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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The objective of this study was to compare the safety, tolerability and clinical response of once- versus twice-daily administration of didanosine given at a dosage of 270 mg/m2/day in children with symptomatic HIV-associated disease who were intolerant to or clinically deteriorated on zidovudine monotherapy. We carried out a randomized, open-label multicentre trial. Didanosine was supplied in buffered tablets, which could be chewed or dispersed in liquid. The children were recruited from 16 paediatric departments participating in the Italian Register for HIV Infection in Children. A total of 53 children (median age 5.5 years) started trial treatment; 26 were given didanosine twice daily and 27 once daily; 85% had AIDS and 98% had clinically deteriorated while on zidovudine therapy. Similar safety and tolerability results were demonstrated for the two schemes of therapy. A total of 11 children (20.7%) required discontinuation of didanosine for severe adverse events (five children (19.2%) in the twice-daily group; six children (22.2%) in the once-daily group, log-rank P = 0.81). Severe hepatic toxicity was uncommon (5.6%) while mild to moderate hepatic dysfunction was demonstrated in about 17% of the participants, without any difference between the two groups. Haematological toxicity was common (about 40% of the children, 11 in the twice- and 19 in the once-daily group) but never severe. Clinical pancreatitis and retinal lesions were never demonstrated. There was no significant difference in progression to death or to a new opportunistic infection between the two treatment regimens (log-rank P = 0.54). The modification of surrogate efficacy parameters during the study period was similar in the two groups. However, weight gain was poorer in children treated once daily. This study suggests that the safety and tolerability of 270 mg/m2/day of didanosine given once daily is substantially similar to that of the traditionally recommended schedule of two divided doses. Owing to the small sample and to the severity of the clinical condition of the children enrolled, no definite conclusions on the comparative efficacy of the two regimens can be drawn.
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PMID:Once versus twice daily administration of didanosine in children with symptomatic HIV-associated disease who were intolerant to or clinically deteriorated on zidovudine. The Italian Pediatric Collaborative Study Group on Didanosine. 1132 66

Researchers at the 12th Worlds AIDS Conference in Geneva provided a strong case for offering alternative drug options to patients. Resistance problems continue to accompany protease inhibitors, but other studies are identifying new options for extended therapy, such as using abacavir or efavirenz in combination therapies, or by using Nevirapine (Viramune) with Stavudine (d4T) and Didanosine (ddI). Hydroxyurea, a cancer fighting drug, is also gaining support as an HIV treatment, because it inhibits the enzyme that HIV needs to replicate. One study revealed that combining Hydroxyurea, ddI, and Indinavir provided quick and long-lasting reductions in viral load. Conference presentations about mother-to-infant HIV transmission showed reductions in the number of vertical transmissions when Zidovudine preventive therapy was used.
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PMID:New drugs garner interest; but inhibitors lose shine. 1136 95

Recent progress in treatment methods and medicines has made HIV more manageable. Factors contributing to this progress include advances in testing; the use and approval of protease inhibitors, non-nucleoside reverse transcriptase inhibitors, and other nucleosides; and the success of highly active antiretroviral regimens (HAART) and combination therapy. Nucleoside reverse transcriptase inhibitors, such as Zidovudine and Didanosine, and non-nucleoside reverse transcriptase inhibitors (NNRTIs) such as Nevirapine (Viramune) and Delavirdine (Rescriptor), are recommended for use in combination therapy. The pharmacology, side effects, and contraindications of these types of drugs are provided. Dosages and common side effects are also mentioned.
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PMID:Understanding the reverse transcriptase inhibitors in HIV. 1136 42

Updates are provided for new anti-HIV drugs currently in development. ABT-378, Tipranavir, and DMP-450 are among the new protease inhibitors discussed. Drugs from other classes that are discussed include emivirine (Coactinon, formerly MKC-442), FTC (emtricitabine, Coviracil), adefovir (Preveon), and pentafuside (T-20). A small study has found that women using Ritonavir (Norvir) may be at a greater risk for anemia (a decrease in red blood cells), caused by excessive menstrual bleeding or hypermenorrhea. New formulations of Ritonavir and ddI (Didanosine, Videx) are described.
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PMID:New anti-HIV drugs in development. 1136 65

This paper summarises some of the oral adverse effects of antiretroviral agents. Some are related to bone marrow suppression which may also predispose to mouth ulcers. Erythema multiforme and toxic epidermal necrolysis are especially well recognized in HIV disease, particularly as reactions to sulphonamides and to antiretroviral agents. Oral lichenoid reactions have been described in HIV disease often relating to zidovudine use. Didanosine has also produced erythema multiforme and not unusually induces xerostomia, again by an unknown mechanism. Xerostomia may be seen in up to one-third of patients taking didanosine. Taste abnormalities are common with the protease inhibitors and oral and perioral paraesthesia can be a disturbing adverse effect. Ritonavir in particular can give rise to circumoral paraesthesia in over 25% of patients. Indinavir can also produce cheilitis.
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PMID:Orofacial effects of antiretroviral therapies. 1157 69

Didanosine is an acid labile drug and hence has been given with buffering agents. To avoid the need for concurrent administration with antacids, an encapsulated enteric-coated bead formulation of didanosine was developed. The objective of this study was to assess the bioequivalence of the encapsulated enteric-coated beads compared to the buffered tablet. Two separate open-label, randomized, two-way crossover studies were conducted, one in healthy subjects and the other in HIV-infected subjects (with CD4 cell counts > 200 cells/mm3). All subjects received a 400-mg dose of the buffered tablet (reference formulation) and the encapsulated enteric-coated beads (test formulation). Blood samples were collected over 12 hours, and plasma levels of didanosine were determined using a validated assay. The 90% confidence interval (CI) of the ratio of the geometric means of log-transformed Cmax and AUCinfinity values were used to assess bioequivalence between the two formulations using the equivalence interval of 0.80 and 1.25. In healthy volunteers (n = 46), the point estimate and 90% CI of the ratios of Cmax and AUCinfinity values were 0.58 (0.52, 0.64) and 1.02 (0.95, 1.01), respectively. In HIV-infected subjects (n = 30), the point estimate and 90% CI of the ratios of Cmax and AUCinfinity values were 0.64 (0.56, 0.72) and 0.95 (0.86, 1.06), respectively. Median t(max) value increased significantly from 0.67 hours for the buffered tablet in both studies to 2.33 hours (in healthy subjects) or 2.0 hours (in HIV-infected subjects) for the enteric-coated beads. The mean half-life of didanosine was similar between treatments and ranged between 1.60 and 1.70 hours across healthy and HIV-infected subjects. It was concluded that the encapsulated enteric-coated bead formulation of didanosine is equivalent to the buffered tablet in the extent of exposure but differs in the rate of absorption. The pharmacokinetic profile of the enteric formulation appears to be similar in healthy and HIV-infected subjects.
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PMID:Bioequivalence of two formulations of didanosine, encapsulated enteric-coated beads and buffered tablet, in healthy volunteers and HIV-infected subjects. 1209 46

An active metabolite, ddATP, of didanosine that is an analogue of purine-nucleoside (a component of nucleic acid) was known to inhibit the activity of DNA polymerase for E. coli. In 1985, Dr. Michiya et al. of NCI reported that didanosine and ddA inhibited replication of the human immunodeficiency virus (HIV). This discovery led to the clinical application of both the compounds. Didanosine, after being uptaken into a cell, becomes an active metabolite, ddATP, to inhibit a reverse transcriptase of HIV. Compared with zidovudine, didanosine has weak cytotoxicity both in vitro and in vivo. Didanosine, which is recommended as a first-line therapy drug in the Japanese Guideline on an anti-HIV Infection Therapy, was approved as twice-daily Videx Tablet and Dry Syrup formulations for launch in June 1992. In March 2001, a once-daily Videx EC Capsule formulation was approved and launched, having expected adherence improvements in HIV/AIDS patients.
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PMID:[Pharmacological and clinical properties of didanosine (VIDEX), a nucleoside reverse transcriptase inhibitor]. 1218 24

Highly active antiretroviral therapy (HAART) has led to significant changes in mortality and morbidity in the human immunodeficiency virus type 1 (HIV-1) epidemic. Nevertheless, because of molecular mechanisms of viral persistence, HAART does not eradicate HIV-1. Didanosine and hydroxyurea were added to the antiretroviral regimens of 3 HIV-1-infected men who were receiving stable HAART and who had HIV-1 RNA levels <50 copies/mL at the initiation of the study protocol, as a novel intensification to attack cryptic viral replication; low-dose OKT3 was then administered, followed by a course of interleukin-2, to stimulate latent provirus. Replication-competent virus was undetectable after treatment, and plasma viral RNA was either undetectable or <5 copies/mL. In trial periods during which no antiretroviral therapy was administered, the patients developed plasma viral rebound. This translational approach combines novel intensification and stimulation therapy to deplete residual HIV-1 reservoirs. Additional experimental approaches must be developed if HIV-1 eradication is to become possible in patients receiving virally suppressive HAART.
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PMID:Intensification and stimulation therapy for human immunodeficiency virus type 1 reservoirs in infected persons receiving virally suppressive highly active antiretroviral therapy. 1240 55

Although once-daily dosing might not be appropriate for all patients, this schedule provides patients with a regimen that can fit more easily into their established routines, thereby increasing treatment adherence. Maintaining strict adherence is especially important in the treatment of HIV infection, because drug-resistant variants of HIV can emerge in suboptimal treatment environments. Didanosine, tenofovir, efavirenz, and lamivudine are the 4 single-agent antiretroviral drugs currently approved for once-daily administration. The combination of amprenavir boosted with ritonavir was FDA-approved for once-daily use in February 2002. Other new antiretroviral drugs are currently in development, as are new dosing schedules for existing antiretroviral drugs. Combinations of antiretroviral drugs, especially protease inhibitors boosted with ritonavir, are also being studied.
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PMID:Can HIV infection be treated successfully with a once-daily regimen? 1249 55

Didanosine remains a cornerstone nucleoside analogue for the treatment of HIV infection. A potential problem with the buffered formulations of didanosine is the likelihood of interactions with other drugs that require an acidic pH for absorption or can be chelated by cations in the buffer. An encapsulated enteric-coated (EC) bead formulation of didanosine has been approved and is routinely used as an alternative to the chewable/dispersible buffered tablet formulation. The objective of this study was to evaluate the single-dose pharmacokinetics of didanosine EC at 240 mg/m2 in 10 HIV-infected children. Didanosine EC was administered at time 0 on an empty stomach with no other concomitant medications. Blood samples were collected at pre-dose, 0.5, 1, 2, 4, 8 and 12 h post-dose. Didanosine was measured in plasma using radioimmunoassay. Ten subjects completed the intensive pharmacokinetic evaluation; data are available for eight participants. Plasma concentrations of didanosine following EC administration were analysed using non-compartmental methods. Median (range) AUCinfinity, Cmax, Tmax and CL/F for didanosine following EC administration were 2385 (1291, 3966) ng x h/ml, 854 (300, 1799) ng/ml, 3.0 (1.0, 8.1) h and 3.3 (2.7-6.4) l/h/kg, respectively. Results from this study indicate that the didanosine Cmax is decreased and Tmax is prolonged, but total exposure of didanosine in plasma following didanosine EC administration appears similar to previous data collected in HIV-infected children following buffered didanosine administration.
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PMID:Single-dose pharmacokinetics of enteric-coated didanosine in HIV-infected children. 1255 81


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