Head of Department of Infectious Diseases and Tropical Medicine
Full Professor of Infectious Diseases
Infectious Diseases Clinics, University Hospital
University of Modena and Reggio Emilia
Cristina Mussini, MD, has disclosed that she has received funds for research support from Gilead Sciences and has served on advisory boards for Gilead Sciences, Janssen, Merck, and ViiV Healthcare.
Although they account for most global HIV infections, women have been historically underrepresented in HIV trials. At the 17th European AIDS Conference (EACS 2019) in Basel, Switzerland, multiple abstracts focused on data exclusively from or applicable to women. Below, I highlight how this moves us closer to a more defined scientific approach for determining and improving outcomes in this population.
Long-Acting Injectable ART
With enrollment targets for women of 1 in 4 and 1 in 5, respectively, the phase III ATLAS and FLAIR studies previously demonstrated the noninferior efficacy of a switch to monthly injectable cabotegravir (CAB) plus rilpivirine (RPV) compared with continued daily oral ART.
At EACS 2019, we saw a pooled analysis of virologic response, safety, and treatment satisfaction by sex. Per FDA Snapshot analysis, 3.1% of women receiving long-acting CAB plus RPV vs 1.4% of men experienced virologic nonresponse (ie, HIV-1 RNA ≥ 50 copies/mL) at Week 48. This complements older studies that identified female sex as a risk factor for worse virologic control. As an example, in the GEPPO cohort of Italian patients 65 years of age or older, the rate of virologic suppression was much lower in women vs men, even though being older has been associated with better virologic control.
In terms of safety and tolerability, women reported numerically lower rates of adverse events in ATLAS and FLAIR, which is important and unlike many previous ART studies. By HIVTSQ scores, the women seemed quite satisfied with and motivated by the infrequent injection schedule; they also reported fewer instances of high-grade injection-site pain (1% vs 5% for men).
Some may think that more recent acknowledgement of the undetectable equals untransmittable (U=U) concept as scientifically sound would improve sexual satisfaction for patients receiving ART. However, in my practice, many women stopped using condoms when they and/or their partners achieved an undetectable viral load well before the U=U campaign became widespread.
One observational cohort study from EACS 2019 showed that despite virologic suppression and immune reconstitution, women of childbearing age receiving stable ART reported lower levels of desire and arousal as well as higher levels of overall sexual dysfunction compared with uninfected women. Thus, increased efforts are needed to improve sexual satisfaction for women with HIV.
ART and Pregnancy
Another important issue for women with HIV is the ongoing assessment of ARV safety just before and during pregnancy. Data from 650 women in the Antiretroviral Pregnancy Registry (APR) with exposure to dolutegravir (DTG) were presented at EACS 2019. Among 312 periconception DTG exposures, 1 neural tube defect (NTD) was identified, resulting in a prevalence of 0.3%. Although this is the exact same NTD prevalence reported by the Tsepamo study in Botswana, the number of examined APR pregnancies is not sufficient to interpret the data on NTD risk at this time. In addition, it should be noted that, although the APR enrolls women with prenatal ARV exposure when the outcome of the pregnancy is unknown, registration is voluntary, likely resulting in selection bias.
Conference data from the EuroSIDA study described pregnancy rates and outcomes between 1996 and 2015 in a cohort of 4217 European women with HIV. In Eastern Europe, women were younger at the time of pregnancy compared with other regions. There was also an increase in the odds of pregnancy after more effective ART became available. This underscores the growing confidence in becoming pregnant among European women with HIV. Pregnancy is an essential part of well-being for many women and should be considered in the care of women with HIV.
In 2016, the Swiss Federal Office of Public Health changed its guidelines to no longer recommend postexposure prophylaxis (PEP) for newborns if maternal HIV-1 RNA was suppressed in the third trimester. At EACS 2019, data were presented on children in the Swiss Mother and Child HIV Cohort Study born between 2010 and 2018. Analyses showed that the new PEP recommendations were implemented rapidly, with 98.9% of children born before 2016 to mothers with suppressed HIV-1 RNA receiving PEP compared with 12.5% after the guideline change. Of note, among the 87 children who received no PEP, zero HIV transmission events occurred. This suggests that PEP can be avoided in newborns if the mother is virologically suppressed, sparing infants the toxicity associated with ARV treatment.
Another study assessing the risk of mother-to-child transmission (MTCT), this time during breastfeeding from mothers receiving ART in rural Tanzania, was presented. The study included 229 infants born to 215 women enrolled on the Kilombero and Ulanga Antiretroviral Cohort who initiated ART before delivery and breastfed exclusively for at least 6 months. Overall, 91% of women had HIV-1 RNA < 1000 copies/mL at follow-up during the breastfeeding period. With 79% of infants having reached their final serostatus assessment (18 months of age), 2 infants (1%) were infected with HIV through breastfeeding—1 born to a mother with a high viral load at delivery and the other to a mother who interrupted treatment during the postpartum period. There was no MTCT through breastfeeding from mothers who maintained virologic suppression. Despite these encouraging data, in settings where safe and affordable feeding alternatives exist, breastfeeding is not typically recommended for mothers with HIV.
Overall, although we remain concerned about the health of infants born to mothers infected with HIV, these data represent our attempts to normalize the reproductive process for women—from natural conception to vaginal delivery all the way to breastfeeding infants in the absence of neonatal PEP.
ART and Weight Gain
Finally, another focus of EACS 2019 was taking a closer look into the reports of increased weight gain with INSTI treatment. Multiple studies have now reported this phenomenon, and women, particularly black women, seem to be at greater risk for large weight increases (eg, 5-10 kg). Strikingly, in the phase III ADVANCE trial in South Africa, some women receiving first-line DTG gained 35-50 kg, and female sex was significantly associated with a ≥ 10% increase in body weight. Researchers are currently trying to understand whether there is a specific immunologic pattern that could lead to weight gain. It will be important to continue investigating the pathomechanism of weight gain with ART in the future.
We must continue to recruit more women with HIV in clinical trials. The only way to ensure equal representation is to set enrollment targets by sex. When these targets are not prespecified, too few women are included, making it difficult to draw definitive conclusions from subset data.
Which data from EACS 2019 will most affect your practice? Join the discussion by posting a comment or answering the poll. Then, for details on the key issues discussed at EACS 2019, review more Conference Coverage from CCO here.