RESUMO
T cell immunity to human cytomegalovirus (HCMV) was assessed in HAART-treated HIV-1 infected patients (9 asymptomatic, CDC group A; and 22 symptomatic, CDC group B), and in eight HIV-1 long term non-progressors. Patients were either prospectively or cross-sectionally examined for CD4(+) T cell counts, HIV RNA load, HCMV leukoDNAemia, HCMV DNA in urine, lymphoproliferative response (LPR) to HCMV and phytohemagglutinin (PHA), and cytokine secretion (IFN-gamma and IL-4) by HCMV-stimulated peripheral blood mononuclear cell (PBMC) cultures. No patient either progressed to clinical AIDS or developed HCMV active infection during the study period. Twenty-nine patients responded to HAART, though 12 patients failed to recover the LPR to HCMV over the study period (three from CDC group A and nine from CDC group B). In contrast to healthy control individuals, most patients displaying positive LPRs LPRs to HCMV had unstable responses. Sustained LPRs to HCMV were significantly associated with high pre-HAART nadir CD4(+) T cell counts. Long-term suppression of HIV viremia correlated with recovery of LPR to HCMV. Sequential PBMC cultures from most patients secreted IFN-gamma (but not IL-4) at normal levels upon HCMV stimulation, irrespective of the pre-HAART nadir CD4(+) T cell counts and CDC group to which patients belonged. Failure to reconstitute IFN-gamma response was associated with very low pre-HAART nadir CD4(+) T cell counts. Control of HCMV infection in the cohort was associated with either recovery or maintenance of IFN-gamma response rather than with reconstitution of LPR to HCMV. A LPR to HCMV was absent in three out of eight long term non-progressors; contrarily, all patients showed preserved IFN-gamma responses.
Assuntos
Citomegalovirus/imunologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Linfócitos T/imunologia , Adolescente , Adulto , Terapia Antirretroviral de Alta Atividade , Citocinas/biossíntese , Feminino , Sobreviventes de Longo Prazo ao HIV , Humanos , Técnicas In Vitro , Ativação Linfocitária , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: The incidence of Human Cytomegalovirus (HCMV) end-organ disease has dramatically decreased since the implementation of highly active antiretroviral therapies (HAARTs), but the precise immune mechanism whereby HCMV is controlled remains to be elucidated. OBJECTIVES: To investigate the effect of (HAART) on CD4+ T-cell immunity to HCMV in AIDS patients with no past or current HCMV disease. STUDY DESIGN: Seventeen patients were prospectively examined for CD4+ (CD45RO+ and CD45 RA+) T-cell counts (flow cytometry), HIV RNA load (Amplicor HIV test), HCMV leukoDNAemia and HCMV DNA in urine (nested PCR), lymphoproliferative response (LPR) to HCMV, phytohemagglutinin (PHA) and purified protein derived from Mycobacterium tuberculosis (PPD) by measurement of 5-bromo-2'-deoxyuridine incorporation to DNA (ELISA) and cytokine secretion (IFN-gamma, IL-4 and IL-10) by HCMV-stimulated peripheral blood mononuclear cell (PBMC) cultures (ELISA). RESULTS: Fifteen patients responded favorably to HAART (virologically, immunologically, or both). Of these, six patients presented LPR to HCMV at least once during follow-up, whereas most displayed detectable LPRs to PHA. IFN-gamma was detected at least once in supernatants of HCMV-stimulated PBMC cultures from 14 of the 17 patients. All but one patient tested negative for HCMV leukoDNAemia and HCMV DNA in urine, and none developed HCMV disease during the observation period. CONCLUSIONS: Control of HCMV replication and the absence of HCMV disease are not consistently associated with recovery and/or maintenance of LPR to HCMV in AIDS patients under HAART and with no prior HCMV disease. Whether detection of IFN-gamma by PBMCs upon HCMV antigenic stimulation may serve as a surrogate marker for protection against HCMV disease requires further investigation.