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Retrovir (Zidovudine)

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Generic Retrovir is used for treating HIV infection when used along with other medicines. It is also used with other medicines to help prevent women from passing the HIV virus to the fetus during pregnancy.

Other names for this medication:

Similar Products:
Sustiva, Combivir, Epivir, Zerit


Also known as:  Zidovudine.


Generic Retrovir is an antiviral. It works by blocking the reproduction of the HIV virus.

Generic name of Generic Retrovir is Zidovudine.

Retrovir is also known as Zidovudine, Azidothymidine, Zidovir, Retrovis.

Brand name of Generic Retrovir is Retrovir.


Do not stop taking it suddenly.


If you overdose Generic Retrovir and you don't feel good you should visit your doctor or health care provider immediately.


Store at room temperature between 15 and 25 degrees C (59 and 77 degrees F) away from moisture and heat. Throw away any unused medicine after the expiration date. Keep out of the reach of children.

Side effects

The most common side effects associated with Retrovir are:

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Side effect occurrence does not only depend on medication you are taking, but also on your overall health and other factors.


Be careful with Generic Retrovir while you are pregnant or have nurseling. Generic Retrovir can pass in breast milk and harm your baby.

Do not use Generic Retrovir if you are allergic to Generic Retrovir components.

Do not use Generic Retrovir if you have an enlarged liver, high lactic acid levels in the blood, or abnormal liver function tests.

Do not use Generic Retrovir if you are taking doxorubicin, ribavirin, stavudine, or any medicine that contains zidovudine.

Be careful with Generic Retrovir if you have a history of liver problems (eg, abnormal liver function tests, hepatitis B infection) or lactic acidosis, kidney problems, a bone marrow disorder, pancreas problems, abnormal blood cell counts, or nerve or muscle problems, bone marrow problems, low white blood cell levels, kidney problems, hepatitis C virus (HCV) infection, or other liver problems.

Be careful with Generic Retrovir if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement.

Be careful with Generic Retrovir if you take zalcitabine because severe pancreas problems may occur, fluconazole, ganciclovir, interferon alfa, probenecid, valproic acid, or any medicine that contains zidovudine because they may increase the risk of Generic Retrovir 's side effects; doxorubicin, ribavirin, or stavudine because they may decrease Generic Retrovir 's effectiveness.

Be careful with Generic Retrovir if you are very overweight.

Avoid alcohol.

Do not stop taking it suddenly.

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Combination therapy with antiretroviral drugs is used for the treatment of patients infected with the human immunodeficiency virus. To achieve optimal drug concentrations for viral suppression and avoidance of drug toxicity, monitoring of drug levels has been considered essential. We set up an analytical procedure for monitoring the plasma concentrations of a total of seven drugs: abacavir, zidovudine, efavirenz, nevirapine, indinavir, lopinavir, and nelfinavir. The plasma samples were liquid/liquid extracted and subjected to high-performance liquid chromatography (HPLC) analysis. The compounds were monitored by ultraviolet detection: indinavir, lopinavir, and nelfinavir at 215 nm; efavirenz at 254 nm, and abacavir, zidovudine, and nevirapine at 266 nm. Two different extraction procedures and two different HPLC eluents on a C(8) reversed-phase HPLC column were used to monitor all seven compounds. Under steady state conditions, the plasma concentrations of antiviral drugs in 175 patients were correlated with the time after the last dosing to define the peak or trough levels. Due to the short plasma elimination half-life of abacavir and zidovudine, only peak levels could be determined for these compounds, whereas both peak and trough levels could be assessed for the other compounds because of a longer plasma elimination half-life. The mean peak concentrations (microg/ml) were 0.69 for abacavir and 0.57 for zidovudine; the mean peak/trough concentrations (microg/ml) were 2.07/1.32 for efavirenz, 2.43/2.23 for nevirapine, 5.48/1.08 for indinavir, 4.69/3.51 for lopinavir, and 3.54/1.45 for nelfinavir. The described analytical method offers a broad-spectrum monitoring of plasma levels of antiretroviral drugs.

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The lack of HIV type-1 (HIV-1) viral load (VL) monitoring in resource-limited settings might favour the accumulation of resistance mutations and thus hamper second-line treatment efficacy. We investigated the factors associated with resistance after the initiation of antiretroviral therapy (ART) in the absence of virological monitoring.

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The effects of antiretroviral drugs on the response to pegylated interferon plus ribavirin remain uncertain. We evaluated whether antiretroviral drugs affected the response to pegylated interferon plus ribavirin in patients co-infected with HIV and hepatitis C virus (HCV).

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We have previously described an in vitro model for the evaluation of the effects of different immunomodulatory agents and immunotoxins (ITs) on cells latently infected with human immunodeficiency virus (HIV). We demonstrated that latently infected, replication-competent cells can be generated in vitro after eliminating CD25+ cells with an IT. Thus, by selectively killing the productively infected cells with an anti-CD25 IT we can generate a population of latently infected cells. CD25- cells generated in this manner were treated with nucleoside analog reverse transcriptase inhibitors and subsequently activated with phytohemagglutinin in the presence of the drugs. The antiviral activities of zidovudine (ZDV), lamivudine (3TC), and abacavir (ABC) were evaluated by using this model. 3TC and ABC demonstrated significant activity in decreasing HIV production from recently infected resting cells following their activation, whereas the effect of ZDV was more modest. These results suggest that the differences in antiviral activity of nucleoside analogs on resting cells should be considered when designing drug combinations for the treatment of HIV infection. The model presented here offers a convenient alternative for evaluating the mechanism of action of new antiretroviral agents (J. Saavedra, C. Johnson, J. Koester, M. St. Claire, E. Vitteta, O. Ramilo, 37th Intersci. Conf. Antimicrob. Agents Chemother., abstr. I-59, 1997).

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Observational cohort study of patients initiating ART between January 2000 and December 2005.

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These results are in line with current World Health Organisation guidelines suggesting equivalence of choice between single-dose NVP and short-course ZDV, and confirm the greater efficacy of ZDV+3TC than with any single antiretroviral drug.

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In HIV-infected adults prolonged monotherapy with zidovudine may be associated with the appearance of HIV strains with decreased zidovudine sensitivity, owing to specific mutations in the reverse transcriptase (RT) gene, and this has been suggested to be a reason for reduced zidovudine efficacy. This study was undertaken to determine the appearance of mutation at codon 215 of the RT gene in proviral DNA from PBMCs in HIV-infected children.

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Anemia is common in patients infected with the human immunodeficiency virus (HIV). The etiology is often multifactorial and may include the HIV infection itself, opportunistic infections, cancer, medications (particularly zidovudine and sulfa-containing drugs), or anemia of chronic disease. Epoetin alfa therapy may play a supportive role in some HIV-infected patients by increasing hemoglobin, decreasing fatigue, and reducing the need for exposure to red blood cell transfusions. A large, placebo-controlled trial in the United States for anemic patients with the acquired immunodeficiency syndrome taking zidovudine demonstrated a statistically significant improvement in hematocrit in patients treated with epoetin alfa compared with placebo. Transfusion requirements decreased in epoetin alfa-treated patients over a 3-month period compared with placebo with a trend toward improvement in quality of life. Epoetin alfa was effective, however, only in patients whose pretreatment erythropoietin levels were less than 500 mU/mL. These advantages of epoetin alfa treatment may become especially important as HIV becomes more of a chronic disease, with the concern that red blood cell transfusion may accelerate progression of HIV.

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HIV-seropositive homosexual and bisexual men in San Francisco (311 men), Denver (120 men) and Chicago (59 men).

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To ascertain if immunization results in the restoration of responses to recall antigens, in the development of responses to presumed neoantigens, and to identify the virologic and immunologic correlates of these responses in persons with HIV-1 infection.

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The number of people taking each antiretroviral in the UK was estimated from 23,655 individuals in the UK CHIC cohort (2012 database). Costs of patented drugs were taken from the British National Formulary database, assuming a 30% discount. Costs of generic antiretrovirals were estimated using an 80% discount from patented prices, or actual costs where available. Two options were analysed: 1 - all patients use single-tablet regimens and patented versions of drugs; prices remain stable over time; 2 - all people switch from patented to generic drugs when available, after patent expiry (dates shown above).

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More than two thirds of patients had anaemia at baseline. The AZT-containing regimen and absence of cotrimoxazole prophylaxis before starting ART were associated with persistent anaemia 12 months, after initiation of treatment. Considering the large proportion of patients with persistence of anaemia at 12 months, we suggest that it is necessary to conduct a large study to assess anaemia among HIV-infected patients in Goma.

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Time and duration of use of drugs used for AIDS and Pneumocystis carinii pneumonia (PCP) treatment and prophylaxis.

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The aim of our study is to compare the tolerability of zidovudine/lamivudine/indinavir when used in post-exposure prophylaxis (PEP) subjects and in HIV-infected patients. HIV-negative patients were enrolled as part of the surveillance protocol for professional exposure at the Luigi Sacco Hospital in Milan. HIV-positive patients were selected among all subjects undergoing treatment with zidovudine/lamivudine/indinavir from the CISAI cohort, an Italian cohort for the evaluation of adverse reactions to HAART. In both studies patients were followed prospectively and the severity of the reactions was evaluated using the AIDS Clinical Trial Group adverse experience grading scales. Up to September 1999, 37 HIV-seronegative subjects had undergone treatment with zidovudine/ lamivudine/indinavir. From a total of 1207 patients belonging to the CISAI cohort, 199 were identified as being treated with the same regimen. The frequency of adverse events in the PEP subjects was 70.3% compared to 11.1% for HIV-infected patients. In the first group, adverse events caused treatment interruption in 21 subjects (56.7%) versus 14 patients (7%) among the HIV-infected group. Only one case of a severe event (grade 3-4) was observed in the prophylaxis group against 12 in the treatment group. Our study shows that treatment interruption is eight times higher in HIV-negative subjects compared to HIV-seropositive patients, and that the incidence of adverse events is approximately six times higher, though such events, are for the most part, not severe.

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Mefenamic acid inhibited AZTG most potently, with an IC(50) value of 0.3 microM, and its inhibition type was not competitive. The IC(50) values for diclofenac, diflunisal, indomethacin, ketoprofen, naproxen, and niflumic acid against AZTG were 6.8, 178, 51, 40, 23, and 83 microM, respectively, while those for acetaminophen and salicylic acid were >100 microM. The IC(50) values for NSAIDs against AZTG in recombinant human UGT2B7 were similar to those obtained in HLM.

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Recent studies suggest that patients with HIV infection are at increased risk for incident diabetes mellitus (DM). We investigated the incidence and risk factors of DM among HIV-infected patients receiving combination antiretroviral therapy (CART) in Taiwan.

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Neutropenia is a common finding in patients with AIDS or AIDS-related complex (ARC), and limits their survival and therapies. We administered recombinant human granulocyte colony-stimulating factor (rG-CSF) 300 micrograms/day to 15 AIDS patients with severe neutropenia (< 1000/microliters). without discontinuing zidovudine, ganciclovir or other myelosuppressive drugs (e.g. antineoplastic chemotherapy). All patients showed correction of neutropenia and/or limitation of drug myelosuppressive action. Neutrophil count was > 1000/microliters during the whole follow-up (11 months). No patient showed sepsis, opportunistic infections or side effects. These data confirm the efficacy and tolerability of rG-CSF in AIDS-related neutropenia.

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Seven HIV-1-infected patients, all but one previously treated with dideoxynucleoside analogues (zidovudine, didanosine, zalcitabine), were treated for 1 year with ritonavir.

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The HIV lymphocyte reservoir is dynamic. Its diversity results mainly from successive archiving of circulating plasma viruses during the course of HIV infection. Archiving of resistant virus must be taken into account in therapeutic decisions.

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At birth there were no differences in ALT values between the groups of children. At 6 weeks of age, ALT levels were significantly higher among the treated groups compared with control group (geometric mean of 11.5 U/l for controls and 16.2-19.1 U/l for treated groups; P < 0.0001). Hematological parameters did not differ between groups at birth. At 6 weeks of age, levels of hemoglobin, hematocrit, granulocytes, and platelets were significantly (P < 0.0001) lower among antiviral drug-treated groups compared with controls. These changes were consistent with grade 1 (mild) toxicity, and were more noticeable among HIV-infected infants.

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Antiretroviral therapy for treatment of human immunodeficiency virus type 1 (HIV-1) infection has improved steadily since the advent of combination therapy in 1996.

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The development and validation of a simple and accurate method based on HPLC with ultraviolet detection for the quantification of zidovudine in rat plasma and its application to a pharmacokinetic study following a single intranasal dose zidovudine is described. Zidovudine was extracted from the plasma using a single-step deproteinization. Chromatographic separation of zidovudine from interfering components was achieved with a C-18 reverse phase column, a mobile phase consisting of a mixture of sodium acetate buffer (55 mM) with pH adjusted to 7.0 and acetonitrile (91:9 v/v) and UV detection set at 265 nm. The method was linear from 100 to 10,000 ng.mL(-1) (r(2) > or = 0.9995), and zidovudine had a mean recovery from plasma of 92.8%. The coefficient of variation of inter-day and intra-day quality control samples was less than 15%. After a single intranasal dose of zidovudine administered to rats, pharmacokinetic parameters (AUC(0-24), C(max), t(max), t(1/2)) were determined. The proposed method was found to be simple, specific, accurate, and precise and could be applied to the quantitative analysis of clinical pharmacokinetic studies of zidovudine in rats.

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buy retrovir 2015-10-12

On 19 September 2002, the Treatment Action Campaign retrovir buy (TAC), the Council of South African Trade Unions (COSATU), the Chemical, Energy, Paper, Printing, Wood and Allied Workers' Union (CEPPWA), and eight individuals (health-care workers and people living with HIV/AIDS) launched a complaint with the country's Competition Commission against two major transnational pharmaceutical companies. TAC and its allies allege that GlaxoSmithKline (GSK) has engaged in excessive pricing for its antiretroviral drugs Retrovir (zidovudine or AZT), 3TC (lamivudine), and Combivir (AZT/lamivudine), and that Boeringer Ingelheim (BI) has engaged in excessive pricing of its antiretroviral drug Viramune (nevirapine).

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3'-azido-3'-deoxythymidine (AZT), the first chemotherapeutic drug approved by FDA for treatment of HIV-infected patients and still used in combination therapy, has been shown to induce, upon prolonged exposure, severe bone marrow toxicity manifested as anemia, neutropenia and siderosis. These toxic effects are caused by inhibition of heme synthesis and, as a consequence, transferrin receptor (TfR) number appears increased and so retrovir buy iron taken up by cells. Since iron overload can promote the frequency and severity of many infections, siderosis is viewed as a further burden for AIDS patients. We have previously demonstrated that AZT-treated K562 cells showed an increase of the number of TfRs located on the surface of the plasma membrane without affecting their biosynthesis, but slowing down their endocytotic pathway. In spite of the higher number of receptors on the plasma-membrane of AZT-treated cells, intracellular accumulation of iron showed a similar level in control and in drug-exposed cells. The chelating ability of AZT and of its phosphorylated derivatives, both in an acellular system and in K562 cells, was also checked. The results demonstrated that AZT and AZTMP were uneffective as iron chelators, while AZTTP displayed a significant capacity to remove iron from transferrin (Tf). Our results suggest that AZT may be not directly involved in the iron overloading observed upon its prolonged use in AIDS therapy. The iron accumulation found in these patients is instead caused by other unknown mechanisms that need further studies to be clarified.

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We used a stochastic simulation of a generalized HIV-1 epidemic in sub-Saharan Africa to compare two strategies for first-line combination antiretroviral treatment including lamivudine, nevirapine and either ZDV or TDF. Model input parameters were derived from literature and, for the simulation of resistance pathways, estimated from drug resistance data obtained after first-line treatment failure in settings without virological monitoring. Treatment failure Bromocriptine Parlodel Dose and cost effectiveness were determined based on WHO definitions. Two scenarios with optimistic (no emergence; base) and pessimistic (extensive emergence) assumptions regarding occurrence of multidrug resistance patterns were tested.

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To determine the frequency of mutations in the connection domain (CD) of HIV reverse transcriptase in treatment-experienced patients in the Medication Zyloprim Used Options in Management with Antiretrovirals trial, their impact on susceptibility to antiretroviral (ARV) drugs, and their impact on virologic outcomes.

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We studied the relationship of CD4+ and CD8+ depletion to initial and late opportunistic infections in 62 patients with AIDS. The mean interval between initial and late infections was 12.2 months. Geometric mean (and 95% confidence intervals) of T-cell counts at the diagnosis of each infection were: (Pneumocystis carinii pneumonia) CD4+ 0.051 (0.044-0.058) x 10(9)/l, CD8+ 0.561 (0.476-0.646) x 10(9)/l; (cytomegalovirus retinitis) CD4+ 0.025 (0.019-0.031) x 10(9)/l, CD8+ 0.333 (0.183-0.483) x 10(9)/l. Mycobacterium avium-intracellulare bacteraemia closely followed cytomegalovirus dissemination. Most patients were free from late opportunistic infections caused Requip Dosage Forms by disseminated cytomegalovirus and M. avium-intracellulare until CD8+ declined below 0.500 x 10(9)/l. Zidovudine improved CD4+, but less so CD8+, and similarly enhanced the survival of patients treated in 1985-1990 and 1991.

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We compared total BMD changes over Diamox Medication 96 weeks in 106 ART-naive HIV-infected subjects who were randomized to receive efavirenz (EFV) + zidovudine/lamivudine (n = 32) or lopinavir/ritonavir (LPV/r) + zidovudine/lamivudine induction (n = 74) for 24-48 weeks followed by LPV/r monotherapy. We also sought to identify factors associated with BMD loss, including markers of systemic inflammation [soluble tumor necrosis factor-alpha receptors (sTNFR I and II)].

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In a prospective, randomized, open-label trial in an HIV clinic in Cameroon, 142 eligible adults (CD4 Antabuse Drug Test count < 350 cells/μL) were randomized to receive 24 weeks of a regimen comprising lamivudine plus nevirapine with either a reduced (400 mg) or standard dose (600 mg) of ZDV. The primary endpoint was the proportion of participants with new/worsening anaemia.

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The relationship between detectable human immunodeficiency virus (HIV) genotypic resistance and virologic response was compared in patients receiving nelfinavir as monotherapy (16 weeks) or in combination with lamuvidine and zidovudine (48 weeks). Two patient groups were defined on the basis of the presence or absence of substitutions associated with nelfinavir, a protease (PR) inhibitor, and/or a reverse transcriptase (RT) inhibitor. HIV RNA levels <50 copies/mL were achieved in 17 (85%) of 20 combination-therapy patients without genotypic resistance (PR-RT(-)) versus only 1 (17%) of 6 patients with genotypic resistance (PR-RT(+)). PR-RT(-) patients exhibited greater and more durable virus suppression compared with PR-RT(+) patients. All 6 PR-RT(+) patients had virus with M184V (lamuvidine resistance); 3 isolates also contained D30N (nelfinavir resistance). M184V preceded D30N in all determinable instances. In this study, suppression of HIV replication to <50 copies/mL was associated with durable response and reduced incidence of resistance. Viagra Mg Results also indicate that combination regimens can fail despite the absence of detectable genotypic PR resistance.

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The detection limit was 78 microIU/L, and within-run CVs <20% were seen for samples with TK1 down to 130 microIU/L. Cross-determination of the mitochondrial isoenzyme TK2 activity was <0.1%. Between-assay imprecision (CV) was 3.5-7.4%, and the within-assay imprecision was 4.1-9.1%. In studies of recovery and linearity on dilution, measured values ranged from 84% to 115% of expected at concentrations of 0.26-10.4 1 Paracetamol Tablet mIU/L. Results of the new assay (mIU/L) = 0.109 x TK REA (U/L) + 0.092. Heterophilic antibodies did not interfere in the assay. The upper 95th percentile, in 100 healthy individuals, was 0.94 mIU/L, and the median value was 0.43 mIU/L.

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The results of Motrin Ibuprofen Suspension this study in patients with HIV-1 recruited in the10 Recover Study and undergoing HAART suggest that long-term treatment with NRTIs is associated with AEs (lipoatrophy, peripheral neuropathy, and lipodystrophy), with morphologic disorders (lipoatrophy, lipodystrophy) being the most common AEs leading to discontinuation. Minimizing these AEs by switching to an NRTI not associated with these AEs (eg, tenofovir) would contribute to adherence and hence efficacy of long-term HAART.

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Of the antiviral agents that are currently in clinical use in the US for therapy for human immunodeficiency virus infections, zalcitabine (ddC) is the most potent and is effective at the lowest plasma concentrations. The two reported procedures for measuring these low concentrations involve a chromatographic technique coupled with mass spectrometry. We have developed a procedure combining solid-phase extraction with a strong cation-exchange resin and commercially available RIA reagents for the quantification of ddC in plasma or serum. The method demonstrates good linearity, specificity, and precision, with overall CVs of < 10% from 2-20 micrograms/L and 17% at 0.8 microgram/L (the lower limit of quantitation). No significant cross-reactivity with nucleoside analogs other than ddC analogs was noted Albenza Generic . The major advantages of this assay are its efficiency and relative simplicity, which should facilitate its performance in many laboratories.

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The spatial distributional pattern of neurons, in the superior frontal gyrus of 32 subjects who died of acquired immune deficiency syndrome, was examined. The patients were classified as nondemented, mildly demented, and severely demented, and some were treated with the anti-retroviral drug zidovudine. Spatial statistical techniques were employed to investigate the degree of clustering in the individual cases and various groups. We found that the cluster pattern of large and small neurons differed significantly with increasing severity of dementia but was not influenced by the duration of zidovudine treatment. We conclude that this is a sensitive technique for clinicopathological correlations and that the differences may result from loss of specific neuronal populations, which could determine the degree of dementia. Suprax Medication

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Enantiomerically pure carbocyclic 2'-deoxy-3'-azidothymidine monophosphate (AZTMP) and carba-2'deoxy-3'-thiocyanatothymidine monophosphate were synthesized to study their behavior toward their phosphorylation by thymidylate kinase. The nucleotides were synthesized starting from the parent nucleosides by an alkaline hydrolysis of the corresponding cycloSal-phosphate triesters.

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The regimen including zidovudine is less costly in the short run when compared to the regimen including tenofovir. Both regimens become financially similar when extending the study horizon.

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The evolution of a cohort of HIV-infected patients, prospectively defined by having suffered a pneumonia, was studied with regards to the occurrence of a new pneumonia or death from a bacterial disease; the evolution of a control cohort of patients matched according to sex, CD4-cell count, previous HIV-disease and zidovudine-treatment was compared to the former cohort by means of survival-analysis techniques.

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The effect of zidovudine (500 mg/day) on 32 asymptomatic subjects seropositive for human immunodeficiency virus (HIV) was evaluated by monitoring the concentrations of infections HIV-carrying blood mononuclear cells and serum virus particles. After 3 months of treatment, a significant reduction in cellular virus load (P < .001) and a marginal decrease in serum viremia (P = .068) were noted. After 6 months, 14 patients (44%) maintained a > or = 50% reduction in virus load, 12 patients (37%) had a virus load that declined by > 50% at 3 months but returned to the initial level at 6 months, and 6 patients (19%) retained their initial virus load. Thus, virus load measurements permit reliable follow-up of antiviral therapy on an individual basis and may enable the identification of patients for whom zidovudine is efficacious.

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To assess if cyclical therapy with four reverse transcriptase inhibitors is less toxic and as active, based on virological and immunological markers, as the same four drugs given together over a 64-week period.

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We evaluated the degree of correlation between the variation of different HIV-1 viral load measures in response to antiretroviral therapy. A quantitative reverse transcriptase polymerase chain reaction (RT-PCR) for plasma HIV-RNA, and HIV plasma infectivity titration, were performed on prospective samples obtained from 86 antiretroviral-naive patients with symptomatic infection and CD4+ < 300/mm3, enrolled in a randomized double-blind trial of the HIV protease inhibitor saquinavir (SQV) in combination with zidovudine (ZDV). Subjects were stratified according to plasma virus infectivity and examined for correlations between distinct response categories with respect to CD4 count and HIV RNA copy number changes. Infectious virus could be titrated in 72% of patients at baseline. A significant reduction (< 1 log10) in HIV plasma infectivity titer was observed during the study in 69% of these patients. The reduction in plasma infectivity was a good predictor of sustained CD4+ cell increases and of sustained decrease in HIV RNA plasma copies. A decrease of at least 0.5 log10 in HIV RNA copy number was observed in 82% of the treated patients. A good correlation was found between HIV plasma infectivity titer and plasma HIV RNA copy number variations (p < 0.001). However, 10 of 17 patients with unchanged plasma infectivity titer showed a significant reduction in HIV RNA copies. While a good correlation was found between plasma infectivity and RNA plasma copies variations, only a minor correlation was found between CD4+ cell count variation and plasma infectivity titer variation. However, reduction in plasma infectivity was a very good predictor of high CD4 changes.

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For patients with HIV/AIDS embarking on treatment today, the durability of HIV suppression in optimal regimens suggests that a normal lifespan is now a realistic outcome of HIV treatment.

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ABC/3TC/ZDV demonstrated comparable virologic efficacy to ATV+3TC/ZDV in this population over 48 weeks. In those with a baseline VL >/= 100,000 c/mL, subjects in the ATV+3TC/ZDV showed better virologic efficacy. Both regimens offer benefits in select therapy-naïve subjects.

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IDU began pre-AIDS antiretroviral therapy significantly later than homosexual men and heterosexuals, even after adjusting for CD4 count. Results from this non-randomized study confirm that antiretroviral treatment has only a short-term clinical benefit. There was a stronger association between antiretroviral treatment and lower risk of AIDS in homosexual men than in IDU.

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To review available drug-resistance patterns of HIV proteinase inhibitors, in particular saquinavir (formerly known as Ro 31-8959), focusing on the implications for disease management.

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The pre-steady-state reaction of Dictyostelium nucleoside diphosphate (NDP) kinase with dideoxynucleotide triphosphates (ddNTP) and AZT triphosphate was studied by quenching of protein fluorescence after manual mixing or by stopped flow. The fluorescence signal, which is correlated with the phosphorylation state of the catalytic histidine in the enzyme active site, decreases upon ddNTP addition according to a monoexponential time course. The pseudo-first order rate constant was determined for different concentrations of the various ddNTPs and was found to be saturable. The data are compatible with a two-step reaction scheme, where fast association of the enzyme with the dideoxynucleotide is followed by a rate-limiting phosphorylation step. The rate constants and dissociation equilibrium constants determined for each dideoxynucleotide were correlated with the steady-state kinetic parameters measured in the enzymatic assay in the presence of the two substrates. It is shown that ddNTPs and AZT triphosphate are poor substrates for NDP kinase with a rate of phosphate transfer of 0.02 to 3.5 s-1 and a KS of 1-5 mM. The equilibrium dissociation constants for ADP, GDP, ddADP, and ddGDP were also determined by fluorescence titration of a mutant F64W NDP kinase, where the introduction of a tryptophan at the nucleotide binding site provides a direct spectroscopic probe. The lack of the 3'-OH in ddNTP causes a 10-fold increase in KD. Contrary to "natural" NTPs, NDP kinase discriminates between various ddNTPs, with ddGTP the more efficient and ddCTP the least efficient substrate within a range of 100 in kcat values.

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K562 lymphoblastoid cells were treated for 74 days with zidovudine or stavudine concentrations corresponding to approximately 1x, 20x and 400x those measured in plasma. Samples were collected longitudinally and assayed for mtDNA, mtRNA and MDR-1 mRNA levels by real-time quantitative PCR. mtDNA deletions were investigated by long PCR.

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The ability of several known anti-HIV substances to inhibit feline immunodeficiency virus (FIV) was tested. The results showed that FIV infection of feline T-cells was almost completely blocked in the presence of all of the agents tested. However, FIV-induced syncytium formation between a human T-cell line (MT-2 cells) and a FIV-infected feline lymphocyte cell line (3201/FIV) was inhibited only by dextran sulfate and pradimicin A. The assay used to measure syncytium inhibition was rapid and did not use potentially hazardous human immunodeficiency virus (HIV)-infected cells. The efficacy results coincided with those of HIV studies.

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In the VA cohort, exposure to both individual drugs and drug combinations was associated with modestly increased risk of a cardiovascular event.

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In this 48-week pilot study, all patients received 600 mg ritonavir and 400 mg saquinavir twice daily. Administration of zidovudine and lamivudine was continued without a change in previous doses. Viral load, CD4 cell count, and the emergence of resistance to the two protease inhibitors were evaluated repeatedly up to week 48.

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To evaluate whether an inter-individual variability in the activity of thymidine kinase (TK) and deoxycytidine kinase (dCK), which are involved in the first step of phosphorylation of some nucleoside analogues, exists in antiretroviral-naive, HIV-seropositive patients.

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Zalcitabine is a dideoxynucleoside antiretroviral agent that is phosphorylated to the active metabolite 2',3'-dideoxycytidine 5'-triphosphate (ddCTP) within both uninfected and HIV-infected cells. At therapeutic concentrations, ddCTP inhibits HIV replication by inhibiting the enzyme reverse transcriptase and terminating elongation of the proviral DNA chain. The results of 3 large pivotal trials comparing zidovudine monotherapy with combination therapy have now clearly established that zalcitabine plus zidovudine combination with an improvement in viral load and CD4+ cell count compared with zidovudine monotherapy. More recently, clinical end-point and surrogate marker data have established the efficacy of zalcitabine in combination with the protease inhibitor saquinavir in zidovudine-experienced patients. Other studies have demonstrated the utility of zalcitabine in combination with ritonavir and the nucleoside analogue lamivudine. Importantly, early use of zalcitabine in the treatment sequence does not appear to limit the therapeutic efficacy of subsequent therapy with other nucleoside analogues such as lamivudine. Peripheral neuropathy is the most frequent dose-limiting adverse effect associated with zalcitabine therapy and is generally reversible on discontinuation of treatment. Stomatitis and mouth ulcers may occur frequently with zalcitabine therapy but tend to resolve with continuing treatment. Haematological toxicity, which is a common adverse effect associated with zidovudine, is reported infrequently with zalcitabine. Overall, combination therapy with zalcitabine plus zidovudine or saquinavir has been shown to have a tolerability profile comparable to that of either agent alone, although treatment with zidovudine plus zalcitabine was associated with a significant increase in the incidence of haematological toxicity compared with zidovudine monotherapy in one study. Therefore, current data suggest that zalcitabine is a useful antiretroviral agent for inclusion as a component of initial double combination therapy with zidovudine or as part of triple combination therapy including zidovudine plus a protease inhibitor in the management of patients with HIV infection.

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Overall, NFV in combination with ZDV and 3TC was well tolerated. The PK target was met in 3/8 AP and 5/7 PP in Cohort 1 and 17/21 AP and 16/17 PP in Cohort 2. When Cohort 2 NFV PK parameters AP and PP were compared, median Cmax (3.90 microg/mL vs. 5.01 microg/mL, p < .05) and AUC0-24 (56.6 vs. 86.8 microg . h/mL, p < .05) were increased PP and oral clearance (Cl/F; 44.2 vs. 28.8 L/h, p < .05) was decreased PP. The average M8/NFV ratio was increased PP compared to AP (0.085 vs. 0.29, p < .001). Placental transfer of NFV was low with a median cord blood:maternal plasma ratio at delivery of 0.05. Maternal mean CD4+ T cell counts increased significantly and plasma HIV-1 RNA levels decreased from entry to delivery and 6 to 12 weeks postpartum.

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Adult male LEW/SsN rats were divided into 3 groups (n=60). Group A as the control. Groups B and C were given diethylnitrosamine (DEN), 5mg/kg/day. In addition, Group C rats received an intraperitoneal injection of 3'-azido2,3'dideoxythymidine azidothymidine (AZT), 0.3mg/kg/day for 14 days starting on week 18. Ten animals in each group were sacrificed at 18, 20, 22 and 24 weeks to evaluate the liver tumor. We compared telomerase mRNA, telomerase activity and Bcl-2 mRNA among the liver tissue of group A rats and tumor tissue of HCC from group B and C rats.

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Capsaicin was efficiently glucuronidated in pooled human liver microsomes (pHLM). UGT1A1, 1A9 and 2B7 (as well as the gastrointestinal enzymes UGT1A7 and 1A8) showed considerable activities. Capsaicin glucuronidation was significantly correlated with 3-O-glucuronidation of β-estradiol (r = 0.637; p = 0.014) and with UGT1A1 protein levels (r = 0.616; p = 0.019) in a bank of individual HLMs (n = 14). Also, capsaicin glucuronidation was strongly correlated with zidovudine glucuronidation (r = 0.765; p < 0.01) and with UGT2B7 protein levels (r = 0.721; p < 0.01). UGT1A1, 1A9 and 2B7 contributed 30.3, 6.0 and 49.0% of total glucuronidation of capsaicin in pHLM, respectively. Further, glucuronidation of capsaicin by liver microsomes showed marked species difference.

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In HIV-1-infected children who switched from zidovudine every 8 h to every 12 h, a pharmacokinetic curve was recorded both before and after the switch. Zidovudine plasma levels were measured by HPLC. Pharmacokinetic parameters were calculated by non-compartmental methods.

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Systematic switching from patented to generic antiretrovirals could potentially save approximately £1.1 billion in the UK over the next five years, compared with continued use of patented versions: this money could be spent on urgently needed HIV prevention programmes. Similar savings are feasible for other European countries, given parallel patent expiry dates. More detailed economic evaluation is required to show when patented single-tablet regimens provide value for money, compared to bioequivalent generic versions of 3-4 pills once daily.

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From April 1991 through December 20, 1993, the cutoff date for the first interim analysis of efficacy, 477 pregnant women were enrolled; during the study period, 409 gave birth to 415 live-born infants. HIV-infection status was known for 363 births (180 in the zidovudine group and 183 in the placebo group). Thirteen infants in the zidovudine group and 40 in the placebo group were HIV-infected. The proportions infected at 18 months, as estimated by the Kaplan-Meier method, were 8.3 percent (95 percent confidence interval, 3.9 to 12.8 percent) in the zidovudine group and 25.5 percent (95 percent confidence interval, 18.4 to 32.5 percent) in the placebo group. This corresponds to a 67.5 percent (95 percent confidence interval, 40.7 to 82.1 percent) relative reduction in the risk of HIV transmission (Z = 4.03, P = 0.00006). Minimal short-term toxic effects were observed. The level of hemoglobin at birth in the infants in the zidovudine group was significantly lower than that in the infants in the placebo group. By 12 weeks of age, hemoglobin values in the two groups were similar.

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We showed how global procurement costs vary by region and time. Such analyses should be done more often to identify and correct market insufficiencies.

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A retrospective dataset of 354 antiretroviral drug resistant genotypes from children failing either abacavir (n = 81) or stavudine (n = 273) based 1st-line regimens, was analysed. Samples were sent to the HIV genotyping laboratory at Charlotte Maxeke Johannesburg Academic Hospital, for routine testing. Pol sequences were submitted to the Stanford HIV drug resistance database for genotypic predictions.