January 1997
Correlation of Cell-free and Cell-associated HIV RNA
Levels in Plasma and Vaginal Secretions
Presenter: T Hart, CDC, Atlanta
Effect of Antiretroviral Therapy on Vaginal HIV RNA
Level
Presenter: Lennox, CDC, Atlanta
The presence of HIV in genital secretions (semen, cervicovaginal
mucous, vaginal lubricating secretions, rectal secretions) is vital for
sexual transmission, whether as proviral DNA in infected cells or as
free virus detected as viral RNA. While epidemiologic studies have
clearly shown that other sexually transmitted diseases increase both the
risk of transmitting HIV, and the risk of catching HIV during sex, many
questions remain. How do STD's increase transmission? Does viral load
in the blood correlate with infectiousness? Perhaps most pressingly,
does lowering viral load in the blood lower it in the genital
secretions, and if so, is a person with an undetectable viral load still
infectious?
A lot of information was presented at the conference on HIV and genital secretions, and for now, the answer seems clear that even people with undetectable viral loads are infectious. Safe sex is still essential (Please don't kill the messenger). However, potent antiviral agents do lower the levels in semen and in vaginal secretions, and this may have a public health impact. It also confirms that potent multidrug regimens are also lowering the amount of HIV in compartments other than blood (see report on David Ho's talk).
A paper from the University of Washington investigated the effect of genital herpes outbreaks on the presence of HIV on the genitals of HIV infected persons, and found that herpes dramatically increased the presence of HIV. Twelve HIV-infected men were followed and genital swabs were obtained both during outbreaks and asymptomatic periods. Swabs from herpes lesions were positive for HIV RNA (free virus) in 96% of outbreaks. Half of the swabs from lesions had more than 5,000 copies. HIV was found from herpes lesions both from men with high viral loads and very low viral loads. This clearly helps explain why genital herpes is a cofactor in HIV transmission. By extension, controlling herpes may help decrease sexual transmission of HIV.
A group from the Centers for Disease Control and Emory University headed by Ted Ellerbrock has launched an ambitious study of women's health and HIV, called the EVE study. At this meeting they reported on the correlation of HIV in the vagina with plasma HIV RNA as measured by a 10 cc cervicovaginal washing. All patients had detectable plasma HIV RNA. Cell free virus was detected in 67% of women and cell associated virus in 63%. Viral loads in vaginal washings ranged from 453 to 100,000 copies. The amount of virus in vaginal washings correlated with plasma viremia, meaning that those with the highest plasma viral load had the highest levels in vaginal washings. This fits with what is known about viral load and mother to infant transmission, and would suggest that sexual transmission will be more likely from women with higher viral loads.
In a nested case control study, this group reported on the changes in viral load in vaginal washings after initiating or changing antiretroviral therapy in 14 women. Changes included adding or changing 1 drug (6 women) and adding or changing 2 or 3 drugs (8 women). Changes were modest in the group with 1 new drug. In contrast, 6/6 women had RNA drop to undetectable levels after adding or changing 2 or 3 drugs. It must be pointed out though that this technique probably has a fairly high limit of detection, since 10 cc of saline is washed in the vagina, and only a small amount of genital secretions are likely to be obtained in the washings. In addition, cell associated virus (cDNA) is still present. Nonetheless, the message seems to be that combinations which can lower plasma viral load most effectively are likely to have the greatest impact in a woman's genital tract.
HIV in genital secretions - Part 2 deals with semen - which is of particular interest since the testicles could be a "sancturary" site where drugs penetrate poorly.