PubMed · 12282182
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B De Valicourt. 1989-06-21. [AIDS. Should we be optimistic?].. https://pubmed.ncbi.nlm.nih.gov/12282182/
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Are there specific genes that control the pathogenesis of HIV infection? This question, which is of fundamental importance in designing personalized strategies of gene therapy to control HIV infection, can be examined by genetic mapping approaches. In this article, we present a new statistical model for unravelling the genetic mechanisms for the dynamic change of HIV that causes AIDS by marker-based linkage disequilibrium (LD) analyses. This new model is the extension of our functional mapping theory to integrate viral load trajectories within a genetic mapping framework. Earlier studies of HIV dynamics have led to various mathematical functions for modelling the kinetic curves of plasma virions and CD4 lymphocytes in HIV patients. Through incorporating these functions into the LD-based mapping procedure, we can identify and map individual quantitative trait loci (or QTL) responsible for viral pathogenesis. We derive a closed-form solution for estimating QTL allele frequency and marker-QTL linkage disequilibrium in the context of EM algorithm and implement the simplex algorithm to estimate the mathematical parameters describing the curve shapes of HIV pathogenesis. We performed different simulation scenarios based on currently used clinical designs in AIDS/HIV research to illustrate the utility and power of our model for genetic mapping of HIV dynamics. The implications of our model for genetic and genomic research into AIDS pathogenesis are discussed.
OBJECTIVE: To describe the clinical course and risk factors of death in highly active antiretroviral therapy (HAART)-treated patients with progressive multifocal leukencephalopathy (PML); to evaluate the efficacy of cidofovir in addition to HAART. METHODS: Retrospective multicenter cohort study of PML in HIV-1-infected patients. Diagnosis of PML was confirmed by histology or by positive polymerase chain reaction for JC virus (JCV) in cerebrospinal fluid (CSF) or was made by typical radiologic and clinical findings. RESULTS: Thirty-five cases of PML were identified. The diagnosis was made by histology (9 cases), detection of JCV in CSF (17 cases), and by radiologic findings (9 cases). Upon manifestation of PML, 15/35 patients had never received HAART, and 11/35 were on HAART for >6 months (median 1126 days). In 9/35 cases, clinical manifestation of PML occurred within 6 months after initiation of HAART. All patients received HAART after PML diagnosis. After a median follow-up of 553 days (range 28-2694 days), the median survival time was not reached. In 12 patients who were treated concomitantly with cidofovir, cumulative survival was significantly shorter than in patients without cidofovir (P = 0.03). Patients in whom PML was diagnosed while on HAART demonstrated a trend toward a shorter survival than HAART-naive patients (P = 0.15). CONCLUSIONS: PML continues to occur in HIV-1-infected patients even when they are treated with HAART. Patients developing PML on HAART had a trend toward a shorter median survival compared with treatment-naive patients, and cidofovir therapy was not associated with improved survival in this cohort.