Viral load in vaginal fluid

There have been fewer studies in women, compared to men, examining the association between viral loads in the blood plasma with that in the genital tract . Although genital tract viral load will usually mirror the plasma viral load there is some evidence of compartmentalisation between the plasma and genital tract. Consequently, antiretroviral therapy may not always result in an undetectable viral load in the female genital tract, even when a genital infection is not present.

The largest study so far included 122 women in Italy¹ who were divided into four categories according to their experience of antiretroviral therapy: 55 women were naive to therapy; 21 women were taking a break from antiretroviral treatment due to treatment failure; 19 women were on treatment with one or two NRTIs; and 28 were on highly active antiretroviral therapy (HAART). 

Since the study only compared viral loads during a single time-point, it could only provide a 'snapshot' of the association between viral load in plasma and genital fluids.  It found that the higher the blood plasma viral load, the more likely cervicovaginal viral load would also be detectable, but that it was possible to have discordant viral loads in either compartment.

Whereas all of the women taking a break from treatment had detectable HIV in both plasma and cervicovaginal secretions, and most of the treatment-naive women had detectable HIV in both plasma (83%) and cervicovaginal secretions (79%), almost three quarters of the women on non-HAART regimens had detectable plasma viral load (73%) and detectable (78%) cervicovaginal viral load, and 50% of women taking HAART had a detectable plasma viral load with 40% having detectable HIV in cervicovaginal secretions.

However, all of the women with an undetectable plasma viral load who were on HAART also had undetectable cervicovaginal viral loads. This was not the case for the four treatment-naive women and three women on non-HAART regimens who had undetectable plasma viral loads – all still had evidence of cervicovaginal shedding.

In 14 women the opposite was true – an undetectable HIV viral load in their cervicovaginal secretions, but a detectable viral load in their plasma. Six of these women were naive to therapy, two were on non-HAART regimens and six were taking HAART.

A later US longitudinal study in 97 women² confirmed these findings: blood HIV levels were directly linked to the amount of virus shed in the genitals. Women who had detectable blood levels were almost 14 times more likely to have virus in the genital tract than women who had undetectable blood levels. As the blood virus levels rose and fell, so did the levels in the genital tract. The study also found that virus levels in the genital tract seem to lag slightly behind those in the blood. When women achieved undetectable virus levels in both the blood and vagina, rebound of virus occurred in the blood first or at about the same time

In addition, all of the women with an undetectable viral load in the blood, and who were on HAART, also had undetectable cervicovaginal viral loads. Although some women not on treatment achieved undetectable plasma viral loads, some still had evidence of cervicovaginal shedding – 5% of the time there were greater levels of virus in the vagina than in the blood.

Successful antiretroviral therapy, however, cannot guarantee that there will be no cervicovaginal shedding. A four-week study of 20 sex workers in Mombasa, Kenya,³ thirteen of whom had a sexually transmitted infection at baseline, found that genital shedding of HIV decreased rapidly after starting antiretroviral therapy. Although HIV was detectable in both the cervical (median 5000 copies/ml) and vaginal (6000 copies/ml) secretions of all the women at baseline, these levels were significantly lower than in plasma (> 300,000 copies/ml). Within two days of starting antiretroviral therapy, median cervical viral load fell to 650 copies/ml, and then fell below 50 copies/ml where it remained for the duration of the study; median vaginal viral load fell to 250 copies/ml by day four, and by day 14 it was undetectable. However, seven women (35%) continued to have detectable viral load in their genital secretions at the end of the study.

Although antiretroviral treatment significantly reduced the frequency of genital shedding of HIV in a study conducted in Burkina Faso,⁴ HIV remained detectable in the genital tract of a significant proportion of women even when they had an undetectable viral load in their blood. However, all the women in the study were infected with the genital herpes virus HSV-2, and it is known that this can increase genital shedding of HIV.

Other studies have found that viral load in the female genital tract can vary during the course of a menstrual cycle, even among women on antiretroviral treatment. A 2004 study of viral load changes during the menstrual cycle⁵ found that viral load levels in vaginal fluid tended to peak at the time of menstruation and fell to the lowest level just prior to ovulation.

The role of drug penetration into the female genital tract is still not well understood. In a study of 34 women in the US,⁶ even though PIs and NNRTIs appeared in much lower concentrations in the female genital tract compared to the blood, viral load remained suppressed in the genital tract of all the women with undetectable viral loads in the blood, regardless of the individual components of their antiretroviral regimen. Similar to studies in semen, drugs from the NRTI class of antiretrovirals were found to achieve good concentrations in the female genital tract and particularly high concentrations of 3TC (lamivudine, Epivir) and tenofovir (Viread) were observed.