Disagreement over best treatment regimes for pregnant women with HIV
A BMJ international panel made up of women living with HIV, specialist doctors, and general practitioners recommends non-tenofovir based treatment regimes for pregnant women living with HIV.
Clinical practice guidelines published by the BMJ (formerly known as the British Medical Journal) support the use of older antiretroviral treatment (ART) combinations for pregnant women living with HIV over current guidelines which recommend the treatment backbone tenofovir/emtricitabine (FTC) – the most commonly prescribed antiretroviral combination and recommended by the World Health Organization (WHO) and the US Centers for Diseases Control (CDC).
The BMJ’s guidelines now ‘strongly recommend’ tenofovir/FTC be discontinued in women living with HIV, because of an increased risk of stillbirth and neonatal mortality, while making a ‘weak recommendation’ that the older nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) backbone zidovudine (AZT)/ lamivudine be used instead.
The BMJ Rapid Recommendations take a patient-centred approach to treatment guidelines, based on evidence that reveal pregnant women prefer to prioritise their unborn child’s health when considering antiretroviral treatment options. This differs from the public health approach taken by bodies such as the WHO, who must take into account resources, treatment availability and operational factors in their treatment recommendations.
The BMJ guidelines were developed as a result of a systematic review that compared tenofovir-based regimens on maternal and child health outcomes with alternative NRTIs.
The recommendations drew largely from evidence from the Promoting Maternal and Infant Survival Everywhere (PROMISE) trial, published in late 2016. The PROMISE trial compared the efficacy of zidovudine with single-dose nevirapine, and a protease inhibitor-based regime of ritonavir-boosted lopinavir using AZT/3TC or tenofovir/FTC backbone to prevent mother-to-child transmission in women.
The BMJ panel judged with moderate certainty that tenofovir/FTC —when combined with lopinavir/ritonavir in the doses used in the PROMISE trial—increased stillbirth and early neonatal mortality compared with AZT/lamivudine, as well as early premature labour before 34 weeks gestational age.
Another systematic review, published at the same time, found pregnant women’s ART preferences to be influenced by a number of factors, including risk of onward HIV transmission, child’s health, side-effects for both mother and child, and pill burden. But ultimately, it was the health outcomes for the child that was the most important factor for expectant mothers.
In an accompanying BMJ Opinion article, Alice Welbourn, founding director of the Salamander Trust said that women should be given all the options to make choices based on their own desires.
“Women’s rights to informed choices about what happens to their bodies are often contested—especially if they are pregnant or have HIV. Yet informed choices about risks and benefits form a critical part of long term prognosis,” said Welbourn.
But the Rapid Recommendations have been criticised by some. Simon Collins of i-base called the systematic review ‘controversial’. “The BMJ review has significant methodological problems that also challenge the paper's conclusion,” he commented.
The British HIV Association (BHIVA) also issued a statement declaring that it does not agree with the BMJ recommendations, stating that numerous other trials have shown tenofovir to be safe for pregnant women living with HIV.
“As both arms received lopinavir/ritonavir the BMJ panel postulates that tenofovir/emtricitabine is the cause of the difference. Despite the BMJ panel’s assertion that pharmacokinetic interactions between tenofovir and lopinavir/ritonavir are not relevant there are data reporting increased levels of both drugs in the host when co-administered at standard doses,” said the BHIVA.
What all parties agreed on, however, is that women should be included in the discussion about what antiretroviral treatment works best for them. But in some contexts, drug availability may mean that this is not plausible.