Lower HIV viral load in women in the early years of HIV infection cannot be explained by the sex-based differences in the strength of HIV-specific CD8 cell response, according to a small US study published in the March 15th edition of The Journal of Infectious Diseases. The investigators did however find that the strength of CD8 cell response in women was associated with a lower CD4 cell count than that seen in men five to seven years after initial infection with HIV.
Several studies have demonstrated a close relationship between HIV viral load and the strength of HIV-specific CD8 cell response. In the period after initial infection with HIV, CD8 response is associated with control of HIV replication and a lower viral load. Loss of CD8 cell response is associated with increased levels of HIV and faster disease progression.
Investigators hypothesised that the lower HIV viral load seen in women in the early years of HIV infection was associated with a stronger CD8 HIV-specific response than that seen in men. They also reasoned that the strength of this response weakened in women during the course of HIV infection, just as sex-based differences in viral load diminished.
To test these hypotheses investigators studied frozen blood samples obtained between 1988 and 1989 from injecting drug users enrolled in a longitudinal study. A documented date of HIV seroconversion was available for all the blood samples. Frozen blood samples were available for two time periods: period A, zero to two years after the estimated date of HIV seroconversion and period B, five to seven years after initial infection with HIV.
The date of HIV seroconversion was estimated as the midpoint between the individuals’ last negative HIV test and the date of their HIV diagnosis.
A total of 18 men and 15 women were included in the investigators analysis. During period A the investigators were surprised to see that more men (39%) had a CD8 HIV-specific response than women (13%). By period B, 67% of both men and women had a CD8 HIV-specific response.
Although viral load was higher in men than women at both period A (approximately 30,000 copies/ml versus 15, 000 copies/ml, p = 0.94) and period B (58,000 copies/ml versus 43, 000 copies/ml, p = 0.84), at neither period was the difference significant.
In addition, the investigators were surprised to see that at time B a strong HIV-specific CD8 cell response was associated with a significantly lower CD4 cell count in women (p = 0.05).
“The most significant finding of this study was that a correlation between immune status and CD8 effector response was found in women but not men, particularly at time B”, write the investigators, adding “in women, but not men, a stronger CD8 effector response was associated with a lower number of CD4 lymphocytes.”
The investigators’ initial hypotheses, that lower HIV viral load in women would be associated with stronger HIV-specific CD8 cell response was not confirmed, in fact, although the difference was not statistically significant, men were found to have a stronger HIV-specific CD8 cell response at period A.
Sterling TR et al. Sex-based differences in T lymphocyte responses in HIV-1-seropositive individuals. J Infect Dis: 191: 881 – 885, 2005.