of ART response for patients starting treatment and exaggerates the efficacy of treatment programs administering it. PMID:25131801

  20. 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.

  1. Predictors of Delayed Antiretroviral Therapy Initiation, Mortality, and Loss to Followup in HIV Infected Patients Eligible for HIV Treatment: Data from an HIV Cohort Study in India

    PubMed Central

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

    2013-01-01

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

  2. 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

  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. 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

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

    PubMed

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

    2013-10-01

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

  6. 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 (0.951.56); non-PCV13 serotypes: aRR 1.72, 95% CI 1.132.62]. 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

  7. 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

  8. Antiretroviral drug expenditure, pricing and judicial demand: an analysis of federal procurement data in Brazil from 20042011

    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 20042011 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 Brazils 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 20042011. 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

  9. 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

  10. The Impact of the New WHO Antiretroviral Treatment Guidelines on HIV Epidemic Dynamics and Cost in South Africa

    PubMed Central

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

    2011-01-01

    Background Since November 2009, WHO recommends that adults infected with HIV should initiate antiretroviral therapy (ART) at CD4+ cell counts of ?350 cells/l rather than ?200 cells/l. South Africa decided to adopt this strategy for pregnant and TB co-infected patients only. We estimated the impact of fully adopting the new WHO guidelines on HIV epidemic dynamics and associated costs. Methods and Finding We used an established model of the transmission and control of HIV in specified sexual networks and healthcare settings. We quantified the model to represent Hlabisa subdistrict, KwaZulu-Natal, South Africa. We predicted the HIV epidemic dynamics, number on ART and program costs under the new guidelines relative to treating patients at ?200 cells/l for the next 30 years. During the first five years, the new WHO treatment guidelines require about 7% extra annual investments, whereas 28% more patients receive treatment. Furthermore, there will be a more profound impact on HIV incidence, leading to relatively less annual costs after seven years. The resulting cumulative net costs reach a break-even point after on average 16 years. Conclusions Our study strengthens the WHO recommendation of starting ART at ?350 cells/l for all HIV-infected patients. Apart from the benefits associated with many life-years saved, a modest frontloading appears to lead to net savings within a limited time-horizon. This finding is robust to alternative assumptions and foreseeable changes in ART prices and effectiveness. Therefore, South Africa should aim at rapidly expanding its healthcare infrastructure to fully embrace the new WHO guidelines. PMID:21799755

  11. 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 112 years-old, CD4 1524% 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

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

    PubMed Central

    Shahapur, Praveen R.; Bidri, Rajendra C.

    2014-01-01

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

  13. "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

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

    PubMed Central

    Lert, France; Kazatchkine, Michel D.

    2007-01-01

    AIDS-related mortality and the rate of progression to AIDS have dramatically decreased since the advent of highly-active antiretroviral treatment (HAART). The overall benefit from antiretroviral HIV treatment has, however, been lesser in HIV-infected IDUs than in other patient groups (e.g. men who have sex with men). Poorer outcomes in HIV-infected IDUs are related to a variety of factors, including increased rates of non-HIV related deaths, hepatitis C, delayed access to effective treatment, lower adherence to care and treatment regimens, continuation of illicit drug use, depression and negative life events. The available evidence strongly suggests the need for the large-scale implementation of comprehensive treatment and care strategies for IDUs that include both treatment of drug-dependence and HAART. PMID:17689373

  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. 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

  18. 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

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

    PubMed Central

    Molt, Jos; 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

  20. 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

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

    PubMed Central

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

    2014-01-01

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

  2. 'I am also a human being!' Antiretroviral treatment in local moral worlds.

    PubMed

    Mattes, Dominik

    2012-04-01

    The experiences and practices of antiretroviral drug consumers in Tanzania are shaped by economic scarcity, limited state-provided social welfare, and fragile kinship-based solidarity. Embedding antiretroviral therapy (ART) in patients' 'local moral worlds' brings further existential dimensions to the fore that articulate closely with the priority the treatment acquires in their lives. An exemplary case study of a middle-aged HIV-positive man suggests that dignity, social recognition, and belonging may be of central interest and temporarily overshadow patients' concern for mere survival. A stronger focus on patients' moral concerns contributes to a better understanding of the complex dynamics that prevent HIV-positive people from becoming the 'pharmaceutical selves' that are promoted during treatment enrolment. Moreover, it is indispensable to account for the lived experiences of patients struggling with what too readily has been termed a 'chronic disease'. PMID:22612493

  3. 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

  4. 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

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

    PubMed Central

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

    2001-01-01

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

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

    PubMed

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

    2001-12-01

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

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

    PubMed

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

    2002-02-01

    Highly active antiretroviral therapy (HAART) is responsible for a striking reduction in AIDS related morbidity and mortality by partly restoring immune function. However, HAART can also precipitate the development of clinically apparent opportunistic infections in patients with latent infections. We report a case of an HIV infected patient who developed granulomatous nodular and cavitatory lesions of the lungs due to Mycobacterium xenopi as a manifestation of the immune restoration syndrome. PMID:11872863

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

    PubMed

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

    2013-09-10

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

  9. 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

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

    PubMed Central

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

    2014-01-01

    Objective To evaluate associations of perinatal HIV infection (PHIV), HIV disease severity, and combination antiretroviral treatment with age at pubertal onset. Design Analysis of data from two U.S. longitudinal cohort studies [IMPAACT 219C and PHACS AMP], conducted 20002012, including PHIV and HIV-exposed uninfected (HEU) youth. Tanner stage assessments of pubertal status (breast and pubic hair in girls; genitalia and pubic hair in boys) were conducted annually. Methods We compared the timing of pubertal onset (Tanner stage ?2) between PHIV and HEU youth using interval-censored models. For PHIV youth, we evaluated associations of HIV disease severity and combination antiretroviral treatment with age at pubertal onset, adjusting for race/ethnicity and birth cohort. Results The mean age at pubertal onset was significantly later for the 2086 PHIV youth compared to 453 HEU children (10.3 vs 9.6, 10.5 vs 10.0, 11.3 vs 10.4, and 11.5 vs 10.7 years according to female breast, female pubic hair, male genitalia, and male pubic hair staging, respectively, all p<0.001). PHIV youth with HIV-1 RNA viral load >10,000 copies/mL (vs ?10,000 copies/mL) or CD4% <15% (vs ?15%) had significantly later pubertal onset (by 413 months). Each additional year of combination antiretroviral treatment was associated with a 0.6- to1.2-month earlier mean age at pubertal onset, but this trend did not persist after adjustment for birth cohort. Conclusions Pubertal onset occurs significantly later in PHIV than in HEU youth, especially among those with more severe HIV disease. However, in the current era, combination antiretroviral treatment may result in more normal timing of pubertal onset. PMID:24145244

  11. Gender differences in non-adherence among Brazilian patients initiating antiretroviral therapy

    PubMed Central

    de Fatima Bonolo, Palmira; Ceccato, Maria das Graas Braga; Rocha, Gustavo Machado; de Assis Acrcio, Francisco; Campos, Lorenza Nogueira; Guimares, Mark Drew Crosland

    2013-01-01

    OBJECTIVE: We conducted a study to identify gender differences in factors associated with the first episode of non-adherence in the 12 months following the first antiretroviral prescription. METHODS: A concurrent prospective study of patients initiating antiretroviral therapy in Brazil was conducted from 2001-2002. The self-reported measurement of adherence was defined as an intake of less than 95% of the prescribed number of doses. Only the first occurrence of non-adherence was considered in this analysis. All analyses were stratified by gender. A Cox proportional hazard model was used to estimate the risk of non-adherence, and the time to non-adherence was estimated using the Kaplan-Meier method. RESULTS: The cumulative incidence of non-adherence was 34.6% (29.7% and 43.9% among men and women, respectively; p?=?0.010). Marital status (being married or in stable union; p?=?0.022), alcohol use in the month prior to the baseline interview (p?=?0.046), and current tobacco use (p?=?0.005) increased the risk of non-adherence among female participants only, whereas a self-reported difficulty with the antiretroviral treatment was associated with non-adherence in men only. For both men and women, we found that a longer time between the HIV test and first antiretroviral therapy prescription (p?=?0.028) also presented an increased risk of non-adherence. CONCLUSIONS: In this cohort study, the incidence of non-adherence was 1.5 times greater among women compared to men. Our results reinforce the need to develop interventions that account for gender differences in public referral centers. Additionally, we emphasize that, to achieve and maintain appropriate adherence levels, it is important to understand the barriers to seeking and utilizing health care services. PMID:23778401

  12. Stability starts with the purchase specification

    NASA Astrophysics Data System (ADS)

    Gould, Gerald

    1990-11-01

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

  13. Locality Aware Concurrent Start for Stencil Applications

    SciTech Connect

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

    2015-02-10

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

  14. Danish Ophthalmology - from start to 1865.

    PubMed

    Norn, Mogens

    2016-03-01

    This short paper mentioned the medical treatment using the 'holy' springs, the first 'eye doctor' in Denmark, the first picture of spectacles which was found in Viborg Cathedral of the high priest before he performs circumcisio praeputii on Jesus Christ, further cataract reclination in Denmark from around year zero and cataract extraction in 1667 in Denmark on a goose by Francisco Borri and on humans by the Danish Georg Heuermann in 1755. Epidemic military eye diseases in 1807, 1856 and 1865 are also described in this study. From 1856, a new ophthalmological period started in Denmark with the first eye hospital (lazaret only for eye diseases), and in 1864, patients with eye diseases were transported from the few beds in the surgical departments in the municipal hospital to the first civil eye department in Denmark, the eye hospital Sct. Annae in Copenhagen. The new scientific period started with Jacob Christian Bentz (ophthalmia granulosa, joint editor of the Danish Medical Journal) and Heinrich Lehmann. PMID:26899921

  15. The GlueX Start Counter

    NASA Astrophysics Data System (ADS)

    Llodra, Anthony; Pooser, Eric; GlueX Collaboration

    2015-04-01

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

  16. The GlueX Start Counter

    NASA Astrophysics Data System (ADS)

    Pooser, Eric; GlueX Collaboration

    2014-09-01

    The GlueX experiment will study meson photoproduction with unprecedented precision. This experiment will use the coherent bremsstrahlung technique to produce a 9 GeV linearly polarized photon beam incident on a liquid H2 target. A Start Counter detector has been fabricated to identify the accelerator electron beam buckets, approximately 2 ns apart, and to provide accurate timing information which is used in the level-1 trigger of the experiment. This detector is designed to operate at photon intensities of up to 108 ? / s in the coherent peak and provide a timing resolution <350 ps so as to provide successful identification of the electron beam buckets to within 99% accuracy. Furthermore, the Start Counter detector will provide excellent solid angle coverage, ~90% of 4? hermeticity, and a high degree of segmentation for background rejection. It consists of a cylindrical array of 30 scintillators with pointed ends that bend towards the beam at the downstream end. Silicon PhotoMultiplier (SiPM) detectors have been selected as the readout system. The physical properties of the scintillators, have been studied extensively at FIU. The results of these studies are discussed.

  17. Perspectives on pharmacogenomics of antiretroviral medications and HIV-associated comorbidities

    PubMed Central

    Haas, David W.; Tarr, Philip E.

    2015-01-01

    Purpose of review To summarize current knowledge and provide perspective on relationships between human genetic variants, antiretroviral medications, and aging-related complications of HIV-1 infection. Recent findings Human genetic variants have been convincingly associated with interindividual variability in antiretroviral toxicities, drug disposition, and aging-associated complications in HIV-1 infection. Screening for HLA-B*5701 to avoid abacavir hypersensitivity reactions has become a routine part of clinical care, and has markedly improved drug safety. There are well established pharmacogenetic associations with other agents (efavirenz, nevirapine, atazanavir, dolutegravir, and others), but this knowledge has yet to have substantial impact on HIV-1 clinical care. As metabolic complications including diabetes mellitus, dyslipidemia, osteoporosis, and cardiovascular disease are becoming an increasing concern among individuals who are aging with well controlled HIV-1 infection, human genetic variants that predispose to these complications also become more relevant in this population. Summary Pharmacogenetic knowledge has already had considerable impact on antiretroviral prescribing. With continued advances in the field of human genomics, the impact of pharmacogenomics on HIV-1 clinical care and research is likely to continue to grow in importance and scope. PMID:25565175

  18. Antiretroviral drugs to prevent mother-to-child transmission of HIV during breastfeeding.

    PubMed

    Shetty, Avinash K; Maldonado, Yvonne

    2013-03-01

    In low and middle-income countries (LMIC), transmission of HIV during breastfeeding represents a major public health challenge. Several viral, maternal clinical, immunological and genetic factors, as well as maternal-infant host factors and type of infant feeding may influence the risk of breastfeeding transmission of HIV. The mechanisms of breast milk HIV transmission are poorly understood. For mothers who are healthy and do not need combination antiretroviral therapy for their own health, randomized controlled trials have proven that administration of extended maternal triple-drug antiretroviral (ARV) prophylaxis or extended infant ARV prophylaxis can significantly reduce the risk of HIV transmission during breastfeeding. Based on this evidence, the World Health Organization (WHO) published new guidance in 2010 on the use of ARVs for treating pregnant women, and preventing mother-to-child HIV transmission (PMTCT). Although, remarkable advances have occurred in prevention of postnatal transmission during breastfeeding using antiretroviral strategies, a number of challenges remain. Future research must focus on field studies to evaluate programmatic implementation of new WHO PMTCT regimens, monitor long-term safety of ART exposure during pregnancy and lactation, and study emergence of ARV resistance (in mothers and infected infants despite prophylaxis). PMID:23432487

  19. Depression and patterns of self-reported adherence to antiretroviral therapy in Rwanda.

    PubMed

    Wroe, Emily B; Hedt-Gauthier, Bethany L; Franke, Molly F; Nsanzimana, Sabin; Turinimana, Jean Bosco; Drobac, Peter

    2015-03-01

    We determined the prevalence of depression in HIV-infected adults on antiretroviral therapy in rural Rwanda and measured the association of depression with non-adherence. In all, 292 patients on antiretroviral therapy for ?6 months were included. Adherence was self-reported by four-day recall, two- and seven-day treatment interruptions, and the CASE Index, which is a composite score accounting for difficulty taking medications on time, the average number of days per week a dose is missed, and the most recent missed dose. A total of 84% and 87% of participants reported good adherence by the four-day recall and CASE Index, respectively; 13% of participants reported two-day treatment interruptions; and 11% were depressed. Depression was significantly associated with two-day treatment interruptions but not with other measures of non-adherence. Self-reported adherence to antiretroviral therapy in rural Rwanda is high. Adherence assessments that do not consider treatment interruptions may miss important patterns of non-adherence, which may be especially prevalent among depressed individuals. Mental health interventions incorporated into routine HIV care may lead to improvements in mental health and adherence. PMID:24828554

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

    PubMed Central

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

    2009-01-01

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