Peripheral blood mononuclear cells (PBMC) were isolated from venous blood and their TK and dCK activities evaluated. CD4 T cells and HIV-RNA were measured in HIV-infected patients, too.
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A modified long course Paediatric AIDS Clinical Trial Group 076 protocol was used. None of the infants was breast-fed. Maternal CD4 T lymphocyte counts and viral loads were not monitored. Infants were followed for clinical progress, and serial serologic testing was performed to the age of 24 months, or until two successive HIV (enzyme-linked immunosorbent assay) tests were negative. In a historically case-controlled prospective study, the transmission rate in ZDV-untreated mother-infant pairs in which infants were born during 1991 through 1995 was compared with the transmission rate in ZDV-treated mother-infant pairs in which infants were born between 1996 and 2000.
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Additionally to a neurological examination, two lumbar punctures, a cerebral MRI and a neuropsycological test were performed. HIV-1 viral load in plasma and in CSF was quantified using Cobas TaqMan HIV-1 version 2.0 (Cobas Ampliprep, Roche diagnostic, Basel, Switzerland) with a detection limit of 20 copies/mL. Drug resistance mutations in HIV-1 reverse transcriptase and protease were evaluated using bulk sequencing.
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Of 75,308 women who gave birth between July 1998 and June 1999, 74,511 (98.9%) had antenatal care, 51,492 (69.1%) in the same district and 23,019 (30.9%) outside the district where they gave birth. HIV test results were available at delivery for 46,648 (61.9%) women, 410 (0.9%) of whom tested positive. Of these HIV-infected women, 259 (63.2%) participated in the zidovudine program and 6 (1.5%) received zidovudine from other sources. The proportion of women whose HIV test results were known and proportion of HIV-infected women who received zidovudine increased significantly during the year.
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Three thousand mothers (1499 HIV-infected) and their 3033 children (1515 HIV-exposed) were enrolled. During pregnancy 58 % received three-drug ART, 23 % received zidovudine alone, 11 % received no antiretrovirals (8 % unknown); 2.1 % of children were HIV-infected by 24 months. Vital status at 24 months was known for 3018 (99.5 %) children; 106 (3.5 %) died including 12 (38 %) HIV-infected, 70 (4.7 %) HIV-exposed uninfected, and 24 (1.6 %) HIV-unexposed. Risk factors for mortality were child HIV-infection (aHR 22.6, 95 % CI 10.7, 47.5 %), child HIV-exposure (aHR 2.7, 95 % CI 1.7, 4.5) and maternal death (aHR 8.9, 95 % CI 2.1, 37.1). Replacement feeding predicted mortality when modeled separately from HIV-exposure (aHR 2.3, 95 % CI 1.5, 3.6), but colinearity with HIV-exposure status precluded investigation of its independent effect. Applied at the population level (26 % maternal HIV prevalence), an estimated 52 % of child mortality occurs among HIV-exposed or HIV-infected children.
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Acquired immunodeficiency syndrome (AIDS) dementia complex (ADC) is a common effect of the AIDS virus. We studied the regional cerebral blood flow of patients with early ADC and its response to atevirdine mesylate.
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In symptomatic HIV-infected children, treatment with either didanosine alone or zidovudine plus didanosine was more effective than treatment with zidovudine alone. The efficacy of didanosine alone was similar to that of the combination therapy and was associated with less hematologic toxicity.
To evaluate HIV-1 reverse transcriptase (RT) drug resistance in patients receiving abacavir, lamivudine and zidovudine therapy.
Two large studies, Delta and ACTG 175, comparing single drug antiviral treatment to combination therapy, are discussed. Three tables supply data showing mortality rates between patients receiving AZT monotherapy and AZT plus either ddI or ddC, and ddI monotherapy. All the combination therapies show lower mortality rates than AZT monotherapy. Based on these results, AZT monotherapy as a standard of practice should not continue.
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We sought to evaluate the tolerability and feasibility of establishing an HIV postexposure prophylaxis (PEP) program at our hospital using the guidelines for children and adolescents after sexual assault.
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Nevirapine and cotrimoxazole are associated with hematologic toxicities and skin-rash. Safety of their concurrent use for prophylaxis over extended periods among HIV-exposed uninfected infants has not been previously assessed.
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Effective prophylaxis for infection with the human immunodeficiency virus (HIV) is important for health care providers at risk for exposure to infected blood. The average risk from percutaneous exposure is approximately 0.3%, but exposures involving a high titer of HIV or a large volume of infections material are apt to be much riskier. A convergence of indirect evidence strongly suggests that chemoprophylaxis with zidovudine after exposure to HIV may be efficacious. Treatment with zidovudine after percutaneous exposure appears to reduce the odds of infection by almost 80%. Zidovudine prophylaxis effectively prevents perinatal HIV transmission, and treatment during acute retroviral infection may attenuate HIV disease. Reports of "aborted" HIV infection among health care providers who have been stuck with contaminated needles suggest that antiretroviral treatment in the window of opportunity after exposure to HIV could prevent virus propagation and allow local cutaneous host defenses to clear the infection. Although efficacy has not been shown in controlled clinical trials, these data support a potential benefit from treatment after exposure. It is difficult to define the optimal regiment that should be used for prophyaxis, given the emergence of antiretroviral resistance among source patients. Current recommendations favor the use of zidovudine plus lamivudine for 4 weeks. Use of indinavir or other protease inhibitors is advised when the source patient is likely to harbor resistant virus or when exposure is especially hazardous.
The influence of antiretroviral drug zidovudine treatment during pregnancy on mandible development in newborn rats was studied. The fluorescence of mandibles from 7-, 14- and 28-days old individuals was measured by means of fiber-optical fluorescence analyzer with 407 nm laser excitation. Obtained results revealed disturbing effect of maternal zidovudine administration on mandible fluorescence intensity which should decrease with bone development. Small changes in fluorescence of porphyrin forms are maintaining in the first month of newborns life while the changes observed in 440-585 nm range disappear.
Virological failure rate among 599 eligible patients was 10.7 failures per 100 person-years. Cumulative failure incidence was 13.2% in the first year and 16.5% over 2 years. Patients initiated on tenofovir had a significantly lower rate of virological failure than those on stavudine or zidovudine (6.7 vs. 11.9 failures per 100 person-years, P = 0.013). Virological failure was independently associated with age <40 years, mean adherence <95%, non-tenofovir-containing regimens and presence of primary drug resistance. In a subset of 311 patients who were reassessed after treatment failure, 19% (11/58) patients resuppressed their viral load to <400 copies/ml after confirmed virological failure.
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Body circumferences and skinfold thicknesses were similar regardless of zidovudine exposure (P > 0.1), except for subscapular and supra-iliac skinfolds-for-age which were greater with long-term zidovudine (0.006 < P < 0.047). Circumferences/skinfolds were also similar with efavirenz and nevirapine (adjusted P > 0.09; 0.02 < P < 0.03 for waist/waist-hip-ratio). Total and high-density lipoprotein (HDL)-cholesterol, HDL/triglyceride-ratio (P < 0.0001) and triglycerides (P = 0.01) were lower with long-term zidovudine. Low-density lipoprotein (LDL)-cholesterol was higher with efavirenz than nevirapine (P < 0.001). Most lipids remained within normal ranges (75% cholesterol, 85% LDL and 100% triglycerides) but more on long-term zidovudine (3 NRTI) had abnormal HDL-cholesterol (88% vs. 40% short/no-zidovudine, P < 0.0001). Only 8/579(1.4%) children had clinical fat wasting (5 grade 1; 3 grade 2); 2(0.3%) had grade 1 fat accumulation.
CR and PR > 75% were observed in 56% of patients; 25% of the patients died during the induction phase. These results were analogous to those of the previous study (63% and 14%, respectively). Neither hematological tolerance nor dose intensity were improved. With a mean follow-up of 23.5 months, median survival was 6.7 months. The rate of non-NHL AIDS-related death during CR was not reduced (22% in our study vs. 16% in our previous one).
DNA and mRNA quantification using real-time PCR methods was performed on adipose tissue samples from 31 HIV-infected individuals, of whom 11 were treatment-naive and 20 were receiving HAART. mtDNA depletion was measured as mtDNA copies/cell, and mitochondrial proliferation by quantification of mitochondrial protein mass. Regulation of mitochondrial biogenesis was assessed by NRF-1 and mtTFA mRNA. PPARgamma, UCP2 and UCP1 mRNA expression was used to assess adipocyte differentiation and phenotype.
Occupational exposure to blood and body fluids is common among health care workers but most exposures confer a low risk of blood borne infection. The introduction of an occupational exposure assessment program has many benefits, including optimal management of injuries and acquisition of data on infection control measures, and may protect health care institutions from false claims for compensation.
Certain antiretroviral medications for human immunodeficiency virus (HIV) have been implicated in increasing risk of cardiovascular disease. However, antiretroviral drugs are typically prescribed in combination. We characterized the association of current exposure to antiretroviral drug combinations on risk of cardiovascular events including myocardial infarction, stroke, percutaneous coronary intervention, and coronary artery bypass surgery. We used the Veterans Health Administration Clinical Case Registry to analyze data from 24 510 patients infected with HIV from January 1996 through December 2009. We assessed the association of current exposure to 15 antiretroviral drugs and 23 prespecified combinations of agents on the risk of cardiovascular event by using marginal structural models and Cox models extended to accommodate time-dependent variables.
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Altogether these results indicate that AZT may be a highly effective agent against cancer parathyroid cells proliferation, which is an extremely important observation for a neoplasia which shows lack of response to classical pharmacological and physical antiblastic treatments.
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A total of 3,195 patients (total follow-up 4,593 person-years) were included in the analysis. AZT+ddC was associated with a higher incidence of PN (6.2 cases/100 person-years) compared with AZT monotherapy (3.0 cases/100 person-years) and AZT+ddl (2.2 cases/100 person-years). The risk of PN peaked around day 90 following randomization (at 8.9 events/100 person-years in the AZT+ddC arm). PN was also associated with age at entry (hazard ratio (HR)=2.35 for those aged 35-44 years compared with <30) and current CD4+ T-cell count (HR=2.27 for CD4+ T-cell counts <150 cell/mm3 compared with >350).
In July 2007, amid some controversy over cost, Zambia was the first African country to introduce tenofovir (TDF) as a component of first-line antiretroviral therapy (ART) on a wide scale.
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Episodes of viremia are common in African antiretroviral therapy (ART) programs. We sought to describe viremia, resuppression, and accumulation of resistance during first-line combination ART (cART) in South Africa.
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Patients had a higher incidence of anemia and leukopenia after substitution from D4T to ZDV, but hematologic toxicity was not a major complication in this population. Patients on ZDV-containing HAART regimens are still at risk for anemia and need close monitoring.
Computer modeling studies have been performed on the several pairs of D- and L-nucleoside inhibitors with the HIV-1 RT model. Additionally, clinically important M184V mutation, which confers the viral resistance against 3TC and FTC, were studied by the same modeling system.