An ongoing dialogue on HIV/AIDS, infectious diseases,
October 15th, 2017
The Best Antiretroviral Therapy for Pregnant Women? The Controversy Continues
There’s considerable controversy in an area of HIV medicine that one would think should be all but solved by now.
It’s what HIV treatment we should give pregnant women.
The issue isn’t how to prevent the virus from being transmitted to the newborn — suppress the virus in mom, baby doesn’t get it — it’s what’s safest for the pregnancy outcome.
The uncertainty spills over to the HIV perinatal guidelines, which are notable for how different they are from those for non-pregnant adults:
Taken literally, these guidelines would support a regimen of ABC/3TC and twice-daily DRV/r for a pregnant woman — something we’d never prescribe a non pregnant treatment-naive patient for several obvious reasons.
Additionally, there is only one integrase inhibitor-based regimen — TDF/FTC, raltegravir — while INSTI-based regimens dominate the general recommendations for HIV treatment. There just aren’t enough data yet on the use dolutegravir in pregnancy, though we did see some encouraging information during the IAS meeting this summer. And information on tenofovir alafenamide are scant.
Now, potentially making HIV treatment during pregnancy even more divergent from standard-of-care, non-pregnancy treatment, comes a surprising new set of recommendations from the British Medical Journal.
Entitled Antiretroviral therapy in pregnant women living with HIV: a clinical practice guideline, the paper recommends using zidovudine/lamivudine over tenofovir DF/emtricitabine during pregnancy:
Here’s their stated reason for this surprising recommendation:
Tenofovir and emtricitabine probably increase the risk of early neonatal death and preterm delivery <34 weeks compared with zidovudine and lamivudine; this is more certain when they are combined with lopinavir/ritonavir.
Importantly, most of the data they cite in support of this recommendation come from the PROMISE study, which did show higher rates of very preterm delivery before 34 weeks and early infant death with TDF/FTC compared with ZDV (a.k.a. AZT)/3TC. But an important caveat is that the drugs were given with LPV/r at high dose, a regimen we rarely use today, and which substantially increases tenofovir levels.
The authors of the PROMISE study themselves responded to the BMJ piece, stating that they do not agree with the recommendation to use ZDV/3TC over TDF/FTC for several reasons. While I encourage people interested in this topic to read their full comment, they cite important observational data on the use of TDF/FTC/EFV:
Compared with a regimen of TDF-emtricitabine (FTC)-EFV, all other regimens, including AZT-based ART, were associated with higher risk of adverse outcome; increased risk of preterm birth, very preterm birth and neonatal death were observed for infants exposed to AZT-lamivudine (3TC)-lopinavir-ritonavir.
Plus, we can add to these reassuring data a new paper, just published in the Journal of Infectious Diseases. In a prospective evaluation of 422 pregnancies, the researchers found that TDF was not associated with adverse perinatal outcomes, and that preterm birth occurred less frequently among pregnancies exposed to TDF.
My take? We know from thirty years (yep, it’s been that long) of experience that ZDV has considerable toxicity — subjective side effects such as nausea and headache, and additional problems related to mitochondrial toxicity, including bone marrow suppression, lipoatrophy, and lactic acidosis.
As a result, it’s very hard to imagine prescribing zidovudine again under any circumstances, including during pregnancy. Today, the most commonly used initial regimen at our hospital during pregnancy is TDF/FTC and raltegravir; if patients are on a successful treatment and become pregnant, we generally continue that, almost regardless of what it is.
And we eagerly await the results of a three-arm study in pregnant women, led by my colleague Shahin Lockman, which is just getting started. It compares TAF/FTC plus dolutegravir, TDF/FTC plus dolutegravir, and TDF/FTC/EFV.
This, we hope, will move treatment of pregnant women with HIV closer to the treatment we offer non-pregnant adults.