Levels of HIV RNA in rectal mucosa secretions from men who have sex with men (MSM) are higher than those in blood and semen, according to a study presented in the July 1st edition of The Journal of Infectious Diseases. The results suggest that unprotected insertive anal intercourse may involve exposure to higher levels of free virus than previously believed, even where the receptive partner's plasma viral load is undetectable on HAART.
In contrast to previous studies, which have examined HIV levels in rectal biopsies (tissue samples) or swabs from the anus in men with suppressed viral loads, this study looked at secretions from the rectum in a group of men with varying degrees of viral suppression and antiretroviral drug exposure.
“HIV RNA was often found at high levels in rectal secretions, even in men receiving antiretroviral therapy, and paired HIV RNA levels in rectal secretions were greater than those in either the blood or seminal plasma among HIV-infected MSM,” state the authors. Furthermore, “antiretroviral therapy had a greater direct effect on levels of HIV in seminal plasma than in rectal secretions.”
The investigators recruited 64 HIV-positive MSM from sexually transmitted disease clinics in Seattle, USA, and Lima, Peru between December 1999 and January 2001. Twenty-seven (42%) of the men had been on a stable antiretroviral regimen for at least 30 days, and the remainder were drug-naive.
HIV viral loads were measured two to three times over four weeks in swabs taken from the rectum, and in the blood and semen. Because the samples were diluted at different ratios, the lower limit of detection was not equal in the three samples (rectal secretions: 8000 copies/ml; blood: 400 copies/ml; semen: 800 copies/ml). However, the authors used a mathematical correction to estimate the distribution of viral loads in samples below the limits of detection.
Overall, HIV viral loads were higher in rectal secretions (median 91,200 copies/ml) than in blood (median 17,400 copies/ml; p < 0.05) or semen (median 3550 copies/ml; p < 0.05). Nevertheless, HIV viral loads in the blood were correlated with those in the rectum (p < 0.001) and the semen (p < 0.001).
A similar pattern of viral loads was observed in the men who were taking antiretroviral therapy. Rectal secretions contained a median of 3980 copies/ml, compared with 200 copies/ml in blood (p < 0.05) and 1000 copies/ml in semen (p < 0.05). Ten (37%) of 27 rectal samples from these men had detectable viral loads, nine (35%) of 26 blood samples, and eleven (55%) of 20 semen samples, a much higher level than observed in most other studies, the authors note.
In the men who were not taking antiretroviral therapy, HIV viral loads differed significantly among all three samples, with rectal secretions containing the highest viral loads (median 316,000 copies/ml), compared with a median of 63,100 copies/ml in the blood and 12,600 copies/ml in semen (p < 0.05 for all comparisons). These men also had higher rates of detectable viral loads in the rectum (35 [95%] of 37 samples; p < 0.05), and blood (37 [100%] samples; p < 0.05), but not in the semen (28 [78%] of 36 samples; p = 0.08).
Using mixed-effects model analysis without controlling for blood viral loads, the authors demonstrated that the use of antiretroviral therapy caused a 1.3-log10 reduction in rectal viral loads (p < 0.001) and a 1.4-log10 reduction in seminal viral loads (p < 0.001). Lower CD4 cell counts were also associated with higher viral loads in both samples (p = 0.03 and 0.004 respectively).
When blood viral loads were included in the model, the authors found that a one-log10 reduction in blood viral loads caused a 0.5-log10 reduction in both rectal and seminal viral loads (p = 0.006 and 0.02 respectively). However, use of HAART was found to reduce viral loads in the semen, but not rectal secretions (p = 0.003 and 0.5 respectively).
This leads the authors to suggest that the effect of HAART on rectal viral load occurs as a result of viral load reductions in the blood. In contrast, antiretrovirals may affect viral levels in the semen directly. This “may be due to differential levels of antiretroviral drugs or to anatomic and immunologic differences in the male genital tract versus rectal mucosa.”
Reference
Zuckerman R A et al. Higher concentrations of HIV RNA in rectal mucosa secretions than in blood and seminal plasma, among men who have sex with men, independent of antiretroviral therapy. J Infect Dis 189: 156-161, 2004.