Johns Hopkins Bloomberg School of Public Health: The INFO Project

The 2003 Expert Working Group made several changes to the MEC to indicate that women often can safely use IUDs in conditions related to HIV and other sexually transmitted infections (STIs). Taken together, these changes should help reduce some providers’ concerns about offering IUDs in areas where HIV infection and other STIs are common.

At the meeting the WHO Expert Working Group concluded that a woman generally can start using an IUD, if she wishes, even if she has AIDS—provided she is receiving ARV therapy and is clinically well—or if she has HIV infection or she is at high risk of HIV infection. The Expert Working Group changed these conditions from category 3 to category 2 for starting IUD use (see Table 2). According to the bulk of research considered at the WHO meeting, IUD use does not increase a woman’s chances of acquiring HIV infection (2, 3, 14, 15, 22-24, 35, 37, 39, 43).

Women generally can keep their IUDs if they become infected with HIV or develop AIDS while using IUDs (category 2), although IUD users with AIDS should be carefully monitored for pelvic infection. Limited evidence shows that complications of IUD use are no more common among IUD users infected with HIV than among IUD users who are not infected with HIV (29, 40). Also, IUD use does not increase HIV transmission to sexual partners (2, 30, 38).

Concerning other STIs, the WHO Expert Working Group concluded that a woman generally can keep her IUD (category 2) even if she develops an STI or pelvic inflammatory disease (PID) while using the method, provided the infection is successfully treated. The shift to category 2 makes the MEC consistent with WHO’s Selected Practice Recommendations concerning PID and IUDs, issued in 2002 (52). These changes rest on findings that there is no difference in the clinical course of PID whether the IUD is removed or left in place during treatment (18, 42, 45). Furthermore, a woman usually can start IUD use even if she has an STI other than chlamydial infection or gonorrhea (category 2). These other STIs include ulcerative diseases such as syphilis and herpes.

After considering evidence on IUD use in situations where STIs are common, the Expert Working Group concluded that a woman can usually have an IUD inserted unless she faces a very high individual likelihood of exposure to chlamydia or gonorrhea. A study in Kenya found that women at high individual risk of these STIs were more likely to develop IUD-related complications after the device was inserted than those not at high risk (28). The Expert Working Group distinguished individual likelihood of exposure from high prevalence of these STIs in an area.

A provider still usually should not insert an IUD in a woman known to have AIDS (category 3) unless she is clinically well on ARV therapy (category 2). Nor should a woman receive an IUD if she has PID, chlamydial infection, gonorrhea, or purulent cervicitis (category 4). The MEC meeting did not change these classifications. Chlamydial infection and gonorrhea can manifest themselves as purulent cervicitis.

For two other conditions—obesity, and uterine fibroids that do not distort the uterine cavity—the Expert Working Group saw no evidence supporting a need for restrictions on IUD use (see Table 2).

Table 2. IUDs: Medical Eligibility Criteria Considered by the 2003 WHO Expert Working Group
Condition	Method
	Cu-IUD		LNG-IUD
	Initiation	Continuation	Initiation	Continuation
PID—current*	4	3 --> 2a	4	3 --> 2a
STIs
a) Current purulent cervicitis or chlamydial infection or gonorrhea**	4	4 --> 2a	4	4 --> 2a
b) Other STIs (excluding HIV and hepatitis)	2	2	2	2
c) Vaginitis (including trichomonas vaginalis and bacterial vaginosis)	2	2	2	2
d) Increased risk of STIs	3 --> 2/3b	3 --> 2	3 --> 2/3b	3 --> 2
High risk of HIV	3 --> 2	3 --> 2	3 --> 2	3 --> 2
HIV-infected†	3 --> 2	3 --> 2	3 --> 2	3 --> 2
AIDS	3	3 --> 2c	3	3 --> 2c
Clinically well on ARV therapy	2	2	2	2
Uterine fibroids that do not distort the uterus	2 --> 1	2 --> 1	2 --> 1	2 --> 1
Obesity	1	1	2 --> 1	1
Source: World Health Organization, 2003 (55) Refer to Table 1 for category definitions. Conventions used in the tables of this report: --> Indicates that category changed in 2003 MEC meeting; previous category is shown to the left of the arrow; new category, to the right. Italics and bold on condition and categories indicate a new condition added to the MEC. Italics on condition only indicate a redefined condition; see specific footnote for explanation of change. Shading in a cell of the table indicates that the current classification is category 3 (usually do not use) or 4 (do not use). Cu-IUD = copper-bearing IUD LNG-IUD = levonorgestrel-releasing IUD *Formerly, “PID—current or within the last 3 months” (51) **Formerly, STI “current or within 3 months (including purulent cervicitis)” (51) †Formerly, “HIV-positive” (51) Clarifications: a“Treat the PID/STI using appropriate antibiotics. There is usually no need for removal of the IUD if the client wishes to continue its use.” (55) b“If a woman has a very high individual likelihood of exposure to gonorrhea or chlamydia, the condition is a Category 3.” (55) c“IUD users with AIDS should be closely monitored for pelvic infection.” (55)

In light of perhaps 1 million people worldwide now using ARV therapy for HIV and a United Nations goal of treating 3 million, about half of whom will be women, by the end of 2005 (54), the MEC meeting assessed whether and how ARV drugs and contraceptive hormones interact. The chief concern is that ARV drugs might reduce the effectiveness of hormonal contraceptives and so increase the risk of pregnancy.

The few pharmacokinetic studies of certain ARV therapies used with limited courses of combined oral contraceptives (COCs) showed both positive and negative effects on hormone levels, and so the Expert Working Group expressed caution by categorizing hormonal contraceptives a Category 2 for users of ARV therapy. The evidence is not sufficient, however, to conclude that women on ARV therapy should avoid hormonal contraceptives. No studies of actual clinical outcomes, such as pregnancy rates or indicators of ovulation, have been completed. Thus there is not sufficient evidence yet whether or not the effectiveness of either hormonal contraceptives or ARV therapy is compromised. Clinical and pharmacokinetic studies involving the injectable progestin depot medroxyprogesterone acetate (DMPA) (Depo-Provera) are underway. Concern about lessened contraceptive effectiveness would focus, however, on lower-dose methods, such as COCs and progestin-only pills, and not so much on injectables. A woman who is infected with HIV should use condoms to prevent HIV transmission and to avoid reinfection. Consistent and correct use of condoms may compensate for any decrease in the effectiveness of hormonal methods (53).

Experts do not expect several classes of ARV drugs to interact with hormones because ARV drugs in these classes appear to have no effect on liver enzymes. Such drugs include nucleoside reverse transcriptase inhibitors (NsRTIs) such as zidovudine, stavudine, and lamivudine; nucleotide reverse transcriptase inhibitors (NtRTIs) such as tenofovir; and fusion inhibitors such as enfurvitide (31). Evidence is insufficient, however, to conclude that no interactions exist between these classes of drugs and contraceptive hormones.

Concerns focus on non-nucleoside reverse transcriptase inhibitors (NNRTIs) such as nevirapine and efavirenz and protease inhibitors such as saquinavir and ritonavir. Concerning the effectiveness of hormonal contraceptives, the few published pharmacokinetic studies of drug levels find conflicting effects on hormone levels after a single dose of COC hormones (25, 26, 36, 44). Concerning the effectiveness of ARV drugs, package labeling indicates that the level of the ARV drug amprenavir decreases when taken along with contraceptive hormones, while a study found levels of saquinavir unchanged. Currently, no more than one study report is available on any one ARV drug. For many ARV drugs no studies are available.

The ARV therapies proposed by WHO for use in limited-resource settings consist of two NsRTIs—lamivudine plus either stavudine or zidovudine—and an NNRTI—either nevirapine or efavirenz (53).

In another deliberation related to HIV/AIDS, the Expert Working Group concluded that evidence does not support any restrictions on hormonal contraceptives for women at high risk of HIV infection or with HIV infection, including those with AIDS. These health conditions remain category 1 for all hormonal methods. Exceptions are (1) initiation of the levonorgestrel-releasing IUD (category 3), where the concern is with insertion in women with AIDS, not with the hormone, and (2) ARV therapy (category 2/3; see previous section).

Hormonal methods do not protect against HIV infection. Condoms are the only family planning method that helps prevent HIV/AIDS and other STIs, as WHO guidance emphasizes (44).

This evidence, which included a randomized controlled trial conducted by UNAIDS (47), moved the 2003 MEC meeting to reclassify spermicide to category 4 (not to be used) and diaphragms used with spermicide to category 3 (usually not recommended) for the conditions related to HIV/AIDS (see Table 3).