National Partnership for Women & Families

Monthly Women's Health Research Review

Study examines risks related to IUD use among women with HIV

Summary of "Safety of intrauterine devices among women with HIV: A systematic review," Tepper et al., Contraception, June 17, 2016.

"Use of highly effective contraception by women living with HIV is critical in order to prevent unintended pregnancy and potential risks of maternal complications and perinatal HIV transmission," according to Naomi Tepper of CDC's Division of Reproductive Health and colleagues. They noted that about "8300 women in the United States were diagnosed with HIV in 2014, and over 220,000 women are estimated to be living with HIV."

The U.S. Medical Eligibility Criteria for Contraceptive Use notes that "highly effective contraceptive methods may be the best choice" for women with HIV/AIDS, which is "associated with increased risk for adverse health events as a result of unintended pregnancy." Specifically, the researchers cited intrauterine devices (IUDs), which are "long acting and highly effective with typical use."

According to the researchers, "Women with more advanced HIV disease are likely to be at highest risk for complications of pregnancy and transmission to the infant and would likely benefit most from use of IUDs." That said, the researchers noted that there are concerns surrounding the use of IUDs among HIV-infected women, including "the potential for ascending genital tract infection, worsening of HIV disease and transmission to noninfected sexual partners."

The researchers conducted a research review "to identify evidence on risks related to IUD use among women with HIV, with particular focus on women with advanced disease."

Materials and methods

In the research review, the researchers aimed to answer three key questions:

  • Do women with advanced HIV who are using IUDs have a higher risk of pelvic infection, compared with noninfected women or those in less advanced stages?
  • Does IUD use among women in advanced stages of HIV increase the risk of HIV progression, compared with hormonal contraception or IUD nonuse?; and
  • Does IUD use among women in advanced stages of HIV increase the transmission risk to noninfected sexual partners, compared with hormonal contraception or IUD nonuse?

The researchers conducted the review by searching the PubMed database for all relevant articles published from between the database's launch and January 2016. They selected articles based on whether they were "primary research articles on adverse outcomes among women with HIV using IUDs."

The researchers examined studies utilizing copper, levonorgestrel (LNG) and "unspecified types" of IUDs. Meanwhile, the "[o]utcomes of interest included pelvic inflammatory disease (PID), pelvic infection, sepsis or any infectious complication," as well as IUD complications related to HIV disease severity.

Results

The researchers included 16 articles in the final review. Of those, three articles evaluated two randomized controlled trials, four articles assessed cohort studies, two articles examined cross-sectional studies and seven focused on follow-up studies that did not have comparison groups. Meanwhile, eight of the 16 studies examined the use of copper IUDs, five examined the use of LNG IUDs and four did not specify the type of IUD examined.

Pelvic infections

According to the researchers, eight articles addressed pelvic infection complications related to IUD use.

The researchers wrote that the sole randomized controlled trial addressing pelvic infections compared postparturm HIV-infected women assigned copper IUDs with women assigned oral contraception. In two years of follow-up, the study identified one case of PID in the group utilizing IUDs and none in the oral contraception group.

The researchers also found two articles on a prospective cohort study involving "156 women with HIV compared with 493 women without HIV using copper IUDs." Neither article found any difference in the rate of complications for women at less severe stages of the disease compared with women at more advanced stages of the disease.

According to the researchers, five articles reviewed pelvic infections among IUD users, but they did not have comparison groups. Of those, three examined HIV-infected women using LNG IUDs and "found no cases of pelvic infection or PID during 6 months, 45 months and 5 years of follow up." A separate study, which examined 703 HIV-infected women using IUDs for one year, "found that 0.6% of copper IUD users and 0.9% of LNG-IUD users developed PID."

HIV disease progression

The researchers identified eight articles that addressed the progression of HIV.

According to the researchers, three of the articles examined a randomized controlled trial and found that women using hormonal contraception were slightly more likely than those using copper IUDs to report declines in their CD4 count, or the number of a type of white blood cell that supports immune system function. There was not a statistically significant difference in the death rate between the two groups. An analysis on a separate randomized controlled trial, which similarly compared HIV-infected women using copper IUDs with those using hormonal contraception, found that at 48-weeks follow up, there was no change in the mean CD4 count in either group and no significant difference in the number of women in each group who altered their antiretroviral therapy (ART) regimen.

A cohort study compared HIV-infected women using IUDs to those using undisclosed contraception and found, at one-year follow up, no significant change in plasma HIV RNA among women not using ART. At five-years follow up, "there were no statistically significant differences between the IUD and control groups in CD4 count, when stratified by ART use, or proportion of women initiating ART."

According to the researchers, "Four follow-up studies without comparison groups reported HIV disease progression among IUD users." Specifically, one study found that "there was no significant change in CD4 count" at one-year follow up on women using LNG IUDs. A second study "found that among six women using LNG-IUDs, there was no statistically significant change in CD4 count during 24 months of follow up," the researchers wrote. They also pointed to a third study, which "found that among 30 women with HIV using LNG-IUDs, during 6 months of follow up, the mean CD4 count decreased" and "[t]here was no statistically significant change in plasma HIV-1 RNA." The fourth study, according to the researchers, "found that among 29 women with HIV using copper IUDs, there were no significant changes in CD4 count or HIV RNA at 6 months of follow up."

HIV transmission

Six articles reviewed HIV transmission, one of which "provided direct evidence on transmission from women with HIV to noninfected male partners. This study was a cohort study that found "no significant difference in rate of seroconversion of males whose HIV-infected female partners used IUDs ... or no contraceptive."

The researchers outlined the remaining studies, which were all "cross-sectional or follow-up studies without comparison groups." One of the studies "found that rate of detection of cervical HIV-1 DNA did not differ between IUD users (n=6) compared with no contraceptive method (n=182)." Another study found that "there were no statistically significant differences in prevalence of cervical HIV-1 DNA shedding at 4 months (43%) compared with baseline (50%)." According to the researchers, a third study found "no association of IUD use with genital shedding." A fourth study "found that among 12 women using LNG-IUDs and who were using ART at baseline, there was no difference in genital HIV RNA at 12 months of follow up." That study also found that, "[a]mong two women not using ART, genital HIV RNA was present in half of samples," with "RNA levels increas[ing] in one woman and decreas[ing] in one woman after IUD initiation." The fifth study found "no statistically significant change in levels of genital HIV-1 RNA during the 6 months of follow up."

Discussion

The researchers noted that among the studies examining pelvic infections, there was "an overall low incidence of PID among women with HIV using IUDs." Meanwhile, among the eight articles on HIV disease progression, the researchers wrote there was "generally no difference between women using IUDs compared with other contraceptives, nor ... [any] changes between baseline ... and follow-up," the researchers wrote. Similarly, the sole study focused on HIV transmission and the five articles focused on markers of HIV infectivity found "no difference in transmission or genital viral shedding among women using IUDs."

However, the researchers noted, "This body of evidence is of fair to poor quality and is subject to several limitations," including small sample size, low rates of follow-up and unstandardized definitions of HIV severity.

The researchers found that there was limited evidence on the "risk of ascending infection and PID" among HIV-infected women using IUDs. The researchers wrote that the lack of evidence spurred them to assess "analogous situations, such as similar procedures among women with HIV or IUD insertions among women with other immunocompromised conditions." According to the researchers, studies on such analogous situations "have generally not found statistical differences in infectious complications compared with noninfected women."

Regarding the potential "worsening of HIV disease and transmission to noninfected male partners" among HIV-infected women using IUDs, the researchers wrote that one of the reviewed studies "found that neither copper nor LNG-IUDs affected genital tract immune cells in HIV noninfected women." According to the researchers, it is unclear whether conflicting evidence on whether certain cervical procedures increase cervical HIV RNA levels can be extrapolated to IUD use.

The researchers noted that "[t]he limited body of evidence on safety of IUDs among women with HIV highlights the need for further study on the issue." They called for the standardization of HIV severity definitions and recommended that "[f]uture studies ... clearly define comparison groups, IUD type and timing of initiation and outcomes, and ... account for important confounders such as ART, condom use and [sexually transmitted infections]."

The researchers concluded that "limited evidence found no differences in infectious complications when comparing IUD complication rates among women with varying levels of HIV disease severity." In addition, the researchers wrote that while "[s]tudies generally found that IUD use was not associated with HIV transmission, infectivity or disease progression ..., there was little direct evidence to address potential differences related to HIV severity." Nonetheless, "the evidence identified by this review does not demonstrate additional risk for women with HIV who use IUDs," the researchers stated.