Diagnosis and treatment of CMV retinitis in resource-limited settings achievable and a must, say MSF

The diagnosis and treatment of CMV retinitis in resource-poor countries is realistic, but is being over-looked in current HIV treatment scale-up plans, according to investigators from Medecins Sans Frontieres (MSF), writing in the December edition of PLoS Medicine. The article is freely available online here

Cytomegalovirus (CMV) is a member of the herpes virus family and was a frequent cause of blindness in individuals with advanced HIV disease in western countries before effective antiretroviral therapy became available.

Since potent anti-HIV treatment became available the incidence of CMV retinitis in countries like the UK has become rare. Furthermore, in industrialised countries there is now a well-established protocol for the diagnosis and treatment of CMV retinitis in that includes retinal examinations for patients with low CD4 cell counts and treatment with effective anti-CMV drugs, such as ganciclovir, with concurrent antiretroviral therapy.

But in resource-poor settings CMV retinitis is a neglected disease, being under-diagnosed and under-treated. Indeed the diagnosis and management of the disease are absent from WHO HIV treatment guidelines, nor is the condition mentioned in the WHO “Vision 2020” programme.

It is uncertain how many HIV-positive patients in resource-limited settings are affected by CMV retinitis. Therefore investigators from MSF looked at the prevalence of the condition in patients receiving care from their HIV projects in Cambodia, South Africa, Lesotho, Myanmar, Thailand and China. Between 2% and 32% of patients receiving HIV care from MSF were found to have the condition.

The gold standard for diagnosis of CMV retinitis is examination of the retina through a dilated pupil by a skilled clinician using an opthalmoscope.

CMV retinitis is characterised by dense whitening of the retina. Without treatment, CMV retinitis destroys the entire retina within three to six months, causing permanent blindness.

Common symptoms of CMV retinitis include floaters or blurred vision. But limiting retinal examinations only to patients who complain of vision problems is not reliable, and in resource-rich countries it is recommended that all patients with a CD4 cell count of 50 cells/mm³ (when CMV retinitis becomes a real risk) should have regular retinal examinations.

“We believe that systematic screening examination of the retina should be a fundamental requirement of HIV-related care in resource-poor settings”, write the investigators. They note, “in our recent work in Myanmar 31% of patients diagnosed with CMV retinitis had no symptoms”.

Successful treatment of CMV retinitis requires the use of both CMV-specific medication and antiretrovirals.

Ganciclovir is the current gold standard CMV therapy. The drug can be used as a systemic CMV therapy or can be injected directly into the eye as a local treatment for CMV retinitis. Valganciclovir achieves the same blood levels as ganciclovir and has the advantage of being an oral treatment.

But cost considerations mean that the direct injection of ganciclovir into the eye is the only treatment for CMV retinitis that is available in resource-limited settings. Such therapy costs 57 US cents per week compared to $57 per day for oral valganciclovir.

Moreover access to ganciclovir eye injections in resource-limited settings is very limited, particularly as clinicians who are qualified to administer them are in short supply. Furthermore, the injections are frightening to patients and may deter asymptomatic individuals, who have the most to gain from therapy, from accessing treatment.

“We believe that systemic treatment with oral valganciclovir should be used routinely as the primary treatment strategy because (1) systemic treatment of CMV retinitis reduces extraocular disease; (2) systemic treatment reduces mortality; and (3) with only local treatment there is a 22% - 33% incidence of new CMV retinitis in the untreated eye”, write the investigators, “intraocular ganciclovir as the primary treatment strategy is simply not medically adequate.”

The costs of failing to treat CMV retinitis are considerable, causing blindness, resulting in loss of employment, and ultimately death. Expanding HIV treatment programmes are likely to mean that more patients with advanced HIV disease come forward for diagnosis and therapy. Many of these patients will be at risk of CMV retinitis and failure to treat the illness and resulting blindness will, the investigators believe, cause of “loss of faith in HIV treatment…and in the worst case scenario…may lead to reluctance to start taking this life-saving treatment.”

Two specific recommendations are made by the investigators. Firstly, diagnostic capacity should be expanded, with HIV treatment programmes designating a clinician to be trained to offer retinal examinations. A sturdy and portable opthalmoscope costs a little over $1000 and has been successfully field-tested in South Africa by MSF. Secondly, valganciclovir must be made available and affordable.

“Ongoing CMV-related mortality should no longer go unrecognised or be accepted as part of advanced HIV mortality. Patients should not be left vulnerable to blindness while clinicians are in the process of treating and controlling underlying infection with HIV”, conclude the investigators.