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  2nd International Workshop on HIV & Women
January 9-10, 2012
Bethesda, Maryland
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Hormonal Contraceptives Tied to Non-AIDS Disease or Death in HIV+ US Women: 'doubles Non-AIDS Risks'
  2nd International Workshop on HIV & Women. January 9-10, 2012, Bethesda, Maryland

Mark Mascolini

Taking hormonal contraceptives doubled the risk of a major non-AIDS disease (especially cardiovascular disease) and the risk of a non-AIDS disease or death in a study of 467 HIV-positive women at Vanderbilt University in Nashville [1]. Hormonal contraceptive use did not affect the risk of death alone, the risk of AIDS, or the risk of AIDS or death.

Studies of hormonal contraceptive impact on HIV-positive women have yielded conflicting results, and most of these studies involve women in low- or middle-income countries. No study of hormonal contraceptives has probed for potential associations between their use and non-AIDS diseases in women with HIV.

A study of 248 Kenyan women with newly acquired HIV infection found that use of injectable DMPA at the time of HIV infection was associated with a 0.33-log (about 2-fold) higher viral load set point (P = 0.03) [2]. Women who used DMPA or oral hormonal contraceptives at the time of HIV infection were almost 3 times more likely to be infected with multiple viral variants. And women who acquired multiple viral variants had a significantly lower CD4 count 4 to 24 months after infection (median 416 versus 617, P = 0.01).

A 595-woman, secondary analysis of a trial that randomized Zambian women to an intrauterine device or hormonal contraception found that those who took oral contraceptives or injected DMPA ran about a 65% higher risk of HIV disease progression or death [3].

In contrast, a prospective 4109-woman study at 13 sites in Africa and Asia found no association between implanted or injectable hormonal contraceptives (adjusted hazard ratio 1.0, 95% confidence interval 0.8 to 1.1) or oral hormonal contraceptives (adjusted hazard ratio 0.8, 95% confidence interval 0.6 to 1.1) and disease progression [4].

The retrospective Nashville study involved 467 hormonal contraceptive-eligible women without a history of pulmonary embolism, deep venous thromboembolism, hysterectomy, bilateral tubal ligation, breast cancer, or pregnancy [1]. The investigators assessed rates of AIDS-defining events, non-AIDS events (cardiovascular, renal, hepatic, or metabolic disease, and non-AIDS malignancies, but not osteoporosis), and death. They defined contraceptive exposure as 30 or more days of oral, patch, or injectable use, and they defined baseline as a period of 90 days around the first clinic visit for those on contraceptives or first contraceptive use for those starting contraceptives.

A propensity score for hormonal contraceptive use considered age, race, year of cohort entry, baseline and nadir CD4 count, baseline viral load, history of AIDS and non-AIDS diseases, prior antiretroviral use, current antiretroviral use, baseline hemoglobin, and time from first clinic visit until first hormonal contraceptive use.

Of the 476 women assessed, 112 (24%) used hormonal contraceptives and 355 did not. Of those who used contraceptives, 51 took pills and 61 injected. Compared with women who did not use hormonal contraceptives, those who did were younger (median 28.6 versus 35.6, P < 0.001), had a higher baseline CD4 count (median 523 versus 364, P < 0.01), had a lower viral load (median 3.1 versus 4.1 log, P < 0.001), and were more likely to have taken combination antiretroviral therapy (30.4% versus 26.8%, not a significant difference). A higher proportion of contraceptive users had a history of AIDS (13% versus 5%), and a lower proportion had a history of a non-AIDS disease (25% versus 38%).

During follow-up a lower proportion of women who used hormonal contraception died (6% versus 15%). However, a higher proportion of contraceptive users had a new non-AIDS disease (30% versus 20%). Both of these differences were statistically significant. Contraceptive users and nonusers did not differ significantly in proportions with a new AIDS diagnosis (11% and 12%), new AIDS or death (14% and 21%), or new non-AIDS disease or death (34% and 32%). Of non-AIDS diseases analyzed, cardiovascular disease (hypertension in 90%, myocardial infarction in the rest) was significantly more frequent in contraceptive users than in nonusers (12% versus 5%).

A propensity score-adjusted analysis determined that hormonal contraceptive use doubled the risk of a new non-AIDS disease (hazard ratio [HR] 1.9, P = 0.02) and nearly doubled the risk of a non-AIDS disease or death (HR 1.7, P = 0.03). Hormonal contraceptive use did not affect the risk of AIDS, death alone, or AIDS or death.

Focusing only on injectable contraceptive users, the researchers again found higher risks of a new non-AIDS disease (HR 2.0, P = 0.03) and a new non-AIDS disease or death (HR 1.9, P = 0.03). Oral contraceptive use by itself did not independently affect the risk of AIDS, a non-AIDS disease, or death.

Although hormonal contraceptive users were generally healthier at baseline, the researchers concluded, they had higher risks of non-AIDS disease and non-AIDS disease or death. The researchers cautioned that their findings are limited by the retrospective nature of the study, by lack of hormonal contraceptive adherence data, and by not including osteoporosis or body mass index in the analysis.

"As the number of women with HIV infection who are of child-bearing age increases," the researchers warned, "it is important to better understand any negative effect of hormonal contraceptives on patient health."


1. Melekhin V, Turner M, Shepherd B, Sterling T. Hormonal contraceptive use is associated with a higher risk of non-AIDS-defining events in HIV-1-infected women. 2nd International Workshop on HIV & Women. January 9-10, 2012, Bethesda, Maryland. Abstract O_13.

2. Baeten JM, Lavreys L, Sagar M, et al. Effect of contraceptive methods on natural history of HIV: studies from the Mombasa cohort. J Acquir Immune Defic Syndr. 2005;38(suppl 1):S18-S21.

3. Stringer EM, Levy J, Sinkala M, Chi BH, Matongo I, Chintu N, Stringer JS. HIV disease progression by hormonal contraceptive method: secondary analysis of a randomized trial. AIDS. 2009;23:1377-1382.

4. Stringer EM, Giganti M, Carter RJ, El-Sadr W, Abrams EJ, Stringer JS; MTCT-Plus Initiative. Hormonal contraception and HIV disease progression: a multicountry cohort analysis of the MTCT-Plus Initiative. AIDS. 2009;23(Suppl 1):S69-S77.