Possible mechanism explains increased HIV risk caused by progestin-only contraceptives
Recent findings published in The Lancet showed that injectable progestin-only contraceptives and high endogenous progesterone use are both associated with an increased number of HIV target cells at the cervix, which may help explain the reported increase of HIV in women with high exposure to progestin.
“Defining the role of injectable progestin-only contraceptives in HIV acquisition is of utmost relevance, particularly in regions of the world where HIV transmission is highest,” Douglas S. Kwon, MD, assistant professor at the Ragon Institute of MGH, MIT and Harvard, and colleagues wrote. “These findings support a role for both endogenous and exogenous progestins in modulating the frequency of cervical target cells.”
Injectable progestin-only hormonal contraceptives are the favored form of contraception in Sub-Saharan Africa, where they are used by more than 8 million women, as the contraceptives can be taken discreetly and are available in long-acting formulations that are more than 99% effective, according to the researchers.
The role of progestin in HIV risk
Between Nov. 19, 2012 and May 31, 2015, Kwon and colleagues conducted a prospective cohort study that included 432 women aged 18 to 23 years who were not pregnant, did not have HIV, and who were living in Umlazi, South Africa, as part of the Females Rising through Education, Support and Health study. The researchers tested for HIV twice weekly and collected demographic and behavioral data as well as blood and cervical samples. They sought to characterize the risk for HIV acquisition associated with injectable progestin-only contraceptive use.
The researchers found that women using injectable progestin-only contraceptives were at higher risk for acquiring HIV and had 3.92 times as many cervical HIV target cells (P = .0241) — specifically CCR5+ CD4 T cells — compared with women using no long-term contraception (adjusted HR = 2.93; 95% CI, 1.09-7.86). In addition, women using no long-term contraceptives in the luteal phase of the menstrual cycle, when the natural progesterone state is the highest, had 3.25 times as many HIV target cells compared with those in the follicular phase (P = .0488). This finding suggests that a naturally high progestin state produced similar immunological changes as injectable progestin-only contraception, according to the researchers.
The risks of injectable progestin-only contraceptives must be weighed against those associated with other contraceptives and communicated to women, the researchers said.
“In areas with both widespread injectable progestin-only contraceptive use and high HIV incidence, including many regions in sub-Saharan Africa, the questions of whether and how injectable progestin-only contraceptives affect HIV acquisition risk are of utmost importance,” Kwon and colleagues wrote. “Decisions regarding the use of injectable progestin-only contraceptives must carefully balance the risk of HIV acquisition with that of unwanted pregnancy.”
In a related editorial, Gita Ramjee, PhD, director of the HIV Prevention Unit at South African Medical Research Council, and Sheena McCormack, MD, senior clinical scientist in the MRC Clinical Trials Unit at University College London, wrote that the study by Kwon and colleagues did not sufficiently explain the reason why progestin-only contraceptives increase the risk for HIV.
“The study provides some insight into the biological pathway, but does not sufficiently explain the mechanism for us to understand any differences in risk according to the source of progestin, particularly to differentiate between different methods of contraception,” they wrote.
Ramjee and McCormack suggested that other immune cells, and not necessarily T cells found in the cervix, could play a role in this finding. – by Will Offit
Disclosures: The researchers report no relevant financial disclosures. McCormack reports grants and nonfinancial support from Gilead Sciences outside the submitted work and reports having a patent UK HCV HIV vaccine issued.