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Female HIV acquisition per sex act is elevated in late pregnancy and postpartum
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Reported by Jules Levin
CROI 2018 March 4-7 Boston MA
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Kerry A. Thomson,1James Hughes,1Jared M. Baeten,1Grace John-Stewart,1Connie Celum,1Craig R. Cohen,2Nelly Mugo,1James Kiarie,1,3andRenee Heffron1
for the Partners in Prevention HSV/HIV Transmission Study and Partners PrEP Study Teams
1University of Washington, Seattle, WA, USA 2University of California, San Francisco, CA, USA 3World Health Organization, Reproductive Health and Research Human Reproduction Programme, Geneva, Switzerland
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JID March 3 2018 Accepted Manuscript Editor's Choice
Increased Risk of Female HIV-1 Acquisition Throughout Pregnancy and Postpartum: A Prospective Per-coital Act Analysis Among Women with HIV-1 Infected Partners
"This study provides strong evidence that the risk of HIV-1 acquisition per-sex act steadily increases throughout pregnancy and is highest during postpartum."
Results
At total of 686 pregnancies were identified and 82 incident HIV-1 infections occurred. After adjustment for condom use, age, PrEP use, and HIV-1 viral load, the per act probability of HIV-1 acquisition was higher in late pregnancy (aRR 2.82, p=0.01) and postpartum (aRR 3.97, p=0.01) compared to non-pregnant periods. The HIV-1 acquisition probability per condomless sex act for a 25 year old woman not taking PrEP with an HIV-1 infected male partner with viral load of 10,000 copies/ml was 0.0011 (95% CI: 0.005, 0.0019), 0.0022 (95% CI: 0.0004, 0.0093), 0.0030 (95% CI: 0.0007, 0.0108), and 0.0042 (95% CI: 0.0007, 0.0177) in the non-pregnant, early pregnant, late pregnant, and postpartum periods, respectively.
Conclusion
The HIV-1 acquisition probability per condomless sex act steadily increased through pregnancy and was highest during the postpartum period, suggesting that biological changes during pregnancy and postpartum increase female HIV-1 susceptibility.
Our results suggest that biological factors associated with pregnancy increase female HIV-1 susceptibility. The high levels of estrogen and progesterone that accompany pregnancy can induce a cascade of synergistic changes within the female genital tract) including changes in CCR5 and CXCR4 expression, increased inflammation, decreased integrity of the vaginal epithelium, and alterations in vaginal microbiota, all of which have been associated with increased HIV-1 susceptibility [25]. Pregnancy activates innate immunity, increasing inflammation and HIV-1 target cells in the female genital tract [4, 9], while simultaneously suppressing adaptive immunity and reducing natural killer cells, changes that can persist as long as nine months after delivery [5, 7]. Results from animal, ex vivo, and human epidemiological studies have demonstrated that such immune activation and the ensuing inflammation are associated with increased risk of HIV-1 acquisition [10-12, 26].
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Program Abstract:
In many settings with high HIV prevalence, fertility rates are also high and women spend a significant proportion of their reproductive years pregnant, postpartum, or breastfeeding. Some, but not all, studies have demonstrated significantly higher HIV incidence during pregnancy. Per sex act analyses contribute an understanding of the absolute and relative risks of HIV transmission, and can provide insight into whether increased risk during pregnancy and postpartum is attributable to biological or sexual behavior changes. These data are critical to inform the delivery of HIV prevention interventions for women.
2,751 African HIV serodiscordant couples with HIV uninfected female partners were followed prospectively for ≤48 months in two HIV prevention studies. Sexual frequency and condom use was reported monthly. HIV and pregnancy testing occurred monthly or quarterly depending on the study. Study time was categorized by reproductive stage as early pregnancy, late pregnancy, up to 6 months postpartum, or non-pregnant. HIV events that could not be linked between study partners by genetic sequencing were excluded. We used a complementary log-log model to compare the probability of male-to-female HIV transmission per sex act by reproductive stage. The reference case for HIV transmission probability is a condomless sex act between a 25 year old woman not using PrEP and a male partner with HIV RNA of 10,000 copies/ml.
Pregnancy incidence was 12.50 per 100 woman-years (95% CI: 11.52-13.55) and 82 HIV transmission events occurred. The HIV transmission probability was 1.05 per 1,000 sex acts when women were not pregnant, 2.19 in early pregnancy, 2.97 in late pregnancy, and 4.18 in postpartum women (Figure). After adjustment for condom use, age, use of PrEP, and HIV viral load, the probability of HIV transmission per sex act was significantly higher in late pregnancy (aRR 2.82, p=0.01) and postpartum (aRR 3.97, p=0.01) compared to non-pregnant time.
The risk of HIV transmission per sex act steadily increased through pregnancy and was highest during postpartum, even after accounting for sexual behavior, PrEP, and HIV viral load, suggesting that biological changes during these periods increase HIV risk. While further research is needed to better understand biological susceptibility, scale-up of HIV prevention and testing in antenatal and postpartum care in high HIV prevalence settings is warranted to prevent sexual transmission and identify acute maternal HIV infections.
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