HIV disease progression by hormonal contraceptive method: secondary analysis of a randomized trial

Stringer, Elizabeth M.; Levy, Jens; Sinkala, Moses; Benjamin, H.; Matongo, Inutu; Chintu, Namwinga; Stringer, Jeffrey S. A.

doi:10.1097/qad.0b013e32832cbca8

Cited by 47 publications

(44 citation statements)

References 16 publications

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“…It is difficult to predict whether post-menopausal women afflicted with HIV will benefit from the available hormone replacement therapies currently used. Evidence indicates that non-metabolizing synthetic progestins may actually worsen the progression of HIV (Baeten et al, 2005; Stringer et al, 2007, 2009), whereas natural P 4 may be beneficial (Vassiliadou et al, 1999). In the present study, we observed chronic P 4 co-administration with Tat-induction to be beneficial for anxiety-like behavior among OVX mice, adding to its therapeutic potential which is already recognized for its intravenous efficacy in treating brain injury (Stein, 2014).…”

Section: Discussionmentioning

confidence: 99%

Progesterone protects normative anxiety-like responding among ovariectomized female mice that conditionally express the HIV-1 regulatory protein, Tat, in the CNS

Paris

Fenwick

McLaughlin

2014

Hormones and Behavior

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Increased anxiety is co-morbid with human immunodeficiency virus (HIV) infection. Actions of the neurotoxic HIV-1 regulatory protein, Tat, may contribute to affective dysfunction. We hypothesized that Tat expression would increase anxiety-like behavior of female GT-tg bigenic mice that express HIV-1 Tat protein in the brain in a doxycycline-dependent manner. Furthermore, given reports that HIV-induced anxiety may occur at lower rates among women, and that the neurotoxic effects of Tat are ameliorated by sex steroids in vitro, we hypothesized that 17β-estradiol and/or progesterone would ameliorate Tat-induced anxiety-like effects. Among naturally-cycling proestrous and diestrous mice, Tat-induction via 7 days of doxycycline treatment significantly increased anxiety-like responding in an open field, elevated plus maze and a marble-burying task, compared to treatment with saline. Proestrous mice demonstrated less anxiety-like behavior than diestrous mice in the open field and elevated plus maze, but these effects did not significantly interact with Tat-induction. Among ovariectomized mice, doxycycline-induced Tat protein significantly increased anxiety-like behavior in an elevated plus maze and a marble burying task compared to saline-treated mice, but not an open field (where anxiety-like responding was already maximal). Co-administration of progesterone (4 mg/kg), but not 17β-estradiol (0.09 mg/kg), with doxycycline significantly ameliorated anxiety-like responding in the elevated plus maze and marble burying tasks. When administered together, 17β-estradiol partially antagonized the protective effects of progesterone on Tat-induced anxiety-like behavior. These findings support evidence of steroid-protection over HIV-1 proteins, and extend them by demonstrating the protective capacity of progesterone on Tat-induced anxiety-like behavior of ovariectomized female mice.

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Section: Discussionmentioning

confidence: 99%

Progesterone protects normative anxiety-like responding among ovariectomized female mice that conditionally express the HIV-1 regulatory protein, Tat, in the CNS

Paris

Fenwick

McLaughlin

2014

Hormones and Behavior

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“…A secondary analysis from a randomized trial of 595 women showed an increased risk of declining CD4+ count (a marker of immune system function and predictor of HIV disease progression) among the 302 women randomized to hormonal contraceptives [DMPA or COC] when compared with the 293 women randomized to the copper IUD (HR [95% CI]: 1.56 [1.08–2.26] for DMPA and 1.69 [1.09–2.64] for COC) [72]. However, loss to follow-up and contraceptive method switching were common; therefore, the intent-to-treat analysis failed to show an association between hormonal contraception and HIV disease progression.…”

Section: 0 Hormonal Contraceptive Use and Hiv Disease Progressionmentioning

confidence: 99%

“…Overall, only one outlying study with the methodologic limitations described above has indicated concern for HIV disease progression with use of hormonal contraception [72], but others show either no effect or reduced disease progression with use of hormonal contraception [11]. Therefore, the available data indicate that hormonal contraceptives do not impact the rate of disease progression for women living with HIV.…”

Section: 0 Hormonal Contraceptive Use and Hiv Disease Progressionmentioning

confidence: 99%

Drug–Drug Interactions, Effectiveness, and Safety of Hormonal Contraceptives in Women Living with HIV

et al. 2016

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Family planning options, including hormonal contraceptives, are essential for improving reproductive health among the more than 17 million women living with human immunodeficiency virus (HIV) worldwide. For these women, prevention of unintended pregnancy decreases maternal and child mortality, as well as reduces the risk of perinatal HIV transmission. Similarly, treatment of HIV with antiretroviral therapy (ART) is essential for reducing morbidity and mortality among HIV-positive individuals, as well as preventing HIV transmission between sexual partners or from mother to child. Importantly, despite the benefits of hormonal contraceptives, barriers to effective family planning methods exist for HIV-positive women. Specifically, drug-drug interactions can occur between some antiretroviral medications and some hormonal contraceptives, which may influence both contraceptive efficacy and tolerability. In addition, safety concerns have been raised about the impact of hormonal contraceptives on HIV disease progression, tolerability and the risk of female-to-male HIV transmission. This review article summarizes the potential for drug-drug interactions, tolerability, and contraceptive effectiveness when hormonal contraceptives are combined with ART. In addition, the evidence surrounding the influence of hormonal contraceptives on HIV transmission and HIV disease progression in women living with HIV are summarized.

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“…In a treatment naïve cohort of 595 HIV-1 positive women, Stringer who did not use hormonal contraceptives [12]. However, a longitudinal study conducted among postpartum women in Kenya found no association between hormonal contraceptive use and increases in VL or decreases in CD4 + T cell counts [13].…”

Section: Introductionmentioning

confidence: 99%

Hormonal contraceptive use and response to antiretroviral therapy among adolescent females

et al. 2011

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a b s t r a c tBackground: To assess hormonal contraceptive use and response to antiretroviral therapy (ART) as measured by changes in HIV-1 RNA viral load (VL) and CD4 + cell counts in HIV positive female adolescents on ART. Material and Methods: This study used prospective longitudinal data from the REACH cohort to compare the response to ART in adolescent females using hormonal contraception to the response to ART in adolescent females not using hormonal contraception. Outcome measures were VL and CD4 + T cell counts assessed every 3 months. The association between hormonal contraception exposure and the response to ART was assessed using repeated measures multivariate analysis while adjusting for additional covariates. Results: The majority of participants were African American (73%). Median baseline age was 17 years . VL of ART users decreased over time in both hormonal contraception users (−0.0152 log copies/ml per day) and non-users (−0.0154 log copies/ml per day). However, the decrease was slightly lower (1.2 × 10 −3 , 95%CI: 6.2 × 10 −5 -2.4 × 10 −3 copies/ml log VL per day, p-value = 0.03) among hormonal contraceptive users. Conclusions: This study shows a significant association between hormonal contraception use and a diminished response to ART. However, the impact of hormonal contraception on HIV-1 acquisition, progression, and treatment is still not clear.

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HIV disease progression by hormonal contraceptive method: secondary analysis of a randomized trial

Cited by 47 publications

References 16 publications

Progesterone protects normative anxiety-like responding among ovariectomized female mice that conditionally express the HIV-1 regulatory protein, Tat, in the CNS

Progesterone protects normative anxiety-like responding among ovariectomized female mice that conditionally express the HIV-1 regulatory protein, Tat, in the CNS

Drug–Drug Interactions, Effectiveness, and Safety of Hormonal Contraceptives in Women Living with HIV

Hormonal contraceptive use and response to antiretroviral therapy among adolescent females

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