Efavirenz Conceptions and Regimen Management in a Prospective Cohort of Women on Antiretroviral Therapy

Sheree Schwartz,Shruti Mehta,Taha E Taha,Vivian Black,Willem Daniel Francois Venter,Helen Rees

doi:10.1155/2012/723096

Abstract

Use of the antiretroviral drug efavirenz (EFV) is not recommended by the WHO or South African HIV treatment guidelines during the first trimester of pregnancy due to potential fetal teratogenicity; there is little evidence of how clinicians manage EFV-related fertility concerns. Women on antiretroviral therapy (ART) were enrolled into a prospective cohort in four public clinics in Johannesburg, South Africa. Fertility intentions, ART regimens, and pregnancy testing were routinely assessed during visits. Women reporting that they were trying to conceive while on EFV were referred for regimen changes. Kaplan-Meier estimators were used to assess incidence across ART regimens. From the 822 women with followup visits between August 2009–March 2011, 170 pregnancies were detected during study followup, including 56 EFV conceptions. Pregnancy incidence rates were comparable across EFV, nevirapine, and lopinavir/ritonavir person-years (95% 100/users (P = 0.25)); incidence rates on EFV were 18.6 Confidence Interval: 14.2–24.2). Treatment substitution from EFV was made for 57 women, due to pregnancy intentions or actual pregnancy; however, regimen changes were not systematically applied across women. High rates of pregnancy on EFV and inconsistencies in treatment management suggest that clearer guidelines are needed regarding how to manage fertility-related issues in. women on EFV-based regimens.

Highlights

HIV reduces fertility, an increase in pregnancy incidence has been documented in HIV-infected women using antiretroviral therapy (ART) [1,2,3]
Efavirenz-related pregnancy concerns are largely based on a study in cynomolgus monkeys in which anencephaly, a neural tube defect (NTD), was linked to EFV exposure during pregnancy; a case of microphthalmia and one case of cleft palate were observed in the monkeys exposed to EFV [5]
EFV remains contraindicated during the first trimester of pregnancy in South African guidelines, the pregnancy incidence rate on EFV was very high, 18.6/100 PY

Summary

Introduction

HIV reduces fertility, an increase in pregnancy incidence has been documented in HIV-infected women using antiretroviral therapy (ART) [1,2,3]. Six retrospective cases and one prospective NTD have been reported in human infants exposed to EFV during pregnancy [6] Based on this evidence, EFV is considered potentially teratogenic and is contra-indicated for the first trimester of pregnancy when NTDs occur. Systematic reviews, have found no association between EFV exposure and birth defects [7,8,9]; recent reports from West Africa and South Africa found no evidence of EFV-related teratogenicity [10, 11] Despite these assurances, concerns remain and the most recent adult HIV treatment guidelines from the World Health Organization (WHO) and the South African Department of Health, which has the largest ART treatment program in the world, counsel against first trimester EFV exposure [12, 13]

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