Women who take NNRTI have more cervical HIV shedding than those who take a PI

A substantial number of antiretroviral-treated women with an undetectable or very low (below 500 copies/ml) plasma viral load were nevertheless shedding potentially infectious amounts of HIV from their cervix in an American study published in the January 1^st edition of the Journal of Acquired Immune Deficiency Syndromes. In addition, the investigators found that women who took a non-nucleoside reverse transcriptase inhibitor (NNRTI) were more likely to have cervical shedding of HIV than women who took a protease inhibitor as part of their HIV treatment regimen. Use of illicit drugs such as crack, cocaine and heroin was also associated with cervical HIV shedding.

Cervical shedding of HIV points to the potential for HIV transmission during vaginal intercourse and during childbirth, even when a woman has undetectable plasma viral load.

Investigators from the ongoing Women Interagency Health study (WIHs) have previously shown that as many as a third of women who are taking virologically successful HIV therapy have detectable HIV in their cervixes. Studies involving men have shown that antiretrovirals have differing penetration into the genital tract and the WIHs study hypothesised that this would also be the case with women.

The WIHs investigators therefore conducted a retrospective analysis of cervical swabs obtained from 290 antiretroviral-treated women who either had an undetectable plasma (below 50 copies/ml) or a very low plasma viral load (between 50 – 500 copies/ml) to see if any factors could predict cervical shedding. In particular, they wished to see if women taking different antiretroviral regimens were more or less likely to be shedding HIV in the cervix.

The investigators stressed the importance of this research, writing that vertical and sexual transmission of HIV is known to have occurred when a woman had an undetectable plasma viral load and it was important to understand if this was connected with the use of particular treatment strategies.

Of the 290 in the study, 44 (15%) had cervical shedding of HIV. This included 23 (13%) of women taking a protease inhibitor and 21 (19%) of the women receiving therapy with an NNRTI. Analysis also revealed that women who had had more than one recent male sexual partner, as well as women who smoked, or used illicit drugs were also more likely to have cervical HIV shedding. Although there was no link between genital inflammation or a current sexually transmitted infection and cervical HIV shedding, the investigators did find an association between the shedding of HIV from the cervix and a past history of syphilis.

In multivariate analysis, the investigators found that women who took an NNRTI as opposed to a protease inhibitor were significantly more likely to be shedding HIV from the cervix (p

Although they did not monitor the levels of individual antiretrovirals in the cervix, they write that their findings appear to be consistent with some earlier pharmacokinetic studies. In particular they note that efavirenz (Sustiva) has been shown to have poor penetration into the genital tract. But they also record they did not expect to find that women treated with a protease inhibitor had lower cervical shedding of HIV “given the reportedly decreased protease inhibitor penetration into female genital secretions.”

They conclude, “the finding of more frequent cervical viral RNA shedding among women treated with an NNRTI-based antiretrvorial regimen deserves further prospective investigation.”