Role of avidity and breadth of the CD4 T cell response in progression to AIDS

The great variability in the time between infection with HIV and the onset of AIDS has been the object of intense study. In the current work, we examine a mathematical model that focuses on the role of immune response variability between patients. We study the effect of variation in both the avidity and the breadth of the immune response on within-patient disease dynamics, viral setpoint and time to AIDS. We conclude that immune response variability can explain the observed variability in disease progression to a large extent. It turns out that the avidity, more than the breadth of the immune response, determines disease progression, and that the average avidity of the five best clones is a much better correlate for disease progression than the total number of clones responding. For the design of vaccines, this would suggest that, if given the choice between stimulating a broader, but average avidity response or a narrower high-avidity response, the latter option would yield better control of virus load and consequently slow down disease progression

Morbidity and survival in advanced AIDS in Rio de Janeiro, Brazil Morbidade e sobrevida em AIDS avançada no Rio de Janeiro, Brasil

Opportunistic diseases (OD) are the most common cause of death in AIDS patients. To access the incidence of OD and survival in advanced immunodeficiency, we included 79 patients with AIDS treated at Hospital Evandro Chagas (FIOCRUZ) from September 1997 to December 1999 with at least one CD4 count <=100 cells/mm³. The incidence of OD was analyzed by Poisson's regression, and survival by Kaplan Meier and Cox analysis, considering a retrospective (before CD4 <=100 cells/mm³) and a prospective (after CD4 <=100 cells/mm³) period, and controlling for demographic, clinical and laboratory characteristics. The confidence interval estipulated was 95%. Mean follow-up period was 733 days (CI = 683-782). During the study 9 (11.4%) patients died. Survival from AIDS diagnosis was a mean of 2589 days (CI = 2363-2816) and from the date of the CD4 count CD4 <=100 cells/mm³ was a mean of 1376 (CI = 1181-1572) days. Incidence of OD was 0.51 pp/y before CD4 <= 100 cells/mm³ and 0.29 pp/y after CD4 <= 100 cells/mm³. A lower number of ODs before CD4 < 100 cells/mm³ was associated with lower incidence rates after CD4 <= 100 cells/mm³. AIDS diagnosis based on CD4+ counts <= 200 cells/mm³ was associated with lower incidence rates after CD4 <= 100 cells/mm³. Baseline CD4 counts above 50 cells/mm³ (HR = 0.13) and restoration of baseline CD4+ counts above 100 cells/mm³ (HR = 0.16) were associated with a lower risk of death. Controling both variables, only restoration of baseline counts was statistically significant (HR = 0.22, p = 0.04). We found a very low incidence of OD and long survival after CD4 < 100 cells/mm³. Survival was significantly associated with restoration of baseline CD4 counts above 100 cells/mm³.<br>As doenças oportunistas (DO) são a causa mais comum de morte em pacientes com AIDS. Para acessar a incidência de DO e a sobrevida na imunodeficiência avançada, foram incluídos 79 pacientes com AIDS tratados no Hospital Evandro Chagas (FIOCRUZ) no período de Setembro de 1997 a Dezembro de 1999, com ao menos uma contagem de células CD4 <= 100/mm³. A incidência de DO foi analisada pela regressão de Poisson e a sobrevida pela analise de Kaplan Meier e Cox, considerando um período retrospectivo (anterior à contagem de CD4 <= 100 cels/mm³) e um prospectivo (após a contagem de CD4 <= 100 cels/mm³) e controlando-se características demográficas clínicas e laboratoriais. O intervalo de confiança estipulado foi o de 95%. O período médio de acompanhamento foi de 733 dias (IC = 683 - 782). Durante o estudo, nove (11,4%) pacientes morreram. A sobrevida a partir do diagnóstico de AIDS foi em média de 2589 dias (IC = 2363 - 2816) e da data da contagem de CD4 <= 100 cels/mm³ foi em média de 1376 dias (IC = 1181 - 1572). A incidência de DO foi de 0,51 pp/ano no período pré-CD4 <= 100 cels/mm³ e 0,29 pp/ano no período pós-CD4 <= 100 cels/mm³. Um menor número de DO acumuladas no período pré-CD4 <= 100 cels/mm³ foi associado com taxas de incidência menores no período pós-CD4 <= 100 cels/mm³.O diagnóstico de AIDS baseado em contagem de CD4+ <= 200 cels/mm³ foi associado com menores taxas de incidência durante o período pós-CD4 <= 100 cels/mm³. As contagens basais de células CD4 acima de 50 cel/mm³ (HR = 0,16) foram associadas a um menor risco de morte assim como a restauração da contagem basal acima de 100 cels/mm³ (HR = 0,16). Controlando-se ambas, somente a restauração da contagem basal manteve sua significância estatística (HR = 0,22, p = 0,04) Encontramos uma baixa incidência de DO durante o período pós-CD4 <= 100 cels/mm³ e uma sobrevida longa após CD4 <= 100 cels/mm³. A sobrevida foi significativamente associada com a restauração das contagens de CD4 basais