Women infected with HIV through sexual intercourse appear to experience the slowest decline in CD4 counts, according to the results of a major study from CASCADE, an international collaboration that pools 20 cohorts of seroconverters in Europe and Australia and tracks their progress throughout their HIV disease. The paper was published in the September 1st issue of the Journal of Infectious Diseases.
Almost 5800 individuals were included in the analysis, which looked at the effect of age, gender, exposure group and other factors at the time of seroconversion on the rates of CD4 cell decline during the course of HIV infection. Follow-up included 2254 people (39.3%) infected between 1979-1988 and 2569 (44.8%) infected between 1989-1994. The vast majority (92.7%) were identified by a positive HIV antibody test rather than severe seroconversion illness, which in itself results in a faster decline in CD4 counts.
Due to the extremely large and diverse study population, the authors were able to distinguish certain demographic differences not seen previously.
Women were found to have higher CD4 counts than men at seroconversion - between 30-60 cells/mm3, on average (p
This could be due to a combination of factors. Women tend to have a lower HIV viral load than men; female sex hormones may affect CD4 levels; and various social and economic factors could also be at play. The authors suggest that further research is needed to ascertain whether differences between the sexes are important enough to change current guidelines on when to initiate HAART.
The study also found that both men and women who were infected through heterosexual sex had, on average, a less steep CD4 cell decline than gay men, and male or female IDUs or haemophiliacs. Men with haemophilia who acquired HIV through blood clotting agents had substantially higher CD4 counts at seroconversion, but they also tended to have steeper CD4 cell declines (p = 0.014). The reasons for both of these differences remain unclear.
Gay men and male IDUs had a lower CD4 count at the time of seroconversion compared with other risk groups in this study. This contradicts other studies which have found that all men have lower CD4 counts than women at the time of seroconversion. The authors suggest that the lifestyle factors of gay men and male IDUs (for example, use of drugs or constant immune activation due to STIs) may explain the observed differences.
Shortly after seroconversion people over 40 have, on average, a lower CD4 cell count than younger people; and five years after seroconversion, the difference in the median CD4 count between youngest (15-20) and the oldest (over 40) was about 90 cells/mm3. Other studies have reported similar findings, however, and the authors suggest that there may be a more rapid decline in the immune system after 40 due to shrinkage of the thymus - the organ which produces naive CD4 cells.
Finally, although two prior studies have suggested that people infected with HIV more recently are taking less time to reach lower CD4 counts - suggesting the possibility of more virulent strains of HIV emerging - this study found no such correlation. In fact, there was a marginal tendency for faster CD4 declines prior to 1994, and the authors state “there was certainly no suggestion of a faster loss of CD4 cells in those seroconverting more recently.”
The authors conclude that until more studies tease out the differences between methods of HIV transmission, age and sex, “before the initiation of HAART or other interventions based on immune status, consideration of demographic factors may be worthwhile.”
Further information on this website
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CASCADE Collaboration. Differences in CD4 Cell Counts at Seroconversion and Decline Among 5739 HIV-1-Infected Individuals with Well-Estimated Dates of Seroconversion. J Acquir Immune Defic Syndr 34 (1): 76-83, 2003.