Research Is Still Exploring Best Treatment Strategies for Pregnant and Breastfeeding Women, Interactions With Contraceptives
Although women comprise more than half of adults living with HIV across the globe, they are considered a special population worthy of more intensive research. Now, several new studies presented at the annual Conference on Retroviruses and Opportunistic Infections (CROI) underscore the complex ways that HIV risk and treatment adherence manifest among women of childbearing age.
"Everyone here is familiar with the global expansion of access to antiretroviral therapy in pregnant and postpartum women," said Landon Myer, M.B.B.C.H., Ph.D., University of Cape Town, South Africa, addressing the audience during the oral abstract session, "Critical Issues in Women's Health and Early Treatment of Pediatric HIV Infection."
Yet, that expansion of treatment has raised new questions about the interaction that antiretroviral therapy (ART) might have with hormonal birth control, pregnancy, and the postpartum period. Five presenters attempted to tackle some of these big, complicated questions during their 15-minute presentations on Wednesday, March 7.
While the new data presented at CROI addressed different issues related to HIV in women, each new analysis offered valuable insights for clinicians working to ensure that these women can live healthy and fulfilled lives regardless of their decision to have children or to avoid pregnancy altogether.
Myer highlighted some of the big unknowns related to HIV in pregnant and postpartum women during his presentation, "ART Detection and Resistance During Viraemic Episodes in Pregnancy and Breastfeeding."
As Myer told the audience, "everyone is familiar with the major concerns that have emerged around elevated viral load in women who initiate ART during pregnancy, followed up in the postpartum period," yet the etiology "remains unclear."
Meanwhile, "there are growing concerns around pre-treatment antiretroviral resistance," Myers said, adding, "There's a standing question around how much of the viral load can be attributable to nonadherence or to drug resistant mutations."
To answer that question, Myer and his colleagues conducted an analysis of 528 women who initiated HIV treatment during pregnancy as part of routine care in Cape Town, South Africa, following the women to track any episodes of viremia. Upon final analysis, Myer found that only 7% of viremic episodes were attributed to pre-treatment resistant strains, while 75% were attributed to non-adherence.
One audience member piped up to congratulate Myer on his excellent, yet "depressing," work. Myer used the opportunity to remind the audience that, despite the hype surrounding dolutegravir (Tivicay) as an exciting new option for women with HIV, the underlying issues related to treatment adherence mean that dolutegravir might not be a panacea for the persistent challenge of treating HIV among women of childbearing age.
Further sobering data was presented by Amita Gupta, M.D., Johns Hopkins Center for Clinical Global Health Education, Baltimore, who revealed results of the first randomized trial looking at pre-exposure tuberculosis (TB) therapy isoniazid after pregnancy.
Although pre-exposure isoniazid is recommended by the World Health Organization (WHO) in combination with ART in pregnant women with HIV and at-risk of TB, the results did not demonstrate a distinct advantage to starting isoniazid treatment during pregnancy. In fact, they raise the question of whether it might be better to delay prophylactic treatment with isoniazid until after birth, Gupta noted.
More Power Needed
Two researchers at the oral abstract session presented different analyses of the massive PROMISE study, which enrolled thousands of HIV-positive women. Both analyses attempted to tease out the difference in outcomes among women in the study who continued ART after birth and breastfeeding, and those who didn't. Yet, neither found overwhelming evidence that continued ART dramatically improves outcomes.
(Of note, this research was initiated prior to evidence from the START trial that led to new recommendations to begin ART as quickly as possible in all HIV-positive patients.)
The first analysis, presented by Risa M. Hoffman, M.D., David Geffen School of Medicine at University of California Los Angeles, compared clinical outcomes between women who continued ART after birth and those who did not. Participants were further separated into women who breast-fed their children and those who used formula.
Hoffman found that ART was safe and well tolerated among postpartum women, and results were comparable between breastfeeding and women who used formula. Meanwhile, she found that rates of AIDS-defining adverse events were slightly more common among women who discontinued treatment, but not enough to be statistically significant. Yet, when measured based on the WHO's definition of stage 2 or stage 3 adverse events, the rate of such events was halved in women who continued ART after birth.
A second analysis of the PROMISE study was presented by Taha E. Taha, Ph.D., Johns Hopkins University, Baltimore. Unlike Hoffman's analysis, Taha focused on the period after women stopped breastfeeding, comparing women who discontinued ART during this period to those who continued ART, followed for a period of 84 weeks.
Worryingly, adverse events were significantly higher in the women who continued ART compared with those who discontinued treatment. This result prompted one audience member to ask whether we should even be treating women after breastfeeding discontinuation, noting, "We may be doing more harm than good."
However, Taha emphasized that "the study was done at a time when the recommendations were different," and "studies of newer ARTs are needed to improve outcomes for postpartum women."
Ring Around Pregnancy
Today, many HIV clinicians are excited about the idea of preventing pregnancy and HIV with a single intra-vaginal ring. Yet, even as research into this new technology is ongoing, we know very little about the interplay between hormones used for ring-based contraception methods and antiretroviral medications.
Kimberly K. Scarsi, Pharm.D., University of Nebraska Medical Center, Omaha, presented data finding that vaginal contraceptive hormone exposure was profoundly impacted by efavirenz (Sustiva, Stocrin)-based and atazanavir (Reyataz)-based ART.
Overall, Scarsi found that the vaginal contraceptive ring, or Nuvaring, was safe and well tolerated in all 74 participants included for analysis. Those who were taking atazanavir-based regimens had lower estrogen exposure and higher progesterone exposure, which made Scarsi and her colleagues comfortable in assuming that the effectiveness of hormonal contraception was preserved.
"In contrast," Scarsi said, "the efavirenz-based antiretroviral therapy decreased both hormone components dramatically, which we feel could impair the effectiveness of hormones administered via vaginal ring."
As researchers are working diligently to develop multi-purpose vaginal rings that contain both hormonal contraceptives and HIV treatment or prevention medicines, Scarsi's research highlights the importance of carefully conducted pharmacokinetics studies.
Researchers are now just beginning to scratch the surface of how hormones, pregnancy, and even the vaginal microbiome interact with HIV transmission risk and the effectiveness of HIV medication.
"In that context, we have to think very careful about these drugs as they're being developed," Scarsi said.