Does hormonal contraception speed HIV progression?

Does the use of hormonal contraception during the early stages of HIV infection affect disease progression? Likewise, does its use during the later stages of infection affect disease progression?

These questions cannot be answered yet. The only evidence so far that hormonal contraceptive use might affect HIV disease progression comes from a prospective study conducted among sex workers in Mombasa, Kenya. (1) This evidence suggests that using hormonal contraception at the time of infection--before women know that they are infected--may accelerate HIV-related deterioration of the immune system and thus speed the natural course of the infection.

If other studies confirm this finding, it could provide additional incentive for hormonal contraceptive users who are at high risk of HIV infection to also use condoms consistently for HIV prevention. It could also lead to changes in recommendations for hormonal contraceptive use by women at high risk of HIV infection. To date, however, the evidence of such a risk is considered insufficient to warrant any restrictions on hormonal contraceptive use by women with HIV/AIDS or women at high risk of infection.

Analyses consider viral set point, viral diversity

The association between hormonal contraceptive use and clinical progression of HIV has not been studied directly. But the research in Kenya showed associations between hormonal contraceptive use and two strong predictors of HIV disease progression, AIDS, and death: low CD4+ cell counts and high viral set point. CD4+ cells are immune system cells that are destroyed by HIV as the virus replicates. CD4+ count (the number of functioning CD4+ cells per liter of blood) indicates the strength of an infected person's immune system and whether antiretroviral treatment is needed. Viral set point is the level of HIV in the blood (viral load) after the immune system's initial response to the virus, generally three or four months after a person is infected.

In the Kenya study, researchers found that median viral set point was significantly higher among women using the injectable contraceptive depot-medroxyprogesterone acetate (DMPA) at the estimated time of HIV infection than it was among women using no hormonal contraception at that time. This difference between the two groups of women persisted during follow-up (median of 34 months). However, continuing use of DMPA did not appear to further increase viral load.

Overall, study participants' use of oral contraceptive pills was not associated with higher viral set points. (2) But in a subset of 156 HIV-infected sex workers (82 of whom used any hormonal contraception), use of either oral contraceptives or DMPA at the time of HIV infection was associated with acquiring genetically diverse virus populations from one partner. The women who had acquired these genetically diverse virus populations also had significantly higher viral set points and significantly lower CD4+ counts four to 24 months after infection than did those with only one strain of the virus. (3)

The study results suggest that greater viral genetic diversity in early HIV infection could be a mechanism by which hormonal contraception affects viral load and, ultimately, disease progression, says Dr. Ludo Lavreys, former field director of the HIV research site of the University of Washington/University of Nairobi in Mombasa.

Research on the possible relationship between hormonal contraception and HIV disease progression is hampered by the same methodological challenges facing studies of hormonal contraceptive use and the risk of HIV acquisition or transmission (see articles, pages 5 and 14). One strength of the Kenya analyses is that researchers were able to estimate the dates of HIV infection with some precision because data were drawn from a larger prospective study of women who were HIV-negative at enrollment and were subsequently tested each month for HIV.

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But findings from this research among Kenyan sex workers may not apply to other populations, and they have not been confirmed by other studies. (4) For example, data from the large, FHI-led, prospective study of hormonal contraceptive use and HIV acquisition (see article, page 4) and a sub-study of 186 women with primary HIV infection found that hormonal contraceptive use at the time of HIV infection was not significantly associated with a higher HIV viral set point. This data was collected primarily from family planning clients in Uganda and Zimbabwe. (5) Further research among other populations in different geographic areas is needed to clarify the relationship between hormonal contraceptive use and HIV disease progression.

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The limited evidence from Kenya suggests that any impact hormonal contraceptive use may have on HIV disease progression occurs during the early stages of the infection. But as part of their continuing research in Kenya, scientists from the University of Nairobi, Coast Provincial General Hospital in Mombasa, and the University of Washington at Seattle plan to evaluate the relationship between hormonal contraceptive use and HIV disease progression during the later, chronic stage of HIV infection. The study in Uganda and Zimbabwe will also explore whether hormonal contraception affects disease progression over time.

References

(1) Sagar M, Lavreys L, Baeten J, et al. Infection with multiple human immunodeficiency virus type 1 variants is associated with faster disease progression. J Virol 2003;77(23):12921-26.

(2) Lavreys L, Baeten J, Kreiss JK, et al. Injectable contraceptive use and genital ulcer disease during the early phase of HIV-1. J Infect Dis 2004;189(2):303-11.

(3) Sagar M, Lavreys L, Baeten J, et al. Identification of modifiable factors that affect the genetic diversity of the transmitted HIV-1 population. AIDS 2004;18(4): 615-19; Baeten J, 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):18-20.

(4) Cejtin HE, Jacobson L, Springer G, et al. Effect of hormonal contraceptive use on plasma HIV-1 RNA levels among HIV-infected women. AIDS 2003; 17(11):1702-4.

(5) Morrison C, Kwok C, Chen P, et al. Predictors of viral setpoint among African women with primary HIV-1 infection [abstract]. XVIth International Conference on AIDS, Toronto, Canada, August 13-18, 2006.