Genital tract viral load in women with below detectable plasma viral load

Polly Clayden, HIV i-Base

Plasma viral load levels are frequently used as surrogate markers for genital tract viral loads when quantifying transmission risk – both sexual and mother to child – in HIV-positive women.

A paper, authored by Susan Cu-Uvin and published ahead of print in AIDS showed findings from an investigation to determine patterns of genital tract shedding in women receiving HAART with viral loads below detection in plasma.

The study enrolled women who had undetectable plasma viral load (< 80 copies/mL) for 6 months and were receiving care at the Miriam Hospital Immunology Centre, Providence, Rhode Island, USA.

The investigators measured paired plasma and genital tract viral loads every four weeks. Women were classified as persistent (at least two consecutive monthly visits with detectable genital tract viral load), intermittent (detectable genital viral load on visits preceded and followed with undetectable) or non-shedders (undetectable genital viral load). They used longitudinal analysis to investigate rates of genital tract shedding and the association with plasma viral load, CD4 count and genital tract infections. Markov transition models were used to describe the temporal dynamics of viral load in the
plasma and genital tract.

Out of 62 women who completed screening, 59 women contributed 582 study visits. Of these 95% and 98% had undetectable plasma and genital tract viral load respectively. Their median baseline CD4 was 458 cells/mm3 (range 120-1346). About half (49%) were receiving NNRTI-based regimens and the majority of the remainder (42%) protease inhibitor-based HAART.

Thirty-two of the 59 women (54%) had at least one detectable genital tract viral load measurement during the study period and 22/59 (37%) had detectable genital viral load when plasma viral load was undetectable. Four women (6.8%) were classified as persistent shedders, 18 (31%) as intermittent shedders and 27 (46%) as nonshedders.

When the investigators sampled three subcompartments, genital viral load detection increased compared to a single compartment. It was more likely (72% of visits) for just one subcompartment to have HIV shedding than more than one subcompartment, p=0.05. They found the maximum viral load measurement in the genital tract when viral load was undetectable was 456,000 copies/mL in the endocervix, 648,000 copies/mL in the ectocervix and 480,000 copies/mL in the vagina.

Overall the estimated probabilities of genital tract shedding were between 6 and 8% of visits in each of the three subcompartments. Genital shedding in at least one subcompartment was estimated to occur at 13% of visits (95% CI 9-18%). This occurred in 9% (95% CI 6-14%) of visits when plasma viral load was undetectable. Genital tract viral load was significantly more likely to be detectable when plasma viral load was detectable at the previous visit OR 2.15 (95% CI 1.1-4.3) but plasma viral load was not significantly more likely to be detectable when genital tract viral load was detectable at the previous visit OR 0.91 (95% CI 0.27-3.1).

The investigators wrote: “The findings of the present study add to the growing evidence that in the HAART era, women with below detection plasma viral load may have less risk of HIV sexual transmission on a population level, but may continue to be possibly infectious on an individual level.”

Ref: Susan Cu-Uvin et al. Genital tract HIV-1 RNA shedding among women with below detectable plasma viral load. AIDS 2010, Vol 24. Published ahead of print 25 August 2010.

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