CMV retinitis in China and SE Asia: the way forward

AIDS-related CMV retinitis is a common clinical problem in patients with advanced HIV/AIDS in China and Southeast Asia. The disease is causing blindness, and current clinical management, commonly characterized by delayed diagnosis and inadequate treatment, results in poor clinical outcomes: 21% - 36% of eyes with CMV retinitis are already blind at the time the diagnosis is first established by an ophthalmologist. CMV retinitis also identifies a group of patients at extraordinary risk of mortality, and the direct or indirect contribution of extra-ocular CMV disease to AIDS-related morbidity and mortality is currently unmeasured and clinically often overlooked. The obvious way to improve clinical management of CMV retinitis is to screen all patients with CD4 counts < 100 cells/μL with indirect ophthalmoscopy at the time they first present for care, and to provide systemic treatment with oral valganciclovir when active CMV retinitis is detected. Treatment of opportunistic infections is an integral part of HIV management, and, with appropriate training and support, CMV retinitis screening and treatment can be managed by the HIV clinicians, like all other opportunistic infections. Access to ophthalmologist has been problematic for HIV patients in China, and although non-ophthalmologists can perform screening, sophisticated ophthalmological skills are required for the management of retinal detachment and immune recovery uveitis, the major complications of CMV retinitis. CMV retinitis has been clinically ignored, in part, because of the perceived complexity and expense of treatment, and this obstacle can be removed by making valganciclovir affordable and widely available. Valganciclovir is an essential drug for developing successful programs for management of CMV retinitis in China and throughout SE Asia

Immunodominant cytomegalovirus-specific CD8+ T-cell responses in sub-Saharan African populations

<div><p>More than 90% of children in Africa are infected with cytomegalovirus (CMV) by the age of 12 months. However, the high-frequency, immunodominant CD8+ T-cell responses that control CMV infection have not been well studied in African populations. We therefore sought to define the immunodominant CMV-specific CD8+ T-cell responses within sub-Saharan African study subjects. Among 257 subjects, we determined the CD8+ T-cell responses to overlapping peptides spanning three of the most immunogenic CMV proteins, pp65, IE-1 and IE-2, using IFN-γ ELISpot assays. A bioinformatics tool was used to predict optimal epitopes within overlapping peptides whose recognition was statistically associated with expression of particular HLA class I molecules. Using this approach, we identified 16 predicted novel CMV-specific epitopes within CMV-pp65, IE-1 and IE-2. The immunodominant pp65-specific, IE-1, IE-2 responses were all either previously well characterised or were confirmed using peptide-MHC tetramers. The novel epitopes identified included an IE-2-specific epitope restricted by HLA*B*44:03 that induced high-frequency CD8+ T-cell responses (mean 3.4% of CD8+ T-cells) in 95% of HLA-B*44:03-positive subjects tested, in one individual accounting for 18.8% of all CD8+ T-cells. These predicted novel CMV-specific CD8+ T-cell epitopes identified in an African cohort will facilitate future analyses of immune responses in African populations where CMV infection is almost universal during infancy.</p></div