A new meta-analysis has revealed that a woman's HIV risk increases substantially during the late stage of pregnancy and in the weeks after giving birth -- a finding that re-emphasizes the importance of women-controlled HIV prevention strategies, such as oral pre-exposure prophylaxis (PrEP).
In addition, the analysis hints at yet-unknown physiological changes associated with pregnancy that increase a woman's susceptibility to HIV infection. The research, led by Kerry A. Thomson, Ph.D., M.P.H., University of Washington, was published in the Journal of Infectious Diseases on March 5 and presented at the 2018 Conference on Retroviruses and Opportunistic Infections (CROI) in Boston by Renee Heffron, Ph.D., M.P.H., assistant professor, University of Washington at Seattle.
The researchers pooled multiple studies to analyze 2,751 African serodiscordant couples. They compared a woman's risk of contracting HIV when not pregnant, during early pregnancy, during late pregnancy, and during the postpartum period. As a benchmark, they determined the risk of HIV infection per condomless sex act for a non-pregnant, 25-year-old woman not taking PrEP and having sex with an HIV-positive partner with a viral load over 10,000 copies/mL.
During the studies they reviewed, about a quarter of women became pregnant and 82 women became HIV positive. Ultimately, 78 of those who were positive were included for analysis. The researchers found that, compared with non-pregnant periods, an HIV-negative woman's infection risk jumped nearly threefold during late-stage pregnancy and fourfold during the postpartum period.
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Specifically, for every 1,000 sex acts, the infectivity rate for non-pregnant and non-postpartum women was 1.05. That rate jumped to 2.19 during early pregnancy and 2.97 during late pregnancy. The rate jumped dramatically during the postpartum period to 4.18.
This risk remained even when researchers accounted for other possible confounding factors, such as condom use, age, PrEP use, and the viral load of an HIV-positive partner.
"We conducted a number of sensitivity analysis to examine the possibility of miscalculation or bias in our results, and in all of these analysis, we saw very similar results," Heffron said.
This research has important public health implications. Chiefly, the findings highlight the need for frequent HIV testing throughout pregnancy and the importance of promoting "women-controlled" HIV prevention strategies during pregnancy and in the months after birth or miscarriage, said Heffron.
Heffron and Thomson both pointed to PrEP as a highly effective, female-controlled HIV prevention strategy. PrEP is "an important option for women who are unable to engage their male partner(s) in other HIV prevention methods," said Thomson. In addition, antenatal and postnatal health care visits create an important window of opportunity for providers to offer PrEP, Thompson and Heffron noted.
"Kenya is one country currently offering pregnant women PrEP as part of their antenatal care," said Thomson. "Results from implementation studies evaluating different delivery models for PrEP use, such as PrIYA and PrIMA will provide additional evidence on how to integrate PrEP into routine service delivery for pregnant and postpartum women living in settings with high HIV prevalence."
In addition to the public health implications, these results suggest that a poorly understood biological change associated with pregnancy may contribute to an increased risk of HIV acquisition. Although the study did not look at biological mechanisms specifically, Heffron and Thomson hypothesized that the increased susceptibility to HIV might be influenced by physiological changes during pregnancy and the postpartum period -- changes that could include hormone levels, innate immunity, and suppression of the adaptive immune system.
Thomson noted that future research into this area could include a non-randomized longitudinal study that collects biological specimens from women before, during, and after pregnancy for laboratory analysis.
Although this study raises many new questions for HIV researchers, it also helps to resolve a debate on the relationship between pregnancy and HIV risk.
According to Heffron, prior studies looking at this relationship have seen mixed results, "with some studies showing no association between pregnancy and HIV risk and other studies estimating a doubling of HIV risk," she said.
One possible explanation for the mixed results is that different researchers might have applied different ways of measuring sexual behavior in their analysis. Because pregnancy is often associated with changes in sexual behavior, it's important to collect data frequently throughout a study.
The 2,751 African couples included for analysis were pulled from two longitudinal HIV preventions studies, Partners in Prevention and Partners PrEP. Both studies frequently tested for HIV status and pregnancy and collected monthly data on sexual behavior. The analysis accounted for decreases in sexual frequency and condom use as pregnancy progressed, said Heffron.
In cases of new HIV infection, the researchers were also able to test HIV strains to ensure that they were counting infections traced to a woman's study partner and not an external partner.
The analysis not only answers the question of whether a woman's risk of HIV infection increases during pregnancy but also creates a "call to action" for care providers, according to an editorial accompanying the meta-analysis written by Lynne Mofenson, M.D., of the Elizabeth Glaser Pediatric AIDS Foundation.
In many countries in Africa, this call to action is especially urgent. For example, in Kenya, female life expectancy is 63 years old, and women spend, on average, seven years either pregnant or breastfeeding -- meaning that a woman's risk of HIV is substantially increased for about 10% of her life, Heffron explained.
"In areas like Kenya where women bear a heavy burden of the HIV epidemic and spend a substantial proportion of their lives pregnant or postpartum, understanding a potential link between pregnancy and postpartum and HIV risk could have a big impact on HIV prevention," Heffron said.