Study Summary: Risk of Mother-to-Baby-HIV Trasmission Among Mothers Coinfected with Other STIs

Background

An estimated 250 million new cases of treatable bacterial sexually transmitted infections (STIs) occur worldwide each year. The complications of these infections have a substantial impact on pregnant women, especially younger women living in low- and middle-income countries. For example, untreated STIs caused by Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and Treponema pallidum (TP) lead to various pregnancy complications, such as miscarriage, stillbirth, and preterm labor and delivery. STIs caused by viruses can also have harmful effects during pregnancy. In particular, transmission of cytomegalovirus (CMV) from the mother to the fetus during pregnancy can lead to considerable neurodevelopmental morbidity. Indeed, congenital CMV infection among infants is a leading infectious cause of sensorineural hearing loss and developmental delay. In this study, Adachi and colleagues evaluated the impact of maternal coinfection with STIs on mother-to-child transmission (MTCT) of HIV among high-risk, HIV-infected women who were naïve to antiretroviral treatment during pregnancy.¹

Study Design

The researchers performed a retrospective, cross-sectional substudy in which they examined clinical specimens and data from mother—infant pairs from the phase 3, randomized National Institute of Child Health and Human Development HIV Prevention Trials Network 040 trial, also known as the International Maternal Pediatric Adolescent AIDS Clinical Trials Network (IMPAACT) P1043.² The IMPAACT trial took place from 2004 to 2011 at multiple international locations in the Americas and South Africa and included 1684 infants born to HIV-infected pregnant women. These women were considered at high risk for MTCT of HIV because they were diagnosed with HIV late in pregnancy or at delivery, and they had not received antiretroviral therapy. The trial excluded infants born prior to 32 weeks’ gestation.²

In their substudy, Adachi and colleagues included only those mother—infant pairs for whom maternal blood and urine samples were available to test for CT, NG, and TP, and CMV infection. Maternal urine samples were collected either at labor and delivery or within 48 hours of delivery and frozen until testing; the infants’ urine samples were also collected within 48 hours of birth.¹

Maternal urine samples were utilized to test for CT and NG with a CT/NG assay. Whenever possible, the researchers used polymerase chain reaction to test the maternal urine for CMV; in cases where sufficient maternal urine was not available, infant urine was tested for CMV. To detect syphilis, titers with confirmatory treponemal syphilis antibody tests were performed using maternal blood samples. In addition, maternal blood samples were used to measure HIV RNA levels and T-lymphocyte subsets. Finally, infant blood samples were tested for HIV at multiple timepoints: within 48 hours of birth, at 14 days, between 4 and 6 weeks, and at 3 and 6 months.¹

The researchers also collected information about the mothers, including sociodemographic characteristics, obstetric history (including information about their prenatal care and whether they had a history of stillbirth), and high-risk behaviors (including alcohol use and substance abuse) during pregnancy. Investigators analyzed the data using statistical software to evaluate the risk factors associated with STIs (CT, NG, TP, and CMV) and their impact on MTCT of HIV among this high-risk patient population.¹

Results

The substudy included 899 mother—infant pairs. Most of the mothers included in the substudy (86.2%) were from the Americas (Brazil, Argentina, and the United States), with a mean age of 26.5 years (SD, 6.3) (Table 1).¹ Although most of the women (69.4%) had received some prenatal care, they reported high rates of high-risk behaviors during pregnancy and poor outcomes during previous pregnancies (Table 1).

Preterm delivery (delivery before 37 weeks) affected about 1 in 10 infants, and about 1 in 6 were born with low birth weight (<2500 grams). Overall, infants experienced a high rate (38.9%) of adverse events during the study.¹

The researchers noted high rates of STIs among the mothers, with almost one-third testing positive for either CT, NG, TP, and/or CMV at delivery (Table 1), with the rates of these STIs highest among women between the ages of 13 and 24. Ten percent of the infants tested positive for HIV (Table 2).¹ Babies born to women with any STI were almost twice as likely to become infected with HIV as babies born to women without an STI (Table 2). Approximately 43% of HIV-infected infants were born to mothers with at least 1 STI, and the MTCT rates were significantly higher among mothers with 2 of the 4 STIs of interest (Table 2). High viral load and elevated CD4+ count were also significantly associated with MTCT of HIV (Table 2).¹

The researchers noted that HIV transmission rates varied according to the specific comorbid maternal STI. Because they had limited samples to perform maternal CMV tests, investigators relied on infant CMV testing to extrapolate maternal CMV status. Based on infant CMV testing results, the highest risk of MTCT of HIV was observed among infants with congenital CMV infection (26.3%); the next highest transmission risk (12.5%) was among women with CT coinfection.¹

Conclusions

The results of this study demonstrated that HIV-infected pregnant women are frequently coinfected with other STIs, and that these coinfections are associated with increased risk of MTCT of HIV. The risk of HIV transmission was greatest among mothers with concurrent CMV infection, although the study authors noted that the association between HIV and CMV infection is complicated and not completely understood. The researchers speculated that maternal STI coinfections with CT, NG, TP, and CMV may trigger several different mechanisms that could result in MTCT of HIV. For example, such coinfections may result in cervical or placental inflammation, which may facilitate MTCT of HIV. This inflammation may also lead to immune activation and subsequent upregulation of certain T-cell receptors and inflammatory cell co-receptors, increasing the odds of HIV infection. Overall, the results of this study highlighted the importance of including STI screening as part of routine prenatal care, especially for high-risk pregnant women, such as those who are young and infected with HIV.

References

1. Adachi K, Xu J, Yeganeh N, et al; NICHD HPTN 040 Study Team. Combined evaluation of sexually transmitted infections in HIV-infected pregnant women and infant HIV transmission. PLoS One. 2018; 13(1):e0189851. doi: 10.1371/journal.pone.0189851.

2. Nielsen-Saines K, Watts DH, Veloso VG, et al; NICHD HPTN 040/PACTG 1043 Protocol Team. Three postpartum antiretroviral regimens to prevent intrapartum HIV infection. N Engl J Med. 2012;366(25):2368-2379. doi: 10.1056/NEJMoa1108275.