HIV-related blindness increasing in developing countries

Increasing patients’ with AIDS lifespans paradoxically increases their chances of contracting opportunistic infections, including CMV retinitis.

ByDebra L. Beck

The village children lead the blind elders.

Antiretroviral drugs are finally being made available to AIDS patients in the world’s poorest countries. Paradoxically, researchers fear that one consequence of this advance may be an epidemic of HIV-related blindness affecting as many as 6 million people with HIV living in underdeveloped nations.

“AIDS patients in the developing world are getting antiretroviral therapies but they’re not getting full-complement highly active antiretroviral therapy (HAART),” said Emmett T. Cunningham Jr., MD, PhD, MPH, co-author of a recently published report. As such, their life expectancies may be increased, but their CD4+ T-cell counts may remain below 50 cells/µL blood serum — an advanced stage of HIV infection — leaving these patients vulnerable to ocular complications such as cytomegalovirus (CMV) retinitis.

Dr. Cunningham, director of the Uveitis Service and the Kimura Ocular Immunology Laboratory at the University of California, San Francisco Medical Center in the United States, and colleague Philippe Kestelyn, MD, professor of ophthalmology at Ghent University Hospital in Belgium, published their findings in the March Bulletin of the World Health Organization.

HAART part of the problem

“HAART makes the immune system stronger but it costs $10,000 to $20,000 per year per patient, so most patients in developing countries will be limited to treatment with one or two antiretroviral drugs and be treated incompletely,” Dr. Cunningham told Ocular Surgery News. In addition, because HAART requires that patients follow a complex schedule of medications, many of which cause significant side effects, compliance and drug toxicities are problematic.

An eye exam is performed on a village resident in Ghana.

“Even with educated, professional American patients, it is a challenge to treat them completely. Most of the 30 million people with AIDS in sub-Saharan Africa, South Asia and South East Asia have very limited personal resources and virtually no access to support systems,” Dr. Cunningham said.

Until just a few years ago, CMV retinitis was more commonly reported among AIDS patients in industrialized countries than among those in the developing world.

Since 1995, however, consistent progress in antiretroviral therapies has resulted in significant improvement in immune function in AIDS patients and a subsequent decline in morbidity and mortality caused by opportunistic infection.

Also, the addition of effective anti-CMV drugs — including ganciclovir, foscarnet, fomivirsen, valganciclovis and cidofovir — has markedly improved the prognosis for patients with CMV retinitis.

Although CMV retinitis is by far the main cause of HIV-related blindness, several other diseases have been found to cause vision loss in AIDS sufferers. These include acute retinal necrosis (including its variant, progressive outer retinal necrosis), HIV-related ischemic microvasculopathy, ocular syphilis, ocular tuberculosis, cryptococcal meningitis and ocular toxic or allergic drug reactions.

Blindness a consequence of therapy

Before antiretroviral therapies became available, infected people in developing countries seldom went blind from AIDS. A 1999 meta-analysis indicated the rate of CMV retinitis among African patients with AIDS was between 0% and 8.5%. Simply put, CMV retinitis and other AIDS-related ocular complications occur more frequently in the advanced stages of HIV infection — once the CD4+ T-cell count has fallen below 50 cells/µL — when life expectancy is very short. If AIDS patients did go blind, this usually occurred shortly before their deaths.

The availability of antiretroviral agents is changing the face of CMV retinitis in developing countries, Drs. Kestelyn and Cunningham wrote in their review.

“Life expectancy may increase but immune reconstitution will not.” The re searchers’ goal in publishing their re port was to get people thinking and talking about AIDS-related blindness. “AIDS is already a major cause of blindness globally. We want to point out that it may get even worse,” Dr. Cunningham said.

A blind villager finds her way with the help of sticks and the younger children.

Future hard to predict

“For patients who have not yet developed ocular complications, treatment with antiretroviral therapy should improve survival via immunologic benefit, which in turn may also reduce the risk of ocular complications during the period of benefit,” commented John H. Kempen, MD, PhD, an ocular immunologist at Wilmer Eye Institute. “However, once their immunity starts bottoming out again, it is hard to know if they would progress less rapidly to death, thereby staying alive longer at greater risk for ocular complications.”

Dr. Kempen was unsure whether the widespread use of antiretroviral mono therapy will increase the rate of ocular complications, but thought that partial antiretroviral therapy combined with prophylaxis against opportunistic infections other than CMV could result in the effect Drs. Kestelyn and Cunningham describe. Dr. Kempen noted that such a pattern occurred in the U.S. in the early 1990s.

“We don’t really know how long these patients might live after they contract CMV retinitis,” added Thomas M. Lietman, MD, director of the WHO Collaborating Center for the Prevention of Blindness. “In the past, a huge number of people were protected from CMV retinitis because they didn’t live long enough to contract it. Now with some treatment, they’re going to be at risk for it, and we should be aware of that.” He cautions, however, “The point that Drs. Kestelyn and Cunningham make is important, but it’s not a fact. We don’t really know what will happen.”

“There are no easy solutions,” Dr. Cunningham said. HAART requires huge amounts of money and the professional resources to prescribe and supervise therapies. Anti-CMV drugs are not much cheaper than HAART but require either intraocular implants or long-term systemic therapy. Drs. Kestelyn and Cunningham hope that the developed world will eventually accept responsibility, and help prevent a massive epidemic of AIDS-related blindness.

For Your Information:

Emmett T. Cunningham Jr., MD, PhD, MPH, can be reached at the F.I. Proctor Foundation, 95 Kirkham St., San Francisco, CA 94122 U.S.A.; +(1) 415-502-2669; fax: +(1) 415-514-1574; e-mail: emmett@ itsa.ucsf.edu.

John H. Kempen, MD, PhD, can be reached at 550 North Broadway, Suite 700, Baltimore, MD 21205 U.S.A.; +(1) 410-955-1966; fax: +(1) 410-955-0629; e-mail: jkempen@jhmi.edu.

Thomas M. Lietman, MD, can be reached at the F.I. Proctor Foundation, 95 Kirkham St., San Francisco, CA 94122 U.S.A.; +(1) 415-502-2662; fax: +(1) 415-476-0527; e-mail: tml@itsa.ucsf.edu.

References:

Kestelyn P, Cunningham E Jr. HIV/AIDS and blindness. Bulletin of the World Health Organization. 2001;79:208-213.

Kestelyn P. The epidemiology of CMV retinitis in Africa. Ocular Immunology and Inflammation. 1999;7:173-177.