Safety and Effectiveness of Giving Isotretinoin to HIV-Infected Women to Treat Cervical Tumors

A Randomized Phase III Trial of Oral Isotretinoin Versus Observation for Low-Grade Squamous Intraepithelial Lesions in HIV-Infected Women

The purpose of this study is to see if it is safe and effective to give isotretinoin to HIV-infected women with cervical tumors to prevent these tumors from becoming cancerous.

Cervical tumors are found in both HIV-infected and HIV-negative women. However, HIV-infected women are at a greater risk, and often their tumors become cancerous more quickly than those in HIV-negative women. Isotretinoin may be able to prevent this from happening. However, since these tumors tend to disappear over time, many doctors are hesitant to give their patients isotretinoin since this drug causes birth defects. This study looks at whether it is better to treat cervical tumors in HIV-infected women or to wait and see if they will disappear by themselves.

Cervical neoplasia is frequently seen in HIV-infected women, apparently resulting from immunosuppression and common risk factors, including sexual behavior patterns. In HIV seronegative women, progression of preinvasive neoplasia is relatively slow, and up to 40 percent of low grade squamous intraepithelial lesions (grade I CIN/HPV-associated changes) regress to a normal appearance over time. Many clinicians have opted not to treat CIN I/HPV-associated changes due to this high spontaneous regression rate. Currently, retinoids, principally isotretinoin, are the most consistently effective medical therapy for CIN/HPV-associated changes, but use of isotretinoin in HIV-infected patients has not been extensively documented. (AS PER AMENDMENT 6/10/97)

Patients are randomized to receive oral isotretinoin for 6 months or be observed only for 6 months, with 12 additional months of follow-up. [AS PER AMENDMENT 7/23/99: Follow-up time has been decreased to 9 months from the last patient enrolled.]

Inclusion Criteria

You may be eligible for this study if you:

• Are an HIV-positive female.
• Are at least 13 years old. (Need consent of parent or guardian if under 18.)
• Have cervical tumors, as determined by a biopsy performed by a doctor.
• Agree to use both condoms and the pill during the study.

Exclusion Criteria

You will not be eligible for this study if you:

• Have received certain cancer therapies (such as chemotherapy) within the past 3 or 4 months.
• Have had a hysterectomy (uterus removed) within the past 4 months.
• Are taking tetracycline or Vitamin A.
• Have taken certain medications. (Approved anti-HIV drugs and medications to prevent AIDS-related opportunistic infections are okay.)
• Are pregnant.