E-drug: NEJM on perinatal prevention of HIV
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New England Journal of Medicine Volume 351 July 15, 2004 Number 3
[copied as fair use. BS]
Antiretroviral Agents - How Best to Protect Infants from HIV and Save
Their Mothers from AIDS
H. Coovadia
http://content.nejm.org/cgi/content/full/351/3/289
Since this article has no abstract, NEJM have provided an extract of
the first 100 words of the full text and any section headings.
Preventing transmission of human immunodeficiency virus type 1
(HIV-1) and caring for those already infected are essential services
in any comprehensive program, and enhancing the mutually beneficial
effect of each is an international goal. 1These reinforcing effects
are clearly illustrated in the two articles from the Perinatal HIV
Prevention Trial (PHPT) Group in this issue of the Journal . The
first report, by Lallemant et al., demonstrates the considerable
efficacy of a dual antiretroviral regimen in reducing mother-to-child
transmission of HIV-1, 2whereas the second, by Jourdain et al.,
evaluates the effects of subsequent provision of highly active
antiretroviral .
Single-Dose Perinatal Nevirapine plus Standard Zidovudine to Prevent
Mother-to-Child Transmission of HIV-1 in Thailand
M. Lallemant and
Others
http://content.nejm.org/cgi/content/full/351/3/217
ABSTRACT
Background Although zidovudine prophylaxis decreases the rate of
transmission of the human immunodeficiency virus (HIV) type 1
substantially, a large number of infants still become infected. We
hypothesized that the administration, in addition to zidovudine, of a
single dose of oral nevirapine to mothers during labor and to
neonates would further reduce transmission of HIV.
Methods We conducted a randomized, double-blind trial of three
treatment regimens in Thai women who were receiving zidovudine
therapy during the third trimester of pregnancy. In one group,
mothers and infants received a single dose of nevirapine
(nevirapine-nevirapine regimen); in another, mothers and infants
received nevirapine and placebo, respectively (nevirapine-placebo
regimen); and in the last, mothers and infants received placebo
(placebo-placebo regimen). The infants also received one week of
zidovudine therapy and were formula-fed. The end point of the study
was infection with HIV in the infants, established by virologic
testing.
Results Between January 15, 2001, and February 28, 2003, a total of
1844 Thai women were enrolled. At the first interim analysis, the
independent data monitoring committee stopped enrollment in the
placebo-placebo group. Among women who delivered before the interim
analysis, the as-randomized Kaplan-Meier estimates of the
transmission rates were 1.1 percent (95 percent confidence interval,
0.3 to 2.2) in the nevirapine-nevirapine group and 6.3 percent (95
percent confidence interval, 3.8 to 8.9) in the placebo-placebo group
(P<0.001). The final per-protocol transmission rate in the
nevirapine-nevirapine group, 1.9 percent (95 percent confidence
interval, 0.9 to 3.0), was not significantly inferior to the rate in
the nevirapine-placebo group (2.8 percent; 95 percent confidence
interval, 1.5 to 4.1). Nevirapine had an effect within subgroups
defined by known risk factors such as viral load and CD4 count. No
serious adverse effects were associated with nevirapine therapy.
Conclusions A single dose of nevirapine to the mother, with or
without a dose of nevirapine to the infant, added to oral zidovudine
prophylaxis starting at 28 weeks' gestation, is highly effective in
reducing mother-to-child transmission of HIV.
Intrapartum Exposure to Nevirapine and Subsequent Maternal Responses
to Nevirapine-Based Antiretroviral Therapy
G. Jourdain and
Others
http://content.nejm.org/cgi/content/full/351/3/229
ABSTRACT
Background A single intrapartum dose of nevirapine for the prevention
of mother-to-child transmission of human immunodeficiency virus (HIV)
leads to the selection of resistance mutations. Whether there are
clinically significant consequences in mothers who are subsequently
treated with a nevirapine-containing regimen is unknown.
Methods We randomly assigned 1844 women in Thailand who received
zidovudine during the third trimester of pregnancy to receive
intrapartum nevirapine or placebo. In the postpartum period, 269 of
the women with a CD4 count below 250 cells per cubic millimeter began
a nevirapine-containing antiretroviral regimen. Plasma samples were
obtained 10 days post partum and analyzed for resistance mutations.
Plasma HIV type 1 (HIV-1) RNA was measured before the initiation of
therapy and three and six months thereafter.
Results After six months of therapy, the HIV-1 RNA level was less
than 50 copies per milliliter in 49 percent of the women who had
received intrapartum nevirapine, as compared with 68 percent of the
women who had not received intrapartum nevirapine (P=0.03).
Resistance mutations to nonnucleoside reverse-transcriptase
inhibitors were detectable in blood samples obtained 10 days post
partum from 32 percent of the women who had received intrapartum
nevirapine; the most frequent mutations were K103N, G190A, and Y181C.
Among the women who had received intrapartum nevirapine, viral
suppression was achieved at six months in 38 percent of those with
resistance mutations and 52 percent of those without resistance
mutations (P=0.08). An HIV-1 RNA level at or above the median of 4.53
log 10 copies per milliliter before therapy and intrapartum exposure
to nevirapine were independently associated with virologic failure.
After six months of therapy, there was no significant difference
between groups in the CD4 count (P=0.65).
Conclusions Women who received intrapartum nevirapine were less
likely to have virologic suppression after six months of postpartum
treatment with a nevirapine-containing regimen. Our data suggest the
need for strategies to maximize the benefits of both antiretroviral
prophylaxis against mother-to-child transmission of HIV and
antiretroviral therapy for mothers.
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