Long-Term Follow-Up of HIV-Infected Women with Cervical Dysplasia.

HIV infections in women were first recognized in New Orleans, Louisiana, in the mid-1980s, as were coinfections with human papilloma virus (HPV). In 1993, the rate of HIV infection in the Charity Hospital Colposcopy Clinic was much higher than in the previously mentioned (and adjacent) Obstetric Clinic, and the Centers for Disease Control (CDC) recognized invasive cervical cancer as an AIDS-defining condition. AIDS Clinical Trials Group (ACTG) protocols 200 and 293 were subsequently sponsored by the AIDS Clinical Trials Group, a federally-funded, cooperative research program, to characterize and treat cervical neoplasia in HIVinfected women. ACTG 200 compared 5-fluorouracil (5-FU) versus observation after excisional treatment of cervical intraepithelial neoplasia (CIN) 2–3. 5-FU was found to decrease the overall recurrence rate. Significant local toxicity, however, was reported in the 5-FU arm. ACTG 293 evaluated oral isotretinoin to reduce the rate of progression or increase the rate of regression of low-grade cervical dysplasia. Subjects were randomized to receive either oral isotretinoin 0.5 mg/kg daily for 6 months or observation. However, shortly after ACTG 293 opened, Highly Active Anti-Retroviral Therapy (HAART) came into widespread use for HIV infection in the U.S. The number of progression events declined below the level predicted in the statistical design, which led the authors to conclude that the use of HAART had unexpectedly confounded the study. A numerical but nonstatistically significant decrease in progression was seen in the study arm. Two hundred eighteen total subjects were enrolled to ACTG #200 or #293 between 1994–1998. Of note, health care in New Orleans was massively disrupted in August, 2005 by Hurricane Katrina. Declines in a number of healthcare outcomes, including heart disease and mental health, have been reported since the storm. This report analyzes 20 years of follow-up in women enrolled to ACTG 200 and 293 in New Orleans, including post-Katrina data. There are minimal published data on long-term outcomes or the effect of natural disaster on CIN in HIV-infected women. Thirty-two subjects were enrolled in ACTG #200 or ACTG #293 from the Tulane/LSU ACTG site between February, 1994–March, 1998. Data collection continued and were summarized through 2014 as part of a local QI program. This study was not sponsored by the ACTG, nor is it an official substudy of ACTG #200 or ACTG #293. Data included: CIN disease course, performance of gynecologic procedures, (hysterectomy, tubal sterilization, dilation and curettage, etc.) and adherence to HAART therapy. Chisquare was used for statistical analysis, with a p value of < 0.05. In ACTG 200, patients underwent excisional procedures for CIN 2–3 before enrollment. The recurrence rate of CIN in the ACTG #200 group was significantly higher than that seen in a similar, age-matched (but not otherwise controlled) group of non-HIV-infected women previously reported from the same institution (Table 1). In ACTG 293, all patients were diagnosed with CIN 1 but had no excisional therapy prior to enrollment. The progression rate in the ACTG #293 group was compared to that seen in a similar, previously reported group of non-HIV-infected women from the same institution. The risk of progression of CIN at 5 years was very low (5% or less) in both groups (Table 2). Anal dysplasia was not assessed in either ACTG 200 or 293. Routine use of HAART in this community began in mid1996, prior to ACTG #293 (June 1996–July 1998), but after ACTG #200 (March, 1994–June, 1996). Twenty-two of 23 subjects in ACTG #293 versus 1/9 in ACTG #200 used HAART during the study. No new cases of cervical cancer were diagnosed in either group through 20 years of follow up. Six deaths were identified in the study group, including two from pneumocystis pneumonia, and one each from non-Hodgkins lymphoma, heart disease, breast cancer, and gunshot wound. Eight of 32 (25%) subjects underwent hysterectomy with 15 years follow-up. In contrast, 42/93 (45%) ( p < 0.05) underwent hysterectomy in the non-infected group. No differences