The dynamics of CD4+ T-lymphocyte decline in HIV-infected individuals: A Markov modeling approach

Article Abstract:

The human immunodeficiency virus (HIV) infects and destroys T-lymphocytes known as CD4+ cells, which are involved in the immune response. The destruction of these cells is associated with the deterioration of the immune system, causing the disease state of AIDS. The decline in the number of CD4+ cells is thus an indicator of the status of a patient with HIV infection. This decline is used to indicate when treatment with antiviral agents or prophylactic agents to prevent opportunistic infections should be initiated. The process of decline in the number of CD4+ T-lymphocytes was analyzed using the continuous-time Markov analytical process. This mathematical model divides the infectious period into eight states based on the decline in CD4+ cells. Progression rates based on various cofactors were estimated. The model was tested using data from 1,796 individuals infected with HIV who were in the United States Army. The mean waiting time for the number of CD4+ cells to fall between 500 and 349 per cubic millimeter of blood was 4.1 years. Drug treatment generally begins when the CD4+ cell count is below 500. The mean time period for the CD4+ cells to drop below 200 was 8.0 years. The decline in CD4+ cells was slower for individuals who initially had high numbers of these cells. However, once the cell count was lower than 500, the drop occurred at the same rate as in those whose initial counts were lower. The mean time from when viral antibodies in the blood were detected to the point when opportunistic infections began to show up was 9.6 years. However, the age of the individual affected this time. The mean time for individuals 25 years of age or younger was 11.1 years; for 26- to 30-year-olds, it was 10.0 years; and for individuals over 30 years old, the average time was 8.9 years. The time period for the CD4+ cells to initially drop to 500 did not depend on the age of the individuals. However, the decline in the number of CD4+ cells below 500 generally did occur faster in the individuals 26 years or older. The results of this type of model are consistent with those obtained with other models. (Consumer Summary produced by Reliance Medical Information, Inc.)

Usage, Measurement, Markov processes, CD4 lymphocytes

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AIDS and mucosal immunity: usefulness of the SIV macaque model of genital mucosal transmission

Article Abstract:

Although heterosexual contact is the main route of human immunodeficiency virus (HIV) transmission worldwide, the biology of this transmission is little understood. Safe sex education and condom use have not stopped the AIDS epidemic and development of a preventive vaccine is years away. Further understanding of how HIV is transmitted heterosexually is of vital importance to the prevention of HIV disease and AIDS. Of particular importance is greater knowledge about genital mucosal immunity and infection, as this is the suspected route of most heterosexually obtained infections. Genital mucosal transmission of simian immunodeficiency virus (SIV) in macaque monkeys has been studied in depth. This animal model has shown that SIV infection can be established via exposure of intact vaginal or urethral mucosa to the virus. Although dissemination of SIV by this route is slower than when the virus is transmitted intravenously, infection with either type of exposure eventually leads to simian AIDS. This model is of significant importance to the study of heterosexual transmission of HIV and its prevention. The macaque model can be used to examine factors that either decrease or increase the likelihood of infection upon exposure to HIV. It can be employed to examine genital mucosal immune response to HIV. In addition, it may be possible to utilize the model to develop a vaccine geared to elicit a localized genital mucosal immune response when the tissue is exposed to HIV. The SIV macaque model should be very useful in helping to understand heterosexual transmission of HIV. (Consumer Summary produced by Reliance Medical Information, Inc.)

Editorial, Physiological aspects, HIV (Viruses), HIV, Disease transmission, Simian immunodeficiency virus

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Asking the right questions

Article Abstract:

AIDS researchers need a cohesive plan that will allow for a more efficient synthesis of their efforts. Too often AIDS research focuses on the minutiae of the disease rather than the effect that research will, or will not, have on the patient. Scientists often seem divorced from the reality of the suffering of AIDS patients. It is important that scientists realize their commitment to the public and the betterment of humanity. Strengthening communication between the various disciplines is discussed as a good starting point for scientists interested in working together.

Beliefs, opinions and attitudes, Medical research

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