- Dapivirine vaginal ring, developed to protect against HIV, has been
found to be safe and effective in protecting against the deadly infection
in 4500 women in sub-Saharan Africa.
- New early Phase I clinical trial to test safety of dapivirine in
breastfeeding women, indicate that concentrations in breast milk may be
safe for babies.
- Future studies aim to find out whether dapivirine
be extended to pregnant and breastfeeding women.
vaginal ring created by the International Partnership for
Microbicides (IPM), a non-profit organization, may be safe to use in
breastfeeding women to protect against HIV infection, according to a recent
National Institutes of Health (NIH)-funded Microbicide Trials Network (MTN)
study conducted at the University of Pittsburgh-affiliated Magee-Womens
Hospital and the University of Alabama at Birmingham.
The work was presented at the 9th IAS
Conference on HIV Science (IAS 2017) in Paris. Further safety trials are being
planned to validate the initial findings.
‘If found safe for use in pregnancy and breastfeeding, dapivirine ring could potentially protect a much larger proportion of women from HIV infection.’
Dapivirine Ring Safety In Breastfeeding Population -
Reason For Study
Since many women remain sexually active
during pregnancy and breastfeeding, they may be at a greater risk of acquiring
HIV, especially because it is difficult for women to negotiate the use of
condoms with their partners. This assumes importance
in regions where HIV prevalence is high, such as in
where the proportion of women of reproductive age who are either pregnant,
breastfeeding or both is high.
ring has been found to be safe,
in women in the reproductive age group in Africa and is used as
a monthly vaginal ring. This study hopes
to determine the safety of this drug in breastfeeding women so that this
population can be protected
from HIV infection,
as the disease incidence remains high here.
Dapivirine Levels In Breast Milk - The MTN-029/IPM 039 Study
The Phase I trial dubbed MTN-029/IPM 039 Study
was conducted at
the University of Pittsburgh-affiliated Magee-Womens Hospital and the
University of Alabama at Birmingham in the US.
Dr. Noguchi CNM, Ph.D., research
associate in the department of epidemiology at the Johns Hopkins Bloomberg
School of Public Health, and MTN's scientific director for pregnancy research,
led the MTN-029/IPM 039 study with Richard Beigi, MD, MSc, an associate
professor of reproductive health sciences at the University of Pittsburgh.
This trial follows two Phase III trials, namely the ASPIRE and The Ring Study
that found dapivirine ring was safe and helped protect against HIV among more
than 4,500 women in sub-Saharan Africa.
The MTN-029/IPM 039 enrolled 16 participants
, that included women who had ceased to breastfeed their babies although they could
breast milk. This ensured that babies were not exposed
to the drug during this study.
Women were asked to leave the dapivirine vaginal ring in place for 14 days
. The study
team collected blood samples and breast milk prior to insertion of the ring,
and then after three hours, six hours, 24 hours, seven days and 14 days, when the ring was removed
. Samples were
collected again two days later.
the Levels of Dapivirine in Blood and Breast Milk - Findings of the Study
- All participants showed detectable
drug levels in milk and plasma, starting at three hours with concentrations
gradually increasing and achieving a plateau between seven and 14 days.
- Peak concentration for breast milk
and plasma were 676 pg/mL and 327 pg/mL, respectively.
- Two days after the ring was removed,
drug levels had reduced by 60 percent.
Based on concentrations measured in
maternal breast milk, the research team estimated that a breastfed baby's daily
exposure to dapivirine would be very low. A 6-month old baby, for example, weighing 8 kg (about 18 lbs) would
probably ingest about 600 ng (or 6/10,000 of a milligram) of dapivirine on a
- To give a sense of the low levels of
dapivirine exposure of the baby, a similar weight baby being breastfed by
a mother taking the antiretroviral combination Truvada, would be exposed
to about 4,000 ng of tenofovir and 300,000 ng of emtricitabine each day.
These levels have not been found to be unsafe for breastfed infants in
"There is little doubt that safe and
are needed for women during all times of their
lives," commented Sharon Hillier, Ph.D., principal investigator of the
MTN, and professor and vice chair of the department of obstetrics, gynecology
and reproductive sciences at the University of Pittsburgh School of Medicine.
"With the dapivirine ring,
conducting this study was an important first step. If the ring is approved, we'd want it to ultimately be
made available to all women, including those who are breastfeeding."
Dr Noguchi echoes these sentiments and is
happy that they were able to conduct this early trial without actually exposing
infants to the drug.
Vaginal Ring To Prevent HIV Transmission
The International Partnership for
Microbicides (IPM), a non-profit organization developed dapivirine monthly vaginal ring
as a method to protect against HIV
transmission to sexually active women.
When placed inside the vagina, the ring
slowly releases dapivirine over a month. The ring is made of a flexible
plastic, and women can easily insert and replace the ring themselves each
IPM is seeking regulatory approval to use
dapivirine ring for women ages 18-45 based on results of ASPIRE, which was
conducted by MTN, and The Ring Study, led by IPM. Future Plans to Evaluate Safety of Dapivirine
Three new studies are being planned as a follow-up to MTN-029/IPM
039 at four MTN-associated trial sites in Malawi, Uganda, South Africa and
- MTN-041, a qualitative study hopes
to obtain public sentiments about use of a vaginal ring and oral
pre-exposure prophylaxis (PrEP) during pregnancy and breastfeeding among
women who are themselves pregnant and/or breastfeeding, their male
partners and key community gatekeepers, such as health care providers,
traditional healers and religious and traditional leaders. The study is
expected to start early 2018 pending approvals.
- In MTN-042, the scientists are
planning to evaluate the safety of the ring as well as oral PrEP in
approximately 750 pregnant women.
- MTN-043 plans to extend the study to
include approximately 100 women who are breastfeeding and their infants.
In conclusion, the results of these studies
would be eagerly awaited to see if dapivirine protection could be extended to
pregnant and breastfeeding women as well.Source: Medindia