Cidofovir Therapy Research Articles

Resolution of Recalcitrant Molluscum Contagiosum Virus Lesions in Human Immunodeficiency Virus-Infected Patients Treated With Cidofovir

Molluscum contagiosum virus (MCV) causes cutaneous skin growths that mainly affect children, sexually active adults, and immunocompromised individuals. Lesions of MCV in patients infected with human immunodeficiency virus can be large and numerous, and response to available treatments is often unsatisfactory. We describe 3 men infected with human immunodeficiency virus who presented with extensive MCV lesions that were not responsive to various treatments. Patient 1 demonstrated dramatic clearing of his MCV lesions when intravenous cidofovir therapy was started for his treatment-resistant bilateral CMV retinitis and because of cidofovir's possible activity against MCV. In case 2, cidofovir was compounded as a 3% cream in a combination vehicle (Dermovan) for extensive facial involvement, and complete resolution of MCV was seen after 1 month of therapy. In case 3, intravenous cidofovir therapy was started both for CMV retinitis and in an attempt to clear 90% facial MCV involvement; after 1 month of treatment, all clinical evidence of MCV had resolved. All 3 patients remain clear of recurrence. Cidofovir, a nucleotide analog of deoxycytidine monophosphate, appears to have contributed to clearing of advanced MCV lesions in these 3 patients, thus providing suggestive evidence of clinical activity against MCV. Controlled trials of cidofovir therapy for MCV in persons infected with human immunodeficiency virus are warranted.

Iritis and hypotony after treatment with intravenous cidofovir for cytomegalovirus retinitis.

To describe intraocular inflammation due to treatment with intravenous cidofovir dihydrate for cytomegalovirus retinitis. Retrospective cohort. Three university outpatient ophthalmology clinics. All patients treated with intravenous cidofovir therapy before October 31, 1996. Treatment with intravenous cidofovir was given according to standardized protocols. Intraocular inflammation was treated according to the best medical judgment. The presence of new intraocular inflammation, the severity of inflammation, visual acuity, and intraocular pressure. Eleven cases of iritis (26%) occurred among 43 patients. In 6 cases, the iritis was bilateral. Patients who experienced iritis were more likely to have been previously treated for cytomegalovirus retinitis (P = .03), to be diabetic (P = .05), or to be receiving protease inhibitors (P < .001). Four patients and 15 control subjects had also taken rifabutin (P = .70). The onset of iritis occurred at a mean (+/-SD) of 4.9 +/- 1.8 days after a cidofovir dose and after a mean (+/-SD) of 4.2 +/- 1.6 doses of cidofovir. Six eyes of 4 patients had hypotony. Five eyes of 5 patients had a persistent decrease in visual acuity of at least 2 Snellen lines. Acute intraocular inflammation may occur with or without hypotony after intravenous cidofovir therapy, similar to the reactions seen after intravitreous administration. Although the manifestations may be severe, they are manageable with topical corticosteroid therapy in most cases. Cidofovir therapy can be continued in some patients if medical necessity warrants, but recurrent inflammation or permanent hypotony may occur.

Low-dose Intravitreal Cidofovir (HPMPC) Therapy of Cytomegalovirus Retinitis in Patients with Acquired Immune Deficiency Syndrome

Purpose: The authors have shown that long-term treatment of cytomegalovirus (CMV) retinitis with 20-μg intravitreal injections of cidofovir (HPMPC) is highly effective but may be associated with iritis and profound hypotony. They evaluated the efficacy and safety of 10-μg intravitreal injections of cidofovir and made comparisons with their findings of 20-μg injections.Methods: The current study was conducted as a nonrandomized consecutive case series at the AIDS Ocular Research Unit of the University of California at San Diego. Twenty-seven eyes of 18 patients were injected with 10 μg intravitreal cidofovir and had complete follow-up. These were compared with another consecutive series of 24 eyes of 17 patients injected with 20 μg of cidofovir.Main Outcome Measures: The main outcome in this study was the incidence of failure to respond to treatment with 10-Mg injections. The authors also compared the time to progression of CMV retinitis after the initial intravitreal injections of 10 mg and 20 μg of cidofovir. Secondary outcomes included incidence of iritis and changes in intraocular pressure (IOP) after cidofovir injections.Results: The median time to retinitis progression was 45 days after a single intravitreal injection of 10 μg cidofovir compared with 55 days with the authors' series of 20-μg injections. This difference was statistically significant (P = 0.033, log-rank test) and appeared to be due principally to a 26% incidence of primary failure in the 10-yg group (progression ≥ 750 ym within 28 days, P = 0.0017 Wilcoxon test). Progression after a second injection of 10 μg cidofovir was more rapid (32 days, P = 0.037). The incidence of iritis after 10-μg injections was 2.2% compared with 23% with 20-μg injections (P = 0.003, Fisher's exact test, two-tailed). There was less decrease in IOP between the baseline injection and subsequent visits in the 10-μg group.Conclusions: Treatment of CIVIV retinitis with 10-1-tg intravitreal cidofovir injection was not as effective as with 20 μg and may allow development of drug resistance, but there were fewer side effects with the 10-μg dose. The drug appears to have a narrow therapeutic index, and other attempts at reducing the side effects while preserving the long-acting effect, such as liposome delivery, may be warranted.

QED: quick and early diagnosis

528 Vol 348 • August 24, 1996 J Med 1994; 330: 438–39. 14 Saran BR, Maguire AM, Nichols C, et al. Hypopyon uveitis in patients with acquired immunodeficiency syndrome treated for systemic Mycobacterium avium complex infection with rifabutin. Arch Ophthalmol 1994; 112: 1159–65. 15 Rosenberg PR, Uliss AE, Friedland GH, et al. Acquired immunodeficiency syndrome: ophthalmic manifestations in ambulatory patients. Ophthalmology 1983; 90: 874–78. 16 Freeman WR, Lerner CW, Mines JA, et al. A prospective study of the ophthalmologic findings in the acquired immune deficiency syndrome. Am J Ophthalmol 1984; 97: 133–42. 17 Humphry RC, Weber JN, Marsh RJ. Ophthalmic findings in a group of ambulatory patients infected by human immunodeficiency virus (HIV): a prospective study. Br J Ophthalmol 1987; 71: 565–69. 18 Rummelt V, Rummelt C, Jahn G, et al. Triple retinal infection with human immunodeficiency virus type 1, cytomegalovirus, and herpes simplex virus type 1: light and electron microscopy, immunohistochemistry and in situ hybridization. Ophthalmology 1994; 101: 270–79. 19 Studies of Ocular Complications of AIDS Research Group. Mortality in patients with the acquired immunodeficiency syndrome treated with either foscarnet or ganciclovir for cytomegalovirus retinitis. N Engl J Med 1992; 326: 213–20. 20 Heinemann M-H. Long-term intravitreal ganciclovir therapy for cytomegalovirus retinopathy. Arch Ophthalmol 1989; 107: 1767–72. 21 Anand R, Nightingale SD, Fish RH, et al. Control of cytomegalovirus retinitis using sustained release of intraocular ganciclovir. Arch Ophthalmol 1993; 111: 223–27. 22 Kupperman BD, Gordon JF, the Ganciclovir Implant Study Group. A multicenter study to evaluate the safety and efficacy of an intravitreal ganciclovir implant in patients with CMV retinitis. Invest Ophthalmol Vis Sci 1996; 37: S898. 23 Taskintuna I, Rahhal FM, Arevalo JF, et al. Low dose intravitreal HPMPC (Cidofovir) therapy for CMV retinitis in patients with AIDS. Invest Ophthalmol Vis Sci 1996; 37: S669. 24 Schimkat M, Althaus C, Sundmacher R. Prophylactic argon-laser coagulation for rhegmatogenous retinal detachment in AIDS patients with cytomegalovirus retinitis. Invest Ophthalmol Vis Sci 1996; 37: S370. 25 Katz DA, Berger JR. Neurosyphilis in acquired immunodeficiency syndrome. Arch Neurol 1989; 46: 895–98. 26 McLeish WM, Pulido JS, Holland S, et al. The ocular manifestations of syphilis in the human immunodeficiency virus type 1-infected host. Ophthalmology 1990; 97: 196–203. 27 Keane JR. Neuro-ophthalmologic signs of AIDS: 50 patients. Neurology 1991; 97: 196–203. 28 Hamed LM, Schatz NJ, Galetta SL. Brainstem ocular motility and AIDS. Am J Ophthalmol 1988; 106: 437–42. 29 Friedman DI. Neuro-ophthalmic manifestations of human immunodeficiency virus infection. Neurol Clin 1991; 9: 55–72. 30 Dennehy PJ, Warman R, Flynn JT, et al. Ocular manifestations in pediatric patients with acquired immunodeficiency syndrome. Arch Ophthalmol 1989; 107: 978–82.