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IAS 2015: Intensification of ART Reduces Risk of Late-term Mother-to-Child HIV Transmission

Maternal and infant antiretroviral therapy (ART) intensification is very effective in preventing HIV transmission during labor and birth from pregnant women with HIV in Thailand who present late for care, with less than 8 weeks of standard ART, Marc Lallemant reported at the 8th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2015) last month in Vancouver.

[Produced in collaboration with Aidsmap.com]

Overall, 88 mother/infant pairs took extra antiretrovirals in addition to a standard combination ART regimen (intensification) in this multicenter Phase 3 adaptive single-arm trial conducted from December 2011 to July 2014. There were no HIV transmissions during labor and delivery.

The longer a woman living with HIV has been taking antiretroviral treatment, the greater the chance of her attaining and maintaining an undetectable viral load. This greatly reduces the risk of transmitting HIV to her child. Pregnant women with HIV who are not seen in health care services until late in their pregnancy (often referred to as "presenting late") are at increased risk of transmission during delivery. Late diagnosis puts their own health at risk, as well as that of their child. Reasons for late diagnosis are many and include distance to health care facilities, lack of transportation, and fear of disclosure and stigma, as well as financial constraints. Maternal/infant ART intensification during and immediately following delivery may significantly reduce the risk of vertical transmission.

With the aim of preventing HIV transmission during labor and delivery, 88 pregnant women with HIV who had taken less than 8 weeks of standard combination ART using lopinavir/ritonavir (Kaletra), zidovudine (AZT or Retrovir), and lamivudine (3TC or Epivir) and their infants were given more antiretrovirals in addition to the standard regimen (intensification).

Women took a single dose of nevirapine during labor and continued with ART for 4 weeks. Formula-fed newborns received zidovudine, lamivudine, and nevirapine for 2 weeks, followed by 2 weeks of zidovudine and lamivudine instead of the standard one week of zidovudine.

Infants were tested for HIV at birth and then at 1, 2, 4, and 6 months. Intrapartum transmission was defined as a negative HIV DNA polymerase chain reaction (PCR) at less than 48 hours of age followed by a positive PCR result.

With data from 3737 mother/infant pairs, which included 84 transmissions during delivery, in 3 randomized perinatal HIV prevention trials (PHPT) undertaken in the same setting, Lallemant and colleagues defined a historical control and built an intrapartum transmission model. (The PHPT-5 trial comprising these 3 arms was stopped early due to changes in national and international treatment guidelines. However, while transmission rates were similar across the 3 arms, over 80% of the observed transmissions were among mothers who had received ART for a short time during pregnancy.)

Lallement outlined the principles of Bayesian inference, the method used to determine probability distributions. Unlike traditional scientific methods which assume no prior knowledge, this method comprises what data are known today [from the PHPT trials] (prior), what the new data could tell us, and what we would then know (posterior probabilities).

Viral load during pregnancy was modeled according to antiretroviral regimen. A logistic model predicted intrapartum transmission with viral load, maternal/infant antiretrovirals, delivery mode, and prematurity status as co-variables. Intrapartum transmission rates with and without ART intensification can then be predicted.

Of 1054 women screened, 336 consented and agreed not to breastfeed in accordance with national guidelines. 248 were observed and 88 received the intervention.

The women’s baseline characteristics at enrolment were similar with the exception of gestational age. Median age was 27.7 years and 26.3 years in the observed and intervention arms, respectively, with median CD4 cell counts of 359 and 379 cells/mm³, respectively.

Median gestational age at the start of ART was 19 weeks and 34 weeks in the observation and intervention arms, respectively. Median gestational age at delivery was approximately 38.6 weeks in both arms. However, the median duration of ART at delivery differed, 19.5 weeks and 4.3 weeks in the observed and intervention arms. In both groups, the percentage of women undergoing caesarean section was similar, 41.5 % and 36.4%, respectively. Median infant birth weight was also similar in both arms, 2.8 kg and 2.9 kg, respectively.

Infant intensification quickly followed the birth, with a median delay of 0.7 hours.

There were no HIV transmissions at the first interim analysis, but due to slow enrollment and corresponding small sample size (58), enrollment continued. At the second interim analysis (3 had been planned), with no further reported transmissions, the study's Data and Safety Monitoring Board (DSMB) recommended stopping enrollment, reporting the efficacy of intensification.

The posterior probability of transmission during delivery was 0.4% (95% credibility interval 0.1%-1.4% with intensification compared to 2.0% (0.3%-5.2%) without.

Intensification appeared safe, providing over 80% probability of a 2-fold reduced risk of HIV transmission (RR <0.5) and 94% probability of superiority over the standard of care (RR<1).

Lallemant and colleagues concluded that ART intensification for women presenting late in pregnancy and only having had a short course of antiretrovirals is very effective in preventing HIV transmission during labor and delivery.

8/5/15

Reference

M Lallemant, B Amzal, S Urien, et al. Antiretroviral intensification to prevent intrapartum HIV transmission in late comers.8th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention. Vancouver, July 19-22, 2015. Abstract MOAC0204.