The initial CD4 cell counts of patients newly infected with HIV fell significantly between 1985 and 2001, US research published in the May 1st edition of Clinical Infectious Diseases has shown. This suggests that the virus may have evolved to become more virulent during this time period, which could have clinical implications, shortening the interval between infection with HIV and the need to start HIV treatment.
In people with HIV, CD4 cell counts provide an important indication of the strength of the immune system, of HIV disease progression and of when to start antiretroviral treatment.
At the time of HIV infection a massive loss of CD4 cells occurs. The immune system then mounts a response to HIV, virus levels fall, and the CD4 cell count recovers - although often it fails to return to levels seen in healthy individuals. The CD4 count soon after infection with HIV is a strong indicator of the subsequent risk of disease progression: in cases where the CD4 count stabilises at a level below 350, an individual has a higher short-term risk of disease progression.
It is generally assumed that there will be an interval of several years between initial infection with HIV and a fall in CD4 cell count to such levels that the initiation of HIV treatment is warranted. However, there is some evidence in recent years of patients having lower CD4 cell counts shortly after their infection with HIV, and of more rapid disease progression, requiring HIV treatment soon after diagnosis.
US investigators therefore analysed the initial CD4 cell counts of patients recently infected with HIV between 1985 and 2007. The study population was racially diverse and came from HIV treatment centres across the country.
A total of 2174 people were included in the investigators’ analysis. All had had an HIV-negative test result at most four years before their diagnosis with HIV.
The mean age was 29 years; 96% were men; 45% were African American, 44% white and 11% other ethnicities.
Just over a third (35%) were diagnosed with HIV within a year of a previous negative test result, 41% were diagnosed within one to two years of testing HIV-negative, 17% within two to three years, and 7% within three to four years. A CD4 cell measurement was taken within three months of HIV diagnosis in 90% of patients.
Changes in initial CD4 cell count were examined in four separate time periods: 1985 to 1990; 1991 to 1995; 1996 to 2001; and 2002 to 2007.
Between 1985 and 1990, the mean initial CD4 cell count of individuals recently infected with HIV was 632 cells/mm3. This fell to a mean of 553 cells/mm3 for the period 1991 and 1995, and to a mean of 493 cells/mm3 between 1996 and 2001. The figure then stabilised at a mean of 514 cells/mm3 between 2002 and 2007.
The fall in initial CD4 cell count between the period 1985 and 1990 and 1991 to 1995 was highly significant (p
Further analysis showed that the proportion of individuals with an initial CD4 cell count below 200 cells/mm3 (an AIDS diagnosis), and 350 cells/mm3, the point at which it is now recommended to start antiretroviral therapy, increased significantly between 1985 and 2001.
The investigators then conducted statistical analysis to control for possible confounding factors. This showed that compared to the period 1985 to 1990, initial CD4 cell count was 65 cells/mm3 lower in the period 1991 to 1995 (p 3 lower in the period 1996 to 2001 (p 3 lower in the period 2002 to 2007 (p
Similar declines were observed in initial CD4 cell percentage: from 30% in the period 1985 to 1990 to 28% between 1991 and 1995, and 27% in both the later time periods. Adjusted analysis showed that these falls in CD4 cell percentage were significant in all time periods.
Finally the investigators analysed the possible effect of race on their results. They found that in both African-American and white patients initial CD4 cell count declined by a mean of 111 cells/mm3.
“We observed that initial CD4 cell count among documented HIV seroconverters in the United States significantly decreased during the HIV epidemic,” write the investigators.
This decline reached a plateau after the use of antiretroviral therapy became widespread. The investigators speculate that the fall in initial CD4 cell counts was likely to be because HIV had evolved to become more virulent.
Crum-Cianflone N et al. Is HIV becoming more virulent? Initial CD4 cell counts among HIV seroconverters during the course of the HIV epidemic: 1985 – 2007. Clin Infect Dis 48: 1285-1292, 2009.