Zidovudine in HIV infection

Polis M, Haneiwich S, Kovacs J, et al. Dose escalation study to determine the safety, maximally tolerated dose and pharmacokinetics of clarithromycin with zidovudine in HIV-infected patients. In Interscience Conference on Antimicrobial Agents and Chemotherapy American Society for Microbiology, 1991. 

Several large-scale studies of the efficacy of combined antiretroviral treatment with zalcitabine and zidovudine in HIV-infected patients (compared with zidovudine monotherapy or a combination of zidovudine and dida-nosine) have not shown unexpected adverse effects (1-4). The most common adverse effects in patients taking zalcitabine were peripheral neuropathy and aphthous mouth ulcers. 

Burger DM Meenhorst PL, ten Napel CHH, Mulder JW, Neef C, Koks CHW, Bull A, Bei-jnen JH. Pharmacokinetic variability of zidovudine in HIV-infected individuals sutgroup analysis and drug interactions. AIDS (1994) 8,1683-9. 

Several trials have evaluated the antiviral efQcacy of standard IFN-a in HIV-infected patients also receiving zidovudine, in comparison with zidovudine alone. 

Fernandez-Cruz E, Lang JM, Frissen J, Fumer V, Chateauvert M, Boucher CA, Dowd P, Stevens J (1995) Zidovudine plus interferon-alpha versus zidovudine alone in HIV-infected symptomatic or asymptomatic persons with CD4+ cell counts > 150 x 10(6)/L results of the Zidon trial. AIDS 9 1025-1035... 

The answer is d. (Katzung, pp 831-832.) Zidovudine competitively inhibits HIV-1 nucleoside reverse transcriptase. It is also incorporated in the growing viral DNA chain to cause termination. Each action requires activation via phosphorylation of cellular enzymes. Zidovudine decreases the rate of clinical disease progression and prolongs survival in HIV-infected patients. 

AIDS is associated with aberrant lymphocyte production and it has been proposed that Li+ may have a potential role in reversing this. Additionally, 3 -azido-3"deoxythymidine (AZT, zidovudine), an effective inhibitor of viral reverse transcriptase that reduces mortality in AIDS patients, induces hematopoietic suppression in patients resulting in anemia, neutropenia, and overall bone-marrow failure [220]. In murine AIDS, the coadministration of Li+ effectively moderates this toxicity of AZT in vivo [221,222]. There are several case reports where Li+ has been administered to help reduce the hematopoietic suppression in HIV-infected patients taking AZT (for example, see ref. 223). To date, the use of Li+ has been limited to a few weeks of treatment, and varying degrees of success have been achieved nevertheless the outlook in this field is quite hopeful. 

Treatment of anemia related to zidovudine therapy in HIV-infected patients To elevate or maintain the red blood cell level (as manifested by the hematocrit or hemoglobin determinations) and to decrease the need for transfusions in these patients when the endogenous erythropoietin level is less than or equal to 500 milliunits/mL and the dose of zidovudine is less than or equal to 4200 mg/week. Treatment of anemia in cancer patients on chemotherapy Jreatment of anemia in patients with nonmyeloid malignancies where anemia is due to the effect of concomitantly administered chemotherapy. It is intended to decrease the need for transfusions in patients who will be receiving chemotherapy for a minimum of 2 months. 

Children Safety and efficacy of zalcitabine in combination with zidovudine or as monotherapy in HIV-infected children younger than 13 years of age have not been established. 

Children Zidovudine has been studied in HIV-infected pediatric patients over 3 months of age who had HIV-related symptoms or who were asymptomatic with abnormal laboratory values indicating significant HIV-related immunosuppression. Zidovudine also has been studied in neonates perinatally exposed to HIV. 

Epoetin Alfa [Erythropoietin/ EPO] (Epogen/ Procrit) [Recombinant Human Erythropoietin] WARNING Use lowest dose possible may be associated w/1 CV, thromboembolic events /or mortality D/C if Hgb >12 g/dL Uses CRF associated anemia zidovudine Rx in HIV-infected pts, CA chemo -1- transfusions associated w/ surgery Action Induces ery-thropoiesis Dose Adul Peds. 50-150 Units/kg IV/SQ 3x/wk adjust dose q4-6wk PRN Surgery 300 Units/kg/d x 10 d before to 4 d after -I dose if Hct 36% or Hgb, T > 12 g/dL or Hgb t >1 g/dL in 2-wk pmod hold dose if Hgb >12 g/dL Caution [C, +] Contra Uncontrolled HTN Disp Inj SE HTN, HA, fatigue, fever, tach, NA Interactions None noted EMS Monitor ECG for hypokalemia (peaked T waves) t risk of CV thrombotic events OD May cause HA, dizziness, SOB and polycythemia symptomatic and supportive... 

J, Vazquez G. Fat distribution and metabolic abnormalities in HIV-infected patients on first combination antiretroviral therapy including stavudine or zidovudine role of physical activity as a protective factor. Antivir Ther 2003 8 223-31. 

Moeller AA, Oechsner M, Backmund HC, Popescu M, Emminger C, Holsboer F. Self-reported sleep quality in HIV infection correlation to the stage of infection and zidovudine therapy. J AIDS 1991 4 1000-1003. 

Anemia of chronic renal failure patients, zidovudine-treated HIV-infected patients and cancer patients on chemotherapy reduction of allogeneic blood transfusion in surgery patients... 

Mayers D, Jemesk J, Eyster E, et al. In A double-blind, placebo-controlled study to assess the safety, tolerability and antiretroviral activity of efavirenz (EFV DMP 266) in combination with open-label zidovudine (ZDV) and lamivudine (3TC) in HIV infected patients (DMP 266-004)38th Interscience Conference on Antimicrobial Agents and Chemotherapy (San Diego). Washington DC American Society for Microbiology, 1998 22340. 

Abacavir is a guanidine analogue that inhibits HIV reverse transcriptase. In vitro, its potency is similar to that of zidovudine, protease inhibitors, and dual nucleoside combinations. There is evidence that abacavir is effective in reducing viral load and increasing the CD4 count in HIV-infected patients. Viral resistance is not rapidly selected for, but cross-resistance has been shown to other analogues of cytosine and guanidine (didanosine, lamivudine, and zalcitabine). 

Delta Coordinating Committee. Delta a randomised doubleblind controlled trial comparing combinations of zidovudine plus didanosine or zalcitabine with zidovudine alone in HIV-infected individuals Lancet 1996 348(9023) 283-91. 

At a concentration of 100 gg/ml, valproic acid inhibits the glucuronidation of zidovudine in human liver microsomes by 50% (143). This observation explains the previously reported effect of valproate to increase plasma zidovudine concentrations in HIV-infected patients. 

Zidovudine alone or in combination with didanosine or zalcitabine in HIV-infected patients with the acquired immunodeficiency syndrome or fewer than 200 CD4 cells per cubic millimeter. Investigators for the Terry Beirn Community Programs for Chnical Research on AIDS. N Engl J Med 1996 335(15) 1099-106. 

The main dose-hmiting adverse reactions of zidovudine therapy in HIV-infected adults and children are hematological comphcations (12). When zidovudine was introduced it was given in about twice the dosage used today. Consequently, hematological adverse effects occur at a much lower frequency than previously reported (13,14). 

Gustavson LE, Chu SY, Mackenthun A, Gupta MS, Craft JC. Drug interaction between clarithromycin and oral zidovudine in HIV-1 infected patients. Clin Pharmacol Ther 1993 53 163. 

GaUicano KD, Sahai J, Shukla VK, Seguin I, Pakuts A, Kwok D, Foster BC, Cameron DW. Induction of zidovudine glucuronidation and amination pathways by rifampicin in HIV-infected patients. Br J Chn Pharmacol 1999 48(2) 168-79. 

Treatment of anemia in HIV-infected patients starts with therapy of HIV and correction of reversible canses of anemia. For zidovudine-treated HIV-infected patients, an initial TV or snbcnta-... 

Saquinavir mesylate is a protease inhibitor that inhibits human immunodeficiency virus (HIV) protease, the enzyme required to form functional proteins in HIV-infected cells. It is indicated in the treatment of advanced HIV infection. Saquinavir is given in combination with nucleoside analogs (e.g., zidovudine). 

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