Women can safely use a monthly, antiretroviral-containing vaginal ring to prevent HIV infection during late pregnancy and while breastfeeding with no risk to their babies, new research released this week shows. The ring is expected to become available at selected clinics and private pharmacies this year alongside the HIV prevention injection and the HIV prevention pill.
Inserted at home, the silicon vaginal ring slowly releases the antiretroviral dapivirine and can reduce women's risk of contracting HIV by 27% to 75%, according to Katherine Bunge, Assistant Professor of obstetrics, gynaecology, and reproductive sciences at the University of Pittsburgh School of Medicine in the United States.
The ring is one of three forms of pre-exposure prophylaxis (PrEP) that use antiretrovirals to prevent HIV infection. Currently, only the daily HIV prevention pill is widely available in South Africa and has been shown to slash a person's risk of contracting HIV by around 99% when used as prescribed. Still, in clinical trials, people who used an every-other-month injection of the antiretroviral cabotegravir were about 80% less likely to contract HIV than those on the HIV prevention pill, sometimes known by its brand name Truvada. The bi-monthly shot likely outperformed the pill because it was easier for people to take than daily pills, the World Health Organization explains. The injection is not a vaccine.
As Spotlight reported in November last year, the trio of prevention options is expected to become available at selected clinics and private pharmacies in South Africa this year.
PrEP in pregnancy: New data, better options for a risky time
South Africa has offered the HIV prevention pill to pregnant women since 2019. A study published earlier this month in The Lancet HIV confirmed that women who took the pill from as early as 14 weeks of pregnancy showed no increased risk of premature or underweight babies or stillbirths. Similarly, early research presented last year at the International AIDS Conference found no risk to women who conceived on injectable cabotegravir but studies are ongoing.
The ring is one of three forms of pre-exposure prophylaxis (PrEP) that use antiretrovirals to prevent HIV infection.
Early but limited data in 2018 also suggested the vaginal ring to be safe during conception and very early pregnancy. Still, this research came from a study testing how well the ring worked and had not been specifically designed to evaluate safety during pregnancy.
Now, the first study examining the ring's safety during pregnancy has found that the ring can be safely used from at least the seventh month of pregnancy onwards, according to research presented by Bunge late Monday at the Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle, United States. Findings from additional research on the use of the ring from 12 to 29 weeks of pregnancy are expected later this year. Meanwhile, a second study released earlier today, also at CROI, found the ring is also safe for breastfeeding women and their babies.
#CROI2023 @USAmbPEPFAR Dr John Nkengasong joined #CROI2023' Monday plenary session virtually from Jhb. His presentation was titled "20 years of #PEPFAR: Looking back, striding forward". @SECTION27news @WitsRHI @SAHIVSoc @iasociety @FrancoisVenter3 @TAC @UNAIDS_ESA @ygpillay pic.twitter.com/DzSxRZNbHj
-- Spotlight (@SpotlightNSP) February 20, 2023
Scientists say these latest findings pave the way for policymakers to feel confident about including pregnant and breastfeeding people in new national rollouts or pilots of the ring slated for South Africa and other African countries such as Eswatini, Kenya, and Zimbabwe.
In South Africa, the results will likely fuel increasing calls for the government to offer PrEP to pregnant people and new mothers routinely.
Pregnant people are three times more likely to contract HIV than their non-pregnant peers, a 2018 study published in The Journal of Infectious Diseases showed. The research found that women's HIV risk peaked during the six months after giving birth when they were up to four times as likely to become infected. Scientists believe biological changes during pregnancy and soon after likely explain this increased risk.
Now, the first study examining the ring's safety during pregnancy has found that the ring can be safely used from at least the seventh month of pregnancy onwards.
People who contract HIV during pregnancy or while breastfeeding are also more likely to pass the virus to their infants during labour via their breast milk.
How the study worked
To confirm whether the dapivirine-containing vaginal ring was safe to use in pregnancy, researchers recruited about 300 healthy, pregnant women between the ages of 18 and 40 in four countries: South Africa, Uganda, Malawi, and Zimbabwe. Women were then randomised to take either the monthly vaginal ring or the daily HIV prevention pill.
This kind of randomisation means that any characteristics, such as age or location that could have a bearing on the study's outcome, should be equally present in both groups. Studies designed in this way - called randomised controlled clinical trials - are better at determining cause and effect than other types of studies and are often called the "gold standard" in research.
Dapivirine vaginal ring safe to use in third trimester of pregnancy and during breastfeeding https://t.co/C64kx7llgU pic.twitter.com/xdu5Kpl1cZ
-- NAM aidsmap (@aidsmap) February 22, 2023
In the interest of safety, scientists then split the study into three sequential phases - The first phase was conducted among 150 women who were eight or nine months pregnant and were at the least risk of any side effects. Only once an independent expert panel reviewed data from this first phase and found no safety concerns, did scientists start roughly an equal number of women who were about seven to eight months pregnant onto the study.
Bunge says that not only did this study design help protect women and their foetuses, but many women appreciated this added level of caution. But she says, it also allowed the study to report data sooner, as each phase was completed.
No increased risk of pregnancy or birth complications
Researchers followed up with women until six weeks after delivery, checking to see whether they experienced higher than normal rates of miscarriages, or still or premature births. Additionally, study participants were monitored for a range of dangerous yet common conditions related to high blood pressure, haemorrhages, fevers, and other infections.
For years, we've suffered from a lack of high-quality data about whether a drug is safe or not to use in pregnancy. I am an obstetrician and gynaecologist, and I can't tell you how frustrating it is when I have a patient that needs medication, and I can't reassure her about the safety of it in pregnancy. - Prof Katherine Bunge
Ultimately, the study found no risk of pregnancy or birth complications associated with either the pill or the vaginal ring.
The third phase of the study will look at the safety of the ring and pill in women between three to about seven months of pregnancy. This phase is ongoing and is expected to conclude around May.
"For years, we've suffered from a lack of high-quality data about whether a drug is safe or not to use in pregnancy," Bunge says. "I am an obstetrician and gynaecologist, and I can't tell you how frustrating it is when I have a patient that needs medication, and I can't reassure her about the safety of it in pregnancy,"
Safe to use during breastfeeding
A separate study conducted in the same countries and also reported at CROI has also become the first to report on the safety of the vagina ring during breastfeeding. The research included about 200 breastfeeding mothers on PrEP and their six- to 12-week-old infants. Women were then randomly assigned to use the ring or the HIV prevention pill, which has already been shown to be safe during breastfeeding.
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The study found very low concentrations of dapivirine in women's breastmilk and even lower amounts in their infant's blood, posing no safety concerns for the babies.
"Women need safe and effective methods for HIV prevention they can use at all times of their lives, perhaps especially when they are breastfeeding, which we know to be a time of heightened risk for infection," said researcher Maxie Owor, who helped lead the study and is based at Uganda's Makerere University-Johns Hopkins University (MU-JHU) Research Collaboration centre. "This is why these results are so important."
A right to access PrEP
The results presented at CROI this year are likely to strengthen calls for PrEP for expecting or new mothers to be better integrated into antenatal and early infant care.
Mathematical modelling published in 2020 in the journal AIDS estimated that offering PrEP to pregnant or breastfeeding people could prevent up to 136 000 new HIV infections between 2020 and 2030. The bulk of these averted infections would be among infants who would otherwise contract HIV via breast milk.
In the two years since the study was published, there have been repeated calls for PrEP to be made more readily available to women via antenatal clinics and after delivery.
"All pregnant women who test HIV-negative at their first antenatal visit should receive the offer to start PrEP," wrote study author Dr Dvora Joseph Davey in The Conversation in 2021. Joseph Davey is a University of Cape Town honorary senior lecturer in Biostatistics and Epidemiology. The piece was co-authored by Desmond Tutu HIV Centre Director Professor Linda-Gail Bekker. "This must be accompanied by comprehensive HIV prevention services, including counselling to support them to take daily PrEP while pregnant and breastfeeding."
"These women have the right to access PrEP to protect themselves against HIV during this high-risk period," they wrote.
