The effect of SDF1-3'A on the progression of HIV-1 infection to AIDS was investigated in a number of populations or cohorts. Three possible SDF-1 genotypes were analyzed: +/+, +/3'A, and 3'A/3'A. Since the definition of AIDS has changed over time, the results of the protection offered by SDF1-3'A were compared accordingly. Below are the definitions of AIDS from 1987,and 1993. The results were also compared using death as the endpoint.
Which one of these two definitions is more stringent? Answer The 1987 definition is more stringent because it does not use a low T cell count as one of the possible criteria for being diagnosed as having AIDS. The low T cell count could be because of some other reason and not necessarily because of the HIV infection.
Following are the results of a disease progression analysis of 639 seroconverters Seroconversion refers to going from having a negative blood test for HIV to a positive one. from four different cohorts. Is it important to have a well characterized date of seroconversion?
Yes Correct. It is important to have a well characterized date of seroconversion so that the time the disease has had to progress can be taken into account. No Incorrect. It is important ot have a well characterized date of seroconversion so that the time the disease has had to progress can be taken into account.
Compare the fraction of AIDS-free individuals with 3'A/3'A genotype from 1987 and 1993 definition based studies. Keeping in mind that the 1987 had a more stringent definition of AIDS (which excluded the criteria for a low T cell count as a sign of AIDS), what do the results suggest regarding the impact of 3'A/3'A genotype? Answer This suggests that the protective effect of 3'A/3'A is more acute for some subpopulations with AIDS.
Are your conclusions supported by the results shown in Fig 1.3? Yes Correct. The protective effect of 3'A/3'A is most pronounced here. About 16 years after seroconversion approximately 85 % of individuals with 3'A/3'A genotype survive while only about 38% of those with either +/+ or +/3'A are living. As the definition gets more stringent, the level of apparent protection provided by 3'A/3'A increases. or No Incorrect. The protective effect of 3'A/3'A is most pronounced here and your conclusions are supported.. About 16 years after seroconversion approximately 85 % of individuals with 3'A/3'A genotype survive while only about 38% of those with either +/+ or +/3'A are living. As the definition gets more stringent, the level of apparent protection provided by 3'A/3'A increases.
Once the protective effect of 3'A/3'A genotype was realized, the experimenters progressed to determine the prevalence of this genotype in both the patients who proceeded to the particular endpoint The term refers to AIDS as defined by the 1987 definition or the 1993 definition or death. and those who didn't. In which one of the two groups would you expect to find a higher frequency of the 3'A/3'A genotype -- those who progressed Incorrect. Those who progressed to the particular endpoints either have AIDS or are dead. There is going to be a lower number of individuals with the protective 3'A/3'A genotype in this group. to the particular endpoint or in those who did not progress Correct. Individuals in this group would be more likely have the protective effect of the 3'A/3'A genotype. to the particular endpoint?
The experimenters measured the frequency of 3'A/3'A genotype in caucasians in three different cohorts (MACS, MHCS and SFCC). White bars refer to the individuals who did not proceed to the respective endpoint where the black bars represent the individuals who did. The triangles indicate the 3'A/3'A frequencies for all ethnic groups. The respective endpoints are at the top of the graph.
Please answer the following questions to see whether you understand the data being presented.
The disparity in frequency of the 3'A/3'A genotype between those who proceeded and those who didn't the greatest in the graph for which endpoint ? For this question consider only the MHCS cohort and only the frequency for caucasians (top of the bar and not the triangle).
Is it AIDS 1987 Incorrect. The difference in the percentage of individuals with the 3'A/3'A genotype is only about 18% (55% in those who did not progress to 37% in those who did) or AIDS 1993 Correct. The difference in the percentage of individuals with the 3'A/3'A genotype is the greates here at about 29% (56% in those who did not progress to 27% in those who did) or Death Incorrect. The difference in the percentage of individuals with the 3'A/3'A genotype is neary zero in both groups: those who progressed to the endpoint and those who didn't at around 56%.
Now reconsider the above question using only the SFCC cohort and the frequency for all ethnic groups (the triangles). Is the disparity greater in AIDS 1987 Incorrect. The difference in the percentage values for the frequency of 3'A/3'A genotype is only 29% (48% in those who did not progree to the enpoint to 19% in those who did) or AIDS 1993 Incorrect. The difference in the percentage values for the frequency of 3'A/3'A genotype is only 17% (44% in those who did not progress to the enpoint to 27% in those who did) or Death Correct. The difference in the percentage values for the frequency of 3'A/3'A genotype is the greates here at 49% (49% in those who did not progress to the enpoint to 0% in those who did)
Recall the trend observed in the protective effect of 3'A/3'A genotype from Fig. 1 -- as the definition of AIDS got more stringent, a higher level of apparent protection was provided by 3'A/3'A genotype. Can that same trend be observed in Fig. 2? Consider only the combined data (All) and the frequencies of all ethnic groups (triangles).
Yes Correct. The trend is observed in this figure as well. The disparity in the percentage values of the frequency in those who progressed to the endpoints and those who didn't is reflective of this fact. The difference according to AIDS 1993 definition, the least strict of the three, is about 30% (47% in those who did not progress to 17% in those who did). The difference according to the endpoint Death is about 41% (53% to 12%) or No Incorrect. The trend is observed in this figure as well. The disparity in the percentage values of the frequency in those who progressed to the endpoints and those who didn't is reflective of this fact. The difference according to AIDS 1993 definition, the least strict of the three, is about 30% (47% in those who did not progress to 17% in those who did). The difference according to the endpoint Death is about 41% (53% to 12%)
Well done!! You now see that the SDF1-3'A/3'A genotype has a protective effect in an individual with this genotype; it delays the onset of AIDS (1987 or 1993) or death. So would this polymorphism of the SDF-1 beta transcript complement other protective genotypes for receptors and coreceptors that facilitate the binding of the HIV particle to the cell? It is recomended that you review the introduction on the main page before proceeding further.
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