Prevalence of CMV retinitis remains high among people living with HIV in resource-limited settings, results of a systematic review of 65 studies published in the online edition of Clinical Infectious Diseases show. Prevalence of this AIDS-defining condition was 14% in Asia and 2% in Africa. Approximately three-quarters of cases involved people with a CD4 cell count below 50 cells/mm3.
“This review found that the prevalence of CMV retinitis in resource-limited settings, notably Asian countries, remains high,” write the authors. “Part of the explanation for the enduring high prevalence of CMV retinitis in Asia can be found in the fact that, despite considerable progress in scaling up access to ART [antiretroviral therapy], the proportion of patients who present late for HIV care remains high.”
Cytomegalovirus (CMV) is a late-stage opportunistic infection in people with HIV, typically occurring when CD4 cell count falls below 100 cells/mm3. The most frequent manifestation of CMV disease in people living with HIV is CMV retinitis, which is responsible for over 90% of cases of HIV-related blindness.
Largely thanks to antiretroviral therapy, new cases of CMV retinitis are very rare in richer countries.
There is also an assumption that CMV retinitis is no longer a major concern in resource-limited settings, especially as access to antiretroviral therapy is increasing.
But an international team of investigators was concerned that access to CMV diagnostic and treatment services is limited in many low- and middle-income countries. Moreover, the researchers noted that studies have reported widely varying rates of the condition.
They therefore conducted a systematic review and meta-analysis of research published between 1996 and early 2013 that reported on the prevalence of CMV retinitis among people living with HIV in resource-limited countries. Studies were included if they assessed the occurrence of CMV retinitis by fundoscopic examination and had a cohort of at least ten adults living with HIV.
A total of 65 studies involving 20,280 people met the investigators’ inclusion criteria. Most of these studies were conducted in Asia (39 studies, 12,931 participants), followed by Africa (18 studies, 4325 participants) and Latin America (five studies, 2836 participants). The age of participants at the time of screening ranged from 21 to 41 years. The majority of studies (50) were conducted in hospital settings. Just under a fifth (18%) were carried out between 1993 and 2002; a third between 2003 and 2005; 24% between 2006 and 2008; and 26% between 2009 and 2013.
The overall quality of the studies was rated as low to moderate. The majority (52) had a prospective design and reported using indirect ophthalmoscopy with dilation of the pupils. In 30 studies an ophthalmologist conducted the screening. Only 30 studies stratified outcomes according to CD4 cell count.
Prevalence of CMV retinitis ranged from a low of 0.2% in a study conducted in Nigeria, to 72% in a Thai study. Prevalence exceeded 5% in four countries: Thailand, 24% (five studies, 1397 patients); Myanmar, 25% (five studies, 2928 patients); China, 15% (nine studies, 2357 patients); and India, 7% (13 studies, 4305 patients).
By region, the highest prevalence was in Asia (14%) and lowest in Africa (2%). Only 19 studies reported whether disease affected one or both eyes. Their findings showed that 43% of patients had CMV retinitis in both eyes. Almost a third (32%) of patients had lost vision in one or both eyes.
Almost three-quarters (73%) of cases involved people with a CD4 cell count below 50 cells/mm3. A further 16% of patients had a CD4 cell count between 50-100 cells/mm3 at the time of diagnosis.
“This review indicates the important clinical burden of CMV retinitis, predominantly in patients with CD4<100 cells/mm3, and that the disease is commonly bilateral and commonly associated with vision loss,” comment the investigators.
Prevalence did not differ over time, and was similar in studies conducted between 1993 and 2002 (12%) and between 2009 and 2013 (17%).
There was no difference in prevalence according to whether screening was conducted by an ophthalmologist or an HIV clinician trained in retinal examination. “From an operational perspective, this is encouraging, and points towards the potential for integrating routine retinal examination as part of basic care for all late presenters,” the researchers suggest.
They believe their findings have important clinical implications, especially the need to improve the detection of people with CMV retinitis: “routine retinal screening by indirect ophthalmoscopy of all late presenters with CD4 below 100 cells should be considered.” The investigators also suggest that CMV prophylaxis may be beneficial for some patients and that pressure needs to be exerted to make oral therapies for CMV retinitis affordable for resource-limited countries.
The Medicines Patent Pool and Roche announced an agreement to provide valganciclovir to treat CMV retinitis at low cost in 138 countries earlier this month.
Ford N et al. Burden of HIV-related CMV retinitis in resource-limited settings: a systematic review. Clin Infect Dis, online edition, 2013.