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Editor,—It is becoming clear that some patients with cytomegalovirus (CMV) retinitis who respond to highly active antiretroviral therapy in terms of their CD4 count and reduced HIV viral load, undergo no further reactivations of their retinitis despite having no specific anti-CMV therapy. However, the factors underlying this improved immunity to CMV are not entirely clear. We report the case of a patient on highly active antiretroviral therapy (HAART) who has had no reactivation of CMV retinitis after 6 months without anti-CMV treatment. The unusual feature of this case is that the CD4 count has remained persistently low.
We discuss factors that may be relevant in the improved immune response to CMV infection and may be useful in isolating a group of patients on HAART who do not require lifelong maintenance with anti-CMV therapy.
A 33 year old man with a CD4 count of 27 cells × 106/l who had been diagnosed with AIDS in 1992 developed CMV retinitis in zones 1, 2, and 3 of the left eye in March 1996.
Treatment was commenced with intravenous ganciclovir 10 mg/kg and maintenance therapy consisted of oral ganciclovir. After 3 months reactivation and progression of the retinitis necessitated a further induction course of intravenous ganciclovir with subsequent maintenance therapy with daily intravenous foscarnet.
Further reactivation led to the use of intravitreal ganciclovir and further re-induction course of intravenous foscarnet. As a result of difficulties with intravenous line sepsis intravenous cidofovir was commenced. In March 1997 the patient was started on HAART including proteinase therapy but despite this the CD4 count remained low at 22 cells × 106/l.
The patient decided to discontinue anti-CMV therapy in April 1997 and has undergone frequent ophthalmological review since. He has received no anti-CMV therapy for 6 months and despite a continuing low CD4 count of 28 cells × 106/l and a HIV-1 viral load of 201 637 RNA copies/ml there has been no further reactivation of CMV retinitis.
Before the use of HAART, maintenance therapy with anti-CMV medication was required in all patients with CMV retinitis. Without therapy the average time to progression of retinitis was 2–3 weeks.1
Several cases have been reported which describe lack of progression of CMV retinitis in patients treated with HAART and in each of these cases there was an associated rise in CD4 counts.2 3 There have also been reports of newly diagnosed CMV retinitis after commencement of HAART with improving CD4 counts,4 although considerable doubt has been shed on whether these were in fact new cases of CMV retinitis and not just reactivation of previously undetected disease.5 In this case the CD4 count remains persistently low and the HIV viral load high despite HAART.
This suggests that the immune response to CMV is not solely related to the CD4 count and that other factors are also involved in the recovery of immunity to CMV following treatment with HAART.
Bowen et al have demonstrated by quantitative and qualitative measurements of CMV DNA by polymerase chain reaction based assays that CMV viral load may be an indicator of patients at increased risk of reactivation of CMV retinitis.6 They suggest that this measurement can help with clinical management. It has also been shown that the detection of the early CMV antigen (p65 antigen) suggests elevated susceptibility to CMV infection.7
Transforming growth factor β (TGF-β) inhibits the IL-2 induced proliferation of T lymphocytes, and expression of TGF-β may be increased in CMV infection.8 9 Measurement of TGF-β and other cytokines may also be useful in the monitoring of patients at risk of CMV disease.
By performing a controlled prospective trial involving measurement of CMV and HIV viral load, together with these immunological markers it may be possible to identify a subgroup of patients on HAART who do not require long term anti-CMV therapy.
However, early reports from Martin et al on the results of their study of the use of combined oral ganciclovir and intravitreal implant for treatment of CMV retinitis suggest that there is still a survival benefit from continued use of oral ganciclovir in the HAART environment.10
This once again raises the debate over whether CMV is just an opportunist taking advantage of immunosuppression or is it a cofactor acting in partnership with HIV.
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