|
The researchers studied 648 consecutive patients with AIDS and CMV retinitis seen between August 1983 and March 2000. They evaluated the prevalence of visual impairment at the time of retinitis diagnosis and its incidence during follow-up. The cohort receiving HAART had a 75% lower risk of visual impairment compared to patients not on the therapy. HAART therapy utilises a combination of three antiretroviral drugs and includes at least one protease inhibitor or at least one non-nucleoside reverse transcriptase inhibitor. Some 33% of patients had 20/50 or worse when diagnosed, with 17% of affected eyes having visual acuity of 20/200. At one year of follow up, 56% of all eyes with CMV retinitis had an acuity of 20/50 or worse, and 37% had 20/200 or worse. Patients who received HAART did much better than those who were not on the therapy. Among patients with an initial visual acuity of 20/50 or worse, patients responding to HAART had a 79% lower risk of vision loss compared to patients not on HAART. For those with an initial vision loss of 20/200 or worse, HAART reduced the risk of further impairment by 83%. Even patients on HAART who were considered "nonresponders" to the therapy had about a 45% lower risk of visual loss during the first year after CMV diagnosis compared to patients not receiving the antiviral regimen. Response to therapy was defined only in terms of CD4+ T-cell counts. The ability to control CMV retinitis is more accurately predicted by the CD4+ count than by HIV load, according to John Kempen MD, PhD, principal investigator of the study. The median initial CD4+ T-cell count was about 12 cells/microlitre. Immune recovery was defined as a rise of at least 50 cells/microlitre and a count of less than100 cells/microlitre. Such a count would be sufficient to regain control of CMV. Testing for blood levels of the human immunodeficiency virus (HIV) was not available until very late in the study period, so such data were not reported in this study. Therefore, it is unknown whether any of the "non-responders" may have had reductions in their virus levels. "Patients that had more severe immunodeficiency at enrollment had a higher risk. Patients that had large lesions and patients that had lesions at the back of the eye where the fovea and the macula are had a higher risk of vision loss," he noted.Injection drug use increased the risk of vision loss. White race was associated with a lower risk. These factors may have influenced how promptly the patients accessed care. The researchers also looked at the effect of the route of administration of specific anti-CMV therapy. They found no difference in the incidence of the loss of visual acuity for eyes treated with systemic anti-CMV therapy only, initial ganciclovir implants, or systemic therapy followed by implants. Since HAART was introduced into practice at about the same time as implant therapy, HAART may have confounded the results comparing the anti-CMV therapies. CMV may cause vision loss in several ways. Probably the most common manifestation is the necrotizing retinitis destroying the macula or the disk. Another major mechanism is retinal detachment, he noted. Clinicians have been concerned about immune recovery uveitis (IRU) among patients with CMV retinitis who experience immune reconstitution with HAART. Estimates of IRU have ranged from 10.9 to 83% per person-year. In this study patients with IRU did not show a corresponding worsening in visual symptoms. Indeed, the patients with immune recovery showed the greatest improvements. Dr Kempen advises ophthalmologists to reinforce to their patients the need for AIDS treatment, comparing the message to those about diabetic retinopathy: "One of the main things that you want to tell them is they need to control their systemic disease. Highly active anti-retroviral therapy benefits vision in a way that's similar to the way it benefits risk of mortality, so it reduces the risk of vision loss dramatically." The researchers consistently observed a nearly one-half reduction in the estimated rate of vision loss even for those patients who were HAART non-responders. But the patients who developed immune recovery had "outstanding" improvements. This confirms that HAART overall is associated with a reduced risk of vision loss, Dr. Kempen said. While this study involved patients who already had CMV retinitis when they presented for care, HAART has greatly reduced the incidence of the condition. Before its introduction, 30% of AIDS patients would develop CMV retinitis sometime during their lives. Dr. Kempen estimated that with the advent of HAART, the incidence has decreased to 7.5%. |
