monotherapy achieves satisfactory levels of virological suppression in pregnant
women taking antiretroviral therapy to prevent mother-to-child transmission of
HIV, French investigators report in the online edition of Clinical Infectious Diseases.
Eight weeks after starting therapy, 90% of women taking Kaletra monotherapy had a viral load
below 200 copies/ml compared to 94% of women taking triple therapy consisting
of Kaletra with Combivir (3TC/AZT). Treatment was started during week 26 of
pregnancy and none of the women needed HIV therapy for their own health.
Protease inhibitor monotherapy is not recommended for routine antiretroviral treatment. However, the results of this preliminary research suggest that it could be an option for a sub-set of women with a high CD4 cell count, to prevent mother-to-child transmission of HIV.
countries, antiretroviral therapy is recommended for all pregnant women with
HIV. This is one of the reasons why there is a very low rate of mother-to-child
transmission in these countries, where it is typically well below 1%.
A combination of
two nucleoside reverse transcriptase inhibitors (NRTIs) and a ritonavir-boosted
protease inhibitor is recommended for use during pregnancy. The most widely
used combination in Europe and the United States consists of Combivir as the NRTI backbone with the
protease inhibitor Kaletra.
However, there is
an ongoing debate about the safety of NRTI therapy during pregnancy. NRTIs
cross the placenta, and there is some evidence that in utero exposure to AZT
can lead to some toxicities, the long-term clinical significance of which are
France therefore evaluated a nucleoside-sparing regimen for the prevention of
mother-to-child HIV transmission. They selected Kaletra because the drug is widely used in pregnancy and because
monotherapy with the drug has been shown to have potency in non-pregnant
adults. Viral resistance is unlikely should monotherapy with the drug fail to
suppress viral load. Moreover, Kaletra
has a low placental transfer, limiting the risk of in utero toxicities.
The study (ANRS
135 PRIMEVA) involved 105 women living with HIV. All had a viral load below 30,000
copies/ml and a CD4 cell count above 350 cells/mm3. None therefore
required HIV therapy for their own health.
The study was
open-label and multicentre. Participants were recruited between weeks 20 and 24
of pregnancy. At week 26 they were randomised on a 2:1 basis to
start therapy with either Kaletra
monotherapy (n=69) or Kaletra with Combivir (n=36), all at standard doses. All
the women received intravenous AZT during labour.
considered to be efficacious if at least 59 women in that arm achieved a
viral load below 200 copies/ml after eight weeks of treatment. The authors
emphasised that the study was not designed to show the equivalence of
monotherapy with triple therapy “as this would require a very large sample
endpoints included the proportion of women with a viral load below 50
copies/ml at delivery and the safety of therapy.
At screening, the
women had a median viral load of approximately 3000 copies/ml and a median CD4
cell count of 525 cells/mm3. Treatment was stopped by two women in the
monotherapy arm and by two women in the triple-therapy arm before week
efficacy criterion of the study was achieved. After eight weeks of treatment,
62 women (90%) in the monotherapy arm had a viral load below 200 copies/ml. This
compared to 94% of women taking triple-drug therapy, not a statistically significant
At delivery, 93%
of women taking monotherapy and 97% of those taking triple-therapy had a viral
load below 200 copies/ml. Once again, this difference was not statistically significant.
monotherapy was associated with lower rates of viral suppression below 50
copies/ml at delivery than standard treatment (78 vs 97%, p = 0.01).
All the women
discontinued therapy after delivery, and four weeks later the women treated
with monotherapy had a significantly higher viral load compared to woman taking
triple-drug treatment. However, this difference had decreased by week twelve
and no resistance was detected in the women taking monotherapy.
concentrations among the women taking monotherapy were within therapeutic
during the first weeks of therapy were similar between the two arms of the
study, with 25% of women taking monotherapy reporting missing doses compared to
14% of women in the triple-drug arm.
Only 1% of women taking monotherapy changed treatment because of toxicities compared to
11% of those treated with a three-drug combination (p = 0.0046).
There was no
difference in gestational age, mode of delivery, maternal and infant severe
adverse events and serious laboratory abnormalities between the two study arms.
occurred in the monotherapy group, but there was one case in the triple therapy
“This is the first
randomised trial to evaluate a NRTI-sparing strategy of antiretroviral
monotherapy during pregnancy in order to prevent mother-to-child transmission
of HIV,” write the authors. “We showed that this strategy achieved satisfactory
virologic efficacy at 8 weeks of treatment, with 90% of women achieving VL <
200 copies/ml at 34 [weeks of gestation]. Moreover, although the trial was not
designed to show equivalence, the proportion was on the same order as with
their results “are a step towards the proof of concept that [prevention of
mother-to-child-transmission] without NRTI might be an alternative for pregnant
immunocompetent women with spontaneously low viral load…the present study may open the way for other novel nucleoside-sparing strategies.”