CD4 counts declining more rapidly among recent seroconverters in US military cohort

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In a study of over 1000 mostly male seroconverters in the United States military, CD4 cell counts appear to be declining more quickly in those who seroconverted in more recent years. In people who seroconverted between 2002 and 2008, CD4 cell counts were 42% more likely to fall below 500 cells/mm3 within four years, compared to those who seroconverted between 1986 and 1990.

This study used longitudinal data from the US Military HIV Natural History Study. Due to routine HIV screening of US military personnel, study participants could be confirmed as seroconverting within a window of four years or less (mean, 1.4 years).

The study group consisted of 1085 personnel from diverse locations within the US who seroconverted between 1986 and 2008. Mean age was 28 years, 95% were male, 48% were Caucasian and 41% African American. The mean CD4 count at diagnosis was 720 cells/mm3.

Glossary

seroconversion

The transition period from infection with HIV to the detectable presence of HIV antibodies in the blood. When seroconversion occurs (usually within a few weeks of infection), the result of an HIV antibody test changes from HIV negative to HIV positive. Seroconversion may be accompanied with flu-like symptoms.

 

hazard

Expresses the risk that, during one very short moment in time, a person will experience an event, given that they have not already done so.

multivariate analysis

An extension of multivariable analysis that is used to model two or more outcomes at the same time.

trend

In everyday language, a general movement upwards or downwards (e.g. every year there are more HIV infections). When discussing statistics, a trend often describes an apparent difference between results that is not statistically significant. 

hazard ratio

Comparing one group with another, expresses differences in the risk of something happening. A hazard ratio above 1 means the risk is higher in the group of interest; a hazard ratio below 1 means the risk is lower. Similar to ‘relative risk’.

The investigators looked at trends in CD4 counts during four different time periods: 1986 to 1990, 1991 to 1995, 1996 to 2001, and 2002 to 2008. For participants who seroconverted during each period, investigators estimated the risk of reaching a CD4 count <500 cells/mm3 during the following four years and before beginning any antiretroviral use. (Those with CD4 counts already below 500 cells/mm3 at diagnosis were excluded.)

The multivariate analysis adjusted for gender, ethnicity, body mass index, window of seroconversion, CD4 count and viral load at diagnosis, and time from diagnosis to initial CD4 count.

In this analysis, the likelihood of reaching a CD4 count <500 cells/mm3 within four years of seroconversion increased over the time period of the study. Compared to those who seroconverted between 1986 and 1990, the hazard ratio [HR] for each period was:

  • 1.27 (95% conference interval [CI] 1.03 to 1.57) for those seroconverting between 1991 and 1995,
  • 1.25 (95% CI, 0.88 to 1.79) for 1996 to 2001, and
  • 1.42 (95% CI, 1.01 to 2.00) for 2002 to 2008.

The analysis was then repeated for only the 402 participants whose time of seroconversion was known to within twelve months. For this group, the hazard ratios were:

  • 1.27 (95% CI, 0.86 to 1.88) for 1991 to 1995,
  • 1.44 (95% CI, 0.76 to 2.73) for 1996 to 2001, and
  • 1.85 (95% CI, 0.98 to 3.49) for 2002 to 2008.

These figures strongly suggest that CD4 counts are declining more rapidly in more recent seroconverters in this study group. However, there are several limitations. The study group itself is confined to mostly male US military personnel, which is not representative of the population at large.

There are also issues of statistical significance, since confidence intervals that overlap 1.0 cannot be considered significant. Hence, in the overall group, only the difference between the 1991-1995 and 2002-2008 periods can be considered significant. For the smaller group whose seroconversion date was more precisely known, none of the figures can be considered significant, although they strongly suggest a trend.

Further studies of larger groups are needed to determine whether there is any general trend toward faster CD4 cell count declines in seroconverters at large.

Further information

You can view the abstract on the official conference website.

References

Crum-Cianflone N. Are HIV-infected persons progressing faster after HIV diagnosis over the epidemic? Seventeenth Conference on Retroviruses and Opportunistic Infections, San Francisco, abstract 980, 2010.