Pregnant women taking efavirenz-based antiretroviral therapy had significantly better virologic
outcomes at the time of delivery compared to those taking
lopinavir/ritonavir in a randomised study in rural Uganda, Dr Deborah
Cohan, reporting on behalf of the PROMOTE study team, told attendees at the 21st
Conference on Retroviruses and Opportunistic Infections (CROI) in Boston last
regimens, overall, had very high virologic suppression rates and were extremely
effective in preventing HIV transmission during pregnancy and breastfeeding Dr
These data provide reassurance that high levels of viral suppression are achievable, [and] demonstrate that infants have a low risk of HIV acquisition with these regimens.
from this secondary analysis of a randomised open-label study evaluating efavirenz (Sustiva, Stocrin) compared
to lopinavir boosted with ritonavir (Kaletra) for the prevention of placental malaria, support the 2013 World Health
Organization (WHO) guidelines recommending efavirenz-based combination anitretroviral therapy (cART) for all
pregnant women regardless of CD4 count (known as 'Option B+') as a first-line option with
cART based on lopinavir/ritonavir as an alternative.
guidelines, however, were recommended within the context of significant
research gaps that included maternal and infant outcomes, antiretroviral
toxicity and alternative ART regimens.
enrolled pregnant women living with HIV who had not previously taken HIV treatment at between 12 and 28 weeks of
gestation. The women were randomised to receive AZT (zidovudine, Retrovir) and 3TC (lamivudine, Epivir) with
either lopinavir/ritonavir or efavirenz at enrolment up until one year of breastfeeding and
followed-up for six weeks after cessation of breastfeeding. The dose of lopinavir/ritonavir increased from
400mg/100mg twice daily to 600mg/150mg twice daily at thirty weeks. All women
received cotrimoxazole prophylaxis and insecticide-treated bednets, and infants
received AZT or nevirapine (Viramune) prophylaxis in accordance with Ugandan
guidelines. Women received nutritional counselling to breastfeed for one year
compared virologic, immunologic and safety outcomes between the two arms of the study.
Of the 593
women screened, 389 were eligible and enrolled, of whom 348 completed the
study, and data were available for 377 at delivery.
there were no significant differences in the two arms of the study. Mean age was 29 years
and median gestation at enrolment was 21 weeks. This was a first pregnancy
for fewer than 10%, with over two-thirds having three or more children at home.
Median CD4 cell count in both arms was over 350 cells/mm3 yet over 90%
were WHO stage 1. Malnutrition was a significant issue, with a mean body mass
index (BMI) at enrolment of 21.8. At baseline, median log10 HIV RNA was 4.3
and 4.1 for the efavirenz and lopinavir/ritonavir arms, respectively.
Women taking efavirenz
were significantly more likely to achieve viral suppression (<400 copies/ml)
at delivery compared to women on lopinavir/ritonavir, 98% (166/170) and 86% (153/178),
respectively (p<0.001). However, no differences were seen at eight weeks
after starting ART while pregnant, with close to 90% of women achieving viral suppression in
both arms of the study, and with similar findings at weeks 24 and 48 after delivery.
all viral loads measured (1335 measurements in 374 women), a 50% lower odds of
viral suppression among women on lopinavir/ritonavir (OR:0.51, 95% CI: 0.31-0.82, p = 0.0062) was
seen. Dr Cohan noted, however, this is within a context of overall very high
levels of virologic suppression for both regimens.
Women taking lopinavir/ritonavir had greater CD4 cell count recovery compared to women taking efavirenz at delivery,
(+57 and -7 cells/mm3, p = 0.002, respectively) and at 24 weeks postpartum (+178
and +109 cells/mm3, p<0.01, respectively),
WHO grade 4
adverse events were rare and did not differ by arm. Kaposi’s sarcoma was
diagnosed in one woman in the efavirenz arm and pulmonary TB in one woman in the lopinavir/ritonavir
arm. However, diarrhoea and nausea and vomiting (grades 1 and 2) were
significantly more likely among women taking lopinavir/ritonavir both before and after
There were no
differences in preterm birth, miscarriage, stillbirth or neonatal
death between the arms.
transmission rate was 0.5% (2/374 live births). Both were in the lopinavir/ritonavir arm, one
in utero and one during breastfeeding. HIV-free survival was high and did not
differ between the efavirenz and lopinavir/ritonavir arms, 97.2% and 92.9%, p = 0.10, respectively. Grade 3 and 4 events, mostly anaemia and
neutropaenia, were similar between the arms; the incidence rate ratio (IRR):
1.25; 95% CI: 0.87-1.81, p = 0.21 (lopinavir/ritonavir compared to efavirenz).
at delivery may potentially be explained by efavirenz being more potent than lopinavir/ritonavir as
well as by adherence and drug exposure during pregnancy Dr Cohan noted.
Self-reported adherence rates were high in both arms but self-reporting is
vulnerable to social desirability bias, she added.
pharmacokinetic (PK) studies suggest lopinavir/ritonavir exposure may be inadequate before
delivery, it is unclear whether this explains the differential virologic
suppression Dr Cohan said.
concluded “these data provide reassurance that high levels of viral suppression
are achievable, demonstrate that infants have a low risk of HIV acquisition
with these regimens, and show that women
can successfully initiate ART when they present to the antenatal clinic and
maintain therapy thereafter.”
“the ultimate goal of lifelong suppressive therapy is to keep these women healthy.”