High genital HIV levels may persist in women who appear to achieve viral suppression with use of ART

HIV-positive women whose plasma HIV RNA viral loads drop to undetectable levels following initiation of ART still may have intermittent surges in the amount of virus in their genital secretions, according to a US study.

The study analysed changes over the course of one year in the plasma and genital tract HIV levels of US women taking ART. The journal AIDS has published the findings in an online article released in advance of print publication.

The findings have important HIV prevention implications in light of recent debates about the extent to which HIV-positive people with undetectable plasma viral load are still at risk of transmitting HIV to others.

In particular they highlight the need for evidence of viral load levels in genital secretions to be measured longitudinally in studies which monitor rates of HIV transmission in HIV-discordant sexual partnerships. Gathering these data would permit a better understanding of the clinical significance of episodic shedding of HIV in genital fluids when plasma viral load is suppressed.

Women who had plasma HIV viral load levels below 75 copies/mL at least six months before being screened for the study were eligible to participate. Fifty-nine women who met this requirement, all patients at an HIV clinic in the US state of Rhode Island, contributed a total of 582 study visits at which they underwent plasma and genital tract viral load testing.

More than half of all study participants had detectable genital tract viral load levels (>3300 copies/mL), a condition referred to as “HIV shedding,” at least once during the study period. Almost 40% of women had HIV shedding when HIV was undetectable in plasma.

Among women who had not undergone hysterectomies, the highest genital viral load levels observed in conjunction with undetectable plasma viral load were 456,000 copies/mL in the endocervix; 648,000 copies/mL in the ectocervix; and 480,000 copies/mL in the vagina.

The endocervix, ectocervix and vagina had about the same likelihood of yielding samples with detectable viral load during plasma viral load suppression.

Researchers tested vaginal samples from women who had undergone hysterectomies. In that group, the highest vaginal viral load level when HIV was undetectable in plasma was 68,000 copies/mL.

Researchers considered the potential role of STIs in increasing genital tract HIV shedding, but data on STIs in the study population did not suggest associations of that nature.

Overall, women without hysterectomies had HIV shedding in at least one of the three parts of the vaginal tract at 9% of study visits at which they also had undetectable plasma viral load levels (95% CI, 6% – 14%). Shedding was observed at 13% of all study visits (95% CI, 9% – 18%).

A component of the study looked at genital tract HIV levels over time in women who maintained undetectable plasma HIV viral load levels (less than 80 copies/mL) for at least three consecutive study visits.

Researchers assigned those women one of three classifications.

• “Persistent shedders” were those who had at least two consecutive study visits with undetectable plasma HIV levels but detectable genital tract HIV levels.

• “Intermittent shedders” had undetectable plasma HIV levels but detectable genital tract HIV levels at one visit in between two visits at which both genital tract and plasma HIV levels were undetectable.

• “Nonshedders” never had detectable HIV in the genital tract at the same time that their plasma viral load was below the level of detection.

Four of the 59 study participants (6.8%) were found to be persistent shedders; 18 (31%), intermittent shedders; and 27 (46%), nonshedders. The remaining 10 women did not meet the criterion of having three consecutive study visits with undetectable plasma viral load levels.

Researchers compared the combined group of persistent and intermittent shedders to nonshedders to try to identify sociodemographic and health-related factors that might help account for variations in genital viral load levels.

Women with hysterectomies, who constituted 19% of the study population, were less likely than other women to have genital HIV shedding (risk ratio 0.14, 95% confidence interval [CI], 0.02 – 0.99). No other differences were observed, but researchers noted that some other risk factors could not be ruled out on the basis of the statistical results.

In the full study cohort, having detectable plasma HIV viral load increased the odds of having detectable genital tract HIV viral load at the next visit. The inverse was not true – a detectable genital tract viral load level did not predict a subsequent detectable plasma viral load level.

Antiretroviral treatment failure was not an outcome for any study participant experiencing detectable genital tract HIV levels at the same time that plasma HIV levels were undetectable.

The paper suggests that the “episodic, unpredictable nature of genital tract shedding” in study participants with undetectable plasma HIV viral load levels may make it difficult to assess the HIV transmission risk in such situations.

It concludes, “Whereas genital tract shedding is primarily driven by plasma viremia, clinicians may not be able to solely rely on [ART] to eradicate the potential for the sexual and perinatal transmission of HIV.”

Cu-Uvin S et al. Genital tract HIV-1 RNA shedding among women with below detectable plasma viral load. AIDS: advance online publication, August 31, 2010. DOI: 10.1097/QAD.0b013e32833e5043. (Link to abstract and full text article).