Women’s Response to Anti-HIV Therapy Improved If Treatment Begins Six Months After Earlier Preventive Regimen
Response to Treatment Diminished If Treatment Begins Within Six Months Of Preventive Regimen
A woman’s response to HIV treatment with drug combinations that
contain nevirapine is improved if at least six months have passed
after she received the drug as a single dose during labor to prevent
passing HIV on to her child. (The response to treatment is measured
by the reduction of HIV in the blood.)
Conversely, the response to treatment with nevirapine-containing
combinations is diminished if less than six months has passed since
the preventive regimen.
These findings were reported by researchers funded in part by
the National Institutes of Health and appear in the January 11 New
England Journal of Medicine.
Nevirapine, given once during labor, alone or in combination with
a short course of zidovudine (AZT) during pregnancy, provides an
inexpensive, effective way to reduce the chances that a pregnant
woman will pass HIV on to her child.
A single dose of nevirapine is a common preventive regimen given
to pregnant women during labor in resource-poor countries where
the standard, more expensive, multi-drug treatments are not widely
available. Previous studies have indicated, however, that the single
nevirapine dose could make the virus resistant to the drug, which
may make it less likely that a woman will respond to nevirapine
if she needs it later, as part of a multi-drug anti-HIV regimen,
to safeguard her own health. The single dose of nevirapine eliminates
most of the copies of HIV that infect a patient, except for a few
mutant copies that are genetically resistant to the drug. Researchers
were concerned that as these remaining mutants multiplied, mutant
HIV would not respond to nevirapine when it was used later as part
of a multi-drug regimen to treat HIV infection.
In many resource poor countries, nevirapine is a cornerstone of
the three drug anti-retroviral therapy (ART) used to treat HIV
disease in pregnant and non-pregnant women who need therapy for
their own health. Typically, nevirapine is given in combination
with AZT and lamivudine. In the United States and other developed
countries, three drug combination therapy is also used to treat
pregnant women and non-pregnant women who require therapy for their
own health. However, in developed countries, the three-drug combinations
usually include the more expensive protease inhibitors, instead
“The findings show that single dose nevirapine during labor alone — or
with short course AZT during pregnancy — remains a viable
option in resource-poor settings for preventing the spread of HIV
from mother to child among pregnant women who do not yet require
anti-HIV treatment for their own health,” said Duane Alexander,
M.D., director of the National Institute of Child Health and Human
Development. “The findings also underscore the importance of immediately
beginning a multi-drug treatment regimen for pregnant women who
require treatment for their own health, but which does not contain
The study findings are consistent with World Health Organization
recommendations that all HIV-infected pregnant women be tested
to identify those in immediate need of treatment, explained the
NIH project officer for the study, Lynne Mofenson, M.D., Chief
of the Pediatric, Adolescent and Maternal AIDS Branch at NICHD.
NIH support for the study was provided by the NICHD and the John
E. Fogarty International Center for Advanced Study in the Health
Shahin Lockman, M.D., of the Harvard School of Public Health and
Brigham and Women’s Hospital, Beth Israel Deaconess Medical Center,
both in Boston and Max Essex, D.V. M., Ph.D., Botswana-Harvard
School of Public Health Project, led the research team on the study.
To conduct the current study, the researchers followed 218 women
in Botswana, who volunteered for a prior study to test the effectiveness
of nevirapine in combination with AZT in preventing the spread
of HIV from mothers to their children. In the prior study, which
enrolled 1,200 women and infants between March 2001 and October
2003, all women received a course of AZT from the 34th week of
pregnancy to delivery. Women and their infants were randomized
during the study. Women received a single dose of nevirapine given
at the beginning of labor, or a placebo. Infants received a single
dose of nevirapine at 48 to 72 hours after birth, or placebo.
Combination antiretroviral therapy, which included nevirapine,
became available starting in October 2002 for all study participants
who required treatment for their own health.
The current study enrolled volunteers from the earlier study who
later needed multi-drug therapy for their own health after they
had given birth. Of these volunteers, 112 women originally had
been randomized to receive single dose nevirapine and another 106
women originally had been randomized to receive nevirapine placebo
in the original study.
In the current study, 60 women required ART within six months
after receiving either single dose nevirapine or placebo during
labor. Of the women in the nevirapine group, 41.7 percent still
had detectable HIV levels in the blood after receiving six months
of ART, indicating that the ART was not effective. In the placebo
group, none of the women receiving the nevirapine placebo had detectable
HIV in the blood after six months of ART.
However, the rates of detection of HIV in the blood did not differ
significantly among the other 158 women, who started treatment
at least six months after receiving single dose nevirapine or placebo.
Of these, 12 percent of the nevirapine group and 7.8 percent of
the placebo group still had detectable HIV levels after receiving
six months of ART, indicating equal effectiveness of ART in both
The study authors wrote that their findings are consistent with
observations that while nevirapine-resistant strains of HIV could
be present after a single dose nevirapine regimen, these strains
begin to fade with time and eventually make up a minor proportion
of HIV strains in a patient.
The study authors concluded that nevirapine-based ART is an option
for women who require therapy six months or more after receiving
a single dose nevirapine preventive regimen. They also wrote that
some women given single dose nevirapine will require ART treatment
before six months have passed, and these women should receive ART
that does not include nevirapine.
The authors added that “every effort should be made” to provide
combination ART during pregnancy to women who need it for their
own health, as these women are at highest risk for AIDS-related
complications or death, for passing HIV on to their infants, and
for developing nevirapine resistance after a single dose of the
The researchers also evaluated the response of HIV in the blood
to ART in a subgroup of infants from the prior study that had become
infected despite preventive drugs and who later required ART. The
researchers were able to follow 24 infants for six months, with
13 having received single dose nevirapine and 11 having received
placebo; one infant in the placebo group, and 10 infants in the
nevirapine group had HIV detectable in the blood after 6 months
The study authors noted, however, that it was difficult to draw
firm conclusions from the small number of infants studied, and
added that additional information from other studies would be helpful.
A randomized, controlled clinical trial to evaluate the best treatment
for infected infants with and without single dose nevirapine exposure
is currently being conducted by the International Maternal, Pediatric,
Adolescent AIDS Clinical Trials Group, sponsored by the NIH’s National
Institute of Allergy and Infectious Diseases and the NICHD.
The NICHD sponsors research on development, before and after
birth; maternal, child, and family health; reproductive biology
and population issues; and medical rehabilitation. For more information,
visit the Institute’s Web site at http://www.nichd.nih.gov/.
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the international component of the NIH, addresses global health
challenges through innovative and collaborative research and
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