PubMed · 2355968
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1990. AIDS scan.. https://pubmed.ncbi.nlm.nih.gov/2355968/
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In this study, immunoglobulin variable (Ig V) region genes, c-myc re-arrangement and sequence and p53 status were analyzed in clones derived from a Burkitt's lymphoma cell line (LAM) in which it was previously demonstrated that Epstein-Barr virus (EBV) infection occurred late during lymphomagenesis. Such evidence was based on the finding that 2 groups of cellular clones, characterized by the same c-myc re-arrangement but different EBV-fused termini, were obtained from the LAM cell line. The Ig V gene sequences were identical for the 2 groups of clones with different EBV-fused termini. The Ig variable heavy (V(H)) gene sequence displayed a substantial accumulation of point mutations (but no intra-clonal diversification), whereas the productive Ig V lambda (V(lambda)) gene sequence was virtually unmutated. Studies on the Ig V kappa (V(kappa)) locus suggested a receptor revision event (with a switch from kappa to lambda chain production) prior to EBV infection. Likewise, it was determined that the mutations observed in both p53 alleles and in the re-arranged c-myc gene occurred before EBV infection. Based on these findings, we present a model for the various steps of lymphomagenesis. It is proposed that stimulation by an antigen or a superantigen initially favored the clonal expansion and accumulation of other cytogenetic changes, including those involved in receptor editing. These events occurred prior to or during the germinal center (GC) phase of B-cell maturation. Thereafter, possibly upon exit of the cells from the GC, EBV infection occurred, further promoting lymphomagenesis.
PURPOSE: To outline the incidence, presenting features, treatment response, and outcome of human immunodeficiency virus (HIV)-associated malignancies in infancy and childhood, together with the estimated risk of HIV-associated cancer in children born to mothers infected with HIV. PATIENTS AND METHODS: The Italian Register for HIV Infection in Children collected data by specific registration and follow-up forms. By March 1999, 5,060 children were recruited, including 4,889 with perinatal exposure to HIV-1. Overall, 1,331 infected children were enrolled onto the Register and classified according to current Centers for Disease Control criteria; of them, 1,163 were vertically infected (24% of those with perinatal exposure). Of these 1,163, 569 (49%) were considered to have been prospectively followed-up since they had been registered at birth or within the first 3 months of age. RESULTS: Of the 1,331 children observed for a median time of 6.5 years, 35 developed 36 malignancies, four of which occurred in patients with blood-borne risk. For the 1,163 vertically infected children, the cumulative number of years of observation was 7,178 child-years and the cumulative incidence of HIV-associated tumors was 4.18 per 1,000 children/yr (95% confidence interval [CI], 2.92 to 5.98). When only the 569 vertically infected children prospectively followed up since birth were considered, the cumulative number of years of observation was 2,803 child-years. In this group, 10 tumors were observed, with a cumulative incidence of HIV-associated tumors of 3.57 per 1,000 children per year (95% CI, 1.92 to 6.63). CONCLUSION: The risk of cancer was significantly higher but not restricted to symptomatic and/or immune-compromised children. Cancer-directed treatment should be given promptly to these patients, who have a fair chance to survive their tumor in view of potential highly aggressive antiretroviral therapy-associated improvement in survival and quality of life.
BACKGROUND: Recently published research based on selected samples of patients treated at human immunodeficiency virus clinics documents that use of more intensive antiretroviral drug therapies is responsible for significant declines in morbidity and mortality in persons living with human immunodeficiency virus or acquired immunodeficiency syndrome (PLWHAs). In this study, we evaluate whether receipt of more recently developed antiretroviral therapies varies by sex and race/ethnicity in a large population-based sample of PLWHAs and whether receipt of such drugs has any impact on survival. METHODS: Analysis of Florida Medicaid eligibility, enrollment, and claims data for PLWHAs for 1993 through 1997. Receipt of 2 nucleoside analogs (TWONUKES) and receipt of 1 protease inhibitor and a nucleoside combination (PI+NUKES) was constructed from claims data. The probability of dying was constructed from eligibility and enrollment data. RESULTS: The probabilities of receiving TWONUKES and PI+NUKES are 0.16 and 0.09, respectively, lower for women relative to men (P<.01 for both). Blacks are more likely to receive TWONUKES than whites, whereas the reverse is true for Hispanics; this probability is almost 0.04 higher for blacks and 0.03 lower for Hispanics relative to whites (P<.01). In contrast, blacks are significantly less likely to receive PI+NUKES (P<.01). Both drug variables have large statistically significant negative effects on the probability of death. The PLWHAs who received PI+NUKES are 60% as likely to die each month (P<.01). Receipt of TWONUKES lowers the relative hazard of death by close to 66% each month (P<.01). Survival varies significantly by sex and race/ethnicity. Controlling for receipt of drug therapy and diagnosed health throughout the period, women are 56% as likely to die as men (P<.01). Hispanics are almost 14% less likely to die each month relative to whites (relative hazard, 0.87), and blacks are 20% more likely to die than whites (relative hazard, 1.21). CONCLUSIONS: States need to investigate why women are less likely to receive antiretroviral drug therapies than men and to consider policies that might foster better access to antiretroviral therapies for women with acquired immunodeficiency syndrome because these efforts might yield even further reductions in mortality in women. Given the large reductions in mortality that accompany receipt of antiretroviral therapies, states need to foster policies that promote widespread use of new drug treatment protocols.