Both valganciclovir and intraocular ganciclovir (IOG) should be utilized more for patients with HIV-associated cytomegalovirus retinitis (CMVR) in low- and middle-income countries (LMICs), according to an analysis published in BMC Infectious Diseases. The study is the first to record the safety and efficacy of valganciclovir, a standard CMVR drug in high-income countries (HICs), in an LMIC.
Investigators performed a retrospective analysis of data from 53 HIV-positive CMVR patients treated at a Médecins Sans Frontières HIV clinic in Dawei, Myanmar, between February 2013 and April 2017. The study’s primary outcome was change in visual acuity (VA) post-treatment. Patients were stratified into two groups for comparison: systemic treatment, which included valganciclovir (n = 32), and local treatment, which was IOG alone (n = 21). Mortality was the secondary outcome.
The cohort’s median CD4 count was 18 (interquartile range [IQR], 10–44) cells/µL, and 49 (92%) had anemia at the time of CMVR diagnosis. Before CMVR diagnosis, 19 (36%) patients were on antiretroviral therapy (ART) and 3 (5.7%) had interrupted ART.
At program enrollment, 20 (38%) patients had evidence of bilateral retinitis and 32 (60%) had monocular retinitis. Of the 72 eyes with evidence of CMVR analyzed for VA, 53 (74%) had mild or no visual impairment, 9 (12.5%) had moderate impairment, and 9 (12.5%) were blind.
At treatment completion, 44 (61%) eyes had mild or no impairment, 6 (8%) had moderate impairment, and 7 (10%) were blind. Data were available for 57 (79%) of the 72 eyes. No eyes developed new blindness during treatment. Analysis of VA outcomes by patient showed 7 (13%) patients had improved VA, 30 (57%) had no change, and 3 (6%) had VA deterioration (P =.665). There was no statistically significant difference in VA outcomes between the local and systemic treatment groups.
The mortality was 17% (n = 9); 5 (24%) of the deceased patients had received local treatment compared with 4 (12.5%) who received systemic treatment. Hemoglobin values decreased in 20 (62.5%) of the systemic treatment patients and in none of the local treatment patients.
Limitations of the study included its retrospective design, lack of patient randomization to treatment groups, and the possibility of selection bias for more stable patients with less-advanced CMVR.
CMVR is typically a neglected disease in LMICs. The study’s high percentage (74%) of eyes with mild or no visual impairment at CMVR diagnosis combined with the existence of CMVR in ART-exposed patients reinforce the need for universal and early screening and treatment in patients with a CD4 less than 100 cells/µL to avoid irreversible blindness.
Though blindness can be a complication of IOG injection, no new blindness occurred in the cohort, indicating that primary HIV clinicians can be safely trained to administer IOG in LMIC settings. IOG is an important treatment alternative for CMVR patients with baseline anemia, which affected 92% of patients in this analysis.
The higher mortality in the local treatment group (24%) versus the systemic treatment group (12.5%) points to the benefit of valganciclovir, which is usually not used in LMICs because ganciclovir is less expensive.
“The need for systemic therapy is frequently overlooked, as diagnosis of non-ocular end-organ CMV disease is not possible in resource-limited settings, where biopsy, histology and PCR testing are often unavailable,” the study authors wrote. “We urge national programmes to access” valganciclovir, which is now on the World Health Organization (WHO) Essential Medicines List.
Murray J, Hilbig A, Soe TT, Ei WLSS, Soe KP, Ciglenecki I. Treating HIV-associated cytomegalovirus with oral valganciclovir and intra-ocular ganciclovir by primary HIV clinicians in southern Myanmar: a retrospective analysis of routinely collected data. BMC Infect Dis. 2020;20(842). doi:10.1186/s12879-020-05579-2