HIV
and Hepatitis.com Coverage of the 14th
Annual Conference on Retroviruses and Opportunistic Infections (14th CROI) February
25 - 28, 2007, Los Angeles, CA
Short-course
Antiretroviral Therapy to Prevent Mother-to-child HIV Transmission May Compromise
Women's Treatment
Widespread
use of prophylactic antiretroviral therapy has dramatically lowered the risk of
mother-to-child transmission of HIV.
In developed countries, pregnant women
with HIV are typically advised to receive combination HAART, but in resource-limited
settings, a short course of AZT
(Retrovir), with or without 3TC
(Epivir), or a single dose of nevirapine
(Viramune) are often used during delivery.
In
a late-breaker presentation at the 14th Conference on Retroviruses
and Opportunistic Infections, held last month in Los Angeles, researchers
reported that short-course antiretroviral therapy may compromise mothers' response
when they later begin combination therapy to treat their own disease.
The
investigators studied 247 HIV-positive mothers in Côte d'Ivoire, Africa,
who started regimens containing AZT
or d4T (Zerit) plus
3TC plus either nevirapine
or efavirenz (Sustiva). Of these
women, 86 had received short-course AZT/3TC plus single-dose nevirapine during
a previous pregnancy, 52 had received short-course AZT plus single-dose nevirapine,
5 had received short-course AZT/3TC without nevirapine, 2 had received single-dose
nevirapine alone, and 109 were unexposed to any prior antiretroviral therapy.
The women started HAART a median of 19 months after exposure to prophylactic therapy
to prevent mother-to-child transmission.
Results
•
None of the 115 women who underwent genotypic resistance testing had AZT-resistance
mutations.
•
15.0% of the 73 tested 3TC-exposed women had 3TC-resistance mutations.
•
38.1% of women exposed to
short-course AZT plus single-dose nevirapine developed nevirapine-resistance mutations,
as did 4.1% of those exposed to AZT/3TC plus single-dose nevirapine.
•
19.2% of women experienced virological failure after starting HAART.
•
In a multivariate analysis,
factors associated with virological
failure were:
- poor self-reported adherence; -
post-partum 3TC-resistance mutations ; - baseline CD4
cell count less than 200 cells/mm3.
•
Half of the women with 3TC-resistance mutations experienced virological failure.
•
Women exposed to 3TC who
did not develop resistance mutations were not at significantly increased risk
of virological failure.
•
Exposure to single-dose nevirapine
was not associated with a significantly increased risk of virological failure.
•
27.8% of nevirapine-exposed
women with nevirapine-resistance mutations experienced virological failure, compared
18.6% of women without resistance mutations.
Conclusion The
researchers concluded that short course AZT with or without 3TC and single-dose
nevirapine "may induce viral resistance to nevirapine or 3TC that can impair
the subsequent women's response to HAART, an adverse phenomenon to be taken into
account in [prevention of mother-to-child
transmission] guidelines."
Unlike the current study, several past
studies have shown that single-dose nevirapine can lead to resistance mutations
that compromise treatment for the mother, although HIV typically reverts to wild-type
(fully drug susceptible) after 6 months.
As reported in the March 15, 2007
Journal of Infectious Diseases, a group of researchers developed a stochastic
simulation model to predict survival and mortality associated with use of single-dose
nevirapine in sub-Saharan Africa. The model predicted that if all women exposed
to single-dose nevirapine during pregnancy later started HAART, mortality attributable
to single-dose nevirapine would be 1.1% at 5 years and 3.5% at 10 years after
exposure.
The researchers wrote that their model "provides strong
arguments that single-dose nevirapine for [prevention of mother-to-child transmission]
should not be delayed because of fear of compromising the survival of women after
[prevention of mother-to-child transmission] therapy." Nevertheless, the
Côte D'Ivoire results suggest that wherever possible, HIV positive women
should receive triple antiretroviral therapy during pregnancy, as recommended
by the World Health Organization.
03/13/07
References
P
Coffie, D Ekouevi, M L Chaix, and others. Short-course zidovudine and lamivudine
or single-dose nevirapine-containing PMTCT compromises 12-month response to HAART
in African women, Abidjan, Côte d'Ivoire (2003-2006). 14th
Conference on Retroviruses and Opportunistic Infections. Los Angeles, February
25-28, 2007. Abstract 93LB (oral).
D Westreich, J Eron, F Behets, and others.
Survival in women exposed to single-dose nevirapine for prevention of mother-to-child
transmission of HIV: a stochastic model. Journal of Infectious Diseases 195(6):
837-846. March 15, 2007.
