Development of cytomegalovirus (CMV) disease may be predicted in HIV-infected patients by CMV polymerase chain reaction and the antigenemia test.

OBJECTIVE: Cytomegalovirus (CMV) is a frequent opportunistic viral pathogen in patients with AIDS leading to retinitis and other serious manifestations. CMV disease may be successfully treated. Prophylactic antiviral therapy has been shown to reduce the risk of CMV disease if initiated early. We evaluated PCR and the antigenemia tests as methods for early detection of CMV disease. METHODS: Two-hundred HIV-seropositive subjects with CD4 T-cell counts below 100 x 10(6)/l were monitored with CMV polymerase chain reaction (PCR), the antigenemia test, blood cultures and CMV immunoglobulin (Ig) G and IgM titres every second month for 1 year. RESULTS: Thirty-eight patients (19%) developed CMV disease. The PCR test detected CMV DNA a median of 46 days before onset of disease. This was earlier than the median of 34 for the antigenemia test and a median of 1 day for CMV blood cultures. Univariate analysis showed that the CMV PCR, the antigenemia test and blood cultures all had significant predictive values for subsequent development of CMV disease with odds ratios (OR) of 30, 22 and 20. CMV serology had no predictive value. Multivariate analysis showed that the PCR method was superior to the other tests; OR: CMV PCR 10.0, antigenemia test 4.4 and CMV cultures 4.3. No clinical parameters had any significant predictive value in the stepwise multivariate model. CONCLUSIONS: The CMV PCR and the CMV antigenemia tests are both sensitive methods that may predict development of CMV disease up to several months prior to clinical disease. These methods make it possible to select patients at high risk for CMV disease and suitable for prophylactic therapy against CMV.

Human herpes virus-8 DNA in bronchoalveolar lavage samples from patients with AIDS-associated pulmonary Kaposi's sarcoma.

Kaposi's sarcoma (KS) is the most frequent AIDS-associated neoplasm, and often disseminates to visceral organs, including the lungs. An ante-mortem diagnosis of pulmonary KS is difficult. Recently, DNA sequences resembling a new human herpes virus (HHV-8), have been identified in various forms of KS. We hypothesized that these sequences are present in samples obtained by bronchoalveolar lavage (BAL) in patients with pulmonary KS. Utilizing a nested polymerase chain reaction (PCR), 7/12 BAL cell samples from HIV-infected patients with endobronchial KS were positive for HHV-8 DNA. In contrast, only 2/39 samples from HIV-infected patients without evidence of KS were positive (p = 0.007). Detection of HHV-8 in BAL cells of patients with pulmonary KS was highly specific (95%), with a sensitivity of 58% and a positive predictive value of 78%. In conclusion, HHV-8 is associated with pulmonary KS, and PCR amplification of HHV-8 in BAL cells provides a non-invasive method with a high positive predictive value.

Increased levels of soluble tumour necrosis factor receptor-I (P55) and decreased IgG1 reactivities in HIV-1 patients with cytomegalovirus disease.

The purpose of the study was to investigate potential associations between tumour necrosis factor (TNF), soluble TNF receptors (sTNF-Rs), immunoglobulin (Ig)G subclasses and development of cytomegalovirus (CMV) disease amongst human immunodeficiency virus (HIV)-1 patients. We enrolled HIV-1 patients with CD4 counts less than 100/microl in a prospective study and followed them over 1 year for development of CMV disease. Concentrations of TNF, sTNF-RI, sTNF-RII and IgG subclass reactivities were measured by ELISA; levels of CMV pp65 antigenaemia were determined as numbers of pp65 expressing cells/100,000 cells and were measured by staining of leucocytes; and HIV-1 RNA loads were measured by polymerase chain reaction (PCR). Eighteen patients studied with CMV disease had higher levels of sTNF-RI than 18 similar patients without CMV disease. Concentrations of sTNF-RI correlated with levels of CMV antigenaemia in blood samples collected before the development of CMV disease. Patients with CMV disease had lower levels of IgG1 reactivities to CMV than patients without CMV disease. We conclude that increased levels of sTNF-RI and decreased IgG1 reactivities are associated with an increased risk of development of CMV disease among HIV-1 patients.