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  20th Conference on Retroviruses and
Opportunistic Infections
Atlanta, GA March 3 - 6, 2013
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European cART Failure Rate During Pregnancy 19% and Falling Fast
  20th Conference on Retroviruses and Opportunistic Infections, March 3-6, 2013, Atlanta
Mark Mascolini
Combination antiretroviral therapy (cART) failed in nearly one fifth of pregnant women in Western Europe over the past decade, but that rate dropped steeply throughout the study period [1]. Treatment with an unboosted protease inhibitor (PI) and longer time since HIV diagnosis hiked the risk of failure.
Growing proportions of pregnant HIV-positive women in Western Europe are conceiving while taking cART. Virologic failure during pregnancy has weighty implications for the woman's health and for HIV transmission. Undetected failure can provoke emergence of resistant HIV, which may then be transmitted vertically.
To get a better understanding of rates and reasons for cART failure among HIV-positive pregnant women in Western Europe, University College London researchers conducted this study of 396 women who conceived on cART while enrolled in Western European sites of the European Collaborative Study between 2000 and 2011. All women had taken cART for at least 28 days before conception and had a viral load available after at least 24 weeks of uninterrupted therapy during pregnancy or within 28 days of conception. The researchers defined virologic failure as a viral load above 200 copies.
The 396 women had a median age of 33 years (interquartile range [IQR] 30 to 37), and 222 (56%) were from sub-Saharan Africa. Fifty-five women (14%) had a history of injecting drugs. About one third of women were having their first child and another third their second child. One third had a CD4 count below 350 when the count was first measured in pregnancy, and 23% had CDC stage C disease. A median of 5.5 years (IQR 2.9 to 8.6) had passed since HIV diagnosis, and women had taken their current regimen for a median of 1.5 years (IQR 0.9 to 2.6).
Half of all study participants were taking a PI regimen. The proportion getting a ritonavir boost to their PI rose from 17% (10 of 60) in 2000-2001 to 92% (22 of 24) in 2010-2011, a significant change (P < 0.01). While 37% of women were taking a nonnucleoside-based regimen (usually nevirapine), 11% were taking a nonnucleoside plus a PI, and 2% were taking three nucleosides.
Women had their viral load measured a median of 18.5 months after starting their current regimen at a median of 13.2 weeks of gestation. Those assays documented virologic failure in 74 of 396 women (19%) at a median viral load of 1370 copies (IQR 480 to 6000). Timing of viral load testing did not differ significantly between women with detectable versus undetectable viral loads (P = 0.74). The proportion of women with virologic failure dropped 10-fold from 34% (32 of 93 women) in 2000-2001 to 3% (1 of 33) in 2010-2011 (P < 0.01). Of the 74 women with virologic failure, 64 (86%) enrolled in their cohort before 2006.
Poisson regression analysis adjusted for country of delivery and cART duration identified three factors associated with a higher risk of virologic failure and two factors associated with a lower risk, at the following adjusted prevalence ratios (aPR) (and 95% confidence intervals [CI]):
Higher risk of failure:
Two or more pregnancies during cohort enrollment vs none: aPR 3.08 (1.49 to 6.36), P < 0.01
Unboosted PI vs nonnucleoside: aPR 2.26 (1.28 to 4.00), P < 0.01 Every additional year since HIV diagnosis before conception: aPR 1.06 (1.01 to 1.10), P < 0.01
Lower risk of failure:
Every additional year of age: aPR 0.95 (0.91 to 0.99), P = 0.02
Every later calendar year of delivery: aPR 0.80 (0.72 to 0.89), P < 0.01
Taking a boosted PI regimen rather than a nonnucleoside regimen tended to raise chances of virologic failure (aPR 1.90, 95% CI 0.96 to 3.78, P = 0.07). Sub-Saharan origin and injection drug use history did not affect chances of virologic failure in the multivariate analysis.
Among 291 women with data from late pregnancy, 271 (94%) were virologically suppressed to within 4 weeks of delivery. Among 65 women with virologic failure and continued follow-up, 41 (63%) regained virologic suppression at a median 32.8 weeks of gestation. Virologic resuppression improved from 36% (10 to 28 women) in 2000-2001 to 80% (8 of 10) in 2006-2011 (P < 0.01).
The researchers speculated that virologic failure may have become less common over time independently of cART type because regimens became more tolerable, pill burden eased, adherence support improved, and treatment options grew. The investigators proposed that groups they identified at higher risk of virologic failure during pregnancy may need closer monitoring and better adherence support.
1. Bailey H, Townsend C, Cortina-Borja M, et al. Trends and factors associated with virological failure among women conceiving on cART: Western Europe. 20th Conference on Retroviruses and Opportunistic Infections. March 3-6, 2013. Atlanta. Abstract 909. http://www.retroconference.org/2013b/PDFs/909.pdf