To the Editor

In a recent report, O'Sullivan et al. [1] showed that immune reconstitution secondary to initiation of highly active antiretroviral therapy (HAART) in 23 human immunodeficiency virus (HIV)-infected subjects with low CD4 T cell counts (median, 35 cells/mm³) resulted in a progressive decline in cytomegalovirus (CMV) DNAemia (as measured by the Digene [Beltsville, MD] hybrid capture system) in the absence of specific anti-CMV therapy. In their study, the CMV DNA load was determined after a median of ∼1, 3, and 12 months of therapy, with a significant reduction in the CMV load noted after time point 2. To contribute to these findings, we report results of a detailed analysis of CMV viremia (conventional cell culture), antigenemia (pp65 antigen, CINApool; Biosoft, Varilhes, France), and DNAemia by means of a quantitative polymerase chain reaction (PCR) on plasma and leukocytes (Amplicor Monitor CMV test; Roche Diagnostics, Branchburg, NJ) in an antiretroviral-naive HIV-infected subject in whom HAART was initiated.

A 32-year-old Haitian heterosexual man was diagnosed with an HIV infection at the end of 1997 and initially presented with toxoplasma encephalitis. On stabilization of his condition, antiretroviral therapy was initiated with stavudine (30 mg twice a day), lamivudine (150 mg twice a day), and nelfinavir (750 mg 3 times/day). Before therapy, he had a CD4 count of 56 cells/mm³ and an HIV RNA load of 110,000 copies/mL, or 5.0 log₁₀(Quantiplex HIV RNA 2.0 assay [bDNA]; Chiron, Emeryville, CA; table 1). As part of the patient's workup, a CMV pp65 antigenemia assay was found to be highly positive (75 positive cells/10⁵ leukocytes). This was confirmed by use of the Roche PCR test on plasma (1640 copies/mL or 3.2 log₁₀) and leukocytes (16,820 copies or 4.2 Iog₁₀/10⁶) (table 1). A blood viral culture was also positive for CMV after only 7 days of incubation. There were no specific features of symptomatic CMV disease, and the results of an ophthalmologic examination by a trained specialist were entirely normal.

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Table 1

HIV and CMV loads in a patient who received HAART.

Within a month of starting HAART, the patient's CD4 T cell count increased to 190 cells/mm³, with an important decrease in the HIV RNA load (—2.3 log₁₀) and moderate decrease in the CMV load in leukocytes, as determined by PCR (−0.7 log₁₀) and pp65 antigenemia assays (table 1). After 2 months of HAART, the HIV RNA load became undetectable (<500 copies/mL), as did the CMV PCR test on plasma (<400 copies/mL), the CMV pp65 antigenemia assay, and the CMV blood culture. The PCR test on leukocytes was the last CMV assay to become negative after ∼3 months of HAART. After 5 months of antiretroviral therapy, the HIV RNA load increased to 17,290 copies/mL (4.2 log₁₀), and the CD4 T cell count dropped slightly to 139 cells/mm³ because of poor compliance. However, CMV remained undetectable in the blood by all methods (table 1). The patient was counseled and reevaluated 1 month later. The HIV load then decreased to 3899 copies/mL (3.6 log₁₀) and the CD4 T cell count rose to 227 cells/m³. Again, all assays showed no signs of active CMV replication in the blood, and the patient remained asymptomatic during this period.

In agreement with the study by O'Sullivan et al. [1], our data confirm the decline in the CMV load following initiation of HAART, probably through restoration of a functional CMV-specific CD4 repertoire [2]. The decline in the CMV DNA load in leukocytes of our patient was progressive over 3 months (from 4.2 to 2.0 log₁₀). Of interest, we noted a more rapid clearance of CMV-mediated cytopathic effect, CMV pp65 antigens, and CMV DNA in plasma. Absence of CMV replication was continually maintained after 3 months of HAART in the presence of a CD4 T cell count ⩾139 cells/mm³, despite a rebound in HIV load because of poor compliance. This could suggest that the CD4 T cell count or function is more important than the HIV load for protection against opportunistic infections. It is noteworthy that the CMV DNA load decline after HAART was considerably less rapid than that seen in patients treated with ganciclovir, as reported in our previous study [3]. In the latter case, the mean CMV DNA load in leukocytes decreased by ∼ 1.5 log₁₀ after only 10 days of induction therapy. Thus, although potent anti-HIV therapy with sustained immune response can permit safe withdrawal of maintenance therapy for CMV [4], we suggest that specific anti-CMV therapy is still needed in the presence of active CMV disease to rapidly inhibit CMV replication.