used to suppress herpes simplex virus 2 (HSV-2) in HIV co-infected pregnant and
post-partum women in Nairobi, Kenya, slowed HIV disease progression and reduced
viral load in breast milk, according to researchers from the Universities of
Washington, Nairobi and the Fred Hutchinson Cancer Research Center at the sixth International AIDS Society conference (IAS 2011) in Rome last week.
Another study from Kenya showed valaciclovir reduced viral load in adults while a third from Uganda found that another herpes drug, aciclovir, also helped reduce disease progression.
viral load during pregnancy and breastfeeding determines the risk of
mother-to-child transmission (MTCT), so reducing maternal viral load is one of
the main objectives of all prevention of mother-to-child transmission (PMTCT)
infection is a risk factor for vertical transmission. Studies have shown
suppression of HSV-2 with valaciclovir decreases viral load but its effect has
not been studied in pregnant and breastfeeding HIV-positive women. The
prevalence of HSV-2 infection among HIV-positive women is between 75 and 95%.
researchers hypothesised that HSV-2 therapy offers a
strategy to reduce postnatal MTCT that is inexpensive, safe and easily
incorporated into existing PMTCT programmes.
researchers wanted to see whether the positive effects of herpes suppressive
drugs on viral load, seen in previous trials from which pregnant women had
been excluded, would improve maternal health and reduce disease progression
among co-infected pregnant and breastfeeding women in sub-Saharan Africa.
was chosen in preference to aciclovir because it is easier to adhere to, longer
acting, more potent, does not need laboratory monitoring in pregnant and postpartum
women, and is available as a generic.
evaluate the effects of HSV-2 suppression on HIV disease progression and
vertical transmission of HIV, 148 HIV/HSV-2 co-infected pregnant women were
enroled in a randomised, double-blind, placebo-controlled trial in Nairobi, Kenya,
from April 2008 to June 2009 and followed until August 2010. At 34 weeks of
pregnancy they were randomised to 500mg of valaciclovir twice a day or placebo
until 12 months after having given birth.
women all had CD4 cell counts over 250 cells/mm3 and World Health Organization
(WHO) stage 1 or 2 clinical disease and were not eligible for ART at the time
of the study according to Kenyan guidelines. The women received AZT (zidovudine, Retrovir) at
28 weeks of pregnancy or later, and single-dose nevirapine (Viread) during labour or
delivery for PMTCT, with a one-week tail of 3TC (lamivudine, Epivir). At the time of
enrolment approximately 70% of the women in both arms were receiving AZT.
"HIV viral load reductions of this nature could lengthen the time to development of AIDS by 1.9 years in similar asymptomatic patients." Dr Alison Roxby
women in both arms had similar demographic and clinical characteristics with an
average age of 25; most had one or two previous pregnancies and all breastfed.
levels were measured in the genital tract, breast milk and plasma.
Drake, one of the co-investigators, presented on the effect of valaciclovir on
viral levels in plasma and in breast milk. Plasma and breast milk samples for viral load testing were taken during
pregnancy (plasma alone), and then at 2, 6, 14 weeks and 6 and 12 months
the 148 women, 145 had a postpartum visit.
plasma viral load at baseline was similar in both arms at approximately 3.9
log10 copies/ml. At 6 and 14 weeks after birth, the risks of detecting
viral load in breast milk were 30% (p= 0.04) and 46%, (p= 0.01) lower,
the valaciclovir arm than in the placebo arm.
the six-month period after giving birth, plasma viral load in the valaciclovir arm
was significantly lower than in the placebo group (0.51 log10
mother-to-child transmission rate at 13 months was 7% with no difference
between arms. Dr Drake added that the trial was not designed to look at the
effects of valaciclovir on vertical transmission.
Drake added that it is conceivable that valaciclovir has a different effect in peripartum
HIV transmission when compared to sexual transmission, because of the prolonged
exposure to HIV-containing bodily fluids during pregnancy, labour and delivery
and post partum through breast milk.
Roxby, another co-investigator, presented findings on the effects of valaciclovir
suppression of HSV-2 on HIV disease progression in the same cohort. CD4 cell
counts and viral loads were measured at baseline (34 weeks of pregnancy) and at 12
months after giving birth.
median baseline CD4 cell counts in the valaciclovir arm and placebo arm were
452 cells/mm3 and 481 cells/mm3, respectively.
Ninety-two per cent (132) of the women completed one year of follow-up after giving birth. Three
women died (one in the valaciclovir arm), all after giving birth. This
highlights the risk of childbearing for HIV-positive mothers in Africa, Dr Roxby stressed. Six cases of tuberculosis
(four in the valaciclovir arm) were reported.
cell counts continued to increase at 12 months after giving birth in the valaciclovir
arm, and were 73 cells/mm3 (p = 0.03) higher than in the placebo arm.
all began with similar viral loads, by 6and 12 months viral loads were 0.40
log lower in the valaciclovir arm.
monthly adherence measured by monthly pill count was high at 86% with many
attaining 100% adherence.
Roxby cited modelling studies that “suggest HIV viral load reductions of this
nature could lengthen the time to development of AIDS by 1.9 years in similar
of valaciclovir, she added, is a cost-effective option in resource-poor settings
where access to HIV treatment remains limited.
findings suggest valaciclovir could be used during pregnancy and breastfeeding
to improve outcomes in HIV/HSV-2 co-infected women and their infants as an
adjunct to ART prophylaxis in resource-poor settings.