Statistics from Altmetric.com
Editor,—The only established risk factor for the development and progression of cytomegalovirus retinitis (CMVR) in individuals with HIV disease is a low CD4+ T lymphocyte count. The initiation of highly active antiretroviral treatment (HAART) has brought a significant change in the clinical outcome of CMV retinitis1 with studies reporting longer times to CMV relapse. These findings correlate with increased CD4+ T lymphocyte counts and reduced HIV viral loads.
We report the case of an HIV-2 positive patient who showed no reactivation of CMV retinitis for 25 months despite a low CD4+ T lymphocyte count and a lack of response to HAART treatment. The role of HIV-2 seropositivity in our case is assessed and other relevant factors discussed.
A 47 year old black African male was diagnosed with AIDS (HIV-2 positive) in September 1996. The AIDS defining illness was enteric non-Hodgkin's lymphoma. He was given saquinavir, stavudine (d4T), and zalcitabine (DDC). Owing to his persistently low CD4+ T lymphocyte count (30 cells ×106/l) he was referred for ophthalmic evaluation in August 1997. He was diagnosed with peripheral zone III inactive CMV retinitis in his left eye (Fig 1) and was started on maintenance treatment with oral ganciclovir (3 g per day).
Three weeks later this area of retinitis reactivated. He was then given intravenous ganciclovir 5 mg/kg twice daily for 4 weeks and then restarted on oral ganciclovir. His CD4+ T lymphocytes remained low with a peak reaching 70 cells ×106/l in January 1998. In April 1998 antiretroviral treatment was discontinued because he showed no response to therapy.
The patient underwent frequent ophthalmic reviews during which inactive CMV retinitis was recorded on funduscopic and photographic assessment. No new lesions have been recorded in either eye. His current CD4+ T lymphocyte count is 7 cells × 106/l and his visual acuity is 6/5 in each eye.
In a group of patients not responding to HAART therapy Mitchellet al 2 showed a median time to CMVR progression of 18 days (95% CI: 8,91). Walker and Popescu3 showed a median time to CMVR reactivation of 122 days (95% CI: 93-186) in patients receiving oral ganciclovir as maintenance treatment.
This remission period far exceeds reactivation rates in patients with low CD4+ T lymphocyte counts, further suggesting that the immune response to CMV is not solely related to the CD4+ T lymphocyte count4.
We believe that HIV-2 seropositivity in this case is a relevant factor in modifying the natural history of CMVR. HIV-2 is biologically similar to HIV-1 but it has a reduced virulence.5 The only study to our knowledge comparing ocular lesions between HIV-1 and HIV-2 infected individuals is by Monteiro-Grillo et al.6 They reported less severe complications in patients infected by HIV-2.
Other factors relating to the immune response to CMV have also been suggested in the literature. Schrier et al 7 demonstrated that HIV infected individuals with HLA phenotypes A2B44, B51, and DR7 have low T cell immune responses to CMV and are predisposed to CMV retinitis as immunodeficiency progresses.
More studies with HIV-2 infected individuals are required to monitor the clinical course of CMVR in this group of patients and clarify whether HIV-2 virulence is an important factor modifying the immune response to CMV.
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.