Early Trials Suggest Anti-HIV Drug Dapivirine Levels in Breast Milk Safe For Babies

Highlights:

• 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 protection can be extended to pregnant and breastfeeding women.

Dapivirine 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.

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 sub-Saharan Africa, where the proportion of women of reproductive age who are either pregnant, breastfeeding or both is high.

Dapivirine ring has been found to be safe, and protects against HIV 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.

Evaluating 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 still pump 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.

Testing 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 daily basis.

• 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 studies conducted.

"There is little doubt that safe and effective HIV prevention methods 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.

Dapivirine 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 month.

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 Zimbabwe

• 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