Summary
Synopsis
Zidovudine (azidothymidine) is a thymidine analogue antiretroviral drug active against human immunodeficiency virus (HIV). In acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC) patients, orally and intravenously administered zidovudine is effective in reducing the incidence of opportunistic infections and neoplasms, increasing helper T lymphocyte numbers, and improving survival rates and quality of life. Adverse effects include serious haematological abnormalities and severe headache, abdominal discomfort, nausea, myalgia and insomnia. In addition, neutropenia and other anaemias frequently limit zidovudine therapy and may result in a need for multiple blood transfusions, dose reductions or withdrawal of the drug. However, despite these problems and the lack of information about some aspects of zidovudine use, zidovudine provides a major hope for HIV-infected patients, and it has rapidly become the standard therapy for improving the quality and duration of the lives of AIDS and ARC patients.
Antiviral Activity
Zidovudine has no effect on extracellular virions. Against purified viral reverse transcriptase zidovudine is inactive in unphosphorylated form and largely inactive as the threo isomer, but the triphosphate of the erythro isomeric form of zidovudine is active as a competitive inhibitor, with a high affinity for this enzyme. Zidovudine is incorporated into viral DNA by dose-related competitive blockade of the uptake of thymidine (but not of adenosine, guanosine, or cytidine) into retroviral DNA.
In animal cell lines in vitro, zidovudine prevented viral cytopathic effects and reduced viral replication when added to cultures prior to retroviral exposure; activity declined with increasing intervals between viral inoculation and administration of zidovudine. As the cells of different species produce different levels of thymidine kinase, resulting in different concentrations of phosphorylated zidovudine, the in vitro antiviral activity of zidovudine is variable.
In human T lymphocytes in vitro, zidovudine at concentrations of approximatelyl μmol/L has been found to greatly reduce HIV-induced cytopathogenicity, reverse transcriptase activity, p24 antigen expression, viral replication and particle release. Inhibition of viral effects by zidovudine in vitro is concentration-related, and removal of the drug allows rapid viral spread. Exposure of T lymphocytes to zidovudine prior to and shortly after the time of inoculation with virus is more effective in inhibiting HIV antigen expression than later exposure. With time, T lymphocytes inoculated with HIV and exposed to zidovudine will begin to produce virus at the same rate as untreated infected cultures. Zidovudine has also been found to be active against Epstein-Barr virus and hepatitis B virus in cell culture.
The combinations of zidovudine plus recombinant β-interferon, castanospermine or acyclovir have been found to possess synergistic activity against HIV in T lymphocytes in vitro, as have zidovudine plus granulocyte-macrophage colony stimulating factor against HIV in monocytes, and zidovudine plus foscarnet (phosphonoformate) against HIV in peripheral blood mononuclear cells. The combination of dextran sulphate plus zidovudine has at least additive effects against HIV in monocytes and T lymphocytes. The zidovudine concentrations needed to inhibit HIV infection in T lymphocytes can be reduced by a factor of 5, or may be increased, with the addition of ampligen, a mismatched double-stranded RNA. Zidovudine plus either γ- or α-interferons was additive in effects against Epstein-Barr virus in human umbilical cord lymphocyte cultures, while recombinant α-interferon plus zidovudine acted synergistically against HIV in peripheral blood monocytes. Amphotericin B methyl ester and dideoxycytidine have both shown additive anti-HIV effects when combined with zidovudine in vitro. By contrast, ribavirin antagonised the effects of zidovudine on HIV in vitro.
Feline leukaemia virus (FeLV), murine leukaemia virus (MuLV), and murine sarcoma virus (MSV) are model in vivo retroviral infections aiding screening of anti-HIV agents. In cats inoculated with FeLV, zidovudine prevented viraemia if used as a pretreatment, and decreased the proportion of animals with viraemia in a dose-related fashion when treatment was started after inoculation. In MuLV-infected mice, zidovudine prolonged survival, with greater efficacy when given early after inoculation. Zidovudine protected mice from MSV-induced tumour formation, and increased survival rates were seen with higher doses. Coadministration of human α-interferon was found to enhance the protective effects of zidovudine in MuLV-infected mice.
Resistant strains have not been isolated when virus production in cell culture has again increased following zidovudine exposure, although such strains have been produced artificially by genetic manipulation.
Zidovudine acts by inhibiting viral replication through 2 mechanisms. Firstly, phosphorylated zidovudine inhibits the incorporation of thymidine into viral DNA by competitively inhibiting viral reverse transcriptase. With its 300-fold greater affinity for viral than for cellular polymerases, phosphorylated zidovudine reduces viral DNA production by filling 1 of every 1.5 to 2.4 sites available for thymidine. Secondly, once incorporated into viral DNA, zidovudine terminates the DNA chain by preventing additional phosphodiester linkages to its unreactive 3′-azido group.
Pharmacokinetics
Zidovudine pharmacokinetic data are still incomplete, although it has been studied in adult and paediatric HIV-infected patients and in some animal models. Intravenous administration of 1, 2.5, and 5 mg/kg doses of zidovudine over 1 hour to HIV-infected patients resulted in peak plasma concentrations of 1.5 to 2.5, 4 to 6, and 6 to 10 μmol/L, respectively. Similar peak plasma concentrations were obtained with oral zidovudine administered at double the intravenous doses. Thus, peak plasma concentration varied in an approximately linear fashion with dosage. Oral zidovudine is approximately 60% systemically available, with peak plasma concentrations seen 0.5 to 1.5 hours after administration. Intravenous zidovudine doses of up to 7.5 mg/kg for 2 weeks followed by oral doses of up to 15 mg/kg for 4 weeks, administered every 4 hours, did not produce indications of accumulation. Only limited information is available on the distribution of zidovudine. Studies in rats have shown that the drug distributes to most tissues, with lower concentrations in the brain and testes. In patients with AIDS, the mean volume of distribution is 1.4 L/kg. It is 15% plasma protein bound in dog plasma in vitro, and crosses the placenta and is found in the milk of mice. In humans, zidovudine concentrates in semen and crosses the blood-brain barrier, resulting in cerebrospinal fluid (CSF) concentrations that may only briefly exceed the 1 μmol/L viral inhibitory concentration between doses. Zidovudine is metabolised in the liver by glucuronidation to 3′-azido-3′-deoxy-5′-β-D-glucopyranosyl thymidine, which is excreted in the urine by renal tubular secretion. Zidovudine has a short half-life of about 1 to 1.5 hours in patients with AIDS, a plasma clearance rate of 1.3 L/h/kg and a mean renal clearance rate of 0.23 L/h/kg.
In children, peak plasma concentrations of 2.96 and 5.9 μmol/L followed administration of zidovudine 80 mg/m2 oral and intravenous doses, respectively. The terminal half-life in children was approximately 1.5 hours. Cerebrospinal fluid (CSF): plasma concentration ratios appear to vary widely in children and in adults.
Therapeutic Trials
The safety and efficacy of zidovudine in patients with HIV infections was initially established on the basis of a 6-week non-comparative phase I study of 19 patients with AIDS or ARC, and a 24-week phase II double-blind placebo-controlled randomised multicentre trial in 282 AIDS or ARC patients. The phase I trial showed zidovudine 3, 7.5, 15 or 30 mg/kg/day intravenously for 2 weeks followed by 4 weeks of oral treatment at double the intravenous dosage to improve T4 lymphocyte counts, T4: T8 cell ratios and total lymphocyte counts, and to reverse skin anergy. Most patients showed general improvement in immune status, weight gain and well-being, with reduced virus titres and improvements in chronic infections. The phase II trial of zidovudine 250mg orally every 4 hours was discontinued early due to the significantly (p <0.001) greater number of deaths in the placebo group: 19 deaths versus 1 in the zidovudine group. Zidovudine resulted in a statistically significant survival advantage (p <0.001), with a lower incidence of opportunistic infections and more reversals of skin test anergy than seen with placebo. Short term improvements in Karnofsky score, bodyweight and T4 lymphocyte counts, and reductions in viraemia and antigenaemia, were also seen with zidovudine therapy.
Further studies have shown zidovudine to raise T4 lymphocyte and platelet counts of HIV-infected patients. Natural killer cell activity may increase with zidovudine treatment. Serum HIV p24 antigen concentrations are usually significantly decreased during the early phases of zidovudine therapy, even at low dosages, and antigen levels in the CSF decline with treatment and rise with discontinuation of therapy. Lower initial p24 antigen levels have been associated with higher T4 cell counts, and declines in p24 antigen during zidovudine treatment are associated with decreased mortality. However, virus, and thus p24 antigen production, tends to return to pre-treatment levels with time, usually in tandem with declines in T4 lymphocyte counts.
Zidovudine has reduced the neurological effects of HIV infection when these were not too severe prior to treatment, improving cognitive, motor and behavioural functioning. However, certain severe neurological deficits may be unaffected by zidovudine treatment. In one study, Kaposi’s sarcoma lesions occasionally were reduced, and only rarely progressed, in zidovudine-treated compared to placebo-treated patients. Additionally, a lower incidence of new Kaposi’s lesions occurred in zidovudine-treated versus placebo-treated patients in another study. Observation of AIDS patients with Kaposi’s sarcoma in combination with other opportunistic infections is less encouraging; however, preliminary results from recent studies show progression of Kaposi’s sarcoma occurring in only one-third of zidovudine recipients, with the remaining two-thirds of patients being evenly split between stable and regressing disease. Further study of zic udine in Kaposi’s sarcoma is needed. Zidovudine appears to cause clearing or remission in reported cases of HIV-associated psoriasis. Zidovudine-treated patients tended to have fewer opportunistic infections than did placebo patients, and tended to show clearing of existing opportunistic infections such as fungal infections, cryptosporidiosis, and lymphoid interstitial pneumonitis. Progression of some opportunistic infections or neoplasms may occur, however, and results of zidovudine therapy may be highly individual. Preliminary evidence suggests that zidovudine efficacy extends to children, where it may be effective in improving immunological and neurological status and reducing opportunistic infections.
Zidovudine has been compared with ribavirin in a study in humans and found to cause greater decreases in HIV p24 antigen concentrations. Improved survival appears to accompany the combination of zidovudine and prophylaxis for Pneumocystis carinii pneumonia provided that combined adverse effects do not limit therapy. Oral zidovudine has been used in combination with intravitreous (injection into the vitreous humour) ganciclovir in the treatment of a small number of HIV-infected patients with cytomegalovirus (CMV) retinitis, with no adverse effects and with clearing of the CMV, but further study is needed before this can be widely recommended. Recent placebo-controlled studies have shown patients receiving the combination of zidovudine plus acyclovir to have significant survival advantages after long term therapy. The combination of dideoxycytidine and zidovudine, alternated on a weekly basis, provided clinical benefit in HIV-infected patients, but dideoxycytidine-induced adverse effects tended to limit treatment.
Over 5,000 patients with AIDS or ARC have been treated with oral zidovudine in non-controlled studies lasting from 24 weeks to 1 year. These studies show tolerability of zidovudine and survival rates to be best in patients with less severe and shorter durations of disease, and in those with higher pretreatment T4 cell and total lymphocyte counts, haemoglobin levels and Karnofsky scores. In over 200 patients with ARC treated for 24 weeks in a double-blind study, oral zidovudine was significantly (p < 0.05) superior to placebo in preventing progression to full-blown AIDS.
Adverse Effects
In a large placebo-controlled trial, 84% of zidovudine-treated and 72% of placebo-treated patients complained of adverse effects, with severe headaches, insomnia, myalgia, and nausea occurring more commonly with zidovudine. Serious haematological changes occurred in most zidovudine-treated patients, with neutropenia, leucopenia and anaemia occurring frequently, often requiring transfusions, and indicating bone marrow depression in 45% of cases. Dosage adjustments necessitated by adverse haematological effects occurred in 50% and 10% of zidovudine and placebo patients, respectively. A higher incidence of neutropenia occurred in patients with less than 100 T4 lymphocytes/mm3, low initial neutrophil and leucocyte counts, and low haemoglobin and vitamin B2 levels.
In another study, megaloblastic anaemia, severe anaemia and neutropenia occurred in 48, 42, and 45%, respectively, of patients on long term zidovudine therapy. Although blood profiles were normal prior to therapy in a third study, bone marrow aspirates after 4 or more months of zidovudine treatment showed erythroid and myeloid aplasia and hypoplasia, megaloblastic changes, cellular necrosis, serous fat atrophy and other abnormalities, and cellularity was reduced below 30% of normal in many patients. Biweekly monitoring for blood abnormalities is recommended, and blood transfusions are often required but need not necessarily interrupt zidovudine therapy.
In the follow-up of 4,805 patients with AIDS, 19.7% required 1 or more transfusions, and 11.4% and 8.3% had serious anaemia or granulocytopenia, respectively. Seizures were seen in 32 patients and 1 case of Stevens-Johnson syndrome developed.
Other adverse effects of zidovudine therapy include seizures, confusion, mania, and other neurological abnormalities, altered liver function tests, nail pigmentation changes, rash and abdominal discomfort. The incidence of adverse effects in children receiving zidovudine appears to be similar to that seen in adults.
Drug Interactions
Interactions between paracetamol (acetaminophen) and zidovudine, and between probenecid and zidovudine, have caused increased adverse effects, possibly due to decreased metabolism and excretion of zidovudine. Dideoxycytidine and zidovudine act by similar mechanisms and are expected to interact if given concomitantly, although alternation of these treatments on a weekly basis was not more hazardous than the individual components. Acyclovir plus zidovudine administered in combined therapy has been reported to cause insomnia, taste alterations, dry mouth, headache, lethargy, fatigue and somnolence, although these are likely due more to the zidovudine than the acyclovir component of therapy. Combined with agents for prophylaxis of Pneumocystis carinii pneumonia, zidovudine usually does not interact and can often be continued if the other drug must be halted. Zidovudine plus pyrimethamine-sulphadoxine resulted in neutropenia in one patient, but the patient was able to continue zidovudine once pyrimethamine-sulphadoxine was discontinued. The manufacturer recommends that drugs causing cytotoxic, nephrotoxic or adverse haematological effects should not be combined with zidovudine.
Dosage and Administration
Zidovudine is administered orally in a dosage of 200mg every 4 hours throughout each 24-hour period in AIDS and ARC patients. Dosage reduction or discontinuation is recommended in cases of neutropenia, anaemia, granulocytopenia or thrombocytopenia. However, it is not as yet certain that lower dosages will maintain a therapeutic effect. Optimum dosages in children, elderly patients and patients with renal or hepatic function insufficiency have not been established.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Agut H, Rosenheim M, Devillechabrolle A, Katlama C, Dohin E, et al. Evaluation of HIV antigen in serum during treatment by zidovudine. Abstract no. 3647, IV International Conference on AIDS, Stockholm, June 12–16, 1988
Andrews JC, McManus M, Rogers G, et al. Clinical benefits of concurrent administration of zidovudine and therapy for the suppression of Pneumocystis carinii.Abstract no. 7140, IV International Conference on AIDS, Stockholm, June 12–16, 1988
Anonymous. AIDS weekly surveillance report. Atlanta, Centers for Disease Control, 1987
Ayers KM. Preclinical toxicology of zidovudine: an overview. American Journal of Medicine 85: 186–188, 1988
Baba M, Pauwels R, Balzarini J, De Clerq E, Johns DG. Inhibitory effect of various reverse transcriptase inhibitors on tumor induction by Moloney murine sarcoma virus in vivo.III International Conference on Acquired Immunodeficiency Syndrome, Washington, DC, June 1–5, 1987. Abstract No. T.4.2, p. 54, 1987
Bach MC. Possible drug interaction during therapy with azido-thymidine and acyclovir for AIDS. New England Journal of Medicine 316: 547, 1987
Bach MC. Zidovudine for lymphocytic interstitial pneumonia associated with AIDS. Lancet 2: 796, 1987
Bagasra O, Lischner HW. Effects of 3′-azido-23′-dideoxythymidine (AZT), mismatched double-stranded RNA (dsRNA) and dextran sulfate (DS) on HIV-induced syncytium formation. Abstract no. 3141, IV International Conference on AIDS, Stockholm, June 12–16, 1988
Balis F, Pizzo P, Murphy R, Eddy J, Falloon J, et al. The pharmacokinetics of azidothymidine (AZT) administered by IV bolus (IVB) and continuous infusion (CI) in children with HIV infection. Proceedings of the American Society of Clinical Oncology 7: 1, 1988
Ballem P, Belzberg A, Doubroff P, Spurston B, Chambers H, et al. HIV-associated ITP: mechanism of the thrombocytopenia and its response to AZT. Abstract no. 7648, IV International Conference on AIDS, Stockholm, June 12–16, 1988
Balzarini J, Baba M, Pauwels R, Herdewijn P, Wood SG, et al. Potent and selective activity of 3′-azido-2,6-diaminopurine-2′,3′- dideoxyriboside,3′-fluoro-2,6-diaminopurine-2′,3′-dideoxyriboside, and 3′-fluoro-2′,3′-dideoxyguanosine against human immunodeficiency virus. Molecular Pharmacology 33: 243–249, 1988
Balzarini J, Herdewijn P, Pauwels R, Broder S, De Clerq E. α,β- and β,γ-methylene 5′-phosphonate derivatives of 3′-azido-2’3’-dideoxythymidine-5′-triphosphate. Correlation between affinity for reverse transcriptase, susceptibility to hydrolysis by phosphodiesterases and anti-retrovirus activity. Biochemical Pharmacology 37: 2395–2403, 1988
Balzarini J, Pauwels R, Baba M, De Clerq E, Broder S, et al. Correlation between metabolism and antiretroviral effect of Azddthd (AZT) and ddCyd in murine and human cell systems in vitroand in vivo.HI International Conference on Acquired Immunodeficiency Syndrome, Washington, DC, June 1–5, 1987. Abstract No. TP.1, p. 62, 1987
Barbaro DJ, Emanuele T, Fredenburg L, Luby JP. Open trial of azidothymidine (AZT) in AIDS patients at Parkland Memorial Hospital (PMH), Dallas, Texas. III International Conference on Acquired Immunodeficiency Syndrome, Washington, DC, June 1–5, 1987. Abstract No. THP. 229, p. 201, 1987
Bessen LJ, Greene JB, Louie E, Seitzman P, Weinberg H. Severe polymyositis-like syndrome associated with zidovudine therapy of AIDS and ARC. New England Journal of Medicine 318: 708, 1988
Bilello JA, MacAuley C, Forman S, Eiseman JL, Yetter RA. 3′-Azidothymidine (AZT) prevents the dissemination of retro-virus in LP-BM5 MuLV-infected C57BL/6 mice. Antiviral Research 9: 86, 1988
Blanche S, Caniglia M, Fischer A, Rouzioux C, Burgard M, et al. Zidovudine therapy in children with acquired immunodeficiency syndrome. American Journal of Medicine 85: 203–207, 1988
Blum MR, Liao SHT, Good SS, de Miranda P. Pharmacokinetics and bioavailability of zidovudine in humans. American Journal of Medicine 85: 189–194, 1988
Bratzke B, Stadler R, Tiel H, Ehlers G, Orfanos CE. Combination of interferon (rα2a-IFN) and zidovudine for therapy of HIV-associated Kaposi-sarcoma (KS). Abstract no. 3631, IV International Conference on AIDS, Stockholm, June 12–16, 1988
Buchi ER, Borey EH, Michel AE, Erard PA, Chave J-P. Can AZT treatment in AIDS patients aggravate pre-existing CMV retinitis? British Journal of Ophthalmology 72: 239, 1988
Carron WC, Colby CB, Ho DD. Anti-HIV activity of beta-interferon in combination with zidovudine. Abstract no. 3633, IV International Conference on AIDS, Stockholm, June 12–16, 1988
Causey DM, Leedon JM, Heseltine PN. Major opportunistic infections in AIDS patients after more than eight weeks of azidothymidine (AZT) therapy. III International Conference on Acquired Immunodeficiency Syndrome, Washington, DC, June 1–5, 1987. Abstract No. WP.221, p. 147, 1987
Chaisson RE, Allain J-P, Leuther M, Parks W, Lehrman S, et al. Decline in serum HIV p24 antigen (Ag) in patients treated with AZT. HI International Conference on Acquired Immunodeficiency Syndrome, Washington, DC, June 1–5, 1987. Abstract No. T.8.1, p. 58, 1987
Chaisson RE, Allain J-P, Leuther M, Volberding PA. Significant changes in HIV antigen level in the serum of patients treated with azidothymidine. New England Journal of Medicine 315: 1610–1611, 1986
Chandrasekar PH. ‘Cure’ of chronic cryptosporidiosis during treatment with azidothymidine in a patient with the acquired immune deficiency syndrome. American Journal of Medicine 83: 187, 1987
Chiuten DF, Mansell P, McCrory L, Kurowski P, Hernandez M, et al. Effects of 3′-azido-3′-deoxythymidine (AZT) in patients with acquired immune deficiency syndrome (AIDS) post-Pneumocystis cariniipneumonia infection. III International Conference on Acquired Immunodeficiency Syndrome, Washington, DC, June 1–5, 1987. Abstract No. THP.234, p. 202, 1987
Claman HN. The biology of the immune response. Journal of the American Medical Association 258: 2834–2840, 1987
Cohn J, Shapiro C, Keyes C, Smothers K. Neurologic disease associated with zidovudine (AZT). 27th Interscience Conference on Antimicrobial Agents and Chemotherapy, New York, October 4–7, 1987. Abstract No. 381, p. 163, 1987
Colarian J. Clostridium difficile colitis following antiviral therapy in the acquired immunodeficiency syndrome. American Journal of Medicine 84: 1081, 1988
Coldiron BM, Orcutt VL, Barbaro DJ. Resolution of resistant chronic herpetic lesions with zidovudine in a patient with the acquired immunodeficiency syndrome. Archives of Dermatology 124: 1571–1572, 1988
Collaborative AZT Study Group. Tolerance of AZT in association with trimethoprim-sulfamethoxazole (TS), pyrimethamine (Py) or rifampine (R). Abstract no. 3654, IV International Conference on AIDS, Stockholm, June 12–16, 1988
Collier AC, Coombe R, Gianola F, Kidd P, Nikora B, et al. Preliminary urologic and clinical effects of combination zidovudine (ZVD) and acyclovir (ACV) therapy for HIV. Abstract no. 3137, IV International Conference on AIDS, Stockholm, June 12–16, 1988
Collins JM, Klecker RW, Kelley JA, Roth JS, McCully CL, et al. Pyrimidine dideoxyribonucleosides: selective penetration into cerebrospinal fluid. Journal of Pharmacology and Experimental Therapeutics 245: 466–470, 1988
Connolly GM, Dryden MS, Shanson DC, Gazzard BG. Cryptosporidial diarrhoea in AIDS and its treatment. Gut 29: 593–597, 1988
Cooper D. The use of zidovudine in earlier symptomatic HIV infection (AIDS-related complex.) Abstract. Retrovir zidovudine (formerly AZT), an update of its use in HIV therapy. Stockholm International Fairs, June 12, 1988
Costello C, Mir N, Luckit J. The blood transfusion service and zidovudine treatment for AIDS. British Medical Journal 295: 1486, 1987
Creagh-Kirk T, Doi P, Andrews E, Nusinoff-Lehrman S, Tilson H, et al. Survival experience among patients with AIDS receiving zidovudine. Journal of the American Medical Association 260: 3009–3015, 1988
Dahlberg JE, Mitsuya H, Blam SB, Broder S, Aaronson SA. Broad spectrum antiretroviral activity of 2-dideoxynucleosides. Proceedings of the National Academy of Sciences (USA) 84: 2469–2473, 1987
Davtyan DG, Vinters HV. Wernicke’s encephalopathy in AIDS patients treated with zidovudine. Lancet 1: 919–920, 1987
Dazza MC, Salmon D, Dournon E, Gaudebout C, Detruchis P, et al. Evolution of HIV antigenemia in 125 HIV infected patients treated with zidovudine (AZT). Abstract no. 3648, IV International Conference on AIDS, Stockholm, June 12–16, 1988
De Clerq E, Balzarini J, Descamps J, Eckstein F. Antiviral, antimetabolic and antineoplastic activities of 3′-amino or -azido substituted deoxyribonucleosides. Biochemical Pharmacology 29: 1849–1851, 1980
De Clerq E. Suramin in the treatment of AIDS: mechanism of action. Antiviral Research 7: 1–10, 1987
De Gans J, Lange JMA, Derix MMA, de Wolf F, Schattenkerk JKME, et al. Decline of HIV-antigen levels in cerebrospinal fluid during treatment with low-dose zidovudine. AIDS 2: 37–40, 1988
De Miranda P, Burnette TC, Good SS. Disposition and pharmacokinetics of the antiviral drug 3′-azido-3′-deoxythymidine (Retrovir) in monkeys and rats. 27th Interscience Conference on Antiviral Agents and Chemotherapy, New York, October 4–7, 1987. Abstract No. 378, p. 162, 1987
De Miranda P, Good SS, Blum MR, Thomas RV, Yarchoan R, et al. The effects of probenecid on the pharmacokinetic disposition of azidothymidine (AZT). International Conference on Acquired Immunodeficiency Syndrome, Paris, France, June 23–25, 1986. Abstract No. 558, p. 67, 1986
De Miranda P, Weiler S, Maha M, Lifson AR, Piccini MA, et al. Pharmacokinetics of zidovudine (ZVD) and acyclovir (ACV) during concurrent drug administration in asymptomatic men with HIV infection. Abstract no. 3136, IV International Conference on AIDS, Stockholm, June 12–16, 1988
De Wolf F, Lange JMA, Goudsmit J, Cload P, de Gans J, et al. Effect of zidovudine on serum human immunodeficiency virus antigen levels in symptom-free subjects. Lancet 1: 373–376, 1988
Deyton L, Kovacs J, Masur H, Metcalf J, Lee D, et al. Combination trial (phase I–II) of zidovudine with lymphoblastoid interferon alpha in patients with AIDS and Kaposi’s sarcoma. Abstract no. 3628, IV International Conference on AIDS, Stockholm, June 12–16, 1988
Donahue RE, Johnson MM, Zon LI, Clark SC, Groopman JE. Suppression of in vitrohaematopoiesis following human immunodeficiency virus infection. Nature 326: 200–203, 1987
Dournon E, Matheron S, Rozenbaum W, Gharakhanian S, Michon C, et al. Effects of zidovudine in 365 consecutive patients with AIDS or AIDS-related complex. Lancet 2: 1297–1302, 1988
Drach JC, Thomas MA, Barnett JW, Smith SH, Shipman C. Tritiated thymidine incorporation does not measure DNA synthesis in ribavirin-treated human cells. Science 212: 549–551, 1981
Dubin G, Braffmann MN. Zidovudine-induced hepatotoxicity. Annals of Internal Medicine 110: 85–86, 1989
Duvic M, Johnson TM, Rapini RP, Freese T, Brewton G, et al. Acquired immunodeficiency syndrome - associated psoriasis and Reiter’s syndrome. Archives of Dermatology 123: 1622–1632, 1987
Duvic M, Rios A, Brewton GW. Remission of AIDS-associated psoriasis with zidovudine. Lancet 2: 627, 1987
Eeftinck Schattenkerk JKM, Reiss P, Mulder JW, Lange JMA, Danner SA. Influence of zidovudine on HIV related Kaposi’s sarcoma. Abstract no. 3638, IV International Conference on AIDS, Stockholm, June 12–16, 1988
Elwell LP, Ferone R, Freeman GA, Fyfe JA, Hill JA, et al. Antibacterial activity and mechanism of action of 3′-azido-3′-deoxythymidine (BW A509U). Antimicrobial Agents and Chemotherapy 31: 274–280, 1987
Eppes SC, Wilfert CM, Weinhold KJ, Maha MA, Lehrman SN. Improvement in lymphoid interstitial pneumonitis in a child treated with azidothymidine. III International Conference on Acquired Immunodeficiency Syndrome, Washington, DC, June 1–5, 1987. Abstract No. THP.235, p. 202, 1987
Eriksson B, Vrang L, Bazin H, Chattopadhyaya J, Oberg B. Different patterns of inhibition of avian myeloblastosis virus reverse transcriptase activity by 3′-azido-3′-deoxythymidine 5′-triphosphate and its threoisomer. Antimicrobial Agents and Chemotherapy 31: 600–604, 1987
Fauci AS, Lane HC. The acquired immunodeficiency syndrome (AIDS). In Braunwald et al. (Eds) Harrison’s principles of internal medicine, 11th ed., pp. 1392–1396, McGraw-Hill, New York, 1987
Feeney GFX, Frazer I. AIDS-associated psoriasis responds to azidothymidine. Medical Journal of Australia 148: 155, 1988
Finaud M, Gallais H, Gastaut JA, Tamalet J, Casanova P. Thrombocytopenia H.I.V. mediated is reversible with A.Z.T. therapy. Abstract no. 3636, IV International Conference on AIDS, Stockholm, June 12–16, 1988
Fischl MA, Reese J, Dearmas L, Dickinson G, Parks W. Long-term experience with zidovudine (AZT) in patients with AIDS and AIDS-related complex. 27th Interscience Conference on Antimicrobial Agents and Chemotherapy, New York, October 4–7, 1987. Abstract No. 386, p. 164, 1987
Fischl MA, Richman DD, Grieco MH, Gottlieb MS, Volberding PA, et al. The efficacy of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial. New England Journal of Medicine 317: 185–191, 1987
Flanigan T, Shapiro E, Graham R. Prophylaxis against Pneumocystis cariniipneumonia in patients receiving azidothymidine. New England Journal of Medicine 317: 1155, 1987
Fleury HJA, Morere G, Delord B, Faivre R. Isolation of HIV from mononuclear cells of patients receiving zidovudine. Lancet 1: 880–881, 1988
Forester G. Profound cytopenia secondary to azidothymidine. New England Journal of Medicine 317: 772, 1987
Frick LW, Nelson DJ, St. Clair MH, Furman PA, Krenitsky TA. Effects of 3′-azido-3′-deoxythymidine on the deoxynucleotide triphosphate pools of cultured human cells. Biochemical and Biophysical Research Communications 154: 124–129, 1988
Furman PA, Fyfe JA, St Clair MH, Weinhold K, Rideout JL, et al. Phosphorylation of 3′-azido-3′-deoxythymidine and selective interaction of the 5′-triphosphate with human immunodeficiency virus reverse transcriptase. Proceedings of the National Academy of Sciences (USA) 83: 8333–8337, 1986
Furth PA, Kazakis AM. Nail pigmentation changes associated with azidothymidine (zidovudine). Annals of Internal Medicine 107: 350, 1987
Fyfe JA, Furman P, Vogt M, Sherman P. Mechanism of ribavirin antagonism of anti-HIV activity of azidothymidine. Abstract no. 3617, IV International Conference on AIDS, Stockholm, June 12–16, 1988
Gallo RC, Salahuddin SZ, Popovic M, Shearer GM, Kaplan M, et al. Frequent detection and isolation of cytopathic retroviruses (HTLV-iii) from patients with AIDS and at risk for AIDS. Science 224: 500–503, 1984
Gill PS, Rarick M, Brynes RK, Causey D, Loureiro C, et al. Azidothymidine associated with bone marrow failure in the acquired immunodeficiency syndrome (AIDS). Annals of Internal Medicine 107: 502–505, 1987
Gil-Fernandez C, De Clerq E. Comparative efficacy of broad-spectrum antiviral agents of African swine fever virus replication in vitro.Antiviral Research 7: 151–160, 1987
Goldman L, Worthington M, Riordan MA, Kreczko S, Dainiak N. Azidothymidine (AZT) inhibits proliferation of cultured human marrow hematopoietic progenitors. Clinical Research 35: 424A, 1987
Good SS, Durack DT, De Miranda P. Biotransformation in various species and in humans of 3′-azido-3′-deoxy-thymidine, a potential agent for the treatment of AIDS. Federation Proceedings 45: 444 (Abstract No. 1690), 1986
Good SS, Reynolds DJ. Simultaneous quantitation of the anti-HIV agent 3′-azido-3′-deoxythymidine, and its glucuronide in human serum by high-performance liquid chromatography (HPLC). 27th Interscience Conference on Antimicrobial Agents and Chemotherapy, New York, October 4–7, 1987. Abstract No. 377, p. 162, 1987
Gorard DH, Henry K, Guiloff RJ. Necrotising myopathy and zidovudine. Lancet 1: 1050, 1988
Gottlieb MS, Schroff R, Schanker HM, Weisman JD, Fan PT, et al. Pneumocystis cariniipneumonia and mucosal candidiasis in previously healthy homosexual men. New England Journal of Medicine 305: 1425–1431, 1981
Goudsmit J, De Wolf F, Paul DA, Epstein LG, Lange JMA, et al. Expression of human immunodeficiency virus antigen (HIV-Ag) in serum and cerebrospinal fluid during acute and chronic infection. Lancet 2: 177–180, 1986
Hagler DN, Frame PT, Azidothymidine neurotoxicity. Lancet 2: 1392–1393, 1986
Hamamoto Y, Nakashima H, Matsui T, Matsuda A, Ueda T, et al. Inhibitory effect of 2′,3′-didehydro-2′,3′-dideoxynucleosides on infectivity, cytopathic effects, and replication of human immunodeficiency virus. Antimicrobial Agents and Chemotherapy 31: 907–910, 1987
Hammer SM, Gillis JM, Groopman JE, Rose RM. In vitromodification of human immunodeficiency virus infection by gran-ulocyte-macrophage colony-stimulating factor and γ interferon. Proceedings of the National Academy of Sciences (USA) 83: 8734–8738, 1986
Hammer SM, Gillis JM. Synergistic activity of granulocyte-macrophage colony-stimulating factor and 3′-azido-3′-deoxythymidine against human immunodeficiency virus in vitro.Antimicrobial Agents and Chemotherapy 31: 1046–1050, 1987
Hargreaves M, Fuller G, Costello C, Gazzard B. Zidovudine overdose. Lancet 2: 509, 1988
Harris PJ, Caceres CA. Azidothymidine in the treatment of AIDS. New England Journal of Medicine 318: 250, 1988
Hartshorn KL, Vogt MW, Chou T-C, Blumberg RS, Byington R, et al. Synergistic inhibition of human immunodeficiency virus in vitroby azidothymidine and recombinant alpha interferon. Antimicrobial Agents and Chemotherapy 31: 168–172, 1987
Haynes BF, Fauci AS. Introduction to clinical immunology. In Braunwald et al. (Eds) Harrison’s principles of internal medicine, 11th ed., pp. 328–337, McGraw-Hill, New York, 1987
Helbert M, Fletcher T, Peddle B, Harris JRW, Pinching AJ. Zidovudine-associated myopathy. Lancet 2: 689, 1988
Helbert M, Robinson D, Peddle B, Forster S, Kocsis A, et al. Acute meningo-encephalitis on dose reduction of zidovudine. Lancet 1: 1249–1252, 1988
Helbert M, Stoneham C, Mitchell D, Pinching AJ. Zidovudine for lymphocytic interstitial pneumonitis in AIDS. Lancet 2: 1333, 1987
Henry K, Cantrill H, Kish MA. Intravitreous ganciclovir for patients receiving zidovudine. Journal of the American Medical Association 257: 3066, 1987
Henry K, Chinnock BJ, Quinn RP, Fletcher CV, De Miranda P, et al. Concurrent zidovudine levels in semen and serum determined by radioimmunoassay in patients with AIDS or AIDS-related complex. Journal of the American Medical Association 259: 3023–3026, 1988
Hochster H, Dieterich D, Laverty M, Reichman R, Plank C, et al. Toxicity of coadministered AZT and ganciclovir (DHPG) for CMV infection: (AIDS treatment evaluation unit #004). Abstract no. 3666, IV International Conference on AIDS, Stockholm, June 12–16, 1988
Hollander H, Lifson AR, Maha MA, Piccini MA, O’Malley PM, et al. A phase I study evaluating combination zidovudine and acyclovir in asymptomatic HIV-infected men: virologic and immunologic effects. Abstract no. 3135, IV International Conference on AIDS, Stockholm, June 12–16, 1988
Hymes KB, Greene JB, Karpatkin S. The effect of azidothymidine on HIV-related thrombocytopenia. New England Journal of Medicine 318: 516–517, 1988
Ito M, Nakashima H, Baba M, Pauwels R, De Clerq E, et al. Inhibitory effect of glycyrrhizin on the in vitroinfectivity and cytopathic activity of the human immunodeficiency virus [HIV (HTLV-III/LAV)]. Antiviral Research 7: 127–137, 1987
Jackson GG, Paul DA, Falk LA, Rubenis M, Despotes JC, et al. Human immunodeficiency virus (HIV) antigenemia (p24) in the acquired immunodeficiency syndrome (AIDS) and the effect of treatment with zidovudine (AZT). Annals of Internal Medicine 108: 175–180, 1988
Jacobson MA, de Miranda P, Gordon SM, Blum MR, Volberding P, et al. Prolonged pancytopenia due to combined ganciclovir and zidovudine therapy. Journal of Infectious Diseases 158: 489–490, 1988
Johnson VA, Walker BD, Paradis TJ, Barlow PA, Sodroski J, et al. Synergistic inhibition of HIV-1 replication by castanospermine (CAS) and either zidovudine (AZT) or recombinant soluble CD4 (rsT4). Abstract no. 3618, IV International Conference on AIDS, Stockholm, June 12–16, 1988
Kaplan MH, Sadick N, Farber B, Weider J. Dramatic improvement in HIV1 associated psoriasis with zidovudine. Abstract no. 7639, IV International Conference on AIDS, Stockholm, June 12–16, 1988
Kennedy CJ, Teschke RS, Hesselink J, Berger J, Fischl M, et al. Clinical evaluation of the central nervous syustem in HIV infected patients on azidothymidine. III International Conference on Acquired Immunodeficiency Syndrome, Washington, DC, June 1–5, 1987. Abstract No. T.8.3, p. 58, 1987
Klecker RW, Collins JM, Yarchoan R, Thomas R, Jenkins JF, et al. Plasma and cerebrospinal fluid pharmacokinetics of 3′-azido-3′-deoxythymidine: a novel pyrimidine analog with potential application for the treatment of patients with AIDS and related diseases. Clinical Pharmacology & Therapeutics 41: 407–412, 1987
Krasny HC, Good SS. Pharmacokinetics and metabolism of azidothymidine in the dog. Federation Proceedings 45: 207, 1986
Krieg CJ, Ostertag W, Clauss U, Pragneil IB, Swetly P, et al. Increase in intracisternal A-type particles in Friend cells during inhibition of Friend virus (SFFV) release by interferon or azidothymidine. Experimental Cell Research 116: 21–29, 1978
Lane HC, Masur H, Kovacs JA, Walker R, Carleton S, et al. A phase II, placebo-controlled trial of azidothymidine in acquired immunodeficiency syndrome patients with Kaposi’s sarcoma. Clinical Research 35: 480A, 1987
Larder BA, Purifoy DJM, Powell KL, Darby G. Site-specific mutagenesis of AIDS virus reverse transcriptase. Nature 327: 716–717, 1987
Lin JC, Zhang ZX, Sim I, Pagano JS. Inhibition of Epstein-Barr virus transformation of B-cells by 3′-azido-3′-deoxythymidine and interferon alpha and gamma. Proceedings of the American Association of Cancer Research 28: 452 (Abstract No. 1793), 1987
Lin J-C, Zhang Z-X, Smith MC, Biron K, Pagano JS. Anti-human immunodeficiency virus agent 3′-azido-3′-deoxythymidine inhibits replication of Epstein-Barr virus. Antimicrobial Agents and Chemotherapy 32: 265–267, 1988
Lin TS, Schinazi RF, Chen MS, Kinney-Thomas E, Prusoff WH. Antiviral activity of 2′,3′-dideoxycytidin-2′-ene (2′3′-dideoxy2′,3′-didehydrocytidine) against human immunodeficiency virus in vitro.Biochemical Pharmacology 36: 311–316, 1987
Little RJ, Brewster ME, Bodor NS. Brain-targetting of azidothymidine (AZT). 27th Interscience Conference on Antimicrobial Agents and Chemotherapy, New York, October 4–7, 1987. Abstract No. 380, p. 163, 1987
Lyerly HK, Cohen OJ, Weinhold KJ. Transmission of HIV by antigen presenting cells during T-cell activation: prevention by 3′-azido-3′-deoxythymidine. AIDS Research and Human Retroviruses 3: 87–94, 1987
Matheron S, Rozenbaum W, Navarette M, Deluol AM, Perrone C, et al. Effects of AZT on AIDS-related cryptosporidiosis. Abstract no. 3672, IV International Conference on AIDS, Stockholm, June 12–16, 1988
Matthes J, Walker LA, Watson JG, Bird AG. AIDS encephalopathy with response to treatment. Archives of Disease in Childhood 63: 545–548, 1988
Maxwell S, Scheftner WA, Kessler HA, Busch K. Manic syndrome associated with zidovudine treatment. Journal of the American Medical Association 259: 3406, 1988
McCloskey SE, Rege AB, Lertora JJL, George WJ, Agrawal KC, et al. Zidovudine pharmacokinetics and plasma levels in patients with HIV infection. Clinical Research 36: 21 A, 1988
McGrady G A, Jason JM, Evat BL. The course of the acquired immunodeficiency syndrome in the United States hemophilia population. American Journal of Epidemiology 126: 25–30, 1987
Melamed AJ, Muller RJ, Gold JWM, Campbell SW, Kleinberg ML, et al. Possible zidovudine-induced hepatotoxicity. Journal of the American Medical Association 258: 2063, 1987
Mitchell WM, Montefiori DC, Robinson WE, Strayer DR, Carter WA. Mismatched double-stranded RNA (ampligen) reduces concentration of zidovudine (azidothymidine) required for in vitroinhibition of human immunodeficiency virus. Lancet 1: 890, 1987
Mitsuya H, Broder S. Strategies for antiviral therapy in AIDS. Nature 325: 773–778, 1987
Mitsuya H, Matsukura M, Broder S. Rapid in vitrosystems for assessing activity of agents against HTLV-III/LAV. In Broder S (Ed.) AIDS: modern concepts and therapeutic challenges, pp. 303–333, Marcel Dekker Inc., New York, 1987
Mitsuya H, Weinhold KJ, Furman PA, St Clair MH, Nusinoff-Lehrman S, et al. 3′-Azido-3′-deoxythymidine (BWA509U): an antiviral agent that inhibits the infectivity and cytopathic effect of human T-lymphotropic virus type-III/lymphadenopathy-associated virus in vitro.Proceedings of the National Academy of Sciences (USA) 82: 7096–7100, 1985
Nakashima H, Matsui T, Harada S, Kobayashi N, Matsuda A, et al. Inhibition of replication and cytopathic effect of human T cell lymphotropic virus type III/lymphadenopathy associated virus by 3′-azido-3′-deoxythymidine in vitro.Antimicrobial Agents and Chemotherapy 30: 933–937, 1986
Nakashima H, Tochikura T, Kobayashi N, Matsuda A, Ueda T, et al. Effect of 3′-azido-2′,3′-dideoxythymidine (AZT) and neutralizing antibody on human immunodeficiency virus (HIV)- induced cytopathic effects: implication of giant cell-formation for the spread of virus in vivo.Virology 159: 169–173, 1987
Navia BA, Jordan BD, Price RW. The AIDS dementia complex: I. Clinical features. Annals of Neurology 19: 517–524, 1986
Nightingale SL. Retrovir approved. Journal of the American Medical Association 257: 2403, 1987
Nordenfelt E, Lofgren B, Chattopadhyaya J, Oberg B. Inhibition of hepatitis B virus DNA polymerase by 3′-azido-3′-deoxythymidine triphosphate but not its threoanalog. Journal of Medical Virology 22: 231–236, 1987
Olsen JC, Furman P, Fyfe JA, Swanstrom R. 3′-Azido-3′-deoxythymidine inhibits the replication of avian leukosis virus. Journal of Virology 61: 2800–2806, 1987
Orholm M, Pedersen C, Mathiesen L, Nielsen JO. Effect on serum p24 antigen of a combination therapy with low dose interferon and zidovudine. Abstract no. 3626, IV International Conference on AIDS, Stockholm, June 12–16, 1988
Ostertag W, Roesler G, Krieg CJ, Kind J, Cole T, et al. Induction of endogenous virus and of thymidine kinase by bromode-oxyuridine in cell cultures transformed by Friend virus. Proceedings of the National Academy of Sciences (USA) 71: 4980–4985, 1974
Pauwels R, De Clerq E, Desmyter J, Balzarini J, Goubau P, et al. Sensitive and rapid assay on HT-4 cells for detection of antiviral compounds against the AIDS virus. Journal of Virological Methods 16: 171–185,1987
Pediatric Zidovudine Study Group. Pharmacokinetics of zidovudine (ZDV, Retrovir) in children of 14 years or less. Pediatric Research 23: 381 A, 1988
Pediatric Zidovudine Study Group. Safety and tolerance of zidovudine (ZVD, Retrovir) during a phase I study in children. Pediatric Research 23: 380A, 1988
Perno CF, Yarchoan R, Tosato G, Cooney D, Mitsuya H, et al. Activity of diedeoxynucleosides against HTLV-III/LAV in vitroin different human cells. III International Conference on Acquired Immunodeficiency Syndrome, Washington, DC, June 1–5, 1987. Abstract No. THP.10, p. 165, 1987
Pickus OB. Overdose of zidovudine. New England Journal of Medicine 318: 1206, 1988
Pizzo PA, Eddy J, Falloon J, Balis FM, Murphy RF, et al. Effects of continuous intravenous infusion of zidovudine (AZT) in children with symptomatic HIV infection. New England Journal of Medicine 319: 889–896, 1988
Pontani D, Sun D, Brown J, Shahied SI, Plescia O, et al. Synergistic activity of amphotericin B methyl ester and azidothymidine. Abstract no. 3128, IV International Conference on AIDS, Stockholm, June 12–16, 1988
Popovic M, Sarngadharan MG, Read E, Gallo RC. Detection, isolation and continuous production of cytopathic retroviruses (HTLV-III) from patients with AIDS and pre-AIDS. Science 224: 497–500, 1984
Rappocciolo G, Cai Q, Ho M, Gupta P, Rinaldo CR. Enhancement of natural killer cell response to HIV-infected cells in AZT-treated AIDS patients. Journal of Leukocyte Biology 42: 434, 1987
Reiss P, Lange JMA, Boucher CA, Danner SA, Goudsmit J. Resumption of HIV antigen production during continuous zidovudine treatment. Lancet 1: 421, 1988
Resnick L, Mian AM. Enhanced in vitrosuppression of HIV infectivity by a combination of nucleoside analogs. III International Conference on Acquired Immunodeficiency Syndrome, Washington, DC, June 1–5, 1987. Abstract No. WP.l, p. 110, 1987
Richman DD, Andrews J. Results of continued monitoring of participants in the placebo-controlled trial of zidovudine for serious human immunodeficiency virus infection. American Journal of Medicine 85: 208–213, 1988
Richman DD, Fischl MA, Grieco MH, Gottlieb MS, Volberding PA, et al. The toxicity of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial. New England Journal of Medicine 317: 192–197, 1987
Roberts DE, Berman SM, Nakasato S, Wyle FA, Wishnow RM, et al. Effect of lithium carbonate on zidovudine-associated neutropenia in the acquired immunodeficiency syndrome. American Journal of Medicine 85: 428–431, 1988
Rothenburg R, Woelfel M, Stoneburner R, Milburg J, Parker R, et al. Survival with the acquired immunodeficiency syndrome. New England Journal of Medicine 317: 1297–1302, 1987
Ruprecht RM, O’Brien LG, Rossoni LD, Nusinoff-Lehrman S. Suppression of mouse viraemia and retroviral disease by 3′-azido-3′-deoxythymidine. Nature 323: 467–469, 1986
Ruprecht R, O’Brien L, Rosas D, Andersen J. Recombinant human interferon alpha A/D (RHUIFN-aA/D) enhances the anti-retroviral effect of 3′-azido-3′-deoxythymidine (AZT) in mice. Proceedings of the American Association of Cancer Research 28: 456 (Abstract No. 1810), 1987
Ruzicka T, Froschl M, Hohenleutner U, Holzmann H, Braun-Falco O. Treatment of HIV-induced retinoid-resistant psoriasis with zidovudine. Lancet 2: 1469–1470, 1987
Schinazi RF, Cannon DL, Arnold BH. Interaction of isoprinosine with 3′-azido-3′-deoxythymidine (AZT) in HIV-1 infected human peripheral blood mononuclear (PBM) cells and in FMuLV/ SFFV infected BALB/C mice. Abstract no. 3635, IV International Conference on AIDS, Stockholm, June 12–16, 1988
Schinazi RF, Chu CK, Kahlon JB, Shannon WM, Canonico P. Anti-human immunodeficiency virus (HIV-I) activity of 3′-azido-2′,3′-dideoxyuridine in different cell lines. 27th Interscience Conference on Antimicrobial Agents and Chemotherapy, New York, October 4–7, 1987. Abstract No. 369, p. 161, 1987
Schinazi RF, Eriksson BFH, Arnold BH, Cannon DL. Synergistic activity of 3′-azido-3′-deoxythymidine (zidovudine) and phosphonoformate (foscarnet) against human immunodeficiency virus type I in vitro.Antiviral Research 9: 119, 1988
Seligmann M. Zidovudine, plus or minus acyclovir, in the treatment of AIDS patients post-opportunistic infection. Abstract. Retrovir zidovudine (formerly AZT) an update of its use in HIV therapy. Stockholm International Fairs, June 12, 1988
Sharpe AH, Jaenisch R, Ruprecht RM. Retroviruses and mouse embryos: a rapid model for neurovirulence and transplacental antiviral therapy. Science 236: 1671–1674, 1987
Smith MS, Brian EL, Pagano JS. Resumption of virus production after human immunodeficiency virus infection of T lymphocytes in the presence of azidothymidine. Journal of Virology 61: 3769–3773, 1987
Sommadossi J-P, Carlisle R, Schinazi RF, Zhou Z. Uridine reverses the toxicity of 3′-azido-3′-deoxythymidine in normal human granulocyte-macrophage progenitor cells in vitrowithout impairment of antiretroviral activity. Antimicrobial Agents and Chemotherapy 32: 997–1001, 1988
Sommadossi J-P, Carlisle R. Toxicity of 3′-azido-3′-deoxythymidine and 9-(l,3-dihydroxy-2-propoxymethyl) guanine for normal human hematopoietic progenitor cells in vitro.Antimicrobial Agents and Chemotherapy 31: 452, 1987
Spear JB, Kessler HA, Nusinoff Lehrman S, de Miranda P. Zidovudine overdosage. Annals of Internal Medicine 109: 76, 1988
Spear J, Steinberg J, Phair J, Pottage J, Benson C, et al. AZT treatment of AIDS patients: clinical and laboratory parameters. 27th Interscience Conference on Antimicrobial Agents and Chemotherapy, New York, October 4–7, 1987. Abstract No. 384, p. 163, 1987
Spector SA, Kennedy C, McCutchan JA, Straube RC, Connor JD, et al. Antiviral effect of zidovudine (AZT) and ribavirin in clinical trials. 27th Interscience Conference on Antimicrobial Agents and Chemotherapy, New York, October 4–7, 1987. Abstract No. 389, p. 164, 1987
Spector SA, Ripley D, Hsia K. Human immunodeficiency virus (HIV) inhibition is sustained by alternating zidovudine (AZT) and 2′,3′-dideoxycytidine (DDC) but not by AZT alone. Abstract no. 3151, IV International Conference on AIDS, Stockholm, June 12–16, 1988
Spicehandler D, Dehovitz J, Gagliardi A, Grossman H, Markowitz M, et al. An experience with zidovudine (AZT) in AIDS. 27th Interscience Conference on Antimicrobial Agents and Chemotherapy, New York, October 4–7, 1987. Abstract No. 385, p. 164, 1987
St Clair MH, Richards CA, Spector T, Weinhold KJ, Miller WH, et al. 3′-Azido-3′-deoxythymidine tri phosphate as an inhibitor and substrate of purified human immunodeficiency virus reverse transcriptase. Antimicrobial Agents and Chemotherapy 31: 1972–1977, 1987
Stambuk D, Farthing C, Hawkins D, Youle M, Lawrence D, et al. The effect of azidothymidine (AZT) treatment on Kaposi’s sarcoma (KS) in human immunodeficiency virus (HIV) infected patients. Abstract no. 3639, IV International Conference on AIDS, Stockholm, June 12–16, 1988
Stambuk D, Farthing C, Shanson D, Youle M, Hawkins D, et al. The effect of azidothymidine (AZT) treatment on HIV p24 antigen levels. Abstract no. 3596, IV International Conference on AIDS, Stockholm, June 12–16, 1988
Steinberg J, Spear J, Murphy R, Kessler H, Pottage J, et al. Predictors of outcome on azidothymidine (AZT). 27th Interscience Conference on Antimicrobial Agents and Chemotherapy, New York, October 4–7, 1987. Abstract No. 388, p. 164, 1987
Summers J, Mason WS. Replication of the genome of a hepatitis B-like virus by reverse transcription of an RN A intermediate. Cell 29: 403–415, 1982
Surbone A, Yarchoan R, McAtee N, Blum R, Maha M, et al. Treatment of the acquired immunodeficiency syndrome (AIDS) and AIDS-related complex with a regimen of 3′-azido-2′3′-dideoxythymidine (azidothymidine or zidovudine) and acyclovir. Annals of Internal Medicine 108: 534–540, 1988
Swiss Group for Clinical Studies on the Acquired Immunodeficiency Syndrome (AIDS). Zidovudine for the treatment of thrombocytopenia associated with human immunodeficiency virus (HIV). A prospective study. Annals of Internal Medicine 109: 718–721, 1988
Tartaglione TA, Collier AC, Cummings DK, Coombs RW, Opheim KE, et al. Cerebrospinal fluid (CSF) findings in patients with AIDS following chronic oral treatment with zidovudine (ZVD). 27th Interscience Conference on Antimicrobial Agents and Chemotherapy, New York, October 4–7, 1987. Abstract No. 382, p. 163, 1987
Tartaglione T, Opheim KE, Collier AC, Gianola F, Unadkat J, et al. Pharmacokinetics (PK) of zidovudine (ZDV) and concomitant acyclovir (ACV) in symptomatic HIV infected patients. Abstract no. 3138, IV International Conference on AIDS, Stockholm, June 12–16, 1988
Tavares L, Roneker C, Johnston K, Nusinoff-Lehrman S, de Noronha F. 3′-Azido-3′-deoxythymidine in feline leukemia virus-infected cats: a model for therapy and prophylaxis of AIDS. Cancer Research 47: 3190–3194, 1987
Tochikura TS, Nakashima H, Kaneko Y, Kobayashi N, Yamamoto N. Suppression of human immunodeficiency virus replication by 3′-azido-3′-deoxythymidine in various human hematopoietic cell lines in vitro: augmentation of the effect by lentinan. Japanese Journal of Cancer Research (Gann) 78: 583–589, 1987
Tsai C-C, Follis KE, Lin T-S. Inhibition of the in vitroinfectivity of simian acquired immunodeficiency syndrome (SAIDS)-associated virus by azidothymidine (AZT). Proceedings of the Society of Experimental Biology and Medicine 185: 240, 1987
Tornevik Y, Eriksson S. Cellular metabolism of antiretroviral nucleoside analogs in cultured human T-lymphoblasts: effects of combinations of 2′,3′-dideoxycytidine, 3′-azido-3′-deoxythymidine and thymidine. Abstract no. 3150, IV International Conference on AIDS, Stockholm, June 12–16, 1988
Ueno R, Kuno S. Dextran sulphate, a potent anti-HIV agent in vitrohaving synergism with zidovudine. Lancet 1: 1379, 1987
Vaiopoulos G, Mangakis J, Karabinis A, Kourtis A, Fourtounis P, et al. Nail pigmentation and azidothymidine. Annals of Internal Medicine 108: 777, 1988
Viens P, Thyss A, Garnier G, Ayela P. Thrombocytopenia, the acquired immunodeficiency syndrome (AIDS), and zidovudine. Annals of Internal Medicine 109: 681, 1988
Vogt MW, Hartshorn KL, Furman PA, Chou T-C, Fyfe JA, et al. Ribavirin antagonizes the effect of azidothymidine on HIV replication. Science 235: 1376, 1987
Vrang L, Bazin H, Remaud G, Chattopadhyaya J, Oberg B. Inhibition of the reverse transcriptase from HIV by 3′-azido-3′-deoxythymidine triphosphate and its threoanalogue. Antiviral Research 7: 139, 1987
Walker R, Lane HC, Masur H, Kovacs J, Carleton S, et al. Therapy of AIDS patients with early Kaposi’s sarcoma with 3′-azido-3′-deoxythymidine. III International Conference on Acquired Immunodeficiency Syndrome, Washington, DC, June 1–5, 1987. Abstract No. T.8.2, p. 58, 1987
Walker R, Parker R, Kovacs J, Masur H, Gralnick H, et al. 3′-Azido-3′-deoxythymidine causes red cell aplasia and hypoplasia in AIDS patients with Kaposi’s sarcoma. Clinical Research 35: 435A, 1987
Weerts D, Cauchie E, De Wit S, Hermans P, Van Laethem Y, et al. One year experience of azidothymidine (AZT) administered 6 hourly in 40 patients (P) with AIDS or AIDS related complex (ARC). Abstract no. 3604, IV International Conference on AIDS, Stockholm, June 12–16, 1988
Williams GJ. Combined effects of r Interferon-β and AZT on HIV replication in vitro.Antiviral Research 9: 138, 1988
Wong RJ, Jacobson MA. Azidothymidine (AZT) tolerance in patients with acquired immunodeficiency syndrome (AIDS) post Pneumocystis cariniipneumonia (PCP). 27th Interscience Conference on Antimicrobial Agents and Chemotherapy, New York, October 4–7, 1987. Abstract No. 387, p. 164, 1987
Yarchoan R, Berg G, Brouwers P, Fischl MA, Spitzer AR, et al. Response of human-immunodeficiency-virus-associated neurological disease to 3′-azido-3′-deoxythymidine. Lancet 1: 132–135, 1987
Yarchoan R, Klecker RW, Weinhold KJ, Markham PD, Lyerly HK, et al. Administration of 3′-azido-3′-deoxythymidine, an inhibitor of HTLV-III/LAV replication, to patients with AIDS or AIDS-related complex. Lancet 1: 575–580, 1986
Yarchoan R, Perno CF, Thomas RV, Klecker RW, Allain J-P, et al. Phase I studies of 2′,3′-dideoxycytidine in severe human immunodeficiency virus infection as a single agent and alternating with zidovudine (AZT). Lancet 1: 76–81, 1988
Yarchoan R, Pluda JM, Thomas RV, Perno CF, McAtee N, et al. Long-term treatment of AIDS and AIDS-related complex (ARC) with an alternating weekly regimen of AZT and 2′3′-dideoxycytidine (DDC). Abstract no. 3149, IV International Conference on AIDS, Stockholm, June 12–16, 1988
Yarchoan R, Thomas RV, Grafman J, Wichman A, Dalakas M, et al. Long-term administration of 3′-azido-2′,3′-dideoxythymidine to patients with AIDS-related neurological disease. Annals of Neurology 23 (Suppl. 1): S82–87, 1988
Zimmerman TP, Mahony WB, Prus KL. 3′-Azido-3′-deoxythymidine: an unusual nucleoside analogue that permeates the membrane of human erythrocytes and lymphocytes by non-facilitated diffusion. Journal of Biological Chemistry 262: 5748–5754, 1987
Author information
Authors and Affiliations
Additional information
Various sections of the manuscript reviewed by: E. De Clerq, Department of Human Biology, Katholieke Universiteit Leuven, Leuven, Belgium; R.B. Ellis-Pegler, Infectious Disease Unit, Auckland Hospital, Auckland, New Zealand; A. Matsuda, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan; J.-P. Sommadossi, Division of Clinical Pharmacology, University of Alabama at Birmingham, Birmingham, Alabama, USA; D.J. Temple, Welsh School of Pharmacy, Cardiff, Wales; M.W. Vogt, Department of Internal Medicine, University Hospital, Zürich, Switzerland; N. Yamamoto, Department of Virology and Parasitology, Yamaguchi University School of Medicine, Yamaguchi, Japan; R. Yarchoan, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Rights and permissions
About this article
Cite this article
Langtry, H.D., Campoli-Richards, D.M. Zidovudine. Drugs 37, 408–450 (1989). https://doi.org/10.2165/00003495-198937040-00003
Published:
Issue Date:
DOI: https://doi.org/10.2165/00003495-198937040-00003