The risk of HIV disease progression and hormonal contraception

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AidsHIV-positive women can safely use hormonal contraception, according to research. Hormonal implants and injectable contraceptives were associated with a reduced mortality risk, and use of injectables delayed the need for antiretroviral therapy (ART). Pregnancy did not increase the risk of death or the need to start ART, while breastfeeding was protective against both these outcomes.

The study was conducted in Lusaka, Zambia, and involved 1,656 HIV-positive women. The authors recommend that all effective contraception methods – including injectables and implants – can be promoted for the prevention of unintended pregnancy.

In the general population, hormonal contraceptive use is associated with decreased mother/child mortality, a reduction in the risk of unwanted pregnancy and improved reproductive autonomy in women. Use of hormonal contraception is a mainstay of the World Health Organisation’s strategy for the prevention of mother-to-child transmission (PMTCT) of HIV. Despite this, there are conflicting data regarding the safety of hormonal contraceptives in terms of HIV disease progression. It is also uncertain if the hormonal changes associated with pregnancy and breastfeeding have an adverse effect on the health of women with HIV.

Investigators therefore designed a prospective study involving HIV-positive women recruited between 1994 and 2012. All the women were in relationships with HIV-negative men and were followed-up at three-monthly intervals.
The authors gathered data on use of contraceptives, pregnancy and breastfeeding. Contraceptive methods were categorised as hormonal (injectables, implant, oral contraceptive pills) or non-hormonal (e.g. condoms, copper IUD, hysterectomy or vasectomy). Participants also provided information on pregnancy and breastfeeding.

Study outcomes were time to death or initiation of ART (excluding short-course for prevention of PMTCT). ART become available in Zambia in late 2003, so analysis of ART restricted to November 2003-2012. The investigators explored the association between these outcomes and hormonal contraception, pregnancy and breastfeeding, controlling for other factors known to be associated with HIV disease progression.

The 1,656 women contributed 3,359 person-years of follow-up. There were 224 deaths, a mortality rate of 7 per 100 person-years. Compared to women using non-hormonal contraception, those using implants (HR = 0.32, p = 0.051) and injectables (HR = 0.60, p = 0.04) experienced lower mortality rates. Women who used oral contraceptives had similar death rates to women who used non-hormonal methods of birth control.

Mortality rates were comparable between non-pregnant and pregnant women, while breastfeeding women had lower rates of death compared to non-breastfeeding women (HR = 0.32; p < 0.001).

Between 2003-2012 a total of 290 initiated ART (15 per 100 person-years of follow-up). Compared to women using non-hormonal contraception, patients using implants (HR = 0.45, p = 0.04) and oral contraceptives (HR = 0.65, p = 0.044) experienced lower rates of ART initiation. There was no significant association between implants and need for ART. Compared to women who were not pregnant, pregnant women had a non-significant increase in ART initiation rates, but women who were breastfeeding experienced significantly lower rates of ART initiation (HR = 0.45, p = 0.003).

Other factors associated with starting ART included enrolment before 2007, older age, higher levels of literacy, more advanced HIV disease and increased viral load.

In the statistical model that controlled for potential confounders, implants and injectables both reduced the risk of death compared to non-hormonal contraceptives. There was no association between pregnancy and mortality risk, but breastfeeding significantly delayed time to death. A model that took into account pregnancy interval showed that implants (p = 0.04), injectables (p = 0.032) and breastfeeding (p < 0.001) were all protective against mortality. More advanced HIV disease at enrolment was associated with an increased risk of death during follow-up.
Implants were shown to delay the need for ART. There was no significant association between pregnancy and ART initiation. However, breastfeeding provided significant protection against the need for ART. The model that took into account pregnancy interval revealed that implant use (p = 0.04) and breastfeeding (p < 0.001) significantly protected against the need to start ART. Older age, literacy, and more advanced HIV disease stage at enrolment were all associated with faster time to ART.

“Hormonal contraceptive implants and injectable contraceptives were associated with significantly lower mortality rates among HIV infected women. Hormonal implants were also protective for ART initiation. Oral contraceptive pills and pregnancy were not associated with death or ART initiation, while breastfeeding was protective for both,” conclude the authors. “For HIV-positive women who wish to delay fertility, our findings support the conclusion that hormonal implants and injectables can be used without concerns about deleterious health effects and with possible health benefits.”

Background: Some studies suggest hormonal contraception, pregnancy, and/or breastfeeding may influence rates of HIV disease progression.
Methods: From 1994-2012, HIV discordant couples recruited at couples’ voluntary HIV counseling and testing centers in Lusaka were followed 3-monthly. Multivariate survival analyses explored associations between time-varying contraception, pregnancy, and breastfeeding and two outcomes among HIV-positive women: 1) time-to-death and 2) time-to-antiretroviral treatment (ART) initiation.
Results: Among 1,656 female seropositive, male seronegative couples followed for 3,359 person years (PY), 224 women died (6.7/100PY;95%CI:5.8-7.6). After 2003, 290 women initiated ART (14.5/100PY;95%CI:12.9-16.2). In a multivariate model of time-to-death, hormonal implant (aHR=0.30;95%CI:0.01-0.98) and injectable (aHR=0.59;95%CI:0.36-0.97) were significantly protective relative to non-hormonal method use while OCP use was not (aHR=1.08;95%CI:0.74-1.57) controlling for baseline HIV disease stage, time-varying pregnancy, time-varying breastfeeding, and year of enrollment. In a multivariate model of time-to-ART initiation, implant was protective (aHR=0.54;95%CI:0.31-0.95) while OCP (aHR=0.70;95%CI:0.44-1.10) and injectable (aHR=0.85;95%CI:0.55-1.32) were not relative to non-hormonal method use controlling for variables above, woman’s age, and literacy. Pregnancy was not significantly associated with death (aHR=1.07;95%CI:0.68-1.66) or ART initiation (aHR=1.24;95%CI:0.83-1.86) while breastfeeding was protective for death (aHR=0.34;95%CI:0.19-0.62) and ART initiation (aHR=0.49;95%CI:0.29-0.85).
Conclusions: Hormonal implants and injectables significantly predicted lower mortality; implants were protective for ART initiation. OCPs and pregnancy were not associated with death or ART initiation, while breastfeeding was protective for both. Findings from this 18-year cohort study suggest 1) HIV-positive women desiring pregnancy can be counseled to do so and breastfeed, and 2) all effective contraceptive methods including injectables and implants should be promoted to prevent unintended pregnancy.

Aidsmap material
Journal of Acquired Immune Deficiency Syndromes abstract

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