Nevirapine
Reduces Mother-to-Child HIV Transmission, Does Not Impair Mothers' Long-Term Response
to Therapy By
Liz Highleyman Mother-to-child
transmission of HIV remains a major concern in resource-limited countries,
though prophylactic treatment with antiretroviral drugs including nevirapine
(Viramune), AZT (zidovudine,
Retrovir), and 3TC (lamivudine,
Epivir) has dramatically reduced transmission rates. Breast-feeding also can
transmit HIV, but in some poor countries HIV positive women are nevertheless advised
to breast-feed due to the lack of safe and affordable alternatives. Single-dose
nevirapine administered to the mother during delivery and to the baby after
birth is widely used to prevent mother-to-child HIV transmission in developing
countries, though this practice has come into questions since research showed
that this practice can lead to the development of drug resistance, which could
potentially limit future treatment options for the mother. Several
studies presented at the XVI International AIDS Conference in Toronto looked at
nevirapine, with or without other drugs, for the prevention of mother-to-child
transmission. Nevirapine
Outside Clinical Trials in Zimbabwe Nevirapine
prophylaxis has been used in Zimbabwe since 2002, but it was not known how well
this intervention worked in "real-life" settings outside of clinical
trials and demonstration projects. Researchers
undertook a retrospective cohort study to assess the effectiveness of nevirapine
in reducing mother-to-child transmission in a non-clinical trial setting the Murehwa
District. All infants at least 16 months of age whose mothers tested HIV positive
between November 2002 and December 2003 were included. Results
| A
total of 94 HIV-exposed infants were studied, of whom 42 had full nevirapine exposure
(both mother and infant received nevirapine) and 25 were not exposed to nevirapine.
| | More
than 75% of infants in both groups had mixed feeding (breast and bottle). | | 9%
of the infants exposed to nevirapine were HIV positive at 18 months, compared
with 33% of those not exposed. | | Nevirapine
was shown to be protective against HIV infection (RR = 0.26; P = 0.047). | | The
"preventive fraction" of nevirapine was 74% for surviving infants. |
Conclusion In
conclusion, the authors wrote, "Nevirapine was effective in reducing mother-to-
child transmission of HIV in Murehwa, Zimbabwe in a non-clinical trial setting."
They added, "We recommended that the [prevention of mother-to-child transmission]
programme continue to use nevirapine and increase the number of HIV-exposed infants
who benefit from this intervention." Antiretroviral
Prophylaxis and Bottle-Feeding Another
mother-to-child transmission study was conducted between 2001 and 2005 in Abidjan,
Ivory Coast, by researchers with the French National Agency for Research on AIDS.
This study included 808 HIV-positive pregnant women who gave birth to 711 babies.
The women received
either AZT during the last 4 weeks of pregnancy plus a single dose of nevirapine
during labor, or else treatment with AZT plus 3TC during the last 8 weeks of pregnancy
plus a single dose of nevirapine during labor. All babies received a single dose
of nevirapine after birth plus AZT for 7 days. The mothers either exclusively
bottle-fed their babies starting at birth (free formula was provided), or else
exclusively breast-fed for the first 4 months, then weaned their babies early.
Results |
The rate of mother-to-child transmission was lowest among the mothers who received
AZT/3TC and exclusively bottle-fed their infants (5.6% contracted HIV). | | The
rate of transmission was highest in the group that received AZT monotherapy during
pregnancy followed by short-term breast-feeding (15.9%). | | At
18 months, 60 children were HIV-infected, of whom 12 (20%) were determined to
have been infected postnatally rather than before or during birth (11 in the breast-fed
group, 1 in the bottle-fed group). | | Overall,
low maternal CD4 cell count (below 500 cells/mm3) and use of AZT monotherapy during
pregnancy were both significantly associated with infant HIV infection. | | Short-term
breast-feeding was not a determinant of infection; that is, exclusive bottle-feeding
and exclusive breast-feeding with early weaning at 4 months were associated with
similar rates of transmission. |
Conclusion The
researchers concluded that a combination of perinatal AZT plus 3TC plus single-dose
nevirapine, associated with infant-feeding interventions, significantly reduced
mother-to-child transmission of HIV with long-term benefit through 18 months of
age. "This
is the first demonstration in Africa of the benefit of managing HIV-infected pregnant
women with a combination of antiretroviral treatment and alternatives to prolonged
maternal feeding," said lead researcher Valeriane Leroy. A
related study by the same research team found that over a 2-year follow-up period,
37% of bottle-fed and 34% of breast-fed children remained free of adverse health
outcomes (an insignificant difference), leading them to conclude that, "Given
appropriate nutritional counseling and care, access to clean water and supply
of breast-milk substitutes, formula-feeding can be a safe intervention to prevent
postnatal HIV transmission in urban African settings." Efficacy
of Nevirapine as Ongoing Therapy Finally,
another African study examined whether nevirapine was effective as part of ongoing
combination antiretroviral therapy in women who had previously received single-dose
nevirapine to prevent mother-to-child transmission. The
study, conducted in Lusaka, Zambia, included 4,552 women taking HAART, of whom
445 (10%) had received single-dose nevirapine a median of 502 days (range 9-1701)
prior to starting combination therapy; about 80% were exposed to single-dose nevirapine
6 months or more before starting HAART. Results
| After
1 year, no significant differences were observed in rates of treatment failure,
disease progression, or death between women who had and had not previously taken
single-dose nevirapine. | | The
mean CD4 cell increase did not differ significantly after receiving combination
therapy for 6 months (150 cells/mm3 for women exposed to single-dose nevirapine
vs 145 cells/mm3 for unexposed women) or 12 months (184 vs 181 cells/mm3, respectively).
| | Among
women with prior nevirapine use, the mean 6-month CD4 cell increase was similar
among those with recent (within 6 months) or remote (more than 6 months ago) exposure
to single-dose nevirapine (161 vs 147 cells/mm3). | | Overall,
18% of the women experienced treatment failure, disease progression, or death,
but there was no difference based on prior nevirapine exposure in multivariate
analysis. | | When
compared with non-exposed individuals, women with recent or remote nevirapine
exposure appeared to have a similar risk of treatment failure. |
Conclusion The
researchers concluded that in this large cohort, "exposure to nevirapine
for prevention of mother-to-child transmission was not associated with attenuated
maternal immune response or worse clinical outcomes overall." However, they
added that, "Further studies are needed to determine the potential impact
on treatment failure of timing between [single-dose] nevirapine exposure and antiretroviral
therapy initiation, particularly among women reporting recent nevirapine use." The
findings from this study agree with those of past research showing that while
nevirapine resistance may emerge after use of single-dose nevirapine, these resistance
mutations typically disappear within a few months. 08/29/06 References A
Muchedzi, M Tshimanga, D Jones, and others. Effectiveness of nevirapine in reducing
mother to child transmission of HIV in a non-clinical trial setting, Zimbabwe,
2005. XVI International AIDS Conference. Toronto, August 13-18, 2006. Abstract
CDC1832/2170. V
Leroy, D K Ekouevi, L Dequae-Merchadou, and others. 18-month effectiveness of
short-course perinatal antiretroviral regimens combined to infant-feeding interventions
for PMTCT in Abidjan, Côte d'Ivoire. Ditrame Plus ANRS 1201/1202 2001-2005.
XVI International AIDS Conference. Abstract 16646. R
Becquet, D K Ekouevi, C Sakarovitch, and others. Two-year morbidity and mortality
in breastfed and formula-fed children born to HIV-infected mothers, ANRS 1201/1202
Ditrame Plus, Abidjan, Côte d'Ivoire. XVI International AIDS Conference.
Abstract 9262. Chi
B, Sinkala M, Levy J, et al. Maternal immune response and clinical outcomes on
NNRTI-based antiretroviral therapy following exposure to single-dose nevirapine
for prevention of mother-to-child HIV transmission. XVI International AIDS Conference.
Abstract WEAB0104/14427.
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