Further details of the Botswana surveillance study were
presented at AIDS 2018 on Tuesday by Dr Rebecca Zash on behalf of the Tsepamo study team. The Tsepamo surveillance study looked at birth outcomes at eight
government hospitals in Botswana between August 2014 and May 2018 and covered
around 45% of all babies delivered during the period.
The study was originally designed to collect information
about birth outcomes in women who took antiretroviral therapy at the time of
conception and during pregnancy. It was able to collect information about birth
outcomes in women exposed to efavirenz, to dolutegravir or protease
inhibitor-based regimens. Tsepamo began in 2014 when efavirenz-based ART was the preferred option for first-line treatment and Botswana had just begin a treat-all policy. In 2016, Botswana switched to
a first-line regime of dolutegravir, tenfovir and lamivudine for all adults.
A new analysis, looking at women who started
dolutegravir-based treatment or another antiretroviral regimen prior to
conception, was conducted in 2018 in preparation for the development of new
World Health Organization treatment guidelines.
This analysis looked specifically at neural tube defects. A
neural tube defect occurs when the spinal cord, brain, and related structures
do not form properly. The neural tube develops between 2 and 8 weeks of
gestation. Spina bifida – a malformed spinal cord – is the most common neural
tube defect. The most common cause of neural tube defects is lack of folic acid
during pregnancy but defects can also be caused by some medications. The risk
of neural tube defects is highest at the time of conception and in the first
trimester of pregnancy, so it is important to rule out any harmful effects of
drugs taken at this time.
Researchers compared birth outcomes in women exposed to
dolutegravir at the time of conception, women exposed to efavirenz-based ART at
the time of conception, women taking other ART regimens at the time of
conception, women who started dolutegravir during pregnancy and in HIV-negative
The surveillance study has previously reported that women
who started dolutegravir during pregnancy did not have an elevated risk of an
adverse birth outcome (stillbirth, preterm birth, small for gestational age or
neonatal death) compared to women who started efavirenz.
A total of 89,064 births were captured in this surveillance
study for neural tube defects (426 in women taking dolutegravir, 5,787 in women
taking efavirenz and 5,513 taking another antiretroviral regimen at the time of
99.7% of infants underwent a physical examination by a
midwife after delivery to check for neural tube defects. Midwives reported 86
cases (an incidence of 0.10%, 95% CI 0.08-0.12%), of which 42 were spina bifida
(incomplete development of the spine leading to protrusion of the neural tube
through vertebrae). The remainder were more severe defects affecting the brain
and skull. Twenty-two of 86 cases occurred in stillborn infants.
The prevalence of neural tube defects was higher in infants
born to women exposed to dolutegravir at the time of conception compared to
women exposed to efavirenz or other regimens. Four cases occurred in women
taking dolutegravir at the time of conception; none was taking folate
supplements prior to pregnancy. No neural tube defects were identified in
infants born to women who started dolutegravir treatment during pregnancy.
The prevalence of neural tube defects was 0.94% (95% CI
0.37%-2.4%) in women exposed to dolutegravir at conception compared to a
prevalence of 0.12% (95% CI 0.07%-0.21%) in women exposed to any non-DTG
regimen at conception, a risk difference of 0.82%. The prevalence of neural tube defects in women exposed to efavirenz at the time of conception was 0.05% (95% CI 0.02% - 0.05%) and in HIV-negative women the prevalence was 0.09% (0.07%-0.12%).