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Unlabelled: The effectiveness and tolerance of antiretroviral therapy with a combination of three reverse transcriptase inhibitors starting at the time of diagnosis (before 2 months of age) was evaluated in four infants with vertically acquired HIV-1 infection. Plasma HIV-1 RNA levels ranged from 230,000 to 1,000,000 copies/ml before onset of triple therapy and fell below 50 copies/ml at 12 to 33 weeks of life in three of the infants. These three children, currently aged 158, 105 and 72 weeks, are asymptomatic, have normal lymphocyte subsets and no hypergammaglobulinaemia. Two children experienced a profound reduction in the amount of proviral DNA detected in blood and have become HIV-1 seronegative, although one of them has had HIV-1 RNA detectable on a single occasion at 114 weeks of life (303 copies/ml). Transient interruption of therapy resulted in a rapid but reversible increase in HIV-1 RNA levels in the third child and was associated with the production of HIV-specific antibodies. The fourth child whose parents were not compliant to treatment and follow-up had a poor virological response.Conclusion: Early treatment of vertically acquired human immunodeficiency virus type 1 infection with three reverse transcriptase inhibitors is well tolerated and can result in such suppression of viral replication that specific antibodies are not produced, that proviral DNA falls to the lower limit of quantitation in blood and that all clinical and immunological manifestations of infection are avoided. Parental adhesion is crucial to the effectiveness of therapy. [ABSTRACT FROM AUTHOR]

Initial evaluations of the Cobas AmpliPrep/Cobas TaqMan human immunodeficiency virus type 1 (HIV-1) test (CAP/CTM) demonstrated good performance but, afterwards, reports about underquantification were published. We investigated whether the problem was solved with a second version of this assay, the Cobas AmpliPrep/Cobas TaqMan HIV-1 test, version 2.0 (CAP/CTM v2.0). The remaining plasma of 375 consecutive HIV-1 positive samples with a viral load of >or=4,000 copies/ml was collected in three laboratories. The samples were diluted and retested with our routine method Cobas AmpliPrep/Cobas Amplicor HIV-1 monitor test v1.5 in ultrasensitive mode (CAP/CA PHS), as well as with the CAP/CTM and CAP/CTM v2.0 tests. An absolute difference between the results of two methods of >or=0.71 log(10) copies/ml was defined as moderately discrepant, and an absolute difference of >or=0.93 log(10) copies/ml was defined as severely discrepant. In addition, criteria for considering the new methods equivalent to the routine method were formulated. (i) For CAP/CTM compared to CAP/CA PHS, 36 (9.5%) and 20 (5.3%) samples were, respectively, considered moderately and severely underquantified by CAP/CTM. The mean difference between CAP/CTM and CAP/CA PHS was -0.32 log(10) copies/ml. Eight of nineteen of the severely underquantified samples were from patients infected with HIV-1 subtype B strain. (ii) For CAP/CTM v2.0 compared to CAP/CA PHS, no sample was moderately or severely underquantified by CAP/CTM v2.0. A mean difference of 0.08 log(10) copies/ml was found with CAP/CTM v2.0 compared to CAP/CA PHS. The underquantification problem of the CAP/CTM kit was clearly demonstrated. The criteria for the equivalence of CAP/CTM v2.0 to the routine test CAP/CA PHS were fulfilled.

Objectives: To evaluate the immune reconstitution in HIV-1-infected children in whom highly active antiretroviral therapy (HAART) controlled viral replication and to assess the existence of a relation between the magnitude of this restoration and age., Methods: All HIV-1-infected children in whom a new HAART decreased plasma viral load below 400 copies/ml after 3 months of therapy were prospectively enrolled in a study of their immune reconstitution. Viral load, lymphocyte phenotyping, determination of CD4+ and CD8+ T cell receptor repertoires and proliferative responses to mitogens and recall antigens were assessed every 3 months during 1 year., Results: Nineteen children were evaluated. Naive and memory CD4+ percentages were already significantly increased after 3 months of HAART. In contrast to memory CD4+ percentages, naive CD4+ percentages continued to rise until 12 months. Age at baseline was inversely correlated with the magnitude of the rise in naive CD4+ cells after 3, 6 and 9 months of therapy but not after 12 months. Although memory and activated CD8+ cells were already decreasing after 3 months, abnormalities of the CD8 T cell receptor repertoire and activation of CD8+ cells persisted at 1 year. HAART increased the response to mitogens as early as 3 months after starting therapy., Conclusions: In children the recovery of naive CD4+ cells occurs more rapidly if treatment is started at a younger age, but after 1 year of viral replication control, patients of all ages have achieved the same level of restoration. Markers of chronic activation in CD8+ cells persist after 1 year of HAART.

Objectives: To estimate the prevalence and the evolution over time (1995-1998) of genotypic resistance to antiviral drugs in antiretroviral drug-naive HIV-1-infected patients in Belgium., Design: Belgian Aids Reference Laboratories provided retrospective samples and clinical data from antiretroviral drug-naive HIV-1-infected patients who visited the hospital for the first time in 1995 (n=45), 1997 (n=75) and 1998 (n=111). Genotypic resistance to the three available classes of drugs was monitored using the Line Probe Assay (Innogenetics, Gent, Belgium). Additionally, ARMS-151 was performed for scoring multinucleoside resistance., Results: The prevalence of genotypic resistance at baseline to nucleoside analogue reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs) were each between 10% and 20% for 1995, 1997 and 1998 without an increasing trend over time. For NRTIs, resistance mutations were mainly related to zidovudine in 1995, whereas in 1997 and 1998 baseline resistance was scored for zidovudine, lamivudine or for both drugs simultaneously. No patients displayed the multi-nucleoside resistance Q151M mutation. Baseline resistance mutations to protease inhibitors (PIs) did not rise significantly: 4.4% in 1995, 8% in 1997 and 9.9% in 1998. When scoring any resistance-related mutation, 26.6% displayed genotypic baseline resistance in 1995, 26.6% in 1997 and 31.5% in 1998., Discussion: The prevalence of genotypic baseline resistance to any drug, as scored with LiPA, in naive HIV-1 patients in Belgium is 29%, with baseline resistance mutations to one or several drugs from all available classes of antiviral drugs. The ability of LiPA to pick up minor variants could be an explanation for the higher overall prevalence we observe, when compared to recent estimates in other countries of 16.3% and 22%, which were based on sequencing methods. According to the European guidelines for resistance testing, resistance testing in Belgium before starting antiviral therapy should be considered.

Three commercial assays for quantifying plasma human immunodeficiency virus type 1 (HIV-1) RNA were evaluated. The assays differed in their sample volumes, the means of preparing samples, and methods of amplification and detection. Plasma samples were obtained from 36 HIV-1-infected patients representing all stages of HIV-1 infection and were analyzed as coded specimens. Measurement of HIV-1 RNA baseline levels revealed no significant difference in sensitivity between the three assays. The assays were also applied to the quantitation of HIV-1 RNA levels in the plasma of patients who were changing their antiretroviral therapy. The changes measured in HIV-1 RNA levels in plasma in response to therapy were comparable by the three assays. No close correlation was found between the amount of HIV-1 RNA and the CD4 T-cell count; HIV-1 RNA assays were more sensitive than p24 antigen assays as an indicator of plasma viremia. Overall, the study demonstrates that all three quantitative assays for HIV-1 RNA can be used to measure the HIV-1 RNA copy number representing the HIV-1 viremia status in patients with HIV-1 infection. Since this copy number is likely to be useful in monitoring the effectiveness of antiviral therapy, these quantitative assays for HIV-1 RNA are ready to be built into clinical trials.

We have developed a series of monoclonal antibodies against the calf strain RIT 4237 (subgroup 1) and the human strain 82-561 (subgroup 3) of rotavirus, both grown in tissue culture, and also against the human rotavirus 81-2162 (subgroup 2), extracted from a fecal specimen. A variety of different specificities was observed among these antibodies, namely, antibodies against group and subgroup determinants, as well as neutralizing antibodies. By using monoclonal antibodies against the subgroup antigen in an enzyme-linked immunoassay system, the constant predominance of subgroup 2 viruses in humans was confirmed in 74 stools collected from children in Brussels who suffered a diarrheal illness between July 1981 and June 1983. The availability of these antibodies also made it possible to improve the sensitivity and the specificity of the test system.

Because of the morbidity and mortality from infection with rotaviruses in children under 2 years, in many parts of the world but especially in developing countries, an urgent need for a vaccine has been recognized. At present, a vaccine candidate of bovine origin, the RIT 4237 strain vaccine developed from a strain received from Mebus et al., is available. This strain has been shown to induce cross protection by challenge of colostrum deprived piglets with human rotavirus strains. Before testing its protective effect in children, preliminary studies in adult volunteers are required to evaluate its degree attenuation and immunogenicity. With regard to the latter we have studied the antibody profile of 87 healthy adults, ages 25 to 40 years, from whom blood samples were taken between January and June 1982. Antibodies versus RIT 4237 were measured both by neutralization and ELISA techniques. Analysis of the results revealed a significant difference in antibody levels according to sex, since high neutralizing antibody titers (greater than 1:320) were observed about 7 times more frequently in women than in men. Furthermore, no seasonal variation in the level and the distribution of serum antibody titers was found when comparing blood specimens taken from male volunteers in winter and spring. As far as antibody levels obtained by neutralization and ELISA assays is concerned, a good correlations was noted in 75% of cases. However, in 22 out of 87 sera high levels of neutralizing antibodies were found in association with low ELISA antibody titers or vice versa. These results suggest that screening of adult volunteers should be performed by means of a neutralization assay prior to administration of a candidate vaccine. However, in the absence of such preliminary testing, male volunteers should be chosen since there is a higher probability of low pre-existing antibody levels among such subjects.

The relative prevalence of human rotavirus subgroups was studied during a 3-year period (1978-1981) by means of a sensitive complement fixation technique. Among 93 rotavirus isolates from children with acute gastroenteritis in Brussels, the prevalence of subgroups 1, 2, and 3 was, respectively 24, 17, and 32%. The remaining 27% of strains could not be typed, but no evidence for the existence of any new subgroup was found. The proportion of strains belonging to the different subgroups remained roughly constant during the study period, showing the simultaneous occurrence of the various subgroups of viruses, even during the annual winter peak of rotavirus gastroenteritis.