A Study to Evaluate the Effects of Stopping Maintenance Therapy for Cytomegalovirus (CMV) Retinitis After Effective Anti-HIV Therapy

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID) (NIH)

Overall Status

Completed

CT.gov ID

NCT00000905

Collaborator

(none)

Enrollment

Locations

Patients Per Site

Study Details

Study Description

Brief Summary

The purpose of this study is to see if it is safe to stop maintenance therapy in HIV-positive patients with treated and healed CMV retinitis (eye disease) who have responded well to anti-HIV (antiretroviral) therapy.

The current therapies available to treat CMV retinitis are long-term therapies. However, it may be safe to stop long-term anti-CMV therapy in patients with healed CMV retinitis and stable CD4 counts resulting from taking a combination of at least 2 antiretroviral drugs.

Condition or Disease	Intervention/Treatment	Phase
Cytomegalovirus Retinitis HIV Infections

Detailed Description

This study proposes to assess the hypothesis that, in HIV-infected patients with treated and healed CMV retinitis, an increase in CD4+ T-cells after initiation of potent antiretroviral therapy is either directly related to, or a marker of, immunologic protection for CMV retinitis and is associated with a recovery in specific proliferation responses to CMV antigens.

In this study, 100 patients [AS PER AMENDMENT 7/2/99: 50 patients] with treated and healed, non-immediate sight-threatening CMV retinitis will discontinue maintenance therapy for suppression of CMV retinitis. Patients are studied in 2 groups. Patients enrolled in Group 1 have CD4+ counts greater than 100 cells/mm3. Group 2 patients have CD4+ counts of 50-100 cells/mm3 and a minimum of a 2 log10 decrease in plasma HIV-1 RNA level or plasma HIV-1 RNA levels below the limit of detection while receiving potent antiretroviral therapy for at least 8 weeks prior to entry [AS PER AMENDMENT 7/2/99: Group 2 has been withdrawn]. An additional 25 patients who meet eligibility requirements but who choose to continue to receive maintenance therapy may also participate. All patients are followed to evaluate the relationship between reactivation or progression of CMV disease and changes in CMV DNA, HIV-1 RNA, and CD4+ cell counts. Patients are seen at Weeks 2, 4, 6 and 8, and every 4 weeks until study closure or for 12 months after the last subject is enrolled. [AS PER AMENDMENT 12/24/98: Patients with confirmed moderate to severe "immune recovery vitritis" should receive a 3-week course of systemic steroids (oral prednisone recommended). Moderate immune recovery vitritis is defined as symptomatic decrease in visual acuity of 2 or more Snellen lines along with, in the absence of active CMV disease, either 2+ or greater vitreous haze as defined by Nussenblatt et al., or cystoid macular edema.] [AS PER AMENDMENT 7/2/99: During the course of the study in patients with confirmed cystoid macular edema and a concomitant reduction in visual activity below 20/40, both attributable to immune recovery vitritis/uveitis only, a 21-day course of oral prednisone is recommended. This initial course of steroids helps to determine whether there is an improvement in vision or a decrease in macular edema. Long-term management of immune recovery vitritis/uveitis may include intraocular injection of steroids. Ophthalmoscopic examinations and laboratory tests are performed as per protocol.]

Study Design

Study Type:

Observational

Official Title:

Discontinuation of Maintenance Therapy for Cytomegalovirus (CMV) Retinitis After Immune Reconstitution by Potent Antiretroviral Therapy: Safety, Virology, and Immunology Profiles

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

13 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria

You may be eligible for this study if you:

Are HIV-positive.
Have a CD4 count greater than 100 cells/mm3.
Have healed CMV retinitis after receiving anti-CMV therapy for at least 8 weeks within 3 months prior to study entry.
Have taken antiretroviral therapy for at least 8 weeks prior to study entry; combination therapy must include at least 2 of the following: protease inhibitors (PIs), nucleoside reverse transcriptase inhibitors (NRTIs), or non-nucleoside reverse transcriptase inhibitors (NNRTIs).
Have a life expectancy of at least 6 months.
Are at least 13 years old (need consent if under 18).

Exclusion Criteria

You will not be eligible for this study if you:

Have any unstable or severe medical conditions that would keep you from completing the study.
Require chemotherapy or radiation therapy.
Have a history of certain eye disorders.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Univ of Southern California / LA County USC Med Ctr	Los Angeles	California	United States	900331079
2	UCLA CARE Ctr	Los Angeles	California	United States	90095
3	Willow Clinic	Menlo Park	California	United States	94025
4	Univ of California / San Diego Treatment Ctr	San Diego	California	United States	921036325
5	San Francisco AIDS Clinic / San Francisco Gen Hosp	San Francisco	California	United States	941102859
6	San Francisco Gen Hosp	San Francisco	California	United States	941102859
7	Santa Clara Valley Med Ctr / AIDS Community Rsch Consortium	San Jose	California	United States	951282699
8	San Mateo AIDS Program / Stanford Univ	Stanford	California	United States	943055107
9	Stanford Univ Med Ctr	Stanford	California	United States	943055107
10	Univ of Colorado Health Sciences Ctr	Denver	Colorado	United States	80262
11	Northwestern Univ Med School	Chicago	Illinois	United States	60611
12	Indiana Univ Hosp	Indianapolis	Indiana	United States	462025250
13	Division of Inf Diseases/ Indiana Univ Hosp	Indianapolis	Indiana	United States	46202
14	Johns Hopkins Hosp	Baltimore	Maryland	United States	21287
15	St Louis Regional Hosp / St Louis Regional Med Ctr	St Louis	Missouri	United States	63112
16	SUNY / Erie County Med Ctr at Buffalo	Buffalo	New York	United States	14215
17	Bellevue Hosp / New York Univ Med Ctr	New York	New York	United States	10016
18	Chelsea Ctr	New York	New York	United States	10021
19	Cornell Univ Med Ctr	New York	New York	United States	10021
20	Mount Sinai Med Ctr	New York	New York	United States	10029
21	Univ of North Carolina	Chapel Hill	North Carolina	United States	275997215
22	Univ of Cincinnati	Cincinnati	Ohio	United States	452670405
23	Univ of Pennsylvania at Philadelphia	Philadelphia	Pennsylvania	United States	19104
24	Julio Arroyo	West Columbia	South Carolina	United States	29169
25	Univ of Texas Galveston	Galveston	Texas	United States	775550435