Page 370 - SAHCS HIVMed Journal Vol 20 No 1 2019

Page 9 of 12 Original Research

However, no difference in ABOs was noted when comparing particularly vulnerable population), it is not possible to make
ART initiation before pregnancy against ART initiated after a direct comparison between treated and untreated HIV-
conception 0.90 (95% CI 0.76–1.07; p = 0.237). This was also positive mothers. As there is no particular suspicion of
the case when the timing of the initiation of EFV- and NVP- association between HIV status and CMs, this is probably not
based regimens was assessed (EFV 0.93 (95% CI 0.77–1.12; a major limitation of the ‘Analysis A’. For ‘Analysis B’ which
p = 0.42; NVP 0.57 (95% CI 0.17–1.98; p = 0.379). Moreover, deals with composite ABOs, this shows that differences
there was no significant difference between the risk of ABOs observed between HIV-exposed and HIV-unexposed birth
when comparing pre-pregnancy initiation of EFV-based ART outcomes are composed of mitigation of HIV infection by
with pre-pregnancy initiation of NVP-based ART (adjusted ART, possible adverse effects of ART and residual
risk ratio: 0.80 95% CI 0.54–1.19; p = 0.267). confounding. The effect size appeared to be bigger with
NVP-based regimens than with EFV-based regimens,
Discussion although a head-to-head comparison between EFV-based
and NVP-based regimens in the first trimester yielded no
These data represent the findings of the first year of a drug significant difference in ABOs. Our findings of the lack of
safety surveillance system aimed at improving our effect of timing of exposure on ABOs as a composite endpoint
understanding of the safety of medicines commonly used by supports similar findings by Malaba and others. 7,32
6
both HIV-infected and HIV-uninfected pregnant women in
South Africa. A substantial proportion of the women (4013, Due to pragmatic challenges with implementation during the
38.5%) were HIV-infected, the majority of whom were on first year of surveillance, coverage rates for neonatal death
ART (3932, 96.8%) and of whom 3467 (93.4%) were receiving (53.1%) at the hospital were found to be lower than the total
the recommended first-line regimen of TDF/FTC/EFV coverage for all deliveries (71.4%), suggesting an under-
according to SA NDoH guidelines. Only 96 women were on representation of these outcomes and a diminished chance of
a NVP-based regimen during the pregnancy, mostly initiated assessing risk factor associations.
prior to conception (Table 3). The very small number of
women (40) receiving PI-containing regimens precludes the The overall detection rate for CMs identifiable by surface
assessment of their association with primary outcomes. examination was lower (0.5%) compared to 0.67% reported in
other LMIC settings as only malformations identified
35
Risk analysis was conducted only on the subset of CM through a surface examination conducted at the time of birth
(‘included CM’) which could plausibly have been caused by were identified and included in the analysis. The incomplete
teratogenic exposures, as assessed by clinical geneticists coverage of stillbirths that were cremated or taken home by
using predefined criteria. Reassuringly, and in line with the family prior to a surface examination being performed by
31
previous studies and review, 16,17,22,23,24,33 we did not find an the surveillance nurses could have contributed to under-
increased risk of CM among infants exposed to EFV in the detection, as well as exclusion of serious CMs requiring
first trimester. The two CMs reported (hypoplastic thumb urgent referral to other institutions, either prenatally for
and club foot) in two infants with first trimester exposure are termination or delivery or postnatally for additional care.
unlike previously reported CM associated with EFV. 13,14 It is Medical termination of pregnancies, miscarriages and early
unlikely that the reported myelomeningocele (a neural tube stillbirths were also not captured in this cohort, as these
defect) in an infant exposed to TDF/FTC/EFV later in the admissions were not seen in the labour wards.
first trimester was causally linked to the treatment given
during the late onset of treatment initiation in the pregnancy. 34 We have no evidence to suggest that the HIV status of the
women influenced the coverage in a way that would
There was a significant statistical association between first introduce a bias into the analysis, although it is possible that
trimester exposure to NVP-based regimens and the the under-ascertainment of CMs would make detection of an
occurrence of congenital malformations. This statistical increased birth prevalence of CMs related to ART more
association will require accrual of further evidence over time difficult. Improved capacity for the detection and assessment
(preferably prospectively collected data). Note: (1) the lack of of CMs, including the capture of terminations of pregnancies,
a postulated common mechanism for these defects; (2) the was identified as a priority measure for refining the
small number of cases (3 cases) and (3) potential confounders surveillance system at the site.
such as maternal age, underlying disease severity, nutritional
state, evidence of alcohol and illicit substance abuse and The surveillance programme was initiated approximately
other potential teratogenic exposures which should be 18 months after NVP-based first-line regimen was replaced
explored. by the EFV-based regimen. Therefore, the cohort of women
on NVP-based treatment had been initiated on treatment
Our findings of an increased risk of other ABOs in HIV- before the new guidelines were implemented and, therefore,
exposed infants compared to HIV-unexposed infants assessed probably on ART treatment for longer than those on the EFV-
in Analysis B (Table 6) are well described. 6,7,10,16,17,35 Given the based regimens. As most women have likely been switched
exclusion of HIV-positive untreated pregnancies (noted from NVP-based regimens to an EFV-based regimen as the
above as representative of substandard access to care and a cohort expands, it is unlikely that South African sites alone

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