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Editor,—Highly active antiretroviral therapy (HAART) can reduce HIV replication and increase the CD4+ cell count.1 Some cytomegalovirus (CMV) disease relapses have been described within the first 3 months of HAART.2However, after this critical phase, quiescent retinitis and an unusually prolonged relapse free interval suggest restoration of immune functions. Maintenance therapy can be discontinued for the majority of HAART responders.3-6 The duration of CMV disease remission is actually unknown.
A 29 year old, HIV infected woman was affected by CMV retinitis in the left eye in August 1996. Her CD4+ T lymphocyte count was 15 cells ×106/l at that time. CMV retinitis was treated with intravenous foscarnet. HAART was initiated in June 1996 (d4T, 3TC, and ritonavir). In June 1997, her CD4+ cell count increased to 400 cells ×106/l and the HIV-1 viral load became undetectable. CMV maintenance therapy was discontinued in December 1997 without any relapse until May 1999 when a relapse of CMV retinitis, associated with inferior retinal detachment, was noted. At that time, her CD4+ cell count was 380 cells ×106/l, CMV viraemia was negative, but HIV viral load had increased to 31 000 copies/ml. The lymphoproliferative test against CMV antigens was negative. The patient was treated with intravenous ganciclovir and vitreoretinal surgery was performed. CMV DNA was found in the vitreous by polymerase chain reaction.
A 69 year old HIV infected man was referred to our department in November 1996 for bilateral CMV retinitis. CD4+ T lymphocyte count was 35 cells ×106/l at onset. Retinitis was treated with intravenous foscarnet. HAART (3TC, d4T, nevirapine) was initiated in September 1997. For 2 years, the HIV-1 viral load remained undetectable, and CD4+ cell count rose to 120 cells ×106/l. In October 1998, the HIV viral load started to increase, reaching 6100 copies/ml. In May 1999, a relapse of CMV retinitis was diagnosed and treated successfully with intravitreal ganciclovir injections. At that time, the HIV viral load rose to 22 000 copies/ml, and CD4+ cell count was 180 cells ×106/l. The lymphoproliferative test against CMV antigens was negative. CMV viraemia and pp65 antigenaemia always remained negative.
Several studies suggest that selected patients with healed CMV retinitis who have both immunological and virological response to HAART can temporarily discontinue maintenance therapy.3-6 In our patients on HAART, CMV retinitis was quiet for months, as long as the HIV-1 replication remained under control. CMV retinitis relapse occurred when the viral load started to increase even though the CD4+ T lymphocyte count remained stable (mean 280 cells ×106/l). Autran et al have studied in vitro lymphocyte proliferation to specific antigens such as CMV and reported positive effects of HAART on CD4+ T cell functions.1 The CD4+ T cell reactivity to recall antigens that restore a certain immune competence is linked to the control of HIV replication.7For our patients, the T cell reactivity to CMV antigens was negative. These immunological tests are not routinely performed and their usefulness in predicting CMV diseases is not established. Casado et al showed that a positive CMV polymerase chain reaction test is the most predictive test associated with the development of CMV diseases.8
In a prospective multicentre study, Mazeron et alshowed that HIV viral load is a predictive marker, independent of the CD4+ cell count.9 Our findings suggest that an increase in the HIV viral load increases the risk of CMV retinitis relapse despite a high CD4+ T lymphocyte count.
Our case reports emphasise the importance of close ophthalmological follow up in patients on HAART when the HIV-1 viral load starts to increase despite a CD4 T lymphocyte count of over 100 cells ×106/l.