Zidovudine and lamivudine should be used instead of tenofovir or emtricitabine for pregnant women with HIV, according to a clinical practice guideline published in the BMJ. Additionally, the independent international panel recommends using alternative therapies in place of the combination of tenofovir, emtricitabine, and lopinavir/ritonavir.
Major guidelines currently recommend tenofovir and emtricitabine as a first-line therapy in pregnant women. However, recent data from the PROMISE trial, published in late 2016, demonstrated that tenofovir and emtricitabine may increase early prematurity, stillbirth, and neonatal death compared with zidovudine and lamivudine when combined with ritonavir-boosted lopinavir.
Reed Siemieniuk, MD, McMaster University, Hamilton, Canada, and University of Toronto, Canada, and a panel of experts used GRADE framework to make recommendations for the optimal choice of combination antiretroviral therapy for pregnant women with HIV. The patient-centered recommendations consider patient values and preferences, a balance of outcomes, patient uncertainty, and practical issues.
Key components of the guideline include:
- Zidovudine and lamivudine should be used instead of tenofovir or emtricitabine (weak recommendation). Alternatives should be used in place of the combination of tenofovir, emtricitabine, and lopinavir/ritonavir (strong recommendation).
- Tenofovir and emtricitabine increases the risk of early neonatal death and preterm delivery <34 weeks compared with zidovudine and lamivudine. The association is more certain when tenofovir and emtricitabine are combined with lopinavir/ritonavir.
- Almost all women place extremely high value on avoiding early neonatal death, and most women do not consider pill burden very important during pregnancy.
- Women with hepatitis B may be more likely to choose treatment based on tenofovir and emtricitabine if they have high risk of vertical hepatitis B transmission, severe anemia, drug allergies, or zidovudine or lamivudine resistant HIV or hepatitis B.
The panel notes that recommendations with a public health perspective, rather than an individual patient perspective, should consider resource use and may make different recommendations based on the same evidence. The WHO currently recommends a single tablet combination of tenofovir and emtricitabine plus efavirenz as the first-line combination regimen for all adults.
“Recommending alternative treatment options for women living with HIV who are pregnant may introduce operational challenges,” the authors note. “For example, many treatment programmes negotiate more affordable medication purchases in bulk. Other influential guidelines either have not yet had the opportunity to consider the evidence from the PROMISE trial or did not have the opportunity to consider the evidence systematically.”
Siemieniuk RAC, Lytvyn L, Ming JM, et al. Antiretroviral therapy in pregnant women living with HIV: a clinical practice guideline [published online September 11, 2017]. BMJ. doi:10.1136/bmj.j3961