Disease relevance of zidovudine

• Primary infection with zidovudine-resistant HIV [1].
• The results of this study support the hypothesis that in HIV-1 infection, early treatment with zidovudine and PCP prophylaxis improves survival in addition to slowing the progression to AIDS [2].
• Absence of cardiac toxicity of zidovudine in infants [3].
• A randomized controlled trial of a reduced daily dose of zidovudine in patients with the acquired immunodeficiency syndrome. The AIDS Clinical Trials Group [4].
• In a subgroup analysis, combination therapy delayed disease progression or death in patients who had previously received zidovudine for 12 months or less [5].

Psychiatry related information on zidovudine

• Antiretroviral drugs other than zidovudine might be useful in the prevention of AIDS dementia complex [6].
• Intrathecal zidovudine for AIDS dementia [7].
• Wernicke's encephalopathy in AIDS patient treated with zidovudine [8].
• Human immunodeficiency virus-associated autonomic neuropathy, drug addiction, and zidovudine treatment [9].
• Adding a second nucleoside analogue (didanosine, lamivudine, zalcitabine) to zidovudine does not further improve psychomotor performance [10].

High impact information on zidovudine

• Efavirenz plus zidovudine and lamivudine, efavirenz plus indinavir, and indinavir plus zidovudine and lamivudine in the treatment of HIV-1 infection in adults. Study 006 Team [11].
• The incidence of dilated cardiomyopathy was higher in patients with a CD4 count of less than 400 cells per cubic millimeter (as compared with a CD4 count of > or =400 cells per cubic millimeter) and in those who received therapy with zidovudine [12].
• At the end of the study, didanosine alone had an efficacy similar to that of zidovudine plus didanosine (median follow-up, 32 months) (relative risk of disease progression or death, 0.98; 95 percent confidence interval, 0.70 to 1.37; P=0.91) [13].
• Zidovudine was effective regardless of the HIV-1 RNA level or the CD4+ count at entry [14].
• CONCLUSIONS: In patients with advanced HIV infection, combination therapy with zidovudine and either didanosine or zalcitabine is not superior to zidovudine therapy alone [5].

Chemical compound and disease context of zidovudine

• The reverse-transcriptase inhibitor lamivudine has in vitro synergy with zidovudine against the human immunodeficiency virus (HIV) [15].
• Changing treatment from zidovudine to 500 mg per day of didanosine appears to slow the progression of HIV disease [16].
• Acyclovir has been reported to potentiate the effect of zidovudine on HIV in vitro [17].
• In this double-blind trial, patients with HIV infection were randomly assigned to receive either saquinavir (1800 mg per day) plus both zidovudine (600 mg per day) and zalcitabine (2.25 mg per day) or zidovudine plus either saquinavir or zalcitabine [18].
• Treatment assignment was stratified according to whether the patients had a history of one or more serious bacterial infections, had previously been treated with zidovudine, or were currently receiving prophylaxis with trimethoprim-sulfamethoxazole [19].
• Using an optimized pharmacokinetic design, this study indicated men exhibit significantly higher zidovudine-monophosphate and zidovudine-triphosphate exposure following zidovudine oral administration, having implications for drug toxicity and overall tolerance of zidovudine therapy [20].
• Our findings indicate that zidovudine, but not zalcitabine, induces mitochondrial myopathy, which is substantially antagonized by uridine supplementation [21].

Biological context of zidovudine

• In asymptomatic, HIV-infected adults with 500 or more CD4 cells per cubic millimeter, treatment with zidovudine slows the decline in the CD4 cell count but does not significantly prolong either AIDS-free or overall survival [22].
• Perinatal pharmacokinetics of zidovudine [23].
• Ethical challenges posed by zidovudine treatment to reduce vertical transmission of HIV [24].
• We asked pediatricians and obstetricians at the AIDS (acquired immunodeficiency syndrome) Clinical Trials Units to report information about pregnant women infected with the human immunodeficiency virus (HIV) who were continuing their pregnancies and had received, or were receiving, zidovudine during gestation [25].
• Mean platelet survival was also significantly decreased in the HIV-infected patients with normal platelet counts (untreated, 162 +/- 23 hours, P < 0.01; zidovudine-treated, 166 +/- 35 hours, P < 0.05) [26].

Anatomical context of zidovudine

• In the multivariate analysis, progression to AIDS was best predicted by low numbers and percentages of CD4+ lymphocytes, nonuse of zidovudine, and the presence of oral candidiasis, bacterial infections, or tuberculosis [27].
• Bone marrow suppression and anemia are frequent side effects of treatment of the acquired immunodeficiency syndrome (AIDS) with zidovudine (formerly azidothymidine [AZT]) [28].
• To produce concentrations of zidovudine (AZT) in plasma and cerebrospinal fluid that would provide constant inhibition of the replication of human immunodeficiency virus (HIV), we gave AZT by continuous intravenous infusion to 21 children ranging in age from 14 months to 12 years who had acquired HIV infection through transfusions or perinatally [29].
• The numbers and percentages of CD8+ cells and macrophages were similar in both the zidovudine-treated and the untreated HIV-positive patients [30].
• Numerous "ragged-red" fibers, indicative of abnormal mitochondria with paracrystalline inclusions, were found in the biopsy specimens from the zidovudine-treated patients but not in those from the other patients [30].

Associations of zidovudine with other chemical compounds

• There were significantly fewer new AIDS-defining events and deaths among the 298 subjects assigned to 500 mg per day of didanosine than among the subjects who continued to receive zidovudine (relative risk, 1.39; 95 percent confidence interval, 1.06 to 1.82; P = 0.015) [16].
• METHODS: The 391 subjects, each of whom entered the study with a single screening CD4 cell count of 200 to 500 per cubic millimeter, were randomly assigned to receive zidovudine alone, didanosine alone, zidovudine plus didanosine, or zidovudine plus zalcitabine [31].
• The normalized area under the curve for the CD4+ count was greater with the three-drug combination than with either saquinavir and zidovudine (P=0.017) or zalcitabine and zidovudine (P<0.001) [18].
• In patients with AIDS who are receiving zidovudine, trimethoprim-sulfamethoxazole is more effective than aerosolized pentamidine in conventional doses for the prevention of recurrent pneumocystis infection [32].
• Mutants resistant to 3'-azidothymidine (AZT, zidovudine) became phenotypically sensitive in vitro by mutation of residue 184 of viral reverse transcriptase to valine, which also induced resistance to (-)2'-deoxy-3'-thiacytidine (3TC) [33].

Gene context of zidovudine

• 10 HIV+ patients with CD4 cell counts between 200 and 500 cells/mm3 were treated with six cycles of subcutaneous recombinant IL-2 administration, in combination with zidovudine and didanosine [34].
• MRP4 overexpression is associated with high-level resistance to the nucleoside analogues 9-(2-phosphonylmethoxyethyl) adenine and azidothymidine, both of which are used as anti-human immunodeficiency virus drugs [35].
• METHODS: P-gp and MRP expression in response to long-term zidovudine (3'-azido-3'-deoxythymidine; AZT) or indinavir treatment was quantified by RT-PCR [36].
• Zidovudine-based HAART recipients (n=7) also displayed significant mtDNA depletion (34.45% of control, P=0.031), increased mitochondrial protein mass (5.7-fold of control, P=0.009), and markedly increased UCP1 (18-fold of control, P=0.009) mRNA [37].
• Reduced POT1 expression was observed in GC cell lines with telomeres shortened by treatment with azidothymidine [38].

Analytical, diagnostic and therapeutic context of zidovudine

• Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment. Pediatric AIDS Clinical Trials Group Protocol 076 Study Group [39].
• We present data from that trial showing the number of infected infants at 18 months of age and the relation between the maternal viral load, the risk of HIV-1 transmission, and the efficacy of zidovudine treatment [14].
• METHODS: The requisition form used by the PCR testing service included information on the demographic characteristics of the infants and the timing of any perinatal treatment with zidovudine [40].
• After treatment with zidovudine, however, overall left ventricular mass was increased (P = 0.02), as was peak wall stress (a stimulus to ventricular hypertrophy) (P = 0.01) [41].
• We examined the effects of abbreviated zidovudine regimens on perinatal HIV transmission using data from the HIV polymerase-chain-reaction (PCR) testing service of the New York State Department of Health. Pregnant women who received abbreviated regimens rather than the recommended regimens did so because of limited prenatal care or by choice [40].

References